A multicentric, double-blind randomized, homoeopathic pathogenetic trial of Allium sativum

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Raj K Manchanda

2016-01-01

Conclusion: The pathogenetic response elicited during the proving trial expands the scope of use of the drug A. sativum and will benefit the research scholars and clinicians. The generated symptoms of this drug will carry more value when verified clinically.

Sirt1 Protects against Oxidative Stress-Induced Apoptosis in Fibroblasts from Psoriatic Patients: A New Insight into the Pathogenetic Mechanisms of Psoriasis

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Matteo Becatti

2018-05-01

Full Text Available Psoriasis, a multisystem chronic disease characterized by abnormal keratinocyte proliferation, has an unclear pathogenesis where systemic inflammation and oxidative stress play mutual roles. Dermal fibroblasts, which are known to provide a crucial microenvironment for epidermal keratinocyte function, represented the selected experimental model in our study which aimed to clarify the potential role of SIRT1 in the pathogenetic mechanisms of the disease. We firstly detected the presence of oxidative stress (lipid peroxidation and total antioxidant capacity, significantly reduced SIRT1 expression level and activity, mitochondrial damage and apoptosis (caspase-3, -8 and -9 activities in psoriatic fibroblasts. Upon SIRT1 activation, redox balance was re-established, mitochondrial function was restored and apoptosis was no longer evident. Furthermore, we examined p38, ERK and JNK activation, which was strongly altered in psoriatic fibroblasts, in response to SIRT1 activation and we measured caspase-3 activity in the presence of specific MAPK inhibitors demonstrating the key role of the SIRT1 pathway against apoptotic cell death via MAPK modulation. Our results clearly demonstrate the involvement of SIRT1 in the protective mechanisms related to fibroblast injury in psoriasis. SIRT1 activation exerts an active role in restoring both mitochondrial function and redox balance via modulation of MAPK signaling. Hence, SIRT1 can be proposed as a specific tool for the treatment of psoriasis.

Insulin Resistance and Cancer Risk: An Overview of the Pathogenetic Mechanisms

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Biagio Arcidiacono

2012-01-01

Full Text Available Insulin resistance is common in individuals with obesity or type 2 diabetes (T2D, in which circulating insulin levels are frequently increased. Recent epidemiological and clinical evidence points to a link between insulin resistance and cancer. The mechanisms for this association are unknown, but hyperinsulinaemia (a hallmark of insulin resistance and the increase in bioavailable insulin-like growth factor I (IGF-I appear to have a role in tumor initiation and progression in insulin-resistant patients. Insulin and IGF-I inhibit the hepatic synthesis of sex-hormone binding globulin (SHBG, whereas both hormones stimulate the ovarian synthesis of sex steroids, whose effects, in breast epithelium and endometrium, can promote cellular proliferation and inhibit apoptosis. Furthermore, an increased risk of cancer among insulin-resistant patients can be due to overproduction of reactive oxygen species (ROS that can damage DNA contributing to mutagenesis and carcinogenesis. On the other hand, it is possible that the abundance of inflammatory cells in adipose tissue of obese and diabetic patients may promote systemic inflammation which can result in a protumorigenic environment. Here, we summarize recent progress on insulin resistance and cancer, focusing on various implicated mechanisms that have been described recently, and discuss how these mechanisms may contribute to cancer initiation and progression.

URINARY INFECTION IN CHILDREN: PATHOGENETICAL DISORDERS AND THEIR CORRECTION FOR THE PROPHYLAXIS OF EXACERBATION

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V.I. Kirillov

2011-01-01

Full Text Available Authors present the results of a study of pathogenetic mechanisms leading to the urinary tract infections in children with vesicoureteric reflux. Urine pH test with ammonium chloride detected decreasing of acidogenetic function of kidneys in children with urinary tract infection. Conventional antibacterial treatment of acute urinary tract infection combined with herbal medication Canephron N resulted in restoration of acidogenetic function of distal tubules and reducing of inflammation in urinary tract. Supportive treatment with herbal medication normalized urine flow with minimization of residual portion of urine. The treatment resulted in decrease of risk of recurrent urinary tract infections including pyelonephritic ones.Key words: children, urinary infections, vesico-ureter reflux, antibacterial treatment, Canephron N, treatment.(Voprosy sovremennoi pediatrii — Current Pediatrics. 2011; 10 (4: 100–104

Role of growth factors in molecular pathogenetic mechanism of radiation pulmonary fibrosis

International Nuclear Information System (INIS)

Liu Chunjie; Wang Dewen; Gao Yabing

2000-01-01

Objective: To investigate the role of growth factors and their receptors in radiation pulmonary fibrosis(RPF). Methods: Immunohistochemistry, immunocytochemistry and in situ hybridization were used. Results: The normal rat lung tissue weakly expressed TGFβ1 and TGFβ receptor (TGFβR).The expression of TGFβ1 in rat lung increased at 2 weeks after irradiation and its highest level maintained from 8 weeks to 3 months. The positive localization of TGFβ1 in lung was the epithelial cells of bronchi, alveolar macrophages, alveolar epithelial cells, smooth muscle cells of the bronchial and arteriolar wall and fibroblasts. The expression of TGFβ2 was similar to that of TGFβ1. The time of increased expression of TGFβR was later than that of TGFβ1.i,e. It increased at 8 weeks and kept a higher level of expression throughout one year. Stronger expressions of the bFGF and PDGF were also observed in 2-3 months postirradiation. The expression of TGFβ1 in the cells of bronchoalveolar lavage fluid was investigated. The results showed that macrophages were one of the earliest cells showing positive reaction,i,e. they presented positive at 1 week. For the cultured Wistar rat lung fibroblasts, TGFβ1 expression was stronger at 3 months postirradiation. By means of in situ hybridization with TGFβ1 probe and α1(I) oligonucleotide probe, the expression of TGFβ1 mRNA was increased at 2-8 weeks and α1(I) pro-collagen mRAN was increased at 6 weeks, but the expression peak appeared at 3 months postirradiation. The expressions of TGFβ1 and α1(I) pro-collagen were mutually connected and overlapped both in time and space. Conclusion: TGFβ1 may play an important role in the pathogenesis of RPF. TGFβ2, TGFβR, bFGF and PDGF-A also participate in the pathogenetic process

Etiopathogenetic mechanisms of fibromyalgia syndrome

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R.H. Gracely

2011-09-01

Full Text Available Fibromyalgia syndrome (FMS is a common chronic condition of widespread pain with causal mechanisms that are largely unknown. It is characterized by moderate to severe musculoskel - etal pain and allodynia, but its pathogenesis appears confined to the nociceptive structures of the central nervous system. From a pathogenetic point of view, indeed, no clear muscle pathology has been demonstrated in FMS (1, 2, while increasing evidence suggests a disturbance in pain perception that is genetically conditioned. In our review we will consider five “keypoints” that we think determine the origin and maintenance of the pain syndrome that we define as fibromyalgia...

A systematic review of the quality of homeopathic pathogenetic trials published from 1945 to 1995.

Science.gov (United States)

Dantas, F; Fisher, P; Walach, H; Wieland, F; Rastogi, D P; Teixeira, H; Koster, D; Jansen, J P; Eizayaga, J; Alvarez, M E P; Marim, M; Belon, P; Weckx, L L M

2007-01-01

The quality of information gathered from homeopathic pathogenetic trials (HPTs), also known as 'provings', is fundamental to homeopathy. We systematically reviewed HPTs published in six languages (English, German, Spanish, French, Portuguese and Dutch) from 1945 to 1995, to assess their quality in terms of the validity of the information they provide. The literature was comprehensively searched, only published reports of HPTs were included. Information was extracted by two reviewers per trial using a form with 87 items. Information on: medicines, volunteers, ethical aspects, blinding, randomization, use of placebo, adverse effects, assessments, presentation of data and number of claimed findings were recorded. Methodological quality was assessed by an index including indicators of internal and external validity, personal judgement and comments of reviewers for each study. 156 HPTs on 143 medicines, involving 2815 volunteers, produced 20,538 pathogenetic effects (median 6.5 per volunteer). There was wide variation in methods and results. Sample size (median 15, range 1-103) and trial duration (mean 34 days) were very variable. Most studies had design flaws, particularly absence of proper randomization, blinding, placebo control and criteria for analysis of outcomes. Mean methodological score was 5.6 (range 4-16). More symptoms were reported from HPTs of poor quality than from better ones. In 56% of trials volunteers took placebo. Pathogenetic effects were claimed in 98% of publications. On average about 84% of volunteers receiving active treatment developed symptoms. The quality of reports was in general poor, and much important information was not available. The HPTs were generally of low methodological quality. There is a high incidence of pathogenetic effects in publications and volunteers but this could be attributable to design flaws. Homeopathic medicines, tested in HPTs, appear safe. The central question of whether homeopathic medicines in high dilutions can

[Pathogenetic relationship between pterygium and dry eye syndrome (clinical and cytological study)].

Science.gov (United States)

Petraevskiĭ, A V; Trishkin, K S

2014-01-01

To study the prevalence of dry eye syndrome in patients with initial primary pterygium for determination of a possible pathogenetic role of dry eye syndrome in the development of pterygium. 30 patients with initial primary pterygium; besides conventional ophthalmic assessment, cytological examination of bulbar conjunctiva was performed in all cases. Signs of dry eye syndrome, of similar severity in both eyes, were found in 100% of patients. Dry eye can be one of the precipitating factors of primary pterygium.

Relationship between ocular surface temperature and peripheral vasoconstriction in healthy subjects: A thermographic study

DEFF Research Database (Denmark)

Matteoli, Sara; Vannetti, Federica; Finocchio, Lucia

2014-01-01

An impairment of ocular blood flow regulation is commonly considered one of the main pathogenetic mechanisms involved in the development of several eye diseases, like glaucoma. The aim of this study was to investigate whether an alteration of ocular blood supply induced by peripheral vasoconstric......An impairment of ocular blood flow regulation is commonly considered one of the main pathogenetic mechanisms involved in the development of several eye diseases, like glaucoma. The aim of this study was to investigate whether an alteration of ocular blood supply induced by peripheral...

Virological Mechanisms in the Coinfection between HIV and HCV

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Maria Carla Liberto

2015-01-01

Full Text Available Due to shared transmission routes, coinfection with Hepatitis C Virus (HCV is common in patients infected by Human Immunodeficiency Virus (HIV. The immune-pathogenesis of liver disease in HIV/HCV coinfected patients is a multifactorial process. Several studies demonstrated that HIV worsens the course of HCV infection, increasing the risk of cirrhosis and hepatocellular carcinoma. Also, HCV might increase immunological defects due to HIV and risk of comorbidities. A specific cross-talk among HIV and HCV proteins in coinfected patients modulates the natural history, the immune responses, and the life cycle of both viruses. These effects are mediated by immune mechanisms and by a cross-talk between the two viruses which could interfere with host defense mechanisms. In this review, we focus on some virological/immunological mechanisms of the pathogenetic interactions between HIV and HCV in the human host.

AUTOANTIBODIES TO GLUTAMIC ACID DECARBOXYLASE AS A PATHOGENETIC MARKER OF TYPE I DIABETES MELLITUS

OpenAIRE

N. V. Piven; L. N. Lukhverchyk; A. I. Burakovsky; N. V. Polegenkaya; M. V. Karpovich

2011-01-01

Abstract. A new method of enzyme-linked immunosorbent assay (in solid-phase ELISA format) has been developed to determine concentrations of autoantibodies to glutamic acid decarboxylase, as well as an evidencebased methodology is proposed for its medical implications, as a quantitative pathogenetic predictive marker of autoimmune diagnostics in type 1 diabetes mellitus. This technique could be implied for serial production of diagnostic reagent kits, aimed for detection of autoantibodies to g...

Hemorrhagic fever with renal syndrome: clinical, pathogenetic and therapeutic aspects

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Vera F. Pavelkina

2017-09-01

persists after the basic therapy, which pathogenetically substantiates the necessity of using agents with a detoxification and membrane-protective mechanism of action. The use of remaxol in the complex therapy of HFRS reduces the severity of clinical manifest tations of IS, shortens the oliguric and polyuric periods of the disease, contributes to a decrease in the laboratory indicators of IS and hepatic dysfunction. Discussion and Conclusions: The incidence in the Republic of Mordovia remains high. The cyclicity of HFRS was not always noted in the clinic. The infectious process is accompanied by the development of expressed IS and cytolytic hepatocytes. Normalization of the studied homeostasis indices does not occur to the period of clinical recovery of patients. Remaxol as part of the complex therapy reduces the severity of clinical symptoms of IS and its laboratory indicators. All this things confirm the detoxifying and hepatoprotective efficacy of the drug and indicate the promise of remaxol in clinical practice.

Pathogenic Mechanisms of Atrial Fibrillation in Obesity

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O. M. Drapkina

2016-01-01

Full Text Available Atrial fibrillation (AF is one of the most common arrhythmias. It reduces quality of life and its duration due to thromboembolic complications. Obesity contributes to the structural and electrical remodeling of atrial myocardium. This leads to occurrence of ectopic foci in the mouths of the pulmonary veins and the disruption of normal electrical conduction in the atria. Systemic inflammation, myocardial fibrosis, cardiomyocyte overload by Na+ and Ca2+ ions, accumulation in the cells of unoxidized metabolic products, imbalance of the autonomic regulation are considered as the main mechanisms of arrhythmogenic substrate formation. Hypertension, insulin resistance, and obstructive sleep apnea, associated with obesity, increase the risk of development and progression of the arrhythmia. Study of pathogenetic mechanisms of AF in obesity is necessary to develop new strategies for its prevention and the creation of more effective methods of treatment of these patients.

[Complex pathogenetic treatment schemes of vascular dyscirculatory disorders in the remote period after exposure to low dose radiation].

Science.gov (United States)

Holodova, N B; Zhavoronkova, L A; Ryzhov, B N

2013-01-01

Complex studies including modern methods of investigation of structures and functions of nervous system: electroencephalograsphy (EEG), coherent analysis, neuropsychological study and methods of neuroimaging were performed in 517 participants in liquidation of consequences of the accident (LCA) at the Chernobyl NPP in 1986-1987. Dyscirculatory metabolic encephalopathy was revealed to be the main pathology with the etiological mechanism based on dyscirculatorhypoxic and metabolic disorders. Complexity of the revealed symptoms testified to an early organism aging in remote periods after exposure to low dose radiation. Pathogenetic schemes were developed for treatment of dyscirculatory encephalopathy in liquidators, which include drugs improving blood supply, antiaggregants, antioxidants and metabolites of the brains in various combinations. Taking into consideration that early appearance of vascular dyscirculatory disorders observed in liquidators is the sign of early aging of the organism, geroprotectors were added to treatment schemes.

Mechanical design of a high field common coil magnet

CERN Document Server

Caspi, S; Dietderich, D R; Gourlay, S A; Gupta, R; McInturff, A; Millos, G; Scanlan, R M

1999-01-01

A common coil design for high field 2-in-1 accelerator magnets has been previously presented as a "conductor-friendly" option for high field magnets applicable for a Very Large Hadron Collider. This paper presents the mechanical design for a 14 tesla 2-in-1 dipole based on the common coil design approach. The magnet will use a high current density Nb/sub 3/Sn conductor. The design addresses mechanical issues particular to the common coil geometry: horizontal support against coil edges, vertical preload on coil faces, end loading and support, and coil stresses and strains. The magnet is the second in a series of racetrack coil magnets that will provide experimental verification of the common coil design approach. (9 refs).

iPSC-Based Models to Unravel Key Pathogenetic Processes Underlying Motor Neuron Disease Development

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Irene Faravelli

2014-10-01

Full Text Available Motor neuron diseases (MNDs are neuromuscular disorders affecting rather exclusively upper motor neurons (UMNs and/or lower motor neurons (LMNs. The clinical phenotype is characterized by muscular weakness and atrophy leading to paralysis and almost invariably death due to respiratory failure. Adult MNDs include sporadic and familial amyotrophic lateral sclerosis (sALS-fALS, while the most common infantile MND is represented by spinal muscular atrophy (SMA. No effective treatment is ccurrently available for MNDs, as for the vast majority of neurodegenerative disorders, and cures are limited to supportive care and symptom relief. The lack of a deep understanding of MND pathogenesis accounts for the difficulties in finding a cure, together with the scarcity of reliable in vitro models. Recent progresses in stem cell field, in particular in the generation of induced Pluripotent Stem Cells (iPSCs has made possible for the first time obtaining substantial amounts of human cells to recapitulate in vitro some of the key pathogenetic processes underlying MNDs. In the present review, recently published studies involving the use of iPSCs to unravel aspects of ALS and SMA pathogenesis are discussed with an overview of their implications in the process of finding a cure for these still orphan disorders.

Oro-facial gangrene (noma/cancrum oris): pathogenetic mechanisms.

Science.gov (United States)

Enwonwu, C O; Falkler, W A; Idigbe, E O

2000-01-01

Cancrum oris (Noma) is a devastating infectious disease which destroys the soft and hard tissues of the oral and para-oral structures. The dehumanizing oro-facial gangrenous lesion affects predominantly children ages 2 to 16 years, particularly in sub-Saharan Africa, where the estimated frequency in some communities varies from 1 to 7 cases per 1000 population. The risk factors are poverty, malnutrition, poor oral hygiene, residential proximity to livestock in unsanitary environments, and infectious diseases, particularly measles and those due to the herpesviridae. Infections and malnutrition impair the immune system, and this is the common denominator for the occurrence of noma. Acute necrotizing gingivitis (ANG) and oral herpetic ulcers are considered the antecedent lesions, and ongoing studies suggest that the rapid progression of these precursor lesions to noma requires infection by a consortium of micro-organisms, with Fusobacterium necrophorum (Fn) and Prevotella intermedia (Pi) as the suspected key players. Additional to production of a growth-stimulating factor for Pi, Fn displays a classic endotoxin, a dermonecrotic toxin, a cytoplasmic toxin, and a hemolysin. Without appropriate treatment, the mortality rate from noma is 70-90%. Survivors suffer the two-fold afflictions of oro-facial mutilation and functional impairment, which require a time-consuming, financially prohibitive surgical reconstruction.

AUTOANTIBODIES TO GLUTAMIC ACID DECARBOXYLASE AS A PATHOGENETIC MARKER OF TYPE I DIABETES MELLITUS

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N. V. Piven

2011-01-01

Full Text Available Abstract. A new method of enzyme-linked immunosorbent assay (in solid-phase ELISA format has been developed to determine concentrations of autoantibodies to glutamic acid decarboxylase, as well as an evidencebased methodology is proposed for its medical implications, as a quantitative pathogenetic predictive marker of autoimmune diagnostics in type 1 diabetes mellitus. This technique could be implied for serial production of diagnostic reagent kits, aimed for detection of autoantibodies to glutamic acid decarboxylase by means of ELISA approach. (Med. Immunol., 2011, vol. 13, N 2-3, pp 257-260

Disappearance of some autonomously functioning thyroid nodules following TSH stimulation: Pathogenetic hypothesis

Energy Technology Data Exchange (ETDEWEB)

Vattimo, A.; Pisani, M.; Martini, G.

1983-04-01

The disappearance of a hot nodule following TSH stimulation has been observed in 6 subjects with autonomously functioning thyroid nodule, in the thyroid scan obtained using sup(99m)Tc-pertechnetate and /sup 131/I. These findings have been related by many workers to the hyperreactivity of the nodular tissue to TSH: the disappearance of the nodule is due to a more rapid turnover of the tracer. In this work a new pathogenetic hypothesis is proposed: the disappearance of hot thyroid nodules might be due to ischaemia induced by the reaction of the healthy tissue, which had previously been inhibited. This hypothesis is confirmed by the scans performed shortly after administration of the tracers.

Disappearance of some autonomously functioning thyroid nodules following TSH stimulation: Pathogenetic hypothesis

International Nuclear Information System (INIS)

Vattimo, A.; Pisani, M.; Martini, G.

1983-01-01

The disappearance of a hot nodule following TSH stimulation has been observed in 6 subjects with autonomously functioning thyroid nodule, in the thyroid scan obtained using sup(99m)Tc-pertechnetate and 131 I. These findings have been related by many workers to the hyperreactivity of the nodular tissue to TSH: the disappearance of the nodule is due to a more rapid turnover of the tracer. In this work a new pathogenetic hypothesis is proposed: the disappearance of hot thyroid nodules might be due to ischaemia induced by the reaction of the healthy tissue, which had previously been inhibited. This hypothesis is confirmed by the scans performed shortly after administration of the tracers. (orig.) [de

Clinical and imaging features of intracranial arterial aneurysms in the pediatric population; Klinische und radiologische Merkmale des intrakraniellen arteriellen Aneurysmas bei Kindern und Jugendlichen

Energy Technology Data Exchange (ETDEWEB)

Abruzzo, Todd A. [Cincinnati Children' s Hospital Medical Center, Cincinnati, OH (United States). Dept. of Radiology; Aeron, Gunjan; Jones, Blaise V.

2013-07-15

Intracranial arterial aneurysms (IAAs) are rare in children. Nevertheless, IAAs account for at least 10 % - 15 % of hemorrhagic strokes during the first two decades of life. Traditional vascular risk factors, which are common in the adult population, are generally absent in the pediatric population, engendering distinct modes of IAA pathogenesis. Classification of pediatric IAAs according to the pathogenetic mechanism shows eight distinct categories: idiopathic, traumatic, those due to excessive hemodynamic stress, vasculopathic, infectious, noninfectious inflammatory, oncotic, and familial. Pathogenetic mechanism is the best predictor of the clinical course of the disease, response to treatment, and long-term prognosis. The pathogenetic subtypes of pediatric IAA show characteristic and variably overlapping features. In most cases, IAAs manifesting during the first two decades of life are idiopathic. IAAs that are idiopathic, traumatic (second most common type), or due to excessive hemodynamic stresses (third most common type) account for more than 80 % of IAAs in the pediatric age group. Most of the remaining pediatric IAAs are the result of congenital cerebral aneurysmal arteriopathies or infection. Multiple IAAs are unusual in young children except in those with acquired (secondary to immune deficiency states) or congenital cerebral aneurysmal arteriopathies or infectious IAAs. (orig.)

Clinical and imaging features of intracranial arterial aneurysms in the pediatric population

International Nuclear Information System (INIS)

Abruzzo, Todd A.; Aeron, Gunjan; Jones, Blaise V.

2013-01-01

Intracranial arterial aneurysms (IAAs) are rare in children. Nevertheless, IAAs account for at least 10 % - 15 % of hemorrhagic strokes during the first two decades of life. Traditional vascular risk factors, which are common in the adult population, are generally absent in the pediatric population, engendering distinct modes of IAA pathogenesis. Classification of pediatric IAAs according to the pathogenetic mechanism shows eight distinct categories: idiopathic, traumatic, those due to excessive hemodynamic stress, vasculopathic, infectious, noninfectious inflammatory, oncotic, and familial. Pathogenetic mechanism is the best predictor of the clinical course of the disease, response to treatment, and long-term prognosis. The pathogenetic subtypes of pediatric IAA show characteristic and variably overlapping features. In most cases, IAAs manifesting during the first two decades of life are idiopathic. IAAs that are idiopathic, traumatic (second most common type), or due to excessive hemodynamic stresses (third most common type) account for more than 80 % of IAAs in the pediatric age group. Most of the remaining pediatric IAAs are the result of congenital cerebral aneurysmal arteriopathies or infection. Multiple IAAs are unusual in young children except in those with acquired (secondary to immune deficiency states) or congenital cerebral aneurysmal arteriopathies or infectious IAAs. (orig.)

Revisited the relationship between vitamin D level and receptors of BsmI- gene polymorphism with the pathogenetic mechanisms of placental dysfunction development

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G. S. Manasova

2018-03-01

Full Text Available The role of the calcitriol / vitamin D receptor (VD endocrine system and the pleiotropic effects of this system in the pathogenetic mechanisms of various diseases development, in particular complications of pregnancy, has attracted researches’ increasing attention in recent years. The aim of the work: to compare the VD-status and frequency of occurrence of polymorphism of the VDR gene (BsmI (A> G, rs1544410 in patients with a physiological course of the gestation process and in patients with placental dysfunction (PD. Materials and methods. 56 pregnant women with PD (the main group and 40 patients with a physiological pregnancy (control group were examined. VD status was determined by ELISA at level 25 (OH D in serum, the frequency of BsmI polymorphism of the VDR gene (rs1544410 by polymerase chain reaction (PCR. Results. The average index of VD (31.40 ± 8.6 ng / ml in patients with PD is significantly lower than in patients with physiological pregnancy (43.54 ± 11.20 ng / ml, (p ≤ 0.05 . In patients with PD, homozygous carrier for the A-allele was found in 12% of cases, in healthy pregnant women - in 16.7%, (р ≥ 0.05, for the G-allele - in 20% and 47.20%, (р ≤ 0.01 cases, respectively to groups. Heterozygous combination of A / G alleles was noted in 68% of patients with PD and in 36.10% of the control group patients. In pregnant women with BsmI polymorphism of calcitriol gene (genotype A / G PD was 3.7 times more frequent (68% vs 36.10% : RR = 2.1, CI 1.0-6.6, OR = 3.7, CI 1.1-13.1. Conclusions. Vitamin D insufficiency or deficiency can be one of the reasons of PD formation. In carriers of BsmIgene’s polymorphism encoding VD receptor with genotype A / G, the course of pregnancy is complicated by placental dysfunction 3.7 times more often than in women without this polymorphism.

Identification of Toxic Pyrrolizidine Alkaloids and Their Common Hepatotoxicity Mechanism

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Xinmiao Yan

2016-03-01

Full Text Available Pyrrolizidine Alkaloids (PAs are currently one of the most important botanical hepatotoxic ingredients. Glutathion (GSH metabolism is the most reported pathway involved in hepatotoxicity mechanism of PAs. We speculate that, for different PAs, there should be a common mechanism underlying their hepatotoxicity in GSH metabolism. Computational methods were adopted to test our hypothesis in consideration of the limitations of current experimental approaches. Firstly, the potential targets of 22 PAs (from three major PA types in GSH metabolism were identified by reverse docking; Secondly, glutathione S-transferase A1 (GSTA1 and glutathione peroxidase 1 (GPX1 targets pattern was found to be a special characteristic of toxic PAs with stepwise multiple linear regressions; Furthermore, the molecular mechanism underlying the interactions within toxic PAs and these two targets was demonstrated with the ligand-protein interaction analysis; Finally, GSTA1 and GPX1 were proved to be significant nodes in GSH metabolism. Overall, toxic PAs could be identified by GSTA1 and GPX1 targets pattern, which suggests their common hepatotoxicity mechanism: the interfering of detoxication in GSH metabolism. In addition, all the strategies developed here could be extended to studies on toxicity mechanism of other toxins.

Identification of Toxic Pyrrolizidine Alkaloids and Their Common Hepatotoxicity Mechanism.

Science.gov (United States)

Yan, Xinmiao; Kang, Hong; Feng, Jun; Yang, Yiyan; Tang, Kailin; Zhu, Ruixin; Yang, Li; Wang, Zhengtao; Cao, Zhiwei

2016-03-07

Pyrrolizidine Alkaloids (PAs) are currently one of the most important botanical hepatotoxic ingredients. Glutathion (GSH) metabolism is the most reported pathway involved in hepatotoxicity mechanism of PAs. We speculate that, for different PAs, there should be a common mechanism underlying their hepatotoxicity in GSH metabolism. Computational methods were adopted to test our hypothesis in consideration of the limitations of current experimental approaches. Firstly, the potential targets of 22 PAs (from three major PA types) in GSH metabolism were identified by reverse docking; Secondly, glutathione S-transferase A1 (GSTA1) and glutathione peroxidase 1 (GPX1) targets pattern was found to be a special characteristic of toxic PAs with stepwise multiple linear regressions; Furthermore, the molecular mechanism underlying the interactions within toxic PAs and these two targets was demonstrated with the ligand-protein interaction analysis; Finally, GSTA1 and GPX1 were proved to be significant nodes in GSH metabolism. Overall, toxic PAs could be identified by GSTA1 and GPX1 targets pattern, which suggests their common hepatotoxicity mechanism: the interfering of detoxication in GSH metabolism. In addition, all the strategies developed here could be extended to studies on toxicity mechanism of other toxins.

Clinical and pathogenetic approaches to development of parodontitis therapy in patients with chronic hepatitis С

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E.N. Blinnikova

2010-06-01

Full Text Available The research goal in to determine clinical and pathogenetic efficacy of Cycloferon liniment in the combined therapy of parodontitis in patients with chronic hepatitis C. Examination and treatment of 50 patients were conducted. It was revealed that the use of Cycloferon liniment in the combined treatment of patients with parodontitis accompanied by chronic hepatitis C allowed to accelerate process of normalization of lipid peroxidation and antioxidant potential of blood, to decrease infectious inflammation (herpes simplex virus I, candida albicans, staphylococcus aureus in parodontal recess and local inflammation. The described method of treatment provided process of recovery and decrease in frequency of parodontitis recurrences

Anencephaly with incomplete twinning (diprosopus).

Science.gov (United States)

Riccardi, V M; Bergmann, C A

1977-10-01

A case of diprosopus with anencephaly is presented. It is suggested that such concurrence of neural tube defects and incomplete twinning corroborates the notion that a single pathogenetic mechanism may be common to both neural tube defects and monozygotic twinning.

My Non-Restorative Sleep Syndrome

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Chakravarthy Ambar

2000-01-01

Full Text Available Personal experience of systemic effects of late night sleep deprivation and non-restorative sleep-a common experience amongst doctors, has been described. Results of some simple self-experimentations have been mentioned to highlight the possible pathogenetic mechanisms.

The pathogenetic significance of low iodine intake in non-endemic goiter

International Nuclear Information System (INIS)

Harriet, D.P.; Rigshospitalet, Copenhagen

1977-01-01

The blood inorganic iodine concentration (BII), the radioiodide clearance and the absolute iodine uptake (AIU) were determined in 27 patients with simple goiter and in 21 controls. The purpose was to evaluate the pathogenetic significance of low iodine intake for the formation of sporadic goiter. An early thyroid radioiodide clearance was measured by 132 I (5-30 min post injection), and the BII values were bases on the specific activity of I in saliva. The median BII levels of patients and controls were 1.1 and 1.5 μg/l respectively, and the urinary iodine excretion 67 and 79 μg/day respectively, the difference was not significant. The radioiodide clearance was above the normal range in 13 out of 27 patients, and 16 of 27 patients had elevated or high normal AIU values. These patients included 7 out of 9 patients with diffuse, shortlasting goiter; the AIU of those with nodular goiter ranged from slightly subnormal to elevated. Only one exhibited a typical iodine deficiency pattern of very low BII, high radioiodide clearance and normal AIU. (orig.) [de

Mechanisms of protein misfolding in conformational lung diseases.

LENUS (Irish Health Repository)

McElvaney, N G

2012-08-01

Genetic or environmentally-induced alterations in protein structure interfere with the correct folding, assembly and trafficking of proteins. In the lung the expression of misfolded proteins can induce a variety of pathogenetic effects. Cystic fibrosis (CF) and alpha-1 antitrypsin (AAT) deficiency are two major clinically relevant pulmonary disorders associated with protein misfolding. Both are genetic diseases the primary causes of which are expression of mutant alleles of the cystic fibrosis transmembrane conductance regulator (CFTR) and SERPINA1, respectively. The most common and best studied mutant forms of CFTR and AAT are ΔF508 CFTR and the Glu342Lys mutant of AAT called ZAAT, respectively. Non-genetic mechanisms can also damage protein structure and induce protein misfolding in the lung. Cigarette-smoke contains oxidants and other factors that can modify a protein\\'s structure, and is one of the most significant environmental causes of protein damage within the lung. Herein we describe the mechanisms controlling the folding of wild type and mutant versions of CFTR and AAT proteins, and explore the consequences of cigarette-smoke-induced effects on the protein folding machinery in the lung.

Concerning pathogenetic role of breakdown of calcium metabolism in development of angiodystonic syndrome of vibration disease

Energy Technology Data Exchange (ETDEWEB)

Kolomiets, V.V.

1987-10-01

Aim of work is to explain role of disbalance of calcium in vascular disturbances in patients with angiodystonic syndrome of vibration disease (VD), which is accompanied by shifts in calcium metabolism. An experiment was conducted on healthy controls and miners in different stages of VD as follows: condition of hemodynamics was evaluated in subjects (1) at rest; (2) 15 min after internal introduction of calcium chloride (causing hypercalcemia); and (3) after a dose of calcitonin (causing hypocalcemia). Measurements of correlation of concentration of calcium in blood serum and indices of functional condition of cardiovascular system were made in each case. Experiment demonstrated connection between content of calcium in blood serum and tonicity of resistive vessels. For majority of those investigated of all groups, hypercalcemia was accompanied by increased tonicity of peripheral vessels and their reduced blood-filling and more expressed angiodystonia in patients with VD. Introduction of calcitonin lowers level of calcium in blood and reduced tonicity of arterioles and capillaries. These shifts are clear in patients with VD. Experiment demonstrates statistically reliable connection between the tonicity of resistive vessels and the level of serum ionized calcium of individuals with the angiodystonic syndrome of VD. Breakdowns of exchange of calcium along with other mechanisms play a definite pathogenetic role in development of angiodystonic syndrome of VD and must be considered in treating patients with the disease. 14 refs.

The human immune response to streptococcal extracellular antigens: clinical, diagnostic, and potential pathogenetic implications.

Science.gov (United States)

Johnson, Dwight R; Kurlan, Roger; Leckman, James; Kaplan, Edward L

2010-02-15

Determination of an immune response to group A Streptococcus (GAS) antigens, frequently anti-streptolysin O and anti-DNase B, is crucial for documentation of bona fide GAS infection. Although the importance of immunologic confirmation of infection is widely accepted, the immediate and long-term immunokinetics of the human antibody response are incompletely documented and poorly understood. Pediatric study participants (n = 160) were followed during a 2-year study with monthly throat cultures (n = 3491) and blood samples (n = 1679) obtained every 13 weeks. Recovered GAS were characterized; serum anti-streptolysin O and anti-DNase B antibody titers were determined. Antibody titers and GAS culture results were temporally correlated and analyzed. The analyses clearly document, in some instances for the first time, that an increase in antibody titer more accurately defines infection than does an absolute titer (eg, "upper limit of normal"), that antibody titers can remain elevated for many months even without GAS, and that some individuals may harbor GAS continuously for months or years without symptoms of infection and without an associated immune response. Measuring 2 different antibodies is more accurate in defining infection. Single time-point cultures and single antibody titers are often misleading. Sequential samples more accurately define infection, allowing correlation of titer increases with temporal confirmation of GAS acquisition. Understanding kinetics of the immune response(s) to GAS infection is necessary in formulating accurate clinical diagnostic conclusions, to appropriate design of clinical and epidemiological studies examining the association of GAS with subsequent sequelae, and to providing insight into pathogenetic mechanisms associated with this important human pathogen.

Clinical and Pathogenetic Significance of Osteoassociated Microelements in the Joint Diseases. Report I. Microelementosis in the Blood

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O.V. Syniachenko

2016-04-01

Full Text Available Relevance. Microelementosis (imbalance in the body of certain microelements — ME is considered as one of the most important clinical and pathogenetic components of degenerative and inflammatory joint diseases, and ME can play the role of co-factors involved in the processes of articular inflammation. The objective: to study the levels in the blood serum and to assess the clinical and pathogenetic significance of osteoassociated ME (cobalt — Co, copper — Cu, iron — Fe, litium — Li, manganese — Mn, lead — Pb, strontium — Sr, zinc — Zn in a variety of arthritis — rheumatoid (RA, Chlamydia-induced urogenital reactive arthritis (ReA, psoriatic (PsA, gouty (GA and osteoarthritis (OA. Material and methods. There were 262 patients under observation, among them 89 persons suffering from RA, 31 — ReA, 35 — PsA, 49 — GA and 58 — OA. The distribution of males and females in these groups were 1 : 2, 2 : 1, 1 : 1, 11 : 1, 1 : 3, respectively, the average age of the patients was 47, 34, 42, 48 and 58 years, and the duration of clinical manifestations of the disease — 10, 4, 11, 7 and 12 years. ME in the blood serum were studied using atomic absorption spectrometer with electrographite atomizer SolAAr-Mk2-MOZe. Results. Microelementosis in arthritis is manifested by increased blood concentrations of toxic Li, Pb and Sr, moreover, the feature of ReA is a normal ferremia level, PsA — hyperkupremia, and OA — hypozincemia. Microelement blood composition depends on the activity, clinical and laboratory signs of disease, the prevalence of articular process, aggravation of bone destructive changes in the joints (subchondral sclerosis, osteocystosis, bone erosions, epiphyseal osteoporosis, etc, the presence of systemic osteoporosis, spondylopathies (osteochondrosis, spondyloarthrosis and extra-articular manifestations of arthritis (lesions of the skin, muscles, peripheral nervous system, lymph nodes, internal organs. Blood indexes

The Missing Link - Likely Pathogenetic Role of GM3 and Other Gangliosides in the Development of Diabetic Nephropathy

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Igor Vukovic

2015-05-01

Full Text Available Despite scientific advances, diabetic nephropathy remains both a therapeutical challenge, and one of the major diabetic complications. Chemical structure of gangliosides, the most complex of glycosphingolipids, is characterised by one or more sialic acids and carbohydrate groups linked to a ceramide structure. Their potential pathogenetic role in a number of disorders linked to diabetes mellitus has recently been conjectured, due to evidence of their negative modulation of the insulin-mediated signaling and general effects on key cell functions like proliferation, differentiation, apoptosis, cellular signaling and adhesion. Elevated levels of advanced glycation products (AGE usually found in diabetic conditions seem to be responsible for increased concentration of a-series gangliosides in tissues, most notably GM3. GM3 was shown to compromise the renal pericyte and mesangial cell regeneration via the inactivation of VEGF receptor and the receptor-associated Akt signaling pathway. Likewise, the lipid raft theory opened a new research area for GM3 influence, since in the glycosynapse model glycosphingolipids have a key cell-to-cell communication unit with modulating capabilities on signaling receptors. The goal of this review is to provide insight into currently available theories on proposed mechanisms that mark the GM3 as a pathophysiological mediator in the development of diabetic nephropathy.

Overview of mechanisms of cancer chemopreventive agents

International Nuclear Information System (INIS)

De Flora, Silvio; Ferguson, Lynnette R.

2005-01-01

Epidemiological data provide evidence that it is possible to prevent cancer and other chronic diseases, some of which share common pathogenetic mechanisms, such as DNA damage, oxidative stress, and chronic inflammation. An obvious approach is avoidance of exposure to recognized risk factors. As complementary strategies, it is possible to render the organism more resistant to mutagens/carcinogens and/or to inhibit progression of the disease by administering chemopreventive agents. In a primary prevention setting, addressed to apparently healthy individuals, it is possible to inhibit mutation and cancer initiation by triggering protective mechanisms either in the extracellular environment or inside cells, e.g., by modifying transmembrane transport, modulating metabolism, blocking reactive species, inhibiting cell replication, maintaining DNA structure, modulating DNA metabolism and repair, and controlling gene expression. Tumor promotion can be counteracted by inhibiting genotoxic effects, favoring antioxidant and anti-inflammatory activity, inhibiting proteases and cell proliferation, inducing cell differentiation, modulating apoptosis and signal transduction pathways, and protecting intercellular communications. In a secondary prevention setting, when a premalignant lesion has been detected, it is possible to inhibit tumor progression via the same mechanisms, and in addition by affecting the hormonal status and the immune system in various ways, and by inhibiting tumor angiogenesis. Although tertiary prevention, addressed to cancer patients after therapy, is outside the classical definition of chemoprevention, it exploits similar mechanisms. It is also possible to affect cell-adhesion molecules, to activate antimetastasis genes, and to inhibit proteases involved in basement membrane degradation

Five cases of caudal regression with an aberrant abdominal umbilical artery: Further support for a caudal regression-sirenomelia spectrum.

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Duesterhoeft, Sara M; Ernst, Linda M; Siebert, Joseph R; Kapur, Raj P

2007-12-15

Sirenomelia and caudal regression have sparked centuries of interest and recent debate regarding their classification and pathogenetic relationship. Specific anomalies are common to both conditions, but aside from fusion of the lower extremities, an aberrant abdominal umbilical artery ("persistent vitelline artery") has been invoked as the chief anatomic finding that distinguishes sirenomelia from caudal regression. This observation is important from a pathogenetic viewpoint, in that diversion of blood away from the caudal portion of the embryo through the abdominal umbilical artery ("vascular steal") has been proposed as the primary mechanism leading to sirenomelia. In contrast, caudal regression is hypothesized to arise from primary deficiency of caudal mesoderm. We present five cases of caudal regression that exhibit an aberrant abdominal umbilical artery similar to that typically associated with sirenomelia. Review of the literature identified four similar cases. Collectively, the series lends support for a caudal regression-sirenomelia spectrum with a common pathogenetic basis and suggests that abnormal umbilical arterial anatomy may be the consequence, rather than the cause, of deficient caudal mesoderm. (c) 2007 Wiley-Liss, Inc.

PATHOGENETIC MECHANISMS OF CHRONIC ACQUIRED TOXOPLASMOSIS

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Kotsyna S.S.

2015-05-01

Full Text Available Introduction. Toxoplasma gondii is an intracellular protozoan that infects approximately one-third of the world’s population. Infection in human generally occurs through consuming food or drink contaminated with oocysts and tissue cysts from undercooked meat. Although latent infection with Toxoplasma gondii is among the most prevalent of human infections, it has been generally assumed that, except for congenital transmission, it is asymptomatic. Different conditions such as, number of parasite, virulence of the organism, genetic background, sex, and immunological status seem to affect the course of infection The demonstration that Toxoplasma infections can alter behavior, reproductive function in patients has led to a reconsideration of this assumption. During chronic acquired toxoplasmosis (САT identified the regularities of changes in the ratio of the immune system and the basal levels of sex hormones available informative methods, which made it possible to evaluate the severity of the flow chart and predict treatment outcome without resorting to complex research methods. Found that the host-parasite relationships and clinical manifestations of chronic toxoplasmosis depend largely on protective and adaptive responses and compensatory abilities of the human body. Material & methods. 112 patients attended in the 6 Department of Kharkiv Regional Infectious Diseases Hospital №22 (Department of Medical Parasitology and Tropical Diseases of Kharkiv Medical Academy of Postgraduate Education, in Kharkiv, Ukraine were enrolled in the study. Forty four patients (39,3±4,6% were male and sixty eight (60,7±4,6% were female. The age of the patients was 18 till 72 years. Results & discussion. All of 112 CAT patients had subjective clinical symptoms in various combinations: increased fatigue 99,1 ± 0,9%, headache and tiredness 95,5 ± 1,9%, pain in the liver 88,4 ± 3,1%, bitter taste in the mouth 93,8 ± 2,2%, muscle pain 81,3 ± 3,7% and joint pain 69,6 ± 4,3%. Women complained of painful menstruation (57,4 ± 4,7%, irregular menstrual cycle (85,3 ± 3,4%. In the anamnesis of diseases 10,3 ± 2,8% of women had miscarriages and 27,9 ± 4,2% of women had fetal fading. 47,7 ± 4,7% men complained of the decrease in potency. Objective examination: All of 112 CAT patients had lymphadenopathy, 89,3 ± 3,0% patients had subfibryle temperature, 64,3 ± 4,5% of patients had increased sweating, 53.6 ± 4,7% patients had hypertension, increase in liver size was founded in 21,4 ± 3,8% of patients, skin rashes 10,7 ± 3,0%, spleen was enlarged in 66,9 ± 4,4% of patients. Hormonal status: 59 ± 7,4% men have an increased levels of progesterone, 41 ± 7,4% men have an increased levels of estradіol, 13 ± 5,1% men have an decreased levels of testosterone. Women 22±5,0% have an increased levels of testosterone, women 7,0±3,1% have an increased levels of progesterone, 10±3,6% women have an decreased levels of estradіol. Conclusion. The response of host organism to CAT invasion occurs is not the same. It depends on the initial state protective and adaptive capacity of the organism and the liver diseases. This is one of the determining factors of the host-parasite relationship and clinical manifestations of the disease. Prognostic Criterias that determine adaptive-compensatory capacity of the organism in CAT can be basal levels of estradiol, testosterone and progesterone. Physiological differences between men and women play an important role in determining susceptibility to parasitic diseases. The dichotomy in the incidence and severity of many diseases infectious etiology are a strong arguments that the characteristics of men’s physiology and characteristics of women’s physiology are the important factors of the determining susceptibility to disease.

Pathogenetic Mechanisms of Neurogenic Pulmonary Edema

Czech Academy of Sciences Publication Activity Database

Šedý, Jiří; Kuneš, Jaroslav; Zicha, Josef

2015-01-01

Roč. 32, č. 15 (2015), s. 1135-1145 ISSN 0897-7151 R&D Projects: GA ČR(CZ) GAP304/12/0259 Institutional support: RVO:67985823 Keywords : baroreflex-induced bradycardia * blood pressure rise * blood volume redistribution * neurogenic pulmonary edema * spinal cord injury * sympathetic nervous system Subject RIV: ED - Physiology Impact factor: 4.377, year: 2015

PATHOGENETIC MECHANISMS IN EXPERIMENTAL IMMUNE FEVER

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Root, Richard K.; Wolff, Sheldon M.

1968-01-01

When rabbits sensitized to human serum albumin (HSA) are challenged intravenously with specific antigen, fever develops and two transferable pyrogens can be demonstrated in the circulation. The first appears prior to the development of fever and has properties consistent with soluble antigen-antibody complexes. These have been shown to be pyrogenic when prepared in vitro and to produce a state of febrile tolerance when repeatedly administered. The second pyrogen, demonstrable during fever in donor rabbits, appears to be similar to endogenous pyrogen described in other experimental fevers. It is postulated that the formation of antigen-antibody complexes constitutes an important initial phase of the febrile reaction in this type of immune fever. PMID:4873023

Common clinical features of children with enlarged vestibular aqueduct and Mondini dysplasia.

Science.gov (United States)

Wu, Chen-Chi; Chen, Yuh-Shyang; Chen, Pei-Jer; Hsu, Chuan-Jen

2005-01-01

The purpose of the study was to investigate the etiological factors and the audiological data of different types of inner ear malformations, which the authors thought might be helpful in elucidating the inter-relation among malformations and shedding light on pathogenesis. Retrospective study from 1998 to 2002 at a tertiary care university hospital. One hundred sixty consecutive children with a total of 302 affected ears undergoing high-resolution computed tomography of the temporal bone for sensorineural hearing loss were enrolled. The image results were correlated with causes and origins, hearing loss patterns, hearing levels, and audiogram configurations. Inner ear malformation was present in 114 (38%) ears. The most common malformations were enlarged vestibular aqueduct, incomplete partition of cochlea (Mondini dysplasia), large vestibule, and semicircular canal dysplasia, presenting either as isolated finding or in combination. Eighty-four (74%) ears had abnormalities confined to these four malformations; only 30 (26%) ears showed other malformations. Patients with complex of enlarged vestibular aqueduct, Mondini dysplasia, large vestibule, and semicircular canal dysplasia (EMVS complex) demonstrated a significantly higher incidence of fluctuating hearing loss (93%) and a better hearing level compared with those with other malformations. Homogeneity in audiological features among these four malformations was also disclosed. The authors identified a distinct clinical entity, the EMVS complex, which is characterized by fluctuating hearing loss and a better hearing level. The authors proposed that malformations belonging to this complex result from a common pathogenetic mechanism.

The mathematical pathogenetic factors analysis of acute inflammatory diseases development of bronchopulmonary system among infants

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G. O. Lezhenko

2017-10-01

Full Text Available The purpose. To study the factor structure and to establish the associative interaction of pathogenetic links of acute diseases development of the bronchopulmonary system in infants.Materials and methods. The examination group consisted of 59 infants (average age 13.8 ± 1.4 months sick with acute inflammatory bronchopulmonary diseases. Also we tested the level of 25-hydroxyvitamin D (25(ОНD, vitamin D-binding protein, hBPI, cathelicidin LL-37, ß1-defensins, lactoferrin in blood serum with the help of immunoenzymometric analysis. Selection of prognostically important pathogenetic factors of acute bronchopulmonary disease among infants was conducted using ROC-analysis. The procedure for classifying objects was carried out using Hierarchical Cluster Analysis by the method of Centroid-based clustering. Results. Based on the results of the ROC-analysis were selected 15 potential predictors of the development of acute inflammatory diseases of the bronchopulmonary system among infants. The factor analysis made it possible to determine the 6 main components . The biggest influence in the development of the disease was made by "the anemia factor", "the factor of inflammation", "the maternal factor", "the vitamin D supply factor", "the immune factor" and "the phosphorus-calcium exchange factor” with a factor load of more than 0.6. The performed procedure of hierarchical cluster analysis confirmed the initial role of immuno-inflammatory components. The conclusions. The highlighted factors allowed to define a group of parameters, that must be influenced to achieve a maximum effect in carrying out preventive and therapeutic measures. First of all, it is necessary to influence the "the anemia factor" and "the calcium exchange factor", as well as the "the vitamin D supply factor". In other words, to correct vitamin D deficiency and carry out measures aimed at preventing the development of anemia. The prevention and treatment of the pathological course of

Common mechanisms of synaptic plasticity in vertebrates and invertebrates

Science.gov (United States)

Glanzman, David L.

2016-01-01

Until recently, the literature on learning-related synaptic plasticity in invertebrates has been dominated by models assuming plasticity is mediated by presynaptic changes, whereas the vertebrate literature has been dominated by models assuming it is mediated by postsynaptic changes. Here I will argue that this situation does not reflect a biological reality and that, in fact, invertebrate and vertebrate nervous systems share a common set of mechanisms of synaptic plasticity. PMID:20152143

Clinical and pathogenetic interrelation between molecular regulation of apoptosis and cell differentiation in osteoarthritis

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M A Kabalyk

2018-02-01

Full Text Available Aim. To determine clinical and pathogenetic relationship between the levels of apoptosis and growth and differentiation regulation (growth inhibitor 1 induced by oxidative stress, growth/differentiation factor 5 in osteoarthritis. Methods. In a rheumatology office of Vladivostok polyclinic №3 65 patients with knee osteoarthritis Kellgren grade 1-4 aged 66.5±8.0 years were examined. 25 healthy volunteers matched by sex and age without clinical and radiologic manifestations of osteoarthritis were included into control group. To measure concentration of the studied molecules in study patients’ blood, ELISA method was used. Results. Patients with osteoarthritis compared to control group had statistically significantly increased levels of Fas, growth/differentiation factor 5 and ratio of growth/differentiation factor 5/growth inhibitor 1 induced by oxidative stress. Fas levels were significantly lower in late stages 2-4 of osteoarthritis compared to stages 1 and 2. Growth/differentiation factor 5 level was lower in patients with stage 3-4 of osteoarthritis compared to stages 1 and 2. As radiologic signs of osteoarthritis progressed, decrease of the ratio of growth/differentiation factor 5/growth inhibitor 1 induced by oxidative stress, was registered which was significantly lower in stages 2 and 3 compared to stage 1. Conclusion. Extrinsic pathway of apoptosis plays a big role in forming pain syndrome in osteoarthritis, and its maintenance is provided by other mechanisms which include influence of oxidative stress via inhibition of cell cycle mediated by growth inhibitor 1 induced by oxidative stress, reduced involvement of growth/differentiation factor 5 in differentiation processes and regulation of protein synthesis of extracellular cartilaginous tissue matrix.

Osteoarthritis - histology and pathogenetic concepts; Arthrose - Histologie und pathogenetische Ansaetze

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Sulzbacher, I. [Universitaetsklinik Wien (Austria). Klinisches Inst. fuer Klinische Pathologie

2000-12-01

Osteoarthitis is the most common joint disease affecting over 60% of the elderly population. It is characterized by the progressive erosion of articular cartilage leading to incapacity of movement. In the great majority of instances, osteoarthritis appears insidiously, without apparent initiating cause. This primary form is usually oligoarticular involving hip, knee, cervical vertebrae, interphalangeal joints of the fingers or tarsometatarsal joints of the feet. In case of an underlying systemic diasease or local injury the cartilage destruction is considered as secondary osteoarthritis. The pathogenesis of primary osteoarthritis suggests an intrinsic disease of cartilage in which biochemical and metabolic alterations result in its breakdown. Within the last decades different models were stablished which also concentrated on other joint structures such as bone or ligaments. Changes of the subchondral bone were found to precide cartilage damage suggesting a primary alteration of the subchondral region. Other studies concentrated on the metabolic activity of chondrocytes in healthy cartilage of osteoarthritis patients. The precise event that leads to these changes is still not clear. This review concentrates on the histological features in the course of the disease and tries to provide a summary on different pathogenetic concepts. (orig.) [German] Die Arthrosis deformans ist die haeufigste Gelenkerkrankung und betrifft ueber 60% der aelteren Population. Die Erkrankung ist durch fortschreitenden Knorpelverlust gekennzeichnet und fuehrt zu einer limitierteren Bewegungsfreiheit. In den meisten Faellen beginnt der Krankheitsverlauf heimtueckisch ohne ersichtlichen Grund. Diese primaere Form manifestiert sich oft polyartikulaer und betrifft vor allem die Huefte, das Knie, die Halswirbelsaeule, die interphalangealen Gelenke der Finger oder die tarsometatarsalen Gelenke. Bei einer zugrunde liegenden systemischen Erkrankung oder lokal destruierenden Faktoren ist der

[Study on vaginal production of human defensins and the correlated pathogenetic factors of vulvovaginal candidiasis].

Science.gov (United States)

Wang, Wen; DI, Wen; Liao, Qin-ping; Liu, Zhao-hui; Zhang, Ning; Zhang, Hui-ying; Zhang, Dai; Geng, Li; Fan, Shang-rong; Hu, Li-na

2008-07-01

To investigate the correlated pathogenetic factors and vaginal local immunity in vulvovaginal candidiasis (VVC). A case control study was conducted to compare VVC group (60 cases) with normal group (60 cases). All of the women filled up the specific questionnaires. Routine examination, pH test and bacterial culture were done on the vaginal discharge. Cytokines of the vaginal lavage were measured by enzyme linked immunosorbent assay. (1) Outcomes of the questionnaires: there was no significant difference between the two groups in educational background, knowledge of gynecologic infection, history of gynecologic infection, hygienic habit, sex life, or use of medicine (P > 0.05). The incidence of chronic cervicitis in normal group (43%, 26/60) was higher than in VVC group (22%, 13/60; P vaginal pH between the two groups (P > 0.05). (3) Detection rate of candida albicans by vaginal discharge routine examination was 72% (43/60). (4) The concentrations of interleukin (IL) 2, and IL-4 in vaginal lavage did not show significant difference between the two groups (P > 0.05), but the concentrations of human defensin 5, human beta-defensin (HBD) 1, and HBD2 in VVC group [(0.94 +/- 0.44) mg/L, (3.1 +/- 0.4) microg/L, (10 +/- 6) microg/L] were higher than normal group (P < 0.05). VVC is a common vulvovaginitis. There is no significant correlation between the incidence of VVC and educational background, knowledge of gynecologic infection, history of gynecologic infection, hygienic habit, sex life, or use of medicine in the child-bearing period. Human defensin may be closely correlated with the pathogenesis of VVC.

Clinical and Pathogenetic Significance of Osteoassociated Microelements in the Joint Diseases. Report II: Microelementosis in the Hair

Directory of Open Access Journals (Sweden)

O.V. Syniachenko

2016-08-01

Full Text Available The relevance. Microelementosis (imbalance of certain microelements in the body, ME is considered as one of the most important clinical and pathogenetic components of degenerative and inflammatory joint diseases. ME can play the role of co-factors involved in the processes of articular inflammation. Objective. To study the levels in the hair and to assess the clinical and pathogenetic significance of osteoassociated ME (cobalt — Co, copper — Cu, iron — Fe, lithium — Li, manganese — Mn, lead — Pb, strontium — Sr, zinc — Zn at a variety of arthritis — rheumatoid (RA, chlamydia-induced (ReA, psoriatic (PsA, gouty (PA and osteoarthritis (OA. Material and methods. There were 262 patients under observation, among them 89 persons suffered from RA, 31 — ReA, 35 — PsA, 49 — GA and 58 — OA. The distribution of males and females in these groups was 1 : 2, 2 : 1, 1 : 1, 11 : 1, 1 : 3, respectively, the average age of the patients was 47, 34, 42, 48 and 58 years old, while the duration of clinical manifestations of disease was 10, 4, 11, 7 and 12 years. ME in the hair was examined by atomic absorption spectrometer with electrographite atomizer «SolAAr-Mk2-MOZe». Results. All patients with arthritis are prone to have microelementosis in hair. All nosological forms of joint pathology are associated with a significant decrease of Mn level in hair, when the level of Pb and Fe accumulated. Only RA was characterized by the absence of changes in the hair level of Co, PsA — of Cu, PA — Li and Sr. If, in comparison with healthy persons, the PA proceeds with an increased concentration level of Zn in the hair, the OA is characterized by an increased level of ME, that has a certain differential diagnostic value. There is either direct relationship between the hair and blood serum indexes (Mn, Pb or multi-directional (Fe ones. Microelement blood composition depends on the activity level, clinical and laboratory signs of disease, the

Preeclampsia with and without intrauterine growth restriction-Two pathogenetically different entities?

Science.gov (United States)

Milosevic-Stevanovic, Jelena; Krstic, Miljan; Radovic-Janosevic, Dragana; Stefanovic, Milan; Antic, Vladimir; Djordjevic, Ivana

2016-11-01

The objective of this study is to determine the differences in histopathological features of basal decidua and placenta in cases of preeclampsia with or without fetal intrauterine growth restriction (IUGR). A prospective case-control study included a study group consisting of 30 pregnant women with preeclampsia completed by cesarean section (CS), in 19 of whom preeclampsia was associated with IUGR, and in 11 it was not. The control group consisted of 20 healthy pregnant women delivered by elective CS. Placentas and samples of placental bed obtained during CS were histopathologically (HP) analyzed after hematoxylin-eosin staining and immunohistochemical labeling of Cytokeratin 7 (CK7) trophoblastic cells in decidua. Regarding the HP changes in the spiral arteries in preeclampsia, the most frequent features were inadequate transformation of spiral arteries with poor trophoblastic invasion (70.0%) and fibrinoid necrosis of the media (66.7%), and rarely acute atherosis (33.3%) and thrombosis (30.0%). Villous hypermaturity was more frequently found in placentas of patients with preeclampsia with IUGR (p preeclampsia with and without IUGR regarding some of HP alterations of placental bed. Alterations of the placental bed in terms of decidual vasculopathy are more the characteristics of the preeclampsia itself than IUGR, while changes in placental villi primarily follow the presence of IUGR, which could indicate that preeclampsia with and without IUGR are two pathogenetically different entities.

Teaching the Common Aspects in Mechanical, Electromagnetic and Quantum Waves at Interfaces and Waveguides

Science.gov (United States)

Rojas, R.; Robles, P.

2011-01-01

We discuss common features in mechanical, electromagnetic and quantum systems, supporting identical results for the transmission and reflection coefficients of waves arriving perpendicularly at a plane interface. Also, we briefly discuss the origin of special notions such as refractive index in quantum mechanics, massive photons in wave guides and…

A Systems Biology Approach Reveals Converging Molecular Mechanisms that Link Different POPs to Common Metabolic Diseases.

Science.gov (United States)

Ruiz, Patricia; Perlina, Ally; Mumtaz, Moiz; Fowler, Bruce A

2016-07-01

A number of epidemiological studies have identified statistical associations between persistent organic pollutants (POPs) and metabolic diseases, but testable hypotheses regarding underlying molecular mechanisms to explain these linkages have not been published. We assessed the underlying mechanisms of POPs that have been associated with metabolic diseases; three well-known POPs [2,3,7,8-tetrachlorodibenzodioxin (TCDD), 2,2´,4,4´,5,5´-hexachlorobiphenyl (PCB 153), and 4,4´-dichlorodiphenyldichloroethylene (p,p´-DDE)] were studied. We used advanced database search tools to delineate testable hypotheses and to guide laboratory-based research studies into underlying mechanisms by which this POP mixture could produce or exacerbate metabolic diseases. For our searches, we used proprietary systems biology software (MetaCore™/MetaDrug™) to conduct advanced search queries for the underlying interactions database, followed by directional network construction to identify common mechanisms for these POPs within two or fewer interaction steps downstream of their primary targets. These common downstream pathways belong to various cytokine and chemokine families with experimentally well-documented causal associations with type 2 diabetes. Our systems biology approach allowed identification of converging pathways leading to activation of common downstream targets. To our knowledge, this is the first study to propose an integrated global set of step-by-step molecular mechanisms for a combination of three common POPs using a systems biology approach, which may link POP exposure to diseases. Experimental evaluation of the proposed pathways may lead to development of predictive biomarkers of the effects of POPs, which could translate into disease prevention and effective clinical treatment strategies. Ruiz P, Perlina A, Mumtaz M, Fowler BA. 2016. A systems biology approach reveals converging molecular mechanisms that link different POPs to common metabolic diseases. Environ

Clinical Heterogeneity in two patients with Noonan-like Syndrome associated with the same SHOC2 mutation.

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Capalbo, Donatella; Scala, Maria Giuseppa; Melis, Daniela; Minopoli, Giorgia; Improda, Nicola; Palamaro, Loredana; Pignata, Claudio; Salerno, Mariacarolina

2012-09-20

Noonan-like syndrome with loose anagen hair (NS/LAH; OMIM #607721) has been recently related to the invariant c.4A > G missense change in SHOC2. It is characterized by features reminiscent of Noonan syndrome. Ectodermal involvement, short stature associated to growth hormone (GH) deficiency (GHD), and cognitive deficits are common features. We compare in two patients with molecularly confirmed NS/LAH diagnosis, the clinical phenotype and pathogenetic mechanism underlying short stature. In particular, while both the patients exhibited a severe short stature, GH/IGFI axis functional evaluation revealed a different pathogenetic alteration, suggesting in one patient an upstream alteration (typical GHD) and in the other one a peripheral GH insensitivity.

Transcriptomic responses to darkness stress point to common coral bleaching mechanisms

Science.gov (United States)

Desalvo, M. K.; Estrada, A.; Sunagawa, S.; Medina, Mónica

2012-03-01

Coral bleaching occurs in response to numerous abiotic stressors, the ecologically most relevant of which is hyperthermic stress due to increasing seawater temperatures. Bleaching events can span large geographic areas and are currently a salient threat to coral reefs worldwide. Much effort has been focused on understanding the molecular and cellular events underlying bleaching, and these studies have mainly utilized heat and light stress regimes. In an effort to determine whether different stressors share common bleaching mechanisms, we used complementary DNA (cDNA) microarrays for the corals Acropora palmata and Montastraea faveolata (containing >10,000 features) to measure differential gene expression during darkness stress. Our results reveal a striking transcriptomic response to darkness in A. palmata involving chaperone and antioxidant up-regulation, growth arrest, and metabolic modifications. As these responses were previously measured during thermal stress, our results suggest that different stressors may share common bleaching mechanisms. Furthermore, our results point to hypoxia and endoplasmic reticulum stress as critical cellular events involved in molecular bleaching mechanisms. On the other hand, we identified a meager transcriptomic response to darkness in M. faveolata where gene expression differences between host colonies and sampling locations were greater than differences between control and stressed fragments. This and previous coral microarray studies reveal the immense range of transcriptomic responses that are possible when studying two coral species that differ greatly in their ecophysiology, thus pointing to the importance of comparative approaches in forecasting how corals will respond to future environmental change.

Preeclampsia: from Pathophysiology to Treatment

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Kaculini Enton

2016-12-01

Full Text Available Preeclampsia is a multisystem disorder unique to human pregnancy and is its most common glomerular complication. It occurs in 2% to 8% of pregnancies and is a major contributor to maternal mortality worldwide. Although the pathophysiology of this syndrome is not fully understood, many pathogenetic mechanisms are involved in this disorder. The role of the placenta is crucial in the development of this disorder. Some pathogenetic mechanisms involved in this disease comprise defective deep placentation, autoantibodies to type-1 angiotensin II receptor, endothelial dysfunction, oxidative stress, platelet and thrombin activation, intravascular inflammation, and the imbalance between angiogenic and antiangiogenic factors which is thought to be one of the most crucial mechanisms. Further understanding of the full picture could enhance our current knowledge of the pathogenesis of preeclampsia and improve its treatment. Thus, based on specific biomarkers the diagnosis and subclassification of preeclampsia might be more accurate in identifying patients at risk, monitoring disease progression and providing effective interventions

Mechanical stress as the common denominator between chronic inflammation, cancer and Alzheimer’s disease

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Marcel eLevy Nogueira

2015-09-01

Full Text Available The pathogenesis of common diseases such as Alzheimer’s disease (AD and cancer are currently poorly understood. Inflammation is a common risk factor for cancer and AD. Recent data, provided by our group and from others, demonstrate that increased pressure and inflammation are synonymous. There is a continuous increase in pressure from inflammation to fibrosis and then cancer. This in line with the numerous papers reporting high interstitial pressure in cancer. But most authors focus on the role of pressure in the lack of delivery of chemotherapy in the center of the tumor. Pressure may also be a key factor in carcinogenesis. Increased pressure is responsible for oncogene activation and cytokine secretion. Accumulation of mechanical stress plays a key role in the development of diseases of old age such as cardiomyopathy, atherosclerosis and osteoarthritis. Growing evidence suggest also a possible link between mechanical stress in the pathogenesis of AD. The aim of this review is to describe environmental and endogenous mechanical factors possibly playing a pivotal role in the mechanism of chronic inflammation, AD and cancer.

Change is good: variations in common biological mechanisms in the epsilonproteobacterial genera Campylobacter and Helicobacter.

Science.gov (United States)

Gilbreath, Jeremy J; Cody, William L; Merrell, D Scott; Hendrixson, David R

2011-03-01

Microbial evolution and subsequent species diversification enable bacterial organisms to perform common biological processes by a variety of means. The epsilonproteobacteria are a diverse class of prokaryotes that thrive in diverse habitats. Many of these environmental niches are labeled as extreme, whereas other niches include various sites within human, animal, and insect hosts. Some epsilonproteobacteria, such as Campylobacter jejuni and Helicobacter pylori, are common pathogens of humans that inhabit specific regions of the gastrointestinal tract. As such, the biological processes of pathogenic Campylobacter and Helicobacter spp. are often modeled after those of common enteric pathogens such as Salmonella spp. and Escherichia coli. While many exquisite biological mechanisms involving biochemical processes, genetic regulatory pathways, and pathogenesis of disease have been elucidated from studies of Salmonella spp. and E. coli, these paradigms often do not apply to the same processes in the epsilonproteobacteria. Instead, these bacteria often display extensive variation in common biological mechanisms relative to those of other prototypical bacteria. In this review, five biological processes of commonly studied model bacterial species are compared to those of the epsilonproteobacteria C. jejuni and H. pylori. Distinct differences in the processes of flagellar biosynthesis, DNA uptake and recombination, iron homeostasis, interaction with epithelial cells, and protein glycosylation are highlighted. Collectively, these studies support a broader view of the vast repertoire of biological mechanisms employed by bacteria and suggest that future studies of the epsilonproteobacteria will continue to provide novel and interesting information regarding prokaryotic cellular biology.

Characteristic Features of the Exotic Superconductors: Evidence for a Common Pairing Mechanism

International Nuclear Information System (INIS)

Brandow, B.

1999-01-01

We report on a comprehensive examination of the exotic superconductors (the materials so-labelled by Uemura and co-workers), to determine as far as possible the true systematics among their many anomalous features. In the crystal-chemistry aspects as well as in the electronic properties, we find features which appear to be universal for these materials, and also features which are clearly not universal but which are common enough to be considered typical for these materials. A number of implications are presented. It appears that all of these materials are sharing some ''new'' pairing mechanism, usually in addition to the conventional phonon mechanism

Pathogenic mechanisms linking periodontal diseases with adverse pregnancy outcomes.

Science.gov (United States)

Cetin, I; Pileri, P; Villa, A; Calabrese, S; Ottolenghi, L; Abati, S

2012-06-01

In the last 2 decades, a large proportion of studies have focused on the relationship between maternal periodontal disease and poor obstetric outcomes. The aim of the present review is to summarize the current knowledge about human studies on the pathogenetic mechanisms linking periodontal diseases with adverse pregnancy outcomes. A search of the medical literature was conducted using NIH (National Institute of Health) Pubmed through April 2011. Articles were identified with the Medical Subject Heading (MeSH) and free text terms "small for gestational age (SGA)," "preeclampsia," "preterm labor," and "periodontal disease." Experimental human studies have shown that periodontal pathogens may disseminate toward placental and fetal tissues accompanied by an increase in inflammatory mediators in the placenta. As such, new inflammatory reactions within the placental tissues of the pregnant woman may occur, the physiological levels of prostaglandin E(2) (PGE(2)) and tumor necrosis factor-α (TNF-α) in the amniotic fluid may increase and eventually lead to premature delivery. Although many data from clinical trials suggest that periodontal disease may increase the adverse pregnancy outcome, the exact pathogenetic mechanism involved remains controversial. The findings explain the potential link between periodontal infections and adverse pregnancy outcomes. First, periodontal bacteria can directly cause infections both of the uteroplacenta and the fetus; second, systemic inflammatory changes induced by periodontal diseases can activate responses at the maternal-fetal interface. Of note, associative studies have produced different results in different population groups and no conclusive evidence has still been produced for the potential role of preventive periodontal care to reduce the risk factors of preterm birth.

Transcriptional Dysregulation of MYC Reveals Common Enhancer-Docking Mechanism.

Science.gov (United States)

Schuijers, Jurian; Manteiga, John Colonnese; Weintraub, Abraham Selby; Day, Daniel Sindt; Zamudio, Alicia Viridiana; Hnisz, Denes; Lee, Tong Ihn; Young, Richard Allen

2018-04-10

Transcriptional dysregulation of the MYC oncogene is among the most frequent events in aggressive tumor cells, and this is generally accomplished by acquisition of a super-enhancer somewhere within the 2.8 Mb TAD where MYC resides. We find that these diverse cancer-specific super-enhancers, differing in size and location, interact with the MYC gene through a common and conserved CTCF binding site located 2 kb upstream of the MYC promoter. Genetic perturbation of this enhancer-docking site in tumor cells reduces CTCF binding, super-enhancer interaction, MYC gene expression, and cell proliferation. CTCF binding is highly sensitive to DNA methylation, and this enhancer-docking site, which is hypomethylated in diverse cancers, can be inactivated through epigenetic editing with dCas9-DNMT. Similar enhancer-docking sites occur at other genes, including genes with prominent roles in multiple cancers, suggesting a mechanism by which tumor cell oncogenes can generally hijack enhancers. These results provide insights into mechanisms that allow a single target gene to be regulated by diverse enhancer elements in different cell types. Copyright © 2018 The Author(s). Published by Elsevier Inc. All rights reserved.

Common Factor Mechanisms in Clinical Practice and Their Relationship with Outcome.

Science.gov (United States)

Gaitan-Sierra, Carolina; Hyland, Michael E

2015-01-01

This study investigates three common factor mechanisms that could affect outcome in clinical practice: response expectancy, the affective expectation model and motivational concordance. Clients attending a gestalt therapy clinic (30 clients), a sophrology (therapeutic technique) clinic (33 clients) and a homeopathy clinic (31 clients) completed measures of expectancy and the Positive Affect and Negative Affect Schedule (PANAS) before their first session. After 1 month, they completed PANAS and measures of intrinsic motivation, perceived effort and empowerment. Expectancy was not associated with better outcome and was no different between treatments. Although some of the 54 clients who endorsed highest expectations showed substantial improvement, others did not: 19 had no change or deteriorated in positive affect, and 18 had the same result for negative affect. Intrinsic motivation independently predicted changes in negative affect (β = -0.23). Intrinsic motivation (β = 0.24), effort (β = 0.23) and empowerment (β = 0.20) independently predicted positive affect change. Expectancy (β = -0.17) negatively affected changes in positive affect. Clients found gestalt and sophrology to be more intrinsically motivating, empowering and effortful compared with homeopathy. Greater improvement in mood was found for sophrology and gestalt than for homeopathy clients. These findings are inconsistent with response expectancy as a common factor mechanism in clinical practice. The results support motivational concordance (outcome influenced by the intrinsic enjoyment of the therapy) and the affective expectation model (high expectations can lead for some clients to worse outcome). When expectancy correlates with outcome in some other studies, this may be due to confound between expectancy and intrinsic enjoyment. Common factors play an important role in outcome. Intrinsic enjoyment of a therapeutic treatment is associated with better outcome. Active engagement with a

Mechanism of Inflammation in Age-Related Macular Degeneration

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Francesco Parmeggiani

2012-01-01

Full Text Available Age-related macular degeneration (AMD is a multifactorial disease that represents the most common cause of irreversible visual impairment among people over the age of 50 in Europe, the United States, and Australia, accounting for up to 50% of all cases of central blindness. Risk factors of AMD are heterogeneous, mainly including increasing age and different genetic predispositions, together with several environmental/epigenetic factors, that is, cigarette smoking, dietary habits, and phototoxic exposure. In the aging retina, free radicals and oxidized lipoproteins are considered to be major causes of tissue stress resulting in local triggers for parainflammation, a chronic status which contributes to initiation and/or progression of many human neurodegenerative diseases such as AMD. Experimental and clinical evidences strongly indicate the pathogenetic role of immunologic processes in AMD occurrence, consisting of production of inflammatory related molecules, recruitment of macrophages, complement activation, microglial activation and accumulation within those structures that compose an essential area of the retina known as macula lutea. This paper reviews some attractive aspects of the literature about the mechanisms of inflammation in AMD, especially focusing on those findings or arguments more directly translatable to improve the clinical management of patients with AMD and to prevent the severe vision loss caused by this disease.

Mechanism of Inflammation in Age-Related Macular Degeneration

Science.gov (United States)

Parmeggiani, Francesco; Romano, Mario R.; Costagliola, Ciro; Semeraro, Francesco; Incorvaia, Carlo; D'Angelo, Sergio; Perri, Paolo; De Palma, Paolo; De Nadai, Katia; Sebastiani, Adolfo

2012-01-01

Age-related macular degeneration (AMD) is a multifactorial disease that represents the most common cause of irreversible visual impairment among people over the age of 50 in Europe, the United States, and Australia, accounting for up to 50% of all cases of central blindness. Risk factors of AMD are heterogeneous, mainly including increasing age and different genetic predispositions, together with several environmental/epigenetic factors, that is, cigarette smoking, dietary habits, and phototoxic exposure. In the aging retina, free radicals and oxidized lipoproteins are considered to be major causes of tissue stress resulting in local triggers for parainflammation, a chronic status which contributes to initiation and/or progression of many human neurodegenerative diseases such as AMD. Experimental and clinical evidences strongly indicate the pathogenetic role of immunologic processes in AMD occurrence, consisting of production of inflammatory related molecules, recruitment of macrophages, complement activation, microglial activation and accumulation within those structures that compose an essential area of the retina known as macula lutea. This paper reviews some attractive aspects of the literature about the mechanisms of inflammation in AMD, especially focusing on those findings or arguments more directly translatable to improve the clinical management of patients with AMD and to prevent the severe vision loss caused by this disease. PMID:23209345

MECHANISM TRANSFER PRICING AND THE NEED INTRODUCTION COMMON CONSOLIDATED CORPORATE INCOME TAX TRANSNATIONAL

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Gheorghe Grigorescu

2013-06-01

Full Text Available Transfer pricing mechanism is a tool commonly used to transfer the tax base in countries with high tax countries with lower taxation. In the European Union the financial operations generate tax revenue losses. In an attempt to limit manipulation by corporate tax systems, many public authorities have introduced transfer pricing rules, but these rules has shown limited efficacy, however, contribute to the increasing complexity of tax laws and the emergence of additional costs for companies. This paper deals with the concrete examples, the solution to solving the problem of transfer pricing in the European Union by the introduction of common consolidated corporate income tax.

Peripheral Immune Alterations in Major Depression: The Role of Subtypes and Pathogenetic Characteristics

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Frank Euteneuer

2017-11-01

Full Text Available Depression has been associated with peripheral inflammatory processes and alterations in cellular immunity. Growing evidence suggests that immunological alterations may neither be necessary nor sufficient to induce depression in general, but seem to be associated with specific features. Using baseline data from the Outcome of Psychological Interventions in Depression trial, this exploratory study examines associations between depression subtypes and pathogenetic characteristics (i.e., melancholic vs non-melancholic depression, chronic vs non-chronic depression, age of onset, cognitive-affective and somatic symptom dimensions with plasma levels of C-reactive protein (CRP, interleukin (IL-6, IL-10, and numbers of leukocyte subpopulations in 98 patients with major depression (MD and 30 age and sex-matched controls. Patients with MD exhibited higher CRP levels, higher neutrophil and monocyte counts, lower IL-10 levels, and an increased neutrophil to lymphocyte ratio (NLR than controls. Patient with later age of onset had higher levels of two inflammatory markers (CRP, NLR and lower cytotoxic T cell counts after adjusting for sociodemographics, lifestyle factors, and antidepressants. Furthermore, lower anti-inflammatory IL-10 levels were related to more severe somatic depressive symptoms. These results confirm and extend previous findings suggesting that increased levels of CRP are associated with a later onset of depression and demonstrate that also NLR as a subclinical inflammatory marker is related to a later onset of depression.

Transcriptional Dysregulation of MYC Reveals Common Enhancer-Docking Mechanism

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Jurian Schuijers

2018-04-01

Full Text Available Summary: Transcriptional dysregulation of the MYC oncogene is among the most frequent events in aggressive tumor cells, and this is generally accomplished by acquisition of a super-enhancer somewhere within the 2.8 Mb TAD where MYC resides. We find that these diverse cancer-specific super-enhancers, differing in size and location, interact with the MYC gene through a common and conserved CTCF binding site located 2 kb upstream of the MYC promoter. Genetic perturbation of this enhancer-docking site in tumor cells reduces CTCF binding, super-enhancer interaction, MYC gene expression, and cell proliferation. CTCF binding is highly sensitive to DNA methylation, and this enhancer-docking site, which is hypomethylated in diverse cancers, can be inactivated through epigenetic editing with dCas9-DNMT. Similar enhancer-docking sites occur at other genes, including genes with prominent roles in multiple cancers, suggesting a mechanism by which tumor cell oncogenes can generally hijack enhancers. These results provide insights into mechanisms that allow a single target gene to be regulated by diverse enhancer elements in different cell types. : Schuijers et al. show that a conserved CTCF site at the promoter of the MYC oncogene plays an important role in enhancer-promoter looping with tumor-specific super-enhancers. Perturbation of this site provides a potential therapeutic vulnerability. Keywords: gene regulation, super-enhancers, chromosome structure, enhancer docking

Report of National Cancer Institute symposium: comparison of mechanisms of carcinogenesis by radiation and chemical agents. I. Common molecular mechanisms

International Nuclear Information System (INIS)

Borg, D.C.

1984-01-01

Some aspects of molecular mechanisms common to radiation and chemical carcinogenesis are discussed, particularly the DNA damage done by these agents. Emphasis is placed on epidemiological considerations and on dose-response models used in risk assessment to extrapolate from experimental data obtained at high doses to the effects from long-term, low-level exposures. 3 references, 6 figures

Report of National Cancer Institute symposium: comparison of mechanisms of carcinogenesis by radiation and chemical agents. I. Common molecular mechanisms

Energy Technology Data Exchange (ETDEWEB)

Borg, D.C.

1984-01-01

Some aspects of molecular mechanisms common to radiation and chemical carcinogenesis are discussed, particularly the DNA damage done by these agents. Emphasis is placed on epidemiological considerations and on dose-response models used in risk assessment to extrapolate from experimental data obtained at high doses to the effects from long-term, low-level exposures. 3 references, 6 figures. (ACR)

Measures and mechanisms of common ground: backchannels, conversational repair, and interactive alignmentin free and task-oriented social interactions

DEFF Research Database (Denmark)

Fusaroli, Riccardo; Tylén, Kristian; Madsen, Katrine Garly

A crucial aspect of everyday conversational interactions is our ability to establish and maintain common ground. Understanding the relevant mechanisms involved in such social coordination remains an important challenge for cognitive science. While common ground is often discussed in very general ...

Evidence for a Common Mechanism of SIRT1 Regulation by Allosteric Activators

Science.gov (United States)

Hubbard, Basil P.; Gomes, Ana P.; Dai, Han; Li, Jun; Case, April W.; Considine, Thomas; Riera, Thomas V.; Lee, Jessica E.; Sook Yen, E; Lamming, Dudley W.; Pentelute, Bradley L.; Schuman, Eli R.; Stevens, Linda A.; Ling, Alvin J. Y.; Armour, Sean M.; Michan, Shaday; Zhao, Huizhen; Jiang, Yong; Sweitzer, Sharon M.; Blum, Charles A.; Disch, Jeremy S.; Ng, Pui Yee; Howitz, Konrad T.; Rolo, Anabela P.; Hamuro, Yoshitomo; Moss, Joel; Perni, Robert B.; Ellis, James L.; Vlasuk, George P.; Sinclair, David A.

2013-01-01

A molecule that treats multiple age-related diseases would have a major impact on global health and economics. The SIRT1 deacetylase has drawn attention in this regard as a target for drug design. Yet controversy exists around the mechanism of sirtuin-activating compounds (STACs). We found that specific hydrophobic motifs found in SIRT1 substrates such as PGC-1α and FOXO3a facilitate SIRT1 activation by STACs. A single amino acid in SIRT1, Glu230, located in a structured N-terminal domain, was critical for activation by all previously reported STAC scaffolds and a new class of chemically distinct activators. In primary cells reconstituted with activation-defective SIRT1, the metabolic effects of STACs were blocked. Thus, SIRT1 can be directly activated through an allosteric mechanism common to chemically diverse STACs. PMID:23471411

Evidence for a common mechanism of SIRT1 regulation by allosteric activators.

Science.gov (United States)

Hubbard, Basil P; Gomes, Ana P; Dai, Han; Li, Jun; Case, April W; Considine, Thomas; Riera, Thomas V; Lee, Jessica E; E, Sook Yen; Lamming, Dudley W; Pentelute, Bradley L; Schuman, Eli R; Stevens, Linda A; Ling, Alvin J Y; Armour, Sean M; Michan, Shaday; Zhao, Huizhen; Jiang, Yong; Sweitzer, Sharon M; Blum, Charles A; Disch, Jeremy S; Ng, Pui Yee; Howitz, Konrad T; Rolo, Anabela P; Hamuro, Yoshitomo; Moss, Joel; Perni, Robert B; Ellis, James L; Vlasuk, George P; Sinclair, David A

2013-03-08

A molecule that treats multiple age-related diseases would have a major impact on global health and economics. The SIRT1 deacetylase has drawn attention in this regard as a target for drug design. Yet controversy exists around the mechanism of sirtuin-activating compounds (STACs). We found that specific hydrophobic motifs found in SIRT1 substrates such as PGC-1α and FOXO3a facilitate SIRT1 activation by STACs. A single amino acid in SIRT1, Glu(230), located in a structured N-terminal domain, was critical for activation by all previously reported STAC scaffolds and a new class of chemically distinct activators. In primary cells reconstituted with activation-defective SIRT1, the metabolic effects of STACs were blocked. Thus, SIRT1 can be directly activated through an allosteric mechanism common to chemically diverse STACs.

CADASIL: pathogenesis, clinical and radiological findings and treatment

International Nuclear Information System (INIS)

Andre, Charles

2010-01-01

Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) is the most common genetic cause of ischemic strokes and a most important model for the study of subcortical vascular dementia. This unrelentlessly progressive disease affects many hundreds of families all over the world but is not well studied in Brazil. This manuscript reviews pathogenetic, clinical, radiological and therapeutic features of CADASIL. The causal mutations are now very well known, but the same can not be said about its intimate pathogenetic mechanisms. The variable clinical presentation should lead physicians to actively pursue the diagnosis in many settings and to more thoroughly investigate family history in first degree relatives. A rational approach to genetic testing is however needed. Treatment of CADASIL is still largely empiric. High-quality therapeutic studies involving medications and cognitive interventions are strongly needed in CADASIL. (author)

CADASIL: pathogenesis, clinical and radiological findings and treatment

Energy Technology Data Exchange (ETDEWEB)

Andre, Charles [Federal University of Rio de Janeiro (UFRJ), Rio de Janeiro, RJ (Brazil). School of Medicine

2010-04-15

Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) is the most common genetic cause of ischemic strokes and a most important model for the study of subcortical vascular dementia. This unrelentlessly progressive disease affects many hundreds of families all over the world but is not well studied in Brazil. This manuscript reviews pathogenetic, clinical, radiological and therapeutic features of CADASIL. The causal mutations are now very well known, but the same can not be said about its intimate pathogenetic mechanisms. The variable clinical presentation should lead physicians to actively pursue the diagnosis in many settings and to more thoroughly investigate family history in first degree relatives. A rational approach to genetic testing is however needed. Treatment of CADASIL is still largely empiric. High-quality therapeutic studies involving medications and cognitive interventions are strongly needed in CADASIL. (author)

Iron-Induced Damage in Cardiomyopathy: Oxidative-Dependent and Independent Mechanisms

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Elena Gammella

2015-01-01

Full Text Available The high incidence of cardiomyopathy in patients with hemosiderosis, particularly in transfusional iron overload, strongly indicates that iron accumulation in the heart plays a major role in the process leading to heart failure. In this context, iron-mediated generation of noxious reactive oxygen species is believed to be the most important pathogenetic mechanism determining cardiomyocyte damage, the initiating event of a pathologic progression involving apoptosis, fibrosis, and ultimately cardiac dysfunction. However, recent findings suggest that additional mechanisms involving subcellular organelles and inflammatory mediators are important factors in the development of this disease. Moreover, excess iron can amplify the cardiotoxic effect of other agents or events. Finally, subcellular misdistribution of iron within cardiomyocytes may represent an additional pathway leading to cardiac injury. Recent advances in imaging techniques and chelators development remarkably improved cardiac iron overload detection and treatment, respectively. However, increased understanding of the pathogenic mechanisms of iron overload cardiomyopathy is needed to pave the way for the development of improved therapeutic strategies.

Mechanism of the re-buildup phenomenon in moyamoya disease; Analysis of local cerebral hemodynamics with intra-arterial digital subtraction angiography

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Touho, Hajime; Karasawa, Jun; Shishido, Hisashi; Morisako, Toshitaka; Yamada, Keisuke; Nagai, Shigeki; Shibamoto, Kenji [Osaka Neurological Institute, Osaka (Japan)

1990-10-01

The authors investigated the mechanism of the re-buildup phenomenon on electroencephalogram in 14 patients of moyamoya disease with superficial temporal artery-middle cerebral artery anastomosis. Visualization of the lateral view of the common carotid angiography was performed with intra-arterial digital subtraction angiography (IA-DSA), using a 4/sec x 3 sec + 2/sec x 5 sec + 1/sec x 5 sec film sequence. The catheter tip was inserted into C5/6 level and 250 mgl/ml of iopamidol was used as the contrast agent; 6 ml in total was injected over 1.5 seconds. Circulation times of the common carotid artery (C{sub 3} portion)-ascending parietal vein ({delta}TTP{sub s}) and common carotid artery-internal cerebral vein ({delta}TTP{sub D}) were measured before hyperventilation (HV), immediately after HV, and 3 minutes after HV during pre- and postoperative periods. {delta}TTP{sub D} in the preoperative period was prolonged by HV and was normalized at 3 minutes after HV but {delta}TTP{sub S} were prolonged immediately after and 3 minutes after HV. In the postoperative period, however, these values did not change significantly immediately after and 3 minutes after HV. These findings indicate that delayed cerebral blood flow response to HV is a pathogenetic factor of the re-buildup phenomenon in moyamoya disease. (author).

SYNDROME-PATHOGENETIC APPROACH TO MEDICAL REHABILITATION OF PATIENTS AFTER THE TOTAL HIP AND KNEE REPLACEMENT

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Y. Y. Udartsev

2011-01-01

Full Text Available The results of treatment 103 patients in term of 4-6 months after total hip and knee replacement were examined. Established that in the operated limb disorders of regional blood flow in the form of chronic lympho-venous insufficiency and changes in the functional state of neuromuscular apparatus in the form of muscle dysfunction, autonomic dysfunction occured. According to detected characteristics the medical rehabilitation for patients of the 1st group (52 patients was based on the combination of therapeutic factors complex usage, each of which exerts a specific effect on pathogenesis of a certain syndrome or their different combinations, and developing therapeutic factors are summarized and potentiated. That is why balneo-radon-kinesiotherapy, intermittent pneumocompression, low-frequency magnetotherapy, transcranial electroanalgesia, electrical myostimulation, pelotherapy, taking of central myorelexanat tizanidine were included in the treatment program. Among the patients of the 2nd group medical rehabilitation was based exclusively on motion state and bodily exercises. The analysis of treatment showed the advantage of syndrome-pathogenetic approach, applied for the 1st group of patients: joint range of motions increased by 33,1%, venous drainage increased by 24,4%, neuromuscular apparatus duty improved by 51,8%, involuntary nervous system balance normalized, functional outcome of the medical rehabilitation improved by 73,1%.

Intrinsic and extrinsic factors influencing the clinical course of B-cell chronic lymphocytic leukemia: prognostic markers with pathogenetic relevance

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Gaidano Gianluca

2009-08-01

Full Text Available Abstract B-cell chronic lymphocytic leukemia (CLL, the most frequent leukemia in the Western world, is characterized by extremely variable clinical courses with survivals ranging from 1 to more than 15 years. The pathogenetic factors playing a key role in defining the biological features of CLL cells, hence eventually influencing the clinical aggressiveness of the disease, are here divided into "intrinsic factors", mainly genomic alterations of CLL cells, and "extrinsic factors", responsible for direct microenvironmental interactions of CLL cells; the latter group includes interactions of CLL cells occurring via the surface B cell receptor (BCR and dependent to specific molecular features of the BCR itself and/or to the presence of the BCR-associated molecule ZAP-70, or via other non-BCR-dependent interactions, e.g. specific receptor/ligand interactions, such as CD38/CD31 or CD49d/VCAM-1. A putative final model, discussing the pathogenesis and the clinicobiological features of CLL in relationship of these factors, is also provided.

Metal uptake and acute toxicity in zebrafish: Common mechanisms across multiple metals

Energy Technology Data Exchange (ETDEWEB)

Alsop, Derek, E-mail: alsopde@mcmaster.ca [Department of Biology, McMaster University, 1280 Main St. W., Hamilton, ON L8S 4K1 (Canada); Wood, Chris M. [Department of Biology, McMaster University, 1280 Main St. W., Hamilton, ON L8S 4K1 (Canada)

2011-10-15

All metals tested reduced calcium uptake in zebrafish larvae. However, it was whole body sodium loss that was functionally related to toxicity. The zebrafish larvae acute toxicity assay save time, space and resources. - Abstract: Zebrafish larvae (Danio rerio) were used to examine the mechanisms of action and acute toxicities of metals. Larvae had similar physiological responses and sensitivities to waterborne metals as adults. While cadmium and zinc have previously been shown to reduce Ca{sup 2+} uptake, copper and nickel also decreased Ca{sup 2+} uptake, suggesting that the epithelial transport of all these metals is through Ca{sup 2+} pathways. However, exposure to cadmium, copper or nickel for up to 48 h had little or no effect on total whole body Ca{sup 2+} levels, indicating that the reduction of Ca{sup 2+} uptake is not the acute toxic mechanism of these metals. Instead, mortalities were effectively related to whole body Na{sup +}, which decreased up to 39% after 48 h exposures to different metals around their respective 96 h LC50s. Decreases in whole body K{sup +} were also observed, although they were not as pronounced or frequent as Na{sup +} losses. None of the metals tested inhibited Na{sup +} uptake in zebrafish (Na{sup +} uptake was in fact increased with exposure) and the observed losses of Na{sup +}, K{sup +}, Ca{sup 2+} and Mg{sup 2+} were proportional to the ionic gradients between the plasma and water, indicating diffusive ion loss with metal exposure. This study has shown that there is a common pathway for metal uptake and a common mechanism of acute toxicity across groups of metals in zebrafish. The disruption of ion uptake accompanying metal exposure does not appear to be responsible for the acute toxicity of metals, as has been previously suggested, but rather the toxicity is instead due to total ion loss (predominantly Na{sup +}).

Pathogenetic justification of dietary supplement TestogenonTM for complex impact on men's reproductive system

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V. G. Liflyandsky

2015-01-01

Full Text Available The reasonable complex preparation TestogenonTM for prevention and treatment of frustration of reproductive system of men including extracts of plants (bark of a pidzheum, a dioskorea, a yokhimba, a ginseng root and biologically active agents (L-arginin, vitamins C and E, B5, B6 and B12 is created pathogenetic. Harmlessness and safety of a preparation are confirmed in pilot studies. Preclinical researches of specific pharmacological activity of dietary supplement to food TestogenonTM, allowed to establish stimulation at experimental animals of production of own testosterone which concentration was authentically above, than at control animals. Besides, at the rats receiving TestogenonTM activation of all indicators of sexual behavior was observed: average frequency a cage on females was 82 % higher, the quantity of intromissiya exceeded that control animals at 12–15 times, the latent period a cage and an interval between sessions authentically decreased. The preparation is recommended for strengthening of a libido, increase in duration of sexual intercourse, elimination of erektilny dysfunction, simplification of age manifestations of a man's climax, and also within complex therapy of a good-quality hyperplasiya of a prostate gland, chronic not bacterial prostatitis, man's infertility, an incontience of urine, testosterone synthesis stimulation. TestogenonTM is contraindicated at the increased nervous excitability, sleeplessness, arterial hypertension, decrease in coagulability of blood, arrhythmia, the expressed dysfunction of a liver and kidneys. 

The effects of common footwear on stance-phase mechanical properties of the prosthetic foot-shoe system.

Science.gov (United States)

Major, Matthew J; Scham, Joel; Orendurff, Michael

2018-04-01

Prosthetic feet are prescribed based on their mechanical function and user functional level. Subtle changes to the stiffness and hysteresis of heel, midfoot, and forefoot regions can influence the dynamics and economy of gait in prosthesis users. However, the user's choice of shoes may alter the prosthetic foot-shoe system mechanical characteristics, compromising carefully prescribed and rigorously engineered performance of feet. Observe the effects of footwear on the mechanical properties of the prosthetic foot-shoe system including commonly prescribed prosthetic feet. Repeated-measures, Mechanical characterization. The stiffness and energy return was measured using a hydraulic-driven materials test machine across combinations of five prosthetic feet and four common shoes as well as a barefoot condition. Heel energy return decreased by an average 4%-9% across feet in all shoes compared to barefoot, with a cushioned trainer displaying the greatest effect. Foot designs that may improve perceived stability by providing low heel stiffness and rapid foot-flat were compromised by the addition of shoes. Shoes altered prosthesis mechanical characteristics in the sagittal and frontal planes, suggesting that shoe type should be controlled or reported in research comparing prostheses. Understanding of how different shoes could alter certain gait-related characteristics of prostheses may aid decisions on footwear made by clinicians and prosthesis users. Clinical relevance Shoes can alter function of the prosthetic foot-shoe system in unexpected and sometimes undesirable ways, often causing similar behavior across setups despite differences in foot design, and prescribing clinicians should carefully consider these effects on prosthesis performance.

A Glimpse of the Pathogenetic Mechanisms of Wnt/β-Catenin Signaling in Diabetic Nephropathy

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Li Xiao

2013-01-01

Full Text Available The Wnt family of proteins belongs to a group of secreted lipid-modified glycoproteins with highly conserved cysteine residues. Prior results indicate that Wnt/β-catenin signaling plays a prominent role in cell differentiation, adhesion, survival, and apoptosis and is involved in organ development, tumorigenesis, and tissue fibrosis, among other functions. Accumulating evidence has suggested that Wnt/β-catenin exhibits a pivotal function in the progression of diabetic nephropathy (DN. In this review, we focused on discussing the dual role of Wnt/β-catenin in apoptosis and epithelial mesenchymal transition (EMT formation of mesangial cells. Moreover, we also elucidated the effect of Wnt/β-catenin in podocyte dysfunction, tubular EMT formation, and renal fibrosis under DN conditions. In addition, the molecular mechanisms involved in this process are introduced. This information provides a novel molecular target of Wnt/β-catenin for the protection of kidney damage and in delay of the progression of DN.

FUNCTIONAL FECAL INCONTINENCE IN CHILDREN (DIFFERENTIAL DIAGNOSTICS AND TREATMENT APPROACHES

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V.N. Kopeikin

2009-01-01

Full Text Available Impairment of the intestinal content continence, a common clinical situation with various pathogenetic mechanisms. Disease proceeds with the child’s maladjustment events. 33 cases of encopresis have been analyzed. This condition has various clinical and instrumental diagnostic criteria depending on the origin which simplifies differential diagnostics. Using a differential diagnostics table helps expedite the process of making a diagnosis and hence start an adequate treatment in a timely manner.Key words: encopresis, differential diagnostics, treatment, children.

Skeletal muscle repair in a mouse model of nemaline myopathy

OpenAIRE

Sanoudou, Despina; Corbett, Mark A.; Han, Mei; Ghoddusi, Majid; Nguyen, Mai-Anh T.; Vlahovich, Nicole; Hardeman, Edna C.; Beggs, Alan H.

2006-01-01

Nemaline myopathy (NM), the most common non-dystrophic congenital myopathy, is a variably severe neuromuscular disorder for which no effective treatment is available. Although a number of genes have been identified in which mutations can cause NM, the pathogenetic mechanisms leading to the phenotypes are poorly understood. To address this question, we examined gene expression patterns in an NM mouse model carrying the human Met9Arg mutation of alpha-tropomyosin slow (Tpm3). We assessed five d...

Radiation pneumonitis and fibrosis: Mechanisms underlying its pathogenesis and implications for future research

International Nuclear Information System (INIS)

Tsoutsou, Pelagia G.; Koukourakis, Michael I.

2006-01-01

Radiation pneumonitis and subsequent radiation pulmonary fibrosis are the two main dose-limiting factors when irradiating the thorax that can have severe implications for patients' quality of life. In this article, the current concepts about the pathogenetic mechanisms underlying radiation pneumonitis and fibrosis are presented. The clinical course of fibrosis, a postulated acute inflammatory stage, and a late fibrotic and irreversible stage are discussed. The interplay of cells and the wide variety of molecules orchestrating the immunologic response to radiation, their interactions with specific receptors, and the cascade of events they trigger are elucidated. Finally, the implications of this knowledge with respect to the therapeutic interventions are critically presented

A60

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A. Shihlyarova

2015-11-01

Conclusion: Modulating abnormalities in energy metabolism due to metabolic acidosis of tumor microenvironment on the background of systemic chemotherapy, one can achieve activation of additional pathogenetic mechanisms of inhibition of tumor growth and tumor cell death. It is necessary to emphasize the importance of the further search for factors of pathogenetic mechanisms and therapy of the influence on the tumor, including the modulation of acidosis of peritumoraly area that opens up new perspectives in solving this problem.

Divergent regeneration-competent cells adopt a common mechanism for callus initiation in angiosperms.

Science.gov (United States)

Hu, Bo; Zhang, Guifang; Liu, Wu; Shi, Jianmin; Wang, Hua; Qi, Meifang; Li, Jiqin; Qin, Peng; Ruan, Ying; Huang, Hai; Zhang, Yijing; Xu, Lin

2017-06-01

In tissue culture, the formation of callus from detached explants is a key step in plant regeneration; however, the regenerative abilities in different species are variable. While nearly all parts of organs of the dicot Arabidopsis thaliana are ready for callus formation, mature regions of organs in monocot rice ( Oryza sativa ) and other cereals are extremely unresponsive to tissue culture. Whether there is a common molecular mechanism beyond these different regenerative phenomena is unclear. Here we show that the Arabidopsis and rice use different regeneration-competent cells to initiate callus, whereas the cells all adopt WUSCHEL-RELATED HOMEOBOX 11 ( WOX11 ) and WOX5 during cell fate transition. Different from Arabidopsis which maintains regeneration-competent cells in mature organs, rice exhausts those cells during organ maturation, resulting in regenerative inability in mature organs. Our study not only explains this old perplexity in agricultural biotechnology, but also provides common molecular markers for tissue culture of different angiosperm species.

On the common mechanism for initiation of different effects of low doses of ionizing radiations

International Nuclear Information System (INIS)

Ehjdus, L.Kh.

1996-01-01

Main regularities of different endpoints of ionizing radiation low dose effects (adaptive response, stimulation of proliferation, special radiosensitivity of lymphoid cells, and others) have been examined. It has been shown that these endpoints have a commonness for the dose interval, the shape of the dose-response curve, the reverse effect of dose rate, non-specificity toward initiating agents, and others. An explanation is suggested for the common mechanism of the initiation of all the studied low dose effects, basing on the theory of the non-specific reaction of cell to external influences. It is concluded that initiation of the low dose effects is conditioned by radiation induced damage of functions of plasmic and internal membranes

Pathogenetic treatment for knee osteoarthrosis

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Marina Stanislavovna Svetlova

2012-09-01

Full Text Available The paper presents the results of studying the impact of long-term treatment with theraflex (a 3-year follow-up or alflutop (a 5-year follow-up in patients with knee osteoarthosis. Both drugs have been shown to exert a positive effect on the symptoms of the disease. It has been concluded that theraflex affects more actively the pathogenic mechanisms in the progression of gonarthrosis.

Pathogenetic treatment for knee osteoarthrosis

Directory of Open Access Journals (Sweden)

Marina Stanislavovna Svetlova

2012-01-01

Full Text Available The paper presents the results of studying the impact of long-term treatment with theraflex (a 3-year follow-up or alflutop (a 5-year follow-up in patients with knee osteoarthosis. Both drugs have been shown to exert a positive effect on the symptoms of the disease. It has been concluded that theraflex affects more actively the pathogenic mechanisms in the progression of gonarthrosis.

Pathogenetic, Clinical, and Prognostic Features of Adult t(4;11(q21;q23/MLL-AF4 Positive B-Cell Acute Lymphoblastic Leukemia

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F. Marchesi

2011-01-01

Full Text Available Translocation t(4;11(q21;q23 leading to formation of MLL-AF4 fusion gene is found in about 10% of newly diagnosed B-cell acute lymphoblastic leukemia (ALL in adult patients. Patients expressing this chromosomal aberration present typical biological, immunophenotypic, and clinical features. This form of leukemia is universally recognized as high-risk leukemia and treatment intensification with allogeneic hematopoietic stem cell transplantation (HSCT in first complete remission (CR could be a valid option to improve prognosis, but data obtained from the literature are controversial. In this review, we briefly describe pathogenetic, clinical, and prognostic characteristics of adult t(4;11(q21;q23/MLL-AF4 positive ALL and provide a review of the clinical outcome reported by the most important cooperative groups worldwide.

Bicuspid aortic valve syndrome and fibrillinopathies: potential impact on clinical approach

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Rosina De Cario

2014-01-01

Full Text Available Bicuspid aortic valve (BAV is a common heterogeneous disorder whose natural history is determined by hemodynamic valvular impairment and/or increased prevalence of aortic abnormalities ranging from dilatation to aneurysm and dissection. BAV-related aortopathy is frequently associated with relevant aortic pathologic changes leading to structural alterations, characteristic degenerative lesions and histological changes of the aorta very similar to those identified and described in patients with Marfan syndrome (MFS, an inherited connective tissue disorder associated with mutations in fibrillin 1 (FBN1 gene in more than 90% of patients. Recently, a 4-fold increase in the prevalence of BAV in MFS patients has been reported. Subsequently, pathogenetic FBN1 mutations in patients with BAV and aortic dilatation/aneurysm in whom MFS and other more severe type 1 fibrillinopathies were clinically excluded have been identified. In this review we discuss how this evidence, together with that of the wide heterogeneity in pathogenetic mechanisms of BAV-related aortopathy, may impact the clinical management of BAV.

Common and distinct neural mechanisms of attentional switching and response conflict.

Science.gov (United States)

Kim, Chobok; Johnson, Nathan F; Gold, Brian T

2012-08-21

The human capacities for overcoming prepotent actions and flexibly switching between tasks represent cornerstones of cognitive control. Functional neuroimaging has implicated a diverse set of brain regions contributing to each of these cognitive control processes. However, the extent to which attentional switching and response conflict draw on shared or distinct neural mechanisms remains unclear. The current study examined the neural correlates of response conflict and attentional switching using event-related functional magnetic resonance imaging (fMRI) and a fully randomized 2×2 design. We manipulated an arrow-word version of the Stroop task to measure conflict and switching in the context of a single task decision, in response to a common set of stimuli. Under these common conditions, both behavioral and imaging data showed significant main effects of conflict and switching but no interaction. However, conjunction analyses identified frontal regions involved in both switching and response conflict, including the dorsal anterior cingulate cortex (dACC) and left inferior frontal junction. In addition, connectivity analyses demonstrated task-dependent functional connectivity patterns between dACC and inferior temporal cortex for attentional switching and between dACC and posterior parietal cortex for response conflict. These results suggest that the brain makes use of shared frontal regions, but can dynamically modulate the connectivity patterns of some of those regions, to deal with attentional switching and response conflict. Copyright © 2012 Elsevier B.V. All rights reserved.

Crossing the Vascular Wall: Common and Unique Mechanisms Exploited by Different Leukocyte Subsets during Extravasation

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Michael Schnoor

2015-01-01

Full Text Available Leukocyte extravasation is one of the essential and first steps during the initiation of inflammation. Therefore, a better understanding of the key molecules that regulate this process may help to develop novel therapeutics for treatment of inflammation-based diseases such as atherosclerosis or rheumatoid arthritis. The endothelial adhesion molecules ICAM-1 and VCAM-1 are known as the central mediators of leukocyte adhesion to and transmigration across the endothelium. Engagement of these molecules by their leukocyte integrin receptors initiates the activation of several signaling pathways within both leukocytes and endothelium. Several of such events have been described to occur during transendothelial migration of all leukocyte subsets, whereas other mechanisms are known only for a single leukocyte subset. Here, we summarize current knowledge on regulatory mechanisms of leukocyte extravasation from a leukocyte and endothelial point of view, respectively. Specifically, we will focus on highlighting common and unique mechanisms that specific leukocyte subsets exploit to succeed in crossing endothelial monolayers.

Altered consciousness states and endogenous psychoses: a common molecular pathway?

Science.gov (United States)

Ciprian-Ollivier, J; Cetkovich-Bakmas, M G

1997-12-19

Interest in the role of indolamines in the pathogenesis of psychoses has been renewed in recent years by the development of atypical antipsychotic drugs such as clozapine, olanzapine, and risperidone, which act on serotonin receptors. Discovery of the hallucinogenic compounds called methylated indolealkyalamines (MIAs) (e.g. N,N-dimethylserotonin, or bufotenin, and N,N-dimethyltryptamine, or DMT) led proponents of the transmethylation hypothesis of schizophrenia to theorize that through some inborn error of metabolism, serotonin or tryptamine might undergo the addition of extra methyl radicals, thereby forming MIAs with hallucinogenic properties. Various studies have attempted to detect the excretion of MIAs, especially DMT, in the body fluids of psychotic patients and normal controls. Some of these studies have demonstrated elevated MIA concentrations in psychotic patients, including those with schizophrenia, compared with normal persons, and others have not. A number of variables may account for these contradictory findings. The mechanism whereby the beverage ayahuasca, which is used in certain cure and divination rituals in the Amazon Basin, exerts its hallucinogenic effects may serve as a model to explain the mechanism underlying hallucinogenic symptoms in schizophrenia and may lend support to the transmethylation hypothesis. Certain studies suggest that specific perceptual disturbances manifested by schizophrenic patients could contribute to progressive deterioration and negative symptomatology. All these findings point to the need for further study of the neurophysiology of MIAs and their pathogenetic role in endogenous psychoses.

Computer vision syndrome-A common cause of unexplained visual symptoms in the modern era.

Science.gov (United States)

Munshi, Sunil; Varghese, Ashley; Dhar-Munshi, Sushma

2017-07-01

The aim of this study was to assess the evidence and available literature on the clinical, pathogenetic, prognostic and therapeutic aspects of Computer vision syndrome. Information was collected from Medline, Embase & National Library of Medicine over the last 30 years up to March 2016. The bibliographies of relevant articles were searched for additional references. Patients with Computer vision syndrome present to a variety of different specialists, including General Practitioners, Neurologists, Stroke physicians and Ophthalmologists. While the condition is common, there is a poor awareness in the public and among health professionals. Recognising this condition in the clinic or in emergency situations like the TIA clinic is crucial. The implications are potentially huge in view of the extensive and widespread use of computers and visual display units. Greater public awareness of Computer vision syndrome and education of health professionals is vital. Preventive strategies should form part of work place ergonomics routinely. Prompt and correct recognition is important to allow management and avoid unnecessary treatments. © 2017 John Wiley & Sons Ltd.

Teaching assistants’ performance at identifying common introductory student difficulties in mechanics revealed by the Force Concept Inventory

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Alexandru Maries

2016-05-01

Full Text Available The Force Concept Inventory (FCI has been widely used to assess student understanding of introductory mechanics concepts by a variety of educators and physics education researchers. One reason for this extensive use is that many of the items on the FCI have strong distractor choices which correspond to students’ alternate conceptions in mechanics. Instruction is unlikely to be effective if instructors do not know the common alternate conceptions of introductory physics students and explicitly take into account students’ initial knowledge states in their instructional design. Here, we discuss research involving the FCI to evaluate one aspect of the pedagogical content knowledge of teaching assistants (TAs: knowledge of introductory student alternate conceptions in mechanics as revealed by the FCI. For each item on the FCI, the TAs were asked to identify the most common incorrect answer choice of introductory physics students. This exercise was followed by a class discussion with the TAs related to this task, including the importance of knowing student difficulties in teaching and learning. Then, we used FCI pretest and post-test data from a large population (∼900 of introductory physics students to assess the extent to which TAs were able to identify alternate conceptions of introductory students related to force and motion. In addition, we carried out think-aloud interviews with graduate students who had more than two semesters of teaching experience in recitations to examine how they reason about the task. We find that while the TAs, on average, performed better than random guessing at identifying introductory students’ difficulties with FCI content, they did not identify many common difficulties that introductory physics students have after traditional instruction. We discuss specific alternate conceptions, the extent to which TAs are able to identify them, and results from the think-aloud interviews that provided valuable information

Defective angiogenesis delays thrombus resolution: a potential pathogenetic mechanism underlying chronic thromboembolic pulmonary hypertension

Science.gov (United States)

Panzenboeck, Adelheid; Winter, Max P; Schubert, Uwe; Voswinckel, Robert; Frey, Maria K; Jakowitsch, Johannes; Alimohammadi, Arman; Hobohm, Lukas; Mangold, Andreas; Bergmeister, Helga; Sibilia, Maria; Wagner, Erwin F; Mayer, Eckhard; Klepetko, Walter; Hoelzenbein, Thomas J; Preissner, Klaus T; Lang, Irene M

2015-01-01

Objective Restoration of patency is a natural target of vascular remodeling following venous thrombosis that involves vascular endothelial cells and smooth muscle cells as well as leukocytes. Acute pulmonary emboli usually resolve within six months. However, in some instances, thrombi transform into fibrous vascular obstructions, resulting in occlusion of the deep veins, or in chronic thromboembolic pulmonary hypertension (CTEPH). We proposed that dysregulated thrombus angiogenesis may contribute to thrombus persistence. Approach and Results Mice with an endothelial-cell-specific conditional deletion of vascular endothelial growth factor receptor 2/kinase insert domain protein receptor (VEGF-R2/Kdr) were utilized in a model of stagnant flow venous thrombosis closely resembling human deep vein thrombosis. Biochemical and functional analyses were performed on pulmonary endarterectomy specimens from patients with CTEPH, a human model of non-resolving venous thromboembolism. Endothelial cell-specific deletion of Kdr and subsequent ablation of thrombus vascularization delayed thrombus resolution. In accordance with these findings, organized human CTEPH thrombi were largely devoid of vascular structures. Several vessel-specific genes such as KDR, vascular endothelial cadherin and podoplanin were expressed at lower levels in white CTEPH thrombi than in organizing deep vein thrombi and organizing thrombi from aortic aneurysms. In addition, red CTEPH thrombi attenuated the angiogenic response induced by VEGF. Conclusions In the present work, we propose a mechanism of thrombus non-resolution demonstrating that endothelial cell-specific deletion of Kdr abates thrombus vessel formation, misguiding thrombus resolution. Medical conditions associated with the development of CTEPH may be compromising early thrombus angiogenesis. PMID:24526692

QCI Common

Energy Technology Data Exchange (ETDEWEB)

2016-11-18

There are many common software patterns and utilities for the ORNL Quantum Computing Institute that can and should be shared across projects. Otherwise we find duplication of code which adds unwanted complexity. This is a software product seeks to alleviate this by providing common utilities such as object factories, graph data structures, parameter input mechanisms, etc., for other software products within the ORNL Quantum Computing Institute. This work enables pure basic research, has no export controlled utilities, and has no real commercial value.

Common variants at five new loci associated with early-onset inflammatory bowel disease.

Science.gov (United States)

Imielinski, Marcin; Baldassano, Robert N; Griffiths, Anne; Russell, Richard K; Annese, Vito; Dubinsky, Marla; Kugathasan, Subra; Bradfield, Jonathan P; Walters, Thomas D; Sleiman, Patrick; Kim, Cecilia E; Muise, Aleixo; Wang, Kai; Glessner, Joseph T; Saeed, Shehzad; Zhang, Haitao; Frackelton, Edward C; Hou, Cuiping; Flory, James H; Otieno, George; Chiavacci, Rosetta M; Grundmeier, Robert; Castro, Massimo; Latiano, Anna; Dallapiccola, Bruno; Stempak, Joanne; Abrams, Debra J; Taylor, Kent; McGovern, Dermot; Silber, Gary; Wrobel, Iwona; Quiros, Antonio; Barrett, Jeffrey C; Hansoul, Sarah; Nicolae, Dan L; Cho, Judy H; Duerr, Richard H; Rioux, John D; Brant, Steven R; Silverberg, Mark S; Taylor, Kent D; Barmuda, M Michael; Bitton, Alain; Dassopoulos, Themistocles; Datta, Lisa Wu; Green, Todd; Griffiths, Anne M; Kistner, Emily O; Murtha, Michael T; Regueiro, Miguel D; Rotter, Jerome I; Schumm, L Philip; Steinhart, A Hillary; Targan, Stephen R; Xavier, Ramnik J; Libioulle, Cécile; Sandor, Cynthia; Lathrop, Mark; Belaiche, Jacques; Dewit, Olivier; Gut, Ivo; Heath, Simon; Laukens, Debby; Mni, Myriam; Rutgeerts, Paul; Van Gossum, André; Zelenika, Diana; Franchimont, Denis; Hugot, J P; de Vos, Martine; Vermeire, Severine; Louis, Edouard; Cardon, Lon R; Anderson, Carl A; Drummond, Hazel; Nimmo, Elaine; Ahmad, Tariq; Prescott, Natalie J; Onnie, Clive M; Fisher, Sheila A; Marchini, Jonathan; Ghori, Jilur; Bumpstead, Suzannah; Gwillam, Rhian; Tremelling, Mark; Delukas, Panos; Mansfield, John; Jewell, Derek; Satsangi, Jack; Mathew, Christopher G; Parkes, Miles; Georges, Michel; Daly, Mark J; Heyman, Melvin B; Ferry, George D; Kirschner, Barbara; Lee, Jessica; Essers, Jonah; Grand, Richard; Stephens, Michael; Levine, Arie; Piccoli, David; Van Limbergen, John; Cucchiara, Salvatore; Monos, Dimitri S; Guthery, Stephen L; Denson, Lee; Wilson, David C; Grant, Straun F A; Daly, Mark; Silverberg, Mark S; Satsangi, Jack; Hakonarson, Hakon

2009-12-01

The inflammatory bowel diseases (IBD) Crohn's disease and ulcerative colitis are common causes of morbidity in children and young adults in the western world. Here we report the results of a genome-wide association study in early-onset IBD involving 3,426 affected individuals and 11,963 genetically matched controls recruited through international collaborations in Europe and North America, thereby extending the results from a previous study of 1,011 individuals with early-onset IBD. We have identified five new regions associated with early-onset IBD susceptibility, including 16p11 near the cytokine gene IL27 (rs8049439, P = 2.41 x 10(-9)), 22q12 (rs2412973, P = 1.55 x 10(-9)), 10q22 (rs1250550, P = 5.63 x 10(-9)), 2q37 (rs4676410, P = 3.64 x 10(-8)) and 19q13.11 (rs10500264, P = 4.26 x 10(-10)). Our scan also detected associations at 23 of 32 loci previously implicated in adult-onset Crohn's disease and at 8 of 17 loci implicated in adult-onset ulcerative colitis, highlighting the close pathogenetic relationship between early- and adult-onset IBD.

Impairment of leaf photosynthesis after insect herbivory or mechanical injury on common milkweed, Asclepias syriaca.

Science.gov (United States)

Delaney, K J; Haile, F J; Peterson, R K D; Higley, L G

2008-10-01

Insect herbivory has variable consequences on plant physiology, growth, and reproduction. In some plants, herbivory reduces photosynthetic rate (Pn) activity on remaining tissue of injured leaves. We sought to better understand the influence of leaf injury on Pn of common milkweed, Asclepias syriaca (Asclepiadaceae), leaves. Initially, we tested whether Pn reductions occurred after insect herbivory or mechanical injury. We also (1) examined the duration of photosynthetic recovery, (2) compared mechanical injury with insect herbivory, (3) studied the relationship between leaf Pn with leaf injury intensity, and (4) considered uninjured leaf compensatory Pn responses neighboring an injured leaf. Leaf Pn was significantly reduced on mechanically injured or insect-fed leaves in all reported experiments except one, so some factor(s) (cardiac glycoside induction, reproductive investment, and water stress) likely interacts with leaf injury to influence whether Pn impairment occurs. Milkweed tussock moth larval herbivory, Euchaetes egle L. (Arctiidae), impaired leaf Pn more severely than mechanical injury in one experiment. Duration of Pn impairment lasted > 5 d to indicate high leaf Pn sensitivity to injury, but Pn recovery occurred within 13 d in one experiment. The degree of Pn reduction was more severe from E. egle herbivory than similar levels of mechanical tissue removal. Negative linear relationships characterized leaf Pn with percentage tissue loss from single E. egle-fed leaves and mechanically injured leaves and suggested that the signal to trigger leaf Pn impairment on remaining tissue of an injured leaf was amplified by additional tissue loss. Finally, neighboring uninjured leaves to an E. egle-fed leaf had a small (approximately 10%) degree of compensatory Pn to partly offset tissue loss and injured leaf Pn impairment.

Do reflex seizures and spontaneous seizures form a continuum? - triggering factors and possible common mechanisms.

Science.gov (United States)

Irmen, Friederike; Wehner, Tim; Lemieux, Louis

2015-02-01

Recent changes in the understanding and classification of reflex seizures have fuelled a debate on triggering mechanisms of seizures and their conceptual organization. Previous studies and patient reports have listed extrinsic and intrinsic triggers, albeit their multifactorial and dynamic nature is poorly understood. This paper aims to review literature on extrinsic and intrinsic seizure triggers and to discuss common mechanisms among them. Among self-reported seizure triggers, emotional stress is most frequently named. Reflex seizures are typically associated with extrinsic sensory triggers; however, intrinsic cognitive or proprioceptive triggers have also been assessed. The identification of a trigger underlying a seizure may be more difficult if it is intrinsic and complex, and if triggering mechanisms are multifactorial. Therefore, since observability of triggers varies and triggers are also found in non-reflex seizures, the present concept of reflex seizures may be questioned. We suggest the possibility of a conceptual continuum between reflex and spontaneous seizures rather than a dichotomy and discuss evidence to the notion that to some extent most seizures might be triggered. Copyright © 2014 British Epilepsy Association. Published by Elsevier Ltd. All rights reserved.

Type 2 Diabetes Mellitus and Cardiovascular Disease: Genetic and Epigenetic Links

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Salvatore De Rosa

2018-01-01

Full Text Available Type 2 diabetes mellitus (DM is a common metabolic disorder predisposing to diabetic cardiomyopathy and atherosclerotic cardiovascular disease (CVD, which could lead to heart failure through a variety of mechanisms, including myocardial infarction and chronic pressure overload. Pathogenetic mechanisms, mainly linked to hyperglycemia and chronic sustained hyperinsulinemia, include changes in metabolic profiles, intracellular signaling pathways, energy production, redox status, increased susceptibility to ischemia, and extracellular matrix remodeling. The close relationship between type 2 DM and CVD has led to the common soil hypothesis, postulating that both conditions share common genetic and environmental factors influencing this association. However, although the common risk factors of both CVD and type 2 DM, such as obesity, insulin resistance, dyslipidemia, inflammation, and thrombophilia, can be identified in the majority of affected patients, less is known about how these factors influence both conditions, so that efforts are still needed for a more comprehensive understanding of this relationship. The genetic, epigenetic, and environmental backgrounds of both type 2 DM and CVD have been more recently studied and updated. However, the underlying pathogenetic mechanisms have seldom been investigated within the broader shared background, but rather studied in the specific context of type 2 DM or CVD, separately. As the precise pathophysiological links between type 2 DM and CVD are not entirely understood and many aspects still require elucidation, an integrated description of the genetic, epigenetic, and environmental influences involved in the concomitant development of both diseases is of paramount importance to shed new light on the interlinks between type 2 DM and CVD. This review addresses the current knowledge of overlapping genetic and epigenetic aspects in type 2 DM and CVD, including microRNAs and long non-coding RNAs, whose

EPIDEMIOLOGICAL AND PATHOGENETIC ASPECTS OF NICKEL POISONING

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Vladmila Bojanic

2007-04-01

Full Text Available Nickel is widely distributed in the environment. High consumption of nickel containing products inevitably leads to environmental pollution by nickel and its derivatives at all stages of production, utilization, and disposal.Human exposure to nickel occurs primarily via inhalation and ingestion and is particularly high among nickel metallurgy workers. In addition, implantation of nickel-containing endoprostheses and iatrogenic administration of nickel-contaminated medica-tions leads to significant parenteral exposures. Exposure to nickel compounds can produce a variety of adverse effects on human health. Nickel allergy in the form of contact dermatitis is the most common reaction.A frontal headache, vertigo, nausea, vomiting, insomnia, and irritability are the most common signs of acute poisoning with nickel compounds. The respiratory tract, kidneys and liver suffer the most significant changes like nickel pneumoconiosis, chronic rhinitis and sinonasal tumors and transitory nephropathy. Although the accumulation of nickel in the body through chronic exposure can lead to lung fibrosis, cardiovascular and kidney diseases, the most serious concerns relate to nickel’s carcinogenic activity. Nickel compounds are carcinogenic to humans and metallic nickel is possibly carcinogenic to humans.

Juvenile localized scleroderma with port wine stain: Coincidental or possible common pathogenetic association

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Seval Dogruk Kacar

2015-01-01

Full Text Available Port wine stain and juvenile localized scleroderma are two different dermatoses usually encountered in pediatric age group. Up to now, there are reports of morphea patients initially diagnosed and treated as port wine stain. Coexistence of both diseases is not found yet. We herein present a case of juvenile localized scleroderma on the left side of trunk, with congenital port wine stain located on the ipsilateral face at V1-V2 distribution.

Juvenile localized scleroderma with port wine stain: coincidental or possible common pathogenetic association.

Science.gov (United States)

Kacar, Seval Dogruk; Ozuguz, Pinar; Polat, Serap; Kacar, Emre; Polat, Onur; Tokyol, Cigdem

2015-01-01

Port wine stain and juvenile localized scleroderma are two different dermatoses usually encountered in pediatric age group. Up to now, there are reports of morphea patients initially diagnosed and treated as port wine stain. Coexistence of both diseases is not found yet. We herein present a case of juvenile localized scleroderma on the left side of trunk, with congenital port wine stain located on the ipsilateral face at V1-V2 distribution.

SPECIFICITIES OF THE SUBSET PROFILE OF PERIPHERAL BLOOD IN PATIENTS WITH GLIOBLASTOMA: PATHOGENETIC AND CLINICAL ASSESSMENTS

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V. A. Chumakov

2006-01-01

Full Text Available Abstract. In glioblastoma (GB, it is necessary to take into consideration GB-associated secondary immunodeficiency (SID, so-called syndrome of tumor-associated SID (STASID. Cell subsets having effector and regulatory functions, play an important role in developing STASID, and their proportions in patients with different forms of GB can be of pathogenetic importance and have clinical value for treatment and rehabilitation scheduling as well. The most pathogenically and clinically important features of cell subsets profile of peripheral blood were analyzed in patients with different clinical and morphological types of GB. The patients were divided into three groups, i.e., groups I and II were formed by patients with STASID (marked and slightly marked SID, accordingly; group III – patients with SIDTAS (tumor-associated autoimmune syndrome, associated with SID. Marked suppression of cell immunity is typical of group I - imbalance in T-lymphocytes, in a number of specific subsets, and in subsets clusters, as well as disproportions in the immunoregulatory indexes. In group II, the subset profiles of blood were slightly different from the norm. In patients with SIDTAS, activation of cell immunity was evident, forming SID with signs of autoimmune syndrome, affecting effector and regulatory chains of immunity, and influencing the severity and forecast of the disease. Specific features of the immune status in patients with GB identified can be resulted from different clinicalmorphological types of the tumor; the latter are to be considered in differential diagnostics of clinical course of GB and in scheduling of clinical-immunological efficient anti-tumor pharmacotherapy in pre- and postoperative periods.

Sirenomelia of an intracytoplasmic sperm injection conceptus: a case report and review of mechanism.

Science.gov (United States)

Bakhtar, Omid; Benirschke, Kurt; Masliah, Eliezer

2006-01-01

Postmortem dissection of the 18-week male conceptus, product of intracytoplasmic sperm injection (ICSI), demonstrated the hallmark findings of sirenomelia. The lower legs were fused and the left knee was rotated medially. Internal organs showed hypoplastic lungs, a multicystic kidney, and unilateral ureteral hypoplasia. The vitelline artery was absorbed, in a classic fashion, into the umbilical artery and communicated with the aorta at a point proximal to the iliac arteries. The tributaries distal to this point were hypoplastic. This finding is consistent with previously documented cases of sirenomelia and is thought to be the pathogenetic mechanism resulting in a vascular steal from the lower extremities. A rare finding was the presence of a penis on the dorsal side just below a perforate anus. In this case report, we discuss the pertinent clinical history and autopsy findings. A brief review of the mechanism thought to give rise to sirenomelia is provided. To our knowledge, this is the first reported case of sirenomelia in an ICSI conceptus.

Is there an association between coronary atherosclerosis and ...

African Journals Online (AJOL)

Background: Atherosclerotic disease is the most common cause of death in the United States and prostate cancer has the highest incidence among males in the United States. Reports have indicated that atherosclerosis and cancers my share common pathoetiologic and pathogenetic cascades. If atherosclerosis and ...

Cochlear implantation for severe sensorineural hearing loss caused by lightning.

Science.gov (United States)

Myung, Nam-Suk; Lee, Il-Woo; Goh, Eui-Kyung; Kong, Soo-Keun

2012-01-01

Lightning strike can produce an array of clinical symptoms and injuries. It may damage multiple organs and cause auditory injuries ranging from transient hearing loss and vertigo to complete disruption of the auditory system. Tympanic-membrane rupture is relatively common in patients with lightning injury. The exact pathogenetic mechanisms of auditory lesions in lightning survivors have not been fully elucidated. We report the case of a 45-year-old woman with bilateral profound sensorineural hearing loss caused by a lightning strike, who was successfully rehabilitated after a cochlear implantation. Copyright © 2012 Elsevier Inc. All rights reserved.

Gastrointestinal obstruction caused by solidification and coagulation of enteral nutrition: pathogenetic mechanisms and potential risk factors

Directory of Open Access Journals (Sweden)

Leonello G

2018-04-01

Full Text Available Grazia Leonello,1 Antonio Giacomo Rizzo,1 Viviane Di Dio,2 Antonio Soriano,3 Claudia Previti,3 Grazia Giulia Pantè,3 Claudio Mastrojeni,1 Sebastiano Pantè1 1Department of Human Pathology of Adults and Evolutive Era “Gaetano Barresi”, University of Messina, Messina, Italy; 2Health Research Institute Bonino Pulejo, Piemonte Hospital, Messina, Italy; 3Department of Medical and Surgery Science, University of Messina, Messina, Italy Abstract: Enteral nutrition (EN is preferred in order to provide nutrition and reduce catabolism in critically ill patients. Recent studies suggest that the use of EN is successful and complications are rare. However, an underestimated mechanical complication of tube feedings seen in critically ill patients is the coagulation and solidification of the EN causing gastrointestinal obstruction. This report describes two clinical cases (1.23% of all cases seen at our clinic of obstruction and perforation of the small bowel secondary to the solidification of EN. The understanding and early recognition of this potential complication are essential for the prevention and successful treatment of this condition. Keywords: enteral nutrition, gastrointestinal contents, intestinal obstruction, small-bowel bezoar

Syringomyelia

DEFF Research Database (Denmark)

Blegvad, C; Grotenhuis, J A; Juhler, M

2014-01-01

BACKGROUND: The term syringomyelia describes many pathogenetically different disorders, and a variety of attempts to group these based on different criteria have been proposed in the literature. As a consequence a lack of consensus regarding classification and terminology exists. This inconsistency...... pathogenetic theories in relation to syringomyelia. Illustrative cases at our department were included and similar cases of the literature were found using the PubMed database. All material was reviewed with main focus on the classification and terminology used. RESULTS: Despite syringomyelia (G95.......0) and hydromyelia (Q06.4) existing as independent ICD-10 entities, we have shown that the use of classifying terminology for fluid-filled cavities in the spinal cord is indiscriminate and inconsistent. Even though a general agreement on the believed pathogenetic mechanism exists, and the general treatment methods...

Occurrence of crystal arthropathy in patients presenting with ...

African Journals Online (AJOL)

musculo-skeletal) diseases associated with the deposition of mineralized material within joints and periarticular soft tissues. Gout is the most common and pathogenetically best understood crystal arthropathy, followed by basic calcium ...

Primary Sjogren's syndrome associated with inappropriate ...

African Journals Online (AJOL)

A patient in whom primary Sjogren's syndrome and inappropriate antiduretic hormone secretion were associated is reported. This is the first report of such an association. The possible pathophysiological mechanisms are discussed and vasculitis proposed as the underlying pathogenetic mechanism.

Mechanical response of common millet (Panicum miliaceum) seeds under quasi-static compression: Experiments and modeling.

Science.gov (United States)

Hasseldine, Benjamin P J; Gao, Chao; Collins, Joseph M; Jung, Hyun-Do; Jang, Tae-Sik; Song, Juha; Li, Yaning

2017-09-01

The common millet (Panicum miliaceum) seedcoat has a fascinating complex microstructure, with jigsaw puzzle-like epidermis cells articulated via wavy intercellular sutures to form a compact layer to protect the kernel inside. However, little research has been conducted on linking the microstructure details with the overall mechanical response of this interesting biological composite. To this end, an integrated experimental-numerical-analytical investigation was conducted to both characterize the microstructure and ascertain the microscale mechanical properties and to test the overall response of kernels and full seeds under macroscale quasi-static compression. Scanning electron microscopy (SEM) was utilized to examine the microstructure of the outer seedcoat and nanoindentation was performed to obtain the material properties of the seedcoat hard phase material. A multiscale computational strategy was applied to link the microstructure to the macroscale response of the seed. First, the effective anisotropic mechanical properties of the seedcoat were obtained from finite element (FE) simulations of a microscale representative volume element (RVE), which were further verified from sophisticated analytical models. Then, macroscale FE models of the individual kernel and full seed were developed. Good agreement between the compression experiments and FE simulations were obtained for both the kernel and the full seed. The results revealed the anisotropic property and the protective function of the seedcoat, and showed that the sutures of the seedcoat play an important role in transmitting and distributing loads in responding to external compression. Copyright © 2017 Elsevier Ltd. All rights reserved.

Functional dyspepsia. Different mechanisms, comprehensive treatment

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A.E. Dorofeyev

2017-09-01

Full Text Available Functional dyspepsia (FD is a disease with different prevailing pathogenetic mechanisms. The prevalence of FD varies widely from 10 to 30 % of the population, depending on the country and the surveyed cohort. There are two forms of FD: postprandial distress syndrome manifested by a fullness/early satiety after eating, and epigastric pain syndrome — pain/burning in the epigastrium, which may worsen after eating. In a significant part of patients with FD, there are manifestations of both syndromes, the so-called overlap, or a mixed type. In the Ukrainian population, all patients with dyspepsia should be diagnosed and, if found, — undergo mandatory eradication of H.pylori. In patients with persistent symptoms or in those initially not infected with H.pylori, in our opinion, it is advisable to use the combination of proton pomp inhibitor and prokinetic as starting treatment. In our country, a fixed combination of omeprazole and domperidone is available in two dosages. This is Omez D containing 10 mg of both components and a more highly dosed Omez DSR containing 20 mg of omeprazole and 30 mg of domperidone in the form of sustained-release pellets.

[Pathogenetic and therapeutic aspects of secondary anorexia].

Science.gov (United States)

Laviano, A; Cascino, A; Muscaritoli, M; Rossi Fanelli, F

2000-01-01

Anorexia is an often underrated symptom in the clinical management of patients suffering from chronic diseases. Moreover, the anorexia accompanying chronic diseases (secondary anorexia) is often confused with anorexia nervosa, a typically neuropsychiatric disorder involving completely different pathogenic mechanisms and therapeutic strategies. Secondary anorexia is one of the main factors responsible for the development of malnutrition, which in turn negatively affects patient morbidity and mortality. Different mechanisms have been proposed to explain the pathogenesis of secondary anorexia. However, consistent experimental and clinical evidence seems to point to hypothalamic serotonergic system hyperactivity as a preeminent cause; this hyperactivity appears to be triggered by enhanced brain availability of tryptophan, the aminoacid precursor of serotonin. The hyperactive hypothalamic serotonergic system might also represent the final effector where different regulatory and modulating pathways, including cytokines, converge. The involvement of tryptophan and the hypothalamic serotonergic system is further supported by the effectiveness of a therapeutic strategy, based on the inhibition of tryptophan entry into the brain, in increasing the food intake of anorectic patients. Although these results represent an encouraging approach to the treatment of secondary anorexia, with possible beneficial effects on the nutritional status of patients, they need to be validated in larger trials.

The common marmoset monkey: avenues for exploring the prenatal, placental, and postnatal mechanisms in developmental programming of pediatric obesity.

Science.gov (United States)

Riesche, Laren; Tardif, Suzette D; Ross, Corinna N; deMartelly, Victoria A; Ziegler, Toni; Rutherford, Julienne N

2018-05-01

Animal models have been critical in building evidence that the prenatal experience and intrauterine environment are capable of exerting profound and permanent effects on metabolic health through developmental programming of obesity. However, despite physiological and evolutionary similarities, nonhuman primate models are relatively rare. The common marmoset monkey ( Callithrix jacchus) is a New World monkey that has been used as a biomedical model for well more than 50 years and has recently been framed as an appropriate model for exploring early-life impacts on later health and disease. The spontaneous, multifactorial, and early-life development of obesity in the common marmoset make it a valuable research model for advancing our knowledge about the role of the prenatal and placental mechanisms involved in developmental programming of obesity. This paper provides a brief overview of obesity in the common marmoset, followed by a discussion of marmoset reproduction and placental characteristics. We then discuss the occurrence and utility of variable intrauterine environments in developmental programming in marmosets. Evidence of developmental programming of obesity will be given, and finally, we put forward future directions and innovations for including the placenta in developmental programming of obesity in the common marmoset.

Urticaria in children: pathogenetic mechanisms and the possibilities of modern therapy

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A. V. Kudryavceva

2017-01-01

Full Text Available The review collected the latest literature data on urticaria - one of the most frequent skin diseases in children, accompanied by the appearance of blisters. It is notorious that histamine-liberation lies in the basis of the disease pathogenesis, regardless of the cause provoking an exacerbation. Precisely this explains the unified principle of therapy for all variants of urticaria -the administration of non-sedating antihistamines in the first line. Urticaria is classified for acute and chronic based on the duration of the course (up to 6 weeks or more. Experts do not recommend that physicians carry out any special diagnostic measures in the acute form of the disease, paying the utmost attention to the administration of effective treatment. the review describes the causes of disease exacerbation, the pathogenesis and the clinic of urticaria. Attention is paid to various options for managing patients with urticaria, published in the latest expert recommendations in Europe, America and Russia.

Increased BRAF Heterodimerization Is the Common Pathogenic Mechanism for Noonan Syndrome-Associated RAF1 Mutants

Science.gov (United States)

Wu, Xue; Yin, Jiani; Simpson, Jeremy; Kim, Kyoung-Han; Gu, Shengqing; Hong, Jenny H.; Bayliss, Peter; Backx, Peter H.

2012-01-01

Noonan syndrome (NS) is a relatively common autosomal dominant disorder characterized by congenital heart defects, short stature, and facial dysmorphia. NS is caused by germ line mutations in several components of the RAS–RAF–MEK–extracellular signal-regulated kinase (ERK) mitogen-activated protein kinase (MAPK) pathway, including both kinase-activating and kinase-impaired alleles of RAF1 (∼3 to 5%), which encodes a serine-threonine kinase for MEK1/2. To investigate how kinase-impaired RAF1 mutants cause NS, we generated knock-in mice expressing Raf1D486N. Raf1D486N/+ (here D486N/+) female mice exhibited a mild growth defect. Male and female D486N/D486N mice developed concentric cardiac hypertrophy and incompletely penetrant, but severe, growth defects. Remarkably, Mek/Erk activation was enhanced in Raf1D486N-expressing cells compared with controls. RAF1D486N, as well as other kinase-impaired RAF1 mutants, showed increased heterodimerization with BRAF, which was necessary and sufficient to promote increased MEK/ERK activation. Furthermore, kinase-activating RAF1 mutants also required heterodimerization to enhance MEK/ERK activation. Our results suggest that an increased heterodimerization ability is the common pathogenic mechanism for NS-associated RAF1 mutations. PMID:22826437

Measuring Value in the Commons-Based Ecosystem: Bridging the Gap Between the Commons and the Market

OpenAIRE

De Filippi , Primavera; Hassan , Samer

2014-01-01

International audience; Commons-based peer-production (CBPP) constitutes today an important driver for innovation and cultural development, both online and offline. This led to the establishment of an alternative, Commons-based ecosystem, based on peer-production and collaboration of peers contributing to a common good. Yet, to the extent that this operates outside of the market economy, we cannot rely on traditional market mechanisms (such as pricing) to estimate the value of CBPP. We presen...

Influence of obstructive sleep apnea on fatty liver disease: role of chronic intermittent hypoxia.

Science.gov (United States)

Türkay, Cansel; Ozol, Duygu; Kasapoğlu, Benan; Kirbas, Ismail; Yıldırım, Zeki; Yiğitoğlu, Ramazan

2012-02-01

Currently the common pathogenetic mechanisms in nonalcoholic fatty liver disease (NAFLD) and obstructive sleep apnea (OSA) are gaining increased attention. The aim of this study is to find out the influence of chronic intermittent hypoxemia and OSA related parameters to the severity of NAFLD. We examined the liver functions tests and ultrasonographic data of liver as well as markers of OSA severity (apnea-hypopnea index [AHI], oxygen desaturation index, minimum oxygen saturation, percentage of time spent with S(pO(2)) hypoxia during sleep. The prevalence of NAFLD was higher in patients with severe OSA, suggesting a role for nocturnal hypoxemia in the pathogenesis of fatty liver disease.

Malnutrition, anorexia and cachexia in cancer patients: A mini-review on pathogenesis and treatment.

Science.gov (United States)

Nicolini, Andrea; Ferrari, Paola; Masoni, Maria Chiara; Fini, Milena; Pagani, Stefania; Giampietro, Ottavio; Carpi, Angelo

2013-10-01

Malnutrition, anorexia and cachexia are a common finding in cancer patients. They become more evident with tumor growth and spread. However, the mechanisms by which they are sustained often arise early in the history of cancer. For malnutrition, these mechanisms can involve primary tumor or damage by specific treatment such as anticancer therapies (surgery, chemotherapy, radiotherapy) also in cancers that usually are not directly responsible for nutritional and metabolic status alterations (i.e. bone tumors). For anorexia, meal-related neural or hormonal signals and humoral signals related to body fat or energy storage and the interaction of these signals with the hypothalamus or the hypothalamic inappropriate response play a pathogenetic role. Some cytokines are probably involved in these mechanisms. For cachexia, the production of proinflammatory cytokines by tumour cells is the initial mechanism; the main biochemical mechanisms involved include the ubiquitine proteasome-dependent proteolysis and heat shock proteins. Treatment includes pharmaceutical and nutritional interventions. Copyright © 2013 Elsevier Masson SAS. All rights reserved.

A dominant-negative mutant inhibits multiple prion variants through a common mechanism.

Directory of Open Access Journals (Sweden)

Fen Pei

2017-10-01

Full Text Available Prions adopt alternative, self-replicating protein conformations and thereby determine novel phenotypes that are often irreversible. Nevertheless, dominant-negative prion mutants can revert phenotypes associated with some conformations. These observations suggest that, while intervention is possible, distinct inhibitors must be developed to overcome the conformational plasticity of prions. To understand the basis of this specificity, we determined the impact of the G58D mutant of the Sup35 prion on three of its conformational variants, which form amyloids in S. cerevisiae. G58D had been previously proposed to have unique effects on these variants, but our studies suggest a common mechanism. All variants, including those reported to be resistant, are inhibited by G58D but at distinct doses. G58D lowers the kinetic stability of the associated amyloid, enhancing its fragmentation by molecular chaperones, promoting Sup35 resolubilization, and leading to amyloid clearance particularly in daughter cells. Reducing the availability or activity of the chaperone Hsp104, even transiently, reverses curing. Thus, the specificity of inhibition is determined by the sensitivity of variants to the mutant dosage rather than mode of action, challenging the view that a unique inhibitor must be developed to combat each variant.

Missense mutation in GRN gene affecting RNA splicing and plasma progranulin level in a family affected by frontotemporal lobar degeneration.

Science.gov (United States)

Luzzi, Simona; Colleoni, Lara; Corbetta, Paola; Baldinelli, Sara; Fiori, Chiara; Girelli, Francesca; Silvestrini, Mauro; Caroppo, Paola; Giaccone, Giorgio; Tagliavini, Fabrizio; Rossi, Giacomina

2017-06-01

Gene coding for progranulin, GRN, is a major gene linked to frontotemporal lobar degeneration. While most of pathogenic GRN mutations are null mutations leading to haploinsufficiency, GRN missense mutations do not have an obvious pathogenicity, and only a few have been revealed to act through different pathogenetic mechanisms, such as cytoplasmic missorting, protein degradation, and abnormal cleavage by elastase. The aim of this study was to disclose the pathogenetic mechanisms of the GRN A199V missense mutation, which was previously reported not to alter physiological progranulin features but was associated with a reduced plasma progranulin level. After investigating the family pedigree, we performed genetic and biochemical analysis on its members and performed RNA expression studies. We found that the mutation segregates with the disease and discovered that its pathogenic feature is the alteration of GRN mRNA splicing, actually leading to haploinsufficiency. Thus, when facing with a missense GRN mutation, its pathogenetic effects should be investigated, especially if associated with low plasma progranulin levels, to determine its nature of either benign polymorphism or pathogenic mutation. Copyright © 2017 Elsevier Inc. All rights reserved.

The Continuum of Aging and Age-Related Diseases: Common Mechanisms but Different Rates

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Claudio Franceschi

2018-03-01

Full Text Available Geroscience, the new interdisciplinary field that aims to understand the relationship between aging and chronic age-related diseases (ARDs and geriatric syndromes (GSs, is based on epidemiological evidence and experimental data that aging is the major risk factor for such pathologies and assumes that aging and ARDs/GSs share a common set of basic biological mechanisms. A consequence is that the primary target of medicine is to combat aging instead of any single ARD/GSs one by one, as favored by the fragmentation into hundreds of specialties and sub-specialties. If the same molecular and cellular mechanisms underpin both aging and ARDs/GSs, a major question emerges: which is the difference, if any, between aging and ARDs/GSs? The hypothesis that ARDs and GSs such as frailty can be conceptualized as accelerated aging will be discussed by analyzing in particular frailty, sarcopenia, chronic obstructive pulmonary disease, cancer, neurodegenerative diseases such as Alzheimer and Parkinson as well as Down syndrome as an example of progeroid syndrome. According to this integrated view, aging and ARDs/GSs become part of a continuum where precise boundaries do not exist and the two extremes are represented by centenarians, who largely avoided or postponed most ARDs/GSs and are characterized by decelerated aging, and patients who suffered one or more severe ARDs in their 60s, 70s, and 80s and show signs of accelerated aging, respectively. In between these two extremes, there is a continuum of intermediate trajectories representing a sort of gray area. Thus, clinically different, classical ARDs/GSs are, indeed, the result of peculiar combinations of alterations regarding the same, limited set of basic mechanisms shared with the aging process. Whether an individual will follow a trajectory of accelerated or decelerated aging will depend on his/her genetic background interacting lifelong with environmental and lifestyle factors. If ARDs and GSs are

The Pathogenetic Effect of Natural and Bacterial Toxins on Atopic Dermatitis

Science.gov (United States)

Park, Kyung-Duck; Pak, Sok Cheon; Park, Kwan-Kyu

2016-01-01

Atopic dermatitis (AD) is a common allergic skin disease that is associated with chronic, recurrent eczematous and pruritic lesions at the flexural folds caused by interacting factors related to environmental and immune system changes. AD results in dry skin, and immunoglobulin E-mediated allergic reactions to foods and environmental allergens. While steroids and anti-histamines temporarily relieve the symptoms of AD, the possibility of side effects from pharmacological interventions remains. Despite intensive research, the underlying mechanisms for AD have not been clarified. A study of Staphylococcus aureus (S. aureus) established the role of its toxins in the pathogenesis of AD. Approximately 90% of patients with AD experience S. aureus colonization and up to 50%–60% of the colonizing S. aureus is toxin-producing. Any damage to the protective skin barrier allows for the entry of invading allergens and pathogens that further drive the pathogenesis of AD. Some natural toxins (or their components) that have therapeutic effects on AD have been studied. In addition, recent studies on inflammasomes as one component of the innate immune system have been carried out. Additionally, studies on the close relationship between the activation of inflammasomes and toxins in AD have been reported. This review highlights the literature that discusses the pathogenesis of AD, the role of toxins in AD, and the positive and negative effects of toxins on AD. Lastly, suggestions are made regarding the role of inflammasomes in AD. PMID:28025545

Osteoporosis in Сhildren with Itsenko — Cushing Disease: Etiology, Pathogenesis, Diagnosis

Directory of Open Access Journals (Sweden)

M.O. Ryznychuk

2016-03-01

Full Text Available The review describes the etiology, pathogenetic mechanisms of osteoporosis in children with Itsenko — Cushing syndrome. The new methods for the diagnosis of osteoporosis in children were also analyzed.

Cumulative dosage effect of a RAD51L1/HMGA2 fusion and RAD51L1 loss in a case of pseudo-Meigs' syndrome.

NARCIS (Netherlands)

Amant, F.; Debiec-Rychter, M.; Schoenmakers, E.F.P.M.; Hagemeijer-Hausman, A.; Vergote, I.

2001-01-01

Uterine leiomyoma presenting with ascites and pleural fluid is referred to as pseudo-Meigs' syndrome. It is unclear whether common uterine leiomyomas and uterine leiomyomas causing pseudo-Meigs' syndrome are cytogenetically related or whether functionally different primary pathogenetic triggers are

Gastro-esophageal reflux disease and obesity, where is the link?

Science.gov (United States)

Emerenziani, Sara; Rescio, Maria Paola; Guarino, Michele Pier Luca; Cicala, Michele

2013-10-21

The confluence between the increased prevalence of gastro-esophageal reflux disease (GERD) and of obesity has generated great interest in the association between these two conditions. Several studies have addressed the potential relationship between GERD and obesity, but the exact mechanism by which obesity causes reflux disease still remains to be clearly defined. A commonly suggested pathogenetic pathway is the increased abdominal pressure which relaxes the lower esophageal sphincter, thus exposing the esophageal mucosal to gastric content. Apart from the mechanical pressure, visceral fat is metabolically active and it has been strongly associated with serum levels of adipo-cytokines including interleukin-6 and tumor necrosis factor α, which may play a role in GERD or consequent carcinogenesis. This summary is aimed to explore the potential mechanisms responsible for the association between GERD and obesity, and to better understand the possible role of weight loss as a therapeutic approach for GERD.

The stimulation of hematosis on short-term and prolong irradiation

International Nuclear Information System (INIS)

Tukhtaev, T.M.

1978-01-01

This book studies the stimulation of hematosis on short-term and prolong irradiation, pathogenetic mechanisms of lesion and reconstruction of hematosis at critical radiation sickness, action hematosis stimulators in short-term irradiation conditions

Pathophysiology of osteoarthritis: perspectives

Directory of Open Access Journals (Sweden)

O. Viapiana

2011-09-01

Full Text Available Osteoarthritis is generally considered a degenerative disorder driven by mechanical alteration of joint cartilage, with the bone changes being reactive to cartilage changes. According to this pathogenetic mechanism the only strategy to prevent osteoarthritis should be based on the so-called “chondro-protective agents”. However, a number of recent finding suggests that both the initiation and the progression of the disease is driven by subchondral bone changes reactive to mechanical microdamages. These increase osteoblastic activity at the “tide-mark” with consequent enlargement of the epiphyses and osteophyte formation. The increased bone turnover is secondary to overproduction of cytokines that diffuse to cartilage tissue, where they suppress condrocyte activity and activate metallo-proteases. Preliminary observational finding and experimental data showed that inhibitors of bone turnover might slow osteoarthritis progression. The pathogenetic hypothesis for osteoarthritis illustrated here provides the rational for a new therapeutic approach to the disease.

Phenotyping common beans for adaptation to drought

Science.gov (United States)

Beebe, Stephen E.; Rao, Idupulapati M.; Blair, Matthew W.; Acosta-Gallegos, Jorge A.

2013-01-01

Common beans (Phaseolus vulgaris L.) originated in the New World and are the grain legume of greatest production for direct human consumption. Common bean production is subject to frequent droughts in highland Mexico, in the Pacific coast of Central America, in northeast Brazil, and in eastern and southern Africa from Ethiopia to South Africa. This article reviews efforts to improve common bean for drought tolerance, referring to genetic diversity for drought response, the physiology of drought tolerance mechanisms, and breeding strategies. Different races of common bean respond differently to drought, with race Durango of highland Mexico being a major source of genes. Sister species of P. vulgaris likewise have unique traits, especially P. acutifolius which is well adapted to dryland conditions. Diverse sources of tolerance may have different mechanisms of plant response, implying the need for different methods of phenotyping to recognize the relevant traits. Practical considerations of field management are discussed including: trial planning; water management; and field preparation. PMID:23507928

Delayed and accelerated aging share common longevity assurance mechanisms

NARCIS (Netherlands)

Schumacher, B.; van der Pluijm, I.; Moorhouse, M.J.; Kosteas, T.; Robinson, A.R.; Suh, Y.; Breit, T.M.; van Steeg, H.; Niedernhofer, L.J.; van IJcken, W.; Bartke, A.; Spindler, S.R.; Hoeijmakers, J.H.J.; van der Horst, G.T.J.; Garinis, G.A.

2008-01-01

Mutant dwarf and calorie-restricted mice benefit from healthy aging and unusually long lifespan. In contrast, mouse models for DNA repair-deficient progeroid syndromes age and die prematurely. To identify mechanisms that regulate mammalian longevity, we quantified the parallels between the

Delayed and accelerated aging share common longevity assurance mechanisms

NARCIS (Netherlands)

B. Schumacher (Björn); I. van der Pluijm (Ingrid); M.J. Moorhouse (Michael); T. Kosteas (Theodore); A.R. Robinson (Andria Rasile); Y. Suh (Yousin); T.M. Breit (Timo); H. van Steeg (Harry); L.J. Niedernhofer (Laura); W.F.J. van IJcken (Wilfred); A. Bartke (Andrzej); S.R. Spindler (Stephen); J.H.J. Hoeijmakers (Jan); G.T.J. van der Horst (Gijsbertus); G.A. Garinis (George)

2008-01-01

textabstractMutant dwarf and calorie-restricted mice benefit from healthy aging and unusually long lifespan. In contrast, mouse models for DNA repair-deficient progeroid syndromes age and die prematurely. To identify mechanisms that regulate mammalian longevity, we quantified the parallels between

Multidimensional proteomics analysis of amniotic fluid to provide insight into the mechanisms of idiopathic preterm birth.

Directory of Open Access Journals (Sweden)

Irina A Buhimschi

2008-04-01

Full Text Available Though recent advancement in proteomics has provided a novel perspective on several distinct pathogenetic mechanisms leading to preterm birth (inflammation, bleeding, the etiology of most preterm births still remains elusive. We conducted a multidimensional proteomic analysis of the amniotic fluid to identify pathways related to preterm birth in the absence of inflammation or bleeding.A proteomic fingerprint was generated from fresh amniotic fluid using surface-enhanced laser desorbtion ionization time of flight (SELDI-TOF mass spectrometry in a total of 286 consecutive samples retrieved from women who presented with signs or symptoms of preterm labor or preterm premature rupture of the membranes. Inflammation and/or bleeding proteomic patterns were detected in 32% (92/286 of the SELDI tracings. In the remaining tracings, a hierarchical algorithm was applied based on descriptors quantifying similarity/dissimilarity among proteomic fingerprints. This allowed identification of a novel profile (Q-profile based on the presence of 5 SELDI peaks in the 10-12.5 kDa mass area. Women displaying the Q-profile (mean+/-SD, gestational age: 25+/-4 weeks, n = 40 were more likely to deliver preterm despite expectant management in the context of intact membranes and normal amniotic fluid clinical results. Utilizing identification-centered proteomics techniques (fluorescence two-dimensional differential gel electrophoresis, robotic tryptic digestion and mass spectrometry coupled with Protein ANalysis THrough Evolutionary Relationships (PANTHER ontological classifications, we determined that in amniotic fluids with Q-profile the differentially expressed proteins are primarily involved in non-inflammatory biological processes such as protein metabolism, signal transduction and transport.Proteomic profiling of amniotic fluid coupled with non-hierarchical bioinformatics algorithms identified a subgroup of patients at risk for preterm birth in the absence of intra

Influence of X-ray exposure on morphologic composition of blood of sheep

International Nuclear Information System (INIS)

Tukhtaev, T.M.; Badalov, S.

1983-01-01

Present article is devoted influence of X-ray exposure on morphologic composition of blood of sheep. Thus, pathogenetic mechanisms of formation of acute radiation sickness of laboratory animals are studied. The experiments are described.

Component Commonality and Its Cost Implications - Increasing the Commonality of the Right Components

DEFF Research Database (Denmark)

Lyly-Yrjänäinen, Jouni; Suomala, Petri; Israelsen, Poul

Component commonality (Labro 2004, Zhou & Gruppström 2004) can be defined as the use of the same version of a component across multiple products. It is usually seen as a means to manage costs without sacrificing product variety. However, when managing costs with component commonality, the managers...... constructions was identified as the most important bottleneck for the delivery process causing many indirect costs, especially with respect to project-management-related activities. Interestingly, by eliminating the need for mechanical engineering, the context starts to approach assembly-to-order context, also...... should be able to identify rather rapidly which group of components would enable the most significant cost reductions. Unfortunately, the existing literature lacks profound discussion of how to identify the right components for increased component commonality. The objective of the paper is to discuss how...

The Metabolic Role of Gut Microbiota in the Development of Nonalcoholic Fatty Liver Disease and Cardiovascular Disease

Directory of Open Access Journals (Sweden)

Marco Sanduzzi Zamparelli

2016-07-01

Full Text Available The prevalence of metabolic disorders, such as type 2 diabetes (T2D, obesity, and non-alcoholic fatty liver disease (NAFLD, which are common risk factors for cardiovascular disease (CVD, has dramatically increased worldwide over the last decades. Although dietary habit is the main etiologic factor, there is an imperfect correlation between dietary habits and the development of metabolic disease. Recently, research has focused on the role of the microbiome in the development of these disorders. Indeed, gut microbiota is implicated in many metabolic functions and an altered gut microbiota is reported in metabolic disorders. Here we provide evidence linking gut microbiota and metabolic diseases, focusing on the pathogenetic mechanisms underlying this association.

Contrast-induced nephropathy: risks, pathogenetic, prevention

International Nuclear Information System (INIS)

Paskalev, D.; Balev, B.

2006-01-01

Full text: The aim of the presentation is to review the contrast induced nephropathy ? nature, mechanisms of development, risk factors. Summary of the most important ways of prevention, diagnostics and treatment. The definition of CIN according the European Association of Urogenital Radiology is: 'A condition, in which renal function is impaired (elevation of serum creatinine with more than 25% or 44 μmol/l above the initial level) due to intravasal application of contrast media (CM) within 3 days following the application and when no other etiology factors are present'. We summarize the main risk factors of developing CIN - renal failure, diabetic nephropathy, dehydration, congestive heart failure, high blood pressure, age above 70 yrs, nephrotoxic medicines. The most effective ways of preventing CIN are the good hydratation of the patients and the usage of low-osmolar or iso-osmolar CM. Therapeutic treatment is with no proven preventive effect and currently is not routinely recommended. An early hem dialysis does not decrease the risk level of CIN development in patients with chronic renal failure (CRF). In such patients complete elimination of CM is achieved only after several hem dialyses. Hem filtration reliably decreases the risk of CIN in CRF patients, but is expensive and not widely available. We present a case from our hospital of a patient with diabetic nephropathy, who developed CIN following a coronary angiography

Pathogenetic Aspects of Preventive Correction of Cognitive Impairment in Metabolic Syndrome

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T.I. Nasonova

2016-02-01

Full Text Available Objective. To study the opportunities to increase the efficiency of pathogenetic therapy in patients with chronic cerebrovascular diseases (CVD (discirculatory encephalopathy, DE on the background of metabolic syndrome (MS using the drug Vitaxon®. The feature of the work was to identify strategic areas of the brain in cognitive and emotional disorders in patients with MS and its absence. Materials and methods. We observed 49 patients with DE II degree aged 37 to 73 years against the background of MS. The main group — 30 patients — received Vitaxon® as a part of treatment. The control group consisted of 19 patients with DE degree II following MS, comparable in the age and stage of the disease, who were not taking Vitaxon®. Patients were observed for 12 weeks. In addition to neurological, general clinical examinations, detection of MS signs, we have used neuropsychological tests by Mini Mental State Examination (MMSE and Montreal Cognitive Assessment (МоСА, Spielberger anxiety scale; Beck depression scale; study of attention: search of numbers by Schulte tables with the assessment of task-performance time. The brain and its liquor system in 41 patients (27 patients with MS — the first group and 14 patients without MS — the second group were evaluated using the method of volumetry (measuring the volume of certain brain regions, on the magnetic resonance imaging scanner Toshiba Vantage Titan 1.5. Results. Cognitive impairment in both groups manifested by the loss of memory, attention disorders, slowing of mental processes. After 12 weeks, the median by the MMSE significantly increased by 3.3 % (p < 0.05 compared with the first test in patients who received Vitaxon®. By МоСА, which is more sensitive when determining the mild cognitive impairment, in a group of Vitaxon® cognitive functions improved by 5 %, while in the control group — by 1.66 %. By Spielberger scale, state anxiety indicators improved more in the group of

Quantum mechanics, common sense and the black hole information paradox

CERN Document Server

Danielsson, U H; Danielsson, Ulf H.; Schiffer, Marcelo

1993-01-01

The purpose of this paper is to analyse, in the light of information theory and with the arsenal of (elementary) quantum mechanics (EPR correlations, copying machines, teleportation, mixing produced in sub-systems owing to a trace operation, etc.) the scenarios available on the market to resolve the so-called black-hole information paradox. We shall conclude that the only plausible ones are those where either the unitary evolution of quantum mechanics is given up, in which information leaks continuously in the course of black-hole evaporation through non-local processes, or those in which the world is polluted by an infinite number of meta-stable remnants.

The Association between Endometriomas and Ovarian Cancer: Preventive Effect of Inhibiting Ovulation and Menstruation during Reproductive Life.

Science.gov (United States)

Grandi, Giovanni; Toss, Angela; Cortesi, Laura; Botticelli, Laura; Volpe, Annibale; Cagnacci, Angelo

2015-01-01

Although endometriosis frequently involves multiple sites in the pelvis, malignancies associated with this disease are mostly confined to the ovaries, evolving from an endometrioma. Endometriomas present a 2-3-fold increased risk of transformation in clear-cell, endometrioid, and possibly low-grade serous ovarian cancers, but not in mucinous ovarian cancers. These last cancers are, in some aspects, different from the other epithelial ovarian cancers, as they do not appear to be decreased by the inhibition of ovulation and menstruation. The step by step process of transformation from typical endometrioma, through atypical endometrioma, finally to ovarian cancer seems mainly related to oxidative stress, inflammation, hyperestrogenism, and specific molecular alterations. Particularly, activation of oncogenic KRAS and PI3K pathways and inactivation of tumor suppressor genes PTEN and ARID1A are suggested as major pathogenic mechanisms for endometriosis associated clear-cell and endometrioid ovarian cancer. Both the risk for endometriomas and their associated ovarian cancers seems to be highly and similarly decreased by the inhibition of ovulation and retrograde menstruation, suggesting a common pathogenetic mechanism and common possible preventive strategies during reproductive life.

Imaging tumor hypoxia: Blood-borne delivery of imaging agents is fundamentally different in hypoxia subtypes

Directory of Open Access Journals (Sweden)

Peter Vaupel

2014-03-01

Full Text Available Hypoxic tissue subvolumes are a hallmark feature of solid malignant tumors, relevant for cancer therapy and patient outcome because they increase both the intrinsic aggressiveness of tumor cells and their resistance to several commonly used anticancer strategies. Pathogenetic mechanisms leading to hypoxia are diverse, may coexist within the same tumor and are commonly grouped according to the duration of their effects. Chronic hypoxia is mainly caused by diffusion limitations resulting from enlarged intercapillary distances and adverse diffusion geometries and — to a lesser extent — by hypoxemia, compromised perfusion or long-lasting microregional flow stops. Conversely, acute hypoxia preferentially results from transient disruptions in perfusion. While each of these features of the tumor microenvironment can contribute to a critical reduction of oxygen availability, the delivery of imaging agents (as well as nutrients and anticancer agents may be compromised or remain unaffected. Thus, a critical appraisal of the effects of the various mechanisms leading to hypoxia with regard to the blood-borne delivery of imaging agents is necessary to judge their ability to correctly represent the hypoxic phenotype of solid malignancies.

Immunochemical characterization of and isolation of the gene for a Borrelia burgdorferi immunodominant 60-kilodalton antigen common to a wide range of bacteria

DEFF Research Database (Denmark)

Hansen, K; Bangsborg, Jette Marie; Fjordvang, H

1988-01-01

. burgdorferi CA was localized on a 2.3-kilobase fragment of the plasmid pKH1. CA may have pathogenetic implications in Lyme borreliosis, since the CA of mycobacteria recently has been shown to play a role in the etiology of experimental autoimmune arthritis. The extensive cross-reactivity of this antigen may...... account for the low diagnostic specificity of the currently used serological tests in Lyme borreliosis....

Cytokine Regulation of Microenvironmental Cells in Myeloproliferative Neoplasms

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Gregor Hoermann

2015-01-01

Full Text Available The term myeloproliferative neoplasms (MPN refers to a heterogeneous group of diseases including not only polycythemia vera (PV, essential thrombocythemia (ET, and primary myelofibrosis (PMF, but also chronic myeloid leukemia (CML, and systemic mastocytosis (SM. Despite the clinical and biological differences between these diseases, common pathophysiological mechanisms have been identified in MPN. First, aberrant tyrosine kinase signaling due to somatic mutations in certain driver genes is common to these MPN. Second, alterations of the bone marrow microenvironment are found in all MPN types and have been implicated in the pathogenesis of the diseases. Finally, elevated levels of proinflammatory and microenvironment-regulating cytokines are commonly found in all MPN-variants. In this paper, we review the effects of MPN-related oncogenes on cytokine expression and release and describe common as well as distinct pathogenetic mechanisms underlying microenvironmental changes in various MPN. Furthermore, targeting of the microenvironment in MPN is discussed. Such novel therapies may enhance the efficacy and may overcome resistance to established tyrosine kinase inhibitor treatment in these patients. Nevertheless, additional basic studies on the complex interplay of neoplastic and stromal cells are required in order to optimize targeting strategies and to translate these concepts into clinical application.

Prophylaxis against postoperative complications in gastroenterology

DEFF Research Database (Denmark)

Kehlet, H; Moesgaard, F

1996-01-01

Gastrointestinal surgery results in pain, profound endocrine metabolic changes and organ dysfunction, immunosuppression and decreased resistance to infection, fatigue and convalescence. The main pathogenetic mechanism is the surgical stress response, which may be reduced by minimal invasive (lapa...

[Atypical retinitis pigmentosa in Laurence-Moon-Biedl-Bardet syndrome. Report of a case of chronic renal insufficiency under periodic hemodialysis treatment].

Science.gov (United States)

Bianco, G; Carlesimo, S C; Mazzarrino, R; Palestini, M

1993-03-01

A case of Laurence-Moon-Biedl-Bardet syndrome in a patient undergoing hemodialysis is reported. The principal characteristics of this congenital syndrome are described. A possible pathogenetic mechanism of the atypical form of retinitis pigmentosa (sine pigmento) is discussed.

Common cause failures of reactor pressure components

International Nuclear Information System (INIS)

Mankamo, T.

1978-01-01

The common cause failure is defined as a multiple failure event due to a common cause. The existence of common failure causes may ruin the potential advantages of applying redundancy for reliability improvement. Examples relevant to large mechanical components are presented. Preventive measures against common cause failures, such as physical separation, equipment diversity, quality assurance, and feedback from experience are discussed. Despite the large number of potential interdependencies, the analysis of common cause failures can be done within the framework of conventional reliability analysis, utilizing, for example, the method of deriving minimal cut sets from a system fault tree. Tools for the description and evaluation of dependencies between components are discussed: these include the model of conditional failure causes that are common to many components, and evaluation of the reliability of redundant components subjected to a common load. (author)

IMMUNOLOGICAL MECHANISMS FOR THE DEVELOPMENT OF NONALCOHOLIC FATTY LIVER DISEASE IN PATIENTS WITH GOUT AND PSEUDOGOUT: A REVIEW OF LITERATURE

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D. A. Nabieva

2017-01-01

Full Text Available The current ideas of gout include both the traditional metabolic theory of disorders of purine metabolism and environmental exposure and the involvement of immunoinflammatory factors in the pathological process. Inflammation is a hallmark of an acute tissue reaction to monosodium urate the crystals in gout and to calcium pyrophosphate crystals in pseudogout. The crystals interact with the membranes of plasma cells, with the activation of NLRP3, the proteolytic cleavage of pro-interleukin 1β, and the secretion of mature interleukin-1β that modulates a sequence of events leading to the activation of endothelial cells and neutrophils, which is also preceded by fatty degeneration of the liver. This review details recent data on the pathogenetic mechanisms that serve as predictors of metabolic changes and nonalcoholic fatty liver disease in patients with gout.

Cycles and Common Cycles in Property and Related Sectors

OpenAIRE

Peijie Wang

2003-01-01

This paper examines cycles and common cycles in the property market and the economy. While focusing on common cycles, the study also incorporates common trends in the meantime, so it covers the whole spectrum of dynamic analysis. It has been found that property shares common cycles, particularly with those sectors that are the user markets of property. The mechanisms of common cycles and the relative magnitudes of cycles of the sectors related to property are discussed to shed light on proper...

Studies on pathogenesis and treatment of experimental immune complex glomerulonephrtis.

NARCIS (Netherlands)

Fleuren, Gerard Johannes Maria

1976-01-01

Chapter 1. In this thesis an investigation into pathogenetic mechanisms of epimembranous immune complex depostion in the glomeruli was described. For this study we used two related models of experimental immune complex glemerulonephritis: the heterologous and the autologous immune complex

Lympho- and Myeloproliferative Malignancies Occurring in the Same Host: Description of a Nationwide Discovery Cohort

DEFF Research Database (Denmark)

Holst, Johanne Marie; Plesner, Trine Lindhardt; Pedersen, Martin Bjerregård

2017-01-01

Background: So far, myeloid and lymphoid malignancies have been considered as diseases with distinct pathogenetic mechanisms. However, recent studies (Frederiksen H et al, Blood 2011) have reported an increased risk of lymphoid malignancies in patients with chronic myeloproliferative neoplasms (M...

Therapeutic intervention in disseminated intravascular coagulation: have we made any progress in the last millennium?

NARCIS (Netherlands)

Levi, Marcel; de Jonge, Evert; van der Poll, Tom

2002-01-01

Disseminated intravascular coagulation (DIC) is a syndrome characterized by systemic intravascular activation of coagulation, leading to widespread deposition of fibrin in the circulation. Recent knowledge on important pathogenetic mechanisms that may lead to DIC has resulted in novel preventive and

Mechanical stop mechanism for overcoming MEMS fabrication tolerances

International Nuclear Information System (INIS)

Hussein, Hussein; Bourbon, Gilles; Le Moal, Patrice; Lutz, Philippe; Haddab, Yassine

2017-01-01

A mechanical stop mechanism is developed in order to compensate MEMS fabrication tolerances in discrete positioning. The mechanical stop mechanism is designed to be implemented on SOI wafers using a common DRIE etching process. The various fabrication tolerances obtained due to the etching process are presented and discussed in the paper. The principle and design of the mechanism are then presented. Finally, experiments on microfabricated positioning prototypes show accurate steps unaffected by the fabrication tolerances. (technical note)

Current pathogenetic aspects of hepatic encephalopathy and noncirrhotic hyperammonemic encephalopathy.

Science.gov (United States)

Cichoż-Lach, Halina; Michalak, Agata

2013-01-07

Hepatic encephalopathy is a medical phenomenon that is described as a neuropsychiatric manifestation of chronic or acute liver disease that is characterized by psychomotor, intellectual and cognitive abnormalities with emotional/affective and behavioral disturbances. This article focuses on the underlying mechanisms of the condition and the differences between hepatic encephalopathy and noncirrhotic hyperammonemic encephalopathy. Hepatic encephalopathy is a serious condition that can cause neurological death with brain edema and intracranial hypertension. It is assumed that approximately 60%-80% of patients with liver cirrhosis develop hepatic encephalopathy. This review explores the complex mechanisms that lead to hepatic encephalopathy. However, noncirrhotic hyperammonemic encephalopathy is not associated with hepatic diseases and has a completely different etiology. Noncirrhotic hyperammonemic encephalopathy is a severe occurrence that is connected with multiple pathogeneses.

Histochemical and ultrastructural study of an elastofibroma dorsi coexisting with a high grade spindle cell sarcoma

Directory of Open Access Journals (Sweden)

M Alberghini

2009-06-01

Full Text Available Elastofibroma dorsi is a pseudotumoral fibroproliferative lesion characterized by polymorphic fiber-like deposits of elastinophilic material. Several theories have been reported explaining the pathogenesis of elastofibroma. Recent cytogenetic studies have demonstrated chromosomal instability in elastofibromas, not normally observed in non-neoplastic tissues. These chromosomal defects are commonly observed in aggressive fibromatosis too. Such clinical observations suggest a multistage pathogenetic mechanism for the onset of elastofibroma. This study, using histochemical, immunohistochemical staining techniques, and ultrastructural examination, describes the detection of an otherwise typical elastofibroma contextual to a high grade sarcoma. Hence, the coexistence of elastofibroma and high-grade sarcoma may suggest a causal link between the two pathological entities. The results obtained suggest that the coexistence of the two pathological entities is conceivably coincidental.

Vulvovaginitis in childhood.

Science.gov (United States)

Dei, Metella; Di Maggio, Floriana; Di Paolo, Gilda; Bruni, Vincenzina

2010-04-01

Symptoms related to vulvitis and vulvovaginitis are a frequent complaint in the paediatric age. Knowledge of the risk factors and the pathogenetic mechanisms, combined with thorough clinical examination, helps to distinguish between dermatological diseases, non-specific vulvitis and vulvovaginitis proper. On the basis of microbiological data, the most common pathogens prove to be Streptococcus pyogenes, Haemophilus influenzae and Enterobius vermicularis; fungal and viral infections are less frequent. The possibility of isolating opportunistic pathogens should also be considered. In rare situations, the isolation of a micro-organism normally transmitted by sexual contact should prompt a careful evaluation of possible sexual abuse. Current treatments for specific and non-specific forms are outlined, together with pointers for the evaluation of recurrence. Copyright 2009 Elsevier Ltd. All rights reserved.

Microalbuminuria. Implications for micro- and macrovascular disease

DEFF Research Database (Denmark)

Deckert, T; Kofoed-Enevoldsen, A; Nørgaard, K

1992-01-01

Microalbuminuria is diagnosed when the UAER is greater than 20 but less than 200 micrograms/min. The prevalence of microalbuminuria among diabetic patients is 15-20%. Persistent microalbuminuria in diabetic patients is a risk marker not only of renal disease, but also of proliferative retinopathy...... patients with persistent microalbuminuria than in normoalbuminuric diabetic patients of similar age, sex, and diabetes duration. However, these risk factors cannot by themselves explain the cardiovascular overmortality in these patients. In addition, insulin resistance or genetic disposition...... to hypertension or cardiovascular disease fails to be the missing link. Accumulating evidence suggests a common pathogenetic mechanism for microalbuminuria and premature atherosclerosis (i.e., qualitative alterations of the extracellular matrix, including decreased density and sulfation of HS-PG). Decreased...

Formation and malformation of the enteric nervous system

NARCIS (Netherlands)

J.H.C. Meijers (Johan)

1989-01-01

textabstractTo clarify pathogenetic mechanisms of congenital malformations of the ENS, the formation of the ENS was investigated in chicken and murine embryos. The experimental work was concentrated on several aspects of the interaction between neural crest cells and the enteric microenvironment.

De novo development of artistic creativity in Alzheimer's disease.

Science.gov (United States)

Chakravarty, Ambar

2011-10-01

The case of an 82-year-old female with probable Alzheimer's disease (AD), who developed unusual artistic creativity after development of her disease, is described. The possible pathogenetic mechanism is discussed. The patient showed no inclination toward visual arts during her premorbid years. However, 4 years after development of AD suggestive symptoms she started painting beautiful pictures rather impulsively. Some such paintings have been appreciated even by a qualified art expert. Such de novo development of artistic creativity had been described earlier in subjects with the semantic form of fronto-temporal dementia (FTD), but not in AD. The prevailing concept of lateralized compromise and paradoxical functional facilitation, proposed in connection with FTD subjects, may not be applicable in AD subjects where the affection is more diffuse and more posterior in the brain. Hence, the likely pathogenetic mechanism involved in the case described may remain uncertain. Possibilities are discussed.

Necrobiosis lipoidica associated with Hashimoto's thyroiditis and positive detection of ANA and ASMA autoantibodies.

Science.gov (United States)

Borgia, Francesco; Russo, Giuseppina T; Villari, Provvidenza; Guarneri, Fabrizio; Cucinotta, Domenico; Cannavò, Serafinella P

2015-07-01

Necrobiosis lipoidica (NL) is a rare idiopathic cutaneous condition exceptionally associated with autoimmune thyroiditis. We describe the first case of NL, Hashimoto's thyroiditis and positive detection of autoantibodies. Appropriate screening for NL in patients with autoimmune thyroiditis may clarify its real incidence and the existence of a common pathogenetic pathway.

The agricultural policy of Serbia and common agricultural policy

Directory of Open Access Journals (Sweden)

Stanković Milica

2012-01-01

Full Text Available The agricultural sector has a relatively high importance in the economic structure of Serbia. The Common Agricultural Policy (CAP, Common Agricultural Policy is one of the main policies of the European Union. It is very important to point out the fundamental principles and objectives of the Common Agricultural Policy. Harmonization of the national agricultural policy of Serbia with the Common Agricultural Policy and acceptance of its mechanisms is crucial for the development of the agricultural sector as a whole.

Place of phosphatidylcholine in the treatment of inflammatory bowel disease

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A.E. Dorofeev

2017-09-01

Full Text Available In the pathogenesis of most diseases of the intestine, inflammation is important, and, often, critical. Its pathogenetic role in the inflammatory bowel disease was studied broadly and comprehensively. In recent years, research has begun on its contribution to intestinal damage in functional pathology — irritable bowel syndrome. The participation of inflammation in the development of erosive and ulcerative lesions of the lower gastrointestinal tract on the background of non-steroidal anti-inflammatory drugs (NSAID-enterocolopathy seems paradoxical. The role of phospholipids in the construction of cell membranes is well known. One of the main membrane phospholipids of most living organisms (with the exception of microbes is phosphatidylcholine (PC. In membranes of the intestinal epithelium, the content of PC increases from 10 to 50 % in the direction from the apical surface to the basal one, and the maximum amount of PC is located on the outside of the cell membranes. Phosphatidylcholine showed its high efficacy and safety in the treatment of inflammatory bowel diseases, such as non-specific ulcerative colitis. People taking NSAIDs have demonstrated the protective role of PC in preventing damage to the upper and lower gastrointestinal tract. Given the common pathogenetic mechanisms between these diseases and irritable bowel syndrome, the use of PC in patients with irritable bowel syndrome seems promising, especially in its post-infection variant.

Possible Role of the Transglutaminases in the Pathogenesis of Alzheimer's Disease and Other Neurodegenerative Diseases

OpenAIRE

Martin, Antonio; De Vivo, Giulia; Gentile, Vittorio

2011-01-01

Transglutaminases are ubiquitous enzymes which catalyze posttranslational modifications of proteins. Recently, transglutaminase-catalyzed post-translational modification of proteins has been shown to be involved in the molecular mechanisms responsible for human diseases. Transglutaminase activity has been hypothesized to be involved also in the pathogenetic mechanisms responsible for several human neurodegenerative diseases. Alzheimer's disease and other neurodegenerative diseases, such as Pa...

T-cell mediated immunity in Wegener's granulomatosis

NARCIS (Netherlands)

Abdulahad, Wayel Habib

2008-01-01

Although the pathogenetic mechanisms involved in Wegener’s granulomatosis (WG) are not completely understood, considerable evidence support the concepts that activated T-cells play an important role in disease expression. It is, however, not clear which subsets of T-cells are involved in the

Diagnosis of Hymenoptera venom allergy

NARCIS (Netherlands)

Bilo, BM; Rueff, F; Mosbech, H; Bonifazi, F; Oude Elberink, JNG

2005-01-01

The purpose of diagnostic procedure is to classify a sting reaction by history, identify the underlying pathogenetic mechanism, and identify the offending insect. Diagnosis of Hymenoptera venom allergy thus forms the basis for the treatment. In the central and northern Europe vespid (mainly Vespula

Mouse Resource Browser-a database of mouse databases

NARCIS (Netherlands)

Zouberakis, Michael; Chandras, Christina; Swertz, Morris; Smedley, Damian; Gruenberger, Michael; Bard, Jonathan; Schughart, Klaus; Rosenthal, Nadia; Hancock, John M.; Schofield, Paul N.; Kollias, George; Aidinis, Vassilis

2010-01-01

The laboratory mouse has become the organism of choice for discovering gene function and unravelling pathogenetic mechanisms of human diseases through the application of various functional genomic approaches. The resulting deluge of data has led to the deployment of numerous online resources and the

Long-Term Type 1 Diabetes Enhances In-Stent Restenosis after Aortic Stenting in Diabetes-Prone BB Rats

NARCIS (Netherlands)

Onuta, Geanina; Groenewegen, Hendrik C.; Klatter, Flip A.; Boer, Mark Walther; Goris, Maaike; van Goor, Harry; Roks, Anton J. M.; Rozing, Jan; de Smet, Bart J. G. L.; Hillebrands, Jan-Luuk

2011-01-01

Type 1 diabetic patients have increased risk of developing in-stent restenosis following endovascular stenting. Underlying pathogenetic mechanisms are not fully understood partly due to the lack of a relevant animal model to study the effect(s) of long-term autoimmune diabetes on development of

Long-term type 1 diabetes enhances in-stent restenosis after aortic stenting in diabetes-prone BB rats

NARCIS (Netherlands)

J.-L. Hillebrands (Jan-Luuk); G. Onuta (Geanina); H.C. Groenewegen (Hendrik); F.A. Klatter (Flip); M. Walther Boer (Mark); M. Goris (Maaike); H. van Goor (Harry); A.J.M. Roks (Anton); J. Rozing (Jan); B.J.G.L. de Smet (Bart)

2011-01-01

textabstractType 1 diabetic patients have increased risk of developing in-stent restenosis following endovascular stenting. Underlying pathogenetic mechanisms are not fully understood partly due to the lack of a relevant animal model to study the effect(s) of long-term autoimmune diabetes on

Mechanics of machinery

CERN Document Server

Mostafa, Mahmoud A

2012-01-01

MechanismsDefinitions Degrees of Freedom of Planar Mechanisms Four-Revolute-Pairs Chains Single-Slider Chain Double-Slider Mechanisms Mechanisms with Higher Pairs Compound Mechanisms Special Mechanisms Analytical Position Analysis of Mechanisms Velocities and AccelerationsAbsolute Plane Motion of a Particle Relative Motion Applications to Common Links Analysis of Mechanisms: Graphical Method Method of Instantaneous Centers for Determining the VelocitiesAnalytical Analysis CamsIntroduction Types of Cams Modes of Input/Output Motion Follower Configurations Classes of Cams Spur GearsIntroduction

PATHOGENETIC VALIDATION OF ADDITIONAL OBJECTIVE CRITERIA FOR POSSIBLE EFFECTIVE PREGNANCY PROLONGATION AFTER PREMATURE MEMBRANE RUPTURE

Directory of Open Access Journals (Sweden)

L. I. Dyatlova

2015-01-01

Full Text Available The goal of present study was a search for pathogenetical reasoning of an opportunity for prolongation of pregnancy complicated by premature rupture of membranes at a gestational term of 22-34 weeks. The patients were subject to due observation and expectant treatable of pregnancy with prevention of possible infectious and inflammatory complications, as well as monitoring of systemic inflammatory response markers, immune state, and cytokine profile of blood in pregnant women with this disorder. We conducted a comprehensive clinical and laboratory examination of fifty pregnant women, whose pregnancy was complicated by premature membrane rupture at 22-34 weeks of gestation. A control group consisted of 40 women with normal pregnancy. For assessment of cellular composition of the blood, a BC3000+ hematological analyzer was used. Distinct subsets of peripheral blood lymphocytes were studied by flow cytometry using monoclonal antibodies («FACS Calibur» «Becton Dickinson», USA. Blood levels of cytokines (IL-2, IL-6, IL-8, TNFα, IL-4, IL-10 were determined by ELISA using test systems (ZAO “VectorBest”, Novosibirsk, Russia. Stereoultrastructural study of membranes was performed with a scanning electron microscope «Hitachi S-450”. The findings suggest that the failure of membranes emerging du to systemic metabolic disorders and changes in peripheral blood cells (leukocytosis, lymphopenia due to CD19+ B lymphocytes. Moreover, one could observe reduced counts of CD16+CD56+ T cells (natural killer cells that showed certain parallelism with increased levels of proinflammatory cytokines (IL-6, IL-8, TNFα in blood from pregnant PROM, as well as a decrease in IL-10 and IL-4 contents antagonized their proinflammatory effects to certain extent. An opportunity of incomplete pregnancy prolongation for patients with premature rupture of membranes was based on thorough assessment of their somatic and obstetric status and general condition of the fetus

Common Lung Microbiome Identified among Mechanically Ventilated Surgical Patients.

Directory of Open Access Journals (Sweden)

Ashley D Smith

Full Text Available The examination of the pulmonary microbiome in patients with non-chronic disease states has not been extensively examined. Traditional culture based screening methods are often unable to identify bacteria from bronchoalveolar lavage samples. The advancement of next-generation sequencing technologies allows for a culture-independent molecular based analysis to determine the microbial composition in the lung of this patient population. For this study, the Ion Torrent PGM system was used to assess the microbial complexity of culture negative bronchoalveolar lavage samples. A group of samples were identified that all displayed high diversity and similar relative abundance of bacteria. This group consisted of Hydrogenophaga, unclassified Bacteroidetes, Pedobacter, Thauera, and Acinetobacter. These bacteria may be representative of a common non-pathogenic pulmonary microbiome associated within this population of patients.

Integrating Mechanisms for Insulin Resistance: Common Threads and Missing Links

Science.gov (United States)

Samuel, Varman T.; Shulman, Gerald I.

2012-01-01

Insulin resistance is a complex metabolic disorder that defies a single etiological pathway. Accumulation of ectopic lipid metabolites, activation of the unfolded protein response (UPR) pathway and innate immune pathways have all been implicated in the pathogenesis of insulin resistance. However, these pathways are also closely linked to changes in fatty acid uptake, lipogenesis, and energy expenditure that can impact ectopic lipid deposition. Ultimately, accumulation of specific lipid metabolites (diacylglycerols and/or ceramides) in liver and skeletal muscle, may be a common pathway leading to impaired insulin signaling and insulin resistance. PMID:22385956

Sirenomelia and VACTERL association in the offspring of a woman with diabetes.

Science.gov (United States)

Castori, Marco; Silvestri, Evelina; Cappellacci, Sandra; Binni, Francesco; Sforzolini, Giovanna Scassellati; Grammatico, Paola

2010-07-01

Sirenomelia and VACTERL association are defects of blastogenesis of unknown cause. Although they appear clinically distinct, some epidemiological and experimental studies suggest a common pathogenetic mechanism. We report on the reproductive history of a 28-year-old obese, diabetic mother who had three pregnancies. The first resulted in the birth of a sirenomelic child, the second in a miscarriage, while the third was terminated for fetal malformations, diagnosed post-mortem as VACTERL association. This observation supports the relationship between sirenomelia and VACTERL, which probably represent the two ends of the same phenotypic spectrum. Their occurrence in the same sibship also indicates a possible common cause. The coexistence with maternal diabetes seems more than a chance occurrence and the constellation of malformations observed in the present family may be explained as the pleiotropic effect of the same teratogenic agent interacting with genetic predisposition to diabetes and/or obesity. (c) 2010 Wiley-Liss, Inc.

Hypertension in the course of insulin dependent diabetes mellitus and its pathogenetic mechanisms

DEFF Research Database (Denmark)

Feldt-Rasmussen, B; Nørgaard, K; Jensen, T

1990-01-01

All IDDM patients without late complications have blood pressures similar to the nondiabetic background population, and those who develop clinical nephropathy in Denmark have no familial predisposition to hypertension. Blood pressure remains normal until after development of microalbuminuria......, indicating no primary role for hypertension in the pathogenesis of nephropathy. When microalbuminuria is present it does, however, play a crucial role in the progression of nephropathy. Sodium retention, possibly induced by hyperinsulinemia, and perhaps glucose-coupled sodium reabsorption in insulin treated...

Memory, reasoning, and categorization: parallels and common mechanisms.

Science.gov (United States)

Hayes, Brett K; Heit, Evan; Rotello, Caren M

2014-01-01

Traditionally, memory, reasoning, and categorization have been treated as separate components of human cognition. We challenge this distinction, arguing that there is broad scope for crossover between the methods and theories developed for each task. The links between memory and reasoning are illustrated in a review of two lines of research. The first takes theoretical ideas (two-process accounts) and methodological tools (signal detection analysis, receiver operating characteristic curves) from memory research and applies them to important issues in reasoning research: relations between induction and deduction, and the belief bias effect. The second line of research introduces a task in which subjects make either memory or reasoning judgments for the same set of stimuli. Other than broader generalization for reasoning than memory, the results were similar for the two tasks, across a variety of experimental stimuli and manipulations. It was possible to simultaneously explain performance on both tasks within a single cognitive architecture, based on exemplar-based comparisons of similarity. The final sections explore evidence for empirical and processing links between inductive reasoning and categorization and between categorization and recognition. An important implication is that progress in all three of these fields will be expedited by further investigation of the many commonalities between these tasks.

Memory, reasoning and categorization: Parallels and common mechanisms

Directory of Open Access Journals (Sweden)

BRETT eHAYES

2014-06-01

Full Text Available Traditionally, memory, reasoning and categorization have been treated as separate components of human cognition. We challenge this distinction, arguing that there is broad scope for crossover between the methods and theories developed for each task. The links between memory and reasoning are illustrated in a review of two lines of research. The first takes theoretical ideas (two-process accounts and methodological tools (signal detection analysis, receiver operating characteristic curves from memory research and applies them to important issues in reasoning research: relations between induction and deduction, and the belief bias effect. The second line of research introduces a task in which subjects make either memory or reasoning judgments for the same set of stimuli. Other than broader generalization for reasoning than memory, the results were similar for the two tasks, across a variety of experimental stimuli and manipulations. It was possible to simultaneously explain performance on both tasks within a single cognitive architecture, based on exemplar-based comparisons of similarity. The final sections explore evidence for empirical and processing links between inductive reasoning and categorization and between categorization and recognition. An important implication is that progress in all three of these fields will be expedited by further investigation of the many commonalities between these tasks.

Interleukin-6 and diabetes: the good, the bad, or the indifferent?

DEFF Research Database (Denmark)

Kristiansen, Ole P; Mandrup-Poulsen, Thomas

2005-01-01

Inflammatory mechanisms play a key role in the pathogenesis of type 1 diabetes. Individuals who progress to type 2 diabetes display features of low-grade inflammation years in advance of disease onset. This low-grade inflammation has been proposed to be involved in the pathogenetic processes...

sept edition 2008.cdr

African Journals Online (AJOL)

User

known. Among the pathogenetic mechanisms of the neurological defects of CML suggested in literature so far, hyperleucocytosis-induced stasis. (hyperviscosity syndrome) appears to be the most predominant .This is said to slow down the circulation through small blood vessels in the brainstem and results in deafness .

The Common Forces: Conservative or Nonconservative?

Science.gov (United States)

Keeports, David

2006-01-01

Of the forces commonly encountered when solving problems in Newtonian mechanics, introductory texts usually limit illustrations of the definitions of conservative and nonconservative forces to gravity, spring forces, kinetic friction and fluid resistance. However, at the expense of very little class time, the question of whether each of the common…

Common and unique therapeutic mechanisms of stimulant and nonstimulant treatments for attention-deficit/hyperactivity disorder.

Science.gov (United States)

Schulz, Kurt P; Fan, Jin; Bédard, Anne-Claude V; Clerkin, Suzanne M; Ivanov, Iliyan; Tang, Cheuk Y; Halperin, Jeffrey M; Newcorn, Jeffrey H

2012-09-01

CONTEXT Attention-deficit/hyperactivity disorder (ADHD) is a highly prevalent and impairing psychiatric disorder that affects both children and adults. There are Food and Drug Administration-approved stimulant and nonstimulant medications for treating ADHD; however, little is known about the mechanisms by which these different treatments exert their therapeutic effects. OBJECTIVE To contrast changes in brain activation related to symptomatic improvement with use of the stimulant methylphenidate hydrochloride vs the nonstimulant atomoxetine hydrochloride. DESIGN Functional magnetic resonance imaging before and after 6 to 8 weeks of treatment with methylphenidate (n = 18) or atomoxetine (n = 18) using a parallel-groups design. SETTING Specialized ADHD clinical research program at Mount Sinai School of Medicine, New York, New York. PARTICIPANTS Thirty-six youth with ADHD (mean [SD] age, 11.2 [2.7] years; 27 boys) recruited from randomized clinical trials. MAIN OUTCOME MEASURES Changes in brain activation during a go/no-go test of response inhibition and investigator-completed ratings on the ADHD Rating Scale-IV-Parent Version. RESULTS Treatment with methylphenidate vs atomoxetine was associated with comparable improvements in both response inhibition on the go/no-go test and mean (SD) improvements in ratings of ADHD symptoms (55% [30%] vs 57% [25%]). Improvement in ADHD symptoms was associated with common reductions in bilateral motor cortex activation for both treatments. Symptomatic improvement was also differentially related to gains in task-related activation for atomoxetine and reductions in activation for methylphenidate in the right inferior frontal gyrus, left anterior cingulate/supplementary motor area, and bilateral posterior cingulate cortex. These findings were not attributable to baseline differences in activation. CONCLUSIONS Treatment with methylphenidate and atomoxetine produces symptomatic improvement via both common and divergent neurophysiologic

A Common Mechanism Underlying Food Choice and Social Decisions

Science.gov (United States)

Krajbich, Ian; Hare, Todd; Bartling, Björn; Morishima, Yosuke; Fehr, Ernst

2015-01-01

People make numerous decisions every day including perceptual decisions such as walking through a crowd, decisions over primary rewards such as what to eat, and social decisions that require balancing own and others’ benefits. The unifying principles behind choices in various domains are, however, still not well understood. Mathematical models that describe choice behavior in specific contexts have provided important insights into the computations that may underlie decision making in the brain. However, a critical and largely unanswered question is whether these models generalize from one choice context to another. Here we show that a model adapted from the perceptual decision-making domain and estimated on choices over food rewards accurately predicts choices and reaction times in four independent sets of subjects making social decisions. The robustness of the model across domains provides behavioral evidence for a common decision-making process in perceptual, primary reward, and social decision making. PMID:26460812

A Common Mechanism Underlying Food Choice and Social Decisions.

Science.gov (United States)

Krajbich, Ian; Hare, Todd; Bartling, Björn; Morishima, Yosuke; Fehr, Ernst

2015-10-01

People make numerous decisions every day including perceptual decisions such as walking through a crowd, decisions over primary rewards such as what to eat, and social decisions that require balancing own and others' benefits. The unifying principles behind choices in various domains are, however, still not well understood. Mathematical models that describe choice behavior in specific contexts have provided important insights into the computations that may underlie decision making in the brain. However, a critical and largely unanswered question is whether these models generalize from one choice context to another. Here we show that a model adapted from the perceptual decision-making domain and estimated on choices over food rewards accurately predicts choices and reaction times in four independent sets of subjects making social decisions. The robustness of the model across domains provides behavioral evidence for a common decision-making process in perceptual, primary reward, and social decision making.

Mechanisms of population heterogeneity among molting common mergansers on Kodiak Island, Alaska: Implications for genetic assessments of migratory connectivity

Science.gov (United States)

Pearce, John M.; Zwiefelhofer, Denny; Maryanski, Nate

2009-01-01

Quantifying population genetic heterogeneity within nonbreeding aggregations can inform our understanding of patterns of site fidelity, migratory connectivity, and gene flow between breeding and nonbreeding areas. However, characterizing mechanisms that contribute to heterogeneity, such as migration and dispersal, is required before site fidelity and migratory connectivity can be assessed accurately. We studied nonbreeding groups of Common Mergansers (Mergus merganser) molting on Kodiak Island, Alaska, from 2005 to 2007, using banding data to assess rates of recapture, mitochondrial (mt) DNA to determine natal area, and nuclear microsatellite genotypes to assess dispersal. Using baseline information from differentiated mtDNA haplogroups across North America, we were able to assign individuals to natal regions and document population genetic heterogeneity within and among molting groups. Band-recovery and DNA data suggest that both migration from and dispersal among natal areas contribute to admixed groups of males molting on Kodiak Island. A lack of differentiation in the Common Merganser's nuclear, bi-parentally inherited DNA, observed across North America, implies that dispersal can mislead genetic assessments of migratory connectivity and assignments of nonbreeding individuals to breeding areas. Thus multiple and independent data types are required to account for such behaviors before accurate assessments of migratory connectivity can be made.

Mechanical engineers' handbook, materials and engineering mechanics

CERN Document Server

Kutz, Myer

2015-01-01

Full coverage of materials and mechanical design inengineering Mechanical Engineers' Handbook, Fourth Edition provides aquick guide to specialized areas you may encounter in your work,giving you access to the basics of each and pointing you towardtrusted resources for further reading, if needed. The accessibleinformation inside offers discussions, examples, and analyses ofthe topics covered. This first volume covers materials and mechanical design, givingyou accessible and in-depth access to the most common topics you'llencounter in the discipline: carbon and alloy steels, stainlesssteels, a

Reduced Number of Pigmented Neurons in the Substantia Nigra of Dystonia Patients? Findings from Extensive Neuropathologic, Immunohistochemistry, and Quantitative Analyses

Directory of Open Access Journals (Sweden)

Diego Iacono

2015-05-01

Full Text Available Background: Dystonias (Dys represent the third most common movement disorder after essential tremor (ET and Parkinson's disease (PD. While some pathogenetic mechanisms and genetic causes of Dys have been identified, little is known about their neuropathologic features. Previous neuropathologic studies have reported generically defined neuronal loss in various cerebral regions of Dys brains, mostly in the basal ganglia (BG, and specifically in the substantia nigra (SN. Enlarged pigmented neurons in the SN of Dys patients with and without specific genetic mutations (e.g., GAG deletions in DYT1 dystonia have also been described. Whether or not Dys brains are associated with decreased numbers or other morphometric changes of specific neuronal types is unknown and has never been addressed with quantitative methodologies. Methods: Quantitative immunohistochemistry protocols were used to estimate neuronal counts and volumes of nigral pigmented neurons in 13 SN of Dys patients and 13 SN of age‐matched control subjects (C. Results: We observed a significant reduction (∼20% of pigmented neurons in the SN of Dys compared to C (p<0.01. Neither significant volumetric changes nor evident neurodegenerative signs were observed in the remaining pool of nigral pigmented neurons in Dys brains. These novel quantitative findings were confirmed after exclusion of possible co‐occurring SN pathologies including Lewy pathology, tau‐neurofibrillary tangles, β‐amyloid deposits, ubiquitin (ubiq, and phosphorylated‐TAR DNA‐binding protein 43 (pTDP43‐positive inclusions. Discussion: A reduced number of nigral pigmented neurons in the absence of evident neurodegenerative signs in Dys brains could indicate previously unconsidered pathogenetic mechanisms of Dys such as neurodevelopmental defects in the SN.

Genetic mechanisms and age-related macular degeneration: common variants, rare variants, copy number variations, epigenetics, and mitochondrial genetics

Directory of Open Access Journals (Sweden)

Liu Melissa M

2012-08-01

Full Text Available Abstract Age-related macular degeneration (AMD is a complex and multifaceted disease involving contributions from both genetic and environmental influences. Previous work exploring the genetic contributions of AMD has implicated numerous genomic regions and a variety of candidate genes as modulators of AMD susceptibility. Nevertheless, much of this work has revolved around single-nucleotide polymorphisms (SNPs, and it is apparent that a significant portion of the heritability of AMD cannot be explained through these mechanisms. In this review, we consider the role of common variants, rare variants, copy number variations, epigenetics, microRNAs, and mitochondrial genetics in AMD. Copy number variations in regulators of complement activation genes (CFHR1 and CFHR3 and glutathione S transferase genes (GSTM1 and GSTT1 have been associated with AMD, and several additional loci have been identified as regions of potential interest but require further evaluation. MicroRNA dysregulation has been linked to the retinal pigment epithelium degeneration in geographic atrophy, ocular neovascularization, and oxidative stress, all of which are hallmarks in the pathogenesis of AMD. Certain mitochondrial DNA haplogroups and SNPs in mitochondrially encoded NADH dehydrogenase genes have also been associated with AMD. The role of these additional mechanisms remains only partly understood, but the importance of their further investigation is clear to elucidate more completely the genetic basis of AMD.

A Common Mechanism Underlying Food Choice and Social Decisions.

Directory of Open Access Journals (Sweden)

Ian Krajbich

2015-10-01

Full Text Available People make numerous decisions every day including perceptual decisions such as walking through a crowd, decisions over primary rewards such as what to eat, and social decisions that require balancing own and others' benefits. The unifying principles behind choices in various domains are, however, still not well understood. Mathematical models that describe choice behavior in specific contexts have provided important insights into the computations that may underlie decision making in the brain. However, a critical and largely unanswered question is whether these models generalize from one choice context to another. Here we show that a model adapted from the perceptual decision-making domain and estimated on choices over food rewards accurately predicts choices and reaction times in four independent sets of subjects making social decisions. The robustness of the model across domains provides behavioral evidence for a common decision-making process in perceptual, primary reward, and social decision making.

Radiologic evidence for absence of the facial nerve in Mobius syndrome.

NARCIS (Netherlands)

Verzijl, H.T.F.M.; Valk, J.; Vries, R. de; Padberg, G.W.A.M.

2005-01-01

OBJECTIVE: To detail the radiologic findings in Mobius syndrome, in order to clarify its pathogenetic mechanisms. METHODS: High resolution three-dimensional T1 (MP rage) and T2 (CISS) weighted MRI were used to study the cisternal and canalicular portion of the seventh cranial nerve in six Mobius

Editorial

African Journals Online (AJOL)

The dawn of the new millennium held much promise for medi- cine especially for chronic disorders such as hypertension, diabetes mellitus and asthma. Major clinical trials had been published, new therapies developed and the unraveling of pathogenetic mechanisms had opened our minds to a mo- lecular network ...

Common therapeutic mechanisms of pallidal deep brain stimulation for hypo- and hyperkinetic movement disorders

Science.gov (United States)

Iriki, Atsushi; Isoda, Masaki

2015-01-01

Abnormalities in cortico-basal ganglia (CBG) networks can cause a variety of movement disorders ranging from hypokinetic disorders, such as Parkinson's disease (PD), to hyperkinetic conditions, such as Tourette syndrome (TS). Each condition is characterized by distinct patterns of abnormal neural discharge (dysrhythmia) at both the local single-neuron level and the global network level. Despite divergent etiologies, behavioral phenotypes, and neurophysiological profiles, high-frequency deep brain stimulation (HF-DBS) in the basal ganglia has been shown to be effective for both hypo- and hyperkinetic disorders. The aim of this review is to compare and contrast the electrophysiological hallmarks of PD and TS phenotypes in nonhuman primates and discuss why the same treatment (HF-DBS targeted to the globus pallidus internus, GPi-DBS) is capable of ameliorating both symptom profiles. Recent studies have shown that therapeutic GPi-DBS entrains the spiking of neurons located in the vicinity of the stimulating electrode, resulting in strong stimulus-locked modulations in firing probability with minimal changes in the population-scale firing rate. This stimulus effect normalizes/suppresses the pathological firing patterns and dysrhythmia that underlie specific phenotypes in both the PD and TS models. We propose that the elimination of pathological states via stimulus-driven entrainment and suppression, while maintaining thalamocortical network excitability within a normal physiological range, provides a common therapeutic mechanism through which HF-DBS permits information transfer for purposive motor behavior through the CBG while ameliorating conditions with widely different symptom profiles. PMID:26180116

Vascular cognitive impairment

Directory of Open Access Journals (Sweden)

N.V. Vakhnina

2014-01-01

Full Text Available Vascular pathology of the brain is the second most common cause of cognitive impairment after Alzheimer's disease. The article describes the modern concepts of etiology, pathogenetic mechanisms, clinical features and approaches to diagnosis and therapy of vascular cognitive impairment (VCI. Cerebrovascular accident, chronic cerebral circulatory insufficiency and their combination, sometimes in combination with a concomitant neurodegenerative process, are shown to be the major types of brain lesions leading to VCI. The clinical presentation of VCI is characterized by the neuropsychological status dominated by impairment of the executive frontal functions (planning, control, attention in combination with focal neurological symptoms. The diagnosis is based on comparing of the revealed neuropsychological and neurological features with neuroimaging data. Neurometabolic, acetylcholinergic, glutamatergic, and other vasoactive drugs and non-pharmacological methods are widely used to treat VCI. 

Alternating hemiplegia of childhood and a pathogenic variant of ATP1A3

DEFF Research Database (Denmark)

Pavlidis, Elena; Uldall, Peter; Gøbel Madsen, Camilla

2017-01-01

episodes of alternating hemiplegia more often on the right side. A severe epilepsy started at the age of 2 years with episodes of status epilepticus since the onset which frequently recurred, requiring admission to the intensive care unit. MRI showed bilateral mesial temporal sclerosis and a left......-sided ischaemic lesion. Interictal EEG showed bilateral abnormalities, whereas postictal EEG after status epilepticus showed overt slowing on the left side, suggesting a predominant involvement of ictal activity of the left hemisphere. We hypothesize that in our patient, the left hemisphere might have been more...... prominently affected by the pathogenetic abnormalities underlying alternating hemiplegia of childhood, rendering it more prone to early ischaemic lesions and recurrent unilateral status epilepticus. We speculate whether alternating hemiplegia of childhood shares some common pathophysiological mechanisms...

Exploring mechanisms of compaction in salt-marsh sediments using Common Era relative sea-level reconstructions

Science.gov (United States)

Brain, Matthew J.; Kemp, Andrew C.; Hawkes, Andrea D.; Engelhart, Simon E.; Vane, Christopher H.; Cahill, Niamh; Hill, Troy D.; Donnelly, Jeffrey P.; Horton, Benjamin P.

2017-07-01

Salt-marsh sediments provide precise and near-continuous reconstructions of Common Era relative sea level (RSL). However, organic and low-density salt-marsh sediments are prone to compaction processes that cause post-depositional distortion of the stratigraphic column used to reconstruct RSL. We compared two RSL reconstructions from East River Marsh (Connecticut, USA) to assess the contribution of mechanical compression and biodegradation to compaction of salt-marsh sediments and their subsequent influence on RSL reconstructions. The first, existing reconstruction ('trench') was produced from a continuous sequence of basal salt-marsh sediment and is unaffected by compaction. The second, new reconstruction is from a compaction-susceptible core taken at the same location. We highlight that sediment compaction is the only feasible mechanism for explaining the observed differences in RSL reconstructed from the trench and core. Both reconstructions display long-term RSL rise of ∼1 mm/yr, followed by a ∼19th Century acceleration to ∼3 mm/yr. A statistically-significant difference between the records at ∼1100 to 1800 CE could not be explained by a compression-only geotechnical model. We suggest that the warmer and drier conditions of the Medieval Climate Anomaly (MCA) resulted in an increase in sediment compressibility during this time period. We adapted the geotechnical model by reducing the compressive strength of MCA sediments to simulate this softening of sediments. 'Decompaction' of the core reconstruction with this modified model accounted for the difference between the two RSL reconstructions. Our results demonstrate that compression-only geotechnical models may be inadequate for estimating compaction and post-depositional lowering of susceptible organic salt-marsh sediments in some settings. This has important implications for our understanding of the drivers of sea-level change. Further, our results suggest that future climate changes may make salt

Current pathogenetic aspects of hepatic encephalopathy and noncirrhotic hyperammonemic encephalopathy

OpenAIRE

Cichoż-Lach, Halina; Michalak, Agata

2013-01-01

Hepatic encephalopathy is a medical phenomenon that is described as a neuropsychiatric manifestation of chronic or acute liver disease that is characterized by psychomotor, intellectual and cognitive abnormalities with emotional/affective and behavioral disturbances. This article focuses on the underlying mechanisms of the condition and the differences between hepatic encephalopathy and noncirrhotic hyperammonemic encephalopathy. Hepatic encephalopathy is a serious condition that can cause ne...

Martensite and bainite in steels: transformation mechanism and mechanical properties

International Nuclear Information System (INIS)

Bhadeshia, H.K.D.H.

1997-01-01

Many essential properties of iron alloys depend on what actually happens when one allotropic form gives way to another, i.e. on the mechanism of phase change. The dependence of the mechanical properties on the atomic mechanism by which bainite and martensite grow is the focus of this paper. The discussion is illustrated in the context of some common engineering design parameters, and with a brief example of the inverse problem in which the mechanism may be a function of the mechanical properties. (orig.)

Categorization in Infancy: Labeling Induces a Persisting Focus on Commonalities

Science.gov (United States)

Althaus, Nadja; Plunkett, Kim

2016-01-01

Recent studies with infants and adults demonstrate a facilitative role of labels in object categorization. A common interpretation is that labels highlight commonalities between objects. However, direct evidence for such a mechanism is lacking. Using a novel object category with spatially separate features that are either of low or high…

Variability or conservation of hepatitis C virus hypervariable region 1?

Indian Academy of Sciences (India)

The hypervariable region 1 (HVR1) of the E2 protein of hepatitis C virus (HCV) is highly heterogeneous in its primary sequence and is responsible for significant inter- and intra-individual variation of the infecting virus, which may represent an important pathogenetic mechanism leading to immune escape and persistent ...

Radiological contribution to skeletal changes in systemic mastocytosis - urticaria pigmentosa

Energy Technology Data Exchange (ETDEWEB)

Schratter, M.; Canigiani, G.; Schoenbauer, C.; Mach, K.

1983-11-01

Three patients are demonstrated suffering from systemic mastocytosis with skin and skeletal involvement. History, clinical and radiological results are reported. After a brief analysis of the pathogenetic mechanism, the radiological findings on the skeletal system in systemic mastocytosis are discussed. Finally, roentgenological differential diagnosis of the osseous lesions is explained.

DNA repair pathways underlie a common genetic mechanism modulating onset in polyglutamine diseases.

Science.gov (United States)

Bettencourt, Conceição; Hensman-Moss, Davina; Flower, Michael; Wiethoff, Sarah; Brice, Alexis; Goizet, Cyril; Stevanin, Giovanni; Koutsis, Georgios; Karadima, Georgia; Panas, Marios; Yescas-Gómez, Petra; García-Velázquez, Lizbeth Esmeralda; Alonso-Vilatela, María Elisa; Lima, Manuela; Raposo, Mafalda; Traynor, Bryan; Sweeney, Mary; Wood, Nicholas; Giunti, Paola; Durr, Alexandra; Holmans, Peter; Houlden, Henry; Tabrizi, Sarah J; Jones, Lesley

2016-06-01

The polyglutamine diseases, including Huntington's disease (HD) and multiple spinocerebellar ataxias (SCAs), are among the commonest hereditary neurodegenerative diseases. They are caused by expanded CAG tracts, encoding glutamine, in different genes. Longer CAG repeat tracts are associated with earlier ages at onset, but this does not account for all of the difference, and the existence of additional genetic modifying factors has been suggested in these diseases. A recent genome-wide association study (GWAS) in HD found association between age at onset and genetic variants in DNA repair pathways, and we therefore tested whether the modifying effects of variants in DNA repair genes have wider effects in the polyglutamine diseases. We assembled an independent cohort of 1,462 subjects with HD and polyglutamine SCAs, and genotyped single-nucleotide polymorphisms (SNPs) selected from the most significant hits in the HD study. In the analysis of DNA repair genes as a group, we found the most significant association with age at onset when grouping all polyglutamine diseases (HD+SCAs; p = 1.43 × 10(-5) ). In individual SNP analysis, we found significant associations for rs3512 in FAN1 with HD+SCAs (p = 1.52 × 10(-5) ) and all SCAs (p = 2.22 × 10(-4) ) and rs1805323 in PMS2 with HD+SCAs (p = 3.14 × 10(-5) ), all in the same direction as in the HD GWAS. We show that DNA repair genes significantly modify age at onset in HD and SCAs, suggesting a common pathogenic mechanism, which could operate through the observed somatic expansion of repeats that can be modulated by genetic manipulation of DNA repair in disease models. This offers novel therapeutic opportunities in multiple diseases. Ann Neurol 2016;79:983-990. © 2016 The Authors. Annals of Neurology published by Wiley Periodicals, Inc. on behalf of American Neurological Association.

Patient-ventilator trigger dys-synchrony: a common phenomenon with important implications

OpenAIRE

MacIntyre, Neil

2013-01-01

Patient-ventilator trigger dys-synchronies are common with the use of assisted forms of mechanical ventilatory support, including non-invasive mechanical ventilatory support (NIV). Future system designs need to address this in order to improve the effectiveness of NIV.

Institutional property rights structure, common pool resource (CPR), tragedy of the urban commons: A Review

Science.gov (United States)

Ling, G.; Ho, C. S.; Ali, H. M.

2014-02-01

There have been a plethora of researches on the significance of public open space (POS) in contributing to societies' sustainability. However, by virtue of identified maladaptive policy-based-property rights structure, such a shared good becomes vulnerable to tragedy of the urban commons (overexploitation) that subsequently leads to burgeoning number of mismanaged POS e.g., degraded and unkempt urban public spaces. By scrutinising the literatures within property rights domain and commons resources, an objective is highlighted in this paper which is to insightfully discourse institutional property rights structure pertaining to the mechanism, roles and interrelationship between property-rights regimes, bundle of property rights and resource domains; types of goods on how they act upon and tie in the POS with the social quandary. In summary, urban POS tragedy can potentially be triggered by the institutional structure especially if the ownership is left under open-access resource regime and ill-defined property rights which both successively constitute the natures of Common Pool Resource (CPR) within the commons, POS. Therefore, this paper sparks an idea to policy makers that property rights structure is a determinant in sustainably governing the POS in which adaptive assignment of property regimes and property rights are impelled.

Institutional property rights structure, common pool resource (CPR), tragedy of the urban commons: A Review

International Nuclear Information System (INIS)

Ling, G; Ho, C S; Ali, H M

2014-01-01

There have been a plethora of researches on the significance of public open space (POS) in contributing to societies' sustainability. However, by virtue of identified maladaptive policy-based-property rights structure, such a shared good becomes vulnerable to tragedy of the urban commons (overexploitation) that subsequently leads to burgeoning number of mismanaged POS e.g., degraded and unkempt urban public spaces. By scrutinising the literatures within property rights domain and commons resources, an objective is highlighted in this paper which is to insightfully discourse institutional property rights structure pertaining to the mechanism, roles and interrelationship between property-rights regimes, bundle of property rights and resource domains; types of goods on how they act upon and tie in the POS with the social quandary. In summary, urban POS tragedy can potentially be triggered by the institutional structure especially if the ownership is left under open-access resource regime and ill-defined property rights which both successively constitute the natures of Common Pool Resource (CPR) within the commons, POS. Therefore, this paper sparks an idea to policy makers that property rights structure is a determinant in sustainably governing the POS in which adaptive assignment of property regimes and property rights are impelled

Unique and Common Mechanisms of Change across Cognitive and Dynamic Psychotherapies

Science.gov (United States)

Gibbons, Mary Beth Connolly; Crits-Christoph, Paul; Barber, Jacques P.; Stirman, Shannon Wiltsey; Gallop, Robert; Goldstein, Lizabeth A.; Temes, Christina M.; Ring-Kurtz, Sarah

2009-01-01

The goal of this article was to examine theoretically important mechanisms of change in psychotherapy outcome across different types of treatment. Specifically, the role of gains in self-understanding, acquisition of compensatory skills, and improvements in views of the self were examined. A pooled study database collected at the University of…

Commonalities and distinctions among mechanisms of addiction to alcohol and other drugs

Science.gov (United States)

Ozburn, Angela R.; Janowsky, Aaron J.; Crabbe, John C.

2015-01-01

Alcohol abuse is comorbid with abuse of many other drugs, some with similar pharmacology and others quite different. This leads to the hypothesis of an underlying, unitary dysfunctional neurobiological basis for substance abuse risk and consequences. In this review, we discuss commonalities and distinctions of addiction to alcohol and other drugs. We focus on recent advances in pre-clinical studies using rodent models of drug self-administration. While there are specific behavioral and molecular manifestations common to alcohol, psychostimulant, opioid, and nicotine dependence, attempts to propose a unifying theory of the addictions inevitably face details where distinctions are found among classes of drugs. For alcohol, versus other drugs of abuse, we discuss and compare advances in: 1) neurocircuitry important for the different stages of drug dependence; 2) transcriptomics and genetical genomics; and 3) enduring effects. We note in particular the contributions of behavioral genetics and animal models: discussions of progress specifically relevant to treatment development can be found in the accompanying review (Karoly et al, this issue). PMID:26431116

Quantum mechanics as classical statistical mechanics with an ontic extension and an epistemic restriction.

Science.gov (United States)

Budiyono, Agung; Rohrlich, Daniel

2017-11-03

Where does quantum mechanics part ways with classical mechanics? How does quantum randomness differ fundamentally from classical randomness? We cannot fully explain how the theories differ until we can derive them within a single axiomatic framework, allowing an unambiguous account of how one theory is the limit of the other. Here we derive non-relativistic quantum mechanics and classical statistical mechanics within a common framework. The common axioms include conservation of average energy and conservation of probability current. But two axioms distinguish quantum mechanics from classical statistical mechanics: an "ontic extension" defines a nonseparable (global) random variable that generates physical correlations, and an "epistemic restriction" constrains allowed phase space distributions. The ontic extension and epistemic restriction, with strength on the order of Planck's constant, imply quantum entanglement and uncertainty relations. This framework suggests that the wave function is epistemic, yet it does not provide an ontic dynamics for individual systems.

Activation of D1/5 Dopamine Receptors: A Common Mechanism for Enhancing Extinction of Fear and Reward-Seeking Behaviors.

Science.gov (United States)

Abraham, Antony D; Neve, Kim A; Lattal, K Matthew

2016-07-01

Dopamine is critical for many processes that drive learning and memory, including motivation, prediction error, incentive salience, memory consolidation, and response output. Theories of dopamine's function in these processes have, for the most part, been developed from behavioral approaches that examine learning mechanisms in appetitive tasks. A parallel and growing literature indicates that dopamine signaling is involved in consolidation of memories into stable representations in aversive tasks such as fear conditioning. Relatively little is known about how dopamine may modulate memories that form during extinction, when organisms learn that the relation between previously associated events is severed. We investigated whether fear and reward extinction share common mechanisms that could be enhanced with dopamine D1/5 receptor activation. Pharmacological activation of dopamine D1/5 receptors (with SKF 81297) enhanced extinction of both cued and contextual fear. These effects also occurred in the extinction of cocaine-induced conditioned place preference, suggesting that the observed effects on extinction were not specific to a particular type of procedure (aversive or appetitive). A cAMP/PKA biased D1 agonist (SKF 83959) did not affect fear extinction, whereas a broadly efficacious D1 agonist (SKF 83822) promoted fear extinction. Together, these findings show that dopamine D1/5 receptor activation is a target for the enhancement of fear or reward extinction.

Telomeres and viruses: common themes of genome maintenance

Science.gov (United States)

Deng, Zhong; Wang, Zhuo; Lieberman, Paul M.

2012-01-01

Genome maintenance mechanisms actively suppress genetic instability associated with cancer and aging. Some viruses provoke genetic instability by subverting the host’s control of genome maintenance. Viruses have their own specialized strategies for genome maintenance, which can mimic and modify host cell processes. Here, we review some of the common features of genome maintenance utilized by viruses and host chromosomes, with a particular focus on terminal repeat (TR) elements. The TRs of cellular chromosomes, better known as telomeres, have well-established roles in cellular chromosome stability. Cellular telomeres are themselves maintained by viral-like mechanisms, including self-propagation by reverse transcription, recombination, and retrotransposition. Viral TR elements, like cellular telomeres, are essential for viral genome stability and propagation. We review the structure and function of viral repeat elements and discuss how they may share telomere-like structures and genome protection functions. We consider how viral infections modulate telomere regulatory factors for viral repurposing and can alter normal host telomere structure and chromosome stability. Understanding the common strategies of viral and cellular genome maintenance may provide new insights into viral–host interactions and the mechanisms driving genetic instability in cancer. PMID:23293769

Common cause and contextual realization of Bell correlation

International Nuclear Information System (INIS)

Shafiee, A.; Maleeh, R.; Golshani, M.

2008-01-01

Considering the common cause principle, we construct a local-contextual hidden-variable model for the Bohm version of EPR experiment. Our proposed model can reproduce the predictions of quantum mechanics. It can be also extended to classical examples in which similar correlations may be revealed

Evidence for participation of GCS1 in fertilization of the starlet sea anemone Nematostella vectensis: Implication of a common mechanism of sperm–egg fusion in plants and animals

Energy Technology Data Exchange (ETDEWEB)

Ebchuqin, Eerdundagula; Yokota, Naoto; Yamada, Lixy [Sugashima Marine Biological Laboratory, Graduate School of Science, Nagoya University, Sugashima, Toba 517-0004 (Japan); Yasuoka, Yuuri [Marine Genomics Unit, Okinawa Institute of Science and Technology, Onna, Okinawa 904-0495 (Japan); Akasaka, Mari [Laboratory of Molecular Genetics, Graduate School of Science, Nagoya University, Chikusa-ku, Furo-cho, Nagoya 464-8602 (Japan); Arakawa, Mio; Deguchi, Ryusaku [Department of Biology, Miyagi University of Education, Sendai, Miyagi 980-0845 (Japan); Mori, Toshiyuki [Waseda Institute for Advanced Study, Waseda University, Shinjuku, Tokyo 169-8050 (Japan); Sawada, Hitoshi, E-mail: hsawada@bio.nagoya-u.ac.jp [Sugashima Marine Biological Laboratory, Graduate School of Science, Nagoya University, Sugashima, Toba 517-0004 (Japan)

2014-09-05

Highlights: • GCS1 is a sperm transmembrane protein that is essential for gamete fusion in flowering plants. • The GCS1 gene is present not only in angiosperms but also in unicellular organisms and animals. • NvGCS1 gene is expressed in the testis and GCS1 protein exists in sperm of a sea anemone. • Anti-GCS1 antibodies inhibited the fertilization, showing the participation in fertilization. - Abstract: It has been reported that GCS1 (Generative Cell Specific 1) is a transmembrane protein that is exclusively expressed in sperm cells and is essential for gamete fusion in flowering plants. The GCS1 gene is present not only in angiosperms but also in unicellular organisms and animals, implying the occurrence of a common or ancestral mechanism of GCS1-mediated gamete fusion. In order to elucidate the common mechanism, we investigated the role of GCS1 in animal fertilization using a sea anemone (Cnidaria), Nematostella vectensis. Although the existence of the GCS1 gene in N. vectensis has been reported, the expression of GCS1 in sperm and the role of GCS1 in fertilization are not known. In this study, we showed that the GCS1 gene is expressed in the testis and that GCS1 protein exists in sperm by in situ hybridization and proteomic analysis, respectively. Then we made four peptide antibodies against the N-terminal extracellular region of NvGCS1. These antibodies specifically reacted to NvGCS1 among sperm proteins on the basis of Western analysis and potently inhibited fertilization in a concentration-dependent manner. These results indicate that sperm GCS1 plays a pivotal role in fertilization, most probably in sperm–egg fusion, in a starlet sea anemone, suggesting a common gamete-fusion mechanism shared by eukaryotic organisms.

Systems biology: An emerging strategy for discovering novel pathogenetic mechanisms that promote cardiovascular disease

OpenAIRE

Maron, Bradley A.; Leopold, Jane A.

2016-01-01

Reductionist theory proposes that analyzing complex systems according to their most fundamental components is required for problem resolution, and has served as the cornerstone of scientific methodology for more than four centuries. However, technological gains in the current scientific era now allow for the generation of large datasets that profile the proteomic, genomic, and metabolomic signatures of biological systems across a range of conditions. The accessibility of data on such a vast s...

Melanin targets LC3-associated phagocytosis (LAP): A novel pathogenetic mechanism in fungal disease.

Science.gov (United States)

Chamilos, Georgios; Akoumianaki, Tonia; Kyrmizi, Irene; Brakhage, Axel; Beauvais, Anne; Latge, Jean-Paul

2016-05-03

Intracellular swelling of conidia of the major human airborne fungal pathogen Aspergillus fumigatus results in surface exposure of immunostimulatory pathogen-associated molecular patterns (PAMPs) and triggers activation of a specialized autophagy pathway called LC3-associated phagocytosis (LAP) to promote fungal killing. We have recently discovered that, apart from PAMPs exposure, cell wall melanin removal during germination of A. fumigatus is a prerequisite for activation of LAP. Importantly, melanin promotes fungal pathogenicity via targeting LAP, as a melanin-deficient A. fumigatus mutant restores its virulence upon conditional inactivation of Atg5 in hematopoietic cells of mice. Mechanistically, fungal cell wall melanin selectively excludes the CYBA/p22phox subunit of NADPH oxidase from the phagosome to inhibit LAP, without interfering with signaling regulating cytokine responses. Notably, inhibition of LAP is a general property of melanin pigments, a finding with broad physiological implications.

Modern diagnostic and treatment aspects of diabetic macular edema

Directory of Open Access Journals (Sweden)

Alexander Viktorovich Doga

2014-10-01

Full Text Available Diabetic macular oedema (DMO is the leading cause of vision loss and disability in working-age people with diabetes mellitus. This literature review describes pathogenetic mechanisms, concepts, diagnostic techniques and capabilities of novel laser technologies in the treatment of DMO. In recent years, the role of cytokines and growth factors in retinal neurodegeneration has been actively investigated. Modern diagnostic techniques for the treatment of diabetic macular oedema, in addition to conventional techniques, include optical coherence tomography, autofluorescence and microperimetry. These techniques allow the visualization of retinal structures and its functional condition, and they can be used to detect DMO at early stages and to provide the most effective treatment. The evolution of laser technology resulted in the formation of new approaches to DMO treatment. Subthreshold micropulse laser (SML treatment, in conjunction with conventional photocoagulation, has pronounced therapeutic effects. SML shows high selectivity towards retinal pigment epithelium while avoiding neurosensory retina injury. Owing to the chronic nature of DMO and pathogenetic mechanisms recently discovered, further elaboration of the SML technique appears to be a very promising treatment.

Long-Term Type 1 Diabetes Enhances In-Stent Restenosis after Aortic Stenting in Diabetes-Prone BB Rats

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Geanina Onuta

2011-01-01

Full Text Available Type 1 diabetic patients have increased risk of developing in-stent restenosis following endovascular stenting. Underlying pathogenetic mechanisms are not fully understood partly due to the lack of a relevant animal model to study the effect(s of long-term autoimmune diabetes on development of in-stent restenosis. We here describe the development of in-stent restenosis in long-term (~7 months spontaneously diabetic and age-matched, thymectomized, nondiabetic Diabetes Prone BioBreeding (BBDP rats (n=6-7 in each group. Diabetes was suboptimally treated with insulin and was characterized by significant hyperglycaemia, polyuria, proteinuria, and increased HbA1c levels. Stented abdominal aortas were harvested 28 days after stenting. Computerized morphometric analysis revealed significantly increased neointima formation in long-term diabetic rats compared with nondiabetic controls. In conclusion, long-term autoimmune diabetes in BBDP rats enhances in-stent restenosis. This model can be used to study the underlying pathogenetic mechanisms of diabetes-enhanced in-stent restenosis as well as to test new therapeutic modalities.

THE CLINICAL AND PATHOGENETIC RELATIONSHIP BETWEEN BEHCET'S DISEASE AND MENTAL DISORDERS

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Daria Anatolyevna Ishchenko

2013-01-01

Full Text Available The paper analyzes the results of an investigation into the relationship between Behcet's disease (BB and mental disorders. It establishes the importance of an emotional stress factor for developing the clinical symptoms and disease. In its turn, the systemic immune inflammatory disease and its complications become a source of mental disorders. The literature describes different variants of BB, but anxiety-depressive spectrum disorders and moderate cognitive impairments are most common. The presence of depression contributes significantly to lower quality of life in patients with BB.

Crowdsourcing cyber security: a property rights view of exclusion and theft on the information commons

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Gary Shiffman

2013-02-01

Full Text Available Individuals increasingly rely upon the internet for basic economic interaction. Current cyber security mechanisms are unable to stop adversaries and hackers from gaining access to sensitive information stored on government, business, and public computers. Experts propose implementing attribution and audit frameworks in cyberspace to deter, prevent, and prosecute cyber criminals and attackers. However, this method faces significant policy and resource constraints. Social science research, specifically in law and economics, concerning common-pool resources suggests an organic approach to cyber security may yield an appropriate solution. This cyber commons method involves treating the internet as a commons and encouraging individuals and institutions to voluntarily implement innovative and adaptive monitoring mechanisms. Such mechanisms are already in use and in many cases have proven more effective than attribution mechanisms in resisting and tracing the source of cyber attacks.

Towards a taxonomy of common factors in psychotherapy-results of an expert survey.

Science.gov (United States)

Tschacher, Wolfgang; Junghan, Ulrich Martin; Pfammatter, Mario

2014-01-01

How change comes about is hotly debated in psychotherapy research. One camp considers 'non-specific' or 'common factors', shared by different therapy approaches, as essential, whereas researchers of the other camp consider specific techniques as the essential ingredients of change. This controversy, however, suffers from unclear terminology and logical inconsistencies. The Taxonomy Project therefore aims at contributing to the definition and conceptualization of common factors of psychotherapy by analyzing their differential associations to standard techniques. A review identified 22 common factors discussed in psychotherapy research literature. We conducted a survey, in which 68 psychotherapy experts assessed how common factors are implemented by specific techniques. Using hierarchical linear models, we predicted each common factor by techniques and by experts' age, gender and allegiance to a therapy orientation. Common factors differed largely in their relevance for technique implementation. Patient engagement, Affective experiencing and Therapeutic alliance were judged most relevant. Common factors also differed with respect to how well they could be explained by the set of techniques. We present detailed profiles of all common factors by the (positively or negatively) associated techniques. There were indications of a biased taxonomy not covering the embodiment of psychotherapy (expressed by body-centred techniques such as progressive muscle relaxation, biofeedback training and hypnosis). Likewise, common factors did not adequately represent effective psychodynamic and systemic techniques. This taxonomic endeavour is a step towards a clarification of important core constructs of psychotherapy. This article relates standard techniques of psychotherapy (well known to practising therapists) to the change factors/change mechanisms discussed in psychotherapy theory. It gives a short review of the current debate on the mechanisms by which psychotherapy works. We

Obesity and psychotic disorders: uncovering common mechanisms through metabolomics

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Matej Orešič

2012-09-01

Full Text Available Primary obesity and psychotic disorders are similar with respect to the associated changes in energy balance and co-morbidities, including metabolic syndrome. Such similarities do not necessarily demonstrate causal links, but instead suggest that specific causes of and metabolic disturbances associated with obesity play a pathogenic role in the development of co-morbid disorders, potentially even before obesity develops. Metabolomics – the systematic study of metabolites, which are small molecules generated by the process of metabolism – has been important in elucidating the pathways underlying obesity-associated co-morbidities. This review covers how recent metabolomic studies have advanced biomarker discovery and the elucidation of mechanisms underlying obesity and its co-morbidities, with a specific focus on metabolic syndrome and psychotic disorders. The importance of identifying metabolic markers of disease-associated intermediate phenotypes – traits modulated but not encoded by the DNA sequence – is emphasized. Such markers would be applicable as diagnostic tools in a personalized healthcare setting and might also open up novel therapeutic avenues.

Common approach to common interests

Energy Technology Data Exchange (ETDEWEB)

NONE

2001-06-01

In referring to issues confronting the energy field in this region and options to be exercised in the future, I would like to mention the fundamental condition of the utmost importance. That can be summed up as follows: any subject in energy area can never be solved by one country alone, given the geographical and geopolitical characteristics intrinsically possessed by energy. So, a regional approach is needed and it is especially necessary for the main players in the region to jointly address problems common to them. Though it may be a matter to be pursued in the distant future, I am personally dreaming a 'Common Energy Market for Northeast Asia,' in which member countries' interests are adjusted so that the market can be integrated and the region can become a most economically efficient market, thus formulating an effective power to encounter the outside. It should be noted that Europe needed forty years to integrate its market as the unified common market. It is necessary for us to follow a number of steps over the period to eventually materialize our common market concept, too. Now is the time for us to take a first step to lay the foundation for our descendants to enjoy prosperity from such a common market.

Disease: H01864 [KEGG MEDICUS

Lifescience Database Archive (English)

Full Text Available (GH) causes acromegaly (H01483) and pituitary gigantism (H01618). They have the same pathogenetic mechanism...nd IGF-I levels ... See also H01483 Acromegaly and H01618 Pituitary gigantism. ICD-1...0: E22.0 MeSH: D000172 D005877 OMIM: 102200 300943 PMID:22584702 ... AUTHORS ... Herder WW ... TITLE ... Familial gigantism

Is there a common mechanism underlying genomic instability, bystander effects and other nontargeted effects of exposure to ionizing radiation?

Science.gov (United States)

Morgan, William F.

2003-01-01

A number of nontargeted and delayed effects associated with radiation exposure have now been described. These include radiation-induced genomic instability, death-inducing and bystander effects, clastogenic factors and transgenerational effects. It is unlikely that these nontargeted effects are directly induced by cellular irradiation. Instead, it is proposed that some as yet to be identified secreted factor can be produced by irradiated cells that can stimulate effects in nonirradiated cells (death-inducing and bystander effects, clastogenic factors) and perpetuate genomic instability in the clonally expanded progeny of an irradiated cell. The proposed factor must be soluble and capable of being transported between cells by cell-to-cell gap junction communication channels. Furthermore, it must have the potential to stimulate cellular cytokines and/or reactive oxygen species. While it is difficult to imagine a role for such a secreted factor in contributing to transgenerational effects, the other nontargeted effects of radiation may all share a common mechanism.

Common Courses for Common Purposes:

DEFF Research Database (Denmark)

Schaub Jr, Gary John

2014-01-01

(PME)? I suggest three alternative paths that increased cooperation in PME at the level of the command and staff course could take: a Nordic Defence College, standardized national command and staff courses, and a core curriculum of common courses for common purposes. I conclude with a discussion of how...

Osteoarthritis: Key elements in its pathogenesis and current agents for pathogenetic therapy

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Yu. A. Olyunin

2017-01-01

Full Text Available Three main areas can be arbitrarily identified in the modern concept of treatment for osteoarthritis (OA; these are: 1 an impact on the progression of joint destruction; 2 suppression of peripheral pain mechanisms; and 3 inhibition of the central processes involved in the formation of pain sensation. Glucosamine and chondroitin sulfate (CS have become the first agents that are able to retard the development of cartilage degeneration. They have been used in medical practice for more than 40 years. A number of clinical trials of these drugs have yielded favorable results during their use in patients with OA. Another agent containing amino sugars and CS – sea fish cartilage hydrolysate has more recently emerged. Clinical trials have demonstrated that it is able to significantly relieve OA-induced pain. To date, the main agent for the analgesic therapy of OA is considered to be nonsteroidal anti-inflammatory drugs (NSAIDs that act on the peripheral mechanisms of pain and are widely used to treat diseases that are accompanied by chronic pain. However, a large-scale meta-analysis dealing with the experience with NSAIDs used to treat OA has shown that pain relief due to this therapy averaged only about 10 mm on a 100-mm visual analogue scale. To enhance the efficiency of therapy for OA, drug and non-drug treatments that affect the central mechanisms of pain in this disease are also used.

Development of a single-layer Nb3Sn common coil dipole model

Energy Technology Data Exchange (ETDEWEB)

Igor Novitski et al.

2002-12-13

A high-field dipole magnet based on the common coil design was developed at Fermilab for a future Very Large Hadron Collider. A short model of this magnet with a design field of 11 T in two 40-mm apertures is being fabricated using the react-and-wind technique. In order to study and optimize the magnet design two 165-mm long mechanical models were assembled and tested. A technological model consisting of magnet straight section and ends was also fabricated in order to check the tooling and the winding and assembly procedures. This paper describes the design and technology of the common coil dipole magnet and summarizes the status of short model fabrication.The results of the mechanical model tests and comparison with FE mechanical analysis are also presented.

Systems biology elucidates common pathogenic mechanisms between nonalcoholic and alcoholic-fatty liver disease.

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Silvia Sookoian

Full Text Available The abnormal accumulation of fat in the liver is often related either to metabolic risk factors associated with metabolic syndrome in the absence of alcohol consumption (nonalcoholic fatty liver disease, NAFLD or to chronic alcohol consumption (alcoholic fatty liver disease, AFLD. Clinical and histological studies suggest that NAFLD and AFLD share pathogenic mechanisms. Nevertheless, current data are still inconclusive as to whether the underlying biological process and disease pathways of NAFLD and AFLD are alike. Our primary aim was to integrate omics and physiological data to answer the question of whether NAFLD and AFLD share molecular processes that lead to disease development. We also explored the extent to which insulin resistance (IR is a distinctive feature of NAFLD. To answer these questions, we used systems biology approaches, such as gene enrichment analysis, protein-protein interaction networks, and gene prioritization, based on multi-level data extracted by computational data mining. We observed that the leading disease pathways associated with NAFLD did not significantly differ from those of AFLD. However, systems biology revealed the importance of each molecular process behind each of the two diseases, and dissected distinctive molecular NAFLD and AFLD-signatures. Comparative co-analysis of NAFLD and AFLD clarified the participation of NAFLD, but not AFLD, in cardiovascular disease, and showed that insulin signaling is impaired in fatty liver regardless of the noxa, but the putative regulatory mechanisms associated with NAFLD seem to encompass a complex network of genes and proteins, plausible of epigenetic modifications. Gene prioritization showed a cancer-related functional map that suggests that the fatty transformation of the liver tissue is regardless of the cause, an emerging mechanism of ubiquitous oncogenic activation. In conclusion, similar underlying disease mechanisms lead to NAFLD and AFLD, but specific ones depict a

Basic mechanisms of MCD in animal models.

Science.gov (United States)

Battaglia, Giorgio; Becker, Albert J; LoTurco, Joseph; Represa, Alfonso; Baraban, Scott C; Roper, Steven N; Vezzani, Annamaria

2009-09-01

Epilepsy-associated glioneuronal malformations (malformations of cortical development [MCD]) include focal cortical dysplasias (FCD) and highly differentiated glioneuronal tumors, most frequently gangliogliomas. The neuropathological findings are variable but suggest aberrant proliferation, migration, and differentiation of neural precursor cells as essential pathogenetic elements. Recent advances in animal models for MCDs allow new insights in the molecular pathogenesis of these epilepsy-associated lesions. Novel approaches, presented here, comprise RNA interference strategies to generate and study experimental models of subcortical band heterotopia and study functional aspects of aberrantly shaped and positioned neurons. Exciting analyses address impaired NMDA receptor expression in FCD animal models compared to human FCDs and excitatory imbalances in MCD animal models such as lissencephaly gene ablated mice as well as in utero irradiated rats. An improved understanding of relevant pathomechanisms will advance the development of targeted treatment strategies for epilepsy-associated malformations.

ALLERGIC EYE DISEASES IN CHILDREN. MODERN VIEW ON PATHOGENESIS AND TREATMENT

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E. Y. Markova

2017-01-01

Full Text Available The prevalence off allergic diseases has  been  significantly increased among  adults  and children during last 30-40 years. International study has  shown  that  the  frequency  of atopy  in developed  countries, including Russia,   is higher  than  in developing.  Often atopic dermatitis, started in infancy, can develop into an “allergic march”  — food allergy, followed by the formation of allergic rhinitis, allergic conjunctivitis and  other  allergic diseases. The problem  of prophylaxis and  treatment of allergic pathology  becomes actual  for these reasons. An opinion according some  preventive  measures has  changed in recent. It was  noted  that  in families  with many children, where  children  were  often  sick  with respiratory infections,  the  incidence  of allergic  diseases was  lower  than  among  rarely sick children.  It is explained by the  “hygienic theory” — insufficient “training” of the  Th1 response in rarely sick children.  Allergic diseases, which are  based on IgE-mediated inflammation,  have a common  pathogenetic nature and,  consequently, general  principles of therapy, in which, as  is well known,  antihistamines take  a significant  place.  This is cased by the  mandatory involvement of histamine  in the mechanism of development of the main symptoms of allergic diseases. Current  capabilities  of local ophthalmologic  antiallergic therapy includes medicines  with multiple action mechanisms, such as mast cell stabilizers, antihistamines, combined  agents, steroids and nonsteroidal anti-inflammatory effects. The latest generation antihistamine drug — olopatadine hydrochloride  0.2% is a new form of the molecule of olopatadine, which is intended  to increase the duration  of the action.  The article considers the main modern directions in prevention  and treatment of allergic diseases, including allergic eye diseases, which are  a

Pathogenetics. An introductory review

African Journals Online (AJOL)

Mohammad Saad Zaghloul Salem

2015-07-27

Jul 27, 2015 ... minimizing the drastic effects of mutational events on the genetic material and in effective ...... the functioning metabolic networks dependent on these roles, ..... anisms entails exclusive predominance of one parental genome.

Preschool wheeze: pathogenetic factors

African Journals Online (AJOL)

Ehab

trigger wheeze are more likely to have asthma compared to those with ... The role of airway infections in preschool wheeze ... and immunocompromised patients, with children younger than five ... expiratory flows and volumes were observed in.

Common-Sense Realism and the Unimaginable Otherness of Science

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Bradley Monton

2007-12-01

Full Text Available Bas van Fraassen endorses both common-sense realism — the view, roughly, that the ordinary macroscopic objects that we take to exist actually do exist — and constructive empiricism — the view, roughly, that the aim of science is truth about the observable world. But what happens if common-sense realism and science come into conflict? I argue that it is reasonable to think that they could come into conflict, by giving some motivation for a mental monist solution to the measurement problem of quantum mechanics. I then consider whether, in a situation where science favors the mental monist interpretation, van Fraassen would want to give up common-sense realism or would want to give up science.

Targets to treat androgen excess in polycystic ovary syndrome.

Science.gov (United States)

Luque-Ramírez, Manuel; Escobar-Morreale, Héctor Francisco

2015-01-01

The polycystic ovary syndrome (PCOS) is a common androgen disorder in reproductive-aged women. Excessive biosynthesis and secretion of androgens by steroidogenic tissues is its central pathogenetic mechanism. The authors review the potential targets and new drugs to treat androgen excess in PCOS. Besides our lab's experience, a systematic search (MEDLINE, Cochrane library, ClinicalTriasl.gov, EU Clinical Trials Register and hand-searching) regarding observational studies, randomized clinical trials, systematic reviews, meta-analyses and patents about this topic was performed. PCOS has a heterogeneous clinical presentation. It is unlikely that a single drug would cover all its possible manifestations. Available treatments for androgen excess are not free of side effects that are of particular concern in these women who suffer from cardiometabolic risk even without treatment. A precise characterization of the source of androgen excess must tailor antiandrogenic management in each woman, avoiding undesirable side effects.

Medical management of severe local radiation injury after acute X-ray exposure

International Nuclear Information System (INIS)

Bushmanov, A.; Nadezhina, N.; Kretov, A.

2008-01-01

Medical management during acute period in a case of severe local radiation injury after acute X-ray exposure includes 3 stages. During the fist stage patient got conservative treatment according to the common pathogenetic mechanisms of LRI (dis aggregating therapy, stimulation of regeneration, dis intoxication therapy, antibiotic therapy, pain relief therapy, Local anti-burn therapy-specific non-adhesive bandage with antiseptic and anti-burn medicaments); estimation of severity, deepness and area of injury by clinical picture and dates of instrumental methods of examining; defining necessity and volume of surgical treatment; preparing arrangements for surgical treatment. This stage ends with forming of demarcation line of a very hard severity of a Local Radiation Injure. The second stage includes necrectomy of the area of a very hard severity with microsurgical plastic by re vascularized flap and auto dermoplastic. The third stage - adaptation of re vascularized flap and total epithelization of injured area. (author)

INTESTINAL DYSBIOSIS IN CHILDREN WITH FOOD ALLERGY: PATHOGENETIC ASPECTS AND MODERN CORRECTION METHODS

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S.G. Makarova

2008-01-01

Full Text Available Background paper analyses the role of intestinal micro-flora at the stage of forming immunity, the importance of intestinal microflora abnormalities during the periods of allergic diseases development (primarily food allergies, as well as mechanisms of dysbiosis effect on the allergic processes in child's body. The study discusses the mechanisms of treatment and prevention effect of probiotics for cases of child allergic diseases. The work also specifies modern approaches to correcting dysbiotic abnormalities for children with food allergies, reviews the options of diet and medication treatment of food allergy, suggests a new algorithm of gradual treatment that targets correction of dysbiosis in this patient category.Key words: children, food allergy, dysbiosis, probiotics, prebiotics, diet therapy.

Body-induced vortical flows: a common mechanism for self-corrective trimming control in boxfishes.

Science.gov (United States)

Bartol, Ian K; Gharib, Morteza; Webb, Paul W; Weihs, Daniel; Gordon, Malcolm S

2005-01-01

: they produce trimming self-correcting forces, which we measured directly using the force balance. These data together with previous work on smooth trunkfish indicate that body-induced vortical flows are a common mechanism that is probably significant for trim control in all species of tropical boxfishes.

Differential proteomics reveals the hallmarks of seed development in common bean (Phaseolus vulgaris L.)

NARCIS (Netherlands)

Parreira, J R; Bouraada, J; Fitzpatrick, M A; Silvestre, S; Bernardes da Silva, A; Marques da Silva, J; Almeida, A M; Fevereiro, P; Altelaar, A F M; Araújo, S S

2016-01-01

Common bean (Phaseolus vulgaris L.) is one of the most consumed staple foods worldwide. Little is known about the molecular mechanisms controlling seed development. This study aims to comprehensively describe proteome dynamics during seed development of common bean. A high-throughput gel-free

Altered Colonic Environment, a Possible Predisposition to Colorectal Cancer and Colonic Inflammatory Bowel Disease: Rationale of Dietary Manipulation with Emphasis on Disaccharides

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A Szilagyi

1998-01-01

Full Text Available A recurrent theme in the schema of pathogenetic mechanisms attributed to colorectal cancer (CRC and inflammatory bowel disease (IBD is the interaction between genes and environment. Dietary and other environmental factors, and lower intestinal flora and their chemical interactions occur in the pathogenesis of both. Events at the mucosal surface may be influenced by factors in the luminal environment and by contributions of the host. In addition, both forms of IBD - Crohn's disease (CD and ulcerative colitis (UC - have distinctive associated host events. Even within CD and UC, different clinical patterns and prognoses may have different specific host mechanisms. Some of the current putative pathogenetic processes in CRC and IBD are reviewed. Particular attention is given to hypotheses relating to the role of dietetic substances, mainly fibre and dairy products, and how they may affect disease formation. It is argued that within the context of hypotheses proposed for possible beneficial effects of these two dietetic factors, CRC and IBD may be considered together. Further support is lent to arguments that similar and additional hypothetical features ascribed to beneficial effects of fibre may be attributed to disaccharides, lactose and its derivatives, lactulose and lactitol.

Abscessed Uterine and Extrauterine Adenomyomas with Uterus-Like Features in a 56-Year-Old Woman

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Asiye Safak Bulut

2013-01-01

Full Text Available Adenomyosis, also known as endometriosis interna, is the presence of endometrial glands and stroma within the myometrium. Its localised form is called adenomyoma and mimics a leiomyoma. Rarely, adenomyomas are located outside the uterus and some of them form uterus-like masses with a thick muscle wall and an endometrium-lined central cavity. They are generally located in the ovary or broad ligament, and, although they are closely related to endometriosis, their pathogenetic mechanisms are different from each other. Müllerian duct fusion defect and subcoelomic mesenchyme transformation theory are two possible pathogenetic mechanisms for this rare entity. Here we report abscessed uterine and extrauterine adenomyomas forming uterus-like masses in the left and right broad ligament and an ectopic adrenal tissue in the left paraovarian region in a 56-year-old woman. Although there is a reported abscessed adenomyosis in the literature, this is the first abscessed extrauterine uterus-like masses with synchronous pelvic pathologies like endometriosis, leiomyomas, adenomyosis, an endometrial polyp, an endocervical polyp, and an ectopic adrenal tissue. This benign lesion gives the impression of leiomyoma, a uterine malformation, or even malignancy preoperatively. Frozen section helps in differential diagnosis.

RAI1 gene mutations: mechanisms of Smith–Magenis Syndrome

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Falco M

2017-11-01

Full Text Available Mariateresa Falco,1,* Sonia Amabile,1,* Fabio Acquaviva2 1Department of Molecular Medicine and Medical Biotechnology, University of Naples “Federico II”, Naples, Italy; 2Department of Translational Medical Sciences (DISMET, Section of Pediatric Clinical Genetics, University of Naples “Federico II”, Naples, Italy *These authors contributed equally to this work Abstract: Smith–Magenis syndrome (SMS; OMIM #182290 is a complex genetic disorder characterized by distinctive physical features, developmental delay, cognitive impairment, and a typical behavioral phenotype. SMS is caused by interstitial 17p11.2 deletions, encompassing multiple genes and including the retinoic acid-induced 1 gene (RAI1, or by mutations in RAI1 itself. About 10% of all the SMS patients, in fact, carry an RAI1 mutation responsible for the phenotype. RAI1 (OMIM *607642 is a dosage-sensitive gene expressed in many tissues and highly conserved among species. Over the years, several studies have demonstrated that RAI1 (or its homologs in animal models acts as a transcriptional factor implicated in embryonic neurodevelopment, neuronal differentiation, cell growth and cell cycle regulation, bone and skeletal development, lipid and glucose metabolisms, behavioral functions, and circadian activity. Patients with RAI1 pathogenic variants show some phenotypic differences when compared to those carrying the typical deletion. They usually have lower incidence of hypotonia and less cognitive impairment than those with 17p11.2 deletions but more frequently show the behavioral characteristics of the syndrome and overeating issues. These differences reflect the primary pathogenetic role of RAI1 without the pathogenetic contribution of the other genes included in the typical 17p11.2 deletion. The better comprehension of physiological roles of RAI1, its molecular co-workers and interactors, and its contribution in determining the typical SMS phenotype will certainly open a new path

Drug Induced Steatohepatitis: An Uncommon Culprit of a Common Disease

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Liane Rabinowich

2015-01-01

Full Text Available Nonalcoholic fatty liver disease (NAFLD is a leading cause of liver disease in developed countries. Its frequency is increasing in the general population mostly due to the widespread occurrence of obesity and the metabolic syndrome. Although drugs and dietary supplements are viewed as a major cause of acute liver injury, drug induced steatosis and steatohepatitis are considered a rare form of drug induced liver injury (DILI. The complex mechanism leading to hepatic steatosis caused by commonly used drugs such as amiodarone, methotrexate, tamoxifen, valproic acid, glucocorticoids, and others is not fully understood. It relates not only to induction of the metabolic syndrome by some drugs but also to their impact on important molecular pathways including increased hepatocytes lipogenesis, decreased secretion of fatty acids, and interruption of mitochondrial β-oxidation as well as altered expression of genes responsible for drug metabolism. Better familiarity with this type of liver injury is important for early recognition of drug hepatotoxicity and crucial for preventing severe forms of liver injury and cirrhosis. Moreover, understanding the mechanisms leading to drug induced hepatic steatosis may provide much needed clues to the mechanism and potential prevention of the more common form of metabolic steatohepatitis.

End-stage renal disease in Nigeria: An overview of the epidemiology and the pathogenetic mechanisms

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M O Odubanjo

2011-01-01

Full Text Available There is paucity of information on the magnitude of the burden of renal disease in our environment. Obtaining accurate data is hampered by the poor socioeconomic status of most patients with lack of access to specialized care in tertiary institutions, where most of the data is generated. The incidence of chronic renal failure (CRF and end-stage renal disease (ESRD in any specified area is known to be influenced by the prevalence of specific disease entities resulting in CRF. Hypertension, glomerulonephritis (GN, sickle cell disease, quartan malaria nephropathy, urinary tract schistosomiasis and other parasite-related forms of chronic GN are known to contribute significantly to the incidence of CRF in Nigeria. As is the situation in other parts of the world, diabetic nephropathy appears to be of increasing importance in the causation of ESRD in Nigeria. Even though the underlying cause of renal disease can often not be treated, extensive studies in experimental animals and preliminary studies in humans suggest that progression in chronic renal disease may largely be due to secondary factors, attention to which may be important in the prevention and/or control of renal disease.

Pre-Clinical Traumatic Brain Injury Common Data Elements: Toward a Common Language Across Laboratories.

Science.gov (United States)

Smith, Douglas H; Hicks, Ramona R; Johnson, Victoria E; Bergstrom, Debra A; Cummings, Diana M; Noble, Linda J; Hovda, David; Whalen, Michael; Ahlers, Stephen T; LaPlaca, Michelle; Tortella, Frank C; Duhaime, Ann-Christine; Dixon, C Edward

2015-11-15

Traumatic brain injury (TBI) is a major public health issue exacting a substantial personal and economic burden globally. With the advent of "big data" approaches to understanding complex systems, there is the potential to greatly accelerate knowledge about mechanisms of injury and how to detect and modify them to improve patient outcomes. High quality, well-defined data are critical to the success of bioinformatics platforms, and a data dictionary of "common data elements" (CDEs), as well as "unique data elements" has been created for clinical TBI research. There is no data dictionary, however, for preclinical TBI research despite similar opportunities to accelerate knowledge. To address this gap, a committee of experts was tasked with creating a defined set of data elements to further collaboration across laboratories and enable the merging of data for meta-analysis. The CDEs were subdivided into a Core module for data elements relevant to most, if not all, studies, and Injury-Model-Specific modules for non-generalizable data elements. The purpose of this article is to provide both an overview of TBI models and the CDEs pertinent to these models to facilitate a common language for preclinical TBI research.

A current view of Alzheimer's disease.

Science.gov (United States)

Hooli, Basavaraj V; Tanzi, Rudolph E

2009-07-08

Several genes that influence susceptibility to Alzheimer's disease (AD) have been known for over two decades. Recent advances have elucidated novel candidate genes and the pathogenetic mechanisms underlying neurodegeneration in AD. Here, we summarize what we have learned from studies of the known AD genes with regard to the causes of AD and emerging therapies. We also review key recent discoveries that have enhanced our understanding of the etiology and pathogenesis of this devastating disease, based on new investigations into the genes and molecular mechanisms underlying AD.

w∞ algebras, conformal mechanics and black holes

Science.gov (United States)

Cacciatori, Sergio; Klemm, Dietmar; Zanon, Daniela

2000-04-01

We discuss BPS solitons in gauged icons/Journals/Common/calN" ALT="calN" ALIGN="TOP"/> = 2, D = 4 supergravity. The solitons represent extremal black holes interpolating between different vacua of anti-de Sitter spaces. The isometry superalgebras are determined and the motion of a superparticle in the extremal black hole background is studied and confronted with superconformal mechanics. We show that the Virasoro symmetry of conformal mechanics, which describes the dynamics of the superparticle near the horizon of the extremal black hole under consideration, extends to a symmetry under the wicons/Journals/Common/infty" ALT="infty" ALIGN="MIDDLE"/> algebra of area-preserving diffeomorphisms. We find that a Virasoro subalgebra of wicons/Journals/Common/infty" ALT="infty" ALIGN="MIDDLE"/> can be associated with the Virasoro algebra of the asymptotic symmetries of AdS 2 . In this way spacetime diffeomorphisms of AdS 2 translate into diffeomorphisms in phase space: our system offers an explicit realization of the AdS 2 /CFT 1 correspondence. Using the dimensionally reduced action, the central charge is computed. Finally, we also present generalizations of superconformal mechanics which are invariant under icons/Journals/Common/calN" ALT="calN" ALIGN="TOP"/> = 1 and icons/Journals/Common/calN" ALT="calN" ALIGN="TOP"/> = 2 superextensions of wicons/Journals/Common/infty" ALT="infty" ALIGN="MIDDLE"/> .

Biological Treatments in Behçet’s Disease: Beyond Anti-TNF Therapy

OpenAIRE

Francesco Caso; Luisa Costa; Donato Rigante; Orso Maria Lucherini; Paolo Caso; Vittoria Bascherini; Bruno Frediani; Rolando Cimaz; Edoardo Marrani; Laura Nieves-Martín; Mariangela Atteno; Carmela G. L. Raffaele; Giusyda Tarantino; Mauro Galeazzi; Leonardo Punzi

2014-01-01

Behçet's disease (BD) is universally recognized as a multisystemic inflammatory disease of unknown etiology with chronic course and unpredictable exacerbations: its clinical spectrum varies from pure vasculitic manifestations with thrombotic complications to protean inflammatory involvement of multiple organs and tissues. Treatment has been revolutionized by the progressed knowledge in the pathogenetic mechanisms of BD, involving dysfunction and oversecretion of multiple proinflammatory molec...

Hirschsprung's disease - Postsurgical intestinal dysmotility

OpenAIRE

Romaneli, Mariana Tresoldi das Neves; Ribeiro, Antonio Fernando; Bustorff-Silva, Joaquim Murray; de Carvalho, Rita Barbosa; Lomazi, Elizete Aparecida

2016-01-01

Abstract Objective: To describe the case of an infant with Hirschsprung's disease presenting as total colonic aganglionosis, which, after surgical resection of the aganglionic segment persisted with irreversible functional intestinal obstruction; discuss the difficulties in managing this form of congenital aganglionosis and discuss a plausible pathogenetic mechanism for this case. Case description: The diagnosis of Hirschsprung's disease presenting as total colonic aganglionosis was establi...

Medulloblastoma in association with the Coffin-Siris syndrome.

Science.gov (United States)

Rogers, L; Pattisapu, J; Smith, R R; Parker, P

1988-02-01

An 8-year old patient with Coffin-Siris syndrome is presented, who was found to have a medulloblastoma during the evaluation of apnea and ventilator dependency. Although several cases of Dandy Walker cysts and one case of brain-stem heterotopia have been described in this rare syndrome, this is the first report of medulloblastoma in a patient with Coffin-Siris syndrome. Possible pathogenetic mechanisms are briefly discussed.

New approaches to reduce ulcerogenity of nonsteroidal anti-inflammatory drugs: achievements, unsolved issues and ways to optimize

Directory of Open Access Journals (Sweden)

F. V. Hladkykh

2014-04-01

Full Text Available Analysis of the domestic and foreign literature sources devoted to the study of pathogenetic mechanisms of gastropathy caused by non-steroidal anti-inflammatory drugs was done. Current approaches of prevention and treatment of NSAID-induced gastropathy were lined. The appropriateness of drugs with polytropic pharmacological properties (Quercetin, Vinboron and Tiotriazolin to eliminate the side effects of NSAIDs, including ultserogenesis was discusses.

Divided versus selective attention: evidence for common processing mechanisms.

Science.gov (United States)

Hahn, Britta; Wolkenberg, Frank A; Ross, Thomas J; Myers, Carol S; Heishman, Stephen J; Stein, Dan J; Kurup, Pradeep K; Stein, Elliot A

2008-06-18

The current study revisited the question of whether there are brain mechanisms specific to divided attention that differ from those used in selective attention. Increased neuronal activity required to simultaneously process two stimulus dimensions as compared with each separate dimension has often been observed, but rarely has activity induced by a divided attention condition exceeded the sum of activity induced by the component tasks. Healthy participants performed a selective-divided attention paradigm while undergoing functional Magnetic Resonance Imaging (fMRI). The task required participants to make a same-different judgment about either one of two simultaneously presented stimulus dimensions, or about both dimensions. Performance accuracy was equated between tasks by dynamically adjusting the stimulus display time. Blood Oxygenation Level Dependent (BOLD) signal differences between tasks were identified by whole-brain voxel-wise comparisons and by region-specific analyses of all areas modulated by the divided attention task (DIV). No region displayed greater activation or deactivation by DIV than the sum of signal change by the two selective attention tasks. Instead, regional activity followed the tasks' processing demands as reflected by reaction time. Only a left cerebellar region displayed a correlation between participants' BOLD signal intensity and reaction time that was selective for DIV. The correlation was positive, reflecting slower responding with greater activation. Overall, the findings do not support the existence of functional brain activity specific to DIV. Increased activity appears to reflect additional processing demands by introducing a secondary task, but those demands do not appear to qualitatively differ from processes of selective attention.

Innovation and problem solving: a review of common mechanisms.

Science.gov (United States)

Griffin, Andrea S; Guez, David

2014-11-01

Behavioural innovations have become central to our thinking about how animals adjust to changing environments. It is now well established that animals vary in their ability to innovate, but understanding why remains a challenge. This is because innovations are rare, so studying innovation requires alternative experimental assays that create opportunities for animals to express their ability to invent new behaviours, or use pre-existing ones in new contexts. Problem solving of extractive foraging tasks has been put forward as a suitable experimental assay. We review the rapidly expanding literature on problem solving of extractive foraging tasks in order to better understand to what extent the processes underpinning problem solving, and the factors influencing problem solving, are in line with those predicted, and found, to underpin and influence innovation in the wild. Our aim is to determine whether problem solving can be used as an experimental proxy of innovation. We find that in most respects, problem solving is determined by the same underpinning mechanisms, and is influenced by the same factors, as those predicted to underpin, and to influence, innovation. We conclude that problem solving is a valid experimental assay for studying innovation, propose a conceptual model of problem solving in which motor diversity plays a more central role than has been considered to date, and provide recommendations for future research using problem solving to investigate innovation. This article is part of a Special Issue entitled: Cognition in the wild. Copyright © 2014 Elsevier B.V. All rights reserved.

Applications in solid mechanics

DEFF Research Database (Denmark)

Ølgaard, Kristian Breum; Wells, Garth N.

2012-01-01

Problems in solid mechanics constitute perhaps the largest field of application of finite element methods. The vast majority of solid mechanics problems involve the standard momentum balance equation, posed in a Lagrangian setting, with different models distinguished by the choice of nonlinear...... or linearized kinematics, and the constitutive model for determining the stress. For some common models, the constitutive relationships are rather complex. This chapter addresses a number of canonical solid mechanics models in the context of automated modeling, and focuses on some pertinent issues that arise...

Are there common mechanisms in sensation seeking and reality distortion in schizophrenia? A study using memory event-related potentials.

Science.gov (United States)

Guillem, François; Pampoulova, Tania; Stip, Emmanuel; Todorov, Christo; Lalonde, Pierre

2005-05-15

A growing literature suggests that the characteristics of sensation seeking and reality distortion expressed in schizophrenia share several mechanisms. In a previous study, the comparison of patients with high vs. low reality distortion using event-related potentials (ERPs) recorded in a recognition memory task for unfamiliar faces identified neural and cognitive anomalies specifically related to the expression of these symptoms. As a follow-up, this study investigated the ERP correlates of sensation seeking in schizophrenia using the same recognition memory protocol. ERPs have been recorded in controls (N=21) and schizophrenia patients separated into high (HSS; N=13) and low (LSS; N=17) scorers according to Zuckerman's Sensation Seeking Scale. The results show a reduced P2a that was found unrelated to reality distortion in the previous study of reality distortion. It identifies interference inhibition impairment as being specifically related to sensation seeking. On the other hand, HSS scorers display enhanced fronto-central and normal P600 effects also found in high reality distortion patients. These results indicate inappropriate context processing and mnemonic binding common to sensation seeking and reality distortion. LSS scorers also display a reduced temporal N300 similar to that found in low reality distortion patients. This anomaly could reflect the lower reactivity to emotionally significant stimuli that underlies anhedonia symptoms. Finally, the N400 effect and a late frontal effect are found in both HSS and LSS. Since they were unrelated to reality distortion, these indices have been related to basic aspects of schizophrenia, e.g., deficient knowledge integration, or other mechanisms, e.g. anxiety or impulsivity. In summary, the present study examines the strategy of investigating variables, such as temperamental characteristics, in addition to symptoms, to show how discrete impairments may contribute to the expression of the illness.

Common Fluorescence In Situ Hybridization Applications in Cytology.

Science.gov (United States)

Savic, Spasenija; Bubendorf, Lukas

2016-12-01

- Fluorescence in situ hybridization (FISH) is a well-established method for detection of genomic aberrations in diagnostic, prognostic, and predictive marker testing. - To review common applications of FISH in cytology. - The published literature was reviewed. - Cytology is particularly well suited for all kinds of FISH applications, which is highlighted in respiratory tract cytology with an increasing demand for predictive FISH testing in lung cancer. Fluorescence in situ hybridization is the gold standard for detection of predictive anaplastic lymphoma kinase gene (ALK) rearrangements, and the same evaluation criteria as in histology apply to cytology. Several other gene rearrangements, including ROS proto-oncogene 1 receptor tyrosine kinase (ROS1), are becoming clinically important and share the same underlining cytogenetic mechanisms with ALK. MET amplification is one of the most common mechanisms of acquired resistance to epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors and can be targeted by crizotinib. As genomic aberrations are a hallmark of malignant cells, FISH is a valuable objective ancillary diagnostic tool. In urinary tract cytology, atypical urothelial cells equivocal for malignancy are a common diagnostic dilemma and multitarget FISH can help clarify such cells. Diagnosis of malignant mesothelioma remains one of the most challenging fields in effusion cytology, and ancillary FISH is useful in establishing the diagnosis. Fluorescence in situ hybridization is a morphology-based technique, and the prerequisite for reliable FISH results is a targeted evaluation of the cells in question (eg, cancer or atypical cells). Cytopathologists and cytotechnicians should therefore be involved in molecular testing in order to select the best material and to provide their morphologic expertise.

MUS81 promotes common fragile site expression

DEFF Research Database (Denmark)

Ying, Songmin; Minocherhomji, Sheroy; Chan, Kok Lung

2013-01-01

Fragile sites are chromosomal loci with a propensity to form gaps or breaks during early mitosis, and their instability is implicated as being causative in certain neurological disorders and cancers. Recent work has demonstrated that the so-called common fragile sites (CFSs) often impair the fait......Fragile sites are chromosomal loci with a propensity to form gaps or breaks during early mitosis, and their instability is implicated as being causative in certain neurological disorders and cancers. Recent work has demonstrated that the so-called common fragile sites (CFSs) often impair...... the faithful disjunction of sister chromatids in mitosis. However, the mechanisms by which CFSs express their fragility, and the cellular factors required to suppress CFS instability, remain largely undefined. Here, we report that the DNA structure-specific nuclease MUS81-EME1 localizes to CFS loci in early...

Current surgical treatment for chronic pancreatitis.

Science.gov (United States)

Aimoto, Takayuki; Uchida, Eiji; Nakamura, Yoshiharu; Yamahatsu, Kazuya; Matsushita, Akira; Katsuno, Akira; Cho, Kazumitsu; Kawamoto, Masao

2011-01-01

Chronic pancreatitis (CP) is a painful, yet benign inflammatory process of the pancreas. Surgical management should be individualized because the pain is multifactorial and its mechanisms vary from patient to patient. Two main pathogenetic theories for the mechanisms of pain in CP have been proposed: the neurogenic theory and the theory of increased intraductal/intraparenchymal pressures. The latter theory is strongly supported by the good results of drainage procedures in the surgical management of CP. Other possible contributing factors include pancreatic ischemia; a centrally sensitized pain state; and the development of complications, such as pseudocysts and stenosis of the duodenum or common bile duct. Common indications for surgery include intractable pain, suspicion of neoplasm, and complications that cannot be resolved with radiological or endoscopic treatments. Operative procedures have been historically classified into 4 categories: decompression procedures for diseased and obstructed pancreatic ducts; resection procedures for the proximal, distal, or total pancreas; denervation procedures of the pancreas; and hybrid procedures. Pancreaticoduodenectomy and pylorus-preserving pancreaticoduodenectomy, once the standard operations for patients with CP, have been replaced by hybrid procedures, such as duodenum-preserving pancreatic head resection, the Frey procedure, and their variants. These procedures are safe and effective in providing long-term pain relief and in treating CP-related complications. Hybrid procedures should be the operations of choice for patients with CP.

Microarray-Based Gene Expression Analysis for Veterinary Pathologists: A Review.

Science.gov (United States)

Raddatz, Barbara B; Spitzbarth, Ingo; Matheis, Katja A; Kalkuhl, Arno; Deschl, Ulrich; Baumgärtner, Wolfgang; Ulrich, Reiner

2017-09-01

High-throughput, genome-wide transcriptome analysis is now commonly used in all fields of life science research and is on the cusp of medical and veterinary diagnostic application. Transcriptomic methods such as microarrays and next-generation sequencing generate enormous amounts of data. The pathogenetic expertise acquired from understanding of general pathology provides veterinary pathologists with a profound background, which is essential in translating transcriptomic data into meaningful biological knowledge, thereby leading to a better understanding of underlying disease mechanisms. The scientific literature concerning high-throughput data-mining techniques usually addresses mathematicians or computer scientists as the target audience. In contrast, the present review provides the reader with a clear and systematic basis from a veterinary pathologist's perspective. Therefore, the aims are (1) to introduce the reader to the necessary methodological background; (2) to introduce the sequential steps commonly performed in a microarray analysis including quality control, annotation, normalization, selection of differentially expressed genes, clustering, gene ontology and pathway analysis, analysis of manually selected genes, and biomarker discovery; and (3) to provide references to publically available and user-friendly software suites. In summary, the data analysis methods presented within this review will enable veterinary pathologists to analyze high-throughput transcriptome data obtained from their own experiments, supplemental data that accompany scientific publications, or public repositories in order to obtain a more in-depth insight into underlying disease mechanisms.

Convergence of circuit dysfunction in ASD: a common bridge between diverse genetic and environmental risk factors and common clinical electrophysiology.

Science.gov (United States)

Port, Russell G; Gandal, Michael J; Roberts, Timothy P L; Siegel, Steven J; Carlson, Gregory C

2014-01-01

Most recent estimates indicate that 1 in 68 children are affected by an autism spectrum disorder (ASD). Though decades of research have uncovered much about these disorders, the pathological mechanism remains unknown. Hampering efforts is the seeming inability to integrate findings over the micro to macro scales of study, from changes in molecular, synaptic and cellular function to large-scale brain dysfunction impacting sensory, communicative, motor and cognitive activity. In this review, we describe how studies focusing on neuronal circuit function provide unique context for identifying common neurobiological disease mechanisms of ASD. We discuss how recent EEG and MEG studies in subjects with ASD have repeatedly shown alterations in ensemble population recordings (both in simple evoked related potential latencies and specific frequency subcomponents). Because these disease-associated electrophysiological abnormalities have been recapitulated in rodent models, studying circuit differences in these models may provide access to abnormal circuit function found in ASD. We then identify emerging in vivo and ex vivo techniques, focusing on how these assays can characterize circuit level dysfunction and determine if these abnormalities underlie abnormal clinical electrophysiology. Such circuit level study in animal models may help us understand how diverse genetic and environmental risks can produce a common set of EEG, MEG and anatomical abnormalities found in ASD.

Convergence of Circuit Dysfunction in ASD: A common bridge between diverse genetic and environmental risk factors and common clinical neurophysiology.

Directory of Open Access Journals (Sweden)

Russell G Port

2014-12-01

Full Text Available Most recent estimates indicate that 1 in 68 children are affected by an autism spectrum disorder (ASD. Though decades of research have uncovered much about these disorders, the pathological mechanism remains unknown. Hampering efforts is the seeming inability to integrate findings over the micro to macro scales of study, from changes in molecular, synaptic and cellular function to large-scale brain dysfunction impacting sensory, communicative, motor and cognitive activity. In this review, we describe how studies focusing on neuronal circuit function provide unique context for identifying common neurobiological disease mechanisms of ASD. We discuss how recent EEG and MEG studies in subjects with ASD have repeatedly shown alterations in ensemble population recordings (both in simple evoked related potential latencies and specific frequency subcomponents. Because these disease-associated electrophysiological abnormalities have been recapitulated in rodent models, studying circuit differences in these models may provide access to abnormal circuit function found in ASD. We then identify emerging in-vivo and ex-vivo techniques, focusing on how these assays can characterize circuit level dysfunction and determine if these abnormalities underlie abnormal clinical electrophysiology. Such circuit level study in animal models may help us understand how diverse genetic and environmental risks can produce a common set of EEG, MEG and anatomical abnormalities found in ASD.

Convergence of circuit dysfunction in ASD: a common bridge between diverse genetic and environmental risk factors and common clinical electrophysiology

Science.gov (United States)

Port, Russell G.; Gandal, Michael J.; Roberts, Timothy P. L.; Siegel, Steven J.; Carlson, Gregory C.

2014-01-01

Most recent estimates indicate that 1 in 68 children are affected by an autism spectrum disorder (ASD). Though decades of research have uncovered much about these disorders, the pathological mechanism remains unknown. Hampering efforts is the seeming inability to integrate findings over the micro to macro scales of study, from changes in molecular, synaptic and cellular function to large-scale brain dysfunction impacting sensory, communicative, motor and cognitive activity. In this review, we describe how studies focusing on neuronal circuit function provide unique context for identifying common neurobiological disease mechanisms of ASD. We discuss how recent EEG and MEG studies in subjects with ASD have repeatedly shown alterations in ensemble population recordings (both in simple evoked related potential latencies and specific frequency subcomponents). Because these disease-associated electrophysiological abnormalities have been recapitulated in rodent models, studying circuit differences in these models may provide access to abnormal circuit function found in ASD. We then identify emerging in vivo and ex vivo techniques, focusing on how these assays can characterize circuit level dysfunction and determine if these abnormalities underlie abnormal clinical electrophysiology. Such circuit level study in animal models may help us understand how diverse genetic and environmental risks can produce a common set of EEG, MEG and anatomical abnormalities found in ASD. PMID:25538564

Transcriptome analysis of two recombinant inbred lines of common bean contrasting for symbiotic nitrogen fixation

Science.gov (United States)

Common bean (Phaseolus vulgaris L.) is able to fix atmospheric nitrogen (N2) through symbiotic nitrogen fixation (SNF). Effective utilization of existing variability for SNF in common bean for genetic improvement requires an understanding of underlying genes and molecular mechanisms. The utility of ...

Mechanisms of behavior modification in clinical behavioral medicine in China.

Science.gov (United States)

Yang, Zhiyin; Su, Zhonghua; Ji, Feng; Zhu, Min; Bai, Bo

2014-08-01

Behavior modification, as the core of clinical behavioral medicine, is often used in clinical settings. We seek to summarize behavior modification techniques that are commonly used in clinical practice of behavioral medicine in China and discuss possible biobehavioral mechanisms. We reviewed common behavior modification techniques in clinical settings in China, and we reviewed studies that explored possible biobehavioral mechanisms. Commonly used clinical approaches of behavior modification in China include behavior therapy, cognitive therapy, cognitive-behavioral therapy, health education, behavior management, behavioral relaxation training, stress management intervention, desensitization therapy, biofeedback therapy, and music therapy. These techniques have been applied in the clinical treatment of a variety of diseases, such as chronic diseases, psychosomatic diseases, and psychological disorders. The biobehavioral mechanisms of these techniques involve the autonomic nervous system, neuroendocrine system, neurobiochemistry, and neuroplasticity. Behavior modification techniques are commonly used in the treatment of a variety of somatic and psychological disorders in China. Multiple biobehavioral mechanisms are involved in successful behavior modification.

DIABETES-ASSOCIATED OSTEOARTHRITIS: A SYNTROPY?

Directory of Open Access Journals (Sweden)

E. V. Kazygasheva

2016-01-01

Full Text Available This review presents our own and literature data dedicated to predisposing and pathogenetic factors involved in development of a common comorbidity, diabetes-associated osteoarthritis (DAOA. So far, there is no wide-accepted clinical or scientific viewing of DAOA as a distinct clinical phenotype of osteoarthritis (OA. To our knowledge, the role of genetic factors in DAOA development was not discussed in details. Therefore, we have drawn attention to the cross-acting genes involved in both OA and diabetes, i.e., PPARγ, FTO, ADIPOQ, and AGE. These genes encode proteins which can contribute to the pathogenesis of both OA and diabetes. However, some controversies exist about genetic predisposal for OA and diabetes. We review the studies which concern various clinical characteristics of DAOA. We describe a role of chronic hyperglycemia, insulin resistance, advanced glycation end-products (AGE in development of OA and micro- and macrovascular complications of diabetes. The mechanisms of low-grade inflammation, humoral and cellular immune responses to cartilage antigens, and their role in OA progression are discussed. We underline a similarity of low-grade inflammation in OA and microvascular complications in diabetes. In conclusion, OA and diabetes comorbidity is not a mere coincidence of these diseases. They share some common genetic and pathogenetic factors, a distinct phenotype, and may change thinking of physicians and scientists towards a holistic (personalized approach to prevention, diagnosis, treatment and prognosis of this comorbidity. We discuss opportunities of DAOA pharmacotherapy based on the key comorbidity feature, i.e., emergence of a new disease property by coexistence of several diseases. One may hypothesize that studying genetic, molecular, and cellular networks in comorbidities may lead to new treatment strategies (‘network pharmacology” based on targeting the network hubs. We provide examples of such approach in some

Common rugby league injuries. Recommendations for treatment and preventative measures.

Science.gov (United States)

Gibbs, N

1994-12-01

Rugby league is the main professional team sport played in Eastern Australia. It is also very popular at a junior and amateur level. However, injuries are common because of the amount of body contact that occurs and the amount of running that is required to participate in the game. Injuries to the lower limbs account for over 50% of all injuries. The most common specific injuries are ankle lateral ligament tears, knee medial collateral and anterior cruciate ligament tears, groin musculotendinous tears, hamstring and calf muscle tears, and quadriceps muscle contusions. Head injuries are common and consist of varying degrees of concussion as well as lacerations and facial fractures. Serious head injury is rare. Some of the more common upper limb injuries are to the acromioclavicular and glenohumeral joints. Accurate diagnosis of these common injuries using appropriate history, examination and investigations is critical in organising a treatment and rehabilitation plan that will return the player to competition as soon as possible. An understanding of the mechanism of injury is also important in order to develop preventative strategies.

Shared genetic variants suggest common pathways in allergy and autoimmune diseases

DEFF Research Database (Denmark)

Kreiner-Møller, Eskil; Waage, Johannes; Standl, Marie

2017-01-01

Background: The relationship between allergy and autoimmune disorders is complex and poorly understood. Objective: To investigate commonalities in genetic loci and pathways between allergy and autoimmune diseases to elucidate shared disease mechanisms. Methods: We meta-analyzed two GWAS on self-r...

Bipolar affective disorder: A review of novel forms of therapy

Directory of Open Access Journals (Sweden)

Dziwota Ewelina

2015-06-01

Full Text Available Normothymic, antidepressant and antipsychotic pharmaceutics are, in accordance with international guidelines, employed both in the therapy and the prevention of bipolar disorder (BD. Long-term studies on the mechanisms of action of such medications, as well as on the pathogenetic background of BD, have led to the discovery of effective, albeit unconventional pharmacotherapeutic approaches. These methods have the potential to successfully treat mania and depression, as well as to counter affective episode relapse. Allopurinol - commonly used to treat gout, secondary hyperuricemia and Lesch-Nyhan syndrome, acts by inhibiting the synthesis of uric acid, levels of which are often increased in manic patients. Due to this, an evaluation of the potential effect of allopurinol on the reduction of mania symptoms seems to be reasonable. Additionally, the numerable research papers coming out of research regarding the role of purine neurotransmitters in mood alterations, indicate that adenosine agonists act analogously to dopamine antagonists.

Grain dust and the lungs.

Science.gov (United States)

Chan-Yeung, M.; Ashley, M. J.; Grzybowski, S.

1978-01-01

Grain dust is composed of a large number of materials, including various types of grain and their disintegration products, silica, fungi, insects and mites. The clinical syndromes described in relation to exposure to grain dust are chronic bronchitis, grain dust asthma, extrinsic allergic alveolitis, grain fever and silo-filler's lung. Rhinitis and conjunctivitis are also common in grain workers. While the concentration and the quality of dust influence the frequency and the type of clinical syndrome in grain workers, host factors are also important. Of the latter, smoking is the most important factor influencing the frequency of chronic bronchitis. The role of atopy and of bronchial hyperreactivity in grain dust asthma has yet to be assessed. Several well designed studies are currently being carried out in North America not only to delineate the frequency of the respiratory abnormalities, the pathogenetic mechanisms and the host factors, but also to establish a meaningful threshold limit concentration for grain dust. Images p1272-a PMID:348288

The genetics of Alzheimer disease: back to the future.

Science.gov (United States)

Bertram, Lars; Lill, Christina M; Tanzi, Rudolph E

2010-10-21

Three decades of genetic research in Alzheimer disease (AD) have substantially broadened our understanding of the pathogenetic mechanisms leading to neurodegeneration and dementia. Positional cloning led to the identification of rare, disease-causing mutations in APP, PSEN1, and PSEN2 causing early-onset familial AD, followed by the discovery of APOE as the single most important risk factor for late-onset AD. Recent genome-wide association approaches have delivered several additional AD susceptibility loci that are common in the general population, but exert only very small risk effects. As a result, a large proportion of the heritability of AD continues to remain unexplained by the currently known disease genes. It seems likely that much of this "missing heritability" may be accounted for by rare sequence variants, which, owing to recent advances in high-throughput sequencing technologies, can now be assessed in unprecedented detail. Copyright © 2010 Elsevier Inc. All rights reserved.

Late Onset Cobalamin Disorder and Hemolytic Uremic Syndrome: A Rare Cause of Nephrotic Syndrome

Directory of Open Access Journals (Sweden)

Gianluigi Ardissino

2017-01-01

Full Text Available Hemolytic uremic syndrome (HUS is an unrare and severe thrombotic microangiopathy (TMA caused by several pathogenetic mechanisms among which Shiga toxin-producing Escherichia coli infections and complement dysregulation are the most common. However, very rarely and particularly in neonates and infants, disorders of cobalamin metabolism (CblC can present with or be complicated by TMA. Herein we describe a case of atypical HUS (aHUS related to CblC disease which first presented in a previously healthy boy at age of 13.6 years. The clinical picture was initially dominated by nephrotic range proteinuria and severe hypertension followed by renal failure. The specific treatment with high dose of hydroxycobalamin rapidly obtained the remission of TMA and the complete recovery of renal function. We conclude that plasma homocysteine and methionine determinations together with urine organic acid analysis should be included in the diagnostic work-up of any patient with TMA and/or nephrotic syndrome regardless of age.

Transformation of follicular lymphoma to plasmablastic lymphoma with c-myc gene rearrangement.

Science.gov (United States)

Ouansafi, Ihsane; He, Bing; Fraser, Cory; Nie, Kui; Mathew, Susan; Bhanji, Rumina; Hoda, Rana; Arabadjief, Melissa; Knowles, Daniel; Cerutti, Andrea; Orazi, Attilio; Tam, Wayne

2010-12-01

Follicular lymphoma (FL) is an indolent lymphoma that transforms to high-grade lymphoma, mostly diffuse large B-cell lymphoma, in about a third of patients. We present the first report of a case of FL that transformed to plasmablastic lymphoma (PBL). Clonal transformation of the FL to PBL was evidenced by identical IGH/BCL2 gene rearrangements and VDJ gene usage in rearranged IGH genes. IGH/ BCL2 translocation was retained in the PBL, which also acquired c-myc gene rearrangement. Genealogic analysis based on somatic hypermutation of the rearranged IGH genes of both FL and PBL suggests that transformation of the FL to PBL occurred most likely by divergent evolution from a common progenitor cell rather than direct evolution from the FL clone. Our study of this unusual case expands the histologic spectrum of FL transformation and increases our understanding of the pathogenetic mechanisms of transformation of indolent lymphomas to aggressive lymphomas.

Autoimmune pancreatitis type-1 associated with intraduct papillary mucinous neoplasm: report of two cases.

Science.gov (United States)

Vaquero, Eva C; Salcedo, Maria T; Cuatrecasas, Míriam; De León, Hannah; Merino, Xavier; Navarro, Salvador; Ginès, Angels; Abu-Suboh, Monder; Balsells, Joaquim; Fernández-Cruz, Laureano; Molero, Xavier

2014-01-01

Chronic pancreatitis lesions usually embrace both intraduct papillary mucinous neoplasm (IPMN) and pancreatic ductal adenocarcinoma (PDAC). Patients at genetically-determined high risk of PDAC often harbor IPMN and/or chronic pancreatitis, suggesting IPMN, chronic pancreatitis and PDAC may share pathogenetic mechanisms. Chronic autoimmune pancreatitis (AIP) may also herald PDAC. Concurrent IPMN and AIP have been reported in few patients. Here we describe two patients with IPMN who developed type-1 AIP fulfilling the Honolulu and Boston diagnostic criteria. AIP diffusively affected the whole pancreas, as well as peripancreatic lymph nodes and the gallbladder. Previous pancreatic resection of focal IPMN did not show features of AIP. One of the patients carried a CFTR class-I mutation. Of notice, serum IgG4 levels gradually decreased to normal values after IPMN excision. Common risk factors to IPMN and AIP may facilitate its coincidental generation. Copyright © 2014 IAP and EPC. Published by Elsevier B.V. All rights reserved.

The neurobiological link between OCD and ADHD.

Science.gov (United States)

Brem, Silvia; Grünblatt, Edna; Drechsler, Renate; Riederer, Peter; Walitza, Susanne

2014-09-01

Obsessive compulsive disorder (OCD) and attention deficit hyperactivity disorder (ADHD) are two of the most common neuropsychiatric diseases in paediatric populations. The high comorbidity of ADHD and OCD with each other, especially of ADHD in paediatric OCD, is well described. OCD and ADHD often follow a chronic course with persistent rates of at least 40-50 %. Family studies showed high heritability in ADHD and OCD, and some genetic findings showed similar variants for both disorders of the same pathogenetic mechanisms, whereas other genetic findings may differentiate between ADHD and OCD. Neuropsychological and neuroimaging studies suggest that partly similar executive functions are affected in both disorders. The deficits in the corresponding brain networks may be responsible for the perseverative, compulsive symptoms in OCD but also for the disinhibited and impulsive symptoms characterizing ADHD. This article reviews the current literature of neuroimaging, neurochemical circuitry, neuropsychological and genetic findings considering similarities as well as differences between OCD and ADHD.

Idiopathic hypereosinophilic syndrome associated with rheumatoid arthritis A case report

Directory of Open Access Journals (Sweden)

P. Quattrocchi

2011-09-01

Full Text Available The idiopathic hypereosinophilic sindrome (HES is a disease characterized by persistent blood eosinophilia (> 1500 eosinophils/mm3 > 6 months-in absence of other ethiologies for eosinophilia (parasitic, allergic, immunological or malignant diseases-associated with multiple organ involvement (heart, lung, central nervous system, skin, bone marrow, gastrointestinal tract. Reports on rheumatologic manifestations in patients with HES are very rare. In the case we report a typical rheumatoid arthritis developed in a 58-year-old woman with HES treated with glucocorticoids. Because of the marked glucocorticoids side effects shown by the patient(cushingoid habitus, hyperglycemia, we stopped this treatment and replaced it at first by methotrexate and later by cyclosporin, both of them associated with sulfasalazine. These drugs revealed very efficacious both on articular pathology and on the clinical and laboratory manifestations of HES. These data suggest that common pathogenetic mechanisms are likely acting in rheumatoid arthritis and idiopathic hypereosinophilic syndrome.

EPR-technical codes - a common basis for the EPR

International Nuclear Information System (INIS)

Zaiss, W.; Appell, B.

1997-01-01

The design and construction of Nuclear Power Plants implies a full set of codes and standards to define the construction rules of components and equipment. Rules are existing and are currently implemented, respectively in France and Germany (mainly RCCs and KTA safety standards). In the frame of the EPR-project, the common objective requires an essential industrial work programme between engineers from both countries to elaborate a common set of codes and regulations. These new industrial rules are called the ETCs (EPR Technical Codes). In the hierarchy the ETCs are - in case of France - on the common level of basic safety rules (RFS), design and construction rules (RCC) and - in Germany - belonging to RSK guidelines and KTA safety standards. A set of six ETCs will be elaborated to cover: safety and process, mechanical components, electrical equipment, instrumentation and control, civil works, fire protection. (orig.)

Immune Mechanisms in Myelodysplastic Syndrome

DEFF Research Database (Denmark)

Glenthøj, Andreas; Ørskov, Andreas Due; Hansen, Jakob Werner

2016-01-01

diseases are common in patients with MDS, fueling hypotheses of common etiological mechanisms. Both innate and adaptive immune pathways are overly active in the hematopoietic niche of MDS. Although supportive care, growth factors, and hypomethylating agents are the mainstay of MDS treatment, some patients......-especially younger low-risk patients with HLA-DR15 tissue type-demonstrate impressive response rates after immunosuppressive therapy. This is in contrast to higher-risk MDS patients, where several immune activating treatments, such as immune checkpoint inhibitors, are in the pipeline. Thus, the dual role of immune...... mechanisms in MDS is challenging, and rigorous translational studies are needed to establish the value of immune manipulation as a treatment of MDS....

Synchronization as a biological, psychological and social mechanism to create common time: A theoretical frame and a single case study.

Science.gov (United States)

Bao, Yan; Pöppel, Ernst; Wang, Lingyan; Lin, Xiaoxiong; Yang, Taoxi; Avram, Mihai; Blautzik, Janusch; Paolini, Marco; Silveira, Sarita; Vedder, Aline; Zaytseva, Yuliya; Zhou, Bin

2015-12-01

Synchronizing neural processes, mental activities, and social interactions is considered to be fundamental for the creation of temporal order on the personal and interpersonal level. Several different types of synchronization are distinguished, and for each of them examples are given: self-organized synchronizations on the neural level giving rise to pre-semantically defined time windows of some tens of milliseconds and of approximately 3 s; time windows that are created by synchronizing different neural representations, as for instance in aesthetic appreciations or moral judgments; and synchronization of biological rhythms with geophysical cycles, like the circadian clock with the 24-hr rhythm of day and night. For the latter type of synchronization, an experiment is described that shows the importance of social interactions for sharing or avoiding common time. In a group study with four subjects being completely isolated together for 3 weeks from the external world, social interactions resulted both in intra- and interindividual circadian synchronization and desynchronization. A unique phenomenon in circadian regulation is described, the "beat phenomenon," which has been made visible by the interaction of two circadian rhythms with different frequencies in one body. The separation of the two physiological rhythms was the consequence of social interactions, that is, by the desire of a subject to share and to escape common time during different phases of the long-term experiment. The theoretical arguments on synchronization are summarized with the general statement: "Nothing in cognitive science makes sense except in the light of time windows." The hypothesis is forwarded that time windows that express discrete timing mechanisms in behavioral control and on the level of conscious experiences are the necessary bases to create cognitive order, and it is suggested that time windows are implemented by neural oscillations in different frequency domains. © 2015 The

Age-related macular degeneration—emerging pathogenetic and therapeutic concepts

Science.gov (United States)

GEHRS, KAREN M.; ANDERSON, DON H.; JOHNSON, LINCOLN V.; HAGEMAN, GREGORY S.

2014-01-01

Today, the average life expectancy in developed nations is over 80 years and climbing. And yet, the quality of life during those additional years is often significantly diminished by the effects of age-related, degenerative diseases, including age-related macular degeneration (AMD), the leading cause of blindness in the elderly worldwide. AMD is characterized by a progressive loss of central vision attributable to degenerative and neovascular changes in the macula, a highly specialized region of the ocular retina responsible for fine visual acuity. Estimates gathered from the most recent World Health Organization (WHO) global eye disease survey conservatively indicate that 14 million persons are blind or severely visually impaired because of AMD. The disease has a tremendous impact on the physical and mental health of the geriatric population and their families and is becoming a major public health burden. Currently, there is neither a cure nor a means to prevent AMD. Palliative treatment options for the less prevalent, late-stage ‘wet’ form of the disease include anti-neovascular agents, photodynamic therapy and thermal laser. There are no current therapies for the more common ‘dry’ AMD, except for the use of antioxidants that delay progression in 20%–25% of eyes. New discoveries, however, are beginning to provide a much clearer picture of the relevant cellular events, genetic factors, and biochemical processes associated with early AMD. Recently, compelling evidence has emerged that the innate immune system and, more specifically, uncontrolled regulation of the complement alternative pathway plays a central role in the pathobiology of AMD. The complement Factor H gene—which encodes the major inhibitor of the complement alternative pathway—is the first gene identified in multiple independent studies that confers a significant genetic risk for the development of AMD. The emergence of this new paradigm of AMD pathogenesis should hasten the development

Sirenomelia sequence according to the distance between the first sacral vertebra and the ilia

DEFF Research Database (Denmark)

Kjær, Klaus Wilbrandt; Keeling, Jean W; Opitz, John M

2003-01-01

The development of the iliac bones and lower limbs are parallel processes depending on the normal ontogeny of the caudal blastema [O'Rahilly and Müller, 1989; Opitz, 1993; Opitz et al., 2000]. We hypothesized that the pathogenetic mechanisms leading to fused lower limbs would in parallel displace...... the ISD, the shorter the BD. Based on these findings, we propose an extended classification of Sirenomelia to be tested by other researchers....

COMPLEX TREATMENT OF DIARRHEA IN CHILDREN

OpenAIRE

E.G. Tsimbalova

2010-01-01

The article presents modern data on syndrome of acute diarrhea in children, its etiology and mechanisms of development of different types of this disease, its clinical symptoms, differential diagnosis, laboratory and instrumental methods of diagnostics. Author gives review of pathogenetic treatment and opportunities of therapy with enterosorbates, taking into account etiology of diarrhea. Another chapter of the article describes opportunities and methods of oral hydration depending of extent ...

Gender identity disorder and schizophrenia: neurodevelopmental disorders with common causal mechanisms?

Science.gov (United States)

Rajkumar, Ravi Philip

2014-01-01

Gender identity disorder (GID), recently renamed gender dysphoria (GD), is a rare condition characterized by an incongruity between gender identity and biological sex. Clinical evidence suggests that schizophrenia occurs in patients with GID at rates higher than in the general population and that patients with GID may have schizophrenia-like personality traits. Conversely, patients with schizophrenia may experience alterations in gender identity and gender role perception. Neurobiological research, including brain imaging and studies of finger length ratio and handedness, suggests that both these disorders are associated with altered cerebral sexual dimorphism and changes in cerebral lateralization. Various mechanisms, such as Toxoplasma infection, reduced levels of brain-derived neurotrophic factor (BDNF), early childhood adversity, and links with autism spectrum disorders, may account for some of this overlap. The implications of this association for further research are discussed.

Gender Identity Disorder and Schizophrenia: Neurodevelopmental Disorders with Common Causal Mechanisms?

Directory of Open Access Journals (Sweden)

Ravi Philip Rajkumar

2014-01-01

Full Text Available Gender identity disorder (GID, recently renamed gender dysphoria (GD, is a rare condition characterized by an incongruity between gender identity and biological sex. Clinical evidence suggests that schizophrenia occurs in patients with GID at rates higher than in the general population and that patients with GID may have schizophrenia-like personality traits. Conversely, patients with schizophrenia may experience alterations in gender identity and gender role perception. Neurobiological research, including brain imaging and studies of finger length ratio and handedness, suggests that both these disorders are associated with altered cerebral sexual dimorphism and changes in cerebral lateralization. Various mechanisms, such as Toxoplasma infection, reduced levels of brain-derived neurotrophic factor (BDNF, early childhood adversity, and links with autism spectrum disorders, may account for some of this overlap. The implications of this association for further research are discussed.

Commonness of Amazonian palm (Arecaceae) species: Cross-scale links and potential determinants

DEFF Research Database (Denmark)

Kristiansen, Thea; Svenning, J.-C.; Grández, César

2009-01-01

was positively related to topographic niche breadth. Stem height correlated with continental range size and was the only species life-history trait related to any commonness measure. Distance from the study area to a species' range centre did not influence any of the commonness measures. The factors determining......The mechanisms that cause variation in commonness (abundances and range sizes) of species remain debated in ecology, and a repeatedly observed pattern is the positive relation between local abundances and larger scale range sizes. We used the Amazonian palm species (Arecaceae) to investigate...... the dependence between and potential determinants of commonness across three (local, landscape, continental) spatial scales. Commonness at the smaller scales (local abundance, landscape frequency) was estimated using data from 57 transects (5 × 500 m) in primary, non-inundated (terra firme) rainforest...

Disorders of compulsivity: a common bias towards learning habits.

Science.gov (United States)

Voon, V; Derbyshire, K; Rück, C; Irvine, M A; Worbe, Y; Enander, J; Schreiber, L R N; Gillan, C; Fineberg, N A; Sahakian, B J; Robbins, T W; Harrison, N A; Wood, J; Daw, N D; Dayan, P; Grant, J E; Bullmore, E T

2015-03-01

Why do we repeat choices that we know are bad for us? Decision making is characterized by the parallel engagement of two distinct systems, goal-directed and habitual, thought to arise from two computational learning mechanisms, model-based and model-free. The habitual system is a candidate source of pathological fixedness. Using a decision task that measures the contribution to learning of either mechanism, we show a bias towards model-free (habit) acquisition in disorders involving both natural (binge eating) and artificial (methamphetamine) rewards, and obsessive-compulsive disorder. This favoring of model-free learning may underlie the repetitive behaviors that ultimately dominate in these disorders. Further, we show that the habit formation bias is associated with lower gray matter volumes in caudate and medial orbitofrontal cortex. Our findings suggest that the dysfunction in a common neurocomputational mechanism may underlie diverse disorders involving compulsion.

Dermasence refining gel modulates pathogenetic factors of rosacea in vitro.

Science.gov (United States)

Borelli, C; Becker, B; Thude, S; Fehrenbacher, B; Isermann, D

2017-12-01

Over the counter cosmetics sold for local treatment of slight to moderate rosacea often state the claim of actively modulating rosacea pathogenesis. Factors involved in the pathogenesis of this common yet complex skin disorder include kallikrein-related peptidase 5 (KLK5), LL-37, as well as protease-activated receptor 2 (PAR2) and vascular endothelial growth factor (VEGF). The objective was to prove the modulating effect of the cosmetic skin care agent Dermasence Refining Gel (DRG) on factors involved in rosacea pathogenesis. We analyzed the effect of DRG on the expression of KLK5, LL-37, PAR2, and VEGF in an in vitro skin model of human reconstituted epidermis. The expression of CAMP (LL-37 gene, fold change -4.19 [±0.11]), VEGFA (fold change -2.55 [±0.12]) and PAR2 (-1.33 [±0.12]) was reduced, KLK5 expression increased (fold change 2.06 (±0.08)) after 18 h of treatment with DRG in comparison to treatment with the matrix gel only. The reduction in CAMP expression was significant (P<.01). The protein expression of all four inflammatory markers was markedly reduced after 18 hours of DRG treatment in comparison to baseline (0 hour), by measure of fluorescence intensity. We show evidence explaining the anti-inflammatory effect of Dermasence Refining Gel in rosacea pathogenesis in vitro. The adjunctive use of DRG in mild to moderate rosacea as a topical cosmetic seems medically reasonable. © 2017 Wiley Periodicals, Inc.

Dystrophic Cardiomyopathy: Complex Pathobiological Processes to Generate Clinical Phenotype

Directory of Open Access Journals (Sweden)

Takeshi Tsuda

2017-09-01

Full Text Available Duchenne muscular dystrophy (DMD, Becker muscular dystrophy (BMD, and X-linked dilated cardiomyopathy (XL-DCM consist of a unique clinical entity, the dystrophinopathies, which are due to variable mutations in the dystrophin gene. Dilated cardiomyopathy (DCM is a common complication of dystrophinopathies, but the onset, progression, and severity of heart disease differ among these subgroups. Extensive molecular genetic studies have been conducted to assess genotype-phenotype correlation in DMD, BMD, and XL-DCM to understand the underlying mechanisms of these diseases, but the results are not always conclusive, suggesting the involvement of complex multi-layers of pathological processes that generate the final clinical phenotype. Dystrophin protein is a part of dystrophin-glycoprotein complex (DGC that is localized in skeletal muscles, myocardium, smooth muscles, and neuronal tissues. Diversity of cardiac phenotype in dystrophinopathies suggests multiple layers of pathogenetic mechanisms in forming dystrophic cardiomyopathy. In this review article, we review the complex molecular interactions involving the pathogenesis of dystrophic cardiomyopathy, including primary gene mutations and loss of structural integrity, secondary cellular responses, and certain epigenetic and other factors that modulate gene expressions. Involvement of epigenetic gene regulation appears to lead to specific cardiac phenotypes in dystrophic hearts.

Classical and atypical agonists activate M1 muscarinic acetylcholine receptors through common mechanisms

Czech Academy of Sciences Publication Activity Database

Randáková, Alena; Dolejší, Eva; Rudajev, Vladimír; Zimčík, Pavel; Doležal, Vladimír; El-Fakahany, E. E.; Jakubík, Jan

2015-01-01

Roč. 97, Jul 2015 (2015), s. 27-39 ISSN 1043-6618 R&D Projects: GA ČR(CZ) GA305/09/0681; GA ČR(CZ) GBP304/12/G069; GA MŠk(CZ) EE2.3.30.0025 Institutional support: RVO:67985823 Keywords : muscarinic acetylcholine receptors * atypical agonists * xanomeline * activation mechanism Subject RIV: ED - Physiology Impact factor: 4.816, year: 2015

The common mode failures analysis of the redundent system with dependent human error

International Nuclear Information System (INIS)

Kim, M.K.; Chang, S.H.

1983-01-01

Common mode failures (CMFs) have been a serious concern in the nuclear power plant. Thereis a broad category of the failure mechanisms that can cause common mode failures. This paper is a theoretical investigation of the CMFs on the unavailability of the redundent system. It is assumed that the total CMFs consist of the potential CMFs and the dependent human error CMFs. As the human error dependency is higher, the total CMFs are more effected by the dependent human error. If the human error dependence is lower, the system unavailability strongly depends on the potential CMFs, rather than the mechanical failure or the dependent human error. And it is shown that the total CMFs are dominant factor to the unavailability of the redundent system. (Author)

QTL and candidate genes associated with common bacterial blight resistance in the common bean cultivar Longyundou 5 from China

Institute of Scientific and Technical Information of China (English)

Jifeng Zhu; Jing Wu; Lanfen Wang; Matthew W. Blair; Zhendong Zhu; Shumin Wang

2016-01-01

Common bacterial blight (CBB), caused by Xanthomonas axonopodis pv. phaseoli and Xanthomonas fuscans subsp. fuscans (Xff), is a worldwide disease of common bean (Phaseolus vulgaris L.). Longyundou 5, a Chinese cultivar in the Mesoamerican gene pool of common bean, displays resistance to the Xff strain XSC3-1. To identify the genetic mechanisms behind this resistance, we crossed Long 5 with a susceptible genotype to develop a mapping population of F2 plants. Plant resistance to CBB was identified at 14 and 21 days after inoculation with Xff strain XSC3-1. A major QTL at 14 and 21 days after inoculation was mapped on chromosome Pv10 with LOD scores of 6.41 and 5.35, respectively. This locus was associated with SAP6, a previously-identified and much-used dominant marker, but in a 4.2 cM interval between new codominant markers BMp10s174 and BMp10s244. Ten candidate genes were found between markers BMp10s174 and BMp10s244 on chromosome Pv10 and could encode defense response proteins responding to CBB pathogens. Four pairs each of epistatic QTL for CBB resistance were detected at 14 and 21 days after inoculation. Phenotypic variation explained by the epistatic QTL ranged from 7.19%to 12.15%and 7.72%to 8.80%at 14 and 21 days after inoculation, respectively. These results confirmed the importance of epistasis in CBB resistance in common bean. The adjacent markers found may be more efficient for marker assisted selection in common bean breeding for CBB resistance owing to their closer linkage to the target QTL.

QTL and candidate genes associated with common bacterial blight resistance in the common bean cultivar Longyundou 5 from China

Institute of Scientific and Technical Information of China (English)

Jifeng; Zhu; Jing; Wu; Lanfen; Wang; Matthew; W.Blair; Zhendong; Zhu; Shumin; Wang

2016-01-01

Common bacterial blight(CBB), caused by Xanthomonas axonopodis pv. phaseoli and Xanthomonas fuscans subsp. fuscans(Xff), is a worldwide disease of common bean(Phaseolus vulgaris L.).Longyundou 5, a Chinese cultivar in the Mesoamerican gene pool of common bean, displays resistance to the Xff strain XSC3-1. To identify the genetic mechanisms behind this resistance,we crossed Long 5 with a susceptible genotype to develop a mapping population of F2 plants.Plant resistance to CBB was identified at 14 and 21 days after inoculation with Xff strain XSC3-1.A major QTL at 14 and 21 days after inoculation was mapped on chromosome Pv10 with LOD scores of 6.41 and 5.35, respectively. This locus was associated with SAP6, a previouslyidentified and much-used dominant marker, but in a 4.2 cM interval between new codominant markers BMp10s174 and BMp10s244. Ten candidate genes were found between markers BMp10s174 and BMp10s244 on chromosome Pv10 and could encode defense response proteins responding to CBB pathogens. Four pairs each of epistatic QTL for CBB resistance were detected at 14 and 21 days after inoculation. Phenotypic variation explained by the epistatic QTL ranged from 7.19% to 12.15% and 7.72% to 8.80% at 14 and 21 days after inoculation, respectively. These results confirmed the importance of epistasis in CBB resistance in common bean. The adjacent markers found may be more efficient for marker assisted selection in common bean breeding for CBB resistance owing to their closer linkage to the target QTL.

Turboprop Propulsion Mechanic.

Science.gov (United States)

Chanute AFB Technical Training Center, IL.

This instructional package consists of a plan of instruction, glossary, and student handouts and exercises for use in training Air Force personnel to become turboprop propulsion mechanics. Addressed in the individual lessons of the course are the following: common hand tools, hardware, measuring devices, and safety wiring; aircraft and engine…

Aromatic L-amino acid decarboxylase (AADC) is crucial for brain development and motor functions.

Science.gov (United States)

Shih, De-Fen; Hsiao, Chung-Der; Min, Ming-Yuan; Lai, Wen-Sung; Yang, Chianne-Wen; Lee, Wang-Tso; Lee, Shyh-Jye

2013-01-01

Aromatic L-amino acid decarboxylase (AADC) deficiency is a rare pediatric neuro-metabolic disease in children. Due to the lack of an animal model, its pathogenetic mechanism is poorly understood. To study the role of AADC in brain development, a zebrafish model of AADC deficiency was generated. We identified an aadc gene homolog, dopa decarboxylase (ddc), in the zebrafish genome. Whole-mount in situ hybridization analysis showed that the ddc gene is expressed in the epiphysis, locus caeruleus, diencephalic catecholaminergic clusters, and raphe nuclei of 36-h post-fertilization (hpf) zebrafish embryos. Inhibition of Ddc by AADC inhibitor NSD-1015 or anti-sense morpholino oligonucleotides (MO) reduced brain volume and body length. We observed increased brain cell apoptosis and loss of dipencephalic catecholaminergic cluster neurons in ddc morphants (ddc MO-injected embryos). Seizure-like activity was also detected in ddc morphants in a dose-dependent manner. ddc morphants had less sensitive touch response and impaired swimming activity that could be rescued by injection of ddc plasmids. In addition, eye movement was also significantly impaired in ddc morphants. Collectively, loss of Ddc appears to result in similar phenotypes as that of ADCC deficiency, thus zebrafish could be a good model for investigating pathogenetic mechanisms of AADC deficiency in children.

Aromatic L-amino acid decarboxylase (AADC is crucial for brain development and motor functions.

Directory of Open Access Journals (Sweden)

De-Fen Shih

Full Text Available Aromatic L-amino acid decarboxylase (AADC deficiency is a rare pediatric neuro-metabolic disease in children. Due to the lack of an animal model, its pathogenetic mechanism is poorly understood. To study the role of AADC in brain development, a zebrafish model of AADC deficiency was generated. We identified an aadc gene homolog, dopa decarboxylase (ddc, in the zebrafish genome. Whole-mount in situ hybridization analysis showed that the ddc gene is expressed in the epiphysis, locus caeruleus, diencephalic catecholaminergic clusters, and raphe nuclei of 36-h post-fertilization (hpf zebrafish embryos. Inhibition of Ddc by AADC inhibitor NSD-1015 or anti-sense morpholino oligonucleotides (MO reduced brain volume and body length. We observed increased brain cell apoptosis and loss of dipencephalic catecholaminergic cluster neurons in ddc morphants (ddc MO-injected embryos. Seizure-like activity was also detected in ddc morphants in a dose-dependent manner. ddc morphants had less sensitive touch response and impaired swimming activity that could be rescued by injection of ddc plasmids. In addition, eye movement was also significantly impaired in ddc morphants. Collectively, loss of Ddc appears to result in similar phenotypes as that of ADCC deficiency, thus zebrafish could be a good model for investigating pathogenetic mechanisms of AADC deficiency in children.

Toward broadband mechanical spectroscopy

DEFF Research Database (Denmark)

Hecksher, Tina; Torchinsky, Darius; Klieber, Christoph

2017-01-01

Diverse material classes exhibit qualitatively similar behavior when made viscous upon cooling toward the glass transition, suggesting a common theoretical basis. We used seven different measurement methods to determine the mechanical relaxation kinetics of a prototype molecular glass former over...

CURRENT POTENTIALITIES OF THERAPY FOR FIBROCYSTIC DISEASE

Directory of Open Access Journals (Sweden)

I. V. Vysotskaya

2009-01-01

Full Text Available The pathogenetic mechanisms responsible for the development of breast hyperplastic processes have been presently studied rather well. One may advance in the prevention and treatment of the abnormalities occurring on this basis if the major canals for transmitting the signals stimulating breast cell proliferation are blocked. Indinol the use of which is considered in this paper is one of the agents that block the development of hyperplastic processes in hormone-dependent tissues.

Altered Colonic Environment, a Possible Predisposition to Colorectal Cancer and Colonic Inflammatory Bowel Disease: Rationale of Dietary Manipulation with Emphasis on Disaccharides

OpenAIRE

Szilagyi, A

1998-01-01

A recurrent theme in the schema of pathogenetic mechanisms attributed to colorectal cancer (CRC) and inflammatory bowel disease (IBD) is the interaction between genes and environment. Dietary and other environmental factors, and lower intestinal flora and their chemical interactions occur in the pathogenesis of both. Events at the mucosal surface may be influenced by factors in the luminal environment and by contributions of the host. In addition, both forms of IBD - Crohn's disease (CD) and ...

Long-term fundus changes in acquired partial lipodystrophy.

Science.gov (United States)

Jansen, Joyce; Delaere, Lien; Spielberg, Leigh; Leys, Anita

2013-11-18

We describe long-term fundus changes in a patient with partial lipodystrophy (PL). Retinal pigment alterations, drusen and subretinal neovascularisation were seen without evidence for membranoproliferative glomerulonephritis. Fundus alterations similar to those seen in age-related macular degeneration can occur at an earlier age in patients with PL, even without renal disease. Dysregulation of an alternative complement pathway with low serum levels of C3 has been implicated as a pathogenetic mechanism.

The clinical and radiological study of near drowning

International Nuclear Information System (INIS)

Reinhardt, K.

1982-01-01

A survey is given of the literature on near drowning, discussing the aspects for all disciplines emphasising the radiological features. The radological pictures are demonstrated and case descriptions containing radiological features are cited extensively out of the literature. This survey should be of great value for the clinician in therapy and control of course. The correlation of the clinical and radiological features should promote a better interpretation of pathogenetic mechanisms. (orig.) [de

Fossil fuel support mechanisms in Finland

Energy Technology Data Exchange (ETDEWEB)

Lampinen, Ari

2013-10-15

Fossil fuel subsidies and other state support for fossil fuels are forbidden by the Kyoto Protocol and other international treaties. However, they are still commonly used. This publication presents and analyses diverse state support mechanisms for fossil fuels in Finland in 2003-2010. Total of 38 support mechanisms are covered in quantitative analysis and some other mechanisms are mentioned qualitatively only. For some mechanisms the study includes a longer historical perspective. This is the case for tax subsidies for crude oil based traffic fuels that have been maintained in Finland since 1965.

Nutrition, immunological mechanisms and dietary immunomodulation in ADHD

NARCIS (Netherlands)

Verlaet, A.; Briceno Noriega, D.; Hermans, N.; Savelkoul, H.F.J.

2014-01-01

Attention-deficit hyperactivity disorder (ADHD) etiology is not completely understood, but common comorbid dysfunction of the gastrointestinal and immune system suggests that these systems may be affected by a common genetic background and molecular mechanisms. For example, increased levels of

DNA-histone complexes as ligands amplify cell penetration and nuclear targeting of anti-DNA antibodies via energy-independent mechanisms.

Science.gov (United States)

Zannikou, Markella; Bellou, Sofia; Eliades, Petros; Hatzioannou, Aikaterini; Mantzaris, Michael D; Carayanniotis, George; Avrameas, Stratis; Lymberi, Peggy

2016-01-01

We have generated three monoclonal cell-penetrating antibodies (CPAbs) from a non-immunized lupus-prone (NZB × NZW)F1 mouse that exhibited high anti-DNA serum titres. These CPAbs are polyreactive because they bind to DNA and other cellular components, and localize mainly in the nucleus of HeLa cells, albeit with a distinct nuclear labelling profile. Herein, we have examined whether DNA-histone complexes (DHC) binding to CPAbs, before cell entry, could modify the cell penetration of CPAbs or their nuclear staining properties. By applying confocal microscopy and image analysis, we found that extracellular binding of purified CPAbs to DHC significantly enhanced their subsequent cell-entry, both in terms of percentages of positively labelled cells and fluorescence intensity (internalized CPAb amount), whereas there was a variable effect on their nuclear staining profile. Internalization of CPAbs, either alone or bound to DHC, remained unaltered after the addition of endocytosis-specific inhibitors at 37° or assay performance at 4°, suggesting the involvement of energy-independent mechanisms in the internalization process. These findings assign to CPAbs a more complex pathogenetic role in systemic lupus erythematosus where both CPAbs and nuclear components are abundant. © 2015 John Wiley & Sons Ltd.

Integrative analysis of copy number and gene expression data suggests novel pathogenetic mechanisms in primary myelofibrosis.

Science.gov (United States)

Salati, Simona; Zini, Roberta; Nuzzo, Simona; Guglielmelli, Paola; Pennucci, Valentina; Prudente, Zelia; Ruberti, Samantha; Rontauroli, Sebastiano; Norfo, Ruggiero; Bianchi, Elisa; Bogani, Costanza; Rotunno, Giada; Fanelli, Tiziana; Mannarelli, Carmela; Rosti, Vittorio; Salmoiraghi, Silvia; Pietra, Daniela; Ferrari, Sergio; Barosi, Giovanni; Rambaldi, Alessandro; Cazzola, Mario; Bicciato, Silvio; Tagliafico, Enrico; Vannucchi, Alessandro M; Manfredini, Rossella

2016-04-01

Primary myelofibrosis (PMF) is a Myeloproliferative Neoplasm (MPN) characterized by megakaryocyte hyperplasia, progressive bone marrow fibrosis, extramedullary hematopoiesis and transformation to Acute Myeloid Leukemia (AML). A number of phenotypic driver (JAK2, CALR, MPL) and additional subclonal mutations have been described in PMF, pointing to a complex genomic landscape. To discover novel genomic lesions that can contribute to disease phenotype and/or development, gene expression and copy number signals were integrated and several genomic abnormalities leading to a concordant alteration in gene expression levels were identified. In particular, copy number gain in the polyamine oxidase (PAOX) gene locus was accompanied by a coordinated transcriptional up-regulation in PMF patients. PAOX inhibition resulted in rapid cell death of PMF progenitor cells, while sparing normal cells, suggesting that PAOX inhibition could represent a therapeutic strategy to selectively target PMF cells without affecting normal hematopoietic cells' survival. Moreover, copy number loss in the chromatin modifier HMGXB4 gene correlates with a concomitant transcriptional down-regulation in PMF patients. Interestingly, silencing of HMGXB4 induces megakaryocyte differentiation, while inhibiting erythroid development, in human hematopoietic stem/progenitor cells. These results highlight a previously un-reported, yet potentially interesting role of HMGXB4 in the hematopoietic system and suggest that genomic and transcriptional imbalances of HMGXB4 could contribute to the aberrant expansion of the megakaryocytic lineage that characterizes PMF patients. © 2015 UICC.

Gene expression profiles of Arabidopsis Cvi seeds during dormancy cycling indicate a common underlying dormancy control mechanism.

Science.gov (United States)

Cadman, Cassandra S C; Toorop, Peter E; Hilhorst, Henk W M; Finch-Savage, William E

2006-06-01

Physiologically dormant seeds, like those of Arabidopsis, will cycle through dormant states as seasons change until the environment is favourable for seedling establishment. This phenomenon is widespread in the plant kingdom, but has not been studied at the molecular level. Full-genome microarrays were used for a global transcript analysis of Arabidopsis thaliana (accession Cvi) seeds in a range of dormant and dry after-ripened states during cycling. Principal component analysis of the expression patterns observed showed that they differed in newly imbibed primary dormant seeds, as commonly used in experimental studies, compared with those in the maintained primary and secondary dormant states that exist during cycling. Dormant and after-ripened seeds appear to have equally active although distinct gene expression programmes, dormant seeds having greatly reduced gene expression associated with protein synthesis, potentially controlling the completion of germination. A core set of 442 genes were identified that had higher expression in all dormant states compared with after-ripened states. Abscisic acid (ABA) responsive elements were significantly over-represented in this set of genes the expression of which was enhanced when multiple copies of the elements were present. ABA regulation of dormancy was further supported by expression patterns of key genes in ABA synthesis/catabolism, and dormancy loss in the presence of fluridone. The data support an ABA-gibberelic acid hormone balance mechanism controlling cycling through dormant states that depends on synthetic and catabolic pathways of both hormones. Many of the most highly expressed genes in dormant states were stress-related even in the absence of abiotic stress, indicating that ABA, stress and dormancy responses overlap significantly at the transcriptome level.

Poverty and common mental disorders in developing countries.

Science.gov (United States)

Patel, Vikram; Kleinman, Arthur

2003-01-01

A review of English-language journals published since 1990 and three global mental health reports identified 11 community studies on the association between poverty and common mental disorders in six low- and middle-income countries. Most studies showed an association between indicators of poverty and the risk of mental disorders, the most consistent association being with low levels of education. A review of articles exploring the mechanism of the relationship suggested weak evidence to support a specific association with income levels. Factors such as the experience of insecurity and hopelessness, rapid social change and the risks of violence and physical ill-health may explain the greater vulnerability of the poor to common mental disorders. The direct and indirect costs of mental ill-health worsen the economic condition, setting up a vicious cycle of poverty and mental disorder. Common mental disorders need to be placed alongside other diseases associated with poverty by policy-makers and donors. Programmes such as investment in education and provision of microcredit may have unanticipated benefits in reducing the risk of mental disorders. Secondary prevention must focus on strengthening the ability of primary care services to provide effective treatment.

A comparison of maximal bioenergetic enzyme activities obtained with commonly used homogenization techniques.

Science.gov (United States)

Grace, M; Fletcher, L; Powers, S K; Hughes, M; Coombes, J

1996-12-01

Homogenization of tissue for analysis of bioenergetic enzyme activities is a common practice in studies examining metabolic properties of skeletal muscle adaptation to disease, aging, inactivity or exercise. While numerous homogenization techniques are in use today, limited information exists concerning the efficacy of specific homogenization protocols. Therefore, the purpose of this study was to compare the efficacy of four commonly used approaches to homogenizing skeletal muscle for analysis of bioenergetic enzyme activity. The maximal enzyme activity (Vmax) of citrate synthase (CS) and lactate dehydrogenase (LDH) were measured from homogenous muscle samples (N = 48 per homogenization technique) and used as indicators to determine which protocol had the highest efficacy. The homogenization techniques were: (1) glass-on-glass pestle; (2) a combination of a mechanical blender and a teflon pestle (Potter-Elvehjem); (3) a combination of the mechanical blender and a biological detergent; and (4) the combined use of a mechanical blender and a sonicator. The glass-on-glass pestle homogenization protocol produced significantly higher (P pestle homogenization protocol is the technique of choice for studying bioenergetic enzyme activity in skeletal muscle.

Lithium Ion Battery Anode Aging Mechanisms

Science.gov (United States)

Agubra, Victor; Fergus, Jeffrey

2013-01-01

Degradation mechanisms such as lithium plating, growth of the passivated surface film layer on the electrodes and loss of both recyclable lithium ions and electrode material adversely affect the longevity of the lithium ion battery. The anode electrode is very vulnerable to these degradation mechanisms. In this paper, the most common aging mechanisms occurring at the anode during the operation of the lithium battery, as well as some approaches for minimizing the degradation are reviewed. PMID:28809211

Integrated Circuit-Based Biofabrication with Common Biomaterials for Probing Cellular Biomechanics.

Science.gov (United States)

Sung, Chun-Yen; Yang, Chung-Yao; Yeh, J Andrew; Cheng, Chao-Min

2016-02-01

Recent advances in bioengineering have enabled the development of biomedical tools with modifiable surface features (small-scale architecture) to mimic extracellular matrices and aid in the development of well-controlled platforms that allow for the application of mechanical stimulation for studying cellular biomechanics. An overview of recent developments in common biomaterials that can be manufactured using integrated circuit-based biofabrication is presented. Integrated circuit-based biofabrication possesses advantages including mass and diverse production capacities for fabricating in vitro biomedical devices. This review highlights the use of common biomaterials that have been most frequently used to study cellular biomechanics. In addition, the influence of various small-scale characteristics on common biomaterial surfaces for a range of different cell types is discussed. Copyright © 2015 Elsevier Ltd. All rights reserved.

Clinic-like animal model for causal-pathogenetical investigations of hypoxic-ischemic brain injuries. Combined application of the radioactive labelled microsphere method and Positron Emission Tomography. Kliniknahes Tiermodell fuer kausal-pathogenetische Untersuchungen hypoxisch-ischaemischer Hirnschaedigung. Kombinierter Einsatz von Mikrosphaeren-Methode und Positronen-Emissions-Tomographie

Energy Technology Data Exchange (ETDEWEB)

Bauer, R.; Zwiener, U.; Bergmann, R. (Univ. Jena, Inst. fuer Pathologische Physiologie (Germany)); Manfrass, P.; Enghardt, W.; Fromm, W.D. (Zentralinstitut fuer Kernforschung, Bereich Festkoeper- und Kernphysik, Rossendorf (Germany)); Hoyer, D.; Guenther, K. (Leipzig Univ., Radiologische Klinik (Germany)); Schubert, H. (Univ. Jena, Tierexperimentelles Zentrum (Germany)); Beyer, R.; Beyer, G.J.; Steinbach, J.; Kretzschmer, M. (Zentralinstitut fuer Kernforschung, Bereich Radioaktive Isotope, Rossendorf (Germany))

1990-01-01

The complex nature of the pathogenesis in hypoxic-ischemic brain injuries equires the combined determination of the dynamics of main factors in these disturbing processes. The application of suitable methods for registration of such pathogenetic processes is shown in an adequate animal model for simulating the early hypoxic-ischemic brain injuries. That the radioactive labelled microsphere technique is suitable to comprehend quantitively the dynamics of the intracerebral redistribution of the circulating blood due to hypoxia/hypercapnia by simultaneous-multiple measuring of the regional cerebral blood flow. Therefore, at the first time an inadequate hypoxic-induced blood flow increase was shown in large parts of the forebrain in intrauterine growth retarded newborn piglets. For estimation of the regional cerebral glucose utilization in newborn piglets, the {sup 18}F-FDG Positron Emission Tomography is introduced. The measurements were carried out on a stationary high-density avalanche chamber (HIDAC) camera and yielded the fundamental application of this camera model for PET investigations also in the newborn brain due to the very good spatial resolution. (orig.).

Environmental Isocyanate-Induced Asthma: Morphologic and Pathogenetic Aspects of an Increasing Occupational Disease

Directory of Open Access Journals (Sweden)

Joachim Schirren

2011-09-01

Full Text Available Occupational diseases affect more and more people every year. According to the International Labour Organization (ILO, in 2000 an estimated amount of at least 160 million people became ill as a result of occupational-related hazards or injuries. Globally, occupational deaths, diseases and injuries account for an estimated loss of 4% of the Gross Domestic Product. Important substances that are related to occupational diseases are isocyanates and their products. These substances, which are used in a lot of different industrial processes, are not only toxic and irritant, but also allergenic. Although the exposure to higher concentrations could be monitored and restricted by technical means, very low concentrations are difficult to monitor and may, over time, lead to allergic reactions in some workers, ending in an occupational disease. In order to prevent the people from sickening, the mechanisms underlying the disease, by patho-physiological and genetical means, have to be known and understood so that high risk groups and early signs in the development of an allergic reaction could be detected before the exposure to isocyanates leads to an occupational disease. Therefore, this paper reviews the so far known facts concerning the patho-physiologic appearance and mechanisms of isocyanate-associated toxic reactions and possible genetic involvement that might trigger the allergic reactions.

Lung diseases in the elderly. Pathogenetic significance of pollutants and environmental factors

Energy Technology Data Exchange (ETDEWEB)

Heitz, M; Herzog, H

1984-05-03

In the elderly pneumoconioses due to anorganic or organic dusts are not very common. The incidence of mesothelioma is increasing also in the elderly population. Mesothelioma has become the most frequent occupational malignancy. There is also evidence that mesothelioma can be produced by other fibers than asbestos particles. The paper discusses further the effect of passive smoking, where there is new evidence that passive-smokers are exposed to a higher risk for bronchial cancer than non-smokers. The interactions between smoking and air pollution and morbidity of chronic bronchitis are illustrated. New aspects of pathogenesis and pathophysiology of chronic obstructive lung disease and pulmonary emphysema due to smoking as the most frequent environmental lung disease in the elderly are further discussed. A brief overview of the therapeutical approach to chronic obstructive lung disease including new forms of treatment of cor pulmonale is finally given.

The epidemiology of bacterial vaginosis in relation to sexual behaviour

Directory of Open Access Journals (Sweden)

Temmerman Marleen

2010-03-01

Full Text Available Abstract Background Bacterial vaginosis (BV has been most consistently linked to sexual behaviour, and the epidemiological profile of BV mirrors that of established sexually transmitted infections (STIs. It remains a matter of debate however whether BV pathogenesis does actually involve sexual transmission of pathogenic micro-organisms from men to women. We therefore made a critical appraisal of the literature on BV in relation to sexual behaviour. Discussion G. vaginalis carriage and BV occurs rarely with children, but has been observed among adolescent, even sexually non-experienced girls, contradicting that sexual transmission is a necessary prerequisite to disease acquisition. G. vaginalis carriage is enhanced by penetrative sexual contact but also by non-penetrative digito-genital contact and oral sex, again indicating that sex per se, but not necessarily coital transmission is involved. Several observations also point at female-to-male rather than at male-to-female transmission of G. vaginalis, presumably explaining the high concordance rates of G. vaginalis carriage among couples. Male antibiotic treatment has not been found to protect against BV, condom use is slightly protective, whereas male circumcision might protect against BV. BV is also common among women-who-have-sex-with-women and this relates at least in part to non-coital sexual behaviours. Though male-to-female transmission cannot be ruled out, overall there is little evidence that BV acts as an STD. Rather, we suggest BV may be considered a sexually enhanced disease (SED, with frequency of intercourse being a critical factor. This may relate to two distinct pathogenetic mechanisms: (1 in case of unprotected intercourse alkalinisation of the vaginal niche enhances a shift from lactobacilli-dominated microflora to a BV-like type of microflora and (2 in case of unprotected and protected intercourse mechanical transfer of perineal enteric bacteria is enhanced by coitus. A similar

The mechanical role of the cervix in pregnancy

Science.gov (United States)

Myers, Kristin M.; Feltovich, Helen; Mazza, Edoardo; Vink, Joy; Bajka, Michael; Wapner, Ronald J.; Hall, Timothy J.; House, Michael

2015-01-01

Appropriate mechanical function of the uterine cervix is critical for maintaining a pregnancy to term so that the fetus can develop fully. At the end of pregnancy, however, the cervix must allow delivery, which requires it to markedly soften, shorten and dilate. There are multiple pathways to spontaneous preterm birth, the leading global cause of death in children less than 5 years old, but all culminate in premature cervical change, because that is the last step in the final common pathway to delivery. The mechanisms underlying premature cervical change in pregnancy are poorly understood, and therefore current clinical protocols to assess preterm birth risk are limited to surrogate markers of mechanical function, such as sonographically measured cervical length. This is what motivates us to study the cervix, for which we propose investigating clinical cervical function in parallel with a quantitative engineering evaluation of its structural function. We aspire to develop a common translational language, as well as generate a rigorous integrated clinical-engineering framework for assessing cervical mechanical function at the cellular to organ level. In this review, we embark on that challenge by describing the current landscape of clinical, biochemical, and engineering concepts associated with the mechanical function of the cervix during pregnancy. Our goal is to use this common platform to inspire novel approaches to delineation of normal and abnormal cervical function in pregnancy. PMID:25841293

Role of failure-mechanism identification in accelerated testing

Science.gov (United States)

Hu, J. M.; Barker, D.; Dasgupta, A.; Arora, A.

1993-01-01

Accelerated life testing techniques provide a short-cut method to investigate the reliability of electronic devices with respect to certain dominant failure mechanisms that occur under normal operating conditions. However, accelerated tests have often been conducted without knowledge of the failure mechanisms and without ensuring that the test accelerated the same mechanism as that observed under normal operating conditions. This paper summarizes common failure mechanisms in electronic devices and packages and investigates possible failure mechanism shifting during accelerated testing.

Common Input to Motor Units of Intrinsic and Extrinsic Hand Muscles During Two-Digit Object Hold

OpenAIRE

Winges, Sara A.; Kornatz, Kurt W.; Santello, Marco

2008-01-01

Anatomical and physiological evidence suggests that common input to motor neurons of hand muscles is an important neural mechanism for hand control. To gain insight into the synaptic input underlying the coordination of hand muscles, significant effort has been devoted to describing the distribution of common input across motor units of extrinsic muscles. Much less is known, however, about the distribution of common input to motor units belonging to different intrinsic muscles and to intrinsi...

Beta-Glucan induced immune modulation of wound healing in common carp (Cyprinus carpio)

OpenAIRE

Jiménez, Natalia Ivonne Vera; Nielsen, Michael Engelbrecht; Lindenstrøm, Thomas

2012-01-01

Immune modulators are compounds capable to interact with the immune system and to modify the host response. This interaction enhances non-specific defense mechanisms, improving health and promoting survival. β-glucans are glucose polysaccharides present in sea weed, bacteria, fungi and cereal but not in animals. β-glucans are commonly used as immune modulators, but the mechanisms through which the modulation is achieved remains to be understood. Wound healing and tissue regeneration are essen...

Skin mechanical properties and modeling: A review.

Science.gov (United States)

Joodaki, Hamed; Panzer, Matthew B

2018-04-01

The mechanical properties of the skin are important for various applications. Numerous tests have been conducted to characterize the mechanical behavior of this tissue, and this article presents a review on different experimental methods used. A discussion on the general mechanical behavior of the skin, including nonlinearity, viscoelasticity, anisotropy, loading history dependency, failure properties, and aging effects, is presented. Finally, commonly used constitutive models for simulating the mechanical response of skin are discussed in the context of representing the empirically observed behavior.

Common Agency and Coordinated Bids in Sponsored Search Auctions

OpenAIRE

Maris Goldmanis; Antonio Penta; Francesco Decarolis

2012-01-01

As auctions are becoming the main mechanism for selling advertisement space on the web, marketing agencies specialized in bidding in online auctions are proliferating. We analyze theoretically how bidding delegation to a common marketing agency can undermine both revenues and efficiency of the generalized second price auction, the format used by Google and Microsoft-Yahoo!. Our characterization allows us to quantify the revenue losses relative to both the case of full competition and the case...

Discovery of cancer common and specific driver gene sets

Science.gov (United States)

2017-01-01

Abstract Cancer is known as a disease mainly caused by gene alterations. Discovery of mutated driver pathways or gene sets is becoming an important step to understand molecular mechanisms of carcinogenesis. However, systematically investigating commonalities and specificities of driver gene sets among multiple cancer types is still a great challenge, but this investigation will undoubtedly benefit deciphering cancers and will be helpful for personalized therapy and precision medicine in cancer treatment. In this study, we propose two optimization models to de novo discover common driver gene sets among multiple cancer types (ComMDP) and specific driver gene sets of one certain or multiple cancer types to other cancers (SpeMDP), respectively. We first apply ComMDP and SpeMDP to simulated data to validate their efficiency. Then, we further apply these methods to 12 cancer types from The Cancer Genome Atlas (TCGA) and obtain several biologically meaningful driver pathways. As examples, we construct a common cancer pathway model for BRCA and OV, infer a complex driver pathway model for BRCA carcinogenesis based on common driver gene sets of BRCA with eight cancer types, and investigate specific driver pathways of the liquid cancer lymphoblastic acute myeloid leukemia (LAML) versus other solid cancer types. In these processes more candidate cancer genes are also found. PMID:28168295

Reversible Guest Exchange Mechanisms in Supramolecular Host-GuestAssemblies

Energy Technology Data Exchange (ETDEWEB)

Pluth, Michael D.; Raymond, Kenneth N.

2006-09-01

Synthetic chemists have provided a wide array of supramolecular assemblies able to encapsulate guest molecules. The scope of this tutorial review focuses on supramolecular host molecules capable of reversibly encapsulating polyatomic guests. Much work has been done to determine the mechanism of guest encapsulation and guest release. This review covers common methods of monitoring and characterizing guest exchange such as NMR, UV-VIS, mass spectroscopy, electrochemistry, and calorimetry and also presents representative examples of guest exchange mechanisms. The guest exchange mechanisms of hemicarcerands, cucurbiturils, hydrogen-bonded assemblies, and metal-ligand assemblies are discussed. Special attention is given to systems which exhibit constrictive binding, a motif common in supramolecular guest exchange systems.

Constructing Common Information Space across Distributed Emergency Medical Teams

DEFF Research Database (Denmark)

Zhang, Zhan; Sarcevic, Aleksandra; Bossen, Claus

2017-01-01

This paper examines coordination and real-time information sharing across four emergency medical teams in a high-risk and distributed setting as they provide care to critically injured patients within the first hour after injury. Through multiple field studies we explored how common understanding...... of critical patient data is established across these heterogeneous teams and what coordination mechanisms are being used to support information sharing and interpretation. To analyze the data, we drew on the concept of Common Information Spaces (CIS). Our results showed that teams faced many challenges...... in achieving efficient information sharing and coordination, including difficulties in locating and assembling team members, communicating and interpreting information from the field, and accommodating differences in team goals and information needs, all while having minimal technology support. We reflect...

On uncertainty relations in quantum mechanics

International Nuclear Information System (INIS)

Ignatovich, V.K.

2004-01-01

Uncertainty relations (UR) are shown to have nothing specific for quantum mechanics (QM), being the general property valid for the arbitrary function. A wave function of a particle simultaneously having a precisely defined position and momentum in QM is demonstrated. Interference on two slits in a screen is shown to exist in classical mechanics. A nonlinear classical system of equations replacing the QM Schroedinger equation is suggested. This approach is shown to have nothing in common with the Bohm mechanics

Skeletal muscle repair in a mouse model of nemaline myopathy.

Science.gov (United States)

Sanoudou, Despina; Corbett, Mark A; Han, Mei; Ghoddusi, Majid; Nguyen, Mai-Anh T; Vlahovich, Nicole; Hardeman, Edna C; Beggs, Alan H

2006-09-01

Nemaline myopathy (NM), the most common non-dystrophic congenital myopathy, is a variably severe neuromuscular disorder for which no effective treatment is available. Although a number of genes have been identified in which mutations can cause NM, the pathogenetic mechanisms leading to the phenotypes are poorly understood. To address this question, we examined gene expression patterns in an NM mouse model carrying the human Met9Arg mutation of alpha-tropomyosin slow (Tpm3). We assessed five different skeletal muscles from affected mice, which are representative of muscles with differing fiber-type compositions, different physiological specializations and variable degrees of pathology. Although these same muscles in non-affected mice showed marked variation in patterns of gene expression, with diaphragm being the most dissimilar, the presence of the mutant protein in nemaline muscles resulted in a more similar pattern of gene expression among the muscles. This result suggests a common process or mechanism operating in nemaline muscles independent of the variable degrees of pathology. Transcriptional and protein expression data indicate the presence of a repair process and possibly delayed maturation in nemaline muscles. Markers indicative of satellite cell number, activated satellite cells and immature fibers including M-Cadherin, MyoD, desmin, Pax7 and Myf6 were elevated by western-blot analysis or immunohistochemistry. Evidence suggesting elevated focal repair was observed in nemaline muscle in electron micrographs. This analysis reveals that NM is characterized by a novel repair feature operating in multiple different muscles.

Stress-related phenomena and detoxification mechanisms induced by common pharmaceuticals in alfalfa (Medicago sativa L.) plants

International Nuclear Information System (INIS)

Christou, Anastasis; Antoniou, Chrystalla; Christodoulou, Charalampia; Hapeshi, Evroula; Stavrou, Ioannis; Michael, Costas; Fatta-Kassinos, Despo; Fotopoulos, Vasileios

2016-01-01

Pharmaceutically active compounds (PhACs) have been recently shown to exert phytotoxic effects. The present study explores the uptake, systemic translocation, and abiotic stress responses and detoxification mechanisms induced by the exposure of alfalfa plants grown in sand under greenhouse conditions to four common, individually applied PhACs (10 μg L −1 ) (diclofenac, sulfamethoxazole, trimethoprim, 17a-ethinylestradiol) and their mixture. Stress physiology markers (lipid peroxidation, proline, H 2 O 2 and NO content, antioxidant activity assays) and gene expression levels of key plant detoxification components (including glutathione S-transferases, GST7, GST17; superoxide dismutases, CuZnSOD, FeSOD; proton pump, H + -ATP, and cytochrome c oxidase, CytcOx), were evaluated. PhACs were detected in significantly higher concentrations in roots compared with leaves. Stress related effects, manifested via membrane lipid peroxidation and oxidative burst, were local (roots) rather than systemic (leaves), and exacerbated when the tested PhACs were applied in mixture. Systemic accumulation of H 2 O 2 in leaves suggests its involvement in signal transduction and detoxification responses. Increased antioxidant enzymatic activities, as well as upregulated transcript levels of GST7, GST17, H + -ATPase and CytcOx, propose their role in the detoxification of the selected PhACs in plants. The current findings provide novel biochemical and molecular evidence highlighting the studied PhACs as an emerging abiotic stress factor, and point the need for further research on wastewater flows under natural agricultural environments. - Highlights: • PhACs were detected in higher concentrations in roots compared with leaves. • Stress effects were local and exacerbated when PhACs were applied in mixture. • H 2 O 2 may be involved in signal transduction and detoxification responses. • GSTs, H + -ATPase and CytcOx contribute to the detoxification of PhACs in plants. • Results

Stress-related phenomena and detoxification mechanisms induced by common pharmaceuticals in alfalfa (Medicago sativa L.) plants

Energy Technology Data Exchange (ETDEWEB)

Christou, Anastasis [Agricultural Research Institute, P.O. Box 22016, 1516 Nicosia (Cyprus); Antoniou, Chrystalla; Christodoulou, Charalampia [Department of Agricultural Sciences, Biotechnology and Food Science, Cyprus University of Technology, 3603 Lemesos (Cyprus); Hapeshi, Evroula; Stavrou, Ioannis; Michael, Costas [NIREAS-International Water Research Center, University of Cyprus, P.O. Box 20537, 1678 Nicosia (Cyprus); Fatta-Kassinos, Despo [Department of Civil and Environmental Engineering, University of Cyprus, P.O. Box 20537, 1678 Nicosia (Cyprus); NIREAS-International Water Research Center, University of Cyprus, P.O. Box 20537, 1678 Nicosia (Cyprus); Fotopoulos, Vasileios, E-mail: vassilis.fotopoulos@cut.ac.cy [Department of Agricultural Sciences, Biotechnology and Food Science, Cyprus University of Technology, 3603 Lemesos (Cyprus)

2016-07-01

Pharmaceutically active compounds (PhACs) have been recently shown to exert phytotoxic effects. The present study explores the uptake, systemic translocation, and abiotic stress responses and detoxification mechanisms induced by the exposure of alfalfa plants grown in sand under greenhouse conditions to four common, individually applied PhACs (10 μg L{sup −1}) (diclofenac, sulfamethoxazole, trimethoprim, 17a-ethinylestradiol) and their mixture. Stress physiology markers (lipid peroxidation, proline, H{sub 2}O{sub 2} and NO content, antioxidant activity assays) and gene expression levels of key plant detoxification components (including glutathione S-transferases, GST7, GST17; superoxide dismutases, CuZnSOD, FeSOD; proton pump, H{sup +}-ATP, and cytochrome c oxidase, CytcOx), were evaluated. PhACs were detected in significantly higher concentrations in roots compared with leaves. Stress related effects, manifested via membrane lipid peroxidation and oxidative burst, were local (roots) rather than systemic (leaves), and exacerbated when the tested PhACs were applied in mixture. Systemic accumulation of H{sub 2}O{sub 2} in leaves suggests its involvement in signal transduction and detoxification responses. Increased antioxidant enzymatic activities, as well as upregulated transcript levels of GST7, GST17, H{sup +}-ATPase and CytcOx, propose their role in the detoxification of the selected PhACs in plants. The current findings provide novel biochemical and molecular evidence highlighting the studied PhACs as an emerging abiotic stress factor, and point the need for further research on wastewater flows under natural agricultural environments. - Highlights: • PhACs were detected in higher concentrations in roots compared with leaves. • Stress effects were local and exacerbated when PhACs were applied in mixture. • H{sub 2}O{sub 2} may be involved in signal transduction and detoxification responses. • GSTs, H{sup +}-ATPase and CytcOx contribute to the

Advantages and controversy of common agricultural and cohesion policy in the EU

Directory of Open Access Journals (Sweden)

Kostić Vladimir

2016-01-01

Full Text Available The authors explore deals and payments that have a positive effect on the development of Common agricultural and cohesion policy. They particularly emphasize the ways of protecting the European Union from cheap imported products from non-EU countries. They also deal with the mechanisms that are built into the process, with the structural policy regarding 'Agenda 2000', as well as the reforms of Common agricultural and cohesion policy from its beginnings until now. The paper presents problems of guaranteed prices, ecology, quotas, agricultural levies and customs duties. The authors also investigated the Common Agricultural and Rural Policy of the European Union 2014-2020, the ways to accelerate the transfer of technology and strengthen the cooperation between agriculture and research sectors in the future.

History of mechanical ventilation may affect respiratory mechanics evolution in acute respiratory distress syndrome.

Science.gov (United States)

Koutsoukou, Antonia; Perraki, Helen; Orfanos, Stylianos E; Koulouris, Nikolaos G; Tromaropoulos, Andreas; Sotiropoulou, Christina; Roussos, Charis

2009-12-01

The aim of this study was to investigate the effect of mechanical ventilation (MV) before acute respiratory distress syndrome (ARDS) on subsequent evolution of respiratory mechanics and blood gases in protectively ventilated patients with ARDS. Nineteen patients with ARDS were stratified into 2 groups according to ARDS onset relative to the onset of MV: In group A (n = 11), MV was applied at the onset of ARDS; in group B (n = 8), MV had been initiated before ARDS. Respiratory mechanics and arterial blood gas were assessed in early (protectively ventilated patients with ARDS, late alteration of respiratory mechanics occurs more commonly in patients who have been ventilated before ARDS onset, suggesting that the history of MV affects the subsequent progress of ARDS even when using protective ventilation.

Efficacy of zinc against common cold viruses: an overview.

Science.gov (United States)

Hulisz, Darrell

2004-01-01

To review the laboratory and clinical evidence of the medicinal value of zinc for the treatment of the common cold. Published articles identified through Medline (1980-2003) using the search terms zinc, rhinovirus, and other pertinent subject headings. Additional sources were identified from the bibliographies of the retrieved articles. By the author. By the author. Human rhinoviruses, by attaching to the nasal epithelium via the intracellular adhesion molecule-1 (ICAM-1) receptor, cause most colds. Ionic zinc, based on its electrical charge, also has an affinity for ICAM-1 receptor sites and may exert an antiviral effect by attaching to the ICAM-1 receptors in the rhinovirus structure and nasal epithelial cells. Clinical tests of zinc for treatment of common colds have been inconsistent, primarily because of study design, blinding, and lozenge contents. Early formulations of lozenges also were unpalatable. In three trials with similar study designs, methodologies, and efficacy assessments, zinc effectively and significantly shortened the duration of the common cold when it was administered within 24 hours of the onset of symptoms. Recent reports of trials with zinc gluconate administered as a nasal gel have supported these findings; in addition, they have shown that treatment with zinc nasal gel is effective in reducing the duration and severity of common cold symptoms in patients with established illness. Clinical trial data support the value of zinc in reducing the duration and severity of symptoms of the common cold when administered within 24 hours of the onset of common cold symptoms. Additional clinical and laboratory evaluations are warranted to further define the role of ionic zinc for the prevention and treatment of the common cold and to elucidate the biochemical mechanisms through which zinc exerts its symptom-relieving effects.

A Monstrous Alliance: Open Architecture and Common Space

Directory of Open Access Journals (Sweden)

Gökhan Kodalak

2015-06-01

Full Text Available The contemporary built environment is absorbed by a dualist spatial organisation model divided between public and private space. Within this restrictive grammar, public space, despite its democratic promise, is heavily indoctrinated and anesthetised under the hegemony of regulatory apparatuses and control mechanisms, whereas private space has catalysed, if not directly engendered, prevalent spatial problems, such as ever-increasing slums, discriminatory gentrification and ecological catastrophes, despite its self-approving assurance. Underneath this dysfunctional couple lies common space, a third category that constitutes the shared spatial commonwealth of our entire natural and cultural milieu.The multitude, as an emerging body of self-organising political and spatial actors, has already started to unearth the potential of common space, actualising emergent and interactive spatial configurations all around the world. In this new, self-organisational model, architects do not become obsolete; rather, they leave behind their conventional roles as submissive experts and cosmetic speculators. By becoming anomalous architects, they affirm and augment the opening of spatial and architectural milieus to a myriad of new possibilities.This article theorises the possibility of a monstrous alliance between anomalous architects and the multitude, between open architectures and common space. Two specific case studies accompany these theoretical frameworks: the Gezi Event (Istanbul, 2013 demonstrates the actual emancipation of common space through the self-organising activity of the multitude, while Open-Cube (Antalya, 2013 attests to an early open architecture experiment based on the potentiating activity of the anomalous architect. 

Pathogenetic and Clinical Aspects of Anti-Neutrophil Cytoplasmic Autoantibody-Associated Vasculitides

Directory of Open Access Journals (Sweden)

Peter Lamprecht

2018-04-01

Full Text Available Anti-neutrophil cytoplasmic autoantibodies (ANCA targeting proteinase 3 (PR3 and myeloperoxidase expressed by innate immune cells (neutrophils and monocytes are salient diagnostic and pathogenic features of small vessel vasculitis, comprising granulomatosis with polyangiitis (GPA, microscopic polyangiitis, and eosinophilic GPA. Genetic studies suggest that ANCA-associated vasculitides (AAV constitute separate diseases, which share common immunological and pathological features, but are otherwise heterogeneous. The successful therapeutic use of anti-CD20 antibodies emphasizes the prominent role of ANCA and possibly other autoantibodies in the pathogenesis of AAV. However, to elucidate causal effects in AAV, a better understanding of the complex interplay leading to the emergence of B lymphocytes that produce pathogenic ANCA remains a challenge. Different scenarios seem possible; e.g., the break of tolerance induced by a shift from non-pathogenic toward pathogenic autoantigen epitopes in inflamed tissue. This review gives a brief overview on current knowledge about genetic and epigenetic factors, barrier dysfunction and chronic non-resolving inflammation, necro-inflammatory auto-amplification of cellular death and inflammation, altered autoantigen presentation, alternative complement pathway activation, alterations within peripheral and inflamed tissue-residing T- and B-cell populations, ectopic lymphoid tissue neoformation, the characterization of PR3-specific T-cells, properties of ANCA, links between autoimmune disease and infection-triggered pathology, and animal models in AAV.

Clinical and pathogenetic aspects of fever in patients with infectious diseases

Directory of Open Access Journals (Sweden)

K. V. Zhdanov

2013-01-01

Full Text Available About diagnostic valueof fever, in in fectious patients physicians knew from the time of Hippocrates. Significant contribution to thestudy madeby S. Libermeister, SP Botkin, AA Ostroumov, IP Pavlov, II Metchnikoff andothers. Themain centerof thermoregulation is the hypothalamus. The reare three sources of temperature reception – ther more ceptors of the skin, ther mose nsitive of inter oreceptor sand specific thermosensitiveneuronsof theCNS (neuronsnucleusanterior, middle and posteriorhy pothalamus. Ther more ceptors of the skin andthermal of interoceptorsarechannelswith transient receptorpotential (temperature-sensitivetransient receptorpotential (TRP channels of thefreenerveendings, such asthevagusnerve.Current experimental studiesshow that thereareseveral waysto initiatefever. Themain classical pathway of feverisassociated with increasedprostaglandin synthesisby theaction of endogenouspyrogens. Endogenouspyrogensincludea numberof cytokines: interleukin-1 (IL-1, interleukin-6 (IL-6, tumornecrosisfactoralpha (TNF-α; interferon (IFN. Themain secondary pyrogen isconsideredto beIL-1β. Synthesisof IL-1β stimulatedstructuresPAMPs(pathogen-associatedmolecularpatternsandDAMRs(danger-associatedmolecularpatterns, dependson theactivation of caspase–1 with inflammasom. Thestateof thermoregulation andisnow estimatedthermometry. Thefounderoftheclinical thermometerisa German physician C. Wunderlich. Abroad,the«goldstandard» isa measurement of rectal body temperature, asthemost stableandreliable. In ourcountry, in practice, usually measuredaxillary body temperature. Accordingto thetypesof feverandtemperaturecurvesinfectiousdiseasescan predefinenosological formof infectiousdisease. Amonginfectiousdiseasesaremost common, andsometimesalmost pathognomonic (malaria, fora given nosological formof thereaction temperature.

A brief history of mechanical engineering

CERN Document Server

Dixit, Uday Shanker; Davim, J Paulo

2017-01-01

What is mechanical engineering? What a mechanical engineering does? How did the mechanical engineering change through ages? What is the future of mechanical engineering? This book answers these questions in a lucid manner. It also provides a brief chronological history of landmark events and answers questions such as: When was steam engine invented? Where was first CNC machine developed? When did the era of additive manufacturing start? When did the marriage of mechanical and electronics give birth to discipline of mechatronics? This book informs and create interest on mechanical engineering in the general public and particular in students. It also helps to sensitize the engineering fraternity about the historical aspects of engineering. At the same time, it provides a common sense knowledge of mechanical engineering in a handy manner.

Global Governance Mechanisms to Address Antimicrobial Resistance.

Science.gov (United States)

Padiyara, Ponnu; Inoue, Hajime; Sprenger, Marc

2018-01-01

Since their discovery, antibiotics, and more broadly, antimicrobials, have been a cornerstone of modern medicine. But the overuse and misuse of these drugs have led to rising rates of antimicrobial resistance, which occurs when bacteria adapt in ways that render antibiotics ineffective. A world without effective antibiotics can have drastic impacts on population health, global development, and the global economy. As a global common good, antibiotic effectiveness is vulnerable to the tragedy of the commons, where a shared limited resource is overused by a community when each individual exploits the finite resource for their own benefit. A borderless threat like antimicrobial resistance requires global governance mechanisms to mitigate its emergence and spread, and it is the responsibility of all countries and relevant multilateral organizations. These mechanisms can be in the form of legally binding global governance mechanisms such as treaties and regulatory standards or nonbinding mechanisms such as political declarations, resolutions, or guidelines. In this article, we argue that while both are effective methods, the strong, swift, and coordinated action needed to address rising rates of antimicrobial resistance will be better served through legally binding governance mechanisms.

Ischemic colitis complicating reconstruction of the abdominal aorta

DEFF Research Database (Denmark)

Schroeder, T V; Christoffersen, J K; Andersen, J

1985-01-01

A review of 23 patients with ischemic colitis after surgical treatment of the abdominal aorta disclosed a pathogenetic heterogeneous finding. Ligation of the inferior mesenteric artery, abolished collateral blood supply or nonocclusive low flow state, or both, was a common feature. An incidence o...... of 0.5 per cent was revealed for full-thickness necrosis. The mortality was 70 per cent since diagnosis was made first since perforation and peritonitis had occurred. On the basis of these findings vital prophylactic measures and diagnostic possibilities are discussed herein....

The Point of View of Pathophysiologist-Endocrinologist on the Problem of Age-Related Androgen Deficiency in Men (LOH-Syndrome

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A.G. Reznikov

2014-09-01

Full Text Available The paper presents a pathophysiological analysis of age-related androgen deficiency syndrome in men (LOH-syndrome with special reference to current knowledge of molecular mechanisms of testosterone effects and androgen regulation of the structure and function of organs and systems of the male body. There is emphasized etiological and pathogenetic role of stress in this pathology. There is presented author’s concept of cause-effect relations between chronic stress, metabolic syndrome and LOH-syndrome.

ENDOCRINE PANCREATIC FUNCTION IN ACUTE PANCREATITIS

OpenAIRE

P. V. Novokhatny

2014-01-01

Introduction Among the organs of internal secretion pancreas has a special place thanks to active exocrine function and a wide range of physiological actions of produced hormones. Violations of endocrine pancreas arises in 6.5-38 % of patients with acute pancreatitis. However, there is still no clear understanding of the pathogenetic mechanisms of hormonal dysfunction of the pancreas in acute pancreatitis, there is no uniform algorithms for its correction. Aim of the research was to study...

Incorporation of DL-methionine /sup 3/H into the rat brain in the course of triethyl tin sulphate intoxication

Energy Technology Data Exchange (ETDEWEB)

Kozik, M B; Ozarzewska, E; Piechowski, A [Akademia Medyczna, Poznan (Poland)

1976-01-01

The incorporation of DL-methionine /sup 3/H into the rat brain in the course of acute edema caused by the triethyl tin sulphate (TET) was investigated by autoradiography. The results indicate that TET intoxication effects in lower incorporation of methionine into the experimental rat brain in comparison to that in normal animals. The changes in dynamics of DL-methionine /sup 3/H incorporation after TET intoxication are presented. The possible pathogenetic mechanism of the observed changes is discussed.

Vascular myelopathy: causes and mechanisms, possibilities of diagnosis and treatment

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G. V. Ponomarev

2018-01-01

Full Text Available Vascular myelopathy is a rare severe disease caused by a broad spectrum of causes, among which pathology of the aorta and its branches, aortic surgery, spinal diseases, and spinal trauma occupy the main place. The processes of neuroinflammation and glutamate neurotoxicity play a leading role in the pathogenesis of myeloischemia. The clinical picture of the disease is nonspecific and depends on the location and volume of an ischemic focus. Magnetic resonance imaging is a gold standard for diagnosis. However, this method remains insensitive in the acute period and fails to detect spinal cord ischemia at preclinical stages. The investigation and introduction of specific biochemical markers (glutamate receptors and their antibodies for neurotoxicity, which can identify ischemia in the advanced stage and predetermine its development, are promising. The treatment of vascular myelopathy has not currently been standardized and it is mainly pathogenetic and symptomatic.

MECHANISMS OF NITROUS OXIDE FORMATION IN COAL FLAMES

Science.gov (United States)

The paper gives results of a study, using both detailed kinetic modeling and plug-flow simulator experiments, to investigate an unknown mechanism by which N2O is formed in coal flames. This mechanism has considerable importance in determining the influence of common and advanced ...

Mechanisms driving postfire abundance of a generalist mammal

Science.gov (United States)

R. Zwolak; D. E. Pearson; Y. K. Ortega; E. E. Crone

2012-01-01

Changes in vertebrate abundance following disturbance are commonly attributed to shifts in food resources or predation pressure, but underlying mechanisms have rarely been tested. We examined four hypotheses for the commonly reported increase in abundance of deer mouse (Peromyscus maniculatus (Wagner, 1845)) following forest fires: source-sink dynamics, decreased...

The suitability of common compressibility equations for characterizing plasticity of diverse powders.

Science.gov (United States)

Paul, Shubhajit; Sun, Changquan Calvin

2017-10-30

The analysis of powder compressibility data yields useful information for characterizing compaction behavior and mechanical properties of powders, especially plasticity. Among the many compressibility equations proposed in powder compaction research, the Heckel equation and the Kawakita equation are the most commonly used, despite their known limitations. Systematic evaluation of the performance in analyzing compressibility data suggested the Kuentz-Leuenberger equation is superior to both the Heckel equation and the Kawakita equation for characterizing plasticity of powders exhibiting a wide range of mechanical properties. Copyright © 2017 Elsevier B.V. All rights reserved.

Mecanismos de abertura do sulco e adubação nitrogenada no cultivo do feijoeiro em sistema plantio direto Furrows opening mechanism for nitrogen fertilizer application in common bean crop under no-tillage

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Orivaldo Arf

2008-01-01

Full Text Available Algumas culturas têm pouca adaptação ao sistema plantio direto, em vista da maior compactação da camada superficial do solo e, nesse caso, o mecanismo utilizado na semeadora para a abertura dos sulcos para deposição do fertilizante pode ter grande importância no sentido de facilitar a penetração das raízes. Este experimento foi desenvolvido em Selvíria (MS, com o objetivo de avaliar a produtividade do feijão de inverno cultivado em sistema plantio direto, em função da utilização de mecanismos de abertura para distribuição de fertilizantes na semeadura e da adubação nitrogenada em cobertura. O delineamento experimental utilizado foi em blocos casualizados, utilizando-se esquema fatorial 2 x 6, constituído por mecanismos de distribuição de fertilizante (haste escarificadora e disco duplo e doses de N em cobertura (0, 25, 50, 75, 100 e 125 kg ha-1, com quatro repetições. Recomenda-se o uso da haste escarificadora como mecanismo de distribuição do fertilizante, para o cultivo do feijoeiro de inverno. A adubação nitrogenada em cobertura proporciona incrementos à produtividade do feijoeiro de inverno.Some crops have shown no adaptation to no-tillage system as a function of compaction soil superficial layer. In way, the mechanism used in seeder to open furrows for deposition of fertilizer can have great importance to facilitate the penetration of roots. This experiment was carried in Selvíria (MS, with the objective to evaluate the winter common bean crop yield under no-tillage system, as function of fertilizer distribution opening mechanisms in sowing (chisel and coulter blade and sidedressing nitrogen application (0, 25, 50, 75, 100 and 125 kg ha-1. The experimental design was a randomized block, arranged in a 2 x 6 factorial scheme, constituted by fertilizer distribution opening mechanisms in sowing (chisel and coulter blade and sidedressing nitrogen doses (0, 25, 50, 75, 100 and 125 kg ha-1, with four replications

The mechanical role of the cervix in pregnancy.

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Myers, Kristin M; Feltovich, Helen; Mazza, Edoardo; Vink, Joy; Bajka, Michael; Wapner, Ronald J; Hall, Timothy J; House, Michael

2015-06-25

Appropriate mechanical function of the uterine cervix is critical for maintaining a pregnancy to term so that the fetus can develop fully. At the end of pregnancy, however, the cervix must allow delivery, which requires it to markedly soften, shorten and dilate. There are multiple pathways to spontaneous preterm birth, the leading global cause of death in children less than 5 years old, but all culminate in premature cervical change, because that is the last step in the final common pathway to delivery. The mechanisms underlying premature cervical change in pregnancy are poorly understood, and therefore current clinical protocols to assess preterm birth risk are limited to surrogate markers of mechanical function, such as sonographically measured cervical length. This is what motivates us to study the cervix, for which we propose investigating clinical cervical function in parallel with a quantitative engineering evaluation of its structural function. We aspire to develop a common translational language, as well as generate a rigorous integrated clinical-engineering framework for assessing cervical mechanical function at the cellular to organ level. In this review, we embark on that challenge by describing the current landscape of clinical, biochemical, and engineering concepts associated with the mechanical function of the cervix during pregnancy. Our goal is to use this common platform to inspire novel approaches to delineate normal and abnormal cervical function in pregnancy. Copyright © 2015 Elsevier Ltd. All rights reserved.

Axiomation of quantum mechanics

International Nuclear Information System (INIS)

Kotecky, R.

1975-01-01

Deeper understanding of the basic structure of the formalism of the modern quantum theory (as has been established during its 50 years' stormy development) has been brought about by its axiomatization - by founding the formalism merely on experimentally directly accountable postulates without referring to historical development, without any a priori nonessential or empirically nonexplicable assumptions. A summary is given of the common formalism of quantum mechanics and its most significant axiomatizations. The assumptions are discussed under which respective axiomatically described abstract structures may be modelled by means of the common formalisn of quantum theory (established on the theory of Hilbert spaces). (author)

Making the Common Good Common

Science.gov (United States)

Chase, Barbara

2011-01-01

How are independent schools to be useful to the wider world? Beyond their common commitment to educate their students for meaningful lives in service of the greater good, can they educate a broader constituency and, thus, share their resources and skills more broadly? Their answers to this question will be shaped by their independence. Any…

Affective Spectrum Disorders in an Urban Swedish Adult Psychiatric Unit: A Descriptive Study

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M. Scharin

2012-01-01

Full Text Available Background. Several studies have found that patients with affective-/anxiety-/stress-related syndromes present overlapping features such as cooccurrence within families and individuals and response to the same type of pharmacological treatment, suggesting that these syndromes share pathogenetic mechanisms. The term affective spectrum disorder (AfSD has been suggested, emphasizing these commonalities. The expectancy rate, sociodemographic characteristics, and global level of functioning in AfSD has hitherto not been studied neglected. Material and Method. Out of 180 consecutive patients 94 were included after clinical investigations and ICD-10 diagnostics. Further investigations included well-known self-evaluation instruments assessing psychiatric symptoms, personality disorders, psychosocial stress, adaptation, quality of life, and global level of functioning. A neuropsychological screening was also included. Results. The patients were young, had many young children, were well educated, and had about expected (normal distribution of intelligence. Sixty-one percent were identified as belonging to the group of AfSD. Conclusion. The study identifies a large group of patients that presents much suffering and failure of functioning. This group is shared between the levels of medical care, between primary care and psychiatry. The term AfSD facilitates identification of patient groups that share common traits and identifies individuals clinically, besides the referred patients, in need of psychiatric interventions.

Mechanical circulatory treatment of advanced heart failure

DEFF Research Database (Denmark)

Løgstrup, Brian B; Vase, Henrik; Gjedsted, Jakob

2016-01-01

Heart failure is one of the most common causes of morbidity and mortality worldwide. When patients cease to respond adequately to optimal medical therapy mechanical circulatory support has been promising. The advent of mechanical circulatory support devices has allowed significant improvements...... in patient survival and quality of life for those with advanced or end-stage heart failure. We provide a general overview of current mechanical circulatory support devices encompassing options for both short- and long-term ventricular support....

Mineralocorticoid-induced sodium appetite and renal salt retention: Evidence for common signaling and effector mechanisms

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Fu, Yiling; Vallon, Volker

2014-01-01

An increase in renal sodium chloride (salt) retention and an increase in sodium appetite is the body's response to salt restriction or depletion in order to restore salt balance. Renal salt retention and increased sodium appetite can also be maladaptive and sustain the pathophysiology in conditions like salt-sensitive hypertension and chronic heart failure. Here we review the central role of the mineralocorticoid aldosterone in both the increase in renal salt reabsorption and sodium appetite. We discuss the working hypothesis that aldosterone activates similar signaling and effector mechanisms in the kidney and brain, including the mineralocorticoid receptor, the serum-and-glucocorticoid-induced kinase SGK1, the ubiquitin ligase NEDD4-2, and the epithelial sodium channel ENaC. The latter also mediates the gustatory salt sensing in the tongue, which is required for the manifestation of increased salt intake. Effects of aldosterone on both brain and kidney synergize with the effects of angiotensin II. Thus, mineralocorticoids appear to induce similar molecular pathways in the kidney, brain, and possibly tongue, which could provide opportunities for more effective therapeutic interventions. Inhibition of renal salt reabsorption is compensated by stimulation of salt appetite and vice versa; targeting both mechanisms should be more effective. Inhibiting the arousal to consume salty food may improve a patient's compliance to reducing salt intake. While a better understanding of the molecular mechanisms is needed and will provide new options, current pharmacological interventions that target both salt retention and sodium appetite include mineralocorticoid receptor antagonists and potentially inhibitors of angiotensin II and ENaC. PMID:25376899

Mechanisms of dynamic deformation and dynamic failure in aluminum nitride

International Nuclear Information System (INIS)

Hu Guangli; Chen, C.Q.; Ramesh, K.T.; McCauley, J.W.

2012-01-01

Uniaxial quasi-static, uniaxial dynamic and confined dynamic compression experiments have been performed to characterize the failure and deformation mechanisms of a sintered polycrystalline aluminum nitride using a servohydraulic machine and a modified Kolsky bar. Scanning electron microscopy and transmission electron microscopy (TEM) are used to identify the fracture and deformation mechanisms under high rate and high pressure loading conditions. These results show that the fracture mechanisms are strong functions of confining stress and strain rate, with transgranular fracture becoming more common at high strain rates. Dynamic fracture mechanics and micromechanical models are used to analyze the observed fracture mechanisms. TEM characterization of fragments from the confined dynamic experiments shows that at higher pressures dislocation motion becomes a common dominant deformation mechanism in AlN. Prismatic slip is dominant, and pronounced microcrack–dislocation interactions are observed, suggesting that the dislocation plasticity affects the macroscopic fracture behavior in this material under high confining stresses.

Finite element computational fluid mechanics

International Nuclear Information System (INIS)

Baker, A.J.

1983-01-01

This book analyzes finite element theory as applied to computational fluid mechanics. It includes a chapter on using the heat conduction equation to expose the essence of finite element theory, including higher-order accuracy and convergence in a common knowledge framework. Another chapter generalizes the algorithm to extend application to the nonlinearity of the Navier-Stokes equations. Other chapters are concerned with the analysis of a specific fluids mechanics problem class, including theory and applications. Some of the topics covered include finite element theory for linear mechanics; potential flow; weighted residuals/galerkin finite element theory; inviscid and convection dominated flows; boundary layers; parabolic three-dimensional flows; and viscous and rotational flows

Recent Advances in the Pathogenesis of Syndromic Autisms

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A. Benvenuto

2009-01-01

Full Text Available Background. Current advances in genetic technology continue to expand the list of medical conditions associated with autism. Clinicians have to identify specific autistic-related syndromes, and to provide tailored counseling. The aim of this study is to elucidate recent advances in autism research that offer important clues into pathogenetic mechanisms of syndromic autism and relevant implications for clinical practice. Data Sources. The PubMed database was searched with the keywords “autism” and “chromosomal abnormalities,” “metabolic diseases,” “susceptibility loci.” Results. Defined mutations, genetic syndromes, and metabolic diseases account for up to 20% of autistic patients. Metabolic and mitochondrial defects may have toxic effects on the brain cells, causing neuronal loss and altered modulation of neurotransmission systems. Alterations of the neocortical excitatory/inhibitory balance and perturbations of interneurons' development represent the most probable pathogenetic mechanisms underlying the autistic phenotype in Fragile X-Syndrome and Tuberous Sclerosis Complex. Chromosomal abnormalities and potential candidate genes are strongly implicated in the disruption of neural connections, brain growth, and synaptic/dendritic morphology. Conclusion. Metabolic testing may be appropriate if specific symptoms are present. High-resolution chromosome analysis may be recommended if a specific diagnosis is suspected because of obvious dysmorphisms. Identifying cryptic chromosomal abnormalities by whole genome microarray analysis can increase the understanding of the neurobiological pathways to autism.

Depression and Chronic Liver Diseases: Are There Shared Underlying Mechanisms?

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Xiaoqin Huang

2017-05-01

Full Text Available The occurrence of depression is higher in patients with chronic liver disease (CLD than that in the general population. The mechanism described in previous studies mainly focused on inflammation and stress, which not only exists in CLD, but also emerges in common chronic diseases, leaving the specific mechanism unknown. This review was to summarize the prevalence and risk factors of depression in CLD including chronic hepatitis B, chronic hepatitis, alcoholic liver disease, and non-alcoholic fatty liver disease, and to point out the possible underlying mechanism of this potential link. Clarifying the origins of this common comorbidity (depression and CLD may provide more information to understand both diseases.

Fungicidal Drugs Induce a Common Oxidative-Damage Cellular Death Pathway

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Peter Belenky

2013-02-01

Full Text Available Amphotericin, miconazole, and ciclopirox are antifungal agents from three different drug classes that can effectively kill planktonic yeast, yet their complete fungicidal mechanisms are not fully understood. Here, we employ a systems biology approach to identify a common oxidative-damage cellular death pathway triggered by these representative fungicides in Candida albicans and Saccharomyces cerevisiae. This mechanism utilizes a signaling cascade involving the GTPases Ras1 and Ras2 and protein kinase A, and it culminates in death through the production of toxic reactive oxygen species in a tricarboxylic-acid-cycle- and respiratory-chain-dependent manner. We also show that the metabolome of C. albicans is altered by antifungal drug treatment, exhibiting a shift from fermentation to respiration, a jump in the AMP/ATP ratio, and elevated production of sugars; this coincides with elevated mitochondrial activity. Lastly, we demonstrate that DNA damage plays a critical role in antifungal-induced cellular death and that blocking DNA-repair mechanisms potentiates fungicidal activity.

Common developmental genome deprogramming in schizophrenia - Role of Integrative Nuclear FGFR1 Signaling (INFS).

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Narla, S T; Lee, Y-W; Benson, C A; Sarder, P; Brennand, K J; Stachowiak, E K; Stachowiak, M K

2017-07-01

The watershed-hypothesis of schizophrenia asserts that over 200 different mutations dysregulate distinct pathways that converge on an unspecified common mechanism(s) that controls disease ontogeny. Consistent with this hypothesis, our RNA-sequencing of neuron committed cells (NCCs) differentiated from established iPSCs of 4 schizophrenia patients and 4 control subjects uncovered a dysregulated transcriptome of 1349 mRNAs common to all patients. Data reveals a global dysregulation of developmental genome, deconstruction of coordinated mRNA networks, and the formation of aberrant, new coordinated mRNA networks indicating a concerted action of the responsible factor(s). Sequencing of miRNA transcriptomes demonstrated an overexpression of 16 miRNAs and deconstruction of interactive miRNA-mRNA networks in schizophrenia NCCs. ChiPseq revealed that the nuclear (n) form of FGFR1, a pan-ontogenic regulator, is overexpressed in schizophrenia NCCs and overtargets dysregulated mRNA and miRNA genes. The nFGFR1 targeted 54% of all human gene promoters and 84.4% of schizophrenia dysregulated genes. The upregulated genes reside within major developmental pathways that control neurogenesis and neuron formation, whereas downregulated genes are involved in oligodendrogenesis. Our results indicate (i) an early (preneuronal) genomic etiology of schizophrenia, (ii) dysregulated genes and new coordinated gene networks are common to unrelated cases of schizophrenia, (iii) gene dysregulations are accompanied by increased nFGFR1-genome interactions, and (iv) modeling of increased nFGFR1 by an overexpression of a nFGFR1 lead to up or downregulation of selected genes as observed in schizophrenia NCCs. Together our results designate nFGFR1 signaling as a potential common dysregulated mechanism in investigated patients and potential therapeutic target in schizophrenia. Copyright © 2016 The Authors. Published by Elsevier B.V. All rights reserved.

Abiotic stressors and stress responses: What commonalities appear between species across biological organization levels?

International Nuclear Information System (INIS)

Sulmon, Cécile; Baaren, Joan van; Cabello-Hurtado, Francisco; Gouesbet, Gwenola; Hennion, Françoise; Mony, Cendrine; Renault, David; Bormans, Myriam; El Amrani, Abdelhak; Wiegand, Claudia; Gérard, Claudia

2015-01-01

Organisms are regularly subjected to abiotic stressors related to increasing anthropogenic activities, including chemicals and climatic changes that induce major stresses. Based on various key taxa involved in ecosystem functioning (photosynthetic microorganisms, plants, invertebrates), we review how organisms respond and adapt to chemical- and temperature-induced stresses from molecular to population level. Using field-realistic studies, our integrative analysis aims to compare i) how molecular and physiological mechanisms related to protection, repair and energy allocation can impact life history traits of stressed organisms, and ii) to what extent trait responses influence individual and population responses. Common response mechanisms are evident at molecular and cellular scales but become rather difficult to define at higher levels due to evolutionary distance and environmental complexity. We provide new insights into the understanding of the impact of molecular and cellular responses on individual and population dynamics and assess the potential related effects on communities and ecosystem functioning. - Highlights: • Responses to chemical and thermal stressors are reviewed across organization levels. • Common responses between taxa are evident at the molecular and cellular scales. • At individual level, energy allocation connects species-specific stress responses. • Commonality decreases at higher levels due to increasing environmental complexity. - The commonality of stress responses to chemical and thermal stressors among taxa is evident at the molecular and cellular scales but remains unclear at higher levels of organization

Possible pathophysiological roles of transglutaminase-catalyzed reactions in the pathogenesis of human neurodegenerative diseases

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Enrica Serretiello

2015-09-01

Full Text Available Transglutaminases (TG, E.C. 2.3.2.13 are related and ubiquitous enzymes that catalyze the cross linking of a glutaminyl residue of a protein/peptide substrate to a lysyl residue of a protein/peptide co-substrate. These enzymes are also capable of catalyzing other post-translational reactions important for cell life. The distribution and the physiological roles of human TGs have been widely studied in numerous cell types and tissues and recently their roles in several diseases have begun to be identified. It has been hypothesized that transglutaminase activity is directly involved in the pathogenetic mechanisms responsible for several human diseases. In particular, tissue TG (tTG, TG2, a member of the TG enzyme family, has been recently shown to be involved in the molecular mechanisms responsible for a very widespread human pathology, Celiac Disease (CD, one of the most common food intolerances described in the western population. The main food agent that provokes the strong and diffuse clinical symptoms has been known for several years to be gliadin, a protein present in a very large number of human foods derived from vegetables. Recently, some biochemical and immunological aspects of this very common disease have been clarified, and “tissue” transglutaminase, a multifunctional and ubiquitous enzyme, has been identified as one of the major factors. The aim of this review is to summarize the most recent findings concerning the relationships between the biochemical properties of the transglutaminase activity and the basic molecular mechanisms responsible for some human diseases, with particular reference to neuropsychiatric disorders. Possible molecular links between CD and neuropsychiatric disorders, and the use of transglutaminase inhibitors are also discussed.

Bonding mechanisms in spot welded three layer combinations

DEFF Research Database (Denmark)

Moghadam, Marcel; Tiedje, Niels Skat; Seyyedian Choobi, Mahsa

2016-01-01

this interface. It has been shown previously that such a joint can reach relatively high strength resulting in plug failure in tensileshear testing. Additional strength due to these bonding mechanisms is also obtained in common spot welds in the so-called corona band around the weld nugget.......The strength of a spot weld generally stems from fusion bonding of the metal layers, but other solid state bonding mechanisms also contribute to the overall strength. Metallographic analyses are presented to identify the phases formed near and across the weld interfaces and to identify...... the occurring bonding mechanisms. When welding a combination of three galvanized steel layers where one outer layer is a thin low-carbon steel it is a common challenge to obtain nugget penetration into the thin low-carbon steel. It therefore happens in real production that no nugget is formed across...

Toxic metal(loid)-based pollutants and their possible role in autism spectrum disorder.

Science.gov (United States)

Bjørklund, Geir; Skalny, Anatoly V; Rahman, Md Mostafizur; Dadar, Maryam; Yassa, Heba A; Aaseth, Jan; Chirumbolo, Salvatore; Skalnaya, Margarita G; Tinkov, Alexey A

2018-06-11

Autism spectrum disorder (ASD) is a neurodevelopmental disorder characterized by deficits in social interaction, verbal and non-verbal communication, and stereotypic behaviors. Many studies support a significant relationship between many different environmental factors in ASD etiology. These factors include increased daily exposure to various toxic metal-based environmental pollutants, which represent a cause for concern in public health. This article reviews the most relevant toxic metals, commonly found, environmental pollutants, i.e., lead (Pb), mercury (Hg), aluminum (Al), and the metalloid arsenic (As). Additionally, it discusses how pollutants can be a possible pathogenetic cause of ASD through various mechanisms including neuroinflammation in different regions of the brain, fundamentally occurring through elevation of the proinflammatory profile of cytokines and aberrant expression of nuclear factor kappa B (NF-κB). Due to the worldwide increase in toxic environmental pollution, studies on the role of pollutants in neurodevelopmental disorders, including direct effects on the developing brain and the subjects' genetic susceptibility and polymorphism, are of utmost importance to achieve the best therapeutic approach and preventive strategies. Copyright © 2018 Elsevier Inc. All rights reserved.

Recessive omodysplasia: five new cases and review of the literature

International Nuclear Information System (INIS)

Elcioglu, Nursel H.; Gustavson, Karl H.; Wilkie, Andrew O.M.; Yueksel-Apak, Memune; Spranger, Juergen W.

2004-01-01

Autosomal recessive omodysplasia (MIM 258315) is a rare skeletal dysplasia characterized by severe congenital micromelia with shortening and distal tapering of the humeri and femora to give a club-like appearance. Fewer than 20 cases have been reported in the literature so far. The purpose of this study was to more clearly describe the clinical and radiographic phenotypes and their changes with age. Five new patients, including two sibs, with autosomal recessive omodysplasia are presented. Clinical features are rhizomelic dwarfism with limited extension of elbows and knees and a distinct face with a short nose, depressed nasal bridge, long philtrum, midline haemangiomas in infants and cryptorchidism in males. Radiological findings are distal hypoplasia of the short humerus and femur with characteristic radial dislocation and radioulnar diastasis. Based on a review of these and 16 previously reported patients, the regressive nature of the humerofemoral changes and the obvious male predominance are stressed. Phenotypic similarities with the atelosteogenesis group of disorders and with diastrophic dysplasia suggest common pathogenetic mechanisms. (orig.)

[Relationships between psychosomatics and somatopsychiatry in modern medicine].

Science.gov (United States)

Paleev, N R; Krasnov, V N

2009-01-01

Progress in many clinical disciplines and neurobiology for the last decades give reason to reconsider some fundamental provisions of psychosomatic medicine and its relationships with somatopsychiatry. The universally accepted biopsychosocial model of the disease as proposed by V.N.Bekhterev implies involvement of psychological and psychosocial factors at early stages of many forms of somatic pathology. Intricate interplay between somatic and psychic components is exemplified by correlation of cardiovascular disorders and depression. Depression is diagnosed in 17-27% of the patients with coronary heart disease undergoing coronary angiography and in 16-45% of the post-infarction cases. Frequency of depression/hypertensive disease comorbidity is estimated at 30%. Similarity of pathogenetic mechanisms of cardiovascular diseases and depressive states is due to stress as their common provoking factor. Another important aspect of the relationship between medicine and psychiatry (disregarded until recently) is high frequency of somatic disorders in psychiatric patients. Cooperation of psychiatrists and representatives of different medical disciplines in such areas as research and practical health care is needed to address this problem.

020. Coexistence of lung adenocarcinoma and usual interstitial pneumonia: a case report

Science.gov (United States)

Baliaka, Aggeliki; Papaemmanouil, Styliani; Spyratos, Dionysis; Zarogoulidis, Paul; Sakkas, Leonidas

2015-01-01

Background Usual interstitial pneumonia (UIP)/idiopathic pulmonary fibrosis (IPF) is a chronic fibrosing interstitial pneumonia of unknown cause. The most common symptoms are progressively increased shortness of breath and dry cough. Some studies suggest an association between usual interstitial pneumonia and lung cancer through different pathogenetic mechanisms. Objective The case presentation of a patient with lung adenocarcinoma and UIP. Methods A 66-year-old male presented with persistent dry cough, hemoptysis and dyspnea. The chest radiographs revealed a mass in the lower lobe of the left lung, measuring 3 cm, as well as diffuse interstitial changes in the same lobe. Two partial lobectomies were performed. Results Histological examination of the mass showed moderately differentiated adenocarcinoma, focally with bronchoalveolar pattern (Immunohistochemical detection of EGFR: positive). The rest lung parenchyma presented histological appearance of UIP. Conclusions According to clinicopathological studies, the prevalence of lung cancer among patients with UIP/IPF varies between 4% and 9%. The overall median survival of IPF-Ca patients is seven months in comparison with IPF only patients (14 months).

Nutritional evaluation and management of AKI patients.

Science.gov (United States)

Fiaccadori, Enrico; Maggiore, Umberto; Cabassi, Aderville; Morabito, Santo; Castellano, Giuseppe; Regolisti, Giuseppe

2013-05-01

Protein-energy wasting is common in patients with acute kidney injury (AKI) and represents a major negative prognostic factor. Nutritional support as parenteral and/or enteral nutrition is frequently needed because the early phases of this are often a highly catabolic state, although the optimal nutritional requirements and nutrient intake composition remain a partially unresolved issue. Nutrient needs of patients with AKI are highly heterogeneous, depending on different pathogenetic mechanisms, catabolic rate, acute and chronic comorbidities, and renal replacement therapy (RRT) modalities. Thus, quantitative and qualitative aspects of nutrient intake should be frequently evaluated in this clinical setting to achieve better individualization of nutritional support, to integrate nutritional support with RRT, and to avoid under- and overfeeding. Moreover, AKI is now considered a kidney-centered inflammatory syndrome; indeed, recent experimental data indicate that specific nutrients with anti-inflammatory effects could play an important role in the prevention of renal function loss after an episode of AKI. Copyright © 2013 National Kidney Foundation, Inc. Published by Elsevier Inc. All rights reserved.

Dopamine dysregulation hypothesis: the common basis for motivational anhedonia in major depressive disorder and schizophrenia?

Science.gov (United States)

Szczypiński, Jan Józef; Gola, Mateusz

2018-03-24

Abnormalities in reward processing are crucial symptoms of major depressive disorder (MDD) and schizophrenia (SCH). Recent neuroscientific findings regarding MDD have led to conclusions about two different symptoms related to reward processing: motivational and consummatory anhedonia, corresponding, respectively, to impaired motivation to obtain rewards ('wanting'), and diminished satisfaction from consuming them ('liking'). One can ask: which of these is common for MDD and SCH. In our review of the latest neuroscientific studies, we show that MDD and SCH do not share consummatory anhedonia, as SCH patients usually have unaltered liking. Therefore, we investigated whether motivational anhedonia is the common symptom across MDD and SCH. With regard to the similarities and differences between the neural mechanisms of MDD and SCH, here we expand the current knowledge of motivation deficits and present the common underlying mechanism of motivational anhedonia - the dopamine dysregulation hypothesis - stating that any prolonged dysregulation in tonic dopamine signaling that exceeds the given equilibrium can lead to striatal dysfunction and motivational anhedonia. The implications for further research and treatment of MDD and SCH are also discussed.

Common “transmission block” in understanding cardiovascular physiology

Directory of Open Access Journals (Sweden)

Hwee-Ming Cheng

2017-01-01

Full Text Available We obtained responses from 69 medical and 65 pharmacy students who had cardiovascular (CVS physiology taught in the previous academic year. A real-time response exercise using an online game-based learning platform (Kahoot! (https://getkahoot.com/ was conducted during a lecture class using true/false questions that cover certain core aspects of CVS physiology. Comments will be made on some of the common, incomplete understanding of CVS conceptual mechanisms. Some follow-up thoughts on our role as physiology educators in fine-tuning our teaching as we encounter persistent mistakes among our students' learning physiology.

Update on Clinical Trials in Dry Age-related Macular Degeneration

Science.gov (United States)

Taskintuna, Ibrahim; Elsayed, M. E. A. Abdalla; Schatz, Patrik

2016-01-01

This review article summarizes the most recent clinical trials for dry age-related macular degeneration (AMD), the most common cause of vision loss in the elderly in developed countries. A literature search through websites https://www.pubmed.org and https://www.clinicaltrials.gov/, both accessed no later than November 04, 2015, was performed. We identified three Phase III clinical trials that were completed over the recent 5 years Age-Related Eye Disease Study 2 (AREDS2), implantable miniature telescope and tandospirone, and several other trials targeting a variety of mechanisms including, oxidative stress, complement inhibition, visual cycle inhibition, retinal and choroidal blood flow, stem cells, gene therapy, and visual rehabilitation. To date, none of the biologically oriented therapies have resulted in improved vision. Vision improvement was reported with an implantable mini telescope. Stem cells therapy holds a potential for vision improvement. The AREDS2 formulas did not add any further reduced risk of progression to advanced AMD, compared to the original AREDS formula. Several recently discovered pathogenetic mechanisms in dry AMD have enabled development of new treatment strategies, and several of these have been tested in recent clinical trials and are currently being tested in ongoing trials. The rapid development and understanding of pathogenesis holds promise for the future. PMID:26957835

Hyperuricemia and non-dipping blood pressure

Directory of Open Access Journals (Sweden)

Marrone O

2013-12-01

Full Text Available Oreste Marrone,1 Maria Rosaria Bonsignore1,21National Research Council, Institute of Biomedicine and Molecular Immunology, Palermo, Italy; 2Biomedical Department of Internal and Specialistic Medicine, University of Palermo, Palermo, ItalyThe strong association between the metabolic derangements that characterize the metabolic syndrome with arterial hypertension is very well-known, as it is the common finding of hyperuricemia in the patients with the metabolic syndrome. Besides, hyperuricemia has been found to be associated with cardiovascular, renal, and metabolic diseases; including not only gout but also type 2 diabetes mellitus, although its role as a risk factor is still debated.1 We were not aware of previous studies describing an association between uric acid levels and the non-dipping 24-hour blood pressure (BP pattern, and for that reason we were intrigued by Tutal et al’s article, regarding hypertensive patients with the metabolic syndrome.2 The authors explain some possible causes that could determine an increase in uric acid in the metabolic syndrome, and describe some pathogenetic mechanisms of systemic hypertension in their patients. We would like to point out one more possible mechanism that could link hyperuricemia to non-dipping BP.View original paper by Tutal et al

Ruling the Commons. Introducing a new methodology for the analysis of historical commons

Directory of Open Access Journals (Sweden)

Tine de Moor

2016-10-01

Full Text Available Despite significant progress in recent years, the evolution of commons over the long run remains an under-explored area within commons studies. During the last years an international team of historians have worked under the umbrella of the Common Rules Project in order to design and test a new methodology aimed at advancing our knowledge on the dynamics of institutions for collective action – in particular commons. This project aims to contribute to the current debate on commons on three different fronts. Theoretically, it explicitly draws our attention to issues of change and adaptation in the commons – contrasting with more static analyses. Empirically, it highlights the value of historical records as a rich source of information for longitudinal analysis of the functioning of commons. Methodologically, it develops a systematic way of analyzing and comparing commons’ regulations across regions and time, setting a number of variables that have been defined on the basis of the “most common denominators” in commons regulation across countries and time periods. In this paper we introduce the project, describe our sources and methodology, and present the preliminary results of our analysis.

Mechanical appliances, mechanical movements and novelties of construction

CERN Document Server

Hiscox, Gardner D

2008-01-01

From the devices that power ships and trains to the workings of clocks, typewriters, and guns, this engrossing visual narrative profiles the specific and unique properties of hundreds of mechanical devices. Nearly 1,000 detailed illustrations depict steam-powered appliances, spring-powered devices, hydraulic equipment, and other machines, many of which remain in common use today. Each apparatus features a detailed line drawing and an informative explanation of its workings and uses. A final chapter chronicles 400 years of impassioned but futile searching for a perpetual motion machine.The comp

Immune Mechanisms in Myelodysplastic Syndrome

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Andreas Glenthøj

2016-06-01

Full Text Available Myelodysplastic syndrome (MDS is a spectrum of diseases, characterized by debilitating cytopenias and a propensity of developing acute myeloid leukemia. Comprehensive sequencing efforts have revealed a range of mutations characteristic, but not specific, of MDS. Epidemiologically, autoimmune diseases are common in patients with MDS, fueling hypotheses of common etiological mechanisms. Both innate and adaptive immune pathways are overly active in the hematopoietic niche of MDS. Although supportive care, growth factors, and hypomethylating agents are the mainstay of MDS treatment, some patients—especially younger low-risk patients with HLA-DR15 tissue type—demonstrate impressive response rates after immunosuppressive therapy. This is in contrast to higher-risk MDS patients, where several immune activating treatments, such as immune checkpoint inhibitors, are in the pipeline. Thus, the dual role of immune mechanisms in MDS is challenging, and rigorous translational studies are needed to establish the value of immune manipulation as a treatment of MDS.

[Modern view on etiology, pathogenesis and treatment of chronic pelvic pain syndrome].

Science.gov (United States)

Vinarov, A Z

2017-04-01

The manuscript presents the analysis of scientific manuscripts written by Russian and foreign researchers devoted to chronic pelvic pain syndrome (CPPS) studies. In spite of widespread disease, there is no clear understanding on etiopathogenetic mechanisms of CPPS development and it is shown that besides infectious process cardiovascular, neuronal, locomotor, endocrine and immune systems are involved into pathological process of CPPS. Mentioned factors complicate the doctors task on effective therapy choice and stress the reasonability of complex approach to CPPS treatment. Combination drug containing affinity purified antibodies to endothelial NO-synthase and prostate-specific antigen in released-active form influences different pathogenetic mechanisms of CPPS and thereby reveals pronounced clinical efficacy.

Diabetic ketoacidosis: risk factors, mechanisms and management ...

African Journals Online (AJOL)

Diabetic ketoacidosis: risk factors, mechanisms and management strategies in sub-Saharan Africa: a review. ... ketoacidosis is the most common hyperglycaemic emergency in patients with diabetes mellitus, especially type 1 diabetes.

A common currency for the computation of motivational values in the human striatum

NARCIS (Netherlands)

Sescousse, G.T.; Li, Y.; Dreher, J.C.

2015-01-01

Reward comparison in the brain is thought to be achieved through the use of a 'common currency', implying that reward value representations are computed on a unique scale in the same brain regions regardless of the reward type. Although such a mechanism has been identified in the ventro-medial

Reappraising entrapment neuropathies--mechanisms, diagnosis and management.

Science.gov (United States)

Schmid, Annina B; Nee, Robert J; Coppieters, Michel W

2013-12-01

The diagnosis of entrapment neuropathies can be difficult because symptoms and signs often do not follow textbook descriptions and vary significantly between patients with the same diagnosis. Signs and symptoms which spread outside of the innervation territory of the affected nerve or nerve root are common. This Masterclass provides insight into relevant mechanisms that may account for this extraterritorial spread in patients with entrapment neuropathies, with an emphasis on neuroinflammation at the level of the dorsal root ganglia and spinal cord, as well as changes in subcortical and cortical regions. Furthermore, we describe how clinical tests and technical investigations may identify these mechanisms if interpreted in the context of gain or loss of function. The management of neuropathies also remains challenging. Common treatment strategies such as joint mobilisation, neurodynamic exercises, education, and medications are discussed in terms of their potential to influence certain mechanisms at the site of nerve injury or in the central nervous system. The mechanism-oriented approach for this Masterclass seems warranted given the limitations in the current evidence for the diagnosis and management of entrapment neuropathies. Copyright © 2013 Elsevier Ltd. All rights reserved.

Glial Tissue Mechanics and Mechanosensing by Glial Cells

OpenAIRE

Katarzyna Pogoda; Katarzyna Pogoda; Paul A. Janmey

2018-01-01

Understanding the mechanical behavior of human brain is critical to interpret the role of physical stimuli in both normal and pathological processes that occur in CNS tissue, such as development, inflammation, neurodegeneration, aging, and most common brain tumors. Despite clear evidence that mechanical cues influence both normal and transformed brain tissue activity as well as normal and transformed brain cell behavior, little is known about the links between mechanical signals and their bio...

The common good

OpenAIRE

Argandoña, Antonio

2011-01-01

The concept of the common good occupied a relevant place in classical social, political and economic philosophy. After losing ground in the Modern age, it has recently reappeared, although with different and sometimes confusing meanings. This paper is the draft of a chapter of a Handbook; it explains the meaning of common good in the Aristotelian-Thomistic philosophy and in the Social Doctrine of the Catholic Church; why the common good is relevant; and how it is different from the other uses...

Environment-Gene interaction in common complex diseases: New approaches

Directory of Open Access Journals (Sweden)

William A. Toscano, Jr.

2014-10-01

Full Text Available Approximately 100,000 different environmental chemicals that are in use as high production volume chemicals confront us in our daily lives. Many of the chemicals we encounter are persistent and have long half-lives in the environment and our bodies. These compounds are referred to as Persistent Organic Pollutants, or POPS. The total environment however is broader than just toxic pollutants. It includes social capital, social economic status, and other factors that are not commonly considered in traditional approaches to studying environment-human interactions. The mechanism of action of environmental agents in altering the human phenotype from health to disease is more complex than once thought. The focus in public health has shifted away from the study of single-gene rare diseases and has given way to the study of multifactorial complex diseases that are common in the population. To understand common complex diseases, we need teams of scientists from different fields working together with common aims. We review some approaches for studying the action of the environment by discussing use-inspired research, and transdisciplinary research approaches. The Genomic era has yielded new tools for study of gene-environment interactions, including genomics, epigenomics, and systems biology. We use environmentally-driven diabetes mellitus type two as an example of environmental epigenomics and disease. The aim of this review is to start the conversation of how the application of advances in biomedical science can be used to advance public health.

Eating Disorders as Coping Mechanisms

Science.gov (United States)

Wagener, Amy M.; Much, Kari

2010-01-01

This article focuses on the complex nature of eating disorders, specifically highlighting their use as coping mechanisms for underlying emotional and psychological concerns. Case examples of college counseling center clients are discussed in order to illustrate common ways in which eating disorders are utilized by clients with varying…

Relational quantum mechanics

International Nuclear Information System (INIS)

Rovelli, C.

1996-01-01

I suggest that the common unease with taking quantum mechanics as a fundamental description of nature (the open-quotes measurement problemclose quotes) could derive from the use of an incorrect notion, as the unease with the Lorentz transformations before Einstein derived from the notion of observer-independent time. I suggest that this incorrect notion that generates the unease with quantum mechanics is the notion of open-quotes observer-independent stateclose quotes of a system, or open-quotes observer-independent values of physical quantities.close quotes I reformulate the problem of the open-quotes interpretation of quantum mechanicsclose quotes as the problem of deriving the formalism from a set of simple physical postulates. I consider a reformulation of quantum mechanics in terms of information theory. All systems are assumed to be equivalent, there is no observer-observed distinction, and the theory describes only the information that systems have about each other; nevertheless, the theory is complete

A common fixed point for operators in probabilistic normed spaces

International Nuclear Information System (INIS)

Ghaemi, M.B.; Lafuerza-Guillen, Bernardo; Razani, A.

2009-01-01

Probabilistic Metric spaces was introduced by Karl Menger. Alsina, Schweizer and Sklar gave a general definition of probabilistic normed space based on the definition of Menger [Alsina C, Schweizer B, Sklar A. On the definition of a probabilistic normed spaces. Aequationes Math 1993;46:91-8]. Here, we consider the equicontinuity of a class of linear operators in probabilistic normed spaces and finally, a common fixed point theorem is proved. Application to quantum Mechanic is considered.

Design considerations for mechanical snubbers

International Nuclear Information System (INIS)

Severud, L.K.; Summers, G.D.

1980-03-01

The use of mechanical snubbers to restrain piping during an earthquake event is becoming more common in design of nuclear power plants. The design considerations and qualification procedures for mechanical snubbers used on the Fast Flux Test Facility will be presented. Design precautions and requirements for both normal operation and seismic operation are necessary. Effects of environmental vibration (nonseismic) induced through the piping by pump shaft imbalance and fluid flow oscillations will be addressed. Also, the snubber dynamic characteristics of interest to design and snubber design application considerations will be discussed

A common currency for the computation of motivational values in the human striatum

NARCIS (Netherlands)

Sescousse, G.T.; Li, Y.; Dreher, J.C.

2014-01-01

Reward comparison in the brain is thought to be achieved through the use of a ‘common currency’, implying that reward value representations are computed on a unique scale in the same brain regions regardless of the reward type. Although such a mechanism has been identified in the ventro-medial

A etiological factors in mechanical intestinal obstruction

International Nuclear Information System (INIS)

Asad, S.; Khan, H.; Khan, I.A.; Ghaffar, S.; Rehman, Z.U.

2012-01-01

Background: Intestinal obstruction occurs when the normal flow of intestinal contents is interrupted. The most frequent causes of intestinal obstruction are postoperative adhesions and hernias, which cause extrinsic compression of the intestine. Less frequently, tumours or strictures of the bowel can cause intrinsic blockage. Objective of the study was to find out the various a etiological factors of mechanical intestinal obstruction and to evaluate the morbidity and mortality in adult patients presenting to Surgical 'A' unit of Ayub teaching hospital with mechanical intestinal obstruction. Methods: This cross-sectional study was conducted from March 2009 to September, 2009. All patients presenting with intestinal obstruction and were above the age of 12 years were included in the study. Patients with non-mechanical obstruction were excluded from the study and those who responded to conservative measures were also excluded. Results: A total of 36 patients with age ranging from 12 to 80 years (Mean age 37.72+-19.74 years) and male to female ratio of 1.77:1, were treated for mechanical intestinal obstruction. The most common cause for mechanical intestinal obstruction was adhesions (36.1%). Intestinal tuberculosis was the second most common cause (19.4%), while hernias and sigmoid volvulus affected 13.9% patients each. Malignancies were found in 5.6% cases. Conclusion: Adhesions and Tuberculosis are the leading causes of mechanical intestinal obstruction in Pakistan. Although some patients can be treated conservatively, a substantial portion requires immediate surgical intervention. (author)

The Common Good

DEFF Research Database (Denmark)

Feldt, Liv Egholm

At present voluntary and philanthropic organisations are experiencing significant public attention and academic discussions about their role in society. Central to the debate is on one side the question of how they contribute to “the common good”, and on the other the question of how they can avoid...... and concepts continuously over time have blurred the different sectors and “polluted” contemporary definitions of the “common good”. The analysis shows that “the common good” is not an autonomous concept owned or developed by specific spheres of society. The analysis stresses that historically, “the common...... good” has always been a contested concept. It is established through messy and blurred heterogeneity of knowledge, purposes and goal achievements originating from a multitude of scientific, religious, political and civil society spheres contested not only in terms of words and definitions but also...

Common comorbidity of epilepsy: a review of new progress

Directory of Open Access Journals (Sweden)

YANG Xue

2012-10-01

Full Text Available A range of medical and neurologic disorders occurs more frequently in people with epilepsy than in the general population and constitutes somatic comorbidity. Common examples include migraine, depression, schizophrenia, attention-deficit hyperactivity disorder (ADHD, sleep disorder, cognitive damage, developmental abnormality and so on. There are more interesting clinical features in some special types of patients with benign epilepsy of childhood with centrotemporal spikes (BECT, temporal epilepsy and mitochondrial encephalomyopathy. The association between epilepsy and other conditions can be due to a variety of interacting genetic, biologic structural, functional, pharmacological and environmental factors. Co-existence of other disorders in a person with epilepsy can complicate diagnosis, induce adverse prognostic implications and attenuate health?related quality of life. Therefore, recognition and management of comorbidity of epilepsy may facilitate the treatment of epilepsy. In this article, we review recent pathophysiologic and clinical studies to elucidate the etiology, mechanisms, clinical characteristics, differential diagnosis and treatment of common comorbidity of epilepsy.

Recommendations for mechanical ventilation of critically ill children from the Paediatric Mechanical Ventilation Consensus Conference (PEMVECC)

NARCIS (Netherlands)

Kneyber, Martin C. J.; de Luca, Daniele; Calderini, Edoardo; Jarreau, Pierre-Henri; Javouhey, Etienne; Lopez-Herce, Jesus; Hammer, Jurg; Macrae, Duncan; Markhorst, Dick G.; Medina, Alberto; Pons-Odena, Marti; Racca, Fabrizio; Wolf, Gerhard; Biban, Paolo; Brierley, Joe; Rimensberger, Peter C.

2017-01-01

Purpose: Much of the common practice in paediatric mechanical ventilation is based on personal experiences and what paediatric critical care practitioners have adopted from adult and neonatal experience. This presents a barrier to planning and interpretation of clinical trials on the use of specific

Areca nut chewing and systemic inflammation : evidence of a common pathway for systemic diseases

NARCIS (Netherlands)

Shafique, Kashif; Mirza, Saira Saeed; Vart, Priya; Memon, Abdul Rauf; Arain, Moin Islam; Tareen, Muhammad Farooq; Haq, Zia Ul

2012-01-01

Background: Areca nut, the seed of fruit of an oriental palm, known as Areca catechu, is commonly chewed in many countries. Diabetes, hypertension, cardiovascular diseases, oropharyngeal and oesophageal cancers have been associated with areca nut chewing and the mechanism by which areca nut chewing

The CHARA array adaptive optics I: common-path optical and mechanical design, and preliminary on-sky results

Science.gov (United States)

Che, Xiao; Sturmann, Laszlo; Monnier, John D.; ten Brummelaar, Theo A.; Sturmann, Judit; Ridgway, Stephen T.; Ireland, Michael J.; Turner, Nils H.; McAlister, Harold A.

2014-07-01

The CHARA array is an optical interferometer with six 1-meter diameter telescopes, providing baselines from 33 to 331 meters. With sub-milliarcsecond angular resolution, its versatile visible and near infrared combiners offer a unique angle of studying nearby stellar systems by spatially resolving their detailed structures. To improve the sensitivity and scientific throughput, the CHARA array was funded by NSF-ATI in 2011 to install adaptive optics (AO) systems on all six telescopes. The initial grant covers Phase I of the AO systems, which includes on-telescope Wavefront Sensors (WFS) and non-common-path (NCP) error correction. Meanwhile we are seeking funding for Phase II which will add large Deformable Mirrors on telescopes to close the full AO loop. The corrections of NCP error and static aberrations in the optical system beyond the WFS are described in the second paper of this series. This paper describes the design of the common-path optical system and the on-telescope WFS, and shows the on-sky commissioning results.

The activity pattern of shoulder muscles in subjects with and without subacromial impingement

DEFF Research Database (Denmark)

Diederichsen, Louise Pyndt; Nørregaard, Jesper; Dyhre-Poulsen, Poul

2009-01-01

Altered shoulder muscle activity is frequently believed to be a pathogenetic factor of subacromial impingement (SI) and therapeutic interventions have been directed towards restoring normal motor patterns. Still, there is a lack of scientific evidence regarding the changes in muscle activity in p...... that the different motor patterns might be a pathogenetic factor of SI, perhaps due to inappropriate neuromuscular strategies affecting both shoulders....

Uncommon among the Commons? Disentangling the Sustainability of the Peruvian Anchovy Fishery

Directory of Open Access Journals (Sweden)

Milena Arias Schreiber

2013-06-01

Full Text Available The term "commons" refers to collectively exploited resources and their systems of usage; a synonymous term is common pool resources. Fisheries are typical common pool resources and also one of the most conspicuous examples of unsustainable use of natural resources. We examine one of the few globally important fisheries that is held to be sustainable, the Peruvian anchovy fishery, and considers the extent to which the institutional characteristics of the fishery conform to design principles that are considered prerequisites for long-term, successful, community-based common pool resources. Results showed that greater conformity to the principles was found in the sustainable phase of the fishery, compared to its unsustainable phase. For this case study, the conditions that supported the transition towards sustainability were: clearly defined resource boundaries, monitoring of rule enforcement, and conflict resolution mechanisms among users and management authorities. On the other hand, clearly defined user boundaries, collective choice arrangements, and nested enterprises were not required to achieve sustainability. The study concludes that the design principles are a valuable tool for analysis and understanding of large-scale common pool resource systems. At the same time it suggests that the application of the principles to a wider range of systems can generate new insights into what is required for successful management of common pool resources.

Science commons

CERN Multimedia

CERN. Geneva

2007-01-01

SCP: Creative Commons licensing for open access publishing, Open Access Law journal-author agreements for converting journals to open access, and the Scholar's Copyright Addendum Engine for retaining rights to self-archive in meaningful formats and locations for future re-use. More than 250 science and technology journals already publish under Creative Commons licensing while 35 law journals utilize the Open Access Law agreements. The Addendum Engine is a new tool created in partnership with SPARC and U.S. universities. View John Wilbanks's biography

[The mechanisms underlying the therapeutic effects of reflexotherapy and drinking mineral waters in the patients presenting with metabolic syndrome].

Science.gov (United States)

Zhernov, V A; Frolkov, V K; Zubarkina, M M

Both acupuncture and drinking mineral water can influence the metabolism of carbohydrates and lipids as well as their hormonal regulation, but the possibility of the application of these therapeutic factors for the correction of insulin resistance has not been studied in the patients presenting with metabolic syndrome. The objective of the present study was to evaluate the effects produced by the intake of drinking mineral water and acupuncture on the various parameters characterizing the patients suffering from metabolic syndrome in combination with altered insulin resistance. Ninety patients with this condition included in the study underwent the analysis of their the blood pressure, body mass index, blood glucose and lipid levels, insulin and cortisol secretion. We undertook the analysis of the effects of the single and repeated intakes of Essentuki No 17 mineral water included in the combined treatment of the patients with metabolic syndrome and revealed many common responses of the organism to its therapeutic action. Specifically, the stress-type reactions suggested the initiation of the adaptive processes in the system of hormonal regulation of carbohydrate and lipid metabolism. Simultaneously, the manifestations of insulin resistance became less pronounced indicating that both acupuncture and drinking mineral water suppressed the action of the main pathogenic mechanisms underlying the development of metabolic syndrome. Moreover, it was shown that acupuncture had a stronger hypotensive effect in the combination with the decrease of the overproduction of cortisol whereas the intake of the mineral water had a greater metabolic potential and contributed to the intensification of the basal secretion of glucocorticoids. Both reflexotherapy and drinking mineral water have a well apparent effect on the pathogenetic reactions of the metabolic syndrome and therefore can be used in addition to the standard therapy to activate the non-specific, phylogenetically

BRSMG Uai: common bean cultivar with carioca grain type and upright plant architecture

Directory of Open Access Journals (Sweden)

Magno Antonio Patto Ramalho

2016-09-01

Full Text Available The common bean cultivar with carioca grain type, BRSMG Uai, is recommended for cultivation in Minas Gerais and stands out for its upright plant architecture, which facilitates cultivation and mechanical harvesting. This cultivar has high yield potential and is resistant to the major races of anthracnose that occur in region.

Diffuse Idiopathic Skeletal Hyperosteosis: A Review

Directory of Open Access Journals (Sweden)

Sevgi İkbali Afşar

2015-12-01

Full Text Available Diffuse idiopathic skeletal hyperosteosis (DISH is also known as Forestier disease and is a systemic non-inflammatory disorder seen more commonly in males and elderly. It is characterized by calcification of the anterior longitudinal ligament of the vertebral column and various extraspinal ligaments. It is usually asymptomatic while the most common symptoms are spinal pain, limited range of spinal motion and dysphagia due to esophagus compression. The etiopathogenesis is not clear. It is commonly seen together with diabetes mellitus, obesity, hyperinsulinemia, hypertension and lipid and purine metabolism disorders, indicating an association with metabolic disorders. Recent studies have emphasized that the pathological calcification of the anterior longitudinal ligament plays a role in the pathophysiology. The aim of this study was to summarize new pathogenetic, clinical and therapeutic insights of this disease, based on published literature.

Adrenogenital syndrome: molecular mechanisms of development

Directory of Open Access Journals (Sweden)

V.P. Pishak

2017-03-01

Full Text Available On the long multistage pathway of biosynthesis of steroid hormones from cholesterol to cortisol, testo­sterone and estradiol, due to mutations in genes, there is the deficiency of steroidogenesis enzymes in the adrenal glands: cholesterol desmolase, 3β-hydroxysteroid dehydrogenase, 17α-hydroxylase, 21-hydroxylase, and enzymes of steroidogenesis in the testis: 17,20-desmolasis, 17β-hydroxystyrol dehydroreductase and others, as well as a complex of widespread congenital diseases of heterogeneous group with autosomal recessive type of inheritance — adrenogenital syndrome (AGS. Deficiency of any of these enzymes or transport proteins leads to partial or complete loss of their activity. Phenotypic manifestations of AGS are quite polymorphic: phenomenon of hypoadrenocorticism; violation of the nature and rates of sexual development; bilateral increasing of adrenal glands; hypercorticotropinemia sensitive to dexamethasone; oligo- or amenorrhea; anovulatory infertility, miscarriage in early pregnancy. Pathogenetic component of these signs is congenital disorder of steroidogenesis caused by 11β-hydroxylase deficiency and symptoms of androgen excess. In AGS, there are distinguished a phenotype and nonclassical forms of steroidogenesis enzyme deficiency. In most cases, both types of diseases occur in persons of both sexes with different course — from mild to severe forms of the disease.

Periodontal and oral manifestations of marijuana use.

Science.gov (United States)

Rawal, Swati Y; Tatakis, Dimitris N; Tipton, David A

2012-01-01

Marijuana, prepared from the plant Cannabis sativa, is the most widely used illicit drug in the United States. Marijuana use has been associated with adverse psychosocial and health effects, including effects on oral tissues. Periodontal literature has limited references to the periodontal effects of cannabis use. In this report, we present two cases of marijuana-associated gingival enlargement and review the literature on oral complications of marijuana use. Two asymptomatic males, aged 23 and 42 years, presented independently for oral prophylaxis. Both had an unremarkable medical history and related a history of significant marijuana use of 2-16 years duration. Common findings following oral and periodontal examination were nicotinic stomatitis-like lesions, uvulitis and gingival enlargement. Marginal and papillary gingiva of the anterior dentition were the areas primarily affected by gingival enlargement, while some of these areas exhibited a nodular or "pebbly" appearance. Marijuana-associated gingival enlargement was diagnosed in the reported cases. A review of the literature revealed two other reports of marijuana-associated gingival enlargement, all in young adult males with chronic (2 or more years) cannabis use. These authors reported a resemblance to phenytoin-induced enlargement. Biochemical similarities between phenytoin and cannabis active compounds suggest possible common pathogenetic mechanisms. Uvulitis and nicotinic stomatitis appear to be the two most common of the several oral manifestations of marijuana use. Chronic marijuana use may result in gingival enlargement with clinical characteristics similar to phenytoin-induced enlargement.

Metabolic syndrome X as a clinical outcome of hormonal changes on the liquidators of the Chernobyl accident consequences (the problem analysis)

International Nuclear Information System (INIS)

Kovalenko, A.N.

1999-01-01

An analysis of hormonal changes in the liquidators of the Chernobyl accident consequences, which promote the metabolic syndrome X development, was carried out on the base of clinical and experimental data. The system insulin-glucose, the mechanisms of insulinresistance and gyperinslinemia forming, the pathogenetical role of hyperinsulinemia interaction with others hormomes, some aspects of hormone - receptor interaction, an interconnection of hyperinsulinemia and vascular pathology, peculiarities of radiobiological stress as a non-classic adaptive reaction, which frequently resulting with a pathology, were discussed in the article

ICDE project report: collection and analysis of common-cause failures of batteries

International Nuclear Information System (INIS)

2003-12-01

This report documents a study performed on the set of Common Cause Failure (CCF) events of batteries (BT). the events studied here were derived from the International CCF Data Exchange (ICDE) database, with contributions from organizations from several countries. 50 events in the ICDE database were studied by tabulating the data and observing the trends. The data span a period from 1980 through 2000. The database contains general information about event attributes such as root cause, coupling factor, common cause component group (CCCG) size, and corrective action. The objective of the report was also to develop the failure mechanisms and phenomena involved in the events, their relationship to the root causes, and possibilities for improvement

Depression in dementia: epidemiology, mechanisms, and treatment.

Science.gov (United States)

Enache, Daniela; Winblad, Bengt; Aarsland, Dag

2011-11-01

Depression in people with dementia has important implications, such as reduced quality of life of patients and carers, and is associated with increased costs and reduced cognition. Here, we review recent studies of the epidemiology, course, mechanisms and treatment of depression in people with dementia. Depression is both a risk factor and a prodrome of Alzheimer's disease. Depression is a common occurrence in all types of dementias and at all disease stages, including in mild cognitive impairment (MCI). Many studies have explored whether depression in MCI increased the conversion rate to dementia, but findings are inconsistent. Studies of the mechanisms are relatively few and findings inconsistent, but inflammatory, trophic and cerebrovascular factors may contribute, in addition to monoamine deficiency and severity of plaques and tangle pathology. Studies of antidepressants for depression in dementia are inconclusive, with several negative findings reported in recent large studies, suggesting that antidepressant may not confer benefit over placebo. Depression is a common risk factor, prodrome, and accompanying symptom of people with Alzheimer's dementia. The mechanisms are unknown, and there is little evidence of effective therapies.

The cytotoxicity of polycationic iron oxide nanoparticles: Common endpoint assays and alternative approaches for improved understanding of cellular response mechanism

Directory of Open Access Journals (Sweden)

Hoskins Clare

2012-04-01

Our findings indicate that common in vitro cell endpoint assays do not give detailed and complete information on cellular state and it is essential to explore novel approaches and carry out more in-depth studies to elucidate cellular response mechanism to magnetic nanoparticles.

Iatrogenic pneumothorax related to mechanical ventilation

Science.gov (United States)

Hsu, Chien-Wei; Sun, Shu-Fen

2014-01-01

Pneumothorax is a potentially lethal complication associated with mechanical ventilation. Most of the patients with pneumothorax from mechanical ventilation have underlying lung diseases; pneumothorax is rare in intubated patients with normal lungs. Tension pneumothorax is more common in ventilated patients with prompt recognition and treatment of pneumothorax being important to minimize morbidity and mortality. Underlying lung diseases are associated with ventilator-related pneumothorax with pneumothoraces occurring most commonly during the early phase of mechanical ventilation. The diagnosis of pneumothorax in critical illness is established from the patients’ history, physical examination and radiological investigation, although the appearances of a pneumothorax on a supine radiograph may be different from the classic appearance on an erect radiograph. For this reason, ultrasonography is beneficial for excluding the diagnosis of pneumothorax. Respiration-dependent movement of the visceral pleura and lung surface with respect to the parietal pleura and chest wall can be easily visualized with transthoracic sonography given that the presence of air in the pleural space prevents sonographic visualization of visceral pleura movements. Mechanically ventilated patients with a pneumothorax require tube thoracostomy placement because of the high risk of tension pneumothorax. Small-bore catheters are now preferred in the majority of ventilated patients. Furthermore, if there are clinical signs of a tension pneumothorax, emergency needle decompression followed by tube thoracostomy is widely advocated. Patients with pneumothorax related to mechanical ventilation who have tension pneumothorax, a higher acute physiology and chronic health evaluation II score or PaO2/FiO2 < 200 mmHg were found to have higher mortality. PMID:24834397

Application of mechanical embolectomy in acute ischemic stroke

International Nuclear Information System (INIS)

Lu Haitao; Li Minghua; Zhao Jungong

2008-01-01

Acute ischemic stroke is a common disease serevely threatening the public health. The main management involves intravenous thrombolysis, intra-arterial thrombolysis and mechanical embolectomy. Recently, endovascular mechanical embolectomy is attracted more attention because it provides a good outcome for patients either ineligible not responsible for IV thrombolytic therapy. The article reviews the relative aspects with summerization in this field. (authors)

Mechanisms of Distal Axonal Degeneration in Peripheral Neuropathies

Science.gov (United States)

Cashman, Christopher R.; Höke, Ahmet

2015-01-01

Peripheral neuropathy is a common complication of a variety of diseases and treatments, including diabetes, cancer chemotherapy, and infectious causes (HIV, hepatitis C, and Campylobacter jejuni). Despite the fundamental difference between these insults, peripheral neuropathy develops as a combination of just six primary mechanisms: altered metabolism, covalent modification, altered organelle function and reactive oxygen species formation, altered intracellular and inflammatory signaling, slowed axonal transport, and altered ion channel dynamics and expression. All of these pathways converge to lead to axon dysfunction and symptoms of neuropathy. The detailed mechanisms of axon degeneration itself have begun to be elucidated with studies of animal models with altered degeneration kinetics, including the slowed Wallerian degeneration (Wlds) and Sarmknockout animal models. These studies have shown axonal degeneration to occur througha programmed pathway of injury signaling and cytoskeletal degradation. Insights into the common disease insults that converge on the axonal degeneration pathway promise to facilitate the development of therapeutics that may be effective against other mechanisms of neurodegeneration. PMID:25617478

Mechanisms for generating froissaron

International Nuclear Information System (INIS)

Glushko, N.I.; Kobylinski, N.A.; Martynov, E.S.; Shelest, V.P.

1982-01-01

From a common point of view, we consider the mechanisms for generating froissaron which arise due to the quasieikonal approximation, the U-matrix approach and the method of continued unitarity. A realistic model for the input pomeron is suggested and the data on high-energy pp-scattering are described. Likeness and difference of asymptotic and preasymptotic regimes for three variants of froissaron are discussed

Clinical and pathogenetic variants of antroduodenal motility disorders in children and their medicinal correction

Directory of Open Access Journals (Sweden)

A. I. Khavkin

2015-01-01

Full Text Available Antroduodenal motility disorder is a major component of the pathogenesis of most diseases of the upper gastrointestinal tract. Motility regulation is a complex process and it is accomplished by complex balanced neurohumoral mechanisms and depends on the chemical composition of the chyme and on the change in the cyclic membrane potential — slow waves that generate myogenic pacemakers. The electrical activity of the stomach and duodenum may be assessed by electrogastroenterography that shows the motor evacutory function of these digestive tract segments and helps choose therapy for its disorders.

Epigenetic Mechanisms of Genomic Imprinting: Common Themes in the Regulation of Imprinted Regions in Mammals, Plants, and Insects

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William A. MacDonald

2012-01-01

Full Text Available Genomic imprinting is a form of epigenetic inheritance whereby the regulation of a gene or chromosomal region is dependent on the sex of the transmitting parent. During gametogenesis, imprinted regions of DNA are differentially marked in accordance to the sex of the parent, resulting in parent-specific expression. While mice are the primary research model used to study genomic imprinting, imprinted regions have been described in a broad variety of organisms, including other mammals, plants, and insects. Each of these organisms employs multiple, interrelated, epigenetic mechanisms to maintain parent-specific expression. While imprinted genes and imprint control regions are often species and locus-specific, the same suites of epigenetic mechanisms are often used to achieve imprinted expression. This review examines some examples of the epigenetic mechanisms responsible for genomic imprinting in mammals, plants, and insects.

Is there a Common Genetic Basis for Autoimmune Diseases?

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Juan-Manuel Anaya

2006-01-01

Full Text Available Autoimmune diseases (ADs represent a diverse collection of diseases in terms of their demographic profile and primary clinical manifestations. The commonality between them however, is the damage to tissues and organs that arises from the response to self-antigens. The presence of shared pathophysiological mechanisms within ADs has stimulated searches for common genetic roots to these diseases. Two approaches have been undertaken to sustain the “common genetic origin” theory of ADs. Firstly, a clinical genetic analysis showed that autoimmunity aggregates within families of probands diagnosed with primary Sjögren's (pSS syndrome or type 1 diabetes mellitus (T1D. A literature review supported the establishment of a familiar cluster of ADs depending upon the proband's disease phenotype. Secondly, in a same and well-defined population, a large genetic association study indicated that a number of polymorphic genes (i.e. HLA-DRB1, TNF and PTPN22 influence the susceptibility for acquiring different ADs. Likewise, association and linkage studies in different populations have revealed that several susceptibility loci overlap in ADs, and clinical studies have shown that frequent clustering of several ADs occurs. Thus, the genetic factors for ADs consist of two types: those which are common to many ADs (acting in epistatic pleitropy and those that are specific to a given disorder. Their identification and functional characterization will allow us to predict their effect as well as to indicate potential new therapeutic interventions. Both autoimmunity family history and the co-occurrence of ADs in affected probands should be considered when performing genetic association and linkage studies.

Antibacterial activity of Artemisia asiatica essential oil against some common respiratory infection causing bacterial strains and its mechanism of action in Haemophilus influenzae.

Science.gov (United States)

Huang, Jiehui; Qian, Chao; Xu, Hongjie; Huang, Yanjie

2018-01-01

The main objective of the current study was to investigate the chemical composition of the essential oil of Artemisia asiatica together with investigating the antibacterial effects it exerts on several common respiratory infection causing bacteria including Haemophilus influenzae. Its mechanism of action was studied using various state-of-the-art assays like scanning electron microscopy, DNA, RNA and protein leakage assays, growth curve assays etc. The essential oil was extracted from the leaves of A. asiatica by supercritical CO 2 fluid extraction technology. Chemical composition of essential oils was analyzed by gas chromatography-mass-spectrometry (GC-MS). The antibacterial activity was evaluated against 6 bacteria by the paper disc diffusion method. The minimum inhibitory concentration (MIC) and minimum bactericide concentration (MBC) values of the essential oil were estimated by agar dilution method. The antibacterial mechanism was evaluated by growth curve, the integrity of cell membrane and scanning electronmicroscope (SEM). Gas chromatographic analysis of the A. asiatica essential oil led to the identification of 16 chemical constituents accounting for 97.2% of the total oil composition. The major components were found to be Piperitone, (z)-davanone, p-cymene and 1, 8-cineole. The essential oil showed maximum growth inhibition against Haemophilus influenzae with a zone of inhibition of 24.5 mm and MIC/MBC values of 1.9/4.5 mg/mL respectively. Bacteria treated with the essential oil led to a rapid decrease in the number of viable cells. On adding the essential oil of A. asiatica to the bacterial culture, the constituents of the bacterial cell got released into the medium and this cell constituent release increased with increasing doses of the essential oil. SEM showed that the bacterial cells treated with the essential oil showed damaged cell wall, deformed cell morphology and shrunken cells. Copyright © 2017. Published by Elsevier Ltd.

Innate recognition of pheromone and food odors in moths: a common mechanism in the antennal lobe?

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Joshua P Martin

2010-09-01

Full Text Available The survival of an animal often depends on an innate response to a particular sensory stimulus. For an adult male moth, two categories of odors are innately attractive: pheromone released by conspecific females, and the floral scents of certain, often co-evolved, plants. These odors consist of multiple volatiles in characteristic mixtures. Here, we review evidence that both categories of odors are processed as sensory objects, and we suggest a mechanism in the primary olfactory center, the antennal lobe (AL, that encodes the configuration of these mixtures and may underlie recognition of innately attractive odors. In the pheromone system, mixtures of two or three volatiles elicit upwind flight. Peripheral changes are associated with behavioral changes in speciation, and suggest the existence of a pattern recognition mechanism for pheromone mixtures in the AL. Moths are similarly innately attracted to certain floral scents. Though floral scents consist of multiple volatiles that activate a broad array of receptor neurons, only a smaller subset, numerically comparable to pheromone mixtures, is necessary and sufficient to elicit behavior. Both pheromone and floral scent mixtures that produce attraction to the odor source elicit synchronous action potentials in particular populations of output (projection neurons (PNs in the AL. We propose a model in which the synchronous output of a population of PNs encodes the configuration of an innately attractive mixture, and thus comprises an innate mechanism for releasing odor-tracking behavior. The particular example of olfaction in moths may inform the general question of how sensory objects trigger innate responses.

Mechanisms of traumatic shoulder injury in elite rugby players

Science.gov (United States)

Crichton, James; Jones, Doug R; Funk, Lennard

2012-01-01

Background Shoulder injuries in rugby players are common, but the mechanisms of injury are less well understood. This study aims to elucidate common mechanisms of injury and identify the patterns of injury they produce. Materials and methods Twenty-four elite rugby players, referred to the senior author for diagnosis and management of shoulder injuries, were selected. Videos of the injuries were independently reviewed by rugby-medical experts to describe the mechanisms of injury. The mechanisms reported were collated and analysed to determine the level of agreement between reviewers and conclude an overall description of injury mechanisms. Results The authors identified three mechanisms of shoulder injury from the video analysis. These are the ‘Try-Scorer’, characterised by hyperflexion of the outstretched arm such as when scoring a try; the ‘Tackler’, extension of the abducted arm behind the player while tackling; and the ‘Direct Impact’, a direct blow to the arm or shoulder when held by the side in neutral or slight adduction. The Try Scorer and Tackler mechanisms both involve a levering force on the glenohumeral joint (GHJ). These mechanisms predominantly cause GHJ dislocation, with Bankart, reverse Bankart and superior labrum anterior–posterior tears. The Try-Scorer Mechanism also caused the majority (83%) of rotator cuff tears. The Direct Hit mechanism resulted in GHJ dislocation and labral injury in 37.5% of players and was most likely to cause acromioclavicular joint dislocation and scapula fractures, injuries that were not seen with the other mechanisms. Conclusion Greater understanding of the mechanisms involved in rugby shoulder injury is useful in understanding the pathological injuries, guiding treatment and rehabilitation and aiding the development of injury-prevention methods. PMID:22510645

Creative Commons

DEFF Research Database (Denmark)

Jensen, Lone

2006-01-01

En Creative Commons licens giver en forfatter mulighed for at udbyde sit værk i en alternativ licensløsning, som befinder sig på forskellige trin på en skala mellem yderpunkterne "All rights reserved" og "No rights reserved". Derved opnås licensen "Some rights reserved"......En Creative Commons licens giver en forfatter mulighed for at udbyde sit værk i en alternativ licensløsning, som befinder sig på forskellige trin på en skala mellem yderpunkterne "All rights reserved" og "No rights reserved". Derved opnås licensen "Some rights reserved"...

Artificial humidification for the mechanically ventilated patient

OpenAIRE

Selvaraj, Nelson

2010-01-01

Caring for patients who are mechanically ventilated poses many\\ud challenges for critical care nurses. It is important to humidify the\\ud patient’s airways artificially to prevent complications such as\\ud ventilator-associated pneumonia. There is no gold standard to\\ud determine which type of humidification is best for patients who\\ud are artificially ventilated. This article provides an overview of\\ud commonly used artificial humidification for mechanically ventilated\\ud patients and discuss...

Artificial humidification for the mechanically ventilated patient.

Science.gov (United States)

Selvaraj, N

Caring for patients who are mechanically ventilated poses many challenges for critical care nurses. It is important to humidify the patient's airways artificially to prevent complications such as ventilator-associated pneumonia. There is no gold standard to determine which type of humidification is best for patients who are artificially ventilated. This article provides an overview of commonly used artificial humidification for mechanically ventilated patients and discusses nurses' responsibilities in caring for patients receiving artificial humidification.

Maternal steroids and contaminants in common tern eggs: A mechanism of endocrine disruption?

Science.gov (United States)

French, J.B.; Nisbet, I.C.T.; Schwabl, H.

2001-01-01

We looked for evidence for the hypothesis that exposure of female birds to polychlorinated biphenyls (PCBs) results in alteration of blood steroid hormone concentrations and alters subsequent hormone transfer of steroids to eggs. Eggs of three-egg clutches were collected from a PCB-exposed common tern (Sterna hirundo) colony (Ram Island, Buzzards Bay, MA, USA) and from a relatively clean colony (Bodkin Island, Chesapeake Bay, MD, USA), and were analyzed for concentrations of organochlorine contaminants and steroid hormones (17β-estradiol, 5α-dihydrotestosterone, testosterone and androstenedione). There was no relationship between total PCBs and steroid concentrations considering all eggs together, considering eggs of different laying order or considering differences between sequentially laid eggs in a clutch. Similarly, concentrations of di- and tri-chlorinated biphenyls and steroids in eggs were not related. The concentrations of PCBs, mercury and selenium were below estimated thresholds for toxicity to embryos. Maternal steroids, except estradiol, were present in yolk of all eggs, with increasing concentrations in the second and third eggs laid. Our data provided no evidence for a maternal toxicological event that might alter the amount of maternal steroid hormone transferred to eggs.

DETERMINATION OF DEFENSE MECHANISM IN Phaseolus ...

African Journals Online (AJOL)

Administrator

Field studies were conducted to determine the role of defense mechanism in various parameters associated with plant protection subjected to UV-B radiation in Phaseolus trilobus Ait. commonly used as green manure and fodder. Spectrophotometric analysis showed that UV-B radiation decreases the chlorophyll content ...

Inferring common cognitive mechanisms from brain blood-flow lateralisation data obtained with functional transcranial Doppler ultrasound.

Directory of Open Access Journals (Sweden)

Georg eMeyer

2014-06-01

Full Text Available Current neuroimaging techniques with high spatial resolution constrain participant motion so that many natural tasks cannot be carried out. The aim of this paper is to show how a time-locked correlation-analysis of cerebral blood flow velocity (CBFV lateralisation data, obtained with functional TransCranial Doppler (fTCD ultrasound, can be used to infer cerebral activation patterns across tasks. In a first experiment we demonstrate that the proposed analysis method results in data that are comparable with the standard Lateralisation Index (LI for within-task comparisons of CBFV patterns, recorded during cued word generation (CWG at two difficulty levels.In the main experiment we demonstrate that the proposed analysis method shows correlated blood-flow patterns for two different cognitive tasks that are known to draw on common brain areas, CWG and Music Synthesis. We show that CBFV patterns for Music and CWG are correlated only for participants with prior musical training.CBFV patterns for tasks that draw on distinct brain areas, the Tower of London and CWG, are not correlated.The proposed methodology extends conventional fTCD analysis by including temporal information in the analysis of cerebral blood-flow patterns to provide a robust, non-invasive method to infer whether common brain areas are used in different cognitive tasks. It complements conventional high resolution imaging techniques.

Eight common genetic variants associated with serum DHEAS levels suggest a key role in ageing mechanisms.

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Guangju Zhai

2011-04-01

Full Text Available Dehydroepiandrosterone sulphate (DHEAS is the most abundant circulating steroid secreted by adrenal glands--yet its function is unknown. Its serum concentration declines significantly with increasing age, which has led to speculation that a relative DHEAS deficiency may contribute to the development of common age-related diseases or diminished longevity. We conducted a meta-analysis of genome-wide association data with 14,846 individuals and identified eight independent common SNPs associated with serum DHEAS concentrations. Genes at or near the identified loci include ZKSCAN5 (rs11761528; p = 3.15 × 10(-36, SULT2A1 (rs2637125; p =  2.61 × 10(-19, ARPC1A (rs740160; p =  1.56 × 10(-16, TRIM4 (rs17277546; p =  4.50 × 10(-11, BMF (rs7181230; p = 5.44 × 10(-11, HHEX (rs2497306; p =  4.64 × 10(-9, BCL2L11 (rs6738028; p = 1.72 × 10(-8, and CYP2C9 (rs2185570; p = 2.29 × 10(-8. These genes are associated with type 2 diabetes, lymphoma, actin filament assembly, drug and xenobiotic metabolism, and zinc finger proteins. Several SNPs were associated with changes in gene expression levels, and the related genes are connected to biological pathways linking DHEAS with ageing. This study provides much needed insight into the function of DHEAS.

MDEP Common Position CP-DICWG-13. Common position on spurious actuation

International Nuclear Information System (INIS)

2017-01-01

Spurious actuations produced by Instrumentation and Control (I and C) systems are a safety concern if such actuations could challenge plant safety. Spurious actuations can lead to unnecessary challenges to safety equipment, challenge the ability of safety systems to provide their intended functions, or place the plant in an un-analysed state. Spurious actuation of plant equipment can be caused by factors including, but not limited to, single failures, common cause failures, human (e.g. operator) action, maintenance errors, design errors, or missing requirements. Modern I and C systems can have inter-connectivities, dependencies and commonalities that can, if the overall I and C architecture and the individual I and C systems are not adequately developed and operated, facilitate fault propagation, leading to potential spurious actuation of one or more trains of plant equipment. Sources and contributors of spurious actuations of multiple trains of plant equipment may include inadequate independence among redundant portions of I and C systems, inappropriate allocation of I and C functions, inadequate qualification or design of supporting systems (e.g. heating, ventilation and air conditioning (HVAC) system), or non-classified systems that could have been erroneously classified. Spurious actuations are a type of hazard. Generic Common Position (GCP) DICWG-10 'Common Position on Hazard Identification and Controls for Digital Instrumentation and Control Systems' provides a set of common positions pertaining to identifying and controlling hazards in an I and C system. This common position was developed to add special considerations when identifying and controlling hazards that include spurious actuations. It is expected that GCP DICWG-10 and the common positions in this document be used together for a complete analysis of hazards and their controls (e.g. prevention of spurious actuations in the design of the system/component). Spurious actuations of concern

Central serous chorioretinopathy: a pathogenetic model

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et al

2011-02-01

Full Text Available Antonio Caccavale1, Filippo Romanazzi1, Manuela Imparato1, Angelo Negri2, Anna Morano3, Fabio Ferentini21Department of Ophthalmology, Neuropthalmology and Ocular Immunology Service, 2Department of Ophthalmology, Hospital “C. Cantù”, Abbiategrasso, Milan, Italy; 3University Eye Clinic, Foundation IRCCS San Matteo Hospital, Pavia, ItalyAbstract: Despite numerous studies describing predominantly its demography and clinical course, many aspects of central serous chorioretinopathy (CSCR remain unclear. Perhaps the major impediment to finding an effective therapy is the difficulty of performing studies with large enough cohorts, which has meant that clinicians have focused more on therapy than on a deeper understanding of the pathogenesis of the disease. Hypotheses on the pathogenesis of CSCR have ranged from a basic alteration in the choroid to an involvement of the retinal pigment epithelium (RPE. Starting from evidence that affected subjects often present a personality prone to stress with altered pituitary–hypothalamic axis response (HPA and that they have higher levels of serum and urinary cortisol and catecholamines than healthy subjects, we hypothesize a cascade of events that may lead to CSCR through hypercoagulability and augmented platelet aggregation. In particular we investigated the role of tissue plasminogen activator, increasing plasminogen activator inhibitor 1 (PAI-1, and plasmin-α2- plasmin inhibitor complexes. We reviewed the different therapeutic approaches, including adrenergic antagonists, carbonic anhydrase inhibitors, mifepristone, ketoconazole, laser photocoagulation, intravitreal injection of bevacizumab, and photodynamic therapy with verteporfin (PDT and our model of pathogenesis seems to be in agreement with the clinical effects obtained from these treatments. In accord with our thesis, we began to treat a group of patients affected by CSCR with low-dose aspirin (75–100 mg, because of its effectiveness in other vascular diseases and its low ocular and general toxicity with prolonged use. The formulation of a causative model of CSCR enables us to understand how the therapeutic approach cannot be based on a generalized therapy but should be individualized for each patient, and that sometimes a combined strategy of treatment is required. Moreover a complete knowledge of the disease will help to identify patients prone to the most persistent forms of CSCR, and thus help to find a treatment.Keywords: CSCR, aspirin, PAI-1, glucocorticoid, macula, pathogenesis 

[Clinico-pathogenetic variants of chronic gastritis].

Science.gov (United States)

Chernin, V V; Dzhulaĭ, G S

2004-01-01

To evaluate specific features of the course of chronic gastritis (CG), morphofunctional condition of gastric mucosa, vegetative regulation, adrenergic and cholinergic shifts, histamine metabolism and effects of exogenic and endogenic risk factors in CG patients; to study clinicopathogenetic variants of CG. A total of 311 CG patients aged from 16 to 72 years were studied. They were divided into three groups by their gastric mucosa condition. The control group consisted of 30 healthy donors. The following parameters were studied: visual and histological condition of gastric mucosa, total acidity, the levels of free hydrochloric acid, pepsin, bioelectric gastric activity, general autonomic tonicity, cholinesterase activity. Three clinicopathogenetic variants of the disease have been identified. Variant 1 was characterized by a recurrent course, subjective manifestation of the disease only in exacerbation, surface (primarily antral) mucosal affection, normal or enhanced secretory and motor functions of the stomach, adequate reaction of acid production to caffeine and histamine stimulation, parasympathicotonia, absolute hyperhistaminemia, relative hypoacetylcholinemia, subnormal urinary excretion of adrenalin. Variant 2 manifested with rare recurrences, longer and more severe exacerbations, frequent spontaneous and provoked aggravations, moderate focal atrophy of the mucosa, secretory insufficiency with adequate reaction to histamine and minor to caffeine stimuli, hypomotor gastric dyskinesia, vegetative eutonia, normohistaminemia, absolute hypoacetylcholinemia, subnormal urinary excretion of noradrenaline. Variant 3 runs without definite remissions and exacerbations, with continuous abdominal pain and dyspepsia, frequent spontaneous aggravations, marked extended mucosal atrophy with secretory insufficiency up to achlorhydria, no stimulation of acid production in response to caffeine and histamine, gastric hypomotility, sympathicotonia, absolute hypohistaminemia, hypoacetylcholinemia, normal urinary excretion of catecholamines. The findings expand our knowledge about clinicopathogenetic variants of CG and necessitate new approaches to development of effective methods of CG prevention and treatment.

Combined Common Person and Common Item Equating of Medical Science Examinations.

Science.gov (United States)

Kelley, Paul R.

This equating study of the National Board of Medical Examiners Examinations was a combined common persons and common items equating, using the Rasch model. The 1,000-item test was administered to about 3,000 second-year medical students in seven equal-length subtests: anatomy, physiology, biochemistry, pathology, microbiology, pharmacology, and…

Justifying group-specific common morality.

Science.gov (United States)

Strong, Carson

2008-01-01

Some defenders of the view that there is a common morality have conceived such morality as being universal, in the sense of extending across all cultures and times. Those who deny the existence of such a common morality often argue that the universality claim is implausible. Defense of common morality must take account of the distinction between descriptive and normative claims that there is a common morality. This essay considers these claims separately and identifies the nature of the arguments for each claim. It argues that the claim that there is a universal common morality in the descriptive sense has not been successfully defended to date. It maintains that the claim that there is a common morality in the normative sense need not be understood as universalist. This paper advocates the concept of group specific common morality, including country-specific versions. It suggests that both the descriptive and the normative claims that there are country-specific common moralities are plausible, and that a country-specific normative common morality could provide the basis for a country's bioethics.

The promise of common pool resource theory and the reality of commons projects

Directory of Open Access Journals (Sweden)

Fred P. Saunders

2014-08-01

Full Text Available Commons projects, such as community-based natural resource management, have widespread appeal, which has enabled them to shrug off a mixed performance in practice. This paper discusses how the theoretical assumptions of common pool resource (CPR theory may have inadvertently contributed to the unfulfilled expectations of commons projects. The paper argues that the individual ‘rational resource user’, encapsulated in the CPR design principles, struggles to provide clear direction for meaningful consideration of local norms, values and interests in commons projects. The focus of CPR theory on efficiency and functionality results in a tendency in commons projects to overlook how local conditions are forged through relations at multiple scales. Commonly politically complex and changing relations are reduced to institutional design problems based on deriving the incentives and disincentives of ‘rational resource users. The corollary is that CPR theory oversimplifies the project context that it is seeking to change because it offers little or no direction to deal with the social embeddedness of resource use or implications of different stratifications.

Common game injury scenarios in men's and women's lacrosse.

Science.gov (United States)

Carter, Elizabeth A; Westerman, Beverly J; Lincoln, Andrew E; Hunting, Katherine L

2010-06-01

Previous research has found that the location, type and mechanisms of injuries in lacrosse players vary by gender. The patterns and risk factors of injuries in lacrosse players are still not well known. The study population consists of lacrosse players who utilised the accident medical insurance provided to US Lacrosse members. Cluster analysis was used to explore the aetiology of lacrosse-related injuries. Between 2002 and 2006 there were 593 game injuries, 496 in men and 97 in women. There were six clusters of injuries in women and five clusters of injuries in men. Play scenarios resulting in injury differed by the position played. In all the five injury clusters in males, the primary injury mechanism was by contact, either with another player, a stick or a ball. In women, body-to-body and stick-to-body, and no contact were the most common injury mechanisms. In both genders, the majority of injuries occurred during legal play. These results provide a picture of high-risk situations that lead to injuries in male and female lacrosse players. Future efforts should be made to confirm these results through epidemiologic studies. Further research should also address the effectiveness of interventions that could reduce the risk of injury in these situations.

Elimination of cancer stem cells and reactivation of latent HIV-1 via AMPK activation: Common mechanism of action linking inhibition of tumorigenesis and the potential eradication of HIV-1.

Science.gov (United States)

Finley, Jahahreeh

2017-07-01

Although promising treatments are currently in development to slow disease progression and increase patient survival, cancer remains the second leading cause of death in the United States. Cancer treatment modalities commonly include chemoradiation and therapies that target components of aberrantly activated signaling pathways. However, treatment resistance is a common occurrence and recent evidence indicates that the existence of cancer stem cells (CSCs) may underlie the limited efficacy and inability of current treatments to effectuate a cure. CSCs, which are largely resistant to chemoradiation therapy, are a subpopulation of cancer cells that exhibit characteristics similar to embryonic stem cells (ESCs), including self-renewal, multi-lineage differentiation, and the ability to initiate tumorigenesis. Interestingly, intracellular mechanisms that sustain quiescence and promote self-renewal in adult stem cells (ASCs) and CSCs likely also function to maintain latency of HIV-1 in CD4 + memory T cells. Although antiretroviral therapy is highly effective in controlling HIV-1 replication, the persistence of latent but replication-competent proviruses necessitates the development of compounds that are capable of selectively reactivating the latent virus, a method known as the "shock and kill" approach. Homeostatic proliferation in central CD4 + memory T (T CM ) cells, a memory T cell subset that exhibits limited self-renewal and differentiation and is a primary reservoir for latent HIV-1, has been shown to reinforce and stabilize the latent reservoir in the absence of T cell activation and differentiation. HIV-1 has also been found to establish durable and long-lasting latency in a recently discovered subset of CD4 + T cells known as T memory stem (T SCM ) cells. T SCM cells, compared to T CM cells, exhibit stem cell properties that more closely match those of ESCs and ASCs, including self-renewal and differentiation into all memory T cell subsets. It is our hypothesis

Pathogenetic role of Factor VII deficiency and thrombosis in cross-reactive material positive patients.

Science.gov (United States)

Girolami, A; Sambado, L; Bonamigo, E; Ferrari, S; Lombardi, A M

2013-12-01

Congenital Factor VII (FVII) deficiency can be divided into two groups: cases of "true" deficiency, or cross-reactive material (CRM) negative and variants that are cross-reactive material positive.The first form is commonly recognized as Type I condition whereas the second one is known as Type II. FVII deficiency has been occasionally associated with thrombotic events, mainly venous. The reasons underlying this peculiar manifestation are unknown even though in the majority of associated patients thrombotic risk factors are present. The purpose of the present study was to investigate if a thrombotic event was more frequent in Type I or in Type II defect.The majority of patients with FVII deficiency and thrombosis belong to Type II defects. In the following paper we discuss the possible role of the dysfunctional FVII cross-reaction material as a contributory cause for the occurrence of thrombosis.

Developments in mechanical heart valve prosthesis

Indian Academy of Sciences (India)

Artificial heart valves are engineered devices used for replacing diseased or damaged natural valves of the heart. Most commonly used for replacement are mechanical heart valves and biological valves. This paper briefly outlines the evolution, designs employed, materials being used,. and important factors that affect the ...

[Immunosuppresive agents, retinoids and new trends in the therapy of psoriasis].

Science.gov (United States)

Svozil, M

2002-11-01

Some psoriasis forms can be successfully treated with topical medicaments; serious and extensive forms cannot be cured without systemic treatment with retinoids (etretinate, acitretin, tazarotene) or with immunosuppressives (methotrexate, cyclosporine A, tacrolimus, SDZ 281-240). Immunotherapy and nucleotide analogues are being newly introduced, a number of potentially effective substances interfering with pathogenetic mechanisms participating in the emergence and self-prolongation of psoriasis are in the stage of research and clinical trials, and gene therapy possibilities are being investigated. The development and testing of drugs serving therapy for psoriasis correlates with the development of knowledge about the origins of the disease and the mechanisms of how antipsoriatics in current use as well as the new potential ones work.

Five Theses on the Common

Directory of Open Access Journals (Sweden)

Gigi Roggero

2011-01-01

Full Text Available I present five theses on the common within the context of the transformations of capitalist social relations as well as their contemporary global crisis. My framework involves ‘‘cognitive capitalism,’’ new processes of class composition, and the production of living knowledge and subjectivity. The commons is often discussed today in reference to the privatizationand commodification of ‘‘common goods.’’ This suggests a naturalistic and conservative image of the common, unhooked from the relations of production. I distinguish between commons and the common: the first model is related to Karl Polanyi, the second to Karl Marx. As elaborated in the postoperaista debate, the common assumes an antagonistic double status: it is boththe plane of the autonomy of living labor and it is subjected to capitalist ‘‘capture.’’ Consequently, what is at stake is not the conservation of ‘‘commons,’’ but rather the production of the common and its organization into new institutions that would take us beyond the exhausted dialectic between public and private.

Coexistence of morphea and granuloma annulare: a rare case report

Directory of Open Access Journals (Sweden)

Şenay Ağırgöl

2017-11-01

Full Text Available ABSTRACT CONTEXT: Localized scleroderma (morphea is characterized by fibrosis of skin and subcutaneous tissue. Granuloma annulare is a relatively common disease that is characterized by dermal papules and arciform plaques. CASE REPORT: Here, we present the case of a 42-year-old woman who developed granuloma annulare on the dorsum of her feet and abdominal region, and morphea on the anterior side of her lower limbs. We also discuss the etiological and pathogenetic processes that may cause the rare coexistence of these two diseases. CONCLUSION: Only a few cases in the literature have described coexistence of morphea and granuloma annulare.

Isolation and molecular analysis of inv dup(15) and construction of a physical map of a common breakpoint in order to elucidate their mechanism of formation.

Science.gov (United States)

Wandstrat, A E; Schwartz, S

2000-11-01

An inverted duplication of chromosome 15 [inv dup(15)] is the most common supernumerary marker chromosome, comprising approximately 50% of all chromosomes in this class. Structurally, the inv dup(15) is a mirror image with the central axis defining a distal break within either the heterochromatic alpha-satellite array or along the euchromatin in the long (q) arm of the chromosome. There are several types of inv dup(15), classified by the amount of euchromatic material present. Generally, they are bisatellited, pseudodicentric and have a breakpoint in 15q11-q14. A suggested mechanism of formation of inv dup(15) involves illegitimate recombination between homologous chromosomes followed by nondisjunction and centromere inactivation. The proximal portion of chromosome 15 contains several low-copy repeat sequence families and it has been hypothesized that errors in pairing among these repeats may result in structural rearrangements of this chromosome including the inv dup(15). To test this hypothesis and to determine the mechanism of formation, the inv dup(15) from four cases was isolated in somatic cell hybrids and polymerase chain reaction microsatellite markers were used to determine the origin of exchange. Two appeared to result from interchromosomal and two from intrachromosomal exchange, one of which occurred post-recombination. In addition, a detailed physical map of the breakpoint region in the largest inv dup(15) was constructed placing eight new sequence-tagged sites and ten new bacterial artificial chromosome markers in the region.

Technical report on micro-mechanical versus conventional modelling in non-linear fracture mechanics

International Nuclear Information System (INIS)

2001-07-01

While conventional fracture mechanics is capable of predicting crack growth behaviour if sufficient experimental observations are available, micro-mechanical modelling can both increase the accuracy of these predictions and model phenomena that are inaccessible by the conventional theory such as the ductile-cleavage temperature transition. A common argument against micro-mechanical modelling is that it is too complicated for use in routine engineering applications. This is both a computational and an educational problem. That micro-mechanical modelling is unnecessarily complicated is certainly true in many situations. The on-going development of micro-mechanical models, computational algorithms and computer speed will however most probably diminish the computational problem rather rapidly. Compare for instance the rate of development of computational methods for structural analysis. Meanwhile micro-mechanical modelling may serve as a tool by which more simplified engineering methods can be validated. The process of receiving a wide acceptance of the new methods is probably much slower. This involves many steps. First the research community must be in reasonable agreement on the methods and their use. Then the methods have to be implemented into computer software and into code procedures. The development and acceptance of conventional fracture mechanics may serve as an historical example of the time required before a new methodology has received a wide usage. The CSNI Working Group on Integrity and Ageing (IAGE) decided to carry out a report on micro-mechanical modeling to promote this promising and valuable technique. The report presents a comparison with non-linear fracture mechanics and highlights key aspects that could lead to a better knowledge and accurate predictions. Content: - 1. Introduction; - 2. Concepts of non-linear fracture mechanics with point crack tip modelling; - 3. Micro-mechanical models for cleavage fracture; - 4, Micro-mechanical modelling of

BRSMG Realce: Common bean cultivar with striped grains for the state of Minas Gerais

Directory of Open Access Journals (Sweden)

Leonardo Cunha Melo

2014-03-01

Full Text Available The common bean cultivar “BRSMG Realce”, recommended for the state of Minas Gerais, has high yield potential and resistance to powdery mildew, bacterial wilt and to anthracnose pathotypes 65, 73, 77, 81, 91, 475 and 479. The plants and pods are high, resulting in lower loss during mechanical harvest

Quantum Mechanics/Molecular Mechanics Simulations Identify the Ring-Opening Mechanism of Creatininase.

Science.gov (United States)

Jitonnom, Jitrayut; Mujika, Jon I; van der Kamp, Marc W; Mulholland, Adrian J

2017-12-05

Creatininase catalyzes the conversion of creatinine (a biosensor for kidney function) to creatine via a two-step mechanism: water addition followed by ring opening. Water addition is common to other known cyclic amidohydrolases, but the precise mechanism for ring opening is still under debate. The proton donor in this step is either His178 or a water molecule bound to one of the metal ions, and the roles of His178 and Glu122 are unclear. Here, the two possible reaction pathways have been fully examined by means of combined quantum mechanics/molecular mechanics simulations at the SCC-DFTB/CHARMM22 level of theory. The results indicate that His178 is the main catalytic residue for the whole reaction and explain its role as proton shuttle during the ring-opening step. In the first step, His178 provides electrostatic stabilization to the gem-diolate tetrahedral intermediate. In the second step, His178 abstracts the hydroxyl proton of the intermediate and delivers it to the cyclic amide nitrogen, leading to ring opening. The latter is the rate-limiting step with a free energy barrier of 18.5 kcal/mol, in agreement with the experiment. We find that Glu122 must be protonated during the enzyme reaction, so that it can form a stable hydrogen bond with its neighboring water molecule. Simulations of the E122Q mutant showed that this replacement disrupts the H-bond network formed by three conserved residues (Glu34, Ser78, and Glu122) and water, increasing the energy barrier. Our computational studies provide a comprehensive explanation for previous structural and kinetic observations, including why the H178A mutation causes a complete loss of activity but the E122Q mutation does not.

Occupational Contact Dermatitis in Mechanics and Repairers Referred for Patch Testing: Retrospective Analysis From the North American Contact Dermatitis Group 1998-2014.

Science.gov (United States)

Warshaw, Erin M; Hagen, Solveig L; Sasseville, Denis; Maibach, Howard I; DeKoven, Joel G; Belsito, Donald V; Fowler, Joseph F; Zug, Kathryn A; Taylor, James S; Mathias, C G Toby; Fransway, Anthony F; DeLeo, Vincent A; Marks, James G; Pratt, Melanie D; Zirwas, Matthew J; Storrs, Frances J

Contact dermatoses are common in mechanic and repair occupations. This study aimed to (1) estimate the prevalence of occupationally related contact dermatitis among mechanics/repairers patch tested from 1998 to 2014 by the North American Contact Dermatitis Group, (2) characterize responsible allergens and irritants, and their sources, and (3) compare results among 3 occupational subgroups (mechanics, electrical/electronic, and other). A cross-sectional analysis of patients patch tested by the North American Contact Dermatitis Group between 1998 and 2014. Of 38,784 patients patch tested, 691 (1.8%) were mechanics/repairers. Male sex (93.5%) and hand involvement (59.5%) were common overall. Occupationally related skin disease was more prevalent among vehicle and mobile equipment mechanics/repairers (52.7%) and other mechanics/repairers (41.4%) than electrical/electronic equipment mechanics/repairers (21.3%). Overall, carba mix, thiuram mix, and methylchloroisothiazolone/methylisothiazolone were the most common occupation-related clinically relevant allergens. Gloves, automotive vehicles, solvents, oils, lubricants, and fuels were the most common sources of responsible allergens. Common occupationally related allergens included rubber accelerators and the preservative methylchloroisothiazolone/methylisothiazolone.

Clinical correlates of common corneal neovascular diseases:a literature review

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Nizar Saleh Abdelfattah

2015-02-01

Full Text Available A large subset of corneal pathologies involves the formation of new blood and lymph vessels (neovascularization, leading to compromised visual acuity. This article aims to review the clinical causes and presentations of corneal neovascularization (CNV by examining the mechanisms behind common CNV-related corneal pathologies, with a particular focus on herpes simplex stromal keratitis, contact lenses-induced keratitis and CNV secondary to keratoplasty. Moreover, we reviewed CNV in the context of different types of corneal transplantation and keratoprosthesis, and summarized the most relevant treatments available so far.

Introduction to solid mechanics an integrated approach

CERN Document Server

Lubliner, Jacob

2014-01-01

This textbook presents for the first time in one text the concepts and processes covered in statics and mechanics of materials curricula following a systematic, topically integrated approach. Since the turn of the millennium, it has become common in engineering schools to combine the traditional undergraduate offerings in rigid-body statics (usually called “statics”) and deformable body mechanics (known traditionally as “strength of materials” or, more recently, “mechanics of materials”) into a single, introductory course in solid mechanics. Many textbooks for the new course sequentially meld pieces of existing, discrete books—sometimes, but not always, acknowledging the origin—into two halves covering Statics and Mechanics of Materials. In this volume, Professors Lubliner and Papadopoulos methodically combine the essentials of statics and mechanics of materials, illustrating the relationship of concepts throughout, into one "integrated" text. This book also: ·         Offers thorough...

Mutations of the Spliceosome Complex Genes Occur In Adult Patients but Are Very Rare In Children with Myeloid Neoplasia

DEFF Research Database (Denmark)

Hirabayashi, Shinsuke; Moetter, Jessica; Yoshida, Kenichi

-protein complexes that remove noncoding introns from precursor mRNA. We hypothesized that the disruption of the spliceosome complex might play a driving role in the leukemogenesis in pediatric MDS. Using targeted re-sequencing we investigated the 3 exclusive hotspots of 2 spliceosome genes that were found...... negative. The drastically reduced frequency of spliceosome mutations in pediatric compared to adult myeloid malignancies suggests a different pathogenetic mechanism in childhood disease, and fits well with previous reports that somatic mutations of non-Ras-pathway genes, such as DNMT3A, are less prevalent...

CUTANEOUS VASCULITIDES AND CUTANEOUS MANIFESTATIONS OF SYSTEMIC VASCULITIDES

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Vesna Jurčić

2009-06-01

plexes with complement activation. Typical representatives are Henoch-Schönlein purpura, cryoglobulinemic vasculitis and vasculitis in systemic lupus erythematosus. Necrotizing arteriolitis and arteritis of small arteries are usually found in ANCA positive vasculitides. Medium-sized arteries can be involved in both ANCA positive vasculitides and polyarteritis nodosa. Conclusions This article presents the clinical picture, histopathologic characteristics, pathogenetic mechanisms and treatment of some clinicopathologic entities of vasculitides, such as Henoch-Schönlein purpura, urticarial vasculitis, cryoglobulinemic vasculitis, microscopic polyangiitis, Wegener\\'s granulomatosis, Churg-Strauss syndrome and polyarteritis nodosa.

Lumbar Spinal Stenosis Due to Ligamentum Flavum Hypertrophy in a Patient with Multiple Exostosis

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Sevgi Ižkbali Afsar

2016-09-01

Full Text Available Hereditary multiple exostosis is an autosomal dominant disease characterized by multiple exostoses (osteochondromas usually affecting the metaphysical regions of long bones, usually of the lower extremity, and seldom occurring in the axial skeleton. In the literature, hereditary multiple exostosis cases that developed spinal canal stenosis due to spinal osteochondromas have been reported. Lumbar spinal stenosis may occur in a hereditary multiple exostosis patient due to ligamentum flavum hypertrophy, which is a hyperosteotic process that differs from exostosis. We discuss one such case, along with pathogenetic mechanisms and clinical features.

The mode of progression of subperiosteal resorption in the hyperparathyroidism of chronic renal future

International Nuclear Information System (INIS)

Meema, H.E.; Oreopoulos, D.G.; Toronto Univ., Ontario

1983-01-01

Subperiosteal resorption in finger phalanges is usually thought to be the result of osteoclastic bone resorption on the periosteal surface of bone, progressive centripetally with creation of the serrated appearances and ''lace-like'' patterns in periosteal cortical bone. Our longitudinal microradioscopic observations in patients with secondary hyperparathyroidism of chronic renal failure have revealed evidence of another pathogenetic mechanism: by the enlargement of intracortical juxtaperiosteal resorption spaces, the remaining thin layer of bone is broken down from inside the bone, i.e., a centrifugal rather then centripetal process. (orig.)

Liraglutide, leptin and their combined effects on feeding: additive intake reduction through common intracellular signalling mechanisms.

Science.gov (United States)

Kanoski, S E; Ong, Z Y; Fortin, S M; Schlessinger, E S; Grill, H J

2015-03-01

To investigate the behavioural and intracellular mechanisms by which the glucagon like peptide-1 (GLP-1) receptor agonist, liraglutide, and leptin in combination enhance the food intake inhibitory and weight loss effects of either treatment alone. We examined the effects of liraglutide (a long-acting GLP-1 analogue) and leptin co-treatment, delivered in low or moderate doses subcutaneously (s.c.) or to the third ventricle, respectively, on cumulative intake, meal patterns and hypothalamic expression of intracellular signalling proteins [phosphorylated signal transducer and activator of transcription-3 (pSTAT3) and protein tyrosine phosphatase-1B (PTP1B)] in lean rats. A low-dose combination of liraglutide (25 µg/kg) and leptin (0.75 µg) additively reduced cumulative food intake and body weight, a result mediated predominantly through a significant reduction in meal frequency that was not present with either drug alone. Liraglutide treatment alone also reduced meal size; an effect not enhanced with leptin co-administration. Moderate doses of liraglutide (75 µg/kg) and leptin (4 µg), examined separately, each reduced meal frequency, cumulative food intake and body weight; only liraglutide reduced meal size. In combination these doses did not further enhance the anorexigenic effects of either treatment alone. Ex vivo immunoblot analysis showed elevated pSTAT3 in the hypothalamic tissue after liraglutide-leptin co-treatment, an effect which was greater than that of leptin treatment alone. In addition, s.c. liraglutide reduced the expression of PTP1B (a negative regulator of leptin receptor signalling), revealing a potential mechanism for the enhanced pSTAT3 response after liraglutide-leptin co-administration. Collectively, these results show novel behavioural and molecular mechanisms underlying the additive reduction in food intake and body weight after liraglutide-leptin combination treatment. © 2014 John Wiley & Sons Ltd.

Efficient prion disease transmission through common environmental materials.

Science.gov (United States)

Pritzkow, Sandra; Morales, Rodrigo; Lyon, Adam; Concha-Marambio, Luis; Urayama, Akihiko; Soto, Claudio

2018-03-02

Prion diseases are a group of fatal neurodegenerative diseases associated with a protein-based infectious agent, termed prion. Compelling evidence suggests that natural transmission of prion diseases is mediated by environmental contamination with infectious prions. We hypothesized that several natural and man-made materials, commonly found in the environments of wild and captive animals, can bind prions and may act as vectors for disease transmission. To test our hypothesis, we exposed surfaces composed of various common environmental materials ( i.e. wood, rocks, plastic, glass, cement, stainless steel, aluminum, and brass) to hamster-adapted 263K scrapie prions and studied their attachment and retention of infectivity in vitro and in vivo Our results indicated that these surfaces, with the sole exception of brass, efficiently bind, retain, and release prions. Prion replication was studied in vitro using the protein misfolding cyclic amplification technology, and infectivity of surface-bound prions was analyzed by intracerebrally challenging hamsters with contaminated implants. Our results revealed that virtually all prion-contaminated materials transmitted the disease at high rates. To investigate a more natural form of exposure to environmental contamination, we simply housed animals with large contaminated spheres made of the different materials under study. Strikingly, most of the hamsters developed classical clinical signs of prion disease and typical disease-associated brain changes. Our findings suggest that prion contamination of surfaces commonly present in the environment can be a source of disease transmission, thus expanding our understanding of the mechanisms for prion spreading in nature. © 2018 by The American Society for Biochemistry and Molecular Biology, Inc.

Neuroimaging Studies Illustrate the Commonalities Between Ageing and Brain Diseases.

Science.gov (United States)

Cole, James H

2018-07-01

The lack of specificity in neuroimaging studies of neurological and psychiatric diseases suggests that these different diseases have more in common than is generally considered. Potentially, features that are secondary effects of different pathological processes may share common neurobiological underpinnings. Intriguingly, many of these mechanisms are also observed in studies of normal (i.e., non-pathological) brain ageing. Different brain diseases may be causing premature or accelerated ageing to the brain, an idea that is supported by a line of "brain ageing" research that combines neuroimaging data with machine learning analysis. In reviewing this field, I conclude that such observations could have important implications, suggesting that we should shift experimental paradigm: away from characterizing the average case-control brain differences resulting from a disease toward methods that place individuals in their age-appropriate context. This will also lead naturally to clinical applications, whereby neuroimaging can contribute to a personalized-medicine approach to improve brain health. © 2018 WILEY Periodicals, Inc.

A common-path phase-shift interferometry surface plasmon imaging system

Science.gov (United States)

Su, Y.-T.; Chen, Shean-Jen; Yeh, T.-L.

2005-03-01

A biosensing imaging system is proposed based on the integration of surface plasmon resonance (SPR) and common-path phase-shift interferometry (PSI) techniques to measure the two-dimensional spatial phase variation caused by biomolecular interactions upon a sensing chip. The SPR phase imaging system can offer high resolution and high-throughout screening capabilities to analyze microarray biomolecular interaction without the need for additional labeling. With the long-term stability advantage of the common-path PSI technique even with external disturbances such as mechanical vibration, buffer flow noise, and laser unstable issue, the system can match the demand of real-time kinetic study for biomolecular interaction analysis (BIA). The SPR-PSI imaging system has achieved a detection limit of 2×10-7 refraction index change, a long-term phase stability of 2.5x10-4π rms over four hours, and a spatial phase resolution of 10-3 π with a lateral resolution of 100μm.

Pathophysiological mechanisms of severe anaemia in Malawian children.

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Michaël Boele van Hensbroek

2010-09-01

Full Text Available Severe anaemia is a major cause of morbidity and mortality in African children. The aetiology is multi-factorial, but interventions have often targeted only one or a few causal factors, with limited success.We assessed the contribution of different pathophysiological mechanisms (red cell production failure [RCPF], haemolysis and blood loss to severe anaemia in Malawian children in whom etiological factors have been described previously. More complex associations between etiological factors and the mechanisms were explored using structural equation modelling. In 235 children with severe anaemia (haemoglobin<3.2 mMol/L [5.0 g/dl] studied, RCPF, haemolysis and blood loss were found in 48.1%, 21.7% and 6.9%, respectively. The RCPF figure increased to 86% when a less stringent definition of RCPF was applied. RCPF was the most common mechanism in each of the major etiological subgroups (39.7-59.7%. Multiple aetiologies were common in children with severe anaemia. In the final model, nutritional and infectious factors, including malaria, were directly or indirectly associated with RCPF, but not with haemolysis.RCPF was the most common pathway leading to severe anaemia, from a variety of etiological factors, often found in combination. Unlike haemolysis or blood loss, RCPF is a defect that is likely to persist to a significant degree unless all of its contributing aetiologies are corrected. This provides a further explanation for the limited success of the single factor interventions that have commonly been applied to the prevention or treatment of severe anaemia. Our findings underline the need for a package of measures directed against all of the local aetiologies of this often fatal paediatric syndrome.

The Common Fund Initiative and Its Implication for Advancing Exercise and Physical Activity Research in Child Health.

Science.gov (United States)

Cooper, Dan M; Radom-Aizik, Shlomit

2015-08-01

NIH Director Francis Collins noted that the Common Fund initiative would lead to unprecedented insights into the mechanisms responsible for the health effects of physical activity. He noted: “Armed with this knowledge, researchers and clinicians may one day be able to define optimal physical activity recommendations for people at various stages of life, as well as develop precisely targeted regimens for individuals with particular health needs.” Given the ominous burden of physical inactivity-related diseases and conditions in otherwise healthy children, and the growing number of children who survive chronic diseases in whom we know little about what constitutes healthy exercise, it is essential that the community of child health researchers develop compelling strategies and proposals in response to the unique opportunity offered through the Common Fund mechanism.

MDEP Generic Common Position No DICWG-01. Common position on the treatment of common cause failure caused by software within digital safety systems

International Nuclear Information System (INIS)

2013-01-01

Common cause failures (CCF)2 have been a significant safety concern for nuclear power plant systems. The increasing dependence on software-in safety systems for nuclear power plants has increased the safety significance of CCF caused by software, when software in redundant channels or portions of safety systems has some common dependency. For example, the effect of systematic failures can lead to a loss of safety in many ways: unwanted actuations, a safety function is not provided when needed. Therefore, nuclear power plants should be systematically protected from the effects of common cause failures caused by software in DI and C safety systems. Software for nuclear power plant safety systems should be of the high quality necessary to help assure against the loss of safety (i.e. developed with high-quality engineering practices, commensurate quality assurance applied, with continuous improvement through corrective actions based on lessons learned from operating experience). However, demonstrating adequate software quality only through verification and validation activities and controls on the development process has proved to be problematic. Therefore, this common position provides guidance for the assessment of the potential for CCF for software. It is recognized that programmable logic devices do not execute software in the conventional sense; however, the application development process using these devices have many similarities with software development, and the deficiencies that may be introduced during the application development process may induce errors in the programmable logic devices that can result in common cause failures of these devices of a type similar to software common cause failure. Although deficiencies with the potential to give rise to software common cause failures can be introduced at all phases of the software life cycle, this common position will only consider the potential for software common cause failures within digital safety system

Occult spondyloarthritis in inflammatory bowel disease.

Science.gov (United States)

Bandinelli, Francesca; Manetti, Mirko; Ibba-Manneschi, Lidia

2016-02-01

Spondyloarthritis (SpA) is a frequent extra-intestinal manifestation in patients with inflammatory bowel disease (IBD), although its real diffusion is commonly considered underestimated. Abnormalities in the microbioma and genetic predisposition have been implicated in the link between bowel and joint inflammation. Otherwise, up to date, pathogenetic mechanisms are still largely unknown and the exact influence of the bowel activity on rheumatic manifestations is not clearly explained. Due to evidence-based results of clinical studies, the interest on clinically asymptomatic SpA in IBD patients increased in the last few years. Actually, occult enthesitis and sacroiliitis are discovered in high percentages of IBD patients by different imaging techniques, mainly enthesis ultrasound (US) and sacroiliac joint X-ray examinations. Several diagnostic approaches and biomarkers have been proposed in an attempt to correctly classify and diagnose clinically occult joint manifestations and to define clusters of risk for patient screening, although definitive results are still lacking. The correct recognition of occult SpA in IBD requires an integrated multidisciplinary approach in order to identify common diagnostic and therapeutic strategies. The use of inexpensive and rapid imaging techniques, such as US and X-ray, should be routinely included in daily clinical practice and trials to correctly evaluate occult SpA, thus preventing future disability and worsening of quality of life in IBD patients.

Pauses in Striatal Cholinergic Interneurons: What is Revealed by Their Common Themes and Variations?

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Yan-Feng Zhang

2017-10-01

Full Text Available Striatal cholinergic interneurons, the so-called tonically active neurons (TANs, pause their firing in response to sensory cues and rewards during classical conditioning and instrumental tasks. The respective pause responses observed can demonstrate many commonalities, such as constant latency and duration, synchronous occurrence in a population of cells, and coincidence with phasic activities of midbrain dopamine neurons (DANs that signal reward predictions and errors. Pauses can however also show divergent properties. Pause latencies and durations can differ in a given TAN between appetitive vs. aversive outcomes in classical conditioning, initial excitation can be present or absent, and a second pause can variably follow a rebound. Despite more than 20 years of study, the functions of these pause responses are still elusive. Our understanding of pause function is hindered by an incomplete understanding of how pauses are generated. In this mini-review article, we compare pause types, as well as current key hypotheses for inputs underlying pauses that include dopamine-induced inhibition through D2-receptors, a GABA input from ventral tegmental area, and a prolonged afterhyperpolarization induced by excitatory input from the cortex or from the thalamus. We review how each of these mechanisms alone explains some but not all aspects of pause responses. These mechanisms might need to operate in specific but variable sets of sequences to generate a full range of pause responses. Alternatively, these mechanisms might operate in conjunction with an underlying control mechanism within cholinergic interneurons which could potentially provide a framework to generate the common themes and variations seen amongst pause responses.

Pitfall in quantum mechanical/molecular mechanical molecular dynamics simulation of small solutes in solution.

Science.gov (United States)

Hu, Hao; Liu, Haiyan

2013-05-30

Developments in computing hardware and algorithms have made direct molecular dynamics simulation with the combined quantum mechanical/molecular mechanical methods affordable for small solute molecules in solution, in which much improved accuracy can be obtained via the quantum mechanical treatment of the solute molecule and even sometimes water molecules in the first solvation shell. However, unlike the conventional molecular mechanical simulations of large molecules, e.g., proteins, in solutions, special care must be taken in the technical details of the simulation, including the thermostat of the solute/solvent system, so that the conformational space of the solute molecules can be properly sampled. We show here that the common setup for classical molecular mechanical molecular dynamics simulations, such as the Berendsen or single Nose-Hoover thermostat, and/or rigid water models could lead to pathological sampling of the solutes' conformation. In the extreme example of a methanol molecule in aqueous solution, improper and sluggish setups could generate two peaks in the distribution of the O-H bond length. We discuss the factors responsible for this somewhat unexpected result and evoke a simple and ancient technical fix-up to resolve this problem.

Mechanical engineering aspects of TFTR

International Nuclear Information System (INIS)

Citrolo, J.C.

1983-04-01

This paper briefly presents the principles which characterize a tokamak and discusses the mechanical aspects of TFTR, particularly the toroidal field coils and the vacuum chamber, in the context of being key components common to all tokamaks. The mechanical loads on these items as well as other design requirements are considered and the solutions to these requirements as executed in TFTR are presented. Future technological developments beyond the scope of TFTR, which are necessary to bring the tokamak concept to a full fusion-power system, are also presented. Additional methods of plasma heating, current drive, and first wall designs are examples of items in this category

Neural mechanisms underlying morphine withdrawal in addicted patients: a review

Directory of Open Access Journals (Sweden)

Nima Babhadiashar

2015-06-01

Full Text Available Morphine is one of the most potent alkaloid in opium, which has substantial medical uses and needs and it is the first active principle purified from herbal source. Morphine has commonly been used for relief of moderate to severe pain as it acts directly on the central nervous system; nonetheless, its chronic abuse increases tolerance and physical dependence, which is commonly known as opiate addiction. Morphine withdrawal syndrome is physiological and behavioral symptoms that stem from prolonged exposure to morphine. A majority of brain regions are hypofunctional over prolonged abstinence and acute morphine withdrawal. Furthermore, several neural mechanisms are likely to contribute to morphine withdrawal. The present review summarizes the literature pertaining to neural mechanisms underlying morphine withdrawal. Despite the fact that morphine withdrawal is a complex process, it is suggested that neural mechanisms play key roles in morphine withdrawal.

Common Law and Un-common Sense

OpenAIRE

Ballard, Roger

2000-01-01

This paper examines the practical and conceptual differences which arise when juries are invited to apply their common sense in assessing reasonable behaviour in the midst of an ethnically plural society. The author explores the conundrums which the increasing salience of ethnic pluralism has now begun to pose in legal terms, most especially with respect to organisation of system for the equitable administration and delivery of justice in the context of an increasingly heterogeneous society. ...

Resistance of Causing Bacteria of Bovine Mastitis in Regard to Common Antimicrobials

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Darío Martínez Pacheco

2013-05-01

Full Text Available The bacteria develop resistence against to the common antimicrobians, which is a limitant in the control and treatment of infectious diseases. In the sistems of production of bovine milk, one problem that affects the quantity and quality of the produced milk, is the mastitis, which in most cases has a bacterian origen. Addition to correct milking routine is used many antibacterial agents that for pharmacokinetics and pharmacodynamics reasons are the first selection for this disease. Some cases the use of antibacterial agents is effective, while in other cases do not, due to the development of bacterial resistence. Recently, it has been possible to identify different mechanisms of resistence developed by bacteria. This has allowed pharmacology researchers to create new drugs or to modify existing, seeking to decrease the inefficacy caused by the mutation of the bacteria as an adaptative response mechanism. Therefore,the objective of this review is to offer an updated document on resistance mechanisms identified.

Ego defense mechanisms in Pakistani medical students: a cross sectional analysis

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Khalid Roha

2010-01-01

Full Text Available Abstract Background Ego defense mechanisms (or factors, defined by Freud as unconscious resources used by the ego to reduce conflict between the id and superego, are a reflection of how an individual deals with conflict and stress. This study assesses the prevalence of various ego defense mechanisms employed by medical students of Karachi, which is a group with higher stress levels than the general population. Methods A questionnaire based cross-sectional study was conducted on 682 students from five major medical colleges of Karachi over 4 weeks in November 2006. Ego defense mechanisms were assessed using the Defense Style Questionnaire (DSQ-40 individually and as grouped under Mature, Immature, and Neurotic factors. Results Lower mean scores of Immature defense mechanisms (4.78 were identified than those for Neurotic (5.62 and Mature (5.60 mechanisms among medical students of Karachi. Immature mechanisms were more commonly employed by males whereas females employed more Neurotic mechanisms than males. Neurotic and Immature defenses were significantly more prevalent in first and second year students. Mature mechanisms were significantly higher in students enrolled in Government colleges than Private institutions (p Conclusions Immature defense mechanisms were less commonly employed than Neurotic and Mature mechanisms among medical students of Karachi. The greater employment of Neurotic defenses may reflect greater stress levels than the general population. Employment of these mechanisms was associated with female gender, enrollment in a private medical college, and students enrolled in the first 2 years of medical school.

The role of geometry in 4-vertex origami mechanics

Science.gov (United States)

Waitukaitis, Scott; Dieleman, Peter; van Hecke, Martin

Origami offers an interesting design platform metamaterials because it strongly couples mechanics with geometry. Even so, most research carried out so far has been limited to one or two particular patterns. I will discuss the full geometrical space of the most common origami building block, the 4-vertex, and show how exotic geometries can have dramatic effects on the mechanics.

Thermodynamic secrets of multidrug resistance: A new take on transport mechanisms of secondary active antiporters.

Science.gov (United States)

Zhang, Xuejun C; Liu, Min; Lu, Guangyuan; Heng, Jie

2018-03-01

Multidrug resistance (MDR) presents a growing challenge to global public health. Drug extrusion transporters play a critical part in MDR; thus, their mechanisms of substrate recognition are being studied in great detail. In this work, we review common structural features of key transporters involved in MDR. Based on our membrane potential-driving hypothesis, we propose a general energy-coupling mechanism for secondary-active antiporters. This putative mechanism provides a common framework for understanding poly-specificity of most-if not all-MDR transporters. © 2017 The Protein Society.

The common and distinct neural bases of affect labeling and reappraisal in healthy adults

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Lisa Jane Burklund

2014-03-01

Full Text Available Emotion regulation is commonly characterized as involving conscious and intentional attempts to change felt emotions, such as, for example, through reappraisal whereby one intentionally decreases the intensity of one’s emotional response to a particular stimulus or situation by reinterpreting it in a less threatening way. However, there is growing evidence and appreciation that some types of emotion regulation are unintentional or incidental, meaning that affective modulation is a consequence but not an explicit goal. For example, affect labeling involves simply verbally labeling the emotional content of an external stimulus or one’s own affective responses without an intentional goal of altering emotional responses, yet has been associated with reduced affective responses at the neural and experiential levels. Although both intentional and incidental emotional regulation strategies have been associated with diminished limbic responses and self-reported distress, little previous research has directly compared their underlying neural mechanisms. In this study, we examined the extent to which incidental and intentional emotion regulation, namely, affect labeling and reappraisal, produced common and divergent neural and self-report responses to aversive images relative to an observe-only control condition in a sample of healthy older adults (N=39. Affect labeling and reappraisal produced common activations in several prefrontal regulatory regions, with affect labeling producing stronger responses in direct comparisons. Affect labeling and reappraisal were also associated with similar decreases in amygdala activity. Finally, affect labeling and reappraisal were associated with correlated reductions in self-reported distress. Together these results point to common neurocognitive mechanisms involved in affect labeling and reappraisal, supporting the idea that intentional and incidental emotion regulation may utilize overlapping neural processes.

Overlapping Patterns of Rapid Evolution in the Nucleic Acid Sensors cGAS and OAS1 Suggest a Common Mechanism of Pathogen Antagonism and Escape.

Science.gov (United States)

Hancks, Dustin C; Hartley, Melissa K; Hagan, Celia; Clark, Nathan L; Elde, Nels C

2015-05-01

A diverse subset of pattern recognition receptors (PRRs) detects pathogen-associated nucleic acids to initiate crucial innate immune responses in host organisms. Reflecting their importance for host defense, pathogens encode various countermeasures to evade or inhibit these immune effectors. PRRs directly engaged by pathogen inhibitors often evolve under recurrent bouts of positive selection that have been described as molecular 'arms races.' Cyclic GMP-AMP synthase (cGAS) was recently identified as a key PRR. Upon binding cytoplasmic double-stranded DNA (dsDNA) from various viruses, cGAS generates the small nucleotide secondary messenger cGAMP to signal activation of innate defenses. Here we report an evolutionary history of cGAS with recurrent positive selection in the primate lineage. Recent studies indicate a high degree of structural similarity between cGAS and 2'-5'-oligoadenylate synthase 1 (OAS1), a PRR that detects double-stranded RNA (dsRNA), despite low sequence identity between the respective genes. We present comprehensive comparative evolutionary analysis of cGAS and OAS1 primate sequences and observe positive selection at nucleic acid binding interfaces and distributed throughout both genes. Our data revealed homologous regions with strong signatures of positive selection, suggesting common mechanisms employed by unknown pathogen encoded inhibitors and similar modes of evasion from antagonism. Our analysis of cGAS diversification also identified alternately spliced forms missing multiple sites under positive selection. Further analysis of selection on the OAS family in primates, which comprises OAS1, OAS2, OAS3 and OASL, suggests a hypothesis where gene duplications and domain fusion events result in paralogs that provide another means of escaping pathogen inhibitors. Together our comparative evolutionary analysis of cGAS and OAS provides new insights into distinct mechanisms by which key molecular sentinels of the innate immune system have adapted

Overlapping Patterns of Rapid Evolution in the Nucleic Acid Sensors cGAS and OAS1 Suggest a Common Mechanism of Pathogen Antagonism and Escape.

Directory of Open Access Journals (Sweden)

Dustin C Hancks

2015-05-01

Full Text Available A diverse subset of pattern recognition receptors (PRRs detects pathogen-associated nucleic acids to initiate crucial innate immune responses in host organisms. Reflecting their importance for host defense, pathogens encode various countermeasures to evade or inhibit these immune effectors. PRRs directly engaged by pathogen inhibitors often evolve under recurrent bouts of positive selection that have been described as molecular 'arms races.' Cyclic GMP-AMP synthase (cGAS was recently identified as a key PRR. Upon binding cytoplasmic double-stranded DNA (dsDNA from various viruses, cGAS generates the small nucleotide secondary messenger cGAMP to signal activation of innate defenses. Here we report an evolutionary history of cGAS with recurrent positive selection in the primate lineage. Recent studies indicate a high degree of structural similarity between cGAS and 2'-5'-oligoadenylate synthase 1 (OAS1, a PRR that detects double-stranded RNA (dsRNA, despite low sequence identity between the respective genes. We present comprehensive comparative evolutionary analysis of cGAS and OAS1 primate sequences and observe positive selection at nucleic acid binding interfaces and distributed throughout both genes. Our data revealed homologous regions with strong signatures of positive selection, suggesting common mechanisms employed by unknown pathogen encoded inhibitors and similar modes of evasion from antagonism. Our analysis of cGAS diversification also identified alternately spliced forms missing multiple sites under positive selection. Further analysis of selection on the OAS family in primates, which comprises OAS1, OAS2, OAS3 and OASL, suggests a hypothesis where gene duplications and domain fusion events result in paralogs that provide another means of escaping pathogen inhibitors. Together our comparative evolutionary analysis of cGAS and OAS provides new insights into distinct mechanisms by which key molecular sentinels of the innate immune system

The degradation and transport mechanism of a Mg-Nd-Zn-Zr stent in rabbit common carotid artery: A 20-month study.

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Zhang, Jian; Li, Haiyan; Wang, Wu; Huang, Hua; Pei, Jia; Qu, Haiyun; Yuan, Guangyin; Li, Yongdong

2018-03-15

Mg-based stent is a promising candidate of the next generation fully degradable vascular stents. The latest progress includes the CE approval of the Magmaris ® WE43 based drug eluting stent. However, so far, the long term (more than 1 year implantation) in vivo degradation and the physiological effects caused by the degradation products were still unclear. In this study, a 20 month observation was carried out after the bare Mg-Nd-Zn-Zr (abbr. JDBM) stent prototype was implanted into the common carotid artery of New Zealand white rabbit in order to evaluate its safety, efficacy and especially degradation behavior. The degradation of the main second phase Mg 12 Nd was also studied. Results showed that the bare JDBM stent had good safety and efficacy with a complete re-endothelialization within 28 days. The JDBM stent struts were mostly replaced in situ by degradation products in 4 month. The important finding was that the volume and Ca concentration of the degradation products decreased in the long term, eliminating the clinicians' concern of possible vessel calcification. In addition, the alloying elements Mg and Zn in the stent could be safely metabolized as continuous enrichment in any of the main organs were not detected although Nd and Zr showed an abrupt increase in spleen and liver after 1 month implantation. Collectively, the long term in vivo results showed the rapid re-endothelialization of JDBM stent and the long term safety of the degradation products, indicating its great potential as the backbone of the fully degradable vascular stent. Mg-based stent is a promising candidate of the next generation fully degradable stents, especially after the recent market launch of one of its kind (Magmaris). However the fundamental question about the long term degradation and metabolic mechanism of Mg-based stent and its degradation products remain unanswered. We implanted our patented Mg-Nd-Zn-Zr bare stent into the common carotid artery of rabbits and

Dysregulation of Innate Lymphoid Cells in Common Variable Immunodeficiency.

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Maglione, Paul J; Cols, Montserrat; Cunningham-Rundles, Charlotte

2017-10-05

Common variable immunodeficiency (CVID) is the most prevalent symptomatic primary immune deficiency. With widespread use of immunoglobulin replacement therapy, non-infectious complications, such as autoimmunity, chronic intestinal inflammation, and lung disease, have replaced infections as the major cause of morbidity and mortality in this immune deficiency. The pathogenic mechanisms that underlie the development of these complications in CVID are not known; however, there have been numerous associated laboratory findings. Among the most intriguing of these associations is elevation of interferon signature genes in CVID patients with inflammatory/autoimmune complications, as a similar gene expression profile is found in systemic lupus erythematosus and other chronic inflammatory diseases. Linked with this heightened interferon signature in CVID is an expansion of circulating IFN-γ-producing innate lymphoid cells. Innate lymphoid cells are key regulators of both protective and pathogenic immune responses that have been extensively studied in recent years. Further exploration of innate lymphoid cell biology in CVID may uncover key mechanisms underlying the development of inflammatory complications in these patients and may inspire much needed novel therapeutic approaches.

Action and Perception Are Temporally Coupled by a Common Mechanism That Leads to a Timing Misperception

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Astefanoaei, Corina; Daye, Pierre M.; FitzGibbon, Edmond J.; Creanga, Dorina-Emilia; Rufa, Alessandra; Optican, Lance M.

2015-01-01

We move our eyes to explore the world, but visual areas determining where to look next (action) are different from those determining what we are seeing (perception). Whether, or how, action and perception are temporally coordinated is not known. The preparation time course of an action (e.g., a saccade) has been widely studied with the gap/overlap paradigm with temporal asynchronies (TA) between peripheral target onset and fixation point offset (gap, synchronous, or overlap). However, whether the subjects perceive the gap or overlap, and when they perceive it, has not been studied. We adapted the gap/overlap paradigm to study the temporal coupling of action and perception. Human subjects made saccades to targets with different TAs with respect to fixation point offset and reported whether they perceived the stimuli as separated by a gap or overlapped in time. Both saccadic and perceptual report reaction times changed in the same way as a function of TA. The TA dependencies of the time change for action and perception were very similar, suggesting a common neural substrate. Unexpectedly, in the perceptual task, subjects misperceived lights overlapping by less than ∼100 ms as separated in time (overlap seen as gap). We present an attention-perception model with a map of prominence in the superior colliculus that modulates the stimulus signal's effectiveness in the action and perception pathways. This common source of modulation determines how competition between stimuli is resolved, causes the TA dependence of action and perception to be the same, and causes the misperception. PMID:25632126

Common injuries related to weightlifting: MR imaging perspective.

Science.gov (United States)

Yu, Joseph S; Habib, Paula A

2005-12-01

Weightlifting has evolved to become a ubiquitous form of exercise. Resistance training has been shown to have beneficial effects on both muscle and osseous maintenance and development. Competitive weightlifting sports continue to enjoy tremendous popularity, with participants striving to establish new standards in performance and more demanding personal goals. Thus, it is not surprising that we have also seen an increase in injuries related to weightlifting. Many of these injuries are radiographically occult and are best suited for evaluation by magnetic resonance (MR) imaging because many involve the soft tissues. In this article, we discuss some of the factors that contribute to these injuries and address the mechanisms of injury and the MR imaging manifestations of the more common injuries.

Common Misconceptions about Cholesterol

Science.gov (United States)

... Venous Thromboembolism Aortic Aneurysm More Common Misconceptions about Cholesterol Updated:Jan 29,2018 How much do you ... are some common misconceptions — and the truth. High cholesterol isn’t a concern for children. High cholesterol ...

Statistical fracture mechanics approach to the strength of brittle rock

International Nuclear Information System (INIS)

Ratigan, J.L.

1981-06-01

Statistical fracture mechanics concepts used in the past for rock are critically reviewed and modifications are proposed which are warranted by (1) increased understanding of fracture provided by modern fracture mechanics and (2) laboratory test data both from the literature and from this research. Over 600 direct and indirect tension tests have been performed on three different rock types; Stripa Granite, Sierra White Granite and Carrara Marble. In several instances assumptions which are common in the literature were found to be invalid. A three parameter statistical fracture mechanics model with Mode I critical strain energy release rate as the variant is presented. Methodologies for evaluating the parameters in this model as well as the more commonly employed two parameter models are discussed. The experimental results and analysis of this research indicate that surfacially distributed flaws, rather than volumetrically distributed flaws are responsible for rupture in many testing situations. For several of the rock types tested, anisotropy (both in apparent tensile strength and size effect) precludes the use of contemporary statistical fracture mechanics models

Glial Tissue Mechanics and Mechanosensing by Glial Cells

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Katarzyna Pogoda

2018-02-01

Full Text Available Understanding the mechanical behavior of human brain is critical to interpret the role of physical stimuli in both normal and pathological processes that occur in CNS tissue, such as development, inflammation, neurodegeneration, aging, and most common brain tumors. Despite clear evidence that mechanical cues influence both normal and transformed brain tissue activity as well as normal and transformed brain cell behavior, little is known about the links between mechanical signals and their biochemical and medical consequences. A multi-level approach from whole organ rheology to single cell mechanics is needed to understand the physical aspects of human brain function and its pathologies. This review summarizes the latest achievements in the field.

Flavonoids and Melanins: a common strategy across two kingdoms.

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Carletti, Giorgia; Nervo, Giuseppe; Cattivelli, Luigi

2014-01-01

Ultraviolet (UV) radiations alter a number of metabolic functions in vivant. They produce damages to lipids, nucleic acids and proteins, generating reactive oxygen species such as singlet oxygen (O2), hydroxyl radical (HO) and superoxide anion (O2 (-)). Plants and animals, after their water emersion, have developed biochemical mechanisms to protect themselves from that environmental threat through a common strategy. Melanins in animals and flavonoids in plants are antioxidant pigments acting as free radical scavenging mechanisms. Both are phenol compounds constitutively synthesized and enhanced after exposure to UV rays, often conferring a red-brown-dark tissue pigmentation. Noteworthy, beside anti-oxidant scavenging activity, melanins and flavonoids have acquired secondary functions that, both in plants and animals, concern reproductions and fitness. Plants highly pigmented are more resistant to biotic and abiotic stresses. Darker wild vertebrates are generally more aggressive, sexually active and resistant to stress than lighter individuals. Flavonoids have been associated with signal attraction between flowers and insects and with plant-plant interaction. Melanin pigmentation has been proposed as trait in bird communication, acting as honest signals of quality. This review shows how the molecular mechanisms leading to tissue pigmentation have many functional analogies between plants and animals and how their origin lies in simpler organisms such as Cyanobacteria. Comparative studies between plant and animal kingdoms can reveal new insight of the antioxidant strategies in vivant.

On the mechanism of muonium formation in liquid water

International Nuclear Information System (INIS)

Byakov, V.M.; Firsov, V.G.

1986-01-01

The experimental data on the influence of some solutes in water on formation probabilities of muonium, positronium and radiolytic hydrogen are compared. It is shown that the inhibiting action is very similar in all cases. This means that the formation mechanisms of muonium, positronium and radiolytic hydrogen have common features. Taking into account that the formation of radiolytic hydrogen and that of positronium proceeds via recombination mechanism with unsolvated electron as one of the precursors, it is asserted that the muonium formation mechanism is similar. (author)

Vitiligo and Autoimmune Thyroid Disorders

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Enke Baldini

2017-10-01

Full Text Available Vitiligo represents the most common cause of acquired skin, hair, and oral depigmentation, affecting 0.5–1% of the population worldwide. It is clinically characterized by the appearance of disfiguring circumscribed skin macules following melanocyte destruction by autoreactive cytotoxic T lymphocytes. Patients affected by vitiligo usually show a poorer quality of life and are more likely to suffer from depressive symptoms, particularly evident in dark-skinned individuals. Although vitiligo is a non-fatal disease, exposure of affected skin to UV light increases the chance of skin irritation and predisposes to skin cancer. In addition, vitiligo has been associated with other rare systemic disorders due to the presence of melanocytes in other body districts, such as in eyes, auditory, nervous, and cardiac tissues, where melanocytes are thought to have roles different from that played in the skin. Several pathogenetic models have been proposed to explain vitiligo onset and progression, but clinical and experimental findings point mainly to the autoimmune hypothesis as the most qualified one. In this context, it is of relevance the strong association of vitiligo with other autoimmune diseases, in particular with autoimmune thyroid disorders, such as Hashimoto thyroiditis and Graves’ disease. In this review, after a brief overview of vitiligo and its pathogenesis, we will describe the clinical association between vitiligo and autoimmune thyroid disorders and discuss the possible underlying molecular mechanism(s.

Mechanical site preparation for forest restoration

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Magnus Lof; Daniel C. Dey; Rafael M. Navarro; Douglass F. Jacobs

2012-01-01

Forest restoration projects have become increasingly common around the world and planting trees is almost always a key component. Low seedling survival and growth may result in restoration failures and various mechanical site preparation techniques for treatment of soils and vegetation are important tools used to help counteract this. In this article, we synthesize the...

Quantum Backaction Evading Measurement of Collective Mechanical Modes.

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Ockeloen-Korppi, C F; Damskägg, E; Pirkkalainen, J-M; Clerk, A A; Woolley, M J; Sillanpää, M A

2016-09-30

The standard quantum limit constrains the precision of an oscillator position measurement. It arises from a balance between the imprecision and the quantum backaction of the measurement. However, a measurement of only a single quadrature of the oscillator can evade the backaction and be made with arbitrary precision. Here we demonstrate quantum backaction evading measurements of a collective quadrature of two mechanical oscillators, both coupled to a common microwave cavity. The work allows for quantum state tomography of two mechanical oscillators, and provides a foundation for macroscopic mechanical entanglement and force sensing beyond conventional quantum limits.

On interference of cumulative proton production mechanisms

International Nuclear Information System (INIS)

Braun, M.A.; Vechernin, V.V.

1993-01-01

The dynamical picture of the cumulative proton production in hA-collisions by means of diagram analysis with NN interaction described by a non-relativistic NN potential is considered. The contributions of the various mechanisms (spectator, direct and rescattering) for backward hemisphere proton production within the framework of this common approach is calculated. The emphasis is on the comparison of the relative contributions of these mechanisms for various angles, taking into account the interference of these contributions. Comparison with experimental data is also presented. (author)

Quantum mechanical determination of atomic polarizabilities of ionic liquids.

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Heid, Esther; Szabadi, András; Schröder, Christian

2018-04-25

The distribution of a molecule's polarizability to individual atomic sites is inevitable to develop accurate polarizable force fields. We present the direct quantum mechanical calculation of atomic polarizabilities of 27 common ionic liquids. The method is superior to previously published distribution routines based on large databases of the molecular polarizability, and enables the correct description of any ionic liquid and its peculiarities within the quantum mechanical framework.

Potential mechanisms behind contrast medium-induced nephropathy

African Journals Online (AJOL)

How contrast medium-induced nephropathy (CIN) comes about is poorly understood, although CIN is a common cause of acute renal failure. Hitherto, the various studies performed have led to different interpretations and partially contradictory conclusions. This article aimed to review the mechanisms underlying CIN and to ...

Cellular Mechanisms of Somatic Stem Cell Aging

Science.gov (United States)

Jung, Yunjoon

2014-01-01

Tissue homeostasis and regenerative capacity rely on rare populations of somatic stem cells endowed with the potential to self-renew and differentiate. During aging, many tissues show a decline in regenerative potential coupled with a loss of stem cell function. Cells including somatic stem cells have evolved a series of checks and balances to sense and repair cellular damage to maximize tissue function. However, during aging the mechanisms that protect normal cell function begin to fail. In this review, we will discuss how common cellular mechanisms that maintain tissue fidelity and organismal lifespan impact somatic stem cell function. We will highlight context-dependent changes and commonalities that define aging, by focusing on three age-sensitive stem cell compartments: blood, neural, and muscle. Understanding the interaction between extrinsic regulators and intrinsic effectors that operate within different stem cell compartments is likely to have important implications for identifying strategies to improve health span and treat age-related degenerative diseases. PMID:24439814

How Common Is PTSD?

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... Center for PTSD » Public » How Common Is PTSD? PTSD: National Center for PTSD Menu Menu PTSD PTSD Home For the Public ... here Enter ZIP code here How Common Is PTSD? Public This section is for Veterans, General Public, ...

The common ancestry of life

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Wolf Yuri I

2010-11-01

Full Text Available Abstract Background It is common belief that all cellular life forms on earth have a common origin. This view is supported by the universality of the genetic code and the universal conservation of multiple genes, particularly those that encode key components of the translation system. A remarkable recent study claims to provide a formal, homology independent test of the Universal Common Ancestry hypothesis by comparing the ability of a common-ancestry model and a multiple-ancestry model to predict sequences of universally conserved proteins. Results We devised a computational experiment on a concatenated alignment of universally conserved proteins which shows that the purported demonstration of the universal common ancestry is a trivial consequence of significant sequence similarity between the analyzed proteins. The nature and origin of this similarity are irrelevant for the prediction of "common ancestry" of by the model-comparison approach. Thus, homology (common origin of the compared proteins remains an inference from sequence similarity rather than an independent property demonstrated by the likelihood analysis. Conclusion A formal demonstration of the Universal Common Ancestry hypothesis has not been achieved and is unlikely to be feasible in principle. Nevertheless, the evidence in support of this hypothesis provided by comparative genomics is overwhelming. Reviewers this article was reviewed by William Martin, Ivan Iossifov (nominated by Andrey Rzhetsky and Arcady Mushegian. For the complete reviews, see the Reviewers' Report section.

Microvesicles/exosomes as potential novel biomarkers of metabolic diseases

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Müller G

2012-08-01

Full Text Available Günter MüllerDepartment of Biology 1, Genetics, Ludwig-Maximilians University Munich, Biocenter, Munich, GermanyAbstract: Biomarkers are of tremendous importance for the prediction, diagnosis, and observation of the therapeutic success of common complex multifactorial metabolic diseases, such as type II diabetes and obesity. However, the predictive power of the traditional biomarkers used (eg, plasma metabolites and cytokines, body parameters is apparently not sufficient for reliable monitoring of stage-dependent pathogenesis starting with the healthy state via its initiation and development to the established disease and further progression to late clinical outcomes. Moreover, the elucidation of putative considerable differences in the underlying pathogenetic pathways (eg, related to cellular/tissue origin, epigenetic and environmental effects within the patient population and, consequently, the differentiation between individual options for disease prevention and therapy – hallmarks of personalized medicine – plays only a minor role in the traditional biomarker concept of metabolic diseases. In contrast, multidimensional and interdependent patterns of genetic, epigenetic, and phenotypic markers presumably will add a novel quality to predictive values, provided they can be followed routinely along the complete individual disease pathway with sufficient precision. These requirements may be fulfilled by small membrane vesicles, which are so-called exosomes and microvesicles (EMVs that are released via two distinct molecular mechanisms from a wide variety of tissue and blood cells into the circulation in response to normal and stress/pathogenic conditions and are equipped with a multitude of transmembrane, soluble and glycosylphosphatidylinositol-anchored proteins, mRNAs, and microRNAs. Based on the currently available data, EMVs seem to reflect the diverse functional and dysfunctional states of the releasing cells and tissues along the

Alcohol use disorders increase the risk for mechanical ventilation in medical patients.

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de Wit, Marjolein; Best, Al M; Gennings, Chris; Burnham, Ellen L; Moss, Marc

2007-07-01

Annually, more than 300,000 patients receive mechanical ventilation in an intensive care unit in the United States. The hospital mortality for ventilated patients may approach 50%, depending on the primary diagnosis. In trauma and surgical patients, a diagnosis of alcohol use disorder (AUD) is common and is associated with a prolonged duration of mechanical ventilation. The objective of this study is to determine whether the presence of AUD and the development of alcohol withdrawal are associated with an increased use and duration of mechanical ventilation in patients with medical disorders that commonly require intensive care unit admission. We performed a retrospective cohort study using the Nationwide Inpatient Sample, a large all-payer inpatient database representing approximately 1,000 hospitals. For the years 2002 to 2003, adult patients with 1 of the 6 most common diagnoses associated with medical intensive care unit admission were included in the study. Both univariate analysis and multivariable logistic regression were performed to determine whether AUD and alcohol withdrawal were independently associated with the use and duration of mechanical ventilation in these patients. There were a total 785,602 patients who fulfilled 1 of the 6 diagnoses, 26,577 (3.4%) had AUD, 3,967 (0.5%) had alcohol withdrawal, and 65,071 (8.3%) underwent mechanical ventilation (53% or =96 hours). Independent of the medical diagnosis, AUD was associated with an increased risk of requiring mechanical ventilation (13.7 vs 8.1%, odds ratio=1.49, 95% confidence interval [1.414; 1.574], palcohol withdrawal was associated with a longer duration of mechanical ventilation (57 vs 47%> or =96 hours, odds ratio=1.48, 95% confidence interval [1.266; 1.724], palcohol withdrawal is associated with a longer duration of mechanical ventilation.

OCCUPATION COMMONLY ASSOCIATED WITH CONTACT DERMATITIS

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Elice Wijaya

2013-12-01

Full Text Available Normal 0 false false false EN-US X-NONE X-NONE Occupational skin diseases are a widespread problem. Despite numerous protective mechanisms, the skin remains vulnerable to new irritants found in the workplace. As a result, many workers in different occupations suffer from occupational skin diseases. From the data at Sanglah Hospital in Dermatology Department, it should be noted that there is increasing number of new cases of contact dermatitis in period of January 2000 until December 2005, from 10,16% until 13,36% in the next year and relatively stable in the next four years. Occupations commonly associated with contact dermatitis are agriculture workers, construction workers, dental workers, electronic workers, florists, food workers, hairdressers, haousekeeping personnel, machinist, mechanics, medical workers, office workers, photographers, printers, textile workers. /* Style Definitions */ table.MsoNormalTable {mso-style-name:"Table Normal"; mso-tstyle-rowband-size:0; mso-tstyle-colband-size:0; mso-style-noshow:yes; mso-style-priority:99; mso-style-qformat:yes; mso-style-parent:""; mso-padding-alt:0in 5.4pt 0in 5.4pt; mso-para-margin:0in; mso-para-margin-bottom:.0001pt; mso-pagination:widow-orphan; font-size:11.0pt; font-family:"Calibri","sans-serif"; mso-ascii-font-family:Calibri; mso-ascii-theme-font:minor-latin; mso-fareast-font-family:"Times New Roman"; mso-fareast-theme-font:minor-fareast; mso-hansi-font-family:Calibri; mso-hansi-theme-font:minor-latin; mso-bidi-font-family:"Times New Roman"; mso-bidi-theme-font:minor-bidi;}

Advances in mechanics and mathematics

CERN Document Server

Ogden, Ray

2002-01-01

Advances in Mechanics and Mathematics (AMMA) is intended to bridge the gap by providing multi-disciplinary publications. This volume, AMMA 2002, includes two parts with three articles by four subject experts. Part 1 deals with nonsmooth static and dynamic systems. A systematic mathematical theory for multibody dynamics with unilateral and frictional constraints and a brief introduction to hemivariational inequalities together with some new developments in nonsmooth semi-linear elliptic boundary value problems are presented. Part 2 provides a comprehensive introduction and the latest research on dendritic growth in fluid mechanics, one of the most profound and fundamental subjects in the area of interfacial pattern formation, a commonly observed phenomenon in crystal growth and solidification processes.

Mechanics of solids and fluids

International Nuclear Information System (INIS)

Ziegler, F.

1991-01-01

This book is a comprehensive treatise on the mechanics of solids and fluids, with a significant application to structural mechanics. In reading through the text, I can not help being impressed with Dr. Ziegler's command of both historical and contemporary developments of theoretical and applied mechanics. The book is a unique volume which contains information not easily found throughout the related literature. The book opens with a fundamental consideration of the kinematics of particle motion, followed by those of rigid body and deformable medium .In the latter case, both small and finite deformation have been presented concisely, paving the way for the constitutive description given later in the book. In both chapters one and two, the author has provided sufficient applications of the theoretical principles introduced. Such a connection between theory and appication is a common theme throughout every chapter, and is quite an attractive feature of the book

Inheritance Law between Common and Civil Law - As exemplified by life-long support contracts

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Jadranka Đorđević-Crnobrnja

2016-02-01

Full Text Available The dualism between common law and civil law in Serbia has been examined in theoretical and factographical ethnological and legal literature, yet this problem in the sphere of inheritance law has been considered mostly within the context of inequality between the sexes in matters of inheritance. As a result, the question of the connection between life-long support contracts and inheritance remains unexplored, despite the fact that through the analysis of inheritance practices based on this kind of contract the influence of socio-cultural mechanisms on the institution of inheritance can be clearly observed. These insights, together with the fact that a dualism and parallelism of civil and common have existed in Serbia for more than a century, have inspired an analysis of life-long support contracts in order to problematize the relation between common law and civil law in practice.

MDEP Common Position CP-VICWG-01. Common Position: Establishment of Common QA/QM Criteria for the Multinational Vendor Inspection CP-VICWG-01

International Nuclear Information System (INIS)

2015-01-01

This document provides a set of common positions for harmonizing inspection criteria called 'Common QA/QM Criteria' which will be used in Multinational Vendor Inspections. This document was prepared by the Vendor Inspection Co-operation Working Group (VICWG) of the Multinational Design Evaluation Program (MDEP). The 'Common QA/QM Criteria' provides the basic areas for consideration when performing Vendor Inspections. The criteria have been developed in conformity with International Codes and Standards such as IAEA, ISO, etc. that MDEP member countries have adopted

Commons problems, common ground: Earth-surface dynamics and the social-physical interdisciplinary frontier

Science.gov (United States)

Lazarus, E.

2015-12-01

In the archetypal "tragedy of the commons" narrative, local farmers pasture their cows on the town common. Soon the common becomes crowded with cows, who graze it bare, and the arrangement of open access to a shared resource ultimately fails. The "tragedy" involves social and physical processes, but the denouement depends on who is telling the story. An economist might argue that the system collapses because each farmer always has a rational incentive to graze one more cow. An ecologist might remark that the rate of grass growth is an inherent control on the common's carrying capacity. And a geomorphologist might point out that processes of soil degradation almost always outstrip processes of soil production. Interdisciplinary research into human-environmental systems still tends to favor disciplinary vantages. In the context of Anthropocene grand challenges - including fundamental insight into dynamics of landscape resilience, and what the dominance of human activities means for processes of change and evolution on the Earth's surface - two disciplines in particular have more to talk about than they might think. Here, I use three examples - (1) beach nourishment, (2) upstream/downstream fluvial asymmetry, and (3) current and historical "land grabbing" - to illustrate a range of interconnections between physical Earth-surface science and common-pool resource economics. In many systems, decision-making and social complexity exert stronger controls on landscape expression than do physical geomorphological processes. Conversely, human-environmental research keeps encountering multi-scale, emergent problems of resource use made 'common-pool' by water, nutrient and sediment transport dynamics. Just as Earth-surface research can benefit from decades of work on common-pool resource systems, quantitative Earth-surface science can make essential contributions to efforts addressing complex problems in environmental sustainability.

Twenty-First Century Diseases: Commonly Rare and Rarely Common?

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Daunert, Sylvia; Sittampalam, Gurusingham Sitta; Goldschmidt-Clermont, Pascal J

2017-09-20

Alzheimer's drugs are failing at a rate of 99.6%, and success rate for drugs designed to help patients with this form of dementia is 47 times less than for drugs designed to help patients with cancers ( www.scientificamerican.com/article/why-alzheimer-s-drugs-keep-failing/2014 ). How can it be so difficult to produce a valuable drug for Alzheimer's disease? Each human has a unique genetic and epigenetic makeup, thus endowing individuals with a highly unique complement of genes, polymorphisms, mutations, RNAs, proteins, lipids, and complex sugars, resulting in distinct genome, proteome, metabolome, and also microbiome identity. This editorial is taking into account the uniqueness of each individual and surrounding environment, and stresses the point that a more accurate definition of a "common" disorder could be simply the amalgamation of a myriad of "rare" diseases. These rare diseases are being grouped together because they share a rather constant complement of common features and, indeed, generally respond to empirically developed treatments, leading to a positive outcome consistently. We make the case that it is highly unlikely that such treatments, despite their statistical success measured with large cohorts using standardized clinical research, will be effective on all patients until we increase the depth and fidelity of our understanding of the individual "rare" diseases that are grouped together in the "buckets" of common illnesses. Antioxid. Redox Signal. 27, 511-516.