fatal neonatal mitochondrial: Topics by WorldWideScience.org

Sample records for fatal neonatal mitochondrial

EARS2 mutations cause fatal neonatal lactic acidosis, recurrent hypoglycemia and agenesis of corpus callosum.

Science.gov (United States)

Danhauser, Katharina; Haack, Tobias B; Alhaddad, Bader; Melcher, Marlen; Seibt, Annette; Strom, Tim M; Meitinger, Thomas; Klee, Dirk; Mayatepek, Ertan; Prokisch, Holger; Distelmaier, Felix

2016-06-01

Mitochondrial aminoacyl tRNA synthetases are essential for organelle protein synthesis. Genetic defects affecting the function of these enzymes may cause pediatric mitochondrial disease. Here, we report on a child with fatal neonatal lactic acidosis and recurrent hypoglycemia caused by mutations in EARS2, encoding mitochondrial glutamyl-tRNA synthetase 2. Brain ultrasound revealed agenesis of corpus callosum. Studies on patient-derived skin fibroblasts showed severely decreased EARS2 protein levels, elevated reactive oxygen species (ROS) production, and altered mitochondrial morphology. Our report further illustrates the clinical spectrum of the severe neonatal-onset form of EARS2 mutations. Moreover, in this case the live-cell parameters appeared to be more sensitive to mitochondrial dysfunction compared to standard diagnostics, which indicates the potential relevance of fibroblast studies in children with mitochondrial diseases.
A fatal case of hypernatraemic dehydration in a neonate.

Science.gov (United States)

Staub, Eveline; Wilkins, Barry

2012-09-01

Problems with lactation can result in hypernatraemic dehydration in the neonate, with potentially severe adverse consequences. This is illustrated in this fatal case of a 10 day old neonate who presented with excessive hypernatraemic dehydration due to insufficient breast milk intake, resulting in cerebral sinus vein thrombosis with cerebral haemorrhage and infarction. Differential diagnosis included excessive sodium intake (through inappropriately mixed formula or house remedies or through hyperaldosteronism) and high water deficit (renal or gastrointestinal losses, nephrogenic or central diabetes insipidus), all of which were ruled out by specific investigations or history. No evidence was found for inborn error of metabolism. The dehydration in this baby, however, was accentuated by trans-epidermal water loss due to an ichthyosiform skin condition. This first ever reported Australian fatality from neonatal hypernatraemic dehydration supports the concern of health care professionals over rising incidences of this entity in exclusively breastfed infants, and should encourage endorsement of improved monitoring of weight loss in newborns and breastfeeding support for their mothers. © 2012 The Authors. Journal of Paediatrics and Child Health © 2012 Paediatrics and Child Health Division (Royal Australasian College of Physicians).
"Stiff neonate" with mitochondrial DNA depletion and secondary neurotransmitter defects.

LENUS (Irish Health Repository)

Moran, Margaret M

2011-12-01

Mitochondrial disorders comprise a heterogenous group. A neonate who presented with episodes of severe truncal hypertonia and apnea progressed to a hypokinetic rigid syndrome characterized by hypokinesia, tremulousness, profound head lag, absent suck and gag reflexes, brisk deep tendon reflexes, ankle and jaw clonus, and evidence of autonomic dysfunction. Analysis of cerebrospinal fluid neurotransmitters from age 7 weeks demonstrated low levels of amine metabolites (homovanillic acid and 5-hydroxyindoleacetic acid), tetrahydrobiopterin, and pyridoxal phosphate. Mitochondrial DNA quantitative studies on muscle homogenate demonstrated a mitochondrial DNA depletion disorder. Respiratory chain enzymology demonstrated decreased complex IV activity. Screening for mitochondrial DNA rearrangement disorders and sequencing relevant mitochondrial genes produced negative results. No clinical or biochemical response to treatment with pyridoxal phosphate, tetrahydrobiopterin, or l-dopa occurred. The clinical course was progressive, and the patient died at age 19 months. Mitochondrial disorders causing secondary neurotransmitter diseases are usually severe, but are rarely reported. This diagnosis should be considered in neonates or infants who present with hypertonia, hypokinesia rigidity, and progressive neurodegeneration.
Fatal Neonatal Peritoneal Candidiasis Mimicking Mucormycosis-A Case Report and Review of Literature.

Science.gov (United States)

Kashyap, Bineeta; Kusumakar, Kanupriya; Kumar Sarin, Yogesh

2016-10-01

Candida species have been implicated as significant contributors to morbidity in the neonatal period and are associated with 25-50% of mortality in invasive neonatal candidiasis. Peritoneal candidiasis, being paucisymptomatic, cannot often be correctly identified in a preterm neonate. The correct approach to diagnosis of neonatal peritoneal candidiasis is taking into account the epidemiology along with a strong clinical suspicion and appropriate timely diagnostic interventions. We report a case of fatal neonatal peritoneal candidiasis which was misdiagnosed as mucormycosis. © The Author [2016]. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.
Fatal Neonatal Herpes Simplex Infection Likely from Unrecognized Breast Lesions.

Science.gov (United States)

Field, Scott S

2016-02-01

Type 1 herpes simplex virus (HSV-1) is very prevalent yet in rare circumstances can lead to fatal neonatal disease. Genital acquisition of type 2 HSV is the usual mode for neonatal herpes, but HSV-1 transmission by genital or extragenital means may result in greater mortality rates. A very rare scenario is presented in which the mode of transmission was likely through breast lesions. The lesions were seen by nurses as well as the lactation consultant and obstetrician in the hospital after delivery of the affected baby but not recognized as possibly being caused by herpes. The baby died 9 days after birth with hepatic failure and disseminated intravascular coagulation. Peripartum health care workers need to be aware of potential nongenital (including from the breast[s]) neonatal herpes acquisition, which can be lethal. © The Author(s) 2015.
Zika Virus Fatally Infects Wild Type Neonatal Mice and Replicates in Central Nervous System

Directory of Open Access Journals (Sweden)

Shuxuan Li

2018-01-01

Full Text Available Zika virus (ZIKV has been defined as a teratogenic pathogen behind the increased number of cases of microcephaly in French Polynesia, Brazil, Puerto Rico, and other South American countries. Experimental studies using animal models have achieved tremendous insight into understanding the viral pathogenesis, transmission, teratogenic mechanisms, and virus–host interactions. However, the animals used in published investigations are mostly interferon (IFN-compromised, either genetically or via antibody treatment. Herein, we studied ZIKV infection in IFN-competent mice using African (MR766 and Asian strains (PRVABC59 and SZ-WIV01. After testing four different species of mice, we found that BALB/c neonatal mice were resistant to ZIKV infection, that Kunming, ICR and C57BL/6 neonatal mice were fatally susceptible to ZIKV infection, and that the fatality of C57BL/6 neonates from 1 to 3 days old were in a viral dose-dependent manner. The size and weight of the brain were significantly reduced, and the ZIKV-infected mice showed neuronal symptoms such as hind-limb paralysis, tremor, and poor balance during walking. Pathologic and immunofluorescent experiments revealed that ZIKV infected different areas of the central nervous system (CNS including gray matter, hippocampus, cerebral cortex, and spinal cord, but not olfactory bulb. Interestingly, ZIKV replicated in multiple organs and resulted in pathogenesis in liver and testis, implying that ZIKV infection may engender a high health risk in neonates by postnatal infection. In summary, we investigated ZIKV pathogenesis using an animal model that is not IFN-compromised.
Fatal neonatal-onset mitochondrial respiratory chain disease with T cell immunodeficiency.

Science.gov (United States)

Reichenbach, Janine; Schubert, Ralf; Horvàth, Rita; Petersen, Jens; Fütterer, Nancy; Malle, Elisabeth; Stumpf, Andreas; Gebhardt, Boris R; Koehl, Ulrike; Schraven, Burkhart; Zielen, Stefan

2006-09-01

We present the clinical and laboratory features of a boy with a new syndrome of mitochondrial depletion syndrome and T cell immunodeficiency. The child suffered from severe recurrent infectious diseases, anemia, and thrombocytopenia. Clinically, he presented with severe psychomotor retardation, axial hypotonia, and a disturbed pain perception leading to debilitating biting of the thumb, lower lip, and tongue. Brain imaging showed hypoplasia of corpus callosum and an impaired myelinization of the temporo-occipital region with consecutive supratentorial hydrocephalus. Histologic examination of a skeletal muscle biopsy was normal. Biochemical investigation showed combined deficiency of respiratory chain complexes II+III and IV. MtDNA depletion was found by real-time PCR. No pathogenic mutations were identified in the TK2, SUCLA2, DGUOK, and ECGF1 genes. A heterozygous missense mutation was found in POLG1. The pathogenic relevance of this mutation is unclear. Interestingly, a lack of CD8(+) T lymphocytes as well as NK cells was also observed. The percentage of CD45RO-expressing cells was decreased in activated CD8(+) T lymphocytes. Activation of T lymphocytes via IL-2 was diminished. The occurrence of the immunologic deficiency in our patient with mtDNA depletion is a rare finding, implying that cells of the immune system might also be affected by mitochondrial disease.
[Fatal course of neonatal citrobacter infection and its legal evaluation].

Science.gov (United States)

Kokrdová, Z; Janouch, J

2011-02-01

The article describes fatal course of citrobacter central nervous system infection in the neonates and the subsequent legal responsibility of the medical facility. Case report with the review of a lawyer specialized in medical law. Department of Obstetrics and Gynecology, Faculty of Health Studies, University of Pardubice, Pardubice, Faculty of Military Health Science, University of Defence, Hradec Králové. The court granted plaintiff's claim has been fully paid by the insurance company, since it did not show the fault of the medical facility. Health injury was caused by operational activities and the right to compensation is in accordance with Section 420a of the Civil Code.
AKIP1 expression modulates mitochondrial function in rat neonatal cardiomyocytes.

Directory of Open Access Journals (Sweden)

Hongjuan Yu

Full Text Available A kinase interacting protein 1 (AKIP1 is a molecular regulator of protein kinase A and nuclear factor kappa B signalling. Recent evidence suggests AKIP1 is increased in response to cardiac stress, modulates acute ischemic stress response, and is localized to mitochondria in cardiomyocytes. The mitochondrial function of AKIP1 is, however, still elusive. Here, we investigated the mitochondrial function of AKIP1 in a neonatal cardiomyocyte model of phenylephrine (PE-induced hypertrophy. Using a seahorse flux analyzer we show that PE stimulated the mitochondrial oxygen consumption rate (OCR in cardiomyocytes. This was partially dependent on PE mediated AKIP1 induction, since silencing of AKIP1 attenuated the increase in OCR. Interestingly, AKIP1 overexpression alone was sufficient to stimulate mitochondrial OCR and in particular ATP-linked OCR. This was also true when pyruvate was used as a substrate, indicating that it was independent of glycolytic flux. The increase in OCR was independent of mitochondrial biogenesis, changes in ETC density or altered mitochondrial membrane potential. In fact, the respiratory flux was elevated per amount of ETC, possibly through enhanced ETC coupling. Furthermore, overexpression of AKIP1 reduced and silencing of AKIP1 increased mitochondrial superoxide production, suggesting that AKIP1 modulates the efficiency of electron flux through the ETC. Together, this suggests that AKIP1 overexpression improves mitochondrial function to enhance respiration without excess superoxide generation, thereby implicating a role for AKIP1 in mitochondrial stress adaptation. Upregulation of AKIP1 during different forms of cardiac stress may therefore be an adaptive mechanism to protect the heart.
Varicella infection in a neonate with subsequent staphylococcal scalded skin syndrome and fatal shock.

Science.gov (United States)

Singh, Shakal Narayan; Tahazzul, Mohammad; Singh, Anita; Chandra, Surabhi

2012-08-01

A male term neonate, at day 23 of life, presented with vesicular lesions over the trunk, which spread to allover the body on the next day. Five days later, he started developing blistering of the skin over the trunk and extremities, which subsequently ruptured, leaving erythematous, tender raw areas with peeling of the skin. The mother had vesicular eruptions, which started on the second day of delivery and progressed over the next 3 days. Subsequently, similar eruptions were noticed in two of the siblings before affecting the neonate. On the basis of the exposure history and clinical picture, a diagnosis was made of varicella infection with staphylococcal scalded skin syndrome (SSSS). The blood culture and the wound surface culture grew Staphylococcus aureus. Treatment included intravenous fluid, antibiotics, acyclovir and wound care. However, after 72 h of hospitalisation, the neonate first developed shock, refractory to fluid boluses, vasopressors and catecholamine along with other supports; and he then succumbed. In all neonates, staphylococcal infection with varicella can be fatal due to SSSS, the toxic shock syndrome or septicaemia.
Mitochondrial Optic Atrophy (OPA) 1 Processing Is Altered in Response to Neonatal Hypoxic-Ischemic Brain Injury

Science.gov (United States)

Baburamani, Ana A.; Hurling, Chloe; Stolp, Helen; Sobotka, Kristina; Gressens, Pierre; Hagberg, Henrik; Thornton, Claire

2015-01-01

Perturbation of mitochondrial function and subsequent induction of cell death pathways are key hallmarks in neonatal hypoxic-ischemic (HI) injury, both in animal models and in term infants. Mitoprotective therapies therefore offer a new avenue for intervention for the babies who suffer life-long disabilities as a result of birth asphyxia. Here we show that after oxygen-glucose deprivation in primary neurons or in a mouse model of HI, mitochondrial protein homeostasis is altered, manifesting as a change in mitochondrial morphology and functional impairment. Furthermore we find that the mitochondrial fusion and cristae regulatory protein, OPA1, is aberrantly cleaved to shorter forms. OPA1 cleavage is normally regulated by a balanced action of the proteases Yme1L and Oma1. However, in primary neurons or after HI in vivo, protein expression of YmelL is also reduced, whereas no change is observed in Oma1 expression. Our data strongly suggest that alterations in mitochondria-shaping proteins are an early event in the pathogenesis of neonatal HI injury. PMID:26393574
Fetal and neonatal nicotine exposure in Wistar rats causes progressive pancreatic mitochondrial damage and beta cell dysfunction.

Directory of Open Access Journals (Sweden)

Jennifer E Bruin

Full Text Available Nicotine replacement therapy (NRT is currently recommended as a safe smoking cessation aid for pregnant women. However, fetal and neonatal nicotine exposure in rats causes mitochondrial-mediated beta cell apoptosis at weaning, and adult-onset dysglycemia, which we hypothesize is related to progressive mitochondrial dysfunction in the pancreas. Therefore in this study we examined the effect of fetal and neonatal exposure to nicotine on pancreatic mitochondrial structure and function during postnatal development. Female Wistar rats were given saline (vehicle control or nicotine bitartrate (1 mg/kg/d via subcutaneous injection for 2 weeks prior to mating until weaning. At 3-4, 15 and 26 weeks of age, oral glucose tolerance tests were performed, and pancreas tissue was collected for electron microscopy, enzyme activity assays and islet isolation. Following nicotine exposure mitochondrial structural abnormalities were observed beginning at 3 weeks and worsened with advancing age. Importantly the appearance of these structural defects in nicotine-exposed animals preceded the onset of glucose intolerance. Nicotine exposure also resulted in significantly reduced pancreatic respiratory chain enzyme activity, degranulation of beta cells, elevated islet oxidative stress and impaired glucose-stimulated insulin secretion compared to saline controls at 26 weeks of age. Taken together, these data suggest that maternal nicotine use during pregnancy results in postnatal mitochondrial dysfunction that may explain, in part, the dysglycemia observed in the offspring from this animal model. These results clearly indicate that further investigation into the safety of NRT use during pregnancy is warranted.
Ethanol Influences on Bax Associations with Mitochondrial Membrane Proteins in Neonatal Rat Cerebellum

Science.gov (United States)

Heaton, Marieta Barrow; Siler-Marsiglio, Kendra; Paiva, Michael; Kotler, Alexandra; Rogozinski, Jonathan; Kubovec, Stacey; Coursen, Mary; Madorsky, Vladimir

2012-01-01

These studies investigated interactions taking place at the mitochondrial membrane in neonatal rat cerebellum following ethanol exposure, and focused on interactions between pro-apoptotic Bax and proteins of the permeability transition pore (PTP), voltage-dependent anion channel (VDAC), and adenine nucleotide translocator (ANT), of the outer and inner mitochondrial membranes, respectively. Cultured cerebellar granule cells were used to assess the role of these interactions in ethanol neurotoxicity. Analyses were made at the age of maximal cerebellar ethanol vulnerability (P4), compared to the later age of relative resistance (P7), to determine whether differential ethanol sensitivity was mirrored by differences in these molecular interactions. We found that following ethanol exposure, Bax pro-apoptotic associations with both VDAC and ANT were increased, particularly at the age of greater ethanol sensitivity, and these interactions were sustained at this age for at least two hours post-exposure. Since Bax:VDAC interactions disrupt protective VDAC interactions with mitochondrial hexokinase (HXK), we also assessed VDAC:HXK associations following ethanol treatment, and found such interactions were altered by ethanol treatment, but only at two-hours post-exposure, and only in the P4, ethanol-sensitive cerebellum. Ethanol neurotoxicity in cultured neuronal preparations was abolished by pharmacological inhibition of both VDAC and ANT interactions with Bax, but not by a Bax channel blocker. Therefore, we conclude that at this age, within the constraints of our experimental model, a primary mode of Bax-induced initiation of the apoptosis cascade following ethanol insult involves interactions with proteins of the PTP complex, and not channel formation independent of PTP constituents. PMID:22767450
DHA but Not EPA Emulsions Preserve Neurological and Mitochondrial Function after Brain Hypoxia-Ischemia in Neonatal Mice.

Science.gov (United States)

Mayurasakorn, Korapat; Niatsetskaya, Zoya V; Sosunov, Sergey A; Williams, Jill J; Zirpoli, Hylde; Vlasakov, Iliyan; Deckelbaum, Richard J; Ten, Vadim S

2016-01-01

Treatment with triglyceride emulsions of docosahexaenoic acid (tri-DHA) protected neonatal mice against hypoxia-ischemia (HI) brain injury. The mechanism of this neuroprotection remains unclear. We hypothesized that administration of tri-DHA enriches HI-brains with DHA/DHA metabolites. This reduces Ca2+-induced mitochondrial membrane permeabilization and attenuates brain injury. 10-day-old C57BL/6J mice following HI-brain injury received tri-DHA, tri-EPA or vehicle. At 4-5 hours of reperfusion, mitochondrial fatty acid composition and Ca2+ buffering capacity were analyzed. At 24 hours and at 8-9 weeks of recovery, oxidative injury, neurofunctional and neuropathological outcomes were evaluated. In vitro, hyperoxia-induced mitochondrial generation of reactive oxygen species (ROS) and Ca2+ buffering capacity were measured in the presence or absence of DHA or EPA. Only post-treatment with tri-DHA reduced oxidative damage and improved short- and long-term neurological outcomes. This was associated with increased content of DHA in brain mitochondria and DHA-derived bioactive metabolites in cerebral tissue. After tri-DHA administration HI mitochondria were resistant to Ca2+-induced membrane permeabilization. In vitro, hyperoxia increased mitochondrial ROS production and reduced Ca2+ buffering capacity; DHA, but not EPA, significantly attenuated these effects of hyperoxia. Post-treatment with tri-DHA resulted in significant accumulation of DHA and DHA derived bioactive metabolites in the HI-brain. This was associated with improved mitochondrial tolerance to Ca2+-induced permeabilization, reduced oxidative brain injury and permanent neuroprotection. Interaction of DHA with mitochondria alters ROS release and improves Ca2+ buffering capacity. This may account for neuroprotective action of post-HI administration of tri-DHA.
DHA but Not EPA Emulsions Preserve Neurological and Mitochondrial Function after Brain Hypoxia-Ischemia in Neonatal Mice.

Directory of Open Access Journals (Sweden)

Korapat Mayurasakorn

Full Text Available Treatment with triglyceride emulsions of docosahexaenoic acid (tri-DHA protected neonatal mice against hypoxia-ischemia (HI brain injury. The mechanism of this neuroprotection remains unclear. We hypothesized that administration of tri-DHA enriches HI-brains with DHA/DHA metabolites. This reduces Ca2+-induced mitochondrial membrane permeabilization and attenuates brain injury.10-day-old C57BL/6J mice following HI-brain injury received tri-DHA, tri-EPA or vehicle. At 4-5 hours of reperfusion, mitochondrial fatty acid composition and Ca2+ buffering capacity were analyzed. At 24 hours and at 8-9 weeks of recovery, oxidative injury, neurofunctional and neuropathological outcomes were evaluated. In vitro, hyperoxia-induced mitochondrial generation of reactive oxygen species (ROS and Ca2+ buffering capacity were measured in the presence or absence of DHA or EPA.Only post-treatment with tri-DHA reduced oxidative damage and improved short- and long-term neurological outcomes. This was associated with increased content of DHA in brain mitochondria and DHA-derived bioactive metabolites in cerebral tissue. After tri-DHA administration HI mitochondria were resistant to Ca2+-induced membrane permeabilization. In vitro, hyperoxia increased mitochondrial ROS production and reduced Ca2+ buffering capacity; DHA, but not EPA, significantly attenuated these effects of hyperoxia.Post-treatment with tri-DHA resulted in significant accumulation of DHA and DHA derived bioactive metabolites in the HI-brain. This was associated with improved mitochondrial tolerance to Ca2+-induced permeabilization, reduced oxidative brain injury and permanent neuroprotection. Interaction of DHA with mitochondria alters ROS release and improves Ca2+ buffering capacity. This may account for neuroprotective action of post-HI administration of tri-DHA.
DHA but Not EPA Emulsions Preserve Neurological and Mitochondrial Function after Brain Hypoxia-Ischemia in Neonatal Mice

Science.gov (United States)

Sosunov, Sergey A.; Williams, Jill J.; Zirpoli, Hylde; Vlasakov, Iliyan; Deckelbaum, Richard J.; Ten, Vadim S.

2016-01-01

Background and Purpose Treatment with triglyceride emulsions of docosahexaenoic acid (tri-DHA) protected neonatal mice against hypoxia-ischemia (HI) brain injury. The mechanism of this neuroprotection remains unclear. We hypothesized that administration of tri-DHA enriches HI-brains with DHA/DHA metabolites. This reduces Ca2+-induced mitochondrial membrane permeabilization and attenuates brain injury. Methods 10-day-old C57BL/6J mice following HI-brain injury received tri-DHA, tri-EPA or vehicle. At 4–5 hours of reperfusion, mitochondrial fatty acid composition and Ca2+ buffering capacity were analyzed. At 24 hours and at 8–9 weeks of recovery, oxidative injury, neurofunctional and neuropathological outcomes were evaluated. In vitro, hyperoxia-induced mitochondrial generation of reactive oxygen species (ROS) and Ca2+ buffering capacity were measured in the presence or absence of DHA or EPA. Results Only post-treatment with tri-DHA reduced oxidative damage and improved short- and long-term neurological outcomes. This was associated with increased content of DHA in brain mitochondria and DHA-derived bioactive metabolites in cerebral tissue. After tri-DHA administration HI mitochondria were resistant to Ca2+-induced membrane permeabilization. In vitro, hyperoxia increased mitochondrial ROS production and reduced Ca2+ buffering capacity; DHA, but not EPA, significantly attenuated these effects of hyperoxia. Conclusions Post-treatment with tri-DHA resulted in significant accumulation of DHA and DHA derived bioactive metabolites in the HI-brain. This was associated with improved mitochondrial tolerance to Ca2+-induced permeabilization, reduced oxidative brain injury and permanent neuroprotection. Interaction of DHA with mitochondria alters ROS release and improves Ca2+ buffering capacity. This may account for neuroprotective action of post-HI administration of tri-DHA. PMID:27513579
Effect of hyperbaric oxygenation on mitochondrial function of neuronal cells in the cortex of neonatal rats after hypoxic-ischemic brain damage

Directory of Open Access Journals (Sweden)

L. Yang

2016-01-01

Full Text Available The timing and mechanisms of protection by hyperbaric oxygenation (HBO in hypoxic-ischemic brain damage (HIBD have only been partially elucidated. We monitored the effect of HBO on the mitochondrial function of neuronal cells in the cerebral cortex of neonatal rats after HIBD. Neonatal Sprague-Dawley rats (total of 360 of both genders were randomly divided into normal control, HIBD, and HIBD+HBO groups. The HBO treatment began immediately after hypoxia-ischemia (HI and continued once a day for 7 consecutive days. Animals were euthanized 0, 2, 4, 6, and 12 h post-HI to monitor the changes in mitochondrial membrane potential (ΔΨm occurring soon after a single dose of HBO treatment, as well as 2, 3, 4, 5, 6, and 7 days post-HI to study ΔΨm changes after a series of HBO treatments. Fluctuations in ΔΨm were observed in the ipsilateral cortex in both HIBD and HIBD+HBO groups. Within 2 to 12 h after HI insult, the ΔΨm of the HIBD and HIBD+HBO groups recovered to some extent. A secondary drop in ΔΨm was observed in both groups during the 1-4 days post-HI period, but was more severe in the HIBD+HBO group. There was a secondary recovery of ΔΨm observed in the HIBD+HBO group, but not in the HIBD group, during the 5-7 days period after HI insult. HBO therapy may not lead to improvement of neural cell mitochondrial function in the cerebral cortex in the early stage post-HI, but may improve it in the sub-acute stage post-HI.
Ginsenoside Rb1 Protects Neonatal Rat Cardiomyocytes from Hypoxia/Ischemia Induced Apoptosis and Inhibits Activation of the Mitochondrial Apoptotic Pathway

Directory of Open Access Journals (Sweden)

Xu Yan

2014-01-01

Full Text Available Aim. To investigate the effect of Ginsenoside Rb1 (GS-Rb1 on hypoxia/ischemia (H/I injury in cardiomyocytes in vitro and the mitochondrial apoptotic pathway mediated mechanism. Methods. Neonatal rat cardiomyocytes (NRCMs for the H/I groups were kept in DMEM without glucose and serum, and were placed into a hypoxic jar for 24 h. GS-Rb1 at concentrations from 2.5 to 40 µM was given during hypoxic period for 24 h. NRCMs injury was determined by MTT and lactate dehydrogenase (LDH leakage assay. Cell apoptosis, ROS accumulation, and mitochondrial membrane potential (MMP were assessed by flow cytometry. Cytosolic translocation of mitochondrial cytochrome c and Bcl-2 family proteins were determined by Western blot. Caspase-3 and caspase-9 activities were determined by the assay kit. Results. GS-Rb1 significantly reduced cell death and LDH leakage induced by H/I. It also reduced H/I induced NRCMs apoptosis induced by H/I, in accordance with a minimal reactive oxygen species (ROS burst. Moreover, GS-Rb1 markedly decreased the translocation of cytochrome c from the mitochondria to the cytosol, increased the Bcl-2/ Bax ratio, and preserved mitochondrial transmembrane potential (ΔΨm. Its administration also inhibited activities of caspase-9 and caspase-3. Conclusion. Administration of GS-Rb1 during H/I in vitro is involved in cardioprotection by inhibiting apoptosis, which may be due to inhibition of the mitochondrial apoptotic pathway.
Mitochondrial Reactive Oxygen Species in Lipotoxic Hearts Induce Post-Translational Modifications of AKAP121, DRP1, and OPA1 That Promote Mitochondrial Fission.

Science.gov (United States)

Tsushima, Kensuke; Bugger, Heiko; Wende, Adam R; Soto, Jamie; Jenson, Gregory A; Tor, Austin R; McGlauflin, Rose; Kenny, Helena C; Zhang, Yuan; Souvenir, Rhonda; Hu, Xiao X; Sloan, Crystal L; Pereira, Renata O; Lira, Vitor A; Spitzer, Kenneth W; Sharp, Terry L; Shoghi, Kooresh I; Sparagna, Genevieve C; Rog-Zielinska, Eva A; Kohl, Peter; Khalimonchuk, Oleh; Schaffer, Jean E; Abel, E Dale

2018-01-05

Cardiac lipotoxicity, characterized by increased uptake, oxidation, and accumulation of lipid intermediates, contributes to cardiac dysfunction in obesity and diabetes mellitus. However, mechanisms linking lipid overload and mitochondrial dysfunction are incompletely understood. To elucidate the mechanisms for mitochondrial adaptations to lipid overload in postnatal hearts in vivo. Using a transgenic mouse model of cardiac lipotoxicity overexpressing ACSL1 (long-chain acyl-CoA synthetase 1) in cardiomyocytes, we show that modestly increased myocardial fatty acid uptake leads to mitochondrial structural remodeling with significant reduction in minimum diameter. This is associated with increased palmitoyl-carnitine oxidation and increased reactive oxygen species (ROS) generation in isolated mitochondria. Mitochondrial morphological changes and elevated ROS generation are also observed in palmitate-treated neonatal rat ventricular cardiomyocytes. Palmitate exposure to neonatal rat ventricular cardiomyocytes initially activates mitochondrial respiration, coupled with increased mitochondrial polarization and ATP synthesis. However, long-term exposure to palmitate (>8 hours) enhances ROS generation, which is accompanied by loss of the mitochondrial reticulum and a pattern suggesting increased mitochondrial fission. Mechanistically, lipid-induced changes in mitochondrial redox status increased mitochondrial fission by increased ubiquitination of AKAP121 (A-kinase anchor protein 121) leading to reduced phosphorylation of DRP1 (dynamin-related protein 1) at Ser637 and altered proteolytic processing of OPA1 (optic atrophy 1). Scavenging mitochondrial ROS restored mitochondrial morphology in vivo and in vitro. Our results reveal a molecular mechanism by which lipid overload-induced mitochondrial ROS generation causes mitochondrial dysfunction by inducing post-translational modifications of mitochondrial proteins that regulate mitochondrial dynamics. These findings provide a
Aetiology of neonatal sepsis at QECH, Blantyre: 1996-2001 | Phiri ...

African Journals Online (AJOL)

Neonatal sepsis is common and often fatal in Malawi. The aim of this retrospective study was to report causes, antibiotic resistance and outcome of sepsis in Malawian neonates. We reviewed all blood and cerebrospinal fluid isolates collected between January, 1996, and December, 2001, from inpatients aged 0-30 days ...

Mitochondrial phenylalanyl-tRNA synthetase mutations underlie fatal infantile Alpers encephalopathy

DEFF Research Database (Denmark)

Elo, Jenni M; Yadavalli, Srujana S; Euro, Liliya

2012-01-01

was impaired. Our results imply that the three FARS2 mutations directly impair aminoacylation function and stability of mtPheRS, leading to a decrease in overall tRNA charging capacity. This study establishes a new genetic cause of infantile mitochondrial Alpers encephalopathy and reports a new mitochondrial...
Biallelic Mutations in LIPT2 Cause a Mitochondrial Lipoylation Defect Associated with Severe Neonatal Encephalopathy.

Science.gov (United States)

Habarou, Florence; Hamel, Yamina; Haack, Tobias B; Feichtinger, René G; Lebigot, Elise; Marquardt, Iris; Busiah, Kanetee; Laroche, Cécile; Madrange, Marine; Grisel, Coraline; Pontoizeau, Clément; Eisermann, Monika; Boutron, Audrey; Chrétien, Dominique; Chadefaux-Vekemans, Bernadette; Barouki, Robert; Bole-Feysot, Christine; Nitschke, Patrick; Goudin, Nicolas; Boddaert, Nathalie; Nemazanyy, Ivan; Delahodde, Agnès; Kölker, Stefan; Rodenburg, Richard J; Korenke, G Christoph; Meitinger, Thomas; Strom, Tim M; Prokisch, Holger; Rotig, Agnes; Ottolenghi, Chris; Mayr, Johannes A; de Lonlay, Pascale

2017-08-03

Lipoate serves as a cofactor for the glycine cleavage system (GCS) and four 2-oxoacid dehydrogenases functioning in energy metabolism (α-oxoglutarate dehydrogenase [α-KGDHc] and pyruvate dehydrogenase [PDHc]), or amino acid metabolism (branched-chain oxoacid dehydrogenase, 2-oxoadipate dehydrogenase). Mitochondrial lipoate synthesis involves three enzymatic steps catalyzed sequentially by lipoyl(octanoyl) transferase 2 (LIPT2), lipoic acid synthetase (LIAS), and lipoyltransferase 1 (LIPT1). Mutations in LIAS have been associated with nonketotic hyperglycinemia-like early-onset convulsions and encephalopathy combined with a defect in mitochondrial energy metabolism. LIPT1 deficiency spares GCS deficiency and has been associated with a biochemical signature of combined 2-oxoacid dehydrogenase deficiency leading to early death or Leigh-like encephalopathy. We report on the identification of biallelic LIPT2 mutations in three affected individuals from two families with severe neonatal encephalopathy. Brain MRI showed major cortical atrophy with white matter abnormalities and cysts. Plasma glycine was mildly increased. Affected individuals' fibroblasts showed reduced oxygen consumption rates, PDHc, α-KGDHc activities, leucine catabolic flux, and decreased protein lipoylation. A normalization of lipoylation was observed after expression of wild-type LIPT2, arguing for LIPT2 requirement in intramitochondrial lipoate synthesis. Lipoic acid supplementation did not improve clinical condition nor activities of PDHc, α-KGDHc, or leucine metabolism in fibroblasts and was ineffective in yeast deleted for the orthologous LIP2. Copyright © 2017 American Society of Human Genetics. Published by Elsevier Inc. All rights reserved.
Neonatal thyrotoxicosis caused by maternal autoimmune hyperthyroidism.

Science.gov (United States)

Correia, Miguel Fragata; Maria, Ana Teresa; Prado, Sara; Limbert, Catarina

2015-03-06

Neonatal immune hyperthyroidism is a rare but potentially fatal condition. It occurs in 1-5% of infants born to women with Graves' disease (GD). In most of the cases it is due to maternal antibodies transferred from the mother into the fetal compartment, stimulating the fetal thyroid by binding thyrotropin (thyroid-stimulating hormone, TSH) receptor. We present a case of neonatal thyrotoxicosis due to maternal GD detected at 25 days of age and discuss the potential pitfalls in the diagnosis. 2015 BMJ Publishing Group Ltd.
Clinical case of Mitochondrial DNA Depletion

Directory of Open Access Journals (Sweden)

A. V. Degtyareva

2017-01-01

Full Text Available The article reports clinical case of early neonatal manifestation of a rare genetic disease – mitochondrial DNA depletion syndrome, confirmed in laboratory in Russia. Mutations of FBXL4, which encodes an orphan mitochondrial F-box protein, involved in the maintenance of mitochondrial DNA (mtDNA, ultimately leading to disruption of mtDNA replication and decreased activity of mitochondrial respiratory chain complexes. It’s a reason of abnormalities in clinically affected tissues, most of all the muscular system and the brain. In our case hydronephrosis on the right, subependimal cysts of the brain, partial intestinal obstruction accompanied by polyhydramnios were diagnosed antenatal. Baby’s condition at birth was satisfactory and worsened dramatically towards the end of the first day of life. Clinical presentation includes sepsis-like symptom complex, neonatal depression, muscular hypotonia, persistent decompensated lactic acidosis, increase in the concentration of mitochondrial markers in blood plasma and urine, and changes in the basal ganglia of the brain. Imaging of the brain by magnetic resonance imaging (MRI demonstrated global volume loss particularly the subcortical and periventricular white matter with significant abnormal signal in bilateral basal ganglia and brainstem with associated delayed myelination. Differential diagnosis was carried out with hereditary diseases that occur as a «sepsis-like» symptom complex, accompanied by lactic acidosis: a group of metabolic disorders of amino acids, organic acids, β-oxidation defects of fatty acids, respiratory mitochondrial chain disorders and glycogen storage disease. The diagnosis was confirmed after sequencing analysis of 62 mytochondrial genes by NGS (Next Generation Sequencing. Reported disease has an unfavorable prognosis, however, accurate diagnosis is very important for genetic counseling and helps prevent the re-birth of a sick child in the family.
Mitochondrial DNA Depletion Syndrome is Expressed in Amniotic Fluid Cell Cultures

OpenAIRE

Blake, Julian C.; Taanman, Jan-Willem; Morris, Andrew M. M.; Gray, R. George F.; Cooper, J. Mark; McKiernan, Patrick J.; Leonard, James V.; Schapira, Anthony H. V.

1999-01-01

Mitochondrial DNA depletion syndrome is an autosomal inherited disease associated with grossly reduced cellular levels of mitochondrial DNA in infancy. Most patients are born after a full and uncomplicated pregnancy, are normal at birth, but develop symptoms in the early neonatal period. These observations have led to the suggestion that the patients have a defect affecting the control of mitochondrial DNA copy number after birth. Using immunocytochemical techniques, we demonstrated that the ...
Pathogenicity of Bovine Neonatal Pancytopenia-associated vaccine-induced alloantibodies correlates with Major Histocompatibility Complex class 1 expression

NARCIS (Netherlands)

Benedictus, L.; Luteijn, Rutger D.; Otten, H.; Lebbink, Robert Jan; Kooten, van P.J.S.; Wiertz, E.J.H.J.; Rutten, Victor P.M.G.; Koets, A.P.

2015-01-01

Bovine Neonatal Pancytopenia (BNP), a fatal bleeding syndrome of neonatal calves, is caused by maternal alloantibodies absorbed from colostrum and is characterized by lymphocytopenia, thrombocytopenia and bone marrow hypoplasia. An inactivated viral vaccine is the likely source of alloantigens
In situ immune response and mechanisms of cell damage in central nervous system of fatal cases microcephaly by Zika virus.

Science.gov (United States)

Azevedo, Raimunda S S; de Sousa, Jorge R; Araujo, Marialva T F; Martins Filho, Arnaldo J; de Alcantara, Bianca N; Araujo, Fernanda M C; Queiroz, Maria G L; Cruz, Ana C R; Vasconcelos, Beatriz H Baldez; Chiang, Jannifer O; Martins, Lívia C; Casseb, Livia M N; da Silva, Eliana V; Carvalho, Valéria L; Vasconcelos, Barbara C Baldez; Rodrigues, Sueli G; Oliveira, Consuelo S; Quaresma, Juarez A S; Vasconcelos, Pedro F C

2018-01-08

Zika virus (ZIKV) has recently caused a pandemic disease, and many cases of ZIKV infection in pregnant women resulted in abortion, stillbirth, deaths and congenital defects including microcephaly, which now has been proposed as ZIKV congenital syndrome. This study aimed to investigate the in situ immune response profile and mechanisms of neuronal cell damage in fatal Zika microcephaly cases. Brain tissue samples were collected from 15 cases, including 10 microcephalic ZIKV-positive neonates with fatal outcome and five neonatal control flavivirus-negative neonates that died due to other causes, but with preserved central nervous system (CNS) architecture. In microcephaly cases, the histopathological features of the tissue samples were characterized in three CNS areas (meninges, perivascular space, and parenchyma). The changes found were mainly calcification, necrosis, neuronophagy, gliosis, microglial nodules, and inflammatory infiltration of mononuclear cells. The in situ immune response against ZIKV in the CNS of newborns is complex. Despite the predominant expression of Th2 cytokines, other cytokines such as Th1, Th17, Treg, Th9, and Th22 are involved to a lesser extent, but are still likely to participate in the immunopathogenic mechanisms of neural disease in fatal cases of microcephaly caused by ZIKV.
Allogeneic haematopoietic stem cell transplantation for mitochondrial neurogastrointestinal encephalomyopathy

NARCIS (Netherlands)

Halter, Joerg P.; Schuepbach, W. Michael M.; Mandel, Hanna; Casali, Carlo; Orchard, Kim; Collin, Matthew; Valcarcel, David; Rovelli, Attilio; Filosto, Massimiliano; Dotti, Maria T.; Marotta, Giuseppe; Pintos, Guillem; Barba, Pere; Accarino, Anna; Ferra, Christelle; Illa, Isabel; Beguin, Yves; Bakker, Jaap A.; Boelens, Jaap J.; de Coo, Irenaeus F. M.; Fay, Keith; Sue, Carolyn M.; Nachbaur, David; Zoller, Heinz; Sobreira, Claudia; Simoes, Belinda Pinto; Hammans, Simon R.; Savage, David; Marti, Ramon; Chinnery, Patrick F.; Elhasid, Ronit; Gratwohl, Alois; Hirano, Michio

2015-01-01

Haematopoietic stem cell transplantation has been proposed as treatment for mitochondrial neurogastrointestinal encephalomyopathy, a rare fatal autosomal recessive disease due to TYMP mutations that result in thymidine phosphorylase deficiency. We conducted a retrospective analysis of all known
Fatal case of influenza B virus pneumonia in a preterm neonate

NARCIS (Netherlands)

van den Dungen, F. A.; van Furth, A. M.; Fetter, W. P.; Zaaijer, H. L.; van Elburg, R. M.

2001-01-01

Influenza B infection typically has low mortality. A 1020-g neonate had a septic clinical picture and pneumonia. Influenza B virus was isolated from nasopharyngeal and tracheal aspirates. The infant died
Neonatal seizures in a rural Iranian district hospital: etiologies, incidence and predicting factors.

Science.gov (United States)

Sadeghian, Afsaneh; Damghanian, Maryam; Shariati, Mohammad

2012-01-01

Current study determined the overall incidence, common causes as well as main predictors of this final diagnosis among neonates admitted to a rural district hospital in Iran. This study was conducted on 699 neonates who were candidate for admission to the NICU. Study population was categorized in the case group, including patients exposed to final diagnosis of neonatal seizures and the control group without this diagnosis. Neonatal seizure was reported as final diagnosis in 25 (3.6%) of neonates. The most frequent discharge diagnosis in the seizure group was neonatal sepsis and in the non-seizure group was respiratory problems. No significant difference was found in early fatality rate between neonates with and without seizures (8.0% vs. 10.1%). Only gestational age <38 week had a relationship with the appearance of neonatal seizure. Low gestational age has a crucial role for predicting appearance of seizure in Iranian neonates.
Føtal og neonatal alloimmun trombocytopeni er en mulig fatal tilstand

DEFF Research Database (Denmark)

Morling Taaning, Ellen Birkerod; Kjeldsen-Kragh, Jens; Hedegaard, Morten

2011-01-01

Fetal and neonatal alloimmune thrombocytopenia (FNAIT) may lead to intracranial haemorrhage (ICH) resulting in neurological damage or death. In FNAIT, transplacental maternal antibodies cause destruction of fetal platelets. Maternal immunisation occurs to fetal human platelet antigens (HPAs...
Glucose and Intermediary Metabolism and Astrocyte-Neuron Interactions Following Neonatal Hypoxia-Ischemia in Rat.

Science.gov (United States)

Brekke, Eva; Berger, Hester Rijkje; Widerøe, Marius; Sonnewald, Ursula; Morken, Tora Sund

2017-01-01

Neonatal hypoxia-ischemia (HI) and the delayed injury cascade that follows involve excitotoxicity, oxidative stress and mitochondrial failure. The susceptibility to excitotoxicity of the neonatal brain may be related to the capacity of astrocytes for glutamate uptake. Furthermore, the neonatal brain is vulnerable to oxidative stress, and the pentose phosphate pathway (PPP) may be of particular importance for limiting this kind of injury. Also, in the neonatal brain, neurons depend upon de novo synthesis of neurotransmitters via pyruvate carboxylase in astrocytes to increase neurotransmitter pools during normal brain development. Several recent publications describing intermediary brain metabolism following neonatal HI have yielded interesting results: (1) Following HI there is a prolonged depression of mitochondrial metabolism in agreement with emerging evidence of mitochondria as vulnerable targets in the delayed injury cascade. (2) Astrocytes, like neurons, are metabolically impaired following HI, and the degree of astrocytic malfunction may be an indicator of the outcome following hypoxic and hypoxic-ischemic brain injury. (3) Glutamate transfer from neurons to astrocytes is not increased following neonatal HI, which may imply that astrocytes fail to upregulate glutamate uptake in response to the massive glutamate release during HI, thus contributing to excitotoxicity. (4) In the neonatal brain, the activity of the PPP is reduced following HI, which may add to the susceptibility of the neonatal brain to oxidative stress. The present review aims to discuss the metabolic temporal alterations observed in the neonatal brain following HI.
Losing sleep over mitochondria: a new player in the pathophysiology of fatal familial insomnia.

Science.gov (United States)

Glatzel, Markus; Sepulveda-Falla, Diego

2017-01-01

This commentary highlights the study by Frau-Mendez and coworkers in this issue of Brain Pathology (xxx) in which the authors show evidence for involvement of mitochondria in the pathophysiology of fatal familial insomnia (FFI). Using genetic, biochemical and morphological means, they provide a comprehensive picture of the degree of mitochondrial damage in FFI and show that this leads to increased oxidative stress. This adds FFI to the growing list of dementias with mitochondrial involvement. Future studies will have to address the causality dilemma of which came first, mitochondrial damage and subsequent neurodegeneration or vice versa. Either way, these data provide the basis to devise novel therapeutic strategies for FFI. © 2016 International Society of Neuropathology.
Oxygen Glucose Deprivation in Rat Hippocampal Slice Cultures Results in Alterations in Carnitine Homeostasis and Mitochondrial Dysfunction

Science.gov (United States)

Rau, Thomas F.; Lu, Qing; Sharma, Shruti; Sun, Xutong; Leary, Gregory; Beckman, Matthew L.; Hou, Yali; Wainwright, Mark S.; Kavanaugh, Michael; Poulsen, David J.; Black, Stephen M.

2012-01-01

Mitochondrial dysfunction characterized by depolarization of mitochondrial membranes and the initiation of mitochondrial-mediated apoptosis are pathological responses to hypoxia-ischemia (HI) in the neonatal brain. Carnitine metabolism directly supports mitochondrial metabolism by shuttling long chain fatty acids across the inner mitochondrial membrane for beta-oxidation. Our previous studies have shown that HI disrupts carnitine homeostasis in neonatal rats and that L-carnitine can be neuroprotective. Thus, this study was undertaken to elucidate the molecular mechanisms by which HI alters carnitine metabolism and to begin to elucidate the mechanism underlying the neuroprotective effect of L-carnitine (LCAR) supplementation. Utilizing neonatal rat hippocampal slice cultures we found that oxygen glucose deprivation (OGD) decreased the levels of free carnitines (FC) and increased the acylcarnitine (AC): FC ratio. These changes in carnitine homeostasis correlated with decreases in the protein levels of carnitine palmitoyl transferase (CPT) 1 and 2. LCAR supplementation prevented the decrease in CPT1 and CPT2, enhanced both FC and the AC∶FC ratio and increased slice culture metabolic viability, the mitochondrial membrane potential prior to OGD and prevented the subsequent loss of neurons during later stages of reperfusion through a reduction in apoptotic cell death. Finally, we found that LCAR supplementation preserved the structural integrity and synaptic transmission within the hippocampus after OGD. Thus, we conclude that LCAR supplementation preserves the key enzymes responsible for maintaining carnitine homeostasis and preserves both cell viability and synaptic transmission after OGD. PMID:22984394
Neonatal cardiac mitochondria and ischemia/reperfusion injury

Czech Academy of Sciences Publication Activity Database

Milerová, Marie; Charvátová, Zuzana; Škárka, Libor; Ošťádalová, Ivana; Drahota, Zdeněk; Fialová, Martina; Ošťádal, Bohuslav

2010-01-01

Roč. 335, 1-2 (2010), s. 147-153 ISSN 0300-8177 R&D Projects: GA MŠk(CZ) 1M0510 Institutional research plan: CEZ:AV0Z50110509 Keywords : neonatal rat heart * tolerance to ischemia * mitochondrial permeability transition pore Subject RIV: FA - Cardiovascular Diseases incl. Cardiotharic Surgery Impact factor: 2.168, year: 2010
Listeria monocytogenes infection in pregnancy and neonatal sepsis

Directory of Open Access Journals (Sweden)

Francesca Pascale

2008-06-01

Full Text Available Authors report a fatal neonatal sepsis caused by Listeria monocytogenes. While the diagnostic procedure aimed to identify the microrganism is described, it is emphasized the importance to recover Streptococcus agalactiae (GBS and L. monocytogenes by means of vaginal-rectal swab culture. The intrapartum screening for L. monocytogenes, by Polymerase Chain Reaction (PCR providing results in 75 minutes is also evaluated.
A case of near-fatal flecainide overdose in a neonate successfully treated with sodium bicarbonate.

Science.gov (United States)

Jang, David H; Hoffman, Robert S; Nelson, Lewis S

2013-04-01

Flecainide is a class IC antidysrhythmic primarily indicated for ventricular dysrhythmias and supraventricular tachycardia (SVT). Class IC antidysrhythmic overdose has a reported mortality of 22%, and death results from dysrhythmias and cardiovascular collapse. We report a near-fatal flecainide overdose in an 18-day-old treated successfully with sodium bicarbonate. An 18-day-old, 2 weeks premature, 4-kg boy developed persistently high heart rates (220-240 beats/min) and electrocardiographic changes consistent with SVT. There was minimal response to vagal maneuvers, adenosine, and esmolol, and a transthoracic echocardiogram showed no underlying structural abnormality. The patient was then started on flecainide 4 mg orally every 8 h (Q8h). After the fourth dose he developed lethargy, cold clammy skin, and a heart rate of 40 beats/min with no palpable pulse. The patient was given 0.1 mg of atropine intravenously, with an increase of the heart rate to 160 beats/min. The child's cardiac monitor revealed a wide-complex tachycardia with left bundle branch morphology, with associated pallor and poor capillary refill. Sodium bicarbonate was administered intravenously due to suspected flecainide toxicity. Approximately 5 min after intravenous administration of 10 mEq of 8.4% sodium bicarbonate twice, his rhythm converted to a narrow-complex tachycardia. A serum flecainide concentration was 1360 μg/L (therapeutic, 200-1000 μg/L) drawn 1 h before the cardiac arrest. It was later discovered that a twofold dosing error occurred: the patient received 8 mg Q8h instead of 4 mg Q8h for four doses. Flecainide toxicity in children is rare, especially in neonates. It is important for clinicians to be able to identify and treat this uncommon poisoning. Copyright © 2013 Elsevier Inc. All rights reserved.
Selective screening in neonates suspected to have inborn errors of ...

African Journals Online (AJOL)

Rabah M. Shawky

2015-02-16

Feb 16, 2015 ... Objective: The aim of this work was to detect the prevalence of IEM among neonates ... defect, mitochondrial disease, and galactosemia were diagnosed in one patient each (7.7%). ... relation of symptoms to feeding, similar cases in the family, ... The extended metabolic screening test showed high leucine,.
CRISPR/Cas9 and mitochondrial gene replacement therapy: promising techniques and ethical considerations

OpenAIRE

Fogleman, Sarah; Santana, Casey; Bishop, Casey; Miller, Alyssa; Capco, David G

2016-01-01

Thousands of mothers are at risk of transmitting mitochondrial diseases to their offspring each year, with the most severe form of these diseases being fatal [1]. With no cure, transmission prevention is the only current hope for decreasing the disease incidence. Current methods of prevention rely on low mutant maternal mitochondrial DNA levels, while those with levels close to or above threshold (>60%) are still at a very high risk of transmission [2]. Two novel approaches may offer hope for...
Thymidine kinase 2 and alanyl-tRNA synthetase 2 deficiencies cause lethal mitochondrial cardiomyopathy: case reports and review of the literature.

Science.gov (United States)

Mazurova, Stella; Magner, Martin; Kucerova-Vidrova, Vendula; Vondrackova, Alzbeta; Stranecky, Viktor; Pristoupilova, Anna; Zamecnik, Josef; Hansikova, Hana; Zeman, Jiri; Tesarova, Marketa; Honzik, Tomas

2017-07-01

Cardiomyopathy is a common manifestation in neonates and infants with mitochondrial disorders. In this study, we report two cases manifesting with fatal mitochondrial hypertrophic cardiomyopathy, which include the third known patient with thymidine kinase 2 deficiency and the ninth patient with alanyl-tRNA synthetase 2 deficiency. The girl with thymidine kinase 2 deficiency had hypertrophic cardiomyopathy together with regression of gross motor development at the age of 13 months. Neurological symptoms and cardiac involvement progressed into severe myopathy, psychomotor arrest, and cardiorespiratory failure at the age of 22 months. The imaging methods and autoptic studies proved that she suffered from unique findings of leucoencephalopathy, severe, mainly cerebellar neuronal degeneration, and hepatic steatosis. The girl with alanyl-tRNA synthetase 2 deficiency presented with cardiac failure and underlying hypertrophic cardiomyopathy within 12 hours of life and subsequently died at 9 weeks of age. Muscle biopsy analyses demonstrated respiratory chain complex I and IV deficiencies, and histological evaluation revealed massive mitochondrial accumulation and cytochrome c oxidase-negative fibres in both cases. Exome sequencing in the first case revealed compound heterozygozity for one novel c.209T>C and one previously published c.416C>T mutation in the TK2 gene, whereas in the second case homozygozity for the previously described mutation c.1774C>T in the AARS2 gene was determined. The thymidine kinase 2 mutations resulted in severe mitochondrial DNA depletion (to 12% of controls) in the muscle. We present, for the first time, severe leucoencephalopathy and hepatic steatosis in a patient with thymidine kinase 2 deficiency and the finding of a ragged red fibre-like image in the muscle biopsy in a patient with alanyl-tRNA synthetase 2 deficiency.

mtDNA depletion myopathy: elucidation of the tissue specificity in the mitochondrial thymidine kinase (TK2) deficiency.

Science.gov (United States)

Saada, Ann; Shaag, Avraham; Elpeleg, Orly

2003-05-01

Decreased mitochondrial thymidine kinase (TK2) activity is associated with mitochondrial DNA (mtDNA) depletion and respiratory chain dysfunction and is manifested by isolated, fatal skeletal myopathy. Other tissues such as liver, brain, heart, and skin remain unaffected throughout the patients' life. In order to elucidate the mechanism of tissue specificity in the disease we have investigated the expression of the mitochondrial deoxynucleotide carrier, the mtDNA content and the activity of TK2 in mitochondria of various tissues. Our results suggest that low basal TK2 activity combined with a high requirement for mitochondrial encoded proteins in muscle predispose this tissue to the devastating effect of TK2 deficiency.
Diclofenac induces proteasome and mitochondrial dysfunction in murine cardiomyocytes and hearts.

Science.gov (United States)

Ghosh, Rajeshwary; Goswami, Sumanta K; Feitoza, Luis Felipe B B; Hammock, Bruce; Gomes, Aldrin V

2016-11-15

One of the most common nonsteroidal anti-inflammatory drugs (NSAIDs) used worldwide, diclofenac (DIC), has been linked to increased risk of cardiovascular disease (CVD). The molecular mechanism(s) by which DIC causes CVD is unknown. Proteasome activities were studied in hearts, livers, and kidneys from male Swiss Webster mice treated with either 100mg/kg DIC for 18h (acute treatment) or 10mg/kg DIC for 28days (chronic treatment). Cultured H9c2 cells and neonatal cardiomyocytes were also treated with different concentrations of DIC and proteasome function, cell death and ROS generation studied. Isolated mouse heart mitochondria were utilized to determine the effect of DIC on various electron transport chain complex activities. DIC significantly inhibited the chymotrypsin-like proteasome activity in rat cardiac H9c2 cells, murine neonatal cardiomyocytes, and mouse hearts, but did not affect proteasome subunit expression levels. Proteasome activity was also affected in liver and kidney tissues from DIC treated animals. The levels of polyubiquitinated proteins increased in hearts from DIC treated mice. Importantly, the levels of oxidized proteins increased while the β5i immunoproteasome activity decreased in hearts from DIC treated mice. DIC increased ROS production and cell death in H9c2 cells and neonatal cardiomyocytes while the cardioprotective NSAID, aspirin, had no effect on ROS levels or cell viability. DIC inhibited mitochondrial Complex III, a major source of ROS, and impaired mitochondrial membrane potential suggesting that mitochondria are the major sites of ROS generation. These results suggest that DIC induces cardiotoxicity by a ROS dependent mechanism involving mitochondrial and proteasome dysfunction. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.
Chloroquine inhibits autophagy and deteriorates the mitochondrial dysfunction and apoptosis in hypoxic rat neurons.

Science.gov (United States)

Li, Peng; Hao, Lei; Guo, Yan-Yan; Yang, Guang-Lu; Mei, Hua; Li, Xiao-Hua; Zhai, Qiong-Xiang

2018-06-01

Mitochondrial dysfunction (MD) and apoptosis in the neurons are associated with neonatal hypoxic-ischemic (HI) encephalopathy (HIE). The present study was to explore the influence of autophagy on the induction of MD and apoptosis in the neurons in a neonatal HIE rats and in hypoxia-treated neurons in vitro. Ten-day-old HI rat pups were sacrificed for brain pathological examination and immunohistochemical analysis. The induction of autophagy, apoptosis and MD were also determined in the neurons under hypoxia, with or without autophagy inhibitor, chloroquine (CQ) treatment. HI treatment caused atrophy and apoptosis of neurons, with a significantly increased levels of apoptosis- and autophagy-associated proteins, such as cleaved caspase 3 and the B subunit of autophagy-related microtubule-associated protein 1 light chain 3 (LC3-B). in vitro experiments demonstrated that the hypoxia induced autophagy in neurons, as was inhibited by CQ. The hypoxia-induced cytochrome c release, cleaved caspase 3 and cleaved caspase 9 were aggravated by CQ. Moreover, there were higher levels of reactive oxygen species, more mitochondrial superoxide and less mitochondrial membrane potential in the CQ-treated neurons under hypoxia than in the neurons singularly under hypoxia. Apoptosis and autophagy were induced in HI neonatal rat neurons, autophagy inhibition deteriorates the hypoxia-induced neuron MD and apoptosis. It implies a neuroprotection of autophagy in the hypoxic-ischemic encephalopathy. Administration of autophagy inducer agents might be promising in HIE treatment. Copyright © 2018. Published by Elsevier Inc.
Incidence, aetiology and resistance of late-onset neonatal sepsis: a five-year prospective study.

Science.gov (United States)

Hammoud, Majeda S; Al-Taiar, Abdullah; Thalib, Lukman; Al-Sweih, Noura; Pathan, Seema; Isaacs, David

2012-07-01

Investigate the incidence, etiological pattern and the antimicrobial resistance of late-onset neonatal infections over a period of 5 years. Longitudinal audit of neonatal sepsis from January 2005 to December 2009, in the main maternity hospital in Kuwait. Late-onset neonatal infection was defined as the culture of a single potentially pathogenic organism from blood or cerebrospinal fluid from an infant older than 6 days in association with clinical or laboratory findings consistent with infection. The overall incidence was 16.9 (95% confidence interval: 15.8-18.0) episodes per 1000 live births. The commonest pathogen was coagulase-negative Staphylococcus, 339 (35.7%), while Klebsiella was the most common gram-negative infection, 178 (18.8%). Escherichia coli, Enterococcus and Enterobacter spp were each responsible for 6% of all infections. Candida caused 104 (11.0%) infections. The general pattern of infection remained unchanged over the study period. Case fatality was 11.7% (95% confidence interval: 9.7-13.9%) and was high for Pseudomonas (18.4%) and Candida (22.1%) infections. Approximately 24 and 20% of Klebsiella infections were resistant to cefotaxime and gentamicin, respectively, while 28 and 24% of Escherichia coli infections were resistant to cefotaxime and gentamicin, respectively. The incidence of late-onset infection in Kuwait is high, resembling that in resource-poor countries. The high incidence coupled with low case fatality provides an example for settings where tertiary care is introduced without strict measures against nosocomial infections. Prevention against nosocomial infections in neonatal units has the potential to further reduce neonatal mortality in these settings. © 2012 The Authors. Journal of Paediatrics and Child Health © 2012 Paediatrics and Child Health Division (Royal Australasian College of Physicians).
Developmental exposure to second-hand smoke increases adult atherogenesis and alters mitochondrial DNA copy number and deletions in apoE(-/- mice.

Directory of Open Access Journals (Sweden)

Jessica L Fetterman

Full Text Available Cardiovascular disease is a major cause of morbidity and mortality in the United States. While many studies have focused upon the effects of adult second-hand smoke exposure on cardiovascular disease development, disease development occurs over decades and is likely influenced by childhood exposure. The impacts of in utero versus neonatal second-hand smoke exposure on adult atherosclerotic disease development are not known. The objective of the current study was to determine the effects of in utero versus neonatal exposure to a low dose (1 mg/m(3 total suspended particulate of second-hand smoke on adult atherosclerotic lesion development using the apolipoprotein E null mouse model. Consequently, apolipoprotein E null mice were exposed to either filtered air or second-hand smoke: (i in utero from gestation days 1-19, or (ii from birth until 3 weeks of age (neonatal. Subsequently, all animals were exposed to filtered air and sacrificed at 12-14 weeks of age. Oil red-O staining of whole aortas, measures of mitochondrial damage, and oxidative stress were performed. Results show that both in utero and neonatal second-hand smoke exposure significantly increased adult atherogenesis in mice compared to filtered air controls. These changes were associated with changes in aconitase and mitochondrial superoxide dismutase activities consistent with increased oxidative stress in the aorta, changes in mitochondrial DNA copy number and deletion levels. These studies show that in utero or neonatal exposure to second-hand smoke significantly influences adult atherosclerotic lesion development and results in significant alterations to the mitochondrion and its genome that may contribute to atherogenesis.
Developmental exposure to second-hand smoke increases adult atherogenesis and alters mitochondrial DNA copy number and deletions in apoE(-/-) mice.

Science.gov (United States)

Fetterman, Jessica L; Pompilius, Melissa; Westbrook, David G; Uyeminami, Dale; Brown, Jamelle; Pinkerton, Kent E; Ballinger, Scott W

2013-01-01

Cardiovascular disease is a major cause of morbidity and mortality in the United States. While many studies have focused upon the effects of adult second-hand smoke exposure on cardiovascular disease development, disease development occurs over decades and is likely influenced by childhood exposure. The impacts of in utero versus neonatal second-hand smoke exposure on adult atherosclerotic disease development are not known. The objective of the current study was to determine the effects of in utero versus neonatal exposure to a low dose (1 mg/m(3) total suspended particulate) of second-hand smoke on adult atherosclerotic lesion development using the apolipoprotein E null mouse model. Consequently, apolipoprotein E null mice were exposed to either filtered air or second-hand smoke: (i) in utero from gestation days 1-19, or (ii) from birth until 3 weeks of age (neonatal). Subsequently, all animals were exposed to filtered air and sacrificed at 12-14 weeks of age. Oil red-O staining of whole aortas, measures of mitochondrial damage, and oxidative stress were performed. Results show that both in utero and neonatal second-hand smoke exposure significantly increased adult atherogenesis in mice compared to filtered air controls. These changes were associated with changes in aconitase and mitochondrial superoxide dismutase activities consistent with increased oxidative stress in the aorta, changes in mitochondrial DNA copy number and deletion levels. These studies show that in utero or neonatal exposure to second-hand smoke significantly influences adult atherosclerotic lesion development and results in significant alterations to the mitochondrion and its genome that may contribute to atherogenesis.
Changes in mitochondrial dynamics during ceramide-induced cardiomyocyte early apoptosis.

Science.gov (United States)

Parra, Valentina; Eisner, Veronica; Chiong, Mario; Criollo, Alfredo; Moraga, Francisco; Garcia, Alejandra; Härtel, Steffen; Jaimovich, Enrique; Zorzano, Antonio; Hidalgo, Cecilia; Lavandero, Sergio

2008-01-15

In cells, mitochondria are organized as a network of interconnected organelles that fluctuate between fission and fusion events (mitochondrial dynamics). This process is associated with cell death. We investigated whether activation of apoptosis with ceramides affects mitochondrial dynamics and promotes mitochondrial fission in cardiomyocytes. Neonatal rat cardiomyocytes were incubated with C(2)-ceramide or the inactive analog dihydro-C(2)-ceramide for up to 6 h. Three-dimensional images of cells loaded with mitotracker green were obtained by confocal microscopy. Dynamin-related protein-1 (Drp-1) and mitochondrial fission protein 1 (Fis1) distribution and levels were studied by immunofluorescence and western blot. Mitochondrial membrane potential (DeltaPsi(m)) and cytochrome c (cyt c) distribution were used as indexes of early activation of apoptosis. Cell viability and DNA fragmentation were determined by propidium iodide staining/flow cytometry, whereas cytotoxicity was evaluated by lactic dehydrogenase activity. To decrease the levels of the mitochondrial fusion protein mitofusin 2, we used an antisense adenovirus (AsMfn2). C(2)-ceramide, but not dihydro-C(2)-ceramide, promoted rapid fragmentation of the mitochondrial network in a concentration- and time-dependent manner. C(2)-ceramide also increased mitochondrial Drp-1 and Fis1 content, Drp-1 colocalization with Fis1, and caused early activation of apoptosis. AsMfn2 accentuated the decrease in DeltaPsi(m) and cyt c redistribution induced by C(2)-ceramide. Doxorubicin, which induces cardiomyopathy and apoptosis through ceramide generation, also stimulated mitochondrial fragmentation. Ceramides stimulate mitochondrial fission and this event is associated with early activation of cardiomyocyte apoptosis.
Six year trend of neonatal septicaemia in a large Malaysian maternity hospital.

Science.gov (United States)

Boo, N Y; Chor, C Y

1994-02-01

A study carried out in the Maternity Hospital, Kuala Lumpur over a 6 year period from 1986 to 1991, showed that the annual rates of septicaemia ranged from 5.2 to 10.2/100 admissions. Septicaemia accounted for between 11.0 to 30.4% of all neonatal deaths. The case fatality ratios ranged from 23.0 to 52.2%, being highest in 1989 when basic facilities were compromised. Low birthweight neonates accounted for 55.5% of those with septicaemia. The most common causative organisms were Staphylococcus epidermidis and Staphylococcus aureus in 1986 and 1987, but from 1988 Klebsiella species became the most common. More than 50% of neonatal septicaemia occurred after the age of 2 days. The results of the study demonstrated the dynamism of infection control: when control measures introduced earlier were not sustained, outbreaks of nosocomial infection recurred or worsened.
Molecular Mechanisms of Neonatal Brain Injury

Directory of Open Access Journals (Sweden)

Claire Thornton

2012-01-01

Full Text Available Fetal/neonatal brain injury is an important cause of neurological disability. Hypoxia-ischemia and excitotoxicity are considered important insults, and, in spite of their acute nature, brain injury develops over a protracted time period during the primary, secondary, and tertiary phases. The concept that most of the injury develops with a delay after the insult makes it possible to provide effective neuroprotective treatment after the insult. Indeed, hypothermia applied within 6 hours after birth in neonatal encephalopathy reduces neurological disability in clinical trials. In order to develop the next generation of treatment, we need to know more about the pathophysiological mechanism during the secondary and tertiary phases of injury. We review some of the critical molecular events related to mitochondrial dysfunction and apoptosis during the secondary phase and report some recent evidence that intervention may be feasible also days-weeks after the insult.
Diminished exercise capacity and mitochondrial bc1 complex deficiency in tafazzin-knockdown mice.

Directory of Open Access Journals (Sweden)

Corey ePowers

2013-04-01

Full Text Available The phospholipid, cardiolipin, is essential for maintaining mitochondrial structure and optimal function. Cardiolipin-deficiency in humans, Barth syndrome, is characterized by exercise intolerance, dilated cardiomyopathy, neutropenia and 3-methyl-glutaconic aciduria. The causative gene is the mitochondrial acyl-transferase, tafazzin that is essential for remodeling acyl chains of cardiolipin. We sought to determine metabolic rates in tafazzin-deficient mice during resting and exercise, and investigate the impact of cardiolipin deficiency on mitochondrial respiratory chain activities. Tafazzin knockdown in mice markedly impaired oxygen consumption rates during an exercise, without any significant effect on resting metabolic rates. CL-deficiency resulted in significant reduction of mitochondrial respiratory reserve capacity in neonatal cardiomyocytes that is likely to be caused by diminished activity of complex-III, which requires CL for its assembly and optimal activity. Our results may provide mechanistic insights of Barth syndrome pathogenesis.
Lack of mitochondrial trifunctional protein in mice causes neonatal hypoglycemia and sudden death

OpenAIRE

Ibdah, Jamal A.; Paul, Hyacinth; Zhao, Yiwen; Binford, Scott; Salleng, Ken; Cline, Mark; Matern, Dietrich; Bennett, Michael J.; Rinaldo, Piero; Strauss, Arnold W.

2001-01-01

Mitochondrial trifunctional protein (MTP) is a hetero-octamer of four α and four β subunits that catalyzes the final three steps of mitochondrial long chain fatty acid β-oxidation. Human MTP deficiency causes Reye-like syndrome, cardiomyopathy, or sudden unexpected death. We used gene targeting to generate an MTP α subunit null allele and to produce mice that lack MTP α and β subunits. The Mtpa–/– fetuses accumulate long chain fatty acid metabolites and have low birth weight compared with the...
Possible X linked congenital mitochondrial cardiomyopathy in three families.

OpenAIRE

Orstavik, K H; Skjörten, F; Hellebostad, M; Hågå, P; Langslet, A

1993-01-01

Familial cases of childhood congestive cardiomyopathy with X linked recessive inheritance and abnormalities of heart muscle mitochondria have been previously reported. We report here three families with possible X linked congestive cardiomyopathy and specific mitochondrial abnormalities. The heart disorder presented as endocardial fibroelastosis with neonatal death in two brothers in one family, and as heart failure and death in infancy in two brothers in the other two families. In one family...
Developmental Exposure to Second-Hand Smoke Increases Adult Atherogenesis and Alters Mitochondrial DNA Copy Number and Deletions in apoE−/− Mice

Science.gov (United States)

Fetterman, Jessica L.; Pompilius, Melissa; Westbrook, David G.; Uyeminami, Dale; Brown, Jamelle; Pinkerton, Kent E.; Ballinger, Scott W.

2013-01-01

Cardiovascular disease is a major cause of morbidity and mortality in the United States. While many studies have focused upon the effects of adult second-hand smoke exposure on cardiovascular disease development, disease development occurs over decades and is likely influenced by childhood exposure. The impacts of in utero versus neonatal second-hand smoke exposure on adult atherosclerotic disease development are not known. The objective of the current study was to determine the effects of in utero versus neonatal exposure to a low dose (1 mg/m3 total suspended particulate) of second-hand smoke on adult atherosclerotic lesion development using the apolipoprotein E null mouse model. Consequently, apolipoprotein E null mice were exposed to either filtered air or second-hand smoke: (i) in utero from gestation days 1–19, or (ii) from birth until 3 weeks of age (neonatal). Subsequently, all animals were exposed to filtered air and sacrificed at 12–14 weeks of age. Oil red-O staining of whole aortas, measures of mitochondrial damage, and oxidative stress were performed. Results show that both in utero and neonatal second-hand smoke exposure significantly increased adult atherogenesis in mice compared to filtered air controls. These changes were associated with changes in aconitase and mitochondrial superoxide dismutase activities consistent with increased oxidative stress in the aorta, changes in mitochondrial DNA copy number and deletion levels. These studies show that in utero or neonatal exposure to second-hand smoke significantly influences adult atherosclerotic lesion development and results in significant alterations to the mitochondrion and its genome that may contribute to atherogenesis. PMID:23825571
Neonatal Meningoventriculitis Due to Proteus Mirabilis – A Case Report

Science.gov (United States)

Juyal, Deepak; Rathaur, Vyas Kumar; Sharma, Neelam

2013-01-01

A five day old full term born baby was admitted to our Neonatal Intensive Care Unit with seizures, opisthotonous posture and was icteric upto thigh. Baby had a three day history of poor feeding, lethargy and abnormal body movements. Mother was a 29 years old primigravida and had a normal vaginal delivery at home. Sepsis profile of the patient was requested, lumbar puncture and ventricular tap was performed. Patient was put on third generation cephalosporins, aminoglycosides and phenobarbitone. Culture and sensitivity report of blood, Cerebro spinal fluid and ventricular fluid showed Proteus mirabilis. Computerized Tomography scan showed a large parenchymal lesion in the right frontal lobe and diffuse ependymal enhancement along both the lateral ventricles suggestive of meningoventriculitis. We hereby present a fatal case of neonatal meningoventriculitis due to Proteus mirabilis. PMID:23543669
Acute renal failure in asphyxiated term neonates

Directory of Open Access Journals (Sweden)

Pejović Biljana

2002-01-01

fatal. CONCLUSION We conclude that in tgerm neonates with severe perinatal asphyxia oliguric ARF was the predominant type of ARF. There is a good prediction of the severity of oliguric ARF according to the degree of perinatal asphvxia determined by Apgar score at 1 min.
Enhancing mitochondrial calcium buffering capacity reduces aggregation of misfolded SOD1 and motor neuron cell death without extending survival in mouse models of inherited amyotrophic lateral sclerosis.

Science.gov (United States)

Parone, Philippe A; Da Cruz, Sandrine; Han, Joo Seok; McAlonis-Downes, Melissa; Vetto, Anne P; Lee, Sandra K; Tseng, Eva; Cleveland, Don W

2013-03-13

Mitochondria have been proposed as targets for toxicity in amyotrophic lateral sclerosis (ALS), a progressive, fatal adult-onset neurodegenerative disorder characterized by the selective loss of motor neurons. A decrease in the capacity of spinal cord mitochondria to buffer calcium (Ca(2+)) has been observed in mice expressing ALS-linked mutants of SOD1 that develop motor neuron disease with many of the key pathological hallmarks seen in ALS patients. In mice expressing three different ALS-causing SOD1 mutants, we now test the contribution of the loss of mitochondrial Ca(2+)-buffering capacity to disease mechanism(s) by eliminating ubiquitous expression of cyclophilin D, a critical regulator of Ca(2+)-mediated opening of the mitochondrial permeability transition pore that determines mitochondrial Ca(2+) content. A chronic increase in mitochondrial buffering of Ca(2+) in the absence of cyclophilin D was maintained throughout disease course and was associated with improved mitochondrial ATP synthesis, reduced mitochondrial swelling, and retention of normal morphology. This was accompanied by an attenuation of glial activation, reduction in levels of misfolded SOD1 aggregates in the spinal cord, and a significant suppression of motor neuron death throughout disease. Despite this, muscle denervation, motor axon degeneration, and disease progression and survival were unaffected, thereby eliminating mutant SOD1-mediated loss of mitochondrial Ca(2+) buffering capacity, altered mitochondrial morphology, motor neuron death, and misfolded SOD1 aggregates, as primary contributors to disease mechanism for fatal paralysis in these models of familial ALS.
Sodium Pyruvate Reduced Hypoxic-Ischemic Injury to Neonatal Rat Brain

OpenAIRE

Pan, Rui; Rong, Zhihui; She, Yun; Cao, Yuan; Chang, Li-Wen; Lee, Wei-Hua

2012-01-01

Background Neonatal hypoxia-ischemia (HI) remains a major cause of severe brain damage and is often associated with high mortality and lifelong disability. Immature brains are extremely sensitive to hypoxia-ischemia, shown as prolonged mitochondrial neuronal death. Sodium pyruvate (SP), a substrate of the tricarboxylic acid cycle and an extracellular antioxidant, has been considered as a potential treatment for hypoxic-ischemic encephalopathy (HIE), but its effects have not been evaluated in ...
Fatal illness associated with pulmonary hypertension in a neonate caused by intrauterine echovirus 11 infection

NARCIS (Netherlands)

Willems, A.; Benne, CA; Timmer, A; Bergman, K.A.

Nonpolio enterovirus (NPEV) infections are known to cause a wide range of illnesses in the neonatal period. In most cases, NPEV is presumed to be contracted during birth. Intrauterine NPEV infections occur infrequently. A case of Intrauterine echovirus 11 infection with pneumonia, persistent
CRISPR/Cas9 and mitochondrial gene replacement therapy: promising techniques and ethical considerations.

Science.gov (United States)

Fogleman, Sarah; Santana, Casey; Bishop, Casey; Miller, Alyssa; Capco, David G

2016-01-01

Thousands of mothers are at risk of transmitting mitochondrial diseases to their offspring each year, with the most severe form of these diseases being fatal [1]. With no cure, transmission prevention is the only current hope for decreasing the disease incidence. Current methods of prevention rely on low mutant maternal mitochondrial DNA levels, while those with levels close to or above threshold (>60%) are still at a very high risk of transmission [2]. Two novel approaches may offer hope for preventing and treating mitochondrial disease: mitochondrial replacement therapy, and CRISPR/Cas9. Mitochondrial replacement therapy has emerged as a promising tool that has the potential to prevent transmission in patients with higher mutant mitochondrial loads. This method is the subject of many ethical concerns due its use of a donor embryo to transplant the patient's nuclear DNA; however, it has ultimately been approved for use in the United Kingdom and was recently declared ethically permissible by the FDA. The leading-edge CRISPR/Cas9 technology exploits the principles of bacterial immune function to target and remove specific sequences of mutated DNA. This may have potential in treating individuals with disease caused by mutant mitochondrial DNA. As the technology progresses, it is important that the ethical considerations herein emerge and become more established. The purpose of this review is to discuss current research surrounding the procedure and efficacy of the techniques, compare the ethical concerns of each approach, and look into the future of mitochondrial gene replacement therapy.
Congenital Complete Tracheal Ring in a Neonate: A Case Report

Directory of Open Access Journals (Sweden)

Esra ARUN ÖZER

2017-09-01

Full Text Available Abnormalities of the upper airway tract lead to congenital high airway obstruction and may complicate neonatal airway management in the delivery room. Congenital complete tracheal rings are a rare and unusual tracheal anomaly, usually presenting in the neonate or infant as respiratory distress. The clinical presentation can vary from almost asymptomatic patients to near-fatal airway obstruction. It may exist as an isolated entity, or in association with other congenital malformations, in particular, cardiac anomalies along with vascular rings and pulmonary slings. Other associated anomalies have also been reported, for example, chromosomal anomalies, malformation of other parts of the respiratory tract, esophagus and skeletal systems. Here, we report an extreme case of VACTERL/TACRD association presented with congenital complete tracheal ring, encephalocele, bilateral radial agenesis with absent thumbs, equinovalgus deformity on right foot, low-set ears and micrognathia.

In EXOG-depleted cardiomyocytes cell death is marked by a decreased mitochondrial reserve capacity of the electron transport chain

NARCIS (Netherlands)

Tigchelaar, Wardit; De Jong, Anne Margreet; van Gilst, Wiek H.; De Boer, Rudolf A.; Sillje, Herman H. W.

Depletion ofmitochondrial endo/exonuclease G-like (EXOG) in cultured neonatal cardiomyocytes stimulates mitochondrial oxygen consumption rate (OCR) and induces hypertrophy via reactive oxygen species (ROS). Here, we show that neurohormonal stress triggers cell death in endo/exonuclease
Value of CT in the Discrimination of Fatal from Non-Fatal Stercoral Colitis

Energy Technology Data Exchange (ETDEWEB)

Wu, Cheng Hsien; Huang, Chen Chin; Wang, Li Jen; Wong, Yon Cheng; Wang, Chao Jan; Lo, Wang Chak; Lin, Being Chuan; Wan, Yung Liang; Haueh, Chuen [Chang Gung Memorial Hospital, Chang Gung University, Taoyuan (China)

2012-06-15

Clinical presentation and physical signs may be unreliable in the diagnosis of stercoral colitis (SC). This study evaluates the value of computed tomography (CT) in distinguishing fatal from non-fatal SC. Ten patients diagnosed as SC were obtained from inter-specialist conferences. Additional 13 patients with suspected SC were identified via the Radiology Information System (RIS). These patients were divided into two groups; fatal and non-fatal SCs. Their CT images are reviewed by two board-certified radiologists blinded to the clinical data and radiographic reports. SC occurred in older patients and displayed no gender predisposition. There was significant correlation between fatal SC and CT findings of dense mucosa (p 0.017), perfusion defects (p = 0.026), ascites (p = 0.023), or abnormal gas (p = 0.033). The sensitivity, specificity, and accuracy of dense mucosa were 71%, 86%, and 81%, respectively. These figures were 75%, 79%, and 77% for perfusion defects; 75%, 80%, and 78% for ascites; and 50%, 93%, and 78% for abnormal gas, respectively. Each CT sign of mucosal sloughing and pericolonic abscess displayed high specificity of 100% and 93% for diagnosing fatal SC, respectively. However, this did not reach statistical significance in diagnosing fatal SC. CT appears to be valuable in discriminating fatal from non-fatal SC.
Value of CT in the Discrimination of Fatal from Non-Fatal Stercoral Colitis

International Nuclear Information System (INIS)

Wu, Cheng Hsien; Huang, Chen Chin; Wang, Li Jen; Wong, Yon Cheng; Wang, Chao Jan; Lo, Wang Chak; Lin, Being Chuan; Wan, Yung Liang; Haueh, Chuen

2012-01-01

Clinical presentation and physical signs may be unreliable in the diagnosis of stercoral colitis (SC). This study evaluates the value of computed tomography (CT) in distinguishing fatal from non-fatal SC. Ten patients diagnosed as SC were obtained from inter-specialist conferences. Additional 13 patients with suspected SC were identified via the Radiology Information System (RIS). These patients were divided into two groups; fatal and non-fatal SCs. Their CT images are reviewed by two board-certified radiologists blinded to the clinical data and radiographic reports. SC occurred in older patients and displayed no gender predisposition. There was significant correlation between fatal SC and CT findings of dense mucosa (p 0.017), perfusion defects (p = 0.026), ascites (p = 0.023), or abnormal gas (p = 0.033). The sensitivity, specificity, and accuracy of dense mucosa were 71%, 86%, and 81%, respectively. These figures were 75%, 79%, and 77% for perfusion defects; 75%, 80%, and 78% for ascites; and 50%, 93%, and 78% for abnormal gas, respectively. Each CT sign of mucosal sloughing and pericolonic abscess displayed high specificity of 100% and 93% for diagnosing fatal SC, respectively. However, this did not reach statistical significance in diagnosing fatal SC. CT appears to be valuable in discriminating fatal from non-fatal SC.
States with low non-fatal injury rates have high fatality rates and vice-versa.

Science.gov (United States)

Mendeloff, John; Burns, Rachel

2013-05-01

State-level injury rates or fatality rates are sometimes used in studies of the impact of various safety programs or other state policies. How much does the metric used affect the view of relative occupational risks among U.S. states? This paper uses a measure of severe injuries (fatalities) and of less severe injuries (non-fatal injuries with days away from work, restricted work, or job transfer-DART) to examine that issue. We looked at the correlation between the average DART injury rate (from the BLS Survey of Occupational Injuries and Illnesses) and an adjusted average fatality rate (from the BLS Census of Fatal Occupational Injuries) in the construction sector for states for 2003-2005 and for 2006-2008. The RAND Human Subjects Protection Committee determined that this study was exempt from review. The correlations between the fatal and non-fatal injury rates were between -0.30 and -0.70 for all construction and for the subsector of special trade contractors. The negative correlation was much smaller between the rate of fatal falls from heights and the rate of non-fatal falls from heights. Adjusting for differences in the industry composition of the construction sector across states had minor effects on these results. Although some have suggested that fatal and non-fatal injury rates should not necessarily be positively correlated, no one has suggested that the correlation is negative, which is what we find. We know that reported non-fatal rates are influenced by workers' compensation benefits and other factors. Fatality rates appear to be a more valid measure of risk. Efforts to explain the variations that we find should be undertaken. Copyright © 2012 Wiley Periodicals, Inc.
Neonatal Death and Heart Failure in Mouse with Transgenic HSP60 Expression

Directory of Open Access Journals (Sweden)

Tsung-Hsien Chen

2015-01-01

Full Text Available Mitochondrial heat shock proteins, such as HSP60, are chaperones responsible for the folding, transport, and quality control of mitochondrial matrix proteins and are essential for maintaining life. Both prosurvival and proapoptotic roles have been proposed for HSP60, and HSP60 is reportedly involved in the initiation of autoimmune, metabolic, and cardiovascular diseases. The role of HSP60 in pathogenesis of these diseases remains unclear, partly because of the lack of mouse models expressing HSP60. In this study we generated HSP60 conditional transgenic mice suitable for investigating in vivo outcomes by expressing HSP60 at the targeted organ in disease models. Ubiquitous HSP60 induction in the embryonic stage caused neonatal death in mice at postnatal day 1. A high incidence of atrial septal defects was observed in HSP60-expressing mice, with increased apoptosis and myocyte degeneration that possibly contributed to massive hemorrhage and sponge-like cardiac muscles. Our results showed that neonatal heart failure through HSP60 induction likely involves developmental defects and excessive apoptosis. The conditional HSP60 mouse model is useful for studying crucial biological questions concerning HSP60.
Cholescintigraphy in neonatal jaundice using Tc-99m p-butyl IDA

International Nuclear Information System (INIS)

Shimono, Reiko; Itoh, Hisao; Mogami, Hiroshi; Iio, Atsushi; Hamamoto, Ken

1987-01-01

Congenital biliary atresia (BA) is fatal but surgically treatable when diagnosed within 60 days after birth. To evaluate the value of cholescintigraphy in the early diagnosis of BA, 14 babies with neonatal jaundice, ranging in age from 17 to 126 days, underwent cholescintigraphic examinations using Tc-99m N-(p-butylphenylcarbamoyl-methyl) iminodiacetic acid. Cholescintigrams were interpreted as positive or negative for intestinal RI clearance by two independent radiologists. The intensity of pulmonary radioactivity was compared with cardiac-blood-pool radioactivity on a scale of 1 - 4, and expressed as hepatocyte clearance index. Interobserver variations were not observed. Biliary and intestinal clearance was negative in all 7 patients with surgically proven BA. Among 7 others with neonatal hepatitis, intestinal clearance was positive in three, and negative in the other four. The sensitivity, specificity, and accuracy of cholescintigraphy in diagnosing BA were 100 %, 43 %, and 71 %, respectively. Mean hepatic clearance index, examined on 13 scintigrams, was higher in patients with BA than those with neonatal hepatitis (3.3 vs 2.6). (Namekawa, K.)
Abnormal mitochondrial bioenergetics and heart rate dysfunction in mice lacking very-long-chain acyl-CoA dehydrogenase

NARCIS (Netherlands)

Exil, VJ; Gardner, CD; Rottman, JN; Sims, H; Bartelds, B; Khuchua, Z; Sindhal, R; Ni, GM; Strauss, AW

Mitochondrial very-long-chain acyl-CoA dehydrogenase ( VLCAD) deficiency is associated with severe hypoglycemia, cardiac dysfunction, and sudden death in neonates and children. Sudden death is common, but the underlying mechanisms are not fully understood. We report on a mouse model of VLCAD
Novel large-range mitochondrial DNA deletions and fatal multisystemic disorder with prominent hepatopathy

International Nuclear Information System (INIS)

Bianchi, Marzia; Rizza, Teresa; Verrigni, Daniela; Martinelli, Diego; Tozzi, Giulia; Torraco, Alessandra; Piemonte, Fiorella; Dionisi-Vici, Carlo; Nobili, Valerio; Francalanci, Paola; Boldrini, Renata; Callea, Francesco; Santorelli, Filippo Maria; Bertini, Enrico

2011-01-01

Highlights: ► Expanded array of mtDNA deletions. ► Pearson syndrome with prominent hepatopathy associated with single mtDNA deletions. ► Detection of deletions in fibroblasts and blood avoids muscle and liver biopsy. ► Look for mtDNA deletions before to study nuclear genes related to mtDNA depletion. -- Abstract: Hepatic involvement in mitochondrial cytopathies rarely manifests in adulthood, but is a common feature in children. Multiple OXPHOS enzyme defects in children with liver involvement are often associated with dramatically reduced amounts of mtDNA. We investigated two novel large scale deletions in two infants with a multisystem disorder and prominent hepatopathy. Amount of mtDNA deletions and protein content were measured in different post-mortem tissues. The highest levels of deleted mtDNA were in liver, kidney, pancreas of both patients. Moreover, mtDNA deletions were detected in cultured skin fibroblasts in both patients and in blood of one during life. Biochemical analysis showed impairment of mainly complex I enzyme activity. Patients manifesting multisystem disorders in childhood may harbour rare mtDNA deletions in multiple tissues. For these patients, less invasive blood specimens or cultured fibroblasts can be used for molecular diagnosis. Our data further expand the array of deletions in the mitochondrial genomes in association with liver failure. Thus analysis of mtDNA should be considered in the diagnosis of childhood-onset hepatopathies.
Thymidine kinase 2 enzyme kinetics elucidate the mechanism of thymidine-induced mitochondrial DNA depletion.

Science.gov (United States)

Sun, Ren; Wang, Liya

2014-10-07

Mitochondrial thymidine kinase 2 (TK2) is a nuclear gene-encoded protein, synthesized in the cytosol and subsequently translocated into the mitochondrial matrix, where it catalyzes the phosphorylation of thymidine (dT) and deoxycytidine (dC). The kinetics of dT phosphorylation exhibits negative cooperativity, but dC phosphorylation follows hyperbolic Michaelis-Menten kinetics. The two substrates compete with each other in that dT is a competitive inhibitor of dC phosphorylation, while dC acts as a noncompetitive inhibitor of dT phosphorylation. In addition, TK2 is feedback inhibited by dTTP and dCTP. TK2 also phosphorylates a number of pyrimidine nucleoside analogues used in antiviral and anticancer therapy and thus plays an important role in mitochondrial toxicities caused by nucleoside analogues. Deficiency in TK2 activity due to genetic alterations causes devastating mitochondrial diseases, which are characterized by mitochondrial DNA (mtDNA) depletion or multiple deletions in the affected tissues. Severe TK2 deficiency is associated with early-onset fatal mitochondrial DNA depletion syndrome, while less severe deficiencies result in late-onset phenotypes. In this review, studies of the enzyme kinetic behavior of TK2 enzyme variants are used to explain the mechanism of mtDNA depletion caused by TK2 mutations, thymidine overload due to thymidine phosphorylase deficiency, and mitochondrial toxicity caused by antiviral thymidine analogues.
Islamic fatalism

Directory of Open Access Journals (Sweden)

Helmer Ringgren

1967-02-01

Full Text Available The author sketches the historical background, then the teaching of the Koran, and finally, the development of the typical Islamic fatalism. The fatalism of Islam has to be viewed against the background of the ideas of pre-Islamic Arabia. Unfortunately, there is no other evidence from this epoch that a few poems on a very restricted range of topics which have been able to survive Islamic censure. The conventional and stereotyped character of these poems makes it difficult to decide to what extent they reflect commonly accepted views or the ideas of a certain group. In any case, they present a picture of the pagan Arab which is extremely idealized and formed after a rigid pattern. Historically speaking, Islamic 'fatalism' is the result of a combination of pre-Islamic fatalism and Muhammad's belief in God's omnipotence. From another point of view it is an interpretation of destiny that expresses man's feeling of total dependence, not on an impersonal power or universal order, but on an omnipotent God.
Estimating cost ratio distribution between fatal and non-fatal road accidents in Malaysia

Science.gov (United States)

Hamdan, Nurhidayah; Daud, Noorizam

2014-07-01

Road traffic crashes are a global major problem, and should be treated as a shared responsibility. In Malaysia, road accident tragedies kill 6,917 people and injure or disable 17,522 people in year 2012, and government spent about RM9.3 billion in 2009 which cost the nation approximately 1 to 2 percent loss of gross domestic product (GDP) reported annually. The current cost ratio for fatal and non-fatal accident used by Ministry of Works Malaysia simply based on arbitrary value of 6:4 or equivalent 1.5:1 depends on the fact that there are six factors involved in the calculation accident cost for fatal accident while four factors for non-fatal accident. The simple indication used by the authority to calculate the cost ratio is doubted since there is lack of mathematical and conceptual evidence to explain how this ratio is determined. The main aim of this study is to determine the new accident cost ratio for fatal and non-fatal accident in Malaysia based on quantitative statistical approach. The cost ratio distributions will be estimated based on Weibull distribution. Due to the unavailability of official accident cost data, insurance claim data both for fatal and non-fatal accident have been used as proxy information for the actual accident cost. There are two types of parameter estimates used in this study, which are maximum likelihood (MLE) and robust estimation. The findings of this study reveal that accident cost ratio for fatal and non-fatal claim when using MLE is 1.33, while, for robust estimates, the cost ratio is slightly higher which is 1.51. This study will help the authority to determine a more accurate cost ratio between fatal and non-fatal accident as compared to the official ratio set by the government, since cost ratio is an important element to be used as a weightage in modeling road accident related data. Therefore, this study provides some guidance tips to revise the insurance claim set by the Malaysia road authority, hence the appropriate method
Insulin accelerates global and mitochondrial protein synthesis rates in neonatal muscle during sepsis

Science.gov (United States)

In neonatal pigs, sepsis decreases protein synthesis in skeletal muscle by decreasing translation initiation. However, insulin stimulates muscle protein synthesis despite persistent repression of translation initiation signaling. To determine whether the insulin-induced increase in global rates of m...
Two novel mutations in thymidine kinase-2 cause early onset fatal encephalomyopathy and severe mtDNA depletion.

Science.gov (United States)

Lesko, Nicole; Naess, Karin; Wibom, Rolf; Solaroli, Nicola; Nennesmo, Inger; von Döbeln, Ulrika; Karlsson, Anna; Larsson, Nils-Göran

2010-03-01

Deficiency of thymidine kinase-2 (TK2) has been described in children with early onset fatal skeletal myopathy. TK2 is a mitochondrial deoxyribonucleoside kinase required for the phosphorylation of deoxycytidine and deoxythymidine and hence is vital for the maintenance of a balanced mitochondrial dNTP pool in post-mitotic tissues. We describe a patient with two novel TK2 mutations, which caused disease onset shortly after birth and death at the age of three months. One mutation (219insCG) generated an early stop codon, thus preventing the synthesis of a functional protein. The second mutation (R130W) resulted in an amino acid substitution, which caused a severe reduction (TK2 enzyme activity. These two novel TK2 mutations cause an extremely severe phenotype with overwhelming central nervous system symptoms not commonly seen in patients with TK2-deficiency. We conclude that the severe clinical presentation in this patient was due to a virtual lack of mitochondrial TK2 activity. Copyright 2009 Elsevier B.V. All rights reserved.
Experimental studies of mitochondrial function in CADASIL vascular smooth muscle cells

International Nuclear Information System (INIS)

Viitanen, Matti; Sundström, Erik; Baumann, Marc; Poyhonen, Minna; Tikka, Saara; Behbahani, Homira

2013-01-01

Cerebral Autosomal Dominant Arteriopathy with Subcortical Infarcts and Leukoencephalopathy (CADASIL) is a familiar fatal progressive degenerative disorder characterized by cognitive decline, and recurrent stroke in young adults. Pathological features include a dramatic reduction of brain vascular smooth muscle cells and severe arteriopathy with the presence of granular osmophilic material in the arterial walls. Here we have investigated the cellular and mitochondrial function in vascular smooth muscle cell lines (VSMCs) established from CADASIL mutation carriers (R133C) and healthy controls. We found significantly lower proliferation rates in CADASIL VSMC as compared to VSMC from controls. Cultured CADASIL VSMCs were not more vulnerable than control cells to a number of toxic substances. Morphological studies showed reduced mitochondrial connectivity and increased number of mitochondria in CADASIL VSMCs. Transmission electron microscopy analysis demonstrated increased irregular and abnormal mitochondria in CADASIL VSMCs. Measurements of mitochondrial membrane potential (Δψ m ) showed a lower percentage of fully functional mitochondria in CADASIL VSMCs. For a number of genes previously reported to be changed in CADASIL VSMCs, immunoblotting analysis demonstrated a significantly reduced SOD1 expression. These findings suggest that alteration of proliferation and mitochondrial function in CADASIL VSMCs might have an effect on vital cellular functions important for CADASIL pathology. -- Highlights: ► CADASIL is an inherited disease of cerebral vascular cells. ► Mitochondrial dysfunction has been implicated in the pathogenesis of CADASIL. ► Lower proliferation rates in CADASIL VSMC. ► Increased irregular and abnormal mitochondria and lower mitochondrial membrane potential in CADASIL VSMCs. ► Reduced mitochondrial connectivity and increased number of mitochondria in CADASIL VSMCs.
Experimental studies of mitochondrial function in CADASIL vascular smooth muscle cells

Energy Technology Data Exchange (ETDEWEB)

Viitanen, Matti [Division of Clinical Geriatrics, Department of Neurobiology, Care Sciences and Society, Karolinska Institutet, Stockholm (Sweden); Department of Geriatrics, Turku City Hospital and University of Turku, Turku (Finland); Sundström, Erik [Division of Neurodegeneration, Department of Neurobiology, Care Sciences and Society, Karolinska Institutet, Stockholm (Sweden); Baumann, Marc [Protein Chemistry Unit, Institute of Biomedicine/Anatomy, University of Helsinki, Helsinki (Finland); Poyhonen, Minna [Department of Clinical Genetics, Helsinki University Hospital, HUSLAB, Helsinki (Finland); Tikka, Saara [Protein Chemistry Unit, Institute of Biomedicine/Anatomy, University of Helsinki, Helsinki (Finland); Behbahani, Homira, E-mail: homira.behbahani@ki.se [Division of Clinical Geriatrics, Department of Neurobiology, Care Sciences and Society, Karolinska Institutet, Stockholm (Sweden); Karolinska Institutet Alzheimer' s Disease Research Center, Department of Neurobiology, Care Sciences and Society, Karolinska Institutet, Stockholm (Sweden)

2013-02-01

Cerebral Autosomal Dominant Arteriopathy with Subcortical Infarcts and Leukoencephalopathy (CADASIL) is a familiar fatal progressive degenerative disorder characterized by cognitive decline, and recurrent stroke in young adults. Pathological features include a dramatic reduction of brain vascular smooth muscle cells and severe arteriopathy with the presence of granular osmophilic material in the arterial walls. Here we have investigated the cellular and mitochondrial function in vascular smooth muscle cell lines (VSMCs) established from CADASIL mutation carriers (R133C) and healthy controls. We found significantly lower proliferation rates in CADASIL VSMC as compared to VSMC from controls. Cultured CADASIL VSMCs were not more vulnerable than control cells to a number of toxic substances. Morphological studies showed reduced mitochondrial connectivity and increased number of mitochondria in CADASIL VSMCs. Transmission electron microscopy analysis demonstrated increased irregular and abnormal mitochondria in CADASIL VSMCs. Measurements of mitochondrial membrane potential (Δψ{sub m}) showed a lower percentage of fully functional mitochondria in CADASIL VSMCs. For a number of genes previously reported to be changed in CADASIL VSMCs, immunoblotting analysis demonstrated a significantly reduced SOD1 expression. These findings suggest that alteration of proliferation and mitochondrial function in CADASIL VSMCs might have an effect on vital cellular functions important for CADASIL pathology. -- Highlights: ► CADASIL is an inherited disease of cerebral vascular cells. ► Mitochondrial dysfunction has been implicated in the pathogenesis of CADASIL. ► Lower proliferation rates in CADASIL VSMC. ► Increased irregular and abnormal mitochondria and lower mitochondrial membrane potential in CADASIL VSMCs. ► Reduced mitochondrial connectivity and increased number of mitochondria in CADASIL VSMCs.
Novel large-range mitochondrial DNA deletions and fatal multisystemic disorder with prominent hepatopathy

Energy Technology Data Exchange (ETDEWEB)

Bianchi, Marzia; Rizza, Teresa; Verrigni, Daniela [Unit of Molecular Medicine for Neuromuscular and Neurodegenerative Diseases, ' Bambino Gesu' Children' s Hospital, Rome (Italy); Martinelli, Diego [Division of Metabolism, ' Bambino Gesu' Children' s Hospital, Rome (Italy); Tozzi, Giulia; Torraco, Alessandra; Piemonte, Fiorella [Unit of Molecular Medicine for Neuromuscular and Neurodegenerative Diseases, ' Bambino Gesu' Children' s Hospital, Rome (Italy); Dionisi-Vici, Carlo [Division of Metabolism, ' Bambino Gesu' Children' s Hospital, Rome (Italy); Nobili, Valerio [Gastroenterology and Liver Unit, ' Bambino Gesu' Children' s Hospital, Rome (Italy); Francalanci, Paola; Boldrini, Renata; Callea, Francesco [Dept. Pathology, ' Bambino Gesu' Children' s Hospital, Rome (Italy); Santorelli, Filippo Maria [UOC Neurogenetica e Malattie Neuromuscolari, Fondazione Stella Maris, Pisa (Italy); Bertini, Enrico [Unit of Molecular Medicine for Neuromuscular and Neurodegenerative Diseases, ' Bambino Gesu' Children' s Hospital, Rome (Italy); and others

2011-11-18

Highlights: Black-Right-Pointing-Pointer Expanded array of mtDNA deletions. Black-Right-Pointing-Pointer Pearson syndrome with prominent hepatopathy associated with single mtDNA deletions. Black-Right-Pointing-Pointer Detection of deletions in fibroblasts and blood avoids muscle and liver biopsy. Black-Right-Pointing-Pointer Look for mtDNA deletions before to study nuclear genes related to mtDNA depletion. -- Abstract: Hepatic involvement in mitochondrial cytopathies rarely manifests in adulthood, but is a common feature in children. Multiple OXPHOS enzyme defects in children with liver involvement are often associated with dramatically reduced amounts of mtDNA. We investigated two novel large scale deletions in two infants with a multisystem disorder and prominent hepatopathy. Amount of mtDNA deletions and protein content were measured in different post-mortem tissues. The highest levels of deleted mtDNA were in liver, kidney, pancreas of both patients. Moreover, mtDNA deletions were detected in cultured skin fibroblasts in both patients and in blood of one during life. Biochemical analysis showed impairment of mainly complex I enzyme activity. Patients manifesting multisystem disorders in childhood may harbour rare mtDNA deletions in multiple tissues. For these patients, less invasive blood specimens or cultured fibroblasts can be used for molecular diagnosis. Our data further expand the array of deletions in the mitochondrial genomes in association with liver failure. Thus analysis of mtDNA should be considered in the diagnosis of childhood-onset hepatopathies.
Mitochondrial encephalocardio-myopathy with early neonatal onset due to TMEM70 mutation

Czech Academy of Sciences Publication Activity Database

Honzík, T.; Tesařová, M.; Mayr, J. A.; Hansíková, H.; Ješina, P.; Bodamer, O.; Koch, J.; Magner, M.; Freisinger, P.; Huemer, M.; Kostková, O.; Van Coster, R.; Kmoch, S.; Houštěk, Josef; Sperl, W.; Zeman, J.

2010-01-01

Roč. 95, č. 4 (2010), s. 296-301 ISSN 0003-9888 R&D Projects: GA MZd(CZ) NS9759; GA MŠk(CZ) 1M0520 Institutional research plan: CEZ:AV0Z50110509 Keywords : TMEM70 * ATP synthase * mitochondrial disease Subject RIV: FG - Pediatrics Impact factor: 2.616, year: 2010
Pulsed infrared radiation excites cultured neonatal spiral and vestibular ganglion neurons by modulating mitochondrial calcium cycling.

Science.gov (United States)

Lumbreras, Vicente; Bas, Esperanza; Gupta, Chhavi; Rajguru, Suhrud M

2014-09-15

Cochlear implants are currently the most effective solution for profound sensorineural hearing loss, and vestibular prostheses are under development to treat bilateral vestibulopathies. Electrical current spread in these neuroprostheses limits channel independence and, in some cases, may impair their performance. In comparison, optical stimuli that are spatially confined may result in a significant functional improvement. Pulsed infrared radiation (IR) has previously been shown to elicit responses in neurons. This study analyzes the response of neonatal rat spiral and vestibular ganglion neurons in vitro to IR (wavelength = 1,863 nm) using Ca(2+) imaging. Both types of neurons responded consistently with robust intracellular Ca(2+) ([Ca(2+)]i) transients that matched the low-frequency IR pulses applied (4 ms, 0.25-1 pps). Radiant exposures of ∼637 mJ/cm(2) resulted in continual neuronal activation. Temperature or [Ca(2+)] variations in the media did not alter the IR-evoked transients, ruling out extracellular Ca(2+) involvement or primary mediation by thermal effects on the plasma membrane. While blockage of Na(+), K(+), and Ca(2+) plasma membrane channels did not alter the IR-evoked response, blocking of mitochondrial Ca(2+) cycling with CGP-37157 or ruthenium red reversibly inhibited the IR-evoked [Ca(2+)]i transients. Additionally, the magnitude of the IR-evoked transients was dependent on ryanodine and cyclopiazonic acid-dependent Ca(2+) release. These results suggest that IR modulation of intracellular calcium cycling contributes to stimulation of spiral and vestibular ganglion neurons. As a whole, the results suggest selective excitation of neurons in the IR beam path and the potential of IR stimulation in future auditory and vestibular prostheses. Copyright © 2014 the American Physiological Society.
Impairments of hepatic gluconeogenesis and ketogenesis in PPARα-deficient neonatal mice.

Science.gov (United States)

Cotter, David G; Ercal, Baris; d'Avignon, D André; Dietzen, Dennis J; Crawford, Peter A

2014-07-15

Peroxisome proliferator activated receptor-α (PPARα) is a master transcriptional regulator of hepatic metabolism and mediates the adaptive response to fasting. Here, we demonstrate the roles for PPARα in hepatic metabolic adaptations to birth. Like fasting, nutrient supply is abruptly altered at birth when a transplacental source of carbohydrates is replaced by a high-fat, low-carbohydrate milk diet. PPARα-knockout (KO) neonatal mice exhibit relative hypoglycemia due to impaired conversion of glycerol to glucose. Although hepatic expression of fatty acyl-CoA dehydrogenases is imparied in PPARα neonates, these animals exhibit normal blood acylcarnitine profiles. Furthermore, quantitative metabolic fate mapping of the medium-chain fatty acid [(13)C]octanoate in neonatal mouse livers revealed normal contribution of this fatty acid to the hepatic TCA cycle. Interestingly, octanoate-derived carbon labeled glucose uniquely in livers of PPARα-KO neonates. Relative hypoketonemia in newborn PPARα-KO animals could be mechanistically linked to a 50% decrease in de novo hepatic ketogenesis from labeled octanoate. Decreased ketogenesis was associated with diminished mRNA and protein abundance of the fate-committing ketogenic enzyme mitochondrial 3-hydroxymethylglutaryl-CoA synthase (HMGCS2) and decreased protein abundance of the ketogenic enzyme β-hydroxybutyrate dehydrogenase 1 (BDH1). Finally, hepatic triglyceride and free fatty acid concentrations were increased 6.9- and 2.7-fold, respectively, in suckling PPARα-KO neonates. Together, these findings indicate a primary defect of gluconeogenesis from glycerol and an important role for PPARα-dependent ketogenesis in the disposal of hepatic fatty acids during the neonatal period. Copyright © 2014 the American Physiological Society.
[Fatal occupational accidents in Lombardy].

Science.gov (United States)

Pianosi, G

1995-01-01

All fatal occupational accidents compensated in Lombardy from 1984 to 1989 were analyzed (1259 cases): significant differences between geographical distribution of fatal occupational accidents and workers were observed. Males accounted for about 95% of fatalities; an excess of cases was shown in both young and elderly workers. Death was the consequence of injuries involving most frequently the head, thorax and spinal cord. An excess of fatalities was observed in agriculture and, at a lower level, in manufacturing industries; small enterprises were involved in approximately 25% of fatalities occurring in the manufacturing industries and services. Employers were the victims of fatal accidents in 50% of cases in agriculture and in 70% of cases in craft industries. Construction, agriculture and transport accounted for about 50% of all fatalities. About 50% of fatal occupational accidents were related to vehicle use: the victim was the driver in the majority of cases, sometimes the victim was run over by a vehicle or fell from a vehicle. The results agree with some previous observations (e.g.: sex and age distribution; construction, agriculture and transport as working activities at high accident risk); but some original observations have emerged, in particular about the frequency of employers as victims and the role of vehicles in the genesis of fatal occupational accidents. If further studies confirm these latter observations, important developments could follow in preventive action design and implementation.

Estimation of fatality and injury risk by means of in-depth fatal accident investigation data.

Science.gov (United States)

Yannis, George; Papadimitriou, Eleonora; Dupont, Emmanuelle; Martensen, Heike

2010-10-01

In this article the factors affecting fatality and injury risk of road users involved in fatal accidents are analyzed by means of in-depth accident investigation data, with emphasis on parameters not extensively explored in previous research. A fatal accident investigation (FAI) database is used, which includes intermediate-level in-depth data for a harmonized representative sample of 1300 fatal accidents in 7 European countries. The FAI database offers improved potential for analysis, because it includes information on a number of variables that are seldom available, complete, or accurately recorded in road accident databases. However, the fact that only fatal accidents are examined requires for methodological adjustments, namely, the correction for two types of effects on a road user's baseline risk: "accident size" effects, and "relative vulnerability" effects. Fatality and injury risk can be then modeled through multilevel logistic regression models, which account for the hierarchical dependences of the road accident process. The results show that the baseline fatality risk of road users involved in fatal accidents decreases with accident size and increases with the vulnerability of the road user. On the contrary, accident size increases nonfatal injury risk of road users involved in fatal accidents. Other significant effects on fatality and injury risk in fatal accidents include road user age, vehicle type, speed limit, the chain of accident events, vehicle maneuver, and safety equipment. In particular, the presence and use of safety equipment such as seat belt, antilock braking system (ABS), and electronic stability program (ESP) are protection factors for car occupants, especially for those seated at the front seats. Although ABS and ESP systems are typically associated with positive effects on accident occurrence, the results of this research revealed significant related effects on accident severity as well. Moreover, accident consequences are more severe
Fatal dengue hemorrhagic fever in adults: emphasizing the evolutionary pre-fatal clinical and laboratory manifestations.

Directory of Open Access Journals (Sweden)

Ing-Kit Lee

Full Text Available BACKGROUND: A better description of the clinical and laboratory manifestations of fatal patients with dengue hemorrhagic fever (DHF is important in alerting clinicians of severe dengue and improving management. METHODS AND FINDINGS: Of 309 adults with DHF, 10 fatal patients and 299 survivors (controls were retrospectively analyzed. Regarding causes of fatality, massive gastrointestinal (GI bleeding was found in 4 patients, dengue shock syndrome (DSS alone in 2; DSS/subarachnoid hemorrhage, Klebsiella pneumoniae meningitis/bacteremia, ventilator associated pneumonia, and massive GI bleeding/Enterococcus faecalis bacteremia each in one. Fatal patients were found to have significantly higher frequencies of early altered consciousness (≤24 h after hospitalization, hypothermia, GI bleeding/massive GI bleeding, DSS, concurrent bacteremia with/without shock, pulmonary edema, renal/hepatic failure, and subarachnoid hemorrhage. Among those experienced early altered consciousness, massive GI bleeding alone/with uremia/with E. faecalis bacteremia, and K. pneumoniae meningitis/bacteremia were each found in one patient. Significantly higher proportion of bandemia from initial (arrival laboratory data in fatal patients as compared to controls, and higher proportion of pre-fatal leukocytosis and lower pre-fatal platelet count as compared to initial laboratory data of fatal patients were found. Massive GI bleeding (33.3% and bacteremia (25% were the major causes of pre-fatal leukocytosis in the deceased patients; 33.3% of the patients with pre-fatal profound thrombocytopenia (<20,000/µL, and 50% of the patients with pre-fatal prothrombin time (PT prolongation experienced massive GI bleeding. CONCLUSIONS: Our report highlights causes of fatality other than DSS in patients with severe dengue, and suggested hypothermia, leukocytosis and bandemia may be warning signs of severe dengue. Clinicians should be alert to the potential development of massive GI bleeding
Clinical Features of Fatal Asthma

Directory of Open Access Journals (Sweden)

Chiung-Zuei Chen

2006-05-01

Full Text Available To characterize the clinical features of fatal asthma, we retrospectively analyzed the clinical characteristics of patients who died of an acute asthma attack in our hospital during a 15-year period from 1989 to 2003. Twelve patients had fatal asthma during this period, including eight who were dead on arrival in the emergency room (ER and three who died within 1 hour of admission to the ER. Patients were categorized into three groups according to the clinical presentations during the fatal attack: (1 rapid (< 3 hours decompensation in four patients; (2 gradual development of respiratory failure over several days in two patients; and (3 acute deterioration after unstable asthma lasting several days in six patients. All patients in groups 1 and 2 had reported previous near-fatal attacks. The proportion of young patients was highest in group 3, with half of them (3/6 younger than 35 years of age. Only one patient in group 3 had had a previous near-fatal attack. Five of the seven patients, with previous near-fatal attacks, had a pattern of decompensation during their fatal attack that was similar to their previous attacks. In conclusion, nearly all patients with fatal asthma in this study died outside of the hospital or within 1 hour after admission to the ER. Patients had patterns of decompensation during the fatal attack that were similar to those of their previous attacks. Early detection of warning signs, early admission to the ER, adequate treatment, and extremely close observation of patients, especially within 1 hour after ER arrival, may prevent or decrease the incidence of fatal asthmatic attack.
Global earthquake fatalities and population

Science.gov (United States)

Holzer, Thomas L.; Savage, James C.

2013-01-01

Modern global earthquake fatalities can be separated into two components: (1) fatalities from an approximately constant annual background rate that is independent of world population growth and (2) fatalities caused by earthquakes with large human death tolls, the frequency of which is dependent on world population. Earthquakes with death tolls greater than 100,000 (and 50,000) have increased with world population and obey a nonstationary Poisson distribution with rate proportional to population. We predict that the number of earthquakes with death tolls greater than 100,000 (50,000) will increase in the 21st century to 8.7±3.3 (20.5±4.3) from 4 (7) observed in the 20th century if world population reaches 10.1 billion in 2100. Combining fatalities caused by the background rate with fatalities caused by catastrophic earthquakes (>100,000 fatalities) indicates global fatalities in the 21st century will be 2.57±0.64 million if the average post-1900 death toll for catastrophic earthquakes (193,000) is assumed.
Anticipating Early Fatality: Friends', Schoolmates' and Individual Perceptions of Fatality on Adolescent Risk Behaviors

Science.gov (United States)

Soller, Brian; Williams, Kristi

2015-01-01

Past research indicates that anticipating adverse outcomes, such as early death (fatalism), is associated positively with adolescents' likelihood of engaging in risky behaviors. Health researchers and criminologists have argued that fatalism influences present risk taking in part by informing individuals' motivation for delaying gratification for the promise of future benefits. While past findings highlight the association between the anticipation of early death and a number of developmental outcomes, no known research has assessed the impact of location in a context characterized by high perceptions of fatality. Using data from Add Health and a sample of 9,584 adolescents (51 % female and 71 % white) nested in 113 schools, our study builds upon prior research by examining the association between friends', school mates', and individual perceptions of early fatality and adolescent risk behaviors. We test whether friends' anticipation of being killed prior to age 21 or location in a school where a high proportion of the student body subscribes to attitudes of high fatality, is associated with risky behaviors. Results indicate that friends' fatalism is positively associated with engaging in violent delinquency, non-violent delinquency, and drug use after controlling for individual covariates and prior individual risk-taking. Although friends' delinquency accounts for much of the effect of friends' fatalism on violence, none of the potential intervening variables fully explain the effect of friends' fatalism on youth involvement in nonviolent delinquency and drug use. Our results underscore the importance of friendship contextual effects in shaping adolescent risk-taking behavior and the very serious consequences perceptions of fatality have for adolescents' involvement in delinquency and drug use. PMID:23828725
Mis-targeting of the mitochondrial protein LIPT2 leads to apoptotic cell death.

Directory of Open Access Journals (Sweden)

Emanuele Bernardinelli

Full Text Available Lipoyl(Octanoyl Transferase 2 (LIPT2 is a protein involved in the post-translational modification of key energy metabolism enzymes in humans. Defects of lipoic acid synthesis and transfer start to emerge as causes of fatal or severe early-onset disease. We show that the first 31 amino acids of the N-terminus of LIPT2 represent a mitochondrial targeting sequence and inhibition of the transit of LIPT2 to the mitochondrion results in apoptotic cell death associated with activation of the apoptotic volume decrease (AVD current in normotonic conditions, as well as over-activation of the swelling-activated chloride current (IClswell, mitochondrial membrane potential collapse, caspase-3 cleavage and nuclear DNA fragmentation. The findings presented here may help elucidate the molecular mechanisms underlying derangements of lipoic acid biosynthesis.
Dataset on psychosocial risk factors in cases of fatal and near-fatal physical child abuse

Directory of Open Access Journals (Sweden)

Mary Clyde Pierce

2017-10-01

Full Text Available This article presents the psychosocial risk factors identified in the cases of 20 children less than four years of age who were victims of fatal or near-fatal physical abuse during a 12 month period in the Commonwealth of Kentucky. These data are related to the article “History, injury, and psychosocial risk factor commonalities among cases of fatal and near-fatal physical child abuse” (Pierce et al., 2017 [1].
Acute gastrointestinal compromise in neonates with congenital diaphragmatic hernia prior to repair.

Science.gov (United States)

Fox, Catherine; Stewart, Michael; King, Sebastian K; Patel, Neil

2016-12-01

Congenital diaphragmatic hernia (CDH) affects 1 in 3000 live births. Modern management strategies include delayed repair of the diaphragm to permit pre-operative optimization of cardiorespiratory status. We describe a cohort of neonates in whom early emergency operative intervention was required for potentially fatal intestinal compromise. A retrospective review was performed of all neonatal CDH patients managed at a tertiary center in an 8-year period (2005-2012). A total of 126 CDH patients were managed during the 8-year period. Five neonates (male - 1; gestation 37+4-39+7; birth weight 2.9-3.7kg; left CDH - 5) required emergency operative intervention for presumed gastrointestinal compromise. All five neonates demonstrated systemic hypotension despite inotropic support, raised serum lactate (>2mmol/L), and abnormal radiographic findings. Operative intervention occurred within 3days of birth (1-3days). Findings included gastric volvulus, jejunal volvulus, and perforated caecum. All patients underwent primary diaphragmatic repair without a patch. Temporary ileostomy was required in 1 patient. All patients remain alive. Gastrointestinal compromise is a rare, but potentially catastrophic, complication of CDH. Emergency operative intervention may be required in a select cohort of patients. Early deterioration following birth should alert clinicians to the possibility of significant intestinal pathology. Level IV case series with no comparison group. Copyright Â© 2016 Elsevier Inc. All rights reserved.
Biochemical, clinical and molecular findings in LCHAD and general mitochondrial trifunctional protein deficiency

DEFF Research Database (Denmark)

Olpin, S E; Clark, S; Andresen, B S

2005-01-01

General mitochondrial trifunctional protein (TFP) deficiency leads to a wide clinical spectrum of disease ranging from severe neonatal/infantile cardiomyopathy and early death to mild chronic progressive sensorimotor poly-neuropathy with episodic rhabdomyolysis. Isolated long-chain 3-hydroxyacyl...... major presenting feature but usually later accompanied by episodic rhabdomyolysis, is a manifestation of mild TFP protein deficiency. The mild clinical presentation and relative difficulty in diagnosis suggest that this form of TFP is probably underdiagnosed....
Mitochondrial defects associated with β-alanine toxicity: relevance to hyper-beta-alaninemia

Science.gov (United States)

Shetewy, Aza; Shimada-Takaura, Kayoko; Warner, Danielle; Jong, Chian Ju; Mehdi, Abu-Bakr Al; Alexeyev, Mikhail; Takahashi, Kyoko; Schaffer, Stephen W.

2016-01-01

Hyper-beta-alaninemia is a rare metabolic condition that results in elevated plasma and urinary β-alanine levels and is characterized by neurotoxicity, hypotonia, and respiratory distress. It has been proposed that at least some of the symptoms are caused by oxidative stress; however, only limited information is available on the mechanism of reactive oxygen species generation. The present study examines the hypothesis that β-alanine reduces cellular levels of taurine, which are required for normal respiratory chain function; cellular taurine depletion is known to reduce respiratory function and elevate mitochondrial superoxide generation. To test the taurine hypothesis, isolated neonatal rat cardiomyocytes and mouse embryonic fibroblasts were incubated with medium lacking or containing β-alanine. β-alanine treatment led to mitochondrial superoxide accumulation in conjunction with a decrease in oxygen consumption. The defect in β-alanine-mediated respiratory function was detected in permeabilized cells exposed to glutamate/malate but not in cells utilizing succinate, suggesting that β-alanine leads to impaired complex I activity. Taurine treatment limited mitochondrial superoxide generation, supporting a role for taurine in maintaining complex I activity. Also affected by taurine is mitochondrial morphology, as β-alanine-treated fibroblasts undergo fragmentation, a sign of unhealthy mitochondria that is reversed by taurine treatment. If left unaltered, β-alanine-treated fibroblasts also undergo mitochondrial apoptosis, as evidenced by activation of caspases 3 and 9 and the initiation of the mitochondrial permeability transition. Together, these data show that β-alanine mediates changes that reduce ATP generation and enhance oxidative stress, factors that contribute to heart failure. PMID:27023909
An increase in the burden of neonatal admissions to a rural district hospital in Kenya over 19 years

Directory of Open Access Journals (Sweden)

Marsh Kevin

2010-10-01

Full Text Available Abstract Background Most of the global neonatal deaths occur in developing nations, mostly in rural homes. Many of the newborns who receive formal medical care are treated in rural district hospitals and other peripheral health centres. However there are no published studies demonstrating trends in neonatal admissions and outcome in rural health care facilities in resource poor regions. Such information is critical in planning public health interventions. In this study we therefore aimed at describing the pattern of neonatal admissions to a Kenyan rural district hospital and their outcome over a 19 year period, examining clinical indicators of inpatient neonatal mortality and also trends in utilization of a rural hospital for deliveries. Methods Prospectively collected data on neonates is compared to non-neonatal paediatric (≤ 5 years old admissions and deliveries' in the maternity unit at Kilifi District Hospital from January 1st 1990 up to December 31st 2008, to document the pattern of neonatal admissions, deliveries and changes in inpatient deaths. Trends were examined using time series models with likelihood ratios utilised to identify indicators of inpatient neonatal death. Results The proportion of neonatal admissions of the total paediatric ≤ 5 years admissions significantly increased from 11% in 1990 to 20% by 2008 (trend 0.83 (95% confidence interval 0.45 -1.21. Most of the increase in burden was from neonates born in hospital and very young neonates aged 7 mmol/l predicted inpatient neonatal death with a sensitivity of 81% and a specificity of 68%. Conclusions There is clear evidence of increasing burden in neonatal admissions at a rural district hospital in contrast to reducing numbers of non-neonatal paediatrics' admissions aged ≤ 5years. Though the inpatient case fatality for all admissions aged ≤ 5 years declined significantly, neonates now comprise close to 60% of all inpatient deaths. Simple indicators may identify
TMEM70 mutations cause isolated ATP synthase deficiency and neonatal mitochondrial encephalocardiomyopathy

Czech Academy of Sciences Publication Activity Database

Čížková, Alena; Stránecký, V.; Mayr, J. A.; Tesařová, M.; Havlíčková, Vendula; Paul, Jan; Ivánek, R.; Kuss, A. W.; Hansíková, H.; Kaplanová, Vilma; Vrbacký, Marek; Hartmannová, H.; Nosková, L.; Honzík, T.; Drahota, Zdeněk; Magner, M.; Hejzlarová, Kateřina; Sperl, W.; Zeman, J.; Houštěk, Josef; Kmoch, S.

2008-01-01

Roč. 40, č. 11 (2008), s. 1288-1290 ISSN 1061-4036 R&D Projects: GA MŠk(CZ) 1M0520; GA ČR GD305/08/H037; GA ČR(CZ) GD303/03/H065 Grant - others:Univerzita Karlova(CZ) 97807 Institutional research plan: CEZ:AV0Z50110509 Keywords : ATPase biogenesis * TMEM70 * mitochondrial disease Subject RIV: EB - Genetics ; Molecular Biology Impact factor: 30.259, year: 2008
Femme fatale

Directory of Open Access Journals (Sweden)

Francisco Javier Tardío Gastón

2011-12-01

Full Text Available Our history is full of myths and topics. Therefore the image of femme fatale is frequent in the works of all periods and places. The author of this article first analyzes how the history and literature consistently showed and defined these women, and then presents examples that come from ancient Greece. The art is powered by their power of seduction and the article explains how this femme fatale appeared in literature and film. The article concludes with a brief overview of various arguments concerning women and feminism, present in the literary criticism.
A social autopsy of neonatal mortality suggests needed improvements in maternal and neonatal interventions in Balaka and Salima districts of Malawi

Directory of Open Access Journals (Sweden)

Alain K. Koffi

2015-06-01

Full Text Available Background The Every Newborn Action Plan calls for reducing the neonatal mortality rates to fewer than 10 deaths per 1000 live births in all countries by 2035. The current study aims to increase our understanding of the social and modifiable factors that can be addressed or reinforced to improve and accelerate the decline in neonatal mortality in Malawi. Methods The data come from the 2013 Verbal and Social Autopsy (VASA study that collected data in order to describe the biological causes and the social determinants of deaths of children under 5 years of age in Balaka and Salima districts of Malawi. This paper analyses the social autopsy data of the neonatal deaths and presents results of a review of the coverage of key interventions along the continuum of normal maternal and newborn care and the description of breakdowns in the care provided for neonatal illnesses within the Pathway to Survival framework. Results A total of 320 neonatal deaths were confirmed from the VASA survey. While one antenatal care (ANC visit was high at 94%, the recommended four ANC visits was much lower at 41% and just 17% of the mothers had their urines tested during the pregnancy. 173 (54% mothers of the deceased newborns had at least one labor/delivery complication that began at home. The caregivers of 65% (n = 75 of the 180 newborns that were born at home or born and left a health facility alive perceived them to be severely ill at the onset of their illness, yet only 44% (n = 80 attempted and 36% (n = 65could reach the first health provider after an average of 91 minutes travel time. Distance, lack of transport and cost emerged as the most important constraints to formal care–seeking during delivery and during the newborn fatal illness. Conclusions This study suggests that maternal and neonatal health organizations and the local government of Malawi should increase the demand for key maternal and child health interventions, including the recommended 4
Desmin common mutation is associated with multi-systemic disease manifestations and depletion of mitochondria and mitochondrial DNA

Directory of Open Access Journals (Sweden)

Elizabeth eMcCormick

2015-06-01

Full Text Available Desmin (DES is a major muscle scaffolding protein that also functions to anchor mitochondria. Pathogenic DES mutations, however, have not previously been recognized as a cause of multi-systemic mitochondrial disease. Here, we describe a 45-year-old man who presented to The Children’s Hospital of Philadelphia Mitochondrial-Genetics Diagnostic Clinic for evaluation of progressive cardiac, neuromuscular, gastrointestinal, and mood disorders. Muscle biopsy at age 45 was remarkable for cytoplasmic bodies, as well as ragged red fibers and SDH positive/COX negative fibers that were suggestive of a mitochondrial myopathy. Muscle also showed significant reductions in mitochondrial content (16% of control mean for citrate synthase activity and mitochondrial DNA (35% of control mean. His family history was significant for cardiac conduction defects and myopathy in multiple maternal relatives. Multiple single gene and panel-based sequencing studies were unrevealing. Whole exome sequencing identified a known pathogenic p.S13F mutation in DES that had previously been associated with desmin-related myopathy. Desmin-related myopathy is an autosomal dominant disorder characterized by right ventricular hypertrophic cardiomyopathy, myopathy, and arrhythmias. However, neuropathy, gastrointestinal dysfunction, and depletion of both mitochondria and mitochondrial DNA have not previously been widely recognized in this disorder. Recognition that mitochondrial dysfunction occurs in desmin-related myopathy clarifies the basis for the multi-systemic manifestations, as are typical of primary mitochondrial disorders. Understanding the mitochondrial pathophysiology of desmin-related myopathy highlights the possibility of new therapies for the otherwise untreatable and often fatal class of disease. We postulate that drug treatments aimed at improving mitochondrial biogenesis or reducing oxidative stress may be effective therapies to ameliorate the effects of desmin
Work-related fatal motor vehicle traffic crashes: Matching of 2010 data from the Census of Fatal Occupational Injuries and the Fatality Analysis Reporting System.

Science.gov (United States)

Byler, Christen; Kesy, Laura; Richardson, Scott; Pratt, Stephanie G; Rodríguez-Acosta, Rosa L

2016-07-01

Motor vehicle traffic crashes (MVTCs) remain the leading cause of work-related fatal injuries in the United States, with crashes on public roadways accounting for 25% of all work-related deaths in 2012. In the United States, the Bureau of Labor Statistics (BLS) Census of Fatal Occupational Injuries (CFOI) provides accurate counts of fatal work injuries based on confirmation of work relationship from multiple sources, while the National Highway Traffic Safety Administration (NHTSA) Fatality Analysis Reporting System (FARS) provides detailed data on fatal MVTCs based on police reports. Characterization of fatal work-related MVTCs is currently limited by data sources that lack either data on potential risk factors (CFOI) or work-relatedness confirmation and employment characteristics (FARS). BLS and the National Institute for Occupational Safety and Health (NIOSH) collaborated to analyze a merged data file created by BLS using CFOI and FARS data. A matching algorithm was created to link 2010 data from CFOI and FARS using date of incident and other case characteristics, allowing for flexibility in variables to address coding discrepancies. Using the matching algorithm, 953 of the 1044 CFOI "Highway" cases (91%) for 2010 were successfully linked to FARS. Further analysis revealed systematic differences between cases identified as work-related by both systems and by CFOI alone. Among cases identified as work-related by CFOI alone, the fatally-injured worker was considerably more likely to have been employed outside the transportation and warehousing industry or transportation-related occupations, and to have been the occupant of a vehicle other than a heavy truck. This study is the first step of a collaboration between BLS, NHTSA, and NIOSH to improve the completeness and quality of data on fatal work-related MVTCs. It has demonstrated the feasibility and value of matching data on fatal work-related traffic crashes from CFOI and FARS. The results will lead to
An analysis of 332 fatalities infected with pandemic 2009 influenza A (H1N1 in Argentina.

Directory of Open Access Journals (Sweden)

Ana M Balanzat

Full Text Available The apparent high number of deaths in Argentina during the 2009 pandemic led to concern that the influenza A H1N1pdm disease was different there. We report the characteristics and risk factors for influenza A H1N1pdm fatalities.We identified laboratory-confirmed influenza A H1N1pdm fatalities occurring during June-July 2009. Physicians abstracted data on age, sex, time of onset of illness, medical history, clinical presentation at admission, laboratory, treatment, and outcomes using standardize questionnaires. We explored the characteristics of fatalities according to their age and risk group.Of 332 influenza A H1N1pdm fatalities, 226 (68% were among persons aged <50 years. Acute respiratory failure was the leading cause of death. Of all cases, 249 (75% had at least one comorbidity as defined by Advisory Committee on Immunization Practices. Obesity was reported in 32% with data and chronic pulmonary disease in 28%. Among the 40 deaths in children aged <5 years, chronic pulmonary disease (42% and neonatal pathologies (35% were the most common co-morbidities. Twenty (6% fatalities were among pregnant or postpartum women of which only 47% had diagnosed co-morbidities. Only 13% of patients received antiviral treatment within 48 hours of symptom onset. None of children aged <5 years or the pregnant women received antivirals within 48 h of symptom onset. As the pandemic progressed, the time from symptom-onset to medical care and to antiviral treatment decreased significantly among case-patients who subsequently died (p<0.001.Persons with co-morbidities, pregnant and who received antivirals late were over-represented among influenza A H1N1pdm deaths in Argentina, though timeliness of antiviral treatment improved during the pandemic.
Neonatal Death

Science.gov (United States)

... Home > Complications & Loss > Loss & grief > Neonatal death Neonatal death E-mail to a friend Please fill in ... cope with your baby’s death. What is neonatal death? Neonatal death is when a baby dies in ...
Toxins in botanical dietary supplements: blue cohosh components disrupt cellular respiration and mitochondrial membrane potential.

Science.gov (United States)

Datta, Sandipan; Mahdi, Fakhri; Ali, Zulfiqar; Jekabsons, Mika B; Khan, Ikhlas A; Nagle, Dale G; Zhou, Yu-Dong

2014-01-24

Certain botanical dietary supplements have been associated with idiosyncratic organ-specific toxicity. Similar toxicological events, caused by drug-induced mitochondrial dysfunction, have forced the withdrawal or U.S. FDA "black box" warnings of major pharmaceuticals. To assess the potential mitochondrial liability of botanical dietary supplements, extracts from 352 authenticated plant samples used in traditional Chinese, Ayurvedic, and Western herbal medicine were evaluated for the ability to disrupt cellular respiration. Blue cohosh (Caulophyllum thalictroides) methanol extract exhibited mitochondriotoxic activity. Used by some U.S. midwives to help induce labor, blue cohosh has been associated with perinatal stroke, acute myocardial infarction, congestive heart failure, multiple organ injury, and neonatal shock. The potential link between mitochondrial disruption and idiosyncratic herbal intoxication prompted further examination. The C. thalictroides methanol extract and three saponins, cauloside A (1), saponin PE (2), and cauloside C (3), exhibited concentration- and time-dependent mitochondriotoxic activities. Upon treatment, cell respiration rate rapidly increased and then dramatically decreased within minutes. Mechanistic studies revealed that C. thalictroides constituents impair mitochondrial function by disrupting membrane integrity. These studies provide a potential etiological link between this mitochondria-sensitive form of cytotoxicity and idiosyncratic organ damage.
Toxins in Botanical Dietary Supplements: Blue Cohosh Components Disrupt Cellular Respiration and Mitochondrial Membrane Potential

Science.gov (United States)

Datta, Sandipan; Mahdi, Fakhri; Ali, Zulfiqar; Jekabsons, Mika B.; Khan, Ikhlas A.; Nagle, Dale G.; Zhou, Yu-Dong

2014-01-01

Certain botanical dietary supplements have been associated with idiosyncratic organ-specific toxicity. Similar toxicological events, caused by drug-induced mitochondrial dysfunction, have forced the withdrawal or U.S. FDA “Black Box” warnings of major pharmaceuticals. To assess the potential mitochondrial liability of botanical dietary supplements, extracts from 352 authenticated plant samples used in traditional Chinese, Ayurvedic, and Western herbal medicine were evaluated for the ability to disrupt cellular respiration. Blue cohosh (Caulophyllum thalictroides) methanol extract exhibited mitochondriotoxic activity. Used by some U.S. midwives to help induce labor, blue cohosh has been associated with perinatal stroke, acute myocardial infarction, congestive heart failure, multiple organ injury, and neonatal shock. The potential link between mitochondrial disruption and idiosyncratic herbal intoxication prompted further examination. The C. thalictroides methanol extract and three saponins, cauloside A (1), saponin PE (2), and cauloside C (3) exhibited concentration- and time-dependent mitochondriotoxic activities. Upon treatment, cell respiration rate rapidly increased and then dramatically decreased within minutes. Mechanistic studies revealed that C. thalictroides constituents impair mitochondrial function by disrupting membrane integrity. These studies provide a potential etiological link between this mitochondria-sensitive form of cytotoxicity and idiosyncratic organ damage. PMID:24328138

Increased intrinsic mitochondrial function in humans with mitochondrial haplogroup H

DEFF Research Database (Denmark)

Larsen, Steen; Díez-Sánchez, Carmen; Rabøl, Rasmus

2014-01-01

and determined their mitochondrial haplogroup, mitochondrial oxidative phosphorylation capacity (OXPHOS), mitochondrial content (citrate synthase (CS)) and VO2max. Intrinsic mitochondrial function is calculated as mitochondrial OXPHOS capacity divided by mitochondrial content (CS). Haplogroup H showed a 30......% higher intrinsic mitochondrial function compared with the other haplo group U. There was no relationship between haplogroups and VO2max. In skeletal muscle from men with mitochondrial haplogroup H, an increased intrinsic mitochondrial function is present....
Extended investigation on road fatality in Brunei.

Science.gov (United States)

Yusof, N B; Hoque, M A; Steele, M C; Yong, S Y

2018-06-08

Road fatality is one of the leading causes of death in Brunei with 79 deaths in 1993, the highest ever recorded. The Brunei government has been trying to reduce this by implementing new traffic measures and successfully reduced fatalities to 24 fatalities in 2014. Yearly road fatality has been fluctuating, but there has been a declining tendency overall. The aim of this study is to investigate road fatality in Brunei by extending the research. We developed a multiple regression model and carried out an analysis on road fatality in Brunei. Our analysis indicates that the road fatality appears to rise depending on the increase in the number of young drivers between 15 to 24 years and the number of unemployed people. Comparisons of Brunei road fatality rate per 10,000 vehicles are made with some other countries and we conclude that Brunei has approximately the same rate as Australia in 2014.
SOD2 Activity Is not Impacted by Hyperoxia in Murine Neonatal Pulmonary Artery Smooth Muscle Cells and Mice

Directory of Open Access Journals (Sweden)

Anita Gupta

2015-03-01

Full Text Available Pulmonary hypertension (PH complicates bronchopulmonary dysplasia (BPD in 25% of infants. Superoxide dismutase 2 (SOD2 is an endogenous mitochondrial antioxidant, and overexpression protects against acute lung injury in adult mice. Little is known about SOD2 in neonatal lung disease and PH. C57Bl/6 mice and isogenic SOD2+/+ and SOD2−/+ mice were placed in room air (control or 75% O2 (chronic hyperoxia, CH for 14 days. Right ventricular hypertrophy (RVH was assessed by Fulton’s index. Medial wall thickness (MWT and alveolar area were assessed on formalin fixed lung sections. Pulmonary artery smooth muscle cells (PASMC were placed in 21% or 95% O2 for 24 h. Lung and PASMC protein were analyzed for SOD2 expression and activity. Oxidative stress was measured with a mitochondrially-targeted sensor, mitoRoGFP. CH lungs have increased SOD2 expression, but unchanged activity. SOD2−/+ PASMC have decreased expression and activity at baseline, but increased SOD2 expression in hyperoxia. Hyperoxia increased mitochondrial ROS in SOD2+/+ and SOD2−/+ PASMC. SOD2+/+ and SOD2−/+ CH pups induced SOD2 expression, but not activity, and developed equivalent increases in RVH, MWT, and alveolar area. Since SOD2−/+ mice develop equivalent disease, this suggests other antioxidant systems may compensate for partial SOD2 expression and activity in the neonatal period during hyperoxia-induced oxidative stress.
No improvement of neuronal metabolism in the reperfusion phase with melatonin treatment after hypoxic-ischemic brain injury in the neonatal rat.

Science.gov (United States)

Berger, Hester R; Morken, Tora Sund; Vettukattil, Riyas; Brubakk, Ann-Mari; Sonnewald, Ursula; Widerøe, Marius

2016-01-01

Mitochondrial impairment is a key feature underlying neonatal hypoxic-ischemic (HI) brain injury and melatonin is potentially neuroprotective through its effects on mitochondria. In this study, we have used (1) H and (13) C NMR spectroscopy after injection of [1-(13) C]glucose and [1,2-(13) C]acetate to examine neuronal and astrocytic metabolism in the early reperfusion phase after unilateral HI brain injury in 7-day-old rat pups, exploring the effects of HI on mitochondrial function and the potential protective effects of melatonin on brain metabolism. One hour after hypoxia-ischemia, astrocytic metabolism was recovered and glycolysis was normalized, whereas mitochondrial metabolism in neurons was clearly impaired. Pyruvate carboxylation was also lower in both hemispheres after HI. The transfer of glutamate from neurons to astrocytes was higher whereas the transfer of glutamine from astrocytes to neurons was lower 1 h after HI in the contralateral hemisphere. Neuronal metabolism was equally affected in pups treated with melatonin (10 mg/kg) immediately after HI as in vehicle treated pups indicating that the given dose of melatonin was not capable of protecting the neuronal mitochondria in this early phase after HI brain injury. However, any beneficial effects of melatonin might have been masked by modulatory effects of the solvent dimethyl sulfoxide on cerebral metabolism. Neuronal and astrocytic metabolism was examined by (13) C and (1) H NMR spectroscopy in the early reperfusion phase after unilateral hypoxic-ischemic brain injury and melatonin treatment in neonatal rats. One hour after hypoxia-ischemia astrocytic mitochondrial metabolism had recovered and glycolysis was normalized, whereas mitochondrial metabolism in neurons was impaired. Melatonin treatment did not show a protective effect on neuronal metabolism. © 2015 International Society for Neurochemistry.
Mitochondrial Disease

OpenAIRE

Bulent Kurt; Turgut Topal

2013-01-01

Mitochondria are the major energy source of cells. Mitochondrial disease occurs due to a defect in mitochondrial energy production. A valuable energy production in mitochondria depend a healthy interconnection between nuclear and mitochondrial DNA. A mutation in nuclear or mitochondrial DNA may cause abnormalities in ATP production and single or multiple organ dysfunctions, secondarily. In this review, we summarize mitochondrial physiology, mitochondrial genetics, and clinical expression and ...
Neonatal Hyperglycemia due to Transient Neonatal Diabetes Mellitus in Puerto Rico

OpenAIRE

Fargas-Berríos, N.; García-Fragoso, L.; García-García, I.; Valcárcel, M.

2015-01-01

Neonatal hyperglycemia is a metabolic disorder found in the neonatal intensive care units. Neonatal diabetes mellitus (NDM) is a very uncommon cause of hyperglycemia in the newborn, occurring in 1 in every 400,000 births. There are two subtypes of neonatal diabetes mellitus: permanent neonatal diabetes mellitus (PNDM) and transient neonatal diabetes mellitus (TNDM). We describe a term, small for gestational age, female neonate with transient neonatal diabetes mellitus who presented with poor ...
A Case of Fatal Pulmonary Hypoplasia with Congenital Diaphragmatic Hernia, Thoracic Myelomeningocele, and Thoracic Dysplasia.

Science.gov (United States)

Ito, Ai; Fujinaga, Hideshi; Matsui, Sachiko; Tago, Kumiko; Iwasaki, Yuka; Fujino, Shuhei; Nagasawa, Junko; Amari, Shoichiro; Kaneshige, Masao; Wada, Yuka; Takahashi, Shigehiro; Tsukamoto, Keiko; Miyazaki, Osamu; Yoshioka, Takako; Ishiguro, Akira; Ito, Yushi

2017-10-01

Background Congenital diaphragmatic hernia (CDH) is fatal in severe cases of pulmonary hypoplasia. We experienced a fatal case of pulmonary hypoplasia due to CDH, thoracic myelomeningocele (MMC), and thoracic dysplasia. This constellation of anomalies has not been previously reported. Case Report A male infant with a prenatal diagnosis of thoracic MMC with severe hydrocephalus and scoliosis was born at 36 weeks of gestation. CDH was found after birth and the patient died of respiratory failure due to pulmonary hypoplasia and persistent pulmonary hypertension of the newborn at 30 hours of age despite neonatal intensive care. An autopsy revealed a left CDH without herniation of the liver or stomach into the thoracic cavity, severe hydrocephalus, Chiari malformation type II, MMC with spina bifida from Th4 to Th12, hemivertebrae, fused ribs, deformities of the thoracic cage and legs, short trunk, and agenesis of the left kidney. Conclusion We speculate that two factors may be associated with the severe pulmonary hypoplasia: decreased thoracic space due to the herniation of visceral organs caused by CDH and thoracic dysplasia due to skeletal deformity and severe scoliosis.
Mitochondrial Dynamics: Coupling Mitochondrial Fitness with Healthy Aging.

Science.gov (United States)

Sebastián, David; Palacín, Manuel; Zorzano, Antonio

2017-03-01

Aging is associated with a decline in mitochondrial function and the accumulation of abnormal mitochondria. However, the precise mechanisms by which aging promotes these mitochondrial alterations and the role of the latter in aging are still not fully understood. Mitochondrial dynamics is a key process regulating mitochondrial function and quality. Altered expression of some mitochondrial dynamics proteins has been recently associated with aging and with age-related alterations in yeast, Caenorhabditis elegans, mice, and humans. Here, we review the link between alterations in mitochondrial dynamics, aging, and age-related impairment. We propose that the dysregulation of mitochondrial dynamics leads to age-induced accumulation of unhealthy mitochondria and contributes to alterations linked to aging, such as diabetes and neurodegeneration. Copyright © 2017 Elsevier Ltd. All rights reserved.
Alcohol intake in relation to non-fatal and fatal coronary heart disease and stroke

DEFF Research Database (Denmark)

Ricci, Cristian; Wood, Angela; Muller, David

2018-01-01

OBJECTIVE: To investigate the association between alcohol consumption (at baseline and over lifetime) and non-fatal and fatal coronary heart disease (CHD) and stroke. DESIGN: Multicentre case-cohort study. SETTING: A study of cardiovascular disease (CVD) determinants within the European Prospecti...
High third-generation cephalosporin resistant Enterobacteriaceae prevalence rate among neonatal infections in Dakar, Senegal

Directory of Open Access Journals (Sweden)

Sebastien Breurec

2016-10-01

Full Text Available Abstract Background Neonatal infection constitutes one of Senegal’s most important public health problems, with a mortality rate of 41 deaths per 1,000 live births. Methods Between January 2007 and March 2008, 242 neonates with suspected infection were recruited at three neonatal intensive care units in three major tertiary care centers in Dakar, the capital of Senegal. Neonatal infections were confirmed by positive bacterial blood or cerebrospinal fluid culture. The microbiological pattern of neonatal infections and the antibiotic susceptibility of the isolates were characterized. In addition, the genetic basis for antibiotic resistance and the genetic background of third-generation cephalosporin-resistant (3GC-R Enterobacteriaceae were studied. Results A bacteriological infection was confirmed in 36.4 % (88/242 of neonates: 22.7 % (30/132 during the early-onset and 52.7 % (58/110 during the late-onset periods (p > 0.20. Group B streptococci accounted for 6.8 % of the 88 collected bacterial isolates, while most of them were Enterobacteriaceae (n = 69, 78.4 %. Of these, 55/69 (79.7 % were 3GC-R. The blaCTX-M-15 allele, the blaSHV and the blaTEM were highly prevalent (63.5, 65.4 and 53.8 %, respectively, usually associated with qnr genes (65.4 %. Clonally related strains of 3GC-R Klebsiella pneumoniae and 3GC-R Enterobacter cloacae, the two most commonly recovered 3GC-R Enterobacteriaceae (48/55, were detected at the three hospitals, underlining the role of cross-transmission in their spread. The overall case fatality rate was 18.6 %. Conclusions Measures should be taken to prevent nosocomial infections and the selection of resistant bacteria.
Hypertrophic Cardiomyopathy due to Mitochondrial Disease: Prenatal Diagnosis, Management, and Outcome

Directory of Open Access Journals (Sweden)

Lutgardo García-Díaz

2013-01-01

Full Text Available A case of prenatally diagnosed fetal hypertrophic cardiomyopathy is reported. The mother was referred to our department at 37 weeks' gestation because of suspected congenital heart disease. Prenatal echocardiography showed biventricular hypertrophy and pericardial effusion, without additional abnormalities. Postnatal echocardiography confirmed prenatal diagnosis. Neonatal EKG showed biventricular hypertrophy and Wolff-Parkinson-White syndrome. Skeletal muscle biopsy was consistent with mitochondrial oxidative phosphorylation defect involving a combined defect of respiratory complexes I and IV. Echocardiographic followup during the first year of life showed progressive regression of hypertrophy and evolution to left ventricular myocardial noncompaction.
Neonatal Hyperglycemia due to Transient Neonatal Diabetes Mellitus in Puerto Rico.

Science.gov (United States)

Fargas-Berríos, N; García-Fragoso, L; García-García, I; Valcárcel, M

2015-01-01

Neonatal hyperglycemia is a metabolic disorder found in the neonatal intensive care units. Neonatal diabetes mellitus (NDM) is a very uncommon cause of hyperglycemia in the newborn, occurring in 1 in every 400,000 births. There are two subtypes of neonatal diabetes mellitus: permanent neonatal diabetes mellitus (PNDM) and transient neonatal diabetes mellitus (TNDM). We describe a term, small for gestational age, female neonate with transient neonatal diabetes mellitus who presented with poor feeding tolerance and vomiting associated with hyperglycemia (385 mg/dL), glycosuria, and metabolic acidosis within the first 12 hours of life. The neonate was treated with intravenous insulin, obtaining a slight control of hyperglycemia. An adequate glycemia was achieved at 5 weeks of life. The molecular studies showed complete loss of maternal methylation at the TND differentially methylated region on chromosome 6q24. The etiology of this neonate's hyperglycemia was a hypomethylation of the maternal TND locus. A rare cause of neonatal diabetes mellitus must be considered if a neonate presents refractory hyperglycemia. To our knowledge, this is the first case reported in Puerto Rico of transient neonatal mellitus due to the uncommon mechanism of maternal hypomethylation of the TND locus. Its prevalence in Puerto Rico is unknown.
CNTF-ACM promotes mitochondrial respiration and oxidative stress in cortical neurons through upregulating L-type calcium channel activity.

Science.gov (United States)

Sun, Meiqun; Liu, Hongli; Xu, Huanbai; Wang, Hongtao; Wang, Xiaojing

2016-09-01

A specialized culture medium termed ciliary neurotrophic factor-treated astrocyte-conditioned medium (CNTF-ACM) allows investigators to assess the peripheral effects of CNTF-induced activated astrocytes upon cultured neurons. CNTF-ACM has been shown to upregulate neuronal L-type calcium channel current activity, which has been previously linked to changes in mitochondrial respiration and oxidative stress. Therefore, the aim of this study was to evaluate CNTF-ACM's effects upon mitochondrial respiration and oxidative stress in rat cortical neurons. Cortical neurons, CNTF-ACM, and untreated control astrocyte-conditioned medium (UC-ACM) were prepared from neonatal Sprague-Dawley rat cortical tissue. Neurons were cultured in either CNTF-ACM or UC-ACM for a 48-h period. Changes in the following parameters before and after treatment with the L-type calcium channel blocker isradipine were assessed: (i) intracellular calcium levels, (ii) mitochondrial membrane potential (ΔΨm), (iii) oxygen consumption rate (OCR) and adenosine triphosphate (ATP) formation, (iv) intracellular nitric oxide (NO) levels, (v) mitochondrial reactive oxygen species (ROS) production, and (vi) susceptibility to the mitochondrial complex I toxin rotenone. CNTF-ACM neurons displayed the following significant changes relative to UC-ACM neurons: (i) increased intracellular calcium levels (p ACM (p ACM promotes mitochondrial respiration and oxidative stress in cortical neurons through elevating L-type calcium channel activity.
Prophylactic administration of melatonin to the mother throughout pregnancy can protect against oxidative cerebral damage in neonatal rats.

Science.gov (United States)

Watanabe, Kazushi; Hamada, Fumiaki; Wakatsuki, Akihiko; Nagai, Ryuhei; Shinohara, Koichi; Hayashi, Yoshihiro; Imamura, Rina; Fukaya, Takao

2012-08-01

The purpose of this study was to investigate whether prophylactic administration of melatonin to the mother throughout pregnancy could protect against ischemia/reperfusion (I/R)-induced oxidative brain damage in neonatal rats. The utero-ovarian arteries were occluded bilaterally for 30 min in female Wistar rats on day 16 of pregnancy to induce fetal ischemia. Reperfusion was achieved by releasing the occlusion and restoring circulation. A sham operation was performed in control rats. Melatonin solution or vehicle alone was administrated orally throughout pregnancy. We collected brain mitochondria from neonatal rats, evaluated mitochondrial structure by electron microscopy, and measured the respiratory control index (RCI) as an indicator of mitochondrial respiratory activity as well as the concentration of thiobarbituric acid-reactive substances (TBARS), a marker of oxidative stress. Histological analysis was performed at the Cornu Ammonis 1 (CA1) and Cornu Ammonis 3 (CA3) regions of the hippocampus. I/R significantly reduced the RCI and significantly elevated the concentration of TBARS. Melatonin treatment reversed these effects, resulting in values similar to that in untreated, sham-ischemic animals. Electron microscopic evaluation showed that the number of intact mitochondria decreased in the I/R group, while melatonin treatment preserved them. Histological analysis revealed a decrease in the ratio of normal to whole pyramidal cell number in the CA1 and CA3 regions in the I/R group. While melatonin administration protected against degeneration. These results indicate that prophylactic administration of melatonin to the mother throughout pregnancy may prevent I/R-induced oxidative brain damage in neonatal rats.
Transient neonatal diabetes or neonatal hyperglycaemia: A case ...

African Journals Online (AJOL)

Transient neonatal diabetes and neonatal hyperglycaemia both present in the neonatal period with features of hyperglycaemia, dehydration and weight loss. Differentiating these conditions clinically is difficult. We describe the case of a 13 day old female whom we managed recently who could have had either condition.
Drugs taken in fatal and non-fatal self-poisoning : A study in South London

NARCIS (Netherlands)

Neeleman, J; Wessely, S

This study compared the number and type of substances taken in deliberate self-poisoning with fatal (n=127) and non-fatal (n=521) outcome. The aims were (i) to describe substances typically involved in self-poisoning in England and Wales, (ii) to examine the role of drug 'cocktails' and (iii) to
Neonatal Hyperglycemia due to Transient Neonatal Diabetes Mellitus in Puerto Rico

Directory of Open Access Journals (Sweden)

N. Fargas-Berríos

2015-01-01

Full Text Available Neonatal hyperglycemia is a metabolic disorder found in the neonatal intensive care units. Neonatal diabetes mellitus (NDM is a very uncommon cause of hyperglycemia in the newborn, occurring in 1 in every 400,000 births. There are two subtypes of neonatal diabetes mellitus: permanent neonatal diabetes mellitus (PNDM and transient neonatal diabetes mellitus (TNDM. We describe a term, small for gestational age, female neonate with transient neonatal diabetes mellitus who presented with poor feeding tolerance and vomiting associated with hyperglycemia (385 mg/dL, glycosuria, and metabolic acidosis within the first 12 hours of life. The neonate was treated with intravenous insulin, obtaining a slight control of hyperglycemia. An adequate glycemia was achieved at 5 weeks of life. The molecular studies showed complete loss of maternal methylation at the TND differentially methylated region on chromosome 6q24. The etiology of this neonate’s hyperglycemia was a hypomethylation of the maternal TND locus. A rare cause of neonatal diabetes mellitus must be considered if a neonate presents refractory hyperglycemia. To our knowledge, this is the first case reported in Puerto Rico of transient neonatal mellitus due to the uncommon mechanism of maternal hypomethylation of the TND locus. Its prevalence in Puerto Rico is unknown.
Mitochondrial myopathies.

Science.gov (United States)

DiMauro, Salvatore

2006-11-01

Our understanding of mitochondrial diseases (defined restrictively as defects of the mitochondrial respiratory chain) is expanding rapidly. In this review, I will give the latest information on disorders affecting predominantly or exclusively skeletal muscle. The most recently described mitochondrial myopathies are due to defects in nuclear DNA, including coenzyme Q10 deficiency and mutations in genes controlling mitochondrial DNA abundance and structure, such as POLG, TK2, and MPV17. Barth syndrome, an X-linked recessive mitochondrial myopathy/cardiopathy, is associated with decreased amount and altered structure of cardiolipin, the main phospholipid of the inner mitochondrial membrane, but a secondary impairment of respiratory chain function is plausible. The role of mutations in protein-coding genes of mitochondrial DNA in causing isolated myopathies has been confirmed. Mutations in tRNA genes of mitochondrial DNA can also cause predominantly myopathic syndromes and--contrary to conventional wisdom--these mutations can be homoplasmic. Defects in the mitochondrial respiratory chain impair energy production and almost invariably involve skeletal muscle, causing exercise intolerance, cramps, recurrent myoglobinuria, or fixed weakness, which often affects extraocular muscles and results in droopy eyelids (ptosis) and progressive external ophthalmoplegia.
Mitochondrial nucleoid interacting proteins support mitochondrial protein synthesis.

Science.gov (United States)

He, J; Cooper, H M; Reyes, A; Di Re, M; Sembongi, H; Litwin, T R; Gao, J; Neuman, K C; Fearnley, I M; Spinazzola, A; Walker, J E; Holt, I J

2012-07-01

Mitochondrial ribosomes and translation factors co-purify with mitochondrial nucleoids of human cells, based on affinity protein purification of tagged mitochondrial DNA binding proteins. Among the most frequently identified proteins were ATAD3 and prohibitin, which have been identified previously as nucleoid components, using a variety of methods. Both proteins are demonstrated to be required for mitochondrial protein synthesis in human cultured cells, and the major binding partner of ATAD3 is the mitochondrial ribosome. Altered ATAD3 expression also perturbs mtDNA maintenance and replication. These findings suggest an intimate association between nucleoids and the machinery of protein synthesis in mitochondria. ATAD3 and prohibitin are tightly associated with the mitochondrial membranes and so we propose that they support nucleic acid complexes at the inner membrane of the mitochondrion.
[Biochemical diagnostics of fatal opium intoxication].

Science.gov (United States)

Papyshev, I P; Astashkina, O G; Tuchik, E S; Nikolaev, B S; Cherniaev, A L

2013-01-01

Biochemical diagnostics of fatal opium intoxication remains a topical problem in forensic medical science and practice. We investigated materials obtained in the course of forensic medical expertise of the cases of fatal opium intoxication. The study revealed significant differences between myoglobin levels in blood, urine, myocardium, and skeletal muscles. The proposed approach to biochemical diagnostics of fatal opium intoxication enhances the accuracy and the level of evidence of expert conclusions.

Advancing obstetric and neonatal care in a regional hospital in Ghana via continuous quality improvement.

Science.gov (United States)

Srofenyoh, Emmanuel; Ivester, Thomas; Engmann, Cyril; Olufolabi, Adeyemi; Bookman, Laurel; Owen, Medge

2012-01-01

To reduce maternal and neonatal death at a large regional hospital through the use of quality improvement methodologies. In 2007, Kybele and the Ghana Health Service formed a partnership to analyze systems and patient care processes at a regional hospital in Accra, Ghana. A model encompassing continuous assessment, implementation, advocacy, outputs, and outcomes was designed. Key areas for improvement were grouped into "bundles" based on personnel, systems management, and service quality. Primary outcomes included maternal and perinatal mortality, and case fatality rates for hemorrhage and hypertensive disorders. Implementation and outcomes were evaluated tri-annually between 2007 and 2009. During the study period, there was a 34% decrease in maternal mortality despite a 36% increase in patient admission. Case fatality rates for pre-eclampsia and hemorrhage decreased from 3.1% to 1.1% (Pcontinuous quality improvement were developed and employed. Copyright © 2011 International Federation of Gynecology and Obstetrics. Published by Elsevier Ireland Ltd. All rights reserved.
Fatal occupational injuries in Taiwan, 1994-2005.

Science.gov (United States)

Ho, Shu-Chen; Wang, Li-Yu; Ho, Chi-Kung; Yang, Chun-Yuh

2010-04-01

This study examines the trends in rates of fatal occupational injuries in Taiwan by demographic group and occupation for 1994-2005. Data on deaths due to injuries at work from 1994 through 2005 were obtained from the Department of Health which is responsible for the death registration system in Taiwan. Employment data, which were used as the denominators of fatality rates in this study, were retrieved from the Directorate-General of Budget and Accounting Statistics 'Employment and Earnings' database. A Poisson regression model was used to examine the trends in rates of fatal occupational injuries in various occupations while controlling for demographic characteristics. Overall fatal occupational injury rates declined during the study period among all demographic groups and occupations. Adjusted annual changes in rates of fatal injuries ranged from a decrease of 13.6% a year in machine operators/related workers to a decrease of 35.9% in clerks. The annual decrement was faster for males than for females and for older workers compared to young workers. Despite declining rates, the number of fatal occupational injuries in Taiwan remains significant because of the growing work force. Future research should focus on the disparities in fatal injury trends.
Highway Safety: Trends in Highway Fatalities 1975-1987

Science.gov (United States)

1990-03-01

pattern of fatalities as the overall trend. This pattern applies to many of the general fatality statis- tics we present, and, in all cases, it serves as a...Fatalities 1975-87 Appemfx IV Vehicle-Related Statistics Figure IV.17: Vehicle Fatalities by Direction of Principal Impacto NNNumber of PddUlsils lwam 0 1975
Fatal and non-fatal injury outcomes: results from a purposively sampled census of seven rural subdistricts in Bangladesh.

Science.gov (United States)

Alonge, Olakunle; Agrawal, Priyanka; Talab, Abu; Rahman, Qazi S; Rahman, Akm Fazlur; Arifeen, Shams El; Hyder, Adnan A

2017-08-01

90% of the global burden of injuries is borne by low-income and middle-income countries (LMICs). However, details of the injury burden in LMICs are less clear because of the scarcity of data and population-based studies. The Saving of Lives from Drowning project, implemented in rural Bangladesh, did a census on 1·2 million people to fill this gap. This Article describes the epidemiology of fatal and non-fatal injuries from the study. In this study, we used data from the baseline census conducted as part of the Saving of Lives from Drowning (SoLiD) project. The census was implemented in 51 unions from seven purposively sampled rural subdistricts of Bangladesh between June and November, 2013. Sociodemographic, injury mortality, and morbidity information were collected for the whole population in the study area. We analysed the data for descriptive measures of fatal and non-fatal injury outcomes. Age and gender distribution, socioeconomic characteristics, and injury characteristics such as external cause, intent, location, and body part affected were reported for all injury outcomes. The census covered a population of 1 169 593 from 270 387 households and 451 villages. The overall injury mortality rate was 38 deaths per 100 000 population per year, and 104 703 people sustained major non-fatal injuries over a 6-month recall period. Drowning was the leading external cause of injury death for all ages, and falls caused the most number of non-fatal injuries. Fatal injury rates were highest in children aged 1-4 years. Non-fatal injury rates were also highest in children aged 1-4 years and those aged 65 years and older. Males had more fatal and non-fatal injuries than females across all external causes except for burns. Suicide was the leading cause of injury deaths in individuals aged 15-24 years, and more than 50% of the suicides occurred in females. The home environment was the most common location for most injuries. The burden of fatal and non-fatal injuries
The neonatal brain

International Nuclear Information System (INIS)

Flodmark, O.

1987-01-01

The clinical examination of the CNS in the neonate is often difficult in cases of complex pathology. Diagnostic imaging of the neonatal brain has become extremely useful and in the last decade has developed in two main directions: CT and US. MR imaging has been used recently with varying success in the diagnosis of pathology in the neonatal brain. Despite technical difficulties, this imaging method is likely to become increasingly important in the neonate. The paper examines the normal neonatal brain anatomy as seen with the different modalities, followed by pathologic conditions. Attention is directed to the common pathology, in asphyxiated newborns, the patholphysiology of intraventicular hemorrhage and periventricular leukomalacia in the preterm neonate, and hypoxic-ischemic brain injury in the term neonate. Pitfalls, artifacts, and problems in image interpretation are illustrated. Finally, the subsequent appearance of neonatal pathology later in infancy and childhood is discussed
Mitochondrial function in engineered cardiac tissues is regulated by extracellular matrix elasticity and tissue alignment.

Science.gov (United States)

Lyra-Leite, Davi M; Andres, Allen M; Petersen, Andrew P; Ariyasinghe, Nethika R; Cho, Nathan; Lee, Jezell A; Gottlieb, Roberta A; McCain, Megan L

2017-10-01

Mitochondria in cardiac myocytes are critical for generating ATP to meet the high metabolic demands associated with sarcomere shortening. Distinct remodeling of mitochondrial structure and function occur in cardiac myocytes in both developmental and pathological settings. However, the factors that underlie these changes are poorly understood. Because remodeling of tissue architecture and extracellular matrix (ECM) elasticity are also hallmarks of ventricular development and disease, we hypothesize that these environmental factors regulate mitochondrial function in cardiac myocytes. To test this, we developed a new procedure to transfer tunable polydimethylsiloxane disks microcontact-printed with fibronectin into cell culture microplates. We cultured Sprague-Dawley neonatal rat ventricular myocytes within the wells, which consistently formed tissues following the printed fibronectin, and measured oxygen consumption rate using a Seahorse extracellular flux analyzer. Our data indicate that parameters associated with baseline metabolism are predominantly regulated by ECM elasticity, whereas the ability of tissues to adapt to metabolic stress is regulated by both ECM elasticity and tissue alignment. Furthermore, bioenergetic health index, which reflects both the positive and negative aspects of oxygen consumption, was highest in aligned tissues on the most rigid substrate, suggesting that overall mitochondrial function is regulated by both ECM elasticity and tissue alignment. Our results demonstrate that mitochondrial function is regulated by both ECM elasticity and myofibril architecture in cardiac myocytes. This provides novel insight into how extracellular cues impact mitochondrial function in the context of cardiac development and disease. NEW & NOTEWORTHY A new methodology has been developed to measure O 2 consumption rates in engineered cardiac tissues with independent control over tissue alignment and matrix elasticity. This led to the findings that matrix
Neonatal hypertension.

Science.gov (United States)

Sharma, Deepak; Farahbakhsh, Nazanin; Shastri, Sweta; Sharma, Pradeep

2017-03-01

Neonatal hypertension (HT) is a frequently under reported condition and is seen uncommonly in the intensive care unit. Neonatal HT has defined arbitrarily as blood pressure more than 2 standard deviations above the base as per the age or defined as systolic BP more than 95% for infants of similar size, gestational age and postnatal age. It has been diagnosed long back but still is the least studied field in neonatology. There is still lack of universally accepted normotensive data for neonates as per gestational age, weight and post-natal age. Neonatal HT is an important morbidity that needs timely detection and appropriate management, as it can lead to devastating short-term effect on various organs and also poor long-term adverse outcomes. There is no consensus yet about the treatment guidelines and majority of treatment protocols are based on the expert opinion. Neonate with HT should be evaluated in detail starting from antenatal, perinatal, post-natal history, and drug intake by neonate and mother. This review article covers multiple aspects of neonatal hypertension like definition, normotensive data, various etiologies and methods of BP measurement, clinical features, diagnosis and management.
Perinatal risk factors for neonatal encephalopathy: an unmatched case-control study.

Science.gov (United States)

Tann, Cally J; Nakakeeto, Margaret; Willey, Barbara A; Sewegaba, Margaret; Webb, Emily L; Oke, Ibby; Mutuuza, Emmanuel Derek; Peebles, Donald; Musoke, Margaret; Harris, Kathryn A; Sebire, Neil J; Klein, Nigel; Kurinczuk, Jennifer J; Elliott, Alison M; Robertson, Nicola J

2018-05-01

Neonatal encephalopathy (NE) is the third leading cause of child mortality. Preclinical studies suggest infection and inflammation can sensitise or precondition the newborn brain to injury. This study examined perinatal risks factor for NE in Uganda. Unmatched case-control study. Mulago National Referral Hospital, Kampala, Uganda. 210 term infants with NE and 409 unaffected term infants as controls were recruited over 13 months. Data were collected on preconception, antepartum and intrapartum exposures. Blood culture, species-specific bacterial real-time PCR, C reactive protein and placental histology for chorioamnionitis and funisitis identified maternal and early newborn infection and inflammation. Multivariable logistic regression examined associations with NE. Neonatal bacteraemia (adjusted OR (aOR) 8.67 (95% CI 1.51 to 49.74), n=315) and histological funisitis (aOR 11.80 (95% CI 2.19 to 63.45), n=162) but not chorioamnionitis (aOR 3.20 (95% CI 0.66 to 15.52), n=162) were independent risk factors for NE. Among encephalopathic infants, neonatal case fatality was not significantly higher when exposed to early neonatal bacteraemia (OR 1.65 (95% CI 0.62 to 4.39), n=208). Intrapartum antibiotic use did not improve neonatal survival (p=0.826). After regression analysis, other identified perinatal risk factors (n=619) included hypertension in pregnancy (aOR 3.77), male infant (aOR 2.51), non-cephalic presentation (aOR 5.74), lack of fetal monitoring (aOR 2.75), augmentation (aOR 2.23), obstructed labour (aOR 3.8) and an acute intrapartum event (aOR 8.74). Perinatal infection and inflammation are independent risk factors for NE in this low-resource setting, supporting a role in the aetiological pathway of term brain injury. Intrapartum antibiotic administration did not mitigate against adverse outcomes. The importance of intrapartum risk factors in this sub-Saharan African setting is highlighted. © Article author(s) (or their employer(s) unless otherwise stated in the
Haloperidol aggravates transverse aortic constriction-induced heart failure via mitochondrial dysfunction.

Science.gov (United States)

Shinoda, Yasuharu; Tagashira, Hideaki; Bhuiyan, Md Shenuarin; Hasegawa, Hideyuki; Kanai, Hiroshi; Fukunaga, Kohji

2016-07-01

Haloperidol is an antipsychotic drug that inhibits the dopamine D2 receptor among others. Haloperidol also binds the sigma-1 receptor (σ1R) and inhibits it irreversibly. A serious outcome of haloperidol treatment of schizophrenia patients is death due to sudden cardiac failure. Although the cause remains unclear, we hypothesized that these effects were mediated by chronic haloperidol inhibition of cardiac σ1R. To test this, we treated neonatal rat cardiomyocytes with haloperidol, exposed them to angiotensin II and assessed hypertrophy, σ1R expression, mitochondrial Ca(2+) transport and ATP levels. In this context, haloperidol treatment altered mitochondrial Ca(2+) transport resulting in decreased ATP content by inactivating cardiac σ1R and/or reducing its expression. We also performed transverse aortic constriction (TAC) and then treated mice with haloperidol. After two weeks, haloperidol-treated mice showed enhanced heart failure marked by deteriorated cardiac function, reduced ATP production and increasing mortality relative to TAC only mice. ATP supplementation via sodium pyruvate rescued phenotypes seen in haloperidol-treated TAC mice. We conclude that σ1R inactivation or downregulation in response to haloperidol treatment impairs mitochondrial Ca(2+) mobilization, depleting ATP depletion from cardiomyocytes. These findings suggest a novel approach to mitigate haloperidol-related adverse effects in schizophrenia patients by ATP supplementation. Copyright © 2016 The Authors. Production and hosting by Elsevier B.V. All rights reserved.
Haloperidol aggravates transverse aortic constriction-induced heart failure via mitochondrial dysfunction

Directory of Open Access Journals (Sweden)

Yasuharu Shinoda

2016-07-01

Full Text Available Haloperidol is an antipsychotic drug that inhibits the dopamine D2 receptor among others. Haloperidol also binds the sigma-1 receptor (σ1R and inhibits it irreversibly. A serious outcome of haloperidol treatment of schizophrenia patients is death due to sudden cardiac failure. Although the cause remains unclear, we hypothesized that these effects were mediated by chronic haloperidol inhibition of cardiac σ1R. To test this, we treated neonatal rat cardiomyocytes with haloperidol, exposed them to angiotensin II and assessed hypertrophy, σ1R expression, mitochondrial Ca2+ transport and ATP levels. In this context, haloperidol treatment altered mitochondrial Ca2+ transport resulting in decreased ATP content by inactivating cardiac σ1R and/or reducing its expression. We also performed transverse aortic constriction (TAC and then treated mice with haloperidol. After two weeks, haloperidol-treated mice showed enhanced heart failure marked by deteriorated cardiac function, reduced ATP production and increasing mortality relative to TAC only mice. ATP supplementation via sodium pyruvate rescued phenotypes seen in haloperidol-treated TAC mice. We conclude that σ1R inactivation or downregulation in response to haloperidol treatment impairs mitochondrial Ca2+ mobilization, depleting ATP depletion from cardiomyocytes. These findings suggest a novel approach to mitigate haloperidol-related adverse effects in schizophrenia patients by ATP supplementation.
Etiologies of Prolonged Unconjugated Hyperbilirubinemia in Neonates Admitted to Neonatal Wards

Directory of Open Access Journals (Sweden)

Mohammad Kazem Sabzehei

2015-12-01

Full Text Available Background: Jaundice is a common condition among neonates. Prolonged unconjugated hyperbilirubinemia occurs when jaundice persists beyond two weeks in term neonates and three weeks in preterm neonates. This study aimed to determine the etiologies of prolonged unconjugated hyperbilirubinemia in infants admitted to the neonatal ward of Besat Hospital in Hamadan, Iran. Methods: This study was conducted on all infants diagnosed with prolonged unconjugated hyperbilirubinemia during 2007-2012 in the neonatal ward of Besat Hospital in Hamadan, Iran. Demographic characteristics of infants, physical examination and laboratory findings were collected and analyzed to determine the etiologies of neonatal hyperbilirubinemia. Results: In total, 100 infants diagnosed with neonatal hyperbilirubinemia were enrolled in this study, including 49 male and 51 female neonates with mean age of 20±1 days and mean bilirubin level of 17.5±4.0 mg/dL. Main causes of hyperbilirubinemia were urinary tract infection, ABO incompatibility, hypothyroidism and glucose-6-phosphate dehydrogenase deficiency in 14%, 5%, 6% and 5% of neonates, respectively. Moreover, unknown etiologies, such as breastfeeding, were detected in 70% of the studied infants. Conclusion: According to the results of this study, determining the main causes of prolonged unconjugated hyperbilirubinemia in neonates is of paramount importance. In the majority of cases, neonatal hyperbilirubinemia is associated with physiological factors, such as breastfeeding.
Mitochondrial cardiomyopathies

Directory of Open Access Journals (Sweden)

Ayman W. El-Hattab

2016-07-01

Full Text Available Mitochondria are found in all nucleated human cells and perform a variety of essential functions, including the generation of cellular energy. Mitochondria are under dual genome control. Only a small fraction of their proteins are encoded by mitochondrial DNA (mtDNA while more than 99% of them are encoded by nuclear DNA (nDNA. Mutations in mtDNA or mitochondria-related nDNA genes result in mitochondrial dysfunction leading to insufficient energy production required to meet the needs of various organs, particularly those with high energy requirements, including the central nervous system, skeletal and cardiac muscles, kidneys, liver, and endocrine system. Because cardiac muscles are one of the high energy demanding tissues, cardiac involvement occurs in mitochondrial diseases with cardiomyopathies being one of the most frequent cardiac manifestations found in these disorders. Cardiomyopathy is estimated to occur in 20-40% of children with mitochondrial diseases. Mitochondrial cardiomyopathies can vary in severity from asymptomatic status to severe manifestations including heart failure, arrhythmias, and sudden cardiac death. Hypertrophic cardiomyopathy is the most common type; however, mitochondrial cardiomyopathies might also present as dilated, restrictive, left ventricular noncompaction, and histiocytoid cardiomyopathies. Cardiomyopathies are frequent manifestations of mitochondrial diseases associated with defects in electron transport chain (ETC complexes subunits and their assembly factors, mitochondrial tRNAs, rRNAs, ribosomal proteins, and translation factors, mtDNA maintenance, and coenzyme Q10 synthesis. Other mitochondrial diseases with cardiomyopathies include Barth syndrome, Sengers syndrome, TMEM70-related mitochondrial complex V deficiency, and Friedreich ataxia.
Neglecting safety precautions may lead to trenching fatalities.

Science.gov (United States)

Deatherage, J Harold; Furches, Lisa K; Radcliffe, Mike; Schriver, William R; Wagner, John P

2004-06-01

Trench collapses ranked as the seventh leading cause of the possible twenty-nine causes of OSHA-inspected fatal construction events during the period 1991-2001. This study aims to examine why these fatalities occurred. Forty-four case files from OSHA inspections of fatal trench collapses were reviewed. Improper protection of the excavation site where work was taking place was the leading fatality cause. Several organizational or physical conditions were present at many fatal sites; the most frequent was that no training had been provided for trenching. Presence of a competent, diligent person at the site would have prohibited most fatalities. The top cited violation was lack of protection, that is, benching, shoring, sloping, trench boxes, etc. (29 CFR 1926.652 (a) (1)). Copyright 2004 Wiley-Liss, Inc.
Osteoarthritis in the neonate

International Nuclear Information System (INIS)

Weigel, W.; Hayek, W.H.; Bens, G.

1979-01-01

A fatally ending index case of sepsis osteoarthritis that was diagnosed retrospectively initiated this report. This patient had severe, asymmetrically distributed metaphyseal growthdisturbances, many long bones. In order to determine the features of early radiologic diagnosis we report the findings of 7 further patients with neonatal septic osteoarthritis with clinical and radiological follow-up. The most important observation for early radiologic diagnosis of osteoarthritis is the displacement of fat layers along the metaphysis. Other findings of the soft tissues have the same diagnostic value as bone destruction and subperiosteal new bone formation found one to three weeks later on roentgenfilms. Detecting early signs of osteoarthritis helps in localizing the focus for bacteriologic diagnosis, which is to be more successful than blood cultures. Diagnosing a joint empyema initiates surgical intervention for pressure relief in order to avoid necrosis of the epiphysis as seen in the femoral bone in septic arthritis of the hip joint. Early diagnosis and treatment to destruction of growing cartilage is necessary to avoid gross disturbances and length discrepancies of long bones. In cases of sepsis called 'babygram' and a repeat examination 10 to 14 days later is mandatory. (orig.) [de
Effect of case management on neonatal mortality due to sepsis and pneumonia

Directory of Open Access Journals (Sweden)

Black Robert

2011-04-01

Full Text Available Abstract Background Each year almost one million newborns die from infections, mostly in low-income countries. Timely case management would save many lives but the relative mortality effect of varying strategies is unknown. We have estimated the effect of providing oral, or injectable antibiotics at home or in first-level facilities, and of in-patient hospital care on neonatal mortality from pneumonia and sepsis for use in the Lives Saved Tool (LiST. Methods We conducted systematic searches of multiple databases to identify relevant studies with mortality data. Standardized abstraction tables were used and study quality assessed by adapted GRADE criteria. Meta-analyses were undertaken where appropriate. For interventions with biological plausibility but low quality evidence, a Delphi process was undertaken to estimate effectiveness. Results Searches of 2876 titles identified 7 studies. Among these, 4 evaluated oral antibiotics for neonatal pneumonia in non-randomised, concurrently controlled designs. Meta-analysis suggested reductions in all-cause neonatal mortality (RR 0.75 95% CI 0.64- 0.89; 4 studies and neonatal pneumonia-specific mortality (RR 0.58 95% CI 0.41- 0.82; 3 studies. Two studies (1 RCT, 1 observational study, evaluated community-based neonatal care packages including injectable antibiotics and reported mortality reductions of 44% (RR= 0.56, 95% CI 0.41-0.77 and 34% (RR =0.66, 95% CI 0.47-0.93, but the interpretation of these results is complicated by co-interventions. A third, clinic-based, study reported a case-fatality ratio of 3.3% among neonates treated with injectable antibiotics as outpatients. No studies were identified evaluating injectable antibiotics alone for neonatal pneumonia. Delphi consensus (median from 20 respondents effects on sepsis-specific mortality were 30% reduction for oral antibiotics, 65% for injectable antibiotics and 75% for injectable antibiotics on pneumonia-specific mortality. No trials were
Age trajectories of stroke case fatality

DEFF Research Database (Denmark)

Olsen, Tom Skyhøj; Andersen, Zorana Jovanovic; Andersen, Klaus Kaae

2011-01-01

Mortality rates level off at older ages. Age trajectories of stroke case-fatality rates were studied with the aim of investigating prevalence of this phenomenon, specifically in case-fatality rates at older ages....
Knowledge, attitudes and practices of neonatal staff concerning neonatal pain management

Directory of Open Access Journals (Sweden)

Sizakele L.T. Khoza

2014-11-01

Full Text Available Background: Neonatal pain management has received increasing attention over the past four decades. Research into the effects of neonatal pain emphasises the professional, ethical and moral obligations of staff to manage pain for positive patient outcomes. However, evaluation studies continuously report evidence of inadequate neonate pain management and a gap between theory and practice. Objective: This study reviewed current practice in neonatal pain management to describe the knowledge, attitudes and practices of nurses and doctors regarding pain management for neonates in two academic hospitals. Method: A non-experimental, prospective quantitative survey, the modified Infant Pain Questionnaire, was used to collect data from 150 nurses and doctors working in the neonatal wards of two academic hospitals in central Gauteng. Results: The response rate was 35.33% (n = 53, most respondents being professional nurses (88.68%; n = 47 working in neonatal intensive care units (80.77%; n = 42; 24 (45.28% had less than 5 years’ and 29 respondents 6 or more years’ working experience in neonatal care. A review of pain management in the study setting indicated a preference for pharmacological interventions to relieve moderate to severe pain. An association (p < 0.05 was found between pain ratings on 5 procedures and frequency of administration of pharmacological pain management. Two-thirds of respondents (64% reported that there were no pain management guidelines in the neonatal wards in which they worked. Conclusion: The interventions to manage moderate neonatal pain are in line with international guidelines. However, neonatal pain management may not occur systematically based on prior assessment of neonatal pain, choice of most appropriate intervention and evaluation. This study recommends implementation of a guideline to standardise practice and ensure consistent and adequate pain management in neonates.
Fatal work injuries involving natural disasters, 1992-2006.

Science.gov (United States)

Fayard, Gregory M

2009-12-01

Although a goal of disaster preparedness is to protect vulnerable populations from hazards, little research has explored the types of risks that workers face in their encounters with natural disasters. This study examines how workers are fatally injured in severe natural events. A classification structure was created that identified the physical component of the disaster that led to the death and the pursuit of the worker as it relates to the disaster. Data on natural disasters from the Census of Fatal Occupational Injuries for the years 1992 through 2006 were analyzed. A total of 307 natural disaster deaths to workers were identified in 1992-2006. Most fatal occupational injuries were related to wildfires (80 fatalities), hurricanes (72 fatalities), and floods (62 fatalities). Compared with fatal occupational injuries in general, natural disaster fatalities involved more workers who were white and more workers who were working for the government. Most wildfire fatalities stemmed directly from exposure to fire and gases and occurred to those engaged in firefighting, whereas hurricane fatalities tended to occur more independently of disaster-produced hazards and to workers engaged in cleanup and reconstruction. Those deaths related to the 2005 hurricanes occurred a median of 36.5 days after landfall of the associated storm. Nearly half of the flood deaths occurred to passengers in motor vehicles. Other disasters included tornadoes (33 fatalities), landslides (17), avalanches (16), ice storms (14), and blizzards (9). Despite an increasing social emphasis on disaster preparation and response, there has been little increase in expert knowledge about how people actually perish in these large-scale events. Using a 2-way classification structure, this study identifies areas of emphasis in preventing occupational deaths from various natural disasters.
Neonatal retinoblastoma

Directory of Open Access Journals (Sweden)

Tero T Kivelä

2017-01-01

Full Text Available From 7% to 10% of all retinoblastomas and from 44% to 71% of familial retinoblastomas in developed countries are diagnosed in the neonatal period, usually through pre- or post-natal screening prompted by a positive family history and sometimes serendipitously during screening for retinopathy of prematurity or other reasons. In developing countries, neonatal diagnosis of retinoblastoma has been less common. Neonatal retinoblastoma generally develops from a germline mutation of RB1, the retinoblastoma gene, even when the family history is negative and is thus usually hereditary. At least one-half of infants with neonatal retinoblastoma have unilateral tumors when the diagnosis is made, typically the International Intraocular Retinoblastoma Classification (Murphree Group B or higher, but most germline mutation carriers will progress to bilateral involvement, typically Group A in the fellow eye. Neonatal leukokoria usually leads to the diagnosis in children without a family history of retinoblastoma, and a Group C tumor or higher is typical in the more advanced involved eye. Almost all infants with neonatal retinoblastoma have at least one eye with a tumor in proximity to the foveola, but the macula of the fellow eye is frequently spared. Consequently, loss of reading vision from both eyes is exceptional. A primary ectopic intracranial neuroblastic tumor known as trilateral retinoblastoma is no more common after neonatal than other retinoblastoma. For many reasons, neonatal retinoblastoma may be a challenge to eradicate, and the early age at diagnosis and relatively small tumors do not guarantee the preservation of both eyes of every involved child. Oncology nurses can be instrumental in contributing to better outcomes by ensuring that hereditary retinoblastoma survivors receive genetic counseling, by referring families of survivors to early screening programs when they are planning for a baby, and by providing psychological and practical support
SK2 channels regulate mitochondrial respiration and mitochondrial Ca2+ uptake.

Science.gov (United States)

Honrath, Birgit; Matschke, Lina; Meyer, Tammo; Magerhans, Lena; Perocchi, Fabiana; Ganjam, Goutham K; Zischka, Hans; Krasel, Cornelius; Gerding, Albert; Bakker, Barbara M; Bünemann, Moritz; Strack, Stefan; Decher, Niels; Culmsee, Carsten; Dolga, Amalia M

2017-05-01

Mitochondrial calcium ([Ca 2+ ] m ) overload and changes in mitochondrial metabolism are key players in neuronal death. Small conductance calcium-activated potassium (SK) channels provide protection in different paradigms of neuronal cell death. Recently, SK channels were identified at the inner mitochondrial membrane, however, their particular role in the observed neuroprotection remains unclear. Here, we show a potential neuroprotective mechanism that involves attenuation of [Ca 2+ ] m uptake upon SK channel activation as detected by time lapse mitochondrial Ca 2+ measurements with the Ca 2+ -binding mitochondria-targeted aequorin and FRET-based [Ca 2+ ] m probes. High-resolution respirometry revealed a reduction in mitochondrial respiration and complex I activity upon pharmacological activation and overexpression of mitochondrial SK2 channels resulting in reduced mitochondrial ROS formation. Overexpression of mitochondria-targeted SK2 channels enhanced mitochondrial resilience against neuronal death, and this effect was inhibited by overexpression of a mitochondria-targeted dominant-negative SK2 channel. These findings suggest that SK channels provide neuroprotection by reducing [Ca 2+ ] m uptake and mitochondrial respiration in conditions, where sustained mitochondrial damage determines progressive neuronal death.

Incidence of paediatric fatal and non-fatal low speed vehicle run over events in Queensland, Australia: eleven year analysis

Science.gov (United States)

2014-01-01

Background The purpose of this study was to estimate the incidence of fatal and non-fatal Low Speed Vehicle Run Over (LSVRO) events among children aged 0–15 years in Queensland, Australia, at a population level. Methods Fatal and non-fatal LSVRO events that occurred in children resident in Queensland over eleven calendar years (1999-2009) were identified using ICD codes, text description, word searches and medical notes clarification, obtained from five health related data bases across the continuum of care (pre-hospital to fatality). Data were manually linked. Population data provided by the Australian Bureau of Statistics were used to calculate crude incidence rates for fatal and non-fatal LSVRO events. Results There were 1611 LSVROs between 1999–2009 (IR = 16.87/100,000/annum). Incidence of non-fatal events (IR = 16.60/100,000/annum) was 61.5 times higher than fatal events (IR = 0.27/100,000/annum). LSVRO events were more common in boys (IR = 20.97/100,000/annum) than girls (IR = 12.55/100,000/annum), and among younger children aged 0–4 years (IR = 21.45/100000/annum; 39% or all events) than older children (5–9 years: IR = 16.47/100,000/annum; 10–15 years IR = 13.59/100,000/annum). A total of 896 (56.8%) children were admitted to hospital for 24 hours of more following an LSVRO event (IR = 9.38/100,000/annum). Total LSVROs increased from 1999 (IR = 14.79/100,000) to 2009 (IR = 18.56/100,000), but not significantly. Over the 11 year period, there was a slight (non –significant) increase in fatalities (IR = 0.37-0.42/100,000/annum); a significant decrease in admissions (IR = 12.39–5.36/100,000/annum), and significant increase in non-admissions (IR = 2.02-12.77/100,000/annum). Trends over time differed by age, gender and severity. Conclusion This is the most comprehensive, population-based epidemiological study on fatal and non-fatal LSVRO events to date. Results from this study indicate
Work-related agricultural fatalities in Australia, 1982-1984.

Science.gov (United States)

Erlich, S M; Driscoll, T R; Harrison, J E; Frommer, M S; Leigh, J

1993-06-01

Work-related agricultural fatalities were examined as part of a larger population-based study of all work-related fatalities in Australia in the period 1982-1984. A total of 257 farm-related fatalities were identified, of which 223 were deaths of persons in the employed civilian labor force (19.4 deaths per 100,000 persons per year) and 34 were deaths of children less than 15 years of age. The fatality incidence was higher among men, older age groups, and nonmanagers in general and in certain occupations in particular. Mobile mechanical equipment (particularly tractors) was the main fatal agent, roll-overs accounting for many of the fatalities. Better provision of information to agricultural workers, improvements in compliance to and enforcement of legislation, and changes in farming work practices are recommended to improve the safety of farms and farm work.
Mitochondrial tRNA cleavage by tRNA-targeting ribonuclease causes mitochondrial dysfunction observed in mitochondrial disease

Energy Technology Data Exchange (ETDEWEB)

Ogawa, Tetsuhiro, E-mail: atetsu@mail.ecc.u-tokyo.ac.jp; Shimizu, Ayano; Takahashi, Kazutoshi; Hidaka, Makoto; Masaki, Haruhiko, E-mail: amasaki@mail.ecc.u-tokyo.ac.jp

2014-08-15

Highlights: • MTS-tagged ribonuclease was translocated successfully to the mitochondrial matrix. • MTS-tagged ribonuclease cleaved mt tRNA and reduced COX activity. • Easy and reproducible method of inducing mt tRNA dysfunction. - Abstract: Mitochondrial DNA (mtDNA) is a genome possessed by mitochondria. Since reactive oxygen species (ROS) are generated during aerobic respiration in mitochondria, mtDNA is commonly exposed to the risk of DNA damage. Mitochondrial disease is caused by mitochondrial dysfunction, and mutations or deletions on mitochondrial tRNA (mt tRNA) genes are often observed in mtDNA of patients with the disease. Hence, the correlation between mt tRNA activity and mitochondrial dysfunction has been assessed. Then, cybrid cells, which are constructed by the fusion of an enucleated cell harboring altered mtDNA with a ρ{sup 0} cell, have long been used for the analysis due to difficulty in mtDNA manipulation. Here, we propose a new method that involves mt tRNA cleavage by a bacterial tRNA-specific ribonuclease. The ribonuclease tagged with a mitochondrial-targeting sequence (MTS) was successfully translocated to the mitochondrial matrix. Additionally, mt tRNA cleavage, which resulted in the decrease of cytochrome c oxidase (COX) activity, was observed.
Incidence and risk factors for neonatal tetanus in admissions to Kilifi County Hospital, Kenya.

Directory of Open Access Journals (Sweden)

Fredrick Ibinda

Full Text Available Neonatal Tetanus (NT is a preventable cause of mortality and neurological sequelae that occurs at higher incidence in resource-poor countries, presumably because of low maternal immunisation rates and unhygienic cord care practices. We aimed to determine changes in the incidence of NT, characterize and investigate the associated risk factors and mortality in a prospective cohort study including all admissions over a 15-year period at a County hospital on the Kenyan coast, a region with relatively high historical NT rates within Kenya.We assessed all neonatal admissions to Kilifi County Hospital in Kenya (1999-2013 and identified cases of NT (standard clinical case definition admitted during this time. Poisson regression was used to examine change in incidence of NT using accurate denominator data from an area of active demographic surveillance. Logistic regression was used to investigate the risk factors for NT and factors associated with mortality in NT amongst neonatal admissions. A subset of sera from mothers (n = 61 and neonates (n = 47 were tested for anti-tetanus antibodies.There were 191 NT admissions, of whom 187 (98% were home deliveries. Incidence of NT declined significantly (Incidence Rate Ratio: 0.85 (95% Confidence interval 0.81-0.89, P<0.001 but the case fatality (62% did not change over the study period (P = 0.536. Younger infant age at admission (P = 0.001 was the only independent predictor of mortality. Compared to neonatal hospital admittee controls, the proportion of home births was higher among the cases. Sera tested for antitetanus antibodies showed most mothers (50/61, 82% had undetectable levels of antitetanus antibodies, and most (8/9, 89% mothers with detectable antibodies had a neonate without protective levels.Incidence of NT in Kilifi County has significantly reduced, with reductions following immunisation campaigns. Our results suggest immunisation efforts are effective if sustained and efforts should continue to
A mitochondrially targeted compound delays aging in yeast through a mechanism linking mitochondrial membrane lipid metabolism to mitochondrial redox biology

Directory of Open Access Journals (Sweden)

Michelle T. Burstein

2014-01-01

Full Text Available A recent study revealed a mechanism of delaying aging in yeast by a natural compound which specifically impacts mitochondrial redox processes. In this mechanism, exogenously added lithocholic bile acid enters yeast cells, accumulates mainly in the inner mitochondrial membrane, and elicits an age-related remodeling of phospholipid synthesis and movement within both mitochondrial membranes. Such remodeling of mitochondrial phospholipid dynamics progresses with the chronological age of a yeast cell and ultimately causes significant changes in mitochondrial membrane lipidome. These changes in the composition of membrane phospholipids alter mitochondrial abundance and morphology, thereby triggering changes in the age-related chronology of such longevity-defining redox processes as mitochondrial respiration, the maintenance of mitochondrial membrane potential, the preservation of cellular homeostasis of mitochondrially produced reactive oxygen species, and the coupling of electron transport to ATP synthesis.
Fatal versus non-fatal heroin "overdose": blood morphine concentrations with fatal outcome in comparison to those of intoxicated drivers.

Science.gov (United States)

Meissner, Christoph; Recker, Sabine; Reiter, Arthur; Friedrich, Hans Juergen; Oehmichen, Manfred

2002-11-05

The study was performed to distinguish fatal from non-fatal blood concentrations of morphine. For this purpose, blood levels of free morphine and total morphine (free morphine plus morphine conjugates) in 207 cases of heroin-related deaths were compared to those in 27 drivers surviving opiate intoxication. The majority of both survivors and non-survivors were found to show a concomitant use of depressants including alcohol or stimulants. Blood morphine levels in both groups varied widely, with a large area of overlap between survivors (free morphine: 0-128 ng/ml, total morphine: 10-2,110 ng/ml) and non-survivors (free morphine: 0-2,800 ng/ml, total morphine: 33-5,000 ng/ml). Five (18.5%) survivors and 87 (42.0%) non-survivors exhibit intoxication only by morphine. In these cases, too, both groups overlapped (survivors-free morphine: 28-93 ng/ml, total morphine: 230-1,451 ng/ml; non-survivors-free morphine: 0-2,800 ng/ml, total morphine: 119-4,660 ng/ml). Although the blood levels of free or total morphine do not allow a reliable prediction of survival versus non-survival, the ratio of free/total morphine may be a criterion to distinguish lethal versus survived intoxication. The mean of the ratio of free to total morphine for all lethal cases (N=207) was 0.293, for those that survived (N=27) 0.135, in cases of intoxication only by morphine 0.250 (N=87) and 0.080 (N=5), respectively. Applying a cut-off of 0.12 for free/total morphine and performing ROC analyses, fatal outcome can be predicted in 80% of the cases correctly, whereas 16% of the survivors were classified as dead. Nevertheless, in this study, all cases with a blood concentration of 200 ng/ml and more of free morphine displayed a fatal outcome.
Mitochondrial flash as a novel biomarker of mitochondrial respiration in the heart.

Science.gov (United States)

Gong, Guohua; Liu, Xiaoyun; Zhang, Huiliang; Sheu, Shey-Shing; Wang, Wang

2015-10-01

Mitochondrial respiration through electron transport chain (ETC) activity generates ATP and reactive oxygen species in eukaryotic cells. The modulation of mitochondrial respiration in vivo or under physiological conditions remains elusive largely due to the lack of appropriate approach to monitor ETC activity in a real-time manner. Here, we show that ETC-coupled mitochondrial flash is a novel biomarker for monitoring mitochondrial respiration under pathophysiological conditions in cultured adult cardiac myocyte and perfused beating heart. Through real-time confocal imaging, we follow the frequency of a transient bursting fluorescent signal, named mitochondrial flash, from individual mitochondria within intact cells expressing a mitochondrial matrix-targeted probe, mt-cpYFP (mitochondrial-circularly permuted yellow fluorescent protein). This mt-cpYFP recorded mitochondrial flash has been shown to be composed of a major superoxide signal with a minor alkalization signal within the mitochondrial matrix. Through manipulating physiological substrates for mitochondrial respiration, we find a close coupling between flash frequency and the ETC electron flow, as measured by oxygen consumption rate in cardiac myocyte. Stimulating electron flow under physiological conditions increases flash frequency. On the other hand, partially block or slowdown electron flow by inhibiting the F0F1 ATPase, which represents a pathological condition, transiently increases then decreases flash frequency. Limiting electron entrance at complex I by knocking out Ndufs4, an assembling subunit of complex I, suppresses mitochondrial flash activity. These results suggest that mitochondrial electron flow can be monitored by real-time imaging of mitochondrial flash. The mitochondrial flash frequency could be used as a novel biomarker for mitochondrial respiration under physiological and pathological conditions. Copyright © 2015 the American Physiological Society.
Melatonin: A Mitochondrial Targeting Molecule Involving Mitochondrial Protection and Dynamics

Science.gov (United States)

Tan, Dun-Xian; Manchester, Lucien C.; Qin, Lilan; Reiter, Russel J.

2016-01-01

Melatonin has been speculated to be mainly synthesized by mitochondria. This speculation is supported by the recent discovery that aralkylamine N-acetyltransferase/serotonin N-acetyltransferase (AANAT/SNAT) is localized in mitochondria of oocytes and the isolated mitochondria generate melatonin. We have also speculated that melatonin is a mitochondria-targeted antioxidant. It accumulates in mitochondria with high concentration against a concentration gradient. This is probably achieved by an active transportation via mitochondrial melatonin transporter(s). Melatonin protects mitochondria by scavenging reactive oxygen species (ROS), inhibiting the mitochondrial permeability transition pore (MPTP), and activating uncoupling proteins (UCPs). Thus, melatonin maintains the optimal mitochondrial membrane potential and preserves mitochondrial functions. In addition, mitochondrial biogenesis and dynamics is also regulated by melatonin. In most cases, melatonin reduces mitochondrial fission and elevates their fusion. Mitochondrial dynamics exhibit an oscillatory pattern which matches the melatonin circadian secretory rhythm in pinealeocytes and probably in other cells. Recently, melatonin has been found to promote mitophagy and improve homeostasis of mitochondria. PMID:27999288
Fatal poisonings in Oslo: a one-year observational study.

Science.gov (United States)

Bjornaas, Mari A; Teige, Brita; Hovda, Knut E; Ekeberg, Oivind; Heyerdahl, Fridtjof; Jacobsen, Dag

2010-06-06

Acute poisonings are common and are treated at different levels of the health care system. Since most fatal poisonings occur outside hospital, these must be included when studying characteristics of such deaths. The pattern of toxic agents differs between fatal and non-fatal poisonings. By including all poisoning episodes, cause-fatality rates can be calculated. Fatal and non-fatal acute poisonings in subjects aged > or =16 years in Oslo (428 198 inhabitants) were included consecutively in an observational multi-centre study including the ambulance services, the Oslo Emergency Ward (outpatient clinic), and hospitals, as well as medico-legal autopsies from 1st April 2003 to 31st March 2004. Characteristics of fatal poisonings were examined, and a comparison of toxic agents was made between fatal and non-fatal acute poisoning. In Oslo, during the one-year period studied, 103 subjects aged > or =16 years died of acute poisoning. The annual mortality rate was 24 per 100 000. The male-female ratio was 2:1, and the mean age was 44 years (range 19-86 years). In 92 cases (89%), death occurred outside hospital. The main toxic agents were opiates or opioids (65% of cases), followed by ethanol (9%), tricyclic anti-depressants (TCAs) (4%), benzodiazepines (4%), and zopiclone (4%). Seventy-one (69%) were evaluated as accidental deaths and 32 (31%) as suicides. In 70% of all cases, and in 34% of suicides, the deceased was classified as drug or alcohol dependent. When compared with the 2981 non-fatal acute poisonings registered during the study period, the case fatality rate was 3% (95% C.I., 0.03-0.04). Methanol, TCAs, and antihistamines had the highest case fatality rates; 33% (95% C.I., 0.008-0.91), 14% (95% C.I., 0.04-0.33), and 10% (95% C.I., 0.02-0.27), respectively. Three per cent of all acute poisonings were fatal, and nine out of ten deaths by acute poisonings occurred outside hospital. Two-thirds were evaluated as accidental deaths. Although case fatality rates were
Altering pyrroloquinoline quinone nutritional status modulates mitochondrial, lipid, and energy metabolism in rats.

Directory of Open Access Journals (Sweden)

Kathryn Bauerly

Full Text Available We have reported that pyrroloquinoline quinone (PQQ improves reproduction, neonatal development, and mitochondrial function in animals by mechanisms that involve mitochondrial related cell signaling pathways. To extend these observations, the influence of PQQ on energy and lipid relationships and apparent protection against ischemia reperfusion injury are described herein. Sprague-Dawley rats were fed a nutritionally complete diet with PQQ added at either 0 (PQQ- or 2 mg PQQ/Kg diet (PQQ+. Measurements included: 1 serum glucose and insulin, 2 total energy expenditure per metabolic body size (Wt(3/4, 3 respiratory quotients (in the fed and fasted states, 4 changes in plasma lipids, 5 the relative mitochondrial amount in liver and heart, and 6 indices related to cardiac ischemia. For the latter, rats (PQQ- or PQQ+ were subjected to left anterior descending occlusions followed by 2 h of reperfusion to determine PQQ's influence on infarct size and myocardial tissue levels of malondialdehyde, an indicator of lipid peroxidation. Although no striking differences in serum glucose, insulin, and free fatty acid levels were observed, energy expenditure was lower in PQQ- vs. PQQ+ rats and energy expenditure (fed state was correlated with the hepatic mitochondrial content. Elevations in plasma di- and triacylglyceride and β-hydroxybutryic acid concentrations were also observed in PQQ- rats vs. PQQ+ rats. Moreover, PQQ administration (i.p. at 4.5 mg/kg BW for 3 days resulted in a greater than 2-fold decrease in plasma triglycerides during a 6-hour fast than saline administration in a rat model of type 2 diabetes. Cardiac injury resulting from ischemia/reperfusion was more pronounced in PQQ- rats than in PQQ+ rats. Collectively, these data demonstrate that PQQ deficiency impacts a number of parameters related to normal mitochondrial function.
MLN64 induces mitochondrial dysfunction associated with increased mitochondrial cholesterol content

Directory of Open Access Journals (Sweden)

Elisa Balboa

2017-08-01

Full Text Available MLN64 is a late endosomal cholesterol-binding membrane protein that has been implicated in cholesterol transport from endosomal membranes to the plasma membrane and/or mitochondria, in toxin-induced resistance, and in mitochondrial dysfunction. Down-regulation of MLN64 in Niemann-Pick C1 deficient cells decreased mitochondrial cholesterol content, suggesting that MLN64 functions independently of NPC1. However, the role of MLN64 in the maintenance of endosomal cholesterol flow and intracellular cholesterol homeostasis remains unclear. We have previously described that hepatic MLN64 overexpression increases liver cholesterol content and induces liver damage. Here, we studied the function of MLN64 in normal and NPC1-deficient cells and we evaluated whether MLN64 overexpressing cells exhibit alterations in mitochondrial function. We used recombinant-adenovirus-mediated MLN64 gene transfer to overexpress MLN64 in mouse liver and hepatic cells; and RNA interference to down-regulate MLN64 in NPC1-deficient cells. In MLN64-overexpressing cells, we found increased mitochondrial cholesterol content and decreased glutathione (GSH levels and ATPase activity. Furthermore, we found decreased mitochondrial membrane potential and mitochondrial fragmentation and increased mitochondrial superoxide levels in MLN64-overexpressing cells and in NPC1-deficient cells. Consequently, MLN64 expression was increased in NPC1-deficient cells and reduction of its expression restore mitochondrial membrane potential and mitochondrial superoxide levels. Our findings suggest that MLN64 overexpression induces an increase in mitochondrial cholesterol content and consequently a decrease in mitochondrial GSH content leading to mitochondrial dysfunction. In addition, we demonstrate that MLN64 expression is increased in NPC cells and plays a key role in cholesterol transport into the mitochondria.
Advancing Neurologic Care in the Neonatal Intensive Care Unit with a Neonatal Neurologist

Science.gov (United States)

Mulkey, Sarah B.; Swearingen, Christopher J.

2014-01-01

Neonatal neurology is a growing sub-specialty area. Given the considerable amount of neurologic problems present in the neonatal intensive care unit, a neurologist with expertise in neonates is becoming more important. We sought to evaluate the change in neurologic care in the neonatal intensive care unit at our tertiary care hospital by having a dedicated neonatal neurologist. The period post-neonatal neurologist showed a greater number of neurology consultations (Pneurology encounters per patient (Pneurology became part of the multi-disciplinary team providing focused neurologic care to newborns. PMID:23271754
Different features of Vδ2 T and NK cells in fatal and non-fatal human Ebola infections.

Science.gov (United States)

Cimini, Eleonora; Viola, Domenico; Cabeza-Cabrerizo, Mar; Romanelli, Antonella; Tumino, Nicola; Sacchi, Alessandra; Bordoni, Veronica; Casetti, Rita; Turchi, Federica; Martini, Federico; Bore, Joseph A; Koundouno, Fara Raymond; Duraffour, Sophie; Michel, Janine; Holm, Tobias; Zekeng, Elsa Gayle; Cowley, Lauren; Garcia Dorival, Isabel; Doerrbecker, Juliane; Hetzelt, Nicole; Baum, Jonathan H J; Portmann, Jasmine; Wölfel, Roman; Gabriel, Martin; Miranda, Osvaldo; Díaz, Graciliano; Díaz, José E; Fleites, Yoel A; Piñeiro, Carlos A; Castro, Carlos M; Koivogui, Lamine; Magassouba, N'Faly; Diallo, Boubacar; Ruibal, Paula; Oestereich, Lisa; Wozniak, David M; Lüdtke, Anja; Becker-Ziaja, Beate; Capobianchi, Maria R; Ippolito, Giuseppe; Carroll, Miles W; Günther, Stephan; Di Caro, Antonino; Muñoz-Fontela, César; Agrati, Chiara

2017-05-01

Human Ebola infection is characterized by a paralysis of the immune system. A signature of αβ T cells in fatal Ebola infection has been recently proposed, while the involvement of innate immune cells in the protection/pathogenesis of Ebola infection is unknown. Aim of this study was to analyze γδ T and NK cells in patients from the Ebola outbreak of 2014-2015 occurred in West Africa, and to assess their association with the clinical outcome. Nineteen Ebola-infected patients were enrolled at the time of admission to the Ebola Treatment Centre in Guinea. Patients were divided in two groups on the basis of the clinical outcome. The analysis was performed by using multiparametric flow cytometry established by the European Mobile Laboratory in the field. A low frequency of Vδ2 T-cells was observed during Ebola infection, independently from the clinical outcome. Moreover, Vδ2 T-cells from Ebola patients massively expressed CD95 apoptotic marker, suggesting the involvement of apoptotic mechanisms in Vδ2 T-cell loss. Interestingly, Vδ2 T-cells from survivors expressed an effector phenotype and presented a lower expression of the CTLA-4 exhaustion marker than fatalities, suggesting a role of effector Vδ2 T-cells in the protection. Furthermore, patients with fatal Ebola infection were characterized by a lower NK cell frequency than patients with non fatal infection. In particular, both CD56bright and CD56dim NK frequency were very low both in fatal and non fatal infections, while a higher frequency of CD56neg NK cells was associated to non-fatal infections. Finally, NK activation and expression of NKp46 and CD158a were independent from clinical outcome. Altogether, the data suggest that both effector Vδ2 T-cells and NK cells may play a role in the complex network of protective response to EBOV infection. Further studies are required to characterize the protective effector functions of Vδ2 and NK cells.
Different features of Vδ2 T and NK cells in fatal and non-fatal human Ebola infections.

Directory of Open Access Journals (Sweden)

Eleonora Cimini

2017-05-01

Full Text Available Human Ebola infection is characterized by a paralysis of the immune system. A signature of αβ T cells in fatal Ebola infection has been recently proposed, while the involvement of innate immune cells in the protection/pathogenesis of Ebola infection is unknown. Aim of this study was to analyze γδ T and NK cells in patients from the Ebola outbreak of 2014-2015 occurred in West Africa, and to assess their association with the clinical outcome.Nineteen Ebola-infected patients were enrolled at the time of admission to the Ebola Treatment Centre in Guinea. Patients were divided in two groups on the basis of the clinical outcome. The analysis was performed by using multiparametric flow cytometry established by the European Mobile Laboratory in the field. A low frequency of Vδ2 T-cells was observed during Ebola infection, independently from the clinical outcome. Moreover, Vδ2 T-cells from Ebola patients massively expressed CD95 apoptotic marker, suggesting the involvement of apoptotic mechanisms in Vδ2 T-cell loss. Interestingly, Vδ2 T-cells from survivors expressed an effector phenotype and presented a lower expression of the CTLA-4 exhaustion marker than fatalities, suggesting a role of effector Vδ2 T-cells in the protection. Furthermore, patients with fatal Ebola infection were characterized by a lower NK cell frequency than patients with non fatal infection. In particular, both CD56bright and CD56dim NK frequency were very low both in fatal and non fatal infections, while a higher frequency of CD56neg NK cells was associated to non-fatal infections. Finally, NK activation and expression of NKp46 and CD158a were independent from clinical outcome.Altogether, the data suggest that both effector Vδ2 T-cells and NK cells may play a role in the complex network of protective response to EBOV infection. Further studies are required to characterize the protective effector functions of Vδ2 and NK cells.
Targeted Transgenic Overexpression of Mitochondrial Thymidine Kinase (TK2) Alters Mitochondrial DNA (mtDNA) and Mitochondrial Polypeptide Abundance

Science.gov (United States)

Hosseini, Seyed H.; Kohler, James J.; Haase, Chad P.; Tioleco, Nina; Stuart, Tami; Keebaugh, Erin; Ludaway, Tomika; Russ, Rodney; Green, Elgin; Long, Robert; Wang, Liya; Eriksson, Staffan; Lewis, William

2007-01-01

Mitochondrial toxicity limits nucleoside reverse transcriptase inhibitors (NRTIs) for acquired immune deficiency syndrome. NRTI triphosphates, the active moieties, inhibit human immunodeficiency virus reverse transcriptase and eukaryotic mitochondrial DNA polymerase pol-γ. NRTI phosphorylation seems to correlate with mitochondrial toxicity, but experimental evidence is lacking. Transgenic mice (TGs) with cardiac overexpression of thymidine kinase isoforms (mitochondrial TK2 and cytoplasmic TK1) were used to study NRTI mitochondrial toxicity. Echocardiography and nuclear magnetic resonance imaging defined cardiac performance and structure. TK gene copy and enzyme activity, mitochondrial (mt) DNA and polypeptide abundance, succinate dehydrogenase and cytochrome oxidase histochemistry, and electron microscopy correlated with transgenesis, mitochondrial structure, and biogenesis. Antiretroviral combinations simulated therapy. Untreated hTK1 or TK2 TGs exhibited normal left ventricle mass. In TK2 TGs, cardiac TK2 gene copy doubled, activity increased 300-fold, and mtDNA abundance doubled. Abundance of the 17-kd subunit of complex I, succinate dehydrogenase histochemical activity, and cristae density increased. NRTIs increased left ventricle mass 20% in TK2 TGs. TK activity increased 3 logs in hTK1 TGs, but no cardiac phenotype resulted. NRTIs abrogated functional effects of transgenically increased TK2 activity but had no effect on TK2 mtDNA abundance. Thus, NRTI mitochondrial phosphorylation by TK2 is integral to clinical NRTI mitochondrial toxicity. PMID:17322372
Fatal crashes involving large numbers of vehicles and weather.

Science.gov (United States)

Wang, Ying; Liang, Liming; Evans, Leonard

2017-12-01

Adverse weather has been recognized as a significant threat to traffic safety. However, relationships between fatal crashes involving large numbers of vehicles and weather are rarely studied according to the low occurrence of crashes involving large numbers of vehicles. By using all 1,513,792 fatal crashes in the Fatality Analysis Reporting System (FARS) data, 1975-2014, we successfully described these relationships. We found: (a) fatal crashes involving more than 35 vehicles are most likely to occur in snow or fog; (b) fatal crashes in rain are three times as likely to involve 10 or more vehicles as fatal crashes in good weather; (c) fatal crashes in snow [or fog] are 24 times [35 times] as likely to involve 10 or more vehicles as fatal crashes in good weather. If the example had used 20 vehicles, the risk ratios would be 6 for rain, 158 for snow, and 171 for fog. To reduce the risk of involvement in fatal crashes with large numbers of vehicles, drivers should slow down more than they currently do under adverse weather conditions. Driver deaths per fatal crash increase slowly with increasing numbers of involved vehicles when it is snowing or raining, but more steeply when clear or foggy. We conclude that in order to reduce risk of involvement in crashes involving large numbers of vehicles, drivers must reduce speed in fog, and in snow or rain, reduce speed by even more than they already do. Copyright © 2017 National Safety Council and Elsevier Ltd. All rights reserved.
Neonatal hypocalcemia, neonatal seizures, and intellectual disability in 22q11.2 deletion syndrome

Science.gov (United States)

Cheung, Evelyn Ning Man; George, Susan R.; Andrade, Danielle M.; Chow, Eva W. C.; Silversides, Candice K.; Bassett, Anne S.

2015-01-01

Purpose Hypocalcemia is a common endocrinological condition in 22q11.2 deletion syndrome. Neonatal hypocalcemia may affect neurodevelopment. We hypothesized that neonatal hypocalcemia would be associated with rare, more severe forms of intellectual disability in 22q11.2 deletion syndrome. Methods We used a logistic regression model to investigate potential predictors of intellectual disability severity, including neonatal hypocalcemia, neonatal seizures, and complex congenital heart disease, e.g., interrupted aortic arch, in 149 adults with 22q11.2 deletion syndrome. Ten subjects had moderate-to-severe intellectual disability. Results The model was highly significant (P < 0.0001), showing neonatal seizures (P = 0.0018) and neonatal hypocalcemia (P = 0.047) to be significant predictors of a more severe level of intellectual disability. Neonatal seizures were significantly associated with neonatal hypocalcemia in the entire sample (P < 0.0001), regardless of intellectual level. There was no evidence for the association of moderate- to-severe intellectual disability with other factors such as major structural brain malformations in this sample. Conclusion The results suggest that neonatal seizures may increase the risk for more severe intellectual deficits in 22q11.2 deletion syndrome, likely mediated by neonatal hypocalcemia. Neonatal hypocalcemia often remains unrecognized until the postseizure period, when damage to neurons may already have occurred. These findings support the importance of early recognition and treatment of neonatal hypocalcemia and potentially neonatal screening for 22q11.2 deletions. PMID:23765047
Infertility and recurrent miscarriage with complex II deficiency-dependent mitochondrial oxidative stress in animal models.

Science.gov (United States)

Ishii, Takamasa; Yasuda, Kayo; Miyazawa, Masaki; Mitsushita, Junji; Johnson, Thomas E; Hartman, Phil S; Ishii, Naoaki

2016-04-01

Oxidative stress is associated with some forms of both male and female infertility. However, there is insufficient knowledge of the influence of oxidative stress on the maintenance of a viable pregnancy, including pregnancy complications and fetal development. There are a number of animal models for understanding age-dependent decrease of reproductive ability and diabetic embryopathy, especially abnormal spermatogenesis, oogenesis and embryogenesis with mitochondrial dysfunctions. Several important processes occur in mitochondria, including ATP synthesis, calcium ion storage, induction of apoptosis and production of reactive oxygen species (ROS). These events have different effects on the several aspects of reproductive function. Tet-mev-1 conditional transgenic mice, developed after studies with the mev-1 mutant of the nematode C. elegans, offer the ability to carefully regulate expression of doxycycline-induced mutated SDHC(V69E) levels and hence modulate endogenous oxidative stress. The mev-1 models have served to illuminate the effects of complex II deficiency-dependent mitochondrial ROS production, although interestingly they maintain normal mitochondrial and intracellular ATP levels. In this review, the reproductive dysfunctions are presented focusing on fertility potentials in each gamete, early embryogenesis, maternal conditions with placental function and neonatal development. Copyright © 2016. Published by Elsevier Ireland Ltd.
Neonatal pulmonary arterial hypertension and Noonan syndrome: two fatal cases with a specific RAF1 mutation.

Science.gov (United States)

Hopper, Rachel K; Feinstein, Jeffrey A; Manning, Melanie A; Benitz, William; Hudgins, Louanne

2015-04-01

Mutations in RAF1 are associated with Noonan syndrome and hypertrophic cardiomyopathy. We present two infants with Noonan syndrome and an identical RAF1 mutation, p.Ser257Leu (c.770C>T), who developed severe pulmonary arterial hypertension (PAH) that proved to be fatal. The RAF1 gene encodes Raf-1 kinase, part of the Ras/mitogen-activated kinase (MAPK) signaling pathway, which has been linked to the development of PAH. This specific mutation has been associated with dephosphorylation of a critical serine residue and constitutive activation of the Raf-1 kinase. These two cases suggest that abnormal activation of the Ras/MAPK pathway may play a significant role in the development of pulmonary vascular disease in the subset of patients with Noonan syndrome and a specific RAF1 mutation. © 2015 Wiley Periodicals, Inc.
Loss of Mitochondrial Ndufs4 in Striatal Medium Spiny Neurons Mediates Progressive Motor Impairment in a Mouse Model of Leigh Syndrome

Directory of Open Access Journals (Sweden)

Byron Chen

2017-08-01

Full Text Available Inability of mitochondria to generate energy leads to severe and often fatal myoencephalopathies. Among these, Leigh syndrome (LS is one of the most common childhood mitochondrial diseases; it is characterized by hypotonia, failure to thrive, respiratory insufficiency and progressive mental and motor dysfunction, leading to early death. Basal ganglia nuclei, including the striatum, are affected in LS patients. However, neither the identity of the affected cell types in the striatum nor their contribution to the disease has been established. Here, we used a mouse model of LS lacking Ndufs4, a mitochondrial complex I subunit, to confirm that loss of complex I, but not complex II, alters respiration in the striatum. To assess the role of striatal dysfunction in the pathology, we selectively inactivated Ndufs4 in the striatal medium spiny neurons (MSNs, which account for over 95% of striatal neurons. Our results show that lack of Ndufs4 in MSNs causes a non-fatal progressive motor impairment without affecting the cognitive function of mice. Furthermore, no inflammatory responses or neuronal loss were observed up to 6 months of age. Hence, complex I deficiency in MSNs contributes to the motor deficits observed in LS, but not to the neural degeneration, suggesting that other neuronal populations drive the plethora of clinical signs in LS.

Using speeding detections and numbers of fatalities to estimate relative risk of a fatality for motorcyclists and car drivers.

Science.gov (United States)

Huggins, Richard

2013-10-01

Precise estimation of the relative risk of motorcyclists being involved in a fatal accident compared to car drivers is difficult. Simple estimates based on the proportions of licenced drivers or riders that are killed in a fatal accident are biased as they do not take into account the exposure to risk. However, exposure is difficult to quantify. Here we adapt the ideas behind the well known induced exposure methods and use available summary data on speeding detections and fatalities for motorcycle riders and car drivers to estimate the relative risk of a fatality for motorcyclists compared to car drivers under mild assumptions. The method is applied to data on motorcycle riders and car drivers in Victoria, Australia in 2010 and a small simulation study is conducted. Copyright © 2013 Elsevier Ltd. All rights reserved.
Impairment of mitochondrial calcium handling in a mtSOD1 cell culture model of motoneuron disease

Directory of Open Access Journals (Sweden)

Zippelius Annette

2009-06-01

Full Text Available Abstract Background Amyotrophic lateral sclerosis (ALS is a fatal neurodegenerative disorder characterized by the selective loss of motor neurons (MN in the brain stem and spinal cord. Intracellular disruptions of cytosolic and mitochondrial calcium have been associated with selective MN degeneration, but the underlying mechanisms are not well understood. The present evidence supports a hypothesis that mitochondria are a target of mutant SOD1-mediated toxicity in familial amyotrophic lateral sclerosis (fALS and intracellular alterations of cytosolic and mitochondrial calcium might aggravate the course of this neurodegenerative disease. In this study, we used a fluorescence charged cool device (CCD imaging system to separate and simultaneously monitor cytosolic and mitochondrial calcium concentrations in individual cells in an established cellular model of ALS. Results To gain insights into the molecular mechanisms of SOD1G93A associated motor neuron disease, we simultaneously monitored cytosolic and mitochondrial calcium concentrations in individual cells. Voltage – dependent cytosolic Ca2+ elevations and mitochondria – controlled calcium release mechanisms were monitored after loading cells with fluorescent dyes fura-2 and rhod-2. Interestingly, comparable voltage-dependent cytosolic Ca2+ elevations in WT (SH-SY5YWT and G93A (SH-SY5YG93A expressing cells were observed. In contrast, mitochondrial intracellular Ca2+ release responses evoked by bath application of the mitochondrial toxin FCCP were significantly smaller in G93A expressing cells, suggesting impaired calcium stores. Pharmacological experiments further supported the concept that the presence of G93A severely disrupts mitochondrial Ca2+ regulation. Conclusion In this study, by fluorescence measurement of cytosolic calcium and using simultaneous [Ca2+]i and [Ca2+]mito measurements, we are able to separate and simultaneously monitor cytosolic and mitochondrial calcium concentrations
Mitochondrial p38β and manganese superoxide dismutase interaction mediated by estrogen in cardiomyocytes.

Directory of Open Access Journals (Sweden)

Han Liu

Full Text Available While etiology behind the observed acceleration of ischemic heart disease in postmenopausal women is poorly understood, collective scientific data suggest cardioprotective effects of the endogenous female sex hormone, estrogen. We have previously shown that 17β-estradiol (E2 protects cardiomyocytes exposed to hypoxia-reoxygenation (H/R by inhibiting p38α - p53 signaling in apoptosis and activating pro-survival p38β mitogen activated protein kinase (p38β MAPK, leading to suppression of reactive oxygen species (ROS post H/R. However, little is known about the mechanism behind the antioxidant actions of E2-dependent p38β. The aim of this study is to determine whether the cytoprotection by estrogen involves regulation of manganese superoxide dismutase (MnSOD, a major mitochondrial ROS scavenging enzyme, via cardiac p38β.We identified mitochondrial p38β by immunocytochemistry and by immunoblotting in mitochondria isolated from neonatal cardiomyocytes of Sprague-Dawley rats. E2 facilitated the mitochondrial localization of the active form of the kinase, phosphorylated p38β (p-p38β. E2 also reduced the H/R-induced mitochondrial membrane potential decline, augmented the MnSOD activity and suppressed anion superoxide generation, while the dismutase protein expression remained unaltered. Co-immunoprecipitation studies showed physical association between MnSOD and p38β. p38β phosphorylated MnSOD in an E2-dependent manner in in-vitro kinase assays.This work demonstrates for the first time a mitochondrial pool of active p38β and E2-mediated phosphorylation of MnSOD by the kinase. The results shed light on the mechanism behind the cytoprotective actions of E2 in cardiomyocytes under oxidative stress.
Zinc as an adjunct treatment for reducing case fatality due to clinical severe infection in young infants: study protocol for a randomized controlled trial.

Science.gov (United States)

Wadhwa, Nitya; Basnet, Sudha; Natchu, Uma Chandra Mouli; Shrestha, Laxman P; Bhatnagar, Shinjini; Sommerfelt, Halvor; Strand, Tor A; Ramji, Siddarth; Aggarwal, K C; Chellani, Harish; Govil, Anuradha; Jajoo, Mamta; Mathur, N B; Bhatt, Meenakshi; Mohta, Anup; Ansari, Imran; Basnet, Srijana; Chapagain, Ram H; Shah, Ganesh P; Shrestha, Binod M

2017-07-10

An estimated 2.7 of the 5.9 million deaths in children under 5 years of age occur in the neonatal period. Severe infections contribute to almost a quarter of these deaths. Mortality due to severe infections in developing country settings is substantial despite antibiotic therapy. Effective interventions that can be added to standard therapy for severe infections are required to reduce case fatality. This is a double-blind randomized placebo-controlled parallel group superiority trial to investigate the effect of zinc administered orally as an adjunct to standard therapy to infants aged 3 days up to 2 months (59 days) hospitalized with clinical severe infection, that will be undertaken in seven hospitals in Delhi, India and Kathmandu, Nepal. In a 1:1 ratio, we will randomly assign young infants to receive 10 mg of elemental zinc or placebo orally in addition to the standard therapy for a total of 14 days. The primary outcomes hospital case fatality, which is death due to any cause and at any time after enrolment while hospitalized for the illness episode, and extended case fatality, which encompasses the period until 12 weeks after enrolment. A previous study showed a beneficial effect of zinc in reducing the risk of treatment failure, as well as a non-significant effect on case fatality. This study was not powered to detect an effect on case fatality, which this current study is. If the results are consistent with this earlier trial, we would have provided strong evidence for recommending zinc as an adjunct to standard therapy for clinical severe infection in young infants. Universal Trial Number: U1111-1187-6479, Clinical Trials Registry - India: CTRI/2017/02/007966 : Registered on February 27, 2017.
Coffee consumption and risk of fatal cancers.

Science.gov (United States)

Snowdon, D A; Phillips, R L

1984-01-01

In 1960, the coffee consumption habits and other lifestyle characteristics of 23,912 white Seventh-day Adventists were assessed by questionnaire. Between 1960 and 1980, deaths due to cancer were identified. There were positive associations between coffee consumption and fatal colon and bladder cancer. The group consuming two or more cups of coffee per day had an estimated relative risk (RR) of 1.7 for fatal colon cancer and 2.0 for fatal bladder cancer, compared to the group that consumed less than one cup per day (RR = 1.0). These positive associations were apparently not confounded by age, sex, cigarette smoking, or meat consumption habits. In this study, there were no significant or suggestive associations between coffee consumption and fatal pancreatic, breast, and ovarian cancer, or a combined group of all other cancer sites. PMID:6742274
Mitochondrial NUDIX hydrolases: A metabolic link between NAD catabolism, GTP and mitochondrial dynamics.

Science.gov (United States)

Long, Aaron; Klimova, Nina; Kristian, Tibor

2017-10-01

NAD + catabolism and mitochondrial dynamics are important parts of normal mitochondrial function and are both reported to be disrupted in aging, neurodegenerative diseases, and acute brain injury. While both processes have been extensively studied there has been little reported on how the mechanisms of these two processes are linked. This review focuses on how downstream NAD + catabolism via NUDIX hydrolases affects mitochondrial dynamics under pathologic conditions. Additionally, several potential targets in mitochondrial dysfunction and fragmentation are discussed, including the roles of mitochondrial poly(ADP-ribose) polymerase 1(mtPARP1), AMPK, AMP, and intra-mitochondrial GTP metabolism. Mitochondrial and cytosolic NUDIX hydrolases (NUDT9α and NUDT9β) can affect mitochondrial and cellular AMP levels by hydrolyzing ADP- ribose (ADPr) and subsequently altering the levels of GTP and ATP. Poly (ADP-ribose) polymerase 1 (PARP1) is activated after DNA damage, which depletes NAD + pools and results in the PARylation of nuclear and mitochondrial proteins. In the mitochondria, ADP-ribosyl hydrolase-3 (ARH3) hydrolyzes PAR to ADPr, while NUDT9α metabolizes ADPr to AMP. Elevated AMP levels have been reported to reduce mitochondrial ATP production by inhibiting the adenine nucleotide translocase (ANT), allosterically activating AMPK by altering the cellular AMP: ATP ratio, and by depleting mitochondrial GTP pools by being phosphorylated by adenylate kinase 3 (AK3), which uses GTP as a phosphate donor. Recently, activated AMPK was reported to phosphorylate mitochondria fission factor (MFF), which increases Drp1 localization to the mitochondria and promotes mitochondrial fission. Moreover, the increased AK3 activity could deplete mitochondrial GTP pools and possibly inhibit normal activity of GTP-dependent fusion enzymes, thus altering mitochondrial dynamics. Published by Elsevier Ltd.
Liver transplant in ethylmalonic encephalopathy: a new treatment for an otherwise fatal disease.

Science.gov (United States)

Dionisi-Vici, Carlo; Diodato, Daria; Torre, Giuliano; Picca, Stefano; Pariante, Rosanna; Giuseppe Picardo, Sergio; Di Meo, Ivano; Rizzo, Cristiano; Tiranti, Valeria; Zeviani, Massimo; De Ville De Goyet, Jean

2016-04-01

Ethylmalonic encephalopathy is a fatal, rapidly progressive mitochondrial disorder caused by ETHE1 mutations, whose peculiar clinical and biochemical features are due to the toxic accumulation of hydrogen sulphide and of its metabolites, including thiosulphate. In mice with ethylmalonic encephalopathy, liver-targeted adeno-associated virus-mediated ETHE1 gene transfer dramatically improved both clinical course and metabolic abnormalities. Reasoning that the same achievement could be accomplished by liver transplantation, we performed living donor-liver transplantation in an infant with ethylmalonic encephalopathy. Unlike the invariably progressive deterioration of the disease, 8 months after liver transplantation, we observed striking neurological improvement with remarkable achievements in psychomotor development, along with dramatic reversion of biochemical abnormalities. These results clearly indicate that liver transplantation is a viable therapeutic option for ETHE1 disease. © The Author (2016). Published by Oxford University Press on behalf of the Guarantors of Brain. All rights reserved. For Permissions, please email: journals.permissions@oup.com.
Reversible infantile mitochondrial diseases.

Science.gov (United States)

Boczonadi, Veronika; Bansagi, Boglarka; Horvath, Rita

2015-05-01

Mitochondrial diseases are usually severe and progressive conditions; however, there are rare forms that show remarkable spontaneous recoveries. Two homoplasmic mitochondrial tRNA mutations (m.14674T>C/G in mt-tRNA(Glu)) have been reported to cause severe infantile mitochondrial myopathy in the first months of life. If these patients survive the first year of life by extensive life-sustaining measures they usually recover and develop normally. Another mitochondrial disease due to deficiency of the 5-methylaminomethyl-2-thiouridylate methyltransferase (TRMU) causes severe liver failure in infancy, but similar to the reversible mitochondrial myopathy, within the first year of life these infants may also recover completely. Partial recovery has been noted in some other rare forms of mitochondrial disease due to deficiency of mitochondrial tRNA synthetases and mitochondrial tRNA modifying enzymes. Here we summarize the clinical presentation of these unique reversible mitochondrial diseases and discuss potential molecular mechanisms behind the reversibility. Understanding these mechanisms may provide the key to treatments of potential broader relevance in mitochondrial disease, where for the majority of the patients no effective treatment is currently available.
miR-27 regulates mitochondrial networks by directly targeting the mitochondrial fission factor.

Science.gov (United States)

Tak, Hyosun; Kim, Jihye; Jayabalan, Aravinth Kumar; Lee, Heejin; Kang, Hoin; Cho, Dong-Hyung; Ohn, Takbum; Nam, Suk Woo; Kim, Wook; Lee, Eun Kyung

2014-11-28

Mitochondrial morphology is dynamically regulated by forming small, fragmented units or interconnected networks, and this is a pivotal process that is used to maintain mitochondrial homeostasis. Although dysregulation of mitochondrial dynamics is related to the pathogenesis of several human diseases, its molecular mechanism is not fully elucidated. In this study, we demonstrate the potential role of miR-27 in the regulation of mitochondrial dynamics. Mitochondrial fission factor (MFF) mRNA is a direct target of miR-27, whose ectopic expression decreases MFF expression through binding to its 3'-untranslated region. Expression of miR-27 results in the elongation of mitochondria as well as an increased mitochondrial membrane potential and mitochondrial ATP level. Our results suggest that miR-27 is a novel regulator affecting morphological mitochondrial changes by targeting MFF.
Failure to thrive among neonates, associated factors and early neonatal outcome

International Nuclear Information System (INIS)

Thomas, Erica; Manji, Karim; Mpembeni Rose

2005-01-01

Failure to thrive or growth failure is an important feature of problems prevalent in the neonate. It remains one of the greatest challenges for the practicing pediatrician and it is a common pathway or outcome of several different underlaying infant and maternal conditions. To determine the prevalence, possible causes and early neonatal outcome of failure to thrive among young infants admitted to the Neonatal Unit in this hospital. A cross-sectional descriptive hospital based study, was carried for 10 months from April 2001 to January 2002 at the Neonatal Unit at Muhimbili National Hospital. (author)
Risk Factors for Neonatal Mortality Among Very Low Birth Weight Neonates

Directory of Open Access Journals (Sweden)

Fatemeh Nayeri

2013-05-01

Full Text Available The objective of this study is to determine risk factors causing increase in very low birth way (VLBW neonatal mortality. The medical files of all neonates weighing ≤1500 g, born in Vali-e-Asr hospital (2001-2004 were studied. Two groups of neonates (living and dead were compared up to the time of hospital discharge or death. A total of 317 neonates were enrolled. A meaningful relationship existed between occurrence of death and low gestational age (P=0.02, low birth weight, lower than 1000 g (P=0.001, Apgar score <6 at 5th minutes (P=0.001, resuscitation at birth (P=0.001, respiratory distress syndrome (P=0.001 need for mechanical ventilation (P=0.001, neurological complications (P=0.001 and intraventricular hemorrhage (P=0.001. Regression analysis indicated that each 250 g weight increase up to 1250 g had protective effect, and reduced mortality rate. The causes of death of those neonates weighting over 1250 g should be sought in factors other than weight. Survival rate was calculated to be 80.4% for neonates weighing more than 1000 g. The most important high risk factors affecting mortality of neonates are: low birth weight, need for resuscitation at birth, need for ventilator use and intraventricular hemorrhage.
Hiperbilirrubinemia neonatal agravada Aggravated neonatal hyperbilirubinemia

Directory of Open Access Journals (Sweden)

Ana Campo González

2010-09-01

Full Text Available INTRODUCCIÓN. La mayoría de las veces la ictericia en el recién nacido es un hecho fisiológico, causado por una hiperbilirrubinemia de predominio indirecto, secundario a inmadurez hepática e hiperproducción de bilirrubina. El objetivo de este estudio fue determinar el comportamiento de la hiperbilirrubinemia neonatal en el Hospital Docente Ginecoobstétrico de Guanabacoa en los años 2007 a 2009. MÉTODOS. Se realizó un estudio descriptivo y retrospectivo de 173 recién nacidos que ingresaron al Departamento de Neonatología con diagnóstico de hiperbilirrubinemia agravada. RESULTADOS. La incidencia de hiperbilirrubinemia neonatal agravada fue del 3,67 % y predominó en hermanos con antecedentes de ictericia (56,65 %. El tiempo de aparición fue de 48 a 72 h (76,87 % y entre los factores agravantes se hallaron el nacimiento pretérmino y el bajo peso al nacer. La mayoría de los pacientes fueron tratados con luminoterapia (90,17 %. CONCLUSIÓN. La hiperbilirrubinemia neonatal agravada constituye un problema de salud. Los factores agravantes son la prematuridad y el bajo peso al nacer. La luminoterapia es una medida terapéutica eficaz para su tratamiento.INTRODUCTION. Most of times jaundice in newborn is a physiological fact due to hyperbilirubinemia of indirect predominance, secondary to liver immaturity and to bilirubin hyperproduction. The aim of present of present study was to determine the behavior of neonatal hyperbilirubinemia in the Gynecology and Obstetrics Teaching Hospital of Guanabacoa municipality from 2007 to 2009. METHODS. A retrospective and descriptive study was conducted in 173 newborn patients admitted in the Neonatology Department diagnosed with severe hyperbilirubinemia. RESULTS. The incidence of severe neonatal hyperbilirubinemia was of 3,67% with predominance in brothers with a history of jaundice (56,65%. The time of appearance was of 48 to 72 hrs (76,87% and among the aggravating factors were the preterm birth and
Buses involved in fatal accidents codebook 2008.

Science.gov (United States)

2011-03-01

This report provides documentation for UMTRIs file of Buses Involved in Fatal Accidents (BIFA), 2008, : including distributions of the code values for each variable in the file. The 2008 BIFA file is a census of all : buses involved in a fatal acc...
Buses involved in fatal accidents codebook 2007.

Science.gov (United States)

2009-12-01

This report provides documentation for UMTRIs file of Buses Involved in Fatal Accidents (BIFA), 2007, : including distributions of the code values for each variable in the file. The 2007 BIFA file is a census of all : buses involved in a fatal acc...
Mitochondrial dysfunction in alveolar and white matter developmental failure in premature infants.

Science.gov (United States)

Ten, Vadim S

2017-02-01

At birth, some organs in premature infants are not developed enough to meet challenges of the extra-uterine life. Although growth and maturation continues after premature birth, postnatal organ development may become sluggish or even arrested, leading to organ dysfunction. There is no clear mechanistic concept of this postnatal organ developmental failure in premature neonates. This review introduces a concept-forming hypothesis: Mitochondrial bioenergetic dysfunction is a fundamental mechanism of organs maturation failure in premature infants. Data collected in support of this hypothesis are relevant to two major diseases of prematurity: white matter injury and broncho-pulmonary dysplasia. In these diseases, totally different clinical manifestations are defined by the same biological process, developmental failure of the main functional units-alveoli in the lungs and axonal myelination in the brain. Although molecular pathways regulating alveolar and white matter maturation differ, proper bioenergetic support of growth and maturation remains critical biological requirement for any actively developing organ. Literature analysis suggests that successful postnatal pulmonary and white matter development highly depends on mitochondrial function which can be inhibited by sublethal postnatal stress. In premature infants, sublethal stress results mostly in organ maturation failure without excessive cellular demise.
De Novo Mutations in SLC25A24 Cause a Craniosynostosis Syndrome with Hypertrichosis, Progeroid Appearance, and Mitochondrial Dysfunction.

Science.gov (United States)

Ehmke, Nadja; Graul-Neumann, Luitgard; Smorag, Lukasz; Koenig, Rainer; Segebrecht, Lara; Magoulas, Pilar; Scaglia, Fernando; Kilic, Esra; Hennig, Anna F; Adolphs, Nicolai; Saha, Namrata; Fauler, Beatrix; Kalscheuer, Vera M; Hennig, Friederike; Altmüller, Janine; Netzer, Christian; Thiele, Holger; Nürnberg, Peter; Yigit, Gökhan; Jäger, Marten; Hecht, Jochen; Krüger, Ulrike; Mielke, Thorsten; Krawitz, Peter M; Horn, Denise; Schuelke, Markus; Mundlos, Stefan; Bacino, Carlos A; Bonnen, Penelope E; Wollnik, Bernd; Fischer-Zirnsak, Björn; Kornak, Uwe

2017-11-02

Gorlin-Chaudhry-Moss syndrome (GCMS) is a dysmorphic syndrome characterized by coronal craniosynostosis and severe midface hypoplasia, body and facial hypertrichosis, microphthalmia, short stature, and short distal phalanges. Variable lipoatrophy and cutis laxa are the basis for a progeroid appearance. Using exome and genome sequencing, we identified the recurrent de novo mutations c.650G>A (p.Arg217His) and c.649C>T (p.Arg217Cys) in SLC25A24 in five unrelated girls diagnosed with GCMS. Two of the girls had pronounced neonatal progeroid features and were initially diagnosed with Wiedemann-Rautenstrauch syndrome. SLC25A24 encodes a mitochondrial inner membrane ATP-Mg/P i carrier. In fibroblasts from affected individuals, the mutated SLC25A24 showed normal stability. In contrast to control cells, the probands' cells showed mitochondrial swelling, which was exacerbated upon treatment with hydrogen peroxide (H 2 O 2 ). The same effect was observed after overexpression of the mutant cDNA. Under normal culture conditions, the mitochondrial membrane potential of the probands' fibroblasts was intact, whereas ATP content in the mitochondrial matrix was lower than that in control cells. However, upon H 2 O 2 exposure, the membrane potential was significantly elevated in cells harboring the mutated SLC25A24. No reduction of mitochondrial DNA copy number was observed. These findings demonstrate that mitochondrial dysfunction with increased sensitivity to oxidative stress is due to the SLC25A24 mutations. Our results suggest that the SLC25A24 mutations induce a gain of pathological function and link mitochondrial ATP-Mg/P i transport to the development of skeletal and connective tissue. Copyright © 2017 American Society of Human Genetics. All rights reserved.
Colorful story of phototherapy for neonatal jaundice

Science.gov (United States)

Agati, Giovanni; Fusi, Franco; Pratesi, Riccardo; Pratesi, Simone; Donzelli, Gian Paolo

1996-12-01

Colors have always attracted our fantasy and imagination. Medicine, like many other human activities, did not escape their attraction, sometimes with fatal consequences. The scientific literature, magazines, etc. are full of reports on the beneficial, miraculous effects of colors. Even nowadays, where photobiology and photomedicine have been put on very firm bases, chromopaths are still at work. The evolution of light therapy from chromotherapy to photomedicine is presented in brief, with the aim of contributing to the action against the unscientific behavior of researchers and clinicians who support biological and/or clinical results without serious and well documented work. Colors have played an important role in the phototherapy of neonatal jaundice. It is an interesting example of how even a rigorous scientific search for the optimal color has progressed in part by change, due to the lack of an action spectrum, too hurried extrapolations of animal results to man, unsuspected dynamical behavior of bilirubin molecules, etc. The story of its evolution up to present knowledge is reported in this paper.
Left ventricular hypertrophy and risk of fatal and non-fatal stroke EUROSTROKE: a collaborative study among research centres in Europe

NARCIS (Netherlands)

M.L. Bots (Michiel); J. Tuomilehto; D.E. Grobbee (Diederick); P.J. Koudstaal (Peter Jan); Y. Nikitin; J.T. Salonen; P.C. Elwood; S. Malyutina; A. Freire de Concalves; J. Sivenius; A. di Carlo; P. Lagiou

2002-01-01

textabstractBACKGROUND: This study investigated the association between electrocardiographically assessed left ventricular hypertrophy (LVH) and fatal, non-fatal, haemorrhagic and ischaemic stroke in four European cohorts participating in EUROSTROKE. METHODS: EUROSTROKE is a
The mitochondrial transcription factor A functions in mitochondrial base excision repair

DEFF Research Database (Denmark)

Canugovi, Chandrika; Maynard, Scott; Bayne, Anne-Cécile V

2010-01-01

Mitochondrial transcription factor A (TFAM) is an essential component of mitochondrial nucleoids. TFAM plays an important role in mitochondrial transcription and replication. TFAM has been previously reported to inhibit nucleotide excision repair (NER) in vitro but NER has not yet been detected i...
Management of neonatal abstinence syndrome in neonates born to opioid maintained women.

Science.gov (United States)

Ebner, Nina; Rohrmeister, Klaudia; Winklbaur, Bernadette; Baewert, Andjela; Jagsch, Reinhold; Peternell, Alexandra; Thau, Kenneth; Fischer, Gabriele

2007-03-16

Neonates born to opioid-maintained mothers are at risk of developing neonatal abstinence syndrome (NAS), which often requires pharmacological treatment. This study examined the effect of opioid maintenance treatment on the incidence and timing of NAS, and compared two different NAS treatments (phenobarbital versus morphine hydrochloride). Fifty-three neonates born to opioid-maintained mothers were included in this study. The mothers received methadone (n=22), slow-release oral morphine (n=17) or buprenorphine (n=14) throughout pregnancy. Irrespective of maintenance treatment, all neonates showed APGAR scores comparable to infants of non-opioid dependent mothers. No difference was found between the three maintenance groups regarding neonatal weight, length or head circumference. Sixty percent (n=32) of neonates required treatment for NAS [68% in the methadone-maintained group (n=15), 82% in the morphine-maintained group (n=14), and 21% in the buprenorphine-maintained group (n=3)]. The mean duration from birth to requirement of NAS treatment was 33 h for the morphine-maintained group, 34 h for the buprenorphine-maintained group and 58 h for the methadone-maintained group. In neonates requiring NAS treatment, those receiving morphine required a significantly shorter mean duration of treatment (9.9 days) versus those treated with phenobarbital (17.7 days). Results suggest that morphine hydrochloride is preferable for neonates suffering NAS due to opioid withdrawal.

Fatal accidents among Danes with multiple sclerosis

DEFF Research Database (Denmark)

Brønnum-Hansen, Henrik; Hansen, Thomas; Koch-Henriksen, Nils

2006-01-01

We compared the rate of fatal accidents among Danes with multiple sclerosis (MS) with that of the general population. The study was based on linkage of the Danish Multiple Sclerosis Registry to the Cause of Death Registry and covered all 10174 persons in whom MS was diagnosed during the period 19...... for deaths from burns (SMR = 8.90) and suffocation (SMR = 5.57). We conclude that persons with MS are more prone to fatal accidents than the general population. The excess risk is due not to traffic accidents but to burns and suffocation.......-1996. The end of follow-up was 1 January 1999. We calculated standardized mortality ratios (SMRs) for various types of fatal accidents. A total of 76 persons (48 men and 28 women) died from accidents, whereas the expected number of fatalities from such causes was 55.7 (31.4 men and 24.3 women). Thus, the risk...... for death from accidents among persons with MS was 37% higher than that of the general population (SMR = 1.37). We found no significant excess risk for fatal road accidents (SMR = 0.80). The risk for falls was elevated (SMR = 1.29) but not statistically significantly so. The risks were particularly high...
Has the great recession and its aftermath reduced traffic fatalities?

Science.gov (United States)

Noland, Robert B; Zhou, Yuhan

2017-01-01

An analysis of state-level data from 1984 to 2014 provides evidence on the relationship between economic recessions and US traffic fatalities. While there are large reductions associated with decreases in household median income, other policy variables tend to have additional and in some cases, larger effects. An increase in the inequality of the income distribution, measured by the Gini index, has reduced traffic fatalities. Graduated licensing policies, cell phone laws, and motorcycle helmet requirements are all associated with reductions in fatalities. Other factors include a proxy for medical technology, and access to emergency medical services (based on the percent of vehicle miles traveled in rural areas); reductions in the latter accounted for a substantial reduction in fatalities and is likely another indicator of reduced economic activity. Changes in the road network, mainly increases in the percent of collector roads has increased fatalities. Population growth is associated with increased traffic fatalities and changes in age cohorts has a small negative effect. Overall, results suggest that there has been a beneficial impact on traffic fatalities from reduced economic activity, but various policies adopted by the states have also reduced traffic fatalities. Copyright © 2016 Elsevier Ltd. All rights reserved.
Intrapartum-related neonatal encephalopathy incidence and impairment at regional and global levels for 2010 with trends from 1990

Science.gov (United States)

Lee, Anne CC; Kozuki, Naoko; Blencowe, Hannah; Vos, Theo; Bahalim, Adil; Darmstadt, Gary L.; Niermeyer, Susan; Ellis, Matthew; Robertson, Nicola J.; Cousens, Simon; Lawn, Joy E.

2013-01-01

Background: Intrapartum hypoxic events (“birth asphyxia”) may result in stillbirth, neonatal or postneonatal mortality, and impairment. Systematic morbidity estimates for the burden of impairment outcomes are currently limited. Neonatal encephalopathy (NE) following an intrapartum hypoxic event is a strong predictor of long-term impairment. Methods: Linear regression modeling was conducted on data identified through systematic reviews to estimate NE incidence and time trends for 184 countries. Meta-analyses were undertaken to estimate the risk of NE by sex of the newborn, neonatal case fatality rate, and impairment risk. A compartmental model estimated postneonatal survivors of NE, depending on access to care, and then the proportion of survivors with impairment. Separate modeling for the Global Burden of Disease 2010 (GBD2010) study estimated disability adjusted life years (DALYs), years of life with disability (YLDs), and years of life lost (YLLs) attributed to intrapartum-related events. Results: In 2010, 1.15 million babies (uncertainty range: 0.89–1.60 million; 8.5 cases per 1,000 live births) were estimated to have developed NE associated with intrapartum events, with 96% born in low- and middle-income countries, as compared with 1.60 million in 1990 (11.7 cases per 1,000 live births). An estimated 287,000 (181,000–440,000) neonates with NE died in 2010; 233,000 (163,000–342,000) survived with moderate or severe neurodevelopmental impairment; and 181,000 (82,000–319,000) had mild impairment. In GBD2010, intrapartum-related conditions comprised 50.2 million DALYs (2.4% of total) and 6.1 million YLDs. Conclusion: Intrapartum-related conditions are a large global burden, mostly due to high mortality in low-income countries. Universal coverage of obstetric care and neonatal resuscitation would prevent most of these deaths and disabilities. Rates of impairment are highest in middle-income countries where neonatal intensive care was more recently
Results from the Hawaii domestic violence fatality review, 2000-2009

Science.gov (United States)

Pobutsky, Ann; Brown, Melissa; Nakao, Lisa; Reyes-Salvail, Florentina

2014-01-01

Abstract: Background: Patterns of domestic violence fatalities and agency responses in Hawaii have not been explicated. Methods: Retrospective reviews of events leading up to domestic violence related fatalities in Hawaii were assessed from 45 adjudicated cases that resulted in 62 fatalities for the ten year period from 2000-2009. Results: Almost one-half of the fatalities were homicide/suicide combinations. Females were disproportionately more likely to be fatal victims of domestic violence relative to their proportion in the population. Those aged 21-40 years and those over 80 years were more likely to be fatal victims of domestic violence, relative to their proportion in the population. Filipinas and ‘Other” ethnic groups are disproportionately more likely to be fatal victims of domestic violence while Native Hawaiians and Japanese are less likely to be fatal victims, relative to their proportions in the population. In more than two-thirds of the cases, the victim had made some attempt to leave the relationship prior to the fatality. Conclusions: In the majority of cases there was agency involvement in some form: either the victim alone or the perpetrator alone, or both. However, less than one-third (31.1%) of the cases over the past ten years had documentation of prior violence from medical reports, so this may be an area to further document and address domestic violence. PMID:24292165
Results from the Hawaii domestic violence fatality review, 2000-2009

Directory of Open Access Journals (Sweden)

Ann Pobutsky

2014-07-01

Full Text Available Abstract: Background: Patterns of domestic violence fatalities and agency responses in Hawaii have not been explicated. Methods: Retrospective reviews of events leading up to domestic violence related fatalities in Hawaii were assessed from 45 adjudicated cases that resulted in 62 fatalities for the ten year period from 2000-2009. Results: Almost one-half of the fatalities were homicide/suicide combinations. Females were disproportionately more likely to be fatal victims of domestic violence relative to their proportion in the population. Those aged 21-40 years and those over 80 years were more likely to be fatal victims of domestic violence, relative to their proportion in the population. Filipinas and „Other” ethnic groups are disproportionately more likely to be fatal victims of domestic violence while Native Hawaiians and Japanese are less likely to be fatal victims, relative to their proportions in the population. In more than two-thirds of the cases, the victim had made some attempt to leave the relationship prior to the fatality. Conclusions: In the majority of cases there was agency involvement in some form: either the victim alone or the perpetrator alone, or both. However, less than one-third (31.1% of the cases over the past ten years had documentation of prior violence from medical reports, so this may be an area to further document and address domestic violence.
Fatal injuries to teenage construction workers in the US.

Science.gov (United States)

Suruda, Anthony; Philips, Peter; Lillquist, Dean; Sesek, Richard

2003-11-01

The construction industry is second only to agriculture in the annual number of fatal injuries in workers less than 18 years of age. We examined fatal injury reports for youth and adult workers to determine risk factors for injury and applicability of existing child labor regulations. The US Occupational Safety & Health Administration (OSHA) investigation data for fatal work injuries from 1984 through 1998 were reviewed with respect to type of event, employer characteristics, and apparent violations of existing child labor laws under the Fair Labor Standards Act (FLSA). We also examined whether the employer met exemption criteria for federal enforcement of child labor or OSHA regulations. The fatality rate for teenage construction workers age 19 and younger was 12.1 per 100,000 per year, slightly less than for adult workers. Teenage workers who were fatally injured were more likely than adults to have been employed at non-union construction firms (odds ratio (OR) = 4.96, P worker. Fatalities in teenagers were more likely to occur in special construction trades such as roofing. Among fatalities in workers less than 18 years of age, approximately one-half (49%) of the 76 fatal injuries were in apparent violation of existing child labor regulations. We estimated that in 41 of the 76 cases (54%) the employer's gross annual income exceeded the $500,000 threshold for federal enforcement of child labor laws. Only 28 of 76 cases (37%) were at construction firms with 11 or more employees, which are subject to routine OSHA inspections. Fatal injuries in teenage construction workers differed from those in adults in that they were more likely to be at small, non-union firms of which a substantial proportion were exempt from federal enforcement of child labor laws and from routine OSHA inspections. Safety programs for young construction workers should include small, non-union construction firms and those in special construction trades such as roofing. We did not identify
Fatal accidents at railway level crossings in Great Britain 1946-2009.

Science.gov (United States)

Evans, Andrew W

2011-09-01

This paper investigates fatal accidents and fatalities at level crossings in Great Britain over the 64-year period 1946-2009. The numbers of fatal accidents and fatalities per year fell by about 65% in the first half of that period, but since then have remained more or less constant at about 11 fatal accidents and 12 fatalities per year. At the same time other types of railway fatalities have fallen, so level crossings represent a growing proportion of the total. Nevertheless, Britain's level crossing safety performance remains good by international standards. The paper classifies level crossings into three types: railway-controlled, automatic, and passive. The safety performance of the three types of crossings has been very different. Railway-controlled crossings are the best-performing crossing type, with falling fatal accident rates. Automatic crossings have higher accident rates per crossing than railway controlled or passive crossings, and the accident rates have not decreased. Passive crossings are by far the most numerous, but many have low usage by road users. Their fatal accident rate has remained remarkably constant over the whole period at about 0.9 fatal accidents per 1000 crossings per year. A principal reason why fatal accidents and fatalities have not fallen in the second half of the period as they did in the first half is the increase in the number of automatic crossings, replacing the safer railway controlled crossings on some public roads. However, it does not follow that this replacement was a mistake, because automatic crossings have advantages over controlled crossings in reducing delays to road users and in not needing staff. Based on the trends for each type of crossing and for pedestrian and non-pedestrian accidents separately, in 2009 a mean of about 5% of fatal accidents were at railway controlled crossings, 52% were at automatic crossings, and 43% were at passive crossings. Fatalities had similar proportions. About 60% of fatalities were
Neonatal pain

Science.gov (United States)

Walker, Suellen M

2014-01-01

Effective management of procedural and postoperative pain in neonates is required to minimize acute physiological and behavioral distress and may also improve acute and long-term outcomes. Painful stimuli activate nociceptive pathways, from the periphery to the cortex, in neonates and behavioral responses form the basis for validated pain assessment tools. However, there is an increasing awareness of the need to not only reduce acute behavioral responses to pain in neonates, but also to protect the developing nervous system from persistent sensitization of pain pathways and potential damaging effects of altered neural activity on central nervous system development. Analgesic requirements are influenced by age-related changes in both pharmacokinetic and pharmacodynamic response, and increasing data are available to guide safe and effective dosing with opioids and paracetamol. Regional analgesic techniques provide effective perioperative analgesia, but higher complication rates in neonates emphasize the importance of monitoring and choice of the most appropriate drug and dose. There have been significant improvements in the understanding and management of neonatal pain, but additional research evidence will further reduce the need to extrapolate data from older age groups. Translation into improved clinical care will continue to depend on an integrated approach to implementation that encompasses assessment and titration against individual response, education and training, and audit and feedback. PMID:24330444
Common effects of lithium and valproate on mitochondrial functions: protection against methamphetamine-induced mitochondrial damage.

Science.gov (United States)

Bachmann, Rosilla F; Wang, Yun; Yuan, Peixiong; Zhou, Rulun; Li, Xiaoxia; Alesci, Salvatore; Du, Jing; Manji, Husseini K

2009-07-01

Accumulating evidence suggests that mitochondrial dysfunction plays a critical role in the progression of a variety of neurodegenerative and psychiatric disorders. Thus, enhancing mitochondrial function could potentially help ameliorate the impairments of neural plasticity and cellular resilience associated with a variety of neuropsychiatric disorders. A series of studies was undertaken to investigate the effects of mood stabilizers on mitochondrial function, and against mitochondrially mediated neurotoxicity. We found that long-term treatment with lithium and valproate (VPA) enhanced cell respiration rate. Furthermore, chronic treatment with lithium or VPA enhanced mitochondrial function as determined by mitochondrial membrane potential, and mitochondrial oxidation in SH-SY5Y cells. In-vivo studies showed that long-term treatment with lithium or VPA protected against methamphetamine (Meth)-induced toxicity at the mitochondrial level. Furthermore, these agents prevented the Meth-induced reduction of mitochondrial cytochrome c, the mitochondrial anti-apoptotic Bcl-2/Bax ratio, and mitochondrial cytochrome oxidase (COX) activity. Oligoarray analysis demonstrated that the gene expression of several proteins related to the apoptotic pathway and mitochondrial functions were altered by Meth, and these changes were attenuated by treatment with lithium or VPA. One of the genes, Bcl-2, is a common target for lithium and VPA. Knock-down of Bcl-2 with specific Bcl-2 siRNA reduced the lithium- and VPA-induced increases in mitochondrial oxidation. These findings illustrate that lithium and VPA enhance mitochondrial function and protect against mitochondrially mediated toxicity. These agents may have potential clinical utility in the treatment of other diseases associated with impaired mitochondrial function, such as neurodegenerative diseases and schizophrenia.
Mitochondrial Nucleoid: Shield and Switch of the Mitochondrial Genome

Science.gov (United States)

2017-01-01

Mitochondria preserve very complex and distinctively unique machinery to maintain and express the content of mitochondrial DNA (mtDNA). Similar to chromosomes, mtDNA is packaged into discrete mtDNA-protein complexes referred to as a nucleoid. In addition to its role as a mtDNA shield, over 50 nucleoid-associated proteins play roles in mtDNA maintenance and gene expression through either temporary or permanent association with mtDNA or other nucleoid-associated proteins. The number of mtDNA(s) contained within a single nucleoid is a fundamental question but remains a somewhat controversial issue. Disturbance in nucleoid components and mutations in mtDNA were identified as significant in various diseases, including carcinogenesis. Significant interest in the nucleoid structure and its regulation has been stimulated in relation to mitochondrial diseases, which encompass diseases in multicellular organisms and are associated with accumulation of numerous mutations in mtDNA. In this review, mitochondrial nucleoid structure, nucleoid-associated proteins, and their regulatory roles in mitochondrial metabolism are briefly addressed to provide an overview of the emerging research field involving mitochondrial biology. PMID:28680532
Maternal or neonatal infection: association with neonatal encephalopathy outcomes.

Science.gov (United States)

Jenster, Meike; Bonifacio, Sonia L; Ruel, Theodore; Rogers, Elizabeth E; Tam, Emily W; Partridge, John Colin; Barkovich, Anthony James; Ferriero, Donna M; Glass, Hannah C

2014-07-01

Perinatal infection may potentiate brain injury among children born preterm. The objective of this study was to examine whether maternal and/or neonatal infection are associated with adverse outcomes among term neonates with encephalopathy. This study is a cohort study of 258 term newborns with encephalopathy whose clinical records were examined for signs of maternal infection (chorioamnionitis) and infant infection (sepsis). Multivariate regression was used to assess associations between infection, pattern, and severity of injury on neonatal magnetic resonance imaging, as well as neurodevelopment at 30 mo (neuromotor examination, or Bayley Scales of Infant Development, second edition mental development index encephalopathy, chorioamnionitis was associated with a lower risk of brain injury and adverse outcomes, whereas signs of neonatal sepsis carried an elevated risk. The etiology of encephalopathy and timing of infection and its associated inflammatory response may influence whether infection potentiates or mitigates injury in term newborns.
Mitochondrial pharmacology: electron transport chain bypass as strategies to treat mitochondrial dysfunction.

Science.gov (United States)

Atamna, Hani; Mackey, Jeanette; Dhahbi, Joseph M

2012-01-01

Mitochondrial dysfunction (primary or secondary) is detrimental to intermediary metabolism. Therapeutic strategies to treat/prevent mitochondrial dysfunction could be valuable for managing metabolic and age-related disorders. Here, we review strategies proposed to treat mitochondrial impairment. We then concentrate on redox-active agents, with mild-redox potential, who shuttle electrons among specific cytosolic or mitochondrial redox-centers. We propose that specific redox agents with mild redox potential (-0.1 V; 0.1 V) improve mitochondrial function because they can readily donate or accept electrons in biological systems, thus they enhance metabolic activity and prevent reactive oxygen species (ROS) production. These agents are likely to lack toxic effects because they lack the risk of inhibiting electron transfer in redox centers. This is different from redox agents with strong negative (-0.4 V; -0.2 V) or positive (0.2 V; 0.4 V) redox potentials who alter the redox status of redox-centers (i.e., become permanently reduced or oxidized). This view has been demonstrated by testing the effect of several redox active agents on cellular senescence. Methylene blue (MB, redox potential ≅10 mV) appears to readily cycle between the oxidized and reduced forms using specific mitochondrial and cytosolic redox centers. MB is most effective in delaying cell senescence and enhancing mitochondrial function in vivo and in vitro. Mild-redox agents can alter the biochemical activity of specific mitochondrial components, which then in response alters the expression of nuclear and mitochondrial genes. We present the concept of mitochondrial electron-carrier bypass as a potential result of mild-redox agents, a method to prevent ROS production, improve mitochondrial function, and delay cellular aging. Thus, mild-redox agents may prevent/delay mitochondria-driven disorders. Copyright © 2012 International Union of Biochemistry and Molecular Biology, Inc.
Nordic ski jumping fatalities in the United States: a 50-year summary.

Science.gov (United States)

Wright, J R

1988-06-01

Nordic ski-jumping fatalities are rare events. Six jumping fatalities have occurred in the United States during the past 50 years. The fatality rate for nordic ski jumping, estimated to be roughly 12 fatalities/100,000 participants annually, appears to be within the range of fatality rates for other "risky" outdoor sports. Cervical fractures appear to be the most frequent fatal ski-jumping injury.
Macroeconomic fluctuations and motorcycle fatalities in the U.S.

Science.gov (United States)

French, Michael T; Gumus, Gulcin

2014-03-01

The effects of business cycles on health outcomes in general, and on traffic fatalities in particular, have received much attention recently. In this paper, we focus on motorcycle safety and examine the impact of changing levels of economic activity on fatal crashes by motorcyclists in the United States. We analyze state-level longitudinal data with 1,104 state/year observations from the 1988-2010 Fatality Analysis Reporting System (FARS). Using the extensive motorcycle crash characteristics available in FARS, we examine not only total fatality rates but also rates decomposed by crash type, day, time, and the level of the motorcycle operator's blood alcohol content. Our results are consistent with much of the existing literature showing that traffic fatality rates are pro-cyclical. The estimates suggest that a 10% increase in real income per capita is associated with a 10.4% rise in the total motorcycle fatality rate. Along with potential mechanisms, policymakers and public health officials should consider the effects of business cycles on motorcycle safety. Copyright © 2013 Elsevier Ltd. All rights reserved.
Tuberculosis neonatal

OpenAIRE

Pastor Durán, Xavier

1986-01-01

PROTOCOLOS TERAPEUTICOS. TUBERCULOSIS NEONATAL 1. CONCEPTO La tuberculosis neonatal es la infección del recién nacido producida por el bacilo de Koch. Es una situación rara pero grave que requiere un diagnóstico precoz y un tratamiento enérgico..
Characteristics of schools in which fatal shootings occur.

Science.gov (United States)

de Apodaca, Roberto Flores; Brighton, Lauren M; Perkins, Ashley N; Jackson, Kiana N; Steege, Jessica R

2012-04-01

School-based violence, and fatal school shootings in particular, have gained increased attention in the media and psychological literature. Most reports have focused on the characteristics of perpetrators, but there is a growing awareness that school-related factors may also influence the occurrence of fatal school shootings. The current study examined several key characteristics of all schools where random (38) and targeted (96) fatal shootings occurred in the United States between 1966 and 2009. These were compared with a group (138) of schools randomly selected to represent the population of all schools in the United States. The size of a school's enrollment, urban or suburban locale, public funding, and predominantly non-white enrollment were positively associated with fatal shootings. Universities and colleges were disproportionately associated with random shootings and high schools with targeted ones. It was proposed that characteristics of schools that allow feelings of anonymity or alienation among students may help create environmental conditions associated with fatal school shootings. Implications for future research and interventions are considered.
Evidence for the Role of BAG3 in Mitochondrial Quality Control in Cardiomyocytes.

Science.gov (United States)

Tahrir, Farzaneh G; Knezevic, Tijana; Gupta, Manish K; Gordon, Jennifer; Cheung, Joseph Y; Feldman, Arthur M; Khalili, Kamel

2017-04-01

Mitochondrial abnormalities impact the development of myofibrillar myopathies. Therefore, understanding the mechanisms underlying the removal of dysfunctional mitochondria from cells is of great importance toward understanding the molecular events involved in the genesis of cardiomyopathy. Earlier studies have ascribed a role for BAG3 in the development of cardiomyopathy in experimental animals leading to the identification of BAG3 mutations in patients with heart failure which may play a part in the onset of disease development and progression. BAG3 is co-chaperone of heat shock protein 70 (HSP70), which has been shown to modulate apoptosis and autophagy, in several cell models. In this study, we explore the potential role of BAG3 in mitochondrial quality control. We demonstrate that siRNA mediated suppression of BAG3 production in neonatal rat ventricular cardiomyocytes (NRVCs) significantly elevates the level of Parkin, a key component of mitophagy. We found that both BAG3 and Parkin are recruited to depolarized mitochondria and promote mitophagy. Suppression of BAG3 in NRVCs significantly reduces autophagy flux and eliminates clearance of Tom20, an essential import receptor for mitochondria proteins, after induction of mitophagy. These observations suggest that BAG3 is critical for the maintenance of mitochondrial homeostasis under stress conditions, and disruptions in BAG3 expression impact cardiomyocyte function. J. Cell. Physiol. 232: 797-805, 2017. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.
Fatal and non-fatal cardiovascular events in a general population prescribed sibutramine in New Zealand: a prospective cohort study.

Science.gov (United States)

Harrison-Woolrych, Mira; Ashton, Janelle; Herbison, Peter

2010-07-01

The cardiovascular safety of sibutramine is currently under review by medicines regulatory authorities worldwide after the SCOUT (Sibutramine Cardiovascular Outcome Trial) showed an increased risk of cardiovascular events in patients taking sibutramine. Further data regarding the cardiovascular safety of sibutramine in a general population are now required. To quantify the risk of fatal and non-fatal cardiovascular adverse events in a general population prescribed sibutramine in postmarketing use. Observational prospective cohort study of patients dispensed sibutramine during a 3-year period (2001-4) and followed up for at least 1 year after their last prescription. The study included record-linkage to national mortality datasets to identify fatal events. Postmarketing 'real-life' use of sibutramine in a general population in New Zealand. All New Zealand patients dispensed a prescription for sibutramine in a 3-year period (for whom a National Health Identification number could be validated). 15 686 patients were included in the record linkage study for fatal events. A subgroup of 9471 patients was followed up by intensive methods for non-fatal events. (i) Rate of death from all causes and from cardiovascular events; and (ii) rates of non-fatal cardiovascular adverse events. Total exposure to sibutramine for 15 686 patients in the validated cohort was 5431 treatment-years. The rate of death from all causes in this cohort was 0.13 (95% CI 0.05, 0.27) per 100 treatment-years exposure. The rate of death from a cardiovascular event was 0.07 (95% CI 0.02, 0.19) per 100 treatment-years exposure. The most frequent non-fatal cardiovascular events in the intensively followed up cohort were hypertension, palpitations, hypotensive events and tachycardia. Risk of death from a cardiovascular event in this general population of patients prescribed sibutramine was lower than has been reported in other overweight/obese populations. The results of this study suggest that further
Reporting Fatal Neglect in Child Death Review.

Science.gov (United States)

Scott, Debbie

2018-01-01

Child death reviews are conducted with the aim of preventing child deaths however, definitions, inclusion criteria for the review of child deaths and reporting practices vary across Child Death Review Teams (CDRTs). This article aims to identify a common context and understanding of fatal neglect reporting by reviewing definitional issues of fatal neglect and comparing reporting practice across a number of CDRTs. Providing a consistent context for identifying and reporting neglect-related deaths may improve the understanding of the impact of fatal neglect and the risk factors associated with it and therefore, improve the potential of CDRT review to inform prevention programs, policies, and procedures.
Fatal poisoning among patients with drug addiction

DEFF Research Database (Denmark)

Simonsen, Kirsten Wiese; Christoffersen, Dorte J; Banner, Jytte

2015-01-01

INTRODUCTION: Fatal poisonings among drug addicts in Denmark in 2012 were examined. Cause of death, abuse pattern and geographic differences are discussed and data are compared with previous studies. METHODS: All fatal poisonings examined at the three institutes of forensic medicine in Denmark...... on Funen and in South Jutland. Cocaine was most frequently detected in East Denmark, while amphetamine was more frequent in West Denmark. CONCLUSIONS: The number of fatal poisonings among drug addicts has stabilised around 200. The increase in methadone deaths continued and, as in 2007, methadone...... with 2007, indicating that a considerable number of drug addicts also have psychiatric illness. FUNDING: none. TRIAL REGISTRATION: not relevant....

Fatal poisoning among patients with drug addiction

DEFF Research Database (Denmark)

Simonsen, K. W.; Christoffersen, D. J.; Banner, J.

2015-01-01

Introduction: Fatal poisonings among drug addicts in Denmark in 2012 were examined. Cause of death, abuse pattern and geographic differences are discussed and data are compared with previous studies. Methods: All fatal poisonings examined at the three institutes of forensic medicine in Denmark...... on Funen and in South Jutland. Cocaine was most frequently detected in East Denmark, while amphetamine was more frequent in West Denmark. ConclusionS: The number of fatal poisonings among drug addicts has stabilised around 200. The increase in methadone deaths continued and, as in 2007, methadone...... with 2007, indicating that a considerable number of drug addicts also have psychiatric illness....
Mitochondrial morphology and cardiovascular disease

OpenAIRE

Ong, Sang-Bing; Hausenloy, Derek J.

2010-01-01

Mitochondria are dynamic and are able to interchange their morphology between elongated interconnected mitochondrial networks and a fragmented disconnected arrangement by the processes of mitochondrial fusion and fission, respectively. Changes in mitochondrial morphology are regulated by the mitochondrial fusion proteins (mitofusins 1 and 2, and optic atrophy 1) and the mitochondrial fission proteins (dynamin-related peptide 1 and mitochondrial fission protein 1) and have been implicated in a...
Fatal injuries among grounds maintenance workers: United States, 2003--2008.

Science.gov (United States)

2011-05-06

A total of 1,142 grounds maintenance workers (GMWs) were fatally injured at work during 2003--2008, an average of 190 each year. GMWs accounted for 3.4% of all occupational fatalities, and 31% of those GMWs were Hispanic or Latino. Approximately 83% of the Hispanic or Latino GMWs who died were born outside the United States. In 2008, approximately 1.52 million persons were employed as GMWs, constituting 1.0% of the U.S. workforce. During 2003--2007, an average of 13.3 per 100,000 employed GMWs died each year, compared with an overall rate of 4.0 fatalities per 100,000 U.S. workers. The rate of on-the-job fatal injuries among GMWs has remained elevated relative to other workers for >20 years. This report characterizes events leading to GMW fatalities and differences in fatality characteristics across demographic groups among GMWs, based on an evaluation of 2003--2008 data from the U.S. Department of Labor's Bureau of Labor Statistics (BLS) Census of Fatal Occupational Injuries (CFOI) program. The report also identifies workplace interventions that might reduce the incidence of fatal injuries. Major events leading to GMW occupational fatalities included transportation incidents (31%), contact with objects and equipment (25%), falls (23%), and traumatic acute exposures to harmful substances or environments (e.g., electrocution and drowning) (16%). To reduce the incidence of such fatalities, employers, trade and worker associations, and policy makers should focus on effective, targeted workplace safety interventions such as frequent hazard identification and training for specific hazards. Diversity among the populations of workers requires use of culture- and language-appropriate training techniques as part of comprehensive injury and illness prevention programs.
Clinical diagnosis versus autopsy findings in polytrauma fatalities

Directory of Open Access Journals (Sweden)

Fakler Johannes K

2010-10-01

Full Text Available Abstract Objectives The aim of the study was to determine if differences in clinical diagnosis versus autopsy findings concerning the cause of death in polytrauma fatalities would be detected in 19 cases of fatal polytrauma from a Level 1 trauma centre. Methods Clinical diagnoses determining the cause of death in 19 cases of fatal polytrauma (2007 - 2008 from a Level 1 trauma centre were correlated with autopsy findings. Results In 13 cases (68%, the clinical cause of death and the cause of death as determined by autopsy were congruent. Marginal differences occurred in three (16% patients while obvious differences in interpreting the cause of death were found in another three (16% cases. Five fatalities (three with obvious differences and two with marginal differences were remarked as early death (1-4 h after trauma and one fatality with marginal differences as late death (>1 week after trauma. Obvious and marginal discrepancies mostly occurred in the early phase of treatment, especially when severely injured patients were admitted to the emergency room undergoing continued cardiopulmonary resuscitation, i. e. limiting diagnostic procedures, and thus the clinical cause of death was essentially determined by basic emergency diagnostics. Conclusions Autopsy as golden standard to define the cause of death in fatal polytrauma varies from the clinical point of view, depending on the patient's pre-existing condition, mechanism of polytrauma, necessity of traumatic cardiopulmonary resuscitation, survival time, and thus the possibility to perform emergency diagnostics. An autopsy should be performed at least in cases of early fatal polytrauma to help establishing the definite cause of death. Moreover, autopsy data should be included in trauma registries as a quality assessment tool.
PINK1 regulates mitochondrial trafficking in dendrites of cortical neurons through mitochondrial PKA.

Science.gov (United States)

Das Banerjee, Tania; Dagda, Raul Y; Dagda, Marisela; Chu, Charleen T; Rice, Monica; Vazquez-Mayorga, Emmanuel; Dagda, Ruben K

2017-08-01

Mitochondrial Protein Kinase A (PKA) and PTEN-induced kinase 1 (PINK1), which is linked to Parkinson's disease, are two neuroprotective serine/threonine kinases that regulate dendrite remodeling and mitochondrial function. We have previously shown that PINK1 regulates dendrite morphology by enhancing PKA activity. Here, we show the molecular mechanisms by which PINK1 and PKA in the mitochondrion interact to regulate dendrite remodeling, mitochondrial morphology, content, and trafficking in dendrites. PINK1-deficient cortical neurons exhibit impaired mitochondrial trafficking, reduced mitochondrial content, fragmented mitochondria, and a reduction in dendrite outgrowth compared to wild-type neurons. Transient expression of wild-type, but not a PKA-binding-deficient mutant of the PKA-mitochondrial scaffold dual-specificity A Kinase Anchoring Protein 1 (D-AKAP1), restores mitochondrial trafficking, morphology, and content in dendrites of PINK1-deficient cortical neurons suggesting that recruiting PKA to the mitochondrion reverses mitochondrial pathology in dendrites induced by loss of PINK1. Mechanistically, full-length and cleaved forms of PINK1 increase the binding of the regulatory subunit β of PKA (PKA/RIIβ) to D-AKAP1 to enhance the autocatalytic-mediated phosphorylation of PKA/RIIβ and PKA activity. D-AKAP1/PKA governs mitochondrial trafficking in dendrites via the Miro-2/TRAK2 complex and by increasing the phosphorylation of Miro-2. Our study identifies a new role of D-AKAP1 in regulating mitochondrial trafficking through Miro-2, and supports a model in which PINK1 and mitochondrial PKA participate in a similar neuroprotective signaling pathway to maintain dendrite connectivity. © 2017 International Society for Neurochemistry.
Overexpression of mitochondrial sirtuins alters glycolysis and mitochondrial function in HEK293 cells.

Directory of Open Access Journals (Sweden)

Michelle Barbi de Moura

Full Text Available SIRT3, SIRT4, and SIRT5 are mitochondrial deacylases that impact multiple facets of energy metabolism and mitochondrial function. SIRT3 activates several mitochondrial enzymes, SIRT4 represses its targets, and SIRT5 has been shown to both activate and repress mitochondrial enzymes. To gain insight into the relative effects of the mitochondrial sirtuins in governing mitochondrial energy metabolism, SIRT3, SIRT4, and SIRT5 overexpressing HEK293 cells were directly compared. When grown under standard cell culture conditions (25 mM glucose all three sirtuins induced increases in mitochondrial respiration, glycolysis, and glucose oxidation, but with no change in growth rate or in steady-state ATP concentration. Increased proton leak, as evidenced by oxygen consumption in the presence of oligomycin, appeared to explain much of the increase in basal oxygen utilization. Growth in 5 mM glucose normalized the elevations in basal oxygen consumption, proton leak, and glycolysis in all sirtuin over-expressing cells. While the above effects were common to all three mitochondrial sirtuins, some differences between the SIRT3, SIRT4, and SIRT5 expressing cells were noted. Only SIRT3 overexpression affected fatty acid metabolism, and only SIRT4 overexpression altered superoxide levels and mitochondrial membrane potential. We conclude that all three mitochondrial sirtuins can promote increased mitochondrial respiration and cellular metabolism. SIRT3, SIRT4, and SIRT5 appear to respond to excess glucose by inducing a coordinated increase of glycolysis and respiration, with the excess energy dissipated via proton leak.
Neonatal doses from X ray examinations by birth weight in a neonatal intensive care unit

Energy Technology Data Exchange (ETDEWEB)

Ono, K.; Akahane, K.; Aota, T.; Hada, M.; Takano, Y.; Kai, M.; Kusama, T

2003-07-01

The aim of this study was to investigate the frequency and type of X ray examinations performed on neonates classified according to their birth weight in a neonatal intensive care unit (NICU). In this study, the radiology records of 2408 neonates who were admitted to the NICU of Oita Prefectural Hospital between January 1994 and September 1999 were investigated. This study revealed that the neonates with earlier gestational ages and lower birth weights required longer NICU stays and more frequent X ray examinations made using a mobile X ray unit. The average number of X ray examinations performed on neonates of less than 750 g birth weight was 26 films per neonate. In regard to computed tomography and fluoroscopy, no significant relationship was found between the birth weight and number of X rays. This study revealed that the entrance-surface dose per neonate was dependent upon the birth weight, while the maximum dose was not dependent upon the birth weight. The average neonatal dose in the NICU was predominantly from computed tomography and fluoroscopy. The individual dose varied widely among neonates. (author)
Neonatal doses from X ray examinations by birth weight in a neonatal intensive care unit

International Nuclear Information System (INIS)

Ono, K.; Akahane, K.; Aota, T.; Hada, M.; Takano, Y.; Kai, M.; Kusama, T.

2003-01-01

The aim of this study was to investigate the frequency and type of X ray examinations performed on neonates classified according to their birth weight in a neonatal intensive care unit (NICU). In this study, the radiology records of 2408 neonates who were admitted to the NICU of Oita Prefectural Hospital between January 1994 and September 1999 were investigated. This study revealed that the neonates with earlier gestational ages and lower birth weights required longer NICU stays and more frequent X ray examinations made using a mobile X ray unit. The average number of X ray examinations performed on neonates of less than 750 g birth weight was 26 films per neonate. In regard to computed tomography and fluoroscopy, no significant relationship was found between the birth weight and number of X rays. This study revealed that the entrance-surface dose per neonate was dependent upon the birth weight, while the maximum dose was not dependent upon the birth weight. The average neonatal dose in the NICU was predominantly from computed tomography and fluoroscopy. The individual dose varied widely among neonates. (author)
Mitochondrial DNA triplication and punctual mutations in patients with mitochondrial neuromuscular disorders

Energy Technology Data Exchange (ETDEWEB)

Mkaouar-Rebai, Emna, E-mail: emna.mkaouar@gmail.com [Département des Sciences de la Vie, Faculté des Sciences de Sfax, Université de Sfax (Tunisia); Felhi, Rahma; Tabebi, Mouna [Laboratoire de Génétique Moléculaire Humaine, Faculté de Médecine de Sfax, Université de Sfax (Tunisia); Alila-Fersi, Olfa; Chamkha, Imen [Département des Sciences de la Vie, Faculté des Sciences de Sfax, Université de Sfax (Tunisia); Maalej, Marwa; Ammar, Marwa [Laboratoire de Génétique Moléculaire Humaine, Faculté de Médecine de Sfax, Université de Sfax (Tunisia); Kammoun, Fatma [Service de pédiatrie, C.H.U. Hedi Chaker de Sfax (Tunisia); Keskes, Leila [Laboratoire de Génétique Moléculaire Humaine, Faculté de Médecine de Sfax, Université de Sfax (Tunisia); Hachicha, Mongia [Service de pédiatrie, C.H.U. Hedi Chaker de Sfax (Tunisia); Fakhfakh, Faiza, E-mail: faiza.fakhfakh02@gmail.com [Département des Sciences de la Vie, Faculté des Sciences de Sfax, Université de Sfax (Tunisia)

2016-04-29

Mitochondrial diseases are a heterogeneous group of disorders caused by the impairment of the mitochondrial oxidative phosphorylation system which have been associated with various mutations of the mitochondrial DNA (mtDNA) and nuclear gene mutations. The clinical phenotypes are very diverse and the spectrum is still expanding. As brain and muscle are highly dependent on OXPHOS, consequently, neurological disorders and myopathy are common features of mtDNA mutations. Mutations in mtDNA can be classified into three categories: large-scale rearrangements, point mutations in tRNA or rRNA genes and point mutations in protein coding genes. In the present report, we screened mitochondrial genes of complex I, III, IV and V in 2 patients with mitochondrial neuromuscular disorders. The results showed the presence the pathogenic heteroplasmic m.9157G>A variation (A211T) in the MT-ATP6 gene in the first patient. We also reported the first case of triplication of 9 bp in the mitochondrial NC7 region in Africa and Tunisia, in association with the novel m.14924T>C in the MT-CYB gene in the second patient with mitochondrial neuromuscular disorder. - Highlights: • We reported 2 patients with mitochondrial neuromuscular disorders. • The heteroplasmic MT-ATP6 9157G>A variation was reported. • A triplication of 9 bp in the mitochondrial NC7 region was detected. • The m.14924T>C transition (S60P) in the MT-CYB gene was found.
Current perspectives on neonatal hypoglycemia, its management, and cerebral injury risk

Directory of Open Access Journals (Sweden)

Chandran S

2015-02-01

Full Text Available Suresh Chandran,1–4 Victor Samuel Rajadurai,1–3 Abdul Alim Abdul Haium,1–3 Khalid Hussain5,6 1Department of Neonatology, KK Women’s and Children’s Hospital, Singapore; 2Duke-NUS Graduate School of Medicine, Singapore; 3Yong Loo Lin School of Medicine, National University of Singapore, Singapore; 4Lee Kong Chian School of Medicine, Nanyang Technological University, Singapore; 5Department of Paediatric Endocrinology, Great Ormond Street Hospital for Children, NHS Foundation Trust, London, 6The Institute of Child Health, University College London, London, UK Abstract: Glucose is an essential substrate for mammalian cells; in particular, the brain needs glucose continuously as a primary source of energy. Hypoglycemia is the most common biochemical finding in the neonatal period. However, despite the common occurrence, there is still controversy on the definition of hypoglycemia in the newborn period. This has led to the development of guidelines designed to identify infants “at-risk” and the implementation of an “operational threshold” for physicians to consider intervention. In healthy term infants, the optimal hormonal and metabolic adaptations during the immediate neonatal period ensure an adequate energy substrate for the vital organs, whereas the abnormal glucose homeostasis observed in preterm and growth-retarded infants is multifactorial in origin. For these high-risk infants, it is important to identify, screen, and prevent significant hypoglycemia. Detailed investigations are warranted in infants with severe and persistent hypoglycemia. Neonatal hypoglycemia is a major cause of brain injury. The speculated mechanisms of cellular injury include excitatory neurotoxins active at N-methyl-D-aspartate receptors, increased mitochondrial free radical generation with initiation of apoptosis and altered cerebral energetic characteristics. This hypoglycemic brain injury predominantly affects parieto-occipital regions causing
Dehydration Comes on Fast and Can Be Fatal

Science.gov (United States)

... can be fatal Dehydration comes on fast and can be fatal During the hot summer months,the ... and keeping hydrated. “Dehydration is very dangerous. It can lead to an emergency visit, and it can ...
Alcohol Advertising and Motor Vehicle Fatalities

OpenAIRE

Henry Saffer

1994-01-01

The purpose of this paper is to empirically estimate the effect of alcohol advertising on motor vehicle fatalities. The concept of an industry level advertising response function is developed and other empirical issues in estimating the effects of advertising are reviewed. The data set consists of quarterly observations, from 1986 to 1989, for 75 advertising markets in the United States and includes 1200 observations. Since motor vehicle fatalities and alcohol advertising are jointly determin...
No to fatalism

International Nuclear Information System (INIS)

Pecqueur, Michel

1980-01-01

By saying 'No to fatalism', M. Pecqueur is forming the wish that the recent awarness of the energy situation, far from bringing about resignation, speeds up the implementation of the indispensable measures on which the economic and political stability of the world depends in the decade ahead [fr
Neonatal neurosonography

Energy Technology Data Exchange (ETDEWEB)

Riccabona, Michael, E-mail: michael.riccabona@klinikum-graz.at

2014-09-15

Paediatric and particularly neonatal neurosonography still remains a mainstay of imaging the neonatal brain. It can be performed at the bedside without any need for sedation or specific monitoring. There are a number of neurologic conditions that significantly influence morbidity and mortality in neonates and infants related to the brain and the spinal cord; most of them can be addressed by ultrasonography (US). However, with the introduction of first CT and then MRI, neonatal neurosonography is increasingly considered just a basic first line technique that offers only orienting information and does not deliver much relevant information. This is partially caused by inferior US performance – either by restricted availability of modern equipment or by lack of specialized expertise in performing and reading neurosonographic scans. This essay tries to highlight the value and potential of US in the neonatal brain and briefly touching also on the spinal cord imaging. The common pathologies and their US appearance as well as typical indication and applications of neurosonography are listed. The review aims at encouraging paediatric radiologists to reorient there imaging algorithms and skills towards the potential of modern neurosonography, particularly in the view of efficacy, considering growing economic pressure, and the low invasiveness as well as the good availability of US that can easily be repeated any time at the bedside.
Mitochondrial shaping cuts.

Science.gov (United States)

Escobar-Henriques, Mafalda; Langer, Thomas

2006-01-01

A broad range of cellular processes are regulated by proteolytic events. Proteolysis has now also been established to control mitochondrial morphology which results from the balanced action of fusion and fission. Two out of three known core components of the mitochondrial fusion machinery are under proteolytic control. The GTPase Fzo1 in the outer membrane of mitochondria is degraded along two independent proteolytic pathways. One controls mitochondrial fusion in vegetatively growing cells, the other one acts upon mating factor-induced cell cycle arrest. Fusion also depends on proteolytic processing of the GTPase Mgm1 by the rhomboid protease Pcp1 in the inner membrane of mitochondria. Functional links of AAA proteases or other proteolytic components to mitochondrial dynamics are just emerging. This review summarises the current understanding of regulatory roles of proteolytic processes for mitochondrial plasticity.
Socioeconomic factors and adolescent pregnancy outcomes: distinctions between neonatal and post-neonatal deaths?

Directory of Open Access Journals (Sweden)

Flick Louise H

2005-07-01

Full Text Available Abstract Background Young maternal age has long been associated with higher infant mortality rates, but the role of socioeconomic factors in this association has been controversial. We sought to investigate the relationships between infant mortality (distinguishing neonatal from post-neonatal deaths, socioeconomic status and maternal age in a large, retrospective cohort study. Methods We conducted a population-based cohort study using linked birth-death certificate data for Missouri residents during 1997–1999. Infant mortality rates for all singleton births to adolescent women (12–17 years, n = 10,131; 18–19 years, n = 18,954 were compared to those for older women (20–35 years, n = 28,899. Logistic regression was used to estimate adjusted odds ratios (OR and 95% confidence intervals (CI for all potential associations. Results The risk of infant (OR 1.95, CI 1.54–2.48, neonatal (1.69, 1.24–2.31 and post-neonatal mortality (2.47, 1.70–3.59 were significantly higher for younger adolescent (12–17 years than older (20–34 years mothers. After adjusting for race, marital status, age-appropriate education level, parity, smoking status, prenatal care utilization, and poverty status (indicated by participation in WIC, food stamps or Medicaid, the risk of post-neonatal mortality (1.73, 1.14–2.64 but not neonatal mortality (1.43, 0.98–2.08 remained significant for younger adolescent mothers. There were no differences in neonatal or post-neonatal mortality risks for older adolescent (18–19 years mothers. Conclusion Socioeconomic factors may largely explain the increased neonatal mortality risk among younger adolescent mothers but not the increase in post-neonatal mortality risk.
Neonatal adrenal hemorrhage presenting as late onset neonatal jaundice

OpenAIRE

Qureshi, Umar Amin; Ahmad, Nisar; Rasool, Akhter; Choh, Suhail

2009-01-01

Clinical manifestations of adrenal hemorrhage vary depending on the degree and rate of hemorrhage, as well as the amount of adrenal cortex compromised by hemorrhage. We report here a case of neonatal adrenal hemorrhage that presented with late onset neonatal jaundice. The cause of adrenal hemorrhage was birth asphyxia.
The effect of mitochondrial calcium uniporter on mitochondrial fission in hippocampus cells ischemia/reperfusion injury

Energy Technology Data Exchange (ETDEWEB)

Zhao, Lantao; Li, Shuhong; Wang, Shilei, E-mail: wshlei@aliyun.com; Yu, Ning; Liu, Jia

2015-06-05

The mitochondrial calcium uniporter (MCU) transports free Ca{sup 2+} into the mitochondrial matrix, maintaining Ca{sup 2+} homeostasis, thus regulates the mitochondrial morphology. Previous studies have indicated that there was closely crosstalk between MCU and mitochondrial fission during the process of ischemia/reperfusion injury. This study constructed a hypoxia reoxygenation model using primary hippocampus neurons to mimic the cerebral ischemia/reperfusion injury and aims to explore the exactly effect of MCU on the mitochondrial fission during the process of ischemia/reperfusion injury and so as the mechanisms. Our results found that the inhibitor of the MCU, Ru360, decreased mitochondrial Ca{sup 2+} concentration, suppressed the expression of mitochondrial fission protein Drp1, MIEF1 and Fis1, and thus improved mitochondrial morphology significantly. Whereas spermine, the agonist of the MCU, had no significant impact compared to the I/R group. This study demonstrated that the MCU regulates the process of mitochondrial fission by controlling the Ca{sup 2+} transport, directly upregulating mitochondrial fission proteins Drp1, Fis1 and indirectly reversing the MIEF1-induced mitochondrial fusion. It also provides new targets for brain protection during ischemia/reperfusion injury. - Highlights: • We study MCU with primary neuron culture. • MCU induces mitochondrial fission. • MCU reverses MIEF1 effect.
Fatal falls in the US construction industry, 1990 to 1999.

Science.gov (United States)

Derr, J; Forst, L; Chen, H Y; Conroy, L

2001-10-01

The Occupational Safety and Health Administration's (OSHA's) Integrated Management Information System (IMIS) database allows for the detailed analysis of risk factors surrounding fatal occupational events. This study used IMIS data to (1) perform a risk factor analysis of fatal construction falls, and (2) assess the impact of the February 1995 29 CFR Part 1926 Subpart M OSHA fall protection regulations for construction by calculating trends in fatal fall rates. In addition, IMIS data on fatal construction falls were compared with data from other occupational fatality surveillance systems. For falls in construction, the study identified several demographic factors that may indicate increased risk. A statistically significant downward trend in fatal falls was evident in all construction and within several construction categories during the decade. Although the study failed to show a statistically significant intervention effect from the new OSHA regulations, it may have lacked the power to do so.
Cannabis, alcohol and fatal road accidents.

Science.gov (United States)

Martin, Jean-Louis; Gadegbeku, Blandine; Wu, Dan; Viallon, Vivian; Laumon, Bernard

2017-01-01

This research aims to estimate the relative risks of responsibility for a fatal accident linked to driving under the influence of cannabis or alcohol, the prevalence of these influences among drivers and the corresponding attributable risk ratios. A secondary goal is to estimate the same items for three other groups of illicit drugs (amphetamines, cocaine and opiates), and to compare the results to a similar study carried out in France between 2001 and 2003. Police procedures for fatal accidents in Metropolitan France during 2011 were analyzed and 300 characteristics encoded to provide a database of 4,059 drivers. Information on alcohol and four groups of illicit drugs derived from tests for positivity and potential confirmation through blood analysis. The study compares drivers responsible for causing the accident, that is to say having directly contributed to its occurrence, to drivers involved in an accident for which they were not responsible, and who can be assimilated to drivers in general. The proportion of persons driving under the influence of alcohol is estimated at 2.1% (95% CI: 1.4-2.8) and under the influence of cannabis at 3.4% (2.9%-3.9%). Drivers under the influence of alcohol are 17.8 times (12.1-26.1) more likely to be responsible for a fatal accident, and the proportion of fatal accidents which would be prevented if no drivers ever exceeded the legal limit for alcohol is estimated at 27.7% (26.0%-29.4%). Drivers under the influence of cannabis multiply their risk of being responsible for causing a fatal accident by 1.65 (1.16-2.34), and the proportion of fatal accidents which would be prevented if no drivers ever drove under the influence of cannabis is estimated at 4.2% (3.7%-4.8%). An increased risk linked to opiate use has also been found to be significant, but with low prevalence, requiring caution in interpreting this finding. Other groups of narcotics have even lower prevalence, and the associated extra risks cannot be assessed. Almost a

Cannabis, alcohol and fatal road accidents.

Directory of Open Access Journals (Sweden)

Jean-Louis Martin

Full Text Available This research aims to estimate the relative risks of responsibility for a fatal accident linked to driving under the influence of cannabis or alcohol, the prevalence of these influences among drivers and the corresponding attributable risk ratios. A secondary goal is to estimate the same items for three other groups of illicit drugs (amphetamines, cocaine and opiates, and to compare the results to a similar study carried out in France between 2001 and 2003.Police procedures for fatal accidents in Metropolitan France during 2011 were analyzed and 300 characteristics encoded to provide a database of 4,059 drivers. Information on alcohol and four groups of illicit drugs derived from tests for positivity and potential confirmation through blood analysis. The study compares drivers responsible for causing the accident, that is to say having directly contributed to its occurrence, to drivers involved in an accident for which they were not responsible, and who can be assimilated to drivers in general.The proportion of persons driving under the influence of alcohol is estimated at 2.1% (95% CI: 1.4-2.8 and under the influence of cannabis at 3.4% (2.9%-3.9%. Drivers under the influence of alcohol are 17.8 times (12.1-26.1 more likely to be responsible for a fatal accident, and the proportion of fatal accidents which would be prevented if no drivers ever exceeded the legal limit for alcohol is estimated at 27.7% (26.0%-29.4%. Drivers under the influence of cannabis multiply their risk of being responsible for causing a fatal accident by 1.65 (1.16-2.34, and the proportion of fatal accidents which would be prevented if no drivers ever drove under the influence of cannabis is estimated at 4.2% (3.7%-4.8%. An increased risk linked to opiate use has also been found to be significant, but with low prevalence, requiring caution in interpreting this finding. Other groups of narcotics have even lower prevalence, and the associated extra risks cannot be assessed
Aviation-Related Wildland Firefighter Fatalities--United States, 2000-2013.

Science.gov (United States)

Butler, Corey R; O'Connor, Mary B; Lincoln, Jennifer M

2015-07-31

Airplanes and helicopters are integral to the management and suppression of wildfires, often operating in high-risk, low-altitude environments. To update data on aviation-related wildland firefighting fatalities, identify risk factors, and make recommendations for improved safety, CDC's National Institute for Occupational Safety and Health (NIOSH) analyzed reports from multiple data sources for the period 2000-2013. Among 298 wildland firefighter fatalities identified during 2000-2013, 78 (26.2%) were aviation-related occupational fatalities that occurred during 41 separate events involving 42 aircraft. Aircraft crashes accounted for 38 events. Pilots, copilots, and flight engineers represented 53 (68%) of the aviation-related fatalities. The leading causes of fatal aircraft crashes were engine, structure, or component failure (24%); pilot loss of control (24%); failure to maintain clearance from terrain, water, or objects (20%); and hazardous weather (15%). To reduce fatalities from aviation-related wildland firefighting activities, stringent safety guidelines need to be followed during all phases of firefighting, including training exercises. Crew resource management techniques, which use all available resources, information, equipment, and personnel to achieve safe and efficient flight operations, can be applied to firefighting operations.
Mitochondrial Morphology and Fundamental Parameters of the Mitochondrial Respiratory Chain Are Altered in Caenorhabditis elegans Strains Deficient in Mitochondrial Dynamics and Homeostasis Processes.

Directory of Open Access Journals (Sweden)

Anthony L Luz

Full Text Available Mitochondrial dysfunction has been linked to myriad human diseases and toxicant exposures, highlighting the need for assays capable of rapidly assessing mitochondrial health in vivo. Here, using the Seahorse XFe24 Analyzer and the pharmacological inhibitors dicyclohexylcarbodiimide and oligomycin (ATP-synthase inhibitors, carbonyl cyanide 4-(trifluoromethoxy phenylhydrazone (mitochondrial uncoupler and sodium azide (cytochrome c oxidase inhibitor, we measured the fundamental parameters of mitochondrial respiratory chain function: basal oxygen consumption, ATP-linked respiration, maximal respiratory capacity, spare respiratory capacity and proton leak in the model organism Caenhorhabditis elegans. Since mutations in mitochondrial homeostasis genes cause mitochondrial dysfunction and have been linked to human disease, we measured mitochondrial respiratory function in mitochondrial fission (drp-1-, fusion (fzo-1-, mitophagy (pdr-1, pink-1-, and electron transport chain complex III (isp-1-deficient C. elegans. All showed altered function, but the nature of the alterations varied between the tested strains. We report increased basal oxygen consumption in drp-1; reduced maximal respiration in drp-1, fzo-1, and isp-1; reduced spare respiratory capacity in drp-1 and fzo-1; reduced proton leak in fzo-1 and isp-1; and increased proton leak in pink-1 nematodes. As mitochondrial morphology can play a role in mitochondrial energetics, we also quantified the mitochondrial aspect ratio for each mutant strain using a novel method, and for the first time report increased aspect ratios in pdr-1- and pink-1-deficient nematodes.
Fatal Child Maltreatment in England, 2005-2009

Science.gov (United States)

Sidebotham, Peter; Bailey, Sue; Belderson, Pippa; Brandon, Marian

2011-01-01

Objective: This paper presents comprehensive and up-to-date data covering 4 years of Serious Case Reviews into fatal child maltreatment in England. Methods: Information on all notified cases of fatal maltreatment between April 2005 and March 2009 was examined to obtain case characteristics related to a systemic classification of 5 broad groups of…
Effects of urban sprawl and vehicle miles traveled on traffic fatalities.

Science.gov (United States)

Yeo, Jiho; Park, Sungjin; Jang, Kitae

2015-01-01

Previous research suggests that urban sprawl increases auto-dependency and that excessive auto use increases the risk of traffic fatalities. This indirect effect of urban sprawl on traffic fatalities is compared to non-vehicle miles traveled (VMT)-related direct effect of sprawl on fatalities. We conducted a path analysis to examine the causal linkages among urban sprawl, VMT, traffic fatalities, income, and fuel cost. The path diagram includes 2 major linkages: the direct relationship between urban sprawl and traffic fatalities and the indirect effect on fatalities through increased VMT in sprawling urban areas. To measure the relative strength of these causal linkages, path coefficients are estimated using data collected nationally from 147 urbanized areas in the United States. Through both direct and indirect paths, urban sprawl is associated with greater numbers of traffic fatalities, but the direct effect of sprawl on fatalities is more influential than the indirect effect. Enhancing traffic safety can be achieved by impeding urban sprawl and encouraging compact development. On the other hand, policy tools reducing VMT may be less effective than anticipated for traffic safety.
Twinkle overexpression prevents cardiac rupture after myocardial infarction by alleviating impaired mitochondrial biogenesis.

Science.gov (United States)

Inoue, Takahiro; Ikeda, Masataka; Ide, Tomomi; Fujino, Takeo; Matsuo, Yuka; Arai, Shinobu; Saku, Keita; Sunagawa, Kenji

2016-09-01

Cardiac rupture is a fatal complication after myocardial infarction (MI). However, the detailed mechanism underlying cardiac rupture after MI remains to be fully elucidated. In this study, we investigated the role of mitochondrial DNA (mtDNA) and mitochondria in the pathophysiology of cardiac rupture by analyzing Twinkle helicase overexpression mice (TW mice). Twinkle overexpression increased mtDNA copy number approximately twofold and ameliorated ischemic cardiomyopathy at day 28 after MI. Notably, Twinkle overexpression markedly prevented cardiac rupture and improved post-MI survival, accompanied by the suppression of MMP-2 and MMP-9 in the MI border area at day 5 after MI when cardiac rupture frequently occurs. Additionally, these cardioprotective effects of Twinkle overexpression were abolished in transgenic mice overexpressing mutant Twinkle with an in-frame duplication of amino acids 353-365, which resulted in no increases in mtDNA copy number. Furthermore, although apoptosis and oxidative stress were induced and mitochondria were damaged in the border area, these injuries were improved in TW mice. Further analysis revealed that mitochondrial biogenesis, including mtDNA copy number, transcription, and translation, was severely impaired in the border area at day 5 In contrast, Twinkle overexpression maintained mtDNA copy number and restored the impaired transcription and translation of mtDNA in the border area. These results demonstrated that Twinkle overexpression alleviated impaired mitochondrial biogenesis in the border area through maintained mtDNA copy number and thereby prevented cardiac rupture accompanied by the reduction of apoptosis and oxidative stress, and suppression of MMP activity. Copyright © 2016 the American Physiological Society.
What Is Mitochondrial DNA?

Science.gov (United States)

... DNA What is mitochondrial DNA? What is mitochondrial DNA? Although most DNA is packaged in chromosomes within ... proteins. For more information about mitochondria and mitochondrial DNA: Molecular Expressions, a web site from the Florida ...
Insomnia symptoms and risk for unintentional fatal injuries--the HUNT Study.

Science.gov (United States)

Laugsand, Lars Erik; Strand, Linn B; Vatten, Lars J; Janszky, Imre; Bjørngaard, Johan Håkon

2014-11-01

To assess the association between insomnia symptoms and risk of fatal unintentional injuries. Population-based prospective cohort study with a mean follow-up of 14 y, linking health survey data with information on insomnia symptoms to the National Cause of Death Registry. Nord-Trøndelag County, Norway. A total of 54,399 men and women 20-89 y of age who participated in the Nord-Trøndelag Health Study between 1995 and 1997. N/A. There were 277 unintentional fatal injuries, including 57 fatal motor vehicle injuries during follow-up. There was a dose-dependent association between the number of insomnia symptoms and risk of unintentional fatal injuries (P for trend 0.001) and fatal motor vehicle injuries (P for trend 0.023), respectively. The proportion of unintentional fatal injuries cases that could have been prevented in the absence of difficulties initiating sleep, difficulties maintaining sleep, and having a feeling of nonrestorative sleep were 8%, 9%, and 8%, respectively. The corresponding estimates for motor vehicle injuries were 34%, 11%, and 10%. Insomnia is a major contributor to both unintentional fatal injuries in general as well as fatal motor vehicle injuries. Increasing public health awareness about insomnia and identifying persons with insomnia may be important in preventing unintentional fatal injuries.
Crash Fatality Rates After Recreational Marijuana Legalization in Washington and Colorado.

Science.gov (United States)

Aydelotte, Jayson D; Brown, Lawrence H; Luftman, Kevin M; Mardock, Alexandra L; Teixeira, Pedro G R; Coopwood, Ben; Brown, Carlos V R

2017-08-01

To evaluate motor vehicle crash fatality rates in the first 2 states with recreational marijuana legalization and compare them with motor vehicle crash fatality rates in similar states without recreational marijuana legalization. We used the US Fatality Analysis Reporting System to determine the annual numbers of motor vehicle crash fatalities between 2009 and 2015 in Washington, Colorado, and 8 control states. We compared year-over-year changes in motor vehicle crash fatality rates (per billion vehicle miles traveled) before and after recreational marijuana legalization with a difference-in-differences approach that controlled for underlying time trends and state-specific population, economic, and traffic characteristics. Pre-recreational marijuana legalization annual changes in motor vehicle crash fatality rates for Washington and Colorado were similar to those for the control states. Post-recreational marijuana legalization changes in motor vehicle crash fatality rates for Washington and Colorado also did not significantly differ from those for the control states (adjusted difference-in-differences coefficient = +0.2 fatalities/billion vehicle miles traveled; 95% confidence interval = -0.4, +0.9). Three years after recreational marijuana legalization, changes in motor vehicle crash fatality rates for Washington and Colorado were not statistically different from those in similar states without recreational marijuana legalization. Future studies over a longer time remain warranted.
Firearm Legislation and Fatal Police Shootings in the United States.

Science.gov (United States)

Kivisto, Aaron J; Ray, Bradley; Phalen, Peter L

2017-07-01

To examine whether stricter firearm legislation is associated with rates of fatal police shootings. We used a cross-sectional, state-level design to evaluate the effect of state-level firearm legislation on rates of fatal police shootings from January 1, 2015, through October 31, 2016. We measured state-level variation in firearm laws with legislative scorecards from the Brady Center, and for fatal police shootings we used The Counted, an online database maintained by The Guardian. State-level firearm legislation was significantly associated with lower rates of fatal police shootings (incidence rate ratio = 0.961; 95% confidence interval = 0.939, 0.984). When we controlled for sociodemographic factors, states in the top quartile of legislative strength had a 51% lower incidence rate than did states in the lowest quartile. Laws aimed at strengthening background checks, promoting safe storage, and reducing gun trafficking were associated with fewer fatal police shootings. Legislative restrictions on firearms are associated with reductions in fatal police shootings. Public Health Implications. Although further research is necessary to determine causality and potential mechanisms, firearm legislation is a potential policy solution for reducing fatal police shootings in the United States.
Exposure assessment of neonates in israel to x-ray radiation during hospitalization at neonatal intensive care unit

International Nuclear Information System (INIS)

Datz, H.

2005-03-01

Nowadays nearly 10% of all births in western countries are premature. In the last decade, there has been an increase of 45% in the number of neonates that were born in Israel. At the same time, the survival of neonates, especially those with very low birth weight, VLBW, (less than 1,500 gr), has increased dramatically. Diagnostic radiology plays an important role in the assessment and treatment of neonates requiring intensive care. During their prolonged and complex hospitalization, these infants are exposed to multiple radiographic examinations involving X-ray radiation. The extent of the examinations that the infant undergoes depends on its birth weight, gestational age and its medical problems, where most of the treatment effort is focused especially on VLBW neonates. Most of the diagnostic X-ray examinations taken during the hospitalization of neonates in the neonatal intensive care unit (NICU) consist of imaging of the respiratory and gastrointestinal systems, namely, the chest and abdomen. The imaging process is done using mobile X-ray units located at the NICUs. Due to their long hospitalization periods and complex medical condition, all neonates, and neonates with VLBW in particular, are exposed to a much higher level of diagnostic radiation, compared to normal newborns. The goal of this research was to assess the extent of the exposure of neonates in Israel to X-ray radiation during their hospitalization at the neonatal intensive care unit. Five NICUs, located at different geographical zones in Israel and treating 20% of all newborns in Israel every year, participated in this research. The research was conducted in three phases: Phase I: Collection of information on radiographic techniques and exposure parameters (e.g. kV, mAs, focus to skin distance (FSD), examination borders). 499 X-ray examinations (from 157 neonates) were evaluated for necessary and unnecessary exposure of the neonate's organs to X-ray radiation during these examinations. Phase II
Mitochondrial disease and endocrine dysfunction.

Science.gov (United States)

Chow, Jasmine; Rahman, Joyeeta; Achermann, John C; Dattani, Mehul T; Rahman, Shamima

2017-02-01

Mitochondria are critical organelles for endocrine health; steroid hormone biosynthesis occurs in these organelles and they provide energy in the form of ATP for hormone production and trafficking. Mitochondrial diseases are multisystem disorders that feature defective oxidative phosphorylation, and are characterized by enormous clinical, biochemical and genetic heterogeneity. To date, mitochondrial diseases have been found to result from >250 monogenic defects encoded across two genomes: the nuclear genome and the ancient circular mitochondrial genome located within mitochondria themselves. Endocrine dysfunction is often observed in genetic mitochondrial diseases and reflects decreased intracellular production or extracellular secretion of hormones. Diabetes mellitus is the most frequently described endocrine disturbance in patients with inherited mitochondrial diseases, but other endocrine manifestations in these patients can include growth hormone deficiency, hypogonadism, adrenal dysfunction, hypoparathyroidism and thyroid disease. Although mitochondrial endocrine dysfunction frequently occurs in the context of multisystem disease, some mitochondrial disorders are characterized by isolated endocrine involvement. Furthermore, additional monogenic mitochondrial endocrine diseases are anticipated to be revealed by the application of genome-wide next-generation sequencing approaches in the future. Understanding the mitochondrial basis of endocrine disturbance is key to developing innovative therapies for patients with mitochondrial diseases.
Neonatal pain management

Directory of Open Access Journals (Sweden)

Tarun Bhalla

2014-01-01

Full Text Available The past 2-3 decades have seen dramatic changes in the approach to pain management in the neonate. These practices started with refuting previously held misconceptions regarding nociception in preterm infants. Although neonates were initially thought to have limited response to painful stimuli, it was demonstrated that the developmental immaturity of the central nervous system makes the neonate more likely to feel pain. It was further demonstrated that untreated pain can have long-lasting physiologic and neurodevelopmental consequences. These concerns have resulted in a significant emphasis on improving and optimizing the techniques of analgesia for neonates and infants. The following article will review techniques for pain assessment, prevention, and treatment in this population with a specific focus on acute pain related to medical and surgical conditions.
Causes of Neonatal Mortality in the Neonatal Intensive Care Unit of Taleghani Hospital

Directory of Open Access Journals (Sweden)

Ali Hossein Zeinalzadeh

2017-09-01

Full Text Available Background: Neonatal survival is one of the most important challenges today. Over 99% of neonatal mortalities occur in the developing countries, and epidemiologic studies emphasize on this issue in the developed countries, as well. In this study, we attempted to investigate the causes of neonatal mortality in Taleghani Hospital, Tabriz, Iran.Methods: In this cross-sectional study, we studied causes of neonatal mortality in neonatal intensive care unit (NICU of Taleghani Hospital, Tabriz, Iran, during 2013-2014. Data collection was performed by the head nurse and treating physician using a pre-designed questionnaire. Most of the data were extracted from the neonatal records. Information regarding maternal underlying diseases and health care during pregnancy was extracted from mothers' records.Results: A total of 891 neonates were admitted to NICU of Taleghani Hospital of Tabriz, Iran, during 2013-2014, 68 (7.5% of whom died. Among these cases, 37 (%54.4 were male, 29 (29.4% were extremely low birth weight, and 16 (23.5% weighed more than 2.5 kg. The main causes of mortality were congenital anomalies (35.3%, prematurity (26.5%, and sepsis (10.3%, respectively.Conclusion: Congenital anomaly is the most common cause of mortality, and the pattern of death is changing from preventable diseases to unavoidable mortalities
Developments in neonatal care and nursing responses.

Science.gov (United States)

Healy, Patricia; Fallon, Anne

This article reviews the origins and evolution of neonatology and considers the role of the neonatal nurse within this specialty. Neonatal nurses are a vital part of the neonatal team that provides care for sick babies. The nursing care required by sick babies and their families on a neonatal unit can be variable and complex. The past century has seen significant changes in the role of the neonatal nurse. This has come about through dramatic technological developments on neonatal units, an increased understanding of neonatal physiology and pathology, changes in the education of neonatal nurses, and active and ongoing clinical research within the specialty. The resulting significant advances in neonatal care, including that provided by neonatal nurses, have made a crucial and steadfast contribution to marked improvements in neonatal outcomes.
Patterns of admission and factors associated with neonatal mortality among neonates admitted to the neonatal intensive care unit of University of Gondar Hospital, Northwest Ethiopia

Directory of Open Access Journals (Sweden)

Demisse AG

2017-05-01

Full Text Available Abayneh Girma Demisse, Fentahun Alemu, Mahlet Abayneh Gizaw, Zemene Tigabu School of Medicine, College of Medicine and Health Science, University of Gondar, Gondar, Ethiopia Introduction: The neonatal period is a highly vulnerable time for an infant completing many of the physiologic adjustments required for life outside the uterus. As a result, there are high rates of morbidity and mortality. The three major causes of mortality in developing countries include prematurity, infection, and perinatal asphyxia. The aim of this study was to identify the patterns of neonatal admission and factors associated with mortality among neonates admitted at the Neonatal Intensive Care Unit (NICU of University of Gondar Hospital.Materials and methods: A retrospective cross-sectional study was conducted among all admitted neonates in the NICU of University of Gondar referral hospital from December 1, 2015 to August 31, 2016. Information was extracted retrospectively during admission from patient records and death certificates, using a pretested questionnaire. The data were entered and analyzed using SPSS version 20, and p-values <0.05 were considered statistically significant.Results: A total of 769 neonates was included in the study. There were 448 (58.3% male neonates, and 398 (51.8% neonates were rural residents. More than two-thirds of the 587 deliveries (76.3% were performed in tertiary hospitals. Neonatal morbidity included hypothermia 546 (71%, sepsis 522 (67.9%, prematurity 250 (34.9%, polycythemia 242 (31.5%, hypoglycemia 142 (18.5, meconium aspiration syndrome 113 (14.7%, and perinatal asphyxia 96 (12.5%. The overall mortality was 110 (14.3%; 95% confidence interval [CI]: 11.9–16.9 of which 69 (62.7% deaths occurred in the first 24 hours of age. In the multivariate analysis, mortality was associated with perinatal asphyxia (adjusted odds ratio [AOR]: 5.97; 95% CI: 3.06–11.64, instrumental delivery (AOR: 2.99; 95% CI: 1.08–8.31, and early onset
Volume and leak measurements during neonatal CPAP in neonates

OpenAIRE

Fischer, Hendrik S.

2011-01-01

As yet, little is known about the effects of air leakages during CPAP in newborns. The present doctoral dissertation investigates tidal volume and leak measurements during nasal continuous positive airway pressure in neonates using a commercial ventilatory device. Investigations include in vitro studies, modelling and computer simulation as well as a clinical randomized cross-over trial in neonates.
Dengue virus induces mitochondrial elongation through impairment of Drp1-triggered mitochondrial fission

Energy Technology Data Exchange (ETDEWEB)

Barbier, Vincent; Lang, Diane; Valois, Sierra; Rothman, Alan L.; Medin, Carey L., E-mail: cmedin.uri@gmail.com

2017-01-15

Mitochondria are highly dynamic organelles that undergo continuous cycles of fission and fusion to maintain essential cellular functions. An imbalance between these two processes can result in many pathophysiological outcomes. Dengue virus (DENV) interacts with cellular organelles, including mitochondria, to successfully replicate in cells. This study used live-cell imaging and found an increase in mitochondrial length and respiration during DENV infection. The level of mitochondrial fission protein, Dynamin-related protein 1 (Drp1), was decreased on mitochondria during DENV infection, as well as Drp1 phosphorylated on serine 616, which is important for mitochondrial fission. DENV proteins NS4b and NS3 were also associated with subcellular fractions of mitochondria. Induction of fission through uncoupling of mitochondria or overexpression of Drp1 wild-type and Drp1 with a phosphomimetic mutation (S616D) significantly reduced viral replication. These results demonstrate that DENV infection causes an imbalance in mitochondrial dynamics by inhibiting Drp1-triggered mitochondrial fission, which promotes viral replication. - Highlights: •Mitochondrial length and respiration are increased during DENV infection. •DENV inhibits Drp1-triggered mitochondrial fission. •DENV titers are reduced by mitochondrial fragmentation, Drp1 WT and S616D expression. •Viral proteins NS4b and NS3 are associated with subcellular fractions of mitochondria.
Dengue virus induces mitochondrial elongation through impairment of Drp1-triggered mitochondrial fission

International Nuclear Information System (INIS)

Barbier, Vincent; Lang, Diane; Valois, Sierra; Rothman, Alan L.; Medin, Carey L.

2017-01-01

Mitochondria are highly dynamic organelles that undergo continuous cycles of fission and fusion to maintain essential cellular functions. An imbalance between these two processes can result in many pathophysiological outcomes. Dengue virus (DENV) interacts with cellular organelles, including mitochondria, to successfully replicate in cells. This study used live-cell imaging and found an increase in mitochondrial length and respiration during DENV infection. The level of mitochondrial fission protein, Dynamin-related protein 1 (Drp1), was decreased on mitochondria during DENV infection, as well as Drp1 phosphorylated on serine 616, which is important for mitochondrial fission. DENV proteins NS4b and NS3 were also associated with subcellular fractions of mitochondria. Induction of fission through uncoupling of mitochondria or overexpression of Drp1 wild-type and Drp1 with a phosphomimetic mutation (S616D) significantly reduced viral replication. These results demonstrate that DENV infection causes an imbalance in mitochondrial dynamics by inhibiting Drp1-triggered mitochondrial fission, which promotes viral replication. - Highlights: •Mitochondrial length and respiration are increased during DENV infection. •DENV inhibits Drp1-triggered mitochondrial fission. •DENV titers are reduced by mitochondrial fragmentation, Drp1 WT and S616D expression. •Viral proteins NS4b and NS3 are associated with subcellular fractions of mitochondria.
Novel Functional Role of Heat Shock Protein 90 in Mitochondrial Connexin 43-Mediated Hypoxic Postconditioning

Directory of Open Access Journals (Sweden)

Rong-Hui Tu

2017-11-01

Full Text Available Background/Aims: Previous studies have shown that heat shock protein 90 (HSP90-mediated mitochondrial import of connexin 43 (Cx43 is critical in preconditioning cardioprotection. The present study was designed to test whether postconditioning has the same effect as preconditioning in promoting Cx43 translocation to mitochondria and whether mitochondrial HSP90 modulates this effect. Methods: Cellular models of hypoxic postconditioning (HPC from rat heart-derived H9c2 cells and neonatal rat cardiomyocytes were employed. The effects of HPC on cardiomyocytes apoptosis were examined by flow cytometry and Hoechst 33342 fluorescent staining. Reactive oxidative species (ROS production was assessed with the peroxide-sensitive fluorescent probe 2′,7′-dichlorofluorescin in diacetate (DCFH-DA. The anti- and pro-apoptotic markers Bcl-2 and Bax, HSP90 and Cx43 protein levels were studied by Western blot analysis in total cell homogenate and sarcolemmal and mitochondrial fractions. The effects on HPC of the HSP90 inhibitor geldanamycin (GA, ROS scavengers superoxide dismutase (SOD and catalase (CAT, and small interfering RNA (siRNA targeting Cx43 and HSP90 were also investigated. Results: HPC significantly reduced hypoxia/reoxygenation (H/R-induced cardiomyocyte apoptosis. These beneficial effects were accompanied by an increase in Bcl-2 levels and a decrease in Bax levels in both sarcolemmal and mitochondrial fractions. HPC with siRNA targeting Cx43 or the ROS scavengers SOD plus CAT significantly prevented ROS generation and HPC cardioprotection, but HPC with either SOD or CAT did not. These data strongly supported the involvement of Cx43 in HPC cardioprotection, likely via modulation of the ROS balance which plays a central role in HPC protection. Furthermore, HPC increased total and mitochondrial levels of HSP90 and the mitochondria-to-sarcolemma ratio of Cx43; blocking the function of HSP90 with the HSP90 inhibitor geldanamycin (GA or siRNA targeting

Investigation of hot air balloon fatalities.

Science.gov (United States)

McConnell, T S; Smialek, J E; Capron, R G

1985-04-01

The rising popularity of the sport of hot air ballooning has been accompanied by several recent incidents, both in this country and other parts of the world, where mechanical defects and the improper operation of balloons have resulted in several fatalities. A study was conducted to identify the location and frequency of hot air ballooning accidents. Furthermore, the study attempted to identify those accidents that were the result of improper handling on the part of the balloon operators and those that were related to specific defects in the construction of the balloon. This paper presents a background of the sport of hot air ballooning, together with an analysis of the construction of a typical hot air balloon, pointing out the specific areas where defects may occur that could result in a potential fatal balloon crash. Specific attention is given to the two recent balloon crashes that occurred in Albuquerque, N.M., hot air balloon capital of the world, and that resulted in multiple fatalities.
Disruption of mitochondrial DNA replication in Drosophila increases mitochondrial fast axonal transport in vivo.

Directory of Open Access Journals (Sweden)

Rehan M Baqri

Full Text Available Mutations in mitochondrial DNA polymerase (pol gamma cause several progressive human diseases including Parkinson's disease, Alper's syndrome, and progressive external ophthalmoplegia. At the cellular level, disruption of pol gamma leads to depletion of mtDNA, disrupts the mitochondrial respiratory chain, and increases susceptibility to oxidative stress. Although recent studies have intensified focus on the role of mtDNA in neuronal diseases, the changes that take place in mitochondrial biogenesis and mitochondrial axonal transport when mtDNA replication is disrupted are unknown. Using high-speed confocal microscopy, electron microscopy and biochemical approaches, we report that mutations in pol gamma deplete mtDNA levels and lead to an increase in mitochondrial density in Drosophila proximal nerves and muscles, without a noticeable increase in mitochondrial fragmentation. Furthermore, there is a rise in flux of bidirectional mitochondrial axonal transport, albeit with slower kinesin-based anterograde transport. In contrast, flux of synaptic vesicle precursors was modestly decreased in pol gamma-alpha mutants. Our data indicate that disruption of mtDNA replication does not hinder mitochondrial biogenesis, increases mitochondrial axonal transport, and raises the question of whether high levels of circulating mtDNA-deficient mitochondria are beneficial or deleterious in mtDNA diseases.
Mitochondrial DNA depletion syndrome due to mutations in the RRM2B gene.

Science.gov (United States)

Bornstein, Belén; Area, Estela; Flanigan, Kevin M; Ganesh, Jaya; Jayakar, Parul; Swoboda, Kathryn J; Coku, Jorida; Naini, Ali; Shanske, Sara; Tanji, Kurenai; Hirano, Michio; DiMauro, Salvatore

2008-06-01

Mitochondrial DNA depletion syndrome (MDS) is characterized by a reduction in mtDNA copy number and has been associated with mutations in eight nuclear genes, including enzymes involved in mitochondrial nucleotide metabolism (POLG, TK2, DGUOK, SUCLA2, SUCLG1, PEO1) and MPV17. Recently, mutations in the RRM2B gene, encoding the p53-controlled ribonucleotide reductase subunit, have been described in seven infants from four families, who presented with various combinations of hypotonia, tubulopathy, seizures, respiratory distress, diarrhea, and lactic acidosis. All children died before 4 months of age. We sequenced the RRM2B gene in three unrelated cases with unexplained severe mtDNA depletion. The first patient developed intractable diarrhea, profound weakness, respiratory distress, and died at 3 months. The other two unrelated patients had a much milder phenotype and are still alive at ages 27 and 36 months. All three patients had lactic acidosis and severe depletion of mtDNA in muscle. Muscle histochemistry showed RRF and COX deficiency. Sequencing the RRM2B gene revealed three missense mutations and two single nucleotide deletions in exons 6, 8, and 9, confirming that RRM2B mutations are important causes of MDS and that the clinical phenotype is heterogeneous and not invariably fatal in infancy.
Novel mitochondrial extensions provide evidence for a link between microtubule-directed movement and mitochondrial fission

International Nuclear Information System (INIS)

Bowes, Timothy; Gupta, Radhey S.

2008-01-01

Mitochondrial dynamics play an important role in a large number of cellular processes. Previously, we reported that treatment of mammalian cells with the cysteine-alkylators, N-ethylmaleimide and ethacrynic acid, induced rapid mitochondrial fusion forming a large reticulum approximately 30 min after treatment. Here, we further investigated this phenomenon using a number of techniques including live-cell confocal microscopy. In live cells, drug-induced fusion coincided with a cessation of fast mitochondrial movement which was dependent on microtubules. During this loss of movement, thin mitochondrial tubules extending from mitochondria were also observed, which we refer to as 'mitochondrial extensions'. The formation of these mitochondrial extensions, which were not observed in untreated cells, depended on microtubules and was abolished by pretreatment with nocodazole. In this study, we provide evidence that these extensions result from of a block in mitochondrial fission combined with continued application of motile force by microtubule-dependent motor complexes. Our observations strongly suggest the existence of a link between microtubule-based mitochondrial trafficking and mitochondrial fission
Telemedicine in Neonatal Home Care

DEFF Research Database (Denmark)

Holm, Kristina Garne; Brødsgaard, Anne; Zachariassen, Gitte

2016-01-01

participatory design and qualitative methods. Data were collected from observational studies, individual interviews, and focus group interviews. Two neonatal units participated. One unit was experienced in providing neonatal home care with home visits, and the other planned to offer neonatal home care......BACKGROUND: For the majority of preterm infants, the last weeks of hospital admission mainly concerns tube feeding and establishment of breastfeeding. Neonatal home care (NH) was developed to allow infants to remain at home for tube feeding and establishment of breastfeeding with regular home...... visits from neonatal nurses. For hospitals covering large regions, home visits may be challenging, time consuming, and expensive and alternative approaches must be explored. OBJECTIVE: To identify parental needs when wanting to provide neonatal home care supported by telemedicine. METHODS: The study used...
Ionizing radiation induces mitochondrial reactive oxygen species production accompanied by upregulation of mitochondrial electron transport chain function and mitochondrial content under control of the cell cycle checkpoint.

Science.gov (United States)

Yamamori, Tohru; Yasui, Hironobu; Yamazumi, Masayuki; Wada, Yusuke; Nakamura, Yoshinari; Nakamura, Hideo; Inanami, Osamu

2012-07-15

Whereas ionizing radiation (Ir) instantaneously causes the formation of water radiolysis products that contain some reactive oxygen species (ROS), ROS are also suggested to be released from biological sources in irradiated cells. It is now becoming clear that these ROS generated secondarily after Ir have a variety of biological roles. Although mitochondria are assumed to be responsible for this Ir-induced ROS production, it remains to be elucidated how Ir triggers it. Therefore, we conducted this study to decipher the mechanism of Ir-induced mitochondrial ROS production. In human lung carcinoma A549 cells, Ir (10 Gy of X-rays) induced a time-dependent increase in the mitochondrial ROS level. Ir also increased mitochondrial membrane potential, mitochondrial respiration, and mitochondrial ATP production, suggesting upregulation of the mitochondrial electron transport chain (ETC) function after Ir. Although we found that Ir slightly enhanced mitochondrial ETC complex II activity, the complex II inhibitor 3-nitropropionic acid failed to reduce Ir-induced mitochondrial ROS production. Meanwhile, we observed that the mitochondrial mass and mitochondrial DNA level were upregulated after Ir, indicating that Ir increased the mitochondrial content of the cell. Because irradiated cells are known to undergo cell cycle arrest under control of the checkpoint mechanisms, we examined the relationships between cell cycle and mitochondrial content and cellular oxidative stress level. We found that the cells in the G2/M phase had a higher mitochondrial content and cellular oxidative stress level than cells in the G1 or S phase, regardless of whether the cells were irradiated. We also found that Ir-induced accumulation of the cells in the G2/M phase led to an increase in cells with a high mitochondrial content and cellular oxidative stress level. This suggested that Ir upregulated mitochondrial ETC function and mitochondrial content, resulting in mitochondrial ROS production, and that
Neonatal Informatics: Transforming Neonatal Care Through Translational Bioinformatics

Science.gov (United States)

Palma, Jonathan P.; Benitz, William E.; Tarczy-Hornoch, Peter; Butte, Atul J.; Longhurst, Christopher A.

2012-01-01

The future of neonatal informatics will be driven by the availability of increasingly vast amounts of clinical and genetic data. The field of translational bioinformatics is concerned with linking and learning from these data and applying new findings to clinical care to transform the data into proactive, predictive, preventive, and participatory health. As a result of advances in translational informatics, the care of neonates will become more data driven, evidence based, and personalized. PMID:22924023
The Role of Serotonin Transporter in Human Lung Development and in Neonatal Lung Disorders

Directory of Open Access Journals (Sweden)

E. C. C. Castro

2017-01-01

Full Text Available Introduction. Failure of the vascular pulmonary remodeling at birth often manifests as pulmonary hypertension (PHT and is associated with a variety of neonatal lung disorders including a uniformly fatal developmental disorder known as alveolar capillary dysplasia with misalignment of pulmonary veins (ACD/MPV. Serum serotonin regulation has been linked to pulmonary vascular function and disease, and serotonin transporter (SERT is thought to be one of the key regulators in these processes. We sought to find evidence of a role that SERT plays in the neonatal respiratory adaptation process and in the pathomechanism of ACD/MPV. Methods. We used histology and immunohistochemistry to determine the timetable of SERT protein expression in normal human fetal and postnatal lungs and in cases of newborn and childhood PHT of varied etiology. In addition, we tested for a SERT gene promoter defect in ACD/MPV patients. Results. We found that SERT protein expression begins at 30 weeks of gestation, increases to term, and stays high postnatally. ACD/MPV patients had diminished SERT expression without SERT promoter alteration. Conclusion. We concluded that SERT/serotonin pathway is crucial in the process of pulmonary vascular remodeling/adaptation at birth and plays a key role in the pathobiology of ACD/MPV.
Maternal haemoglobin and short-term neonatal outcome in preterm neonates.

Directory of Open Access Journals (Sweden)

Elodie Savajols

Full Text Available To determine whether there is a significant association between maternal haemoglobin measured before delivery and short-term neonatal outcome in very preterm neonates.We included prospectively all live births occurring from 25 to 32+6 weeks of gestation in a tertiary care centre between January 1(st 2009 and December 31(st 2011. Outborn infants and infants presenting with lethal malformations were excluded. Three hundred and thirty-nine mothers and 409 infants met the inclusion criteria. For each mother-infant pair a prospective record of epidemiologic data was performed and maternal haemoglobin concentration recorded within 24 hours before delivery was retrospectively researched. Maternal haemoglobin was divided into quartiles with the second and the third one regarded as reference as they were composed of normal haemoglobin values. Short-term outcome was defined as poor in case of death during hospital stay and/or grades III/IV intraventricular haemorrhage and/or periventricular leukomalacia and/or necessity of ventriculoperitoneal shunt.The global rate of poor short-term neonatal outcome was 11.4% and was significantly associated with low maternal haemoglobin values. This association remained significant after adjustment for antenatal corticosteroids therapy, gestational age, parity, mechanism of preterm birth, mode of delivery and birth weight (aOR = 2.97 CI 95% [1.36-6.47]. There was no relation between short-term neonatal outcome and high maternal haemoglobin concentration values.We show that low maternal haemoglobin concentration at delivery is an independent risk factor for poor short-term neonatal outcome in very preterm neonates. This study is one of the first to show such an association within the preterm population.
Fatal occupational injuries among non-governmental employees in Malaysia.

Science.gov (United States)

Abas, Adinegara Bin Lutfi; Mohd Said, Datuk Abd Razzak B; Aziz Mohammed, Mohammed Azman B; Sathiakumar, Nalini

2013-01-01

In Malaysia, surveillance of fatal occupational injuries is fragmented. We therefore analyzed an alternative data source from Malaysia's Social Security organization, the Pertubuhan Keselamatan Sosial (PERKESO). We conducted a secondary data analysis of the PERKESO database comprised of 7 million employees from 2002 to 2006. Overall, the average annual incidence was 9.2 fatal occupational injuries per 100,000 workers. During the 5-year period, there was a decrease in the absolute number of fatal injuries by 16% and the incidence by 34%. The transportation sector reported the highest incidence of fatal injuries (35.1/100,000), followed by agriculture (30.5/100,000) and construction (19.3/100,000) sectors. Persons of Indian ethnicity were more likely to sustain fatal injuries compared to other ethnic groups. Government and industry should develop rigorous strategies to detect hazards in the workplace, especially in sectors that continuously record high injury rates. Targeted interventions emphasizing worker empowerment coupled with systematic monitoring and evaluation is critical to ensure success in prevention and control measures. Copyright © 2012 Wiley Periodicals, Inc.
Fatal Occupational Injuries among Non-governmental Employees in Malaysia

Science.gov (United States)

Abas, Adinegara bin Lutfi; Mohd Said, Datuk Abd. Razzak B.; Aziz Mohammed, Mohammed Azman B.; Sathiakumar, Nalini

2012-01-01

Background In Malaysia, surveillance of fatal occupational injuries is fragmented. We therefore analyzed an alternative data source from Malaysia’s Social Security organization, the PERKESO. Methods We conducted a secondary data analysis of the PERKESO database comprised of 7 million employees from 2002 to 2006. Results Overall, the average annual incidence was 9.2 fatal occupational injuries per 100,000 workers. During the five-year period, there was a decrease in the absolute number of fatal injuries by 16% and the incidence by 34%. The transportation sector reported the highest incidence of fatal injuries (35.1/100,000), followed by agriculture (30.5/100,000) and construction (19.3/100,000) sectors. Persons of Indian ethnicity were more likely to sustain fatal injuries compared to other ethnic groups. Conclusions Government and industry should develop rigorous strategies to detect hazards in the workplace, especially in sectors that continuously record high injury rates. Targeted interventions emphasizing worker empowerment coupled with systematic monitoring and evaluation is critical to ensure success in prevention and control measures. PMID:22544443
Neonatal tetanus elimination in Pakistan: progress and challenges.

Science.gov (United States)

Lambo, Jonathan A; Nagulesapillai, Tharsiya

2012-12-01

Pakistan is one of the 34 countries that have not achieved the neonatal tetanus (NT) global elimination target set by the World Health Organization (WHO). NT, caused by Clostridium tetani, is a highly fatal infection of the neonatal period. It is one of the most underreported diseases and remains a major but preventable cause of neonatal and infant mortality in many developing countries. In 1989, the World Health Assembly called for the elimination of NT by 1995, and since then considerable progress has been made using the following strategies: clean delivery practices, routine tetanus toxoid (TT) immunization of pregnant women, and immunization of all women of childbearing age with three doses of TT vaccine in high-risk areas during supplementary immunization campaigns. This review presents the activities, progress, and challenges in achieving NT elimination in Pakistan. A review of the literature found TT vaccination coverage in Pakistan ranged from 60% to 74% over the last decade. Low vaccination coverage, the main driver for NT in Pakistan, is due to many factors, including demand failure for TT vaccine resulting from inadequate knowledge of TT vaccine among reproductive age females and inadequate information about the benefits of TT provided by health care workers and the media. Other factors linked to low vaccination coverage include residing in rural areas, lack of formal education, poor knowledge about place and time to get vaccinated, and lack of awareness about the importance of vaccination. A disparity exists in TT vaccination coverage and antenatal care between urban and rural areas due to access and utilization of health care services. NT reporting is incomplete, as cases from the private sector and rural areas are underreported. To successfully eliminate NT, women of reproductive age must be made aware of the benefits of TT vaccine, not only to themselves, but also to their families. Effective communication strategies for TT vaccine delivery and
Mitochondrial protein acetylation mediates nutrient sensing of mitochondrial protein synthesis and mitonuclear protein balance.

Science.gov (United States)

Di Domenico, Antonella; Hofer, Annette; Tundo, Federica; Wenz, Tina

2014-11-01

Changes in nutrient supply require global metabolic reprogramming to optimize the utilization of the nutrients. Mitochondria as a central component of the cellular metabolism play a key role in this adaptive process. Since mitochondria harbor their own genome, which encodes essential enzymes, mitochondrial protein synthesis is a determinant of metabolic adaptation. While regulation of cytoplasmic protein synthesis in response to metabolic challenges has been studied in great detail, mechanisms which adapt mitochondrial translation in response to metabolic challenges remain elusive. Our results suggest that the mitochondrial acetylation status controlled by Sirt3 and its proposed opponent GCN5L1 is an important regulator of the metabolic adaptation of mitochondrial translation. Moreover, both proteins modulate regulators of cytoplasmic protein synthesis as well as the mitonuclear protein balance making Sirt3 and GCN5L1 key players in synchronizing mitochondrial and cytoplasmic translation. Our results thereby highlight regulation of mitochondrial translation as a novel component in the cellular nutrient sensing scheme and identify mitochondrial acetylation as a new regulatory principle for the metabolic competence of mitochondrial protein synthesis. © 2014 International Union of Biochemistry and Molecular Biology.
Neonates need tailored drug formulations.

Science.gov (United States)

Allegaert, Karel

2013-02-08

Drugs are very strong tools used to improve outcome in neonates. Despite this fact and in contrast to tailored perfusion equipment, incubators or ventilators for neonates, we still commonly use drug formulations initially developed for adults. We would like to make the point that drug formulations given to neonates need to be tailored for this age group. Besides the obvious need to search for active compounds that take the pathophysiology of the newborn into account, this includes the dosage and formulation. The dosage or concentration should facilitate the administration of low amounts and be flexible since clearance is lower in neonates with additional extensive between-individual variability. Formulations need to be tailored for dosage variability in the low ranges and also to the clinical characteristics of neonates. A specific focus of interest during neonatal drug development therefore is a need to quantify and limit excipient exposure based on the available knowledge of their safety or toxicity. Until such tailored vials and formulations become available, compounding practices for drug formulations in neonates should be evaluated to guarantee the correct dosing, product stability and safety.
Community Poverty and Child Abuse Fatalities in the United States.

Science.gov (United States)

Farrell, Caitlin A; Fleegler, Eric W; Monuteaux, Michael C; Wilson, Celeste R; Christian, Cindy W; Lee, Lois K

2017-05-01

Child maltreatment remains a problem in the United States, and individual poverty is a recognized risk factor for abuse. Children in impoverished communities are at risk for negative health outcomes, but the relationship of community poverty to child abuse fatalities is not known. Our objective was to evaluate the association between county poverty concentration and rates of fatal child abuse. This was a retrospective, cross-sectional analysis of child abuse fatalities in US children 0 to 4 years of age from 1999 to 2014 by using the Centers for Disease Control and Prevention Compressed Mortality Files. Population and poverty statistics were obtained from US Census data. National child abuse fatality rates were calculated for each category of community poverty concentration. Multivariate negative binomial regression modeling assessed the relationship between county poverty concentration and child abuse fatalities. From 1999 to 2014, 11 149 children 0 to 4 years old died of child abuse; 45% (5053) were poverty concentration had >3 times the rate of child abuse fatalities compared with counties with the lowest poverty concentration (adjusted incidence rate ratio, 3.03; 95% confidence interval, 2.4-3.79). Higher county poverty concentration is associated with increased rates of child abuse fatalities. This finding should inform public health officials in targeting high-risk areas for interventions and resources. Copyright © 2017 by the American Academy of Pediatrics.
The New Zealand child work-related fatal injury study: 1985-1998.

Science.gov (United States)

Lilley, Rebbecca; Feyer, Anne-Marie; Langley, John; Wren, John

2004-05-21

To estimate the numbers and rates of work-related fatal injury for children under the age of 15 years. Potential cases of work-related injury deaths of persons aged workplace work-related fatalities were identified. The vast majority of children identified were fatally injured while a bystander to another person's work. Workplace bystander involvement was found to vary by age, with the majority of workers identified aged 10-14 years old. With a third of all fatalities, the agricultural industry was the most common industry for workplace work-related fatalities in children. In the period 1985-94, children New Zealand's total workplace bystander deaths. Children contribute significantly to the overall burden of work-related fatal injury in New Zealand, especially as bystanders to other people's work. The high contribution to bystander deaths by children aged <15 years suggests that hazard control in certain work settings is lacking.
Mitochondrial matters: Mitochondrial bottlenecks, self-assembling structures, and entrapment in the female germline

Directory of Open Access Journals (Sweden)

Florence L. Marlow

2017-05-01

Full Text Available Mitochondrial replacement therapy, a procedure to generate embryos with the nuclear genome of a donor mother and the healthy mitochondria of a recipient egg, has recently emerged as a promising strategy to prevent transmission of devastating mitochondrial DNA diseases and infertility. The procedure may produce an embryo that is free of diseased mitochondria. A recent study addresses important fundamental questions about the mechanisms underlying maternal inheritance and translational questions regarding the transgenerational effectiveness of this promising therapeutic strategy. This review considers recent advances in our understanding of maternal inheritance of mitochondria, implications for fertility and mitochondrial disease, and potential roles for the Balbiani body, an ancient oocyte structure, in mitochondrial selection in oocytes, with emphasis on therapies to remedy mitochondrial disorders.
Neonatal Nursing

OpenAIRE

Crawford, Doreen; Morris, Maryke

1994-01-01

"Neonatal Nursing" offers a systematic approach to the nursing care of the sick newborn baby. Nursing actions and responsibilities are the focus of the text with relevant research findings, clinical applications, anatomy, physiology and pathology provided where necessary. This comprehensive text covers all areas of neonatal nursing including ethics, continuing care in the community, intranatal care, statistics and pharmokinetics so that holistic care of the infant is described. This book shou...
Case-Based Teaching of Fatal Incidents in Outdoor Education Teacher Preparation Courses

Science.gov (United States)

North, Chris; Brookes, Andrew

2017-01-01

This article examines the use of case-based approaches to fatal incidents in outdoor education (OE) with a view to fatality prevention. Fatalities are rare in OE and therefore it is nearly impossible for teachers to learn how to avoid fatalities from their own past experiences. It is, however, possible to learn from the mistakes of others through…
Neonatal Outcomes of Rh-Negative Pregnancies in a Tertiary Level Neonatal Intensive Care Unit: A Prospective Study

Directory of Open Access Journals (Sweden)

Chacham

2016-07-01

Full Text Available Background Rhesus incompatibility is a preventable cause for severe neonatal hyperbilirubinemia, hydrops fetalis and still births. The prevalence of the Rh-negative blood group among Indian woman varies from 2% - 10%. Despite declining the incidence of Rhesus incompatibility, due to availability of anti-D immunoglobulin, and improved antenatal care of the Rh-negative pregnant woman, it still accounts for a significant proportion of neonatal hyperbilirubinemia and neuro-morbidity. The prevalence of Rh-negative women having Rh-positive neonates is 60%. Objectives This study aimed to estimate the incidence of Rh iso-immunization and evaluate the outcomes of Rh iso-immunized neonates. Methods This prospective observational study was conducted in a tertiary level neonatal intensive care unit, Princess Esra hospital, Deccan college of medical sciences, Hyderabad, Telangana, India. Consecutive intramural and extramural neonates admitted to neonatal intensive care unit with the Rh-negative mother’s blood group and hyperbilirubinemia were enrolled. Neonates born to Rh+ve mothers were excluded. Neonatal gestational age, birth weight, age at admission, duration of phototherapy, duration of hospitalization, neonatal examination and investigations were recorded in a predesigned, pretested performa. Results A total of 90 neonates were born to Rh-negative mothers, of which 70% (63 had the Rh-positive blood group and 30% had the Rh-negative blood group. Of these 63 neonates, 48 (76.2% had hyperbilirubinemia and 43 neonates (68.3% had significant hyperbilirubinemia (total serum bilirubin > 15mg/dL. Among them, 2%, 75% and 23% were born to primi, multi and grandmutli, respectively. Also, 14.5% of the neonates were large for dates (LFD, 75% appropriate for dates (AFD and 10.5% were small for dates (SFD. Premature and SFD neonates had higher incidence of hyperbilirubinemia. Significantly higher incidence of jaundice occurred within 72 hours of life. The mean

SERUM SODIUM CHANGES IN NEONATES RECEIVING PHOTOTHERAPY FOR NEONATAL HYPERBILIRUBINEMIA

Directory of Open Access Journals (Sweden)

Sunil Kumar

2015-07-01

Full Text Available BACKGROUND : Neonates receiving phototherapy have side effects like hypocalcemia and electrolyte changes. Our study is hereby intended to study the serum sodium changes due to phototherapy. AIMS : To evaluate the serum sodium changes in neonates receiving phototherapy f or neonatal hyperbilirubinemia. SETTINGS AND DESIGN : A prospective hospital based comparative study conducted on neonates admitted in the Neonatal Intensive Care Unit receiving phototherapy. METHODS AND MATERIAL : A predesigned proforma has aided the enroll ment of 252 newborns into the study. Serum bilirubin and serum sodium were determined before and after termination of phototherapy. The first samples were considered as controls. A comparative study was made between before and after phototherapy groups to determine the incidence of serum sodium imbalances. STATISTICAL ANALYSIS USED : Proportions will be compared using chi - square test. All data of various groups will be tabulated and statistically analyzed using suitable statistical tests (Student's t test. RESULTS : Male to Female ratio was 1.45 : 1. Incidence of low birth weight babies was 23% and preterm was 20.2%. Mean birth weight and gestational age was 2.84±0.51 kg and 38.44±1.98 wks respectively. Mean duration of phototherapy was 37.65±11.06 hrs. The incidence of hyponatremia post phototherapy found to be 6% which was more in low birth weight (LBW babies (17.2% , p48 hrs (p<0.001. Even the decline in mean serum sodium values after phototherapy found to be statistically significant. CONCLUSION : Our study shows that neonates u nder phototherapy are at higher risk of hyponatremia. This risk is greater in premature and LBW babies and hence this group of babies should be closely monitored for changes in serum sodium and should be managed accordingly.
Can we reduce workplace fatalities by half?

Science.gov (United States)

Koh, David Soo Quee

2012-06-01

Singapore, an island republic of over 5 million inhabitants, has 3.1 million workers. Most are employed in the service, finance and tourist/transport industry. Significant numbers work in manufacturing, construction and heavy industry. Following a series of construction and shipyard accidents with multiple deaths in 2004, the government announced its intention to reduce workplace fatalities from 4.9 to 2.5 per 100,000 by 2015. There was strong political will to achieve this target. The strategic approaches were to build workplace safety and health (WSH) capabilities; implement legislative changes with enforcement; promote benefits of WSH and recognize best practices, and enhance partnership with stakeholders. The anticipated outcomes were to reduce workplace fatality and injury rates; have WSH as an integral part of business; and establish a progressive and pervasive WSH culture. With these measures, the workplace fatality rate declined from 4.9/100,000 in 2004, to 2.2/100,000 in 2010. However, other confounding factors could also account for this decline, and have to be considered. The next target, announced by Singapore's Prime Minister in 2008, is to further reduce the workplace fatality rate to 1.8/100,000 by 2018, and to have "one of the best workplace safety records in the world".
Fatal accidents analysis in Peruvian mining industry

International Nuclear Information System (INIS)

Candia, R. C.; Hennies, W. T.; Azevedo, R. c.; Almeida, I.G.; Soto, J. F.

2010-01-01

Although reductions in the tax of injuries and accidents have been observed in recent years, Mining is still one of the highest risks industries. The basic causes for occurrence of fatalities can be attributed to unsafe conditions and unsafe acts. In this scene is necessary to identify safety problems and to aim the effective solutions. On the other hand, the developing countries dependence on primary industries as mining is evident. In the Peruvian economy, approximately 16% of the GNP and more than 50% of the exportations are due to the mining sector, detaching its competitive position in the worldwide mining. This paper presents fatal accidents analysis in the Peruvian mining industry, having as basis the register of occurred fatal accidents since year 2000 until 2007, identifying the main types of accidents occurred. The source of primary information is the General Mining Direction (DGM) of the Peruvian Mining and Energy Ministry (MEM). The majority of victims belongs to tertiary contractor companies that render services for mine companies. The results of the analysis show also that the majority of accidents happened in the underground mines, and that it is necessary to propose effective solutions to manage risks, aiming at reducing the fatal accidents taxes. (Author)
Can We Reduce Workplace Fatalities by Half?

Directory of Open Access Journals (Sweden)

David Soo Quee Koh

2012-06-01

Full Text Available Singapore, an island republic of over 5 million inhabitants, has 3.1 million workers. Most are employed in the service, finance and tourist/transport industry. Significant numbers work in manufacturing, construction and heavy industry. Following a series of construction and shipyard accidents with multiple deaths in 2004, the government announced its intention to reduce workplace fatalities from 4.9 to 2.5 per 100,000 by 2015. There was strong political will to achieve this target. The strategic approaches were to build workplace safety and health (WSH capabilities; implement legislative changes with enforcement; promote benefits of WSH and recognize best practices, and enhance partnership with stakeholders. The anticipated outcomes were to reduce workplace fatality and injury rates; have WSH as an integral part of business; and establish a progressive and pervasive WSH culture. With these measures, the workplace fatality rate declined from 4.9/100,000 in 2004, to 2.2/100,000 in 2010. However, other confounding factors could also account for this decline, and have to be considered. The next target, announced by Singapore’s Prime Minister in 2008, is to further reduce the workplace fatality rate to 1.8/100,000 by 2018, and to have “one of the best workplace safety records in the world”.
Neonatal Vaccination: Challenges and Intervention Strategies.

Science.gov (United States)

Morris, Matthew C; Surendran, Naveen

2016-01-01

While vaccines have been tremendously successful in reducing the incidence of serious infectious diseases, newborns remain particularly vulnerable in the first few months of their life to life-threatening infections. A number of challenges exist to neonatal vaccination. However, recent advances in the understanding of neonatal immunology offer insights to overcome many of those challenges. This review will present an overview of the features of neonatal immunity which make vaccination difficult, survey the mechanisms of action of available vaccine adjuvants with respect to the unique features of neonatal immunity, and propose a possible mechanism contributing to the inability of neonates to generate protective immune responses to vaccines. We surveyed recent published findings on the challenges to neonatal vaccination and possible intervention strategies including the use of novel vaccine adjuvants to develop efficacious neonatal vaccines. Challenges in the vaccination of neonates include interference from maternal antibody and excessive skewing towards Th2 immunity, which can be counteracted by the use of proper adjuvants. Synergistic stimulation of multiple Toll-like receptors by incorporating well-defined agonist-adjuvant combinations to vaccines is a promising strategy to ensure a protective vaccine response in neonates. © 2016 S. Karger AG, Basel.
Complete deficiency of mitochondrial trifunctional protein due to a novel mutation within the beta-subunit of the mitochondrial trifunctional protein gene leads to failure of long-chain fatty acid beta-oxidation with fatal outcome

NARCIS (Netherlands)

Schwab, Karl Otfried; Ensenauer, Regina; Matern, Dietrich; Uyanik, Gökhan; Schnieders, Birgit; Wanders, Ronald A.; Lehnert, Willy

2003-01-01

The mitochondrial trifunctional protein (MTP) is a multienzyme complex which catalyses three of the four chain-shortening reactions in the beta-oxidation of long-chain fatty acids. Clinically, failure of long-chain fatty acid beta-oxidation leads to hypoketotic hypoglycaemia associated with coma,
Hyperglycemia decreases mitochondrial function: The regulatory role of mitochondrial biogenesis

International Nuclear Information System (INIS)

Palmeira, Carlos M.; Rolo, Anabela P.; Berthiaume, Jessica; Bjork, James A.; Wallace, Kendall B.

2007-01-01

Increased generation of reactive oxygen species (ROS) is implicated in 'glucose toxicity' in diabetes. However, little is known about the action of glucose on the expression of transcription factors in hepatocytes, especially those involved in mitochondrial DNA (mtDNA) replication and transcription. Since mitochondrial functional capacity is dynamically regulated, we hypothesized that stressful conditions of hyperglycemia induce adaptations in the transcriptional control of cellular energy metabolism, including inhibition of mitochondrial biogenesis and oxidative metabolism. Cell viability, mitochondrial respiration, ROS generation and oxidized proteins were determined in HepG2 cells cultured in the presence of either 5.5 mM (control) or 30 mM glucose (high glucose) for 48 h, 96 h and 7 days. Additionally, mtDNA abundance, plasminogen activator inhibitor-1 (PAI-1), mitochondrial transcription factor A (TFAM) and nuclear respiratory factor-1 (NRF-1) transcripts were evaluated by real time PCR. High glucose induced a progressive increase in ROS generation and accumulation of oxidized proteins, with no changes in cell viability. Increased expression of PAI-1 was observed as early as 96 h of exposure to high glucose. After 7 days in hyperglycemia, HepG2 cells exhibited inhibited uncoupled respiration and decreased MitoTracker Red fluorescence associated with a 25% decrease in mtDNA and 16% decrease in TFAM transcripts. These results indicate that glucose may regulate mtDNA copy number by modulating the transcriptional activity of TFAM in response to hyperglycemia-induced ROS production. The decrease of mtDNA content and inhibition of mitochondrial function may be pathogenic hallmarks in the altered metabolic status associated with diabetes
Elastocapillary Instability in Mitochondrial Fission

Science.gov (United States)

Gonzalez-Rodriguez, David; Sart, Sébastien; Babataheri, Avin; Tareste, David; Barakat, Abdul I.; Clanet, Christophe; Husson, Julien

2015-08-01

Mitochondria are dynamic cell organelles that constantly undergo fission and fusion events. These dynamical processes, which tightly regulate mitochondrial morphology, are essential for cell physiology. Here we propose an elastocapillary mechanical instability as a mechanism for mitochondrial fission. We experimentally induce mitochondrial fission by rupturing the cell's plasma membrane. We present a stability analysis that successfully explains the observed fission wavelength and the role of mitochondrial morphology in the occurrence of fission events. Our results show that the laws of fluid mechanics can describe mitochondrial morphology and dynamics.
Occupational fatalities due to electrocutions in the construction industry.

Science.gov (United States)

Janicak, Christopher A

2008-01-01

Occupational fatalities due to contact with electricity account for approximately 9% of all deaths in the construction industry and is the fourth leading cause of death in this industry. Differences in the proportions of electrocutions in the construction industry are significantly different from other industries based upon the age of the worker and the source of the electricity. This study found that, in the construction industry, the proportion of occupational fatalities due to contact with electric current is significantly higher for workers in the 16 to 19 years old age group. Contact with overhead power lines occurred more frequently with younger workers, while contact with electric wiring, transformers, and related equipment was found to occur more frequently with older workers. The proportion of fatalities due to this event was also found to account for a significantly greater proportion of fatalities in the construction industry overall. The proportions of electrocution fatalities in the construction industry were found to be significantly higher for younger workers when compared to all other industries. Focusing prevention measures toward younger workers who work near overhead power lines could have a significant impact upon death rates. For older workers, the focus should be on those who work on or near transformers, electrical wiring, and components. Across the construction industry, implementation of effective lockout-tagout programs, and verification of energy isolation, can prevent approximately 125 fatalities per year in the construction industry.
Uber and Metropolitan Traffic Fatalities in the United States.

Science.gov (United States)

Brazil, Noli; Kirk, David S

2016-08-01

Uber and similar rideshare services are rapidly dispersing in cities across the United States and beyond. Given the convenience and low cost, Uber has been characterized as a potential countermeasure for reducing the estimated 121 million episodes of drunk driving and the 10,000 resulting traffic fatalities that occur annually in the United States. We exploited differences in the timing of the deployment of Uber in US metropolitan counties from 2005 to 2014 to test the association between the availability of Uber's rideshare services and total, drunk driving-related, and weekend- and holiday-specific traffic fatalities in the 100 most populated metropolitan areas in the United States using negative binomial and Poisson regression models. We found that the deployment of Uber services in a given metropolitan county had no association with the number of subsequent traffic fatalities, whether measured in aggregate or specific to drunk-driving fatalities or fatalities during weekends and holidays. © The Author 2016. Published by Oxford University Press on behalf of the Johns Hopkins Bloomberg School of Public Health. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.
Drp1-Dependent Mitochondrial Autophagy Plays a Protective Role Against Pressure Overload-Induced Mitochondrial Dysfunction and Heart Failure.

Science.gov (United States)

Shirakabe, Akihiro; Zhai, Peiyong; Ikeda, Yoshiyuki; Saito, Toshiro; Maejima, Yasuhiro; Hsu, Chiao-Po; Nomura, Masatoshi; Egashira, Kensuke; Levine, Beth; Sadoshima, Junichi

2016-03-29

Mitochondrial autophagy is an important mediator of mitochondrial quality control in cardiomyocytes. The occurrence of mitochondrial autophagy and its significance during cardiac hypertrophy are not well understood. Mice were subjected to transverse aortic constriction (TAC) and observed at multiple time points up to 30 days. Cardiac hypertrophy developed after 5 days, the ejection fraction was reduced after 14 days, and heart failure was observed 30 days after TAC. General autophagy was upregulated between 1 and 12 hours after TAC but was downregulated below physiological levels 5 days after TAC. Mitochondrial autophagy, evaluated by electron microscopy, mitochondrial content, and Keima with mitochondrial localization signal, was transiently activated at ≈3 to 7 days post-TAC, coinciding with mitochondrial translocation of Drp1. However, it was downregulated thereafter, followed by mitochondrial dysfunction. Haploinsufficiency of Drp1 abolished mitochondrial autophagy and exacerbated the development of both mitochondrial dysfunction and heart failure after TAC. Injection of Tat-Beclin 1, a potent inducer of autophagy, but not control peptide, on day 7 after TAC, partially rescued mitochondrial autophagy and attenuated mitochondrial dysfunction and heart failure induced by overload. Haploinsufficiency of either drp1 or beclin 1 prevented the rescue by Tat-Beclin 1, suggesting that its effect is mediated in part through autophagy, including mitochondrial autophagy. Mitochondrial autophagy is transiently activated and then downregulated in the mouse heart in response to pressure overload. Downregulation of mitochondrial autophagy plays an important role in mediating the development of mitochondrial dysfunction and heart failure, whereas restoration of mitochondrial autophagy attenuates dysfunction in the heart during pressure overload. © 2016 American Heart Association, Inc.
Therapies for neonates with congenital malformations admitted to a neonatal unit

Directory of Open Access Journals (Sweden)

Maria Vera Lúcia Moreira Leitão Cardoso

2015-03-01

Full Text Available The aim of this study was to characterize the treatments applied to newborns with congenital malformation hospitalized in a neonatal unit and to identify whether there is an association among the treatments used and the type of malformation. A descriptive, prospective and quantitative study was developed in a public institution in Fortaleza, Ceará, Brazil. Data were collected using the medical records of 30 neonates with congenital malformations. The incidence of malformations was higher among females, regardless of the mother’s age, gestational age or weight at birth; malformations of the central nervous and musculoskeletal systems prevailed. The treatments used varied according to the clinical evolution of the neonate. The data collected did not present statistical significance when associated with the variable of congenital malformation and the treatments used (p>0.05. The treatments are not directly related to the type of malformation, but to the clinical condition of the neonate.
Intraoperative fluid therapy in neonates

African Journals Online (AJOL)

Differences from adults and children in physiology and anatomy of neonates inform our ... is based on energy expenditure indexed to bodyweight.2 Energy ... fragile and poorly keratinised.5 ... neonates means that very conservative fluid regimes in neonates ..... I make an estimation of insensible loss from the skin, viscera,.
Neonatal Tele-Homecare

DEFF Research Database (Denmark)

Holm, Kristina Garne

Neonatal homecare (NH) implies that parents manage tube feeding and care of their preterm infant at home supported by home visits from neonatal nurses, to monitor infant growth and the well-being of the family. Home visits are costly and time consuming in rural areas. The overall aim of this study...
Targeted Transgenic Overexpression of Mitochondrial Thymidine Kinase (TK2) Alters Mitochondrial DNA (mtDNA) and Mitochondrial Polypeptide Abundance : Transgenic TK2, mtDNA, and Antiretrovirals

OpenAIRE

Hosseini, Seyed H.; Kohler, James J.; Haase, Chad P.; Tioleco, Nina; Stuart, Tami; Keebaugh, Erin; Ludaway, Tomika; Russ, Rodney; Green, Elgin; Long, Robert; Wang, Liya; Eriksson, Staffan; Lewis, William

2007-01-01

Mitochondrial toxicity limits nucleoside reverse transcriptase inhibitors (NRTIs) for acquired immune deficiency syndrome. NRTI triphosphates, the active moieties, inhibit human immunodeficiency virus reverse transcriptase and eukaryotic mitochondrial DNA polymerase pol-γ. NRTI phosphorylation seems to correlate with mitochondrial toxicity, but experimental evidence is lacking. Transgenic mice (TGs) with cardiac overexpression of thymidine kinase isoforms (mitochondrial TK2 and cytoplasmic TK...
Mitochondrial functionality in female reproduction

Directory of Open Access Journals (Sweden)

Łukasz Gąsior

2017-01-01

Full Text Available In most animal species female germ cells are the source of mitochondrial genome for the whole body of individuals. As a source of mitochondrial DNA for future generations the mitochondria in the female germ line undergo dynamic quantitative and qualitative changes. In addition to maintaining the intact template of mitochondrial genome from one generation to another, mitochondrial role in oocytes is much more complex and pleiotropic. The quality of mitochondria determines the ability of meiotic divisions, fertilization ability, and activation after fertilization or sustaining development of a new embryo. The presence of normal number of functional mitochondria is also crucial for proper implantation and pregnancy maintaining. This article addresses issues of mitochondrial role and function in mammalian oocyte and presents new approaches in studies of mitochondrial function in female germ cells.
The incidence of multiple fatality accidents in the U.K

International Nuclear Information System (INIS)

Griffiths, R.F.; Fryer, L.S.

1978-03-01

The report presents a compilation of available data showing the frequency of occurrence of accidents resulting in multiple fatalities in the United Kingdom (or Great Britain, as the data permits). Frequency vs. number-of-fatalities graphs are plotted for the following five classes of fatalities:- persons killed in fires in the UK; crew members of UK registered ships; railway passengers in Great Britain; passengers of aircraft on the British register; occupants of Public Service Vehicles in Great Britain. The information needed to compile a more comprehensive set of graphs was found to be unobtainable. The report concludes with the suggestion that procedures for reporting and recording details of fatal accidents should be reviewed. (author)
[Neonatal tumours and congenital malformations].

Science.gov (United States)

Berbel Tornero, O; Ortega García, J A; Ferrís i Tortajada, J; García Castell, J; Donat i Colomer, J; Soldin, O P; Fuster Soler, J L

2008-06-01

The association between pediatric cancer and congenital abnormalities is well known but, there is no exclusive data on the neonatal period and the underlying etiopathogenic mechanisms are unknown. First, to analyze the frequency of neonatal tumours associated with congenital abnormalities; and second, to comment on the likely etiopathogenic hypotheses of a relationship between neonatal tumours and congenital abnormalities. Historical series of neonatal tumours from La Fe University Children's Hospital in Valencia (Spain), from January 1990 to December 1999. Histological varieties of neonatal tumours and associated congenital abnormalities were described. A systematic review of the last 25 years was carried out using Medline, Cancerlit, Index Citation Science and Embase. The search profile used was the combination of "neonatal/congenital-tumors/cancer/neoplasms" and "congenital malformations/birth defects". 72 neonatal tumours were identified (2.8% of all pediatric cancers diagnosed in our hospital) and in 15 cases (20.8%) there was some associated malformation, disease or syndrome. The association between congenital abnormalities and neonatal tumours were: a) angiomas in three patients: two patients with congenital heart disease with a choanal stenosis, laryngomalacia; b) neuroblastomas in two patients: horseshoe kidney with vertebral anomalies and other with congenital heart disease; c) teratomas in two patients: one with cleft palate with vertebral anomalies and other with metatarsal varus; d) one tumour of the central nervous system with Bochdaleck hernia; e) heart tumours in four patients with tuberous sclerosis; f) acute leukaemia in one patient with Down syndrome and congenital heart disease; g) kidney tumour in one case with triventricular hydrocephaly, and h) adrenocortical tumour: hemihypertrophy. The publications included the tumours diagnosed in different pediatric periods and without unified criteria to classify the congenital abnormalities. Little data
Fatal interstitial lung disease associated with icotinib

OpenAIRE

Zhang, Jiexia; Zhan, Yangqing; Ouyang, Ming; Qin, Yinyin; Zhou, Chengzhi; Chen, Rongchang

2014-01-01

The most serious, and maybe fatal, yet rare, adverse reaction of gefitinib and erlotinib is drug-associated interstitial lung disease (ILD), which has been often described. However, it has been less well described for icotinib, a similar orally small-molecule tyrosine kinase inhibitor (TKI). The case of a 25-year-old female patient with stage IV lung adenocarcinoma who developed fatal ILD is reported here. She denied chemotherapy, and received palliative treatment with icotinib (125 mg po, th...
Disentangling age-gender interactions associated with risks of fatal and non-fatal road traffic injuries in the Sultanate of Oman.

Science.gov (United States)

Al-Aamri, Amira K; Padmadas, Sabu S; Zhang, Li-Chun; Al-Maniri, Abdullah A

2017-01-01

Road traffic injuries (RTIs) are the leading cause of disability-adjusted life years lost in Oman, Saudi Arabia and United Arab Emirates. Injury prevention strategies often overlook the interaction of individual and behavioural risk factors in assessing the severity of RTI outcomes. We conducted a systematic investigation of the underlying interactive effects of age and gender on the severity of fatal and non-fatal RTI outcomes in the Sultanate of Oman. We used the Royal Oman Police national database of road traffic crashes for the period 2010-2014. Our study was based on 35 785 registered incidents: of these, 10.2% fatal injuries, 6.2% serious, 27.3% moderate, 37.3% mild injuries and 19% only vehicle damage but no human injuries. We applied a generalised ordered logit regression to estimate the effect of age and gender on RTI severity, controlling for risk behaviours, personal characteristics, vehicle, road, traffic, environment conditions and geographical location. The most dominant group at risk of all types of RTIs was young male drivers. The probability of severe incapacitating injuries was the highest for drivers aged 25-29 (26.6%) years, whereas the probability of fatal injuries was the highest for those aged 20-24 (26.9%) years. Analysis of three-way interactions of age, gender and causes of crash show that overspeeding was the primary cause of different types of RTIs. In particular, the probability of fatal injuries among male drivers attributed to overspeeding ranged from 3%-6% for those aged 35 years and above to 13.4% and 17.7% for those aged 25-29 years and 20-24 years, respectively. The high burden of severe and fatal RTIs in Oman was primarily attributed to overspeed driving behaviour of young male drivers in the 20-29 years age range. Our findings highlight the critical need for designing early gender-sensitive road safety interventions targeting young male and female drivers.

Common effects of lithium and valproate on mitochondrial functions: protection against methamphetamine-induced mitochondrial damage

OpenAIRE

Bachmann, Rosilla F.; Wang, Yun; Yuan, Peixiong; Zhou, Rulun; Li, Xiaoxia; Alesci, Salvatore; Du, Jing; Manji, Husseini K.

2009-01-01

Accumulating evidence suggests that mitochondrial dysfunction plays a critical role in the progression of a variety of neurodegenerative and psychiatric disorders. Thus, enhancing mitochondrial function could potentially help ameliorate the impairments of neural plasticity and cellular resilience associated with a variety of neuropsychiatric disorders. A series of studies was undertaken to investigate the effects of mood stabilizers on mitochondrial function, and against mitochondrially media...
Roles of mitochondrial fragmentation and reactive oxygen species in mitochondrial dysfunction and myocardial insulin resistance

International Nuclear Information System (INIS)

Watanabe, Tomoyuki; Saotome, Masao; Nobuhara, Mamoru; Sakamoto, Atsushi; Urushida, Tsuyoshi; Katoh, Hideki; Satoh, Hiroshi; Funaki, Makoto; Hayashi, Hideharu

2014-01-01

Purpose: Evidence suggests an association between aberrant mitochondrial dynamics and cardiac diseases. Because myocardial metabolic deficiency caused by insulin resistance plays a crucial role in heart disease, we investigated the role of dynamin-related protein-1 (DRP1; a mitochondrial fission protein) in the pathogenesis of myocardial insulin resistance. Methods and Results: DRP1-expressing H9c2 myocytes, which had fragmented mitochondria with mitochondrial membrane potential (ΔΨ m ) depolarization, exhibited attenuated insulin signaling and 2-deoxy-D-glucose (2-DG) uptake, indicating insulin resistance. Treatment of the DRP1-expressing myocytes with Mn(III)tetrakis(1-methyl-4-pyridyl)porphyrin pentachloride (TMPyP) significantly improved insulin resistance and mitochondrial dysfunction. When myocytes were exposed to hydrogen peroxide (H 2 O 2 ), they increased DRP1 expression and mitochondrial fragmentation, resulting in ΔΨ m depolarization and insulin resistance. When DRP1 was suppressed by siRNA, H 2 O 2 -induced mitochondrial dysfunction and insulin resistance were restored. Our results suggest that a mutual enhancement between DRP1 and reactive oxygen species could induce mitochondrial dysfunction and myocardial insulin resistance. In palmitate-induced insulin-resistant myocytes, neither DRP1-suppression nor TMPyP restored the ΔΨ m depolarization and impaired 2-DG uptake, however they improved insulin signaling. Conclusions: A mutual enhancement between DRP1 and ROS could promote mitochondrial dysfunction and inhibition of insulin signal transduction. However, other mechanisms, including lipid metabolite-induced mitochondrial dysfunction, may be involved in palmitate-induced insulin resistance. - Highlights: • DRP1 promotes mitochondrial fragmentation and insulin-resistance. • A mutual enhancement between DRP1 and ROS ipromotes insulin-resistance. • Palmitate increases DRP1 expression and induces insulin-resistance. • Inhibition of DRP or ROS
Roles of mitochondrial fragmentation and reactive oxygen species in mitochondrial dysfunction and myocardial insulin resistance

Energy Technology Data Exchange (ETDEWEB)

Watanabe, Tomoyuki [Internal Medicine III, Hamamatsu University School of Medicine, 1-20-1 Handayama, Higashi-ku, Hamamatsu 431-3192 (Japan); Saotome, Masao, E-mail: msaotome@hama-med.ac.jp [Internal Medicine III, Hamamatsu University School of Medicine, 1-20-1 Handayama, Higashi-ku, Hamamatsu 431-3192 (Japan); Nobuhara, Mamoru; Sakamoto, Atsushi; Urushida, Tsuyoshi; Katoh, Hideki; Satoh, Hiroshi [Internal Medicine III, Hamamatsu University School of Medicine, 1-20-1 Handayama, Higashi-ku, Hamamatsu 431-3192 (Japan); Funaki, Makoto [Clinical Research Center for Diabetes, Tokushima University Hospital, 2-50-1 Kuramoto-cho, Tokushima 770-8503 (Japan); Hayashi, Hideharu [Internal Medicine III, Hamamatsu University School of Medicine, 1-20-1 Handayama, Higashi-ku, Hamamatsu 431-3192 (Japan)

2014-05-01

Purpose: Evidence suggests an association between aberrant mitochondrial dynamics and cardiac diseases. Because myocardial metabolic deficiency caused by insulin resistance plays a crucial role in heart disease, we investigated the role of dynamin-related protein-1 (DRP1; a mitochondrial fission protein) in the pathogenesis of myocardial insulin resistance. Methods and Results: DRP1-expressing H9c2 myocytes, which had fragmented mitochondria with mitochondrial membrane potential (ΔΨ{sub m}) depolarization, exhibited attenuated insulin signaling and 2-deoxy-D-glucose (2-DG) uptake, indicating insulin resistance. Treatment of the DRP1-expressing myocytes with Mn(III)tetrakis(1-methyl-4-pyridyl)porphyrin pentachloride (TMPyP) significantly improved insulin resistance and mitochondrial dysfunction. When myocytes were exposed to hydrogen peroxide (H{sub 2}O{sub 2}), they increased DRP1 expression and mitochondrial fragmentation, resulting in ΔΨ{sub m} depolarization and insulin resistance. When DRP1 was suppressed by siRNA, H{sub 2}O{sub 2}-induced mitochondrial dysfunction and insulin resistance were restored. Our results suggest that a mutual enhancement between DRP1 and reactive oxygen species could induce mitochondrial dysfunction and myocardial insulin resistance. In palmitate-induced insulin-resistant myocytes, neither DRP1-suppression nor TMPyP restored the ΔΨ{sub m} depolarization and impaired 2-DG uptake, however they improved insulin signaling. Conclusions: A mutual enhancement between DRP1 and ROS could promote mitochondrial dysfunction and inhibition of insulin signal transduction. However, other mechanisms, including lipid metabolite-induced mitochondrial dysfunction, may be involved in palmitate-induced insulin resistance. - Highlights: • DRP1 promotes mitochondrial fragmentation and insulin-resistance. • A mutual enhancement between DRP1 and ROS ipromotes insulin-resistance. • Palmitate increases DRP1 expression and induces insulin
Targeted transgenic overexpression of mitochondrial thymidine kinase (TK2) alters mitochondrial DNA (mtDNA) and mitochondrial polypeptide abundance: transgenic TK2, mtDNA, and antiretrovirals.

Science.gov (United States)

Hosseini, Seyed H; Kohler, James J; Haase, Chad P; Tioleco, Nina; Stuart, Tami; Keebaugh, Erin; Ludaway, Tomika; Russ, Rodney; Green, Elgin; Long, Robert; Wang, Liya; Eriksson, Staffan; Lewis, William

2007-03-01

Mitochondrial toxicity limits nucleoside reverse transcriptase inhibitors (NRTIs) for acquired immune deficiency syndrome. NRTI triphosphates, the active moieties, inhibit human immunodeficiency virus reverse transcriptase and eukaryotic mitochondrial DNA polymerase pol-gamma. NRTI phosphorylation seems to correlate with mitochondrial toxicity, but experimental evidence is lacking. Transgenic mice (TGs) with cardiac overexpression of thymidine kinase isoforms (mitochondrial TK2 and cytoplasmic TK1) were used to study NRTI mitochondrial toxicity. Echocardiography and nuclear magnetic resonance imaging defined cardiac performance and structure. TK gene copy and enzyme activity, mitochondrial (mt) DNA and polypeptide abundance, succinate dehydrogenase and cytochrome oxidase histochemistry, and electron microscopy correlated with transgenesis, mitochondrial structure, and biogenesis. Antiretroviral combinations simulated therapy. Untreated hTK1 or TK2 TGs exhibited normal left ventricle mass. In TK2 TGs, cardiac TK2 gene copy doubled, activity increased 300-fold, and mtDNA abundance doubled. Abundance of the 17-kd subunit of complex I, succinate dehydrogenase histochemical activity, and cristae density increased. NRTIs increased left ventricle mass 20% in TK2 TGs. TK activity increased 3 logs in hTK1 TGs, but no cardiac phenotype resulted. NRTIs abrogated functional effects of transgenically increased TK2 activity but had no effect on TK2 mtDNA abundance. Thus, NRTI mitochondrial phosphorylation by TK2 is integral to clinical NRTI mitochondrial toxicity.
Elevated mRNA-levels of distinct mitochondrial and plasma membrane Ca2+ transporters in individual hypoglossal motor neurons of endstage SOD1 transgenic mice.

Directory of Open Access Journals (Sweden)

Tobias eMühling

2014-11-01

Full Text Available Disturbances in Ca2+ homeostasis and mitochondrial dysfunction have emerged as major pathogenic features in familial and sporadic forms of Amyotrophic Lateral Sclerosis (ALS, a fatal degenerative motor neuron disease. However, the distinct molecular ALS-pathology remains unclear. Recently, an activity-dependent Ca2+ homeostasis deficit, selectively in highly vulnerable cholinergic motor neurons in the hypoglossal nucleus (hMNs from a common ALS mouse model, endstage superoxide dismutase SOD1G93A transgenic mice, was described. This functional deficit was defined by a reduced hMN mitochondrial Ca2+ uptake capacity and elevated Ca2+ extrusion across the plasma membrane. To address the underlying molecular mechanisms, here we quantified mRNA-levels of respective potential mitochondrial and plasma membrane Ca2+ transporters in individual, choline-acetyltransferase (ChAT positive hMNs from wildtype (WT and endstage SOD1G93A mice, by combining UV laser microdissection with RT-qPCR techniques, and specific data normalization. As ChAT cDNA levels as well as cDNA and genomic DNA levels of the mitochondrially encoded NADH dehydrogenase ND1 were not different between hMNs from WT and endstage SOD1G93A mice, these genes were used to normalize hMN-specific mRNA-levels of plasma membrane and mitochondrial Ca2+ transporters, respectively. We detected about 2-fold higher levels of the mitochondrial Ca2+ transporters MCU/MICU1, Letm1 and UCP2 in remaining hMNs from endstage SOD1G93A mice. These higher expression-levels of mitochondrial Ca2+ transporters in individual hMNs were not associated with a respective increase in number of mitochondrial genomes, as evident from hMN specific ND1 DNA quantification. Normalized mRNA-levels for the plasma membrane Na2+/Ca2+exchanger NCX1 was also about 2-fold higher in hMNs from SOD1G93A mice. Thus, pharmacological stimulation of Ca2+ transporters in highly vulnerable hMNs might offer a novel neuroprotective strategy for ALS.
Factors associated with the severity of fatal accidents in construction workers.

Science.gov (United States)

Khodabandeh, Farideh; Kabir-Mokamelkhah, Elaheh; Kahani, Mahsa

2016-01-01

Background: Construction work (building houses, roads, workplaces, and repairing and maintaining infrastructures) is a dangerous land-based job. This includes many hazardous tasks and conditions such as working at the following conditions: Height, excavation, noise, dust, power tools and equipment. Construction work has been increased in developed and underdeveloped countries over the past few years. Occupational fatalities have increased with an increase in this type of work. Occupational fatalities refer to individuals who pass way while on the job or performing work related tasks. In the present study, to identify the factors, personal characteristics and work-related factors associated with fatal occupational mortality were assessed using data for Tehran, Iran, 2014-2016. Methods: We conducted a retrospective study, using 967 postmortem reports from fatal occupational injuries collected through postmortem investigations during 2014-2016. A sampling frame of 967 postmortem reports from fatal occupational injuries was used to draw a total sample of 714 fatal construction accidents for this cross-sectional study. Pearson χ2 test and Kruskal-Wallis tests were used for statistical analysis. Results: Based on the results of this study, male gender (n=714; 100%), age range of 30-39 years (n=183; 25.6%), secondary educational level (n=273; 38.2%), being married (317; 44.4%), causal employee (n=389; 54.5%), unskilled performance (389; 54.5%), no insurance coverage (472; 66.1%), and daytime duty work (287; 40.2%) were identified as risk factors for fatality in the event of construction fatal injury. A significant relationship was found between the type of injury and sociodemographic and work related variables. Conclusion: Workers' characteristics such as age, gender, experience, and educational background, and work related variables such as skill training, safety measurement, and close monitoring could be used to discriminate among different severity levels of
Molecular basis for mitochondrial signaling

CERN Document Server

2017-01-01

This book covers recent advances in the study of structure, function, and regulation of metabolite, protein and ion translocating channels, and transporters in mitochondria. A wide array of cutting-edge methods are covered, ranging from electrophysiology and cell biology to bioinformatics, as well as structural, systems, and computational biology. At last, the molecular identity of two important channels in the mitochondrial inner membrane, the mitochondrial calcium uniporter and the mitochondrial permeability transition pore have been established. After years of work on the physiology and structure of VDAC channels in the mitochondrial outer membrane, there have been multiple discoveries on VDAC permeation and regulation by cytosolic proteins. Recent breakthroughs in structural studies of the mitochondrial cholesterol translocator reveal a set of novel unexpected features and provide essential clues for defining therapeutic strategies. Molecular Basis for Mitochondrial Signaling covers these and many more re...
Sarcoma de Kaposi clássico fatal Fatal outcome in classic Kaposi's sarcoma

Directory of Open Access Journals (Sweden)

Eugênia Maria Damásio N. Ohe

2010-06-01

Full Text Available Descrito em 1872, o sarcoma de Kaposi é neoplasia multicêntrica rara originária de células endoteliais com manifestação cutânea e extracutânea. A forma clássica é muito mais frequente em homens idosos, com evolução prolongada e boa resposta a quimioterapia e radioterapia. Apresentaremos um caso de sarcoma de Kaposi clássico com comprometimento cutâneo e visceral em paciente do sexo feminino com rápida evolução fatal.First described in 1872, Kaposi's sarcoma is defined as a rare multifocal tumor that originates in the endothelial cells and presents with cutaneous and extracutaneous manifestations. The classic form is most common in elderly men and progression is slow. This tumor responds well to chemotherapy and radiotherapy. This report describes a classic case of Kaposi's sarcoma in a woman with skin and visceral manifestations in whom the disease rapidly progressed to a fatal outcome.
Unique fatality due to claw injuries in a tiger attack: a case report.

Science.gov (United States)

Pathak, Hrishikesh; Dixit, Pradeep; Dhawane, Shailendra; Meshram, Satin; Shrigiriwar, Manish; Dingre, Niraj

2014-11-01

This paper describes a unique case of a fatal tiger attack in the wild. In the present case, a tiger fatally mauled a 34-year-old female with its claws, instead of the usual mechanism of killing by the bite injury to the neck. The autopsy revealed multiple fatal and non-fatal injuries caused by the tiger claws. The characteristic injuries due to the tooth impacts were absent as the teeth of the offending tiger were either fallen or non-functional. To the best of our knowledge, probably this rare case would be the first reported human fatality due to the tiger claw injuries in the world. The purpose of the present article is to highlight the fatal injuries due to the tiger claws, as the claw-induced fatal injuries in a tiger attack are not reported in the medico-legal literature. Moreover, this report would be an illustrative one for differentiation between the fatal injuries due to the claws and tooth impacts in a tiger attack. Furthermore, the present report establishes the importance of the tiger claws as a source of fatal injuries in a tiger attack. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.
Co-ordinate decrease in the expression of the mitochondrial genome and nuclear genes for mitochondrial proteins in the lactation-induced mitochondrial hypotrophy of rat brown fat.

Science.gov (United States)

Martin, I; Giralt, M; Viñas, O; Iglesias, R; Mampel, T; Villarroya, F

1995-01-01

The relative abundance of the mitochondrial-encoded mRNAs for cytochrome c oxidase subunit II and NADH dehydrogenase subunit I was lower in brown adipose tissue (BAT) from lactating rats than in virgin controls. This decrease was in parallel with a significant decrease in mitochondrial 16 S rRNA levels and in the relative content of mitochondrial DNA in the tissue. BAT from lactating rats showed lowered mRNA expression of the nuclear-encoded genes for the mitochondrial uncoupling protein, subunit IV of cytochrome c oxidase and the adenine nucleotide translocase isoforms ANT1 and ANT2, whereas mRNA levels for the ATP synthase beta-subunit were unchanged. However, the relative content of this last protein was lower in BAT mitochondria from lactating rats than in virgin controls. It is concluded that lactation-induced mitochondrial hypotrophy in BAT is associated with a co-ordinate decrease in the expression of the mitochondrial genome and nuclear genes for mitochondrial proteins. This decrease is caused by regulatory events acting at different levels, including pre- and post-transcriptional regulation. BAT appears to be a useful model with which to investigate the molecular mechanisms involved in the co-ordination of the expression of the mitochondrial and nuclear genomes during mitochondrial biogenesis. Images Figure 1 Figure 2 PMID:8948428
SK2 channels regulate mitochondrial respiration and mitochondrial Ca2+ uptake

NARCIS (Netherlands)

Honrath, Birgit; Matschke, Lina; Meyer, Tammo; Magerhans, Lena; Perocchi, Fabiana; Ganjam, Goutham K; Zischka, Hans; Krasel, Cornelius; Gerding, Albert; Bakker, Barbara M; Bünemann, Moritz; Strack, Stefan; Decher, Niels; Culmsee, Carsten; Dolga, Amalia M

Mitochondrial calcium ([Ca(2+)]m) overload and changes in mitochondrial metabolism are key players in neuronal death. Small conductance calcium-activated potassium (SK) channels provide protection in different paradigms of neuronal cell death. Recently, SK channels were identified at the inner
Urban sprawl as a risk factor in motor vehicle occupant and pedestrian fatalities.

Science.gov (United States)

Ewing, Reid; Schieber, Richard A; Zegeer, Charles V

2003-09-01

We sought to determine the association between urban sprawl and traffic fatalities. We created a sprawl index by applying principal components analysis to data for 448 US counties in the largest 101 metropolitan areas. Regression analysis was used to determine associations between the index and traffic fatalities. For every 1% increase in the index (i.e., more compact, less sprawl), all-mode traffic fatality rates fell by 1.49% (P Urban sprawl was directly related to traffic fatalities and pedestrian fatalities. Subsequent studies should investigate relationships at a finer geographic scale and should strive to improve on the measure of exposure used to adjust pedestrian fatality rates.
Bordetella bronchiseptica and fatal pneumonia of dogs and cats

Science.gov (United States)

Bordetella bronchiseptica frequently causes nonfatal tracheobronchitis, but its role in fatal pneumonia is less well-studied. The objectives of this study were to identify the frequency of Bordetella bronchiseptica infection in fatal cases of bronchopneumonia in dogs and cats and to compare the diag...
Lake tourism fatalities: a 46-year history of death at Lake Powell.

Science.gov (United States)

Heggie, Travis W

2018-05-01

This study investigates tourist mortality at Lake Powell over a 46-year period. To date no comprehensive long-term investigation examining the relationship between the lake environment and tourist mortality exists. A retrospective study was conducted of all tourist fatalities between 1959 and 2005. There were 351 fatal incidents resulting in 386 deaths between 1959 and 2005. Over the 46-year period, the average number of fatalities was 8.4 (±5.26) per year. Out of all fatalities, 282 were classified as accidental, 80 were classified as natural deaths, 13 were suicides and 5 were classified as homicides. Males accounted for 80% of fatalities and tourists aged 20-29 years and 10-19 years accounted for 36% of all fatalities. The highest number of fatalities was recorded in July (74), May (64), August (63) and June (59). Out of all accidental deaths, boating (29%) and swimming (22%) were the most common pre-death activities. High winds capsizing boats and carbon monoxide poisoning from boat engines were common factors contributing to 31 boating fatalities. Fatigue and exhaustion contributed to 22 swimming deaths. Recreational boating and swimming account for over half of all accidental deaths. Tourists visiting Lake Powell for recreational purposes should be informed of the risks associated with the lake environment.
Neonatal mortality in Utah.

Science.gov (United States)

Woolley, F R; Schuman, K L; Lyon, J L

1982-09-01

A cohort study of neonatal mortality (N = 106) in white singleton births (N = 14,486) in Utah for January-June 1975 was conducted. Using membership and activity in the Church of Jesus Christ of Latter-day Saints (LDS or Mormon) as a proxy for parental health practices, i.e., tobacco and alcohol abstinence, differential neonatal mortality rates were calculated. The influence of potential confounding factors was evaluated. Low activity LDS members were found to have an excess risk of neonatal death five times greater than high activity LDS, with an upper bound of a two-sided 95% confidence interval of 7.9. The data consistently indicate a lower neonatal mortality rate for active LDS members. Non-LDS were found to have a lower rate than either medium or low activity LDS.
Assessing the impact of Syrian refugees on earthquake fatality estimations in southeast Turkey

Science.gov (United States)

Wilson, Bradley; Paradise, Thomas

2018-01-01

The influx of millions of Syrian refugees into Turkey has rapidly changed the population distribution along the Dead Sea Rift and East Anatolian fault zones. In contrast to other countries in the Middle East where refugees are accommodated in camp environments, the majority of displaced individuals in Turkey are integrated into local cities, towns, and villages - placing stress on urban settings and increasing potential exposure to strong earthquake shaking. Yet displaced populations are often unaccounted for in the census-based population models used in earthquake fatality estimations. This study creates a minimally modeled refugee gridded population model and analyzes its impact on semi-empirical fatality estimations across southeast Turkey. Daytime and nighttime fatality estimates were produced for five fault segments at earthquake magnitudes 5.8, 6.4, and 7.0. Baseline fatality estimates calculated from census-based population estimates for the study area varied in scale from tens to thousands of fatalities, with higher death totals in nighttime scenarios. Refugee fatality estimations were analyzed across 500 semi-random building occupancy distributions. Median fatality estimates for refugee populations added non-negligible contributions to earthquake fatalities at four of five fault locations, increasing total fatality estimates by 7-27 %. These findings communicate the necessity of incorporating refugee statistics into earthquake fatality estimations in southeast Turkey and the ongoing importance of placing environmental hazards in their appropriate regional and temporal context.
Neuroradiologic findings in children with mitochondrial disorder: correlation with mitochondrial respiratory chain defects

International Nuclear Information System (INIS)

Kim, Jinna; Lee, Seung-Koo; Kim, Dong Ik; Kim, Eung Yeop; Lee, Young-Mock; Lee, Joon Soo; Kim, Heung Dong

2008-01-01

Mitochondrial disorders are a heterogeneous group of disorders affecting energy metabolism that can present at any age with a wide variety of clinical symptoms. We investigated brain magnetic resonance (MR) findings in 40 children with defects of the mitochondrial respiratory chain (MRC) complex and correlated them with the type of MRC defects. Enrolled were 40 children with MRC defects in biochemical enzyme assay of the muscle specimen. Twenty-one children were found to have classical syndromes of mitochondrial disorders and 19 children presented nonspecific mitochondrial encephalomyopathies. Their brain MR imaging findings were retrospectively reviewed and correlated with the biochemical defect in the MRC complex. Children with MRC defects showed various neuroradiologic features on brain MR imaging that resulted from a complex genetic background and a heterogeneous phenotype. Rapid progression of atrophy involving all structures of the brain with variable involvement of deep gray and white matter are the most frequent MR findings in children with MRC defects in both classical syndromes of mitochondrial disorder and nonspecific mitochondrial encephalomyopathies. The type of biochemical defect in the MRC complex enzyme did not correlate with brain MR findings in child patients. (orig.)
Neuroradiologic findings in children with mitochondrial disorder: correlation with mitochondrial respiratory chain defects

Energy Technology Data Exchange (ETDEWEB)

Kim, Jinna; Lee, Seung-Koo; Kim, Dong Ik [Yonsei University College of Medicine, Department of Radiology, Research Institute of Radiological Science, Seoul (Korea); Kim, Eung Yeop [Yonsei University College of Medicine, Department of Radiology, Research Institute of Radiological Science, Brain Korea 21 Project for Medical Science, Seoul (Korea); Lee, Young-Mock; Lee, Joon Soo [Yonsei University College of Medicine, Department of Pediatrics, Pediatric Epilepsy Clinics, Severance Children' s Hospital, Brain Research Institute, Seoul (Korea); Kim, Heung Dong [Yonsei University College of Medicine, Department of Pediatrics, Pediatric Epilepsy Clinics, Severance Children' s Hospital, Brain Research Institute, Seoul (Korea); Yonsei University College of Medicine, Department of Pediatrics, Seoul (Korea)

2008-08-15

Mitochondrial disorders are a heterogeneous group of disorders affecting energy metabolism that can present at any age with a wide variety of clinical symptoms. We investigated brain magnetic resonance (MR) findings in 40 children with defects of the mitochondrial respiratory chain (MRC) complex and correlated them with the type of MRC defects. Enrolled were 40 children with MRC defects in biochemical enzyme assay of the muscle specimen. Twenty-one children were found to have classical syndromes of mitochondrial disorders and 19 children presented nonspecific mitochondrial encephalomyopathies. Their brain MR imaging findings were retrospectively reviewed and correlated with the biochemical defect in the MRC complex. Children with MRC defects showed various neuroradiologic features on brain MR imaging that resulted from a complex genetic background and a heterogeneous phenotype. Rapid progression of atrophy involving all structures of the brain with variable involvement of deep gray and white matter are the most frequent MR findings in children with MRC defects in both classical syndromes of mitochondrial disorder and nonspecific mitochondrial encephalomyopathies. The type of biochemical defect in the MRC complex enzyme did not correlate with brain MR findings in child patients. (orig.)
Predictors of positive blood culture and deaths among neonates with suspected neonatal sepsis in a tertiary hospital, Mwanza- Tanzania

Directory of Open Access Journals (Sweden)

Jeremiah Seni

2010-06-01

Full Text Available Abstract Background Neonatal sepsis is a significant cause of morbidity and mortality in neonates. Appropriate clinical diagnosis and empirical treatment in a given setting is crucial as pathogens of bacterial sepsis and antibiotic sensitivity pattern can considerably vary in different settings. This study was conducted at Bugando Medical Centre (BMC, Tanzania to determine the prevalence of neonatal sepsis, predictors of positive blood culture, deaths and antimicrobial susceptibility, thus providing essential information to formulate a policy for management of neonatal sepsis. Methods This was a prospective cross sectional study involving 300 neonates admitted at BMC neonatal unit between March and November 2009. Standard data collection form was used to collect all demographic data and clinical characteristics of neonates. Blood culture was done on Brain Heart Infusion broth followed by identification of isolates using conventional methods and testing for their susceptibility to antimicrobial agents using the disc diffusion method. Results Among 770 neonates admitted during the study period; 300 (38.9% neonates were diagnosed to have neonatal sepsis by WHO criteria. Of 300 neonates with clinical neonatal sepsis 121(40% and 179(60% had early and late onset sepsis respectively. Positive blood culture was found in 57 (47.1% and 92 (51.4% among neonates with early and late onset neonatal sepsis respectively (p = 0.466. Predictors of positive blood culture in both early and late onset neonatal sepsis were inability to feed, lethargy, cyanosis, meconium stained liquor, premature rupture of the membrane and convulsion. About 49% of gram negatives isolates were resistant to third generation cephalosporins and 28% of Staphylococcus aureus were found to be Methicillin resistant Staphylococcus aureus (MRSA. Deaths occurred in 57 (19% of neonates. Factors that predicted deaths were positive blood culture (p = 0.0001, gram negative sepsis (p = 0.0001 and
NEONATAL TOBACCO SYNDROME

Directory of Open Access Journals (Sweden)

R.A.Kireev

2008-12-01

Full Text Available The objective of the research is to study neonatal adaptation in new-born children from the tobacco abused mothers. A comparative analysis of clinical and neuroendochnal status and lipid metabolism in new-born children from smoking and non-smoking mothers was carried out Neonatal adaptation disorders were revealed in new-born children from the smoking mothers.

Pelayanan Kesehatan Ibu dan Kematian Neonatal

Directory of Open Access Journals (Sweden)

Desy Fitri Yani

2013-03-01

Full Text Available Indonesia bersama seluruh negara berkembang berupaya mencapai kesepakatan Millenium Development Goals (MDGs dengan salah satu sasaran menurunkan angka kematian neonatal dari 20 per 1.000 kelahiran hidup menjadi 15 per 1.000 kelahiran hidup. Penelitian ini bertujuan mengetahui hubungan pelayanan kesehatan ibu dengan kematian neonatal di Kabupaten Lampung Timur tahun 2011. Penelitian dengan desain studi kasus kontrol ini mengamati kasus ibu yang mengalami kematian neonatal dan kontrol ibu yang tidak mengalami kematian neonatal. Analisis multivariat menemukan pelayanan antenatal dan pertolongan persalinan berhubungan secara signifikan dengan kematian neonatal, setelah mengendalikan variabel umur ibu dan riwayat kehamilan (OR = 16,32; nilai p = 0,000; dan (OR = 18,36; nilai p = 0,31. Bayi yang dilahirkan dari Ibu dengan pelayanan antenatal tidak lengkap berisiko mengalami kematian neonatal 16,32 dan 18,36 kali lebih besar daripada bayi yang dilahirkan. Ibu dengan pelayanan antenatal lengkap dan penolong persalinan profesional. Tidak ada hubungan penolong persalinan dengan kematian neonatal, setelah mengontrol variabel pelayanan antenatal, umur ibu, riwayat kehamilan, riwayat penyakit, dan riwayat persalinan. Disarankan meningkatkan kualitas pelayanan antenatal dengan memerhatikan faktor umur ibu dan riwayat persalinan, mengembangkan kegiatan audit maternal perinatal serta meningkatkan keterampilan petugas penolong persalinan. All developing countries including Indonesia seek to reach agreement the Millennium Development Goals (MDG’s. It is objectives include reducing neonatal mortality by 25 percent from 20 per 1,000 live birth to 15 per 1,000 live births. This study aimed to determine the relationship of maternal health services with neonatal mortality in East Lampung District in 2011. This study used case control design to compare between the groups of mother whom have neonatal deaths (cases and neonatal life (control in East Lampung District in
Genetics of mitochondrial dysfunction and infertility.

Science.gov (United States)

Demain, L A M; Conway, G S; Newman, W G

2017-02-01

Increasingly, mitochondria are being recognized as having an important role in fertility. Indeed in assisted reproductive technologies mitochondrial function is a key indicator of sperm and oocyte quality. Here, we review the literature regarding mitochondrial genetics and infertility. In many multisystem disorders caused by mitochondrial dysfunction death occurs prior to sexual maturity, or the clinical features are so severe that infertility may be underreported. Interestingly, many of the genes linked to mitochondrial dysfunction and infertility have roles in the maintenance of mitochondrial DNA or in mitochondrial translation. Studies on populations with genetically uncharacterized infertility have highlighted an association with mitochondrial DNA deletions, whether this is causative or indicative of poor functioning mitochondria requires further examination. Studies on the impact of mitochondrial DNA variants present conflicting data but highlight POLG as a particularly interesting candidate gene for both male and female infertility. © 2016 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.
Distribution of mitochondrial nucleoids upon mitochondrial network fragmentation and network reintegration in HEPG2 cells

Czech Academy of Sciences Publication Activity Database

Tauber, Jan; Dlasková, Andrea; Šantorová, Jitka; Smolková, Katarína; Alán, Lukáš; Špaček, Tomáš; Plecitá-Hlavatá, Lydie; Ježek, Petr

2013-01-01

Roč. 45, č. 3 (2013), s. 593-603 ISSN 1357-2725 R&D Projects: GA ČR(CZ) GAP302/10/0346; GA ČR(CZ) GPP304/10/P204; GA ČR(CZ) GAP305/12/1247 Institutional research plan: CEZ:AV0Z50110509 Institutional support: RVO:67985823 Keywords : mitochondrial DNA nucleoids * mitochondrial fission * mitochondrial network fragmentation * mitochondrial network reintegration Subject RIV: ED - Physiology Impact factor: 4.240, year: 2013
Circumstances of fatal lockout/tagout-related injuries in manufacturing.

Science.gov (United States)

Bulzacchelli, Maria T; Vernick, Jon S; Sorock, Gary S; Webster, Daniel W; Lees, Peter S J

2008-10-01

Over the past few decades, hundreds of manufacturing workers have suffered fatal injuries while performing maintenance and servicing on machinery and equipment. Using lockout/tagout procedures could have prevented many of these deaths. A narrative text analysis of OSHA accident investigation report summaries was conducted to describe the circumstances of lockout/tagout-related fatalities occurring in the US manufacturing industry from 1984 to 1997. The most common mechanisms of injury were being caught in or between parts of equipment, electrocution, and being struck by or against objects. Typical scenarios included cleaning a mixer or blender, cleaning a conveyor, and installing or disassembling electrical equipment. Lockout procedures were not even attempted in the majority (at least 58.8%) of fatal incidents reviewed. Lockout/tagout-related fatalities occur under a wide range of circumstances. Enhanced training and equipment designs that facilitate lockout and minimize worker contact with machine parts may prevent many lockout/tagout-related injuries. Published 2008 Wiley-Liss, Inc.
Interpretation of neonatal chest radiography

International Nuclear Information System (INIS)

Yoon, Hye Kyung

2016-01-01

Plain radiographs for infants in the neonatal intensive care unit are obtained using the portable X-ray equipment in order to evaluate the neonatal lungs and also to check the position of the tubes and catheters used for monitoring critically-ill neonates. Neonatal respiratory distress is caused by a variety of medical or surgical disease conditions. Clinical information about the gestational week, respiratory symptoms, and any events during delivery is essential for interpretation of the neonatal chest radiographs. Awareness of common chest abnormality in the prematurely born or term babies is also very important for chest evaluation in the newborn. Furthermore, knowledge about complications such as air leaks and bronchopulmonary dysplasia following treatment are required to accurately inform the clinicians. The purpose of this article was to briefly review radiographic findings of chest diseases in newborns that are relatively common in daily practice
Interpretation of neonatal chest radiography

Energy Technology Data Exchange (ETDEWEB)

Yoon, Hye Kyung [Dept. of Radiology, Kangwon National University Hospital, Chuncheon (Korea, Republic of)

2016-05-15

Plain radiographs for infants in the neonatal intensive care unit are obtained using the portable X-ray equipment in order to evaluate the neonatal lungs and also to check the position of the tubes and catheters used for monitoring critically-ill neonates. Neonatal respiratory distress is caused by a variety of medical or surgical disease conditions. Clinical information about the gestational week, respiratory symptoms, and any events during delivery is essential for interpretation of the neonatal chest radiographs. Awareness of common chest abnormality in the prematurely born or term babies is also very important for chest evaluation in the newborn. Furthermore, knowledge about complications such as air leaks and bronchopulmonary dysplasia following treatment are required to accurately inform the clinicians. The purpose of this article was to briefly review radiographic findings of chest diseases in newborns that are relatively common in daily practice.
Radiation doses and risks to neonates undergoing common radiographic examinations in the neonatal intensive care unit

International Nuclear Information System (INIS)

McParland, B.J.; Lee, R.

1996-01-01

Neonates in the-Neonatal Intensive Care Unit (NICU) can receive large numbers of radiographs owing to the clinical conditions they may present. More neonatal radiation dosimetry data are required for three fundamental reasons: (1.) to aid in the establishment of reference dose levels for interinstitutional comparisons; (2.) to improve childhood cancer risk estimates following neonatal exposure; and (3.) to indicate appropriate directions for dose reduction. This paper describes an investigation of two different NICU radiological techniques with significantly different neonate doses. While patient-matched images taken with both techniques were assessed in a blind review, this component of the study is beyond the scope of this paper and is not discussed here. (author)
Mitochondrial Dynamics in Diabetic Cardiomyopathy

Science.gov (United States)

Galloway, Chad A.

2015-01-01

Abstract Significance: Cardiac function is energetically demanding, reliant on efficient well-coupled mitochondria to generate adenosine triphosphate and fulfill the cardiac demand. Predictably then, mitochondrial dysfunction is associated with cardiac pathologies, often related to metabolic disease, most commonly diabetes. Diabetic cardiomyopathy (DCM), characterized by decreased left ventricular function, arises independently of coronary artery disease and atherosclerosis. Dysregulation of Ca2+ handling, metabolic changes, and oxidative stress are observed in DCM, abnormalities reflected in alterations in mitochondrial energetics. Cardiac tissue from DCM patients also presents with altered mitochondrial morphology, suggesting a possible role of mitochondrial dynamics in its pathological progression. Recent Advances: Abnormal mitochondrial morphology is associated with pathologies across diverse tissues, suggesting that this highly regulated process is essential for proper cell maintenance and physiological homeostasis. Highly structured cardiac myofibers were hypothesized to limit alterations in mitochondrial morphology; however, recent work has identified morphological changes in cardiac tissue, specifically in DCM. Critical Issues: Mitochondrial dysfunction has been reported independently from observations of altered mitochondrial morphology in DCM. The temporal relationship and causative nature between functional and morphological changes of mitochondria in the establishment/progression of DCM is unclear. Future Directions: Altered mitochondrial energetics and morphology are not only causal for but also consequential to reactive oxygen species production, hence exacerbating oxidative damage through reciprocal amplification, which is integral to the progression of DCM. Therefore, targeting mitochondria for DCM will require better mechanistic characterization of morphological distortion and bioenergetic dysfunction. Antioxid. Redox Signal. 22, 1545–1562. PMID
The work-related fatal injury study: numbers, rates and trends of work-related fatal injuries in New Zealand 1985-1994.

Science.gov (United States)

Feyer, A M; Langley, J; Howard, M; Horsburgh, S; Wright, C; Alsop, J; Cryer, C

2001-01-26

To determine the number and rates of work-related fatal injuries by employment status, occupation, industry, age and gender in New Zealand 1985-1994. Potential cases of work-related injury deaths of persons aged 15-84 years were identified from the national electronic mortality data files. Main exclusions were deaths due to suicide and deaths due to motor vehicle crashes. The circumstances of the deaths of each fatal incident meeting inclusion criteria were then reviewed directly from coronial files to determine work-relatedness. The rate of work-related fatal injury in New Zealand was 5.03/100000 workers per year for the study period. There was a significant decline in crude rate over the study period. However, this was in substantial part accounted for by changes in occupation and industry mix. Older workers, male workers, self-employed workers, and particular occupational groups, all had substantially elevated rates. Agricultural and helicopter pilots, forestry workers and fishery workers had the highest rates. Farmers, forestry workers, and fishery workers also had high numbers of deaths, together accounting for nearly 40% of all deaths. This study has demonstrated that work-related fatal injury remains a pressing problem for New Zealand. Several areas in urgent need of prevention efforts were highlighted.
Habitual physical activity in mitochondrial disease.

Science.gov (United States)

Apabhai, Shehnaz; Gorman, Grainne S; Sutton, Laura; Elson, Joanna L; Plötz, Thomas; Turnbull, Douglass M; Trenell, Michael I

2011-01-01

Mitochondrial disease is the most common neuromuscular disease and has a profound impact upon daily life, disease and longevity. Exercise therapy has been shown to improve mitochondrial function in patients with mitochondrial disease. However, no information exists about the level of habitual physical activity of people with mitochondrial disease and its relationship with clinical phenotype. Habitual physical activity, genotype and clinical presentations were assessed in 100 patients with mitochondrial disease. Comparisons were made with a control group individually matched by age, gender and BMI. Patients with mitochondrial disease had significantly lower levels of physical activity in comparison to matched people without mitochondrial disease (steps/day; 6883±3944 vs. 9924±4088, p = 0.001). 78% of the mitochondrial disease cohort did not achieve 10,000 steps per day and 48% were classified as overweight or obese. Mitochondrial disease was associated with less breaks in sedentary activity (Sedentary to Active Transitions, % per day; 13±0.03 vs. 14±0.03, p = 0.001) and an increase in sedentary bout duration (bout lengths/fraction of total sedentary time; 0.206±0.044 vs. 0.187±0.026, p = 0.001). After adjusting for covariates, higher physical activity was moderately associated with lower clinical disease burden (steps/day; r(s) = -0.49; 95% CI -0.33, -0.63, Pphysical activity between different genotypes mitochondrial disease. These results demonstrate for the first time that low levels of physical activity are prominent in mitochondrial disease. Combined with a high prevalence of obesity, physical activity may constitute a significant and potentially modifiable risk factor in mitochondrial disease.
Allegheny County Fatal Accidental Overdoses

Data.gov (United States)

Allegheny County / City of Pittsburgh / Western PA Regional Data Center — Fatal accidental overdose incidents in Allegheny County, denoting age, gender, race, drugs present, zip code of incident and zip code of residence. Zip code of...
49 CFR 219.207 - Fatality.

Science.gov (United States)

2010-10-01

... TRANSPORTATION CONTROL OF ALCOHOL AND DRUG USE Post-Accident Toxicological Testing § 219.207 Fatality. (a) In the..., United States Code (but not the agent of the Secretary for purposes of the Federal Tort Claims Act...
Understanding mitochondrial myopathies: a review

Directory of Open Access Journals (Sweden)

Abhimanyu S. Ahuja

2018-05-01

Full Text Available Mitochondria are small, energy-producing structures vital to the energy needs of the body. Genetic mutations cause mitochondria to fail to produce the energy needed by cells and organs which can cause severe disease and death. These genetic mutations are likely to be in the mitochondrial DNA (mtDNA, or possibly in the nuclear DNA (nDNA. The goal of this review is to assess the current understanding of mitochondrial diseases. This review focuses on the pathology, causes, risk factors, symptoms, prevalence data, symptomatic treatments, and new research aimed at possible preventions and/or treatments of mitochondrial diseases. Mitochondrial myopathies are mitochondrial diseases that cause prominent muscular symptoms such as muscle weakness and usually present with a multitude of symptoms and can affect virtually all organ systems. There is no cure for these diseases as of today. Treatment is generally supportive and emphasizes symptom management. Mitochondrial diseases occur infrequently and hence research funding levels tend to be low in comparison with more common diseases. On the positive side, quite a few genetic defects responsible for mitochondrial diseases have been identified, which are in turn being used to investigate potential treatments. Speech therapy, physical therapy, and respiratory therapy have been used in mitochondrial diseases with variable results. These therapies are not curative and at best help with maintaining a patient’s current abilities to move and function.
Outbreak of a novel Enterobacter sp. carrying blaCTX-M-15 in a neonatal unit of a tertiary care hospital in Tanzania.

Science.gov (United States)

Mshana, Stephen E; Gerwing, Lisa; Minde, Mercy; Hain, Torsten; Domann, Eugen; Lyamuya, Eligius; Chakraborty, Trinad; Imirzalioglu, Can

2011-09-01

Enterobacter hormaechei and Cronobacter sakazakii are amongst the most important causes of outbreaks of neonatal sepsis associated with powdered milk. In this study, we report for the first time an outbreak of a novel Enterobacter sp. harbouring bla(CTX-M-15) in a neonatal unit in Tanzania. Seventeen Gram-negative enteric isolates from neonatal blood cultures were studied. Antibiotic susceptibility was assessed by disc diffusion testing, and the presence of the bla(CTX-M-15) gene was established by polymerase chain reaction (PCR) and sequencing. Isolates were typed by pulsed-field gel electrophoresis (PFGE). Identification by biochemical profiling was followed by nucleotide sequencing of 16S ribosomal DNA (rDNA), rpoB and hsp60 alleles. Environmental sampling was done and control measures were established. Isolates were initially misidentified based on their fermentation characteristics and agglutination as Salmonella enterica serotype Paratyphi. All isolates were resistant to multiple antibiotics, except for ciprofloxacin and carbapenems, and were found to harbour bla(CTX-M-15) on a 291-kb narrow-range plasmid. PFGE analysis indicated the clonal outbreak of a single strain, infecting 17 neonates with a case fatality rate of 35%. The same strain was isolated from a milk bucket. Phylogenetic analysis using 16S rDNA, rpoB and hsp60 sequences permitted no definitive identification, clustering the strains in the Enterobacter cloacae complex with similarities of 92-98.8%. The data describe an outbreak of a novel bla(CTX-M-15)-positive, multiresistant Enterobacter strain in an African neonatal unit that can easily be misidentified taxonomically. These data highlight the need for constant surveillance of bacteria harbouring extended-spectrum β-lactamases as well as improvements in hygiene measures in developing countries. Copyright © 2011 Elsevier B.V. and the International Society of Chemotherapy. All rights reserved.
Fatal crashes of passenger vehicles before and after adding antilock braking systems.

Science.gov (United States)

Farmer, C M; Lund, A K; Trempel, R E; Braver, E R

1997-11-01

Fatal crash rates of passenger cars and vans were compared for the last model year before four-wheel antilock brakes were introduced and the first model year for which antilock brakes were standard equipment. Vehicles selected for analysis had no other significant design changes between the model years being compared, and the model years with and without antilocks were no more than two years apart. The overall fatal crash rates were similar for the two model years. However, the vehicles with antilocks were significantly more likely to be involved in crashes fatal to their own occupants, particularly single-vehicle crashes. Conversely, antilock vehicles were less likely to be involved in crashes fatal to occupants of other vehicles or nonoccupants (pedestrians, bicyclists). Overall, antilock brakes appear to have had little effect on fatal crash involvement. Further study is needed to better understand why fatality risk has increased for occupants of antilock vehicles.
Neonatal hypokalemia

Directory of Open Access Journals (Sweden)

Sarici D

2012-03-01

Full Text Available Dilek Sarici1, S Umit Sarici21Kecioren Research and Education Hospital, Kecioren, Ankara, 2Chief of Division of Neonatology, Division of Neonatology, Department of Pediatrics, Gulhane Military Medical Academy, Ankara, TurkeyAbstract: In this article, distribution of potassium (K+ in body fluids, pathophysiology, causes, clinical signs and symptoms, and the evaluation and treatment of neonatal hypokalemia are reviewed. K+ is the most important intracellular cation and normal serum K+ is stabilized between 3.5 and 5.5 mEq/L. Hypokalemia may be caused by increased renal losses, increased extrarenal (gastrointestinal losses, redistribution or prolonged insufficient K+ intake. Clinical signs and symptoms occur as the result of functional changes in striated muscle, smooth muscle, and the heart. Hypokalemia is usually asymptomatic when K+ levels are between 3.0 and 3.5 mEq/L; however, there may sometimes be slight muscle weakness. Moderate hypokalemia is observed when serum K+ is between 2.5 and 3.0 mEq/L. Proximal muscle weakness is observed most commonly in lower extremities; cranial muscles are normal, but constipation and distention are prominent. Severe hypokalemia develops when serum K+ falls below 2.5 mEq/L. Rhabdomyolysis, myoglobinuria, severe muscle weakness, paralysis, respiratory distress, and respiratory arrest are observed. The clinical signs and symptoms may be unremarkable in cases of chronically developing hypokalemia; however, appropriate treatment is essential when serum K+ level falls below 2.5 mEq/L as the most dangerous complication of hypokalemia is fatal cardiac arrythmia, and changes visible with electrocardiography may not always correlate with the level of hypokalemia. Sodium (Na+, K+, chloride (Cl-, bicarbonate, creatinine, blood sugar, magnesium (Mg, plasma renin activity, aldosterone, and blood gases should be investigated by laboratory testing. Aspartate aminotransferase, alanine aminotransferase, creatinine kinase, and
Formation and Regulation of Mitochondrial Membranes

Directory of Open Access Journals (Sweden)

Laila Cigana Schenkel

2014-01-01

Full Text Available Mitochondrial membrane phospholipids are essential for the mitochondrial architecture, the activity of respiratory proteins, and the transport of proteins into the mitochondria. The accumulation of phospholipids within mitochondria depends on a coordinate synthesis, degradation, and trafficking of phospholipids between the endoplasmic reticulum (ER and mitochondria as well as intramitochondrial lipid trafficking. Several studies highlight the contribution of dietary fatty acids to the remodeling of phospholipids and mitochondrial membrane homeostasis. Understanding the role of phospholipids in the mitochondrial membrane and their metabolism will shed light on the molecular mechanisms involved in the regulation of mitochondrial function and in the mitochondrial-related diseases.
Modulation of mitochondrial bioenergetics in a skeletal muscle cell line model of mitochondrial toxicity

Directory of Open Access Journals (Sweden)

William Dott

2014-01-01

Full Text Available Mitochondrial toxicity is increasingly being implicated as a contributing factor to many xenobiotic-induced organ toxicities, including skeletal muscle toxicity. This has necessitated the need for predictive in vitro models that are able to sensitively detect mitochondrial toxicity of chemical entities early in the research and development process. One such cell model involves substituting galactose for glucose in the culture media. Since cells cultured in galactose are unable to generate sufficient ATP from glycolysis they are forced to rely on mitochondrial oxidative phosphorylation for ATP generation and consequently are more sensitive to mitochondrial perturbation than cells grown in glucose. The aim of this study was to characterise cellular growth, bioenergetics and mitochondrial toxicity of the L6 rat skeletal muscle cell line cultured in either high glucose or galactose media. L6 myoblasts proliferated more slowly when cultured in galactose media, although they maintained similar levels of ATP. Galactose cultured L6 cells were significantly more sensitive to classical mitochondrial toxicants than glucose-cultured cells, confirming the cells had adapted to galactose media. Analysis of bioenergetic function with the XF Seahorse extracellular flux analyser demonstrated that oxygen consumption rate (OCR was significantly increased whereas extracellular acidification rate (ECAR, a measure of glycolysis, was decreased in cells grown in galactose. Mitochondria operated closer to state 3 respiration and had a lower mitochondrial membrane potential and basal mitochondrial O2·– level compared to cells in the glucose model. An antimycin A (AA dose response revealed that there was no difference in the sensitivity of OCR to AA inhibition between glucose and galactose cells. Importantly, cells in glucose were able to up-regulate glycolysis, while galactose cells were not. These results confirm that L6 cells are able to adapt to growth in a
Muscle regeneration in mitochondrial myopathies

DEFF Research Database (Denmark)

Krag, T O; Hauerslev, S; Jeppesen, T D

2013-01-01

Mitochondrial myopathies cover a diverse group of disorders in which ragged red and COX-negative fibers are common findings on muscle morphology. In contrast, muscle degeneration and regeneration, typically found in muscular dystrophies, are not considered characteristic features of mitochondrial...... myopathies. We investigated regeneration in muscle biopsies from 61 genetically well-defined patients affected by mitochondrial myopathy. Our results show that the perturbed energy metabolism in mitochondrial myopathies causes ongoing muscle regeneration in a majority of patients, and some were even affected...
Mitochondrial signaling in health and disease

National Research Council Canada - National Science Library

Orrenius, Sten; Packer, Lester; Cadenas, Enrique

2012-01-01

.... The text covers themes essential for the maintenance of mitochondrial activity, including electron transport and energy production, mitochondrial biogenesis and dynamics, mitochondrial signaling...

Rising gasoline prices increase new motorcycle sales and fatalities.

Science.gov (United States)

Zhu, He; Wilson, Fernando A; Stimpson, Jim P; Hilsenrath, Peter E

2015-12-01

We examined whether sales of new motorcycles was a mechanism to explain the relationship between motorcycle fatalities and gasoline prices. The data came from the Motorcycle Industry Council, Energy Information Administration and Fatality Analysis Reporting System for 1984-2009. Autoregressive integrated moving average (ARIMA) regressions estimated the effect of inflation-adjusted gasoline price on motorcycle sales and logistic regressions estimated odds ratios (ORs) between new and old motorcycle fatalities when gasoline prices increase. New motorcycle sales were positively correlated with gasoline prices (r = 0.78) and new motorcycle fatalities (r = 0.92). ARIMA analysis estimated that a US$1 increase in gasoline prices would result in 295,000 new motorcycle sales and, consequently, 233 new motorcycle fatalities. Compared to crashes on older motorcycle models, those on new motorcycles were more likely to be young riders, occur in the afternoon, in clear weather, with a large engine displacement, and without alcohol involvement. Riders on new motorcycles were more likely to be in fatal crashes relative to older motorcycles (OR 1.14, 95 % confidence interval (CI) 1.02-1.28) when gasoline prices increase. Our findings suggest that, in response to increasing gasoline prices, people tend to purchase new motorcycles, and this is accompanied with significantly increased crash risk. There are several policy mechanisms that can be used to lower the risk of motorcycle crash injuries through the mechanism of gas prices and motorcycle sales such as raising awareness of motorcycling risks, enhancing licensing and testing requirements, limiting motorcycle power-to-weight ratios for inexperienced riders, and developing mandatory training programs for new riders.
Assessing the impact of Syrian refugees on earthquake fatality estimations in southeast Turkey

Directory of Open Access Journals (Sweden)

B. Wilson

2018-01-01

Full Text Available The influx of millions of Syrian refugees into Turkey has rapidly changed the population distribution along the Dead Sea Rift and East Anatolian fault zones. In contrast to other countries in the Middle East where refugees are accommodated in camp environments, the majority of displaced individuals in Turkey are integrated into local cities, towns, and villages – placing stress on urban settings and increasing potential exposure to strong earthquake shaking. Yet displaced populations are often unaccounted for in the census-based population models used in earthquake fatality estimations. This study creates a minimally modeled refugee gridded population model and analyzes its impact on semi-empirical fatality estimations across southeast Turkey. Daytime and nighttime fatality estimates were produced for five fault segments at earthquake magnitudes 5.8, 6.4, and 7.0. Baseline fatality estimates calculated from census-based population estimates for the study area varied in scale from tens to thousands of fatalities, with higher death totals in nighttime scenarios. Refugee fatality estimations were analyzed across 500 semi-random building occupancy distributions. Median fatality estimates for refugee populations added non-negligible contributions to earthquake fatalities at four of five fault locations, increasing total fatality estimates by 7–27 %. These findings communicate the necessity of incorporating refugee statistics into earthquake fatality estimations in southeast Turkey and the ongoing importance of placing environmental hazards in their appropriate regional and temporal context.
Blast overpressure after tire explosion: a fatal case.

Science.gov (United States)

Pomara, Cristoforo; D'Errico, Stefano; Riezzo, Irene; Perilli, Gabriela; Volpe, Umberto; Fineschi, Vittorio

2013-12-01

Fatal blast injuries are generally reported in literature as a consequence of the detonation of explosives in war settings. The pattern of lesion depends on the position of the victim in relation to the explosion, on whether the blast tracks through air or water, and whether it happens in the open air or within an enclosed space and the distance from the explosion. Tire explosion-related injuries are rarely reported in literature. This study presents a fatal case of blast overpressure due to the accidental explosion of a truck tire occurring in a tire repair shop. A multidisciplinary approach to the fatality involving forensic pathologists and engineers revealed that the accidental explosion, which caused a series of primary and tertiary blast wave injuries, was due to tire deterioration.
Resveratrol induces mitochondrial biogenesis in endothelial cells.

Science.gov (United States)

Csiszar, Anna; Labinskyy, Nazar; Pinto, John T; Ballabh, Praveen; Zhang, Hanrui; Losonczy, Gyorgy; Pearson, Kevin; de Cabo, Rafael; Pacher, Pal; Zhang, Cuihua; Ungvari, Zoltan

2009-07-01

Pathways that regulate mitochondrial biogenesis are potential therapeutic targets for the amelioration of endothelial dysfunction and vascular disease. Resveratrol was shown to impact mitochondrial function in skeletal muscle and the liver, but its role in mitochondrial biogenesis in endothelial cells remains poorly defined. The present study determined whether resveratrol induces mitochondrial biogenesis in cultured human coronary arterial endothelial cells (CAECs). In CAECs resveratrol increased mitochondrial mass and mitochondrial DNA content, upregulated protein expression of electron transport chain constituents, and induced mitochondrial biogenesis factors (proliferator-activated receptor-coactivator-1alpha, nuclear respiratory factor-1, mitochondrial transcription factor A). Sirtuin 1 (SIRT1) was induced, and endothelial nitric oxide (NO) synthase (eNOS) was upregulated in a SIRT1-dependent manner. Knockdown of SIRT1 (small interfering RNA) or inhibition of NO synthesis prevented resveratrol-induced mitochondrial biogenesis. In aortas of type 2 diabetic (db/db) mice impaired mitochondrial biogenesis was normalized by chronic resveratrol treatment, showing the in vivo relevance of our findings. Resveratrol increases mitochondrial content in endothelial cells via activating SIRT1. We propose that SIRT1, via a pathway that involves the upregulation of eNOS, induces mitochondrial biogenesis. Resveratrol induced mitochondrial biogenesis in the aortas of type 2 diabetic mice, suggesting the potential for new treatment approaches targeting endothelial mitochondria in metabolic diseases.
RISK FACTORS IN NEONATAL ANAEROBIC INFECTIONS

Directory of Open Access Journals (Sweden)

M. S. Tabib

2008-06-01

Full Text Available Anaerobic bacteria are well known causes of sepsis in adults but there are few studies regarding their role in neonatal sepsis. In an attempt to define the incidence of neonatal anaerobic infections a prospective study was performed during one year period. A total number of 400 neonates under sepsis study were entered this investigation. Anaerobic as well as aerobic cultures were sent. The patients were subjected to comparison in two groups: anaerobic culture positive and anaerobic culture negative and this comparison were analyzed statistically. There were 7 neonates with positive anaerobic culture and 35 neonates with positive aerobic culture. A significant statistical relationship was found between anaerobic infections and abdominal distention and pneumonia. It is recommended for those neonates with abdominal distention and pneumonia refractory to antibiotic treatment to be started on antibiotics with anaerobic coverage.
Mitochondrial matrix delivery using MITO-Porter, a liposome-based carrier that specifies fusion with mitochondrial membranes

International Nuclear Information System (INIS)

Yasuzaki, Yukari; Yamada, Yuma; Harashima, Hideyoshi

2010-01-01

Mitochondria are the principal producers of energy in cells of higher organisms. It was recently reported that mutations and defects in mitochondrial DNA (mtDNA) are associated with various mitochondrial diseases including a variety of neurodegenerative and neuromuscular diseases. Therefore, an effective mitochondrial gene therapy and diagnosis would be expected to have great medical benefits. To achieve this, therapeutic agents need to be delivered into the innermost mitochondrial space (mitochondrial matrix), which contains the mtDNA pool. We previously reported on the development of MITO-Porter, a liposome-based carrier that introduces macromolecular cargos into mitochondria via membrane fusion. In this study, we provide a demonstration of mitochondrial matrix delivery and the visualization of mitochondrial genes (mtDNA) in living cells using the MITO-Porter. We first prepared MITO-Porter containing encapsulated propidium iodide (PI), a fluorescent dye used to stain nucleic acids to detect mtDNA. We then confirmed the emission of red-fluorescence from PI by conjugation with mtDNA, when the carriers were incubated in the presence of isolated rat liver mitochondria. Finally, intracellular observation by confocal laser scanning microscopy clearly verified that the MITO-Porter delivered PI to the mitochondrial matrix.
Occupational fatality risks in the United States and the United Kingdom.

Science.gov (United States)

Mendeloff, John; Staetsky, Laura

2014-01-01

There are very few careful studies of differences in occupational fatality rates across countries, much less studies that try to account for those differences. We compare the rate of work injury fatalities (excluding deaths due to highway motor vehicle crashes and those due to violence) identified by the US Census of Fatal Occupational Injuries in recent years with the number reported to the Health and Safety Executive in the United Kingdom (UK) and by other European Union (EU) members through Eurostat. In 2010, the fatality rate in the UK was about 1/3 the rate in the US. In construction the rate was about ¼ the US rate, a difference that had grown substantially since the 1990s. Several other EU members had rates almost as low as the UK rate. Across EU countries, lower rates were associated with high-level management attention to safety issues and to in-house preparation of "risk assessments." Although work fatality rates have declined in the US, fatality rates are much lower and have declined faster in recent years in the UK. Efforts to find out the reasons for the much better UK outcomes could be productive. © 2013 Wiley Periodicals, Inc.
Quasi-likelihood generalized linear regression analysis of fatality risk data.

Science.gov (United States)

2009-01-01

Transportation-related fatality risks is a function of many interacting human, vehicle, and environmental factors. Statistically valid analysis of such data is challenged both by the complexity of plausible structural models relating fatality rates t...
Loss of mitochondrial exo/endonuclease EXOG affects mitochondrial respiration and induces ROS mediated cardiomyocyte hypertrophy

NARCIS (Netherlands)

Tigchelaar, Wardit; Yu, Hongjuan; De Jong, Anne Margreet; van Gilst, Wiek H; van der Harst, Pim; Westenbrink, B Daan; de Boer, Rudolf A; Sillje, Herman H W

2015-01-01

Recently, a genetic variant in the mitochondrial exo/endo nuclease EXOG, which has been implicated in mitochondrial DNA repair, was associated with cardiac function. The function of EXOG in cardiomyocytes is still elusive. Here we investigated the role of EXOG in mitochondrial function and
Road Accidents and Road Fatalities in Denmark from 1968 to 2004

DEFF Research Database (Denmark)

Orozova-Bekkevold, Ivanka; Hels, Tove; Bernhoft, Inger Marie

2008-01-01

The purpose of this article is to describe the road accidents and road fatalities in Denmark in the period 1968-2004. Only accidents registered by the police were used. Crude and gender & age specific fatality rates (counts per 1,000,000 inhabitants) were estimated for all road users...... and for bicyclists. The accident and fatality rates have decreased by around 70% from 1968 to 2004, while the motorisation rate has increased by approximately 90%. The sharpest decrease in the fatality rate was observed among the youngest (below 18 years old) and the older (above 64) road users. Gender related...... and actions targeted to improve road safety have indeed led to a significant reduction in injury accidents and fatalities. Further research and more detailed data, especially on traffic volume and individual exposure are necessary in order to investigate properly a causal relation between the number...
Mitochondrial respiration is sensitive to cytoarchitectural breakdown.

Science.gov (United States)

Kandel, Judith; Angelin, Alessia A; Wallace, Douglas C; Eckmann, David M

2016-11-07

An abundance of research suggests that cellular mitochondrial and cytoskeletal disruption are related, but few studies have directly investigated causative connections between the two. We previously demonstrated that inhibiting microtubule and microfilament polymerization affects mitochondrial motility on the whole-cell level in fibroblasts. Since mitochondrial motility can be indicative of mitochondrial function, we now further characterize the effects of these cytoskeletal inhibitors on mitochondrial potential, morphology and respiration. We found that although they did not reduce mitochondrial inner membrane potential, cytoskeletal toxins induced significant decreases in basal mitochondrial respiration. In some cases, basal respiration was only affected after cells were pretreated with the calcium ionophore A23187 in order to stress mitochondrial function. In most cases, mitochondrial morphology remained unaffected, but extreme microfilament depolymerization or combined intermediate doses of microtubule and microfilament toxins resulted in decreased mitochondrial lengths. Interestingly, these two particular exposures did not affect mitochondrial respiration in cells not sensitized with A23187, indicating an interplay between mitochondrial morphology and respiration. In all cases, inducing maximal respiration diminished differences between control and experimental groups, suggesting that reduced basal respiration originates as a largely elective rather than pathological symptom of cytoskeletal impairment. However, viability experiments suggest that even this type of respiration decrease may be associated with cell death.
Habitual physical activity in mitochondrial disease.

Directory of Open Access Journals (Sweden)

Shehnaz Apabhai

Full Text Available Mitochondrial disease is the most common neuromuscular disease and has a profound impact upon daily life, disease and longevity. Exercise therapy has been shown to improve mitochondrial function in patients with mitochondrial disease. However, no information exists about the level of habitual physical activity of people with mitochondrial disease and its relationship with clinical phenotype.Habitual physical activity, genotype and clinical presentations were assessed in 100 patients with mitochondrial disease. Comparisons were made with a control group individually matched by age, gender and BMI.Patients with mitochondrial disease had significantly lower levels of physical activity in comparison to matched people without mitochondrial disease (steps/day; 6883±3944 vs. 9924±4088, p = 0.001. 78% of the mitochondrial disease cohort did not achieve 10,000 steps per day and 48% were classified as overweight or obese. Mitochondrial disease was associated with less breaks in sedentary activity (Sedentary to Active Transitions, % per day; 13±0.03 vs. 14±0.03, p = 0.001 and an increase in sedentary bout duration (bout lengths/fraction of total sedentary time; 0.206±0.044 vs. 0.187±0.026, p = 0.001. After adjusting for covariates, higher physical activity was moderately associated with lower clinical disease burden (steps/day; r(s = -0.49; 95% CI -0.33, -0.63, P<0.01. There were no systematic differences in physical activity between different genotypes mitochondrial disease.These results demonstrate for the first time that low levels of physical activity are prominent in mitochondrial disease. Combined with a high prevalence of obesity, physical activity may constitute a significant and potentially modifiable risk factor in mitochondrial disease.
Fatal motorcycle accidents and alcohol

DEFF Research Database (Denmark)

Larsen, C F; Hardt-Madsen, M

1987-01-01

A series of fatal motorcycle accidents from a 7-year period (1977-1983) has been analyzed. Of the fatalities 30 were operators of the motorcycle, 11 pillion passengers and 8 counterparts. Of 41 operators 37% were sober at the time of accident, 66% had measurable blood alcohol concentration (BAC......); 59% above 0.08%. In all cases where a pillion passenger was killed, the operator of the motorcycle had a BAC greater than 0.08%. Of the killed counterparts 2 were non-intoxicated, 2 had a BAC greater than 0.08%, and 4 were not tested. The results advocate that the law should restrict alcohol...... consumption by pillion passengers as well as by the motorcycle operator. Suggestions made to extend the data base needed for developing appropriate alcohol countermeasures by collecting sociodemographic data on drivers killed or seriously injured should be supported....
Role of amino acid supplementation in the prevention of necrotizing enterocolitis in preterm neonates - a review of current evidences.

Science.gov (United States)

Garg, Bhawan Deep; Kabra, Nandkishor S

2018-09-01

Necrotizing enterocolitis (NEC) is one of the most common acute and fatal gastrointestinal emergency in very low birth weight (VLBW) preterm neonates with mortality range from 15 to 30%. NEC is likely due to multifactorial process such as oxidative injury, ischemic necrosis, and over-reactive inflammatory response to intestinal microbes. To evaluate the role of amino acid supplementation for reduction of neonatal NEC in preterm neonates. The literature search was done for various randomized control trial (RCT) by searching the Cochrane Central Register of Controlled Trials (CENTRAL), PubMed, EMBASE, Web of Science, Scopus, Index Copernicus, African Index Medicus (AIM), Thomson Reuters (ESCI), Chemical Abstracts Service (CAS) and other database. This review included 15 RCTs that fulfilled inclusion criteria. The total neonates enrolled in these different RCT are 3424 (amino acid group 1711 and control 1713). Almost all participating neonates were of VLBW or extremely low birth weight (ELBW). In two trials, birth weight was between 1500-2000 grams. The intervention was started within first few days after birth and continued up to 30th day of postnatal age in most of the trials. In two trials, intervention was continued up to 120th day of postnatal age. Arginine, glutamine and N-acetyl cysteine (NAC) were used at the dose of 1.5 mol/kg/day (261 mg/kg/day), 0.3 grams/kg/day and 16-32 mg/kg/day, respectively. Role of amino acid in the prevention of neonatal NEC is not exclusively supported by the current evidence. Only three studies were able to show reduction in the incidence of NEC with amino acid supplementation (arginine, glutamine), and the remaining studies did not report any positive effect. Amino acid supplementation was not associated with significant reduction in mortality due to any causes. However, arginine supplementation was associated with significant reduction in mortality due to NEC. Two studies on glutamine were reported significant reduction in
Determinants of neonatal mortality in Indonesia.

Science.gov (United States)

Titaley, Christiana R; Dibley, Michael J; Agho, Kingsley; Roberts, Christine L; Hall, John

2008-07-09

Neonatal mortality accounts for almost 40 per cent of under-five child mortality, globally. An understanding of the factors related to neonatal mortality is important to guide the development of focused and evidence-based health interventions to prevent neonatal deaths. This study aimed to identify the determinants of neonatal mortality in Indonesia, for a nationally representative sample of births from 1997 to 2002. The data source for the analysis was the 2002-2003 Indonesia Demographic and Health Survey from which survival information of 15,952 singleton live-born infants born between 1997 and 2002 was examined. Multilevel logistic regression using a hierarchical approach was performed to analyze the factors associated with neonatal deaths, using community, socio-economic status and proximate determinants. At the community level, the odds of neonatal death was significantly higher for infants from East Java (OR = 5.01, p = 0.00), and for North, Central and Southeast Sulawesi and Gorontalo combined (OR = 3.17, p = 0.03) compared to the lowest neonatal mortality regions of Bali, South Sulawesi and Jambi provinces. A progressive reduction in the odds was found as the percentage of deliveries assisted by trained delivery attendants in the cluster increased. The odds of neonatal death were higher for infants born to both mother and father who were employed (OR = 1.84, p = 0.00) and for infants born to father who were unemployed (OR = 2.99, p = 0.02). The odds were also higher for higher rank infants with a short birth interval (OR = 2.82, p = 0.00), male infants (OR = 1.49, p = 0.01), smaller than average-sized infants (OR = 2.80, p = 0.00), and infant's whose mother had a history of delivery complications (OR = 1.81, p = 0.00). Infants receiving any postnatal care were significantly protected from neonatal death (OR = 0.63, p = 0.03). Public health interventions directed at reducing neonatal death should address community, household and individual level factors
The legacy of fear: is fear impacting fatal and non-fatal drowning of African American children?

Science.gov (United States)

Irwin, Carol C; Irwin, Richard L; Ryan, Timothy D; Drayer, Joris

2011-01-01

African American children’s rates for fatal and non-fatal drowning events are alarmingly elevated, with some age groups having three times the rate as compared to White peers. Adequate swimming skills are considered a protective agent toward the prevention of drowning, but marginalized youth report limited swimming ability. This research examined minority children’s and parents/caregivers’ fear of drowning as a possible variable associated with limited swimming ability. Results confirmed that there were significant racial differences concerning the fear of drowning, and adolescent African American females were notably more likely to fear drowning while swimming than any other group. The “fear of drowning” responses by parents/ caregivers of minority children were also significantly different from their White counterparts.
NEONATAL CONJUNCTIVITIS AND ITS DRUG SENSITIVITY PATTERN

Directory of Open Access Journals (Sweden)

Kavitha Thulukkanam

2017-05-01

Full Text Available BACKGROUND Neonatal conjunctivitis is eye discharge in neonates and it is a common infection in neonates in the first month of life. Worldwide, the incidence of neonatal conjunctivitis varies from 1% to 33% depending on the socioeconomic status of the people in the region. In India, the incidence varies from region to region from 0.9 to 35%. MATERIALS AND METHODS Single center prospective study. All neonates of age 0-30 days delivered and referred from neonatal ward of Chengalpattu Medical College and Hospital with complaints of eye swelling, redness, conjunctival discharge to the eye department for treatment are included in the study. RESULTS In this study, age group from 0-7 days were most commonly affected by neonatal conjunctivitis. Both eyes were commonly affected together. Neonates born by both LSCS and normal vaginal delivery were almost equally affected. The most common organism found in culture and Gram staining was staphylococci. CONCLUSION Neonatal conjunctivitis is more likely to be acquired postnatally. It acquires during the 1 st week and responds well to local application of antibiotics, which covers common causative bacteria.
Mitochondrial PKA mediates sperm motility.

Science.gov (United States)

Mizrahi, Rashel; Breitbart, Haim

2014-12-01

Mitochondria are the major source of ATP to power sperm motility. Phosphorylation of mitochondrial proteins has been proposed as a major regulatory mechanism for mitochondrial bioenergetics. Sperm motility was measured by a computer-assisted analyzer, protein detection by western blotting, membrane potential by tetramethylrhodamine, cellular ATP by luciferase assay and localization of PKA by immuno-electron microscopy. Bicarbonate is essential for the creation of mitochondrial electro-chemical gradient, ATP synthesis and sperm motility. Bicarbonate stimulates PKA-dependent phosphorylation of two 60kDa proteins identified as Tektin and glucose-6-phosphate isomerase. This phosphorylation was inhibited by respiration inhibition and phosphorylation could be restored by glucose in the presence of bicarbonate. However, this effect of glucose cannot be seen when the mitochondrial ATP/ADP exchanger was inhibited indicating that glycolytic-produced ATP is transported into the mitochondria and allows PKA-dependent protein phosphorylation inside the mitochondria. Bicarbonate activates mitochondrial soluble adenylyl cyclase (sAC) which catalyzes cAMP production leading to the activation of mitochondrial PKA. Glucose can overcome the lack of ATP in the absence of bicarbonate but it cannot affect the mitochondrial sAC/PKA system, therefore the PKA-dependent phosphorylation of the 60kDa proteins does not occur in the absence of bicarbonate. Production of CO2 in Krebs cycle, which is converted to bicarbonate is essential for sAC/PKA activation leading to mitochondrial membrane potential creation and ATP synthesis. Copyright © 2014 Elsevier B.V. All rights reserved.
Neonatal tetanus mortality in coastal Kenya

DEFF Research Database (Denmark)

Bjerregaard, P; Steinglass, R; Mutie, D M

1993-01-01

In a house-to-house survey in Kilifi District, Kenya, mothers of 2556 liveborn children were interviewed about neonatal mortality, especially from neonatal tetanus (NNT). The crude birth rate was 60.5 per 1000 population, the neonatal mortality rate 21.1 and the NNT mortality rate 3.1 per 1000 li...... indicates that over the past decade the surveyed area has greatly reduced neonatal and NNT mortality. Possible strategies for accelerated NNT control have been identified by the survey....
Effect of High-Carbohydrate Diet on Plasma Metabolome in Mice with Mitochondrial Respiratory Chain Complex III Deficiency

Directory of Open Access Journals (Sweden)

Jayasimman Rajendran

2016-11-01

Full Text Available Mitochondrial disorders cause energy failure and metabolic derangements. Metabolome profiling in patients and animal models may identify affected metabolic pathways and reveal new biomarkers of disease progression. Using liver metabolomics we have shown a starvation-like condition in a knock-in (Bcs1lc.232A>G mouse model of GRACILE syndrome, a neonatal lethal respiratory chain complex III dysfunction with hepatopathy. Here, we hypothesized that a high-carbohydrate diet (HCD, 60% dextrose will alleviate the hypoglycemia and promote survival of the sick mice. However, when fed HCD the homozygotes had shorter survival (mean ± SD, 29 ± 2.5 days, n = 21 than those on standard diet (33 ± 3.8 days, n = 30, and no improvement in hypoglycemia or liver glycogen depletion. We investigated the plasma metabolome of the HCD- and control diet-fed mice and found that several amino acids and urea cycle intermediates were increased, and arginine, carnitines, succinate, and purine catabolites decreased in the homozygotes. Despite reduced survival the increase in aromatic amino acids, an indicator of liver mitochondrial dysfunction, was normalized on HCD. Quantitative enrichment analysis revealed that glycine, serine and threonine metabolism, phenylalanine and tyrosine metabolism, and urea cycle were also partly normalized on HCD. This dietary intervention revealed an unexpected adverse effect of high-glucose diet in complex III deficiency, and suggests that plasma metabolomics is a valuable tool in evaluation of therapies in mitochondrial disorders.

Specialist teams for neonatal transport to neonatal intensive care units for prevention of morbidity and mortality.

Science.gov (United States)

Chang, Alvin S M; Berry, Andrew; Jones, Lisa J; Sivasangari, Subramaniam

2015-10-28

Maternal antenatal transfers provide better neonatal outcomes. However, there will inevitably be some infants who require acute transport to a neonatal intensive care unit (NICU). Because of this, many institutions develop services to provide neonatal transport by specially trained health personnel. However, few studies report on relevant clinical outcomes in infants requiring transport to NICU. To determine the effects of specialist transport teams compared with non-specialist transport teams on the risk of neonatal mortality and morbidity among high-risk newborn infants requiring transport to neonatal intensive care. We used the standard search strategy of the Cochrane Neonatal Review Group to search the Cochrane Central Register of Controlled Trials (CENTRAL 2015, Issue 7), MEDLINE (1966 to 31 July 2015), EMBASE (1980 to 31 July 2015), CINAHL (1982 to 31 July 2015), conference proceedings, and the reference lists of retrieved articles for randomised controlled trials and quasi-randomised trials. randomised, quasi-randomised or cluster randomised controlled trials. neonates requiring transport to a neonatal intensive care unit. transport by a specialist team compared to a non-specialist team. any of the following outcomes - death; adverse events during transport leading to respiratory compromise; and condition on admission to the neonatal intensive care unit. The methodological quality of the trials was assessed using the information provided in the studies and by personal communication with the author. Data on relevant outcomes were extracted and the effect size estimated and reported as risk ratio (RR), risk difference (RD), number needed to treat for an additional beneficial outcome (NNTB) or number needed to treat for an additional harmful outcome (NNTH) and mean difference (MD) for continuous outcomes. Data from cluster randomised trials were not combined for analysis. One trial met the inclusion criteria of this review but was considered ineligible owing to
Multifunctional Mitochondrial AAA Proteases.

Science.gov (United States)

Glynn, Steven E

2017-01-01

Mitochondria perform numerous functions necessary for the survival of eukaryotic cells. These activities are coordinated by a diverse complement of proteins encoded in both the nuclear and mitochondrial genomes that must be properly organized and maintained. Misregulation of mitochondrial proteostasis impairs organellar function and can result in the development of severe human diseases. ATP-driven AAA+ proteins play crucial roles in preserving mitochondrial activity by removing and remodeling protein molecules in accordance with the needs of the cell. Two mitochondrial AAA proteases, i-AAA and m-AAA, are anchored to either face of the mitochondrial inner membrane, where they engage and process an array of substrates to impact protein biogenesis, quality control, and the regulation of key metabolic pathways. The functionality of these proteases is extended through multiple substrate-dependent modes of action, including complete degradation, partial processing, or dislocation from the membrane without proteolysis. This review discusses recent advances made toward elucidating the mechanisms of substrate recognition, handling, and degradation that allow these versatile proteases to control diverse activities in this multifunctional organelle.
Correction of Neonatal Hypovolemia

Directory of Open Access Journals (Sweden)

V. V. Moskalev

2007-01-01

Full Text Available Objective: to evaluate the efficiency of hydroxyethyl starch solution (6% refortane, Berlin-Chemie versus fresh frozen plasma used to correct neonatal hypovolemia.Materials and methods. In 12 neonatal infants with hypoco-agulation, hypovolemia was corrected with fresh frozen plasma (10 ml/kg body weight. In 13 neonates, it was corrected with 6% refortane infusion in a dose of 10 ml/kg. Doppler echocardiography was used to study central hemodynamic parameters and Doppler study was employed to examine regional blood flow in the anterior cerebral and renal arteries.Results. Infusion of 6% refortane and fresh frozen plasma at a rate of 10 ml/hour during an hour was found to normalize the parameters of central hemodynamics and regional blood flow.Conclusion. Comparative analysis of the findings suggests that 6% refortane is the drug of choice in correcting neonatal hypovolemia. Fresh frozen plasma should be infused in hemostatic disorders.
Disaster-related fatalities among US citizens traveling abroad.

Science.gov (United States)

Partridge, Robert; Bouslough, David; Proano, Lawrence

2013-01-01

To describe the locations and risk of death associated with natural disaster fatalities for US citizens traveling abroad. A retrospective database review of US citizen disaster deaths occurring worldwide. None. Information on fatalities due to disasters was abstracted from the US Department of State Web site reporting deaths of US citizens abroad by non-natural causes from October 2002 through June 2012. The main outcome measures were the frequency of disaster deaths and countries where disasters occurred. Descriptive statistics and rates were used to evaluate the study data. There were 7,963 total non-natural deaths of US citizens traveling abroad during the study period. Of these, 163 (2.0 percent) were disaster-related deaths, involving 19 disaster events in 15 countries. Only two disaster-related events resulted in more than two deaths of US travelers-the 2010 earthquake in Haiti causing 121 fatalities (74.2 percent of disaster deaths), and the 2004 tsunami in Thailand causing 22 fatalities (13.5 percent of disaster deaths). The approximate annual mean death rate for US citizen travelers as a result of disaster events is 0.27 deaths/1 million travelers, compared with 1.4 deaths/1 million residents due to disaster annually within the United States. The risk of disaster-related fatality is low for US citizens traveling abroad. Although disaster-related death among travelers is unpredictable, during a period of almost 10 years, there was only one reported death due to disaster in the five countries most frequently visited by US travelers. Further investigation may identify population-, seasonal-, country-, or location-specific risks from which prevention strategies can be developed.
Phototherapy and exchange transfusion for neonatal ...

African Journals Online (AJOL)

The purpose of this document is to address the current lack of consensus regarding the management of hyperbilirubinaemia in neonates in South Africa. If left untreated, severe neonatal hyperbilirubinaemia may cause kernicterus and ultimately death and the severity of neonatal jaundice is often underestimated clinically.
Epidemiology of subway-related fatalities in New York City, 1990-2003.

Science.gov (United States)

Gershon, Robyn R M; Pearson, Julie M; Nandi, Vijay; Vlahov, David; Bucciarelli-Prann, Angela; Tracy, Melissa; Tardiff, Kenneth; Galea, Sandro

2008-01-01

Subway transit is a relatively safe mode of transportation, yet compared to all other forms of mass transit in the United States (U.S.), subways have the highest fatality rate. The aim of this paper is to characterize subway-related fatalities in order to identify opportunities for risk reduction. Medical examiner records for all New York City (NYC) subway-related deaths (1990-2003) were reviewed. Data were abstracted on decedents' demographics and autopsy findings, including laboratory findings. There were 668 subway-related fatalities, of these, 10 (1.5%) were homicides, 343 (51.3%) were determined to be suicides, and 315 (47.2%) were accidental. Although decedent characteristics varied between fatality categories, they were not particularly informative with regard to prevention. Prevention strategies that focus on structural controls are likely to be most efficacious in improving the overall safety of the NYC subway systems. These findings suggest that structural rather than individual-level interventions would be most successful in preventing subway fatalities.
Transcription profiles of mitochondrial genes correlate with mitochondrial DNA haplotypes in a natural population of Silene vulgaris

Directory of Open Access Journals (Sweden)

Olson Matthew S

2010-01-01

Full Text Available Abstract Background Although rapid changes in copy number and gene order are common within plant mitochondrial genomes, associated patterns of gene transcription are underinvestigated. Previous studies have shown that the gynodioecious plant species Silene vulgaris exhibits high mitochondrial diversity and occasional paternal inheritance of mitochondrial markers. Here we address whether variation in DNA molecular markers is correlated with variation in transcription of mitochondrial genes in S. vulgaris collected from natural populations. Results We analyzed RFLP variation in two mitochondrial genes, cox1 and atp1, in offspring of ten plants from a natural population of S. vulgaris in Central Europe. We also investigated transcription profiles of the atp1 and cox1 genes. Most DNA haplotypes and transcription profiles were maternally inherited; for these, transcription profiles were associated with specific mitochondrial DNA haplotypes. One individual exhibited a pattern consistent with paternal inheritance of mitochondrial DNA; this individual exhibited a transcription profile suggestive of paternal but inconsistent with maternal inheritance. We found no associations between gender and transcript profiles. Conclusions Specific transcription profiles of mitochondrial genes were associated with specific mitochondrial DNA haplotypes in a natural population of a gynodioecious species S. vulgaris. Our findings suggest the potential for a causal association between rearrangements in the plant mt genome and transcription product variation.
Role of massage therapy on reduction of neonatal hyperbilirubinemia in term and preterm neonates: a review of clinical trials.

Science.gov (United States)

Garg, Bhawan Deep; Kabra, Nandkishor S; Balasubramanian, Haribalakrishna

2017-09-13

Neonatal hyperbilirubinemia (NNH) is one of the leading causes of admissions in nursery throughout the world. It affects approximately 2.4-15% of neonates during the first 2 weeks of life. To evaluate the role of massage therapy for reduction of NNH in both term and preterm neonates. The literature search was done for various randomized control trials (RCTs) by searching the Cochrane Library, PubMed, and EMBASE. This review included total of 10 RCTs (two in preterm neonates and eight in term neonates) that fulfilled inclusion criteria. In most of the trials, Field massage was given. Six out of eight trials reported reduction in bilirubin levels in term neonates. However, only one trial (out of two) reported significant reduction in bilirubin levels in preterm neonates. Both trials in preterm neonates and most of the trials in term neonates (five trials) reported increased stool frequencies. Role of massage therapy in the management of NNH is supported by the current evidence. However, due to limitations of the trials, current evidences are not sufficient to use massage therapy for the management of NNH in routine practice.
Road traffic fatalities in selected governorates of Iraq from 2010 to 2013: prospective surveillance.

Science.gov (United States)

Leidman, Eva; Maliniak, Maret; Sultan, Abdul-Salam Saleh; Hassan, Ahmed; Hussain, Syed Jaffar; Bilukha, Oleg O

2016-01-01

The insurgency tactics that characterize modern warfare, such as suicide car bombs and roadside bombs, have the potential to significantly impact road traffic injuries in conflict affected-countries. As road traffic incidents are one of the top ten causes of death in Iraq, changes in incidence have important implications for the health system. We aimed to describe patterns of road traffic fatalities for all demographic groups and types of road users in Iraq during a period characterized by a resurgence in insurgency activity. Iraqi Ministry of Health routine prospective injury surveillance collects information on all fatal injuries in eight governorates of Iraq: Baghdad, Al-Anbar, Basrah, Erbil, Kerbala, Maysan, Ninevah, and Al-Sulaimaniya. From all injury fatalities documented at the coroner office, we analyzed only those attributed to road traffic that occurred between 1 January 2010 and 31 December 2013. Coroners ascertain information from physical examinations, police reports and family members. Analysis included 7,976 road traffic fatalities. Overall, 6,238 (78.2 %) fatalities were male and 2,272 (28.5 %) were children under 18 years of age. The highest numbers of road traffic fatalities were among males 15 to 34 years of age and children of both sexes under 5 years of age. 49.2 % of fatalities occurred among pedestrians. Among children and females, the majority of road traffic fatalities were pedestrians, 69.0 % and 56.6 %, respectively. Fatalities among motorcyclists (3.7 %) and bicyclists (0.4 %) were least common. Rates of road traffic fatalities ranged from 8.6 to 10.7 per 100,000 population. The injury surveillance system provides the first data from a conflict-affected country on road traffic fatalities disaggregated by type of road user. The highest numbers of fatalities were among children and young men. Nearly half of fatalities were pedestrians, a proportion nearly double that of any neighboring country. As insurgency activity increased in
Examination of Conservatism in Early/Latent Fatality Estimation in Level 3 PRA

International Nuclear Information System (INIS)

Kim, Sung-yeop; Lee, Haneol; Yim, Man-Sung

2014-01-01

Due to the computational model driven-nature of the work, there exist various sources of uncertainty in level 3 PRA. They are related with source release, environmental transport and deposition, human behavior involved in dosimetry, health effect and risk assessment. For instance, a total of 376 parameters have been considered in Probabilistic Accident Consequence Uncertainty Assessment Using COSYMA and the details on the number of parameters in each analysis are listed in Table 1. In 2012, the report of NPP accident consequence simulation was distributed by the Korean Federation for Environmental Movement (KFEM). They insisted that Kori Nuclear Power Plant (NPP) accident would lead to 48,000 early fatalities and 850,000 cancer fatalities in Busan and Hanbit NPP accident would lead to 550,000 cancer fatalities in Seoul. This report exemplifies the misuse of collective dose, that is effective dose multiplied by population and time. Even though very low effective dose is considered, collective dose could give over-conservative estimate when high population and long time period is multiplied. International Commission on Radiological Protection (ICRP) forewarned about the misuse of collective dose, in their ICRP Publication 103, such as applying it to simplified calculation of fatality and risk. As part of investigation of conservatism in early and latent fatality estimation, the existing methods of early and latent fatality calculation was reviewed and the results from the use of the existing methodology were examined in this study. The method of early and latent fatality estimation in level 3 PRA was investigated and the conservatism in the result was examined in this study. For the purpose of estimating both early and latent fatality, appropriate dose distributions among the affected population are found to be important. This study showed that large conservatism may be involved in the estimated fatality if the distribution of population dose as a function of
Examination of Conservatism in Early/Latent Fatality Estimation in Level 3 PRA

Energy Technology Data Exchange (ETDEWEB)

Kim, Sung-yeop; Lee, Haneol; Yim, Man-Sung [Korea Advanced Institute of Science and Technology, Daejeon (Korea, Republic of)

2014-10-15

Due to the computational model driven-nature of the work, there exist various sources of uncertainty in level 3 PRA. They are related with source release, environmental transport and deposition, human behavior involved in dosimetry, health effect and risk assessment. For instance, a total of 376 parameters have been considered in Probabilistic Accident Consequence Uncertainty Assessment Using COSYMA and the details on the number of parameters in each analysis are listed in Table 1. In 2012, the report of NPP accident consequence simulation was distributed by the Korean Federation for Environmental Movement (KFEM). They insisted that Kori Nuclear Power Plant (NPP) accident would lead to 48,000 early fatalities and 850,000 cancer fatalities in Busan and Hanbit NPP accident would lead to 550,000 cancer fatalities in Seoul. This report exemplifies the misuse of collective dose, that is effective dose multiplied by population and time. Even though very low effective dose is considered, collective dose could give over-conservative estimate when high population and long time period is multiplied. International Commission on Radiological Protection (ICRP) forewarned about the misuse of collective dose, in their ICRP Publication 103, such as applying it to simplified calculation of fatality and risk. As part of investigation of conservatism in early and latent fatality estimation, the existing methods of early and latent fatality calculation was reviewed and the results from the use of the existing methodology were examined in this study. The method of early and latent fatality estimation in level 3 PRA was investigated and the conservatism in the result was examined in this study. For the purpose of estimating both early and latent fatality, appropriate dose distributions among the affected population are found to be important. This study showed that large conservatism may be involved in the estimated fatality if the distribution of population dose as a function of
Opinions regarding neonatal resuscitation training for the obstetric physician: a survey of neonatal and obstetric training program directors.

Science.gov (United States)

Bruno, C J; Johnston, L; Lee, C; Bernstein, P S; Goffman, D

2018-04-01

Our goal was to garner opinions regarding neonatal resuscitation training for obstetric physicians. We sought to evaluate obstacles to neonatal resuscitation training for obstetric physicians and possible solutions for implementation challenges. We distributed a national survey via email to all neonatal-perinatal medicine fellowship directors and obstetrics & gynecology residency program directors in the United States. This survey was designed by a consensus method. Ninety-eight (53%) obstetric and fifty-seven (51%) neonatal program directors responded to our surveys. Eighty-eight percent of neonatologists surveyed believe that obstetricians should be neonatal resuscitation program (NRP) certified. The majority of surveyed obstetricians (>89%) believe that obstetricians should have some neonatal resuscitation training. Eighty-six percent of obstetric residents have completed training in NRP, but only 19% of obstetric attendings are NRP certified. Major barriers to NRP training that were identified include time, lack of national requirement, lack of belief it is helpful, and cost. Most obstetric attendings are not NRP certified, but the majority of respondents believe that obstetric providers should have some neonatal resuscitation training. Our study demonstrates that most respondents support a modified neonatal resuscitation course for obstetric physicians.
The effect of high risk pregnancy on duration of neonatal stay in neonatal intensive care unit.

Science.gov (United States)

Afrasiabi, Narges; Mohagheghi, Parisa; Kalani, Majid; Mohades, Gholam; Farahani, Zahra

2014-08-01

High risk pregnancies increase the risk of neonatal mortality and morbidity. In order to identify the influence of pregnancy complications on the period of neonatal stay in Neonatal Intensive Care Units (NICUs), an analysis has been carried out in our center. In a cross-sectional-descriptive analytical study, the data including NICU length of stay was gathered from 526 medical records of neonates. We also assessed their maternal complications such as premature rapture of membranes (PROM), urinary tract infection (UTI), preeclampsia, oligohydramnios, and twin/triplet pregnancy. Finally we analyzed the relation between variables by SPSS statistics software version 19. The level of significance was considered PUTI (P=0.02), multiple gestation (P=0.03), and oligohydramnios (P=0.003). We found a positive correlation between numbers of gestation and length of NICU stay (P=0.03). A positive correlation existed between neonatal complication and length of NICU stay (P<0.001). By increasing maternal health level and prenatal care services, neonatal outcome can be improved and length of stay in NICUs decreased.
The prevalence of neonatal jaundice and risk factors in healthy term neonates at National District Hospital in Bloemfontein

Science.gov (United States)

2018-01-01

Background Neonatal jaundice affects one in two infants globally. The jaundice is the result of an accumulation of bilirubin as foetal haemoglobin is metabolised by the immature liver. High serum levels of bilirubin result in lethargy, poor feeding and kernicterus of the infant. Aim The main aim of this article was to determine the prevalence of neonatal jaundice and secondly to explore its risk factors in healthy term neonates. Setting Maternity ward, National District Hospital, Bloemfontein, South Africa. Methods In this cross-sectional study, mothers and infants were conveniently sampled after delivery and before discharge. The mothers were interviewed and their case records were reviewed for risk factors for neonatal jaundice and the clinical appearance and bilirubin levels of the infants were measured with a non-invasive transcutaneous bilirubin meter. Results A total of 96 mother-infant pairs were included in the study. The prevalence of neonatal jaundice was 55.2%; however, only 10% of black babies who were diagnosed with jaundice appeared clinically jaundiced. Normal vaginal delivery was the only risk factor associated with neonatal jaundice. Black race and maternal smoking were not protective against neonatal jaundice as in some other studies. Conclusion More than half (55.2%) of healthy term neonates developed neonatal jaundice. As it is difficult to clinically diagnose neonatal jaundice in darker pigmented babies, it is recommended that the bilirubin level of all babies should be checked with a non-invasive bilirubin meter before discharge from hospital or maternity unit as well as during the first clinic visit on day 3 after birth.
Associations between drug use and motorcycle helmet use in fatal crashes.

Science.gov (United States)

Rossheim, Matthew E; Wilson, Fernando; Suzuki, Sumihiro; Rodriguez, Mayra; Walters, Scott; Thombs, Dennis L

2014-01-01

Helmet use reduces mortality risk for motorcyclists, regardless of drug and alcohol use. However, the association between drug use and motorcycle helmet utilization is not well known. This study examines the relationship between drug use and motorcycle helmet use among fatally injured motorcycle riders. Using data from the 2005-2009 Fatality Analysis Reporting System (FARS), we examined the association between drug use and motorcycle helmet use in a multivariable logistic regression analysis of 9861 fatally injured motorcycle riders in the United States. For fatally injured motorcycle riders, use of alcohol, marijuana, or other drugs was associated with increased odds of not wearing a motorcycle helmet, controlling for the effects of state motorcycle helmet laws and other confounding variables. Predicted probabilities indicate that helmet use substantially decreases among fatally injured riders mixing alcohol with marijuana and other drugs. Furthermore, the likelihood of helmet use between marijuana-only users and other drug users is virtually the same across all blood alcohol content (BAC) levels. This study provides evidence that alcohol, marijuana, and other drug use is associated with not wearing a motorcycle helmet in fatal motorcycle crashes. There is a clear need for additional prevention and intervention efforts that seek to change helmet and drug use norms among motorcycle riders.
Bartter syndrome: presentation in an extremely premature neonate.

Science.gov (United States)

Flores, F X; Ojeda, F J; Calhoun, D A

2013-08-01

Reports of Bartter syndrome in premature neonates are rare. We describe the presentation and clinical course of a neonate born at 25.6 weeks estimated gestational age with polyuria, hyponatremia, hypokalemia and hypercalciuria ,who was diagnosed with neonatal Bartter syndrome. The evaluation, diagnosis and management of neonatal Bartter syndrome in this premature neonate are discussed.
Analyses of fatalities from natural catastrophes in different income groups over time

Science.gov (United States)

Grimm, Tobias

2017-04-01

Identifying not only economic and insured losses but also numbers of fatalities from natural catastrophes provides new information on resilience and prevention measures in the countries affected. In this talk, we examine how fatalities from Munich Re's NatCatSERVICE database, caused by natural disasters have developed. In addition to the standard approach based on fatalities by country, we introduced a new measure, "fatalities per million inhabitants", and factored in population development over time. The World Bank definition was used to determine the wealth classification of individual countries. This methodology enables us to compare countries with different population sizes and thus produce an index for humanitarian impact. The analyses are key information on ascertaining whether prevention measures or early-warning systems have in fact reduced the number of fatalities in recent decades (1980-2016).
Mitochondrial quality control in cardiac diseases.

Directory of Open Access Journals (Sweden)

Juliane Campos

2016-10-01

Full Text Available Disruption of mitochondrial homeostasis is a hallmark of cardiac diseases. Therefore, maintenance of mitochondrial integrity through different surveillance mechanisms is critical for cardiomyocyte survival. In this review, we discuss the most recent findings on the central role of mitochondrial quality control processes including regulation of mitochondrial redox balance, aldehyde metabolism, proteostasis, dynamics and clearance in cardiac diseases, highlighting their potential as therapeutic targets.
Factors Associated with Fatal Occupational Accidents among Mexican Workers: A National Analysis

Science.gov (United States)

Gonzalez-Delgado, Mery; Gómez-Dantés, Héctor; Fernández-Niño, Julián Alfredo; Robles, Eduardo; Borja, Víctor H.; Aguilar, Miriam

2015-01-01

Objective To identify the factors associated with fatal occupational injuries in Mexico in 2012 among workers affiliated with the Mexican Social Security Institute. Methods Analysis of secondary data using information from the National Occupational Risk Information System, with the consequence of the occupational injury (fatal versus non-fatal) as the response variable. The analysis included 406,222 non-fatal and 1,140 fatal injuries from 2012. The factors associated with the lethality of the injury were identified using a logistic regression model with the Firth approach. Results Being male (OR=5.86; CI95%: 4.22-8.14), age (OR=1.04; CI95%: 1.03-1.06), employed in the position for 1 to 10 years (versus less than 1 year) (OR=1.37; CI95%: 1.15-1.63), working as a facilities or machine operator or assembler (OR: 3.28; CI95%: 2.12- 5.07) and being a worker without qualifications (OR=1.96; CI95%: 1.18-3.24) (versus an office worker) were associated with fatality in the event of an injury. Additionally, companies classified as maximum risk (OR=1.90; CI 95%: 1.38-2.62), workplace conditions (OR=7.15; CI95%: 3.63-14.10) and factors related to the work environment (OR=9.18; CI95%:4.36-19.33) were identified as risk factors for fatality in the event of an occupational injury. Conclusions Fatality in the event of an occupational injury is associated with factors related to sociodemographics (age, sex and occupation), the work environment and workplace conditions. Worker protection policies should be created for groups with a higher risk of fatal occupational injuries in Mexico. PMID:25790063
The relationship between gasoline price and patterns of motorcycle fatalities and injuries.

Science.gov (United States)

Zhu, He; Wilson, Fernando A; Stimpson, Jim P

2015-06-01

Economic factors such as rising gasoline prices may contribute to the crash trends by shaping individuals' choices of transportation modalities. This study examines the relationship of gasoline prices with fatal and non-fatal motorcycle injuries. Data on fatal and non-fatal motorcycle injuries come from California's Statewide Integrated Traffic Records System for 2002-2011. Autoregressive integrated moving average (ARIMA) regressions were used to estimate the impact of inflation-adjusted gasoline price per gallon on trends of motorcycle injuries. Motorcycle fatalities and severe and minor injuries in California were highly correlated with increasing gasoline prices from 2002 to 2011 (r=0.76, 0.88 and 0.85, respectively). In 2008, the number of fatalities and injuries reached 13,457--a 34% increase since 2002, a time period in which inflation-adjusted gasoline prices increased about $0.30 per gallon every year. The majority of motorcycle riders involved in crashes were male (92.5%), middle-aged (46.2%) and non-Hispanic white (67.9%). Using ARIMA modelling, we estimated that rising gasoline prices resulted in an additional 800 fatalities and 10,290 injuries from 2002 to 2011 in California. Our findings suggest that increasing gasoline prices led to more motorcycle riders on the roads and, consequently, more injuries. Aside from mandatory helmet laws and their enforcement, other strategies may include raising risk awareness of motorcyclists and investment in public transportation as an alternative transportation modality to motorcycling. In addition, universally mandated training courses and strict licensing tests of riding skills should be emphasised to help reduce the motorcycle fatal and non-fatal injuries. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.

Necrotising enterocolitis in preterm infants: epidemiology and antibiotic consumption in the Polish neonatology network neonatal intensive care units in 2009.

Directory of Open Access Journals (Sweden)

Jadwiga Wójkowska-Mach

Full Text Available The aim of this study was to describe the epidemiology of necrotising enterocolitis (NEC, antibiotic consumption and the usefulness of microbiological tests in very low birth weight (VLBW Polish newborns.Prospective surveillance was performed in the year 2009 by local infection control teams. The study covered 910 infants hospitalized in six Polish neonatal intensive care units. Two kinds of indicators were used for the description of antibiotic usage: the duration of treatment (days of treatment, DOTs and the defined daily dose (DDD.NEC incidence was 8.7% and fatality rate was 19%. Chorioamnionitis, late gestational age and low birth weight were identified as risk factors for NEC. Catheterization, mechanical ventilation and other selected procedures were used considerably longer in newborns with NEC than in the remaining neonates. Total usage of antibiotics reached 2.9 DDDs or 1.437 days; the average use of drugs per case of NEC amounted to 0.47 DDD or 23.2 DOTs. The level of antibiotic usage was analysed with correlation to microbiological tests performed and it was non-significantly greater in the group of children with NEC in whom the tests were performed.A high risk of developing NEC is closely associated with VLBW and with inflammation of the amnion during labour. We observed no relationship between the consumption of antibiotics in neonates with NEC and positive results of microbiological testing indicating sepsis accompanying NEC or gut colonization with pathogens.
Mitochondrial Energy and Redox Signaling in Plants

Science.gov (United States)

Schwarzländer, Markus

2013-01-01

Abstract Significance: For a plant to grow and develop, energy and appropriate building blocks are a fundamental requirement. Mitochondrial respiration is a vital source for both. The delicate redox processes that make up respiration are affected by the plant's changing environment. Therefore, mitochondrial regulation is critically important to maintain cellular homeostasis. This involves sensing signals from changes in mitochondrial physiology, transducing this information, and mounting tailored responses, by either adjusting mitochondrial and cellular functions directly or reprogramming gene expression. Recent Advances: Retrograde (RTG) signaling, by which mitochondrial signals control nuclear gene expression, has been a field of very active research in recent years. Nevertheless, no mitochondrial RTG-signaling pathway is yet understood in plants. This review summarizes recent advances toward elucidating redox processes and other bioenergetic factors as a part of RTG signaling of plant mitochondria. Critical Issues: Novel insights into mitochondrial physiology and redox-regulation provide a framework of upstream signaling. On the other end, downstream responses to modified mitochondrial function have become available, including transcriptomic data and mitochondrial phenotypes, revealing processes in the plant that are under mitochondrial control. Future Directions: Drawing parallels to chloroplast signaling and mitochondrial signaling in animal systems allows to bridge gaps in the current understanding and to deduce promising directions for future research. It is proposed that targeted usage of new technical approaches, such as quantitative in vivo imaging, will provide novel leverage to the dissection of plant mitochondrial signaling. Antioxid. Redox Signal. 18, 2122–2144. PMID:23234467
Mitochondrial nucleoid clusters protect newly synthesized mtDNA during Doxorubicin- and Ethidium Bromide-induced mitochondrial stress

Energy Technology Data Exchange (ETDEWEB)

Alán, Lukáš, E-mail: lukas.alan@fgu.cas.cz; Špaček, Tomáš; Pajuelo Reguera, David; Jabůrek, Martin; Ježek, Petr

2016-07-01

Mitochondrial DNA (mtDNA) is compacted in ribonucleoprotein complexes called nucleoids, which can divide or move within the mitochondrial network. Mitochondrial nucleoids are able to aggregate into clusters upon reaction with intercalators such as the mtDNA depletion agent Ethidium Bromide (EB) or anticancer drug Doxorobicin (DXR). However, the exact mechanism of nucleoid clusters formation remains unknown. Resolving these processes may help to elucidate the mechanisms of DXR-induced cardiotoxicity. Therefore, we addressed the role of two key nucleoid proteins; mitochondrial transcription factor A (TFAM) and mitochondrial single-stranded binding protein (mtSSB); in the formation of mitochondrial nucleoid clusters during the action of intercalators. We found that both intercalators cause numerous aberrations due to perturbing their native status. By blocking mtDNA replication, both agents also prevented mtDNA association with TFAM, consequently causing nucleoid aggregation into large nucleoid clusters enriched with TFAM, co-existing with the normal nucleoid population. In the later stages of intercalation (> 48 h), TFAM levels were reduced to 25%. In contrast, mtSSB was released from mtDNA and freely distributed within the mitochondrial network. Nucleoid clusters mostly contained nucleoids with newly replicated mtDNA, however the nucleoid population which was not in replication mode remained outside the clusters. Moreover, the nucleoid clusters were enriched with p53, an anti-oncogenic gatekeeper. We suggest that mitochondrial nucleoid clustering is a mechanism for protecting nucleoids with newly replicated DNA against intercalators mediating genotoxic stress. These results provide new insight into the common mitochondrial response to mtDNA stress and can be implied also on DXR-induced mitochondrial cytotoxicity. - Highlights: • The mechanism for mitochondrial nucleoid clustering is proposed. • DNA intercalators (Doxorubicin or Ethidium Bromide) prevent TFAM
Neonates with reduced neonatal lung function have systemic low-grade inflammation

DEFF Research Database (Denmark)

Chawes, Bo L.K.; Stokholm, Jakob; Bønnelykke, Klaus

2015-01-01

Background: Children and adults with asthma and impaired lung function have been reported to have low-grade systemic inflammation, but it is unknown whether this inflammation starts before symptoms and in particular whether low-grade inflammation is present in asymptomatic neonates with reduced...... lung function. ObjectiveWe sought to investigate the possible association between neonatal lung function and biomarkers of systemic inflammation. Methods: Plasma levels of high-sensitivity C-reactive protein (hs-CRP), IL-1β, IL-6, TNF-α, and CXCL8 (IL-8) were measured at age 6 months in 300 children....... Results: The neonatal forced expiratory volume at 0.5 seconds was inversely associated with hs-CRP (β-coefficient, −0.12; 95% CI, −0.21 to −0.04; P approach, including hs-CRP, IL-6...
The ability of an electrocardiogram to predict fatal and non-fatal cardiac events in asymptomatic middle-aged subjects.

Science.gov (United States)

Terho, Henri K; Tikkanen, Jani T; Kenttä, Tuomas V; Junttila, M Juhani; Aro, Aapo L; Anttonen, Olli; Kerola, Tuomas; Rissanen, Harri A; Knekt, Paul; Reunanen, Antti; Huikuri, Heikki V

2016-11-01

The long-term prognostic value of a standard 12-lead electrocardiogram (ECG) for predicting cardiac events in apparently healthy middle-aged subjects is not well defined. A total of 9511 middle-aged subjects (mean age 43 ± 8.2 years, 52% males) without a known cardiac disease and with a follow-up 40 years were included in the study. Fatal and non-fatal cardiac events were collected from the national registries. The predictive value of ECG was separately analyzed for 10 and 30 years. Major ECG abnormalities were classified according to the Minnesota code. Subjects with major ECG abnormalities (N = 1131) had an increased risk of cardiac death after 10-years (adjusted hazard ratio [HR] 1.7; 95% confidence interval [95% CI], 1.1-2.5, p = 0.009) and 30-years of follow-up (HR 1.3, 95% CI, 1.1-1.5, p electrocardiogram are shown to have prognostic significance for cardiac events in elderly subjects without known cardiac disease. Our results suggest that ECG abnormalities increase the risk of fatal cardiac events also in middle-aged healthy subjects.
Analysis of In-hospital Neonatal Death in the Tertiary Neonatal Intensive Care Unit in China: A Multicenter Retrospective Study

Institute of Scientific and Technical Information of China (English)

Chen-Hong Wang; Li-Zhong Du; Xiao-Lu Ma; Li-Ping Shi; Xiao-Mei Tong; Hong Liu; Guo-Fang Ding

2016-01-01

Background:Globally,the proportion of child deaths that occur in the neonatal period remains a high level of 37-41％.Differences of cause in neonate death exist in different regions as well as in different economic development countries.The specific aim of this study was to investigate the causes,characteristics,and differences of death in neonates during hospitalization in the tertiary Neonatal Intensive Care Unit (NICU) of China.Methods:All the dead neonates admitted to 26 NICUs were included between January 1,2011,and December 31,2011.All the data were collected retrospectively from clinical records by a designed questionnaire.Data collected from each NICU were delivered to the leading institution where the results were analyzed.Results:A total of 744 newborns died during the l-year survey,accounting for 1.2％ of all the neonates admitted to 26 NICUs and 37.6％ of all the deaths in children under 5 years of age in these hospitals.Preterm neonate death accounted for 59.3％ of all the death.The leading causes of death in preterm and term infants were pulmonary disease and infection,respectively.In early neonate period,pulmonary diseases (56.5％) occupied the largest proportion ofpreterm deaths while infection (27％) and neurologic diseases (22％) were the two main causes of term deaths.In late neonate period,infection was the leading cause of both preterm and term neonate deaths.About two-thirds of neonate death occurred after medical care withdrawal.Of the cases who might survive if receiving continuing treatment,parents' concern about the long-term outcomes was the main reason of medical care withdrawal.Conclusions:Neonate death still accounts for a high proportion of all the deaths in children under 5 years of age.Our study showed the majority of neonate death occurred in preterm infants.Cause of death varied with the age of death and gestational age.Accurate and prompt evaluation of the long-term outcomes should be carried out to guide the critical
Determinants of neonatal mortality in Indonesia

Directory of Open Access Journals (Sweden)

Agho Kingsley

2008-07-01

Full Text Available Abstract Background Neonatal mortality accounts for almost 40 per cent of under-five child mortality, globally. An understanding of the factors related to neonatal mortality is important to guide the development of focused and evidence-based health interventions to prevent neonatal deaths. This study aimed to identify the determinants of neonatal mortality in Indonesia, for a nationally representative sample of births from 1997 to 2002. Methods The data source for the analysis was the 2002–2003 Indonesia Demographic and Health Survey from which survival information of 15,952 singleton live-born infants born between 1997 and 2002 was examined. Multilevel logistic regression using a hierarchical approach was performed to analyze the factors associated with neonatal deaths, using community, socio-economic status and proximate determinants. Results At the community level, the odds of neonatal death was significantly higher for infants from East Java (OR = 5.01, p = 0.00, and for North, Central and Southeast Sulawesi and Gorontalo combined (OR = 3.17, p = 0.03 compared to the lowest neonatal mortality regions of Bali, South Sulawesi and Jambi provinces. A progressive reduction in the odds was found as the percentage of deliveries assisted by trained delivery attendants in the cluster increased. The odds of neonatal death were higher for infants born to both mother and father who were employed (OR = 1.84, p = 0.00 and for infants born to father who were unemployed (OR = 2.99, p = 0.02. The odds were also higher for higher rank infants with a short birth interval (OR = 2.82, p = 0.00, male infants (OR = 1.49, p = 0.01, smaller than average-sized infants (OR = 2.80, p = 0.00, and infant's whose mother had a history of delivery complications (OR = 1.81, p = 0.00. Infants receiving any postnatal care were significantly protected from neonatal death (OR = 0.63, p = 0.03. Conclusion Public health interventions directed at reducing neonatal death should
The challenges of neonatal magnetic resonance imaging

International Nuclear Information System (INIS)

Arthurs, Owen J.; Graves, Martin J.; Lomas, David J.; Edwards, Andrea; Austin, Topun

2012-01-01

Improved neonatal survival rates and antenatal diagnostic imaging is generating a growing demand for postnatal MRI examinations. Neonatal brain MRI is now becoming standard clinical care in many settings, but with the exception of some research centres, the technique has not been optimised for imaging neonates and small children. Here, we review some of the challenges involved in neonatal MRI, including recent advances in overall MR practicality and nursing practice, to address some of the ways in which the MR experience could be made more neonate-friendly. (orig.)
Susceptibility weighted imaging of the neonatal brain

International Nuclear Information System (INIS)

Meoded, A.; Poretti, A.; Northington, F.J.; Tekes, A.; Intrapiromkul, J.; Huisman, T.A.G.M.

2012-01-01

Susceptibility weighted imaging (SWI) is a well-established magnetic resonance technique, which is highly sensitive for blood, iron, and calcium depositions in the brain and has been implemented in the routine clinical use in both children and neonates. SWI in neonates might provide valuable additional diagnostic and prognostic information for a wide spectrum of neonatal neurological disorders. To date, there are few articles available on the application of SWI in neonatal neurological disorders. The purpose of this article is to illustrate and describe the characteristic SWI findings in various typical neonatal neurological disorders.
Susceptibility weighted imaging of the neonatal brain

Energy Technology Data Exchange (ETDEWEB)

Meoded, A.; Poretti, A. [Division of Pediatric Radiology and Division of Neuroradiology, Russell H. Morgan Department of Radiology and Radiological Sciences, Johns Hopkins University School of Medicine, Baltimore, MD (United States); Northington, F.J. [Division of Neonatology, Department of Pediatrics, Johns Hopkins University School of Medicine, Baltimore, MD (United States); Tekes, A.; Intrapiromkul, J. [Division of Pediatric Radiology and Division of Neuroradiology, Russell H. Morgan Department of Radiology and Radiological Sciences, Johns Hopkins University School of Medicine, Baltimore, MD (United States); Huisman, T.A.G.M., E-mail: thuisma1@jhmi.edu [Division of Pediatric Radiology and Division of Neuroradiology, Russell H. Morgan Department of Radiology and Radiological Sciences, Johns Hopkins University School of Medicine, Baltimore, MD (United States)

2012-08-15

Susceptibility weighted imaging (SWI) is a well-established magnetic resonance technique, which is highly sensitive for blood, iron, and calcium depositions in the brain and has been implemented in the routine clinical use in both children and neonates. SWI in neonates might provide valuable additional diagnostic and prognostic information for a wide spectrum of neonatal neurological disorders. To date, there are few articles available on the application of SWI in neonatal neurological disorders. The purpose of this article is to illustrate and describe the characteristic SWI findings in various typical neonatal neurological disorders.
On the occurrence of fatal landslides in 2008

Science.gov (United States)

Petley, D.

2009-04-01

This paper represents the latest in an annual review of fatal landslide events worldwide, based upon the Durham Fatal Landslide Database. Landslide events were inevitably dominated by the occurrence of the 12th May Wenchuan Earthquake in Sichuan Province of China, which triggered very extensive landsliding. Whilst it will be very difficult to estimate the true impact of this event in terms of landslides, the Chinese authorities estimate that about 29,000 people were killed by landslides, with several thousand more losing their lives whilst trapped in rubble due to the inability of rescuers to pass through landslide affected areas. Considerable work is needed to understand the reasons for the intensity of the landslide processes. Elsewhere the number of fatal landslides recorded totalled 405 worldwide. These caused 3526 fatalities, giving a total for the year of about 32,526 people. To put this into context, according to the CRED EM-DAT database the recorded number of fatalities from volcanic eruptions in the period 2000 to 2008 inclusive is 221! The distribution of fatal landslides followed the familiar patterns observed in previous years, with distinct clusters in Central China, along the southern edge of the Himalayas, in the Caribbean, in Central America, western S. America, along the western edge of the Philippine Sea plate and in Indonesia, plus a scattering elsewhere. The temporal distribution shows strong seasonality, with the peak occurring during the northern hemisphere summer. Unusually however, the peak month was September (usually it is in July), and there were large numbers of landslide events right through to November. The November landslide clusters occurred in SE. Asia and in Central / S. America, reflecting very heavy rains in these regions at that time. The reasons for this are not clear at present, although may be linked to weakening La Nina conditions that have prevailed through much of the year. An analysis is made of the relationship between
Fatal consequences of synergistic anticoagulation

Directory of Open Access Journals (Sweden)

Sen P

2018-05-01

Full Text Available Objective: Novel oral anticoagulants (NOACs are increasingly being preferred by clinicians (and patients because they have a wide therapeutic window and therefore do not require monitoring of anticoagulant effect. Herein, we describe the unfortunate case of a patient who had fatal consequences as a result of switching from warfarin to rivaroxaban. Case Summary: A 90-year-old Caucasian woman, with atrial fibrillation on chronic anticoagulation with warfarin, was admitted to the hospital for pneumonia. She was treated with levofloxacin. In the same admission, her warfarin was switched to rivaroxaban. On Day 3 after the switch, her INR was found to be 6, and she developed a cervical epidural hematoma from C2 to C7. She ultimately developed respiratory arrest, was put on comfort care and died. Discussion: Rivaroxaban and warfarin are known to have a synergistic anticoagulant effect, usually seen shortly after switching. Antibiotics also increase the effects of warfarin by the inhibition of metabolizing isoenzymes. It is hypothesized that these two effects led to the fatal cervical spinal hematoma. Conclusion: The convenience of a wide therapeutic window and no requirement of laboratory monitoring makes the NOACs a desirable option for anticoagulation. However, there is lack of data and recommendations on how to transition patients from Warfarin to NOACs or even how to transition from one NOAC to another. Care should be taken to ensure continuous monitoring of anticoagulation when stopping, interrupting or switching between NOACS to avoid the possibility of fatal bleeding and strokes.
Non-fatal self-poisoning across age groups, in Sri Lanka.

Science.gov (United States)

Rajapakse, Thilini; Christensen, Helen; Cotton, Sue; Griffiths, Kathleen Margaret

2016-02-01

Attempted or non-fatal self-poisoning in common in Sri Lanka, but little is known about variation of psychiatric morbidity and suicidal intent across differing ages. The aim of this study was to investigate factors associated with non-fatal self-poisoning in Sri Lanka across three different age groups (namely 14-24 years, 25-34 years and ≥ 35 years). It was anticipated that the findings of the study would inform and guide development of preventive interventions for non-fatal self-poisoning in this country. 935 participants were interviewed within one week of admission to hospital for medical management of non-fatal self-poisoning, over a consecutive 14-month period. Socio-demographic factors, types of poison ingested, triggers and psychiatric morbidity was examined as a function of age. Results showed that a majority (83%) of participants were aged below 35 years. Younger participants aged aged 25-34 years, and ≥ 35 years), who were more likely to ingest pesticides. Recent interpersonal conflict was a proximal trigger seen in all age groups, but suicidal intent, depression and alcohol use disorders increased with age. The overall study findings indicate that most who carry out acts of non-fatal self-poisoning in Sri Lanka are young (aged age groups, but psychiatric morbidity and suicidal intent is higher in the older age groups, as is pesticide ingestion. Age specific interventions may be efficacious in the prevention of non-fatal self-poisoning in Sri Lanka. Copyright © 2016 Elsevier B.V. All rights reserved.
Alcohol dehydrogenase accentuates ethanol-induced myocardial dysfunction and mitochondrial damage in mice: role of mitochondrial death pathway.

Directory of Open Access Journals (Sweden)

Rui Guo

2010-01-01

Full Text Available Binge drinking and alcohol toxicity are often associated with myocardial dysfunction possibly due to accumulation of the ethanol metabolite acetaldehyde although the underlying mechanism is unknown. This study was designed to examine the impact of accelerated ethanol metabolism on myocardial contractility, mitochondrial function and apoptosis using a murine model of cardiac-specific overexpression of alcohol dehydrogenase (ADH.ADH and wild-type FVB mice were acutely challenged with ethanol (3 g/kg/d, i.p. for 3 days. Myocardial contractility, mitochondrial damage and apoptosis (death receptor and mitochondrial pathways were examined.Ethanol led to reduced cardiac contractility, enlarged cardiomyocyte, mitochondrial damage and apoptosis, the effects of which were exaggerated by ADH transgene. In particular, ADH exacerbated mitochondrial dysfunction manifested as decreased mitochondrial membrane potential and accumulation of mitochondrial O(2 (*-. Myocardium from ethanol-treated mice displayed enhanced Bax, Caspase-3 and decreased Bcl-2 expression, the effect of which with the exception of Caspase-3 was augmented by ADH. ADH accentuated ethanol-induced increase in the mitochondrial death domain components pro-caspase-9 and cytochrome C in the cytoplasm. Neither ethanol nor ADH affected the expression of ANP, total pro-caspase-9, cytosolic and total pro-caspase-8, TNF-alpha, Fas receptor, Fas L and cytosolic AIF.Taken together, these data suggest that enhanced acetaldehyde production through ADH overexpression following acute ethanol exposure exacerbated ethanol-induced myocardial contractile dysfunction, cardiomyocyte enlargement, mitochondrial damage and apoptosis, indicating a pivotal role of ADH in ethanol-induced cardiac dysfunction possibly through mitochondrial death pathway of apoptosis.
Alcohol dehydrogenase accentuates ethanol-induced myocardial dysfunction and mitochondrial damage in mice: role of mitochondrial death pathway.

Science.gov (United States)

Guo, Rui; Ren, Jun

2010-01-18

Binge drinking and alcohol toxicity are often associated with myocardial dysfunction possibly due to accumulation of the ethanol metabolite acetaldehyde although the underlying mechanism is unknown. This study was designed to examine the impact of accelerated ethanol metabolism on myocardial contractility, mitochondrial function and apoptosis using a murine model of cardiac-specific overexpression of alcohol dehydrogenase (ADH). ADH and wild-type FVB mice were acutely challenged with ethanol (3 g/kg/d, i.p.) for 3 days. Myocardial contractility, mitochondrial damage and apoptosis (death receptor and mitochondrial pathways) were examined. Ethanol led to reduced cardiac contractility, enlarged cardiomyocyte, mitochondrial damage and apoptosis, the effects of which were exaggerated by ADH transgene. In particular, ADH exacerbated mitochondrial dysfunction manifested as decreased mitochondrial membrane potential and accumulation of mitochondrial O(2) (*-). Myocardium from ethanol-treated mice displayed enhanced Bax, Caspase-3 and decreased Bcl-2 expression, the effect of which with the exception of Caspase-3 was augmented by ADH. ADH accentuated ethanol-induced increase in the mitochondrial death domain components pro-caspase-9 and cytochrome C in the cytoplasm. Neither ethanol nor ADH affected the expression of ANP, total pro-caspase-9, cytosolic and total pro-caspase-8, TNF-alpha, Fas receptor, Fas L and cytosolic AIF. Taken together, these data suggest that enhanced acetaldehyde production through ADH overexpression following acute ethanol exposure exacerbated ethanol-induced myocardial contractile dysfunction, cardiomyocyte enlargement, mitochondrial damage and apoptosis, indicating a pivotal role of ADH in ethanol-induced cardiac dysfunction possibly through mitochondrial death pathway of apoptosis.
Ictericia Neonatal

OpenAIRE

Blanco de la Fuente, María Isabel

2014-01-01

El motivo que ha llevado a la realización de este trabajo fin de grado sobre el tema de la ICTERICIA NEONATAL se debe a la elevada frecuencia de su aparición en la población. Un porcentaje elevado de RN la padecen al nacer siendo, en la mayor parte de los casos, un proceso fisiológico resuelto con facilidad debido a una inmadurez del sistema hepático y a una hiperproducción de bilirrubina. La ictericia neonatal es la pigmentación de color amarillo de la piel y mucosas en ...
GIS based analysis of Intercity Fatal Road Traffic Accidents in Iran.

Science.gov (United States)

Alizadeh, A; Zare, M; Darparesh, M; Mohseni, S; Soleimani-Ahmadi, M

2015-01-01

Road traffic accidents including intercity car traffic accidents (ICTAs) are among the most important causes of morbidity and mortality due to the growing number of vehicles, risky behaviors, and changes in lifestyle of the general population. A sound knowledge of the geographical distribution of car traffic accidents can be considered as an approach towards the accident causation and it can be used as an administrative tool in allocating the sources for traffic accidents prevention. This study was conducted to investigate the geographical distribution and the time trend of fatal intercity car traffic accidents in Iran. To conduct this descriptive study, all Iranian intercity road traffic mortality data were obtained from the Police reports in the Statistical Yearbook of the Governor's Budget and Planning. The obtained data were for 17 complete Iranian calendar years from March 1997 to March 2012. The incidence rate (IR) of fatal ICTAs for each year was calculated as the total number of fatal ICTAs in every 100000 population in specified time intervals. Figures and maps indicating the trends and geographical distribution of fatal ICTAs were prepared while using Microsoft Excel and ArcGis9.2 software. The number of fatal car accidents showed a general increasing trend from 3000 in 1996 to 13500 in 2012. The incidence of fatal intercity car accidents has changed from six in 100000 population in 1996 to 18 in 100000 population in 2012. GIS based data showed that the incidence rate of ICTAs in different provinces of Iran was very divergent. The highest incidence of fatal ICTAs was in Semnan province (IR= 35.2), followed by North Khorasan (IR=22.7), and South Khorasan (IR=22). The least incidence of fatal ICTAs was in Tehran province (IR=2.4) followed by Khozestan (IR=6.5), and Eastern Azarbayejan (IR=6.6). The compensation cost of fatal ICTAs also showed an increasing trend during the studied period. Since an increasing amount of money was being paid yearly for the car
GIS based analysis of Intercity Fatal Road Traffic Accidents in Iran

Science.gov (United States)

Alizadeh, A; Zare, M; Darparesh, M; Mohseni, S; Soleimani-Ahmadi, M

2015-01-01

Road traffic accidents including intercity car traffic accidents (ICTAs) are among the most important causes of morbidity and mortality due to the growing number of vehicles, risky behaviors, and changes in lifestyle of the general population. A sound knowledge of the geographical distribution of car traffic accidents can be considered as an approach towards the accident causation and it can be used as an administrative tool in allocating the sources for traffic accidents prevention. This study was conducted to investigate the geographical distribution and the time trend of fatal intercity car traffic accidents in Iran. To conduct this descriptive study, all Iranian intercity road traffic mortality data were obtained from the Police reports in the Statistical Yearbook of the Governor’s Budget and Planning. The obtained data were for 17 complete Iranian calendar years from March 1997 to March 2012. The incidence rate (IR) of fatal ICTAs for each year was calculated as the total number of fatal ICTAs in every 100000 population in specified time intervals. Figures and maps indicating the trends and geographical distribution of fatal ICTAs were prepared while using Microsoft Excel and ArcGis9.2 software. The number of fatal car accidents showed a general increasing trend from 3000 in 1996 to 13500 in 2012. The incidence of fatal intercity car accidents has changed from six in 100000 population in 1996 to 18 in 100000 population in 2012. GIS based data showed that the incidence rate of ICTAs in different provinces of Iran was very divergent. The highest incidence of fatal ICTAs was in Semnan province (IR= 35.2), followed by North Khorasan (IR=22.7), and South Khorasan (IR=22). The least incidence of fatal ICTAs was in Tehran province (IR=2.4) followed by Khozestan (IR=6.5), and Eastern Azarbayejan (IR=6.6). The compensation cost of fatal ICTAs also showed an increasing trend during the studied period. Since an increasing amount of money was being paid yearly for the
Obesity is associated with fatal coronary heart disease independently of traditional risk factors and deprivation.

Science.gov (United States)

Logue, Jennifer; Murray, Heather M; Welsh, Paul; Shepherd, James; Packard, Chris; Macfarlane, Peter; Cobbe, Stuart; Ford, Ian; Sattar, Naveed

2011-04-01

The effect of body mass index (BMI) on coronary heart disease (CHD) risk is attenuated when mediators of this risk (such as diabetes, hypertension and hyperlipidaemia) are accounted for. However, there is now evidence of a differential effect of risk factors on fatal and non-fatal CHD events, with markers of inflammation more strongly associated with fatal than non-fatal events. To describe the association with BMI separately for both fatal and non-fatal CHD risk after accounting for classical risk factors and to assess any independent effects of obesity on CHD risk. In the West of Scotland Coronary Prevention Study BMI in 6082 men (mean age 55 years) with hypercholesterolaemia, but no history of diabetes or CVD, was related to the risk of fatal and non-fatal CHD events. After excluding participants with any event in the first 2 years, 1027 non-fatal and 214 fatal CHD events occurred during 14.7 years of follow-up. A minimally adjusted model (age, sex, statin treatment) and a maximally adjusted model (including known CVD risk factors and deprivation) were compared, with BMI 25-27.4 kg/m² as referent. The risk of non-fatal events was similar across all BMI categories in both models. The risk of fatal CHD events was increased in men with BMI 30.0-39.9 kg/m² in both the minimally adjusted model (HR = 1.75 (95% CI 1.12 to 2.74)) and the maximally adjusted model (HR = 1.60 (95% CI 1.02 to 2.53)). These hypothesis generating data suggest that obesity is associated with fatal, but not non-fatal, CHD after accounting for known cardiovascular risk factors and deprivation. Clinical trial registration WOSCOPS was carried out and completed before the requirement for clinical trial registration.
Laser Photoradiation Therapy For Neonatal Jaundice

Science.gov (United States)

Hamza, Mostafa; Hamza, Mohammad

1987-04-01

This paper describes our leading experience in the clinical application of laser in the treatment of neonatal jaundice. Currently, the irradiation of jaundiced infants during neonatal life to fluorescent light is the most common treatment of neonatal hyperbilirubinemia. The authors have investigated the photodegradation of bilirubin by laser in vitro and in Gunn rats before embarking on its clinical application in the treatment of jaundice in the new born child. This work was done to study the theraputic effect of laser compared to the currently used phototherapy in the treatment of neonatal jaundice. We selected 16 full term neonates with jaundice to be the subject of this study. The neonates of the study were devided into two groups. The first group was treated with continuous phototherapy . The second group recieved photoradiation therapy with gas laser The laser used was a CW argon-ion laser tuned to oscillate at 488.0 nm wavelength. This wavelength selection was based on our previous studies on the effect of laser irradiation of Gunn rats at different wavelengths. Comparison of the results of both methods of treatment will be reported in detail. The advantages and limitations of laser photoradiation therapy for neonatal jaundice will be discussed.

Deconstructing Mitochondrial Dysfunction in Alzheimer Disease

Directory of Open Access Journals (Sweden)

Vega García-Escudero

2013-01-01

Full Text Available There is mounting evidence showing that mitochondrial damage plays an important role in Alzheimer disease. Increased oxygen species generation and deficient mitochondrial dynamic balance have been suggested to be the reason as well as the consequence of Alzheimer-related pathology. Mitochondrial damage has been related to amyloid-beta or tau pathology or to the presence of specific presenilin-1 mutations. The contribution of these factors to mitochondrial dysfunction is reviewed in this paper. Due to the relevance of mitochondrial alterations in Alzheimer disease, recent works have suggested the therapeutic potential of mitochondrial-targeted antioxidant. On the other hand, autophagy has been demonstrated to play a fundamental role in Alzheimer-related protein stress, and increasing data shows that this pathway is altered in the disease. Moreover, mitochondrial alterations have been related to an insufficient clearance of dysfunctional mitochondria by autophagy. Consequently, different approaches for the removal of damaged mitochondria or to decrease the related oxidative stress in Alzheimer disease have been described. To understand the role of mitochondrial function in Alzheimer disease it is necessary to generate human cellular models which involve living neurons. We have summarized the novel protocols for the generation of neurons by reprogramming or direct transdifferentiation, which offer useful tools to achieve this result.
Mitochondrial Fusion Proteins and Human Diseases

Directory of Open Access Journals (Sweden)

Michela Ranieri

2013-01-01

Full Text Available Mitochondria are highly dynamic, complex organelles that continuously alter their shape, ranging between two opposite processes, fission and fusion, in response to several stimuli and the metabolic demands of the cell. Alterations in mitochondrial dynamics due to mutations in proteins involved in the fusion-fission machinery represent an important pathogenic mechanism of human diseases. The most relevant proteins involved in the mitochondrial fusion process are three GTPase dynamin-like proteins: mitofusin 1 (MFN1 and 2 (MFN2, located in the outer mitochondrial membrane, and optic atrophy protein 1 (OPA1, in the inner membrane. An expanding number of degenerative disorders are associated with mutations in the genes encoding MFN2 and OPA1, including Charcot-Marie-Tooth disease type 2A and autosomal dominant optic atrophy. While these disorders can still be considered rare, defective mitochondrial dynamics seem to play a significant role in the molecular and cellular pathogenesis of more common neurodegenerative diseases, for example, Alzheimer’s and Parkinson’s diseases. This review provides an overview of the basic molecular mechanisms involved in mitochondrial fusion and focuses on the alteration in mitochondrial DNA amount resulting from impairment of mitochondrial dynamics. We also review the literature describing the main disorders associated with the disruption of mitochondrial fusion.
MRI of neonatal encephalopathy

International Nuclear Information System (INIS)

Khong, P.L.; Lam, B.C.C.; Tung, H.K.S.; Wong, V.; Chan, F.L.; Ooi, G.C.

2003-01-01

We present the magnetic resonance imaging (MRI) findings in neonatal encephalopathy, including hypoxic-ischaemic encephalopathy, perinatal/neonatal stroke, metabolic encephalopathy from inborn errors of metabolism, congenital central nervous system infections and birth trauma. The applications of advanced MRI techniques, such as diffusion-weighted imaging and magnetic resonance spectroscopy are emphasized
Features of fatal injuries in older cyclists in vehicle-bicycle accidents in Japan.

Science.gov (United States)

Matsui, Yasuhiro; Oikawa, Shoko; Hitosugi, Masahito

2018-01-02

The purpose of this study was to identify and better understand the features of fatal injuries in cyclists aged 75 years and over involved in collisions with either hood- or van-type vehicles. This study investigated the fatal injuries of cyclists aged 75 years old and over by analyzing accident data. We focused on the body regions to which the fatal injury occurred using vehicle-bicycle accident data from the Institute for Traffic Accident Research and Data Analysis (ITARDA) in Japan. Using data from 2009 to 2013, we examined the frequency of fatally injured body region by gender, age, and actual vehicle travel speed. We investigated any significant differences in distributions of fatal injuries by body region for cyclists aged 75 years and over using chi-square tests to compare with cyclists in other age groups. We also investigated the cause of fatal head injuries, such as impact with a road surface or vehicle. The results indicated that head injuries were the most common cause of fatalities among the study group. At low vehicle travel speeds for both hood- and van-type vehicles, fatalities were most likely to be the result of head impacts against the road surface. The percentage of fatalities following hip injuries was significantly higher for cyclists aged 75 years and over than for those aged 65-74 or 13-59 in impacts with hood-type vehicles. It was also higher for women than men in the over-75 age group in impacts with these vehicles. For cyclists aged 75 years and over, wearing a helmet may be helpful to prevent head injuries in vehicle-to-cyclist accidents. It may also be helpful to introduce some safety measures to prevent hip injuries, given the higher level of fatalities following hip injury among all cyclists aged 75 and over, particularly women.
Mitochondrial Stress Signaling Promotes Cellular Adaptations

Directory of Open Access Journals (Sweden)

Jayne Alexandra Barbour

2014-01-01

Full Text Available Mitochondrial dysfunction has been implicated in the aetiology of many complex diseases, as well as the ageing process. Much of the research on mitochondrial dysfunction has focused on how mitochondrial damage may potentiate pathological phenotypes. The purpose of this review is to draw attention to the less well-studied mechanisms by which the cell adapts to mitochondrial perturbations. This involves communication of stress to the cell and successful induction of quality control responses, which include mitophagy, unfolded protein response, upregulation of antioxidant and DNA repair enzymes, morphological changes, and if all else fails apoptosis. The mitochondrion is an inherently stressful environment and we speculate that dysregulation of stress signaling or an inability to switch on these adaptations during times of mitochondrial stress may underpin mitochondrial dysfunction and hence amount to pathological states over time.
Neonatal resuscitation: advances in training and practice

Directory of Open Access Journals (Sweden)

Sawyer T

2016-12-01

Full Text Available Taylor Sawyer, Rachel A Umoren, Megan M Gray Department of Pediatrics, Division of Neonatology, Neonatal Education and Simulation-based Training (NEST Program, University of Washington School of Medicine, Seattle, WA, USA Abstract: Each year in the US, some four hundred thousand newborns need help breathing when they are born. Due to the frequent need for resuscitation at birth, it is vital to have evidence-based care guidelines and to provide effective neonatal resuscitation training. Every five years, the International Liaison Committee on Resuscitation (ILCOR reviews the science of neonatal resuscitation. In the US, the American Heart Association (AHA develops treatment guidelines based on the ILCOR science review, and the Neonatal Resuscitation Program (NRP translates the AHA guidelines into an educational curriculum. In this report, we review recent advances in neonatal resuscitation training and practice. We begin with a review of the new 7th edition NRP training curriculum. Then, we examine key changes to the 2015 AHA neonatal resuscitation guidelines. The four components of the NRP curriculum reviewed here include eSim®, Performance Skills Stations, Integrated Skills Station, and Simulation and Debriefing. The key changes to the AHA neonatal resuscitation guidelines reviewed include initial steps of newborn care, positive-pressure ventilation, endotracheal intubation and use of laryngeal mask, chest compressions, medications, resuscitation of preterm newborns, and ethics and end-of-life care. We hope this report provides a succinct review of recent advances in neonatal resuscitation. Keywords: neonatal resuscitation, Neonatal Resuscitation Program, NRP, simulation, deliberate practice, debriefing, eSIM
Acute symptomatic neonatal seizures in preterm neonates: etiologies and treatments.

Science.gov (United States)

Pisani, Francesco; Spagnoli, Carlotta

2017-12-15

Acute symptomatic neonatal seizures in preterm newborns are a relevant clinical challenge due to the presence of many knowledge gaps. Etiology-wise, acute symptomatic seizures have an age-specific epidemiology, with intraventricular hemorrhage and its complications representing the first cause in extremely and very preterm neonates, whereas other etiologies have similar occurrence rates as in full-term infants. Specific treatment strategies for the premature neonates are not yet available. Studies suggest a similarly low response rate with even more unfavorable prognosis than in full-term infants. Pharmacodynamic and pharmacokinetic changes are likely under way during the preterm period, with the potential to affect both effectiveness and safety of antiepileptic drugs in these patients. However, due to the lack of clear evidence to guide prioritization of second-line drugs, off-label medications are frequently indicated by review papers and flow-charts, and are prescribed in clinical practice. We therefore conclude by exploring potential future lines of research. Copyright © 2017 Elsevier Ltd. All rights reserved.
Melatonin and human mitochondrial diseases

Directory of Open Access Journals (Sweden)

Reza Sharafati-Chaleshtori

2017-01-01

Full Text Available Mitochondrial dysfunction is one of the main causative factors in a wide variety of complications such as neurodegenerative disorders, ischemia/reperfusion, aging process, and septic shock. Decrease in respiratory complex activity, increase in free radical production, increase in mitochondrial synthase activity, increase in nitric oxide production, and impair in electron transport system and/or mitochondrial permeability are considered as the main factors responsible for mitochondrial dysfunction. Melatonin, the pineal gland hormone, is selectively taken up by mitochondria and acts as a powerful antioxidant, regulating the mitochondrial bioenergetic function. Melatonin increases the permeability of membranes and is the stimulator of antioxidant enzymes including superoxide dismutase, glutathione peroxidase, glutathione reductase, and catalase. It also acts as an inhibitor of lipoxygenase. Melatonin can cause resistance to oxidation damage by fixing the microsomal membranes. Melatonin has been shown to retard aging and inhibit neurodegenerative disorders, ischemia/reperfusion, septic shock, diabetes, cancer, and other complications related to oxidative stress. The purpose of the current study, other than introducing melatonin, was to present the recent findings on clinical effects in diseases related to mitochondrial dysfunction including diabetes, cancer, gastrointestinal diseases, and diseases related to brain function.
Mitochondrial Metabolism in Aging Heart

Science.gov (United States)

Lesnefsky, Edward J.; Chen, Qun; Hoppel, Charles L.

2016-01-01

Altered mitochondrial metabolism is the underlying basis for the increased sensitivity in the aged heart to stress. The aged heart exhibits impaired metabolic flexibility, with a decreased capacity to oxidize fatty acids and enhanced dependence on glucose metabolism. Aging impairs mitochondrial oxidative phosphorylation, with a greater role played by the mitochondria located between the myofibrils, the interfibrillar mitochondria. With aging, there is a decrease in activity of complexes III and IV, which account for the decrease in respiration. Furthermore, aging decreases mitochondrial content among the myofibrils. The end result is that in the interfibrillar area there is an approximate 50% decrease in mitochondrial function, affecting all substrates. The defective mitochondria persist in the aged heart, leading to enhanced oxidant production and oxidative injury and the activation of oxidant signaling for cell death. Aging defects in mitochondria represent new therapeutic targets, whether by manipulation of the mitochondrial proteome, modulation of electron transport, activation of biogenesis or mitophagy, or the regulation of mitochondrial fission and fusion. These mechanisms provide new ways to attenuate cardiac disease in elders by preemptive treatment of age-related defects, in contrast to the treatment of disease-induced dysfunction. PMID:27174952
Procedural pain in neonatal units in Kenya.

Science.gov (United States)

Kyololo, O'Brien Munyao; Stevens, Bonnie; Gastaldo, Denise; Gisore, Peter

2014-11-01

To determine the nature and frequency of painful procedures and procedural pain management practices in neonatal units in Kenya. Cross-sectional survey. Level I and level II neonatal units in Kenya. Ninety-five term and preterm neonates from seven neonatal units. Medical records of neonates admitted for at least 24 h were reviewed to determine the nature and frequency of painful procedures performed in the 24 h period preceding data collection (6:00 to 6:00) as well as the pain management interventions (eg, morphine, breastfeeding, skin-to-skin contact, containment, non-nutritive sucking) that accompanied each procedure. Neonates experienced a total of 404 painful procedures over a 24 h period (mean=4.3, SD 2.0; range 1-12); 270 tissue-damaging (mean=2.85, SD 1.1; range 1-6) and 134 non-tissue-damaging procedures (mean=1.41, SD 1.2; range 0-6). Peripheral cannula insertion (27%) and intramuscular injections (22%) were the most common painful procedures. Ventilated neonates and neonates admitted in level II neonatal units had a higher number of painful procedures than those admitted in level I units (mean 4.76 vs 2.96). Only one procedure had a pain intensity score documented; and none had been performed with any form of analgesia. Neonates in Kenya were exposed to numerous tissue-damaging and non-tissue-damaging procedures without any form of analgesia. Our findings suggest that education is needed on how to assess and manage procedural pain in neonatal units in Kenya. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.
Mitochondrial Dysfunction in Parkinson's Disease

Directory of Open Access Journals (Sweden)

P. C. Keane

2011-01-01

Full Text Available Parkinson's disease (PD is a progressive, neurodegenerative condition that has increasingly been linked with mitochondrial dysfunction and inhibition of the electron transport chain. This inhibition leads to the generation of reactive oxygen species and depletion of cellular energy levels, which can consequently cause cellular damage and death mediated by oxidative stress and excitotoxicity. A number of genes that have been shown to have links with inherited forms of PD encode mitochondrial proteins or proteins implicated in mitochondrial dysfunction, supporting the central involvement of mitochondria in PD. This involvement is corroborated by reports that environmental toxins that inhibit the mitochondrial respiratory chain have been shown to be associated with PD. This paper aims to illustrate the considerable body of evidence linking mitochondrial dysfunction with neuronal cell death in the substantia nigra pars compacta (SNpc of PD patients and to highlight the important need for further research in this area.
Endocrine disorders in mitochondrial disease.

Science.gov (United States)

Schaefer, Andrew M; Walker, Mark; Turnbull, Douglass M; Taylor, Robert W

2013-10-15

Endocrine dysfunction in mitochondrial disease is commonplace, but predominantly restricted to disease of the endocrine pancreas resulting in diabetes mellitus. Other endocrine manifestations occur, but are relatively rare by comparison. In mitochondrial disease, neuromuscular symptoms often dominate the clinical phenotype, but it is of paramount importance to appreciate the multi-system nature of the disease, of which endocrine dysfunction may be a part. The numerous phenotypes attributable to pathogenic mutations in both the mitochondrial (mtDNA) and nuclear DNA creates a complex and heterogeneous catalogue of disease which can be difficult to navigate for novices and experts alike. In this article we provide an overview of the endocrine disorders associated with mitochondrial disease, the way in which the underlying mitochondrial disorder influences the clinical presentation, and how these factors influence subsequent management. Copyright © 2013 The Authors. Published by Elsevier Ireland Ltd.. All rights reserved.
Accidental fatal lung injury by compressed air: a case report.

Science.gov (United States)

Rayamane, Anand Parashuram; Pradeepkumar, M V

2015-03-01

Compressed air is being used extensively as a source of energy at industries and in daily life. A variety of fatal injuries are caused by improper and ignorant use of compressed air equipments. Many types of injuries due to compressed air are reported in the literature such as colorectal injury, orbital injury, surgical emphysema, and so on. Most of these injuries are accidental in nature. It is documented that 40 pounds per square inch pressure causes fatal injuries to the ear, eyes, lungs, stomach, and intestine. Openings of body are vulnerable to injuries by compressed air. Death due to compressed air injuries is rarely reported. Many cases are treated successfully by conservative or surgical management. Extensive survey of literature revealed no reports of fatal injury to the upper respiratory tract and lungs caused by compressed air. Here, we are reporting a fatal event of accidental death after insertion of compressed air pipe into the mouth. The postmortem findings are corroborated with the history and discussed in detail.
The role of Omi/HtrA2 protease in neonatal postasphyxial serum-induced apoptosis in human kidney proximal tubule cells

Directory of Open Access Journals (Sweden)

Zhang Yong

2012-01-01

Full Text Available Omi/HtrA2, a proapoptotic mitochondrial serine protease, is involved in both caspase-dependent and caspaseindependent apoptosis. A growing body of evidence indicates that Omi/HtrA2 plays an important role in the pathogenesis of a variety of ischemia-reperfusion (I/R injuries. However, the role of Omi/HtrA2 in renal injuries that occur in neonates with asphyxia remains unknown. The present study was designed to investigate whether Omi/HtrA2 plays an important role in the types of renal injuries that are induced by neonatal postasphyxial serum. Human renal proximal tubular cell line (HK-2 cells were used as targets. A 20% serum taken from neonates one day after asphyxia was applied to target cells as an attacking factor. We initially included control and postasphyxial serum-attacked groups and later included a ucf-101 group in the study. In the postasphyxial serum-treated group, cytosolic Omi/HtrA2 and caspase-3 expression in HK-2 cells was significantly higher than in the control group. Moreover, the concentration of cytosolic caspase-3 was found to be markedly decreased in HK-2 cells in the ucf-101 group. Our results suggest both that postasphyxial serum has a potent apoptosis-inducing effect on HK-2 cells and that this effect can be partially blocked by ucf-101. Taken together, our results demonstrate for the first time that postasphyxial serum from neonates results in Omi/HtrA2 translocation from the mitochondria to the cytosol, where it promotes HK-2 cell apoptosis via a protease activity-dependent, caspase-mediated pathway.
The profile of wounding in civilian public mass shooting fatalities.

Science.gov (United States)

Smith, Edward Reed; Shapiro, Geoff; Sarani, Babak

2016-07-01

The incidence and severity of civilian public mass shootings (CPMS) continue to rise. Initiatives predicated on lessons learned from military woundings have placed strong emphasis on hemorrhage control, especially via use of tourniquets, as means to improve survival. We hypothesize that both the overall wounding pattern and the specific fatal wounds in CPMS events are different from those in military combat fatalities and thus may require a new management strategy. A retrospective study of autopsy reports for all victims involved in 12 CPMS events was performed. Civilian public mass shootings was defined using the FBI and the Congressional Research Service definition. The site of injury, probable site of fatal injury, and presence of potentially survivable injury (defined as survival if prehospital care is provided within 10 minutes and trauma center care within 60 minutes of injury) was determined independently by each author. A total 139 fatalities consisting of 371 wounds from 12 CPMS events were reviewed. All wounds were due to gunshots. Victims had an average of 2.7 gunshots. Relative to military reports, the case fatality rate was significantly higher, and incidence of potentially survivable injuries was significantly lower. Overall, 58% of victims had gunshots to the head and chest, and only 20% had extremity wounds. The probable site of fatal wounding was the head or chest in 77% of cases. Only 7% of victims had potentially survivable wounds. The most common site of potentially survivable injury was the chest (89%). No head injury was potentially survivable. There were no deaths due to exsanguination from an extremity. The overall and fatal wounding patterns following CPMS are different from those resulting from combat operations. Given that no deaths were due to extremity hemorrhage, a treatment strategy that goes beyond use of tourniquets is needed to rescue the few victims with potentially survivable injuries. Prognostic/epidemiologic study, level IV
Fatal neglect of the elderly.

Science.gov (United States)

Ortmann, C; Fechner, G; Bajanowski, T; Brinkmann, B

2001-01-01

Maltreatment of the elderly is a common problem that affects more than 3% of the elderly. We report on two cases of fatal neglect. Risk factors of victims and caregivers were analysed in the context of the social history. In both cases, the victims had a dominant personality and the abusers (the sons) had been strictly controlled and formed by the parent. The victims showed typical risk factors such as living together with the abuser, isolation, dependence on care, income and money administration. Initially, the victims declined help from outside and self-neglect occurred. The unemployed perpetrators lived in social isolation and depended financially and mentally on the victims. In both cases no mental illness was present but there was a decrease of social competence. Legal medicine is predominantly involved in fatal cases in connection with external post-mortem examinations and autopsies. Also in the living, the medico-legal expert can assist in the identification of findings in elderly persons in cases of suspected abuse.
Mitochondrial dynamics in type 2 diabetes: Pathophysiological implications

Directory of Open Access Journals (Sweden)

Susana Rovira-Llopis

2017-04-01

Full Text Available Mitochondria play a key role in maintaining cellular metabolic homeostasis. These organelles have a high plasticity and are involved in dynamic processes such as mitochondrial fusion and fission, mitophagy and mitochondrial biogenesis. Type 2 diabetes is characterised by mitochondrial dysfunction, high production of reactive oxygen species (ROS and low levels of ATP. Mitochondrial fusion is modulated by different proteins, including mitofusin-1 (MFN1, mitofusin-2 (MFN2 and optic atrophy (OPA-1, while fission is controlled by mitochondrial fission 1 (FIS1, dynamin-related protein 1 (DRP1 and mitochondrial fission factor (MFF. PARKIN and (PTEN-induced putative kinase 1 (PINK1 participate in the process of mitophagy, for which mitochondrial fission is necessary. In this review, we discuss the molecular pathways of mitochondrial dynamics, their impairment under type 2 diabetes, and pharmaceutical approaches for targeting mitochondrial dynamics, such as mitochondrial division inhibitor-1 (mdivi-1, dynasore, P110 and 15-oxospiramilactone. Furthermore, we discuss the pathophysiological implications of impaired mitochondrial dynamics, especially in type 2 diabetes.
Effect of mobile phone proliferation on crash notification times and fatality rates.

Science.gov (United States)

Stickles, Jimmy L; Kempema, James M; Brown, Lawrence H

2018-01-01

The purpose of this study was to evaluate whether increased proliferation of mobile telephones has been associated with decreased MVC notification times and/or decreased MVC fatality rates in the United States (US). We used World Bank annual mobile phone market penetration data and US Fatality Analysis Reporting System (FARS) fatal MVC data for 1994-2014. For each year, phone proliferation was measured as mobile phones per 100 population. FARS data were used to calculate MVC notification time (time EMS notified - time MVC occurred) in minutes, and to determine the MVC fatality rate per billion vehicle miles traveled (BVMT). We used basic vector auto-regression modeling to explore relationships between changes in phone proliferation and subsequent changes in median and 90th percentile MVC notification times, as well as MVC fatality rates. From 1994 to 2014, larger year-over-year increases in phone proliferation were associated with larger decreases in 90th percentile notification times for MVCs occurring during daylight hours (p=0.004) and on the national highway system (p=0.046) two years subsequent, and crashes off the national highway system three years subsequent (p=0.023). There were no significant associations between changes in phone proliferation and subsequent changes in median crash notification times, nor with subsequent changes in MVC fatality rates. Between 1994 and 2014 increased mobile phone proliferation in the U.S. was associated with shorter 90th percentile EMS notification times for some subgroups of fatal MVCs, but not with decreases in median notification times or overall MVC fatality rates. Copyright © 2017 Elsevier Inc. All rights reserved.
The value of neonatal autopsy.

LENUS (Irish Health Repository)

Hickey, Leah

2012-01-01

Neonatal autopsy rates were in decline internationally at the end of the last century. Our objective was to assess the current value of neonatal autopsy in providing additional information to families and healthcare professionals.
Guidelines for Mass Fatality Management During Terrorist Incidents Involving Chemical Agents

National Research Council Canada - National Science Library

2003-01-01

.... Outside the United States, an earthquake in India produced over 30,000 fatalities in 2001, while an earthquake in El Salvador the same year produced close to 1,000 fatalities. In Bhopal, India (1984...

A Mitochondrial Genome of Rhyparochromidae (Hemiptera: Heteroptera) and a Comparative Analysis of Related Mitochondrial Genomes.

Science.gov (United States)

Li, Teng; Yang, Jie; Li, Yinwan; Cui, Ying; Xie, Qiang; Bu, Wenjun; Hillis, David M

2016-10-19

The Rhyparochromidae, the largest family of Lygaeoidea, encompasses more than 1,850 described species, but no mitochondrial genome has been sequenced to date. Here we describe the first mitochondrial genome for Rhyparochromidae: a complete mitochondrial genome of Panaorus albomaculatus (Scott, 1874). This mitochondrial genome is comprised of 16,345 bp, and contains the expected 37 genes and control region. The majority of the control region is made up of a large tandem-repeat region, which has a novel pattern not previously observed in other insects. The tandem-repeats region of P. albomaculatus consists of 53 tandem duplications (including one partial repeat), which is the largest number of tandem repeats among all the known insect mitochondrial genomes. Slipped-strand mispairing during replication is likely to have generated this novel pattern of tandem repeats. Comparative analysis of tRNA gene families in sequenced Pentatomomorpha and Lygaeoidea species shows that the pattern of nucleotide conservation is markedly higher on the J-strand. Phylogenetic reconstruction based on mitochondrial genomes suggests that Rhyparochromidae is not the sister group to all the remaining Lygaeoidea, and supports the monophyly of Lygaeoidea.
Epilepsy and Mitochondrial Dysfunction

Directory of Open Access Journals (Sweden)

Russell P. Saneto DO, PhD

2017-10-01

Full Text Available Epilepsy is a common manifestation of mitochondrial disease. In a large cohort of children and adolescents with mitochondrial disease (n = 180, over 48% of patients developed seizures. The majority (68% of patients were younger than 3 years and medically intractable (90%. The electroencephalographic pattern of multiregional epileptiform discharges over the left and right hemisphere with background slowing occurred in 62%. The epilepsy syndrome, infantile spasms, was seen in 17%. Polymerase γ mutations were the most common genetic etiology of seizures, representing Alpers-Huttenlocher syndrome (14%. The severity of disease in those patients with epilepsy was significant, as 13% of patients experienced early death. Simply the loss of energy production cannot explain the development of seizures or all patients with mitochondrial dysfunction would have epilepsy. Until the various aspects of mitochondrial physiology that are involved in proper brain development are understood, epilepsy and its treatment will remain unsatisfactory.
Bupivacaine versus lidocaine analgesia for neonatal circumcision

OpenAIRE

Stolik-Dollberg, Orit C; Dollberg, Shaul

2005-01-01

Abstract Background Analgesia for neonatal circumcision was recently advocated for every male infant, and its use is considered essential by the American Academy of Pediatrics. We compared the post-operative analgesic quality of bupivacaine to that of lidocaine for achieving dorsal penile nerve block (DPNB) when performing neonatal circumcision. Methods Data were obtained from 38 neonates following neonatal circumcision. The infants had received DPNB analgesia with either lidocaine or bupivac...
Parents' experiences with neonatal home care following initial care in the neonatal intensive care unit: a phenomenological hermeneutical interview study.

Science.gov (United States)

Dellenmark-Blom, Michaela; Wigert, Helena

2014-03-01

A descriptive study of parents' experiences with neonatal home care following initial care in the neonatal intensive care unit. As survival rates improve among premature and critically ill infants with an increased risk of morbidity, parents' responsibilities for neonatal care grow in scope and degree under the banner of family-centred care. Concurrent with medical advances, new questions arise about the role of parents and the experience of being provided neonatal care at home. An interview study with a phenomenological hermeneutic approach. Parents from a Swedish neonatal (n = 22) home care setting were extensively interviewed within one year of discharge. Data were collected during 2011-2012. The main theme of the findings is that parents experience neonatal home care as an inner emotional journey, from having a child to being a parent. This finding derives from three themes: the parents' experience of leaving the hospital milieu in favour of establishing independent parenthood, maturing as a parent and processing experiences during the period of neonatal intensive care. This study suggests that neonatal home care is experienced as a care structure adjusted to incorporate parents' needs following discharge from a neonatal intensive care unit. Neonatal home care appears to bridge the gap between hospital and home, supporting the family's adaptation to life in the home setting. Parents become empowered to be primary caregivers, having nurse consultants serving the needs of the whole family. Neonatal home care may therefore be understood as the implementation of family-centred care during the transition from NICU to home. © 2013 John Wiley & Sons Ltd.
The distribution of fatal risk in Ontario industries

International Nuclear Information System (INIS)

Davis, C.K.; Forbes, W.F.; Hayward, L.M.

1986-09-01

The purpose of this study was to estimate non-radiological risks of occupational fatalities in Ontario industries. The distribution of high-risk occupations was found to vary widely between the different industries for a number of reasons including the fact that insufficient data in some instances resulted in less than desirable reliability. However, in spite of various data limitations, a number of occupations had above average fatal risk rates in several industries, including Material Handlers and Related, N.E.C. (SOC-9319), Welders and Flame Cutters (SOC-8335), Truck Drivers (SOC-9175) and Mechanics and Repairmen, except Electrical (SOC-8589). The majority of occupations had rates below or close to the industry average; however, between 15% and 30% of the occupations in any given industry had fatal risk rates above the industry average. When the number of workers involved in different occupations was considered, between 18% and 40% of workers were in occupations with above average risk. Recommendations for future work are also provided
Gasoline Prices and Their Relationship to Rising Motorcycle Fatalities, 1990–2007

Science.gov (United States)

Stimpson, Jim P.; Hilsenrath, Peter E.

2009-01-01

Motor vehicle accidents are the leading cause of death among young adults. Although automobile fatalities have declined in recent years, motorcycle fatalities are rapidly increasing. The purpose of our research was to quantify the relationship between changing fuel prices and motorcycle fatalities. Our findings suggest that people increasingly rely on motorcycles to reduce their fuel costs in response to rising gasoline prices. We estimate that use of motorcycles and scooters instead of 4-wheeled vehicles results in over 1500 additional motorcycle fatalities annually for each dollar increase in gas prices. Motorcycle safety should receive more attention as a leading public health issue. PMID:19696374
An agent based architecture for high-risk neonate management at neonatal intensive care unit.

Science.gov (United States)

Malak, Jaleh Shoshtarian; Safdari, Reza; Zeraati, Hojjat; Nayeri, Fatemeh Sadat; Mohammadzadeh, Niloofar; Farajollah, Seide Sedighe Seied

2018-01-01

In recent years, the use of new tools and technologies has decreased the neonatal mortality rate. Despite the positive effect of using these technologies, the decisions are complex and uncertain in critical conditions when the neonate is preterm or has a low birth weight or malformations. There is a need to automate the high-risk neonate management process by creating real-time and more precise decision support tools. To create a collaborative and real-time environment to manage neonates with critical conditions at the NICU (Neonatal Intensive Care Unit) and to overcome high-risk neonate management weaknesses by applying a multi agent based analysis and design methodology as a new solution for NICU management. This study was a basic research for medical informatics method development that was carried out in 2017. The requirement analysis was done by reviewing articles on NICU Decision Support Systems. PubMed, Science Direct, and IEEE databases were searched. Only English articles published after 1990 were included; also, a needs assessment was done by reviewing the extracted features and current processes at the NICU environment where the research was conducted. We analyzed the requirements and identified the main system roles (agents) and interactions by a comparative study of existing NICU decision support systems. The Universal Multi Agent Platform (UMAP) was applied to implement a prototype of our multi agent based high-risk neonate management architecture. Local environment agents interacted inside a container and each container interacted with external resources, including other NICU systems and consultation centers. In the NICU container, the main identified agents were reception, monitoring, NICU registry, and outcome prediction, which interacted with human agents including nurses and physicians. Managing patients at the NICU units requires online data collection, real-time collaboration, and management of many components. Multi agent systems are applied as
Drug and Alcohol Involvement in Four Types of Fatal Crashes*

Science.gov (United States)

Romano, Eduardo; Voas, Robert B.

2011-01-01

Objective: The aim of this study was to explore the relationship of drunk and drugged driving to the occurrence of fatal crashes associated with speeding, failure to obey/yield, inattention, and seat belt nonuse. Method: We examined data for fatally injured drivers involved in single-vehicle crashes killed in states in which more than 79% of the drivers were tested for drugs other than alcohol and had a known result. Results: About 25% of the drivers tested positive for drugs, a figure almost double that estimated by the 2007 National Roadside Survey. Cannabinoids and stimulants each contributed to about 23% of the drug-positive results (6% among all fatally injured single-vehicle drivers). Stimulants more than cannabinoids were found to be associated with the four types of crashes under study. Some drugs showed a protective effect over the four crash types under study. Significant interactions between drugs and alcohol were observed. Stimulants contributed to the different types of fatal crashes irrespective of the levels of alcohol consumed by the drivers. Conclusions: This study provides further evidence of a link between drug consumption and fatal crashes. It also opens the door to some interesting and sometimes unexpected questions regarding the way drugs contribute to crashes, which we found varies depending on the type of crash considered, the class of drug, and the presence of alcohol. Research is also needed on drugs that could have a protective effect on the occurrence of fatal crashes. These findings could be highly relevant to the design of drug-related traffic laws and programs targeted at curbing drugged driving. PMID:21683038
Neonatal tetanus associated with skin infection.

Science.gov (United States)

Maharaj, M; Dungwa, N

2016-08-03

A 1-week-old infant was brought to a regional hospital with a history of recurrent seizures following lower abdominal septic skin infection. She was found to have neonatal tetanus, and a spatula test was positive. The tetanus infection was associated with a superficial skin infection, common in neonates. Treatment included sedatives (diazepam, chlorpromazine, phenobarbitone and morphine), muscle relaxants, antibiotics and ventilation in the neonatal intensive care unit. Intrathecal and intramuscular immunoglobulin were given, and the wound was treated. The infant recovered, with no seizures by the 16th day from admission, and was off the ventilator by the 18th day. This was shorter than the usual 3 - 4 weeks for neonates with tetanus at the hospital. The question arises whether tetanus immunisation should be considered in infants with skin infections, which frequently occur in the neonatal period.
Perinatal pharmacology: applications for neonatal neurology.

Science.gov (United States)

Smits, Anne; Allegaert, Karel

2011-11-01

The principles of clinical pharmacology also apply to neonates, but their characteristics warrant a tailored approach. We focus on aspects of both developmental pharmacokinetics (concentration/time relationship) and developmental pharmacodynamics (concentration/effect relationship) in neonates. We hereby aimed to link concepts used in clinical pharmacology with compound-specific observations (anti-epileptics, analgosedatives) in the field of neonatal neurology. Although in part anecdotal, we subsequently illustrate the relevance of developmental pharmacology in the field of neonatal neurology by a specific intervention (e.g. whole body cooling), specific clinical presentations (e.g. short and long term outcome following fetal exposure to antidepressive agents, the development of new biomarkers for fetal alcohol syndrome) and specific clinical needs (e.g. analgosedation in neonates, excitocytosis versus neuro-apoptosis/impaired synaptogenesis). Copyright © 2011 European Paediatric Neurology Society. Published by Elsevier Ltd. All rights reserved.
Cathelicidin Insufficiency in Patients with Fatal Leptospirosis.

Science.gov (United States)

Lindow, Janet C; Wunder, Elsio A; Popper, Stephen J; Min, Jin-Na; Mannam, Praveen; Srivastava, Anup; Yao, Yi; Hacker, Kathryn P; Raddassi, Khadir; Lee, Patty J; Montgomery, Ruth R; Shaw, Albert C; Hagan, Jose E; Araújo, Guilherme C; Nery, Nivison; Relman, David A; Kim, Charles C; Reis, Mitermayer G; Ko, Albert I

2016-11-01

Leptospirosis causes significant morbidity and mortality worldwide; however, the role of the host immune response in disease progression and high case fatality (>10-50%) is poorly understood. We conducted a multi-parameter investigation of patients with acute leptospirosis to identify mechanisms associated with case fatality. Whole blood transcriptional profiling of 16 hospitalized Brazilian patients with acute leptospirosis (13 survivors, 3 deceased) revealed fatal cases had lower expression of the antimicrobial peptide, cathelicidin, and chemokines, but more abundant pro-inflammatory cytokine receptors. In contrast, survivors generated strong adaptive immune signatures, including transcripts relevant to antigen presentation and immunoglobulin production. In an independent cohort (23 survivors, 22 deceased), fatal cases had higher bacterial loads (P = 0.0004) and lower anti-Leptospira antibody titers (P = 0.02) at the time of hospitalization, independent of the duration of illness. Low serum cathelicidin and RANTES levels during acute illness were independent risk factors for higher bacterial loads (P = 0.005) and death (P = 0.04), respectively. To investigate the mechanism of cathelicidin in patients surviving acute disease, we administered LL-37, the active peptide of cathelicidin, in a hamster model of lethal leptospirosis and found it significantly decreased bacterial loads and increased survival. Our findings indicate that the host immune response plays a central role in severe leptospirosis disease progression. While drawn from a limited study size, significant conclusions include that poor clinical outcomes are associated with high systemic bacterial loads, and a decreased antibody response. Furthermore, our data identified a key role for the antimicrobial peptide, cathelicidin, in mounting an effective bactericidal response against the pathogen, which represents a valuable new therapeutic approach for leptospirosis.
Cathelicidin Insufficiency in Patients with Fatal Leptospirosis.

Directory of Open Access Journals (Sweden)

Janet C Lindow

2016-11-01

Full Text Available Leptospirosis causes significant morbidity and mortality worldwide; however, the role of the host immune response in disease progression and high case fatality (>10-50% is poorly understood. We conducted a multi-parameter investigation of patients with acute leptospirosis to identify mechanisms associated with case fatality. Whole blood transcriptional profiling of 16 hospitalized Brazilian patients with acute leptospirosis (13 survivors, 3 deceased revealed fatal cases had lower expression of the antimicrobial peptide, cathelicidin, and chemokines, but more abundant pro-inflammatory cytokine receptors. In contrast, survivors generated strong adaptive immune signatures, including transcripts relevant to antigen presentation and immunoglobulin production. In an independent cohort (23 survivors, 22 deceased, fatal cases had higher bacterial loads (P = 0.0004 and lower anti-Leptospira antibody titers (P = 0.02 at the time of hospitalization, independent of the duration of illness. Low serum cathelicidin and RANTES levels during acute illness were independent risk factors for higher bacterial loads (P = 0.005 and death (P = 0.04, respectively. To investigate the mechanism of cathelicidin in patients surviving acute disease, we administered LL-37, the active peptide of cathelicidin, in a hamster model of lethal leptospirosis and found it significantly decreased bacterial loads and increased survival. Our findings indicate that the host immune response plays a central role in severe leptospirosis disease progression. While drawn from a limited study size, significant conclusions include that poor clinical outcomes are associated with high systemic bacterial loads, and a decreased antibody response. Furthermore, our data identified a key role for the antimicrobial peptide, cathelicidin, in mounting an effective bactericidal response against the pathogen, which represents a valuable new therapeutic approach for leptospirosis.
Aspirin increases mitochondrial fatty acid oxidation

International Nuclear Information System (INIS)

Uppala, Radha; Dudiak, Brianne; Beck, Megan E.; Bharathi, Sivakama S.; Zhang, Yuxun; Stolz, Donna B.; Goetzman, Eric S.

2017-01-01

The metabolic effects of salicylates are poorly understood. This study investigated the effects of aspirin on fatty acid oxidation. Aspirin increased mitochondrial long-chain fatty acid oxidation, but inhibited peroxisomal fatty acid oxidation, in two different cell lines. Aspirin increased mitochondrial protein acetylation and was found to be a stronger acetylating agent in vitro than acetyl-CoA. However, aspirin-induced acetylation did not alter the activity of fatty acid oxidation proteins, and knocking out the mitochondrial deacetylase SIRT3 did not affect the induction of long-chain fatty acid oxidation by aspirin. Aspirin did not change oxidation of medium-chain fatty acids, which can freely traverse the mitochondrial membrane. Together, these data indicate that aspirin does not directly alter mitochondrial matrix fatty acid oxidation enzymes, but most likely exerts its effects at the level of long-chain fatty acid transport into mitochondria. The drive on mitochondrial fatty acid oxidation may be a compensatory response to altered mitochondrial morphology and inhibited electron transport chain function, both of which were observed after 24 h incubation of cells with aspirin. These studies provide insight into the pathophysiology of Reye Syndrome, which is known to be triggered by aspirin ingestion in patients with fatty acid oxidation disorders. - Highlights: • Aspirin increases mitochondrial—but inhibits peroxisomal—fatty acid oxidation. • Aspirin acetylates mitochondrial proteins including fatty acid oxidation enzymes. • SIRT3 does not influence the effect of aspirin on fatty acid oxidation. • Increased fatty acid oxidation is likely due to altered mitochondrial morphology and respiration.
[Neonatal anatomical repair of transposition of great vessels associated with atrial septal defect. Apropos of 42 cases].

Science.gov (United States)

Planché, C; Serraf, A; Bruniaux, J; Lacour-Gayet, F; Bouchart, F; Losay, J; Touchot, A

1991-05-01

The good results obtained by anatomic correction of simple transposition of the great arteries (TGA) in the neonatal period have incited some surgical teams to widen the indications to neonates with TGA associated with ventricular septal defect (VSD). The classical management of these patients is a two stage procedure: banding of the pulmonary artery followed by detransposition, which carries a certain risk. Between January 1985 and June 1990, 42 neonates with TGA and VSD underwent a combined procedure consisting in anatomic correction of the TGA and closure of the VSD. The average age of these patients was 16 days, and the average weight was 3.3 kg. Ten patients had coarctation and 6 underwent a complete one stage correction by an anterior approach. The surgical technique consisted in closing the VSD from the right atrium in 20 patients, from the right ventricle in 11 patients and from the pulmonary artery in 11 patients, associated with detransposition of the great arteries and coronary artery reimplantation. Three children died in the preoperative period (7.1%). In two cases, death was related to malposition of the coronary artery. The third fatality was the result of haemorrhage. There has been one late death three years after surgery. Four patients have been reoperated for stenosis of the right ventricular outflow tract (1 case), recurrence of coarctation (2 cases) and stenosis of the superior vena cava (1 case) and have survived. All patients were followed up for an average period of 26.4 +/- 19 months. They are all in the NYHA Class I without treatment. One patient has mild aortic regurgitation.(ABSTRACT TRUNCATED AT 250 WORDS)
Fatal interstitial lung disease associated with icotinib.

Science.gov (United States)

Zhang, Jiexia; Zhan, Yangqing; Ouyang, Ming; Qin, Yinyin; Zhou, Chengzhi; Chen, Rongchang

2014-12-01

The most serious, and maybe fatal, yet rare, adverse reaction of gefitinib and erlotinib is drug-associated interstitial lung disease (ILD), which has been often described. However, it has been less well described for icotinib, a similar orally small-molecule tyrosine kinase inhibitor (TKI). The case of a 25-year-old female patient with stage IV lung adenocarcinoma who developed fatal ILD is reported here. She denied chemotherapy, and received palliative treatment with icotinib (125 mg po, three times daily) on March 1, 2013. One month after treatment initiation, the patient complained of continuous dry cough and rapid progressive dyspnea. Forty one days after icotinib treatment, icotinib associated ILD was suspected when the patient became increasingly dyspnoeic despite of treatment of pericardial effusion, left pleural effusion and lower respiratory tract infection, and X-ray computed tomography (CT) of chest revealed multiple effusion shadows and ground-glass opacities in bilateral lungs. Then, icotinib was discontinued and intravenous corticosteroid was started (methylprednisolone 40 mg once daily, about 1 mg per kilogram) respectively. Forty three days after icotinib treatment, the patient died of hypoxic respiratory failure. ILD should be considered as a rare, but often fatal side effect associated with icotinib treatment.
Geographical Accessibility to Obstetric and Neonatal Care and its Effect on Early Neonatal Mortality in Colombia, 2012-2014

Directory of Open Access Journals (Sweden)

Diego Fernando Rojas Gualdrón

2017-04-01

Full Text Available Introduction: The distribution of health resources influences early neonatal mortality, granting access to obstetric care which is a major public health problem. However, the geographical dimension of this influence has not been studied in Colombia. Objective: To describe the geographical accessibility to obstetric and neonatal care beds and its association with early neonatal mortality in Colombia and its municipalities. Method:An ecological study at municipal level was carried out. Ordinary least squares (OLS regression and a geographically weighted regression (GWR were used to explore statistical and spatial associations. Results: The municipalities in Colombia with Higher mortality tend to have lower geographical accessibility to obstetric and neonatal beds after controlling the fertility and economic characteristics of these municipalities. This association is significant only in municipalities of the west coast. The strength of this association decreases in inner municipalities. Discussion: The centralization of obstetric and neonatal beds in major municipalities around the central region leaves municipalities with high risk of mortality underserved. The decentralization of obstetric and neonatal healthcare resources is a mandatory issue in order to reduce geographical disparities in mortality and to improve neonatal survival, and a healthy beginning of life.
Mitochondrial DNA repair and aging

Energy Technology Data Exchange (ETDEWEB)

Mandavilli, Bhaskar S.; Santos, Janine H.; Van Houten, Bennett

2002-11-30

The mitochondrial electron transport chain plays an important role in energy production in aerobic organisms and is also a significant source of reactive oxygen species that damage DNA, RNA and proteins in the cell. Oxidative damage to the mitochondrial DNA is implicated in various degenerative diseases, cancer and aging. The importance of mitochondrial ROS in age-related degenerative diseases is further strengthened by studies using animal models, Caenorhabditis elegans, Drosophila and yeast. Research in the last several years shows that mitochondrial DNA is more susceptible to various carcinogens and ROS when compared to nuclear DNA. DNA damage in mammalian mitochondria is repaired by base excision repair (BER). Studies have shown that mitochondria contain all the enzymes required for BER. Mitochondrial DNA damage, if not repaired, leads to disruption of electron transport chain and production of more ROS. This vicious cycle of ROS production and mtDNA damage ultimately leads to energy depletion in the cell and apoptosis.
Mitochondrial DNA repair and aging

International Nuclear Information System (INIS)

Mandavilli, Bhaskar S.; Santos, Janine H.; Van Houten, Bennett

2002-01-01

The mitochondrial electron transport chain plays an important role in energy production in aerobic organisms and is also a significant source of reactive oxygen species that damage DNA, RNA and proteins in the cell. Oxidative damage to the mitochondrial DNA is implicated in various degenerative diseases, cancer and aging. The importance of mitochondrial ROS in age-related degenerative diseases is further strengthened by studies using animal models, Caenorhabditis elegans, Drosophila and yeast. Research in the last several years shows that mitochondrial DNA is more susceptible to various carcinogens and ROS when compared to nuclear DNA. DNA damage in mammalian mitochondria is repaired by base excision repair (BER). Studies have shown that mitochondria contain all the enzymes required for BER. Mitochondrial DNA damage, if not repaired, leads to disruption of electron transport chain and production of more ROS. This vicious cycle of ROS production and mtDNA damage ultimately leads to energy depletion in the cell and apoptosis
Clinical practice: neonatal resuscitation. A Dutch consensus

NARCIS (Netherlands)

van den Dungen, F.A.M.; van Veenendaal, M.B.; Mulder, A.L.M.

2010-01-01

The updated Dutch guidelines on Neonatal Resuscitation assimilate the latest evidence in neonatal resuscitation. Important changes with regard to the 2004 guidelines and controversial issues concerning neonatal resuscitation are reviewed, and recommendations for daily practice are provided and
Mitochondrial dysfunction and organophosphorus compounds

Energy Technology Data Exchange (ETDEWEB)

Karami-Mohajeri, Somayyeh [Department of Toxicology and Pharmacology, Faculty of Pharmacy, and Pharmaceutical Sciences Research Center, Tehran University of Medical Sciences, Tehran (Iran, Islamic Republic of); Department of Toxicology and Pharmacology, Faculty of Pharmacy, and Pharmaceutical Sciences Research Center, Kerman University of Medical Sciences, Kerman (Iran, Islamic Republic of); Abdollahi, Mohammad, E-mail: Mohammad.Abdollahi@UToronto.Ca [Department of Toxicology and Pharmacology, Faculty of Pharmacy, and Pharmaceutical Sciences Research Center, Tehran University of Medical Sciences, Tehran (Iran, Islamic Republic of)

2013-07-01

Organophosphorous (OPs) pesticides are the most widely used pesticides in the agriculture and home. However, many acute or chronic poisoning reports about OPs have been published in the recent years. Mitochondria as a site of cellular oxygen consumption and energy production can be a target for OPs poisoning as a non-cholinergic mechanism of toxicity of OPs. In the present review, we have reviewed and criticized all the evidences about the mitochondrial dysfunctions as a mechanism of toxicity of OPs. For this purpose, all biochemical, molecular, and morphological data were retrieved from various studies. Some toxicities of OPs are arisen from dysfunction of mitochondrial oxidative phosphorylation through alteration of complexes I, II, III, IV and V activities and disruption of mitochondrial membrane. Reductions of adenosine triphosphate (ATP) synthesis or induction of its hydrolysis can impair the cellular energy. The OPs disrupt cellular and mitochondrial antioxidant defense, reactive oxygen species generation, and calcium uptake and promote oxidative and genotoxic damage triggering cell death via cytochrome C released from mitochondria and consequent activation of caspases. The mitochondrial dysfunction induced by OPs can be restored by use of antioxidants such as vitamin E and C, alpha-tocopherol, electron donors, and through increasing the cytosolic ATP level. However, to elucidate many aspect of mitochondrial toxicity of Ops, further studies should be performed. - Highlights: • As a non-cholinergic mechanism of toxicity, mitochondria is a target for OPs. • OPs affect action of complexes I, II, III, IV and V in the mitochondria. • OPs reduce mitochondrial ATP. • OPs promote oxidative and genotoxic damage via release of cytochrome C from mitochondria. • OP-induced mitochondrial dysfunction can be restored by increasing the cytosolic ATP.

Mitochondrial dysfunction and organophosphorus compounds

International Nuclear Information System (INIS)

Karami-Mohajeri, Somayyeh; Abdollahi, Mohammad

2013-01-01

Organophosphorous (OPs) pesticides are the most widely used pesticides in the agriculture and home. However, many acute or chronic poisoning reports about OPs have been published in the recent years. Mitochondria as a site of cellular oxygen consumption and energy production can be a target for OPs poisoning as a non-cholinergic mechanism of toxicity of OPs. In the present review, we have reviewed and criticized all the evidences about the mitochondrial dysfunctions as a mechanism of toxicity of OPs. For this purpose, all biochemical, molecular, and morphological data were retrieved from various studies. Some toxicities of OPs are arisen from dysfunction of mitochondrial oxidative phosphorylation through alteration of complexes I, II, III, IV and V activities and disruption of mitochondrial membrane. Reductions of adenosine triphosphate (ATP) synthesis or induction of its hydrolysis can impair the cellular energy. The OPs disrupt cellular and mitochondrial antioxidant defense, reactive oxygen species generation, and calcium uptake and promote oxidative and genotoxic damage triggering cell death via cytochrome C released from mitochondria and consequent activation of caspases. The mitochondrial dysfunction induced by OPs can be restored by use of antioxidants such as vitamin E and C, alpha-tocopherol, electron donors, and through increasing the cytosolic ATP level. However, to elucidate many aspect of mitochondrial toxicity of Ops, further studies should be performed. - Highlights: • As a non-cholinergic mechanism of toxicity, mitochondria is a target for OPs. • OPs affect action of complexes I, II, III, IV and V in the mitochondria. • OPs reduce mitochondrial ATP. • OPs promote oxidative and genotoxic damage via release of cytochrome C from mitochondria. • OP-induced mitochondrial dysfunction can be restored by increasing the cytosolic ATP
New evidence concerning fatal crashes of passenger vehicles before and after adding antilock braking systems.

Science.gov (United States)

Farmer, C M

2001-05-01

Fatal crash rates for passenger cars and vans were compared for the last model year before four-wheel antilock brakes were introduced and the first model year for which antilock brakes were standard equipment. A prior study, based on fatal crash experience through 1995, reported that vehicle models with antilock brakes were more likely than identical but 1-year-earlier models to be involved in crashes fatal to their own occupants, but were less likely to be involved in crashes fatal to occupants of other vehicles. Overall, there was no significant effect of antilocks on the likelihood of fatal crashes. Similar analyses, based on fatal crash experience during 1996-98, yielded very different results. During 1996-98, vehicles with antilock brakes were again less likely than earlier models to be involved in crashes fatal to occupants of other vehicles, but they were no longer overinvolved in crashes fatal to their own occupants.
Mitochondrial dysfunction in obesity.

Science.gov (United States)

de Mello, Aline Haas; Costa, Ana Beatriz; Engel, Jéssica Della Giustina; Rezin, Gislaine Tezza

2018-01-01

Obesity leads to various changes in the body. Among them, the existing inflammatory process may lead to an increase in the production of reactive oxygen species (ROS) and cause oxidative stress. Oxidative stress, in turn, can trigger mitochondrial changes, which is called mitochondrial dysfunction. Moreover, excess nutrients supply (as it commonly is the case with obesity) can overwhelm the Krebs cycle and the mitochondrial respiratory chain, causing a mitochondrial dysfunction, and lead to a higher ROS formation. This increase in ROS production by the respiratory chain may also cause oxidative stress, which may exacerbate the inflammatory process in obesity. All these intracellular changes can lead to cellular apoptosis. These processes have been described in obesity as occurring mainly in peripheral tissues. However, some studies have already shown that obesity is also associated with changes in the central nervous system (CNS), with alterations in the blood-brain barrier (BBB) and in cerebral structures such as hypothalamus and hippocampus. In this sense, this review presents a general view about mitochondrial dysfunction in obesity, including related alterations, such as inflammation, oxidative stress, and apoptosis, and focusing on the whole organism, covering alterations in peripheral tissues, BBB, and CNS. Copyright © 2017 Elsevier Inc. All rights reserved.
The expanding phenotype of mitochondrial myopathy.

Science.gov (United States)

DiMauro, Salvatore; Gurgel-Giannetti, Juliana

2005-10-01

Our understanding of mitochondrial diseases (defined restrictively as defects in the mitochondrial respiratory chain) continues to progress apace. In this review we provide an update of information regarding disorders that predominantly or exclusively affect skeletal muscle. Most recently described mitochondrial myopathies are due to defects in nuclear DNA, including coenzyme Q10 deficiency, and mutations in genes that control mitochondrial DNA (mtDNA) abundance and structure such as POLG and TK2. Barth syndrome, an X-linked recessive mitochondrial myopathy/cardiopathy, is associated with altered lipid composition of the inner mitochondrial membrane, but a putative secondary impairment of the respiratory chain remains to be documented. Concerning the 'other genome', the role played by mutations in protein encoding genes of mtDNA in causing isolated myopathies has been confirmed. It has also been confirmed that mutations in tRNA genes of mtDNA can cause predominantly myopathic syndromes and - contrary to conventional wisdom - these mutations can be homoplasmic. Defects in the mitochondrial respiratory chain impair energy production and almost invariably involve skeletal muscle, causing exercise intolerance, myalgia, cramps, or fixed weakness, which often affects extraocular muscles and results in droopy eyelids (ptosis) and progressive external ophthalmoplegia.
Neonatal and infantile acne vulgaris: an update.

Science.gov (United States)

Serna-Tamayo, Cristian; Janniger, Camila K; Micali, Giuseppe; Schwartz, Robert A

2014-07-01

Acne may present in neonates, infants, and small children. Neonatal and infantile acne vulgaris are not considered to be rare. The presentation of acne in this patient population sometimes represents virilization and may portend later development of severe adolescent acne. Neonatal and infantile acne vulgaris must be distinguished from other cutaneous disorders seen in newborns and infants. Infantile acne tends to be more pleomorphic and inflammatory, thus requiring more vigorous therapy than neonatal acne.
Providing safe surgery for neonates in sub-Saharan Africa.

Science.gov (United States)

Ameh, Emmanuel A; Ameh, Nkeiruka

2003-07-01

Advances in neonatal intensive care, total parenteral nutrition and improvements in technology have led to a greatly improved outcome of neonatal surgery in developed countries. In many parts of sub-Saharan Africa, however, neonatal surgery continues to pose wide-ranging challenges. Delivery outside hospital, delayed referral, poor transportation, and lack of appropriate personnel and facilities continue to contribute to increased morbidity and mortality in neonates, particularly under emergency situations. Antenatal supervision and hospital delivery needs to be encouraged in our communities. Adequate attention needs to be paid to providing appropriate facilities for neonatal transport and support and training of appropriate staff for neonatal surgery. Neonates with surgical problems should be adequately resuscitated before referral where necessary but surgery should not be unduly delayed. Major neonatal surgery should as much as possible be performed by those trained to operate on neonates. Appropriate research and international collaboration is necessary to improve neonatal surgical care in the environment.
Impact of on-site cardiac catheterization on resource utilization and fatal and non-fatal outcomes after acute myocardial infarction

Directory of Open Access Journals (Sweden)

Richard Hugues

2006-11-01

Full Text Available Abstract Background Patterns of care for acute myocardial infarction (AMI strongly depend on the availability of on-site cardiac catheterization facilities. Although the management found at hospitals without on-site catheterization does not lead to increased mortality, little it known about its impact on resource utilization and non-fatal outcomes. Methods We identified all patients (n = 35,289 admitted with a first AMI in the province of Quebec between January 1, 1996 and March 31, 1999 using population-based administrative databases. Medical resource utilization and non-fatal and fatal outcomes were compared among patients admitted to hospitals with and without on-site cardiac catheterization facilities. Results Cardiac catheterization and PCI were more frequently performed among patients admitted to hospitals with catheterization facilities. However, non-invasive procedures were not used more frequently at hospitals without catheterization facilities. To the contrary, echocardiography [odds ratio (OR, 2.04; 95% confidence interval (CI, 1.93–2.16] and multi-gated acquisition imaging (OR, 1.24; 95% CI, 1.17–1.32 were used more frequently at hospitals with catheterization, and exercise treadmill testing (OR, 1.02; 95% CI, 0.91–1.15 and Sestamibi/Thallium imaging (OR, 0.93; 95% CI, 0.88–0.98 were used similarly at hospitals with and without catheterization. Use of anti-ischemic medications and frequency of emergency room and physician visits, were similar at both types of institutions. Readmission rates for AMI-related cardiac complications and mortality were also similar [adjusted hazard ratio, recurrent AMI: 1.02, 95% CI, 0.89–1.16; congestive heart failure: 1.02; 95% CI, 0.90–1.15; unstable angina: 0.93; 95% CI, 0.85–1.02; mortality: 0.99; 95% CI, 0.93–1.05]. Conclusion Although on-site availability of cardiac catheterization facilities is associated with greater use of invasive cardiac procedures, non-availability of
Individual and occupational factors related to fatal occupational injuries: a case-control study.

Science.gov (United States)

Villanueva, Vicent; Garcia, Ana M

2011-01-01

This study has been designed in order to identify factors increasing the risk of a fatal outcome when occupational accidents occur. The aim is to provide further evidence for the design and implementation of preventive measures in occupational settings. The Spanish Ministry of Labour registry of occupational injuries causing absence from work includes information on individual and occupational characteristics of injured workers and events. Registered fatal occupational injuries in 2001 (n=539) were compared to a sample of non-fatal injuries in the same year (n=3493). Risks for a fatal result of occupational injuries, adjusted by individual and occupational factors significantly associated, were obtained through logistic regression models. Compared to non-fatal injuries, fatal occupational injuries were mostly produced by trapping or by natural causes, mostly related to elevation and transport devices and power generators, and injured parts of body more frequently affected were head, multiple parts or internal organs. Adjusted analyses showed increased risk of fatality after an occupational injury for males (adjusted odds ratio aOR=10.92; 95%CI 4.80-24.84) and temporary workers (aOR=5.18; 95%CI 2.63-10.18), and the risk increased with age and with advancing hour of the work shift (p for trends accidents in agricultural or construction companies. These data can help to select and define priorities for programmes aimed to prevent fatal consequences of occupational injuries. Copyright © 2010 Elsevier Ltd. All rights reserved.
Review of fatal and severe cases of box jellyfish envenomation in Thailand.

Science.gov (United States)

Thaikruea, Lakkana; Siriariyaporn, Potjaman; Wutthanarungsan, Rochana; Smithsuwan, Punnarai

2015-03-01

The study aimed to describe severe and fatal cases of box jellyfish stings in Thailand. Medical records were reviewed and patients, relatives, health staffs, and witnesses were interviewed. The pictures of suspected box jellyfish were sent via e-mail to experts in the toxic jellyfish network for further identification. There were at least 8 cases of box jellyfish envenomation, with 4 fatal and 4 near-fatal cases. There were an equal number of male and female patients from 4 to 26 years of age. In each case, there was immediate severe pain followed by systemic reactions. Immediately after exposure to the sting, 7 victims collapsed experiencing severe pain at the tentacle marks, respiratory failure, and cardiac arrest. All patients had tentacle marks on their bodies. In none of the fatal cases was vinegar applied to the tentacle marks as first aid, but 3 out of the 4 near-fatal cases were treated with a vinegar application. © 2012 APJPH.
Trends and factors associated with dengue mortality and fatality in Brazil

Directory of Open Access Journals (Sweden)

Enny Santos Paixão

2015-08-01

Full Text Available AbstractINTRODUCTION:Studies that generate information that may reduce the dengue death risk are essential. This study analyzed time trends and risk factors for dengue mortality and fatality in Brazil from 2001 to 2011.METHODS:Time trends for dengue mortality and fatality rates were analyzed using simple linear regression. Associations between the dengue mortality and the case fatality rates and socioeconomic, demographic, and health care indicators at the municipality level were analyzed using negative binomial regression.RESULTS:The dengue hemorrhagic fever case fatality rate increased in Brazil from 2001 to 2011 (β=0.67; p=0.036, in patients aged 0-14 years (β=0.48; p=0.030 and in those aged ≥15 years (β=1.1; p<0.01. Factors associated with the dengue case fatality rate were the average income per capita (MRR=0.99; p=0.038 and the number of basic health units per population (MRR=0.89; p<0.001. Mortality rates increased from 2001 to 2011 (β=0.350; p=0.002.Factors associated with mortality were inequality (RR=1.02; p=0.001 high income per capita (MRR=0.99; p=0.005, and higher proportions of populations living in urban areas (MRR=1.01; p<0.001.CONCLUSIONS:The increases in the dengue mortality and case fatality rates and the associated socioeconomic and health care factors, suggest the need for structural and intersectoral investments to improve living conditions and to sustainably reduce these outcomes.
Neonatal pressure ulcers: prevention and treatment

Directory of Open Access Journals (Sweden)

García-Molina P

2017-09-01

Full Text Available Pablo García-Molina,1,2 Alba Alfaro-López,1 Sara María García-Rodríguez,1 Celia Brotons-Payá,1 Mari Carmen Rodríguez-Dolz,1,2 Evelin Balaguer-López1,2 1Department of Nursing, University of Valencia, 2Research Group of Pediatric Nutrition, INCLIVA Foundation, Valencia, Spain Abstract: Health professionals should be prepared to respond to the needs of hospitalized neonates. The health team must consider multiple situations, where the neonate is at risk of having an adverse effect. One of the main interventions that health professionals must practice when interacting with hospitalized newborns is skin care. Neonates often suffer from diaper rash or intravenous drugs extravasation. Recently, hospitalized neonates and especially those in an unstable clinical situation are also at a risk of developing pressure ulcers. The presence of a pressure ulcer in a neonate can lead to serious problems to survival (eg, sepsis, clinical instability. This is the reason why, with this literature review, we attempt to answer questions from health professionals caring for neonates about the prevention and treatment of pressure ulcers. Keywords: infant, pressure ulcer, treatment, prevention, wound, assessment
Neurodegenerative and Fatiguing Illnesses, Infections and Mitochondrial Dysfunction: Use of Natural Supplements to Improve Mitochondrial Function

Directory of Open Access Journals (Sweden)

Garth L. Nicolson

2014-01-01

Full Text Available Background: Many chronic diseases and illnesses are associated with one or more chronic infections, dysfunction of mitochondria and reduced production of ATP. This results in fatigue and other symptoms that occur in most if not all chronic conditions and diseases. Methods: This is a review of the published literature on chronic infections in neurodegenerative diseases and fatiguing illnesses that are also typified by mitochondrial dysfunction. This contribution also reviews the use of natural supplements to enhance mitochondrial function and reduce the effects of chronic infections to improve overall function in various chronic illnesses. Results: Mitochondrial function can be enhanced by the use of various natural supplements, notably Lipid Replacement Therapy (LRT using glyerolphospholipids and other mitochondrial supplements. In various chronic illnesses that are characterized by the presence of chronic infections, such as intracellular bacteria (Mycoplasma, Borrelia, Chlamydia and other infections and viruses, LRT has proven useful in multiple clinical trials. For example, in clinical studies on chronic fatigue syndrome, fibromyalgia syndrome and other chronic fatiguing illnesses where a large majority of patients have chronic infections, LRT significantly reduced fatigue by 35-43% in different clinical trials and increased mitochondrial function. In clinical trials on patients with multiple intracellular bacterial infections and intractable fatigue LRT plus other mitochondrial supplements significantly decreased fatigue and improved mood and cognition. Conclusions: LRT formulations designed to improve mitochondrial function appear to be useful as non-toxic dietary supplements for reducing fatigue and restoring mitochondrial and other cellular membrane functions in patients with chronic illnesses and multiple chronic infections.
Imaging approach to persistent neonatal jaundice

International Nuclear Information System (INIS)

Kirks, D.; Coleman, R.E.; Filston, H.C.; Rosenberg, E.R.; Merten, D.F.

1984-01-01

Fifteen patients with persistent neonatal jaundice were evaluated by sonography and radionuclide scintigraphy. The sonographic features of both neonatal hepatitis and biliary atresia are nonspecific. Hepatobiliary scintigraphy after phenobarbital pretreatment in patients with neonatal hepatitis demonstrates normal hepatic extraction and delayed tracer excretion into the gastrointestinal tract. If there is neonatal hepatitis with severe hepatocellular damage, the hepatic extraction of tracer activity is decreased and excretion may be delayed or absent. Patients under 3 months of age with biliary atresia have normal hepatic extraction of tracer with no excretion into the gastrointestinal tract. Sonography in patients with a choledochal cyst shows a cystic mass in the porta hepatis with associated bile-duct dilatation. Hepatobiliary scintigraphy confirms that the choledochal cyst communicates with the biliary system. Initial sonography demonstrates hepatobiliary anatomy; subsequent phenobarbital-enhanced radionuclide scintigraphy determines hepatobiliary function. An expedient diagnostic approach is recommended for the evaluation of persistent neonatal jaundice
A PEARL Study Analysis of National Neonatal, Early Neonatal, Late Neonatal, and Corrected Neonatal Mortality Rates in the State of Qatar during 2011: A Comparison with World Health Statistics 2011 and Qatar's Historic Data over a Period of 36 Years (1975-2011).

Science.gov (United States)

Rahman, Sajjad; Al Rifai, Hilal; El Ansari, Walid; Nimeri, Nuha; El Tinay, Sarrah; Salameh, Khalil; Abbas, Tariq; Jarir, Rawia A; Said, Nawal; Taha, Samer

2012-10-01

To prospectively ascertain Qatar's national Neonatal Mortality Rate (NMR), Early Neonatal Mortality Rate (ENMR), and Late Neonatal Mortality Rate (LNMR) during 2011, compare it with recent data from high-income countries, and analyze trends in Qatar's NMR's between 1975 and 2011 using historic data. A National prospective cohort-study. National data on live births and neonatal mortality was collected from all public and private maternity facilities in Qatar (1(st) January-December 31(st) 2011) and compared with historical neonatal mortality data (1975-2010) ascertained from the database of maternity and neonatal units of Women's Hospital and annual reports of Hamad Medical Corporation. For inter country comparison, country data of 2009 was extracted from World Health Statistics 2011 (WHO) and the European Perinatal Health report (2008). A total of 20583 live births were recorded during the study period. Qatar's national NMR during 2011 was 4.95, ENMR 2.7, LNMR 2.2, and cNMR 3.33. Between 1975 and 2011, Qatar's population increased by 10-fold, number of deliveries by 7.2 folds while relative risk of NMR decreased by 87% (RR 0.13, 95% CI 0.10-0.18, P<0.001), ENMR by 91% (RR 0.09, 95% CI 0.06-0.12, P<0.001) and LNMR by 58% (RR 0.42, 95% CI 0.23-0.74, P=0.002). The comparable ranges of neonatal mortality rates from selected high-income West European countries are: NMR: 2-5.7, ENMR 1.5-3.8, and LNMR 0.5-1.9. The neonatal survival in the State of Qatar has significantly improved between 1975 and 2011. The improvement has been more marked in ENMR than LNMR. Qatar's current neonatal mortality rates are comparable to most high-income West European countries. An in-depth research to assess the correlates and determinants of neonatal mortality in Qatar is indicated.
Neonatal orbital abscess

Directory of Open Access Journals (Sweden)

Khalil M Al-Salem

2014-01-01

Full Text Available Orbital complications due to ethmoiditis are rare in neonates. A case of orbital abscess due to acute ethmoiditis in a 28-day-old girl is presented. A Successful outcome was achieved following antimicrobial therapy alone; spontaneous drainage of the abscess occurred from the lower lid without the need for surgery. From this case report, we intend to emphasize on eyelid retraction as a sign of neonatal orbital abscess, and to review all the available literature of similar cases.
Mitochondrial DNA: A Blind Spot in Neuroepigenetics.

Science.gov (United States)

Manev, Hari; Dzitoyeva, Svetlana; Chen, Hu

2012-04-01

Neuroepigenetics, which includes nuclear DNA modifications such as 5-methylcytosine and 5-hydoxymethylcytosine and modifications of nuclear proteins such as histones, is emerging as the leading field in molecular neuroscience. Historically, a functional role for epigenetic mechanisms, including in neuroepigenetics, has been sought in the area of the regulation of nuclear transcription. However, one important compartment of mammalian cell DNA, different from nuclear but equally important for physiological and pathological processes (including in the brain), mitochondrial DNA has for the most part not had a systematic epigenetic characterization. The importance of mitochondria and mitochondrial DNA (particularly its mutations) in central nervous system physiology and pathology has long been recognized. Only recently have mechanisms of mitochondrial DNA methylation and hydroxymethylation, including the discovery of mitochondrial DNA-methyltransferases and the presence and the functionality of 5-methylcytosine and 5-hydroxymethylcytosine in mitochondrial DNA (e.g., in modifying the transcription of mitochondrial genome), been unequivocally recognized as a part of mammalian mitochondrial physiology. Here we summarize for the first time evidence supporting the existence of these mechanisms and we propose the term "mitochondrial epigenetics" to be used when referring to them. Currently, neuroepigenetics does not include mitochondrial epigenetics - a gap that we expect to close in the near future.
Abdominal surgery in neonatal foals.

Science.gov (United States)

Bryant, James E; Gaughan, Earl M

2005-08-01

Abdominal surgery in foals under 30 days old has become more common with improved neonatal care. Early recognition of a foal at risk and better nursing care have increased the survival rates of foals that require neonatal care. The success of improved neonatal care also has increased the need for accurate diagnosis and treatment of gastrointestinal, umbilical, and bladder disorders in these foals. This chapter focuses on the early and accurate diagnosis of specific disorders that require abdominal exploratory surgery and the specific treatment considerations and prognosis for these disorders.
Hypobaric Hypoxia Imbalances Mitochondrial Dynamics in Rat Brain Hippocampus

Directory of Open Access Journals (Sweden)

Khushbu Jain

2015-01-01

Full Text Available Brain is predominantly susceptible to oxidative stress and mitochondrial dysfunction during hypobaric hypoxia, and therefore undergoes neurodegeneration due to energy crisis. Evidences illustrate a high degree of association for mitochondrial fusion/fission imbalance and mitochondrial dysfunction. Mitochondrial fusion/fission is a recently reported dynamic mechanism which frequently occurs among cellular mitochondrial network. Hence, the study investigated the temporal alteration and involvement of abnormal mitochondrial dynamics (fusion/fission along with disturbed mitochondrial functionality during chronic exposure to hypobaric hypoxia (HH. The Sprague-Dawley rats were exposed to simulated high altitude equivalent to 25000 ft for 3, 7, 14, 21, and 28 days. Mitochondrial morphology, distribution within neurons, enzyme activity of respiratory complexes, Δψm, ADP: ATP, and expression of fission/fusion key proteins were determined. Results demonstrated HH induced alteration in mitochondrial morphology by damaged, small mitochondria observed in neurons with disturbance of mitochondrial functionality and reduced mitochondrial density in neuronal processes manifested by excessive mitochondrial fragmentation (fission and decreased mitochondrial fusion as compared to unexposed rat brain hippocampus. The study suggested that imbalance in mitochondrial dynamics is one of the noteworthy mechanisms occurring in hippocampal neurons during HH insult.
The effectiveness of automatic belts in reducing fatality rates in Toyota Cressidas.

Science.gov (United States)

Nash, C E

1989-12-01

Toyota Cressidas have had motor driven automatic belts since 1981. Their observed use rates have been consistently close to 100%. This paper compares fatality rates in Toyota Cressidas with those in the similar Nissan Maximas (which are equipped with three-point manual belts) using the latest data from the Fatal Accident Reporting System. After making adjustments for differences in the average ages of front seat occupants of the two fleets, the Toyotas have a fatality rate that is about three-quarters that of the Nissans. From this, the fatality-reducing effectiveness for the Toyota automatic belts is estimated to be 40% with an uncertainty of +/- 8%. This effectiveness estimate is consistent with earlier estimates of automatic belt effectiveness.
Understanding fatal older road user crash circumstances and risk factors.

Science.gov (United States)

Koppel, Sjaan; Bugeja, Lyndal; Smith, Daisy; Lamb, Ashne; Dwyer, Jeremy; Fitzharris, Michael; Newstead, Stuart; D'Elia, Angelo; Charlton, Judith

2018-02-28

This study used medicolegal data to investigate fatal older road user (ORU) crash circumstances and risk factors relating to four key components of the Safe System approach (e.g., roads and roadsides, vehicles, road users, and speeds) to identify areas of priority for targeted prevention activity. The Coroners Court of Victoria's Surveillance Database was searched to identify coronial records with at least one deceased ORU in the state of Victoria, Australia, for 2013-2014. Information relating to the ORU, crash characteristics and circumstances, and risk factors was extracted and analyzed. The average rate of fatal ORU crashes per 100,000 population was 8.1 (95% confidence interval [CI] 6.0-10.2), which was more than double the average rate of fatal middle-aged road user crashes (3.6, 95% CI 2.5-4.6). There was a significant relationship between age group and deceased road user type (χ 2 (15, N = 226) = 3.56, p road" (87.0%), on roads that were paved (94.2%), dry (74.2%), and had light traffic volume (38.3%). Road user error was identified by the police and/or coroner for the majority of fatal ORU crashes (57.9%), with a significant proportion of deceased ORU deemed to have "misjudged" (40.9%) or "failed to yield" (37.9%). Road user error was the most significant risk factor identified in fatal ORU crashes, which suggests that there is a limited capacity of the Victorian road system to fully accommodate road user errors. Initiatives related to safer roads and roadsides, vehicles, and speed zones, as well as behavioral approaches, are key areas of priority for targeted activity to prevent fatal older road user crashes in the future.

Pharyngitis – fatal infectious disease or medical error?

Directory of Open Access Journals (Sweden)

Marta Rorat

2015-08-01

Full Text Available Reporting on adverse events is essential to create a culture of safety, which focuses on protecting doctors and patients from medical errors. We present a fatal case of Streptococcus C pharyngitis in a 56-year-old man. The clinical course and the results of additional diagnostics and autopsy showed that sepsis followed by multiple organ failure was the ultimate cause of death. The clinical course appeared fatal due to a chain of adverse events, including errors made by the physicians caring for the patient for 10 days.
The study of thrombocytopenia in sick neonates

International Nuclear Information System (INIS)

Aman, I.; Hassan, K.A.; Ahmad, T.M.

2004-01-01

Objective: To determine the number of cases and manifestations of thrombocytopenia in sick neonates. Subjects and Methods: A total of 365 neonates from 0-28 days of age admitted with different clinical problems irrespective of birth weight and gestational age were evaluated for thrombocytopenia. These neonates were categorized into five different groups (A-E), which were of neonatal infections, asphyxia neonatorum, preterm and smallness for gestational age, jaundice and miscellaneous respectively. Results: Out of 365 cases, 88 were found to have thrombocytopenia (platelet counts < 150,000 per mm/sup 3/) which was 24.1% of the total. In group A (neonatal infections), out of 152 neonates, 62 had low platelet counts (40.78%). In group B (neonatal asphyxia), out of 90 only 11 had thrombocytopenia (12.2%). In group C (preterm and small for gestational age), out of 60 cases only 9 had thrombocytopenia. In group D (jaundice), all 33 cases had normal platelet counts. In group E (miscellaneous), out of 30 cases only 6 had thrombocytopenia. The common manifestations in thrombocytopenic babies were petechiae and bruises followed by gastrointestinal hemorrhages. The percentage of manifest thrombocytopenia cases was 56.8% and of occult thrombocytopenia 43.1 %. Conclusion: The leading causes of thrombocytopenia in sick neonates are infections, asphyxia, complicated pre- maturity and smallness for gestational age. Apart from the platelet counts the bleeding mainfestations also depend upon the underlying ailments. (author)
Estimation of adult and neonatal RBC lifespans in anemic neonates using RBCs labeled at several discrete biotin densities.

Science.gov (United States)

Kuruvilla, Denison J; Widness, John A; Nalbant, Demet; Schmidt, Robert L; Mock, Donald M; An, Guohua; Veng-Pedersen, Peter

2017-06-01

Prior conclusions that autologous neonatal red blood cells (RBC) have substantially shorter lifespans than allogeneic adult RBCs were not based on direct comparison of autologous neonatal vs. allogeneic adult RBCs performed concurrently in the same infant. Biotin labeling of autologous neonatal RBCs and allogeneic adult donor RBCs permits concurrent direct comparison of autologous vs. allogeneic RBC lifespan. RBCs from 15 allogeneic adult donors and from 15 very-low-birth-weight (VLBW) neonates were labeled at separate biotin densities and transfused simultaneously into the 15 neonates. Two mathematical models that account for the RBC differences were employed to estimate lifespans for the two RBC populations. Mean ± SD lifespan for adult allogeneic RBC was 70.1 ± 19.1 d, which is substantially shorter than the 120 d lifespan of both autologous and adult allogeneic RBC in healthy adults. Mean ± SD lifespan for neonatal RBC was 54.2 ± 11.3 d, which is only about 30% shorter than that of the adult allogeneic RBCs. This study provides evidence that extrinsic environmental factors primarily determine RBC survival (e.g., small bore of the capillaries of neonates, rate of oxygenation/deoxygenation cycles) rather than factors intrinsic to RBC.
Mitochondrial Dysfunction in Chemotherapy-Induced Peripheral Neuropathy (CIPN

Directory of Open Access Journals (Sweden)

Annalisa Canta

2015-06-01

Full Text Available The mitochondrial dysfunction has a critical role in several disorders including chemotherapy-induced peripheral neuropathies (CIPN. This is due to a related dysregulation of pathways involving calcium signalling, reactive oxygen species and apoptosis. Vincristine is able to affect calcium movement through the Dorsal Root Ganglia (DRG neuronal mitochondrial membrane, altering its homeostasis and leading to abnormal neuronal excitability. Paclitaxel induces the opening of the mitochondrial permeability transition pore in axons followed by mitochondrial membrane potential loss, increased reactive oxygen species generation, ATP level reduction, calcium release and mitochondrial swelling. Cisplatin and oxaliplatin form adducts with mitochondrial DNA producing inhibition of replication, disruption of transcription and morphological abnormalities within mitochondria in DRG neurons, leading to a gradual energy failure. Bortezomib is able to modify mitochondrial calcium homeostasis and mitochondrial respiratory chain. Moreover, the expression of a certain number of genes, including those controlling mitochondrial functions, was altered in patients with bortezomib-induced peripheral neuropathy.
Mitochondrial Dysfunction in Chemotherapy-Induced Peripheral Neuropathy (CIPN)

Science.gov (United States)

Canta, Annalisa; Pozzi, Eleonora; Carozzi, Valentina Alda

2015-01-01

The mitochondrial dysfunction has a critical role in several disorders including chemotherapy-induced peripheral neuropathies (CIPN). This is due to a related dysregulation of pathways involving calcium signalling, reactive oxygen species and apoptosis. Vincristine is able to affect calcium movement through the Dorsal Root Ganglia (DRG) neuronal mitochondrial membrane, altering its homeostasis and leading to abnormal neuronal excitability. Paclitaxel induces the opening of the mitochondrial permeability transition pore in axons followed by mitochondrial membrane potential loss, increased reactive oxygen species generation, ATP level reduction, calcium release and mitochondrial swelling. Cisplatin and oxaliplatin form adducts with mitochondrial DNA producing inhibition of replication, disruption of transcription and morphological abnormalities within mitochondria in DRG neurons, leading to a gradual energy failure. Bortezomib is able to modify mitochondrial calcium homeostasis and mitochondrial respiratory chain. Moreover, the expression of a certain number of genes, including those controlling mitochondrial functions, was altered in patients with bortezomib-induced peripheral neuropathy. PMID:29056658
Fatal motorcycle crashes: a growing public health problem in Cambodia.

Science.gov (United States)

Roehler, Douglas R; Ear, Chariya; Parker, Erin M; Sem, Panhavuth; Ballesteros, Michael F

2015-01-01

This study examines the risk characteristics of fatal motorcycle crashes in Cambodia over a 5-year period (2007-2011). Secondary data analyses were conducted using the Cambodia Road Crash and Victim Information System, the only comprehensive and integrated road crash surveillance system in the country. Researchers from the Centers for Disease Control and Prevention and Handicap International found that (1) males are dying in motorcycle crashes roughly seven times more frequently than females; (2) motorcyclist fatalities increased by about 30% from 2007 to 2011; (3) the motorcyclist death rates per 100,000 population increased from 7.4 to 8.7 deaths from 2007 to 2011; and (4) speed-related crashes and not wearing motorcycle helmet were commonly reported for motorcyclist fatalities at approximately 50% and over 80% through the study years, respectively. Additionally, this study highlights that Cambodia has the highest motorcycle death rate in South-East Asia, far surpassing Thailand, Malaysia, and Myanmar. By recognising the patterns of fatal motorcycle crashes in Cambodia, local road-safety champions and stakeholders can design targeted interventions and preventative measures to improve road safety among motorcyclists.
Lipophilic triphenylphosphonium cations inhibit mitochondrial electron transport chain and induce mitochondrial proton leak.

Directory of Open Access Journals (Sweden)

Jan Trnka

Full Text Available The lipophilic positively charged moiety of triphenylphosphonium (TPP+ has been used to target a range of biologically active compounds including antioxidants, spin-traps and other probes into mitochondria. The moiety itself, while often considered biologically inert, appears to influence mitochondrial metabolism.We used the Seahorse XF flux analyzer to measure the effect of a range of alkylTPP+ on cellular respiration and further analyzed their effect on mitochondrial membrane potential and the activity of respiratory complexes. We found that the ability of alkylTPP+ to inhibit the respiratory chain and decrease the mitochondrial membrane potential increases with the length of the alkyl chain suggesting that hydrophobicity is an important determinant of toxicity.More hydrophobic TPP+ derivatives can be expected to have a negative impact on mitochondrial membrane potential and respiratory chain activity in addition to the effect of the biologically active moiety attached to them. Using shorter linker chains or adding hydrophilic functional groups may provide a means to decrease this negative effect.
Mutation in the novel nuclear-encoded mitochondrial protein CHCHD10 in a family with autosomal dominant mitochondrial myopathy.

Science.gov (United States)

Ajroud-Driss, Senda; Fecto, Faisal; Ajroud, Kaouther; Lalani, Irfan; Calvo, Sarah E; Mootha, Vamsi K; Deng, Han-Xiang; Siddique, Nailah; Tahmoush, Albert J; Heiman-Patterson, Terry D; Siddique, Teepu

2015-01-01

Mitochondrial myopathies belong to a larger group of systemic diseases caused by morphological or biochemical abnormalities of mitochondria. Mitochondrial disorders can be caused by mutations in either the mitochondrial or nuclear genome. Only 5% of all mitochondrial disorders are autosomal dominant. We analyzed DNA from members of the previously reported Puerto Rican kindred with an autosomal dominant mitochondrial myopathy (Heimann-Patterson et al. 1997). Linkage analysis suggested a putative locus on the pericentric region of the long arm of chromosome 22 (22q11). Using the tools of integrative genomics, we established chromosome 22 open reading frame 16 (C22orf16) (later designated as CHCHD10) as the only high-scoring mitochondrial candidate gene in our minimal candidate region. Sequence analysis revealed a double-missense mutation (R15S and G58R) in cis in CHCHD10 which encodes a coiled coil-helix-coiled coil-helix protein of unknown function. These two mutations completely co-segregated with the disease phenotype and were absent in 1,481 Caucasian and 80 Hispanic (including 32 Puerto Rican) controls. Expression profiling showed that CHCHD10 is enriched in skeletal muscle. Mitochondrial localization of the CHCHD10 protein was confirmed using immunofluorescence in cells expressing either wild-type or mutant CHCHD10. We found that the expression of the G58R, but not the R15S, mutation induced mitochondrial fragmentation. Our findings identify a novel gene causing mitochondrial myopathy, thereby expanding the spectrum of mitochondrial myopathies caused by nuclear genes. Our findings also suggest a role for CHCHD10 in the morphologic remodeling of the mitochondria.
Reanimación neonatal: actualización Neonatal resuscitation: up-date

OpenAIRE

E. Burón Martínez; A. Pino Vázquez

2009-01-01

Las últimas recomendaciones en reanimación neonatal fueron publicadas en el año 2005 por el ERC (European Resuscitation Council), el grupo ILCOR (International Liaison Committee on Resuscitation) y la AHA (American Heart Association). En nuestro país estas normas fueron difundidas por el grupo de RCP Neonatal de la Sociedad Española de Neonatología, introduciendo algunas adaptaciones y ampliando algunos capítulos como la reanimación del recién naci...
Contribution of liver mitochondrial membrane-bound glutathione transferase to mitochondrial permeability transition pores

International Nuclear Information System (INIS)

Hossain, Quazi Sohel; Ulziikhishig, Enkhbaatar; Lee, Kang Kwang; Yamamoto, Hideyuki; Aniya, Yoko

2009-01-01

We recently reported that the glutathione transferase in rat liver mitochondrial membranes (mtMGST1) is activated by S-glutathionylation and the activated mtMGST1 contributes to the mitochondrial permeability transition (MPT) pore and cytochrome c release from mitochondria [Lee, K.K., Shimoji, M., Quazi, S.H., Sunakawa, H., Aniya, Y., 2008. Novel function of glutathione transferase in rat liver mitochondrial membrane: role for cytochrome c release from mitochondria. Toxcol. Appl. Pharmacol. 232, 109-118]. In the present study we investigated the effect of reactive oxygen species (ROS), generator gallic acid (GA) and GST inhibitors on mtMGST1 and the MPT. When rat liver mitochondria were incubated with GA, mtMGST1 activity was increased to about 3 fold and the increase was inhibited with antioxidant enzymes and singlet oxygen quenchers including 1,4-diazabicyclo [2,2,2] octane (DABCO). GA-mediated mtMGST1 activation was prevented by GST inhibitors such as tannic acid, hematin, and cibacron blue and also by cyclosporin A (CsA). In addition, GA induced the mitochondrial swelling which was also inhibited by GST inhibitors, but not by MPT inhibitors CsA, ADP, and bongkrekic acid. GA also released cytochrome c from the mitochondria which was inhibited completely by DABCO, moderately by GST inhibitors, and somewhat by CsA. Ca 2+ -mediated mitochondrial swelling and cytochrome c release were inhibited by MPT inhibitors but not by GST inhibitors. When the outer mitochondrial membrane was isolated after treatment of mitochondria with GA, mtMGST1 activity was markedly increased and oligomer/aggregate of mtMGST1 was observed. These results indicate that mtMGST1 in the outer mitochondrial membrane is activated by GA through thiol oxidation leading to protein oligomerization/aggregation, which may contribute to the formation of ROS-mediated, CsA-insensitive MPT pore, suggesting a novel mechanism for regulation of the MPT by mtMGST1
Pentraxin 3 concentrations of the mothers with preterm premature rupture of membranes and their neonates, and early neonatal outcome.

Science.gov (United States)

Akin, Mustafa Ali; Gunes, Tamer; Coban, Dilek; Ozgun, Mahmut Tuncay; Akgun, Hulya; Kurtoglu, Selim

2015-07-01

Pentraxin 3 (PTX3) is an acute phase reactant which has been used to detect intra-amniotic infections (IAI) in pregnancy, but the prognostic value of PTX3 concentrations on neonates has not been studied. We aimed to investigate the relationship between maternal PTX3-neonatal PTX3 concentrations and early neonatal outcome. The mothers diagnosed with preterm prelabor rupture of membranes (PPROM) (n = 28) and their preterm infants (n = 28) were included in the study. PTX3 concentrations were studied in plasma in the maternal peripheral blood and umbilical/peripheral vein in the neonates. The relationship between the mPTX3-nPTX3 concentrations and neonatal outcome were investigated using non-parametric tests and binary logistic regression analysis. The mean mPTX3 concentration was 10.35 ± 7.82 μg/L. Ten (35.7%) of all mothers were within the normal range and 18 (64.3%) in high percentile (≥ 97.5 percentile). There was no relation between mPTX3 concentrations and clinical or histologic chorioamnionitis, latency of PPROM, and early neonatal outcome. Mean nPTX3 concentrations was 9.18 ± 7.83 μg/L and high nPTX3 concentrations were detected in five (17.8%) neonates. nPTX3 concentrations were inversely correlated with gestational age and correlated with rate of intraventricular hemorrhage (IVH) and mortality. Neonates with high nPTX3 concentrations also have lowered APGAR scores, increased rate of respiratory distress syndrome, clinical sepsis, IVH, necrotizing enterocolitis and prolonged NICU stay. High PTX3 concentrations of the newborns are associated with some worsened early neonatal outcome including lower gestational age at delivery, increased rate of IVH and mortality. Maternal PTX3 concentrations are not an adequate marker in defining clinical or histologic chorioamnionitis and early neonatal outcome.
Fatal occupational accidents in Danish fishing vessels 1989-2005

DEFF Research Database (Denmark)

Laursen, Lise Hedegaard; Hansen, Henrik L; Jensen, Olaf

2008-01-01

training for all fishermen and improved safety measures are needed, especially in the underscored areas of sea disasters concerning small vessels and occupational accidents on big vessels. Better registration of time at risk for fishermen is needed to validate the effect of the safety measures......./capsizing due to stability changes in rough weather and collisions; 39 fatal occupational accidents mainly occurred on the larger inspection obligated trawlers during fishing. In the remaining 14 other fatal accidents, the main causal factors were difficult embarking/disembarking conditions by darkness...... in foreign ports and alcohol intoxication. In the period 1995-2005, the overall incidence rate was 10 per 10,000 fishermen per year with no down-going trend during that period. The fatal accident rates are still too high, despite the efforts to reduce the risk. Increased focus on regular and repeated safety...
Evolution of gastropod mitochondrial genome arrangements

Directory of Open Access Journals (Sweden)

Zardoya Rafael

2008-02-01

Full Text Available Abstract Background Gastropod mitochondrial genomes exhibit an unusually great variety of gene orders compared to other metazoan mitochondrial genome such as e.g those of vertebrates. Hence, gastropod mitochondrial genomes constitute a good model system to study patterns, rates, and mechanisms of mitochondrial genome rearrangement. However, this kind of evolutionary comparative analysis requires a robust phylogenetic framework of the group under study, which has been elusive so far for gastropods in spite of the efforts carried out during the last two decades. Here, we report the complete nucleotide sequence of five mitochondrial genomes of gastropods (Pyramidella dolabrata, Ascobulla fragilis, Siphonaria pectinata, Onchidella celtica, and Myosotella myosotis, and we analyze them together with another ten complete mitochondrial genomes of gastropods currently available in molecular databases in order to reconstruct the phylogenetic relationships among the main lineages of gastropods. Results Comparative analyses with other mollusk mitochondrial genomes allowed us to describe molecular features and general trends in the evolution of mitochondrial genome organization in gastropods. Phylogenetic reconstruction with commonly used methods of phylogenetic inference (ME, MP, ML, BI arrived at a single topology, which was used to reconstruct the evolution of mitochondrial gene rearrangements in the group. Conclusion Four main lineages were identified within gastropods: Caenogastropoda, Vetigastropoda, Patellogastropoda, and Heterobranchia. Caenogastropoda and Vetigastropoda are sister taxa, as well as, Patellogastropoda and Heterobranchia. This result rejects the validity of the derived clade Apogastropoda (Caenogastropoda + Heterobranchia. The position of Patellogastropoda remains unclear likely due to long-branch attraction biases. Within Heterobranchia, the most heterogeneous group of gastropods, neither Euthyneura (because of the inclusion of P
Diffusion Weighted Imaging of the Neonatal Brain

NARCIS (Netherlands)

J. Dudink (Jeroen)

2010-01-01

textabstractAlthough in the last decades advances in fetal and neonatal medicine have reduced mortality in neonatal intensive care units in the Western world, the morbidity due to brain injury remains high. Patterns of neonatal brain injury can be roughly divided in (1) term and (2) preterm
Right paratesticular abscess mimicking neonatal testicular torsion ...

African Journals Online (AJOL)

U.O. Ezomike

Abstract. The clinical presentation of neonatal paratesticular abscess may closely resemble that of, neonatal testicular torsion and the use of scrotal ultrasonography to differentiate the two has low, sensitivity. We propose early operative treatment of suspected neonatal testicular torsion to salvage, the testicle in cases of ...
Malaria parasite positivity among febrile neonates | Enyuma ...

African Journals Online (AJOL)

Background: Malaria, earlier considered rare in neonates, has been reported with increasing frequency in the last decade. Neonatal malaria diagnosis is challenging because the clinical features are non-specific, variable and also overlap with bacterial infection. Aim: To determine the prevalence of neonatal malaria and ...
Loss of laforin or malin results in increased Drp1 level and concomitant mitochondrial fragmentation in Lafora disease mouse models.

Science.gov (United States)

Upadhyay, Mamta; Agarwal, Saloni; Bhadauriya, Pratibha; Ganesh, Subramaniam

2017-04-01

Lafora disease (LD) is an autosomal recessive form of a fatal disorder characterized by the myoclonus epilepsy, ataxia, psychosis, dementia, and dysarthria. A hallmark of LD is the presence of abnormal glycogen inclusions called Lafora bodies in the affected tissues including the neurons. LD can be caused by defects either in the laforin phosphatase coded by the EPM2A gene or in the malin E3 ubiquitin ligase coded by the NHLRC1 gene. The mouse models of LD, created by the targeted disruption of the LD genes, display several neurodegenerative changes. Prominent among them are the autophagic defects, abnormally large lysosomes, neurofibrillary tangles, amyloid beta deposits, and abnormal mitochondria. However, whether or not such neurodegenerative changes are a direct effect of the loss of laforin/malin was not unequivocally established. Here, we show that laforin- or malin-deficient neurons and fibroblasts display a significantly higher number of fragmented mitochondria. Loss of laforin or malin resulted in increased levels of the mitochondrial fission GTPase Drp1, its enhanced mitochondrial targeting, and increased intracellular calcium levels. Intriguingly, laforin and malin display opposite effects on the cellular level of parkin, an ubiquitin ligase of Drp1; loss of laforin led to reduced levels of parkin while the loss of malin resulted in increased parkin levels. Laforin and malin, however, interact with and positively regulate the activity of parkin, thus explaining the molecular basis of increased Drp1 levels in LD tissues. Our results suggest that laforin and malin are novel regulators of mitochondrial quality control pathway and that the mitochondrial dysfunction resulting from the increased Drp1 levels could underlie neuropathology in LD. Copyright Â© 2017 Elsevier Inc. All rights reserved.
Fatal Candidemia in a Patient with Acute Lymphoblastic Leukemia

Science.gov (United States)

2018-02-16

Profoosionaf 7 ,0 Fatal Candidemia in a Patient with Acute Lymphoblastic Leukemia Brittany Lenz, MD, Arturo Dominguez, MD, Adnan Mir, MD, PhD Objectives...with pre-B cell acute lymphoblastic leukemia was admitted for presumed septic shock secondary to an unknown infectious etiology. The patient was...NOTES 14. ABSTRACT Fatal Candidcn1ia in a Patient \\\\ith Acute Lympboblastic Leukemia Brittany Lenz. MD. Arturo Dominguez.. MD. Adnan J’vlir. MD, PhD
Violent and Fatal Youth Trauma: Is There a Missed Opportunity?

Directory of Open Access Journals (Sweden)

Robert Madlinger, DO

2012-05-01

Full Text Available Introduction: Accidents and assaults (homicides are the leading causes of death among the youth of the United States, accounting for 53.3% of deaths among children aged 1 to19 years. Victim recidivism,defined as repeated visits to the emergency department (ED as a victim of violent trauma, is a significantly growing public health problem. As 5-year mortality rates for recidivism are as high as 20%,it is important to determine whether victims with a history of violent trauma are at increased risk for fatal outcome with their next trauma. We hypothesized that victims of violent trauma who have had 1 prior ED visit for violent trauma will have increased odds of fatal outcome.Methods: A retrospective chart review was conducted for patients presenting with penetrating trauma to the ED from January 1, 1999 to December 31, 2009. All patients between the ages of 15 to 25 years who presented to the ED for any penetrating trauma were included. Patients with prior presentations for penetrating trauma were compared to those patients who were first-time presenters to determine the odds ratio of fatal outcome.Results: Overall, 15,395 patients were treated for traumatic presentations. Of these, 1,044 met inclusion criteria. Demographically, 79.4% were Hispanic, 19.4% were African American, and 0.96% were Caucasian. The average age was 21 years, and 98% of the population was male. One hundred and forty-seven (14% had prior presentations, and 897 (86% did not. Forty of the 147 patients (27%with prior presentations had a fatal outcome as compared to 29 patients of the 868 (3% without prior presentations, with odds ratio of 10.8 (95% confidence interval, 6.4–18.1; Pearson v2, P , 0.001. The 5-year mortality rate for those patients with fatal outcomes was calculated at 16.5%.Conclusion: Patients who had prior ED visits for penetrating trauma were at greater risk for fatal outcomes compared to those with no prior visits. Therefore, trauma-related ED visits might
Dosing antibiotics in neonates: review of the pharmacokinetic data.

Science.gov (United States)

Rivera-Chaparro, Nazario D; Cohen-Wolkowiez, Michael; Greenberg, Rachel G

2017-09-01

Antibiotics are often used in neonates despite the absence of relevant dosing information in drug labels. For neonatal dosing, clinicians must extrapolate data from studies for adults and older children, who have strikingly different physiologies. As a result, dosing extrapolation can lead to increased toxicity or efficacy failures in neonates. Driven by these differences and recent legislation mandating the study of drugs in children and neonates, an increasing number of pharmacokinetic studies of antibiotics are being performed in neonates. These studies have led to new dosing recommendations with particular consideration for neonate body size and maturation. Herein, we highlight the available pharmacokinetic data for commonly used systemic antibiotics in neonates.

Loss of Mitochondrial Function Impairs Lysosomes.

Science.gov (United States)

Demers-Lamarche, Julie; Guillebaud, Gérald; Tlili, Mouna; Todkar, Kiran; Bélanger, Noémie; Grondin, Martine; Nguyen, Angela P; Michel, Jennifer; Germain, Marc

2016-05-06

Alterations in mitochondrial function, as observed in neurodegenerative diseases, lead to disrupted energy metabolism and production of damaging reactive oxygen species. Here, we demonstrate that mitochondrial dysfunction also disrupts the structure and function of lysosomes, the main degradation and recycling organelle. Specifically, inhibition of mitochondrial function, following deletion of the mitochondrial protein AIF, OPA1, or PINK1, as well as chemical inhibition of the electron transport chain, impaired lysosomal activity and caused the appearance of large lysosomal vacuoles. Importantly, our results show that lysosomal impairment is dependent on reactive oxygen species. Given that alterations in both mitochondrial function and lysosomal activity are key features of neurodegenerative diseases, this work provides important insights into the etiology of neurodegenerative diseases. © 2016 by The American Society for Biochemistry and Molecular Biology, Inc.
Mitochondrial dynamics in mammalian health and disease.

Science.gov (United States)

Liesa, Marc; Palacín, Manuel; Zorzano, Antonio

2009-07-01

The meaning of the word mitochondrion (from the Greek mitos, meaning thread, and chondros, grain) illustrates that the heterogeneity of mitochondrial morphology has been known since the first descriptions of this organelle. Such a heterogeneous morphology is explained by the dynamic nature of mitochondria. Mitochondrial dynamics is a concept that includes the movement of mitochondria along the cytoskeleton, the regulation of mitochondrial architecture (morphology and distribution), and connectivity mediated by tethering and fusion/fission events. The relevance of these events in mitochondrial and cell physiology has been partially unraveled after the identification of the genes responsible for mitochondrial fusion and fission. Furthermore, during the last decade, it has been identified that mutations in two mitochondrial fusion genes (MFN2 and OPA1) cause prevalent neurodegenerative diseases (Charcot-Marie Tooth type 2A and Kjer disease/autosomal dominant optic atrophy). In addition, other diseases such as type 2 diabetes or vascular proliferative disorders show impaired MFN2 expression. Altogether, these findings have established mitochondrial dynamics as a consolidated area in cellular physiology. Here we review the most significant findings in the field of mitochondrial dynamics in mammalian cells and their implication in human pathologies.
Home delivery and neonatal mortality in North Carolina.

Science.gov (United States)

Burnett, C A; Jones, J A; Rooks, J; Chen, C H; Tyler, C W; Miller, C A

1980-12-19

Neonatal mortality examined by place and circumstances of delivery in North Carolina during 1974 through 1976 with attention given to home delivery. Planned home deliveries by lay-midwives resulted in three neonatal deaths per 1,000 live births; planned home deliveries without a lay-midwife, 30 neonatal deaths per 1,000 live births; and unplanned home deliveries, 120 neonatal deaths per 1,000 live births. The women babies were delivered by lay-midwives were screened in county health departments and found to be medically at low risk of complication, despite having demographic characteristics associated with high-risk of neonatal mortality. Conversely, the women delivered at home without known prenatal screening or a trained attendant had low-risk demographic characteristics but experienced a high rate of neonatal mortality. Planning, prenatal screening, and attendant-training were important in differentiating the risk of neonatal mortality in this uncontrolled, observational study.
Diagnostic imaging in neonatal stroke; Bildgebende Diagnostik des Neonatal stroke

Energy Technology Data Exchange (ETDEWEB)

Kuhle, S.; Ipsiroglu, O.; Weninger, M. [Universitaetsklinik fuer Kinder- und Jugendheilkunde, Wien (Austria). Abt. fuer Neonatologie, angeborene Stoerungen und Intensivmedizin; Puig, S.; Prayer, D. [Universitaetsklinik fuer Radiodiagnostik, Wien (Austria)

2000-01-01

A cerebral artery infarction is an important differential diagnosis in the newborn with neurological abnormalities. Based on clinical data, its incidence is estimated to be 1 in 4000 newborns. Since the course is often subclinical, the true incidence is probably higher. Diagnosis: Cerebral ultrasound and Doppler sonography as readily available screening tools play a central role in the initial diagnosis of neonatal cerebral infarction. Definitive diagnosis is made by computed tomography or magnetic resonance imaging. Beside symptomatic anticonvulsive therapy, treatment aims at the prevention of secondary ischemic injury. Discussion: Three term infants with different clinical courses of neonatal stroke are presented to sensitize the clinician and the radiologist for this probably underdiagnosed entity. The role of imaging modalities in the diagnosis and follow-up of neonatal cerebral infarction is discussed. (orig.) [German] Ein Infarkt im Stromgebiet der Zerebralarterien stellt eine wichtige Differentialdiagnose bei neurologischen Auffaelligkeiten in der Neonatalperiode dar. Die Inzidenz wird anhand von klinischer Daten auf 1:4000 Lebendgeborene geschaetzt. Da der Verlauf oft subklinisch ist, liegt die wahre Inzidenz wahrscheinlich hoeher. Diagnose: Bei der Diagnosestellung kommen dem Schaedelultraschall und der Doppelsonographie als leicht verfuegbaren Screening-Methoden eine zentrale Rolle zu. Die definitive Diagnose wird, je nach Verfuegbarkeit, mittels Computertomographie oder Kernspintomographie gestellt. Die Behandlung ist neben der symptomatischen (antikonvulsiven) Therapie auf die Vermeidung von ischaemischen Sekundaerschaeden gerichtet. Diskussion: Wir wollen mit der vorliegenden Arbeit anhand von 3 Kindern mit verschiedenen klinischen Verlaeufen eines sog. Neonatal stroke den Stellenwert der bildgebenden Verfahren bei der Diagnostik und Verlaufskontrolle aufzeigen und die Sensibilitaet fuer dieses vermutlich unterdiagnostizierte Krankheitsbild erhoehen
Caso fatal de balantidíase intestinal

Directory of Open Access Journals (Sweden)

Maria da Conceição Pinheiro

1991-09-01

Full Text Available Caso fatal de balantidíase em mulher desnutrida de 63 anos, criadora de porcos, da zona rural de Uberaba. A doença evoluiu em oito dias com disenteria, náusea e vômitos, culminando em óbito por enterorragia. A necropsia constatou-se colite ulcerada causada por B. coli, facilmente identificado ao exame histológico do intestino grosso.A fatal case of a 63-year old pig-raising country woman with an eight-day course of nausea, vomiting. dysentery with intestinal bleeding the latter being the direct cause of death. The autopsy showed ulcerative colitis due to B. coli, which was easily observed on histological examination of the large bowel.
Role of polyhydroxybutyrate in mitochondrial calcium uptake

Science.gov (United States)

Smithen, Matthew; Elustondo, Pia A.; Winkfein, Robert; Zakharian, Eleonora; Abramov, Andrey Y.; Pavlov, Evgeny

2013-01-01

Polyhydroxybutyrate (PHB) is a biological polymer which belongs to the class of polyesters and is ubiquitously present in all living organisms. Mammalian mitochondrial membranes contain PHB consisting of up to 120 hydroxybutyrate residues. Roles played by PHB in mammalian mitochondria remain obscure. It was previously demonstrated that PHB of the size similar to one found in mitochondria mediates calcium transport in lipid bilayer membranes. We hypothesized that the presence of PHB in mitochondrial membrane might play a significant role in mitochondrial calcium transport. To test this, we investigated how the induction of PHB hydrolysis affects mitochondrial calcium transport. Mitochondrial PHB was altered enzymatically by targeted expression of bacterial PHB hydrolyzing enzyme (PhaZ7) in mitochondria of mammalian cultured cells. The expression of PhaZ7 induced changes in mitochondrial metabolism resulting in decreased mitochondrial membrane potential in HepG2 but not in U87 and HeLa cells. Furthermore, it significantly inhibited mitochondrial calcium uptake in intact HepG2, U87 and HeLa cells stimulated by the ATP or by the application of increased concentrations of calcium to the digitonin permeabilized cells. Calcium uptake in PhaZ7 expressing cells was restored by mimicking calcium uniporter properties with natural electrogenic calcium ionophore - ferutinin. We propose that PHB is a previously unrecognized important component of the mitochondrial calcium uptake system. PMID:23702223
Effectiveness of antilock braking systems in reducing motorcycle fatal crash rates.

Science.gov (United States)

Teoh, Eric R

2011-04-01

Overbraking and underbraking have been shown to be common factors in motorcycle crashes. Antilock braking systems (ABS) prevent wheels from locking during braking and may make riders less reluctant to apply full braking force. The objective of this study was to evaluate the effect of ABS in fatal motorcycle crashes. Motorcycle drivers involved in fatal crashes per 10,000 registered vehicle years were compared for 13 motorcycle models with optional ABS and those same models without the option during 2003-2008. Motorcycles with optional ABS were included only if the presence of the option could be identified from the vehicle identification number. The rate of fatal motorcycle crashes per 10,000 registered vehicle years was 37 percent lower for ABS models than for their non-ABS versions. ABS appears to be highly effective in preventing fatal motorcycle crashes based on some early adopters of motorcycle ABS technology.
A Study On Neonatal Mortality In Jamnagar District Of Gujarat

Directory of Open Access Journals (Sweden)

Yadav Sudha

1998-01-01

Full Text Available Research question: Which are the maternal, socio-demographic and neonatal attributes responsible for neonatal mortality in rural areas of Gujarat? Objectives: (i To know various maternal, socio-demographic and neonatal factors responsible for neonatal mortality in rural areas of Gujarat (ii To estimate neonatal mortality rate in the area. Setting: Rural areas of six Primary Health Centers of Jamnagar district of Gujarat State. Study design: Community based cohort study. Sample size: Population of 40512 Participants: Members of the family in which neonatal deaths occurred. Outcome variable: Neonatal mortality Analysis: Sample proportions. Results: Neonatal mortality rate on the basis of follow-up of births during one year was found to be 47.27 per thousand live births. The major maternal and socio-demographic factors responsible for neonatal mortality were; maternal age, illiteracy, lack of antenatal care, closely spaced pregnancies, delivery conducted at home, delivery conducted untrained personnel and delayed initiation of breast feeding. The major neonatal factors responsible for mortality in neonates were; low birth weight, prematurity, first order of birth, early phase of neonatal period, male gender of the child. The leading causes of neonatal mortality were found to be prematurity, birth asphyxia, neonatal infections and congenital anomalies.
[Epidemiology of nosocomial infections in neonates].

Science.gov (United States)

Lachassinne, E; Letamendia-Richard, E; Gaudelus, J

2004-03-01

Epidemiology of nosocomial infections in neonates has to be described according to our definitions (early onset GBS diseases excluded) and according to levels of care. Nosocomial risk exists in maternity departments (3% in postnatal beds), incidence rates are 7.5-12.7% or 1.3-8.5 per 1000 days in neonatal care units and 14.2% or 11.7 per 1000 days in neonatal intensive care units (NICU). Gram-positive cocci bloodstream infections are the most common nosocomial infections in NICU but viral gastroenteritis are more frequent in neonatal care units. Risk factors are low birthweight, small gestational age and intravascular catheter in NICU, and for viral nosocomial infections, visits and winter outbreaks.
Potentially harmful excipients in neonatal medicines

DEFF Research Database (Denmark)

Nellis, Georgi; Metsvaht, Tuuli; Varendi, Heili

2015-01-01

OBJECTIVES: We aimed to describe administration of eight potentially harmful excipients of interest (EOI)-parabens, polysorbate 80, propylene glycol, benzoates, saccharin sodium, sorbitol, ethanol and benzalkonium chloride-to hospitalised neonates in Europe and to identify risk factors for exposure....... METHODS: All medicines administered to neonates during 1 day with individual prescription and demographic data were registered in a web-based point prevalence study. Excipients were identified from the Summaries of Product Characteristics. Determinants of EOI administration (geographical region......, gestational age (GA), active pharmaceutical ingredient, unit level and hospital teaching status) were identified using multivariable logistical regression analysis. RESULTS: Overall 89 neonatal units from 21 countries participated. Altogether 2095 prescriptions for 530 products administered to 726 neonates...
Pharmacological modulation of mitochondrial calcium homeostasis.

Science.gov (United States)

Arduino, Daniela M; Perocchi, Fabiana

2018-01-10

Mitochondria are pivotal organelles in calcium (Ca 2+ ) handling and signalling, constituting intracellular checkpoints for numerous processes that are vital for cell life. Alterations in mitochondrial Ca 2+ homeostasis have been linked to a variety of pathological conditions and are critical in the aetiology of several human diseases. Efforts have been taken to harness mitochondrial Ca 2+ transport mechanisms for therapeutic intervention, but pharmacological compounds that direct and selectively modulate mitochondrial Ca 2+ homeostasis are currently lacking. New avenues have, however, emerged with the breakthrough discoveries on the genetic identification of the main players involved in mitochondrial Ca 2+ influx and efflux pathways and with recent hints towards a deep understanding of the function of these molecular systems. Here, we review the current advances in the understanding of the mechanisms and regulation of mitochondrial Ca 2+ homeostasis and its contribution to physiology and human disease. We also introduce and comment on the recent progress towards a systems-level pharmacological targeting of mitochondrial Ca 2+ homeostasis. © 2018 The Authors. The Journal of Physiology © 2018 The Physiological Society.
[Lactose intolerance in neonates with non-infectious diarrhea].

Science.gov (United States)

Su, Hui-Min; Jiang, Yi; Hu, Yu-Lian; Yang, Hui; Dong, Tian-Jin

2016-04-01

To investigate the development of lactose intolerance in neonates with non-infectious diarrhea and its association with diarrhea, and to evaluate the diagnostic values of fecal pH value and urine galactose determination for neonatal lactase deficiency. Seventy hospitalized neonates who developed non-infectious diarrhea between October 2012 and June 2015 were enrolled as the diarrhea group, and 162 hospitalized neonates without non-infectious diarrhea were enrolled as the non-diarrhea group. Test paper was used to determine fecal pH value. The galactose oxidase method was used to detect urine galactose. The neonates with positive galactose oxidase were diagnosed with lactase deficiency, and those with lactase deficiency and diarrhea were diagnosed with lactose intolerance. According to the results of urine galactose detection, 69 neonates in the diarrhea group who underwent urine galactose detection were classified into lactose intolerance group (45 neonates) and lactose tolerance group (24 neonates), and their conditions after treatment were compared between the two groups. The follow-up visits were performed for neonates with diarrhea at 3 months after discharge. Fecal pH value and positive rate of urine galactose (65% vs 54%) showed no significant differences between the diarrhea and non-diarrhea groups (P>0.05). Fecal pH value showed no significant difference between the lactose intolerance and lactose tolerance groups (P>0.05), while the neonates in the lactose intolerance group had a significantly longer time to recovery of defecation than those in the lactose tolerance group (Plactose intolerance tends to occur. Determination of fecal pH value has no significance in the diagnosis of lactose intolerance in neonates with diarrhea.
Causes of fatal accidents for instrument-certified and non-certified private pilots.

Science.gov (United States)

Shao, Bob Siyuan; Guindani, Michele; Boyd, Douglas D

2014-11-01

Instrument certification (IFR) enhances a pilot's skills in precisely controlling the aircraft and requires a higher level of standards in maintaining heading and altitude compared with the less stringent private pilot certificate. However, there have been no prior studies to compare fatal accident causes for airmen with, and without, this rating, The NTSB accident database was queried for general aviation fatal accidents for private pilots with, and without IFR certification. Exact Poisson tests were used to calculate whether two rate parameters were equal (ratio of 1), normalized to the number of IFR-rated pilots and flight hours in the given time period. Proportion tests were used to determine whether there were significant differences in fatal accident causes between IFR-certified and non-certified pilots. A logistic regression for log-odds success was used in determining the trend and effect of age on fatal accident rates. IFR certification was associated with a reduced risk of accidents due to failure to maintain obstacle/terrain clearance and spatial disorientation for day and night operations respectively. In contrast, the likelihood of fatal accident due to equipment malfunction during day operations was higher for IFR-certified pilots. The fatal accident rate decreased over the last decade for IFR-certified but not for non-IFR-certified private pilots. However, the overall accident rate for IFR-certified private pilots was more than double that of the cohort lacking this certification. Finally, we found a trend for an increased fatality rate with advancing age for both group of pilots. Our findings informs on where training and/or technology should be focused. Both training for aerodynamic stalls, which causes over a quarter of all fatal accidents, should be intensified for both IFR-certified and non-certified private pilots. Similarly, adherence to minimum safe altitudes for both groups of pilots should be encouraged toward reducing the fatal accidents
Intergenerational differences in occupational injury and fatality rates among Canada's immigrants.

Science.gov (United States)

Tiagi, R

2016-12-01

Empirical evidence on occupational injury and/or fatality rates among Canada's immigrants has been largely mixed and has almost exclusively focused on the first generation. Over time, as immigrants assimilate into the economy, future generations may be expected to work in less hazardous occupations compared with prior generations. There has been no prior analysis of the differences in occupational injury and fatality rates among later generations. To analyse whether there are intergenerational differences in occupational injury and fatality rates among the first, second and third (or more) immigrant generations in Canada. Data drawn from the 2011 National Household Survey and the Association of Workers' Compensation Boards of Canada were used to determine the difference in occupational injury and fatality rates between the first or the third generation and the second generation, using a Poisson regression framework. Second-generation immigrants worked in jobs with lower occupational injury rates compared with the first generation and the third generation (or more). Similar results were observed for occupational fatality rates. Second-generation immigrants worked in less hazardous jobs compared with the first generation and compared with the third (or more) generations. These results suggest that the second generation may not face the same economic hurdles and challenges, in terms of workplace injuries or fatalities, as those faced by the first or third (or more) generations of immigrants. © The Author 2016. Published by Oxford University Press on behalf of the Society of Occupational Medicine. All rights reserved. For Permissions, please email: journals.permissions@oup.com.
Surgical procedures performed in the neonatal intensive care unit on critically ill neonates: feasibility and safety

International Nuclear Information System (INIS)

Mallick, M.S.; Jado, A.M.; Al-Bassam, A.R.

2008-01-01

Transferring unstable, ill neonates to and from the operating rooms carries significant risks and can lead to morbidity. We report on our experience in performing certain procedures in critically ill neonates in the neonatal intensive care unit (NICU). We examined the feasibility and safety for such an approach. All surgical procedures performed in the NICU between January 1999 and December 2005 were analyzed in terms of demographic data, diagnosis, preoperative stability of the patient, procedures performed, complications and outcome. Operations were performed at beside in the NICU in critically ill, unstable neonates who needed emergency surgery, in neonates of low birth weight (<1000 gm) and in neonates on special equipments like higher frequency ventilators and nitrous oxide. Thirty-seven surgical procedures were performed including 12 laparotomies, bowel resection and stomies, 7 repairs of congenital diaphragmatic hernias, 4 ligations of patent ductus arteriosus and various others. Birth weights ranged between 850 gm and 3500 gm (mean 2000 gm). Gestational age ranged between 25 to 42 weeks (mean, 33 weeks). Age at surgery was between 1 to 30 days (mean, 30 days). Preoperatively, 19 patients (51.3%) were on inotropic support and all were intubated and mechanically ventilated. There was no mortality related to surgical procedures. Postoperatively, one patient developed wound infection and disruption. Performing major surgical procedures in the NICU is both feasible and safe. It is useful in very low birth weight, critically ill neonates who have definite risk attached to transfer to the operating room. No special area is needed in the NICU to perform complication-free surgery, but designing an operating room within the NICU will be ideal. (author)
Modelling Blood Flow and Metabolism in the Preclinical Neonatal Brain during and Following Hypoxic-Ischaemia.

Directory of Open Access Journals (Sweden)

Matthew Caldwell

Full Text Available Hypoxia-ischaemia (HI is a major cause of neonatal brain injury, often leading to long-term damage or death. In order to improve understanding and test new treatments, piglets are used as preclinical models for human neonates. We have extended an earlier computational model of piglet cerebral physiology for application to multimodal experimental data recorded during episodes of induced HI. The data include monitoring with near-infrared spectroscopy (NIRS and magnetic resonance spectroscopy (MRS, and the model simulates the circulatory and metabolic processes that give rise to the measured signals. Model extensions include simulation of the carotid arterial occlusion used to induce HI, inclusion of cytoplasmic pH, and loss of metabolic function due to cell death. Model behaviour is compared to data from two piglets, one of which recovered following HI while the other did not. Behaviourally-important model parameters are identified via sensitivity analysis, and these are optimised to simulate the experimental data. For the non-recovering piglet, we investigate several state changes that might explain why some MRS and NIRS signals do not return to their baseline values following the HI insult. We discover that the model can explain this failure better when we include, among other factors such as mitochondrial uncoupling and poor cerebral blood flow restoration, the death of around 40% of the brain tissue.
Characteristics, Classification, and Prevention of Child Maltreatment Fatalities.

Science.gov (United States)

McCarroll, James E; Fisher, Joscelyn E; Cozza, Stephen J; Robichaux, Renè J; Fullerton, Carol S

2017-01-01

Preventing child maltreatment fatalities is a critical goal of the U.S. society and the military services. Fatality review boards further this goal through the analysis of circumstances of child deaths, making recommendations for improvements in practices and policies, and promoting increased cooperation among the many systems that serve families. The purpose of this article is to review types of child maltreatment death, proposed classification models, risk and protective factors, and prevention strategies. This review is based on scientific and medical literature, national reports and surveys, and reports of fatality review boards. Children can be killed soon after birth or when older through a variety of circumstances, such as with the suicide of the perpetrator, or when the perpetrator kills the entire family. Death through child neglect may be the most difficult type of maltreatment death to identify as neglect can be a matter of opinion or societal convention. These deaths can occur as a result of infant abandonment, starvation, medical neglect, drowning, home fires, being left alone in cars, and firearms. Models of classification for child maltreatment deaths can permit definition and understanding of child fatalities by providing reference points that facilitate research and enhance clinical prediction. Two separate approaches have been proposed: the motives of the perpetrator and the circumstances of death of the child victim. The latter approach is broader and is founded on an ecological model focused on the nature and circumstances of death, child victim characteristics, perpetrator characteristics, family and environmental circumstances, and service provision and need. Many risk factors for maternal and paternal filicide have been found, but most often included are young maternal age, no prenatal care, low education level, mental health problems, family violence, and substance abuse. Many protective factors can be specified at the individual, family
Mitochondrial mutations drive prostate cancer aggression

DEFF Research Database (Denmark)

Hopkins, Julia F.; Sabelnykova, Veronica Y.; Weischenfeldt, Joachim

2017-01-01

Nuclear mutations are well known to drive tumor incidence, aggression and response to therapy. By contrast, the frequency and roles of mutations in the maternally inherited mitochondrial genome are poorly understood. Here we sequence the mitochondrial genomes of 384 localized prostate cancer...... in prostate cancer, and suggest interplay between nuclear and mitochondrial mutational profiles in prostate cancer....
Drug involvement of fatally injured drivers

Science.gov (United States)

2010-11-01

While data focusing on the danger of driving under the influence : of alcohol is readily available and often cited, less is : known or discussed about drivers under the influence of : other drugs. The Fatality Analysis Reporting System (FARS), : a ce...
Validation of the use of an artificial mitochondrial reporter DNA vector containing a Cytomegalovirus promoter for mitochondrial transgene expression.

Science.gov (United States)

Yamada, Yuma; Ishikawa, Takuya; Harashima, Hideyoshi

2017-08-01

Mitochondria have their own gene expression system that is independent of the nuclear system, and control cellular functions in cooperation with the nucleus. While a number of useful technologies for achieving nuclear transgene expression have been reported, only a few have focused on mitochondria. In this study, we validated the utility of an artificial mitochondrial DNA vector with a virus promoter on mitochondrial transgene expression. We designed and constructed pCMV-mtLuc (CGG) that contains a CMV promotor derived from Cytomegalovirus and an artificial mitochondrial genome with a NanoLuc (Nluc) luciferase gene that records adjustments to the mitochondrial codon system. Nluc luciferase activity measurements showed that the pCMV-mtLuc (CGG) efficiently produced the Nluc luciferase protein in human HeLa cells. Moreover, we optimized the mitochondrial transfection of pCMV-mtLuc (CGG) using a MITO-Porter system, a liposome-based carrier for mitochondrial delivery via membrane fusion. As a result, we found that transfection of pCMV-mtLuc (CGG) by MITO-Porter modified with the KALA peptide (cationic amphipathic cell-penetrating peptide) showed a high mitochondrial transgene expression. The developed mitochondrial transgene expression system represents a potentially useful tool for the fields of nanoscience and nanotechnology for controlling the intracellular microenvironment via the regulation of mitochondrial function and promises to open additional innovative research fields of study. Copyright © 2017 Elsevier Ltd. All rights reserved.

Mitochondrial oxodicarboxylate carrier deficiency is associated with mitochondrial DNA depletion and spinal muscular atrophy-like disease.

Science.gov (United States)

Boczonadi, Veronika; King, Martin S; Smith, Anthony C; Olahova, Monika; Bansagi, Boglarka; Roos, Andreas; Eyassu, Filmon; Borchers, Christoph; Ramesh, Venkateswaran; Lochmüller, Hanns; Polvikoski, Tuomo; Whittaker, Roger G; Pyle, Angela; Griffin, Helen; Taylor, Robert W; Chinnery, Patrick F; Robinson, Alan J; Kunji, Edmund R S; Horvath, Rita

2018-03-08

PurposeTo understand the role of the mitochondrial oxodicarboxylate carrier (SLC25A21) in the development of spinal muscular atrophy-like disease.MethodsWe identified a novel pathogenic variant in a patient by whole-exome sequencing. The pathogenicity of the mutation was studied by transport assays, computer modeling, followed by targeted metabolic testing and in vitro studies in human fibroblasts and neurons.ResultsThe patient carries a homozygous pathogenic variant c.695A>G; p.(Lys232Arg) in the SLC25A21 gene, encoding the mitochondrial oxodicarboxylate carrier, and developed spinal muscular atrophy and mitochondrial myopathy. Transport assays show that the mutation renders SLC25A21 dysfunctional and 2-oxoadipate cannot be imported into the mitochondrial matrix. Computer models of central metabolism predicted that impaired transport of oxodicarboxylate disrupts the pathways of lysine and tryptophan degradation, and causes accumulation of 2-oxoadipate, pipecolic acid, and quinolinic acid, which was confirmed in the patient's urine by targeted metabolomics. Exposure to 2-oxoadipate and quinolinic acid decreased the level of mitochondrial complexes in neuronal cells (SH-SY5Y) and induced apoptosis.ConclusionMitochondrial oxodicarboxylate carrier deficiency leads to mitochondrial dysfunction and the accumulation of oxoadipate and quinolinic acid, which in turn cause toxicity in spinal motor neurons leading to spinal muscular atrophy-like disease.GENETICS in MEDICINE advance online publication, 8 March 2018; doi:10.1038/gim.2017.251.
Cold acclimation increases mitochondrial oxidative capacity without inducing mitochondrial uncoupling in goldfish white skeletal muscle

Directory of Open Access Journals (Sweden)

Reinaldo Sousa Dos Santos

2012-11-01

Goldfish have been used for cold acclimation studies, which have focused on changes in glycolytic and oxidative enzymes or alterations in lipid composition in skeletal muscle. Here we examine the effects of cold acclimation on the functional properties of isolated mitochondria and permeabilized fibers from goldfish white skeletal muscle, focusing on understanding the types of changes that occur in the mitochondrial respiratory states. We observed that cold acclimation promoted a significant increase in the mitochondrial oxygen consumption rates. Western blot analysis showed that UCP3 was raised by ∼1.5-fold in cold-acclimated muscle mitochondria. Similarly, we also evidenced a rise in the adenine nucleotide translocase content in cold-acclimated muscle mitochondria compared to warm-acclimated mitochondria (0.96±0.05 vs 0.68±0.02 nmol carboxyatractyloside mg−1 protein. This was followed by a 2-fold increment in the citrate synthase activity, which suggests a higher mitochondrial content in cold-acclimated goldfish. Even with higher levels of UCP3 and ANT, the effects of activator (palmitate and inhibitors (carboxyatractyloside and GDP on mitochondrial parameters were similar in both warm- and cold-acclimated goldfish. Thus, we propose that cold acclimation in goldfish promotes an increase in functional oxidative capacity, with higher mitochondrial content without changes in the mitochondrial uncoupling pathways.
The mitochondrial 60-kDa heat shock protein in marine invertebrates: biochemical purification and molecular characterization.

Science.gov (United States)

Choresh, Omer; Loya, Yossi; Müller, Werner E G; Wiedenmann, Jörg; Azem, Abdussalam

2004-03-01

Sessile marine invertebrates undergo constant direct exposure to the surrounding environmental conditions, including local and global environmental fluctuations that may lead to fatal protein damage. Induction of heat shock proteins (Hsps) constitutes an important defense mechanism that protects these organisms from deleterious stress conditions. In a previous study, we reported the immunological detection of a 60-kDa Hsp (Hsp60) in the sea anemone Anemonia viridis (formerly called Anemonia sulcata) and studied its expression under a variety of stress conditions. In the present study, we show that the sponge Tetilla sp. from tidal habitats with a highly variable temperature regime is characterized by an increased level of Hsp60. Moreover, we show the expression of Hsp60 in various species among Porifera and Cnidaria, suggesting a general importance of this protein among marine invertebrates. We further cloned the hsp60 gene from A viridis, using a combination of conventional protein isolation methods and screening of a complementary deoxyribonucleic acid library by polymerase chain reaction. The cloned sequence (1764 bp) encodes for a protein of 62.8 kDa (588 amino acids). The 62.8-kDa protein, which contains an amino terminal extension that may serve as a mitochondrial targeting signal, shares a significant identity with mitochondrial Hsp60s from several animals but less identity with Hsp60s from either bacteria or plants.
Evaluation of poly-drug use in methadone-related fatalities using segmental hair analysis.

Science.gov (United States)

Nielsen, Marie Katrine Klose; Johansen, Sys Stybe; Linnet, Kristian

2015-03-01

In Denmark, fatal poisoning among drug addicts is often related to methadone. The primary mechanism contributing to fatal methadone overdose is respiratory depression. Concurrent use of other central nervous system (CNS) depressants is suggested to heighten the potential for fatal methadone toxicity. Reduced tolerance due to a short-time abstinence period is also proposed to determine a risk for fatal overdose. The primary aims of this study were to investigate if concurrent use of CNS depressants or reduced tolerance were significant risk factors in methadone-related fatalities using segmental hair analysis. The study included 99 methadone-related fatalities collected in Denmark from 2008 to 2011, where both blood and hair were available. The cases were divided into three subgroups based on the cause of death; methadone poisoning (N=64), poly-drug poisoning (N=28) or methadone poisoning combined with fatal diseases (N=7). No significant differences between methadone concentrations in the subgroups were obtained in both blood and hair. The methadone blood concentrations were highly variable (0.015-5.3, median: 0.52mg/kg) and mainly within the concentration range detected in living methadone users. In hair, methadone was detected in 97 fatalities with concentrations ranging from 0.061 to 211ng/mg (median: 11ng/mg). In the remaining two cases, methadone was detected in blood but absent in hair specimens, suggesting that these two subjects were methadone-naive users. Extensive poly-drug use was observed in all three subgroups, both recently and within the last months prior to death. Especially, concurrent use of multiple benzodiazepines was prevalent among the deceased followed by the abuse of morphine, codeine, amphetamine, cannabis, cocaine and ethanol. By including quantitative segmental hair analysis, additional information on poly-drug use was obtained. Especially, 6-acetylmorphine was detected more frequently in hair specimens, indicating that regular abuse of
Radiologic findings of neonatal sepsis

International Nuclear Information System (INIS)

Kim, Sam Soo; Han, Dae Hee; Choi, Guk Myeong; Jung, Hye Won; Yoon, Hye Kyung; Han, Bokyung Kim; Lee, Nam Yong

1997-01-01

To review the simple radiographic and sonographic findings in infants with neonatal sepsis. We retrospectively analyzed simple chest and abdominal radiographs, and brain sonograms in 36 newborn infants (preterm : term=23 :13). With neonatal sepsis diagnosed by blood culture and clinical manifestations. Pulmonary parenchymal infiltrate excluding respiratory distress syndrome and pulmonary edema or atelectasis was found in 22 infants (61%). Paralytic ileus, hepatosplenomegaly, and necrotizing enterocolitis were present in 18(50%), 9(25%), and 1(3%) infants, respectively, while skeletal changes suggesting osteomyelitis were found in three. Brain sonography was performed in 29 infants and in four, abnormalities were seen ; these comprised three germinal matrix hemorrhages and one intraparenchymal hemorrhage. In six patients(17%) radiologic examinations revealed no abnormality. In patients with neonatal sepsis, pulmonary infiltrates and paralytic ileus were common abnormalities. Although these were nonspecific, radiologic findings may be used to supplement clinical and laboratory findings in diagnosing neonatal sepsis and planning its treatment
Radiologic findings of neonatal sepsis

Energy Technology Data Exchange (ETDEWEB)

Kim, Sam Soo; Han, Dae Hee; Choi, Guk Myeong; Jung, Hye Won [Seoul National Univ. College of Medicine, Seoul (Korea, Republic of); Yoon, Hye Kyung; Han, Bokyung Kim; Lee, Nam Yong [Sansung Medical Center, Seoul (Korea, Republic of)

1997-06-01

To review the simple radiographic and sonographic findings in infants with neonatal sepsis. We retrospectively analyzed simple chest and abdominal radiographs, and brain sonograms in 36 newborn infants (preterm : term=23 :13). With neonatal sepsis diagnosed by blood culture and clinical manifestations. Pulmonary parenchymal infiltrate excluding respiratory distress syndrome and pulmonary edema or atelectasis was found in 22 infants (61%). Paralytic ileus, hepatosplenomegaly, and necrotizing enterocolitis were present in 18(50%), 9(25%), and 1(3%) infants, respectively, while skeletal changes suggesting osteomyelitis were found in three. Brain sonography was performed in 29 infants and in four, abnormalities were seen ; these comprised three germinal matrix hemorrhages and one intraparenchymal hemorrhage. In six patients(17%) radiologic examinations revealed no abnormality. In patients with neonatal sepsis, pulmonary infiltrates and paralytic ileus were common abnormalities. Although these were nonspecific, radiologic findings may be used to supplement clinical and laboratory findings in diagnosing neonatal sepsis and planning its treatment.
Unintentional, non-fatal drowning of children: US trends and racial/ethnic disparities.

Science.gov (United States)

Felton, Heather; Myers, John; Liu, Gil; Davis, Deborah Winders

2015-12-15

The current study aimed to better understand trends and risk factors associated with non-fatal drowning of infants and children in the USA using two large, national databases. A secondary data analysis was conducted using the National Inpatient Sample and the Nationwide Emergency Department Sample databases. The analytic sample (n=19,403) included children near-drowning/non-fatal drowning. Descriptive, χ(2) and analysis of variance techniques were applied, and incidence rates were calculated per 100,000 population. Non-fatal drowning incidence has remained relatively stable from 2006 to 2011. In general, the highest rates of non-fatal drowning occurred in swimming pools and in children from racial/ethnic minorities. However, when compared with non-Hispanic Caucasian children, children from racial/ethnic minorities were more likely to drown in natural waterways than in swimming pools. Despite the overall lower rate of non-fatal drowning among non-Hispanic Caucasian children, the highest rate of all non-fatal drowning was for non-Hispanic Caucasian children aged 0-4 years in swimming pools. Children who were admitted to inpatient facilities were younger, male and came from families with lower incomes. Data from two large US national databases show lack of progress in preventing and reducing non-fatal drowning admissions from 2006 to 2011. Discrepancies are seen in the location of drowning events and demographic characteristics. New policies and interventions are needed, and tailoring approaches by age and race/ethnicity may improve their effectiveness. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/
Neonatal hypothermia in sub-Saharan Africa: a review.

Science.gov (United States)

Onalo, R

2013-01-01

Hypothermia is a major factor in neonatal morbidity and mortality in developing countries. High prevalence of hypothermia has been reported widely even from warmer tropical countries. In spite of the World Health Organization's recommendation of maintenance of warm chain in newborn care, hypothermia continues to be a common neonatal condition which has remained under-recognized, under-documented, and poorly-managed. This review aims at providing the incidence of and risk factors for neonatal hypothermia as well as provides a pathophysiological overview and management options for neonates with the condition in sub-Saharan Africa. All available published literature on neonatal hypothermia was searched electronically and manually. The principal electronic reference libraries and sites searched were PubMed, Embase, Ajol, Cochrane Reference Libraries and Google Scholar. The search terms used included 'neonatal hypothermia,' 'Cold stress in newborn' 'thermal care of the newborn,' 'neonatal thermogenesis,' 'neonatal cold injury,' among others. Pertinent books and monographs were accessed. Data in formats inaccessible to the reviewer were excluded. Neonatal hypothermia is a major condition of public health importance in countries of sub- Saharan Africa. Awareness of the burden of the disease is still low in some communities. Risk factors for neonatal hypothermia in the region include poverty, home delivery, low birthweight, early bathing of babies, delayed initiation of breastfeeding and inadequate knowledge among health workers. Low-tech facilities to prevent heat losses and provide warmth are available in sub-Saharan Africa and are thus recommended as well as continuous efforts at sensitizing caregivers on the thermal needs of newborns.
iNICU - Integrated Neonatal Care Unit: Capturing Neonatal Journey in an Intelligent Data Way.

Science.gov (United States)

Singh, Harpreet; Yadav, Gautam; Mallaiah, Raghuram; Joshi, Preetha; Joshi, Vinay; Kaur, Ravneet; Bansal, Suneyna; Brahmachari, Samir K

2017-08-01

Neonatal period represents first 28 days of life, which is the most vulnerable time for a child's survival especially for the preterm babies. High neonatal mortality is a prominent and persistent problem across the globe. Non-availability of trained staff and infrastructure are the major recognized hurdles in the quality care of these neonates. Hourly progress growth charts and reports are still maintained manually by nurses along with continuous calculation of drug dosage and nutrition as per the changing weight of the baby. iNICU (integrated Neonatology Intensive Care Unit) leverages Beaglebone and Intel Edison based IoT integration with biomedical devices in NICU i.e. monitor, ventilator and blood gas machine. iNICU is hosted on IBM Softlayer based cloud computing infrastructure and map NICU workflow in Java based responsive web application to provide translational research informatics support to the clinicians. iNICU captures real time vital parameters i.e. respiration rate, heart rate, lab data and PACS amounting for millions of data points per day per child. Stream of data is sent to Apache Kafka layer which stores the same in Apache Cassandra NoSQL. iNICU also captures clinical data like feed intake, urine output, and daily assessment of child in PostgreSQL database. It acts as first Big Data hub (of both structured and unstructured data) of neonates across India offering temporal (longitudinal) data of their stay in NICU and allow clinicians in evaluating efficacy of their interventions. iNICU leverages drools based clinical rule based engine and deep learning based big data analytical model coded in R and PMML. iNICU solution aims to improve care time, fills skill gap, enable remote monitoring of neonates in rural regions, assists in identifying the early onset of disease, and reduction in neonatal mortality.
Sleep disorders associated with primary mitochondrial diseases.

Science.gov (United States)

Ramezani, Ryan J; Stacpoole, Peter W

2014-11-15

Primary mitochondrial diseases are caused by heritable or spontaneous mutations in nuclear DNA or mitochondrial DNA. Such pathological mutations are relatively common in humans and may lead to neurological and neuromuscular complication that could compromise normal sleep behavior. To gain insight into the potential impact of primary mitochondrial disease and sleep pathology, we reviewed the relevant English language literature in which abnormal sleep was reported in association with a mitochondrial disease. We examined publication reported in Web of Science and PubMed from February 1976 through January 2014, and identified 54 patients with a proven or suspected primary mitochondrial disorder who were evaluated for sleep disturbances. Both nuclear DNA and mitochondrial DNA mutations were associated with abnormal sleep patterns. Most subjects who underwent polysomnography had central sleep apnea, and only 5 patients had obstructive sleep apnea. Twenty-four patients showed decreased ventilatory drive in response to hypoxia and/ or hyperapnea that was not considered due to weakness of the intrinsic muscles of respiration. Sleep pathology may be an underreported complication of primary mitochondrial diseases. The probable underlying mechanism is cellular energy failure causing both central neurological and peripheral neuromuscular degenerative changes that commonly present as central sleep apnea and poor ventilatory response to hyperapnea. Increased recognition of the genetics and clinical manifestations of mitochondrial diseases by sleep researchers and clinicians is important in the evaluation and treatment of all patients with sleep disturbances. Prospective population-based studies are required to determine the true prevalence of mitochondrial energy failure in subjects with sleep disorders, and conversely, of individuals with primary mitochondrial diseases and sleep pathology. © 2014 American Academy of Sleep Medicine.
Fatal Rocky Mountain spotted fever in the United States, 1999-2007.

Science.gov (United States)

Dahlgren, F Scott; Holman, Robert C; Paddock, Christopher D; Callinan, Laura S; McQuiston, Jennifer H

2012-04-01

Death from Rocky Mountain spotted fever (RMSF) is preventable with prompt, appropriate treatment. Data from two independent sources were analyzed to estimate the burden of fatal RMSF and identify risk factors for fatal RMSF in the United States during 1999-2007. Despite increased reporting of RMSF cases to the Centers for Disease Control and Prevention, no significant changes in the estimated number of annual fatal RMSF cases were found. American Indians were at higher risk of fatal RMSF relative to whites (relative risk [RR] = 3.9), and children less than 10 years of age (RR=5.1) [corrected] and adults ≥ 70 years of age (RR = 3.0) were also at increased risk relative to other ages. Persons with cases of RMSF with an immunosuppressive condition were at increased risk of death (RR = 4.4). Delaying treatment of RMSF was also associated with increased deaths. These results may indicate a gap between recommendations and practice.
DJ-1 KNOCK-DOWN IMPAIRS ASTROCYTE MITOCHONDRIAL FUNCTION

Science.gov (United States)

LARSEN, N. J.; AMBROSI, G.; MULLETT, S. J.; BERMAN, S. B.; HINKLE, D. A.

2012-01-01

Mitochondrial dysfunction has long been implicated in the pathogenesis of Parkinson’s disease (PD). PD brain tissues show evidence for mitochondrial respiratory chain Complex I deficiency. Pharmacological inhibitors of Complex I, such as rotenone, cause experimental parkinsonism. The cytoprotective protein DJ-1, whose deletion is sufficient to cause genetic PD, is also known to have mitochondria-stabilizing properties. We have previously shown that DJ-1 is over-expressed in PD astrocytes, and that DJ-1 deficiency impairs the capacity of astrocytes to protect co-cultured neurons against rotenone. Since DJ-1 modulated, astrocyte-mediated neuroprotection against rotenone may depend upon proper astrocytic mitochondrial functioning, we hypothesized that DJ-1 deficiency would impair astrocyte mitochondrial motility, fission/fusion dynamics, membrane potential maintenance, and respiration, both at baseline and as an enhancement of rotenone-induced mitochondrial dysfunction. In astrocyte-enriched cultures, we observed that DJ-1 knock-down reduced mitochondrial motility primarily in the cellular processes of both untreated and rotenone treated cells. In these same cultures, DJ-1 knock-down did not appreciably affect mitochondrial fission, fusion, or respiration, but did enhance rotenone-induced reductions in the mitochondrial membrane potential. In neuron–astrocyte co-cultures, astrocytic DJ-1 knock-down reduced astrocyte process mitochondrial motility in untreated cells, but this effect was not maintained in the presence of rotenone. In the same co-cultures, astrocytic DJ-1 knock-down significantly reduced mitochondrial fusion in the astrocyte cell bodies, but not the processes, under the same conditions of rotenone treatment in which DJ-1 deficiency is known to impair astrocyte-mediated neuroprotection. Our studies therefore demonstrated the following new findings: (i) DJ-1 deficiency can impair astrocyte mitochondrial physiology at multiple levels, (ii) astrocyte
The cyclophilin D/Drp1 axis regulates mitochondrial fission contributing to oxidative stress-induced mitochondrial dysfunctions in SH-SY5Y cells

International Nuclear Information System (INIS)

Xiao, Anqi; Gan, Xueqi; Chen, Ruiqi; Ren, Yanming; Yu, Haiyang; You, Chao

2017-01-01

Oxidative stress plays a central role in the pathogenesis of various neurodegenerative diseases. Increasing evidences have demonstrated that structural abnormalities in mitochondria are involved in oxidative stress related nerve cell damage. And Drp1 plays a critical role in mitochondrial dynamic imbalance insulted by oxidative stress-derived mitochondria. However, the status of mitochondrial fusion and fission pathway and its relationship with mitochondrial properties such as mitochondrial membrane permeability transition pore (mPTP) have not been fully elucidated. Here, we demonstrated for the first time the role of Cyclophilin D (CypD), a crucial component for mPTP formation, in the regulation of mitochondrial dynamics in oxidative stress treated nerve cell. We observed that CypD-mediated phosphorylation of Drp1 and subsequently augmented Drp1 recruitment to mitochondria and shifts mitochondrial dynamics toward excessive fission, which contributes to the mitochondrial structural and functional dysfunctions in oxidative stress-treated nerve cells. CypD depletion or over expression accompanies mitochondrial dynamics/functions recovery or aggravation separately. We also demonstrated first time the link between the CypD to mitochondrial dynamics. Our data offer new insights into the mechanism of mitochondrial dynamics which contribute to the mitochondrial dysfunctions, specifically the role of CypD in Drp1-mediated mitochondrial fission. The protective effect of CsA, or other molecules affecting the function of CypD hold promise as a potential novel therapeutic strategy for governing oxidative stress pathology via mitochondrial pathways. - Highlights: • Demonstrated first time the link between the mPTP to mitochondrial dynamics. • The role of Cyclophilin D in the regulation of Drp1-mediated mitochondrial fission. • CsA as a potential target for governing oxidative stress related neuropathology.
Fatal outbreak of botulism in Greenland

DEFF Research Database (Denmark)

Hammer, Tóra Hedinsdottir; Jespersen, Sanne; Kanstrup, Jakob

2015-01-01

respiratory muscle paralysis. We present five cases of foodborne botulism occurring in Greenland, two with fatal outcome, caused by ingestion of tradionally preserved eider fowl. In the cases of the survivors, antitoxin and supportive care, including mechanical ventilation, were administered. In these cases...
Fatal anaphylactoid reaction following ioversol administration

NARCIS (Netherlands)

Jansman, Frank G. A.; Kieft, Hans; Harting, Johannes W.

2007-01-01

We report a fatal intravenous ioversol administration in a 60-year old male patient. Although the introduction of new low-osmolar non-ionogenic contrast media with a more favourable efficacy-toxicity balance has diminished the side-effects significantly, everyone involved in radiodiagnostic
21 CFR 880.5270 - Neonatal eye pad.

Science.gov (United States)

2010-04-01

... DEVICES GENERAL HOSPITAL AND PERSONAL USE DEVICES General Hospital and Personal Use Therapeutic Devices § 880.5270 Neonatal eye pad. (a) Identification. A neonatal eye pad is an opaque device used to cover... 21 Food and Drugs 8 2010-04-01 2010-04-01 false Neonatal eye pad. 880.5270 Section 880.5270 Food...
CaMKII determines mitochondrial stress responses in heart

Science.gov (United States)

Joiner, Mei-ling A.; Koval, Olha M.; Jingdong, Li; He, B. Julie; Allamargot, Chantal; Gao, Zhan; Luczak, Elizabeth D.; Hall, Duane D.; Fink, Brian D.; Chen, Biyi; Yang, Jinying; Moore, Steven A.; Scholz, Thomas D.; Strack, Stefan; Mohler, Peter J.; Sivitz, William I.; Song, Long-Sheng; Anderson, Mark E.

2012-01-01

Myocardial cell death is initiated by excessive mitochondrial Ca2+ entry, causing Ca2+ overload, mitochondrial permeability transition pore (mPTP) opening and dissipation of the mitochondrial inner membrane potential (ΔΨm)1,2. However, the signaling pathways that control mitochondrial Ca2+ entry through the inner membrane mitochondrial Ca2+ uniporter (MCU)3–5 are not known. The multifunctional Ca2+ and calmodulin-dependent protein kinase II (CaMKII) is activated in ischemia reperfusion (I/R), myocardial infarction (MI) and neurohumoral injury, common causes of myocardial death and heart failure, suggesting CaMKII could couple disease stress to mitochondrial injury. Here we show that CaMKII promotes mPTP opening and myocardial death by increasing MCU current (IMCU). Mitochondrial-targeted CaMKII inhibitory protein or cyclosporin A (CsA), an mPTP antagonist with clinical efficacy in I/R injury6, equivalently prevent mPTP opening, ΔΨm deterioration and diminish mitochondrial disruption and programmed cell death in response to I/R injury. Mice with myocardial and mitochondrial-targeted CaMKII inhibition are resistant to I/R injury, MI and neurohumoral injury, suggesting pathological actions of CaMKII are substantially mediated by increasing IMCU. Our findings identify CaMKII activity as a central mechanism for mitochondrial Ca2+ entry and suggest mitochondrial-targeted CaMKII inhibition could prevent or reduce myocardial death and heart failure dysfunction in response to common experimental forms of pathophysiological stress. PMID:23051746
Neonatal bacteriemia isolates and their antibiotic resistance pattern in neonatal insensitive care unit (NICU at Beasat Hospital, Sanandaj, Iran.

Directory of Open Access Journals (Sweden)

Parvin Mohammadi

2014-05-01

Full Text Available Bacteremia continues to result in significant morbidity and mortality, particularly among neonates. There is scarce data on neonatal bacteremia in among Iranian neonates. In this study, we determined neonatal bacteremia isolates and their antibiotic resistance pattern in neonatal insensitive care unit at Beasat hospital, Sanandaj, Iran. During one year, all neonates admitted to the NICU were evaluated. Staphylococcal isolates were subjected to determine the prevalence of MRS and mecA gene. A total of 355 blood cultures from suspected cases of sepsis were processed, of which 27 (7.6% were positive for bacterial growth. Of the 27 isolates, 20 (74% were Staphylococcus spp as the leading cause of bacteremia. The incidence of Gram negative bacteria was 04 (14.8%. The isolated bacteria were resistant to commonly used antibiotics. Maximum resistance among Staphylococcus spp was against Penicillin, and Ampicillin. In our study, the isolated bacteria were 7.5 % Vancomycin and Ciprofloxacin sensitive. Oxacillin disk diffusion and PCR screened 35% and 30% mec a positive Staphylococcus spp. The spectrum of neonatal bacteremia as seen in NICU at Beasat hospital confirmed the importance of pathogens such as Staphylococcus spp. Penicillin, Ampicillin and Cotrimoxazol resistance was high in theses isolates with high mecA gene carriage, probably due to antibiotic selection.
Reduced nephron endowment in the neonates of Indigenous Australian peoples.

Science.gov (United States)

Kandasamy, Y; Smith, R; Wright, I M R; Lumbers, E R

2014-02-01

Rates of chronic kidney disease (CKD) among Indigenous groups in Australia exceed non-Indigenous rates eight-fold. Using kidney volume as a surrogate for nephron number, we carried out a study to determine if Indigenous neonates have a smaller kidney volume (and thus a reduced nephron number) from birth compared with non-Indigenous neonates. We recruited term and preterm neonates (Indigenous) and 39 term (13 Indigenous) neonates. TKV of Indigenous neonates was significantly lower at 32 weeks [12.0 (2.0) v. 15.4 (5.1) ml; P=0.03] and 38 weeks CA [18.6 (4.0) v. 22.6 (5.9) ml; P=0.04] respectively. Term Indigenous neonates also had smaller kidney volumes compared with non-Indigenous neonates. Despite a smaller kidney volume (and reduced nephron number), Indigenous neonates did not have a significantly lower eGFR. Indigenous neonates achieve similar eGFRs to Non-Indigenous neonates, presumably through a higher single nephron filtration rate. This places Indigenous neonates at a greater risk of long-term kidney damage later in life.
Neonatal herpes in Denmark 1977-1991

DEFF Research Database (Denmark)

Fonnest, G; de la Fuente Fonnest, I; Weber, Tom

1997-01-01

BACKGROUND: To prevent neonatal herpes, women in labor with genital herpes infection are still delivered by Cesarean section. This policy is currently being debated. The aim of this study was to determine the incidence of neonatal herpes in Denmark and to evaluate the prevention practice. METHODS...... herpes recurrence. Four infants had a serious infection in spite of Cesarean section. This study does not support a policy of Cesarean section in case of maternal recurrent herpes simplex infection at delivery.......BACKGROUND: To prevent neonatal herpes, women in labor with genital herpes infection are still delivered by Cesarean section. This policy is currently being debated. The aim of this study was to determine the incidence of neonatal herpes in Denmark and to evaluate the prevention practice. METHODS......: All newborns with perinatal herpes in Denmark 1977-1991 were identified from hospital-records. RESULTS: Of 862,298 deliveries 136 possible cases were found but only 30 (22%) fulfilled the criteria for neonatal herpes. The incidence increased from 2.36 to 4.56 per 100,000 live births during 1977...

Some links on this page may take you to non-federal websites. Their policies may differ from this site.