Current strategies for non-pharmacological therapy of long-standing persistent atrial fibrillation

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Teiichi Yamane, MD, PhD

2012-06-01

Full Text Available Non-pharmacological rhythm control of atrial fibrillation (AF is becoming increasingly important in our aging society. Advancement of catheter ablation techniques in the last decade has provided a cure for AF patients, with a nearly established efficiency for paroxysmal cases. However, since ablation of persistent/chronic AF cases is still challenging, early treatment of paroxysmal AF before transformation to the persistent/chronic form is mandatory. Although there is a consensus that pulmonary vein isolation is the first-line approach for ablation of long-standing persistent AF, similar to that for paroxysmal AF, there are still wide variations in the adjunctive approach to modify the atrial substrate of persistent AF (anatomical linear ablation, electrogram-based complex fractionated atrial electrogram ablation, ganglionated plexus ablation, etc.. Since data comparing the effectiveness of these adjunctive approaches are still lacking, large-scale controlled trials evaluating the effect of catheter ablation in diverse patient populations on a long-term basis are needed to establish the appropriate approach for long-standing persistent AF. Furthermore, the development of de novo ablation methods (new energies, new targets, etc. is expected to improve ablation outcome in patients with long-standing persistent AF.

Estimation of TiO₂ nanoparticle-induced genotoxicity persistence and possible chronic gastritis-induction in mice.

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Mohamed, Hanan Ramadan Hamad

2015-09-01

Titanium dioxide (TiO2) nanoparticles are widely used as a food additive and coloring agent in many consumer products however limited data is available on the nano-TiO2 induced genotoxicity persistence. Thus, this study investigated the persistence of nano-TiO2 induced genotoxicity and possible induction of chronic gastritis in mice. The mice were orally administered 5, 50 or 500 mg/kg body weight nano-TiO2 for five consecutive days, and then mice from each dosage group were sacrificed 24 h or one or two weeks after the last treatment. The administration of nano-TiO2 resulted in persistent apoptotic DNA fragmentation and mutations in p53 exons (5-8) as well as significant persistent elevations in malondialdehyde and nitric oxide levels and decreases in the reduced glutathione level and catalase activity compared with the control mice in a dose- and time-dependent manner. Necrosis and inflammation were evident upon histological examination. These findings could be attributed to the persistent accumulation of nano-TiO2 at the tested doses at all three time points. Based on these findings, we conclude that the administration of nano-TiO2, even at low doses, leads to persistent accumulation of nano-TiO2 in mice, resulting in persistent inflammation, apoptosis and oxidative stress, ultimately leading to the induction of chronic gastritis. Copyright © 2015 Elsevier Ltd. All rights reserved.

Persistence of Tetracapsuloides bryosalmonae (Myxozoa) in chronically infected brown trout Salmo trutta.

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Abd-Elfattah, Ahmed; Kumar, Gokhlesh; Soliman, Hatem; El-Matbouli, Mansour

2014-08-21

Proliferative kidney disease (PKD) is a widespread disease of farmed and wild salmonid populations in Europe and North America, caused by the myxozoan parasite Tetracapsuloides bryosalmonae. Limited studies have been performed on the epidemiological role in spread of the disease played by fish that survive infection with T. bryosalmonae. The aim of the present study was to evaluate the persistence of T. bryosalmonae developmental stages in chronically infected brown trout Salmo trutta up to 2 yr after initial exposure to laboratory-infected colonies of the parasite's alternate host, the bryozoan Fredericella sultana. Kidney, liver, spleen, intestine, brain, gills and blood were sampled 24, 52, 78 and 104 wk post-exposure (wpe) and tested for T. bryosalmonae by PCR and immunohistochemistry (IHC). Cohabitation trials with specific pathogen free (SPF) F. sultana colonies were conducted to test the viability of T. bryosalmonae. PCR detected T. bryosalmonae DNA in all tissue samples collected at the 4 time points. Developmental stages of T. bryosalmonae were demonstrated by IHC in most samples at the 4 time points. Cohabitation of SPF F. sultana with chronically infected brown trout resulted in successful transmission of T. bryosalmonae to the bryozoan. This study verified the persistence of T. bryosalmonae in chronically infected brown trout and their ability to infect the bryozoan F. sultana up to 104 wpe.

Long-term outcome following splenectomy for chronic and persistent immune thrombocytopenia (ITP) in adults and children : Splenectomy in ITP.

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Ahmed, Rayaz; Devasia, Anup J; Viswabandya, Auro; Lakshmi, Kavitha M; Abraham, Aby; Karl, Sampath; Mathai, John; Jacob, Paul M; Abraham, Deepak; Srivastava, Alok; Mathews, Vikram; George, Biju

2016-09-01

The purpose of this research is to study the outcomes of splenectomy for chronic and persistent immune thrombocytopenia (ITP). This study is a retrospective analysis of 254 patients with chronic or persistent ITP who underwent splenectomy at CMC, Vellore, India between 1995 and 2009. Responses were assessed based on standard criteria. One hundred and sixty seven adults and 87 children with a median age of 29 years (range 2-64) with persistent (n = 103) or chronic ITP (n = 151) was studied. Response was seen in 229 (90.2 %) including CR in 74.4 % at a median time of 1 day (range 1-54). Infections following splenectomy were reported in 16 %. Deaths related to post splenectomy sepsis occurred in 1.57 % and major bleeding in 0.78 %. At median follow-up of 54.3 months (range 1-290), 178 (70.1 %) remain in remission. The 5-year and 10-year overall survival (OS) is 97.4 ± 1.2 % and 94.9 ± 2.1 %, respectively, while the 5-year and 10-year event-free survival (EFS) is 76.5 + 2.9 % and 71.0 + 3.9 %, respectively. Splenectomy is associated with long-term remission rates of >70 % in chronic or persistent ITP.

Thymidine Kinase-Negative Herpes Simplex Virus 1 Can Efficiently Establish Persistent Infection in Neural Tissues of Nude Mice.

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Huang, Chih-Yu; Yao, Hui-Wen; Wang, Li-Chiu; Shen, Fang-Hsiu; Hsu, Sheng-Min; Chen, Shun-Hua

2017-02-15

Herpes simplex virus 1 (HSV-1) establishes latency in neural tissues of immunocompetent mice but persists in both peripheral and neural tissues of lymphocyte-deficient mice. Thymidine kinase (TK) is believed to be essential for HSV-1 to persist in neural tissues of immunocompromised mice, because infectious virus of a mutant with defects in both TK and UL24 is detected only in peripheral tissues, but not in neural tissues, of severe combined immunodeficiency mice (T. Valyi-Nagy, R. M. Gesser, B. Raengsakulrach, S. L. Deshmane, B. P. Randazzo, A. J. Dillner, and N. W. Fraser, Virology 199:484-490, 1994, https://doi.org/10.1006/viro.1994.1150). Here we find infiltration of CD4 and CD8 T cells in peripheral and neural tissues of mice infected with a TK-negative mutant. We therefore investigated the significance of viral TK and host T cells for HSV-1 to persist in neural tissues using three genetically engineered mutants with defects in only TK or in both TK and UL24 and two strains of nude mice. Surprisingly, all three mutants establish persistent infection in up to 100% of brain stems and 93% of trigeminal ganglia of adult nude mice at 28 days postinfection, as measured by the recovery of infectious virus. Thus, in mouse neural tissues, host T cells block persistent HSV-1 infection, and viral TK is dispensable for the virus to establish persistent infection. Furthermore, we found 30- to 200-fold more virus in neural tissues than in the eye and detected glycoprotein C, a true late viral antigen, in brainstem neurons of nude mice persistently infected with the TK-negative mutant, suggesting that adult mouse neurons can support the replication of TK-negative HSV-1. Acyclovir is used to treat herpes simplex virus 1 (HSV-1)-infected immunocompromised patients, but treatment is hindered by the emergence of drug-resistant viruses, mostly those with mutations in viral thymidine kinase (TK), which activates acyclovir. TK mutants are detected in brains of immunocompromised

Pathogen dynamics during invasion and establishment of white-nose syndrome explain mechanisms of host persistence.

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Frick, Winifred F; Cheng, Tina L; Langwig, Kate E; Hoyt, Joseph R; Janicki, Amanda F; Parise, Katy L; Foster, Jeffrey T; Kilpatrick, A Marm

2017-03-01

Disease dynamics during pathogen invasion and establishment determine the impacts of disease on host populations and determine the mechanisms of host persistence. Temporal progression of prevalence and infection intensity illustrate whether tolerance, resistance, reduced transmission, or demographic compensation allow initially declining populations to persist. We measured infection dynamics of the fungal pathogen Pseudogymnoascus destructans that causes white-nose syndrome in bats by estimating pathogen prevalence and load in seven bat species at 167 hibernacula over a decade as the pathogen invaded, became established, and some host populations stabilized. Fungal loads increased rapidly and prevalence rose to nearly 100% at most sites within 2 yr of invasion in six of seven species. Prevalence and loads did not decline over time despite huge reductions in colony sizes, likely due to an extensive environmental reservoir. However, there was substantial variation in fungal load among sites with persisting colonies, suggesting that both tolerance and resistance developed at different sites in the same species. In contrast, one species disappeared from hibernacula within 3 yr of pathogen invasion. Variable host responses to pathogen invasion require different management strategies to prevent disease-induced extinction and to facilitate evolution of tolerance or resistance in persisting populations. © 2016 by the Ecological Society of America.

GLT1 overexpression reverses established neuropathic pain-related behavior and attenuates chronic dorsal horn neuron activation following cervical spinal cord injury.

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Falnikar, Aditi; Hala, Tamara J; Poulsen, David J; Lepore, Angelo C

2016-03-01

Development of neuropathic pain occurs in a major portion of traumatic spinal cord injury (SCI) patients, resulting in debilitating and often long-term physical and psychological burdens. Following SCI, chronic dysregulation of extracellular glutamate homeostasis has been shown to play a key role in persistent central hyperexcitability of superficial dorsal horn neurons that mediate pain neurotransmission, leading to various forms of neuropathic pain. Astrocytes express the major CNS glutamate transporter, GLT1, which is responsible for the vast majority of functional glutamate uptake, particularly in the spinal cord. In our unilateral cervical contusion model of mouse SCI that is associated with ipsilateral forepaw heat hypersensitivity (a form of chronic at-level neuropathic pain-related behavior), we previously reported significant and long-lasting reductions in GLT1 expression and functional GLT1-mediated glutamate uptake in cervical spinal cord dorsal horn. To therapeutically address GLT1 dysfunction following cervical contusion SCI, we injected an adeno-associated virus type 8 (AAV8)-Gfa2 vector into the superficial dorsal horn to increase GLT1 expression selectively in astrocytes. Compared to both contusion-only animals and injured mice that received AAV8-eGFP control injection, AAV8-GLT1 delivery increased GLT1 protein expression in astrocytes of the injured cervical spinal cord dorsal horn, resulting in a significant and persistent reversal of already-established heat hypersensitivity. Furthermore, AAV8-GLT1 injection significantly reduced expression of the transcription factor and marker of persistently increased neuronal activation, ΔFosB, in superficial dorsal horn neurons. These results demonstrate that focal restoration of GLT1 expression in the superficial dorsal horn is a promising target for treating chronic neuropathic pain following SCI. © 2015 Wiley Periodicals, Inc.

An Online Cross-Sectional Comparison of Women With Symptoms of Persistent Genital Arousal, Painful Persistent Genital Arousal, and Chronic Vulvar Pain.

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Jackowich, Robyn A; Pink, Leah; Gordon, Allan; Poirier, Évéline; Pukall, Caroline F

2018-04-01

Persistent genital arousal disorder (PGAD) is an understudied condition characterized by unwanted physiologic genital arousal in the absence of subjective sexual arousal. Markos and Dinsmore (Int J STD AIDS 2013;24:852-858) theorized that PGAD shares a number of similarities with vulvodynia (unexplained chronic vulvar pain [CVP]), including symptom characteristics and comorbidities. To compare medical histories, symptom characteristics, pain characteristics, and daily functioning among women with persistent genital pain (PGA) (n = 42), painful PGA (n = 37), and CVP (n = 42) symptoms. An online cross-sectional survey was conducted from October 2015 through April 2016. Self-report measures of symptoms, diagnosed medical conditions, pain characteristics (McGill Pain Questionnaire), catastrophizing (Pain Catastrophizing Scale), and daily functioning (Functional Status Questionnaire) were collected. All 3 groups reported similar medical diagnoses and high frequencies of other chronic pelvic pain conditions. Women in all 3 groups reported comparable ages at symptom onset and timing of symptom expression (ie, constant vs intermittent). Women in the 2 PGA groups reported significantly greater feelings of helplessness than women in the CVP group. Women in the painful PGA and CVP groups endorsed significantly more sensory terms to describe their symptoms compared with women in the PGA group, whereas women in the painful PGA group reported significantly more affective terms to describe their symptoms compared with women in the CVP group. Women in the 2 PGA groups reported that their symptoms interfered significantly with most areas of daily functioning. Given the similarities between PGA and CVP symptoms, women with PGA may benefit from similar assessment, treatment, and research approaches. Limitations of the present study include its sole use of self-report measures; the presence of PGA or CVP symptoms was not confirmed by clinical assessment. However, the anonymous

Impact of chronic illness timing and persistence at school entry on child and parent outcomes: Australian longitudinal study.

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Quach, Jon; Barnett, Tony

2015-01-01

To understand the prevalence and timing of child chronic illness at school entry; associations with child learning, behavior and health-related quality of life and parent mental health at ages 6 to 7, 8 to 9, and 10 to 11 years; and cumulative health care costs. Data were drawn from the first 4 waves of the Longitudinal Study of Australian Children. Children were aged 4 to 5 years at wave 1, with data collection every 2 years. Parent-reported timing of child chronic illness at school entry was categorized into 4 chronic illness groups based on changes between waves 1 and 2: none, resolving, incident and persistent. Child outcomes included: parent-reported quality of life, parent- and teacher-reported behavior, teacher-reported child learning, teacher-reported child-teacher relationship, directly assessed nonverbal and verbal cognition and parent self-reported mental health. Linear regression, adjusted for gender and socioeconomic position, was used to quantify longitudinal associations between chronic illness timing at school entry with outcomes at age 6 to 7 years, 8 to 9 years and 10 to 11 years. Of the 4983 children enrolled in the study, chronic illness data was available for 4464 children (89.6%) at both waves 1 and 2. From wave 1, 6.1% had a condition that persisted until wave 2, while 14.1% had a condition that resolved. Furthermore, 4.7% had a newly emerging condition at wave 2. Compared with the no chronic illness group, children with persistent or emerging chronic illness during school entry had the poorest outcomes (except father's mental health) at all time points, while children with resolving conditions had smaller differences. Child chronic illness at school entry is associated with poorer longitudinal child and maternal outcomes. Therefore, future research should aim to determine the risk and protective factors that contribute to the poorer child and parent outcomes experienced in this growing population. Copyright © 2015 Academic Pediatric

Multivariate prognostic modeling of persistent pain following lumbar discectomy.

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Hegarty, Dominic

2013-03-04

Persistent postsurgical pain (PPSP) affects between 10% and 50% of surgical patients, the development of which is a complex and poorly understood process. To date, most studies on PPSP have focused on specific surgical procedures where individuals do not suffer from chronic pain before the surgical intervention. Individuals who have a chronic nerve injury are likely to have established peripheral and central sensitization which may increase the risk of developing PPSP. Concurrent analyses of the possible factors contributing to the development of PPSP following lumbar discectomy have not been examined.

Haemophilus influenzae genome evolution during persistence in the human airways in chronic obstructive pulmonary disease.

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Pettigrew, Melinda M; Ahearn, Christian P; Gent, Janneane F; Kong, Yong; Gallo, Mary C; Munro, James B; D'Mello, Adonis; Sethi, Sanjay; Tettelin, Hervé; Murphy, Timothy F

2018-04-03

Nontypeable Haemophilus influenzae (NTHi) exclusively colonize and infect humans and are critical to the pathogenesis of chronic obstructive pulmonary disease (COPD). In vitro and animal models do not accurately capture the complex environments encountered by NTHi during human infection. We conducted whole-genome sequencing of 269 longitudinally collected cleared and persistent NTHi from a 15-y prospective study of adults with COPD. Genome sequences were used to elucidate the phylogeny of NTHi isolates, identify genomic changes that occur with persistence in the human airways, and evaluate the effect of selective pressure on 12 candidate vaccine antigens. Strains persisted in individuals with COPD for as long as 1,422 d. Slipped-strand mispairing, mediated by changes in simple sequence repeats in multiple genes during persistence, regulates expression of critical virulence functions, including adherence, nutrient uptake, and modification of surface molecules, and is a major mechanism for survival in the hostile environment of the human airways. A subset of strains underwent a large 400-kb inversion during persistence. NTHi does not undergo significant gene gain or loss during persistence, in contrast to other persistent respiratory tract pathogens. Amino acid sequence changes occurred in 8 of 12 candidate vaccine antigens during persistence, an observation with important implications for vaccine development. These results indicate that NTHi alters its genome during persistence by regulation of critical virulence functions primarily by slipped-strand mispairing, advancing our understanding of how a bacterial pathogen that plays a critical role in COPD adapts to survival in the human respiratory tract.

Persistence of cerebral metabolic abnormalities in chronic schizophrenia as determined by positron emission tomography

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Wolkin, A.; Jaeger, J.; Brodie, J.D.; Wolf, A.P.; Fowler, J.; Rotrosen, J.; Gomez-Mont, F.; Cancro, R.

1985-01-01

Local cerebral metabolic rates were determined by positron emission tomography and the deoxyglucose method in a group of 10 chronic schizophrenic subjects before and after somatic treatment and in eight normal subjects. Before treatment, schizophrenic subjects had markedly lower absolute metabolic activity than did normal controls in both frontal and temporal regions and a trend toward relative hyperactivity in the basal ganglia area. After treatment, their metabolic rates approached those seen in normal subjects in nearly all regions except frontal. Persistence of diminished frontal metabolism was manifested as significant relative hypofrontality. These findings suggest specific loci of aberrant cerebral functioning in chronic schizophrenia and the utility of positron emission tomography in characterizing these abnormalities

[Characteristics of long-term persisting strains of tick-borne encephalitis virus in different forms of the chronic process in animals].

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Frolova, T V; Pogodina, V V; Frolova, M P; Karmysheva, V Ia

1982-01-01

The properties of the Vasilchenko strain of tick-borne encephalitis (TBE) virus and its 3 variants isolated at various stages of persistent infection (383, 453, and 535 days) in Macaca rhesus monkeys and Syrian hamsters with different forms of the chronic TBE were studied. The process characterized by chronic focal inflammatory-degenerative changes in the brains of hamsters without the disturbance of motor functions was associated with persistence of different kinds of virus-specific antigens without virulent virus production. Brain explants of this group of hamsters yielded a virus with cytopathogenic properties but not pathogenic for mice. In a chronic disease developing without the initial acute period, a virus was recovered from hamsters which proved to be virulent for mice and to possess the hemagglutinating and high invasive activity. The most virulent strain was isolated from monkeys with continuously progressive chronic encephalitis with steady paralysis of the extremities. This isolate differed from the parental Vasilchenko strain by a high pathogenicity for hamsters by intracerebral and subcutaneous routes, and thermostability at 50 degrees C.

A self-regulation perspective on avoidance and persistence behavior in chronic pain: new theories, new challenges?

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Van Damme, Stefaan; Kindermans, Hanne

2015-02-01

Behavioral factors such as avoidance and persistence have received massive theoretical and empirical attention in the attempts to explain chronic pain and disability. The determinants of these pain behaviors remain, however, poorly understood. We propose a self-regulation perspective to increase our understanding of pain-related avoidance and persistence. A narrative review. We identified several theoretical views that may help explaining avoidance and persistence behavior, and organized these views around 4 concepts central in self-regulation theories: (1) identity, (2) affective-motivational orientation, (3) goal cognitions, and (4) coping. The review shows that each of these self-regulation perspectives allows for a broadened view in which pain behaviors are not simply considered passive consequences of fear, but proactive strategies to regulate the self when challenged by pain. Several implications and challenges arising from this review are discussed. In particular, a self-regulation perspective does not consider avoidance and persistence behavior to be intrinsically adaptive or maladaptive, but argues that their effects on disability and well-being rather depend on the goals underlying these behaviors. Such view would require a shift in how avoidance and persistence behavior are assessed and approached in clinical interventions.

RegA Plays a Key Role in Oxygen-Dependent Establishment of Persistence and in Isocitrate Lyase Activity, a Critical Determinant of In vivo Brucella suis Pathogenicity

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Elias Abdou

2017-05-01

Full Text Available For aerobic human pathogens, adaptation to hypoxia is a critical factor for the establishment of persistent infections, as oxygen availability is low inside the host. The two-component system RegB/A of Brucella suis plays a central role in the control of respiratory systems adapted to oxygen deficiency, and in persistence in vivo. Using an original “in vitro model of persistence” consisting in gradual oxygen depletion, we compared transcriptomes and proteomes of wild-type and ΔregA strains to identify the RegA-regulon potentially involved in the set-up of persistence. Consecutive to oxygen consumption resulting in growth arrest, 12% of the genes in B. suis were potentially controlled directly or indirectly by RegA, among which numerous transcriptional regulators were up-regulated. In contrast, genes or proteins involved in envelope biogenesis and in cellular division were repressed, suggesting a possible role for RegA in the set-up of a non-proliferative persistence state. Importantly, the greatest number of the RegA-repressed genes and proteins, including aceA encoding the functional IsoCitrate Lyase (ICL, were involved in energy production. A potential consequence of this RegA impact may be the slowing-down of the central metabolism as B. suis progressively enters into persistence. Moreover, ICL is an essential determinant of pathogenesis and long-term interactions with the host, as demonstrated by the strict dependence of B. suis on ICL activity for multiplication and persistence during in vivo infection. RegA regulates gene or protein expression of all functional groups, which is why RegA is a key regulator of B. suis in adaptation to oxygen depletion. This function may contribute to the constraint of bacterial growth, typical of chronic infection. Oxygen-dependent activation of two-component systems that control persistence regulons, shared by several aerobic human pathogens, has not been studied in Brucella sp. before. This work

Identifying asthma and chronic obstructive pulmonary disease in patients with persistent cough presenting to general practitioners : descriptive study

NARCIS (Netherlands)

Thiadens, HA; de Bock, GH; Deker, FW; Huysman, JAN; Springer, MP; Postma, DS

1998-01-01

Objective: To determine the prevalence of asthma and chronic obstructive pulmonary disease in patients not known to have these disorders, who present in general practice with persistent cough, and to ascertain criteria to help general practitioners in diagnosis. Design: Descriptive study. Setting:

Persistent Coxiella burnetii infection in mice overexpressing IL-10: an efficient model for chronic Q fever pathogenesis.

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Soraya Meghari

2008-02-01

Full Text Available Interleukin (IL-10 increases host susceptibility to microorganisms and is involved in intracellular persistence of bacterial pathogens. IL-10 is associated with chronic Q fever, an infectious disease due to the intracellular bacterium Coxiella burnetii. Nevertheless, accurate animal models of chronic C. burnetii infection are lacking. Transgenic mice constitutively expressing IL-10 in macrophages were infected with C. burnetti by intraperitoneal and intratracheal routes and infection was analyzed through real-time PCR and antibody production. Transgenic mice exhibited sustained tissue infection and strong antibody response in contrast to wild-type mice; thus, bacterial persistence was IL-10-dependent as in chronic Q fever. The number of granulomas was low in spleen and liver of transgenic mice infected through the intraperitoneal route, as in patients with chronic Q fever. Macrophages from transgenic mice were unable to kill C. burnetii. C. burnetii-stimulated macrophages were characterized by non-microbicidal transcriptional program consisting of increased expression of arginase-1, mannose receptor, and Ym1/2, in contrast to wild-type macrophages in which expression of inducible NO synthase and inflammatory cytokines was increased. In vivo results emphasized macrophage data. In spleen and liver of transgenic mice infected with C. burnetii by the intraperitoneal route, the expression of arginase-1 was increased while microbicidal pathway consisting of IL-12p40, IL-23p19, and inducible NO synthase was depressed. The overexpression of IL-10 in macrophages prevents anti-infectious competence of host, including the ability to mount granulomatous response and microbicidal pathway in tissues. To our knowledge, this is the first efficient model for chronic Q fever pathogenesis.

Establishment of chronic hepatitis C virus infection: Translational evasion of oxidative defence

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Chan, Shiu-Wan

2014-01-01

Hepatitis C virus (HCV) causes a clinically important disease affecting 3% of the world population. HCV is a single-stranded, positive-sense RNA virus belonging to the genus Hepacivirus within the Flaviviridae family. The virus establishes a chronic infection in the face of an active host oxidative defence, thus adaptation to oxidative stress is key to virus survival. Being a small RNA virus with a limited genomic capacity, we speculate that HCV deploys a different strategy to evade host oxidative defence. Instead of counteracting oxidative stress, it utilizes oxidative stress to facilitate its own survival. Translation is the first step in the replication of a plus strand RNA virus so it would make sense if the virus can exploit the host oxidative defence in facilitating this very first step. This is particularly true when HCV utilizes an internal ribosome entry site element in translation, which is distinctive from that of cap-dependent translation of the vast majority of cellular genes, thus allowing selective translation of genes under conditions when global protein synthesis is compromised. Indeed, we were the first to show that HCV translation was stimulated by an important pro-oxidant-hydrogen peroxide in hepatocytes, suggesting that HCV is able to adapt to and utilize the host anti-viral response to facilitate its own translation thus allowing the virus to thrive under oxidative stress condition to establish chronicity. Understanding how HCV translation is regulated under oxidative stress condition will advance our knowledge on how HCV establishes chronicity. As chronicity is the initiator step in disease progression this will eventually lead to a better understanding of pathogenicity, which is particularly relevant to the development of anti-virals and improved treatments of HCV patients using anti-oxidants. PMID:24659872

Establishment of chronic hepatitis C virus infection: translational evasion of oxidative defence.

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Chan, Shiu-Wan

2014-03-21

Hepatitis C virus (HCV) causes a clinically important disease affecting 3% of the world population. HCV is a single-stranded, positive-sense RNA virus belonging to the genus Hepacivirus within the Flaviviridae family. The virus establishes a chronic infection in the face of an active host oxidative defence, thus adaptation to oxidative stress is key to virus survival. Being a small RNA virus with a limited genomic capacity, we speculate that HCV deploys a different strategy to evade host oxidative defence. Instead of counteracting oxidative stress, it utilizes oxidative stress to facilitate its own survival. Translation is the first step in the replication of a plus strand RNA virus so it would make sense if the virus can exploit the host oxidative defence in facilitating this very first step. This is particularly true when HCV utilizes an internal ribosome entry site element in translation, which is distinctive from that of cap-dependent translation of the vast majority of cellular genes, thus allowing selective translation of genes under conditions when global protein synthesis is compromised. Indeed, we were the first to show that HCV translation was stimulated by an important pro-oxidant-hydrogen peroxide in hepatocytes, suggesting that HCV is able to adapt to and utilize the host anti-viral response to facilitate its own translation thus allowing the virus to thrive under oxidative stress condition to establish chronicity. Understanding how HCV translation is regulated under oxidative stress condition will advance our knowledge on how HCV establishes chronicity. As chronicity is the initiator step in disease progression this will eventually lead to a better understanding of pathogenicity, which is particularly relevant to the development of anti-virals and improved treatments of HCV patients using anti-oxidants.

A Potential Role of Chronic Exposure to Extremely Low-Frequency Electromagnetic Fields in Triggering Persistent Pain Post Breast Cancer Surgery: A Review

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Azadeh Stark

2017-10-01

Full Text Available Persistent Pain after Breast Cancer Surgery (PPBCS ranks second to amputation of extremities for neuropathic chronic pain. PPBCS is associated with the formation of intercostobrachial neuroma bulbs along the lateral chest. These neuroma bulbs are either un-/thinly myelinated and express hypersensitivity to environmental stimuli. Hypersensitivity is manifested as spontaneous pain in response to innocuous stimuli and exaggerating pain in response to noxious stimuli. Excision of neuromas, a common intervention to alleviate pain, has been reported as ineffective. Experience of individuals with amputation of extremities and experimental models of human nerve injuries confirm anthropogenic EMF evoke excruciating pain. Findings from invitro and animal studies clearly support that EMF exposure depolarizes cell membranes, interrupts voltage gated calcium channels which then activates peripheral sensory neurons and initiates propagation of a train of action potentials along the axons of primary afferent nerve fibers. The World Health Organization guidelines, established based on approximation of the human anatomy are limited and assumes no potential compounding effects of nerve injuries or alterations of physiological milieu of tissues. The objective of this review is to direct the attention of the medical community to the potential role of anthropogenic EMF as a risk factor for persistent pain after breast surgery. Patients rely heavily on the recommendations of their providers to manage their pain. The current epidemic of opioid abuse in the US has been partially attributed to the high prescription rate of opioid-based pain killers. Understanding the potential triggers of chronic pain can reduce dependency on pharmaceutical agents.

Persistent effects of chronic clozapine on the cellular and behavioral responses to LSD in mice

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Moreno, José L.; Holloway, Terrell; Umali, Adrienne; Rayannavar, Vinayak; Sealfon, Stuart C.

2013-01-01

Rationale In schizophrenia patients, optimal treatment with antipsychotics requires weeks to months of sustained drug therapy. However, single administration of antipsychotic drugs can reverse schizophrenia-like behavioral alterations in rodent models of psychosis. This raises questions about the physiological relevance of such antipsychotic-like activity. Objective This study evaluates the effects of chronic treatment with clozapine on the cellular and behavioral responses induced by the hallucinogenic serotonin 5-HT2A receptor agonist lysergic acid diethylamide (LSD) as a mouse model of psychosis. Method Mice were treated chronically (21 days) with 25 mg/kg/day clozapine. Experiments were conducted 1, 7, 14, and 21 days after the last clozapine administration. [3H]Ketanserin binding and 5-HT2A mRNA expression were determined in mouse somatosensory cortex. Head-twitch behavior, expression of c-fos, which is induced by all 5-HT2A agonists, and expression of egr-1 and egr-2, which are LSD-like specific, were assayed. Results Head-twitch response was decreased and [3H]ketanserin binding was downregulated in 1, 7, and 14 days after chronic clozapine. 5-HT2A mRNA was reduced 1 day after chronic clozapine. Induction of c-fos, but not egr-1 and egr-2, was rescued 7 days after chronic clozapine. These effects were not observed after short treatment (2 days) with clozapine or chronic haloperidol (1 mg/kg/day). Conclusion Our findings provide a murine model of chronic atypical antipsychotic drug action and suggest downregulation of the 5-HT2A receptor as a potential mechanism involved in these persistent therapeutic-like effects. PMID:22842765

Positive signature-tagged mutagenesis in Pseudomonas aeruginosa: tracking patho-adaptive mutations promoting airways chronic infection.

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Irene Bianconi

2011-02-01

Full Text Available The opportunistic pathogen Pseudomonas aeruginosa can establish life-long chronic infections in the airways of cystic fibrosis (CF patients. Persistent lifestyle is established with P. aeruginosa patho-adaptive variants, which are clonal with the initially-acquired strains. Several reports indicated that P. aeruginosa adapts by loss-of-function mutations which enhance fitness in CF airways and sustain its clonal expansion during chronic infection. To validate this model of P. aeruginosa adaptation to CF airways and to identify novel genes involved in this microevolution, we designed a novel approach of positive-selection screening by PCR-based signature-tagged mutagenesis (Pos-STM in a murine model of chronic airways infection. A systematic positive-selection scheme using sequential rounds of in vivo screenings for bacterial maintenance, as opposed to elimination, generated a list of genes whose inactivation increased the colonization and persistence in chronic airways infection. The phenotypes associated to these Pos-STM mutations reflect alterations in diverse aspects of P. aeruginosa biology which include lack of swimming and twitching motility, lack of production of the virulence factors such as pyocyanin, biofilm formation, and metabolic functions. In addition, Pos-STM mutants showed altered invasion and stimulation of immune response when tested in human respiratory epithelial cells, indicating that P. aeruginosa is prone to revise the interaction with its host during persistent lifestyle. Finally, sequence analysis of Pos-STM genes in longitudinally P. aeruginosa isolates from CF patients identified signs of patho-adaptive mutations within the genome. This novel Pos-STM approach identified bacterial functions that can have important clinical implications for the persistent lifestyle and disease progression of the airway chronic infection.

Nutrient transitions are a source of persisters in Escherichia coli biofilms.

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Stephanie M Amato

Full Text Available Chronic and recurrent infections have been attributed to persisters in biofilms, and despite this importance, the mechanisms of persister formation in biofilms remain unclear. The plethora of biofilm characteristics that could give rise to persisters, including slower growth, quorum signaling, oxidative stress, and nutrient heterogeneity, have complicated efforts to delineate formation pathways that generate persisters during biofilm development. Here we sought to specifically determine whether nutrient transitions, which are a common metabolic stress encountered within surface-attached communities, stimulate persister formation in biofilms and if so, to then identify the pathway. To accomplish this, we established an experimental methodology where nutrient availability to biofilm cells could be controlled exogenously, and then used that method to discover that diauxic carbon source transitions stimulated persister formation in Escherichia coli biofilms. Previously, we found that carbon source transitions stimulate persister formation in planktonic E. coli cultures, through a pathway that involved ppGpp and nucleoid-associated proteins, and therefore, tested the functionality of that pathway in biofilms. Biofilm persister formation was also found to be dependent on ppGpp and nucleoid-associated proteins, but the importance of specific proteins and enzymes between biofilm and planktonic lifestyles was significantly different. Data presented here support the increasingly appreciated role of ppGpp as a central mediator of bacterial persistence and demonstrate that nutrient transitions can be a source of persisters in biofilms.

Nutrient transitions are a source of persisters in Escherichia coli biofilms.

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Amato, Stephanie M; Brynildsen, Mark P

2014-01-01

Chronic and recurrent infections have been attributed to persisters in biofilms, and despite this importance, the mechanisms of persister formation in biofilms remain unclear. The plethora of biofilm characteristics that could give rise to persisters, including slower growth, quorum signaling, oxidative stress, and nutrient heterogeneity, have complicated efforts to delineate formation pathways that generate persisters during biofilm development. Here we sought to specifically determine whether nutrient transitions, which are a common metabolic stress encountered within surface-attached communities, stimulate persister formation in biofilms and if so, to then identify the pathway. To accomplish this, we established an experimental methodology where nutrient availability to biofilm cells could be controlled exogenously, and then used that method to discover that diauxic carbon source transitions stimulated persister formation in Escherichia coli biofilms. Previously, we found that carbon source transitions stimulate persister formation in planktonic E. coli cultures, through a pathway that involved ppGpp and nucleoid-associated proteins, and therefore, tested the functionality of that pathway in biofilms. Biofilm persister formation was also found to be dependent on ppGpp and nucleoid-associated proteins, but the importance of specific proteins and enzymes between biofilm and planktonic lifestyles was significantly different. Data presented here support the increasingly appreciated role of ppGpp as a central mediator of bacterial persistence and demonstrate that nutrient transitions can be a source of persisters in biofilms.

The variability of hepatitis B envelope is associated with HBs antigen persistence in either chronic or acute HBV genotype A infection.

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Eschlimann, Marine; Malvé, Brice; Velay, Aurélie; Fenaux, Honorine; Berger, Sibel; Frippiat, Jean-Pol; Zoulim, Fabien; Bensenane, Mouni; Bronowicki, Jean-Pierre; Goehringer, François; May, Thierry; Jeulin, Hélène; Schvoerer, Evelyne

2017-09-01

More than 240 million people are chronically infected by hepatitis B virus (HBV) worldwide. Envelope proteins play a crucial role in viral cellular entry and immune recognition. The loss of HBs antigen (HBsAg) correlated with a good clinical prognosis is rarely achieved with or without treatment (3-16%). HBV envelope variability was investigated according to HBsAg persistence. The cohort consisted of 15 HBV genotype A-infected patients divided into "resolvers", with HBsAg clearance, and "non-resolvers", with HBsAg persistence and in subgroups: acute (n=5, AHBV) or chronic infection (n=4, CHBV) and HBV/HIV coinfection (n=6, CHBV/HIV). HBV S and preS sequences were studied by direct and ultra-deep sequencing. Amino acid sequences were analyzed with bioinformatics for predicted antigenicity. In S gene, the complexity was lower in AHBV than in chronic-infected patients (p=0.046). Major mutations, detected using direct sequencing, were more frequent in AHBV developing chronicity (p=0.01) than in AHBV resolvers. In the Major Hydrophilic Region, more frequent mutations were observed in non-resolvers versus resolvers (p=0.047) and non-resolvers tended to have more haplotypes with a reduced predicted antigenicity (p=0.07). Most of the mutations in preS/S region were found rather in epitopic than in non-epitopic areas (p=0.025). Interestingly, the mutation sY161F found in 3/8 non-resolvers was associated with a decrease in predicted antigenicity (28%; AnTheProt). HBsAg persistence was correlated with mutations and deletions in areas playing a key role in immune recognition. These data suggest that variability in HBV envelope could favor immune escape in various clinical settings of HBV genotype A-infected patients. Copyright © 2017 Elsevier B.V. All rights reserved.

Chronic restraint stress after injury and shock is associated with persistent anemia despite prolonged elevation in erythropoietin levels.

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Bible, Letitia E; Pasupuleti, Latha V; Gore, Amy V; Sifri, Ziad C; Kannan, Kolenkode B; Mohr, Alicia M

2015-07-01

Following severe traumatic injury, critically ill patients have a prolonged hypercatacholamine state that is associated with bone marrow (BM) dysfunction and persistent anemia. However, current animal models of injury and shock result in a transient anemia. Daily restraint stress (chronic stress [CS]) has been shown to increase catecholamines. We hypothesize that adding CS following injury or injury and shock in rats will prolong the hypercatecholaminemia and prolong the initial anemia, despite elevated erythropoietin (EPO) levels. Male Sprague-Dawley rats (n = 6-8 per group) underwent lung contusion (LC) or combined LC/hemorrhagic shock (LCHS) followed by 6 days of CS. CS consisted of a 2-hour restraint period interrupted with repositioning and alarms every 30 minutes. At 7 days, urine was assessed for norepinephrine (NE) levels, blood for EPO and hemoglobin (Hgb), and BM for erythroid progenitor growth. Animals undergoing LC or combined LCHS predictably recovered by Day 7; urine NE, EPO, and Hgb levels were normal. The addition of CS to LC and LCHS models was associated with a significant elevation in NE on Day 6. The addition of CS to LC led to a persistent 20% to 25% decrease in the growth of BM hematopoietic progenitor cells. These findings were further exaggerated when CS was added following LCHS, resulting in a 20%q to 40% reduction in BM erythroid progenitor colony growth and a 20% decrease in Hgb when compared with LCHS alone. Exposing injured animals to CS results in prolonged elevation of NE and EPO, which is associated with worsening BM erythroid function and persistent anemia. Chronic restraint stress following injury and shock provides a clinically relevant model to further evaluate persistent injury-associated anemia seen in critically ill trauma patients. Furthermore, alleviating CS after severe injury is a potential therapeutic target to improve BM dysfunction and anemia.

Deficient incorporation of spike protein into virions contributes to the lack of infectivity following establishment of a persistent, non-productive infection in oligodendroglial cell culture by murine coronavirus

International Nuclear Information System (INIS)

Liu Yin; Herbst, Werner; Cao Jianzhong; Zhang Xuming

2011-01-01

Infection of mouse oligodendrocytes with a recombinant mouse hepatitis virus (MHV) expressing a green fluorescence protein facilitated specific selection of virus-infected cells and subsequent establishment of persistence. Interestingly, while viral genomic RNAs persisted in infected cells over 14 subsequent passages with concomitant synthesis of viral subgenomic mRNAs and structural proteins, no infectious virus was isolated beyond passage 2. Further biochemical and electron microscopic analyses revealed that virions, while assembled, contained little spike in the envelope, indicating that lack of infectivity during persistence was likely due to deficiency in spike incorporation. This type of non-lytic, non-productive persistence in oligodendrocytes is unique among animal viruses and resembles MHV persistence previously observed in the mouse central nervous system. Thus, establishment of such a culture system that can recapitulate the in vivo phenomenon will provide a powerful approach for elucidating the mechanisms of coronavirus persistence in glial cells at the cellular and molecular levels.

Infection and cellular defense dynamics in a novel 17β-estradiol murine model of chronic human group B streptococcus genital tract colonization reveal a role for hemolysin in persistence and neutrophil accumulation.

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Carey, Alison J; Tan, Chee Keong; Mirza, Shaper; Irving-Rodgers, Helen; Webb, Richard I; Lam, Alfred; Ulett, Glen C

2014-02-15

Genital tract carriage of group B streptococcus (GBS) is prevalent among adult women; however, the dynamics of chronic GBS genital tract carriage, including how GBS persists in this immunologically active host niche long term, are not well defined. To our knowledge, in this study, we report the first animal model of chronic GBS genital tract colonization using female mice synchronized into estrus by delivery of 17β-estradiol prior to intravaginal challenge with wild-type GBS 874391. Cervicovaginal swabs, which were used to measure bacterial persistence, showed that GBS colonized the vaginal mucosa of mice at high numbers (10(6)-10(7) CFU/swab) for at least 90 d. Cellular and histological analyses showed that chronic GBS colonization of the murine genital tract caused significant lymphocyte and PMN cell infiltrates, which were localized to the vaginal mucosal surface. Long-term colonization was independent of regular hormone cycling. Immunological analyses of 23 soluble proteins related to chemotaxis and inflammation showed that the host response to GBS in the genital tract comprised markers of innate immune activation including cytokines such as GM-CSF and TNF-α. A nonhemolytic isogenic mutant of GBS 874391, Δcyle9, was impaired for colonization and was associated with amplified local PMN responses. Induction of DNA neutrophil extracellular traps, which was observed in GBS-infected human PMNs in vitro in a hemolysin-dependent manner, appeared to be part of this response. Overall, this study defines key infection dynamics in a novel murine model of chronic GBS genital tract colonization and establishes previously unknown cellular and soluble defense responses to GBS in the female genital tract.

Multiple side effects of Efalizumab in a Saudi female with chronic persistent psoriasis followed by severe rebound after Efalizumab discontinuation

International Nuclear Information System (INIS)

Bukhari, Iqubal A.

2007-01-01

We are reporting a case of 23-years-old Saudi female with persistent chronic plaque psoriasis who was given subcutaneous Efalizumab 0.8mg/kg/week for 14 weeks. During that period the patient developed multiple adverse reactions followed by severe rebound. The case is presented to highlight the importance of managing patients on Efalizumab carefully and closely. (author)

Characterization of in vitro phenotypes of Burkholderia pseudomallei and Burkholderia mallei strains potentially associated with persistent infection in mice.

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Bernhards, R C; Cote, C K; Amemiya, K; Waag, D M; Klimko, C P; Worsham, P L; Welkos, S L

2017-03-01

Burkholderia pseudomallei (Bp) and Burkholderia mallei (Bm), the agents of melioidosis and glanders, respectively, are Tier 1 biothreats. They infect humans and animals, causing disease ranging from acute and fatal to protracted and chronic. Chronic infections are especially challenging to treat, and the identification of in vitro phenotypic markers which signal progression from acute to persistent infection would be extremely valuable. First, a phenotyping strategy was developed employing colony morphotyping, chemical sensitivity testing, macrophage infection, and lipopolysaccharide fingerprint analyses to distinguish Burkholderia strains. Then mouse spleen isolates collected 3-180 days after infection were characterized phenotypically. Isolates from long-term infections often exhibited increased colony morphology differences and altered patterns of antimicrobial sensitivity and macrophage infection. Some of the Bp and Bm persistent infection isolates clearly displayed enhanced virulence in mice. Future studies will evaluate the potential role and significance of these phenotypic markers in signaling the establishment of a chronic infection.

Persistence of Coxsackievirus B4 in pancreatic ductal-like cells results in cellular and viral changes.

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Alidjinou, E K; Engelmann, I; Bossu, J; Villenet, C; Figeac, M; Romond, M-B; Sané, F; Hober, D

2017-10-03

Although known as cytolytic viruses, group B coxackieviruses (CVB) are able to establish a persistent infection in vitro and in vivo. Viral persistence has been reported as a key mechanism in the pathogenesis of CVB-associated chronic diseases such as type 1 diabetes (T1D). The impact of CVB4 persistence on human pancreas ductal-like cells was investigated. A persistent CVB4 infection was established in ductal-like cells. PDX-1 expression, resistance to CVB4-induced lysis and CAR expression were evaluated. The profile of cellular microRNAs (miRNAs) was investigated through miRNA-sequencing. Viral phenotypic changes were examined, and genomic modifications were assessed by sequencing of the viral genome. The CVB4 persistence in ductal-like cells was productive, with continuous release of infectious particles. Persistently infected cells displayed a resistance to CVB4-induced lysis upon superinfection and expression of PDX-1 and CAR was decreased. These changes were maintained even after virus clearance. The patterns of cellular miRNA expression in mock-infected and in CVB4-persistently infected ductal-like cells were clearly different. The persistent infection-derived virus (PIDV) was still able to induce cytopathic effect but its plaques were smaller than the parental virus. Several mutations appeared in various PIDV genome regions, but amino acid substitutions did not affect the predicted site of interaction with CAR. Cellular and viral changes occur during persistent infection of human pancreas ductal-like cells with CVB4. The persistence of cellular changes even after virus clearance supports the hypothesis of a long-lasting impact of persistent CVB infection on the cells.

Establishing the Feasibility of Direct Observation in the Assessment of Tics in Children with Chronic Tic Disorders

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Himle, Michael B.; Chang, Susanna; Woods, Douglas W.; Pearlman, Amanda; Buzzella, Brian; Bunaciu, Liviu; Piacentini, John C.

2006-01-01

Behavior analysis has been at the forefront in establishing effective treatments for children and adults with chronic tic disorders. As is customary in behavior analysis, the efficacy of these treatments has been established using direct-observation assessment methods. Although behavior-analytic treatments have enjoyed acceptance and integration…

New-found fundamentals of bacterial persistence.

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Kint, Cyrielle I; Verstraeten, Natalie; Fauvart, Maarten; Michiels, Jan

2012-12-01

Persister cells display tolerance to high doses of bactericidal antibiotics and typically comprise a small fraction of a bacterial population. Recently, evidence was provided for a causal link between therapy failure and the presence of persister cells in chronic infections, underscoring the need for research on bacterial persistence. A series of recent breakthroughs have shed light on the multiplicity of persister genes, the contribution of gene expression noise to persister formation, the importance of active responses to antibiotic tolerance and heterogeneity among persister cells. Moreover, the development of in vivo model systems has highlighted the clinical relevance of persistence. This review discusses these recent advances and how this knowledge fundamentally changes the way in which we will perceive the problem of antibiotic tolerance in years to come. Copyright © 2012 Elsevier Ltd. All rights reserved.

Establishing and maintaining job skills and professional behaviors in chronically unemployed drug abusers.

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Wong, Conrad J; Silverman, Kenneth

2007-01-01

The therapeutic workplace intervention is an employment-based drug user intervention that integrates abstinence reinforcement contingencies into an employment setting, intended for individuals manifesting chronic unemployment and drug addiction. Research on the therapeutic workplace intervention has provided a unique and rare opportunity to collect data and conduct fine-grained analyses of the training and work performance of participants. Results from a series of studies document that chronically unemployed drug users display behaviors that likely limit their success in conventional businesses. This article reviews a systematic line of research showing that targeted and intensive contingency management interventions and training programs have been effective in promoting consistent attendance and high rates of productivity and establishing job skills for employment.

Chronic corticosterone exposure persistently elevates the expression of memory-related genes in the lateral amygdala and enhances the consolidation of a Pavlovian fear memory.

Directory of Open Access Journals (Sweden)

Melissa S Monsey

Full Text Available Chronic exposure to stress has been widely implicated in the development of anxiety disorders, yet relatively little is known about the long-term effects of chronic stress on amygdala-dependent memory formation. Here, we examined the effects of a history of chronic exposure to the stress-associated adrenal steroid corticosterone (CORT on the consolidation of a fear memory and the expression of memory-related immediate early genes (IEGs in the lateral nucleus of the amygdala (LA. Rats received chronic exposure to CORT (50 μg/ml in their drinking water for 2 weeks and were then titrated off the CORT for an additional 6 days followed by a 2 week 'wash-out' period consisting of access to plain water. Rats were then either sacrificed to examine the expression of memory-related IEG expression in the LA or given auditory Pavlovian fear conditioning. We show that chronic exposure to CORT leads to a persistent elevation in the expression of the IEGs Arc/Arg3.1 and Egr-1 in the LA. Further, we show that rats with a history of chronic CORT exposure exhibit enhanced consolidation of a fear memory; short-term memory (STM is not affected, while long-term memory (LTM is significantly enhanced. Treatment with the selective serotonin reuptake inhibitor (SSRI fluoxetine following the chronic CORT exposure period was observed to effectively reverse both the persistent CORT-related increases in memory-related IEG expression in the LA and the CORT-related enhancement in fear memory consolidation. Our findings suggest that chronic exposure to CORT can regulate memory-related IEG expression and fear memory consolidation processes in the LA in a long-lasting manner and that treatment with fluoxetine can reverse these effects.

Chronic corticosterone exposure persistently elevates the expression of memory-related genes in the lateral amygdala and enhances the consolidation of a Pavlovian fear memory.

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Monsey, Melissa S; Boyle, Lara M; Zhang, Melinda L; Nguyen, Caroline P; Kronman, Hope G; Ota, Kristie T; Duman, Ronald S; Taylor, Jane R; Schafe, Glenn E

2014-01-01

Chronic exposure to stress has been widely implicated in the development of anxiety disorders, yet relatively little is known about the long-term effects of chronic stress on amygdala-dependent memory formation. Here, we examined the effects of a history of chronic exposure to the stress-associated adrenal steroid corticosterone (CORT) on the consolidation of a fear memory and the expression of memory-related immediate early genes (IEGs) in the lateral nucleus of the amygdala (LA). Rats received chronic exposure to CORT (50 μg/ml) in their drinking water for 2 weeks and were then titrated off the CORT for an additional 6 days followed by a 2 week 'wash-out' period consisting of access to plain water. Rats were then either sacrificed to examine the expression of memory-related IEG expression in the LA or given auditory Pavlovian fear conditioning. We show that chronic exposure to CORT leads to a persistent elevation in the expression of the IEGs Arc/Arg3.1 and Egr-1 in the LA. Further, we show that rats with a history of chronic CORT exposure exhibit enhanced consolidation of a fear memory; short-term memory (STM) is not affected, while long-term memory (LTM) is significantly enhanced. Treatment with the selective serotonin reuptake inhibitor (SSRI) fluoxetine following the chronic CORT exposure period was observed to effectively reverse both the persistent CORT-related increases in memory-related IEG expression in the LA and the CORT-related enhancement in fear memory consolidation. Our findings suggest that chronic exposure to CORT can regulate memory-related IEG expression and fear memory consolidation processes in the LA in a long-lasting manner and that treatment with fluoxetine can reverse these effects.

Interaction between Galectin-9/TIM-3 pathway and follicular helper CD4+ T cells contributes to viral persistence in chronic hepatitis C.

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Zhuo, Ya; Zhang, Yi-Fu; Wu, Hong-Jie; Qin, Lei; Wang, Yan-Ping; Liu, A-Min; Wang, Xin-Hong

2017-10-01

Both Galectin 9 (Gal-9)/T-cell immunoglobulin and mucin domain-containing protein 3 (TIM-3) pathway and follicular helper CD4 + T (Tfh) cells play important roles in persistent hepatitis C virus (HCV) infection. Thus, we aimed to investigate the regulatory role of interaction between Gal-9/TIM-3 pathway and Tfh cells in chronic hepatitis C. A total of 44 chronic hepatitis C patients and 19 normal controls (NCs) were enrolled in this study. Purified CD4 + T cells were cultured by TIM-3 Fc protein, recombinant Gal-9, or IL-21 for 48h. TIM-3 expression, Tfh proportion, and IL-21 production was measured, respectively. The immunomodulatory role of Gal-9/TIM-3 and IL-21 was also investigated in HCV cell culture system in vitro. We found that the percentage corresponding to both TIM-3-positive and CXCR5 + ICOS + Tfh cells within CD4 + T cells, which correlated with HCV RNA replication, was significantly elevated in patients with chronic hepatitis C in comparison with those in NCs. Moreover, blockade of Gal-9/TIM-3 pathway by TIM-3 Fc protein increased Tfh cells proportion, IL-21 mRNA and protein expression within purified CD4 + T cells, while activation of Gal-9/TIM-3 signaling by Gal-9 stimulation decreased IL-21 production in both patients with chronic HCV infection and healthy individuals. Meanwhile, high concentrations (100 and 200ng/mL) of IL-21 stimulation also elevated TIM-3 expression on CD4 + T cells in chronic hepatitis C. Furthermore, TIM-3 blockage and IL-21 stimulation suppressed mRNA expressions of HCV-induced antiviral proteins (myxovirus resistance A and oligoadenylate synthetase) in Huh7.5 cells without affecting viral replication in HCV cell culture system. The interaction between Gal-9/TIM-3 pathway and Tfh cells contributed to viral persistent in chronic HCV infection, which might be pivotal for development of new therapeutic approaches for chronic hepatitis C. Copyright © 2017 Elsevier Masson SAS. All rights reserved.

[Establishment of a D-galactosamine/lipopolysaccharide induced acute-on-chronic liver failure model in rats].

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Liu, Xu-hua; Chen, Yu; Wang, Tai-ling; Lu, Jun; Zhang, Li-jie; Song, Chen-zhao; Zhang, Jing; Duan, Zhong-ping

2007-10-01

To establish a practical and reproducible animal model of human acute-on-chronic liver failure for further study of the pathophysiological mechanism of acute-on-chronic liver failure and for drug screening and evaluation in its treatment. Immunological hepatic fibrosis was induced by human serum albumin in Wistar rats. In rats with early-stage cirrhosis (fibrosis stage IV), D-galactosamine and lipopolysaccharide were administered. Mortality and survival time were recorded in 20 rats. Ten rats were sacrificed at 4, 8, and 12 hours. Liver function tests and plasma cytokine levels were measured after D-galactosamine/lipopolysaccharide administration and liver pathology was studied. Cell apoptosis was detected by terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling assay. Most of the rats treated with human albumin developed cirrhosis and fibrosis, and 90% of them died from acute liver failure after administration of D-galactosamine/lipopolysaccharide, with a mean survival time of (16.1+/-3.7) hours. Liver histopathology showed massive or submassive necrosis of the regenerated nodules, while fibrosis septa were intact. Liver function tests were compatible with massive necrosis of hepatocytes. Plasma level of TNFalpha increased significantly, parallel with the degree of the hepatocytes apoptosis. Plasma IL-10 levels increased similarly as seen in patients with acute-on-chronic liver failure. We established an animal model of acute-on-chronic liver failure by treating rats with human serum albumin and later with D-galactosamine and lipopolysaccharide. TNFalpha-mediated liver cell apoptoses plays a very important role in the pathogenesis of acute liver failure.

Establishing and sustaining research partnerships in Africa: a case study of the UK-Africa Academic Partnership on Chronic Disease

NARCIS (Netherlands)

de-Graft Aikins, Ama; Arhinful, Daniel K.; Pitchforth, Emma; Ogedegbe, Gbenga; Allotey, Pascale; Agyemang, Charles

2012-01-01

This paper examines the challenges and opportunities in establishing and sustaining north-south research partnerships in Africa through a case study of the UK-Africa Academic Partnership on Chronic Disease. Established in 2006 with seed funding from the British Academy, the partnership aimed to

An annoying persistent cough

Directory of Open Access Journals (Sweden)

Francesco Cipollini

2007-03-01

Full Text Available Chronic cough is a stressful condition and can lead to extensive investigations. We report a case of a 48-year-old woman who had suffered from persistent chronic cough for more than 3 months. She had been treated with cough suppressant. However, her cough was not alleviated by these treatments, and the patient was referred to our hospital. She did not exhibit typical gastroesophageal reflux disease (GERD symptoms heartburn and regurgitation. Esophagoscopy did not disclose reflux esophagitis. The patient was treated with a proton-pump inhibitor, which markedly alleviated her cough. Chronic cough due to GERD was diagnosed. Although the diagnosis of chronic cough due to GERD is not easy when traditionally symptoms are not present, our case report underscores the importance of this association to the differential diagnosis of chronic cough. In these cases a relatively simple test as high dose proton pump-inhibitors trial may be useful to confirm GERD related cough.

Autism Spectrum Disorders May Be Due to Cerebral Toxoplasmosis Associated with Chronic Neuroinflammation Causing Persistent Hypercytokinemia that Resulted in an Increased Lipid Peroxidation, Oxidative Stress, and Depressed Metabolism of Endogenous and Exogenous Substances

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Prandota, Joseph

2010-01-01

Worldwide, approximately 2 billion people are chronically infected with "Toxoplasma gondii" with largely yet unknown consequences. Patients with autism spectrum disorders (ASD) similarly as mice with chronic toxoplasmosis have persistent neuroinflammation, hypercytokinemia with hypermetabolism associated with enhanced lipid peroxidation, and…

Missed diagnosis-persistent delirium

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Aseem Mehra

2014-01-01

Full Text Available Delirium is in general considered as an acute short lasting reversible neuropsychiatric syndrome. However, there is some evidence to suggest that in a small proportion of cases delirium may be a chronic or persistent condition. However, making this diagnosis requires clinical suspicion and ruling other differential diagnosis. In this report, we present a case of a 55-year-old man who had cognitive symptoms, psychotic symptoms and depressive symptoms along with persistent hypokalemia and glucose intolerance. He was seen by 3 psychiatrists with these symptoms and was initially diagnosed as having depressive disorder and later diagnosis of bipolar affective disorder (current episode mania, and psychosis were considered by the third psychiatrist. However, despite the presence of persistent neurocognitive deficits, evening worsening of symptoms, hypokalemia and glucose intolerance diagnosis of delirium was not suspected.

The pain of chronic pancreatitis: a persistent clinical challenge

Science.gov (United States)

2013-01-01

The pain of chronic pancreatitis represents a major challenge to those working in the field, including pain specialists, gastroenterologists and surgeons. This article describes the different aetiologies of chronic pancreatitis and lists the models for the pathogenesis of pain, including novel ideas such as the role of the immune system in the modulation of pain. The patient profile in chronic pancreatitis is discussed along with the social impact of the disease in relation to alcohol misuse. The range of treatment strategies including medical, endoscopic and surgical approaches are evaluated. Common analgesic regimes and their limitations are reviewed. The pain of chronic pancreatitis remains refractory to effective treatment in many cases and further study and understanding of the underlying pathophysiology are required. PMID:26516493

Dualities in persistent (co)homology

International Nuclear Information System (INIS)

De Silva, Vin; Morozov, Dmitriy; Vejdemo-Johansson, Mikael

2011-01-01

We consider sequences of absolute and relative homology and cohomology groups that arise naturally for a filtered cell complex. We establish algebraic relationships between their persistence modules, and show that they contain equivalent information. We explain how one can use the existing algorithm for persistent homology to process any of the four modules, and relate it to a recently introduced persistent cohomology algorithm. We present experimental evidence for the practical efficiency of the latter algorithm

Persister formation in Staphylococcus aureus is associated with ATP depletion

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Conlon, Brian P.; Rowe, Sarah E.; Gandt, Autumn Brown; Nuxoll, Austin S.; Donegan, Niles P.; Zalis, Eliza A.; Clair, Geremy; Adkins, Joshua N.; Cheung, Ambrose L.; Lewis, Kim

2016-04-18

Persisters are dormant phenotypic variants of bacterial cells that are tolerant to killing by antibiotics1. Persisters are associated with chronic bacterial infection and antibiotic treatment failure. In Escherichia coli, toxin/antitoxin (TA) modules are responsible for persister formation. The mechanism of persister formation in Gram positive bacteria is unknown. Staphylococcus aureus is a major human pathogen, responsible for a variety of chronic and relapsing infections such as osteomyelitis, endocarditis and infections of implanted devices. Deleting TA modules in S. aureus did not affect the level of persisters. Here we show that S. aureus persisters are produced due to a stochastic entrance to stationary phase accompanied by a drop in intracellular ATP. Cells expressing stationary state markers are present throughout the growth phase, increasing in frequency with cell density. Cell sorting revealed that expression of stationary markers was associated with a 100-1000 fold increased likelihood of survival to antibiotic challenge. We find that the antibiotic tolerance of these cells is due to a drop in intracellular ATP. The ATP level of the cell is predictive of bactericidal antibiotic efficacy and explains bacterial tolerance to antibiotic treatment.

Establishment of an Italian chronic migraine database: a multicenter pilot study.

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Barbanti, Piero; Fofi, L; Cevoli, S; Torelli, P; Aurilia, C; Egeo, G; Grazzi, L; D'Amico, D; Manzoni, G C; Cortelli, P; Infarinato, F; Vanacore, N

2018-05-01

To optimize chronic migraine (CM) ascertainment and phenotype definition, provide adequate clinical management and health care procedures, and rationalize economic resources allocation, we performed an exploratory multicenter pilot study aimed at establishing a CM database, the first step for developing a future Italian CM registry. We enrolled 63 consecutive CM patients in four tertiary headache centers screened with face-to-face interviews using an ad hoc dedicated semi-structured questionnaire gathering detailed information on life-style, behavioral and socio-demographic factors, comorbidities, and migraine features before and after chronicization and healthcare resource use. Our pilot study provided useful insights revealing that CM patients (1) presented in most cases symptoms of peripheral trigeminal sensitization, a relatively unexpected feature which could be useful to unravel different CM endophenotypes and to predict trigeminal-targeted treatments' responsiveness; (2) had been frequently admitted to emergency departments; (3) had undergone, sometime repeatedly, unnecessary or inappropriate investigations; (4) got rarely illness benefit exemption or disability allowance only. We deem that the expansion of the database-shortly including many other Italian headache centers-will contribute to more precisely outline CM endophenotypes, hence improving management, treatment, and economic resource allocation, ultimately reducing CM burden on both patients and health system.

Establishing and sustaining research partnerships in Africa: a case study of the UK-Africa Academic Partnership on Chronic Disease

Directory of Open Access Journals (Sweden)

de-Graft Aikins Ama

2012-08-01

Full Text Available Abstract This paper examines the challenges and opportunities in establishing and sustaining north–south research partnerships in Africa through a case study of the UK-Africa Academic Partnership on Chronic Disease. Established in 2006 with seed funding from the British Academy, the partnership aimed to bring together multidisciplinary chronic disease researchers based in the UK and Africa to collaborate on research, inform policymaking, train and support postgraduates and create a platform for research dissemination. We review the partnership’s achievements and challenges, applying established criteria for developing successful partnerships. During the funded period we achieved major success in creating a platform for research dissemination through international meetings and publications. Other goals, such as engaging in collaborative research and training postgraduates, were not as successfully realised. Enabling factors included trust and respect between core working group members, a shared commitment to achieving partnership goals, and the collective ability to develop creative strategies to overcome funding challenges. Barriers included limited funding, administrative support, and framework for monitoring and evaluating some goals. Chronic disease research partnerships in low-income regions operate within health research, practice, funding and policy environments that prioritise infectious diseases and other pressing public health and developmental challenges. Their long-term sustainability will therefore depend on integrated funding systems that provide a crucial capacity building bridge. Beyond the specific challenges of chronic disease research, we identify social capital, measurable goals, administrative support, creativity and innovation and funding as five key ingredients that are essential for sustaining research partnerships.

Establishing and sustaining research partnerships in Africa: a case study of the UK-Africa Academic Partnership on Chronic Disease

Science.gov (United States)

2012-01-01

This paper examines the challenges and opportunities in establishing and sustaining north–south research partnerships in Africa through a case study of the UK-Africa Academic Partnership on Chronic Disease. Established in 2006 with seed funding from the British Academy, the partnership aimed to bring together multidisciplinary chronic disease researchers based in the UK and Africa to collaborate on research, inform policymaking, train and support postgraduates and create a platform for research dissemination. We review the partnership’s achievements and challenges, applying established criteria for developing successful partnerships. During the funded period we achieved major success in creating a platform for research dissemination through international meetings and publications. Other goals, such as engaging in collaborative research and training postgraduates, were not as successfully realised. Enabling factors included trust and respect between core working group members, a shared commitment to achieving partnership goals, and the collective ability to develop creative strategies to overcome funding challenges. Barriers included limited funding, administrative support, and framework for monitoring and evaluating some goals. Chronic disease research partnerships in low-income regions operate within health research, practice, funding and policy environments that prioritise infectious diseases and other pressing public health and developmental challenges. Their long-term sustainability will therefore depend on integrated funding systems that provide a crucial capacity building bridge. Beyond the specific challenges of chronic disease research, we identify social capital, measurable goals, administrative support, creativity and innovation and funding as five key ingredients that are essential for sustaining research partnerships. PMID:22897937

Rarity and persistence.

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Vermeij, Geerat J; Grosberg, Richard K

2018-01-01

Rarity is a population characteristic that is usually associated with a high risk of extinction. We argue here, however, that chronically rare species (those with low population densities over many generations across their entire ranges) may have individual-level traits that make populations more resistant to extinction. The major obstacle to persistence at low density is successful fertilisation (union between egg and sperm), and chronically rare species are more likely to survive when (1) fertilisation occurs inside or close to an adult, (2) mate choice involves long-distance signals, (3) adults or their surrogate gamete dispersers are highly mobile, or (4) the two sexes are combined in a single individual. In contrast, external fertilisation and wind- or water-driven passive dispersal of gametes, or sluggish or sedentary adult life habits in the absence of gamete vectors, appear to be incompatible with sustained rarity. We suggest that the documented increase in frequency of these traits among marine genera over geological time could explain observed secular decreases in rates of background extinction. Unanswered questions remain about how common chronic rarity actually is, which traits are consistently associated with chronic rarity, and how chronically rare species are distributed among taxa, and among the world's ecosystems and regions. © 2017 John Wiley & Sons Ltd/CNRS.

[Morphologic characteristic of chronic toxic hepatitis for treatment with Neoselen].

Science.gov (United States)

Isroilov, R I; Salikhodzhaeva, U Sh

2011-01-01

The purpose of the given research work was to study the features of morphologic changes arising for treatment of chronic hepatitis with Neoselen. It was established a picture of chronic active hepatitis in the liver of rats with the following development of chronic persisting hepatitis by the 40 daily administration of heliotrine and its transmission into cirrhosis in a certain part of animals. Hepatic cirrhosis has a small nodal portal character by its pathognomonic morphologic signs. A noticeable remittance of destructive necrotic changes in hepatic parenchymatous elements and reduction in a volume of proliferative inflammatory infiltration with an acceleration in process of its fibrozation in only periportal zones of hepatic lobules found to be for treatment of chronic hepatitis with Neoselen. That prevents from transmission of chronic hepatitis into cirrhosis in a greater part of animals that is a morphologic evidence of importance of selenium in a restorative process of biologic membranes and its involvement in a remittance process of destructive and inflammatory changes in the liver and prevention from development of agressive hepatitis and its transmission into cirrhosis.

Variable Persister Gene Interactions with (pppGpp for Persister Formation in Escherichia coli

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Shuang Liu

2017-09-01

Full Text Available Persisters comprise a group of phenotypically heterogeneous metabolically quiescent bacteria with multidrug tolerance and contribute to the recalcitrance of chronic infections. Although recent work has shown that toxin-antitoxin (TA system HipAB depends on stringent response effector (pppGppin persister formation, whether other persister pathways are also dependent on stringent response has not been explored. Here we examined the relationship of (pppGpp with 15 common persister genes (dnaK, clpB, rpoS, pspF, tnaA, sucB, ssrA, smpB, recA, umuD, uvrA, hipA, mqsR, relE, dinJ using Escherichia coli as a model. By comparing the persister levels of wild type with their single gene knockout and double knockout mutants with relA, we divided their interactions into five types, namely A “dependent” (dnaK, recA, B “positive reinforcement” (rpoS, pspF, ssrA, recA, C “antagonistic” (clpB, sucB, umuD, uvrA, hipA, mqsR, relE, dinJ, D “epistasis” (clpB, rpoS, tnaA, ssrA, smpB, hipA, and E “irrelevant” (dnaK, clpB, rpoS, tnaA, sucB, smpB, umuD, uvrA, hipA, mqsR, relE, dinJ. We found that the persister gene interactions are intimately dependent on bacterial culture age, cell concentrations (diluted versus undiluted culture, and drug classifications, where the same gene may belong to different groups with varying antibiotics, culture age or cell concentrations. Together, this study represents the first attempt to systematically characterize the intricate relationships among the different mechanisms of persistence and as such provide new insights into the complexity of the persistence phenomenon at the level of persister gene network interactions.

Chronic pancreatitis.

Science.gov (United States)

Kleeff, Jorg; Whitcomb, David C; Shimosegawa, Tooru; Esposito, Irene; Lerch, Markus M; Gress, Thomas; Mayerle, Julia; Drewes, Asbjørn Mohr; Rebours, Vinciane; Akisik, Fatih; Muñoz, J Enrique Domínguez; Neoptolemos, John P

2017-09-07

Chronic pancreatitis is defined as a pathological fibro-inflammatory syndrome of the pancreas in individuals with genetic, environmental and/or other risk factors who develop persistent pathological responses to parenchymal injury or stress. Potential causes can include toxic factors (such as alcohol or smoking), metabolic abnormalities, idiopathic mechanisms, genetics, autoimmune responses and obstructive mechanisms. The pathophysiology of chronic pancreatitis is fairly complex and includes acinar cell injury, acinar stress responses, duct dysfunction, persistent or altered inflammation, and/or neuro-immune crosstalk, but these mechanisms are not completely understood. Chronic pancreatitis is characterized by ongoing inflammation of the pancreas that results in progressive loss of the endocrine and exocrine compartment owing to atrophy and/or replacement with fibrotic tissue. Functional consequences include recurrent or constant abdominal pain, diabetes mellitus (endocrine insufficiency) and maldigestion (exocrine insufficiency). Diagnosing early-stage chronic pancreatitis is challenging as changes are subtle, ill-defined and overlap those of other disorders. Later stages are characterized by variable fibrosis and calcification of the pancreatic parenchyma; dilatation, distortion and stricturing of the pancreatic ducts; pseudocysts; intrapancreatic bile duct stricturing; narrowing of the duodenum; and superior mesenteric, portal and/or splenic vein thrombosis. Treatment options comprise medical, radiological, endoscopic and surgical interventions, but evidence-based approaches are limited. This Primer highlights the major progress that has been made in understanding the pathophysiology, presentation, prevalence and management of chronic pancreatitis and its complications.

EBV CHRONIC INFECTIONS

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Eligio Pizzigallo

2010-08-01

Full Text Available The infection from Epstein-Barr virus (EBV or virus of infectious mononucleosis, together with other herpesviruses’ infections, represents a prototype of persistent viral infections characterized by the property of the latency. Although the reactivations of the latent infection are associated with the resumption of the viral replication and eventually with the “shedding”, it is still not clear if this virus can determine chronic infectious diseases, more or less evolutive. These diseases could include some pathological conditions actually defined as “idiopathic”and characterized by the “viral persistence” as the more credible pathogenetic factor. Among the so-called idiopathic syndromes, the “chronic fatigue syndrome” (CFS aroused a great interest around the eighties of the last century when, just for its relationship with EBV, it was called “chronic mononucleosis” or “chronic EBV infection”. Today CFS, as defined in 1994 by the CDC of Atlanta (USA, really represents a multifactorial syndrome characterized by a chronic course, where reactivation and remission phases alternate, and by a good prognosis. The etiopathogenetic role of EBV is demonstrated only in a well-examined subgroup of patients, while in most of the remaining cases this role should be played by other infectious agents - able to remain in a latent or persistent way in the host – or even by not infectious agents (toxic, neuroendocrine, methabolic, etc.. However, the pathogenetic substrate of the different etiologic forms seems to be the same, much probably represented by the oxidative damage due to the release of pro-inflammatory cytokines as a response to the triggering event (infectious or not infectious. Anyway, recently the scientists turned their’s attention to the genetic predisposition of the subjects affected by the syndrome, so that in the last years the genetic studies, together with those of molecular biology, received a great impulse

Altered T cell memory and effector cell development in chronic lymphatic filarial infection that is independent of persistent parasite antigen.

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Cathy Steel

2011-04-01

Full Text Available Chronic lymphatic filarial (LF infection is associated with suppression of parasite-specific T cell responses that persist even following elimination of infection. While several mechanisms have been implicated in mediating this T cell specific downregulation, a role for alterations in the homeostasis of T effector and memory cell populations has not been explored. Using multiparameter flow cytometry, we investigated the role of persistent filarial infection on the maintenance of T cell memory in patients from the filarial-endemic Cook Islands. Compared to filarial-uninfected endemic normals (EN, microfilaria (mf positive infected patients (Inf had a reduced CD4 central memory (T(CM compartment. In addition, Inf patients tended to have more effector memory cells (T(EM and fewer effector cells (T(EFF than did ENs giving significantly smaller T(EFF:T(EM ratios. These contracted T(CM and T(EFF populations were still evident in patients previously mf+ who had cleared their infection (CLInf. Moreover, the density of IL-7Rα, necessary for T memory cell maintenance (but decreased in T effector cells, was significantly higher on memory cells of Inf and CLInf patients, although there was no evidence for decreased IL-7 or increased soluble IL7-Rα, both possible mechanisms for signaling defects in memory cells. However, effector cells that were present in Inf and CLInf patients had lower percentages of HLA-DR suggesting impaired function. These changes in T cell populations appear to reflect chronicity of infection, as filarial-infected children, despite the presence of active infection, did not show alterations in the frequencies of these T cell phenotypes. These data indicate that filarial-infected patients have contracted T(CM compartments and a defect in effector cell development, defects that persist even following clearance of infection. The fact that these global changes in memory and effector cell compartments do not yet occur in infected children

Transposon mutagenesis identifies novel genes associated with Staphylococcus aureus persister formation

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Wang ewenjie

2015-12-01

Full Text Available Pathogenic bacterial persisters are responsible for the recalcitrance of chronic and persistent infections to antimicrobial therapy. Although the mechanisms of persister formation and survival have been widely studied in Escherichia coli, persistence mechanisms in S. aureus remain largely unknown. Here, we screened a transposon mutant library of a clinical methicillin-resistant Staphylococcus aureus（MRSA）strain, USA500 (ST8, under antibiotic pressure and identified 13 genes whose insertion mutations resulted in a defect in persistence. These candidate genes were further confirmed by evaluating the survival of the mutants upon exposure to levofloxacin and several other stress conditions. We found 13 insertion mutants with significantly lower persister numbers under several stress conditions, including sdhA, sdhB, ureG, mnhG1, fbaA, ctaB, clpX, parE, HOU_0223, HOU_0587, HOU_2091, HOU_2315 and HOU_2346, which mapped into pathways of oxidative phosphorylation, TCA cycle, glycolysis, cell cycle and ABC transporters, suggesting that these genes and pathways may play an important role in persister formation and survival. The newly constructed knockout strains of ureG, sdhA and sdhB and their complemented strains were also tested for defect in persisters following exposure to levofloxacin and several other stress conditions. The results from these experiments were consistent with the screening results, which indicated that deletion of these genes in MRSA USA500 leads to persister defect. These findings provide novel insights into the mechanisms of persister formation and survival in S. aureus and offer new targets for the development of persister-directed antibiotics for the improved treatment of chronic and persistent infections.

Endorectal magnetic resonance imaging in persistent hemospermia

International Nuclear Information System (INIS)

Prando, Adilson

2008-01-01

Objective: To present the spectrum of abnormalities found at endorectal magnetic resonance imaging (E-MRI), in patients with persistent hemospermia. Materials and methods: A review of E-MRI findings observed in 86 patients with persistent hemospermia was performed and results compared with those reported in the literature. Follow-up was possible in 37 of 86 (43%) patients with hemospermia. Results: E-MRI showed abnormal findings in 52 of 86 (60%) patients with hemospermia. These findings were: a) hemorrhagic seminal vesicle and ejaculatory duct, isolated (n = 11 or 21%) or associated with complicated midline prostatic cyst (n = 10 or 19.0%); b) hemorrhagic chronic seminal vesiculitis, isolated (n = 14 or 27%) or associated with calculi within dilated ejaculatory ducts (n = 2 or 4 %); c) hemorrhagic seminal vesicle associated with calculi within dilated ejaculatory duct (n = 4 or 7.7%) or within seminal vesicle (n = 4 or 7.7%); d) non-complicated midline prostatic cyst (n = 6 or 11.5%); and e) prostate cancer (n = 1 or 2%). Successful treatment was more frequent in patients with chronic inflammatory and/or obstructive abnormalities. Conclusion: E-MRI should be considered the modality of choice, for the evaluation of patients with persistent hemospermia. (author)

Endorectal magnetic resonance imaging in persistent hemospermia

Energy Technology Data Exchange (ETDEWEB)

Prando, Adilson [Vera Cruz Hospital, Campinas, SP (Brazil). Dept. of Radiology and Diagnostic Imaging

2008-03-15

Objective: To present the spectrum of abnormalities found at endorectal magnetic resonance imaging (E-MRI), in patients with persistent hemospermia. Materials and methods: A review of E-MRI findings observed in 86 patients with persistent hemospermia was performed and results compared with those reported in the literature. Follow-up was possible in 37 of 86 (43%) patients with hemospermia. Results: E-MRI showed abnormal findings in 52 of 86 (60%) patients with hemospermia. These findings were: a) hemorrhagic seminal vesicle and ejaculatory duct, isolated (n = 11 or 21%) or associated with complicated midline prostatic cyst (n = 10 or 19.0%); b) hemorrhagic chronic seminal vesiculitis, isolated (n = 14 or 27%) or associated with calculi within dilated ejaculatory ducts (n = 2 or 4 %); c) hemorrhagic seminal vesicle associated with calculi within dilated ejaculatory duct (n = 4 or 7.7%) or within seminal vesicle (n = 4 or 7.7%); d) non-complicated midline prostatic cyst (n = 6 or 11.5%); and e) prostate cancer (n = 1 or 2%). Successful treatment was more frequent in patients with chronic inflammatory and/or obstructive abnormalities. Conclusion: E-MRI should be considered the modality of choice, for the evaluation of patients with persistent hemospermia. (author)

New daily persistent headache

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Alok Tyagi

2012-01-01

Full Text Available New daily persistent headache (NDPH is a chronic headache developing in a person who does not have a past history of headaches. The headache begins acutely and reaches its peak within 3 days. It is important to exclude secondary causes, particularly headaches due to alterations in cerebrospinal fluid (CSF pressure and volume. A significant proportion of NDPH sufferers may have intractable headaches that are refractory to treatment. The condition is best viewed as a syndrome rather than a diagnosis. The headache can mimic chronic migraine and chronic tension-type headache, and it is also important to exclude secondary causes, particularly headaches due to alterations in CSF pressure and volume. A large proportion of NDPH sufferers have migrainous features to their headache and should be managed with treatments used for treating migraine. A small group of NDPH sufferers may have intractable headaches that are refractory to treatment.

Intrathecal Administration of Morphine Decreases Persistent Pain after Cesarean Section: A Prospective Observational Study.

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Kumi Moriyama

Full Text Available Chronic pain after cesarean section (CS is a serious concern, as it can result in functional disability. We evaluated the prevalence of chronic pain after CS prospectively at a single institution in Japan. We also analyzed perioperative risk factors associated with chronic pain using logistic regression analyses with a backward-stepwise procedure.Patients who underwent elective or emergency CS between May 2012 and May 2014 were recruited. Maternal demographics as well as details of surgery and anesthesia were recorded. An anesthesiologist visited the patients on postoperative day (POD 1 and 2, and assessed their pain with the Prince Henry Pain Scale. To evaluate the prevalence of chronic pain, we contacted patients by sending a questionnaire 3 months post-CS.Among 225 patients who questionnaires, 69 (30.7% of patients complained of persistent pain, although no patient required pain medication. Multivariate analyses identified lighter weight (p = 0.011 and non-intrathecal administration of morphine (p = 0.023 as determinant factors associated with persistent pain at 3 months. The adjusted odds ratio of intrathecal administration of morphine to reduce persistent pain was 0.424, suggesting that intrathecal administration of morphine could decrease chronic pain by 50%. In addition, 51.6% of patients had abnormal wound sensation, suggesting the development of neuropathic pain. Also, 6% of patients with abnormal wound sensation required medication, yet no patients with persistent pain required medication.Although no effect on acute pain was observed, intrathecal administration of morphine significantly decreased chronic pain after CS.

DNA-crosslinker cisplatin eradicates bacterial persister cells.

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Chowdhury, Nityananda; Wood, Thammajun L; Martínez-Vázquez, Mariano; García-Contreras, Rodolfo; Wood, Thomas K

2016-09-01

For all bacteria, nearly every antimicrobial fails since a subpopulation of the bacteria enter a dormant state known as persistence, in which the antimicrobials are rendered ineffective due to the lack of metabolism. This tolerance to antibiotics makes microbial infections the leading cause of death worldwide and makes treating chronic infections, including those of wounds problematic. Here, we show that the FDA-approved anti-cancer drug cisplatin [cis-diamminodichloroplatinum(II)], which mainly forms intra-strand DNA crosslinks, eradicates Escherichia coli K-12 persister cells through a growth-independent mechanism. Additionally, cisplatin is more effective at killing Pseudomonas aeruginosa persister cells than mitomycin C, which forms inter-strand DNA crosslinks, and cisplatin eradicates the persister cells of several pathogens including enterohemorrhagic E. coli, Staphylococcus aureus, and P. aeruginosa. Cisplatin was also highly effective against clinical isolates of S. aureus and P. aeruginosa. Therefore, cisplatin has broad spectrum activity against persister cells. Biotechnol. Bioeng. 2016;113: 1984-1992. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

Novel protocol for persister cells isolation.

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Silvia J Cañas-Duarte

Full Text Available Bacterial persistence, where a fraction of a population presents a transient resistance to bactericidal substances, has great medical importance due to its relation with the appearance of antibiotic resistances and untreatable bacterial chronic infections. The mechanisms behind this phenomenon remain largely unknown in spite of recent advances, in great part because of the difficulty in isolating the very small fraction of the population that is in this state at any given time. Current protocols for persister isolation have resulted in possible biases because of the induction of this state by the protocol itself. Here we present a novel protocol that allows rapid isolation of persister cells both from exponential and stationary phase. Moreover, it is capable of differentiating between type I and type II persister cells, which should allow the field to move beyond its current state of studying only one type. While this protocol prompts a revision of many of the current results, it should greatly facilitate further advances in the field.

Ethnic Differences in Persistence with COPD Medications

DEFF Research Database (Denmark)

Hu, Yusun; Cantarero-Arévalo, Lourdes; Frølich, Anne

2017-01-01

BACKGROUND: Long-acting bronchodilators (LABDs) are recommended as a first-line maintenance therapy in patients with moderate or severe chronic obstructive pulmonary disease (COPD). The aim of the study was to explore potential ethnic differences in persistence with LABD in COPD patients. METHODS...

Evaluation of the chronic disease management program for appropriateness of medication adherence and persistence in hypertension and type-2 diabetes patients in Korea.

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Kim, Jung-Ae; Kim, Eun-Sook; Lee, Eui-Kyung

2017-04-01

The chronic disease management program (CDMP), a multilevel intervention including copayment reduction and physician incentives, was introduced in 2012 in Korea to improve blood pressure and glycemic control by strengthening the function of clinic as primary care institutions in managing hypertension and diabetes. This study, therefore, aimed to evaluate the effect of CDMP on the appropriateness of medication adherence and persistence in hypertension or type-2 diabetes patients.A pre-post retrospective study was conducted using claims cohort data from 2010 to 2013. Hypertension or type-2 diabetes patients were selected as the CDMP group, while dyslipidemia patients were the control group. Study groups were further categorized as clinic shifters or non-shifters on the basis of whether hospital use changed to clinic use during the study period. Pre-post changes in adherence and persistence were assessed. Adherence was measured by medication possession ratio (MPR) and categorized as under (1.1). Persistence was measured by 12-month cumulative persistence rate.The pre-post change was significantly improved for appropriate-adherence (hypertension, +6.0%p; diabetes, +6.1%p), 12-month cumulative persistence (hypertension, +6.5%p; diabetes, +10.8%p), and over-adherence (hypertension, -5.3%p; diabetes, -2.8%p) only among the shifters in the CDMP group. Among these, patients visiting the same, single clinic showed a significant increase in appropriate-adherence, whereas those who changed their clinics showed a nonsignificant increase. No significant improvement was verified among the non-shifters in the CDMP group.CDMP improved medication adherence and persistence by significantly increasing appropriate-adherence and 12-month cumulative persistence rate in hypertension and type-2 diabetes patients. Particularly, CDMP significantly improved over-adherence, which was associated with increasing healthcare costs and hospitalization risk.

Persistence of chromosomal abnormalities additional to the Philadelphia chromosome after Philadelphia chromosome disappearance during imatinib therapy for chronic myeloid leukemia.

Science.gov (United States)

Zaccaria, Alfonso; Valenti, Anna Maria; Donti, Emilio; Gozzetti, Alessandro; Ronconi, Sonia; Spedicato, Francesco

2007-04-01

Five Philadelphia chromosome positive (Ph+) chronic myeloid leukemia (CML) patients with additional chromosome abnormalities at diagnosis have been followed during Imatinib therapy. In all, the Ph chromosome disappeared, while the 5 cases, additional abnormalities [dup(1); del(5), +8 (2 patients) and +14] persisted in the subsequent studies, performed over a period of 11 to 49 months, either alone or together with a karyotypically normal cell population. This finding is consistent with a secondary origin of the Ph chromosome in these patients. It is still to early to evaluate the possible prognostic value of these additional abnormalities.

Self-reported moderate-to-vigorous leisure time physical activity predicts less pain and disability over 12 months in chronic and persistent low back pain

DEFF Research Database (Denmark)

Pinto, R Z; Ferreira, P H; Kongsted, Alice

2014-01-01

Physical deconditioning in combination with societal and emotional factors has been hypothesized to compromise complete recovery from low back pain (LBP). However, there is a lack of longitudinal studies designed to specifically investigate physical activity as an independent prognostic factor. We...... conducted a prognostic study to investigate whether levels of leisure time physical activity are independently associated with clinical outcomes in people seeking care for chronic and persistent LBP....

HBV-Specific shRNA is Capable of Reducing the Formation of Hepatitis B Virus Covalently Closed Circular DNA, but has No Effect on Established Covalently Closed Circular DNA in vitro

OpenAIRE

Starkey, Jason L.; Chiari, Estelle F.; Isom, Harriet C.

2009-01-01

Hepatitis B virus (HBV) covalently closed circular DNA (CCC DNA) is the source of HBV transcripts and persistence in chronically infected patients. The novel aspect of this study was to determine the effect of RNA interference (RNAi) on HBV CCC DNA when administered prior to establishment of HBV replication or during chronic HBV infection. HBV replication was initiated in HepG2 cells by transduction with HBV baculovirus. Subculture of HBV expressing HepG2 cells at 10 days post-transduction ge...

Pseudomonas aeruginosa biofilm aggravates skin inflammatory response in BALB/c mice in a novel chronic wound model

DEFF Research Database (Denmark)

Trøstrup, Hannah; Thomsen, Kim; Christophersen, Lars J

2013-01-01

model in C3H/HeN and BALB/c mice. The chronic wound was established by an injection of seaweed alginate-embedded P. aeruginosa PAO1 beneath a third-degree thermal lesion providing full thickness skin necrosis, as in human chronic wounds. Cultures revealed growth of PA, and both alginate with or without......Chronic wounds are presumed to persist in the inflammatory state, preventing healing. Emerging evidence indicates a clinical impact of bacterial biofilms in soft tissues, including Pseudomonas aeruginosa (PA) biofilms. To further investigate this, we developed a chronic PA biofilm wound infection...... bacteria organized in clusters, resembling biofilms, and inflammation located adjacent to the PA. The chronic wound infection showed a higher number of PAO1 in the BALB/c mice at day 4 after infection as compared to C3H/HeN mice (p

New daily-persistent headache versus tension-type headache.

Science.gov (United States)

Robbins, Matthew S; Crystal, Sara C

2010-12-01

New daily-persistent headache (NDPH) and chronic tension-type headache (CTTH) are two forms of primary chronic daily headache of long duration that often are similar in their headache manifestations. NDPH distinguishes itself from CTTH and the other forms of chronic daily headache by its continuous head pain from onset. However, despite formalized criteria that specify NDPH must resemble the acute onset of a headache identical to that of CTTH, NDPH commonly has migraine features. Here, we review the available literature on NDPH and compare its clinical features, epidemiology, prognosis, inciting factors, and treatment to CTTH.

Chronic fatigue syndrome after infectious mononucleosis in adolescents.

Science.gov (United States)

Katz, Ben Z; Shiraishi, Yukiko; Mears, Cynthia J; Binns, Helen J; Taylor, Renee

2009-07-01

The goal was to characterize prospectively the course and outcome of chronic fatigue syndrome in adolescents during a 2-year period after infectious mononucleosis. A total of 301 adolescents (12-18 years of age) with infectious mononucleosis were identified and screened for nonrecovery 6 months after infectious mononucleosis by using a telephone screening interview. Nonrecovered adolescents underwent a medical evaluation, with follow-up screening 12 and 24 months after infectious mononucleosis. After blind review, final diagnoses of chronic fatigue syndrome at 6, 12, and 24 months were made by using established pediatric criteria. Six, 12, and 24 months after infectious mononucleosis, 13%, 7%, and 4% of adolescents, respectively, met the criteria for chronic fatigue syndrome. Most individuals recovered with time; only 2 adolescents with chronic fatigue syndrome at 24 months seemed to have recovered or had an explanation for chronic fatigue at 12 months but then were reclassified as having chronic fatigue syndrome at 24 months. All 13 adolescents with chronic fatigue syndrome 24 months after infectious mononucleosis were female and, on average, they reported greater fatigue severity at 12 months. Reported use of steroid therapy during the acute phase of infectious mononucleosis did not increase the risk of developing chronic fatigue syndrome. Infectious mononucleosis may be a risk factor for chronic fatigue syndrome in adolescents. Female gender and greater fatigue severity, but not reported steroid use during the acute illness, were associated with the development of chronic fatigue syndrome in adolescents. Additional research is needed to determine other predictors of persistent fatigue after infectious mononucleosis.

Persistent pain and comorbidity among Operation Enduring Freedom/Operation Iraqi Freedom/operation New Dawn veterans.

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Higgins, Diana M; Kerns, Robert D; Brandt, Cynthia A; Haskell, Sally G; Bathulapalli, Harini; Gilliam, Wesley; Goulet, Joseph L

2014-05-01

Chronic pain is a significant concern for the Veterans Health Administration (VHA), with chronic pain conditions among those most frequently reported by Operation Enduring Freedom (OEF)/Operation Iraqi Freedom (OIF)/Operation New Dawn (OND) veterans. The current study examined VHA electronic medical record data to examine variation in demographics and high prevalence and high impact medical and mental health conditions in order to characterize the differences between patients with persistent pain and no pain. A conservative operational definition of chronic or "persistent pain" based on multiple indicators of pain (i.e., pain intensity ratings, prescription opioids, pain clinic visits, International Classification of Diseases, Ninth Revision codes) was employed. Analyses included the entire roster of longitudinal clinical data on OEF/OIF/OND veterans who used VHA care to compare those with persistent pain with those with no clinical evidence of pain. Results of logistic regression models suggest that sex, race, education, military variables, body mass index (BMI), traumatic brain injury (TBI), and mental health conditions, but not age, reliably discriminate the two groups. Those with persistent pain were more likely to be Black, female, on active duty, enlisted, Army service members, have a high school education or less, and have diagnoses of mood disorders, post-traumatic stress disorder, substance use disorders, anxiety disorders, TBI, and have a BMI consistent with overweight and obesity. The operational definition of chronic pain used in this study may have research implications for examining predictors of incident and chronic pain. These data have important clinical implications in that addressing comorbid conditions of persistent pain may improve adaptive coping and functioning in these patients. Wiley Periodicals, Inc.

TCR stimulation strength is inversely associated with establishment of functional brain-resident memory CD8 T cells during persistent viral infection.

Science.gov (United States)

Maru, Saumya; Jin, Ge; Schell, Todd D; Lukacher, Aron E

2017-04-01

Establishing functional tissue-resident memory (TRM) cells at sites of infection is a newfound objective of T cell vaccine design. To directly assess the impact of antigen stimulation strength on memory CD8 T cell formation and function during a persistent viral infection, we created a library of mouse polyomavirus (MuPyV) variants with substitutions in a subdominant CD8 T cell epitope that exhibit a broad range of efficiency in stimulating TCR transgenic CD8 T cells. By altering a subdominant epitope in a nonstructural viral protein and monitoring memory differentiation of donor monoclonal CD8 T cells in immunocompetent mice, we circumvented potentially confounding changes in viral infection levels, virus-associated inflammation, size of the immunodominant virus-specific CD8 T cell response, and shifts in TCR affinity that may accompany temporal recruitment of endogenous polyclonal cells. Using this strategy, we found that antigen stimulation strength was inversely associated with the function of memory CD8 T cells during a persistent viral infection. We further show that CD8 TRM cells recruited to the brain following systemic infection with viruses expressing epitopes with suboptimal stimulation strength respond more efficiently to challenge CNS infection with virus expressing cognate antigen. These data demonstrate that the strength of antigenic stimulation during recruitment of CD8 T cells influences the functional integrity of TRM cells in a persistent viral infection.

Juvenile chronic arthritis into adulthood: a long-term follow-up study

DEFF Research Database (Denmark)

Zak, M; Pedersen, F K

2000-01-01

To evaluate a group of 65 adults with a history of or persistent juvenile chronic arthritis (JCA), on average, 26.4 yr after disease onset.......To evaluate a group of 65 adults with a history of or persistent juvenile chronic arthritis (JCA), on average, 26.4 yr after disease onset....

A Mouse Model of Chronic West Nile Virus Disease.

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Jessica B Graham

2016-11-01

Full Text Available Infection with West Nile virus (WNV leads to a range of disease outcomes, including chronic infection, though lack of a robust mouse model of chronic WNV infection has precluded identification of the immune events contributing to persistent infection. Using the Collaborative Cross, a population of recombinant inbred mouse strains with high levels of standing genetic variation, we have identified a mouse model of persistent WNV disease, with persistence of viral loads within the brain. Compared to lines exhibiting no disease or marked disease, the F1 cross CC(032x013F1 displays a strong immunoregulatory signature upon infection that correlates with restraint of the WNV-directed cytolytic response. We hypothesize that this regulatory T cell response sufficiently restrains the immune response such that a chronic infection can be maintained in the CNS. Use of this new mouse model of chronic neuroinvasive virus will be critical in developing improved strategies to prevent prolonged disease in humans.

Changes in IgA protease expression are conferred by changes in genomes during persistent infection by nontypeable Haemophilus influenzae in chronic obstructive pulmonary disease.

Science.gov (United States)

Gallo, Mary C; Kirkham, Charmaine; Eng, Samantha; Bebawee, Remon S; Kong, Yong; Pettigrew, Melinda M; Tettelin, Hervé; Murphy, Timothy F

2018-05-14

Nontypeable Haemophilus influenzae (NTHi) is an exclusively human pathobiont that plays a critical role in the course and pathogenesis of chronic obstructive pulmonary disease (COPD). NTHi causes acute exacerbations of COPD and also causes persistent infection of the lower airways. NTHi expresses four IgA protease variants (A1, A2, B1, and B2) that play different roles in virulence. Expression of IgA proteases varies among NTHi strains, but little is known about the frequency and mechanisms by which NTHi modulates IgA protease expression during infection in COPD. To assess expression of IgA protease during natural infection in COPD, we studied IgA protease expression of 101 persistent strains (median duration of persistence 161 days, range 2 to 1422) collected longitudinally from patients enrolled in a 20-year study of COPD upon initial acquisition and immediately before clearance from the host. Upon acquisition, 89 (88%) expressed IgA protease. A total of 16 of 101 (16%) strains of NTHi altered expression of IgA protease during persistence. Indels and slipped-strand mispairing of mononucleotide repeats conferred changes in expression of igaA1, igaA2, and igaB1 Strains with igaB2 underwent frequent changes in expression of IgA protease B2 during persistence, mediated by slipped-strand mispairing of a 7-nucleotide repeat, TCAAAAT, within the open reading frame of igaB2 We conclude that changes in iga gene sequences result in changes in expression of IgA proteases by NTHi during persistent infection in the respiratory tract of patients with COPD. Copyright © 2018 American Society for Microbiology.

Long-stay psychiatric patients: a prospective study revealing persistent antipsychotic-induced movement disorder.

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P Roberto Bakker

Full Text Available OBJECTIVE: The purpose of this study was to assess the frequency of persistent drug-induced movement disorders namely, tardive dyskinesia (TD, parkinsonism, akathisia and tardive dystonia in a representative sample of long-stay patients with chronic severe mental illness. METHOD: Naturalistic study of 209, mainly white, antipsychotic-treated patients, mostly diagnosed with psychotic disorder. Of this group, the same rater examined 194 patients at least two times over a 4-year period, with a mean follow-up time of 1.1 years, with validated scales for TD, parkinsonism, akathisia, and tardive dystonia. RESULTS: The frequencies of persistent movement disorders in the sample were 28.4% for TD, 56.2% for parkinsonism, 4.6% for akathisia and 5.7% for tardive dystonia. Two-thirds of the participants displayed at least one type of persistent movement disorder. CONCLUSIONS: Persistent movement disorder continues to be the norm for long-stay patients with chronic mental illness and long-term antipsychotic treatment. Measures are required to remedy this situation.

Left atrial volume index as a predictor for persistent left ventricular dysfunction after aortic valve surgery in patients with chronic aortic regurgitation: the role of early postoperative echocardiography.

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Cho, In-Jeong; Chang, Hyuk-Jae; Hong, Geu-Ru; Heo, Ran; Sung, Ji Min; Lee, Sang-Eun; Chang, Byung-Chul; Shim, Chi Young; Ha, Jong-Won; Chung, Namsik

2015-06-01

This study aimed to explore whether echocardiographic measurements during the early postoperative period can predict persistent left ventricular systolic dysfunction (LVSD) after aortic valve surgery in patients with chronic aortic regurgitation (AR). We prospectively recruited 54 patients (59 ± 12 years) with isolated chronic severe AR who subsequently underwent aortic valve surgery. Standard transthoracic echocardiography was performed before the operation, during the early postoperative period (≤2 weeks), and then 1 year after the surgery. Twelve patients with preoperative LVSD demonstrated LVSD at early after the surgery. Of the 42 patients without LVSD at preoperative echocardiography, 15 patients (36%) developed early postoperative LVSD after surgical correction. All 27 patients without LVSD at early postoperative echocardiography maintained LV function at 1 year after surgery. In the other 27 patients with postoperative LVSD, 17 patients recovered from LVSD and 10 patients did not at 1 year after surgery. Multiple logistic analysis demonstrated that postoperative left atrial volume index (LAVI) was the only independent predictor for persistent LVSD at 1 year after surgery in patients with postoperative LVSD (OR 1.180, 95% CI, 1.003-1.390, P = 0.046). The optimal LAVI cutoff value (>34.9 mL/m(2) ) had a sensitivity of 80% and a specificity of 88% for the prediction of persistent LVSD. Prevalence of early postoperative LVSD was relatively high, even in the patients without LVSD at preoperative echocardiography. Postoperative LAVI could be useful to predict persistent LVSD after aortic valve surgery in patients with early postoperative LVSD. © 2014, Wiley Periodicals, Inc.

Characterization of Sendai virus persistently infected L929 cells and Sendai virus pi strain: recombinant Sendai viruses having Mpi protein shows lower cytotoxicity and are incapable of establishing persistent infection

International Nuclear Information System (INIS)

Nishio, Machiko; Tsurudome, Masato; Ito, Morihiro; Kawano, Mitsuo; Komada, Hiroshi; Ito, Yasuhiko

2003-01-01

It is commonly accepted that the temperature-sensitive phenotype of Sendai virus (SeV) persistently infected cells is caused by the M and/or HN proteins. Expression level of the L, M, HN, and V proteins is extremely low in L929 cells persistently infected with SeVpi (L929/SeVpi cells) incubated at 38 deg. C. The HN protein quickly disappears in L929/SeVpi cells following a temperature shift up to 38 deg. C, and pulse-chase experiments show that the Lpi, HNpi, and Mpi proteins are unstable at 38 deg. C. Following a temperature shift either upward or downward, M protein is translocated into the nucleus and then localizes to the perinuclear region. None of virus-specific polypeptides are detected in the cells primarily infected with SeVpi and incubated at 38 deg. C and virus proteins are not pulse-labeled at 38 deg. C, indicating that temperature-sensitive step is at an early stage of infection. The Mpi protein is transiently located in the nucleus of the SeVpi primarily infected cells. Recombinant SeVs possessing the HNpi or/and Mpi proteins are not temperature-sensitive. The HN protein is expressed at very low levels and the F protein localizes to the perinuclear region in rSeV(Mpi)-infected cells incubated at 38 deg. C for 18 h. rSeVs having the Mpi protein exhibit lower cytotoxicity and are incapable of establishing persistent infection. Amino acid 116 of the Mpi protein is related to the nuclear translocation and lower cytopathogenesis, whereas aa183 is involved in the interaction between M protein and viral glycoproteins

TCR stimulation strength is inversely associated with establishment of functional brain-resident memory CD8 T cells during persistent viral infection.

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Saumya Maru

2017-04-01

Full Text Available Establishing functional tissue-resident memory (TRM cells at sites of infection is a newfound objective of T cell vaccine design. To directly assess the impact of antigen stimulation strength on memory CD8 T cell formation and function during a persistent viral infection, we created a library of mouse polyomavirus (MuPyV variants with substitutions in a subdominant CD8 T cell epitope that exhibit a broad range of efficiency in stimulating TCR transgenic CD8 T cells. By altering a subdominant epitope in a nonstructural viral protein and monitoring memory differentiation of donor monoclonal CD8 T cells in immunocompetent mice, we circumvented potentially confounding changes in viral infection levels, virus-associated inflammation, size of the immunodominant virus-specific CD8 T cell response, and shifts in TCR affinity that may accompany temporal recruitment of endogenous polyclonal cells. Using this strategy, we found that antigen stimulation strength was inversely associated with the function of memory CD8 T cells during a persistent viral infection. We further show that CD8 TRM cells recruited to the brain following systemic infection with viruses expressing epitopes with suboptimal stimulation strength respond more efficiently to challenge CNS infection with virus expressing cognate antigen. These data demonstrate that the strength of antigenic stimulation during recruitment of CD8 T cells influences the functional integrity of TRM cells in a persistent viral infection.

Identification of an Antimicrobial Agent Effective against Methicillin-Resistant Staphylococcus aureus Persisters Using a Fluorescence-Based Screening Strategy.

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Wooseong Kim

Full Text Available Persisters are a subpopulation of normal bacterial cells that show tolerance to conventional antibiotics. Persister cells are responsible for recalcitrant chronic infections and new antibiotics effective against persisters would be a major development in the treatment of these infections. Using the reporter dye SYTOX Green that only stains cells with permeabilized membranes, we developed a fluorescence-based screening assay in a 384-well format for identifying compounds that can kill methicillin-resistant Staphylococcus aureus (MRSA persisters. The assay proved robust and suitable for high throughput screening (Z`-factor: >0.7. In screening a library of hits from a previous screen, which identified compounds that had the ability to block killing of the nematode Caenorhabditis by MRSA, we discovered that the low molecular weight compound NH125, a bacterial histidine kinase inhibitor, kills MRSA persisters by causing cell membrane permeabilization, and that 5 μg/mL of the compound can kill all cells to the limit of detection in a 108 CFU/mL culture of MRSA persisters within 3h. Furthermore, NH125 disrupts 50% of established MRSA biofilms at 20 μg/mL and completely eradicates biofilms at 160 μg/mL. Our results suggest that the SYTOX Green screening assay is suitable for large-scale projects to identify small molecules effective against MRSA persisters and should be easily adaptable to a broad range of pathogens that form persisters. Since NH125 has strong bactericidal properties against MRSA persisters and high selectivity to bacteria, we believe NH125 is a good anti-MRSA candidate drug that should be further evaluated.

Identification of an Antimicrobial Agent Effective against Methicillin-Resistant Staphylococcus aureus Persisters Using a Fluorescence-Based Screening Strategy.

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Kim, Wooseong; Conery, Annie L; Rajamuthiah, Rajmohan; Fuchs, Beth Burgwyn; Ausubel, Frederick M; Mylonakis, Eleftherios

2015-01-01

Persisters are a subpopulation of normal bacterial cells that show tolerance to conventional antibiotics. Persister cells are responsible for recalcitrant chronic infections and new antibiotics effective against persisters would be a major development in the treatment of these infections. Using the reporter dye SYTOX Green that only stains cells with permeabilized membranes, we developed a fluorescence-based screening assay in a 384-well format for identifying compounds that can kill methicillin-resistant Staphylococcus aureus (MRSA) persisters. The assay proved robust and suitable for high throughput screening (Z`-factor: >0.7). In screening a library of hits from a previous screen, which identified compounds that had the ability to block killing of the nematode Caenorhabditis by MRSA, we discovered that the low molecular weight compound NH125, a bacterial histidine kinase inhibitor, kills MRSA persisters by causing cell membrane permeabilization, and that 5 μg/mL of the compound can kill all cells to the limit of detection in a 108 CFU/mL culture of MRSA persisters within 3h. Furthermore, NH125 disrupts 50% of established MRSA biofilms at 20 μg/mL and completely eradicates biofilms at 160 μg/mL. Our results suggest that the SYTOX Green screening assay is suitable for large-scale projects to identify small molecules effective against MRSA persisters and should be easily adaptable to a broad range of pathogens that form persisters. Since NH125 has strong bactericidal properties against MRSA persisters and high selectivity to bacteria, we believe NH125 is a good anti-MRSA candidate drug that should be further evaluated.

Alcohol intake alters immune responses and promotes CNS viral persistence in mice.

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Loftis, Jennifer M; Taylor, Jonathan; Raué, Hans-Peter; Slifka, Mark K; Huang, Elaine

2016-10-01

Chronic hepatitis C virus (HCV) infection leads to progressive liver disease and is associated with a variety of extrahepatic effects, including central nervous system (CNS) damage and neuropsychiatric impairments. Alcohol abuse can exacerbate these adverse effects on brain and behavior, but the molecular mechanisms are not well understood. This study investigated the role of alcohol in regulating viral persistence and CNS immunopathology in mice infected with lymphocytic choriomeningitis virus (LCMV), a model for HCV infections in humans. Female and male BALB/c mice (n=94) were exposed to alcohol (ethanol; EtOH) and water (or water only) using a two-bottle choice paradigm, followed one week later by infection with either LCMV clone 13 (causes chronic infection similar to chronic HCV), LCMV Armstrong (causes acute infection), or vehicle. Mice were monitored for 60days post-infection and continued to receive 24-h access to EtOH and water. Animals infected with LCMV clone 13 drank more EtOH, as compared to those with an acute or no viral infection. Six weeks after infection with LCMV clone 13, mice with EtOH exposure evidenced higher serum viral titers, as compared to mice without EtOH exposure. EtOH intake was also associated with reductions in virus-specific CD8(+) T cell frequencies (particularly CD11a(hi) subsets) and evidence of persistent CNS viremia in chronically infected mice. These findings support the hypothesis that EtOH use and chronic viral infection can result in combined toxic effects accelerating CNS damage and neuropsychiatric dysfunction and suggest that examining the role of EtOH in regulating viral persistence and CNS immunopathology in mice infected with LCMV can lead to a more comprehensive understanding of comorbid alcohol use disorder and chronic viral infection. Published by Elsevier B.V.

Low-Grade Persistent Hyperparathyroidism After Pediatric Renal Transplant.

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Gulleroglu, Kaan; Baskin, Esra; Moray, Gokhan; Haberal, Mehmet

2016-06-01

Hyperparathyroidism, a frequent complication of chronic kidney disease, persists after renal transplant. Our aims were to examine the status of parathyroid hormone levels and to determine the clinical and biochemical risk factors of persistent hyperparathyroidism after transplant. Our study included 44 pediatric renal transplant recipients with stable graft function. Median follow-up after transplant was 17.5 months (range, 12-126 mo). Patients did not receive routine vitamin D or calcium supplements after transplant, and none had undergone previous parathyroidectomy. Bone mineral densitometry of the lumbar spine was measured. Fifteen patients (34%) had parathyroid hormone levels greater than 70 pg/mL (normal range, 10-70 pg/mL). Duration of dialysis before transplant was longer in patients with persistent hyperparathyroidism. Mean serum bicarbonate levels were significantly lower in patients with persistent hyperparathyroidism than in patients without persistent hyperparathyroidism after transplant. A significant negative correlation was noted between parathyroid hormone level and serum bicarbonate level. Another significant negative correlation was shown between parathyroid hormone level and z score. We found that persistent hyperparathyroidism is related to longer dialysis duration, lower serum bicarbonate level, and lower z score. Pretransplant dialysis duration is an important predictor of persistent hyperparathyroidism. Early identification of factors that contribute to persistent hyperparathyroidism after transplant could lead to treatment strategies to minimize or prevent its detrimental effects on bone health and growth in pediatric transplant recipients.

Altering attentional control settings causes persistent biases of visual attention.

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Knight, Helen C; Smith, Daniel T; Knight, David C; Ellison, Amanda

2016-01-01

Attentional control settings have an important role in guiding visual behaviour. Previous work within cognitive psychology has found that the deployment of general attentional control settings can be modulated by training. However, research has not yet established whether long-term modifications of one particular type of attentional control setting can be induced. To address this, we investigated persistent alterations to feature search mode, also known as an attentional bias, towards an arbitrary stimulus in healthy participants. Subjects were biased towards the colour green by an information sheet. Attentional bias was assessed using a change detection task. After an interval of either 1 or 2 weeks, participants were then retested on the same change detection task, tested on a different change detection task where colour was irrelevant, or were biased towards an alternative colour. One experiment included trials in which the distractor stimuli (but never the target stimuli) were green. The key finding was that green stimuli in the second task attracted attention, despite this impairing task performance. Furthermore, inducing a second attentional bias did not override the initial bias toward green objects. The attentional bias also persisted for at least two weeks. It is argued that this persistent attentional bias is mediated by a chronic change to participants' attentional control settings, which is aided by long-term representations involving contextual cueing. We speculate that similar changes to attentional control settings and continuous cueing may relate to attentional biases observed in psychopathologies. Targeting these biases may be a productive approach to treatment.

Modeling routes of chronic wasting disease transmission: Environmental prion persistence promotes deer population decline and extinction

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Almberg, Emily S.; Cross, Paul C.; Johnson, Christopher J.; Heisey, Dennis M.; Richards, Bryan J.

2011-01-01

Chronic wasting disease (CWD) is a fatal disease of deer, elk, and moose transmitted through direct, animal-to-animal contact, and indirectly, via environmental contamination. Considerable attention has been paid to modeling direct transmission, but despite the fact that CWD prions can remain infectious in the environment for years, relatively little information exists about the potential effects of indirect transmission on CWD dynamics. In the present study, we use simulation models to demonstrate how indirect transmission and the duration of environmental prion persistence may affect epidemics of CWD and populations of North American deer. Existing data from Colorado, Wyoming, and Wisconsin's CWD epidemics were used to define plausible short-term outcomes and associated parameter spaces. Resulting long-term outcomes range from relatively low disease prevalence and limited host-population decline to host-population collapse and extinction. Our models suggest that disease prevalence and the severity of population decline is driven by the duration that prions remain infectious in the environment. Despite relatively low epidemic growth rates, the basic reproductive number, R0, may be much larger than expected under the direct-transmission paradigm because the infectious period can vastly exceed the host's life span. High prion persistence is expected to lead to an increasing environmental pool of prions during the early phases (i.e. approximately during the first 50 years) of the epidemic. As a consequence, over this period of time, disease dynamics will become more heavily influenced by indirect transmission, which may explain some of the observed regional differences in age and sex-specific disease patterns. This suggests management interventions, such as culling or vaccination, will become increasingly less effective as CWD epidemics progress.

Modelling the role of Tax expression in HTLV-I persistence in vivo.

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Li, Michael Y; Lim, Aaron G

2011-12-01

Human T-lymphotropic virus type I (HTLV-I) is a persistent human retrovirus characterized by life-long infection and risk of developing HAM/TSP, a progressive neurological and inflammatory disease, and adult T-cell leukemia (ATL). Chronically infected individuals often harbor high proviral loads despite maintaining a persistently activated immune response. Based on a new hypothesis for the persistence of HTLV-I infection, a three-dimensional compartmental model is constructed that describes the dynamic interactions among latently infected target cells, target-cell activation, and immune responses to HTLV-I, with an emphasis on understanding the role of Tax expression in the persistence of HTLV-I.

Persistent idiopathic facial pain

DEFF Research Database (Denmark)

Maarbjerg, Stine; Wolfram, Frauke; Heinskou, Tone Bruvik

2017-01-01

Introduction: Persistent idiopathic facial pain (PIFP) is a poorly understood chronic orofacial pain disorder and a differential diagnosis to trigeminal neuralgia. To address the lack of systematic studies in PIFP we here report clinical characteristics and neuroimaging findings in PIFP. Methods...... pain 7 (13%), hypoesthesia 23 (48%), depression 16 (30%) and other chronic pain conditions 17 (32%) and a low prevalence of stabbing pain 21 (40%), touch-evoked pain 14 (26%) and remission periods 10 (19%). The odds ratio between neurovascular contact and the painful side was 1.4 (95% Cl 0.4–4.4, p = 0.......565) and the odds ratio between neurovascular contact with displacement of the trigeminal nerve and the painful side was 0.2 (95% Cl 0.0–2.1, p = 0.195). Conclusion: PIFP is separated from trigeminal neuralgia both with respect to the clinical characteristics and neuroimaging findings, as NVC was not associated...

Trends in the treatment changes and medication persistence of chronic myeloid leukemia in Taiwan from 1997 to 2007: a longitudinal population database analysis

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Chang Chao-Sung

2012-10-01

Full Text Available Abstract Background Few studies have examined the longitudinal changes in the patterns, selection, and utilization of treatments for chronic myeloid leukemia (CML in routine clinical practice since the introduction of imatinib. Therefore, we investigated the trends in CML therapy, including changes, patterns, and persistence to imatinib therapy among patients with newly diagnosed CML. Methods We conducted a cross-sectional and longitudinal analysis of 11 years of claims data for patients with newly diagnosed CML included in the Taiwan National Health Insurance program. Pharmacy and diagnosis claims for newly diagnosed CML recorded between 1997 and 2007 year were extracted from the database. Annual overall use, new use of CML therapy, and persistence to imatinib therapy were estimated. The Anatomical Therapeutic Chemical codes for CML therapy [i.e., imatinib and conventional therapy: busulfan, hydroxyurea, interferon-α (IFNα, and cytarabine], and the process code for hematopoietic stem cell transplantation were used to categorize treatment patterns. Associations with patients characteristics were analyzed by multivariate logistic regression. Results Overall, the proportion of patients with newly diagnosed CML to all patients with CML increased by approximately 4-fold between 1998 and 2007. There were steady increases in the proportions of all treated patients and those starting therapy from 2003 to 2007. Fewer comorbid conditions and lower severity of CML were associated with treatment initiation. Medication persistence varied according to treatment duration, as 38.7% patients continued imatinib for ≥ 18 months without interruption but only 7.7% continued imatinib for ≥ 5 years. Factors associated with persistence to imatinib therapy were removal of the need for prior authorization for imatinib, and prior use of hydroxyurea and IFNα, whereas having undergone hematopoietic stem cell transplantation led to reduced likelihood

A novel model of chronic wounds: importance of redox imbalance and biofilm-forming bacteria for establishment of chronicity.

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Sandeep Dhall

Full Text Available Chronic wounds have a large impact on health, affecting ∼6.5 M people and costing ∼$25B/year in the US alone. We previously discovered that a genetically modified mouse model displays impaired healing similar to problematic wounds in humans and that sometimes the wounds become chronic. Here we show how and why these impaired wounds become chronic, describe a way whereby we can drive impaired wounds to chronicity at will and propose that the same processes are involved in chronic wound development in humans. We hypothesize that exacerbated levels of oxidative stress are critical for initiation of chronicity. We show that, very early after injury, wounds with impaired healing contain elevated levels of reactive oxygen and nitrogen species and, much like in humans, these levels increase with age. Moreover, the activity of anti-oxidant enzymes is not elevated, leading to buildup of oxidative stress in the wound environment. To induce chronicity, we exacerbated the redox imbalance by further inhibiting the antioxidant enzymes and by infecting the wounds with biofilm-forming bacteria isolated from the chronic wounds that developed naturally in these mice. These wounds do not re-epithelialize, the granulation tissue lacks vascularization and interstitial collagen fibers, they contain an antibiotic-resistant mixed bioflora with biofilm-forming capacity, and they stay open for several weeks. These findings are highly significant because they show for the first time that chronic wounds can be generated in an animal model effectively and consistently. The availability of such a model will significantly propel the field forward because it can be used to develop strategies to regain redox balance that may result in inhibition of biofilm formation and result in restoration of healthy wound tissue. Furthermore, the model can lead to the understanding of other fundamental mechanisms of chronic wound development that can potentially lead to novel therapies.

Chronic Abdominal Wall Pain.

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Koop, Herbert; Koprdova, Simona; Schürmann, Christine

2016-01-29

Chronic abdominal wall pain is a poorly recognized clinical problem despite being an important element in the differential diagnosis of abdominal pain. This review is based on pertinent articles that were retrieved by a selective search in PubMed and EMBASE employing the terms "abdominal wall pain" and "cutaneous nerve entrapment syndrome," as well as on the authors' clinical experience. In 2% to 3% of patients with chronic abdominal pain, the pain arises from the abdominal wall; in patients with previously diagnosed chronic abdominal pain who have no demonstrable pathological abnormality, this likelihood can rise as high as 30% . There have only been a small number of clinical trials of treatment for this condition. The diagnosis is made on clinical grounds, with the aid of Carnett's test. The characteristic clinical feature is strictly localized pain in the anterior abdominal wall, which is often mischaracterized as a "functional" complaint. In one study, injection of local anesthesia combined with steroids into the painful area was found to relieve pain for 4 weeks in 95% of patients. The injection of lidocaine alone brought about improvement in 83-91% of patients. Long-term pain relief ensued after a single lidocaine injection in 20-30% of patients, after repeated injections in 40-50% , and after combined lidocaine and steroid injections in up to 80% . Pain that persists despite these treatments can be treated with surgery (neurectomy). Chronic abdominal wall pain is easily diagnosed on physical examination and can often be rapidly treated. Any physician treating patients with abdominal pain should be aware of this condition. Further comparative treatment trials will be needed before a validated treatment algorithm can be established.

Interventions for treating persistent pain in survivors of torture

DEFF Research Database (Denmark)

Baird, Emma; Williams, Amanda C de C; Amris, Kirstine

2017-01-01

BACKGROUND: Persistent (chronic) pain is a frequent complaint in survivors of torture, particularly but not exclusively pain in the musculoskeletal system. Torture survivors may have no access to health care; where they do, they may not be recognised when they present, and the care available often...... falls short of their needs. There is a tendency in state and non-governmental organisations' services to focus on mental health, with poor understanding of persistent pain, while survivors may have many other legal, welfare, and social problems that take precedence over health care. OBJECTIVES...

Observations on the Current Bacteriological Profile of Chronic ...

African Journals Online (AJOL)

Department of Otolaryngology,. University of Nigeria Teaching. Hospital, Enugu, Nigeria. E‑mail: tochiorji@yahoo.com. Introduction. Chronic suppurative otitis media (CSOM) is the most common infection of the ear characterized by persistent or recurrent purulent drainage from the middle ear through a persistent nonintact ...

Hallucinogen persisting perception disorder after psilocybin consumption: a case study.

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Espiard, Marie-Laure; Lecardeur, Laurent; Abadie, Pascale; Halbecq, Isabelle; Dollfus, Sonia

2005-08-01

The recurrence of flashbacks without acute or chronic hallucinogen consumption has been recognized in the DSM IV criteria as the hallucinogen persisting perception disorder (HPPD). Perceptual disturbances may last for 5 years or more and represent a real psychosocial distress. We reported here a case of a 18-year-old young man presenting HPPD after a mixed intoxication with psylocibin and cannabis. This report shows symptomatic recurrences persisting more than 8 months. Various differential diagnoses were evoked and our therapeutic strategies were described.

[Establishing self-management for chronic spinal cord injury patients: a qualitative investigation].

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Okochi, Ayako; Tadaka, Etsuko

2015-01-01

Self-management is essential for individuals with chronic cervical spinal cord injury, but some cases of self-neglect have been reported. The objective of this study was to examine the establishment of self-management in order to help inform community care practice. This was a qualitative study applying a grounded theory approach with semi-structured home interviews. We interviewed 29 individuals with cervical spinal cord injuries (aged 26-77 years) who were members of each of the three branches of the nationwide self-help group, or the clients of a home-visit nursing care station. Qualitative analysis was implemented from a time transition perspective consisting of the faint awareness period, the seeking period, and the adaptation period. The analysis included the perceptions and methods of self-management. The process of establishing self-management was abstracted into a core category of "continuous adaptation to minimize the extent to which the individual's life was disrupted and to allow them to continue to live within the community". This in turn consisted of seven categories. In the faint awareness period, subjects perceived that they "hardly recognized health maintenance needs", that they had difficulties in acknowledging the necessity of controlling physical conditions, and that they were dependent on caregivers. In the seeking period, they were "driven by handling uncontrollable changes" and they coped with those changes in their own way and sometimes did not consider it necessary to see a doctor. In this period, a process of "searching for the methods of being healthy somehow" begun and they started to understand the degree to which they could cope without medication, together with their own responsibilities, and searched for the best coping methods and acted on advice. In the adaptation period, individuals were "struggling to continue the established health methods"; "managing stress"; "prioritizing their own beliefs over medical regimens"; and

Persistence of DNA damage following exposure of human bladder cells to chronic monomethylarsonous acid

International Nuclear Information System (INIS)

Wnek, S.M.; Medeiros, M.K.; Eblin, K.E.; Gandolfi, A.J.

2009-01-01

Malignant transformation was demonstrated in UROtsa cells following 52-weeks of exposure to 50 nM monomethylarsonous acid (MMA III ); the result was the malignantly transformed cell line, URO-MSC. URO-MSC cells were used to study the induction of DNA damage and the alteration of DNA repair enzymes in both the presence of MMA III [URO-MSC(+)] and after subsequent removal of MMA III [URO-MSC(-)] following chronic, low-level exposure. In the presence of MMA III , URO-MSC(+) cells demonstrated a sustained increase in DNA damage following 12-weeks of exposure; in particular, a significant increase in DNA single-strand breaks at 12-weeks of exposure consistently elevated through 52 weeks. The persistence of DNA damage in URO-MSC cells was assessed after a 2-week removal of MMA III . URO-MSC(-) cells demonstrated a decrease in DNA damage compared to URO-MSC(+); however, DNA damage in URO-MSC(-) remained significantly elevated when compared to untreated UROtsa and increased in a time-dependent manner. Reactive oxygen species (ROS) were demonstrated to be a critical component in the generation of DNA damage determined through the incubation of ROS scavengers with URO-MSC cells. Poly (ADP-ribose) polymerase (PARP) is a key repair enzyme in DNA single-strand break repair. URO-MSC(+) resulted in a slight increase in PARP activity after 36-weeks of MMA III exposure, suggesting the presence of MMA III is inhibiting the increase in PARP activity. In support, PARP activity in URO-MSC(-) increased significantly, coinciding with a subsequent decrease in DNA damage demonstrated in URO-MSC(-) compared to URO-MSC(+). These data demonstrate that chronic, low-level exposure of UROtsa cells to 50 nM MMA III results in: the induction of DNA damage that remains elevated upon removal of MMA III ; increased levels of ROS that play a role in MMA III induced-DNA damage; and decreased PARP activity in the presence of MMA III .

Persistence and extinction for a stochastic logistic model with infinite delay

OpenAIRE

Chun Lu; Xiaohua Ding

2013-01-01

This article, studies a stochastic logistic model with infinite delay. Using a phase space, we establish sufficient conditions for the extinction, nonpersistence in the mean, weak persistence, and stochastic permanence. A threshold between weak persistence and extinction is obtained. Our results state that different types of environmental noises have different effects on the persistence and extinction, and that the delay has no impact on the persistence and ext...

Self-rated health and chronic conditions are associated with blood concentrations of persistent organic pollutants in the general population of Catalonia, Spain.

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Gasull, Magda; Pallarès, Natàlia; Salcedo, Natalia; Pumarega, José; Alonso, Jordi; Porta, Miquel

2015-11-01

Self-rated health (SRH) is a powerful predictor of mortality, morbidity, and need for health services. SRH generally increases with educational level, and decreases with age, number of chronic conditions, and body mass index (BMI). Because human concentrations of most persistent organic pollutants (POPs) also vary by age, education, and BMI, and because of the physiological and clinical effects of POPs, we hypothesized that body concentrations of POPs are inversely associated with SRH. To analyze the relation between serum concentrations of POPs and SRH in the general population of Catalonia, Spain, taking into account sociodemographic factors and BMI, as well as chronic health conditions and mental disorders, measured by the General Health Questionnaire-12 (GHQ-12). POP serum concentrations were measured by gas chromatography with electron-capture detection in 919 participants of the Catalan Health Interview Survey. Individuals with higher concentrations of POPs had significantly poorer SRH; e.g., the median concentration of HCB in subjects with poor SRH was twice as high as in subjects with excellent SRH (366 ng/g vs. 169 ng/g, respectively; p-valuehigher in subjects with POP concentrations in the top quartile. In models adjusted for age or for chronic conditions virtually all ORs were near unity. No associations were found between POP levels and GHQ-12. Individuals with higher concentrations of POPs had significantly poorer SRH, an association likely due to age and chronic conditions, but not to sex, education, social class, BMI, or mental disorders. Copyright © 2015 Elsevier Inc. All rights reserved.

Immune Evasion Strategies and Persistence of Helicobacter pylori.

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Mejías-Luque, Raquel; Gerhard, Markus

Helicobacter pylori infection is commonly acquired during childhood, can persist lifelong if not treated, and can cause different gastric pathologies, including chronic gastritis, peptic ulcer disease, and eventually gastric cancer. H. pylori has developed a number of strategies in order to cope with the hostile conditions found in the human stomach as well as successful mechanisms to evade the strong innate and adaptive immune responses elicited upon infection. Thus, by manipulating innate immune receptors and related signaling pathways, inducing tolerogenic dendritic cells and inhibiting effector T cell responses, H. pylori ensures low recognition by the host immune system as well as its persistence in the gastric epithelium. Bacterial virulence factors such as cytotoxin-associated gene A, vacuolating cytotoxin A, or gamma-glutamyltranspeptidase have been extensively studied in the context of bacterial immune escape and persistence. Further, the bacterium possesses other factors that contribute to immune evasion. In this chapter, we discuss in detail the main evasion and persistence strategies evolved by the bacterium as well as the specific bacterial virulence factors involved.

Chronic daily headaches

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Fayyaz Ahmed

2012-01-01

Full Text Available Chronic Daily Headache is a descriptive term that includes disorders with headaches on more days than not and affects 4% of the general population. The condition has a debilitating effect on individuals and society through direct cost to healthcare and indirectly to the economy in general. To successfully manage chronic daily headache syndromes it is important to exclude secondary causes with comprehensive history and relevant investigations; identify risk factors that predict its development and recognise its sub-types to appropriately manage the condition. Chronic migraine, chronic tension-type headache, new daily persistent headache and medication overuse headache accounts for the vast majority of chronic daily headaches. The scope of this article is to review the primary headache disorders. Secondary headaches are not discussed except medication overuse headache that often accompanies primary headache disorders. The article critically reviews the literature on the current understanding of daily headache disorders focusing in particular on recent developments in the treatment of frequent headaches.

EBV CHRONIC INFECTIONS

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Delia Racciatti

2010-02-01

Full Text Available

The infection from Epstein-Barr virus (EBV or virus of infectious mononucleosis, together with other herpesviruses’ infections, represents a prototype of persistent viral infections characterized by the property of the latency. Although the reactivations of the latent infection are associated with the resumption of the viral replication and eventually with the “shedding”, it is still not clear if this virus can determine chronic infectious diseases, more or less evolutive. These diseases could include some pathological conditions actually defined as “idiopathic”and characterized by the “viral persistence” as the more credible pathogenetic factor. Among the so-called idiopathic syndromes, the “chronic fatigue syndrome” (CFS aroused a great interest around the eighties of the last century when, just for its relationship with EBV, it was called “chronic mononucleosis” or “chronic EBV infection”.

Today CFS, as defined in 1994 by the CDC of Atlanta (USA, really represents a multifactorial syndrome characterized by a chronic course, where reactivation and remission phases alternate, and by a good prognosis

Viral Interference and Persistence in Mosquito-Borne Flaviviruses

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Juan Santiago Salas-Benito

2015-01-01

Full Text Available Mosquito-borne flaviviruses are important pathogens for humans, and the detection of two or more flaviviruses cocirculating in the same geographic area has often been reported. However, the epidemiological impact remains to be determined. Mosquito-borne flaviviruses are primarily transmitted through Aedes and Culex mosquitoes; these viruses establish a life-long or persistent infection without apparent pathological effects. This establishment requires a balance between virus replication and the antiviral host response. Viral interference is a phenomenon whereby one virus inhibits the replication of other viruses, and this condition is frequently associated with persistent infections. Viral interference and persistent infection are determined by several factors, such as defective interfering particles, competition for cellular factors required for translation/replication, and the host antiviral response. The interaction between two flaviviruses typically results in viral interference, indicating that these viruses share common features during the replicative cycle in the vector. The potential mechanisms involved in these processes are reviewed here.

Photocarcinogenesis and persistent hyperplasia in UV-irradiated SENCAR mouse skin

International Nuclear Information System (INIS)

Strickland, P.T.

1986-01-01

Susceptibility to photocarcinogenesis has been examined in several mouse strains and stocks including SENCAR, CD-1, BALB/c, C3H, C57Bl, and NZB. SENCAR mice are hypersusceptible to tumorigenesis caused by single high dose exposures to ultraviolet (UV) radiation but not by chronic low-dose exposures. SENCAR mice also exhibit an exaggerated and persistent epidermal hyperplasia in response to UV-induced tissue damage. The persistent hyperplasia is apparently due to a sustained proliferation of the epithelial basal cells, rather than to delayed cell differentiation. SENCAR mice did not exhibit persistent hyperplasia following other forms of tissue damage (surgical or thermal). In related studies, the levels of thymine dimers induced in SENCAR epidermis by UV radiation were comparable to those observed in BALB/c epidermis. In addition, no differences were found in the tissue distribution or persistence of thymine dimers in SENCAR and BALB/c skin

Persistent systemic inflammation is associated with poor clinical outcomes in COPD

DEFF Research Database (Denmark)

Agustí, Alvar; Edwards, Lisa D; Rennard, Stephen I

2012-01-01

Because chronic obstructive pulmonary disease (COPD) is a heterogeneous condition, the identification of specific clinical phenotypes is key to developing more effective therapies. To explore if the persistence of systemic inflammation is associated with poor clinical outcomes in COPD we assessed...

Toxoplasma depends on lysosomal consumption of autophagosomes for persistent infection.

Science.gov (United States)

Di Cristina, Manlio; Dou, Zhicheng; Lunghi, Matteo; Kannan, Geetha; Huynh, My-Hang; McGovern, Olivia L; Schultz, Tracey L; Schultz, Aric J; Miller, Alyssa J; Hayes, Beth M; van der Linden, Wouter; Emiliani, Carla; Bogyo, Matthew; Besteiro, Sébastien; Coppens, Isabelle; Carruthers, Vern B

2017-06-19

Globally, nearly 2 billion people are infected with the intracellular protozoan Toxoplasma gondii 1 . This persistent infection can cause severe disease in immunocompromised people and is epidemiologically linked to major mental illnesses 2 and cognitive impairment 3 . There are currently no options for curing this infection. The lack of effective therapeutics is due partly to a poor understanding of the essential pathways that maintain long-term infection. Although it is known that Toxoplasma replicates slowly within intracellular cysts demarcated with a cyst wall, precisely how it sustains itself and remodels organelles in this niche is unknown. Here, we identify a key role for proteolysis within the parasite lysosomal organelle (the vacuolar compartment or VAC) in turnover of autophagosomes and persistence during neural infection. We found that disrupting a VAC-localized cysteine protease compromised VAC digestive function and markedly reduced chronic infection. Death of parasites lacking the VAC protease was preceded by accumulation of undigested autophagosomes in the parasite cytoplasm. These findings suggest an unanticipated function for parasite lysosomal degradation in chronic infection, and identify an intrinsic role for autophagy in the T. gondii parasite and its close relatives. This work also identifies a key element of Toxoplasma persistence and suggests that VAC proteolysis is a prospective target for pharmacological development.

Enhanced Gamma Oscillatory Activity in Rats with Chronic Inflammatory Pain

OpenAIRE

Wang, Jing; Wang, Jing; Xing, Guo-Gang; Li, Xiaoli; Wan, You

2016-01-01

It has been reported that oscillatory gamma activity participates in brief acute pain and tonic ongoing pain. It is of great interest to determine whether the gamma activity is involved in chronic pain since chronic pain is a more severe pathological condition characterized by pain persistency. To investigate the oscillatory gamma activity in chronic pain, in the present study, we recorded spontaneous electrocorticogram (ECoG) signals during chronic pain development in rats with chronic infla...

Association Between Persistent Pain and Memory Decline and Dementia in a Longitudinal Cohort of Elders.

Science.gov (United States)

Whitlock, Elizabeth L; Diaz-Ramirez, L Grisell; Glymour, M Maria; Boscardin, W John; Covinsky, Kenneth E; Smith, Alexander K

2017-08-01

Chronic pain is common among the elderly and is associated with cognitive deficits in cross-sectional studies; the population-level association between chronic pain and longitudinal cognition is unknown. To determine the population-level association between persistent pain, which may reflect chronic pain, and subsequent cognitive decline. Cohort study with biennial interviews of 10 065 community-dwelling older adults in the nationally representative Health and Retirement Study who were 62 years or older in 2000 and answered pain and cognition questions in both 1998 and 2000. Data analysis was conducted between June 24 and October 31, 2016. "Persistent pain," defined as a participant reporting that he or she was often troubled with moderate or severe pain in both the 1998 and 2000 interviews. Coprimary outcomes were composite memory score and dementia probability, estimated by combining neuropsychological test results and informant and proxy interviews, which were tracked from 2000 through 2012. Linear mixed-effects models, with random slope and intercept for each participant, were used to estimate the association of persistent pain with slope of the subsequent cognitive trajectory, adjusting for demographic characteristics and comorbidities measures in 2000 and applying sampling weights to represent the 2000 US population. We hypothesized that persistent pain would predict accelerated memory decline and increased probability of dementia. To quantify the impact of persistent pain on functional independence, we combined our primary results with information on the association between memory and ability to manage medications and finances independently. Of the 10 065 eligible HRS sample members, 60% were female, and median baseline age was 73 years (interquartile range, 67-78 years). At baseline, persistent pain affected 10.9% of participants and was associated with worse depressive symptoms and more limitations in activities of daily living. After covariate

Laboratory diagnosis of persistent human chlamydial infection

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Mirja ePuolakkainen

2013-12-01

Full Text Available Diagnostic assays for persistent chlamydial infection are much needed to conduct high-quality, large-scale studies investigating the persistent state in vivo, its disease associations and the response to therapy. Yet in most studies the distinction between acute and persistent infection is based on the interpretation of the data obtained by the assays developed to diagnose acute infections or on complex assays available for research only and/or difficult to establish for clinical use. Novel biomarkers for detection of persistent chlamydial infection are urgently needed. Chlamydial whole genome proteome arrays are now available and they can identify chlamydial antigens that are differentially expressed between acute infection and persistent infection. Utilizing these data will lead to the development of novel diagnostic assays. Carefully selected specimens from well-studied patient populations are clearly needed in the process of translating the proteomic data into assays useful for clinical practice. Before such antigens are identified and validated assays become available, we face a challenge of deciding whether the persistent infection truly induced appearance of the proposed marker or do we just base our diagnosis of persistent infection on the presence of the suggested markers. Consequently, we must bear this in mind when interpreting the available data.

Patient-reported outcomes (PROs) in chronic urticaria

DEFF Research Database (Denmark)

Moestrup, Kristian; Ghazanfar, Misbah N.; Thomsen, Simon F.

2017-01-01

Chronic urticaria is an itching skin disease which persists for more than 6 weeks. Chronic urticaria has great impact on the daily life of the patient, and the fluctuating nature of the symptoms complicates the monitoring and treatment of the disease. Currently, there are no reliable biomarkers...... to identify and measure disease activity in chronic spontaneous urticaria. Consequently, use of patient-reported outcomes (PROs) is crucial when evaluating and monitoring different aspects of chronic urticaria such as disease activity/severity, disease control, and quality of life. We present an overview...... of seven different PROs used in chronic urticaria and highlight their strengths, limitations, and use in clinical practice and research....

Persistence and extinction for a stochastic logistic model with infinite delay

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Chun Lu

2013-11-01

Full Text Available This article, studies a stochastic logistic model with infinite delay. Using a phase space, we establish sufficient conditions for the extinction, nonpersistence in the mean, weak persistence, and stochastic permanence. A threshold between weak persistence and extinction is obtained. Our results state that different types of environmental noises have different effects on the persistence and extinction, and that the delay has no impact on the persistence and extinction for the stochastic model in the autonomous case. Numerical simulations illustrate the theoretical results.

[Exposure to persistent and non-persistent pesticides in a non-occupationally exposed population in Tenerife Island (Spain)].

Science.gov (United States)

Burillo-Putze, Guillermo; Luzardo, Octavio P; García, Carlos Pérez; Zumbado, Manuel; Yanes, Carmen; Trujillo-Martín, María del Mar; Boada Fernández del Campo, Carlos; Boada, Luis D

2014-01-01

Chronic exposure to non-persistent pesticides (NPPs) is of concern because these substances have been associated with chronic diseases. However, few studies have addressed chronic exposure to NPPs in Spanish populations. We determined the presence of 24 pesticide residues by gas chromatography/mass spectrometry in 363 serum samples obtained from non-occupationally exposed adults from Tenerife island in 2007. Most of the samples (99.45%) showed detectable residues (6 ± 2 pesticides per sample). The most frequently detected pesticides were pyrethrins (96.1%), organophosphates (93.9%) and organochlorines (92.3%). The neurotoxicants bifenthrin and malathion were detected in 81% of the samples and hexachlorobenzene DDT and buprofezin in more than 50%. Malation, an "environmental obesogen", was detected in 82%, and "endocrine disrupter" pesticides were present in 97.2% of the samples. Because there is clear, continuous and inadvertent exposure to NPPs that may be inducing adverse effects on human health, NPPs should be included in biomonitoring studies. Copyright © 2013 SESPAS. Published by Elsevier Espana. All rights reserved.

Evolution of a Cell Culture-Derived Genotype 1a Hepatitis C Virus (H77S.2) during Persistent Infection with Chronic Hepatitis in a Chimpanzee

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Yi, MinKyung; Hu, Fengyu; Joyce, Michael; Saxena, Vikas; Welsch, Christoph; Chavez, Deborah; Guerra, Bernadette; Yamane, Daisuke; Veselenak, Ronald; Pyles, Rick; Walker, Christopher M.; Tyrrell, Lorne; Bourne, Nigel; Lanford, Robert E.

2014-01-01

ABSTRACT Persistent infection is a key feature of hepatitis C virus (HCV). However, chimpanzee infections with cell culture-derived viruses (JFH1 or related chimeric viruses that replicate efficiently in cell culture) have been limited to acute-transient infections with no pathogenicity. Here, we report persistent infection with chronic hepatitis in a chimpanzee challenged with cell culture-derived genotype 1a virus (H77S.2) containing 6 cell culture-adaptive mutations. Following acute-transient infection with a chimeric H77/JFH1 virus (HJ3-5), intravenous (i.v.) challenge with 106 FFU H77S.2 virus resulted in immediate seroconversion and, following an unusual 4- to 6-week delay, persistent viremia accompanied by alanine aminotransferase (ALT) elevation, intrahepatic innate immune responses, and diffuse hepatopathy. This first persistent infection with cell culture-produced HCV provided a unique opportunity to assess evolution of cell culture-adapted virus in vivo. Synonymous and nonsynonymous nucleotide substitution rates were greatest during the first 8 weeks of infection. Of 6 cell culture-adaptive mutations in H77S.2, Q1067R (NS3) had reverted to Q1067 and S2204I (NS5A) was replaced by T2204 within 8 weeks of infection. By 62 weeks, 4 of 6 mutations had reverted to the wild-type sequence, and all reverted to the wild-type sequence by 194 weeks. The data suggest H77S.2 virus has greater potential for persistence and pathogenicity than JFH1 and demonstrate both the capacity of a nonfit virus to persist for weeks in the liver in the absence of detectable viremia as well as strong selective pressure against cell culture-adaptive mutations in vivo. IMPORTANCE This study shows that mutations promoting the production of infectious genotype 1a HCV in cell culture have the opposite effect and attenuate replication in the liver of the only fully permissive animal species other than humans. It provides the only example to date of persistent infection in a chimpanzee

Evolution of a cell culture-derived genotype 1a hepatitis C virus (H77S.2) during persistent infection with chronic hepatitis in a chimpanzee.

Science.gov (United States)

Yi, MinKyung; Hu, Fengyu; Joyce, Michael; Saxena, Vikas; Welsch, Christoph; Chavez, Deborah; Guerra, Bernadette; Yamane, Daisuke; Veselenak, Ronald; Pyles, Rick; Walker, Christopher M; Tyrrell, Lorne; Bourne, Nigel; Lanford, Robert E; Lemon, Stanley M

2014-04-01

Persistent infection is a key feature of hepatitis C virus (HCV). However, chimpanzee infections with cell culture-derived viruses (JFH1 or related chimeric viruses that replicate efficiently in cell culture) have been limited to acute-transient infections with no pathogenicity. Here, we report persistent infection with chronic hepatitis in a chimpanzee challenged with cell culture-derived genotype 1a virus (H77S.2) containing 6 cell culture-adaptive mutations. Following acute-transient infection with a chimeric H77/JFH1 virus (HJ3-5), intravenous (i.v.) challenge with 10(6) FFU H77S.2 virus resulted in immediate seroconversion and, following an unusual 4- to 6-week delay, persistent viremia accompanied by alanine aminotransferase (ALT) elevation, intrahepatic innate immune responses, and diffuse hepatopathy. This first persistent infection with cell culture-produced HCV provided a unique opportunity to assess evolution of cell culture-adapted virus in vivo. Synonymous and nonsynonymous nucleotide substitution rates were greatest during the first 8 weeks of infection. Of 6 cell culture-adaptive mutations in H77S.2, Q1067R (NS3) had reverted to Q1067 and S2204I (NS5A) was replaced by T2204 within 8 weeks of infection. By 62 weeks, 4 of 6 mutations had reverted to the wild-type sequence, and all reverted to the wild-type sequence by 194 weeks. The data suggest H77S.2 virus has greater potential for persistence and pathogenicity than JFH1 and demonstrate both the capacity of a nonfit virus to persist for weeks in the liver in the absence of detectable viremia as well as strong selective pressure against cell culture-adaptive mutations in vivo. This study shows that mutations promoting the production of infectious genotype 1a HCV in cell culture have the opposite effect and attenuate replication in the liver of the only fully permissive animal species other than humans. It provides the only example to date of persistent infection in a chimpanzee challenged with cell

The High Costs of Low-Grade Inflammation: Persistent Fatigue as a Consequence of Reduced Cellular-Energy Availability and Non-adaptive Energy Expenditure.

Science.gov (United States)

Lacourt, Tamara E; Vichaya, Elisabeth G; Chiu, Gabriel S; Dantzer, Robert; Heijnen, Cobi J

2018-01-01

Chronic or persistent fatigue is a common, debilitating symptom of several diseases. Persistent fatigue has been associated with low-grade inflammation in several models of fatigue, including cancer-related fatigue and chronic fatigue syndrome. However, it is unclear how low-grade inflammation leads to the experience of fatigue. We here propose a model of an imbalance in energy availability and energy expenditure as a consequence of low-grade inflammation. In this narrative review, we discuss how chronic low-grade inflammation can lead to reduced cellular-energy availability. Low-grade inflammation induces a metabolic switch from energy-efficient oxidative phosphorylation to fast-acting, but less efficient, aerobic glycolytic energy production; increases reactive oxygen species; and reduces insulin sensitivity. These effects result in reduced glucose availability and, thereby, reduced cellular energy. In addition, emerging evidence suggests that chronic low-grade inflammation is associated with increased willingness to exert effort under specific circumstances. Circadian-rhythm changes and sleep disturbances might mediate the effects of inflammation on cellular-energy availability and non-adaptive energy expenditure. In the second part of the review, we present evidence for these metabolic pathways in models of persistent fatigue, focusing on chronic fatigue syndrome and cancer-related fatigue. Most evidence for reduced cellular-energy availability in relation to fatigue comes from studies on chronic fatigue syndrome. While the mechanistic evidence from the cancer-related fatigue literature is still limited, the sparse results point to reduced cellular-energy availability as well. There is also mounting evidence that behavioral-energy expenditure exceeds the reduced cellular-energy availability in patients with persistent fatigue. This suggests that an inability to adjust energy expenditure to available resources might be one mechanism underlying persistent fatigue.

Establishment of a chronic activity-based anorexia rat model

NARCIS (Netherlands)

Frintrop, Linda; Trinh, Stefanie; Liesbrock, Johanna; Paulukat, Lisa; Kas, Martien J; Tolba, Rene; Konrad, Kerstin; Herpertz-Dahlmann, Beate; Beyer, Cordian; Seitz, Jochen

2018-01-01

BACKGROUND: Anorexia nervosa (AN) is often a chronic eating disorder characterised by body image disturbance and low body weight often associated with starvation-induced amenorrhoea and excessive exercise. Activity-based anorexia (ABA) is an animal model representing many somatic aspects of this

Establishment of a chronic activity-based anorexia rat model

NARCIS (Netherlands)

Frintrop, Linda; Trinh, Stefanie; Liesbrock, Johanna; Paulukat, Lisa; Kas, Martien J.; Tolba, Rene; Konrad, Kerstin; Herpertz-Dahlmann, Beate; Beyer, Cordian; Seitz, Jochen

2018-01-01

AbstractBackground Anorexia nervosa (AN) is often a chronic eating disorder characterised by body image disturbance and low body weight often associated with starvation-induced amenorrhoea and excessive exercise. Activity-based anorexia (ABA) is an animal model representing many somatic aspects of

Value-based cognitive-behavioural therapy for the prevention of chronic whiplash associated disorders: protocol of a randomized controlled trial.

Science.gov (United States)

Andersen, Tonny Elmose; Ravn, Sophie Lykkegaard; Roessler, Kirsten Kaya

2015-09-01

Whiplash injury is the most common traffic-related injury affecting thousands of people every year. Conservative treatments have not proven effective in preventing persistent symptoms and disability after whiplash injury. Early established maladaptive pain behaviours within the first weeks after the injury may explain part of the transition from acute to chronic whiplash associated disorder (WAD). Hence, early targeting of psychological risk factors such as pain catastrophizing, fear-avoidance-beliefs, depression, and symptoms of posttraumatic stress disorder (PTSD) may be important in preventing the development of chronic WAD. Some evidence exists that targeting fear-avoidance beliefs and PTSD with exposure strategies and value-based actions may prevent development of persistent disability after whiplash injury. Yet, the results have to be tested in a randomized controlled trial (RCT). The primary objective of the present study is to test whether a specifically tailored value-based cognitive-behavioural therapy program (V-CBT) is able to prevent the development of persistent disability, pain, and psychological distress if delivered within the first three months after a whiplash injury. The current study is a two-armed randomized controlled study with a crossover design. Group A is scheduled for V-CBT within one week of randomization and group B with a delayed onset 3 months after randomization. If the study detects significant effects of V-CBT as a preventive intervention, the study will provide new insights of preventive treatment for patients with WAD and thereby serve as an important step towards preventing the chronic condition. Current Controlled Trials Registration September 19, 2014: NCT02251028.

Self-rated health and chronic conditions are associated with blood concentrations of persistent organic pollutants in the general population of Catalonia, Spain

International Nuclear Information System (INIS)

Gasull, Magda; Pallarès, Natàlia; Salcedo, Natalia; Pumarega, José; Alonso, Jordi; Porta, Miquel

2015-01-01

Background: Self-rated health (SRH) is a powerful predictor of mortality, morbidity, and need for health services. SRH generally increases with educational level, and decreases with age, number of chronic conditions, and body mass index (BMI). Because human concentrations of most persistent organic pollutants (POPs) also vary by age, education, and BMI, and because of the physiological and clinical effects of POPs, we hypothesized that body concentrations of POPs are inversely associated with SRH. Objectives: To analyze the relation between serum concentrations of POPs and SRH in the general population of Catalonia, Spain, taking into account sociodemographic factors and BMI, as well as chronic health conditions and mental disorders, measured by the General Health Questionnaire-12 (GHQ-12). Methods: POP serum concentrations were measured by gas chromatography with electron-capture detection in 919 participants of the Catalan Health Interview Survey. Results: Individuals with higher concentrations of POPs had significantly poorer SRH; e.g., the median concentration of HCB in subjects with poor SRH was twice as high as in subjects with excellent SRH (366 ng/g vs. 169 ng/g, respectively; p-value<0.001). In crude models and in models adjusted for sex and BMI, the POPs-SRH association was often dose-dependent, and the likelihood of poor or regular SRH was 2 to 4-times higher in subjects with POP concentrations in the top quartile. In models adjusted for age or for chronic conditions virtually all ORs were near unity. No associations were found between POP levels and GHQ-12. Conclusions: Individuals with higher concentrations of POPs had significantly poorer SRH, an association likely due to age and chronic conditions, but not to sex, education, social class, BMI, or mental disorders. - Highlights: • The relation between POPs and self-rated and mental health has seldom been studied. • Subjects with higher POP levels had poorer self-rated health (SRH) (dose

Self-rated health and chronic conditions are associated with blood concentrations of persistent organic pollutants in the general population of Catalonia, Spain

Energy Technology Data Exchange (ETDEWEB)

Gasull, Magda; Pallarès, Natàlia [Hospital del Mar Medical Research Institute (IMIM), Barcelona, Catalonia (Spain); CIBER de Epidemiología y Salud Pública (CIBERESP) (Spain); School of Medicine, Universitat Autònoma de Barcelona (Spain); Salcedo, Natalia [Hospital del Mar Medical Research Institute (IMIM), Barcelona, Catalonia (Spain); School of Medicine, Universitat Autònoma de Barcelona (Spain); Pumarega, José [Hospital del Mar Medical Research Institute (IMIM), Barcelona, Catalonia (Spain); CIBER de Epidemiología y Salud Pública (CIBERESP) (Spain); Alonso, Jordi [Hospital del Mar Medical Research Institute (IMIM), Barcelona, Catalonia (Spain); CIBER de Epidemiología y Salud Pública (CIBERESP) (Spain); Universitat Pompeu Fabra, Catalonia (Spain); Porta, Miquel, E-mail: mporta@imim.es [Hospital del Mar Medical Research Institute (IMIM), Barcelona, Catalonia (Spain); CIBER de Epidemiología y Salud Pública (CIBERESP) (Spain); School of Medicine, Universitat Autònoma de Barcelona (Spain)

2015-11-15

Background: Self-rated health (SRH) is a powerful predictor of mortality, morbidity, and need for health services. SRH generally increases with educational level, and decreases with age, number of chronic conditions, and body mass index (BMI). Because human concentrations of most persistent organic pollutants (POPs) also vary by age, education, and BMI, and because of the physiological and clinical effects of POPs, we hypothesized that body concentrations of POPs are inversely associated with SRH. Objectives: To analyze the relation between serum concentrations of POPs and SRH in the general population of Catalonia, Spain, taking into account sociodemographic factors and BMI, as well as chronic health conditions and mental disorders, measured by the General Health Questionnaire-12 (GHQ-12). Methods: POP serum concentrations were measured by gas chromatography with electron-capture detection in 919 participants of the Catalan Health Interview Survey. Results: Individuals with higher concentrations of POPs had significantly poorer SRH; e.g., the median concentration of HCB in subjects with poor SRH was twice as high as in subjects with excellent SRH (366 ng/g vs. 169 ng/g, respectively; p-value<0.001). In crude models and in models adjusted for sex and BMI, the POPs-SRH association was often dose-dependent, and the likelihood of poor or regular SRH was 2 to 4-times higher in subjects with POP concentrations in the top quartile. In models adjusted for age or for chronic conditions virtually all ORs were near unity. No associations were found between POP levels and GHQ-12. Conclusions: Individuals with higher concentrations of POPs had significantly poorer SRH, an association likely due to age and chronic conditions, but not to sex, education, social class, BMI, or mental disorders. - Highlights: • The relation between POPs and self-rated and mental health has seldom been studied. • Subjects with higher POP levels had poorer self-rated health (SRH) (dose

On the causes of persistent apical periodontitis: a review.

Science.gov (United States)

Nair, P N R

2006-04-01

Apical periodontitis is a chronic inflammatory disorder of periradicular tissues caused by aetiological agents of endodontic origin. Persistent apical periodontitis occurs when root canal treatment of apical periodontitis has not adequately eliminated intraradicular infection. Problems that lead to persistent apical periodontitis include: inadequate aseptic control, poor access cavity design, missed canals, inadequate instrumentation, debridement and leaking temporary or permanent restorations. Even when the most stringent procedures are followed, apical periodontitis may still persist as asymptomatic radiolucencies, because of the complexity of the root canal system formed by the main and accessory canals, their ramifications and anastomoses where residual infection can persist. Further, there are extraradicular factors -- located within the inflamed periapical tissue -- that can interfere with post-treatment healing of apical periodontitis. The causes of apical periodontitis persisting after root canal treatment have not been well characterized. During the 1990s, a series of investigations have shown that there are six biological factors that lead to asymptomatic radiolucencies persisting after root canal treatment. These are: (i) intraradicular infection persisting in the complex apical root canal system; (ii) extraradicular infection, generally in the form of periapical actinomycosis; (iii) extruded root canal filling or other exogenous materials that cause a foreign body reaction; (iv) accumulation of endogenous cholesterol crystals that irritate periapical tissues; (v) true cystic lesions, and (vi) scar tissue healing of the lesion. This article provides a comprehensive overview of the causative factors of non-resolving periapical lesions that are seen as asymptomatic radiolucencies post-treatment.

A Systematic Review of Early Prognostic Factors for Persistent Pain Following Acute Orthopedic Trauma

Directory of Open Access Journals (Sweden)

Fiona J Clay

2012-01-01

Full Text Available Persistent or chronic pain is prevalent in many developed countries, with estimates ranging from 10% to higher than 50%, and is a major economic burden to individuals and societies. However, the variation in pain outcomes after acute orthopedic trauma and treatment confronts treating physicians with uncertainty in providing prognostic advice regarding long-term recovery. Although several previous reviews have addressed the determinants of chronic pain outcomes secondary to acute trauma, they have primarily focused on specific injury samples and, furthermore, lack consistency with respect to the important prognostic factors, which limits the generalizability of findings. This review, however, aimed specifically to identify the early prognostic factors associated with variation in persistent pain outcomes following acute orthopedic trauma presenting with a spectrum of pathologies.

Concurrent proinflammatory and apoptotic activity of a Helicobacter pylori protein (HP986 points to its role in chronic persistence.

Directory of Open Access Journals (Sweden)

Ayesha Alvi

Full Text Available Helicobacter pylori induces cytokine mediated changes in gastroduodenal pathophysiology, wherein, the activated macrophages at the sub-mucosal space play a central role in mounting innate immune response against the antigens. The bacterium gains niche through persistent inflammation and local immune-suppression causing peptic ulcer disease or chronic gastritis; the latter being a significant risk factor for the development of gastric adenocarcinoma. What favors persistence of H. pylori in the gastric niches is not clearly understood. We report detailed characterization of a functionally unknown gene (HP986, which was detected in patient isolates associated with peptic ulcer and gastric carcinoma. Expression and purification of recombinant HP986 (rHP986 revealed a novel, ∼29 kDa protein in biologically active form which associates with significant levels of humoral immune responses in diseased individuals (p<0.001. Also, it induced significant levels of TNF-α and Interleukin-8 in cultured human macrophages concurrent to the translocation of nuclear transcription factor-κB (NF-κB. Further, the rHP986 induced apoptosis of cultured macrophages through a Fas mediated pathway. Dissection of the underlying signaling mechanism revealed that rHP986 induces both TNFR1 and Fas expression to lead to apoptosis. We further demonstrated interaction of HP986 with TNFR1 through computational and experimental approaches. Independent proinflammatory and apoptotic responses triggered by rHP986 as shown in this study point to its role, possibly as a survival strategy to gain niche through inflammation and to counter the activated macrophages to avoid clearance.

A new class of synthetic retinoid antibiotics effective against bacterial persisters.

Science.gov (United States)

Kim, Wooseong; Zhu, Wenpeng; Hendricks, Gabriel Lambert; Van Tyne, Daria; Steele, Andrew D; Keohane, Colleen E; Fricke, Nico; Conery, Annie L; Shen, Steven; Pan, Wen; Lee, Kiho; Rajamuthiah, Rajmohan; Fuchs, Beth Burgwyn; Vlahovska, Petia M; Wuest, William M; Gilmore, Michael S; Gao, Huajian; Ausubel, Frederick M; Mylonakis, Eleftherios

2018-04-05

A challenge in the treatment of Staphylococcus aureus infections is the high prevalence of methicillin-resistant S. aureus (MRSA) strains and the formation of non-growing, dormant 'persister' subpopulations that exhibit high levels of tolerance to antibiotics and have a role in chronic or recurrent infections. As conventional antibiotics are not effective in the treatment of infections caused by such bacteria, novel antibacterial therapeutics are urgently required. Here we used a Caenorhabditis elegans-MRSA infection screen to identify two synthetic retinoids, CD437 and CD1530, which kill both growing and persister MRSA cells by disrupting lipid bilayers. CD437 and CD1530 exhibit high killing rates, synergism with gentamicin, and a low probability of resistance selection. All-atom molecular dynamics simulations demonstrated that the ability of retinoids to penetrate and embed in lipid bilayers correlates with their bactericidal ability. An analogue of CD437 was found to retain anti-persister activity and show an improved cytotoxicity profile. Both CD437 and this analogue, alone or in combination with gentamicin, exhibit considerable efficacy in a mouse model of chronic MRSA infection. With further development and optimization, synthetic retinoids have the potential to become a new class of antimicrobials for the treatment of Gram-positive bacterial infections that are currently difficult to cure.

Helicobacter pylori gene silencing in vivo demonstrates urease is essential for chronic infection.

Science.gov (United States)

Debowski, Aleksandra W; Walton, Senta M; Chua, Eng-Guan; Tay, Alfred Chin-Yen; Liao, Tingting; Lamichhane, Binit; Himbeck, Robyn; Stubbs, Keith A; Marshall, Barry J; Fulurija, Alma; Benghezal, Mohammed

2017-06-01

Helicobacter pylori infection causes chronic active gastritis that after many years of infection can develop into peptic ulceration or gastric adenocarcinoma. The bacterium is highly adapted to surviving in the gastric environment and a key adaptation is the virulence factor urease. Although widely postulated, the requirement of urease expression for persistent infection has not been elucidated experimentally as conventional urease knockout mutants are incapable of colonization. To overcome this constraint, conditional H. pylori urease mutants were constructed by adapting the tetracycline inducible expression system that enabled changing the urease phenotype of the bacteria during established infection. Through tight regulation we demonstrate that urease expression is not only required for establishing initial colonization but also for maintaining chronic infection. Furthermore, successful isolation of tet-escape mutants from a late infection time point revealed the strong selective pressure on this gastric pathogen to continuously express urease in order to maintain chronic infection. In addition to mutations in the conditional gene expression system, escape mutants were found to harbor changes in other genes including the alternative RNA polymerase sigma factor, fliA, highlighting the genetic plasticity of H. pylori to adapt to a changing niche. The tet-system described here opens up opportunities to studying genes involved in the chronic stage of H. pylori infection to gain insight into bacterial mechanisms promoting immune escape and life-long infection. Furthermore, this genetic tool also allows for a new avenue of inquiry into understanding the importance of various virulence determinants in a changing biological environment when the bacterium is put under duress.

Helicobacter pylori gene silencing in vivo demonstrates urease is essential for chronic infection.

Directory of Open Access Journals (Sweden)

Aleksandra W Debowski

2017-06-01

Full Text Available Helicobacter pylori infection causes chronic active gastritis that after many years of infection can develop into peptic ulceration or gastric adenocarcinoma. The bacterium is highly adapted to surviving in the gastric environment and a key adaptation is the virulence factor urease. Although widely postulated, the requirement of urease expression for persistent infection has not been elucidated experimentally as conventional urease knockout mutants are incapable of colonization. To overcome this constraint, conditional H. pylori urease mutants were constructed by adapting the tetracycline inducible expression system that enabled changing the urease phenotype of the bacteria during established infection. Through tight regulation we demonstrate that urease expression is not only required for establishing initial colonization but also for maintaining chronic infection. Furthermore, successful isolation of tet-escape mutants from a late infection time point revealed the strong selective pressure on this gastric pathogen to continuously express urease in order to maintain chronic infection. In addition to mutations in the conditional gene expression system, escape mutants were found to harbor changes in other genes including the alternative RNA polymerase sigma factor, fliA, highlighting the genetic plasticity of H. pylori to adapt to a changing niche. The tet-system described here opens up opportunities to studying genes involved in the chronic stage of H. pylori infection to gain insight into bacterial mechanisms promoting immune escape and life-long infection. Furthermore, this genetic tool also allows for a new avenue of inquiry into understanding the importance of various virulence determinants in a changing biological environment when the bacterium is put under duress.

The Role of Enteropathogenic E.coli in the Development and Progression of Chronic Non-Ulcerative Colitis

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L.I. Sydorchuk

2016-04-01

Full Text Available Objective. The analysis of the literature has shown that in patients with chronic non-ulcerative colitis, there were isolated E.coli that cause dysentery-like, cholera-like diseases and escherichioses. Thus, the aim of our study was to establish the level of persistence of enteropathogenic Escherichia in the colon of patients with chronic non-ulcerative colitis and their importance in the ecological system «macroorganism — microbiota». Material and methods. During 2000–2015, there has been conducted a bacteriological examination of the colon content in patients with chronic non-ulcerative colitis aged 27–41 years (average age 37.74 ± 3.62 years. The resulting cultures were examined in the indicative agglutination tests with OKA polyvalent serum. Positive cultures were tested with polyvalent serum of narrow spectrum ОКВ, ОКС, ОКD and ОКЕ. Results. In patients, in colon cavity of which E.coli O18ac:K77; O26:K60; O55:K59; O128ab:K67 were detected, the disease occurs by nosology of colienteritis. In those patients, in whom O25:K11; O144:K; O124:K72 serotypes have been identified, disease occurred as bacterial dysentery, and O25:K11 and O128:K67 — in chole­ra-like form. Discussion. In 94.50 % of patients, common E.coli were detected, but in 55 (35.03 % of them enteropathogenic Escherichia persist, in 41 (26.11 % — E.coli Hly+, in 37 (23.57 % — E.coli Lac–, in 18 (11.46 % — enterotoxigenic E.coli, in 14 (8.42 % — enteroinvasive, and in 11 (7.01 % — enterohemorragic Escherichia. Conclusions. It was determined that the main serotypes of opportunistic Escherichia, which colonize and persist in the colon cavity of patients with chronic non-ulcerative colitis, were O114:K90; O25:K11; O124:K72; O128:K67; O18ac:K77, the persistence of which affects clinical manifestation from colitis to dysentery-like or cholera-like disease.

Chronic post-concussion neurocognitive deficits. II. Relationship with persistent symptoms

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Jun eMaruta

2016-02-01

Full Text Available Individuals who sustain a concussion may continue to experience problems long after their injury. However, it has been postulated in the literature that the relationship between a concussive injury and persistent complaints attributed to it is mediated largely by the development of symptoms associated with posttraumatic stress disorder and depression. We sought to characterize cognitive deficits of adult patients who had persistent symptoms after a concussion and determine whether the original injury retains associations with these deficits after accounting for the developed symptoms that overlap with posttraumatic stress disorder and depression. We compared the results of neurocognitive testing from 33 patients of both genders aged 18-55 at three months to five years post-injury with those from 140 control subjects. Statistical comparisons revealed that patients generally produced accurate responses on reaction time-based tests, but with reduced efficiency. On visual tracking, patients increased gaze position error variability following an attention demanding task, an effect that may reflect greater fatigability. When neurocognitive performance was examined in the context of demographic- and symptom-related variables, the original injury retained associations with reduced performance at a statistically significant level. For some patients, reduced cognitive efficiency and fatigability may represent key elements of interference when interacting with the environment, leading to varied paths of recovery after a concussion. Poor recovery may be better understood when these deficits are taken into consideration.

Viral (hepatitis C virus, hepatitis B virus, HIV) persistence and immune homeostasis

Science.gov (United States)

Zhou, Yun; Zhang, Ying; Moorman, Jonathan P; Yao, Zhi Q; Jia, Zhan S

2014-01-01

Immune homeostasis is a host characteristic that maintains biological balance within a host. Humans have evolved many host defence mechanisms that ensure the survival of individuals upon encountering a pathogenic infection, with recovery or persistence from a viral infection being determined by both viral factors and host immunity. Chronic viral infections, such as hepatitis B virus, hepatitis C virus and HIV, often result in chronic fluctuating viraemia in the face of host cellular and humoral immune responses, which are dysregulated by multi-faceted mechanisms that are incompletely understood. This review attempts to illuminate the mechanisms involved in this process, focusing on immune homeostasis in the setting of persistent viral infection from the aspects of host defence mechanism, including interferon-stimulated genes, apolipoprotein B mRNA editing enzyme catalytic polypeptide 3 (APOBEC3), autophagy and interactions of various immune cells, cytokines and regulatory molecules. PMID:24965611

Sympathetic arousal as a marker of chronicity in childhood stuttering.

Science.gov (United States)

Zengin-Bolatkale, Hatun; Conture, Edward G; Walden, Tedra A; Jones, Robin M

2018-01-01

This study investigated whether sympathetic activity during a stressful speaking task was an early marker for stuttering chronicity. Participants were 9 children with persisting stuttering, 23 children who recovered, and 17 children who do not stutter. Participants performed a stress-inducing picture-naming task and skin conductance was measured across three time points. Findings indicated that at the initial time point, children with persisting stuttering exhibited higher sympathetic arousal during the stressful speaking task than children whose stuttering recovered. Findings are taken to suggest that sympathetic activity may be an early marker of heightened risk for chronic stuttering.

Persistent postsurgical pain: risk factors and prevention

DEFF Research Database (Denmark)

Kehlet, Henrik; Jensen, Troels Staehelin; Woolf, Clifford J.

2006-01-01

therapy for postoperative pain should be investigated, since the intensity of acute postoperative pain correlates with the risk of developing a persistent pain state. Finally, the role of genetic factors should be studied, since only a proportion of patients with intraoperative nerve damage develop...... chronic pain. Based on information about the molecular mechanisms that affect changes to the peripheral and central nervous system in neuropathic pain, several opportunities exist for multimodal pharmacological intervention. Here, we outline strategies for identification of patients at risk...

[Current alternatives in the surgical treatment of chronic pancreatitis--a review article].

Science.gov (United States)

Kat'uchová, Jana; Radonak, Jozef

2011-01-01

Chronic pancreatitis is characterized as an inflammatory process affecting the pancreas that causes progressive destruction of the gland and fibrosis, with subsequent endocrine and exocrine insufficiency. The most common cause of chronic pancreatitis is alcohol use in combination with nicotine. Manifestations are persistent or recurrent painful attacks. The only parameter of successful treatment of chronic pancreatitis is a relieve from long-lasting pain and improvement of the quality of life. Surgical treatment options include drainage operations on the pancreas, pancreatic resection or a combination of both. With optimal surgical treatment performed and good patient's compliance, operations for chronic pancreatitis have low number of post-operative complications and relatively good long-term results. The continued consumption of alcohol and drugs bring about worse outcomes, sometimes even a complete failure of therapy. Chronic pancreatitis also has considerable socio-economic consequences. Due to the persisting pain and frequent hospitalization it can lead to long-term disability and early retirement predominantly in young patients.

Great Expectations: The Persistent Effect of Institutions on Culture

OpenAIRE

Litina, Anastasia

2014-01-01

This research exploits the event of immigration to establish that institutions have a persistent effect on culture. It is argued that immigrants coming from corrupt countries, tend to overtrust the institutions at the host country. This inflated trust of immigrants is documented as the Great Expectations effect. This result is interesting and intriguing for several reasons. First, it highlights the persistent effect of institutions (at the origin coun- try) on the cultural attitudes of immigr...

An animal model of schizophrenia based on chronic LSD administration: old idea, new results.

Science.gov (United States)

Marona-Lewicka, Danuta; Nichols, Charles D; Nichols, David E

2011-09-01

Many people who take LSD experience a second temporal phase of LSD intoxication that is qualitatively different, and was described by Daniel Freedman as "clearly a paranoid state." We have previously shown that the discriminative stimulus effects of LSD in rats also occur in two temporal phases, with initial effects mediated by activation of 5-HT(2A) receptors (LSD30), and the later temporal phase mediated by dopamine D2-like receptors (LSD90). Surprisingly, we have now found that non-competitive NMDA antagonists produced full substitution in LSD90 rats, but only in older animals, whereas in LSD30, or in younger animals, these drugs did not mimic LSD. Chronic administration of low doses of LSD (>3 months, 0.16 mg/kg every other day) induces a behavioral state characterized by hyperactivity and hyperirritability, increased locomotor activity, anhedonia, and impairment in social interaction that persists at the same magnitude for at least three months after cessation of LSD treatment. These behaviors, which closely resemble those associated with psychosis in humans, are not induced by withdrawal from LSD; rather, they are the result of neuroadaptive changes occurring in the brain during the chronic administration of LSD. These persistent behaviors are transiently reversed by haloperidol and olanzapine, but are insensitive to MDL-100907. Gene expression analysis data show that chronic LSD treatment produced significant changes in multiple neurotransmitter system-related genes, including those for serotonin and dopamine. Thus, we propose that chronic treatment of rats with low doses of LSD can serve as a new animal model of psychosis that may mimic the development and progression of schizophrenia, as well as model the established disease better than current acute drug administration models utilizing amphetamine or NMDA antagonists such as PCP. Copyright © 2011 Elsevier Ltd. All rights reserved.

AN ANIMAL MODEL OF SCHIZOPHRENIA BASED ON CHRONIC LSD ADMINISTRATION: OLD IDEA, NEW RESULTS

Science.gov (United States)

Marona-Lewicka, Danuta; Nichols, Charles D.; Nichols, David E.

2011-01-01

Many people who take LSD experience a second temporal phase of LSD intoxication that is qualitatively different, and was described by Daniel Freedman as “clearly a paranoid state.” We have previously shown that the discriminative stimulus effects of LSD in rats also occur in two temporal phases, with initial effects mediated by activation of 5-HT2A receptors (LSD30), and the later temporal phase mediated by dopamine D2-like receptors (LSD90). Surprisingly, we have now found that non-competitive NMDA antagonists produced full substitution in LSD90 rats, but only in older animals, whereas in LSD30, or in younger animals, these drugs did not mimic LSD. Chronic administration of low doses of LSD (>3 months, 0.16 mg/kg every other day) induces a behavioral state characterized by hyperactivity and hyperirritability, increased locomotor activity, anhedonia, and impairment in social interaction that persists at the same magnitude for at least three months after cessation of LSD treatment. These behaviors, which closely resemble those associated with psychosis in humans, are not induced by withdrawal from LSD; rather, they are the result of neuroadaptive changes occurring in the brain during the chronic administration of LSD. These persistent behaviors are transiently reversed by haloperidol and olanzapine, but are insensitive to MDL-100907. Gene expression analysis data show that chronic LSD treatment produced significant changes in multiple neurotransmitter system-related genes, including those for serotonin and dopamine. Thus, we propose that chronic treatment of rats with low doses of LSD can serve as a new animal model of psychosis that may mimic the development and progression of schizophrenia, as well as model the established disease better than current acute drug administration models utilizing amphetamine or NMDA antagonists such as PCP. PMID:21352832

Comparing chronic interpersonal and noninterpersonal stress domains as predictors of depression recurrence in emerging adults.

Science.gov (United States)

Sheets, Erin S; Craighead, W Edward

2014-12-01

Understanding how persistent interpersonal difficulties distinctly affect the course of major depressive disorder (MDD) during emerging adulthood is critical, given that early experiences impact future coping resources and functioning. Research on stress and MDD has mostly concentrated on stressful life events, while chronic stress largely has not been explored. The present study examined interpersonal (intimate relationship, close friendships, social life, family relationships) and noninterpersonal (academic, work, financial, personal health, and family members' health) domains of chronic stress as time-varying predictors of depressive recurrence in emerging adults. Baseline assessments identified previously depressed emerging adults (N = 119), who subsequently completed 6-month, 12-month and 18-month follow-up interviews to determine chronic stress experiences and onset of new major depressive episodes. Survival analyses indicated that time-varying total chronic stress and chronic interpersonal stress predicted higher risk for depression recurrence; however, chronic noninterpersonal stress was not associated with recurrence. Intimate relationship stress, close friendship stress, family relationship stress, personal health, and family members' health independently predicted MDD recurrence, over and above well-established depression risk factors of dysfunctional cognitions and personality disorder symptoms. Evidence that interpersonal stress could have substantial impact on course of depression is consistent with theories of emerging adulthood, a time when young people are individuating from the family and experiencing significant social transition. Copyright © 2014 Elsevier Ltd. All rights reserved.

Stress, intrusive imagery, and chronic distress

International Nuclear Information System (INIS)

Baum, A.

1990-01-01

Discusses the nature of stress in the context of problems with its definition and sources of confusion regarding its usefulness and specificity. Stress can be defined as a negative emotional experience accompanied by predictable biochemical, physiological, and behavioral changes that are directed toward adaptation either by manipulating the situation to alter the stressor or by accommodating its effects. Chronic stress is more complex than most definitions suggest and is clearly not limited to situations in which stressors persist for long periods of time. Responses may habituate before a stressor disappears or may persist long beyond the physical presence of the stressor. This latter case, in which chronic stress and associated biobehavioral changes outlast their original cause, is considered in light of research at Three Mile Island and among Vietnam veterans. The role of intrusive images of the stressor or uncontrollable thoughts about it in maintaining stress is explored

YfiBNR mediates cyclic di-GMP dependent small colony variant formation and persistence in Pseudomonas aeruginosa.

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Jacob G Malone

2010-03-01

Full Text Available During long-term cystic fibrosis lung infections, Pseudomonas aeruginosa undergoes genetic adaptation resulting in progressively increased persistence and the generation of adaptive colony morphotypes. This includes small colony variants (SCVs, auto-aggregative, hyper-adherent cells whose appearance correlates with poor lung function and persistence of infection. The SCV morphotype is strongly linked to elevated levels of cyclic-di-GMP, a ubiquitous bacterial second messenger that regulates the transition between motile and sessile, cooperative lifestyles. A genetic screen in PA01 for SCV-related loci identified the yfiBNR operon, encoding a tripartite signaling module that regulates c-di-GMP levels in P. aeruginosa. Subsequent analysis determined that YfiN is a membrane-integral diguanylate cyclase whose activity is tightly controlled by YfiR, a small periplasmic protein, and the OmpA/Pal-like outer-membrane lipoprotein YfiB. Exopolysaccharide synthesis was identified as the principal downstream target for YfiBNR, with increased production of Pel and Psl exopolysaccharides responsible for many characteristic SCV behaviors. An yfi-dependent SCV was isolated from the sputum of a CF patient. Consequently, the effect of the SCV morphology on persistence of infection was analyzed in vitro and in vivo using the YfiN-mediated SCV as a representative strain. The SCV strain exhibited strong, exopolysaccharide-dependent resistance to nematode scavenging and macrophage phagocytosis. Furthermore, the SCV strain effectively persisted over many weeks in mouse infection models, despite exhibiting a marked fitness disadvantage in vitro. Exposure to sub-inhibitory concentrations of antibiotics significantly decreased both the number of suppressors arising, and the relative fitness disadvantage of the SCV mutant in vitro, suggesting that the SCV persistence phenotype may play a more important role during antimicrobial chemotherapy. This study establishes Yfi

Defining the neurotoxin derived illness chronic ciguatera using markers of chronic systemic inflammatory disturbances: a case/control study.

Science.gov (United States)

Shoemaker, Ritchie C; House, Dennis; Ryan, James C

2010-01-01

Ciguatoxins are extremely potent neurotoxins, produced by tropical marine dinoflagellates, that persistently enter into our food web. Over 100,000 people annually experience acute ciguatera poisoning from consuming toxic fish. Roughly 5% of these victims will develop chronic ciguatera (CC), a widespread, multisymptom, multisystem, chronic illness that can last tens of years. CC is marked by disproportionate disability and non-specific refractory symptoms such as fatigue, cognitive deficits and pain, and is suggestive of other illnesses. Its unknown pathophysiology makes both diagnosis and treatment difficult. We wanted to compare objective parameters of visual contrast sensitivity testing, measures of innate immune response and genetic markers in cases to controls to assess the potential for the presence of persistent inflammatory parameters that are demonstrated in other biotoxin associated illnesses at a single specialty clinic. Using 59 CC cases and 59 controls we present in retrospective review, in all cases, abnormalities in immune responses paralleling the chronic systemic inflammatory response syndrome seen in several other chronic diseases. This study defines a preliminary case definition using medical history, total symptoms, visual contrast sensitivity, HLA DR genotype analysis, reduction of regulatory neuropeptides VIP and MSH, and multiple measures of inflammatory immune response, especially C4a and TGFβ1, thereby providing a basis for identification and targeted therapy. CC provides a model for chronic human illness associated with initiation of inflammatory responses by biologically produced neurotoxins. Copyright © 2010 Elsevier Inc. All rights reserved.

HLA-DQB1*03 confers susceptibility to chronic hepatitis C in Japanese: a genome-wide association study.

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Daiki Miki

Full Text Available Hepatitis C virus (HCV establishes a chronic infection in 70-80% of infected individuals. Many researchers have examined the effect of human leukocyte antigen (HLA on viral persistence because of its critical role in the immune response against exposure to HCV, but almost all studies have proven to be inconclusive. To identify genetic risk factors for chronic HCV infection, we analyzed 458,207 single nucleotide polymorphisms (SNPs in 481 chronic HCV patients and 2,963 controls in a Japanese cohort. Next, we performed a replication study with an independent panel of 4,358 cases and 1,114 controls. We further confirmed the association in 1,379 cases and 25,817 controls. In the GWAS phase, we found 17 SNPs that showed suggestive association (P < 1 × 10⁻⁵. After the first replication study, we found one intronic SNP in the HLA-DQ locus associated with chronic HCV infection, and when we combined the two studies, the association reached the level of genome-wide significance. In the second replication study, we again confirmed the association (P(combined = 3.59 × 10⁻¹⁶, odds ratio [OR] = 0.79. Subsequent analysis revealed another SNP, rs1130380, with a stronger association (OR=0.72. This nucleotide substitution causes an amino acid substitution (R55P in the HLA-DQB1 protein specific to the DQB1*03 allele, which is common worldwide. In addition, we confirmed an association with the previously reported IFNL3-IFNL4 locus and propose that the effect of DQB1*03 on HCV persistence might be affected by the IFNL4 polymorphism. Our findings suggest that a common amino acid substitution in HLA-DQB1 affects susceptibility to chronic infection with HCV in the Japanese population and may not be independent of the IFNL4 genotype.

Chronic Actinic Dermatitis

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Bengü Çevirgen Cemil

2017-06-01

Full Text Available Chronic actinic dermatitis (CAD is characterized by persistent eczema-like lesions, mainly on sun-exposed sites, induced by ultraviolet B, sometimes ultraviolet A, and occasionally visible light. CAD is a rare photodermatitis. It is often associated with contact allergens including airborne allergens such as fragrances, plant antigens and topical medications. A 62 year old farmer is applied with eczematous lesions restricted to sun-exposed areas. Clinical findings and histopathologic features were consistent with the diagnosis of chronic actinic dermatitis. The patient also had contact allergy to multiple allergens. We present this case to emphasize the significance of patch test on CAD treatment and the success of topical tacrolimus and azathioprine.

Down-regulation of NR2B receptors partially contributes to analgesic effects of Gentiopicroside in persistent inflammatory pain.

Science.gov (United States)

Chen, Lei; Liu, Jin-cheng; Zhang, Xiao-nan; Guo, Yan-yan; Xu, Zhao-hui; Cao, Wei; Sun, Xiao-li; Sun, Wen-ji; Zhao, Ming-Gao

2008-06-01

Gentiopicroside is one of the secoiridoid compound isolated from Gentiana lutea. It exhibits analgesic activities in the mice. The anterior cingulate cortex (ACC) is a forebrain structure known for its roles in pain transmission and modulation. Painful stimuli potentiate the prefrontal synaptic transmission and induce glutamate NMDA NR2B receptor expression in the ACC. But little is known about Gentiopicroside on the persistent inflammatory pain and chronic pain-induced synaptic transmission changes in the ACC. The present study was undertaken to investigate its analgesic activities and central synaptic modulation to the peripheral painful inflammation. Gentiopicroside produced significant analgesic effects against persistent inflammatory pain stimuli in mice. Systemic administration of Gentiopicroside significantly reversed NR2B over-expression during the chronic phases of persistent inflammation caused by hind-paw administration of complete Freunds adjuvant (CFA) in mice. Whole-cell patch clamp recordings revealed that Gentiopicroside significantly reduced NR2B receptors mediated postsynaptic currents in the ACC. Our findings provide strong evidence that analgesic effects of Gentiopicroside involve down-regulation of NR2B receptors in the ACC to persistent inflammatory pain.

Chronic Pain and Chronic Stress: Two Sides of the Same Coin?

Science.gov (United States)

Abdallah, Chadi G; Geha, Paul

2017-02-01

Pain and stress share significant conceptual and physiological overlaps. Both phenomena challenge the body's homeostasis and necessitate decision-making to help animals adapt to their environment. In addition, chronic stress and chronic pain share a common behavioral model of failure to extinguish negative memories. Yet, they also have discrepancies such that the final brain endophenotype of posttraumatic stress disorder, depression, and chronic pain appears to be different among the three conditions, and the role of the hypothalamic-pituitary-adrenal axis remains unclear in the physiology of pain. Persistence of either stress or pain is maladaptive and could lead to compromised well-being. In this brief review, we highlight the commonalities and differences between chronic stress and chronic pain, while focusing particularly on the central role of the limbic brain. We assess the current attempts in the field to conceptualize and understand chronic pain, within the context of knowledge gained from the stress literature. The limbic brain-including hippocampus, amygdala, and ventromedial pre-frontal cortex-plays a critical role in learning. These brain areas integrate incoming nociceptive or stress signals with internal state, and generate learning signals necessary for decision-making. Therefore, the physiological and structural remodeling of this learning circuitry is observed in conditions such as chronic pain, depression, and posttraumatic stress disorder, and is also linked to the risk of onset of these conditions.

Dopaminergic and serotonergic modulation of persistent behaviour in the reinforced spatial alternation model of obsessive-compulsive disorder.

Science.gov (United States)

Kontis, Dimitris; Boulougouris, Vasileios; Papakosta, Vasiliki Maria; Kalogerakou, Stamatina; Papadopoulos, Socrates; Poulopoulou, Cornelia; Papadimitriou, George N; Tsaltas, Eleftheria

2008-11-01

We have proposed rewarded T-maze alternation as a model of obsessive-compulsive disorder (OCD): the serotonin agonist m-chlorophenylpiperazine (mCPP) increments persistence therein, while chronic pretreatment with selective serotonin reuptake inhibitor (SSRI fluoxetine) but not benzodiazepine or desipramine abolishes mCPP effects. However, we noted that acute SSRI administration also causes transient persistence increase, counteracted by mCPP pretreatment. This study (a) further explores the cross-tolerance between fluoxetine and mCPP and (b) extends the model by investigating its sensitivity to dopaminergic manipulations (D2, 3 agonism--quinpirole). In both experiments, baseline and drug testing were carried out under daily T-maze alternation training. Exp. 1: Matched group (n = 8) pairs of rats received one of the following 20-day pretreatments (daily intraperitoneal administration): (1) saline, (2) low-dose fluoxetine (2.5 mg/kg), (3) low-dose mCPP (0.5 mg/kg) or (4) combined fluoxetine + mCPP. One group per pretreatment then received a 4-day challenge with high-dose fluoxetine (10 mg/kg), the other with high-dose mCPP (2.5 mg/kg). Exp. 2: One group (n = 12) of rats received 20-day treatment with saline, another with quinpirole (0.5 mg/kg). Exp. 1: Saline and low-dose mCPP- or fluoxetine-pretreated animals showed significant persistence increases under both challenges, while combined low-dose fluoxetine + mCPP pretreatment afforded full protection from either challenge. Exp. 2: Quinpirole significantly increased directional persistence after 13 administration days. These results establish the sensitivity of the rewarded alternation OCD model to D2, 3 receptor activation, thereby extending its profile of pharmacological isomorphism with OCD. Furthermore, they suggest a common mechanism of action of an SSRI and a serotonin agonist in the control of directional persistence.

Persistent low-grade inflammation and regular exercise

DEFF Research Database (Denmark)

Astrom, Maj-Briit; Feigh, Michael; Pedersen, Bente Klarlund

2010-01-01

Persistent low-grade systemic inflammation is a feature of chronic diseases such as cardiovascular disease (CVD), type 2 diabetes and dementia and evidence exists that inflammation is a causal factor in the development of insulin resistance and atherosclerosis. Regular exercise offers protection ...... diabetes and dementia. We suggest that the anti-inflammatory effects of exercise may be mediated via a long-term effect of exercise leading to a reduction in visceral fat mass and/or by induction of anti-inflammatory cytokines with each bout of exercise....

Cav1.2 channels mediate persistent chronic stress-induced behavioral deficits that are associated with prefrontal cortex activation of the p25/Cdk5-glucocorticoid receptor pathway

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Charlotte C. Bavley

2017-12-01

Full Text Available Chronic stress is known to precipitate and exacerbate neuropsychiatric symptoms, and exposure to stress is particularly pathological in individuals with certain genetic predispositions. Recent genome wide association studies have identified single nucleotide polymorphisms (SNPs in the gene CACNA1C, which codes for the Cav1.2 subunit of the L-type calcium channel (LTCC, as a common risk variant for multiple neuropsychiatric conditions. Cav1.2 channels mediate experience-dependent changes in gene expression and long-term synaptic plasticity through activation of downstream calcium signaling pathways. Previous studies have found an association between stress and altered Cav1.2 expression in the brain, however the contribution of Cav1.2 channels to chronic stress-induced behaviors, and the precise Cav1.2 signaling mechanisms activated are currently unknown. Here we report that chronic stress leads to a delayed increase in Cav1.2 expression selectively within the prefrontal cortex (PFC, but not in other stress-sensitive brain regions such as the hippocampus or amygdala. Further, we demonstrate that while Cav1.2 heterozygous (Cav1.2+/− mice show chronic stress-induced depressive-like behavior, anxiety-like behavior, and deficits in working memory 1–2 days following stress, they are resilient to the effects of chronic stress when tested 5–7 days later. Lastly, molecular studies find a delayed upregulation of the p25/Cdk5-glucocorticoid receptor (GR pathway in the PFC when examined 8 days post-stress that is absent in Cav1.2+/− mice. Our findings reveal a novel Cav1.2-mediated molecular mechanism associated with the persistent behavioral effects of chronic stress and provide new insight into potential Cav1.2 channel mechanisms that may contribute to CACNA1C-linked neuropsychiatric phenotypes.

Neural Consequences of Chronic Short Sleep: Reversible or Lasting?

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Zhengqing Zhao

2017-05-01

Full Text Available Approximately one-third of adolescents and adults in developed countries regularly experience insufficient sleep across the school and/or work week interspersed with weekend catch up sleep. This common practice of weekend recovery sleep reduces subjective sleepiness, yet recent studies demonstrate that one weekend of recovery sleep may not be sufficient in all persons to fully reverse all neurobehavioral impairments observed with chronic sleep loss, particularly vigilance. Moreover, recent studies in animal models demonstrate persistent injury to and loss of specific neuron types in response to chronic short sleep (CSS with lasting effects on sleep/wake patterns. Here, we provide a comprehensive review of the effects of chronic sleep disruption on neurobehavioral performance and injury to neurons, astrocytes, microglia, and oligodendrocytes and discuss what is known and what is not yet established for reversibility of neural injury. Recent neurobehavioral findings in humans are integrated with animal model research examining long-term consequences of sleep loss on neurobehavioral performance, brain development, neurogenesis, neurodegeneration, and connectivity. While it is now clear that recovery of vigilance following short sleep requires longer than one weekend, less is known of the impact of CSS on cognitive function, mood, and brain health long term. From work performed in animal models, CSS in the young adult and short-term sleep loss in critical developmental windows can have lasting detrimental effects on neurobehavioral performance.

Chronic tooth pulp inflammation induces persistent expression of phosphorylated ERK (pERK) and phosphorylated p38 (pp38) in trigeminal subnucleus caudalis

Science.gov (United States)

Worsley, M.A.; Allen, C.E.; Billinton, A.; King, A.E.; Boissonade, F.M.

2014-01-01

Background Extracellular signal-regulated kinase (ERK) and p38 mitogen-activated protein kinase are transiently phosphorylated (activated) in the spinal cord and trigeminal nucleus by acute noxious stimuli. Acute stimulation of dental pulp induces short-lived ERK activation in trigeminal subnucleus caudalis (Vc), and p38 inhibition attenuates short-term sensitization in Vc induced by acute pulpal stimulation. We have developed a model to study central changes following chronic inflammation of dental pulp that induces long-term sensitization. Here, we examine the effects of chronic inflammation and acute stimulation on the expression of phosphorylated ERK (pERK), phosphorylated p38 (pp38) and Fos in Vc. Results Chronic inflammation alone induced bilateral expression of pERK and pp38 in Vc, but did not induce Fos expression. Stimulation of both non-inflamed and inflamed pulps significantly increased pERK and pp38 bilaterally; expression was greatest in inflamed, stimulated animals, and was similar following 10-min and 60-min stimulation. Stimulation for 60 min, but not 10 min, induced Fos in ipsilateral Vc; Fos expression was significantly greater in inflamed, stimulated animals. pERK was present in both neurons and astrocytes; pp38 was present in neurons and other non-neuronal, non-astrocytic cell types. Conclusions This study provides the first demonstration that chronic inflammation of tooth pulp induces persistent bilateral activation of ERK and p38 within Vc, and that this activation is further increased by acute stimulation. This altered activity in intracellular signaling is likely to be linked to the sensitization that is seen in our animal model and in patients with pulpitis. Our data indicate that pERK and pp38 are more accurate markers of central change than Fos expression. In our model, localization of pERK and pp38 within specific cell types differs from that seen following acute stimulation. This may indicate specific roles for different cell types in

Acute and chronic whiplash disorders--a review.

Science.gov (United States)

Sterner, Ylva; Gerdle, Björn

2004-09-01

This review examines acute and chronic whiplash-associated disorders to facilitate assessment, treatment and rehabilitation for further research and evidence-based practices. A review of the literature. Whiplash-associated disorders account for a large proportion of the overall impairment and disability caused by traffic injuries. Rarely can a definite injury be determined in the acute (or chronic) phase. Crash-related factors have been identified, and several trauma mechanisms possibly causing different injuries have been described. Most whiplash trauma will not cause injury, and the majority of patients (92-95%) will return to work. Litigation is not a major factor. Cognitive impairments are not the same as brain injury. Variables such as pain intensity, restricted motion, neurological symptoms and signs, together with central nervous system symptoms can be used to predict a situation with risk of remaining complaints. Influences of other factors--the same as for other chronic pain conditions--also exist. Persistent/chronic pain is not merely acute pain that persists over time; changes occur at different levels of the pain transmission system. Chronic whiplash-associated disorders are associated with problems concerning social functioning, daily anxieties and satisfaction with different aspects of life. Adequate information, advice and pain medication together with active interventions might be more effective in the acute stage. Early multidisciplinary rehabilitation focusing on cognitive-behavioural changes might be of value. To develop specific treatment and rehabilitation, it is important to identify homogenous subgroups.

Bioactive Lipids and Chronic Inflammation: Managing the Fire Within

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Valerio Chiurchiù

2018-01-01

Full Text Available Inflammation is an immune response that works as a contained fire that is pre-emptively sparked as a defensive process during infections or upon any kind of tissue insult, and that is spontaneously extinguished after elimination or termination of the damage. However, persistent and uncontrolled immune reactions act as a wildfire that promote chronic inflammation, unresolved tissue damage and, eventually, chronic diseases. A wide network of soluble mediators, among which endogenous bioactive lipids, governs all immune processes. They are secreted by basically all cells involved in inflammatory processes and constitute the crucial infrastructure that triggers, coordinates and confines inflammatory mechanisms. However, these molecules are also deeply involved in the detrimental transition from acute to chronic inflammation, be it for persistent or excessive action of pro-inflammatory lipids or for the impairment of the functions carried out by resolving ones. As a matter of fact, bioactive lipids have been linked, to date, to several chronic diseases, including rheumatoid arthritis, atherosclerosis, diabetes, cancer, inflammatory bowel disease, systemic lupus erythematosus, and multiple sclerosis. This review summarizes current knowledge on the involvement of the main classes of endogenous bioactive lipids—namely classical eicosanoids, pro-resolving lipid mediators, lysoglycerophospholipids/sphingolipids, and endocannabinoids—in the cellular and molecular mechanisms that lead to the pathogenesis of chronic disorders.

Limitations associated with managing chronic low back pain.

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Beland, Paul

2016-04-20

Non-specific chronic low back pain is an occupational hazard for nurses. It may result in persistent and disabling pain for some people. There are many techniques for investigating, assessing and treating chronic low back pain. However, research to support some of these interventions and the assumptions that underlie them is limited. Interventions that may be beneficial are not always available to those who need them. Changes to service provision are required to rectify this situation and provide effective treatment for patients with non-specific chronic low back pain.

Mental health problems among individuals with persistent health challenges from adolescence to young adulthood: a population-based longitudinal study in Norway

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Sølvi Helseth

2016-09-01

Full Text Available Abstract Background Persistent health challenges are increasing throughout the world. It has been shown that adolescents with persistent health challenges are at greater risk of having mental health problems than their healthy peers. However, these studies are mainly cross-sectional, and little is known about the transition to adulthood. Thus, the aim of this study was to examine how mental health problems in adolescents and young adults with persistent health challenges vary during adolescence and in the transition to young adulthood. Methods The study used longitudinal and time-series data from the “Young in Norway” study. A sample of adolescents was prospectively followed from adolescence to young adulthood with measures at four different time points (n = 3,087; T1–T4: 2921 adolescents (12–19 years participated at T1 and T2, while 2448 young adults participated at T3 and T4. Persistent health challenges, age, gender, mental health problems and parental socio-economic status were measured in the longitudinal survey. Regression models were applied to estimate associations between persistent health challenges (understood as having a chronic health condition or disability and mental health problems during adolescence and young adulthood. Different models were tested for chronic health conditions and disability. Results Adolescents with disability had higher scores for depressive and anxiety symptoms, loneliness and self-concept instability, and lower scores for self-worth, appearance satisfaction, scholastic competence and social acceptance compared with adolescents without disability. In young adulthood, there were also significant associations between disability and most mental health problems. The longitudinal associations between chronic health conditions and mental health problems during adolescence and young adulthood showed that significant associations between chronic health conditions and mental health problems were only

DEET potentiates the development and persistence of anticholinesterase dependent chronic pain signs in a rat model of Gulf War Illness pain

International Nuclear Information System (INIS)

Flunker, L.K.; Nutter, T.J.; Johnson, R.D.; Cooper, B.Y.

2017-01-01

Exposure to DEET (N,N-diethyl-meta-toluamide) may have influenced the pattern of symptoms observed in soldiers with GWI (Gulf War Illness; Haley and Kurt, 1997). We examined how the addition of DEET (400 mg/kg; 50% topical) to an exposure protocol of permethrin (2.6 mg/kg; topical), chlorpyrifos (CP; 120 mg/kg), and pyridostigmine bromide (PB;13 mg/kg) altered the emergence and pattern of pain signs in an animal model of GWI pain (). Rats underwent behavioral testing before, during and after a 4 week exposure: 1) hindlimb pressure withdrawal threshold; 2) ambulation (movement distance and rate); and 3) resting duration. Additional studies were conducted to assess the influence of acute DEET (10–100 μM) on muscle and vascular nociceptor K v 7, K DR , Na v 1.8 and Na v 1.9. We report that a 50% concentration of DEET enhanced the development and persistence of pain-signs. Rats exposed to all 4 compounds exhibited ambulation deficits that appeared 5–12 weeks post-exposure and persisted through weeks 21–24. Rats exposed to only three agents (CP or PB excluded), did not fully develop ambulation deficits. When PB was excluded, rats also developed rest duration pain signs, in addition to ambulation deficits. There was no evidence that physiological doses of DEET acutely modified nociceptor K v 7, K DR , Na v 1.8 or Na v 1.9 activities. Nevertheless, DEET augmented protocols decreased the conductance of K v 7 expressed in vascular nociceptors harvested from chronically exposed rats. We concluded that DEET enhanced the development and persistence of pain behaviors, but the anticholinesterases CP and PB played a determinant role. - Highlights: • DEET accelerated and prolonged pain-like behaviors in a rat model of Gulf War Illness. • The development of pain behaviors were dependent upon chlorpyrifos and pyridostigmine. • Conductance of vascular nociceptor Kv7 was diminished 12 weeks following exposures. • DEET did not have any acute influence on nociceptor Kv7

Persistent estrus rat models of polycystic ovary disease: an update.

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Singh, Krishna B

2005-10-01

To critically review published articles on polycystic ovary (PCO) disease in rat models, with a focus on delineating its pathophysiology. Review of the English-language literature published from 1966 to March 2005 was performed through PubMed search. Keywords or phrases used were persistent estrus, chronic anovulation, polycystic ovary, polycystic ovary disease, and polycystic ovary syndrome. Articles were also located via bibliographies of published literature. University Health Sciences Center. Articles on persistent estrus and PCO in rats were selected and reviewed regarding the methods for induction of PCO disease. Changes in the reproductive cycle, ovarian morphology, hormonal parameters, and factors associated with the development of PCO disease in rat models were analyzed. Principal methods for inducing PCO in the rat include exposure to constant light, anterior hypothalamic and amygdaloidal lesions, and the use of androgens, estrogens, antiprogestin, and mifepristone. The validated rat PCO models provide useful information on morphologic and hormonal disturbances in the pathogenesis of chronic anovulation in this condition. These studies have aimed to replicate the morphologic and hormonal characteristics observed in the human PCO syndrome. The implications of these studies to human condition are discussed.

Persistent hyperCKemia: fourteen patients studied in retrospect

NARCIS (Netherlands)

Brewster, L. M.; de Visser, M.

1988-01-01

Fourteen patients with persistently raised serum creatine kinase activity (hyperCKemia) were studied in retrospect. Clinical and laboratory findings did not point to any established neuromuscular disorder. In 8, manual occupation with local muscle strain apparently caused the hyperCKemia despite a

Modest Amounts of Voluntary Exercise Reduce Pain- and Stress-Related Outcomes in a Rat Model of Persistent Hind Limb Inflammation.

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Pitcher, Mark H; Tarum, Farid; Rauf, Imran Z; Low, Lucie A; Bushnell, Catherine

2017-06-01

Aerobic exercise improves outcomes in a variety of chronic health conditions, yet the support for exercise-induced effects on chronic pain in humans is mixed. Although many rodent studies have examined the effects of exercise on persistent hypersensitivity, the most used forced exercise paradigms that are known to be highly stressful. Because stress can also produce analgesic effects, we studied how voluntary exercise, known to reduce stress in healthy subjects, alters hypersensitivity, stress, and swelling in a rat model of persistent hind paw inflammation. Our data indicate that voluntary exercise rapidly and effectively reduces hypersensitivity as well as stress-related outcomes without altering swelling. Moreover, the level of exercise is unrelated to the analgesic and stress-reducing effects, suggesting that even modest amounts of exercise may impart significant benefit in persistent inflammatory pain states. Modest levels of voluntary exercise reduce pain- and stress-related outcomes in a rat model of persistent inflammatory pain, independently of the amount of exercise. As such, consistent, self-regulated activity levels may be more relevant to health improvement in persistent pain states than standardized exercise goals. Published by Elsevier Inc.

FIV establishes a latent infection in feline peripheral blood CD4+ T lymphocytes in vivo during the asymptomatic phase of infection

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Murphy Brian

2012-02-01

Full Text Available Abstract Background Feline immunodeficiency virus (FIV is a lentivirus of cats that establishes a lifelong persistent infection with immunologic impairment. Results In an approximately 2 year-long experimental infection study, cats infected with a biological isolate of FIV clade C demonstrated undetectable plasma viral loads from 10 months post-infection onward. Viral DNA was detected in CD4+CD25+ and CD4+CD25- T cells isolated from infected cats whereas viral RNA was not detected at multiple time points during the early chronic phase of infection. Viral transcription could be reactivated in latently infected CD4+ T cells ex vivo as demonstrated by detectable FIV gag RNA and 2-long terminal repeat (LTR circle junctions. Viral LTR and gag sequences amplified from peripheral blood mononuclear cells during early and chronic stages of infection demonstrated minimal to no viral sequence variation. Conclusions Collectively, these findings are consistent with FIV latency in peripheral blood CD4+ T cells isolated from chronically infected cats. The ability to isolate latently FIV-infected CD4+ T lymphocytes from FIV-infected cats provides a platform for the study of in vivo mechanisms of lentiviral latency.

Mechanisms mediating vibration-induced chronic musculoskeletal pain analyzed in the rat.

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Dina, Olayinka A; Joseph, Elizabeth K; Levine, Jon D; Green, Paul G

2010-04-01

While occupational exposure to vibration is a common cause of acute and chronic musculoskeletal pain, eliminating exposure produces limited symptomatic improvement, and reexposure precipitates rapid recurrence or exacerbation. To evaluate mechanisms underlying these pain syndromes, we have developed a model in the rat, in which exposure to vibration (60-80Hz) induces, in skeletal muscle, both acute mechanical hyperalgesia as well as long-term changes characterized by enhanced hyperalgesia to a proinflammatory cytokine or reexposure to vibration. Exposure of a hind limb to vibration-produced mechanical hyperalgesia measured in the gastrocnemius muscle of the exposed hind limb, which persisted for approximately 2 weeks. When nociceptive thresholds had returned to baseline, exposure to a proinflammatory cytokine or reexposure to vibration produced markedly prolonged hyperalgesia. The chronic prolongation of vibration- and cytokine-hyperalgesia was prevented by spinal intrathecal injection of oligodeoxynucleotide (ODN) antisense to protein kinase Cepsilon, a second messenger in nociceptors implicated in the induction and maintenance of chronic pain. Vibration-induced hyperalgesia was inhibited by spinal intrathecal administration of ODN antisense to receptors for the type-1 tumor necrosis factor-alpha (TNFalpha) receptor. Finally, in TNFalpha-pretreated muscle, subsequent vibration-induced hyperalgesia was markedly prolonged. These studies establish a model of vibration-induced acute and chronic musculoskeletal pain, and identify the proinflammatory cytokine TNFalpha and the second messenger protein kinase Cepsilon as targets against which therapies might be directed to prevent and/or treat this common and very debilitating chronic pain syndrome. Copyright 2010 American Pain Society. All rights reserved.

Persistent high serum bicarbonate and the risk of heart failure in patients with chronic kidney disease (CKD): A report from the Chronic Renal Insufficiency Cohort (CRIC) study.

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Dobre, Mirela; Yang, Wei; Pan, Qiang; Appel, Lawrence; Bellovich, Keith; Chen, Jing; Feldman, Harold; Fischer, Michael J; Ham, L L; Hostetter, Thomas; Jaar, Bernard G; Kallem, Radhakrishna R; Rosas, Sylvia E; Scialla, Julia J; Wolf, Myles; Rahman, Mahboob

2015-04-20

Serum bicarbonate varies over time in chronic kidney disease (CKD) patients, and this variability may portend poor cardiovascular outcomes. The aim of this study was to conduct a time-updated longitudinal analysis to evaluate the association of serum bicarbonate with long-term clinical outcomes: heart failure, atherosclerotic events, renal events (halving of estimated glomerular filtration rate [eGFR] or end-stage renal disease), and mortality. Serum bicarbonate was measured annually, in 3586 participants with CKD, enrolled in the Chronic Renal Insufficiency Cohort (CRIC) study. Marginal structural models were created to allow for integration of all available bicarbonate measurements and proper adjustment for time-dependent confounding. During the 6 years follow-up, 512 participants developed congestive heart failure (26/1000 person-years) and 749 developed renal events (37/1000 person-years). The risk of heart failure and death was significantly higher for participants who maintained serum bicarbonate >26 mmol/L for the entire duration of follow-up (hazard ratio [HR] 1.66; 95% confidence interval [CI], 1.23 to 2.23, and HR 1.36, 95% CI 1.02 to 1.82, respectively) compared with participants who kept their bicarbonate 22 to 26 mmol/L, after adjusting for demographics, co-morbidities, medications including diuretics, eGFR, and proteinuria. Participants who maintained serum bicarbonate renal disease progression (HR 1.97; 95% CI, 1.50 to 2.57) compared with participants with bicarbonate 22 to 26 mmol/L. In this large CKD cohort, persistent serum bicarbonate >26 mmol/L was associated with increased risk of heart failure events and mortality. Further studies are needed to determine the optimal range of serum bicarbonate in CKD to prevent adverse clinical outcomes. © 2015 The Authors. Published on behalf of the American Heart Association, Inc., by Wiley Blackwell.

Persistent High Serum Bicarbonate and the Risk of Heart Failure in Patients With Chronic Kidney Disease (CKD): A Report From the Chronic Renal Insufficiency Cohort (CRIC) Study

Science.gov (United States)

Dobre, Mirela; Yang, Wei; Pan, Qiang; Appel, Lawrence; Bellovich, Keith; Chen, Jing; Feldman, Harold; Fischer, Michael J.; Ham, L. L.; Hostetter, Thomas; Jaar, Bernard G.; Kallem, Radhakrishna R.; Rosas, Sylvia E.; Scialla, Julia J.; Wolf, Myles; Rahman, Mahboob

2015-01-01

Background Serum bicarbonate varies over time in chronic kidney disease (CKD) patients, and this variability may portend poor cardiovascular outcomes. The aim of this study was to conduct a time‐updated longitudinal analysis to evaluate the association of serum bicarbonate with long‐term clinical outcomes: heart failure, atherosclerotic events, renal events (halving of estimated glomerular filtration rate [eGFR] or end‐stage renal disease), and mortality. Methods and Results Serum bicarbonate was measured annually, in 3586 participants with CKD, enrolled in the Chronic Renal Insufficiency Cohort (CRIC) study. Marginal structural models were created to allow for integration of all available bicarbonate measurements and proper adjustment for time‐dependent confounding. During the 6 years follow‐up, 512 participants developed congestive heart failure (26/1000 person‐years) and 749 developed renal events (37/1000 person‐years). The risk of heart failure and death was significantly higher for participants who maintained serum bicarbonate >26 mmol/L for the entire duration of follow‐up (hazard ratio [HR] 1.66; 95% confidence interval [CI], 1.23 to 2.23, and HR 1.36, 95% CI 1.02 to 1.82, respectively) compared with participants who kept their bicarbonate 22 to 26 mmol/L, after adjusting for demographics, co‐morbidities, medications including diuretics, eGFR, and proteinuria. Participants who maintained serum bicarbonate renal disease progression (HR 1.97; 95% CI, 1.50 to 2.57) compared with participants with bicarbonate 22 to 26 mmol/L. Conclusion In this large CKD cohort, persistent serum bicarbonate >26 mmol/L was associated with increased risk of heart failure events and mortality. Further studies are needed to determine the optimal range of serum bicarbonate in CKD to prevent adverse clinical outcomes. PMID:25896890

Genetic Screen Reveals the Role of Purine Metabolism in Staphylococcus aureus Persistence to Rifampicin

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Rebecca Yee

2015-12-01

Full Text Available Chronic infections with Staphylococcus aureus such as septicemia, osteomyelitis, endocarditis, and biofilm infections are difficult to treat because of persisters. Despite many efforts in understanding bacterial persistence, the mechanisms of persister formation in S. aureus remain elusive. Here, we performed a genome-wide screen of a transposon mutant library to study the molecular mechanisms involved in persistence of community-acquired S. aureus. Screening of the library for mutants defective in persistence or tolerance to rifampicin revealed many genes involved in metabolic pathways that are important for antibiotic persistence. In particular, the identified mutants belonged to metabolic pathways involved in carbohydrate, amino acid, lipid, vitamin and purine biosynthesis. Five mutants played a role in purine biosynthesis and two mutants, purB, an adenylosuccinate lyase, and purM, a phosphoribosylaminoimidazole synthetase, were selected for further confirmation. Mutants purB and purM showed defective persistence compared to the parental strain USA300 in multiple stress conditions including various antibiotics, low pH, and heat stress. The defect in persistence was restored by complementation with the wildtype purB and purM gene in the respective mutants. These findings provide new insights into the mechanisms of persistence in S. aureus and provide novel therapeutic targets for developing more effective treatment for persistent infections due to S. aureus.

Initial Pseudomonas aeruginosa infection in patients with cystic fibrosis: characteristics of eradicated and persistent isolates

DEFF Research Database (Denmark)

Tramper-Stranders, G. A.; van der Ent, C. K.; Molin, Søren

2012-01-01

Clin Microbiol Infect 2012; 18: 567574 Abstract Despite intensive eradication therapy, some CF patients with early Pseudomonas aeruginosa infection rapidly develop a chronic infection. To elucidate factors associated with this persistence, bacterial characteristics of early P. aeruginosa isolates...

Mechanisms of Disease Persistence in Chronic Myelogenous Leukemia (CML)

Science.gov (United States)

2006-10-01

9.2 1.4 0.03 K-Ras* 6.7 1.3 0.04 RALA 5.4 1.1 0.13 Opioid receptor mu1 4.4 1.1 0.36 Jak2 4.3 1.2 0.14 TRF1 4.3 1.5 0.06 WT-1* n/a 1.3 0.008 c...2002 American Society of Hematology, Scientific Committee on Neoplasia 2000-2004 American Medical Informatics Association: Global Trial Bank...kinase in the blast crisis of chronic myeloid leukemia and acute lymphoblastic leukemia with the Philadelphia chromosome. N Engl J Med 344:1038-1042

A Secure Trust Establishment Scheme for Wireless Sensor Networks

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Farruh Ishmanov

2014-01-01

Full Text Available Trust establishment is an important tool to improve cooperation and enhance security in wireless sensor networks. The core of trust establishment is trust estimation. If a trust estimation method is not robust against attack and misbehavior, the trust values produced will be meaningless, and system performance will be degraded. We present a novel trust estimation method that is robust against on-off attacks and persistent malicious behavior. Moreover, in order to aggregate recommendations securely, we propose using a modified one-step M-estimator scheme. The novelty of the proposed scheme arises from combining past misbehavior with current status in a comprehensive way. Specifically, we introduce an aggregated misbehavior component in trust estimation, which assists in detecting an on-off attack and persistent malicious behavior. In order to determine the current status of the node, we employ previous trust values and current measured misbehavior components. These components are combined to obtain a robust trust value. Theoretical analyses and evaluation results show that our scheme performs better than other trust schemes in terms of detecting an on-off attack and persistent misbehavior.

Clinical worsening in Chronic Thromboembolic Pulmonary Hypertension

NARCIS (Netherlands)

Schölzel, B.E.

2015-01-01

Chronic thromboembolic pulmonary hypertension (CTEPH) is defined as a raised mean pulmonary artery pressure (of at least 25 mmHg at rest) caused by persistent obstruction of pulmonary arteries after pulmonary embolism that has not resolved despite at least 3 months of therapeutic anticoagulation.

Persistent spiking fever in a child with acute myeloid leukemia and disseminated infection with enterovirus

NARCIS (Netherlands)

Murk, J. L.; de Vries, A. C.; GeurtsvanKessel, C. H.; Aron, G.; Osterhaus, A. D.; Wolthers, K. C.; Fraaij, P. L.

2014-01-01

We here report a 7 year old acute myeloid leukemia patient with persistent spiking fever likely caused by chronic echovirus 20 infection. After immunoglobulin substitution fevers subsided and the virus was cleared. Enterovirus infection should be considered in immunocompromised patients with

Using animal models to overcome temporal, spatial and combinatorial challenges in HIV persistence research

DEFF Research Database (Denmark)

Denton, Paul W.; Søgaard, Ole Schmeltz; Tolstrup, Martin

2016-01-01

Research challenges associated with understanding HIV persistence during antiretroviral therapy can be categorized as temporal, spatial and combinatorial. Temporal research challenges relate to the timing of events during establishment and maintenance of HIV persistence. Spatial research challeng...... for directly addressing these research challenges. The aim of this manuscript is to provide a comprehensive review of these recent translational advances made in animal models of HIV persistence....... will improve our understanding of HIV persistence and move the field closer to achieving eradication of persistent HIV. Given that humanized mice and non-human primate HIV models permit rigorous control of experimental conditions, these models have been used extensively as in vivo research platforms...

Chronic Musculoskeletal Disabilities following Snake Envenoming in Sri Lanka: A Population-Based Study.

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Subashini Jayawardana

2016-11-01

Full Text Available Snakebite is a major public health problem in agricultural communities in the tropics leading to acute local and systemic impairments with resultant disabilities. Snakebite related long-term musculoskeletal disabilities have been a neglected area of research. We conducted a population-based, cross-sectional study in an agricultural community to describe the chronic musculoskeletal disabilities of snake envenoming.A sample representative of residents of a single district in a region of high incidence of snake envenoming was recruited to identify ever snakebite victims. They were evaluated for chronic musculoskeletal disabilities that had developed immediately or within four weeks after the snakebite and persisted over three months. In-depth interviews, validated musculoskeletal functional assessment criteria and specialists' examinations were utilised. Among the 816 victims, 26 (3.2%, 95% confidence interval: 2.2-4.6% had musculoskeletal disabilities, persisting on average for 13.4 years (SD = 14.4. The disabilities were mostly in lower limbs (61.5% and ranged from swelling (34.6%, muscle wasting (46.1%, reduced motion (61.5%, reduced muscle power (50%, impaired balance (26.9%, chronic non-healing ulcers (3.85%, abnormal gait (3.85%, fixed deformities (19.2% to amputations (15.4%. Based on disability patterns, six snakebite-related musculoskeletal syndromes were recognised. The offending snakes causing disabilities were cobra (30.8%, Russell's viper (26.9% and hump-nosed viper (7.7%. Cobra bites manifested muscle wasting (87.5%, reduced muscle power (87.5%, joint stiffness (62.5% and deformities (37.5% while viper bites manifested impaired balance (42.8%, pain (71.4% and swelling (71.4%.Snakebite envenoming is associated with considerable long-term musculoskeletal disabilities. Facilities for specialized care and rehabilitation need to be established in high risk areas.

Assessment of bone mineral density in adults with a history of juvenile chronic arthritis: a cross-sectional long-term followup study

DEFF Research Database (Denmark)

Zak, M; Hassager, C; Lovell, D J

1999-01-01

To assess bone mineral density (BMD) and bone turnover in adults with a history of juvenile chronic arthritis (JCA) or persistent JCA, and to identify predictors of reduced BMD.......To assess bone mineral density (BMD) and bone turnover in adults with a history of juvenile chronic arthritis (JCA) or persistent JCA, and to identify predictors of reduced BMD....

Establishment and Evaluation of a Rat Model of Sidestream Cigarette Smoke-Induced Chronic Obstructive Pulmonary Disease

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Genfa Wang

2018-02-01

Full Text Available Chronic obstructive pulmonary disease (COPD is a common cause of mortality worldwide. The current lack of an animal model that can be established within a certain time frame and imitate the unique features of the disease is a major limiting factor in its study. The present study established and evaluated an animal model of COPD that represents the early and advanced stage features using short-, middle-, and long-term sidestream cigarette smoke (CS exposure. One hundred and nine Sprague–Dawley rats were randomly divided into 10 groups for different periods of sidestream CS exposure or no exposure (i.e., normal groups. The rats were exposed to CS from 3R4F cigarettes in an exposure chamber. Histological analysis was performed to determine pathological changes. We also conducted open-field tests, lung function evaluations, and cytokine analysis of the blood serum, bronchoalveolar lavage fluid, and lung tissue. The lung tissue protein levels, blood gases, and were also analyzed. As the CS exposure time increased, the indicators associated with oxidative stress, inflammatory responses, and airway remodeling were greater in the CS exposure groups than in the normal group. At 24 and 36 weeks, the COPD model rats displayed the middle- and advanced-stage features of COPD, respectively. In the 8-week CS exposure group, after the CS exposure was stopped for 4 weeks, inflammatory responses and oxidative responses were ameliorated and lung function exacerbation was reduced compared with the 12-week CS exposure group. Therefore, we established a more adequate rat model of sidestream CS induced COPD, which will have great significance for a better understanding of the pathogenesis of COPD and drug effectiveness evaluation.

Conservative treatment of chronic pancreatitis.

Science.gov (United States)

Löhr, J-Matthias; Haas, Stephen L; Lindgren, Fredrik; Enochsson, Lars; Hedström, Aleksandra; Swahn, Fredrik; Segersvärd, Ralf; Arnelo, Urban

2013-01-01

Chronic pancreatitis is a progressive inflammatory disease giving rise to several complications that need to be treated accordingly. Because pancreatic surgery has significant morbidity and mortality, less invasive therapy seems to be an attractive option. This paper reviews current state-of-the-art strategies to treat chronic pancreatitis without surgery and the current guidelines for the medical therapy of chronic pancreatitis. Endoscopic therapy of complications of chronic pancreatitis such as pain, main pancreatic duct strictures and stones as well as pseudocysts is technically feasible and safe. The long-term outcome, however, is inferior to definitive surgical procedures such as resection or drainage. On the other hand, the medical therapy of pancreatic endocrine and exocrine insufficiency is well established and evidence based. Endoscopic therapy may be an option to bridge for surgery and in children/young adolescents and those unfit for surgery. Pain in chronic pancreatitis as well as treatment of pancreatic exocrine insufficiency follows established guidelines. Copyright © 2013 S. Karger AG, Basel.

Establishment and validation of a predictive nomogram model for non-small cell lung cancer patients with chronic hepatitis B viral infection.

Science.gov (United States)

Chen, Shulin; Lai, Yanzhen; He, Zhengqiang; Li, Jianpei; He, Xia; Shen, Rui; Ding, Qiuying; Chen, Hao; Peng, Songguo; Liu, Wanli

2018-05-04

This study aimed to establish an effective predictive nomogram for non-small cell lung cancer (NSCLC) patients with chronic hepatitis B viral (HBV) infection. The nomogram was based on a retrospective study of 230 NSCLC patients with chronic HBV infection. The predictive accuracy and discriminative ability of the nomogram were determined by a concordance index (C-index), calibration plot and decision curve analysis and were compared with the current tumor, node, and metastasis (TNM) staging system. Independent factors derived from Kaplan-Meier analysis of the primary cohort to predict overall survival (OS) were all assembled into a Cox proportional hazards regression model to build the nomogram model. The final model included age, tumor size, TNM stage, treatment, apolipoprotein A-I, apolipoprotein B, glutamyl transpeptidase and lactate dehydrogenase. The calibration curve for the probability of OS showed that the nomogram-based predictions were in good agreement with the actual observations. The C-index of the model for predicting OS had a superior discrimination power compared with the TNM staging system [0.780 (95% CI 0.733-0.827) vs. 0.693 (95% CI 0.640-0.746), P  20.0). The proposed nomogram model resulted in more accurate prognostic prediction for NSCLC patients with chronic HBV infection.

Chronic radiation exposure: possibility of studying mutation process in generations based on the established DNA bank of exposed individuals and their offspring

International Nuclear Information System (INIS)

Rusinova, Galina G.; Adamova, Galina V.; Dudchenko, Natalya N.; Azizova, Tamara V.; Kurbatov, Andrey V.

2002-01-01

Data were summarized on the DNA Bank establishment for workers of the Mayak nuclear facility in Southern Ural, who were exposed to different doses of chronic radiation from γ -rays during the first years of the enterprise operations (1948-1958) and their families. Some workers were exposed to combined radiation (external + internal radiation from incorporated 239 Pu). The DNA Bank was established to store the unique genetic material from these individuals and their offspring for future risk estimation of the late consequences of radiation exposure using modern molecular-genetic technologies. Today, DNA Bank contains genetic material from 1,500 individuals and 218 families. The computer database was generated for the DNA Bank. It included individual medical-demographic, occupational descriptions and doses, quantitative and qualitative DNA data. Literature data on radiation-induced genome instability (variability of hypervariable areas) were also analyzed. Prospects of the DNA Bank establishment are also presented. The work is carried out on extension of the DNA Bank of exposed individuals and their offspring

Microbial analysis in primary and persistent endodontic infections by using pyrosequencing.

Science.gov (United States)

Hong, Bo-Young; Lee, Tae-Kwon; Lim, Sang-Min; Chang, Seok Woo; Park, Joonhong; Han, Seung Hyun; Zhu, Qiang; Safavi, Kamran E; Fouad, Ashraf F; Kum, Kee Yeon

2013-09-01

The aim of this study was to investigate the bacterial community profile of intracanal microbiota in primary and persistent endodontic infections associated with asymptomatic chronic apical periodontitis by using GS-FLX Titanium pyrosequencing. The null hypothesis was that there is no difference in diversity of overall bacterial community profiles between primary and persistent infections. Pyrosequencing analysis from 10 untreated and 8 root-filled samples was conducted. Analysis from 18 samples yielded total of 124,767 16S rRNA gene sequences (with a mean of 6932 reads per sample) that were taxonomically assigned into 803 operational taxonomic units (3% distinction), 148 genera, and 10 phyla including unclassified. Bacteroidetes was the most abundant phylum in both primary and persistent infections. There were no significant differences in bacterial diversity between the 2 infection groups (P > .05). The bacterial community profile that was based on dendrogram showed that bacterial population in both infections was not significantly different in their structure and composition (P > .05). The present pyrosequencing study demonstrates that persistent infections have as diverse bacterial community as primary infections. Copyright © 2013 American Association of Endodontists. Published by Elsevier Inc. All rights reserved.

Reoperation for persistent or recurrent secondary hyperparathyroidism.

Science.gov (United States)

Abruzzo, Alida; Gioviale, Maria Concetta; Damiano, Giuseppe; Palumbo, Vincenzo Davide; Buscemi, Salvatore; Lo Monte, Giulia; Gulotta, Leonardo; Buscemi, Giuseppe; Lo Monte, Attilio Ignazio

2017-10-23

Secondary hyperparathyroidism is a common acquired disorder seen in chronic renal failure. Its pathophysiology is mainly due to hyperphosphatemia and vitamin D deficiency and resistance. When medical treatment fails, subtotal and total parathyroidectomy with autotransplantation are the standard procedures, although both are associated with high recurrence rates. 4 patients experienced persistence and 9 relapse. The first 4 were subjected to reoperation after 6 months for the persistence of symptoms due to the finding of a supernumerary adenomatous gland while the remaining patients at the reoperation showed in 5 cases 2 more glands in over thymic position, and 4 an hyperplasia of the residual glandular tissue. A classic cervicotomy was sufficient to remove the residual parathyroid in patients with persistent hyperparathyroidism. For cases of recurrent hyperparathyroidism it was enough a medial approach and sometimes lateral for the complete excision of the hyperplastic tissue. The advent of the intraoperative technique of parathyroid hormone dosage allowed a better performance of the surgical technique for the last 3 patients undergoing reoperation. After reoperation all patients had immediate regression of clinical symptoms with normalization of serum calcium and PTH levels. On the basis of these considerations, diagnostic imaging has a not negligible role because during the first intervention helps to have an idea of the possible location of the glands and thus to avoid the risk of recurrence and relapse due to ectopic or supernumerary tissue.

Exopolysaccharide Productivity and Biofilm Phenotype on Oral Commensal Bacteria as Pathogenesis of Chronic Periodontitis

Science.gov (United States)

2012-01-01

2 Exopolysaccharide Productivity and Biofilm Phenotype on Oral Commensal Bacteria as Pathogenesis of Chronic Periodontitis Takeshi Yamanaka1...species biofilm in the oral cavity can cause persistent chronic periodontitis along with the importance of dental plaque formation and maturation...independent manner could be pathogenic for periodontal tissues and can cause chronic periodontitis lesions. 2.1 Initial colonizers on the tooth surface

Ratio-based estimators for a change point in persistence.

Science.gov (United States)

Halunga, Andreea G; Osborn, Denise R

2012-11-01

We study estimation of the date of change in persistence, from [Formula: see text] to [Formula: see text] or vice versa. Contrary to statements in the original papers, our analytical results establish that the ratio-based break point estimators of Kim [Kim, J.Y., 2000. Detection of change in persistence of a linear time series. Journal of Econometrics 95, 97-116], Kim et al. [Kim, J.Y., Belaire-Franch, J., Badillo Amador, R., 2002. Corringendum to "Detection of change in persistence of a linear time series". Journal of Econometrics 109, 389-392] and Busetti and Taylor [Busetti, F., Taylor, A.M.R., 2004. Tests of stationarity against a change in persistence. Journal of Econometrics 123, 33-66] are inconsistent when a mean (or other deterministic component) is estimated for the process. In such cases, the estimators converge to random variables with upper bound given by the true break date when persistence changes from [Formula: see text] to [Formula: see text]. A Monte Carlo study confirms the large sample downward bias and also finds substantial biases in moderate sized samples, partly due to properties at the end points of the search interval.

Persistent effects of chronic Δ9-THC exposure on motor impulsivity in rats.

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Irimia, Cristina; Polis, Ilham Y; Stouffer, David; Parsons, Loren H

2015-08-01

In humans, long-term marijuana use is associated with impaired impulse control and attentional capacity, though it has been difficult to distinguish pre-existing cognitive deficits from possible consequences of prolonged marijuana exposure. To evaluate the effects of long-term exposure to Δ9-Tetrahydrocannabinol (Δ9-THC), the primary psychoactive constituent in marijuana, on indices of impulse control and attentional capacity using the rat 5-Choice Serial Reaction Time Task (5-CSRTT). Ten 14-day cycles of Δ9-THC dosing and 5-CSRTT testing were employed, each comprised of 5-day Δ9-THC dosing (0.3 or 3 mg/kg b.i.d.) and 5-CSRTT testing during the 9 days of drug abstinence. Subsequent 5-CSRTT testing continued during 5 weeks of protracted abstinence. Dose-dependent increases in motor impulsivity (premature responses) and behavioral disinhibition (perseverative responses) emerged following 5 cycles of Δ9-THC exposure that persisted for the remaining dosing and testing cycles. Δ9-THC-related disruptions in motor impulsivity and behavioral inhibition were most pronounced during cognitively challenging 5-CSRTT sessions incorporating varying novel inter-trial intervals (ITIs), and these disruptions persisted for at least 5 weeks of Δ9-THC abstinence. Δ9-THC-related impairments in attentional capacity (response accuracy) were also evident during variable ITI challenge tests, though these attentional disruptions abated within 3 weeks of Δ9-THC abstinence. These observations demonstrate that long-term intermittent exposure to clinically meaningful Δ9-THC doses induces persistent impairments in impulse control and attentional function. If present in humans, these disruptions may impact academic and professional performance.

Persistence and extinction of an n-species mutualism model with random perturbations in a polluted environment

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He, Xin; Shan, Meijing; Liu, Meng

2018-02-01

An n-species stochastic Lotka-Volterra cooperative model in a polluted environment is proposed and studied. For each species, sufficient conditions for extinction, non-persistence in the mean and weak persistence in the mean are established. The threshold between weak persistence in the mean and extinction is obtained. Several numerical figures are also worked out to validate the theoretical results.

DEET potentiates the development and persistence of anticholinesterase dependent chronic pain signs in a rat model of Gulf War Illness pain

Energy Technology Data Exchange (ETDEWEB)

Flunker, L.K., E-mail: lflunker@dental.ufl.edu [Division of Neuroscience, Dept. of Oral and Maxillofacial Surgery, Box 100416, JHMHC, University of Florida College of Dentistry, Gainesville, FL 32610 (United States); Nutter, T.J., E-mail: tnutter@dental.ufl.edu [Division of Neuroscience, Dept. of Oral and Maxillofacial Surgery, Box 100416, JHMHC, University of Florida College of Dentistry, Gainesville, FL 32610 (United States); Johnson, R.D., E-mail: rdjohnso@ufl.edu [Dept. of Physiological Sciences, University of Florida College of Veterinary Science, Gainesville, FL 32610 (United States); Cooper, B.Y., E-mail: bcooper@dental.ufl.edu [Division of Neuroscience, Dept. of Oral and Maxillofacial Surgery, Box 100416, JHMHC, University of Florida College of Dentistry, Gainesville, FL 32610 (United States)

2017-02-01

Exposure to DEET (N,N-diethyl-meta-toluamide) may have influenced the pattern of symptoms observed in soldiers with GWI (Gulf War Illness; Haley and Kurt, 1997). We examined how the addition of DEET (400 mg/kg; 50% topical) to an exposure protocol of permethrin (2.6 mg/kg; topical), chlorpyrifos (CP; 120 mg/kg), and pyridostigmine bromide (PB;13 mg/kg) altered the emergence and pattern of pain signs in an animal model of GWI pain (). Rats underwent behavioral testing before, during and after a 4 week exposure: 1) hindlimb pressure withdrawal threshold; 2) ambulation (movement distance and rate); and 3) resting duration. Additional studies were conducted to assess the influence of acute DEET (10–100 μM) on muscle and vascular nociceptor K{sub v}7, K{sub DR}, Na{sub v}1.8 and Na{sub v}1.9. We report that a 50% concentration of DEET enhanced the development and persistence of pain-signs. Rats exposed to all 4 compounds exhibited ambulation deficits that appeared 5–12 weeks post-exposure and persisted through weeks 21–24. Rats exposed to only three agents (CP or PB excluded), did not fully develop ambulation deficits. When PB was excluded, rats also developed rest duration pain signs, in addition to ambulation deficits. There was no evidence that physiological doses of DEET acutely modified nociceptor K{sub v}7, K{sub DR}, Na{sub v}1.8 or Na{sub v}1.9 activities. Nevertheless, DEET augmented protocols decreased the conductance of K{sub v}7 expressed in vascular nociceptors harvested from chronically exposed rats. We concluded that DEET enhanced the development and persistence of pain behaviors, but the anticholinesterases CP and PB played a determinant role. - Highlights: • DEET accelerated and prolonged pain-like behaviors in a rat model of Gulf War Illness. • The development of pain behaviors were dependent upon chlorpyrifos and pyridostigmine. • Conductance of vascular nociceptor Kv7 was diminished 12 weeks following exposures. • DEET did not have any

Persistent Neutrophilic Meningitis in an Immunocompetent Patient after Basilar Skull Fracture: Case Report

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Uslan Daniel Z

2011-05-01

Full Text Available Abstract Background Persistent neutrophilic meningitis is an unusual form of chronic meningitis that is defined as clinical meningitis with a neutrophilic pleocytosis that persists for greater than 7 days despite empiric antimicrobial therapy. Although numerous disease processes can cause this syndrome, the majority of cases are due to opportunistic pathogens infecting immunocompromised hosts. Case Presentation A 47 year-old female presented after basilar skull fracture with persistent neutrophilic meningitis unresponsive to empiric broad-spectrum antibiotics. After more than weeks of intensive therapy, 4 hospitalizations and 3 relapses, Nocardia cyriacigeorgica was identified from cerebral spinal fluid. Induction therapy was begun with Ceftriaxone and trimethoprim-sulfamethoxazole (TMP-SMX for 6 weeks followed by therapy with TMP-SMX and doxycycline for one year. The patient made a complete recovery without sequelae. Conclusions Due to the difficulty in obtaining a microbiologic diagnosis, appropriate treatment in cases of persistent neutrophilic meningitis is often delayed leading to morbidity, This case highlights a number of the unique features of Nocardia meningitis and the importance of considering Nocardia infection as a cause of persistent neutrophilic meningitis even in immunocompetent patients.

Mixed infections with Chlamydia and porcine epidemic diarrhea virus - a new in vitro model of chlamydial persistence.

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Borel, Nicole; Dumrese, Claudia; Ziegler, Urs; Schifferli, Andrea; Kaiser, Carmen; Pospischil, Andreas

2010-07-27

Chlamydiae induce persistent infections, which have been associated with a wide range of chronic diseases in humans and animals. Mixed infections with Chlamydia and porcine epidemic diarrhea virus (PEDV) may result in generation of persistent chlamydial infections. To test this hypothesis, an in vitro model of dual infection with cell culture-adapted PEDV and Chlamydia abortus or Chlamydia pecorum in Vero cells was established. Infected cultures were investigated by immunofluorescence (IF), transmission electron microscopy (TEM) and re-infection experiments. By IF, Chlamydia-infected cells showed normal inclusions after 39 hpi. Dual infections with Chlamydia abortus revealed a heterogenous mix of inclusion types including small inclusions consisting of aberrant bodies (ABs), medium-sized inclusions consisting of ABs and reticulate bodies and normal inclusions. Only aberrant inclusions were observable in dual infection experiments with Chlamydia pecorum and PEDV. TEM examinations of mixed infections with Chlamydia abortus and Chlamydia pecorum revealed aberrant chlamydial inclusions containing reticulate-like, pleomorphic ABs, which were up to 2 microm in diameter. No re-differentiation into elementary bodies (EBs) was detected. In re-infection experiments, co-infected cells produced fewer EBs than monoinfected cells. In the present study we confirm that PEDV co-infection alters the developmental cycle of member species of the family Chlamydiaceae, in a similar manner to other well-described persistence induction methods. Interestingly, this effect appears to be partially species-specific as Chlamydia pecorum appears more sensitive to PEDV co-infection than Chlamydia abortus, as evidenced by TEM and IF observations of a homogenous population of aberrant inclusions in PEDV - Chlamydia pecorum co-infections.

The effect of acceptance training on psychological and physical health outcomes in elders with chronic conditions.

Science.gov (United States)

McDonald, Patricia E; Zauszniewski, Jaclene A; Bekhet, Abir K; DeHelian, Laura; Morris, Diana L

2011-12-01

This pilot trial investigated the short and long-term effects of Acceptance Training (ACT) intervention on acceptance, perceived health, functional status, anxiety, and depression in elders with chronic conditions living in retirement communities (RCs). The ACT intervention combined Rational Emotive Behavior Therapy with music, relaxation, and guided imagery during six weekly 2-hour sessions. Face-to-face interviews were conducted with 16 African-American and 46 White elders across four data collection points in six randomly selected RCs using well-established measures of perceived health, functional status, anxiety, and depression, and a measure of acceptance of chronic conditions adapted from a previous measure of acceptance of diabetes. While changes were found in perceived health, functional status, anxiety, and depression, the most significant changes occurred in the elders' acceptance of chronic conditions immediately after the intervention (t = -2.62, p < .02), and these changes persisted for 6 and 12 weeks (t's = -2.74, -3.32, p's < .01), respectively. Although a 40% attrition rate reduced the sample size from 62 (N = 62) to 37 (N = 37), the significant increases in acceptance over time provide initial evidence for the fidelity of the ACT intervention.

Treatment for Chronic Depression Using Schema Therapy

NARCIS (Netherlands)

Renner, F.; Arntz, A.; Leeuw, I.; Huibers, M.J.H.

2013-01-01

Schema therapy (ST) is an integrative treatment approach to chronic lifelong problems with an established effectiveness for treating personality disorders. This article describes the adaptation of ST to chronic depression by reviewing the literature on the underlying risk factors to chronic

Primary headache diagnosis among chronic daily headache patients

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Krymchantowski Abouch Valenty

2003-01-01

Full Text Available Chronic daily headache (CDH refers to a group of non-paroxysmal daily or near-daily headaches with peculiar characteristics that are highly prevalent in populations of neurological clinics and not uncommon among non-patient populations. Most of the patients with CDH had, as primary diagnosis, episodic migraine, which, with the time, presented a progressive frequency, pattern modification and loss of specific migraine characteristics. Other CDH patients had chronic tension-type headache, new daily persistent headache and hemicrania continua, which evolved thru the time to the daily or near-daily presentation. The objective of this study was to determine the primary headache diagnosis among a population of chronic daily headache patients attending a tertiary center for headache treatment. During a 5-year period 651 consecutive chronic daily headache patients attending a private subspecialty center were studied prospectively. The criteria adopted were those proposed by Silberstein et al (1994, revised 1996. Five hundred seventy four patients (88.1% had episodic migraine as primary headache before turning into daily presentation, 52 (8% had chronic tension-type headache, 14 (2.2% had hemicrania continua and 11 patients (1.7% had new daily persistent headache. CDH is quite frequent in patients from clinic-based studies suggesting a high degree of disability. Emphasis on education of patients suffering from frequent primary headaches with regard to measures that are able to decrease suffering and disability as well as better medical education directed to more efficient ways to handle these patients are necessary to improve outcome of such a prevalent condition.

Chronic sleep deprivation differentially affects short and long-term operant memory in Aplysia.

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Krishnan, Harini C; Noakes, Eric J; Lyons, Lisa C

2016-10-01

The induction, formation and maintenance of memory represent dynamic processes modulated by multiple factors including the circadian clock and sleep. Chronic sleep restriction has become common in modern society due to occupational and social demands. Given the impact of cognitive impairments associated with sleep deprivation, there is a vital need for a simple animal model in which to study the interactions between chronic sleep deprivation and memory. We used the marine mollusk Aplysia californica, with its simple nervous system, nocturnal sleep pattern and well-characterized learning paradigms, to assess the effects of two chronic sleep restriction paradigms on short-term (STM) and long-term (LTM) associative memory. The effects of sleep deprivation on memory were evaluated using the operant learning paradigm, learning that food is inedible, in which the animal associates a specific netted seaweed with failed swallowing attempts. We found that two nights of 6h sleep deprivation occurring during the first or last half of the night inhibited both STM and LTM. Moreover, the impairment in STM persisted for more than 24h. A milder, prolonged sleep deprivation paradigm consisting of 3 consecutive nights of 4h sleep deprivation also blocked STM, but had no effect on LTM. These experiments highlight differences in the sensitivity of STM and LTM to chronic sleep deprivation. Moreover, these results establish Aplysia as a valid model for studying the interactions between chronic sleep deprivation and associative memory paving the way for future studies delineating the mechanisms through which sleep restriction affects memory formation. Copyright © 2016 Elsevier Inc. All rights reserved.

Cytokines and T-Lymphocute count in patients in the acute and chronic phases of Bartonella bacilliformis infection in an endemic area in peru: a pilot study

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Erick Huarcaya

2011-06-01

Full Text Available Human Bartonellosis has an acute phase characterized by fever and hemolytic anemia, and a chronic phase with bacillary angiomatosis-like lesions. This cross-sectional pilot study evaluated the immunology patterns using pre- and post-treatment samples in patients with Human Bartonellosis. Patients between five and 60 years of age, from endemic areas in Peru, in the acute or chronic phases were included. In patients in the acute phase of Bartonellosis a state of immune peripheral tolerance should be established for persistence of the infection. Our findings were that elevation of the anti-inflammatory cytokine IL-10 and numeric abnormalities of CD4+ and CD8+ T-Lymphocyte counts correlated significantly with an unfavorable immune state. During the chronic phase, the elevated levels of IFN-γ and IL-4 observed in our series correlated with previous findings of endothelial invasion of B. henselae in animal models.

Cytokines and T-Lymphocute count in patients in the acute and chronic phases of Bartonella bacilliformis infection in an endemic area in peru: a pilot study.

Science.gov (United States)

Huarcaya, Erick; Best, Ivan; Rodriguez-Tafur, Juan; Maguiña, Ciro; Solórzano, Nelson; Menacho, Julio; Lopez De Guimaraes, Douglas; Chauca, Jose; Ventosilla, Palmira

2011-01-01

Human Bartonellosis has an acute phase characterized by fever and hemolytic anemia, and a chronic phase with bacillary angiomatosis-like lesions. This cross-sectional pilot study evaluated the immunology patterns using pre- and post-treatment samples in patients with Human Bartonellosis. Patients between five and 60 years of age, from endemic areas in Peru, in the acute or chronic phases were included. In patients in the acute phase of Bartonellosis a state of immune peripheral tolerance should be established for persistence of the infection. Our findings were that elevation of the anti-inflammatory cytokine IL-10 and numeric abnormalities of CD4(+) and CD8(+) T-Lymphocyte counts correlated significantly with an unfavorable immune state. During the chronic phase, the elevated levels of IFN-γ and IL-4 observed in our series correlated with previous findings of endothelial invasion of B. henselae in animal models.

Persistence and extinction for stochastic logistic model with Levy noise and impulsive perturbation

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Chun Lu

2015-09-01

Full Text Available This article investigates a stochastic logistic model with Levy noise and impulsive perturbation. In the model, the impulsive perturbation and Levy noise are taken into account simultaneously. This model is new and more feasible and more accordance with the actual. The definition of solution to a stochastic differential equation with Levy noise and impulsive perturbation is established. Based on this definition, we show that our model has a unique global positive solution and obtains its explicit expression. Sufficient conditions for extinction are established as well as nonpersistence in the mean, weak persistence and stochastic permanence. The threshold between weak persistence and extinction is obtained.

The Enigmatic Persistence of Anorexia Nervosa

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Walsh, B. Timothy

2014-01-01

Objective In this review, based on recent advances in cognitive neuroscience, the author presents a formulation in which the marked persistence of anorexia nervosa can be usefully understood as a well-ingrained maladaptive habit. Method The author reviewed the relevant literature on the development and course of anorexia nervosa and interpreted critical features in light of developments in cognitive neuroscience. Results Anorexia nervosa is a well characterized disorder with remarkable persistence both across history and among affected individuals. Food restriction, the salient behavioral feature of the disorder, often begins innocently but gradually takes on a life of its own. Over time, it becomes highly entrenched and resistant to change through either psychological or pharmacological treatment. Cognitive neuroscience has described two related but distinct processes that underlie the acquisition of new patterns of behavior, namely, action-outcome and stimulus-response learning. It is likely that both processes are engaged in the development of anorexia nervosa and that stimulus-response learning (that is, habit formation) is critical to the persistence of the dieting behavior. Conclusions The formulation of the dieting behavior characteristic of anorexia nervosa as a well-entrenched habit provides a basis for understanding the striking persistence of this disorder. This model helps explain the resistance of anorexia nervosa to interventions that have established efficacy in related disorders and implies that addressing the dieting behavior is critical, especially early in the course of the illness, before it has become ingrained. PMID:23429750

Mycobacterium Lysine ε-aminotransferase is a novel alarmone metabolism related persister gene via dysregulating the intracellular amino acid level.

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Duan, Xiangke; Li, Yunsong; Du, Qinglin; Huang, Qinqin; Guo, Siyao; Xu, Mengmeng; Lin, Yanping; Liu, Zhidong; Xie, Jianping

2016-01-25

Bacterial persisters, usually slow-growing, non-replicating cells highly tolerant to antibiotics, play a crucial role contributing to the recalcitrance of chronic infections and treatment failure. Understanding the molecular mechanism of persister cells formation and maintenance would obviously inspire the discovery of new antibiotics. The significant upregulation of Mycobacterium tuberculosis Rv3290c, a highly conserved mycobacterial lysine ε-aminotransferase (LAT) during hypoxia persistent model, suggested a role of LAT in persistence. To test this, a lat deleted Mycobacterium smegmatis was constructed. The expression of transcriptional regulator leucine-responsive regulatory protein (LrpA) and the amino acids abundance in M. smegmatis lat deletion mutants were lowered. Thus, the persistence capacity of the deletion mutant was impaired upon norfloxacin exposure under nutrient starvation. In summary, our study firstly reported the involvement of mycobacterium LAT in persister formation, and possibly through altering the intracellular amino acid metabolism balance.

A new class of synthetic retinoid antibiotics effective against bacterial persisters

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Kim, Wooseong; Zhu, Wenpeng; Hendricks, Gabriel Lambert; van Tyne, Daria; Steele, Andrew D.; Keohane, Colleen E.; Fricke, Nico; Conery, Annie L.; Shen, Steven; Pan, Wen; Lee, Kiho; Rajamuthiah, Rajmohan; Fuchs, Beth Burgwyn; Vlahovska, Petia M.; Wuest, William M.; Gilmore, Michael S.; Gao, Huajian; Ausubel, Frederick M.; Mylonakis, Eleftherios

2018-04-01

A challenge in the treatment of Staphylococcus aureus infections is the high prevalence of methicillin-resistant S. aureus (MRSA) strains and the formation of non-growing, dormant ‘persister’ subpopulations that exhibit high levels of tolerance to antibiotics and have a role in chronic or recurrent infections. As conventional antibiotics are not effective in the treatment of infections caused by such bacteria, novel antibacterial therapeutics are urgently required. Here we used a Caenorhabditis elegans–MRSA infection screen to identify two synthetic retinoids, CD437 and CD1530, which kill both growing and persister MRSA cells by disrupting lipid bilayers. CD437 and CD1530 exhibit high killing rates, synergism with gentamicin, and a low probability of resistance selection. All-atom molecular dynamics simulations demonstrated that the ability of retinoids to penetrate and embed in lipid bilayers correlates with their bactericidal ability. An analogue of CD437 was found to retain anti-persister activity and show an improved cytotoxicity profile. Both CD437 and this analogue, alone or in combination with gentamicin, exhibit considerable efficacy in a mouse model of chronic MRSA infection. With further development and optimization, synthetic retinoids have the potential to become a new class of antimicrobials for the treatment of Gram-positive bacterial infections that are currently difficult to cure.

Persistent Inflammation Alters the Function of the Endogenous Brain Stem Cell Compartment

OpenAIRE

Pluchino, Stefano; Muzio, Luca; Alfaro-Cervello, Clara; Salani, Giuliana; Porcheri, Cristina; Brambilla, Elena; Cavasinni, Francesca; Bergamaschi, Andrea; Garcia-Verdugo, Jose Manuel; Comi, Giancarlo; Martino, Gianvito; Imitola, Jaime; Deleidi, Michela; Khoury, Samia Joseph

2008-01-01

Endogenous neural stem/precursor cells (NPCs) are considered a functional reservoir for promoting tissue homeostasis and repair after injury, therefore regenerative strategies that mobilize these cells have recently been proposed. Despite evidence of increased neurogenesis upon acute inflammatory insults (e.g. ischaemic stroke), the plasticity of the endogenous brain stem cell compartment in chronic CNS inflammatory disorders remains poorly characterized. Here we show that persistent brain in...

The Capacity of Mycobacterium tuberculosis To Survive Iron Starvation Might Enable It To Persist in Iron-Deprived Microenvironments of Human Granulomas.

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Kurthkoti, Krishna; Amin, Hamel; Marakalala, Mohlopheni J; Ghanny, Saleena; Subbian, Selvakumar; Sakatos, Alexandra; Livny, Jonathan; Fortune, Sarah M; Berney, Michael; Rodriguez, G Marcela

2017-08-15

This study was conducted to investigate the role of iron deprivation in the persistence of Mycobacterium tuberculosis We present evidence of iron restriction in human necrotic granulomas and demonstrate that under iron starvation M. tuberculosis persists, refractive to antibiotics and capable of restarting replication when iron is made available. Transcriptomics and metabolomic analyses indicated that the persistence of M. tuberculosis under iron starvation is dependent on strict control of endogenous Fe utilization and is associated with upregulation of pathogenicity and intrinsic antibiotic resistance determinants. M. tuberculosis mutants compromised in their ability to survive Fe starvation were identified. The findings of this study advance the understanding of the physiological settings that may underpin the chronicity of human tuberculosis (TB) and are relevant to the design of effective antitubercular therapies. IMPORTANCE One-third of the world population may harbor persistent M. tuberculosis , causing an asymptomatic infection that is refractory to treatment and can reactivate to become potentially lethal tuberculosis disease. However, little is known about the factors that trigger and maintain M. tuberculosis persistence in infected individuals. Iron is an essential nutrient for M. tuberculosis growth. In this study, we show, first, that in human granulomas the immune defense creates microenvironments in which M. tuberculosis likely experiences drastic Fe deprivation and, second, that Fe-starved M. tuberculosis is capable of long-term persistence without growth. Together, these observations suggest that Fe deprivation in the lung might trigger a state of persistence in M. tuberculosis and promote chronic TB. We also identified vulnerabilities of iron-restricted persistent M. tuberculosis , which can be exploited for the design of new antitubercular therapies. Copyright © 2017 Kurthkoti et al.

Establishment of a rat model of chronic Prostatitis/Chronic Pelvic Pain Syndrome (CP/CPPS) induced by immunization with a novel peptide T2.

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Ihsan, Awais Ullah; Khan, Farhan Ullah; Nawaz, Waqas; Khan, Muhammad Zahid; Yang, Mengqi; Zhou, Xiaohui

2017-07-01

The exact etiological mechanism of Chronic Prostatitis/chronic pelvic pain syndrome (CP/CPPS) is still unclear however autoimmunity is the most valid theory. We developed a rat model of Chronic Prostatitis/chronic pelvic pain syndrome by using a novel peptide (T2) isolated from TRPM8. This model might be beneficial in elucidating mechanisms involved in the pathogenesis of Chronic Prostatitis/Chronic Pelvic Pain Syndrome (CP/CPPS). 40 male Sprague-Dawley rats with an average weight of 180-220g were equally distributed into five groups. The normal control group was injected with normal saline (.9% NACL), the CFA group with CFA, AL(OH)3 group was given AL(OH)3 injection, T2 group using a novel peptide T2 and T2+AL(OH)3+CFA group was injected with T2+AL(OH)3+CFA. Dosing to all rat groups were injected subcutaneously. Hematoxylin and eosin staining and Immunohistochemistry were used to investigate inflammatory cell infiltration and IL-1β in the prostate tissue respectively. ELISA technique was used to measure the serum level of CRP and TNF-α. T-test was used to analyze the results. Maximum infiltration of inflammatory cells and the highest level of IL-1β in the prostate tissue was observed in T2+AL(OH)3+CFA group as revealed by histopathology and Immunohistochemistry, respectively. Furthermore, T2+AL(OH)3+CFA group attained the peak value of serum TNF-α and CRP as determined by ELISA technique. Our results demonstrated that T2 in combination with AL(OH)3 and CFA induced severe Prostatitis in rats. We believe that our present model will be highly beneficial for investigation of the pathophysiology of Chronic Prostatitis/Chronic Pelvic Pain Syndrome. Copyright © 2017 Elsevier Masson SAS. All rights reserved.

The effect of factors related to prior schooling on student persistence ...

African Journals Online (AJOL)

... of factors related to prior schooling on student persistence in higher education. ... Once reliable profiles of these students have been established and related to ... school counsellors, teachers in both schooling and higher education, and for ...

Minimal cross-intolerance with nilotinib in patients with chronic myeloid leukemia in chronic or accelerated phase who are intolerant to imatinib

Science.gov (United States)

Hochhaus, Andreas; le Coutre, Philipp D.; Rosti, Gianantonio; Pinilla-Ibarz, Javier; Jabbour, Elias; Gillis, Kathryn; Woodman, Richard C.; Blakesley, Rick E.; Giles, Francis J.; Kantarjian, Hagop M.; Baccarani, Michele

2011-01-01

Nilotinib has significant efficacy in patients with newly diagnosed chronic myeloid leukemia in chronic phase (CML-CP) and in patients with CML-CP or CML in accelerated phase (CML-AP) after imatinib failure. We investigated the occurrence of cross-intolerance to nilotinib in imatinib-intolerant patients with CML. Only 1/75 (1%) patients with nonhematologic imatinib intolerance experienced a similar grade 3/4 adverse event (AE), and 3/75 (4%) experienced a similar persistent grade 2 nonhematologic AE on nilotinib. Only 7/40 (18%) patients with hematologic imatinib intolerance discontinued nilotinib, all because of grade 3/4 thrombocytopenia. Ninety percent of imatinib-intolerant patients with CML-CP who did not have complete hematologic response (CHR) at baseline (n = 52) achieved CHR on nilotinib. Nilotinib induced a major cytogenetic response in 66% and 41% of patients with imatinib-intolerant CML-CP and CML-AP (complete cytogenetic response in 51% and 30%), respectively. Minimal cross-intolerance was confirmed in patients with imatinib-intolerant CML. The favorable tolerability of nilotinib in patients with imatinib intolerance leads to alleviation of AE-related symptoms and significant and durable responses. In addition to its established clinical benefit in patients with newly diagnosed CML and those resistant to imatinib, nilotinib is effective and well-tolerated for long-term use in patients with imatinib intolerance. This study is registered at http://www.clinicaltrials.gov as NCT00471497 PMID:21467546

Zika Virus Persistently and Productively Infects Primary Adult Sensory Neurons In Vitro

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Brianna K. Swartwout

2017-10-01

Full Text Available Zika virus (ZIKV has recently surged in human populations, causing an increase in congenital and Guillain-Barré syndromes. While sexual transmission and presence of ZIKV in urine, semen, vaginal secretions, and saliva have been established, the origin of persistent virus shedding into biological secretions is not clear. Using a primary adult murine neuronal culture model, we have determined that ZIKV persistently and productively infects sensory neurons of the trigeminal and dorsal root ganglia, which innervate glands and mucosa of the face and the genitourinary tract, respectively, without apparent injury. Autonomic neurons that innervate these regions are not permissive for infection. However, productive ZIKV infection of satellite glial cells that surround and support sensory and autonomic neurons in peripheral ganglia results in their destruction. Persistent infection of sensory neurons, without affecting their viability, provides a potential reservoir for viral shedding in biological secretions for extended periods of time after infection. Furthermore, viral destruction of satellite glial cells may contribute to the development of Guillain-Barré Syndrome via an alternative mechanism to the established autoimmune response.

Zika Virus Persistently and Productively Infects Primary Adult Sensory Neurons In Vitro.

Science.gov (United States)

Swartwout, Brianna K; Zlotnick, Marta G; Saver, Ashley E; McKenna, Caroline M; Bertke, Andrea S

2017-10-13

Zika virus (ZIKV) has recently surged in human populations, causing an increase in congenital and Guillain-Barré syndromes. While sexual transmission and presence of ZIKV in urine, semen, vaginal secretions, and saliva have been established, the origin of persistent virus shedding into biological secretions is not clear. Using a primary adult murine neuronal culture model, we have determined that ZIKV persistently and productively infects sensory neurons of the trigeminal and dorsal root ganglia, which innervate glands and mucosa of the face and the genitourinary tract, respectively, without apparent injury. Autonomic neurons that innervate these regions are not permissive for infection. However, productive ZIKV infection of satellite glial cells that surround and support sensory and autonomic neurons in peripheral ganglia results in their destruction. Persistent infection of sensory neurons, without affecting their viability, provides a potential reservoir for viral shedding in biological secretions for extended periods of time after infection. Furthermore, viral destruction of satellite glial cells may contribute to the development of Guillain-Barré Syndrome via an alternative mechanism to the established autoimmune response.

Identification and characterization of a spore-like morphotype in chronically starved Mycobacterium avium subsp. paratuberculosis cultures.

Directory of Open Access Journals (Sweden)

Elise A Lamont

Full Text Available Mycobacteria are able to enter into a state of non-replication or dormancy, which may result in their chronic persistence in soil, aquatic environments, and permissive hosts. Stresses such as nutrient deprivation and hypoxia provide environmental cues to enter a persistent state; however, a clear definition of the mechanism that mycobacteria employ to achieve this remains elusive. While the concept of sporulation in mycobacteria is not novel, it continues to spark controversy and challenges our perceptions of a non-replication. We investigated the potential role of sporulation in one-year old broth cultures of Mycobacterium subsp. paratuberculosis (MAP. We show that dormant cultures of MAP contain a mix of vegetative cells and a previously unknown morphotype resembling a spore. These spore-like structures can be enriched for using sporulating media. Furthermore, purified MAP spore forms survive exposure to heat, lysozyme and proteinase K. Heat-treated spores are positive for MAP 16SrRNA and IS900. MAP spores display enhanced infectivity as well as maintain acid-fast characteristics upon germination in a well-established bovine macrophage model. This is the first study to demonstrate a new MAP morphotype possessing spore-like qualities. Data suggest that sporulation may be a viable mechanism by which MAP accomplishes persistence in the host and/or environment. Thus, our current understanding of mycobacterial persistence, pathogenesis, epidemiology and rational drug and vaccine design may need to be reevaluated.

Leptin Is Associated With Persistence of Hyperglycemia in Acute Pancreatitis

Science.gov (United States)

Kennedy, James I.C.; Askelund, Kathryn J.; Premkumar, Rakesh; Phillips, Anthony R.J.; Murphy, Rinki; Windsor, John A.; Petrov, Maxim S.

2016-01-01

Abstract Adipokines have many homeostatic roles, including modulation of glucose metabolism, but their role in the pathophysiology of hyperglycemia associated with acute and critical illnesses in general, and acute pancreatitis (AP) in particular, is largely unknown. This study aimed to investigate the relationship between a panel of adipokines and hyperglycemia in the early course of AP, as well as the role of adipokines as predictors of AP severity. Adiponectin, leptin, omentin, resistin, and visfatin were measured on a daily basis in the first 72 hours after hospital admission. A first set of analyses was undertaken with admission glycemia stratified by severity, and a second set of analyses was undertaken based on persistence of early hyperglycemia. All of the analyses were adjusted for confounders. A total of 32 patients with AP were included in this study. None of the studied adipokines was significantly associated with glucose level on admission. Leptin was significantly (P = 0.003) increased in patients with persistent hyperglycemia. Adiponectin was significantly associated with the Acute Physiology and Chronic Health Evaluation II (APACHE II) score in patients with persistent hyperglycemia (P = 0.015), visfatin with APACHE II score in patients with persistent hyperglycemia (P = 0.014), and omentin with APACHE II score in all of the patients regardless of the presence or absence of hyperglycemia (P = 0.021). Leptin is significantly associated with persistent hyperglycemia in the early course of AP. Omentin has a potential to become an accurate predictor of AP severity. PMID:26871770

Acupuncture Therapy in a Group Setting for Chronic Pain.

Science.gov (United States)

Kligler, Benjamin; Nielsen, Arya; Kohrherr, Corinne; Schmid, Tracy; Waltermaurer, Eve; Perez, Elidania; Merrell, Woodson

2018-02-01

This project was designed to test the feasibility and effectiveness of acupuncture therapy given in a group setting for chronic pain. Nonrandomized, repeated measures quasi-experimental trial. Care was delivered in a primary care clinic waiting area after clinic hours. Included were primary care patients (≥18 years old) with chronic pain of the neck, back, shoulder, or osteoarthritis of any site of at least three months' duration. Subjects received eight weekly acupuncture therapy sessions in a group setting. Acupuncture therapy included a combination of palpation, acupuncture needling, Tui na, Gua sha, and auricular treatment. Baseline pain levels were established in a two- to four-week run-in; assessment of the intervention impact on pain intensity, mood, and functional status were made at the end of the treatment period (eight weeks) and 16 weeks after completion of intervention (24 weeks). Of the total 113 participants recruited for the trial, 96 completed the 24-week protocol. We found a statistically and clinically significant decrease in pain severity, pain interference, and depression in our study population. There were no serious adverse events. Acupuncture therapy offered in the group setting was effective in reducing pain severity, pain interference, and depression in patients with chronic neck, back, or shoulder pain or osteoarthritis. Benefit persisted through the 24-week measure despite no additional treatment. This finding has potentially important implications for improving access to effective acupuncture treatment for patients with limited financial resources. © 2017 American Academy of Pain Medicine. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com

Persistent left superior vena cava with absent right superior vena cava: image findings

International Nuclear Information System (INIS)

Araujo Junior, Cyrillo Rodrigues de; Carvalho, Tarcisio Nunes; Fraguas Filho, Sergio Roberto; Costa, Marlos Augusto Bitencourt; Jacob, Beatriz Mahmud; Machado, Marcio Martins; Teixeira, Kim-Ir-Sen Santos; Ximenes, Carlos Alberto

2003-01-01

Persistent left superior vena cava absent right superior vena cava is a rare anomaly, with less than 150 cases reported in the literature. Congenitally persistent left superior vena cava is the most common variant of systemic venous return to the heart, resulting embryologically from failure of the left anterior cardinal vein to become obliterated. Its incidence varies from 0.3% in patients with otherwise normal heart to 4.3% in patients with congenital heart disease. In the majority of the patients, a right superior vena cava is present as well, but rarely the right anterior cardinal vein degenerates resulting in the absence of the normal right superior vena cava. The blood from the right side is carried by the persistent left superior vena cava to the right atrium through the coronary sinus. We report the case of a patient with a persistent left superior vena cava and absence of right superior vena cava identified by chance during a chest radiograph and computed tomography examination for investigation of chronic pulmonary obstructive disease. The patient had no congenital heart disease and the blood from the right side was drained by the persistent left superior vena cava into the right atrium through the coronary sinus. (author)

Effect of pain chronification and chronic pain on an endogenous pain modulation circuit in rats.

Science.gov (United States)

Miranda, J; Lamana, S M S; Dias, E V; Athie, M; Parada, C A; Tambeli, C H

2015-02-12

We tested the hypothesis that chronic pain development (pain chronification) and ongoing chronic pain (chronic pain) reduce the activity and induce plastic changes in an endogenous analgesia circuit, the ascending nociceptive control. An important mechanism mediating this form of endogenous analgesia, referred to as capsaicin-induced analgesia, is its dependence on nucleus accumbens μ-opioid receptor mechanisms. Therefore, we also investigated whether pain chronification and chronic pain alter the requirement for nucleus accumbens μ-opioid receptor mechanisms in capsaicin-induced analgesia. We used an animal model of pain chronification in which daily subcutaneous prostaglandin E2 (PGE2) injections into the rat's hind paw for 14 days, referred to as the induction period of persistent hyperalgesia, induce a long-lasting state of nociceptor sensitization referred to as the maintenance period of persistent hyperalgesia, that lasts for at least 30 days following the cessation of the PGE2 treatment. The nociceptor hypersensitivity was measured by the shortening of the time interval for the animal to respond to a mechanical stimulation of the hind paw. We found a significant reduction in the duration of capsaicin-induced analgesia during the induction and maintenance period of persistent mechanical hyperalgesia. Intra-accumbens injection of the μ-opioid receptor selective antagonist Cys(2),Tyr(3),Orn(5),Pen(7)amide (CTOP) 10 min before the subcutaneous injection of capsaicin into the rat's fore paw blocked capsaicin-induced analgesia. Taken together, these findings indicate that pain chronification and chronic pain reduce the duration of capsaicin-induced analgesia, without affecting its dependence on nucleus accumbens μ-opioid receptor mechanisms. The attenuation of endogenous analgesia during pain chronification and chronic pain suggests that endogenous pain circuits play an important role in the development and maintenance of chronic pain. Copyright © 2014 IBRO

A etiological factors of chronic liver disease in children

International Nuclear Information System (INIS)

Tahir, A.; Malik, F.R.; Akhtar, P.

2011-01-01

Background: Chronicity of liver disease is determined either by duration of liver disease or by evidence of either severe liver disease or physical stigmata of chronic liver disease. Chronic liver disease may be caused commonly by persistent viral infections, metabolic diseases, drugs, autoimmune hepatitis, or unknown factors. The objective of this study was to find out the aetiology of chronic liver disease (CLD) in children. Methodology: It was a descriptive, prospective study which used a structured proforma designed to collect data of cases of CLD from both indoor and outdoor Paediatrics units of Fauji Foundation Hospital, Rawalpindi, and Children Hospital, Pakistan Institute of Medical Sciences, Islamabad. All children under 12 years having either clinical or biochemical evidence of liver disease and/or elevated liver enzymes for more than 3 months were included in this study. Results: Sixty cases of CLD were enrolled from indoor and outdoor units from January 2010 to July 201. Thirty nine (65%) cases were male and 21 (35%) were female. Eleven children were less than 1 year, 18 were 1-5 years old and 31 were 5-12 years of age. Viral hepatitis was the most common cause found in 22 (36.7%) cases. Out of these 22 patients with viral aetiology 19 (31.66%) patients had Hepatitis C and 3 (5%) had Hepatitis B. Glycogen storage disease was seen in 8.3% cases, and biliary atresia and Wilson disease in 6.7% each. Other less commonly found cases were autoimmune hepatitis, TORCH infections, hepatoma and drug induced hepatitis (1.7% each). Cause couldn't be established in 35% cases which remained idiopathic. Conclusion: Viral hepatitis is the leading cause of chronic liver disease in children, with the highest incidence of chronic Hepatitis C followed by metabolic disorders (glycogen storage disease and Wilson disease) and biliary atresia. Chronic viral hepatitis was most prevalent between 11 months to 12 years of age. Wilson disease was common in 3-7 years age group, and

aerobic bacteria in safe type chronic suppurative otitis media

African Journals Online (AJOL)

PUBLICATIONS1

Ciprofloxacin and gentamicin appear to be the best choices for empiric therapy in patients with CSOM. In contrast, the use of amoxyclav, cotrimoxazole, cefuroxime, cefaclor and ceftriaxone should be discour- aged. INTRODUCTION. Chronic suppurative otitis media (CSOM) is a persistent inflammatory disorder of the middle.

Salt stress-induced transcription of σB- and CtsR-regulated genes in persistent and non-persistent Listeria monocytogenes strains from food processing plants.

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Ringus, Daina L; Ivy, Reid A; Wiedmann, Martin; Boor, Kathryn J

2012-03-01

Listeria monocytogenes is a foodborne pathogen that can persist in food processing environments. Six persistent and six non-persistent strains from fish processing plants and one persistent strain from a meat plant were selected to determine if expression of genes in the regulons of two stress response regulators, σ(B) and CtsR, under salt stress conditions is associated with the ability of L. monocytogenes to persist in food processing environments. Subtype data were also used to categorize the strains into genetic lineages I or II. Quantitative reverse transcriptase-polymerase chain reaction (qRT-PCR) was used to measure transcript levels for two σ(B)-regulated genes, inlA and gadD3, and two CtsR-regulated genes, lmo1138 and clpB, before and after (t=10 min) salt shock (i.e., exposure of exponential phase cells to BHI+6% NaCl for 10 min at 37°C). Exposure to salt stress induced higher transcript levels relative to levels under non-stress conditions for all four stress and virulence genes across all wildtype strains tested. Analysis of variance (ANOVA) of induction data revealed that transcript levels for one gene (clpB) were induced at significantly higher levels in non-persistent strains compared to persistent strains (p=0.020; two-way ANOVA). Significantly higher transcript levels of gadD3 (p=0.024; two-way ANOVA) and clpB (p=0.053; two-way ANOVA) were observed after salt shock in lineage I strains compared to lineage II strains. No clear association between stress gene transcript levels and persistence was detected. Our data are consistent with an emerging model that proposes that establishment of L. monocytogenes persistence in a specific environment occurs as a random, stochastic event, rather than as a consequence of specific bacterial strain characteristics.

Altered gut microbiota in female mice with persistent low body weights following removal of post-weaning chronic dietary restriction.

Science.gov (United States)

Chen, Jun; Toyomasu, Yoshitaka; Hayashi, Yujiro; Linden, David R; Szurszewski, Joseph H; Nelson, Heidi; Farrugia, Gianrico; Kashyap, Purna C; Chia, Nicholas; Ordog, Tamas

2016-10-03

Nutritional interventions often fail to prevent growth failure in childhood and adolescent malnutrition and the mechanisms remain unclear. Recent studies revealed altered microbiota in malnourished children and anorexia nervosa. To facilitate mechanistic studies under physiologically relevant conditions, we established a mouse model of growth failure following chronic dietary restriction and examined microbiota in relation to age, diet, body weight, and anabolic treatment. Four-week-old female BALB/c mice (n = 12/group) were fed ad libitum (AL) or offered limited food to abolish weight gain (LF). A subset of restricted mice was treated with an insulin-like growth factor 1 (IGF1) analog. Food access was restored in a subset of untreated LF (LF-RF) and IGF1-treated LF mice (TLF-RF) on day 97. Gut microbiota were determined on days 69, 96-99 and 120 by next generation sequencing of the V3-5 region of the 16S rRNA gene. Microbiota-host factor associations were analyzed by distance-based PERMANOVA and quantified by the coefficient of determination R 2 for age, diet, and normalized body weight change (Δbwt). Microbial taxa on day 120 were compared following fitting with an overdispersed Poisson regression model. The machine learning algorithm Random Forests was used to predict age based on the microbiota. On day 120, Δbwt in AL, LF, LF-RF, and TLF-RF mice was 52 ± 3, -6 ± 1*, 40 ± 3*, and 46 ± 2 % (*, P < 0.05 versus AL). Age and diet, but not Δbwt, were associated with gut microbiota composition. Age explained a larger proportion of the microbiota variability than diet or Δbwt. Random Forests predicted chronological age based on the microbiota and indicated microbiota immaturity in the LF mice before, but not after, refeeding. However, on day 120, the microbiota community structure of LF-RF mice was significantly different from that of both AL and LF mice. IGF1 mitigated the difference from the AL group. Refed groups had a higher

Chronic post-inflammatory fatigue in sarcoidosis : from cytokines to behavior

NARCIS (Netherlands)

Korenromp, I.H.E.

2011-01-01

Sarcoidosis is a systemic inflammatory disorder that is characterized by granuloma formation in different organs. Sarcoidosis patients frequently report fatigue. Even when the clinical symptoms of the inflammatory disease sarcoidosis have resolved, chronic fatigue may persist. In this study 75

Mixed infections with Chlamydia and porcine epidemic diarrhea virus - a new in vitro model of chlamydial persistence

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Kaiser Carmen

2010-07-01

Full Text Available Abstract Background Chlamydiae induce persistent infections, which have been associated with a wide range of chronic diseases in humans and animals. Mixed infections with Chlamydia and porcine epidemic diarrhea virus (PEDV may result in generation of persistent chlamydial infections. To test this hypothesis, an in vitro model of dual infection with cell culture-adapted PEDV and Chlamydia abortus or Chlamydia pecorum in Vero cells was established. Results Infected cultures were investigated by immunofluorescence (IF, transmission electron microscopy (TEM and re-infection experiments. By IF, Chlamydia-infected cells showed normal inclusions after 39 hpi. Dual infections with Chlamydia abortus revealed a heterogenous mix of inclusion types including small inclusions consisting of aberrant bodies (ABs, medium-sized inclusions consisting of ABs and reticulate bodies and normal inclusions. Only aberrant inclusions were observable in dual infection experiments with Chlamydia pecorum and PEDV. TEM examinations of mixed infections with Chlamydia abortus and Chlamydia pecorum revealed aberrant chlamydial inclusions containing reticulate-like, pleomorphic ABs, which were up to 2 μm in diameter. No re-differentiation into elementary bodies (EBs was detected. In re-infection experiments, co-infected cells produced fewer EBs than monoinfected cells. Conclusions In the present study we confirm that PEDV co-infection alters the developmental cycle of member species of the family Chlamydiaceae, in a similar manner to other well-described persistence induction methods. Interestingly, this effect appears to be partially species-specific as Chlamydia pecorum appears more sensitive to PEDV co-infection than Chlamydia abortus, as evidenced by TEM and IF observations of a homogenous population of aberrant inclusions in PEDV - Chlamydia pecorum co-infections.

Parathyroidectomy in chronic kidney disease patients in Argentina: pre surgical studies, types of surgery, recurrence and persistence

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Adriana Peñalba

2014-01-01

Full Text Available Introduction: Parathyroidectomy (PTx is the selecte treatment for patients with severe secondary hyperparathyroidism, refractory to medical treatment. There is not enough information about this procedure in Argentina, that is the reason why we performed this study. Methods: 255 patients with PTx were included from the year 2003 to 2007 on a voluntary register. Studies of pre-surgical localization, phosphocalcic metabolism laboratories before and after surgery were evaluated, and the type of surgical technique used. The persistence and recurrence of post-surgical hyperparathyroidism was analyzed. Results: The PTx rate was 2,7/1000 patients year. 83% of the patients had neck echography and 59% Sestamibi scans with Tc 99. There was a positive correlation (p<0,001 between the number of detected glands by echography and Sestamibi. The parathyroidectomy performed was: subtotal in 77%, total with self-implant in 14% and total without self-implant in 9%. There were significant falls of Ca and P, Alkaline Phosphatase and PTH (1744±788 pg/ml to 247±450 pg/ml; p<0.0001 post-surgical. 2.4 ±2,5 months after the PTx, 72% of patients had PTH <2 50 pg/ml, 19,8% had persistence and 8,3% had recurrence. According to the type of surgery, the persistence and recurrence were for subtotal PTx 22% and 8,3%, total PTx with implant 11% and 11%, and total PTx without selfimplant 13% and 4% respectively. The performance of the Sestamibi scan did not affect the PTx results. No noticeable differences were observed among the centers for persistence and recurrence. Conclusions: The PTx rate was very low, echography was the preferred method of pre-surgical localization, and subtotal PTx was the most used surgical technique. PTx was successful in most of the patients, and persistence and recurrence were not related to the technique.

Rate and Predictors of Persistent Major Depressive Disorder in a Nationally Representative Sample.

Science.gov (United States)

Walker, Elizabeth Reisinger; Druss, Benjamin G

2015-08-01

This study examined predictors of persistent major depressive disorder over 10 years, focusing on the effects of clinical variables, physical health, and social support. Data from the National Survey of Midlife Development in the United States in 1995-1996 and 2004-2006 were analyzed. Logistic regression was used to predict non-recovery from major depression among individuals who met clinical-based criteria for major depressive disorder at baseline. Fifteen percent of the total sample was classified as having major depression in 1995-1996; of these individuals, 37 % had major depression in 2004-2006. Baseline variables that were significantly associated with persistent major depression at follow-up were being female, having never married, having two or more chronic medical conditions, experiencing activity limitation, and less contact with family. Therefore, treatment strategies focused on physical health, social support, and mental health needs are necessary to comprehensively address the factors that contribute to persistent major depressive disorder.

Impact of innate and environmental factors on wheezing persistence during childhood.

Science.gov (United States)

Just, Jocelyne; Belfar, Samira; Wanin, Stéphanie; Pribil, Céline; Grimfeld, Alain; Duru, Gérard

2010-05-01

Persistent asthma in adults starts often early in childhood and is associated with alterations in respiratory function that occur early in life. The aim of this study was to evaluate the importance of innate and environmental factors associated with occurrence of asthma during childhood in a population of recurrent wheezing infants followed prospectively. A cohort of infants less than 30 months old with recurrent wheezing was established in order to assess severity of respiratory symptoms and to look for the presence of atopy and environmental risk factors. At the age of 6 years, they were reevaluated with respect to remission or persistence of wheezing over the previous 12-month period. Data were available for 219 subjects aged 15 +/- 5 months. In 27% of the infants with recurrent wheeze, wheezing persisted until the age of 6 years. In multivariate analysis, stepwise logit analysis showed that the risk factors for persistent wheezing are eosinophilia >or=470/mm(3), allergenic sensitization, and a father with asthma. Environmental factors present during the first year of life that protect from persistence of wheezing are ( 1 ) breastfeeding for longer than 3 months, ( 2 ) pets at home, and ( 3 ) >or=3 siblings. The detection rate for persistent wheezing in this model is 72%. The persistence score showed good specificity 91% but low sensitivity 35%. This study confirms the role of atopic host factors on wheezing persistence during childhood and detected protective environmental factors.

An Italian multicentre study on adult atopic dermatitis: persistent versus adult-onset disease.

Science.gov (United States)

Megna, Matteo; Patruno, Cataldo; Balato, Anna; Rongioletti, Franco; Stingeni, Luca; Balato, Nicola

2017-08-01

Atopic dermatitis (AD) is a chronic, recurrent, inflammatory skin disease which predominantly affects children. However, AD may persist until adulthood (persistent AD), or directly start in adults (adult-onset AD). AD often shows a non-flexural rash distribution, and atypical morphologic variants in adults and specific diagnostic criteria are lacking. Moreover, adult AD prevalence as well as detailed data which can characterize persistent vs adult-onset subtype are scant. The aim of this study was to investigate on the main features of adult AD particularly highlighting differences between persistent vs adult-onset form. An Italian multicentre observational study was conducted between April 2015-July 2016 through a study-specific digital database. 253 adult AD patients were enrolled. Familiar history of AD was negative in 81.0%. Erythemato-desquamative pattern was the most frequent clinical presentation (74.3%). Flexural surface of upper limbs was most commonly involved (47.8%), followed by eyelid/periocular area (37.9%), hands (37.2%), and neck (32%). Hypertension (7.1%) and thyroiditis (4.3%) were the most frequent comorbidities. A subgroup analysis between persistent (59.7%) vs adult-onset AD patients (40.3%) showed significant results only regarding AD severity (severe disease was more common in persistent group, p adult-onset disease), and comorbidities (hypertension was more frequent in adult-onset group, p Adult AD showed uncommon features such as significant association with negative AD family history and lacking of association with systemic comorbidities respect to general population. No significant differences among persistent vs adult-onset subgroup were registered except for hypertension, itch intensity, and disease severity.

Bronchodilator responsiveness as a phenotypic characteristic of established chronic obstructive pulmonary disease

DEFF Research Database (Denmark)

Albert, Paul; Agusti, Alvar; Edwards, Lisa

2012-01-01

Bronchodilator responsiveness is a potential phenotypic characteristic of chronic obstructive pulmonary disease (COPD). We studied whether change in lung function after a bronchodilator is abnormal in COPD, whether stable responder subgroups can be identified, and whether these subgroups experience...

Attitudes to Chronic Poverty in the "Global Village"

Science.gov (United States)

Barrientos, Armando; Neff, Daniel

2011-01-01

The paper explores attitudes to chronic poverty in a cross-section of developed and developing countries contributing data to the World Values Survey Wave Three (1994-1998). The analysis finds a consistent belief among a majority of respondents that poverty is persistent. The paper also explores the factors influencing public attitudes to chronic…

surgical treatment for chronic pancreatitis: report of three cases

Directory of Open Access Journals (Sweden)

Abdollahi A

2009-01-01

Full Text Available "nBackground: Chronic pancreatitis is a progressive fibrosis of the pancreas that leads to loss of endocrine and exocrine function of pancreas. The most common symptom is intractable pain. Which adversely effects quality of life, remains the most common indication for surgery in patients with chronic pancreatitis. Case report: Three patients underwent operations for chronic pancreatitis at the Ghaem hospital, Mashhad University of Medical Sciences Mashhad, Iran. Indication for operation in all cases were intractable abdominal pain. In all of the three patients complete relief of symptoms was obtained. There was no morbidity and mortality. In one patient exocrine function of pancreas and malabsorpation resolved after surgery. Conclusions: Although chronic pancreatitis is uncommon, but in persistent abdominal pain surgery should be considered. Surgery for patients with chronic pancreatitis can be performed safely with minimal morbidity and effective in control of pain and malabsorption.  

[Chronic urticaria in childhood : Rational diagnostics and treatment].

Science.gov (United States)

Ott, H

2017-07-01

Chronic urticaria (CU) is defined by episodes of urticaria with or without angioedema, which recur daily or nearly daily over more than 6 weeks. Sudden manifestations of CU with or without known causes are termed chronic spontaneous urticaria, which is differentiated from chronic inducible urticaria. The differential diagnoses of CU in childhood range from self-limiting dermatoses to severe systemic diseases. Further targeted steps are taken to detect potential trigger factors or underlying illnesses only if suspicion arises on anamnestic grounds and CU is best treated in accordance with international guidelines. First-line therapy consists of non-sedating H 1 -antihistamines at approved or even higher doses. If symptoms persist, additional treatment with omalizumab, cyclosporine or montelukast can be initiated after careful individual consideration.

Hippocampal activation of microglia may underlie the shared neurobiology of comorbid posttraumatic stress disorder and chronic pain.

Science.gov (United States)

Sun, Rao; Zhang, Zuoxia; Lei, Yishan; Liu, Yue; Lu, Cui'e; Rong, Hui; Sun, Yu'e; Zhang, Wei; Ma, Zhengliang; Gu, Xiaoping

2016-01-01

The high comorbidity rates of posttraumatic stress disorder and chronic pain have been widely reported, but the underlying mechanisms remain unclear. Emerging evidence suggested that an excess of inflammatory immune activities in the hippocampus involved in the progression of both posttraumatic stress disorder and chronic pain. Considering that microglia are substrates underlying the initiation and propagation of the neuroimmune response, we hypothesized that stress-induced activation of hippocampal microglia may contribute to the pathogenesis of posttraumatic stress disorder-pain comorbidity. We showed that rats exposed to single prolonged stress, an established posttraumatic stress disorder model, exhibited persistent mechanical allodynia and anxiety-like behavior, which were accompanied by increased activation of microglia and secretion of pro-inflammatory cytokines in the hippocampus. Correlation analyses showed that hippocampal activation of microglia was significantly correlated with mechanical allodynia and anxiety-like behavior. Our data also showed that both intraperitoneal and intra-hippocampal injection of minocycline suppressed single prolonged stress-induced microglia activation and inflammatory cytokines accumulation in the hippocampus, and attenuated both single prolonged stress-induced mechanical allodynia and anxiety-like behavior. Taken together, the present study suggests that stress-induced microglia activation in the hippocampus may serve as a critical mechanistic link in the comorbid relationship between posttraumatic stress disorder and chronic pain. The novel concept introduces the possibility of cotreating chronic pain and posttraumatic stress disorder. © The Author(s) 2016.

[Persistent diarrhea

Science.gov (United States)

Andrade, J A; Moreira, C; Fagundes Neto, U

2000-07-01

INTRODUCTION: Persistent diarrhea has high impact on infantile morbidity and mortality rates in developing countries. Several studies have shown that 3 to 20% of acute diarrheal episodes in children under 5 years of age become persistent. DEFINITION: Persistent diarrhea is defined as an episode that lasts more than 14 days. ETIOLOGY: The most important agents isolated in persistent diarrhea are: Enteropathogenic E. coli (EPEC), Salmonella, Enteroaggregative E. coli (EAEC), Klebisiella and Cryptosporidium. CLINICAL ASPECTS: In general, the clinical characteristics of patients with persistent diarrhea do not change with the pathogenic agent. Persistent diarrhea seems to represent the final result of a several insults a infant suffers that predisposes to a more severe episode of diarrhea due to a combination of host factors and high rates of enviromental contamination. Therefore, efforts should be made to promptly treat all episodes of diarrhea with apropriate follow-up. THERAPY: The aim of the treatment is to restore hydroelectrolytic deficits and to replace losses until the diarrheal ceases. It is possible in the majority of the cases, using oral rehydration therapy and erly an appropriate type of diet. PREVENTION: It is imperative that management strategies also focus on preventive aspects. The most effective diarrheal prevention strategy in young infants worldwide is promotion of exclusive breast feeding.

Astrogliosis During Acute and Chronic Cuprizone Demyelination and Implications for Remyelination

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Norah Hibbits

2012-10-01

Full Text Available In multiple sclerosis, microglia/macrophage activation and astrocyte reactivity are important components of the lesion environment that can impact remyelination. The current study characterizes these glial populations relative to expression of candidate regulatory molecules in cuprizone demyelinated corpus callosum. Importantly, periods of recovery after acute or chronic cuprizone demyelination are examined to compare conditions of efficient versus limited remyelination, respectively. Microglial activation attenuates after early demyelination. In contrast, astrocyte reactivity persists throughout demyelination and a 6-week recovery period following either acute or chronic demyelination. This astrocyte reaction is characterized by (a early proliferation, (b increased expression of GFAP (glial fibrillary acidic protein, Vim (vimentin, Fn1 (fibronectin and CSPGs (chondroitin sulphate proteoglycans and (c elaboration of a dense network of processes. Glial processes elongated in the axonal plane persist throughout lesion areas during both the robust remyelination that follows acute demyelination and the partial remyelination that follows chronic demyelination. However, prolonged astrocyte reactivity with chronic cuprizone treatment does not progress to barrier formation, i.e. dense compaction of astrocyte processes to wall off the lesion area. Multiple candidate growth factors and inflammatory signals in the lesion environment show strong correlations with GFAP across the acute cuprizone demyelination and recovery time course, yet there is more divergence across the progression of chronic cuprizone demyelination and recovery. However, differential glial scar formation does not appear to be responsible for differential remyelination during recovery in the cuprizone model. The astrocyte phenotype and lesion characteristics in this demyelination model inform studies to identify triggers of non-remyelinating sclerosis in chronic multiple sclerosis

Chronic lymphadenopathy caused by a Brazilian strain of Bartonella henselae.

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Velho, Paulo Eduardo Neves Ferreira; Drummond, Marina Rovani; Adad, Marcio Antonio Haro; Cintra, Maria Letícia; Sowy, Stanley; Diniz, Pedro Paulo Vissotto de Paiva

2017-09-04

Bartonella henselae is a relevant causative agent of bartonelloses in humans. We described an immunocompetent patient with clinical manifestation of chronic cervical lymphadenopathy after a cat-scratch in her forearm. This case shows B. henselae infection persistence even after prolonged antibiotic treatment.

Persistent Hypotony Associated with Immunosuppressive Therapy in Glaucoma Drainage Implant Surgery

Directory of Open Access Journals (Sweden)

Susana Duch

2016-09-01

Full Text Available Purpose: To describe the histopathology of non-valved implant capsules in three cases of persistent postoperative hypotony after the restrictive tube ligature was released in patients receiving immunosuppressive therapy. Observations: The macroscopic appearance of the capsules 3 and 4 months postoperatively was immature and loose. Microscopic examination disclosed extremely irregular thin tissue, with thicknesses ranging from 0.02 to 0.6 mm, depending on the capsular location studied. Withdrawal of immunosuppressive therapy did not facilitate rebuilding of new capsules. Replacement with a valved implant device was necessary in two cases; the third case recovered with tapering of prednisone. Conclusions and Importance: The use of chronic systemic immunosuppressive therapy might interfere with capsular formation around the plates of drainage devices inducing persistent hypotony. In these cases, the use of valved implants might be safer.

Persistence and extinction of a stochastic single-species population model in a polluted environment with impulsive toxicant input

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Meng Liu

2013-10-01

Full Text Available A stochastic single-species population system in a polluted environment with impulsive toxicant input is proposed and studied. Sufficient conditions for extinction, non-persistence in the mean, strong persistence in the mean and stochastic permanence of the population are established. The threshold between strong persistence in the mean and extinction is obtained. Some simulation figures are introduced to illustrate the main results.

The number of granule cells in rat hippocampus is reduced after chronic mild stress and re-established after chronic escitalopram treatment

DEFF Research Database (Denmark)

Jayatissa, Magdalena N; Bisgaard, Christina; West, Mark J

2008-01-01

mild stress and chronic escitalopram treatment. Furthermore, we investigated which classes of immature granule cells are affected by stress and targeted by escitalopram. Rats were initially exposed to 2weeks of CMS and 4weeks of escitalopram treatment with concurrent exposure to stress. The behavioral...... changes, indicating a decrease in sensitivity to a reward, were assessed in terms of sucrose consumption. We found a significant 22.4% decrease in the total number of granule cells in the stressed rats. This decrease was reversed in the stressed escitalopram treated rats that responded to the treatment......, but not in the rats that did not respond to escitalopram treatment. These changes were not followed by alterations in the volume of the granule cell layer. We also showed a differential regulation of dentate neurons, in different stages of development, by chronic stress and chronic escitalopram treatment. Our study...

Persistent pain after breast cancer treatment: a critical review of risk factors and strategies for prevention

DEFF Research Database (Denmark)

Andersen, Kenneth Geving; Kehlet, Henrik

2011-01-01

for prevention and treatment. However, nerve damage and radiotherapy appear to be significant risk factors for chronic pain. A proposal for the design of future prospective studies is presented. PERSPECTIVE: A comprehensive and systematic approach to research in chronic pain after breast cancer treatment......Chronic pain after breast cancer treatment is a major clinical problem, affecting 25 to 60% of patients. Development of chronic pain after breast cancer treatment, as well as other surgical procedures, involves a complex pathophysiology that involves pre-, intra- and post-operative factors....... This review is a systematic analysis on methodology and evidence in research into persistent pain after breast cancer treatment during the period 1995 to 2010, in order to clarify the significance and relative role of potential risk factors. Literature was identified by a search in PubMed and OVID, as well...

Myalgic encephalomyelitis, chronic fatigue syndrome: An infectious disease.

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Underhill, R A

2015-12-01

The etiology of myalgic encephalomyelitis also known as chronic fatigue syndrome or ME/CFS has not been established. Controversies exist over whether it is an organic disease or a psychological disorder and even the existence of ME/CFS as a disease entity is sometimes denied. Suggested causal hypotheses have included psychosomatic disorders, infectious agents, immune dysfunctions, autoimmunity, metabolic disturbances, toxins and inherited genetic factors. Clinical, immunological and epidemiological evidence supports the hypothesis that: ME/CFS is an infectious disease; the causal pathogen persists in patients; the pathogen can be transmitted by casual contact; host factors determine susceptibility to the illness; and there is a population of healthy carriers, who may be able to shed the pathogen. ME/CFS is endemic globally as sporadic cases and occasional cluster outbreaks (epidemics). Cluster outbreaks imply an infectious agent. An abrupt flu-like onset resembling an infectious illness occurs in outbreak patients and many sporadic patients. Immune responses in sporadic patients resemble immune responses in other infectious diseases. Contagion is shown by finding secondary cases in outbreaks, and suggested by a higher prevalence of ME/CFS in sporadic patients' genetically unrelated close contacts (spouses/partners) than the community. Abortive cases, sub-clinical cases, and carrier state individuals were found in outbreaks. The chronic phase of ME/CFS does not appear to be particularly infective. Some healthy patient-contacts show immune responses similar to patients' immune responses, suggesting exposure to the same antigen (a pathogen). The chronicity of symptoms and of immune system changes and the occurrence of secondary cases suggest persistence of a causal pathogen. Risk factors which predispose to developing ME/CFS are: a close family member with ME/CFS; inherited genetic factors; female gender; age; rest/activity; previous exposure to stress or toxins

Elevations in vascular markers and eosinophils in chronic spontaneous urticarial weals with low-level persistence in uninvolved skin

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Kay, AB; Ying, S; Ardelean, E; Mlynek, A; Kita, H; Clark, P; Maurer, M

2014-01-01

Background In chronic spontaneous urticaria (CSU) mast cell activation together with inflammatory changes in the skin are well documented and may play an important role in mechanisms of tissue oedema. Objectives To confirm and extend these observations by measuring microvascular markers, leucocytes and mast cell numbers in lesional and uninvolved skin and to compare findings with a control group. Methods Paired biopsies (one from 4–8-h spontaneous weals and one from uninvolved skin) were taken from eight patients with CSU and nine control subjects and studied using immunohistochemistry and confocal microscopy using the lectin Ulex europaeus agglutinin 1 (UEA-1). Results Lesional skin in CSU contained significantly more CD31+ endothelial cells; CD31+ blood vessels, neutrophils, eosinophils, basophils and macrophages; and CD3+ T cells than nonlesional skin. Increased vascularity was confirmed by confocal imaging using the lectin UEA-1. Uninvolved skin from CSU contained significantly more CD31+ endothelial cells, CD31+ blood vessels and eosinophils compared with the control subjects. There was a threefold increase in mast cell numbers when CSU was compared with controls but no difference was observed between lesional and uninvolved skin. Conclusions Increased vascular markers together with eosinophil and neutrophil infiltration are features of lesional skin in CSU and might contribute to tissue oedema. Eosinophils and microvascular changes persist in uninvolved skin, which, together with increased mast cells, suggests that nonlesional skin is primed for further wealing. PMID:24665899

Persistence of canine distemper virus in the Greater Yellowstone Ecosystem's carnivore community

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Almberg, E.S.; Cross, P.C.; Smith, D.W.

2010-01-01

Canine distemper virus (CDV) is an acute, highly immunizing pathogen that should require high densities and large populations of hosts for long-term persistence, yet CDV persists among terrestrial carnivores with small, patchily distributed groups. We used CDV in the Greater Yellowstone ecosystem's (GYE) wolves (Canis lupus) and coyotes (Canis latrans) as a case study for exploring how metapopulation structure, host demographics, and multi-host transmission affect the critical community size and spatial scale required for CDV persistence. We illustrate how host spatial connectivity and demographic turnover interact to affect both local epidemic dynamics, such as the length and variation in inter-epidemic periods, and pathogen persistence using stochastic, spatially explicit susceptible-exposed-infectious-recovered simulation models. Given the apparent absence of other known persistence mechanisms (e.g., a carrier or environmental state, densely populated host, chronic infection, or a vector), we suggest that CDV requires either large spatial scales or multi-host transmission for persistence. Current GYE wolf populations are probably too small to support endemic CDV. Coyotes are a plausible reservoir host, but CDV would still require 50 000-100 000 individuals for moderate persistence (>50% over 10 years), which would equate to an area of 1-3 times the size of the GYE (60000-200000 km2). Coyotes, and carnivores in general, are not uniformly distributed; therefore, this is probably a gross underestimate of the spatial scale of CDV persistence. However, the presence of a second competent host species can greatly increase the probability of long-term CDV persistence at much smaller spatial scales. Although no management of CDV is currently recommended for the GYE, wolf managers in the region should expect periodic but unpredictable CDV-related population declines as often as every 2-5 years. Awareness and monitoring of such outbreaks will allow corresponding

Persistence of canine distemper virus in the Greater Yellowstone ecosystem's carnivore community.

Science.gov (United States)

Almberg, Emily S; Cross, Paul C; Smith, Douglas W

2010-10-01

Canine distemper virus (CDV) is an acute, highly immunizing pathogen that should require high densities and large populations of hosts for long-term persistence, yet CDV persists among terrestrial carnivores with small, patchily distributed groups. We used CDV in the Greater Yellowstone ecosystem's (GYE) wolves (Canis lupus) and coyotes (Canis latrans) as a case study for exploring how metapopulation structure, host demographics, and multi-host transmission affect the critical community size and spatial scale required for CDV persistence. We illustrate how host spatial connectivity and demographic turnover interact to affect both local epidemic dynamics, such as the length and variation in inter-epidemic periods, and pathogen persistence using stochastic, spatially explicit susceptible-exposed-infectious-recovered simulation models. Given the apparent absence of other known persistence mechanisms (e.g., a carrier or environmental state, densely populated host, chronic infection, or a vector), we suggest that CDV requires either large spatial scales or multi-host transmission for persistence. Current GYE wolf populations are probably too small to support endemic CDV. Coyotes are a plausible reservoir host, but CDV would still require 50000-100000 individuals for moderate persistence (> 50% over 10 years), which would equate to an area of 1-3 times the size of the GYE (60000-200000 km2). Coyotes, and carnivores in general, are not uniformly distributed; therefore, this is probably a gross underestimate of the spatial scale of CDV persistence. However, the presence of a second competent host species can greatly increase the probability of long-term CDV persistence at much smaller spatial scales. Although no management of CDV is currently recommended for the GYE, wolf managers in the region should expect periodic but unpredictable CDV-related population declines as often as every 2-5 years. Awareness and monitoring of such outbreaks will allow corresponding adjustments

Imaging studies in chronic low back pain

International Nuclear Information System (INIS)

Alcalay, M.; Bourgeois, P.; Lazennec, J.Y.; Roger, B.; Dehais, J.; Dousse, V.; Laredo, J.D.; Morvan, G.; Ristori, J.M.

1994-01-01

Imaging brings to difficult problems in chronic low back pain incomplete data showing that it will need a lot of time to find therapeutic solutions. Some comparisons are made between tomodensitometry, nuclear magnetic imaging, the disco-scanner, these technologies allow to find small lesions but the problem is complete when it is not possible to find anything with persistent pains. 125 refs

IQ Score of Children with Persistent or Perennial Allergic Rhinitis: A Comparison with Healthy Children.

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Ghaffari, Javad; Abbaskhanian, Ali; Jalili, Masumeh; Yazdani Charati, Jamshid

2014-01-01

Prevalence of allergies is different around the world. Allergic rhinitis is a common chronic disease in children. Intelligence quotient (IQ) is an indicator of efficacy and many factors including chronic diseases may affect it. This study compares the IQs of children diagnosed with persistent or perennial allergic rhinitis with healthy children. This was a comparative study that was conducted from June 2011-May 2013 in an academic referral clinic. In this study, 90 patients aged 6- to 14-yearsold who were diagnosed with persistent or perennial allergic rhinitis and were compared to 90 age and gender match healthy patients from their respective families. The Wechsler Intelligence Scale for Children was used to divide and calculate overall IQ, verbal IQ, and practical IQ. The t-test and chi square were used to analyze quantitative variables and qualitative variables, respectively. In this study, out of total 180 children, 90 (50%) in the case group and 90 children (50%), the control group participated for IQ comparison. One hundred (57%) were male and 80 (43%) were female. The overall IQ for allergic rhinitis patients and healthy patients was 109.2 and 107.5, respectively. This difference was not considered significant. Furthermore, there was no significant difference between the IQ scores of males and females. Although allergic rhinitis is a chronic disease and effects quality of life, there were no identifiable negative effects on IQ.

Identification of anti-virulence compounds that disrupt quorum-sensing regulated acute and persistent pathogenicity.

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Melissa Starkey

2014-08-01

Full Text Available Etiological agents of acute, persistent, or relapsing clinical infections are often refractory to antibiotics due to multidrug resistance and/or antibiotic tolerance. Pseudomonas aeruginosa is an opportunistic Gram-negative bacterial pathogen that causes recalcitrant and severe acute chronic and persistent human infections. Here, we target the MvfR-regulated P. aeruginosa quorum sensing (QS virulence pathway to isolate robust molecules that specifically inhibit infection without affecting bacterial growth or viability to mitigate selective resistance. Using a whole-cell high-throughput screen (HTS and structure-activity relationship (SAR analysis, we identify compounds that block the synthesis of both pro-persistence and pro-acute MvfR-dependent signaling molecules. These compounds, which share a benzamide-benzimidazole backbone and are unrelated to previous MvfR-regulon inhibitors, bind the global virulence QS transcriptional regulator, MvfR (PqsR; inhibit the MvfR regulon in multi-drug resistant isolates; are active against P. aeruginosa acute and persistent murine infections; and do not perturb bacterial growth. In addition, they are the first compounds identified to reduce the formation of antibiotic-tolerant persister cells. As such, these molecules provide for the development of next-generation clinical therapeutics to more effectively treat refractory and deleterious bacterial-human infections.

Therapeutic regulatory T-cell adoptive transfer ameliorates established murine chronic GVHD in a CXCR5-dependent manner

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McDonald-Hyman, Cameron; Flynn, Ryan; Panoskaltsis-Mortari, Angela; Peterson, Nicholas; MacDonald, Kelli P. A.; Hill, Geoffrey R.; Luznik, Leo; Serody, Jonathan S.; Murphy, William J.; Maillard, Ivan; Munn, David H.; Turka, Laurence A.; Koreth, John; Cutler, Corey S.; Soiffer, Robert J.; Antin, Joseph H.; Ritz, Jerome

2016-01-01

Chronic graft-versus-host disease (cGVHD) is a major complication of allogeneic hematopoietic stem cell transplantation. In cGVHD, alloreactive T cells and germinal center (GC) B cells often participate in GC reactions to produce pathogenic antibodies. Although regulatory T cells (Tregs) can inhibit GC reactions, Treg numbers are reduced in cGVHD, contributing to cGVHD pathogenesis. Here, we explored 2 means to increase Tregs in cGVHD: interleukin-2/monoclonal antibody (IL-2/mAb) complexes and donor Treg infusions. IL-2/mAb complexes given over 1 month were efficacious in expanding Tregs and treating established cGVHD in a multi-organ-system disease mouse model characterized by GC reactions, antibody deposition, and lung dysfunction. In an acute GVHD (aGVHD) model, IL-2/mAb complexes given for only 4 days resulted in rapid mortality, indicating IL-2/mAb complexes can drive conventional T-cell (Tcon)-mediated injury. In contrast, Treg infusions, which uniformly suppress aGVHD, increased Treg frequency and were effective in preventing the onset of, and treating, established cGVHD. Efficacy was dependent upon CXCR5-sufficient Tregs homing to, and inhibiting, GC reactions. These studies indicate that the infusion of Tregs, especially ones enriched for GC homing, may be desirable for cGVHD therapy. Although IL-2/mAb complexes can be efficacious in cGVHD, a cautious approach needs to be taken in settings in which aGVHD elements, and associated Tcon, are present. PMID:27385791

Stress-Induced Chronic Visceral Pain of Gastrointestinal Origin

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Beverley Greenwood-Van Meerveld

2017-11-01

Full Text Available Visceral pain is generally poorly localized and characterized by hypersensitivity to a stimulus such as organ distension. In concert with chronic visceral pain, there is a high comorbidity with stress-related psychiatric disorders including anxiety and depression. The mechanisms linking visceral pain with these overlapping comorbidities remain to be elucidated. Evidence suggests that long term stress facilitates pain perception and sensitizes pain pathways, leading to a feed-forward cycle promoting chronic visceral pain disorders such as irritable bowel syndrome (IBS. Early life stress (ELS is a risk-factor for the development of IBS, however the mechanisms responsible for the persistent effects of ELS on visceral perception in adulthood remain incompletely understood. In rodent models, stress in adult animals induced by restraint and water avoidance has been employed to investigate the mechanisms of stress-induce pain. ELS models such as maternal separation, limited nesting, or odor-shock conditioning, which attempt to model early childhood experiences such as neglect, poverty, or an abusive caregiver, can produce chronic, sexually dimorphic increases in visceral sensitivity in adulthood. Chronic visceral pain is a classic example of gene × environment interaction which results from maladaptive changes in neuronal circuitry leading to neuroplasticity and aberrant neuronal activity-induced signaling. One potential mechanism underlying the persistent effects of stress on visceral sensitivity could be epigenetic modulation of gene expression. While there are relatively few studies examining epigenetically mediated mechanisms involved in visceral nociception, stress-induced visceral pain has been linked to alterations in DNA methylation and histone acetylation patterns within the brain, leading to increased expression of pro-nociceptive neurotransmitters. This review will discuss the potential neuronal pathways and mechanisms responsible for

Stress-Induced Chronic Visceral Pain of Gastrointestinal Origin

Science.gov (United States)

Greenwood-Van Meerveld, Beverley; Johnson, Anthony C.

2017-01-01

Visceral pain is generally poorly localized and characterized by hypersensitivity to a stimulus such as organ distension. In concert with chronic visceral pain, there is a high comorbidity with stress-related psychiatric disorders including anxiety and depression. The mechanisms linking visceral pain with these overlapping comorbidities remain to be elucidated. Evidence suggests that long term stress facilitates pain perception and sensitizes pain pathways, leading to a feed-forward cycle promoting chronic visceral pain disorders such as irritable bowel syndrome (IBS). Early life stress (ELS) is a risk-factor for the development of IBS, however the mechanisms responsible for the persistent effects of ELS on visceral perception in adulthood remain incompletely understood. In rodent models, stress in adult animals induced by restraint and water avoidance has been employed to investigate the mechanisms of stress-induce pain. ELS models such as maternal separation, limited nesting, or odor-shock conditioning, which attempt to model early childhood experiences such as neglect, poverty, or an abusive caregiver, can produce chronic, sexually dimorphic increases in visceral sensitivity in adulthood. Chronic visceral pain is a classic example of gene × environment interaction which results from maladaptive changes in neuronal circuitry leading to neuroplasticity and aberrant neuronal activity-induced signaling. One potential mechanism underlying the persistent effects of stress on visceral sensitivity could be epigenetic modulation of gene expression. While there are relatively few studies examining epigenetically mediated mechanisms involved in visceral nociception, stress-induced visceral pain has been linked to alterations in DNA methylation and histone acetylation patterns within the brain, leading to increased expression of pro-nociceptive neurotransmitters. This review will discuss the potential neuronal pathways and mechanisms responsible for stress

Information persistence using XML database technology

Science.gov (United States)

Clark, Thomas A.; Lipa, Brian E. G.; Macera, Anthony R.; Staskevich, Gennady R.

2005-05-01

The Joint Battlespace Infosphere (JBI) Information Management (IM) services provide information exchange and persistence capabilities that support tailored, dynamic, and timely access to required information, enabling near real-time planning, control, and execution for DoD decision making. JBI IM services will be built on a substrate of network centric core enterprise services and when transitioned, will establish an interoperable information space that aggregates, integrates, fuses, and intelligently disseminates relevant information to support effective warfighter business processes. This virtual information space provides individual users with information tailored to their specific functional responsibilities and provides a highly tailored repository of, or access to, information that is designed to support a specific Community of Interest (COI), geographic area or mission. Critical to effective operation of JBI IM services is the implementation of repositories, where data, represented as information, is represented and persisted for quick and easy retrieval. This paper will address information representation, persistence and retrieval using existing database technologies to manage structured data in Extensible Markup Language (XML) format as well as unstructured data in an IM services-oriented environment. Three basic categories of database technologies will be compared and contrasted: Relational, XML-Enabled, and Native XML. These technologies have diverse properties such as maturity, performance, query language specifications, indexing, and retrieval methods. We will describe our application of these evolving technologies within the context of a JBI Reference Implementation (RI) by providing some hopefully insightful anecdotes and lessons learned along the way. This paper will also outline future directions, promising technologies and emerging COTS products that can offer more powerful information management representations, better persistence mechanisms and

Fisetin and Its Role in Chronic Diseases.

Science.gov (United States)

Pal, Harish C; Pearlman, Ross L; Afaq, Farrukh

2016-01-01

Chronic inflammation is a prolonged and dysregulated immune response leading to a wide variety of physiological and pathological conditions such as neurological abnormalities, cardiovascular diseases, diabetes, obesity, pulmonary diseases, immunological diseases, cancers, and other life-threatening conditions. Therefore, inhibition of persistent inflammation will reduce the risk of inflammation-associated chronic diseases. Inflammation-related chronic diseases require chronic treatment without side effects. Use of traditional medicines and restricted diet has been utilized by mankind for ages to prevent or treat several chronic diseases. Bioactive dietary agents or "Nutraceuticals" present in several fruits, vegetables, legumes, cereals, fibers, and certain spices have shown potential to inhibit or reverse the inflammatory responses and several chronic diseases related to chronic inflammation. Due to safe, nontoxic, and preventive benefits, the use of nutraceuticals as dietary supplements or functional foods has increased in the Western world. Fisetin (3,3',4',7-tetrahydroxyflavone) is a dietary flavonoid found in various fruits (strawberries, apples, mangoes, persimmons, kiwis, and grapes), vegetables (tomatoes, onions, and cucumbers), nuts, and wine that has shown strong anti-inflammatory, anti-oxidant, anti-tumorigenic, anti-invasive, anti-angiogenic, anti-diabetic, neuroprotective, and cardioprotective effects in cell culture and in animal models relevant to human diseases. In this chapter, we discuss the beneficial pharmacological effects of fisetin against different pathological conditions with special emphasis on diseases related to chronic inflammatory conditions.

Palliative psychiatry for severe persistent mental illness as a new approach to psychiatry? Definition, scope, benefits, and risks.

Science.gov (United States)

Trachsel, Manuel; Irwin, Scott A; Biller-Andorno, Nikola; Hoff, Paul; Riese, Florian

2016-07-22

As a significant proportion of patients receiving palliative care suffer from states of anxiety, depression, delirium, or other mental symptoms, psychiatry and palliative care already collaborate closely in the palliative care of medical conditions. Despite this well-established involvement of psychiatrists in palliative care, psychiatry does not currently explicitly provide palliative care for patients with mental illness outside the context of terminal medical illness. Based on the WHO definition of palliative care, a, a working definition of palliative psychiatry is proposed. Palliative psychiatry focuses on mental health rather than medical/physical issues. We propose that the beneficiaries of palliative psychiatry are patients with severe persistent mental illness, who are at risk of therapeutic neglect and/or overly aggressive care within current paradigms. These include long-term residential care patients with severe chronic schizophrenia and insufficient quality of life, those with therapy-refractory depressions and repeated suicide attempts, and those with severe long-standing therapy-refractory anorexia nervosa. An explicitly palliative approach within psychiatry has the potential to improve quality of care, person-centredness, outcomes, and autonomy for patients with severe persistent mental illness. The first step towards a palliative psychiatry is to acknowledge those palliative approaches that already exist implicitly in psychiatry. Basic skills for a palliative psychiatry include communication of diagnosis and prognosis, symptom assessment and management, support for advance (mental health) care planning, assessment of caregiver needs, and referral to specialized services. Some of these may already be considered core skills of psychiatrists, but for a truly palliative approach they should be exercised guided by an awareness of the limited functional prognosis and lifespan of patients with severe persistent mental illness.

Serum Albumin Is Independently Associated with Persistent Organ Failure in Acute Pancreatitis

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Wandong Hong

2017-01-01

Full Text Available Background and Aims. To investigate the association between serum albumin levels within 24 hrs of patient admission and the development of persistent organ failure in acute pancreatitis. Methods. A total of 700 patients with acute pancreatitis were enrolled. Multivariate logistic regression and subgroup analysis determined whether decreased albumin was independently associated with persistent organ failure and mortality. The diagnostic performance of serum albumin was evaluated by the area under Receiver Operating Characteristic (ROC curves. Results. As levels of serum albumin decrease, the risk of persistent organ failure significantly increases (Ptrend<0.001. The incidence of organ failure was 3.5%, 10.6%, and 41.6% in patients with normal albumin and mild and severe hypoalbuminaemia, respectively. Decreased albumin levels were also proportionally associated with prolonged hospital stay (Ptrend<0.001 and the risk of death (Ptrend<0.001. Multivariate analysis suggested that biliary etiology, chronic concomitant diseases, hematocrit, blood urea nitrogen, and the serum albumin level were independently associated with persistent organ failure. Blood urea nitrogen and the serum albumin level were also independently associated with mortality. The area under ROC curves of albumin for predicting organ failure and mortality were 0.78 and 0.87, respectively. Conclusion. A low serum albumin is independently associated with an increased risk of developing of persistent organ failure and death in acute pancreatitis. It may also be useful for the prediction of the severity of acute pancreatitis.

Drinking typography established by scheduled induction predicts chronic heavy drinking in a monkey model of ethanol self-administration.

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Grant, Kathleen A; Leng, Xiaoyan; Green, Heather L; Szeliga, Kendall T; Rogers, Laura S M; Gonzales, Steven W

2008-10-01

We have developed an animal model of alcohol self-administration that initially employs schedule-induced polydipsia (SIP) to establish reliable ethanol consumption under open access (22 h/d) conditions with food and water concurrently available. SIP is an adjunctive behavior that is generated by constraining access to an important commodity (e.g., flavored food). The induction schedule and ethanol polydipsia generated under these conditions affords the opportunity to investigate the development of drinking typologies that lead to chronic, excessive alcohol consumption. Adult male cynomolgus monkeys (Macaca fascicularis) were induced to drink water and 4% (w/v in water) ethanol by a Fixed-Time 300 seconds (FT-300 seconds) schedule of banana-flavored pellet delivery. The FT-300 seconds schedule was in effect for 120 consecutive sessions, with daily induction doses increasing from 0.0 to 0.5 g/kg to 1.0 g/kg to 1.5 g/kg every 30 days. Following induction, the monkeys were allowed concurrent access to 4% (w/v) ethanol and water for 22 h/day for 12 months. Drinking typographies during the induction of drinking 1.5 g/kg ethanol emerged that were highly predictive of the daily ethanol intake over the next 12 months. Specifically, the frequency in which monkeys ingested 1.5 g/kg ethanol without a 5-minute lapse in drinking (defined as a bout of drinking) during induction strongly predicted (correlation 0.91) subsequent ethanol intake over the next 12 months of open access to ethanol. Blood ethanol during induction were highly correlated with intake and with drinking typography and ranged from 100 to 160 mg% when the monkeys drank their 1.5 g/kg dose in a single bout. Forty percent of the population became heavy drinkers (mean daily intakes >3.0 g/kg for 12 months) characterized by frequent "spree" drinking (intakes >4.0 g/kg/d). This model of ethanol self-administration identifies early alcohol drinking typographies (gulping the equivalent of 6 drinks) that evolve into

Interactions between social structure, demography, and transmission determine disease persistence in primates.

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Ryan, Sadie J; Jones, James H; Dobson, Andrew P

2013-01-01

Catastrophic declines in African great ape populations due to disease outbreaks have been reported in recent years, yet we rarely hear of similar disease impacts for the more solitary Asian great apes, or for smaller primates. We used an age-structured model of different primate social systems to illustrate that interactions between social structure and demography create 'dynamic constraints' on the pathogens that can establish and persist in primate host species with different social systems. We showed that this varies by disease transmission mode. Sexually transmitted infections (STIs) require high rates of transmissibility to persist within a primate population. In particular, for a unimale social system, STIs require extremely high rates of transmissibility for persistence, and remain at extremely low prevalence in small primates, but this is less constrained in longer-lived, larger-bodied primates. In contrast, aerosol transmitted infections (ATIs) spread and persist at high prevalence in medium and large primates with moderate transmissibility;, establishment and persistence in small-bodied primates require higher relative rates of transmissibility. Intragroup contact structure - the social network - creates different constraints for different transmission modes, and our model underscores the importance of intragroup contacts on infection prior to intergroup movement in a structured population. When alpha males dominate sexual encounters, the resulting disease transmission dynamics differ from when social interactions are dominated by mother-infant grooming events, for example. This has important repercussions for pathogen spread across populations. Our framework reveals essential social and demographic characteristics of primates that predispose them to different disease risks that will be important for disease management and conservation planning for protected primate populations.

Sigma Factor SigB Is Crucial to Mediate Staphylococcus aureus Adaptation during Chronic Infections.

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Lorena Tuchscherr

2015-04-01

Full Text Available Staphylococcus aureus is a major human pathogen that causes a range of infections from acute invasive to chronic and difficult-to-treat. Infection strategies associated with persisting S. aureus infections are bacterial host cell invasion and the bacterial ability to dynamically change phenotypes from the aggressive wild-type to small colony variants (SCVs, which are adapted for intracellular long-term persistence. The underlying mechanisms of the bacterial switching and adaptation mechanisms appear to be very dynamic, but are largely unknown. Here, we analyzed the role and the crosstalk of the global S. aureus regulators agr, sarA and SigB by generating single, double and triple mutants, and testing them with proteome analysis and in different in vitro and in vivo infection models. We were able to demonstrate that SigB is the crucial factor for adaptation in chronic infections. During acute infection, the bacteria require the simultaneous action of the agr and sarA loci to defend against invading immune cells by causing inflammation and cytotoxicity and to escape from phagosomes in their host cells that enable them to settle an infection at high bacterial density. To persist intracellularly the bacteria subsequently need to silence agr and sarA. Indeed agr and sarA deletion mutants expressed a much lower number of virulence factors and could persist at high numbers intracellularly. SigB plays a crucial function to promote bacterial intracellular persistence. In fact, ΔsigB-mutants did not generate SCVs and were completely cleared by the host cells within a few days. In this study we identified SigB as an essential factor that enables the bacteria to switch from the highly aggressive phenotype that settles an acute infection to a silent SCV-phenotype that allows for long-term intracellular persistence. Consequently, the SigB-operon represents a possible target to develop preventive and therapeutic strategies against chronic and therapy

Sigma Factor SigB Is Crucial to Mediate Staphylococcus aureus Adaptation during Chronic Infections.

Science.gov (United States)

Tuchscherr, Lorena; Bischoff, Markus; Lattar, Santiago M; Noto Llana, Mariangeles; Pförtner, Henrike; Niemann, Silke; Geraci, Jennifer; Van de Vyver, Hélène; Fraunholz, Martin J; Cheung, Ambrose L; Herrmann, Mathias; Völker, Uwe; Sordelli, Daniel O; Peters, Georg; Löffler, Bettina

2015-04-01

Staphylococcus aureus is a major human pathogen that causes a range of infections from acute invasive to chronic and difficult-to-treat. Infection strategies associated with persisting S. aureus infections are bacterial host cell invasion and the bacterial ability to dynamically change phenotypes from the aggressive wild-type to small colony variants (SCVs), which are adapted for intracellular long-term persistence. The underlying mechanisms of the bacterial switching and adaptation mechanisms appear to be very dynamic, but are largely unknown. Here, we analyzed the role and the crosstalk of the global S. aureus regulators agr, sarA and SigB by generating single, double and triple mutants, and testing them with proteome analysis and in different in vitro and in vivo infection models. We were able to demonstrate that SigB is the crucial factor for adaptation in chronic infections. During acute infection, the bacteria require the simultaneous action of the agr and sarA loci to defend against invading immune cells by causing inflammation and cytotoxicity and to escape from phagosomes in their host cells that enable them to settle an infection at high bacterial density. To persist intracellularly the bacteria subsequently need to silence agr and sarA. Indeed agr and sarA deletion mutants expressed a much lower number of virulence factors and could persist at high numbers intracellularly. SigB plays a crucial function to promote bacterial intracellular persistence. In fact, ΔsigB-mutants did not generate SCVs and were completely cleared by the host cells within a few days. In this study we identified SigB as an essential factor that enables the bacteria to switch from the highly aggressive phenotype that settles an acute infection to a silent SCV-phenotype that allows for long-term intracellular persistence. Consequently, the SigB-operon represents a possible target to develop preventive and therapeutic strategies against chronic and therapy-refractory infections.

EcoHIV infection of mice establishes latent viral reservoirs in T cells and active viral reservoirs in macrophages that are sufficient for induction of neurocognitive impairment.

Science.gov (United States)

Gu, Chao-Jiang; Borjabad, Alejandra; Hadas, Eran; Kelschenbach, Jennifer; Kim, Boe-Hyun; Chao, Wei; Arancio, Ottavio; Suh, Jin; Polsky, Bruce; McMillan, JoEllyn; Edagwa, Benson; Gendelman, Howard E; Potash, Mary Jane; Volsky, David J

2018-06-01

Suppression of HIV replication by antiretroviral therapy (ART) or host immunity can prevent AIDS but not other HIV-associated conditions including neurocognitive impairment (HIV-NCI). Pathogenesis in HIV-suppressed individuals has been attributed to reservoirs of latent-inducible virus in resting CD4+ T cells. Macrophages are persistently infected with HIV but their role as HIV reservoirs in vivo has not been fully explored. Here we show that infection of conventional mice with chimeric HIV, EcoHIV, reproduces physiological conditions for development of disease in people on ART including immunocompetence, stable suppression of HIV replication, persistence of integrated, replication-competent HIV in T cells and macrophages, and manifestation of learning and memory deficits in behavioral tests, termed here murine HIV-NCI. EcoHIV established latent reservoirs in CD4+ T lymphocytes in chronically-infected mice but could be induced by epigenetic modulators ex vivo and in mice. In contrast, macrophages expressed EcoHIV constitutively in mice for up to 16 months; murine leukemia virus (MLV), the donor of gp80 envelope in EcoHIV, did not infect macrophages. Both EcoHIV and MLV were found in brain tissue of infected mice but only EcoHIV induced NCI. Murine HIV-NCI was prevented by antiretroviral prophylaxis but once established neither persistent EcoHIV infection in mice nor NCI could be reversed by long-acting antiretroviral therapy. EcoHIV-infected, athymic mice were more permissive to virus replication in macrophages than were wild-type mice, suffered cognitive dysfunction, as well as increased numbers of monocytes and macrophages infiltrating the brain. Our results suggest an important role of HIV expressing macrophages in HIV neuropathogenesis in hosts with suppressed HIV replication.

Adolescents' experience of complex persistent pain.

Science.gov (United States)

Sørensen, Kari; Christiansen, Bjørg

2017-04-01

Persistent (chronic) pain is a common phenomenon in adolescents. When young people are referred to a pain clinic, they usually have amplified pain signals, with pain syndromes of unconfirmed ethology, such as fibromyalgia and complex regional pain syndrome (CRPS). Pain is complex and seems to be related to a combination of illness, injury, psychological distress, and environmental factors. These young people are found to have higher levels of distress, anxiety, sleep disturbance, and lower mood than their peers and may be in danger of entering adulthood with mental and physical problems. In order to understand the complexity of persistent pain in adolescents, there seems to be a need for further qualitative research into their lived experiences. The aim of this study was to explore adolescents' experiences of complex persistent pain and its impact on everyday life. The study has an exploratory design with individual in-depth interviews with six youths aged 12-19, recruited from a pain clinic at a main referral hospital in Norway. A narrative approach allowed the informants to give voice to their experiences concerning complex persistent pain. A hermeneutic analysis was used, where the research question was the basis for a reflective interpretation. Three main themes were identified: (1) a life with pain and unpleasant bodily expressions; (2) an altered emotional wellbeing; and (3) the struggle to keep up with everyday life. The pain was experienced as extremely strong, emerging from a minor injury or without any obvious causation, and not always being recognised by healthcare providers. The pain intensity increased as the suffering got worse, and the sensation was hard to describe with words. Parts of their body could change in appearance, and some described having pain-attacks or fainting. The feeling of anxiety was strongly connected to the pain. Despair and uncertainty contributed to physical disability, major sleep problems, school absence, and withdrawal from

[Thermometric diagnostics of chronic ulcerous pulpitis].

Science.gov (United States)

Zvetkova, P; Mostrova, I

1989-01-01

Thermometric measurements were performed of 408 teeth of the upper and lower jaw with clinically confirmed initial and advanced stage of chronic ulcerous pulpitis in 398 subjects, aged from 18 to 30. Temperature elevation within the range from 1.4 to 3.2 degrees C was established in the initial form of chronic pulpitis and from 1 to 2.5 degrees C in advanced form of chronic pulpitis as compared with the norm. Significant difference in the temperature deviations exists in both forms of chronic pulpitis between the teeth of the upper and lower jaw.

Clinicoroentgenological control in chronic pneumonia

International Nuclear Information System (INIS)

Mamilyaev, R.M.

1984-01-01

A comprehensive clinicoroentgenological study was used to examine 494 patients with chronic pneumonia. Morphological and functional changes observed in the pulmonary pare and functional changes observed in the pulmonary parenchyma and bronchial tree were studied. Types of pneumosclerosis, tigns of exacerbation of chronic pneumonia and abscess formation, morphological and functional disorders of bronchial penetrability in the pneumonic zone were described. Three forms of chronic pneumonia: bronchial, bronchiectatic and abscessing are signled out. The bronchial form is subdivided into chronic pneumonia with chronic bronchitis without deformity and wi.th deforming chronic bronchitis. In the bronchiectatic form pneumonia can be with cylindrical, saccular and cyst-like bronchiectasia. The general diagnosis of chronic pneumonia is established clinically depending on type and variants in 89-94% of cases, by X-ray and sonographic findings in all patients; types and variants of disease are most frequently defined after bronchography

Chronic Pharyngitis And Multiple Soft Palate Peforation In An HIV ...

African Journals Online (AJOL)

This report is at advocating the need for repeated investigation and screening for HIV particularly when there is persistent clinical feature strongly suggestive of AIDS. Should we even start to contemplate therapeutic of antiretroviral dugs in some cases? KEY WORDS: Chronic pharyngitis, Soft palate perforation, AIDS, HIV ...

Chronic 'speech catatonia' with constant logorrhea, verbigeration and echolalia successfully treated with lorazepam: a case report.

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Lee, Joseph W Y

2004-12-01

Logorrhea, verbigeration and echolalia persisted unremittingly for 3 years, with occasional short periods of motoric excitement, in a patient with mild intellectual handicap suffering from chronic schizophrenia. The speech catatonic symptoms, previously refractory to various antipsychotics, responded promptly to lorazepam, a benzodiazepine with documented efficacy in the treatment of acute catatonia but not chronic catatonia. It is suggested that pathways in speech production were selectively involved in the genesis of the chronic speech catatonic syndrome, possibly a rare form of chronic catatonia not previously described.

Non-Monotonic Survival of Staphylococcus aureus with Respect to Ciprofloxacin Concentration Arises from Prophage-Dependent Killing of Persisters

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Elizabeth L. Sandvik

2015-11-01

Full Text Available Staphylococcus aureus is a notorious pathogen with a propensity to cause chronic, non-healing wounds. Bacterial persisters have been implicated in the recalcitrance of S. aureus infections, and this motivated us to examine the persistence of S. aureus to ciprofloxacin, a quinolone antibiotic. Upon treatment of exponential phase S. aureus with ciprofloxacin, we observed that survival was a non-monotonic function of ciprofloxacin concentration. Maximal killing occurred at 1 µg/mL ciprofloxacin, which corresponded to survival that was up to ~40-fold lower than that obtained with concentrations ≥ 5 µg/mL. Investigation of this phenomenon revealed that the non-monotonic response was associated with prophage induction, which facilitated killing of S. aureus persisters. Elimination of prophage induction with tetracycline was found to prevent cell lysis and persister killing. We anticipate that these findings may be useful for the design of quinolone treatments.

Persistent colonization of Helicobacter pylori in human gut induces gastroduodenal diseases

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Animesh Sarker

2014-12-01

Full Text Available Helicobacter pylori are gut bacteria colonize in the epithelial cell lining of the stomach and persist there for long du­ration. Around two-thirds of the world’s populations are infected with H. pylori and cause more than 90 percent of ulcers. The development of persistent inflammation is the main cause of chronic gastritis that finally results in a severe consequence known as stomach cancer. Two major virulence factors cytotoxin-associated gene product (cagA and the vacuolating toxin (vacA are mostly investigated as their close association with gastric carcinoma. In this review, host im­munity against H. pylori infection and their evasion mechanism are intensely explored. It is the fact, that understanding pin point molecular mechanisms of any infection is critical to develop novel strategies to prevent pertinent diseases. .J Microbiol Infect Dis 2014; 4(4: 170-176

Foxp3+ regulatory T cells control persistence of viral CNS infection.

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Dajana Reuter

Full Text Available We earlier established a model of a persistent viral CNS infection using two week old immunologically normal (genetically unmodified mice and recombinant measles virus (MV. Using this model infection we investigated the role of regulatory T cells (Tregs as regulators of the immune response in the brain, and assessed whether the persistent CNS infection can be modulated by manipulation of Tregs in the periphery. CD4(+ CD25(+ Foxp3(+ Tregs were expanded or depleted during the persistent phase of the CNS infection, and the consequences for the virus-specific immune response and the extent of persistent infection were analyzed. Virus-specific CD8(+ T cells predominantly recognising the H-2D(b-presented viral hemagglutinin epitope MV-H(22-30 (RIVINREHL were quantified in the brain by pentamer staining. Expansion of Tregs after intraperitoneal (i.p. application of the superagonistic anti-CD28 antibody D665 inducing transient immunosuppression caused increased virus replication and spread in the CNS. In contrast, depletion of Tregs using diphtheria toxin (DT in DEREG (depletion of regulatory T cells-mice induced an increase of virus-specific CD8(+ effector T cells in the brain and caused a reduction of the persistent infection. These data indicate that manipulation of Tregs in the periphery can be utilized to regulate virus persistence in the CNS.

Hypnotherapy for persistent genital arousal disorder: a case study.

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Elkins, Gary R; Ramsey, Derek; Yu, Yimin

2014-01-01

Persistent genital arousal disorder (PGAD) is characterized by intrusive sexual arousal that is unresolvable via sexual activity and persists for an extended period of time. PGAD's etiology is unknown, and it has no established treatments. This case study reports on a 71-year-old female patient diagnosed with PGAD who received 9 sessions of hypnotherapy. The following measures were administered at baseline and follow-up: Hospital Anxiety and Depression Scale, Center for Epidemiologic Studies Depression Scale, Pittsburgh Sleep Quality Index, and visual analogue measurements of quality of life, intensity of symptoms, and marital interference. At follow-up, there were significant improvements in all measures. Given the currently limited alternatives for treatment, this case study suggests that hypnotherapy may be beneficial for some patients with PGAD.

CD4 T Cell Responses in Latent and Chronic Viral Infections

Science.gov (United States)

Walton, Senta; Mandaric, Sanja; Oxenius, Annette

2013-01-01

The spectrum of tasks which is fulfilled by CD4 T cells in the setting of viral infections is large, ranging from support of CD8 T cells and humoral immunity to exertion of direct antiviral effector functions. While our knowledge about the differentiation pathways, plasticity, and memory of CD4 T cell responses upon acute infections or immunizations has significantly increased during the past years, much less is still known about CD4 T cell differentiation and their beneficial or pathological functions during persistent viral infections. In this review we summarize current knowledge about the differentiation, direct or indirect antiviral effector functions, and the regulation of virus-specific CD4 T cells in the setting of persistent latent or active chronic viral infections with a particular emphasis on herpes virus infections for the former and chronic lymphocytic choriomeningitis virus infection for the latter. PMID:23717308

[Chronic diarrhea: etiologies and diagnostic evaluation].

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Schoepfer, A

2008-04-30

Chronic diarrhea is defined as a decrease in fecal consistency lasting for four or more weeks. A myriad of disorders are associated with chronic diarrhea. In developed countries, chronic diarrhea is mostly caused by non-infectious diseases. There are four pathogenic mechanisms leading to chronic diarrhea: osmotic diarrhea, secretory diarrhea, inflammatory diarrhea, and dysmotility. Overlaps between these mechanisms are possible. A 72-hour fecal collection as well as the fasting test are important diagnostic tools to identify the underlying pathomechanism. The identification of the pathomechanism narrows down the possible etiologies of chronic diarrhea and allows therefore a cost-saving diagnostic workup. The endoscopy is well established in the workup of chronic diarrhea. This article gives an overview about the main causes and mechanisms leading to chronic diarrhea and proposes an algorithm for the diagnostic evalution.

Congenital vascular malformations: the persistence of marginal and embryonal veins.

Science.gov (United States)

Weber, J; Daffinger, N

2006-05-01

In about 18% of cases with conginental vascular malformations we find a perspective of an atypical truncular vein, located along the outside of the leg, frequently extended from the dorsal foot up to the bottom. In presence of a normally developed system of the deep collecting veins of the lower limb and within the pelvic outflow we are talking about a persisting marginal vein (MV). Hypoplasia or even aplasia of the main deep veins in contrary defines the persisting embryonal vein (EV). Already in childhood these truncular dysplastic veins tend to develop varicose enlargement, causing severe reflux of a huge volume of blood--even more when being associated with av-fistulas (46%). In consequence a rapidly growing chronic venous insufficiency will guide to additional injuries. We have analysed 97 patients showing a persisting MV (n: 92 ) within a total of 102 legs. A persistent embryonal vein (EV) was seen 10 times within this clientel. The persisting truncular veins, associated with phlebectasias and typical clinical symptoms have been examined in a diagnostic "step-by-step" procedure, mainly phlebographically (ascending leg phlebography and varicography), including direct venous blood pressure measurements (phlebodynamometry) and--if needed--by arteriography, showing av-shunting fistulae in 46% of cases. CT and MRI were consulted for the exact therapy planing (frequently initially offered as a non-invasive, however, inadequate key of diagnostic). Actually now these techniques cannot replace pre-operatively the angiographic imaging techniques. The analysis of clinical, morphologic and functional signs, guiding to a specific therapy-relevant classification of MV's and EV's will be presented. And a specific strategy of surgical repair, interventional treatment of av-fistulas and conservative compressive follow-up treatment attempting palliative recompensation of the diseased venous outflow will be discussed also.

Acute and chronic otitis media.

Science.gov (United States)

Morris, Peter S; Leach, Amanda J

2009-12-01

Otitis media (OM) is a common illness in young children. OM has historically been associated with frequent and severe complications. Nowadays it is usually a mild condition that often resolves without treatment. For most children, progression to tympanic membrane perforation and chronic suppurative OM is unusual (low-risk populations); this has led to reevaluation of many interventions that were used routinely in the past. Evidence from a large number of randomized controlled trials can help when discussing treatment options with families. Indigenous children in the United States, Canada, Northern Europe, Australia, and New Zealand experience more OM than other children. In some places, Indigenous children continue to suffer from the most severe forms of the disease. Communities with more than 4% of the children affected by chronic tympanic membrane perforation have a major public health problem (high-risk populations). Higher rates of invasive pneumococcal disease, pneumonia, and chronic suppurative lung disease (including bronchiectasis) are also seen. These children will often benefit from effective treatment of persistent (or recurrent) bacterial infection.

Soluble tumor necrosis factor receptor-1 in preterm infants with chronic lung disease.

Science.gov (United States)

Sato, Miho; Mori, Masaaki; Nishimaki, Shigeru; An, Hiromi; Naruto, Takuya; Sugai, Toshiyuki; Shima, Yoshio; Seki, Kazuo; Yokota, Shumpei

2010-04-01

It is clear that inflammation plays an important role in developing chronic lung disease in preterm infants. The purpose of the present study is to investigate changes of serum soluble tumor necrosis factor receptor-1 levels over time in infants with chronic lung disease. The serum levels of soluble tumor necrosis factor receptor-1 were measured after delivery, and at 7, 14, 21 and 28 days of age in 10 infants with chronic lung disease and in 18 infants without chronic lung disease. The serum level of soluble tumor necrosis factor receptor-1 was significantly higher in infants with chronic lung disease than in infants without chronic lung disease after delivery. The differences between these two groups remained up to 28 days of age. Prenatal inflammation with persistence into postnatal inflammation may be involved in the onset of chronic lung disease.

Emerging Fabric of Science: Persistent Identifiers and Knowledge Networks

Science.gov (United States)

Hugo, W.

2017-12-01

There is an increasing emphasis on the use of persistent identifiers in the description of scientific activity, whether this is done to cite scholarly publications and research output, reliably identify role players such as funders and researchers, or to provide long-lasting references to controlled vocabulary. The ICSU World Data System has been promoting the establishment of a "Knowledge Network" to describe research activity, realising that parts of the network will be established as a federated `system', based on linkages between registries of persistent identifiers. In addition, there is a growing focus on not only the relationship between these major role players and associated digital objects, but also on the processes of science: provenance, reproducibility, and re-usability being significant topics of discussion. The paper will focus on description of the `Fabric of Science' from the perspectives of both structure and processes, review the state of implementation of real services and infrastructure in support of it. A case is made for inclusion of persistent identifiers into the mainstream activities of scientists and data infrastructure managers, and for the development of services, such as Scholix, to make better use of the relationships between digital objects and major role players. A proposal is made for the adoption of a federated system of services that are based on a hybrid graph-object framework similar to Scholix for recording the activity of scientific research. Finally, links to related ideas are explored: novel ways of representing of knowledge (such as Nanopublications) and the possibility that the publication paradigm currently in use may have to be amended.

[Differential diagnostic considerations using ICD-10 in chronic back pain with special regard to persistent somatoform pain disorder with somatic and psychological factors (ICD-10 F45.41)].

Science.gov (United States)

Wolff, D

2016-06-01

It is often difficult to pass an expert opinion in cases of chronic back pain. This article analyses the differential diagnostic considerations related to coding various causes in line with ICD-10. It emphasises the I importance of making a careful distinction between orthopoedic and psychiatric conditions and disorders. Simultaneous coding of orthopoedic and psychiatric illnesses and disorders based on a distinct cluster of symptoms necessitates an interdisciplinary approach that consistently applies the ICD-10 definitions of mental an behavioural disorders in order to clearly identify the main reason for a functional impairment in the insurance and sociomedical context. Persistant somatoform pain disorder with somatic and psychological factors (ICD-10 F45.41) should be regarded as related to the underlying disease and be used primarily as an additional and descriptive diagnosis.

Biological Stress Systems, Adverse Life Events, and the Improvement of Chronic Multisite Musculoskeletal Pain Across a 6-Year Follow-Up

NARCIS (Netherlands)

Generaal, Ellen; Vogelzangs, Nicole; Macfarlane, Gary J; Geenen, Rinie; Smit, Johannes H; de Geus, Eco J C N; Dekker, Joost; Penninx, Brenda W J H

Dysfunction of biological stress systems and adverse life events, independently and in interaction, have been hypothesized to predict chronic pain persistence. Conversely, these factors may hamper the improvement of chronic pain. Longitudinal evidence is currently lacking. We examined whether: 1)

Destructive arthritis in a patient with chikungunya virus infection with persistent specific IgM antibodies

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Receveur Marie-Catherine

2009-12-01

Full Text Available Abstract Background Chikungunya fever is an emerging arboviral disease characterized by an algo-eruptive syndrome, inflammatory polyarthralgias, or tenosynovitis that can last for months to years. Up to now, the pathophysiology of the chronic stage is poorly understood. Case presentation We report the first case of CHIKV infection with chronic associated rheumatism in a patient who developed progressive erosive arthritis with expression of inflammatory mediators and persistence of specific IgM antibodies over 24 months following infection. Conclusions Understanding the specific features of chikungunya virus as well as how the virus interacts with its host are essential for the prevention, treatment or cure of chikungunya disease.

Persistence and extinction of a stochastic single-specie model under regime switching in a polluted environment.

Science.gov (United States)

Liu, Meng; Wang, Ke

2010-06-07

A new single-species model disturbed by both white noise and colored noise in a polluted environment is developed and analyzed. Sufficient criteria for extinction, stochastic nonpersistence in the mean, stochastic weak persistence in the mean, stochastic strong persistence in the mean and stochastic permanence of the species are established. The threshold between stochastic weak persistence in the mean and extinction is obtained. The results show that both white and colored environmental noises have sufficient effect to the survival results. Copyright (c) 2010 Elsevier Ltd. All rights reserved.

Persistent asthma in adults: comparison of high resolution computed tomography of the lungs after one year of follow-up

International Nuclear Information System (INIS)

Cukier, Alberto; Stelmach, Rafael; Kavakama, Jorge Issamu; Terra Filho, Mario; Vargas, Francisco

2001-01-01

The aims of this study were to evaluate the role of high resolution computed tomography of the thorax in detecting abnormalities in chronic asthmatic patients and to determine the behavior of these lesions after at least one year. Fourteen persistent asthmatic patients with a mean forced expiratory volume in 1-second that was 63% of predicted and a mean forced expiratory volume in 1-second /forced vital capacity of 60% had two high resolution computed tomography separated by an interval of at least one year. All 14 patients had abnormalities on both scans. The most common abnormality was bronchial wall thickening, which was present in all patients on both computed tomography. Bronchiectasis was suggested on the first computed tomography in 5 of the 14 (36%) patients, but on follow-up, the bronchial dilatation had disappeared in 2 and diminished in a third. Only one patient had any emphysematous changes; a minimal persistent area of para septal emphysema was present on both scans. In 3 patients, a 'mosaic' appearance was observed on the first scan, and this persisted on the follow-up computed tomography. Two patients had persistent areas of mucoid impaction. In a third patient, mucus plugging was detected only on the second computed tomography. We conclude that there are many abnormalities on the high resolution computed tomography of patients with persistent asthma. Changes suggestive of bronchiectasis, namely bronchial dilatation, frequently resolve spontaneously. Therefore, the diagnosis of bronchiectasis by high resolution computed tomography in asthmatic patients must be made with caution, since bronchial dilatation can be reversible or can represent false dilatation. Non smoking chronic asthmatic subjects in this study had no evidence of centrilobular or panacinar emphysema. (author)

Postnatal persistent infection with classical Swine Fever virus and its immunological implications.

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Sara Muñoz-González

Full Text Available It is well established that trans-placental transmission of classical swine fever virus (CSFV during mid-gestation can lead to persistently infected offspring. The aim of the present study was to evaluate the ability of CSFV to induce viral persistence upon early postnatal infection. Two litters of 10 piglets each were infected intranasally on the day of birth with low and moderate virulence CSFV isolates, respectively. During six weeks after postnatal infection, most of the piglets remained clinically healthy, despite persistent high virus titres in the serum. Importantly, these animals were unable to mount any detectable humoral and cellular immune response. At necropsy, the most prominent gross pathological lesion was a severe thymus atrophy. Four weeks after infection, PBMCs from the persistently infected seronegative piglets were unresponsive to both, specific CSFV and non-specific PHA stimulation in terms of IFN-γ-producing cells. These results suggested the development of a state of immunosuppression in these postnatally persistently infected pigs. However, IL-10 was undetectable in the sera of the persistently infected animals. Interestingly, CSFV-stimulated PBMCs from the persistently infected piglets produced IL-10. Nevertheless, despite the addition of the anti-IL-10 antibody in the PBMC culture from persistently infected piglets, the response of the IFN-γ producing cells was not restored. Therefore, other factors than IL-10 may be involved in the general suppression of the T-cell responses upon CSFV and mitogen activation. Interestingly, bone marrow immature granulocytes were increased and targeted by the virus in persistently infected piglets. Taken together, we provided the first data demonstrating the feasibility of CSFV in generating a postnatal persistent disease, which has not been shown for other members of the Pestivirus genus yet. Since serological methods are routinely used in CSFV surveillance, persistently infected pigs

Regulatory components for treating persistent pain in long-term care.

Science.gov (United States)

Planton, Jonathan; Edlund, Barbara J

2010-04-01

Persistent or chronic pain is frequently reported by older adults and has the potential to dramatically influence quality of life. Estimates indicate that 25% to 50% of community-dwelling older adults experience this kind of pain. This rate is even higher in long-term care facilities, where 50% to 75% of residents have chronic pain syndromes that are untreated or undertreated. To promote optimal pain management and enumerate the responsibilities of skilled nursing facilities to effectively treat and prevent pain, the Centers for Medicare & Medicaid Services released a new pain management surveyor guidance, F-Tag 309, which endorses the presence of an interdisciplinary team approach to pain management that involves the resident. The guidance delineates pain management principles, the need for ongoing professional education in all components of pain management, and emphasizes the important role of appropriate pharmacological treatment in conjunction with nonpharmacological interventions to aggressively manage pain. This directive will help skilled nursing facilities achieve optimal pain management for their residents. Copyright 2010, SLACK Incorporated.

Quantitative analysis of the cellular inflammatory response against biofilm bacteria in chronic wounds

DEFF Research Database (Denmark)

Fazli, Mustafa; Bjarnsholt, Thomas; Kirketerp-Møller, Klaus

2011-01-01

Chronic wounds are an important problem worldwide. These wounds are characterized by a persistent inflammatory stage associated with excessive accumulation and elevated cell activity of neutrophils, suggesting that there must be a persistent stimulus that attracts and recruits neutrophils...... counting on the tissue sections from wounds containing either Pseudomonas aeruginosa or Staphylococcus aureus. The P. aeruginosa-containing wounds had significantly higher numbers of neutrophils accumulated compared with the S. aureus-containing wounds. These results are discussed in relation...

The persistence of women in STEM: A constructivist grounded theory study

Science.gov (United States)

Gamm, Ryan

Men and women have reached relative parity in most sectors of the United States workforce. Yet women remain underrepresented in science, technology, engineering, and mathematics (STEM) fields (AAUW, 2010). Underrepresentation persists despite several decades of research, legislation, and intervention focused on gender equality in STEM fields (Clewell, 2002). The underrepresentation or shortage of women in STEM fields is identifiable primarily in degree attainment, in workforce demographics, and in a gender wage gap. Situated in constructivist grounded theory, this study asks how do women in science, technology, engineering, and mathematics (STEM) fields, particularly those in established career positions, persist when encountering personal and institutional barriers, resistance, and hostility? I use an interpretive-constructivist lens to conduct a grounded theory study exploring the experiences of women who persist in STEM fields, their relation to extant literature on this topic, and the connections to K-12 education practices, specifically curriculum. To understand the connections to curriculum I employ Pinar's (2012) method of currere. Pinar (2012) contends currere "provides a strategy for students of curriculum to study the relations between academic knowledge and life history in the interests of self-understanding and social reconstruction" (p.44). This qualitative study explored nine female STEM workers stories of persistence as each respondent works in STEM fields were gender parity has yet to be established. This study presents a substantive theory: As women persist in STEM fields they reframe themselves to be situated in the overlapping intersection of the social processes that correspond to "engagement" and "persistence." This reframing is possible by interpreting one's present day circumstances by independently removing oneself from current circumstances to understand the cumulative effect of both past and present. The findings highlight the importance

Chronic Cough in Otorhinolaryngologic Routine

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Palheta Neto, Francisco Xavier

2011-04-01

Full Text Available Introduction: The chronic cough is sometimes manifested as an imprecise symptom, but of great importance for both the diagnosis and the prognosis. In an otorhinolaryngologic approach, several illnesses that can occur with it can be numbered, including 2 of the 3 main causes of chronic cough. Objective: To identify the main otorhinolaryngologic diseases showing the chronic cough as one of their manifestations. Method: A literature's revision was performed in several scientific articles, specialized books and consultation in Birene and Scielo databases. Literature's revision: cough production in the upper airways is usually associated with an inflammatory reaction by stimulating sensitive receptors of these areas or by mechanic stimulus. The main cause of the chronic cough in the otorhinolaryngology day-to-day is the post-nasal drip, gathering together by itself 02 of the most common diseases: rhinitis and sinusitis. Laryngitis as a result of gastroesophageal reflux (GER stands out in the index of chronic cough etiology, but it is not as severe as GER . Neoplasias are also somewhat frequent causes of cough, and the difficulty in diagnosing the cough cause is common in this disease group. Motility disorder, laryngeal irritation persistence, parasitic disease and injuries by inhalation of toxic products were also found as a cause of cough for longer than 03 months. Conclusion:Chronic cough is a frequent and important finding in otorhinolaryngology and cannot be underestimated, and a careful anamnesis is the best way to determine the etiology and perform a correct treatment for the patient's disease.

The effects of distant healing performed by a spiritual healer on chronic pain: a randomized controlled trial.

Science.gov (United States)

Tsubono, Kenjiro; Thomlinson, Paul; Shealy, C Norman

2009-01-01

Many individuals suffer from various kinds of chronic pain. Some controlled studies on distant healing for chronic pain exist, but no definitive conclusion has been established. To study the effects of distant healing performed by a professional Japanese healer on chronic pain. A double-blind randomized controlled study. Holos University, Fair Grove, Missouri. People suffering from chronic pain (not caused by clear organic diseases or that persists long after a reasonable period of healing following injuries or surgery) were recruited through local radio and newspaper advertising. Subjects were randomly assigned to a treatment group or control group using a double-blind procedure. All subjects met the healer at the initial session at Holos University. At the session, a 20-minute group meditation was performed. The healer went back to Japan after the session and started distant healing only to the treatment group for a 2-month period. All participants were asked to meditate for 20 minutes every day during this 2-month period. The visual analog scale and McGill Pain Questionnaire. A total of 17 subjects were recruited, and 16 subjects completed the study. Comparison of pretreatment and posttreatment visual analog scale indicated a slightly significant effect of distant healing (P=.056). The Present Pain Intensity Scale showed significant improvement in the treatment group compared to the control group (P=.0016). The Pain Rating Index showed improvement in the treatment group, but the difference between both groups was not statistically significant (P=.12).

Irritable bowel syndrome and chronic fatigue 6 years after giardia infection: a controlled prospective cohort study.

Science.gov (United States)

Hanevik, Kurt; Wensaas, Knut-Arne; Rortveit, Guri; Eide, Geir Egil; Mørch, Kristine; Langeland, Nina

2014-11-15

Functional gastrointestinal disorders and fatigue may follow acute infections. This study aimed to estimate the persistence, prevalence, and risk of irritable bowel syndrome and chronic fatigue 6 years after Giardia infection. We performed a controlled prospective study of a cohort of 1252 individuals who had laboratory-confirmed Giardia infection during a waterborne outbreak in 2004. In total, 748 cohort cases (exposed) and 878 matched controls responded to a postal questionnaire 6 years later (in 2010). Responses were compared to data from the same cohort 3 years before (in 2007). The prevalences of irritable bowel syndrome (39.4%) by Rome III criteria and chronic fatigue (30.8%) in the exposed group 6 years after giardiasis were significantly elevated compared with controls, with adjusted relative risks (RRs) of 3.4 (95% confidence interval [CI], 2.9-3.9) and 2.9 (95% CI, 2.3-3.4), respectively. In the exposed group, the prevalence of irritable bowel syndrome decreased by 6.7% (RR, 0.85 [95% CI, .77-.93]), whereas the prevalence of chronic fatigue decreased by 15.3% from 3 to 6 years after Giardia infection (RR, 0.69 [95% CI, .62-.77]). Giardia exposure was a significant risk factor for persistence of both conditions, and increasing age was a risk factor for persisting chronic fatigue. Giardia infection in a nonendemic setting is associated with an increased risk for irritable bowel syndrome and chronic fatigue 6 years later. The prevalences of both conditions decrease over time, indicating that this intestinal protozoan parasite may elicit very long-term, but slowly self-limiting, complications. © The Author 2014. Published by Oxford University Press on behalf of the Infectious Diseases Society of America.

Human embryonic mesenchymal stem cell-derived conditioned medium rescues kidney function in rats with established chronic kidney disease.

Directory of Open Access Journals (Sweden)

Arianne van Koppen

Full Text Available Chronic kidney disease (CKD is a major health care problem, affecting more than 35% of the elderly population worldwide. New interventions to slow or prevent disease progression are urgently needed. Beneficial effects of mesenchymal stem cells (MSC have been described, however it is unclear whether the MSCs themselves or their secretome is required. We hypothesized that MSC-derived conditioned medium (CM reduces progression of CKD and studied functional and structural effects in a rat model of established CKD. CKD was induced by 5/6 nephrectomy (SNX combined with L-NNA and 6% NaCl diet in Lewis rats. Six weeks after SNX, CKD rats received either 50 µg CM or 50 µg non-CM (NCM twice daily intravenously for four consecutive days. Six weeks after treatment CM administration was functionally effective: glomerular filtration rate (inulin clearance and effective renal plasma flow (PAH clearance were significantly higher in CM vs. NCM-treatment. Systolic blood pressure was lower in CM compared to NCM. Proteinuria tended to be lower after CM. Tubular and glomerular damage were reduced and more glomerular endothelial cells were found after CM. DNA damage repair was increased after CM. MSC-CM derived exosomes, tested in the same experimental setting, showed no protective effect on the kidney. In a rat model of established CKD, we demonstrated that administration of MSC-CM has a long-lasting therapeutic rescue function shown by decreased progression of CKD and reduced hypertension and glomerular injury.

Biological stress systems, adverse life events and the improvement of chronic multi-site musculoskeletal pain across a 6-year follow-up

NARCIS (Netherlands)

Generaal, E.; Vogelzangs, N.; Macfarlane, G.J.; Geenen, R.; Smit, J.H.; de Geus, E.J.C.N.; Dekker, J.; Penninx, B.W.J.H.

Dysfunction of biological stress systems and adverse life events, independently and in interaction, have been hypothesized to predict chronic pain persistence. Conversely, these factors may hamper the improvement of chronic pain. Longitudinal evidence is currently lacking. We examined whether: 1)

Persistent Bacterial Bronchitis: Time to Venture beyond the Umbrella

Directory of Open Access Journals (Sweden)

Andrew Bush

2017-12-01

Full Text Available Chronic cough in children is common and frequently mismanaged. In the past, cough was diagnosed as asthma and inappropriate asthma therapies prescribed and escalated. It has been realized that persistent bacterial bronchitis (PBB is a common cause of wet cough and responds to oral antibiotics. The initial definition comprised a history of chronic wet cough, positive bronchoalveolar (BAL cultures for a respiratory pathogen and response to a 2-week course of oral amoxicillin–clavulanic acid. This is now termed PBB-micro; PBB-clinical eliminates the need for BAL. PBB-extended is PBB-micro or PBB-clinical but resolution necessitating 4 weeks of antibiotics; and recurrent PBB is >3 attacks of PBB-micro or-clinical/year. However, the airway has only a limited range of responses to chronic inflammation and infection, and neutrophilic airway disease is seen in many other conditions, such as cystic fibrosis and primary ciliary dyskinesia, both chronic suppurative lung disease endotypes, whose recognition has led to huge scientific and clinical advances. There is an urgent need to extend endotyping into PBB, especially PBB-recurrent. We need to move from associative studies and, in particular, deploy sophisticated modern –omics technologies and systems biology, rather as has been done in the context of asthma in U-BIOPRED. In summary, the use of the term PBB has done signal service in pointing us away from prescribing asthma therapies to children with infected airways, but we now need to move beyond a simple description to teasing out underlying endotypes.

Microenvironmental characteristics and physiology of biofilms in chronic infections of CF patients are strongly affected by the host immune response

DEFF Research Database (Denmark)

Jensen, Peter Østrup; Kolpen, Mette; Kragh, Kasper Nørskov

2017-01-01

in chronic lung infections of cystic fibrosis (CF) patients is very different from what is observed in vitro, for example, in biofilms grown in flow chambers. Dense in vitro biofilms of P. aeruginosa exhibit rapid O2 depletion within ... investigations show that P. aeruginosa persists in the chronically infected CF lung as relatively small cell aggregates that are surrounded by numerous PMNs, where the activity of PMNs is the major cause of O2 depletion rendering the P. aeruginosa aggregates anoxic. High levels of nitrate and nitrite enable P....... aeruginosa to persist fueled by denitrification in the PMN-surrounded biofilm aggregates. This configuration creates a potentially long-term stable ecological niche for P. aeruginosa in the CF lung, which is largely governed by slow growth and anaerobic metabolism and enables persistence and resilience...

Chronic intestinal pseudoobstruction syndrome

Energy Technology Data Exchange (ETDEWEB)

Yeon, Kyung Mo; Seo, Jeong Kee; Lee, Yong Seok [Seoul National University Children' s Hospital, Seoul (Korea, Republic of)

1992-03-15

Chronic intestinal pseudoobstruction syndrome is a rare clinical condition in which impaired intestinal peristalsis causes recurrent symptoms of bowel obstruction in the absence of a mechanical occlusion. This syndrome may involve variable segments of small or large bowel, and may be associated with urinary bladder retention. This study included 6 children(3 boys and 3 girls) of chronic intestinal obstruction. Four were symptomatic at birth and two were of the ages of one month and one year. All had abdominal distension and deflection difficulty. Five had urinary bladder distension. Despite parenteral nutrition and surgical intervention(ileostomy or colostomy), bowel obstruction persisted and four patients expired from sepses within one year. All had gaseous distension of small and large bowel on abdominal films. In small bowel series, consistent findings were variable degree of dilatation, decreased peristalsis(prolonged transit time) and microcolon or microrectum. This disease entity must be differentiated from congenital megacolon, ileal atresia and megacystis syndrome.

Increased incidence and clinical correlation of persistently abnormal technetium pyrophosphate myocardial scintigrams following acute myocardial infarction in patients with diabetes mellitus

International Nuclear Information System (INIS)

Nicod, P.; Lewis, S.E.; Corbett, J.C.; Buja, L.M.; Henderson, G.; Raskin, P.; Rude, R.E.; Willerson, J.T.

1982-01-01

Persistently abnormal /sup 99m/Tc stannous pyrophosphate myocardial scintigrams (PPi+) appear to be associated with a relatively poor prognosis after acute myocardial infarction (AMI). To assess the incidence and implications of PPi+, we performed a retrospective analysis in 29 patients with and 25 patients without diabetes mellitus who had abnormal myocardial scintigrams within 4 days of AMI and who had follow-up scintigrams at least 3 months after hospital discharge. There were no significant differences between patients with and without diabetes as regards age, incidence of transmural or nontransmural AMI, or degree of left ventricular dysfunction after AMI. Persistently abnormal PPi+ occurred more commonly in patients with diabetes than in nondiabetic patients (18 of 29, 62%, compared to 3 of 25, 12%; p less than 0.001). Patients with chronic PPi+ had more frequent cardiac complications following hospital discharge (p less than 0.005) including death, recurrent AMI, unstable angina, and intractable congestive heart failure. Postmortem analysis in two patients with diabetes and chronic PPi+ revealed marked myocytolysis. Thus, patients with diabetes mellitus have an increased incidence of post-AMI persistently abnormal technetium (PPi+) scintigrams and relatively poor prognosis following myocardial infarction

Definition of "persistent vomiting" in current medical literature: A systematic review.

Science.gov (United States)

Morra, Mostafa Ebraheem; Elshafay, Abdelrahman; Kansakar, Aswin Ratna; Mehyar, Ghaleb Muhammad; Dang, Nguyen Phan Hoang; Mattar, Omar Mohamed; Iqtadar, Somia; Mostafa, Mostafa Reda; Hai, Vu Ngoc; Vu, Tran Le-Huy; Ghazy, Ahmed Abdelmotaleb; Kaboub, Fatima; Huy, Nguyen Tien; Hirayama, Kenji

2017-11-01

Persistent vomiting is mentioned as a symptom of a large variety of systemic disorders. It is commonly used interchangeably with chronic, recurrent, or intractable vomiting and widely used as a warning sign of severe illness in dengue infection. However, it has been poorly defined in the medical literature. Therefore, we aimed to systematically review a definition of persistent vomiting in the medical literature. A systematic search was done through; PubMed, Google Scholar, Web of Science, Scopus, VHL, WHO-GHL, Grey Literature Report, POPLINE, and SIGLE for the last 10 years. Consensus on the definition was considered to be reached if at least 50% of studies described the same definition using the Delphi consensus technique. Of 2362 abstracts reviewed, 15 studies were selected based on the inclusion criteria. Three studies used the same definition. Another 2 studies defined it as vomiting of all foods and fluid in 24 hours. Three studies defined persistent vomiting in the units of days or weeks. Four studies used the number of episodes: ≥2 episodes 15 minutes apart, >3 episodes in 12 hours, and >3 episodes within 24 hours. No consensus for the definition was found among authors. This is a point of concern that needs to be addressed by further studies.

Blow-up, Global Existence and Persistence Properties for the Coupled Camassa–Holm equations

International Nuclear Information System (INIS)

Zhu Mingxuan

2011-01-01

In this paper, we consider the coupled Camassa–Holm equations. First, we present some new criteria on blow-up. Then global existence and blow-up rate of the solution are also established. Finally, we discuss persistence properties of this system.

Managing painful chronic wounds: the Wound Pain Management Model

DEFF Research Database (Denmark)

Price, Patricia; Fogh, Karsten; Glynn, Chris

2007-01-01

of the pain experience: location, duration, intensity, quality, onset and impact on activities of daily living. Holistic management must be based on a safe and effective mix of psychosocial approaches together with local and systemic pain management. It is no longer acceptable to ignore or inadequately...... to the wound should be handled as one of the main priorities in chronic wound management together with addressing the cause. Management of pain in chronic wounds depends on proper assessment, reporting and documenting patient experiences of pain. Assessment should be based on six critical dimensions...... document persistent wound pain and not to develop a treatment and monitoring strategy to improve the lives of persons with chronic wounds. Unless wound pain is optimally managed, patient suffering and costs to health care systems will increase. Udgivelsesdato: 2007-Apr...

Persistent low-grade inflammation and regular exercise

DEFF Research Database (Denmark)

Åström, Maj-brit; Feigh, Michael; Pedersen, Bente Klarlund

2010-01-01

against all of these diseases and recent evidence suggests that the protective effect of exercise may to some extent be ascribed to an anti-inflammatory effect of regular exercise. Visceral adiposity contributes to systemic inflammation and is independently associated with the occurrence of CVD, type 2...... diabetes and dementia. We suggest that the anti-inflammatory effects of exercise may be mediated via a long-term effect of exercise leading to a reduction in visceral fat mass and/or by induction of anti-inflammatory cytokines with each bout of exercise.......Persistent low-grade systemic inflammation is a feature of chronic diseases such as cardiovascular disease (CVD), type 2 diabetes and dementia and evidence exists that inflammation is a causal factor in the development of insulin resistance and atherosclerosis. Regular exercise offers protection...

Reduced muscle fiber force production and disrupted myofibril architecture in patients with chronic rotator cuff tears.

Science.gov (United States)

Mendias, Christopher L; Roche, Stuart M; Harning, Julie A; Davis, Max E; Lynch, Evan B; Sibilsky Enselman, Elizabeth R; Jacobson, Jon A; Claflin, Dennis R; Calve, Sarah; Bedi, Asheesh

2015-01-01

A persistent atrophy of muscle fibers and an accumulation of fat, collectively referred to as fatty degeneration, commonly occur in patients with chronic rotator cuff tears. The etiology of fatty degeneration and function of the residual rotator cuff musculature have not been well characterized in humans. We hypothesized that muscles from patients with chronic rotator cuff tears have reduced muscle fiber force production, disordered myofibrils, and an accumulation of fat vacuoles. The contractility of muscle fibers from biopsy specimens of supraspinatus muscles of 13 patients with chronic full-thickness posterosuperior rotator cuff tears was measured and compared with data from healthy vastus lateralis muscle fibers. Correlations between muscle fiber contractility, American Shoulder and Elbow Surgeons (ASES) scores, and tear size were analyzed. Histology and electron microscopy were also performed. Torn supraspinatus muscles had a 30% reduction in maximum isometric force production and a 29% reduction in normalized force compared with controls. Normalized supraspinatus fiber force positively correlated with ASES score and negatively correlated with tear size. Disordered sarcomeres were noted, along with an accumulation of lipid-laden macrophages in the extracellular matrix surrounding supraspinatus muscle fibers. Patients with chronic supraspinatus tears have significant reductions in muscle fiber force production. Force production also correlates with ASES scores and tear size. The structural and functional muscle dysfunction of the residual muscle fibers is independent of the additional area taken up by fibrotic tissue. This work may help establish future therapies to restore muscle function after the repair of chronically torn rotator cuff muscles. Copyright © 2015 Journal of Shoulder and Elbow Surgery Board of Trustees. Published by Elsevier Inc. All rights reserved.

Treatment of Established Status Epilepticus.

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Falco-Walter, Jessica J; Bleck, Thomas

2016-04-25

Status epilepticus is the most severe form of epilepsy, with a high mortality rate and high health care costs. Status epilepticus is divided into four stages: early, established, refractory, and super-refractory. While initial treatment with benzodiazepines has become standard of care for early status epilepticus, treatment after benzodiazepine failure (established status epilepticus (ESE)) is incompletely studied. Effective treatment of ESE is critical as morbidity and mortality increases dramatically the longer convulsive status epilepticus persists. Phenytoin/fosphenytoin, valproic acid, levetiracetam, phenobarbital, and lacosamide are the most frequently prescribed antiseizure medications for treatment of ESE. To date there are no class 1 data to support pharmacologic recommendations of one agent over another. We review each of these medications, their pharmacology, the scientific evidence in support and against each in the available literature, adverse effects and safety profiles, dosing recommendations, and limitations of the available evidence. We also discuss future directions including the established status epilepticus treatment trial (ESETT). Substantial further research is urgently needed to identify these patients (particularly those with non-convulsive status epilepticus), elucidate the most efficacious antiseizure treatment with head-to-head randomized prospective trials, and determine whether this differs for convulsive vs. non-convulsive ESE.

Chronic relapsing pancreatitis in a child. Use of the Puestow procedure to achieve ductal drainage.

Science.gov (United States)

Duncan, N D; McDonald, A; James, M; Brown, B; Mitchell, D I

2000-09-01

A case of chronic relapsing pancreatitis presenting in an 8-year-old African Jamaican girl is outlined. Aggressive supportive management failed to control pain and vomiting. The Puestow Procedure effectively procedure aborted these symptoms. The use of the Puestow procedure should not be inordinately delayed in chronic relapsing pancreatitis if symptoms persist, since it may not only control pain but also halt declining pancreatic function.

Persistent pain after spinal cord injury is maintained by primary afferent activity.

Science.gov (United States)

Yang, Qing; Wu, Zizhen; Hadden, Julia K; Odem, Max A; Zuo, Yan; Crook, Robyn J; Frost, Jeffrey A; Walters, Edgar T

2014-08-06

Chronic pain caused by insults to the CNS (central neuropathic pain) is widely assumed to be maintained exclusively by central mechanisms. However, chronic hyperexcitablility occurs in primary nociceptors after spinal cord injury (SCI), suggesting that SCI pain also depends upon continuing activity of peripheral sensory neurons. The present study in rats (Rattus norvegicus) found persistent upregulation after SCI of protein, but not mRNA, for a voltage-gated Na(+) channel, Nav1.8, that is expressed almost exclusively in primary afferent neurons. Selectively knocking down Nav1.8 after SCI suppressed spontaneous activity in dissociated dorsal root ganglion neurons, reversed hypersensitivity of hindlimb withdrawal reflexes, and reduced ongoing pain assessed by a conditioned place preference test. These results show that activity in primary afferent neurons contributes to ongoing SCI pain. Copyright © 2014 the authors 0270-6474/14/3410765-05$15.00/0.

Microbial Biofilms: Persisters, Tolerance and Dosing

Science.gov (United States)

Cogan, N. G.

2005-03-01

Almost all moist surfaces are colonized by microbial biofilms. Biofilms are implicated in cross-contamination of food products, biofouling, medical implants and various human infections such as dental cavities, ulcerative colitis and chronic respiratory infections. Much of current research is focused on the recalcitrance of biofilms to typical antibiotic and antimicrobial treatments. Although the polymer component of biofilms impedes the penetration of antimicrobials through reaction-diffusion limitation, this does not explain the observed tolerance, it merely delays the action of the agent. Heterogeneities in growth-rate also slow the eradication of the bacteria since most antimicrobials are far less effective for non-growing, or slowly growing bacteria. This also does not fully describe biofilm tolerance, since heterogeneities arr primairly a result of nutrient consumption. In this investigation, we describe the formation of `persister' cells which neither grow nor die in the presence of antibiotics. We propose that the cells are of a different phenotype than typical bacterial cells and the expression of the phenotype is regulated by the growth rate and the antibiotic concentration. We describe several experiments which describe the dynamics of persister cells and which motivate a dosing protocol that calls for periodic dosing of the population. We then introduce a mathematical model, which describes the effect of such a dosing regiment and indicates that the relative dose/withdrawal times are important in determining the effectiveness of such a treatment. A reduced model is introduced and the similar behavior is demonstrated analytically.

Psychiatric morbidity in patients with chronic whiplash-associated disorder.

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Kivioja, Jouko; Själin, Mikael; Lindgren, Urban

2004-06-01

Prospective cohort with age- and gender-matched controls. To compare psychiatric morbidity between two groups: patients having chronic symptoms after a whiplash injury and patients who recovered completely. Psychiatric morbidity may influence the outcome of somatic diseases, and it has been suggested that psychological factors are often involved in the development of chronic symptoms after whiplash injuries, but there is no study assessing psychiatric morbidity in whiplash-associated disorder (WAD) using the Structured Clinical Interview for DSM-IV. We studied a consecutive sample of 278 patients with a whiplash injury. Eighty-five had persisting neck pain after 1 year, and 38 of these participated in this study. For each patient with chronic neck pain at the 1 year follow-up, a gender- and age-matched recovered patient was selected from the study cohort of 278 cases. Psychiatric morbidity was determined using the Structured Clinical Interview for DSM-IV (SCID). The interview was conducted at 1 year after the accident (360 days, SD 2 days). The chronic WAD group had a significantly (P factor for chronic symptoms after a whiplash injury. The development of chronic symptoms after awhiplash injury seems to be associated with psychiatric vulnerability.

Damage of hippocampal neurons in rats with chronic alcoholism

OpenAIRE

Du, Ailin; Jiang, Hongbo; Xu, Lei; An, Na; Liu, Hui; Li, Yinsheng; Zhang, Ruiling

2014-01-01

Chronic alcoholism can damage the cytoskeleton and aggravate neurological deficits. However, the effect of chronic alcoholism on hippocampal neurons remains unclear. In this study, a model of chronic alcoholism was established in rats that were fed with 6% alcohol for 42 days. Endogenous hydrogen sulfide content and cystathionine-beta-synthase activity in the hippocampus of rats with chronic alcoholism were significantly increased, while F-actin expression was decreased. Hippocampal neurons i...

Nora virus persistent infections are not affected by the RNAi machinery.

Science.gov (United States)

Habayeb, Mazen S; Ekström, Jens-Ola; Hultmark, Dan

2009-05-29

Drosophila melanogaster is widely used to decipher the innate immune system in response to various pathogens. The innate immune response towards persistent virus infections is among the least studied in this model system. We recently discovered a picorna-like virus, the Nora virus which gives rise to persistent and essentially symptom-free infections in Drosophila melanogaster. Here, we have used this virus to study the interaction with its host and with some of the known Drosophila antiviral immune pathways. First, we find a striking variability in the course of the infection, even between flies of the same inbred stock. Some flies are able to clear the Nora virus but not others. This phenomenon seems to be threshold-dependent; flies with a high-titer infection establish stable persistent infections, whereas flies with a lower level of infection are able to clear the virus. Surprisingly, we find that both the clearance of low-level Nora virus infections and the stability of persistent infections are unaffected by mutations in the RNAi pathways. Nora virus infections are also unaffected by mutations in the Toll and Jak-Stat pathways. In these respects, the Nora virus differs from other studied Drosophila RNA viruses.

Use of a General Magnetotherapy for Correction of the Lipoperoxidation Values in Patients with a Chronic Cervicitis Combined with a Chronic Adnexitis

OpenAIRE

Fatalieva G.G.; Chandra D'Mello R.

2010-01-01

Aim of investigation is detection of the lipid peroxidation (LPO) state in patients with a chronic cervicitis combined with a chronic adnexitis and possibility of a general magnetotherapy use in its correction. Materials and Methods. 80 patients with a chronic nonspecific cervicitis combined with a chronic adnexitis are examined. A general magnetotherapy was used in one of the groups together with antibacterial therapy. Results. It is established, that a normalization of the disease c...

Natural course of chronic fatigue syndrome/myalgic encephalomyelitis in adolescents.

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Norris, Tom; Collin, Simon M; Tilling, Kate; Nuevo, Roberto; Stansfeld, Stephen A; Sterne, Jonathan Ac; Heron, Jon; Crawley, Esther

2017-06-01

Little is known about persistence of or recovery from chronic fatigue syndrome/myalgic encephalomyelitis (CFS/ME) in adolescents. Previous studies have small sample sizes, short follow-up or have focused on fatigue rather than CFS/ME or, equivalently, chronic fatigue, which is disabling. This work aimed to describe the epidemiology and natural course of CFS/ME in adolescents aged 13-18 years. Longitudinal follow-up of adolescents enrolled in the Avon Longitudinal Study of Parents and Children. Avon, UK. We identified adolescents who had disabling fatigue of >6 months duration without a known cause at ages 13, 16 and 18 years. We use the term 'chronic disabling fatigue' (CDF) because CFS/ME was not verified by clinical diagnosis. We used multiple imputation to obtain unbiased estimates of prevalence and persistence. The estimated prevalence of CDF was 1.47% (95% CI 1.05% to 1.89%) at age 13, 2.22% (1.67% to 2.78%) at age 16 and 2.99% (2.24% to 3.75%) at age 18. Among adolescents with CDF of 6 months duration at 13 years 75.3% (64.0% to 86.6%) were not classified as such at age 16. Similar change was observed between 16 and 18 years (75.0% (62.8% to 87.2%)). Of those with CDF at age 13, 8.02% (0.61% to 15.4%) presented with CDF throughout the duration of adolescence. The prevalence of CDF lasting 6 months or longer (a proxy for clinically diagnosed CFS/ME) increases from 13 to 18 years. However, persistent CDF is rare in adolescents, with approximately 75% recovering after 2-3 years. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/.

Bystander chronic infection negatively impacts development of CD8+ T cell memory

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Stelekati, Erietta; Shin, Haina; Doering, Travis A.; Dolfi, Douglas V.; Ziegler, Carly G.; Beiting, Daniel P.; Dawson, Lucas; Liboon, Jennifer; Wolski, David; Ali, Mohammed-Alkhatim A.; Katsikis, Peter D.; Shen, Hao; Roos, David S.; Haining, W. Nicholas; Lauer, Georg M.; Wherry, E. John

2014-01-01

Summary Epidemiological evidence suggests that chronic infections impair immune responses to unrelated pathogens and vaccines. The underlying mechanisms, however, are unclear and distinguishing effects on priming versus development of immunological memory has been challenging. We investigated whether bystander chronic infections impact differentiation of memory CD8+ T cells, the hallmark of protective immunity against intracellular pathogens. Chronic bystander infections impaired development of memory CD8+ T cells in several mouse models and humans. These effects were independent of initial priming and were associated with chronic inflammatory signatures. Chronic inflammation negatively impacted the number of bystander CD8+ T cells and their memory development. Distinct underlying mechanisms of altered survival and differentiation were revealed with the latter regulated by the transcription factors T-bet and Blimp-1. Thus, exposure to prolonged bystander inflammation impairs the effector to memory transition. These data have relevance for immunity and vaccination during persisting infections and chronic inflammation. PMID:24837104

Persistence of Brazilian isolates of the entomopathogenic fungi Metarhizium anisopliae and M. robertsii in strawberry crop soil after soil drench application

DEFF Research Database (Denmark)

Castro, Thiago; Mayerhofer, Johanna; Enkerli, Jürg

2016-01-01

Establishment, persistence and local dispersal of the entomopathogenic fungi Metarhizium anisopliae (ESALQ1037) and M. robertsii (ESALQ1426) (Ascomycota: Hypocreales) were investigated in the soil and rhizosphere following soil drench application in strawberries between 2012 and 2013 at a single...... sequence repeat analysis. Both applied fungal isolates were frequently recovered from bulk soil and rhizosphere samples of the treated plots, suggesting that they were able to establish and disperse within the soil. Persistence within the soil and strawberry rhizosphere for both fungal isolates...

Drosophila Insulin receptor regulates the persistence of injury-induced nociceptive sensitization

Science.gov (United States)

Patel, Atit A.

2018-01-01

ABSTRACT Diabetes-associated nociceptive hypersensitivity affects diabetic patients with hard-to-treat chronic pain. Because multiple tissues are affected by systemic alterations in insulin signaling, the functional locus of insulin signaling in diabetes-associated hypersensitivity remains obscure. Here, we used Drosophila nociception/nociceptive sensitization assays to investigate the role of Insulin receptor (Insulin-like receptor, InR) in nociceptive hypersensitivity. InR mutant larvae exhibited mostly normal baseline thermal nociception (absence of injury) and normal acute thermal hypersensitivity following UV-induced injury. However, their acute thermal hypersensitivity persists and fails to return to baseline, unlike in controls. Remarkably, injury-induced persistent hypersensitivity is also observed in larvae that exhibit either type 1 or type 2 diabetes. Cell type-specific genetic analysis indicates that InR function is required in multidendritic sensory neurons including nociceptive class IV neurons. In these same nociceptive sensory neurons, only modest changes in dendritic morphology were observed in the InRRNAi-expressing and diabetic larvae. At the cellular level, InR-deficient nociceptive sensory neurons show elevated calcium responses after injury. Sensory neuron-specific expression of InR rescues the persistent thermal hypersensitivity of InR mutants and constitutive activation of InR in sensory neurons ameliorates the hypersensitivity observed with a type 2-like diabetic state. Our results suggest that a sensory neuron-specific function of InR regulates the persistence of injury-associated hypersensitivity. It is likely that this new system will be an informative genetically tractable model of diabetes-associated hypersensitivity. PMID:29752280

Chronic alcohol intake during adolescence, but not adulthood, promotes persistent deficits in risk-based decision making.

Science.gov (United States)

Schindler, Abigail G; Tsutsui, Kimberly T; Clark, Jeremy J

2014-06-01

Adolescent alcohol use is a major public health concern and is strongly correlated with the development of alcohol abuse problems in adulthood. Adolescence is characterized by maturation and remodeling of brain regions implicated in decision making and therefore may be uniquely vulnerable to environmental insults such as alcohol exposure. We have previously demonstrated that voluntary alcohol consumption in adolescence results in maladaptive risk-based decision making in adulthood. However, it is unclear whether this effect on risk-based decision making can be attributed to chronic alcohol use in general or to a selective effect of alcohol use during the adolescent period. Ethanol (EtOH) was presented to adolescent (postnatal day [PND] 30 to 49) and adult rats (PND 80 to 99) for 20 days, either 24 hours or 1 h/d, in a gel matrix consisting of distilled water, gelatin, polycose (10%), and EtOH (10%). The 24-hour time course of EtOH intake was measured and compared between adolescent and adult animals. Following 20 days of withdrawal from EtOH, we assessed risk-based decision making with a concurrent instrumental probability-discounting task. Blood EtOH concentrations (BECs) were taken from trunk blood and assessed using the Analox micro-stat GM7 in separate groups of animals at different time points. Unlike animals exposed to EtOH during adolescence, animals exposed to alcohol during adulthood did not display differences in risk preference compared to controls. Adolescent and adult rats displayed similar EtOH intake levels and patterns when given either 24- or 1-hour access per day. In addition, while both groups reached significant BEC levels, we failed to find a difference between adult and adolescent animals. Here, we show that adolescent, but not adult, EtOH intake leads to a persistent increase in risk preference which cannot be attributed to differences in intake levels or BECs attained. Our findings support previous work implicating adolescence as a time

ERP in chronic pancreatitis - ductal morphology, relation to exocrine function and pain - clinical value

International Nuclear Information System (INIS)

Norup Lauridsen, K.; Raahede, J.; Kruse, A.; Thommesen, P.; Aarhus Univ.

1985-01-01

ERP was analyzed in 87 patients with chronic pancreatitis with special reference to its clinical value in management of pain, the dominating symptom in uncomplicated chronic pancreatitis. A significant correlation was found between ductal changes due to pancreatitis and decrease in pancreatic function. However, no association was found between severe pancreatic pain and pancreatic function or pancreatic morphology. The significance of ERP in management of patients with persistent severe pancreatic pain is discussed. (orig.) [de

Negative beliefs about low back pain are associated with persistent high intensity low back pain.

Science.gov (United States)

Ng, Sin Ki; Cicuttini, Flavia M; Wang, Yuanyuan; Wluka, Anita E; Fitzgibbon, Bernadette; Urquhart, Donna M

2017-08-01

While previous cross-sectional studies have found that negative beliefs about low back pain are associated with pain intensity, the relationship between back beliefs and persistent low back pain is not well understood. This cohort study aimed to examine the role of back beliefs in persistent low back pain in community-based individuals. A hundred and ninety-two participants from a previous musculoskeletal health study were invited to take part in a two-year follow-up study. Beliefs about back pain were assessed by the Back Beliefs Questionnaire (BBQ) at baseline and low back pain intensity was measured by the Chronic Pain Grade Questionnaire at baseline and follow-up. Of the 150 respondents (78.1%), 16 (10.7%) reported persistent high intensity low back pain, 12 (8.0%) developed high intensity low back pain, in 16 (10.7%) their high intensity low back pain resolved and 106 (70.7%) experienced no high intensity low back pain. While participants were generally positive about low back pain (BBQ mean (SD) = 30.2 (6.4)), those with persistent high intensity pain reported greater negativity (BBQ mean (SD) = 22.6 (4.9)). Negative beliefs about back pain were associated with persistent high intensity low back pain after adjusting for confounders (M (SE) = 23.5 (1.6) vs. >30.1 (1.7), p back beliefs were associated with persistent high intensity low back pain over 2 years in community-based individuals. While further longitudinal studies are required, these findings suggest that targeting beliefs in programs designed to treat and prevent persistent high intensity low back pain may be important.

Persistence and extinction of a single-species population system in a polluted environment with random perturbations and impulsive toxicant input

International Nuclear Information System (INIS)

Liu Meng; Wang Ke

2012-01-01

Highlights: ► Random population model with pulse toxicant input in polluted environments. ► Threshold between persistence and extinction is obtained. ► Different random noises have different effects on the persistence of the population. ► Impulsive period plays a key role in determining persistence of the population. ► Simulation figures support the analytical findings. - Abstract: Taking both white noises and colored noises into account, a stochastic single-species model with Markov switching and impulsive toxicant input in a polluted environment is proposed and investigated. Sufficient conditions for extinction, non-persistence in the mean, weak persistence and stochastic permanence are established. The threshold between weak persistence and extinction is obtained. Some simulation figures are introduced to illustrate the main results.

Chronicity, crisis, and the 'end of AIDS'.

Science.gov (United States)

Sangaramoorthy, Thurka

2018-01-11

In biomedical, public health, and popular discourses, the 'end of AIDS' has emerged as a predominant way to understand the future of HIV research and prevention. This approach is predicated on structuring and responding to HIV in ways that underscore its presumed lifelong nature. In this article, I examine the phenomenon of HIV chronicity that undergirds the 'end of AIDS' discourse. In particular, I explore how the logic of HIV chronicity, induced by technological advances in treatment and global financial and political investments, intensifies long-term uncertainty and prolonged crisis. Focusing on over 10 years of anthropological and public health research in the United States, I argue that HIV chronicity, and subsequently, the 'end of AIDS' discourse, obscure the on-going HIV crisis in particular global communities, especially among marginalised and ageing populations who live in under-resourced areas. By tracing the 'end of AIDS' discourse in my field sites and in other global locations, I describe how HIV chronicity signals a continuing global crisis and persistent social precarity rather than a 'break' with a hopeless past or a promising future free from AIDS.

Moisture availability limits subalpine tree establishment.

Science.gov (United States)

Andrus, Robert A; Harvey, Brian J; Rodman, Kyle C; Hart, Sarah J; Veblen, Thomas T

2018-03-01

In the absence of broad-scale disturbance, many temperate coniferous forests experience successful seedling establishment only when abundant seed production coincides with favorable climate. Identifying the frequency of past establishment events and the climate conditions favorable for seedling establishment is essential to understanding how climate warming could affect the frequency of future tree establishment events and therefore future forest composition or even persistence of a forest cover. In the southern Rocky Mountains, USA, research on the sensitivity of establishment of Engelmann spruce (Picea engelmannii) and subalpine fir (Abies lasiocarpa)-two widely distributed, co-occurring conifers in North America-to climate variability has focused on the alpine treeline ecotone, leaving uncertainty about the sensitivity of these species across much of their elevation distribution. We compared annual germination dates for >450 Engelmann spruce and >500 subalpine fir seedlings collected across a complex topographic-moisture gradient to climate variability in the Colorado Front Range. We found that Engelmann spruce and subalpine fir established episodically with strong synchrony in establishment events across the study area. Broad-scale establishment events occurred in years of high soil moisture availability, which were characterized by above-average snowpack and/or cool and wet summer climatic conditions. In the recent half of the study period (1975-2010), a decrease in the number of fir and spruce establishment events across their distribution coincided with declining snowpack and a multi-decadal trend of rising summer temperature and increasing moisture deficits. Counter to expected and observed increases in tree establishment with climate warming in maritime subalpine forests, our results show that recruitment declines will likely occur across the core of moisture-limited subalpine tree ranges as warming drives increased moisture deficits. © 2018 by the

Mechanisms of virus immune evasion lead to development from chronic inflammation to cancer formation associated with human papillomavirus infection.

Science.gov (United States)

Senba, Masachika; Mori, Naoki

2012-10-02

Human papillomavirus (HPV) has developed strategies to escape eradication by innate and adaptive immunity. Immune response evasion has been considered an important aspect of HPV persistence, which is the main contributing factor leading to HPV-related cancers. HPV-induced cancers expressing viral oncogenes E6 and E7 are potentially recognized by the immune system. The major histocompatibility complex (MHC) class I molecules are patrolled by natural killer cells and CD8+ cytotoxic T lymphocytes, respectively. This system of recognition is a main target for the strategies of immune evasion deployed by viruses. The viral immune evasion proteins constitute useful tools to block defined stages of the MHC class I presentation pathway, and in this way HPV avoids the host immune response. The long latency period from initial infection to persistence signifies that HPV evolves mechanisms to escape the immune response. It has now been established that there are oncogenic mechanisms by which E7 binds to and degrades tumor suppressor Rb, while E6 binds to and inactivates tumor suppressor p53. Therefore, interaction of p53 and pRb proteins can give rise to an increased immortalization and genomic instability. Overexpression of NF-κB in cervical and penile cancers suggests that NF-κB activation is a key modulator in driving chronic inflammation to cancer. HPV oncogene-mediated suppression of NF-κB activity contributes to HPV escape from the immune system. This review focuses on the diverse mechanisms of the virus immune evasion with HPV that leads to chronic inflammation and cancer.

The obesity paradox in stable chronic heart failure does not persist after matching for indicators of disease severity and confounders.

Science.gov (United States)

Frankenstein, Lutz; Zugck, Christian; Nelles, Manfred; Schellberg, Dieter; Katus, Hugo A; Remppis, B Andrew

2009-12-01

To verify whether controlling for indicators of disease severity and confounders represents a solution to the obesity paradox in chronic heart failure (CHF). From a cohort of 1790 patients, we formed 230 nested matched triplets by individually matching patients with body mass index (BMI) > 30 kg/m(2) (Group 3), BMI 20-24.9 k/m(2) (Group 1) and BMI 25-29.9 kg/m(2) (Group 2), according to NT-proBNP, age, sex, and NYHA class (triplet = one matched patient from each group). Although in the pre-matching cohort, BMI group was a significant univariable prognostic indicator, it did not retain significance [heart rate (HR): 0.91, 95% CI: 0.78-1.05, chi(2): 1.67] when controlled for group propensities as covariates. Furthermore, in the matched cohort, 1-year mortality and 3-year mortality did not differ significantly. Here, BMI again failed to reach statistical significance for prognosis, either as a continuous or categorical variable, whether crude or adjusted. This result was confirmed in the patients not selected for matching. NT-proBNP, however, remained statistically significant (log(NT-proBNP): HR: 1.49, 95% CI: 1.13-1.97, chi(2): 7.82) after multivariable adjustment. The obesity paradox does not appear to persist in a matched setting with respect to indicators of disease severity and other confounders. NT-proBNP remains an independent prognostic indicator of adverse outcome irrespective of obesity status.

Persistent Atrial Fibrillation Ablation in Females: Insight from the MAGIC-AF Trial.

Science.gov (United States)

Singh, Sheldon M; D'Avila, Andre; Aryana, Arash; Kim, Young-Hoon; Mangrum, J Michael; Michaud, Gregory F; Dukkipati, Srinivas R; Heist, E Kevin; Barrett, Conor D; Thorpe, Kevin E; Reddy, Vivek Y

2016-07-27

Atrial fibrillation (AF) ablation is less frequently performed in women when compared to men. There are conflicting data on the safety and efficacy of AF ablation in women. The objective of this study was to compare the clinical characteristics and outcomes in a contemporary cohort of men and women undergoing persistent AF ablation procedures. A total of 182 men and 53 women undergoing a first-ever persistent AF catheter ablation procedure in The Modified Ablation Guided by Ibutilide Use in Chronic Atrial Fibrillation (MAGIC-AF) trial were evaluated. Clinical and procedural characteristics were compared between each gender. The primary efficacy endpoint was the 1-year single procedure freedom from atrial arrhythmia off anti-arrhythmic drugs. Women undergoing catheter ablation procedures were older than men (P Single procedure drug-free atrial arrhythmia recurrence occurred in 53% of the cohort with no difference based on gender (men = 54%, women = 53%; P = 1.0). Procedural (P = 0.04), fluoroscopic (P = 0.02), and ablation times (P = 0.003) were shorter in women compared to men. Periprocedural complications and postablation improvement in quality of life were similar between men and women. Women undergoing a first-ever persistent AF ablation procedure were older but had similar clinical outcomes and complications when compared with men. © 2016 Wiley Periodicals, Inc.

Reverting antibiotic tolerance of Pseudomonas aeruginosa PAO1 persister cells by (Z-4-bromo-5-(bromomethylene-3-methylfuran-2(5H-one.

Directory of Open Access Journals (Sweden)

Jiachuan Pan

Full Text Available BACKGROUND: Bacteria are well known to form dormant persister cells that are tolerant to most antibiotics. Such intrinsic tolerance also facilitates the development of multidrug resistance through acquired mechanisms. Thus persister cells are a promising target for developing more effective methods to control chronic infections and help prevent the development of multidrug-resistant bacteria. However, control of persister cells is still an unmet challenge. METHODOLOGY/PRINCIPAL FINDINGS: We show in this report that (Z-4-bromo-5-(bromomethylene-3-methylfuran-2(5H-one (BF8 can restore the antibiotic susceptibility of Pseudomonas aeruginosa PAO1 persister cells at growth non-inhibitory concentrations. Persister control by BF8 was found to be effective against both planktonic and biofilm cells of P. aeruginosa PAO1. Interestingly, although BF8 is an inhibitor of quorum sensing (QS in Gram-negative bacteria, the data in this study suggest that the activities of BF8 to revert antibiotic tolerance of P. aeruginosa PAO1 persister cells is not through QS inhibition and may involve other targets. CONCLUSION: BF8 can sensitize P. aeruginosa persister cells to antibiotics.

Adherence and persistence to urate-lowering therapies in the Irish setting

LENUS (Irish Health Repository)

McGowan, Bernie

2014-11-01

To identify adherence and persistence levels with urate-lowering therapies using the national administrative pharmacy claim database. This was a retrospective, pharmacy claims-based analysis of dispensed anti-gout medications on the Irish national HSE-PCRS scheme database between January 2008 and December 2012. Adherence is defined by the medication possession ratio (MPR), and patients were considered to be adherent if the MPR ≥80 % (good adherers) in any given time period. Persistence was defined as continued use of therapy with no periods exceeding a refill gap of >63 days (9 weeks). Logistic regression analysis was used to predict odd ratios (OR) and 95 % confidence interval (CI) for persistence and adherence in relation to age, gender and level of comorbidity. There was a 53 % increase in the number of patients prescribed anti-gout medications between 2008 and 2012 with an increase of 27 % in the associated ingredient cost of these medications. Allopurinol accounted for 87 % of the prescribing and febuxostat accounted for a further 9 %. In patients who started on 100 mg allopurinol, only 14.6 % were titrated to the 300 mg dose. For all those initiating urate-lowering therapies, 45.8 % of patients were persistent with treatment at 6 months decreasing to 22.6 % at 12 months. In multivariate analysis, females had poorer adherence (OR = 0.83 (0.77-0.90)), and increasing age was associated with increased adherence (OR = 4.19 (2.53-6.15)) Increasing comorbidity score was associated with increased adherence and persistence at 6 months (OR = 0.68 (0.59-0.79)). Adherence with anti-gout medications in this study cohort was relatively low. Sustained treatment for gouty arthritis is essential in the prevention of serious adverse outcomes.Significance and Innovations-Poor adherence to medications prescribed to patients for the management of chronic diseases such as gout is an ongoing problem which urgently needs to be addressed.-Some of the reasons identified

20 Years of persistent identifiers - Which systems are here to stay?

Science.gov (United States)

Klump, Jens; Huber, Robert; Lehnert, Kerstin

2016-04-01

Web-based persistent identifiers have been around for more than 20 years, a period long enough to start observing patterns of success and failure. Persistent identifiers were invented to address challenges arising from the distributed and disorganised nature of the internet, which not only allowed new technologies to emerge, it also made it difficult to maintain a persistent record of science. Persistent identifiers now allow unambiguous identification of resources on the net. The expectations were that persistent identifiers would lead to greater accessibility, transparency and reproducibility of research results. Over the past two decades a number of persistent identifier systems have been built, one of them being Digital Object Identifiers (DOI). While DOI were originally invented by the publishing industry, they quickly became an established way for the identification of research resources. At first, these resources referred to scholarly literature and related resources. Other identifier systems, some of them using DOI as an example, were developed as grass-roots efforts by the scientific community. The concept of using persistent identifiers has since been expanded to other, non-textual resources, like datasets (DOI, EPIC) and geological specimens (IGSN), and more recently to authors and contributors of scholarly works (ORCID), and to software and instruments. A common witticism states that "a great thing about standards is that there are so many to choose from." Setting up identifier systems is technically trivial. The real challenge lies in creating a governance system for the respective identifiers. Which systems will stand the test of time? Drawing on data from the Registry of Research Data Repositories (re3data.org) and our own experience in the field, this presentation looks at the history and adoption of existing identifier systems and how this gives us some indications towards factors influencing sustainability of these systems.

Chronic Intermittent Hypoxia Induces Atherosclerosis

OpenAIRE

Savransky, Vladimir; Nanayakkara, Ashika; Li, Jianguo; Bevans, Shannon; Smith, Philip L.; Rodriguez, Annabelle; Polotsky, Vsevolod Y.

2007-01-01

Rationale: Obstructive sleep apnea, a condition leading to chronic intermittent hypoxia (CIH), is associated with hyperlipidemia, atherosclerosis, and a high cardiovascular risk. A causal link between obstructive sleep apnea and atherosclerosis has not been established.

Numeric invariants from multidimensional persistence

Energy Technology Data Exchange (ETDEWEB)

Skryzalin, Jacek [Sandia National Lab. (SNL-NM), Albuquerque, NM (United States); Carlsson, Gunnar [Stanford Univ., Stanford, CA (United States)

2017-05-19

In this paper, we analyze the space of multidimensional persistence modules from the perspectives of algebraic geometry. We first build a moduli space of a certain subclass of easily analyzed multidimensional persistence modules, which we construct specifically to capture much of the information which can be gained by using multidimensional persistence over one-dimensional persistence. We argue that the global sections of this space provide interesting numeric invariants when evaluated against our subclass of multidimensional persistence modules. Lastly, we extend these global sections to the space of all multidimensional persistence modules and discuss how the resulting numeric invariants might be used to study data.

Persistent Aerial Tracking

KAUST Repository

Mueller, Matthias

2016-01-01

persistent, robust and autonomous object tracking system for unmanned aerial vehicles (UAVs) called Persistent Aerial Tracking (PAT). A computer vision and control strategy is applied to a diverse set of moving objects (e.g. humans, animals, cars, boats, etc

Establishment probability in newly founded populations

Directory of Open Access Journals (Sweden)

Gusset Markus

2012-06-01

Full Text Available Abstract Background Establishment success in newly founded populations relies on reaching the established phase, which is defined by characteristic fluctuations of the population’s state variables. Stochastic population models can be used to quantify the establishment probability of newly founded populations; however, so far no simple but robust method for doing so existed. To determine a critical initial number of individuals that need to be released to reach the established phase, we used a novel application of the “Wissel plot”, where –ln(1 – P0(t is plotted against time t. This plot is based on the equation P0t=1–c1e–ω1t, which relates the probability of extinction by time t, P0(t, to two constants: c1 describes the probability of a newly founded population to reach the established phase, whereas ω1 describes the population’s probability of extinction per short time interval once established. Results For illustration, we applied the method to a previously developed stochastic population model of the endangered African wild dog (Lycaon pictus. A newly founded population reaches the established phase if the intercept of the (extrapolated linear parts of the “Wissel plot” with the y-axis, which is –ln(c1, is negative. For wild dogs in our model, this is the case if a critical initial number of four packs, consisting of eight individuals each, are released. Conclusions The method we present to quantify the establishment probability of newly founded populations is generic and inferences thus are transferable to other systems across the field of conservation biology. In contrast to other methods, our approach disaggregates the components of a population’s viability by distinguishing establishment from persistence.

Dasatinib or imatinib in newly diagnosed chronic-phase chronic myeloid leukemia : 2-year follow-up from a randomized phase 3 trial (DASISION)

NARCIS (Netherlands)

Kantarjian, Hagop M.; Shah, Neil P.; Cortes, Jorge E.; Baccarani, Michele; Agarwal, Mohan B.; Soledad Undurraga, Maria; Wang, Jianxiang; Kassack Ipina, Juan Julio; Kim, Dong-Wook; Ogura, Michinori; Pavlovsky, Carolina; Junghanss, Christian; Milone, Jorge H.; Nicolini, Franck E.; Robak, Tadeusz; Van Droogenbroeck, Jan; Vellenga, Edo; Bradley-Garelik, M. Brigid; Zhu, Chao; Hochhaus, Andreas

2012-01-01

Dasatinib is a highly potent BCR-ABL inhibitor with established efficacy and safety in imatinib-resistant/-intolerant patients with chronic myeloid leukemia (CML). In the phase 3 DASISION trial, patients with newly diagnosed chronic-phase (CP) CML were randomized to receive dasatinib 100 mg (n =

Pathogenic characteristics of persistent feline enteric coronavirus infection in cats

Science.gov (United States)

Vogel, Liesbeth; Van der Lubben, Mariken; Te Lintelo, Eddie G.; Bekker, Cornelis P.J.; Geerts, Tamara; Schuijff, Leontine S.; Grinwis, Guy C.M.; Egberink, Herman F.; Rottier, Peter J.M.

2010-01-01

Feline coronaviruses (FCoV) comprise two biotypes: feline enteric coronaviruses (FECV) and feline infectious peritonitis viruses (FIPV). FECV is associated with asymptomatic persistent enteric infections, while FIPV causes feline infectious peritonitis (FIP), a usually fatal systemic disease in domestic cats and some wild Felidae. FIPV arises from FECV by mutation. FCoV also occur in two serotypes, I and II, of which the serotype I viruses are by far the most prevalent in the field. Yet, most of our knowledge about FCoV infections relates to serotype II viruses, particularly about the FIPV, mainly because type I viruses grow poorly in cell culture. Hence, the aim of the present work was the detailed study of the epidemiologically most relevant viruses, the avirulent serotype I viruses. Kittens were inoculated oronasally with different doses of two independent FECV field strains, UCD and RM. Persistent infection could be reproducibly established. The patterns of clinical symptoms, faecal virus shedding and seroconversion were monitored for up to 10 weeks revealing subtle but reproducible differences between the two viruses. Faecal virus, i.e. genomic RNA, was detected during persistent FECV infection only in the large intestine, downstream of the appendix, and could occasionally be observed also in the blood. The implications of our results, particularly our insights into the persistently infected state, are discussed. PMID:20663472

Suicide in Tourette's and Chronic Tic Disorders.

Science.gov (United States)

Fernández de la Cruz, Lorena; Rydell, Mina; Runeson, Bo; Brander, Gustaf; Rück, Christian; D'Onofrio, Brian M; Larsson, Henrik; Lichtenstein, Paul; Mataix-Cols, David

2017-07-15

Persons with neuropsychiatric disorders are at increased risk of suicide, but there is little data concerning Tourette's and chronic tic disorders (TD/CTD). We aimed to quantify the risk of suicidal behavior in a large nationwide cohort of patients with TD/CTD, establish the contribution of psychiatric comorbidity to this risk, and identify predictors of suicide. Using a validated algorithm, we identified 7736 TD/CTD cases in the Swedish National Patient Register during a 44-year period (1969-2013). Using a matched case-cohort design, patients were compared with general population control subjects (1:10 ratio). Risk of suicidal behavior was estimated using conditional logistic regressions. Predictors of suicidal behavior in the TD/CTD cohort were studied using Cox regression models. In unadjusted models, TD/CTD patients, compared with control subjects, had an increased risk of both dying by suicide (odds ratio: 4.39; 95% confidence interval [CI]: 2.89-6.67) and attempting suicide (odds ratio: 3.86; 95% CI: 3.50-4.26). After adjusting for psychiatric comorbidities, the risk was reduced but remained substantial. Persistence of tics beyond young adulthood and a previous suicide attempt were the strongest predictors of death by suicide in TD/CTD patients (hazard ratio: 11.39; 95% CI: 3.71-35.02, and hazard ratio: 5.65; 95% CI: 2.21-14.42, respectively). TD/CTD are associated with substantial risk of suicide. Suicidal behavior should be monitored in these patients, particularly in those with persistent tics, history of suicide attempts, and psychiatric comorbidities. Preventive and intervention strategies aimed to reduce the suicidal risk in this group are warranted. Copyright © 2016 Society of Biological Psychiatry. Published by Elsevier Inc. All rights reserved.

Treatment of Established Status Epilepticus

Science.gov (United States)

Falco-Walter, Jessica J.; Bleck, Thomas

2016-01-01

Status epilepticus is the most severe form of epilepsy, with a high mortality rate and high health care costs. Status epilepticus is divided into four stages: early, established, refractory, and super-refractory. While initial treatment with benzodiazepines has become standard of care for early status epilepticus, treatment after benzodiazepine failure (established status epilepticus (ESE)) is incompletely studied. Effective treatment of ESE is critical as morbidity and mortality increases dramatically the longer convulsive status epilepticus persists. Phenytoin/fosphenytoin, valproic acid, levetiracetam, phenobarbital, and lacosamide are the most frequently prescribed antiseizure medications for treatment of ESE. To date there are no class 1 data to support pharmacologic recommendations of one agent over another. We review each of these medications, their pharmacology, the scientific evidence in support and against each in the available literature, adverse effects and safety profiles, dosing recommendations, and limitations of the available evidence. We also discuss future directions including the established status epilepticus treatment trial (ESETT). Substantial further research is urgently needed to identify these patients (particularly those with non-convulsive status epilepticus), elucidate the most efficacious antiseizure treatment with head-to-head randomized prospective trials, and determine whether this differs for convulsive vs. non-convulsive ESE. PMID:27120626

The role of biofilms in persistent infections and factors involved in ica-independent biofilm development and gene regulation in Staphylococcus aureus.

Science.gov (United States)

Figueiredo, Agnes Marie Sá; Ferreira, Fabienne Antunes; Beltrame, Cristiana Ossaille; Côrtes, Marina Farrel

2017-09-01

Staphylococcus aureus biofilms represent a unique micro-environment that directly contribute to the bacterial fitness within hospital settings. The accumulation of this structure on implanted medical devices has frequently caused the development of persistent and chronic S. aureus-associated infections, which represent an important social and economic burden worldwide. ica-independent biofilms are composed of an assortment of bacterial products and modulated by a multifaceted and overlapping regulatory network; therefore, biofilm composition can vary among S. aureus strains. In the microniches formed by biofilms-produced by a number of bacterial species and composed by different structural components-drug refractory cell subpopulations with distinct physiological characteristics can emerge and result in therapeutic failures in patients with recalcitrant bacterial infections. In this review, we highlight the importance of biofilms in the development of persistence and chronicity in some S. aureus diseases, the main molecules associated with ica-independent biofilm development and the regulatory mechanisms that modulate ica-independent biofilm production, accumulation, and dispersion.

Chronic Prurigo: An Unusual Presentation of Hodgkin Lymphoma

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Shireen Dumont

2018-05-01

Full Text Available Background: Prurigo nodularis is a condition of unknown origin defined by papulonodular eruption and intense pruritus. Hodgkin lymphoma often presents nonspecific initial symptoms. An association between systemic malignancy and cutaneous manifestations has long been documented. We report a case of prurigo nodularis as a first presentation of Hodgkin lymphoma. Case: A 35-year-old woman presented with a 2-year history of pruritus. Previously diagnosed with bedbugs, the pruritus persisted even after insect eradication, with the appearance of papulonodular lesions consistent with chronic prurigo. The pruritus and the pain were refractory to all treatments. She had no past medical history or clinical, radiological, or laboratory findings. A lymphadenopathy was revealed 2 years after onset of the symptoms. Lymph node biopsy showed a nodular sclerosis Hodgkin lymphoma. The patient was initiated on chemotherapy and the skin lesions decreased. Conclusion: This case report of chronic prurigo as the first manifestation of a systemic malignancy reminds us of the importance of a systematic diagnostic approach to this kind of patients initially and throughout time, especially if the symptoms do not respond to treatment. Our case may question the role of imaging examinations in the management and follow-up of a persistent prurigo nodularis.

[Management of chronic daily headache in children and adolescents].

Science.gov (United States)

Cuvellier, J-C

2009-01-01

Chronic daily headache (CDH) affects 2 to 4% of adolescent females and 0,8 to 2% of adolescent males. CDH is diagnosed when headaches occur more than 4 hours a day, for greater than or equal to 15 headache days per month, over a period of 3 consecutive months, without an underlying pathology. It is manifested by severe intermittent headaches, that are migraine-like, as well as a chronic baseline headache. Silberstein and Lipton divided patients into four diagnostic categories: transformed migraine, chronic tension-type headache, new daily-persistent headache, and hemicrania continua. The second edition of the International Classification of Headache Disorders did not comprise any CDH category as such, but provided criteria for all four types of CDH: chronic migraine, chronic tension-type headache, new daily-persistent headache, and hemicrania continua. Evaluation of CDH needs to include a complete history and physical examination to identify any possibility of the headache representing secondary headaches. Children and adolescents with CDH frequently have sleep disturbance, pain at other sites, dizziness, medication-overuse headache and a psychiatric comorbidity (anxiety and mood disorders). CDH frequently results in school absence. CDH management plan is dictated by CDH subtype, the presence or absence of medication overuse, functional disability and presence of attacks of full-migraine superimposed. Reassuring, explaining, and educating the patient and family, starting prophylactic therapy and limiting aborting medications are the mainstay of treatment. It includes pharmacologic (acute and prophylactic therapy) and nonpharmacologic measures (biobehavioral management, biofeedback-assisted relaxation therapy, and psychologic or psychiatric intervention). Part of the teaching process must incorporate life-style changes, such as regulation of sleep and eating habits, regular exercise, avoidance of identified triggering factors and stress management. Emphasis must be

A survey on doctors' knowledge and attitude of treating chronic pain ...

African Journals Online (AJOL)

Background: Chronic non-cancer pain (CP) is one of the most common complaints that bring patients to the hospital. When pain persists, people move from doctor-to-doctor seeking for help, thus the burden of CP is huge. This study, therefore was aimed at assessing attitude and knowledge of doctors in three teaching ...

Persistent angina

DEFF Research Database (Denmark)

Jespersen, L.; Abildstrom, S. Z.; Hvelplund, Anders

2013-01-01

To evaluate persistent angina in stable angina pectoris with no obstructive coronary artery disease (CAD) compared to obstructive CAD and its relation to long-term anxiety, depression, quality of life (QOL), and physical functioning. We invited 357 patients (men = 191; women = 166; response rate 83......-obstructive CAD or normal coronary arteries than in patients with obstructive CAD. Persistent angina symptoms were associated with long-term anxiety, depression, impaired physical functioning, and QOL irrespective of the degree of CAD. Contrary to common perception, excluding obstructive CAD in stable angina does...... %) with no prior cardiovascular disease who had a first-time coronary angiography (CAG) in 2008-2009 due to suspected stable angina to participate in a questionnaire survey in 2011 with the Seattle Angina Questionnaire and the Hospital Anxiety and Depression Scale as key elements. Long-term persistent angina (i...

Acute ecological toxicity and environmental persistence of simulants

Energy Technology Data Exchange (ETDEWEB)

Cataldo, D.A.; Ligotke, M.W.; McVeety, B.D.; Fellows, R.J.; Bolton, H. Jr.; Li, S.W.; Van Voris, P.; Wentsel, R.S.

1988-06-01

The objectives of these studies are to establish the comparative environmental behavior and chemical fate of chemical simulants. Laboratory studies were undertaken to establish: (1) deposition efficiency (deposition velocities, Vd) for receptor surfaces including plant foliage and soils; (2) dose/response relationships for important environmental components including plants and soil microflora; and (3) the environmental persistence of the simulants. Chemical agent simulants are employed for a range of testing and training activities where use of chemical agents is less than suitable from a safety and environmental standpoint. A variety of chemical simulant materials are used to simulate either nerve agents or blister agents. The following research describes the environmental effects and persistence of four simulants. These are the nerve agent stimulants diisopropyl methylphosphonate (DIMP), diisopropyl fluorophosphate (DFP), and bis (2-ethylhexyl) phosphonate (BIS), and the mustard stimulant 2-chloroethyl ethyl sulfide (CEES). The vapor pressures for DIMP, DFP, and CEES are relatively high, reported to be 0.17, 0.58 and 3.4 mm Hg, respectively; while that of BIS is substantially less at 5.8 /times/ 10/sup /minus/5/ mm Hg at 25/degree/C. The chemical characteristics of DFP and CEES are very similar to G/VX-agents and mustard, respectively, and are employed for materials evaluation under controlled conditions. However, their toxicity precludes their use in the environment. DIMP and BIS are currently used for testing in the open air. 3 figs., 3 tabs.

Persistent proteinuria as an indicator of renal disease in HIV-infected children

Directory of Open Access Journals (Sweden)

Yuni Hisbiiyah

2017-01-01

Full Text Available Background Persistent proteinuria (microalbuminuria has been reported to be a precursor of HIV-related renal disease. Screening allows for early management in order to prevent the progression of renal disease and decrease morbidity and mortality associated with chronic kidney disease in HIV. Several studies have been done on renal manifestation in HIV-infected children from American and African regions, but similar studies from Asia are lacking. Objective To determine the prevalence of persistent proteinuria in HIV-positive children on antiretroviral therapy (ARV in Dr. Soetomo Hospital, Surabaya. Methods A cross-sectional study on children with HIV and treated with  highly active antiretroviral therapy (HARRT was done from August 2014 to February 2015. Microalbuminuria was measured by the ratio of urine albumin to creatinine (ACR, while proteinuria was measured by dipstick. Measurements were performed 3 times in 4-8 weeks. All subjects underwent complete evaluation of blood tests, serum creatinine, blood urea nitrogen (BUN, CD4 counts, and urinalysis. Data were analyzed using Chi-square and logistic regression tests. Results Of 38 children on HARRT enrolled in this study, 2 subjects developed acute kidney injury (AKI, 4 subjects were suspected to have urinary tract infection (UTI, and 1 subject was suspected to have urinary tract stones. The prevalence of persistent microalbuminuria was 2.6%. There was no correlation between immunological status, WHO clinical stage, or duration of ARV and the incidence of persistent proteinuria (P>0.05. Conclusion The prevalence of persistent proteinuria is  lower in younger HIV-infected children at a non-advanced stage and HIV-infected children with normal immunological status who are on HAART. We provide baseline data on the renal conditions of HIV-infected children in the era of HAART, before tenovofir is  increasingly used as an antiretroviral therapy regimen in Indonesia.

Effect of chronic pain on fentanyl self-administration in mice.

Directory of Open Access Journals (Sweden)

Carrie L Wade

Full Text Available The development of opioid addiction in subjects with established chronic pain is an area that is poorly understood. It is critically important to clearly understand the neurobiology associated with propensity toward conversion to addiction under conditions of chronic pain. To pose the question whether the presence of chronic pain influences motivation to self-administer opioids for reward, we applied a combination of rodent models of chronic mechanical hyperalgesia and opioid self-administration. We studied fentanyl self-administration in mice under three conditions that induce chronic mechanical hyperalgesia: inflammation, peripheral nerve injury, and repeated chemotherapeutic injections. Responding for fentanyl was compared among these conditions and their respective standard controls (naïve condition, vehicle injection or sham surgery. Acquisition of fentanyl self-administration behavior was reduced or absent in all three conditions of chronic hyperalgesia relative to control mice with normal sensory thresholds. To control for potential impairment in ability to learn the lever-pressing behavior or perform the associated motor tasks, all three groups were evaluated for acquisition of food-maintained responding. In contrast to the opioid, chronic hyperalgesia did not interfere with the reinforcing effect of food. These studies indicate that the establishment of chronic hyperalgesia is associated with reduced or ablated motivation to seek opioid reward in mice.

Chronic pain: the burden of disease and treatment innovations

Directory of Open Access Journals (Sweden)

S. Monti

2015-10-01

Full Text Available Musculoskeletal conditions are the most frequent cause of chronic pain and affect around 1 in 5 adults in Europe. When chronic pain occurs, it becomes disease itself, with substantial clinical, social and economic impact. Effi cacy and tolerability problems are encountered with all therapeutic strategies available to treat musculoskeletal pain. This often limits effective analgesia and patients’ long term compliance, with the result that chronic pain is persistently underestimated and undertreated. Tapentadol is a novel, centrally acting analgesic that has been recently commercialized for the treatment of chronic pain. This new molecule, by combining two distinct mechanisms of action, μ-opioid receptor agonism (MOR and noradrenaline reuptake inhibition (NRI, introduces a new pharmacological class called MOR-NRI. Several studies demonstrated promising results in the management of both nociceptive and neuropathic pain and good tolerability profi le, particularly concerning side effects, compared to traditional opioids. This novel analgesic represents a possible therapeutic option also in the rheumatologic fi eld, particularly in the treatment of osteoarthritis and low back pain.

The Role of Employee-Driven Relations and Persistence in University-Industry Collaboration on Regional Innovation

DEFF Research Database (Denmark)

Østergaard, Christian Richter; Drejer, Ina

important driving factor for current collaboration than the existence of employee-driven relations. This suggest that firms’ hiring a university graduate is important for establishing a university connection, but once they have initiated a collaboration, then collaboration patterns tend to persists. However...... in the innovation literature about drivers of and persistence in university-industry collaborations. More specifically, it explores the role of employee-driven relations and persistence for firms’ collaboration on innovation with specific universities. The existing studies of university-industry interaction based......Promoting university-industry collaboration on innovation has an important role in regional innovation policy. Despite apparent advantages of such collaborations, several studies have shown that most innovative firms do not collaborate with universities. The paper addresses the dearth of knowledge...

Chronic Osteoporotic Pain in Mice: Cutaneous and Deep Musculoskeletal Pain Are Partially Independent of Bone Resorption and Differentially Sensitive to Pharmacological Interventions

Directory of Open Access Journals (Sweden)

Miyako Suzuki

2017-01-01

Full Text Available Although the pathological changes in osteoporotic bones are well established, the characterization of the osteoporotic pain and its appropriate treatment are not fully elucidated. We investigated the behavioral signs of cutaneous and deep musculoskeletal pain and physical function; time-dependent changes in bone mineral density (BMD and the emergence of the behavioral phenotype; and the effects of pharmacological interventions having different mechanisms of action (chronic intraperitoneal administration of pamidronate [0.25 mg/kg, 5x/week for 5 weeks] versus acute treatment with intraperitoneal morphine [10 mg/kg] and pregabalin [100 mg/kg] in a mouse model of ovariectomized or sham-operated mice 6 months following surgery. We observed reduced BMD associated with weight gain, referred cutaneous hypersensitivity, and deep musculoskeletal pain that persisted for 6 months. Chronic bisphosphonate treatment, 6 months after ovariectomy, reversed bone loss and hypersensitivity to cold, but other behavioral indices of osteoporotic pain were unchanged. While the efficacy of acute morphine on cutaneous pain was weak, pregabalin was highly effective; deep musculoskeletal pain was intractable. In conclusion, the reversal of bone loss alone is insufficient to manage pain in chronic osteoporosis. Additional treatments, both pharmacological and nonpharmacological, should be implemented to improve quality of life for osteoporosis patients.

JOINT MOBILIZATION IN THE MANAGEMENT OF PERSISTENT INSERTIONAL ACHILLES TENDINOPATHY: A CASE REPORT.

Science.gov (United States)

Jayaseelan, Dhinu J; Post, Andrew A; Mischke, John J; Sault, Josiah D

2017-02-01

Insertional Achilles tendinopathy (IAT) can be a challenging condition to manage conservatively. Eccentric exercise is commonly used in the management of chronic tendinopathy; however, it may not be as helpful for insertional tendon problems as compared to mid-portion dysfunction. While current evidence describing the physical therapy management of IAT is developing, gaps still exist in descriptions of best practice. The purpose of this case report is to describe the management of a patient with persistent IAT utilizing impairment-based joint mobilization, self-mobilization, and exercise. A 51-year-old male was seen in physical therapy for complaints of posterior heel pain and reduced running capacity. He was seen by multiple physical therapists previously, but reported continued impairment, and functional restriction. Joint-based non-thrust mobilization and self-mobilization exercise were performed to enhance his ability to run and reduce symptoms. The subject was seen for four visits over the course of two months. He made clinically significant improvements on the Foot and Ankle Activity Measure and Victorian Institute of Sport Assessment-Achilles tendon outcomes, was asymptomatic, and participated in numerous marathons. Improvements were maintained at one-year follow-up. Mobility deficits can contribute to the development of tendinopathy, and without addressing movement restrictions, symptoms and functional decline related to tendinopathy may persist. Joint-directed manual therapy may be a beneficial intervention in a comprehensive plan of care in allowing patients with chronic tendon changes to optimize function. Therapy, Level 4.

Persistence of Overseeded Cool-Season Grasses in Bermudagrass Turf

Directory of Open Access Journals (Sweden)

Thomas Serensits

2011-01-01

Full Text Available Cool-season grass species are commonly overseeded into bermudagrass turf for winter color. When the overseeded grass persists beyond the spring; however, it becomes a weed. The ability of perennial ryegrass, Italian (annual ryegrass, intermediate ryegrass, and hybrid bluegrass to persist in bermudagrass one year after seeding was determined. Perennial ryegrass, intermediate ryegrass, and Italian ryegrass produced acceptable ground cover in the spring after fall seeding. Hybrid bluegrass did not establish well, resulting in unacceptable cover. Perennial ryegrass generally persisted the most one year after seeding, either because of summer survival of plants or because of new germination the following fall. Plant counts one year after seeding were greater in the higher seeding rate treatment compared to the lower seeding treatment rate of perennial ryegrass, suggesting new germination had occurred. Plant counts one year after seeding plots with intermediate ryegrass or Italian ryegrass were attributed primarily to latent germination and not summer survival. Applications of foramsulfuron generally did not prevent overseeded species stand one year after seeding, supporting the conclusion of new germination. Although quality is less with intermediate ryegrass compared to perennial ryegrass, it transitions out easier than perennial ryegrass, resulting in fewer surviving plants one year later.

Combined persistent mullerian duct syndrome, transverse testicular ectopia and mosaic klinefelter's syndrome

International Nuclear Information System (INIS)

Rehman, A.; Hassan, S.; Zaidi, A.

2008-01-01

Persistent Mullerian Duct Syndrome (PMDS), a rare form of male pseudohermaphroditism, is characterized by the persistence of Mullerian duct structures (uterus, fallopian tubes and upper two-thirds of vagina) in otherwise normallyvirilized males (Karyotype 46XY). Patients suffering from PMDS present with cryptorchidism, inguinal hernia and infertility. Diagnosis is established when Mullerian duct structures are discovered either during ultrasonography for localization of undescended testis(s), during surgical exploration for cryptorchidism or herniorrhaphy (hernii uteri inguinalis). Presence of both testes on one side of the scrotum is known as Transverse Testicular Ectopia (TTE). Co-existence of PMDS and transverse testicular ectopia in a patient of mosaic Klinefelter's syndrome (Karyotype 46XY/47XXY) is a unique genetic association. (author)

[Characterization of patients with chronic hepatitis B virus infection without indication for treatment].

Science.gov (United States)

Planas, Ramon

2014-07-01

Chronic infection by the hepatitis B virus (HBV) is a dynamic process that results from the interaction between HBV replication and the host's immune response. In accordance with the consensus document of the European Association for the Study of the Liver, treatment is not indicated for the immune tolerant and inactive carrier phases. However, there are situations in the 2 phases (which we could call gray areas of chronic HBV infection) in which the correct categorization of patients is not easy and in which the start of treatment can be proposed. In the immune tolerant phase, treatment could be indicated for health professionals whose responsibilities require their participation in invasive procedures. Treatment could also be indicated for pregnant women who are HBeAg-positive, ALT normal and have high HBV DNA values and for whom oral antiviral treatment is indicated during the last trimester of pregnancy to reduce the risk of vertical HBV transmission from mother to child. For patients in the inactive carrier phase who are HBeAg-negative with persistent normal ALT levels and HBV DNA ≥ 2000 IU/mL, the intensity of the hepatic lesion will determine the indication for treatment. If these patients already have established cirrhosis then treatment is indicated if the HBV DNA is detectable, regardless of the ALT level. Copyright © 2014 Elsevier España, S.L. All rights reserved.

Persistence and extinction of a stochastic single-species model under regime switching in a polluted environment II.

Science.gov (United States)

Liu, Meng; Wang, Ke

2010-12-07

This is a continuation of our paper [Liu, M., Wang, K., 2010. Persistence and extinction of a stochastic single-species model under regime switching in a polluted environment, J. Theor. Biol. 264, 934-944]. Taking both white noise and colored noise into account, a stochastic single-species model under regime switching in a polluted environment is studied. Sufficient conditions for extinction, stochastic nonpersistence in the mean, stochastic weak persistence and stochastic permanence are established. The threshold between stochastic weak persistence and extinction is obtained. The results show that a different type of noise has a different effect on the survival results. Copyright © 2010 Elsevier Ltd. All rights reserved.

Characterization of persistent postoperative pain by quantitative sensory testing

DEFF Research Database (Denmark)

Werner, Mads U.; Kehlet, Henrik

2010-01-01

Postoperative pain remains inadequately treated, and it has been estimated that 5-10% undergoing surgery will develop moderate to severe persistent pain leading to chronic physical disability and psychosocial distress. Quantitative sensory testing (QST) is a graded, standardized activation...... research tool in studies investigating the correlation between responses to preoperatively applied experimental pain stimuli and clinical postoperative pain. Second, the use of QST as a valuable prognostic, sequential assessment tool in surgical procedure specific research is presented. Third......, the implications of these findings for use of QST in future research are discussed. More rational design of predictive studies in PPP, based on surgical procedure specific approaches, is needed in order to improve our understanding of prevention and management of this debilitating postsurgical condition....

Characterization of persistent postoperative pain by quantitative sensory testing

DEFF Research Database (Denmark)

Werner, Mads U.; Kehlet, Henrik

2010-01-01

, the implications of these findings for use of QST in future research are discussed. More rational design of predictive studies in PPP, based on surgical procedure specific approaches, is needed in order to improve our understanding of prevention and management of this debilitating postsurgical condition.......Postoperative pain remains inadequately treated, and it has been estimated that 5-10% undergoing surgery will develop moderate to severe persistent pain leading to chronic physical disability and psychosocial distress. Quantitative sensory testing (QST) is a graded, standardized activation...... research tool in studies investigating the correlation between responses to preoperatively applied experimental pain stimuli and clinical postoperative pain. Second, the use of QST as a valuable prognostic, sequential assessment tool in surgical procedure specific research is presented. Third...

Persistence and Nonpersistence of a Predator Prey System with Stochastic Perturbation

Directory of Open Access Journals (Sweden)

Haihong Li

2014-01-01

show that this system has a unique positive solution. Then, we deduce conditions that the system is persistent in time average. Furthermore, we show the conditions that there is a stationary distribution of the system which implies that the system is permanent. After that, conditions for the system going extinct in probability are established. At last, numerical simulations are carried out to support our results.

Research design considerations for chronic pain prevention clinical trials: IMMPACT recommendations.

Science.gov (United States)

Gewandter, Jennifer S; Dworkin, Robert H; Turk, Dennis C; Farrar, John T; Fillingim, Roger B; Gilron, Ian; Markman, John D; Oaklander, Anne Louise; Polydefkis, Michael J; Raja, Srinivasa N; Robinson, James P; Woolf, Clifford J; Ziegler, Dan; Ashburn, Michael A; Burke, Laurie B; Cowan, Penney; George, Steven Z; Goli, Veeraindar; Graff, Ole X; Iyengar, Smriti; Jay, Gary W; Katz, Joel; Kehlet, Henrik; Kitt, Rachel A; Kopecky, Ernest A; Malamut, Richard; McDermott, Michael P; Palmer, Pamela; Rappaport, Bob A; Rauschkolb, Christine; Steigerwald, Ilona; Tobias, Jeffrey; Walco, Gary A

2015-07-01

Although certain risk factors can identify individuals who are most likely to develop chronic pain, few interventions to prevent chronic pain have been identified. To facilitate the identification of preventive interventions, an IMMPACT meeting was convened to discuss research design considerations for clinical trials investigating the prevention of chronic pain. We present general design considerations for prevention trials in populations that are at relatively high risk for developing chronic pain. Specific design considerations included subject identification, timing and duration of treatment, outcomes, timing of assessment, and adjusting for risk factors in the analyses. We provide a detailed examination of 4 models of chronic pain prevention (ie, chronic postsurgical pain, postherpetic neuralgia, chronic low back pain, and painful chemotherapy-induced peripheral neuropathy). The issues discussed can, in many instances, be extrapolated to other chronic pain conditions. These examples were selected because they are representative models of primary and secondary prevention, reflect persistent pain resulting from multiple insults (ie, surgery, viral infection, injury, and toxic or noxious element exposure), and are chronically painful conditions that are treated with a range of interventions. Improvements in the design of chronic pain prevention trials could improve assay sensitivity and thus accelerate the identification of efficacious interventions. Such interventions would have the potential to reduce the prevalence of chronic pain in the population. Additionally, standardization of outcomes in prevention clinical trials will facilitate meta-analyses and systematic reviews and improve detection of preventive strategies emerging from clinical trials.

The commensal infant gut meta-mobilome as a potential reservoir for persistent multidrug resistance integrons.

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Ravi, Anuradha; Avershina, Ekaterina; Foley, Steven L; Ludvigsen, Jane; Storrø, Ola; Øien, Torbjørn; Johnsen, Roar; McCartney, Anne L; L'Abée-Lund, Trine M; Rudi, Knut

2015-10-28

Despite the accumulating knowledge on the development and establishment of the gut microbiota, its role as a reservoir for multidrug resistance is not well understood. This study investigated the prevalence and persistence patterns of an integrase gene (int1), used as a proxy for integrons (which often carry multiple antimicrobial resistance genes), in the fecal microbiota of 147 mothers and their children sampled longitudinally from birth to 2 years. The study showed the int1 gene was detected in 15% of the study population, and apparently more persistent than the microbial community structure itself. We found int1 to be persistent throughout the first two years of life, as well as between mothers and their 2-year-old children. Metagenome sequencing revealed integrons in the gut meta-mobilome that were associated with plasmids and multidrug resistance. In conclusion, the persistent nature of integrons in the infant gut microbiota makes it a potential reservoir of mobile multidrug resistance.

Detection of antibiotic resistance genes in samples from acute and chronic endodontic infections and after treatment.

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Rôças, Isabela N; Siqueira, José F

2013-09-01

The purpose of this study was twofold: survey samples from acute and chronic endodontic infections for the presence of genes encoding resistance to beta-lactams, tetracycline and erythromycin, and evaluate the ability of treatment to eliminate these genes from root canals. DNA extracts from samples of abscess aspirates (n=25) and root canals of teeth with asymptomatic apical periodontitis (n=24) were used as template for direct detection of the genes blaTEM, cfxA, tetM, tetQ, tetW, and ermC using real-time polymerase chain reaction (PCR). Bacterial presence was determined using PCR with universal bacterial primers. Root canals of the asymptomatic cases were also sampled and evaluated after chemomechanical procedures using NiTi instruments with 2.5% NaOCl irrigation. All abscess and initial root canal samples were positive for bacteria. At least one of the target resistance genes was found in 36% of the abscess samples and 67% of the asymptomatic cases. The most prevalent genes in abscesses were blaTEM (24%) and ermC (24%), while tetM (42%) and tetW (29%) prevailed in asymptomatic cases. The blaTEM gene was significantly associated with acute cases (p=0.02). Conversely, tetM was significantly more prevalent in asymptomatic cases (p=0.008). Treatment eliminated resistance genes from most cases. Acute and chronic endodontic infections harboured resistance genes for 3 classes of widely used antibiotics. In most cases, treatment was effective in eliminating these genes, but there were a few cases in which they persisted. The implications of persistence are unknown. Direct detection of resistance genes in abscesses may be a potential method for rapid diagnosis and establishment of proactive antimicrobial therapy. Copyright © 2013 Elsevier Ltd. All rights reserved.

The Bordetella Bps polysaccharide is required for biofilm formation and persistence in the lower respiratory tract of swine

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Bordetella bronchiseptica is pervasive in swine populations and plays multiple roles in respiratory disease. Additionally, B. bronchiseptica is capable of establishing long-term or chronic infections in swine. Bacterial biofilms are increasingly recognized as important contributors to chronic bacter...

Extensive chromatin remodelling and establishment of transcription factor 'hotspots' during early adipogenesis

DEFF Research Database (Denmark)

Siersbæk, Rasmus; Nielsen, Ronni; John, Sam

2011-01-01

hypersensitive site analysis to investigate the genome-wide changes in chromatin structure that accompany the binding of adipogenic transcription factors. These analyses revealed a dramatic and dynamic modulation of the chromatin landscape during the first hours of adipocyte differentiation that coincides...... and chromatin remodelling and is required for their establishment. Furthermore, a subset of early remodelled C/EBP-binding sites persists throughout differentiation and is later occupied by PPARγ, indicating that early C/EBP family members, in addition to their well-established role in activation of PPARγ...

Poor outcomes of chronic active Epstein-Barr virus infection and hemophagocytic lymphohistiocytosis in non-Japanese adult patients

OpenAIRE

Sonke, Gabe; Ludwig, Inge; Oosten, Hannah; Baars, Joke; Meijer, Ellen; Kater, Arnon; Jong, Daphne

2008-01-01

textabstractChronic active Epstein-Barr virus infection manifests as a combination of persistent infectious mononucleosis-like symptoms and high viral load in apparently immunocompetent patients. It is closely related to Epstein-Barr virus-associated hemophagocytic lymphohistiocytosis. These 2 abnormal Epstein-Barr virus-associated diseases are seldom reported in individuals other than Japanese children and adolescents. We report a series of 2 adult non-Japanese patients with fatal chronic ac...

Interferon-gamma in progression to chronic demyelination and neurological deficit following acute EAE

DEFF Research Database (Denmark)

Renno, T; Taupin, V; Bourbonnière, L

1998-01-01

The cytokine interferon-gamma (IFNgamma) is implicated in the induction of acute CNS inflammation, but it is less clear what role if any IFNgamma plays in progression to chronic demyelination and neurological deficit. To address this issue, we have expressed IFNgamma in myelinating oligodendrocytes....... In contrast to control mice, which remit from EAE with resolution of glial reactivity and leukocytic infiltration, transgenics showed chronic neurological deficits. While activated microglia/macrophages persisted in demyelinating lesions for over 100 days, CD4(+) T lymphocytes were no longer present in CNS...

Fatigue, burnout, and chronic fatigue syndrome among employees on sick leave: do attributions make the difference?

NARCIS (Netherlands)

Huibers, M.J.H.; Beurskens, A.J.H.M.; Prins, J.B.; Kant, I.J.; Bazelmans, H.M.; Schayck, C.P. van; Knottnerus, J.A.; Bleijenberg, G.

2003-01-01

BACKGROUND: Persistent fatigue among employees, burnout, and chronic fatigue syndrome (CFS) are three fatigue conditions that share some characteristics in theory. However, these conditions have not been compared in empirical research, despite conceptual similarities. METHODS: This cross sectional

INCIDENCE AND RISK FACTORS FOR CHRONIC PELVIC PAIN AFTER HYSTEROSCOPIC STERILIZATION

Science.gov (United States)

YUNKER, Amanda C.; RITCH, Jessica M. B.; ROBINSON, Erica F.; GOLISH, Cara T.

2014-01-01

Objective To investigate the incidence and pre-operative risk factors for developing pelvic pain after hysteroscopic sterilization using the Essure™ micro-inserts Design Retrospective cohort study (Canadian Task Force classification II-2). Setting University Medical Center Patients A total of 458 patients who underwent hysteroscopic sterilization with Essure™ between January 1, 2005 and June 30, 2012. Results The incidence of acute pelvic pain after hysteroscopic sterilization was 8.1%, and the incidence of persistent pain after 3 months post-procedure was 4.2%. The range of presentation with pain was 1 to 469 days, with a mean time of 56 days. Of the patients that developed chronic pelvic pain after the procedure, 75% presented within 130 days of the procedure. Patients with previous diagnoses of any chronic pain (chronic pelvic pain, chronic low back pain, chronic headache, and fibromyalgia) were more likely to report both acute pain (OR 6.81, 95% CI 2.95,15.73) and chronic pain (OR 6.15, 95% CI 2.10,18.10) after hysteroscopic sterilization. Conclusions Pelvic pain may develop after hysteroscopic sterilization. Patients with preexisting chronic pain diagnoses may be at increased risk of developing pelvic pain after the procedure. Fifty percent of new pelvic pain after Essure™ placement will resolve by 3 months. PMID:24952343

CD16(+) monocytes with smooth muscle cell characteristics are reduced in human renal chronic transplant dysfunction

NARCIS (Netherlands)

Boersema, M.; van den Born, Joost; van Ark, J.; Harms, Geertruida; Seelen, M. A.; van Dijk, M. C. R. F.; van Goor, H.; Navis, G. J.; Popa, E. R.; Hillebrands, J. L.

In chronic transplant dysfunction (CTD), persistent (allo)immune-mediated inflammation eventually leads to tissue remodeling including neointima formation in intragraft arteries. We previously showed that recipient-derived neointimal alpha-SMA(+) smooth muscle-like cells are present in human renal

Chronic subdural hematoma secondary to traumatic subdural hygroma

International Nuclear Information System (INIS)

Hong, Deok Hwa; Lim, Han Hyuk; Bae, Won Kyung; Kim, Pyo Nyun; Kim, Il Young; Lee, Byung Ho; Lee, Kyeong Seok

1994-01-01

Sometimes chronic subdural hematoma can be developed following posttraumatic subdural hygroma. The purpose of this study is to investigate its incidence, the duration required for their conversion, and characteristic CT and MR findings of subdural hygroma and chronic subdural hamatoma. We studied 8 patients with persistent posttraumatic subdural hygroma which consequently developed chronic subdural hamatoma. The patients were examined with CT initially and followed-up with CT in 3 and MR in 5. We analyzed the location of the lesion, the change of the density or signal intensity, the change of the size, and the degree of enhancement and mass effect. The duration required for the formation of hematoma was 48-166 days (mean, 76 days). The characteristic CT findings of subdural hygroma were a crescentric lesion with CSF density along the inner table with-out contrast enhancement. The mass effect was minimal. The CT findings of chronic subdural hematoma were higher density than that of hygroma in all cases, increase in thickness and size in 3 cases, and contrast enhancement along the inner membrane of the hematoma in 5 cases. The signal intensities of the subdural hygroma were identical to those of CSF on both T1 and T2 weighted images, whereas, those of chronic subdural hamatoma were higher. The increased signal intensity on T1 weighted MR images and increased attenuation or contrast enhancement of the lesion on CT may suggest the conversion of subdural hygroma into chronic subdural hematoma

Chronic subdural hematoma secondary to traumatic subdural hygroma

Energy Technology Data Exchange (ETDEWEB)

Hong, Deok Hwa; Lim, Han Hyuk; Bae, Won Kyung; Kim, Pyo Nyun; Kim, Il Young; Lee, Byung Ho; Lee, Kyeong Seok [Soonchunhyang University Chonan Hospital, Cheonan (Korea, Republic of)

1994-02-15

Sometimes chronic subdural hematoma can be developed following posttraumatic subdural hygroma. The purpose of this study is to investigate its incidence, the duration required for their conversion, and characteristic CT and MR findings of subdural hygroma and chronic subdural hamatoma. We studied 8 patients with persistent posttraumatic subdural hygroma which consequently developed chronic subdural hamatoma. The patients were examined with CT initially and followed-up with CT in 3 and MR in 5. We analyzed the location of the lesion, the change of the density or signal intensity, the change of the size, and the degree of enhancement and mass effect. The duration required for the formation of hematoma was 48-166 days (mean, 76 days). The characteristic CT findings of subdural hygroma were a crescentric lesion with CSF density along the inner table with-out contrast enhancement. The mass effect was minimal. The CT findings of chronic subdural hematoma were higher density than that of hygroma in all cases, increase in thickness and size in 3 cases, and contrast enhancement along the inner membrane of the hematoma in 5 cases. The signal intensities of the subdural hygroma were identical to those of CSF on both T1 and T2 weighted images, whereas, those of chronic subdural hamatoma were higher. The increased signal intensity on T1 weighted MR images and increased attenuation or contrast enhancement of the lesion on CT may suggest the conversion of subdural hygroma into chronic subdural hematoma.

Inflation persistence and flexible prices

OpenAIRE

Robert Dittmar; William T. Gavin; Finn E. Kydland

2004-01-01

If the central bank follows an interest rate rule, then inflation is likely to be persistence, even when prices are fully flexible. Any shock, whether persistent or not, may lead to inflation persistence. In equilibrium, the dynamics of inflation are determined by the evolution of the spread between the real interest rate and the central bank’s target. Inflation persistence in U.S. data can be characterized by a vector autocorrelation function relating inflation and deviations of output from ...

Chronic pyelonephritis: Modulation of host defenses by cyclosporin A

International Nuclear Information System (INIS)

Findon, G.; Miller, T.E.

1989-01-01

Chronic experimental pyelonephritis is characterized by a stable level of infection, which persists for many months. Administration of cyclosporin A (CsA) reactivated previously healed renal lesions and caused a marked increase in bacterial numbers in the kidney. Studies were then carried out to compare the effects of CsA, and the nonselective cytodepletive agents irradiation and cyclophosphamide, on both host defenses and the bacteriologic status of chronically infected kidneys. Two different responses were observed. In animals treated with CsA, bacterial numbers increased markedly, although circulating neutrophil numbers were relatively unaffected. This observation was in contrast to the severe ablation of leukocyte numbers and competence needed to achieve an equivalent effect when irradiation and cyclophosphamide were used. One possible explanation for the adverse effect of CsA on the host-parasite balance in chronic pyelonephritis is that CsA affects mediators that control the inflammatory response or induces a qualitative change in a critical cellular defense compartment

Analysis of electrocardiogram in chronic obstructive pulmonary disease patients.

Science.gov (United States)

Lazović, Biljana; Svenda, Mirjana Zlatković; Mazić, Sanja; Stajić, Zoran; Delić, Marina

2013-01-01

Chronic obstructive pulmonary disease is the fourth leading cause of mortality worldwide. It is defined as a persistent airflow limitation usually progressive and not fully reversible to treatment. The diagnosis of chronic obstructive pulmonary disease and severity of disease is confirmed by spirometry. Chronic obstructive pulmonary disease produces electrical changes in the heart which shows characteristic electrocardiogram pattern. The aim of this study was to observe and evaluate diagnostic values of electrocardiogram changes in chronic obstructive pulmonary disease patients with no other comorbidity. We analyzed 110 electrocardiogram findings in clinically stable chronic obstructive pulmonary disease patients and evaluated the forced expiratory volume in the first second, ratio of forces expiratory volume in the first second to the fixed vital capacity, chest radiographs and electrocardiogram changes such as p wave height, QRS axis and voltage, right bundle branch block, left bundle branch block, right ventricular hypertrophy, T wave inversion in leads V1-V3, S1S2S3 syndrome, transition zone in praecordial lead and QT interval. We found electrocardiogram changes in 64% patients, while 36% had normal electrocardiogram. The most frequent electrocardiogram changes observed were transition zone (76.36%) low QRS (50%) and p pulmonale (14.54%). Left axis deviation was observed in 27.27% patients. Diagnostic values of electrocardiogram in patients with chronic obstructive pulmonary disease suggest that chronic obstructive pulmonary disease patients should be screened electrocardiographically in addition to other clinical investigations.

Modulation of the immune response by Fonsecaea pedrosoi morphotypes in the course of experimental chromoblastomycosis and their role on inflammatory response chronicity.

Directory of Open Access Journals (Sweden)

Isaque Medeiros Siqueira

2017-03-01

Full Text Available A common theme across multiple fungal pathogens is their ability to impair the establishment of a protective immune response. Although early inflammation is beneficial in containing the infection, an uncontrolled inflammatory response is detrimental and may eventually oppose disease eradication. Chromoblastomycosis (CBM, a cutaneous and subcutaneous mycosis, caused by dematiaceous fungi, is capable of inducing a chronic inflammatory response. Muriform cells, the parasitic form of Fonsecaea pedrosoi, are highly prevalent in infected tissues, especially in long-standing lesions. In this study we show that hyphae and muriform cells are able to establish a murine CBM with skin lesions and histopathological aspects similar to that found in humans, with muriform cells being the most persistent fungal form, whereas mice infected with conidia do not reach the chronic phase of the disease. Moreover, in injured tissue the presence of hyphae and especially muriform cells, but not conidia, is correlated with intense production of pro-inflammatory cytokines in vivo. High-throughput RNA sequencing analysis (RNA-Seq performed at early time points showed a strong up-regulation of genes related to fungal recognition, cell migration, inflammation, apoptosis and phagocytosis in macrophages exposed in vitro to muriform cells, but not conidia. We also demonstrate that only muriform cells required FcγR and Dectin-1 recognition to be internalized in vitro, and this is the main fungal form responsible for the intense inflammatory pattern observed in CBM, clarifying the chronic inflammatory reaction observed in most patients. Furthermore, our findings reveal two different fungal-host interaction strategies according to fungal morphotype, highlighting fungal dimorphism as an important key in understanding the bipolar nature of inflammatory response in fungal infections.

Diagnosis and treatment of chronic bacterial prostatitis and chronic prostatitis/chronic pelvic pain syndrome: a consensus guideline.

Science.gov (United States)

Rees, Jon; Abrahams, Mark; Doble, Andrew; Cooper, Alison

2015-10-01

To improve awareness and recognition of chronic bacterial prostatitis (CBP) and chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS) among non-specialists and patients. To provide guidance to healthcare professionals treating patients with CBP and CP/CPPS, in both non-specialist and specialist settings. To promote efficient referral of care between non-specialists and specialists and the involvement of the multidisciplinary team (MDT). The guideline population were men with CBP or CP/CPPS (persistent or recurrent symptoms and no other urogenital pathology for ≥3 of the previous 6 months). Consensus recommendations for the guidelines were based on a search to identify literature on the diagnosis and management of CBP and CP/CPPS (published between 1999 and February 2014). A Delphi panel process was used where high-quality, published evidence was lacking. CBP and CP/CPPS can present with a wide range of clinical manifestations. The four main symptom domains are urogenital pain, lower urinary tract symptoms (LUTS - voiding or storage symptoms), psychological issues and sexual dysfunction. Patients should be managed according to their individual symptom pattern. Options for first-line treatment include antibiotics, α-adrenergic antagonists (if voiding LUTS are present) and simple analgesics. Repeated use of antibiotics, such as quinolones, should be avoided if there is no obvious symptomatic benefit from infection control or cultures do not support an infectious cause. Early use of treatments targeting neuropathic pain and/or referral to specialist services should be considered for patients who do not respond to initial measures. An MDT approach (urologists, pain specialists, nurse specialists, specialist physiotherapists, general practitioners, cognitive behavioural therapists/psychologists, and sexual health specialists) is recommended. Patients should be fully informed about the possible underlying causes and treatment options, including an explanation of

The evolution of the surgical treatment of chronic pancreatitis.

Science.gov (United States)

Andersen, Dana K; Frey, Charles F

2010-01-01

To establish the current status of surgical therapy for chronic pancreatitis, recent published reports are examined in the context of the historical advances in the field. The basis for decompression (drainage), denervation, and resection strategies for the treatment of pain caused by chronic pancreatitis is reviewed. These divergent approaches have finally coalesced as the head of the pancreas has become apparent as the nidus of chronic inflammation. The recent developments in surgical methods to treat the complications of chronic pancreatitis and the results of recent prospective randomized trials of operative approaches were reviewed to establish the current best practices. Local resection of the pancreatic head, with or without duct drainage, and duodenum-preserving pancreatic head resection offer outcomes as effective as pancreaticoduodenectomy, with lowered morbidity and mortality. Local resection or excavation of the pancreatic head offers the advantage of lowest cost and morbidity and early prevention of postoperative diabetes. The late incidences of recurrent pain, diabetes, and exocrine insufficiency are equivalent for all 3 surgical approaches. Local resection of the pancreatic head appears to offer best outcomes and lowest risk for the management of the pain of chronic pancreatitis.

Physical trust-based persistent authentication

DEFF Research Database (Denmark)

Fujita, Masahiro; Jensen, Christian D.; Arimura, Shiori

2015-01-01

propose a new type of persistent authentication, called Persistent Authentication Based On physical Trust (PABOT). PABOT uses a context of “physical trust relationship” that is built by visual contact between users, and thus can offer a persistent authentication mechanism with better usability and higher...

Increased serum concentration of G-CSF in cystic fibrosis patients with chronic Pseudomonas aeruginosa pneumonia

DEFF Research Database (Denmark)

Jensen, Peter Østrup; Moser, C; Kharazmi, A

2006-01-01

BACKGROUND: Chronic Pseudomonas aeruginosa lung infection is the major reason for premature death in patients with cystic fibrosis (CF). Infected patients experience a progressive deterioration of the lung tissue caused by a persistent accumulation of PMNs. We investigated if the pulmonary...... was reduced. CONCLUSION: G-CSF in the sera may contribute to the pulmonary inflammation in CF patients with chronic P. aeruginosa lung infection by regulating the number of PMNs available for migration and may be considered as an indicator of clinical status....

Course of Skin Symptoms and Quality of Life in Children Referred for Patch Testing

DEFF Research Database (Denmark)

Simonsen, Anne B; Sommerlund, Mette; Deleuran, Mette

2015-01-01

Children are patch tested in the same manner as adults, but little has been done to establish whether positive or negative findings influence the course of skin symptoms. To uncover the course of skin symptoms and the impact of persistent eczema on life quality in paediatric patients referred...... to follow-up. Among patients without atopic dermatitis, 23.5% reported to suffer from chronic eczema. Persistent eczema increased the risk of severe impairment of life quality. Our findings indicate a significant risk of childhood eczema becoming chronic and affecting life quality considerably. Patch...

Families of Children with Chronic Illness and the Relational Family Model

Directory of Open Access Journals (Sweden)

Tanja Pate

2016-09-01

Full Text Available Families of children with chronic illness experience persistent stress. Facing the diagnosis and learning how to cope with it is a stressful experience not only for the child but also for the parents and for the whole family. The illness, with its unpredictability and treatment, disturbs their daily routine and threatens the whole family system. Parental involvement in the child’s disease management and their emotional support are crucial for effective coping and adaptation to the child’s chronic illness. The aim of this article is to present the importance of the parental role in these families through theoretical findings of the relational family model.

[Prevention of Chronic Kidney Disease and strategies to counteract chronic diseases in Italy].

Science.gov (United States)

Mastrilli, Valeria; D'Elia, Roberto; Galeone, Daniela

2016-01-01

The Prevention of Chronic Kidney Disease (CKD) is placed in the more general context of prevention of major chronic Non Communicable Diseases (NCDs): cardiovascular diseases, diabetes, chronic lung diseases and tumors that are the main problem for public health worldwide. Any health policy strategy aimed to the prevention of NCDs has to provide knowledge of health and socioeconomic status of the population, to reduce the level of exposure to risk factors and to adapt health services to the request for assistance. To this purpose, population monitoring systems have been implemented in the last years. The NCDs share some risk factors that are related, in large part, to unhealthy individual behaviours: smoking, alcohol abuse, unhealthy diet and physical inactivity. NCDs prevention has to be understood as the set of all actions, sanitary and not, aiming to prevent or delay the onset of diseases or their complications. Preventive measures should, therefore, involve not only the health sector but also all the actors that can help to prevent that disease. As for the Prevention of CKD, the Ministry of Health has established a working table, which handled the Drafting of the "Position paper for the CKD", approved in the State-Regions Conference on august 8th 2014. The document draws a national strategy to combat this disease through primary prevention, early diagnosis and the establishment of diagnostic - therapeutic pathways (DTP).

Analogue Between Dynamic Hamiltonian-Operators of a Mesoscopic Ring Carrying Persistent Current and a Josephson Junction

International Nuclear Information System (INIS)

Fan Hongyi; Wang Jisuo

2006-01-01

By making the analogy between the operator Hamiltonians of a mesoscopic ring carrying the persistent current and a Josephson junction we have introduced a phase operator and entangled state representation to establish a theoretical formalism for the ring system.

Chronic, refractory CRPS involving 3 limbs: a case report.

Science.gov (United States)

Zyluk, A

2013-06-01

We report the case of a 26-year-old woman with CRPS involving consecutively 3 extremities during 8 years. None of the treatments used was effective and each CRPS episode resulted in persistence and chronification of the disease. We suggest that this patient presents a specific subtype of the disease, called "chronic, refractory CRPS" which is extremely severe, disabling and resistant to treatment. © Georg Thieme Verlag KG Stuttgart · New York.

Histopathological analysis of Salmonella chronic carriage in the mouse hepatopancreatobiliary system.

Directory of Open Access Journals (Sweden)

Geoffrey Gonzalez-Escobedo

Full Text Available Salmonella Typhi asymptomatic chronic carriage represents a challenge for the diagnosis and prevention of typhoid fever in endemic areas. Such carriers are thought to be reservoirs for further spread of the disease. Gallbladder carriage has been demonstrated to be mediated by biofilm formation on gallstones and by intracellular persistence in the gallbladder epithelium of mice. In addition, both gallstones and chronic carriage have been associated with chronic inflammation and the development of gallbladder carcinoma. However, the pathogenic relationship between typhoid carriage and the development of pre-malignant and/or malignant lesions in the hepatopancreatobiliary system as well as the host-pathogen interactions occurring during chronic carriage remains unclear. In this study, we monitored the histopathological features of chronic carriage up to 1 year post-infection. Chronic cholecystitis and hepatitis ranging from mild to severe were present in infected mice regardless of the presence of gallstones. Biliary epithelial hyperplasia was observed more commonly in the gallbladder of mice with gallstones (uninfected or infected. However, pre-malignant lesions, atypical hyperplasia and metaplasia of the gallbladder and exocrine pancreas, respectively, were only associated with chronic Salmonella carriage. This study has implications regarding the role of Salmonella chronic infection and inflammation in the development of pre-malignant lesions in the epithelium of the gallbladder and pancreas that could lead to oncogenesis.

Persistent Identifiers for Dutch cultural heritage institutions

Science.gov (United States)

Ras, Marcel; Kruithof, Gijsbert

2016-04-01

Over the past years, more and more collections belonging to archives, libraries, media, museums, and knowledge institutes are being digitised and made available online. These are exciting times for ALM institutions. They are realising that, in the information society, their collections are goldmines. Unfortunately most heritage institutions in the Netherlands do not yet meet the basic preconditions for long-term availability of their collections. The digital objects often have no long lasting fixed reference yet. URL's and web addresses change. Some digital objects that were referenced in Europeana and other portals can no longer be found. References in scientific articles have a very short life span, which is damaging for scholarly research. In 2015, the Dutch Digital Heritage Network (NDE) has started a two-year work program to co-ordinate existing initiatives in order to improve the (long-term) accessibility of the Dutch digital heritage for a wide range of users, anytime, anyplace. The Digital Heritage Network is a partnership established on the initiative of the Ministry of Education, Culture and Science. The members of the NDE are large, national institutions that strive to professionally preserve and manage digital data, e.g. the National Library, The Netherlands Institute for Sound and Vision, the Netherlands Cultural Heritage Agency, the Royal Netherlands Academy of Arts and Sciences, the National Archive of the Netherlands and the DEN Foundation, and a growing number of associations and individuals both within and outside the heritage sector. By means of three work programmes the goals of the Network should be accomplished and improve the visibility, the usability and the sustainability of digital heritage. Each programme contains of a set of projects. Within the sustainability program a project on creating a model for persistent identifiers is taking place. The main goals of the project are (1) raise awareness among cultural heritage institutions on the

Renal perfusion in chronic liver diseases: Evaluation by radiotechnetium renography

International Nuclear Information System (INIS)

Fanfani, G.; Fratello, A.; Mele, M.; Conte, E.; D'Addabbo, A.; Greco, L.

1985-01-01

Twenty-four patients with chronic liver diseases and seven normal controls were studied using renal and hepatic radiotechnetium angiography. The time-activity histograms generated were employed to calculate both the renal perfusion index (RPI) and the hepatic perfusion index (HPI). Renal perfusion proved to be reduced not only in cirrhotic patients but also in patients with aggressive chronic hepatitis, as well as in those with persistent chronic hepatitis. The HPI, which is to be considered as being strictly dependent on portal flow, only fell significantly in the group of cirrhotic patients. In all patient groups, the correlation coefficient between the HPI and RPI (mean of the two kidneys) was low (r=0.275) and not significant (P>0.05). After Warren's splenorenal derivation, renal perfusion did not improve but worsened, particularly in the left kidney where derivation anastomosis probably caused a venous overload. (orig.)

Chronic perfluorooctane sulfonate (PFOS) exposure induces hepatic steatosis in zebrafish

International Nuclear Information System (INIS)

Cheng, Jiangfei; Lv, Suping; Nie, Shangfei; Liu, Jing; Tong, Shoufang; Kang, Ning; Xiao, Yanyan; Dong, Qiaoxiang; Huang, Changjiang; Yang, Dongren

2016-01-01

Highlights: • PFOS chronic exposure induces sex-dependent hepatic steotosis in zebrafish. • PFOS interferes with β-oxidation, lipid synthesis, and lipid hepatic export process. • Zebrafish could be used as an alternative model for PFOS chronic toxicity screening. - Abstract: Perfluorooctane sulfonate (PFOS), one persistent organic pollutant, has been widely detected in the environment, wildlife and human. Currently few studies have documented the effects of chronic PFOS exposure on lipid metabolism, especially in aquatic organisms. The underlying mechanisms of hepatotoxicity induced by chronic PFOS exposure are still largely unknown. The present study defined the effects of chronic exposure to low level of PFOS on lipid metabolism using zebrafish as a model system. Our findings revealed a severe hepatic steatosis in the liver of males treated with 0.5 μM PFOS as evidenced by hepatosomatic index, histological assessment and liver lipid profiles. Quantitative PCR assay further indicated that PFOS significantly increase the transcriptional expression of nuclear receptors (nr1h3, rara, rxrgb, nr1l2) and the genes associated with fatty acid oxidation (acox1, acadm, cpt1a). In addition, chronic PFOS exposure significantly decreased liver ATP content and serum level of VLDL/LDL lipoprotein in males. Taken together, these findings suggest that chronic PFOS exposure induces hepatic steatosis in zebrafish via disturbing lipid biosynthesis, fatty acid β-oxidation and excretion of VLDL/LDL lipoprotein, and also demonstrate the validity of using zebrafish as an alternative model for PFOS chronic toxicity screening.

Chronic perfluorooctane sulfonate (PFOS) exposure induces hepatic steatosis in zebrafish

Energy Technology Data Exchange (ETDEWEB)

Cheng, Jiangfei; Lv, Suping; Nie, Shangfei; Liu, Jing; Tong, Shoufang; Kang, Ning; Xiao, Yanyan; Dong, Qiaoxiang [Zhejiang Provincial Key Laboratory for Technology and Application of Model Organisms (China); Institute of Environmental Safety and Human Health, Wenzhou Medical University, Wenzhou, 325035 (China); Huang, Changjiang, E-mail: cjhuang5711@163.com [Zhejiang Provincial Key Laboratory for Technology and Application of Model Organisms (China); Institute of Environmental Safety and Human Health, Wenzhou Medical University, Wenzhou, 325035 (China); Yang, Dongren, E-mail: yangdongren@yahoo.com [Zhejiang Provincial Key Laboratory for Technology and Application of Model Organisms (China); Institute of Environmental Safety and Human Health, Wenzhou Medical University, Wenzhou, 325035 (China)

2016-07-15

Highlights: • PFOS chronic exposure induces sex-dependent hepatic steotosis in zebrafish. • PFOS interferes with β-oxidation, lipid synthesis, and lipid hepatic export process. • Zebrafish could be used as an alternative model for PFOS chronic toxicity screening. - Abstract: Perfluorooctane sulfonate (PFOS), one persistent organic pollutant, has been widely detected in the environment, wildlife and human. Currently few studies have documented the effects of chronic PFOS exposure on lipid metabolism, especially in aquatic organisms. The underlying mechanisms of hepatotoxicity induced by chronic PFOS exposure are still largely unknown. The present study defined the effects of chronic exposure to low level of PFOS on lipid metabolism using zebrafish as a model system. Our findings revealed a severe hepatic steatosis in the liver of males treated with 0.5 μM PFOS as evidenced by hepatosomatic index, histological assessment and liver lipid profiles. Quantitative PCR assay further indicated that PFOS significantly increase the transcriptional expression of nuclear receptors (nr1h3, rara, rxrgb, nr1l2) and the genes associated with fatty acid oxidation (acox1, acadm, cpt1a). In addition, chronic PFOS exposure significantly decreased liver ATP content and serum level of VLDL/LDL lipoprotein in males. Taken together, these findings suggest that chronic PFOS exposure induces hepatic steatosis in zebrafish via disturbing lipid biosynthesis, fatty acid β-oxidation and excretion of VLDL/LDL lipoprotein, and also demonstrate the validity of using zebrafish as an alternative model for PFOS chronic toxicity screening.

Postoperative course of chronic subdural hematoma

International Nuclear Information System (INIS)

Takahashi, Toshiaki; Tsubone, Kyoji; Kyuma, Yoshikazu; Kuwabara, Takeo

1983-01-01

1) Fourty cases of chronic subdural hematoma were operated on by trephination, irrigation and external drainage. Postoperative neurological recovery and decrease of hematoma cavity on CT scan were followed. 2) Operation were effective for recovery of neurological grade in 28 cases, moderately effective in 7 cases and not effective in 5 cases. 3) Withinthe tenth postoperative day, more than half residual hematoma cavity existed in 53% of examined cases. After that, more than half residual cavity existed in only 17%. 4) Preoperative feature of neurologically unimproved cases were no definite history of head trauma and water like low density of hematoma cavity. Postoperative feature was persistence of more than three fourth of residual hematoma cavity on CT scan. 5) A group of unimproved cases described above are thought to have a feature of subdural hygroma rather than subdural hematoma. When possibility of subdural hygroma is high in preoperative differential diagnosis, indication of operation should be different from chronic subdural hematoma. (author)

PERSISTENCE IN PERFORMANCE FOR MUTUAL FUNDS IN PERIODS OF CRISIS

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Theodoros KARGIDIS

2012-09-01

Full Text Available The study investigates the persistence in performance for a sample of South European funds, domiciled in Portugal, Italy, Greece and Spain. Employing the Sharpe ratio, risk adjusted performance is measured in an attempt to judge the influence of the 2008 crisis and the current debt crisis on funds’ inclination to persist in their previous returns record. Examination period extends from January 2004 to December 2010 incorporating stages of relative stability in the stock and bond markets while also capturing the early stages of the eurozone crisis. We categorize funds as winners and losers in consecutive 6-monthly periods, thus being able to judge persistence in the short run, while our results suggest that the identification of winners and losers could enable us to investigate the possibility to gain investment advantages through this finding. Overall results suggest evidence of persistent results, whether positive or negative, both during the 2008 crisis and the current debt crisis, leading us to deduce that factors leading to performance persistence are not affected by market changes, since medium to long term persistence bypasses any temporary market mischief. This finding could be of use for fund managers aiming at establishing viable investment strategies, at their epicenter being the exploitation of such clues, suggesting persistence in returns. A fund of funds manager employing funds both in equities and fixed income could potentially choose to invest exclusively or more heavily in the winners of previous periods and avoid accordingly poor performers, thus achieving higher returns on average. For this purpose simple investment strategies are employed where we test the outcome of an investment strategy that would invest on fixed income securities by choosing those funds that were winners in the distribution of returns in the previous 6-monthly period, while disinvesting from poor performers and funds switching sides in performance

Clinical effects of chronic irradiation in conditions of Chernobyl exclusion zone

International Nuclear Information System (INIS)

Nyagu, A.I.; Loganovskij, K.N.; Kostyuchenko, V.G.

1999-01-01

Threshold doses for des adaptation syndrome development during chronic external and internal irradiation were found. Effects of small dose accumulation were established. Chronic irradiation is resulted in different dystrophic processes, psychosomatic violations and in increase of stochastic effects

Nerve Wrapping of the Sciatic Nerve With Acellular Dermal Matrix in Chronic Complete Proximal Hamstring Ruptures and Ischial Apophyseal Avulsion Fractures

Science.gov (United States)

Haus, Brian M.; Arora, Danny; Upton, Joseph; Micheli, Lyle J.

2016-01-01

Background: Patients with chronic injuries of the proximal hamstring can develop significant impairment because of weakness of the hamstring muscles, sciatic nerve compression from scar formation, or myositis ossificans. Purpose: To describe the surgical outcomes of patients with chronic injury of the proximal hamstrings who were treated with hamstring repair and sciatic neurolysis supplemented with nerve wrapping with acellular dermal matrix. Study Design: Retrospective case series; Level of evidence, 4. Methods: Fifteen consecutive patients with a diagnosis of chronic complete proximal hamstring rupture or chronic ischial tuberosity apophyseal avulsion fracture (mean age, 39.67 years; range, 14-69 years) were treated with proximal hamstring repair and sciatic neurolysis supplemented with nerve wrapping with acellular dermal matrix. Nine patients had preoperative sciatica, and 6 did not. Retrospective chart review recorded clinical outcomes measured by the degree of pain relief, the rate of return to activities, and associated postoperative complications. Results: All 15 patients were followed in the postoperative period for an average of 16.6 months. Postoperatively, there were 4 cases of transient sciatic nerve neurapraxia. Four patients (26%) required postoperative betamethasone sodium phosphate (Celestone Soluspan) injectable suspension USP 6 mg/mL. Among the 9 patients with preoperative sciatica, 6 (66%) had a good or excellent outcome and were able to return to their respective activities/sports; 3 (33%) had persistent chronic pain. One of these had persistent sciatic neuropathy that required 2 surgical reexplorations and scar excision after development of recurrent extraneural scar formation. Among the 6 without preoperative sciatica, 100% had a good or excellent outcomes and 83% returned to their respective activities/sports. Better outcomes were observed in younger patients, as the 3 cases of persistent chronic sciatic pain were in patients older than 45

Damage of hippocampal neurons in rats with chronic alcoholism.

Science.gov (United States)

Du, Ailin; Jiang, Hongbo; Xu, Lei; An, Na; Liu, Hui; Li, Yinsheng; Zhang, Ruiling

2014-09-01

Chronic alcoholism can damage the cytoskeleton and aggravate neurological deficits. However, the effect of chronic alcoholism on hippocampal neurons remains unclear. In this study, a model of chronic alcoholism was established in rats that were fed with 6% alcohol for 42 days. Endogenous hydrogen sulfide content and cystathionine-beta-synthase activity in the hippocampus of rats with chronic alcoholism were significantly increased, while F-actin expression was decreased. Hippocampal neurons in rats with chronic alcoholism appeared to have a fuzzy nuclear membrane, mitochondrial edema, and ruptured mitochondrial crista. These findings suggest that chronic alcoholism can cause learning and memory decline in rats, which may be associated with the hydrogen sulfide/cystathionine-beta-synthase system, mitochondrial damage and reduced expression of F-actin.

Genome-wide linkage analysis of bronchodilator responsiveness and post-bronchodilator spirometric phenotypes in chronic obstructive pulmonary disease

NARCIS (Netherlands)

Palmer, LJ; Celedon, JC; Chapman, HA; Speizer, FE; Weiss, ST; Silverman, EK

2003-01-01

Chronic obstructive pulmonary disease (COPD) is a common, complex disease associated with significant and increasing morbidity and mortality. The cardinal feature of COPD is persistent airflow obstruction, measured by reductions in quantitative spirometric indices including forced expiratory volume

Poor outcomes of chronic active Epstein-Barr virus infection and hemophagocytic lymphohistiocytosis in non-Japanese adult patients

NARCIS (Netherlands)

Sonke, Gabe S.; Ludwig, Inge; van Oosten, Hannah; Baars, Joke W.; Meijer, Ellen; Kater, Arnon P.; de Jong, Daphne

2008-01-01

Chronic active Epstein-Barr virus infection manifests as a combination of persistent infectious mononucleosis-like symptoms and high viral load in apparently immunocompetent patients. It is closely related to Epstein-Barr virus associated hemophagocytic lymphohistiocytosis. These 2 abnormal

Poor outcomes of chronic active Epstein-Barr virus infection and hemophagocytic lymphohistiocytosis in non-Japanese adult patients

NARCIS (Netherlands)

G.S. Sonke (Gabe); I. Ludwig (Inge); H. van Oosten (Hannah); J.W. Baars (Joke); E. Meijer (Ellen); A.P. Kater (Arnon); D. de Jong (Daphne)

2008-01-01

textabstractChronic active Epstein-Barr virus infection manifests as a combination of persistent infectious mononucleosis-like symptoms and high viral load in apparently immunocompetent patients. It is closely related to Epstein-Barr virus-associated hemophagocytic lymphohistiocytosis. These 2

Exogenous BMP7 in aortae of rats with chronic uremia ameliorates expression of profibrotic genes, but does not reverse established vascular calcification

DEFF Research Database (Denmark)

Gravesen, Eva; Lerche Mace, Maria; Nordholm, Anders

2018-01-01

Hyperphosphatemia and vascular calcification are frequent complications of chronic renal failure and bone morphogenetic protein 7 (BMP7) has been shown to protect against development of vascular calcification in uremia. The present investigation examined the potential reversibility of established...... uremic vascular calcification by treatment of uremic rats with BMP7. A control model of isogenic transplantation of a calcified aorta from uremic rats into healthy littermates examined whether normalization of the uremic environment reversed vascular calcification. Uremia and vascular calcification were...... induced in rats by 5/6 nephrectomy, high phosphate diet and alfacalcidol treatment. After 14 weeks severe vascular calcification was present and rats were allocated to BMP7, vehicle or aorta transplantation. BMP7 treatment caused a significant decrease of plasma phosphate to 1.56 ± 0.17 mmol/L vs 2.06 ± 0...

Biomarker Guided Therapy in Chronic Heart Failure

Science.gov (United States)

Bektas, Sema

2015-01-01

This review article addresses the question of whether biomarker-guided therapy is ready for clinical implementation in chronic heart failure. The most well-known biomarkers in heart failure are natriuretic peptides, namely B-type natriuretic peptide (BNP) and N-terminal pro-BNP. They are well-established in the diagnostic process of acute heart failure and prediction of disease prognosis. They may also be helpful in screening patients at risk of developing heart failure. Although studied by 11 small- to medium-scale trials resulting in several positive meta-analyses, it is less well-established whether natriuretic peptides are also helpful for guiding chronic heart failure therapy. This uncertainty is expressed by differences in European and American guideline recommendations. In addition to reviewing the evidence surrounding the use of natriuretic peptides to guide chronic heart failure therapy, this article gives an overview of the shortcomings of the trials, how the results may be interpreted and the future directions necessary to fill the current gaps in knowledge. Therapy guidance in chronic heart failure using other biomarkers has not been prospectively tested to date. Emerging biomarkers, such as galectin-3 and soluble ST2, might be useful in this regard, as suggested by several post-hoc analyses. PMID:28785440

Persistent homology of complex networks

International Nuclear Information System (INIS)

Horak, Danijela; Maletić, Slobodan; Rajković, Milan

2009-01-01

Long-lived topological features are distinguished from short-lived ones (considered as topological noise) in simplicial complexes constructed from complex networks. A new topological invariant, persistent homology, is determined and presented as a parameterized version of a Betti number. Complex networks with distinct degree distributions exhibit distinct persistent topological features. Persistent topological attributes, shown to be related to the robust quality of networks, also reflect the deficiency in certain connectivity properties of networks. Random networks, networks with exponential connectivity distribution and scale-free networks were considered for homological persistency analysis

Persistent Tachypnea and Alveolar Hemorrhage in an Infant: An Unexpected Etiology

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John Bishara

2016-01-01

Full Text Available Persistent tachypnea and failure to thrive during infancy have a broad differential diagnosis which includes pulmonary and cardiovascular disorders. Diffuse alveolar hemorrhage (DAH is a rare entity in children. DAH requires an extensive work-up as certain conditions may need chronic therapy. Cardiovascular disorders are included in the etiology of DAH. We present a case of an 8-month-old female with a moderate, restrictive patent ductus arteriosus (PDA admitted to the hospital with respiratory distress and failure to thrive. An extensive work-up into tachypnea including multiple echocardiograms did not find an etiology. Open lung biopsy was performed and consistent with pulmonary hypertension. After closure of the PDA, patient’s tachypnea improved, and she was discharged home with periodic follow-up showing a growing, thriving child. When an infant presents with tachypnea, a respiratory viral illness is often a common cause. The diagnosis of persistent tachypnea requires further investigation. Echocardiography, although readily available, may not always be sensitive in detecting clinically significant pulmonary hypertension. A clinician must have a heightened index of suspicion to proceed in evaluating for causes of tachypnea with a nonrespiratory etiology.

Neuroendocrine Associations Underlying the Persistent Therapeutic Effects of Classic Serotonergic Psychedelics

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Emmanuelle A. D. Schindler

2018-03-01

Full Text Available Recent reports on the effects of psychedelic-assisted therapies for mood disorders and addiction, as well as the effects of psychedelics in the treatment of cluster headache, have demonstrated promising therapeutic results. In addition, the beneficial effects appear to persist well after limited exposure to the drugs, making them particularly appealing as treatments for chronic neuropsychiatric and headache disorders. Understanding the basis of the long-lasting effects, however, will be critical for the continued use and development of this drug class. Several mechanisms, including biological and psychological ones, have been suggested to explain the long-lasting effects of psychedelics. Actions on the neuroendocrine system are some such mechanisms that warrant further investigation in the study of persisting psychedelic effects. In this report, we review certain structural and functional neuroendocrinological pathologies associated with neuropsychiatric disorders and cluster headache. We then review the effects that psychedelic drugs have on those systems and provide preliminary support for potential long-term effects. The circadian biology of cluster headache is of particular relevance in this area. We also discuss methodologic considerations for future investigations of neuroendocrine system involvement in the therapeutic benefits of psychedelic drugs.

Bone scintigraphy in two cases of chronic brucellosis

International Nuclear Information System (INIS)

Kujat, C.; Neidl, K.; Mueller-Leisse, C.; Berg, D.

1989-01-01

As shown in the case reports, bone scintigraphy plays an important part considering the diagnosis of chronic brucellosis, an infectious disease which occurs rarely in Germany. To establish the diagnosis knowledge of symptoms and signs of the disease is necessary. Chronic brucellosis may occur in each organ, ionvolving especially bones and joints. The disease may manifest as spondilytis (especially of the lumbar spine) or arthritis of large joints, sacroiliacal joints or costotransverse joints. Chronic brucellosis has to be considered if a bone scan reveals a typical pattern even without a typical history. (orig.) [de

Trustworthy persistent identifier systems of the future

Science.gov (United States)

Golodoniuc, Pavel; Klump, Jens; Car, Nicholas

2016-04-01

Over the last two decades, persistent identifier (PID) systems have seen some significant changes in their governance policies, system capabilities, and technology. The development of most systems was driven by two main application areas, namely archives and libraries. Guidelines and criteria for trustworthy PID systems have been clearly devised (Bütikofer, 2009) and many PID system implementations for the identification of static digital objects have been built (e.g., PURL). However systems delivering persistent identifiers for dynamic datasets are not yet mature. There has been a rapid proliferation of different PID systems caused by the specific technical or organisational requirements of various communities that could not be met by existing systems such as DOI, ISBN, and EAN. Many of these different systems were limited by their inability to provide native means of persistent identifier resolution. This has prompted a decoupling of PID-associated data from the resolution service and this is where the Handle system has played a significant role. The Handle allowed to build a distributed system of independently managed resolver services. A trustworthy PID system must be designed to outlive the objects it provides persistent identifiers for, which may cease to exist or otherwise be deprecated, and the technology used to implement it, which will certainly need to change with time. We propose that such a system should rest on four pillars of agreements - (i) definitions, (ii) policies, (iii) services, and (iv) data services, to ensure longevity. While we believe all four pillars are equally important, we intentionally leave regulating aspects of issuing of identifiers and their registration out of the scope of this paper and focus on the agreements that have to be established between PID resolver services and the data sources indicated by the persistent identifiers. We propose an approach to development of PID systems that combines the use of (a) the Handle system

[Long term persistence of yellow fever neutralising antibodies in elderly persons].

Science.gov (United States)

Coulange Bodilis, H; Benabdelmoumen, G; Gergely, A; Goujon, C; Pelicot, M; Poujol, P; Consigny, P H

2011-10-01

The activity of the yellow fever virus is reemerging in areas without recent transmission history, such as northern Argentina and Paraguay, and persists in an epidemic mode in other countries in Africa and Latin America. Thus more and more travelers are at risk of being exposed to this disease. The population is becoming older, sometimes suffering from multiple pathologies. Moreover, the risk of serious adverse events associated with live-attenuated YF17D vaccine, such as multiple organ failure (YEL-AVD), reaches 1/50,000 vaccines in people over 65 versus 1/200,000 in the general population. We analyzed, in a retrospective study, the results of neutralizing antibody titers against yellow fever in people aged 60 and older, who had been previously vaccinated against yellow fever and had visited the International Vaccination Centre of the Institut Pasteur between January 2005 and February 2009. In this population of 84 persons (median age 69 years), the date of the last vaccination was always more than 10 years: it was precisely known in 68 subjects and alleged in 16 subjects. The median time since the previous vaccination was 14 years, with a maximum of 60 years. The indications of serology were: immunosuppressive therapy (19% of cases), cancer (32%), hemopathy (10.7%), HIV infection (3.6%), chronic hepatitis/chronic renal failure/dialysis (2.4%), autoimmune diseases (2.4%), and in 29.8% of cases, age alone was the indication of serology. The antibody titer was at a protective level in 95.2% of cases. The four individuals with negative serology had no formal documented proof of a previous vaccination against yellow fever. This serological study was able to show a persistent protective antibody titer, after a previous vaccination, even going back 60 years, allowing patients to travel in a yellow-fever endemic area despite a contraindication, and without requiring any vaccine booster.

Persistent injury-associated anemia: the role of the bone marrow microenvironment.

Science.gov (United States)

Millar, Jessica K; Kannan, Kolenkode B; Loftus, Tyler J; Alamo, Ines G; Plazas, Jessica; Efron, Philip A; Mohr, Alicia M

2017-06-15

The regulation of erythropoiesis involves hematopoietic progenitor cells, bone marrow stroma, and the microenvironment. Following severe injury, a hypercatecholamine state develops that is associated with increased mobilization of hematopoietic progenitor cells to peripheral blood and decreased growth of bone marrow erythroid progenitor cells that manifests clinically as a persistent injury-associated anemia. Changes within the bone marrow microenvironment influence the development of erythroid progenitor cells. Therefore, we sought to determine the effects of lung contusion, hemorrhagic shock, and chronic stress on the hematopoietic cytokine response. Bone marrow was obtained from male Sprague-Dawley rats (n = 6/group) killed 7 d after lung contusion followed by hemorrhagic shock (LCHS) or LCHS followed by daily chronic restraint stress (LCHS/CS). End point polymerase chain reaction was performed for interleukin-1β, interleukin-10, stem cell factor, transforming growth factor-β, high-mobility group box-1 (HMGB-1), and B-cell lymphoma-extra large. Seven days following LCHS and LCHS/CS, bone marrow expression of prohematopoietic cytokines (interleukin-1β, interleukin-10, stem cell factor, and transforming growth factor-β) was significantly decreased, and bone marrow expression of HMGB-1 was significantly increased. B-cell lymphoma-extra large bone marrow expression was not affected by LCHS or LCHS/CS (naïve: 44 ± 12, LCHS: 44 ± 12, LCHS/CS: 37 ± 1, all P > 0.05). The bone marrow microenvironment was significantly altered following severe trauma in a rodent model. Prohematopoietic cytokines were downregulated, and the proinflammatory cytokine HMGB-1 had increased bone marrow expression. Modulation of the bone marrow microenvironment may represent a therapeutic strategy following severe trauma to alleviate persistent injury-associated anemia. Copyright © 2017 Elsevier Inc. All rights reserved.

[Strategy for choosing antibiotics for treating bacterial infections associated with chronic tick-borne encephalitis].

Science.gov (United States)

Malenko, G V; Pogodina, V V; Frolova, M P; Ivannikova, T A

1996-01-01

The capacity of wide-spectrum antibiotics kefzol and ristomycin to activate the persisting tick-borne encephalitis (TBE) virus and cause an exacerbation of chronic process was investigated in Syrian hamsters in whom a prolonged (77 to 270 days) persistent TBE infection was induced by three TBE strains: Vasilchenko, V-383, and 205. The degree of antibiotic-induced activation was assessed using the criteria characterizing the reproduction and peculiarities of persisting TBE virus, immunodepression, and morphologic changes in the central nervous system. Effects of kefzol and ristomycin were compared with those of 8 antibiotics studied previously. Ristomycin, levomycetin (chloramphycin), penicillin, ampicillin (ampital), and levoridan were referred to drugs devoid of evident provoking effect. Kefzol (cefamezin), florimycin (viomycin), and kanamycin (kanamytrex) were characterized as weak activators and streptomycin and tetracycline as potent activators of the persisting TBE virus. These data may be used when selecting alternative agents for therapy of secondary bacterial infections concomitant with TBE.

Ossifying fibroma misdiagnosed as chronic apical periodontitis.

Science.gov (United States)

de Moraes Ramos-Perez, Flávia Maria; Soares, Ulysses Nicida; Silva-Sousa, Yara Teresinha Corrêa; da Cruz Perez, Danyel Elias

2010-03-01

Ossifying fibroma mimicking chronic apical periodontitis is extremely rare. This report describes a case of ossifying fibroma located in the periapical region of the mandibular right canine that was misdiagnosed as chronic apical periodontitis. A 40-year-old woman complained of slight pain in the right anterior mandibular region without mucosal abnormalities or swelling. Radiographically, a well-circumscribed, unilocular, radiolucent lesion was observed that was located in the periapical region of the mandibular right canine, which presented an endodontically treated root canal. Under local anesthesia, the lesion was fully excised. Microscopically, there was fibrocellular connective tissue associated with a mineralized component, which consisted of lamellar or trabecular and woven bone, compatible with the diagnosis of ossifying fibroma. Although it is very rare, ossifying fibroma should be considered in the differential diagnosis of unusual or persistent apical radiolucencies. Copyright (c) 2010 American Association of Endodontists. Published by Elsevier Inc. All rights reserved.

Asthenia in Children with Chronic Viral Hepatitis

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I.S. Lembryk

2015-02-01

Full Text Available In the article results of own researches concerning peculiarities of the course of asthenic syndrome in school-aged children with chronic hepatitis B, C and mixed forms are provided. It is established that chronic hepatitis C as well as a mixed hepatitis are accompanied by more evident symptoms of deadaptation and somatogenic asthenia than hepatitis B in which psychogenic manifestations prevailed. The degree of endogenous intoxication was also higher at hepatitis C.

Critical factors in the establishment of allopolyploids.

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Fowler, Norma L; Levin, Donald A

2016-07-01

The growth and spread of new polyploid populations have been explained in terms of fitness advantages over their diploid progenitors. However, a fitness advantage is not sufficient to insure the establishment of a polyploid; it must also overcome the obstacles of demographic stochasticity and minority disadvantage. Several studies have addressed the population dynamics of autopolyploids, but the present study is the first to consider allopolyploids, which are affected by more factors than autopolyploids. We constructed a population dynamic model of four types of plants (two parent species, hybrids, allopolyploids) that also included an explicit breeding system. The numbers of plants of each type were the most important factors determining whether the new allopolyploid would become established. More polyploid plants greatly increased the likelihood of polyploid persistence. More plants of the parent species and more hybrids resulted in more polyploids being produced. The model parameters with the most effect on polyploid establishment were potential population size (K), individual plant fecundity, and niche separation (α). The most important breeding system parameters were selfing rates, which mitigated minority disadvantage imposed by pollen limitation. The importance of population sizes, and the parameters that controlled them, in overcoming demographic stochasticity parallels the well-recognized role of propagule pressure in determining the success of invasive species. We modeled the establishment of a new allopolyploid; analogous considerations would affect the establishment of a new autopolyploid. The critical role of population sizes in polyploid establishment should be more widely recognized. © 2016 Botanical Society of America.

Severity of chronic Lyme disease compared to other chronic conditions: a quality of life survey

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Lorraine Johnson

2014-03-01

Full Text Available Overview. The Centers for Disease Control and Prevention (CDC health-related quality of life (HRQoL indicators are widely used in the general population to determine the burden of disease, identify health needs, and direct public health policy. These indicators also allow the burden of illness to be compared across different diseases. Although Lyme disease has recently been acknowledged as a major health threat in the USA with more than 300,000 new cases per year, no comprehensive assessment of the health burden of this tickborne disease is available. This study assesses the HRQoL of patients with chronic Lyme disease (CLD and compares the severity of CLD to other chronic conditions.Methods. Of 5,357 subjects who responded to an online survey, 3,090 were selected for the study. Respondents were characterized as having CLD if they were clinically diagnosed with Lyme disease and had persisting symptoms lasting more than 6 months following antibiotic treatment. HRQoL of CLD patients was assessed using the CDC 9-item metric. The HRQoL analysis for CLD was compared to published analyses for the general population and other chronic illnesses using standard statistical methods.Results. Compared to the general population and patients with other chronic diseases reviewed here, patients with CLD reported significantly lower health quality status, more bad mental and physical health days, a significant symptom disease burden, and greater activity limitations. They also reported impairment in their ability to work, increased utilization of healthcare services, and greater out of pocket medical costs.Conclusions. CLD patients have significantly impaired HRQoL and greater healthcare utilization compared to the general population and patients with other chronic diseases. The heavy burden of illness associated with CLD highlights the need for earlier diagnosis and innovative treatment approaches that may reduce the burden of illness and concomitant costs posed

Severity of chronic Lyme disease compared to other chronic conditions: a quality of life survey

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Johnson, Lorraine; Wilcox, Spencer; Mankoff, Jennifer

2014-01-01

Overview. The Centers for Disease Control and Prevention (CDC) health-related quality of life (HRQoL) indicators are widely used in the general population to determine the burden of disease, identify health needs, and direct public health policy. These indicators also allow the burden of illness to be compared across different diseases. Although Lyme disease has recently been acknowledged as a major health threat in the USA with more than 300,000 new cases per year, no comprehensive assessment of the health burden of this tickborne disease is available. This study assesses the HRQoL of patients with chronic Lyme disease (CLD) and compares the severity of CLD to other chronic conditions. Methods. Of 5,357 subjects who responded to an online survey, 3,090 were selected for the study. Respondents were characterized as having CLD if they were clinically diagnosed with Lyme disease and had persisting symptoms lasting more than 6 months following antibiotic treatment. HRQoL of CLD patients was assessed using the CDC 9-item metric. The HRQoL analysis for CLD was compared to published analyses for the general population and other chronic illnesses using standard statistical methods. Results. Compared to the general population and patients with other chronic diseases reviewed here, patients with CLD reported significantly lower health quality status, more bad mental and physical health days, a significant symptom disease burden, and greater activity limitations. They also reported impairment in their ability to work, increased utilization of healthcare services, and greater out of pocket medical costs. Conclusions. CLD patients have significantly impaired HRQoL and greater healthcare utilization compared to the general population and patients with other chronic diseases. The heavy burden of illness associated with CLD highlights the need for earlier diagnosis and innovative treatment approaches that may reduce the burden of illness and concomitant costs posed by this

THE MOLECULAR MECHANISMS OF EPSTEINBARR VIRUS PERSISTENCE IN THE HUMAN ORGANISM

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Volyanskiy A.Yu.

2014-12-01

latency programs. During I phase of latency latent EBV genomes can multiply in dividing memory B cells, during II phase of latency virus can induce and modulate B-cell differentiation, during III phase of latency virus can activate proliferation of the naïve B cells, during 0 phase of latency virus completely down regulates expression all protein coding genes. Latently infected B cells can occasionally be stimulated to reactivate EBV. Viral proteins BZLF1 and BRLF1 act as transactivators of the viral lytic program. The early reactivated virus gene products have such function as replication, metabolism and blockade of antigen processing. DNA polymerase replicates linear viral genome during the lytic phase. The late products code the structural proteins such as the viral capsid antigens (VCA and gene products used for immune evasion. In healthy carriers virus exists in resting memory B lymphocytes in 0 phase of latency. The intensive virus reactivation in lytic replication phase or virus persistence in I, II and III latent phases promotes the development of such disease as lymphomas, rheumatoid arthritis, systemic erythematous lupus, chronic fatigue syndrome, etc. EBNA1 is expressed in the type I latency program, which is active in Burkitt’s lymphoma. EBNA1 and LMP1/2 are expressed in the type II latency program, which is observed in Hodgkin’s lymphoma. LMP1 and LMP2 expression activate proliferation program in the cell. The type III latency program, in which all of the latency gene products are expressed, is often detected during acute infectious mononucleosis or in virus infected B cell line and in inimmunocompromised individuals after tissue transplantation. Immunodeficiency-related Bcell posttransplant lymphoproliferative disorders (PTLDs are caused directly by EBV Chronic active EBV (CAEBV infection develops due to the inappropriate viral load. This disease is characterized by chronic infectious mononucleosis-like symptoms with illness lasting for 6-24 months and

Persistent myalgia following whiplash.

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Dommerholt, Jan

2005-10-01

Persistent myalgia following whiplash is commonly considered the result of poor psychosocial status, illness behavior, or failing coping skills. However, there is much evidence that persistent myalgia may be due to neurophysiologic mechanisms involving peripheral and central sensitization. Myofascial trigger points may play a crucial role in maintaining sensitization. Recent research suggests that the chemical environment of myofascial trigger points is an important factor. Several consequences are reviewed when central pain mechanisms and myofascial trigger points are included in the differential diagnosis and in the management of patients with persistent pain following whiplash.

Altered cerebral blood flow in chronic neck pain patients but not in whiplash patients: a 99mTc-HMPAO rCBF study

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Sundström, Torbjörn; Guez, Michel; Hildingsson, Christer; Toolanen, Göran; Nyberg, Lars; Riklund, Katrine

2006-01-01

A cross-sectional study to investigate regional cerebral blood flow (rCBF) in patients with chronic whiplash syndrome and chronic neck pain patients without previous history of trauma along with a healthy control group. Chronic neck pain is a common disorder and a history of cervical spine injury including whiplash trauma constitute a risk factor for persistent neck pain. The aetiology of the late whiplash syndrome is unknown with no specific diagnostic criteria based on imaging, physiologica...

[Persistence of the omphalomesenteric duct. Childhood differential diagnosis of umbilical granuloma].

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Sánchez-Castellanos, M E; Sandoval-Tress, C; Hernández-Torres, M

2006-01-01

The omphalomesenteric duct is an embryonic structure which communicates the vitelline duct with the midgut. It normally disappears between the fifth and ninth weeks of intrauterine life. Anomalies related with the total or partial absence of this involution are show in 2 % of the population. We report a case of persistence of the omphalomesenteric duct and review the bibliography to establish the differences between this anomaly and umbilical granuloma, which is the main differential diagnosis.

Hippocampal morphology mediates biased memories of chronic pain

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Berger, Sara E.; Vachon-Presseau, Étienne; Abdullah, Taha B.; Baria, Alex T.; Schnitzer, Thomas J.; Apkarian, A. Vania

2018-01-01

Experiences and memories are often mismatched. While multiple studies have investigated psychological underpinnings of recall error with respect to emotional events, the neurobiological mechanisms underlying the divergence between experiences and memories remain relatively unexplored in the domain of chronic pain. Here we examined the discrepancy between experienced chronic low back pain (CBP) intensity (twice daily ratings) and remembered pain intensity (n = 48 subjects) relative to psychometric properties, hippocampus morphology, memory capabilities, and personality traits related to reward. 77% of CBP patients exaggerated remembered pain, which depended on their strongest experienced pain and their most recent mood rating. This bias persisted over nearly 1 year and was related to reward memory bias and loss aversion. Shape displacement of a specific region in the left posterior hippocampus mediated personality effects on pain memory bias, predicted pain memory bias in a validation CBP group (n = 21), and accounted for 55% of the variance of pain memory bias. In two independent groups (n = 20/group), morphology of this region was stable over time and unperturbed by the development of chronic pain. These results imply that a localized hippocampal circuit, and personality traits associated with reward processing, largely determine exaggeration of daily pain experiences in chronic pain patients. PMID:29080714

Persistent luminescence nanothermometers

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Martín Rodríguez, Emma; López-Peña, Gabriel; Montes, Eduardo; Lifante, Ginés; García Solé, José; Jaque, Daniel; Diaz-Torres, Luis Armando; Salas, Pedro

2017-08-01

Persistent phosphorescence nanoparticles emitting in the red and near-infrared spectral regions are strongly demanded as contrast nanoprobes for autofluorescence free bioimaging and biosensing. In this work, we have developed Sr4Al14O25:Eu2+, Cr3+, Nd3+ nanopowders that produce persistent red phosphorescence peaking at 694 nm generated by Cr3+ ions. This emission displays temperature sensitivity in the physiological temperature range (20-60 °C), which makes these nanoparticles potentially useful as fluorescence (contactless) nanothermometers operating without requiring optical excitation. Nd3+ ions, which act as shallow electron traps for the red Cr3+ persistent emission, also display infrared emission bands, extending the fluorescence imaging capability to the second biological window. This unique combination of properties makes these nanoparticles multifunctional luminescent probes with great potential applications in nanomedicine.

Omalizumab therapy in a 13-year-old boy with severe persistent asthma and concomitant eosinophilic esophagitis.

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Arasi, Stefania; Costa, Stefano; Magazzù, Giuseppe; Ieni, Antonio; Crisafulli, Giuseppe; Caminiti, Lucia; Chiera, Fernanda; Vaccaro, Mario; Del Giudice, Michele Miraglia; Pajno, Giovanni Battista

2016-03-22

Eosinophilic esophagitis (EoE) has been defined as "asthma of the esophagus" for the large number of similarities between the two diseases. Omalizumab is an anti-Immunoglobulin E (IgE) antibody currently approved only in allergic IgE-mediated severe persistent uncontrolled asthma and in chronic spontaneous urticaria unresponsive to antihistamines, but it has been tried in other diseases, too. We present herein the case of a 13-year-old boy, affected from preschool age by severe chronic allergic asthma poorly controlled despite a generous long-term therapy, and, since he was 8 years old, by eosinophilic esophagitis, responsive to courses of strict elimination diet and semi-elemental diet, even if very burdensome for his quality of life. At the age of 11.5 years, for inadequate asthma control, he started to receive therapy with omalizumab. After the first month and for the entire duration (18 months) of omalizumab treatment, asthma was well controlled, long-term conventional therapy was gradually withdrawn and lung- function improved. Concerning EoE, after an initial clinical but not histological remission during the first few months of treatment with omalizumab, the patient experienced an exacerbation of gastrointestinal symptoms. Therefore, he started treatment with topical steroids which was effective to improve gastrointestinal symptoms. However, EoE is still steroid-dependent. Currently, he continues both treatments: omalizumab for asthma and topical steroid for EoE. This case report confirms that omalizumab is an effective treatment in patients with severe persistent, uncontrolled asthma. On the other hand, in our patient it did not produce persistent improvement neither on symptoms nor on biopsy findings of EoE. The outcome of this case might indicate different pathogenic mechanism(s) of the two diseases.

Persistent Microvascular Obstruction After Myocardial Infarction Culminates in the Confluence of Ferric Iron Oxide Crystals, Proinflammatory Burden, and Adverse RemodelingCLINICAL PERSPECTIVE

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Kali, Avinash; Cokic, Ivan; Tang, Richard; Dohnalkova, Alice; Kovarik, Libor; Yang, Hsin-Jung; Kumar, Andreas; Prato, Frank S.; Wood, John C.; Underhill, David; Marban, Eduardo; Dharmakumar, Rohan

2016-11-01

Emerging evidence now supports the notion that persistent microvascular obstruction (PMO) may be more predictive of major adverse cardiovascular events than MI size itself. But, how PMO, a phenomenon limited to the acute/sub-acute period of MI, imparts adverse remodeling throughout the post MI period, particularly after its resolution, is incompletely understood. We hypothesized that PMOs resolve into chronic iron crystals within MI territories and actively impart a proinflammatory burden and adverse remodeling of infarction and LV in the chronic phase of MI. Canine models reperfused (n=20) and non-reperfused (n=20) with and without PMO were studied with serial cardiac MRI to characterize the spatiotemporal relationships between PMO, iron deposition, and infarct and LV remodeling indices between acute (day 7, post MI) and chronic (week 8, post MI). Histopathology and immunohistochemistry were used to validate the iron deposition, microscopically map and quantify the relationship between iron-rich chronic MI regions against pro-inflammatory macrophages, proinflammatory cytokines and matrix metalloproteinase. Atomic resolution transmission electron microscopy (TEM) was used to determine the crystallinity of iron and assess the physical effects of iron on lysosomes within macrophages, and energy-dispersive X-ray spectroscopy (EDS) to identify the chemical composition of the iron composite. Results showed that PMOs lead to iron deposition within chronic MI and that the extent of chronic iron deposition is strongly related to PMO Volume (r>0.6, p<0.001). TEM and EDS analysis showed that iron within chronic MI is found within macrophages as aggregates of nanocrystals of ~2.5 nm diameter in ferric state. Correlative histological studies showed that iron content, proinflammatory burden and collagen degrading enzyme were highly correlated (r >0.7, p<0.001). Iron within chronic MI was significantly associated with infarct resorption (r>0.5, p<0.001) and adverse structural (r

The effect of chronic pain on life satisfaction: evidence from Australian data.

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McNamee, Paul; Mendolia, Silvia

2014-11-01

Chronic pain is associated with significant costs to individuals directly affected by this condition, their families, the healthcare system, and the society as a whole. This paper investigates the relationship between chronic pain and life satisfaction using a sample of around 90,000 observations from the first ten waves of the Household, Income and Labour Dynamics of Australia Survey (HILDA), which is a representative survey of the Australian population that started in 2000. We estimate the negative impact on life satisfaction and examine the persistence of the effect over multiple years. Chronic pain is associated with poor health conditions, disability, decreased participation in the labour market and lower quality of life. We calculate the compensating income variation of chronic pain, based on the measurement of chronic pain, the life satisfaction of individuals and the income of households. Panel data models with random and fixed effects are used to control for characteristics of individuals that do not vary over time. Further, we investigate whether individuals who experience chronic pain exhibit adaptation and recovery in life satisfaction after 3 years. Overall, we find that chronic pain has a large negative association with life satisfaction, and that the compensating income variation is substantial (around 640 US$ per day). Copyright © 2014 Elsevier Ltd. All rights reserved.

Cross-cultural adaptation and clinimetric property of Korean version of the Chronic Pain Coping Inventory-42 in patients with chronic low back pain.

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Ko, Young-Mi; Park, Won-Beom; Lim, Jae-Young

2010-03-15

Validation of a translated, culturally adapted questionnaire. We developed a Korean version of the Chronic Pain Coping Inventory-42 (CPCI-42) by performing a cross-cultural adaptation, and evaluated its reliability and validity. The CPCI is widely used and validated instruments for measuring coping strategies in chronic pain. However, no validated and culturally adapted version was available in Asian countries. We assessed 142 patients with chronic low back pain using the CPCI-42 and measures of physical disability, pain, and quality of life. Results for 93 of the 142 patients exhibited test-retest reliability. The interval time of collecting retest data varied from 2 weeks to 1 month. Criterion validity was evaluated using correlations between the CPCI-42 and the Oswestry Disability Index, the Brief Pain Inventory, and the Short Form 36-item Health Survey (version 2.0). Construct validity was computed using exploratory factor analysis. The Korean version of the CPCI-42 had a high internal consistency (Cronbach's alpha >0.70) with the exception of results for task persistence and relaxation. Illness-focused coping (guarding, resting, asking for assistance) and other-focused coping (seeking social support) were most significantly correlated with Oswestry Disability Index, Brief Pain Inventory, and Short Form 36-item Health Survey, respectively. Outcomes for task persistence were contrary to other subscales in wellness-focused coping. Construct validity by factor analysis produced similar results to the original CPCI subscale. However, several factors showed cross-loading in 8 factor solutions. Despite linguistic and cultural differences, the Korean version of the CPCI-42 is overall a meaningful tool, and produces results sufficiently similar to the original CPCI-42.

Nutrition and prevention of chronic diseases: a unifying eco-nutritional strategy.

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Wahlqvist, M L

2004-02-01

Increasing efforts are being made to address, in public health policy (PHP), both the persistence of nutritional deprivation in economically disadvantaged communities, and the increase in so-called "chronic disease" (abdominal obesity, diabetes, cardiovascular disease, certain cancers, osteoporosis, arthritides, and inflammatory disease) in communities at all stages of economic development. The problems in the "chronic disease" descriptor are that its origins may be as early as conception, rather than during the postnatal lifespan, or even in previous generations; it may appear abruptly or slowly; and it may be amenable to environmental and behavioural intervention well into its course and in older age groups. It is also not necessarily "non-communicable", a qualifier often used for "chronic disease" (chronic non-communicable disease or CNCD) and often has inflammatory features, for example the inflammatory marker C-reactive protein is a predictor of macrovascular disease and ischaemic events can, in part, be prevented in the affected by influenzal vaccination. The nexus between immunodeficiency, inflammatory processes and nutritional status which is characteristic of "infective" and food-borne illness, is also more and more evident in "chronic disease". It may be more helpful to consider "chronic disease" as "eco-disease" with its environmental and behavioural contributors, and to regard that which is clearly nutritionally dependent as "eco-nutritional disease".

Effects of the swimming exercise on the consolidation and persistence of auditory and contextual fear memory.

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Faria, Rodolfo Souza; Gutierres, Luís Felipe Soares; Sobrinho, Fernando César Faria; Miranda, Iris do Vale; Reis, Júlia Dos; Dias, Elayne Vieira; Sartori, Cesar Renato; Moreira, Dalmo Antonio Ribeiro

2016-08-15

Exposure to negative environmental events triggers defensive behavior and leads to the formation of aversive associative memory. Cellular and molecular changes in the central nervous system underlie this memory formation, as well as the associated behavioral changes. In general, memory process is established in distinct phases such as acquisition, consolidation, evocation, persistence, and extinction of the acquired information. After exposure to a particular event, early changes in involved neural circuits support the memory consolidation, which corresponds to the short-term memory. Re-exposure to previously memorized events evokes the original memory, a process that is considered essential for the reactivation and consequent persistence of memory, ensuring that long-term memory is established. Different environmental stimuli may modulate the memory formation process, as well as their distinct phases. Among the different environmental stimuli able of modulating memory formation is the physical exercise which is a potent modulator of neuronal activity. There are many studies showing that physical exercise modulates learning and memory processes, mainly in the consolidation phase of the explicit memory. However, there are few reports in the literature regarding the role of physical exercise in implicit aversive associative memory, especially at the persistence phase. Thus, the present study aimed to investigate the relationship between swimming exercise and the consolidation and persistence of contextual and auditory-cued fear memory. Male Wistar rats were submitted to sessions of swimming exercise five times a week, over six weeks. After that, the rats were submitted to classical aversive conditioning training by a pairing tone/foot shock paradigm. Finally, rats were evaluated for consolidation and persistence of fear memory to both auditory and contextual cues. Our results demonstrate that classical aversive conditioning with tone/foot shock pairing induced

Oxidative Stress in Diabetic Nephropathy with Early Chronic Kidney Disease

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Alejandra Guillermina Miranda-Díaz

2016-01-01

Full Text Available The increase in the prevalence of diabetes mellitus (DM and the secondary kidney damage produces diabetic nephropathy (DN. Early nephropathy is defined as the presence of microalbuminuria (30–300 mg/day, including normal glomerular filtration rate (GFR or a mildly decreased GFR (60–89 mL/min/1.73 m2, with or without overt nephropathy. The earliest change caused by DN is hyperfiltration with proteinuria. The acceptable excretion rate of albumin in urine is 300 mg/day. Chronic kidney disease (CKD is characterized by abnormalities in renal function that persist for >3 months with health implications. Alterations in the redox state in DN are caused by the persistent state of hyperglycemia and the increase in advanced glycation end products (AGEs with ability to affect the renin-angiotensin system and the transforming growth factor-beta (TGF-β, producing chronic inflammation and glomerular and tubular hypertrophy and favoring the appearance of oxidative stress. In DN imbalance between prooxidant/antioxidant processes exists with an increase in reactive oxygen species (ROS. The overproduction of ROS diminishes expression of the antioxidant enzymes (manganese superoxide dismutase, glutathione peroxidase, and catalase. The early detection of CKD secondary to DN and the timely identification of patients would permit decreasing its impact on health.

Pilot study of a cell phone-based exercise persistence intervention post-rehabilitation for COPD

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Huong Q Nguyen

2009-08-01

Full Text Available Huong Q Nguyen1, Dawn P Gill1, Seth Wolpin1, Bonnie G Steele2, Joshua O Benditt11University of Washington, seattle, WA, USA; 2VA Puget Sound Health Care System, Seattle, WA, USAObjective: To determine the feasibility and efficacy of a six-month, cell phone-based exercise persistence intervention for patients with chronic obstructive pulmonary disease (COPD following pulmonary rehabilitation.Methods: Participants who completed a two-week run-in were randomly assigned to either MOBILE-Coached (n = 9 or MOBILE-Self-Monitored (n = 8. All participants met with a nurse to develop an individualized exercise plan, were issued a pedometer and exercise booklet, and instructed to continue to log their daily exercise and symptoms. MOBILE-Coached also received weekly reinforcement text messages on their cell phones; reports of worsening symptoms were automatically flagged for follow-up. Usability and satisfaction were assessed. Participants completed incremental cycle and six minute walk (6MW tests, wore an activity monitor for 14 days, and reported their health-related quality of life (HRQL at baseline, three, and six months.Results: The sample had a mean age of 68 ± 11 and forced expiratory volume in one second (FEV1 of 40 ± 18% predicted. Participants reported that logging their exercise and symptoms was easy and that keeping track of their exercise helped them remain active. There were no differences between groups over time in maximal workload, 6MW distance, or HRQL (p > 0.05; however, MOBILE-Self-Monitored increased total steps/day whereas MOBILE-Coached logged fewer steps over six months (p = 0.04.Conclusions: We showed that it is feasible to deliver a cell phone-based exercise persistence intervention to patients with COPD post-rehabilitation and that the addition of coaching appeared to be no better than self-monitoring. The latter finding needs to be interpreted with caution since this was a purely exploratory study.Trial registration: Clinical

Resurgence of persisting non-cultivable Borrelia burgdorferi following antibiotic treatment in mice.

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Emir Hodzic

Full Text Available The agent of Lyme borreliosis, Borrelia burgdorferi, evades host immunity and establishes persistent infections in its varied mammalian hosts. This persistent biology may pose challenges to effective antibiotic treatment. Experimental studies in dogs, mice, and non-human primates have found persistence of B. burgdorferi DNA following treatment with a variety of antibiotics, but persisting spirochetes are non-cultivable. Persistence of B. burgdorferi DNA has been documented in humans following treatment, but the significance remains unknown. The present study utilized a ceftriaxone treatment regimen in the C3H mouse model that resulted in persistence of non-cultivable B. burgdorferi in order to determine their long-term fate, and to examine their effects on the host. Results confirmed previous studies, in which B. burgdorferi could not be cultured from tissues, but low copy numbers of B. burgdorferi flaB DNA were detectable in tissues at 2, 4 and 8 months after completion of treatment, and the rate of PCR-positive tissues appeared to progressively decline over time. However, there was resurgence of spirochete flaB DNA in multiple tissues at 12 months, with flaB DNA copy levels nearly equivalent to those found in saline-treated mice. Despite the continued non-cultivable state, RNA transcription of multiple B. burgdorferi genes was detected in host tissues, flaB DNA was acquired by xenodiagnostic ticks, and spirochetal forms could be visualized within ticks and mouse tissues by immunofluorescence and immunohistochemistry, respectively. A number of host cytokines were up- or down-regulated in tissues of both saline- and antibiotic-treated mice in the absence of histopathology, indicating host response to the presence of non-cultivable, despite the lack of inflammation in tissues.

Is bacterial persistence a social trait?

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Andy Gardner

Full Text Available The ability of bacteria to evolve resistance to antibiotics has been much reported in recent years. It is less well-known that within populations of bacteria there are cells which are resistant due to a non-inherited phenotypic switch to a slow-growing state. Although such 'persister' cells are receiving increasing attention, the evolutionary forces involved have been relatively ignored. Persistence has a direct benefit to cells because it allows survival during catastrophes-a form of bet-hedging. However, persistence can also provide an indirect benefit to other individuals, because the reduced growth rate can reduce competition for limiting resources. This raises the possibility that persistence is a social trait, which can be influenced by kin selection. We develop a theoretical model to investigate the social consequences of persistence. We predict that selection for persistence is increased when: (a cells are related (e.g. a single, clonal lineage; and (b resources are scarce. Our model allows us to predict how the level of persistence should vary with time, across populations, in response to intervention strategies and the level of competition. More generally, our results clarify the links between persistence and other bet-hedging or social behaviours.

Challenges and opportunities in establishing a collaborative multisite observational study of chronic diseases and lifestyle factors among adults in Puerto Rico

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Josiemer Mattei

2017-01-01

Full Text Available Abstract Background Prevalence of chronic diseases and unhealthy lifestyle behaviors among the adult population of Puerto Rico (PR is high; however, few epidemiological studies have been conducted to address these. We aimed to document the methods and operation of establishing a multisite cross-sectional study of chronic diseases and risk factors in PR, in partnership with academic, community, clinical, and research institutions. Methods The Puerto Rico Assessment of Diet, Lifestyle and Diseases (PRADLAD documented lifestyle and health characteristics of adults living in PR, with the goal of informing future epidemiological and intervention projects, as well as public health, policy, and clinical efforts to help improve the population’s health. The study was conducted in three primary care clinics in the San Juan, PR metropolitan area. Eligible volunteers were 30–75y, living in PR for at least 10 months of the previous year, and able to answer interviewer-administered questionnaires without assistance. Questions were recorded electronically by trained interviewers, and included socio-demographic characteristics, lifestyle behaviors, self-reported medically-diagnosed diseases, and psychosocial factors. Waist and hip circumferences were measured following standardized protocols. A subset of participants answered a validated food frequency questionnaire, a legumes questionnaire, and had medical record data abstracted. Process and outcome evaluation indicators were assessed. Results The study screened 403 participants in 5 months. Of these, 396 (98% were eligible and 380 (94% had reliable and complete information. A subset of 242 participants had valid dietary data, and 236 had medical record data. The mean time to complete an interview was 1.5 h. Participants were generally cooperative and research collaborators were fully engaged. Having multiple sites helped enhance recruitment and sociodemographic representation. Diagnosed conditions were

Persistent modification of Nav1.9 following chronic exposure to insecticides and pyridostigmine bromide

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Nutter, Thomas J.; Cooper, Brian Y.

2014-01-01

Many veterans of the 1991 Gulf War (GW) returned from that conflict with a widespread chronic pain affecting deep tissues. Recently, we have shown that a 60 day exposure to the insecticides permethrin, chlorpyrifos, and pyridostigmine bromide (NTPB) had little influence on nociceptor action potential forming Na v 1.8, but increased K v 7 mediated inhibitory currents 8 weeks after treatment. Using the same exposure regimen, we used whole cell patch methods to examine whether the influences of NTPB could be observed on Na v 1.9 expressed in muscle and vascular nociceptors. During a 60 day exposure to NTPB, rats exhibited lowered muscle pain thresholds and increased rest periods, but these measures subsequently returned to normal levels. Eight and 12 weeks after treatments ceased, DRG neurons were excised from the sensory ganglia. Whole cell patch studies revealed little change in voltage dependent activation and deactivation of Na v 1.9, but significant increases in the amplitude of Na v 1.9 were observed 8 weeks after exposure. Cellular studies, at the 8 week delay, revealed that NTPB also significantly prolonged action potential duration and afterhyperpolarization (22 °C). Acute application of permethrin (10 μM) also increased the amplitude of Na v 1.9 in skin, muscle and vascular nociceptors. In conclusion, chronic exposure to Gulf War agents produced long term changes in the amplitude of Na v 1.9 expressed in muscle and vascular nociceptors. The reported increases in K v 7 amplitude may have been an adaptive response to increased Na v 1.9, and effectively suppressed behavioral pain measures in the post treatment period. Factors that alter the balance between Na v 1.9 and K v 7 could release spontaneous discharge and produce chronic deep tissue pain. - Highlights: • Rats were treated 60 days with permethrin, chlorpyrifos and pyridostigmine bromide. • 8 weeks after treatments, Nav1.9 activation and deactivation were unchanged. • The amplitude and

Optimism, Positive and Negative Affect, and Goal Adjustment Strategies: Their Relationship to Activity Patterns in Patients with Chronic Musculoskeletal Pain

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Rosa Esteve

2018-01-01

Full Text Available Objective. Activity patterns are the product of pain and of the self-regulation of current goals in the context of pain. The aim of this study was to investigate the association between goal management strategies and activity patterns while taking into account the role of optimism/pessimism and positive/negative affect. Methods. Two hundred and thirty-seven patients with chronic musculoskeletal pain filled out questionnaires on optimism, positive and negative affect, pain intensity, and the activity patterns they employed in dealing with their pain. Questionnaires were also administered to assess their general goal management strategies: goal persistence, flexible goal adjustment, and disengagement and reengagement with goals. Results. Structural equation modelling showed that higher levels of optimism were related to persistence, flexible goal management, and commitment to new goals. These strategies were associated with higher positive affect, persistence in finishing tasks despite pain, and infrequent avoidance behaviour in the presence or anticipation of pain. Conclusions. The strategies used by the patients with chronic musculoskeletal pain to manage their life goals are related to their activity patterns.

Optimism, Positive and Negative Affect, and Goal Adjustment Strategies: Their Relationship to Activity Patterns in Patients with Chronic Musculoskeletal Pain.

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Esteve, Rosa; López-Martínez, Alicia E; Peters, Madelon L; Serrano-Ibáñez, Elena R; Ruiz-Párraga, Gema T; Ramírez-Maestre, Carmen

2018-01-01

Activity patterns are the product of pain and of the self-regulation of current goals in the context of pain. The aim of this study was to investigate the association between goal management strategies and activity patterns while taking into account the role of optimism/pessimism and positive/negative affect. Two hundred and thirty-seven patients with chronic musculoskeletal pain filled out questionnaires on optimism, positive and negative affect, pain intensity, and the activity patterns they employed in dealing with their pain. Questionnaires were also administered to assess their general goal management strategies: goal persistence, flexible goal adjustment, and disengagement and reengagement with goals. Structural equation modelling showed that higher levels of optimism were related to persistence, flexible goal management, and commitment to new goals. These strategies were associated with higher positive affect, persistence in finishing tasks despite pain, and infrequent avoidance behaviour in the presence or anticipation of pain. The strategies used by the patients with chronic musculoskeletal pain to manage their life goals are related to their activity patterns.

Understanding Desisting and Persisting Forms of Delinquency: The Unique Contributions of Disruptive Behavior Disorders and Interpersonal Callousness

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Byrd, Amy L.; Loeber, Rolf; Pardini, Dustin A.

2012-01-01

Background: While associations between conduct disorder (CD), oppositional defiant disorder (ODD), attention deficit hyperactivity disorder (ADHD), and interpersonal callousness (IC) symptoms and delinquency onset are well established, less is known about whether these characteristics differentiate desisting and persisting delinquency. The current…

Persistent maternal depressive symptoms trajectories influence children's IQ: The EDEN mother-child cohort.

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van der Waerden, Judith; Bernard, Jonathan Y; De Agostini, Maria; Saurel-Cubizolles, Marie-Josèphe; Peyre, Hugo; Heude, Barbara; Melchior, Maria

2017-02-01

This study assessed the association between timing and course of maternal depression from pregnancy onwards and children's cognitive development at ages 5 to 6. Potential interaction effects with child sex and family socioeconomic status were explored. One thousand thirty-nine mother-child pairs from the French EDEN mother-child birth cohort were followed from 24 to 28 weeks of pregnancy onwards. Based on Center for Epidemiological Studies Depression (CES-D) and Edinburgh Postnatal Depression Scale (EPDS) scores assessed at six timepoints, longitudinal maternal depressive symptom trajectories were calculated with a group-based semiparametric method. Children's cognitive function was assessed at ages 5 to 6 by trained interviewers with the Wechsler Preschool and Primary Scale of Intelligence Third Edition (WPPSI-III), resulting in three composite scores: Verbal IQ (VIQ), Performance IQ (PIQ), and Full-Scale IQ (FSIQ). Five trajectories of maternal symptoms of depression could be distinguished: no symptoms, persistent intermediate-level depressive symptoms, persistent high depressive symptoms, high symptoms in pregnancy only, and high symptoms in the child's preschool period only. Multiple linear regression analyses showed that, compared to children of mothers who were never depressed, children of mothers with persistent high levels of depressive symptoms had reduced VIQ, PIQ, and FSIQ scores. This association was moderated by the child's sex, boys appearing especially vulnerable in case of persistent maternal depression. Chronicity of maternal depression predicts children's cognitive development at school entry age, particularly in boys. As maternal mental health is an early modifiable influence on child development, addressing the treatment needs of depressed mothers may help reduce the associated burden on the next generation. © 2016 Wiley Periodicals, Inc.

Longitudinal course and outcome of chronic insomnia in Hong Kong Chinese children: a 5-year follow-up study of a community-based cohort.

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Zhang, Jihui; Lam, Siu Ping; Li, Shirley Xin; Li, Albert Martin; Lai, Kelly Y C; Wing, Yun-Kwok

2011-10-01

There are limited data on the long-term outcome of childhood insomnia. We explored the longitudinal course, predictors, and impact of childhood insomnia in a community-based cohort. 5-year prospective follow-up. Community-based. 611 children (49% boys) aged 9.0 ± 1.8 years at baseline; 13.7 ± 1.8 years at follow-up. NA. Chronic insomnia was defined as difficulty initiating sleep, difficulty maintaining sleep and/or early morning awakening ≥ 3 times/week in the past 12 months. General health, upper airway inflammatory diseases, and behavioral problems in recent one year were assessed at both time points, while mental health and lifestyle practice were assessed at follow-up study. The questionnaires at baseline and follow-up were reported by parents/caretakers and adolescents themselves, respectively. The prevalence of chronic insomnia was 4.2% and 6.6% for baseline and follow-up, respectively. The incidence and persistence rates of chronic insomnia were 6.2% and 14.9%, respectively. New incidence of insomnia was associated with lower paternal education level, baseline factors of frequent temper outbursts and daytime fatigue as well as alcohol use and poor mental health at follow-up. Baseline chronic medical disorders, frequent temper outbursts, and poor mental health at follow-up were associated with the persistence of insomnia in adolescents. Baseline insomnia was associated with frequent episodes of laryngopharyngitis and lifestyle practice (coffee and smoking) at follow-up. Chronic insomnia is a common problem with moderate persistent rate in children. The associations of adverse physical and mental health consequences with maladaptive lifestyle coping (smoking and alcohol) argue for rigorous intervention of childhood insomnia.

HoBi-like virus challenge of pregnant cows that had previously given birth to calves persistently infected with bovine viral diarrhea virus

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The ability of bovine viral diarrhea viruses (BVDV) to establish persistent infection (PI) following fetal infection is central to keeping these viruses circulating. Similarly, an emerging species of pestivirus, HoBi-like viruses, is also able to establish PIs. Dams that are not PI, but carrying PI ...

Persistent User Bias in Case-Crossover Studies in Pharmacoepidemiology

DEFF Research Database (Denmark)

Hallas, Jesper; Pottegård, Anton; Wang, Shirley

2016-01-01

Studying the effect of chronic medication exposure by means of a case-crossover design may result in an upward-biased odds ratio. In this study, our aim was to assess the occurrence of this bias and to evaluate whether it is remedied by including a control group (the case-time-control design...... for the retinal detachment controls were similar, leading to near-null case-time-control estimates for all 3 medication classes. For wrist fracture and stroke, the odds ratios were higher for cases than for controls, and case-time-control odds ratios were consistently above unity, thus implying significant...... residual bias. In case-crossover studies of medications, contamination by persistent users confers a moderate bias upward, which is partly remedied by using a control group. The optimal strategy for dealing with this problem is currently unknown....

Recognition, survival and persistence of Staphylococcus aureus in the model host Tenebrio molitor.

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Dorling, Jack; Moraes, Caroline; Rolff, Jens

2015-02-01

The degree of specificity of any given immune response to a parasite is governed by the complexity and variation of interactions between host and pathogen derived molecules. Here, we assess the extent to which recognition and immuno-resistance of cell wall mutants of the pathogen Staphylococcus aureus may contribute to establishment and maintenance of persistent infection in the model insect host, Tenebrio molitor. The cell surface of S. aureus is decorated with various molecules, including glycopolymers such as wall teichoic acid (WTA). WTA is covalently bound to peptidoglycan (PGN) and its absence has been associated with increased recognition of PGN by host receptors (PGRPs). WTA is also further modified by other molecules such as D-alanine (D-alanylation). Both the level of WTA expression and its D-alanylation were found to be important in the mediation of the host-parasite interaction in this model system. Specifically, WTA itself was seen to influence immune recognition, while D-alanylation of WTA was found to increase immuno-resistance and was associated with prolonged persistence of S. aureus in T. molitor. These results implicate WTA and its D-alanylation as important factors in the establishment and maintenance of persistent infection, affecting different critical junctions in the immune response; through potential evasion of recognition by PGRPs and resistance to humoral immune effectors during prolonged exposure to the immune system. This highlights a mechanism by which specificity in this host-parasite interaction may arise. Copyright © 2014 Elsevier Ltd. All rights reserved.

CKD.QLD: establishment of a chronic kidney disease [CKD] registry in Queensland, Australia.

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Venuthurupalli, Sree K; Hoy, Wendy E; Healy, Helen G; Cameron, Anne; Fassett, Robert G

2017-06-07

Chronic kidney disease [CKD] is recognised as a global public health problem. Until recently, the majority of information informing on CKD has been generated from renal registries reporting on patients with end-stage kidney disease [ESKD] and on renal replacement therapy [RRT]. There has been a paucity of information on pre-dialysis CKD cohorts, and many issues related to these poorly described populations are unresolved. To this end, international organizations have called for CKD surveillance systems across all countries. In Australia, we have responded by developing the Chronic Kidney Disease in Queensland [CKD.QLD] with three main platforms consisting of CKD Registry, clinical trials and development of biobank. This registry which is the core component of CKD surveillance was conceptualized specifically for the pre-dialysis population in the public health system in Queensland, Australia. Recruitment started in May 2011, and to date the Registry has evolved as one of the largest CKD cohorts in the world with recruitment close to 7000 patients. The Registry has had many outcomes, including being the nidus for Australia's first National Health and Medical Research Council [NHMRC] CKD Centre of Research Excellence [CKD.CRE]. The Registry, with its linkage to Queensland Health datasets, is reporting, and is expected to continue generating, significant information on multiple aspects of CKD, its trajectory, management and patient outcomes. Intent of the CKD.CRE is to facilitate an expanded Registry network that has representation from health services, both public and private, across Australia.

Multiple bacterial species reside in chronic wounds

DEFF Research Database (Denmark)

Gjødsbøl, Kristine; Christensen, Jens Jørgen; Karlsmark, Tonny

2006-01-01

. aeruginosa were found to be significantly larger than ulcers without the presence of P. aeruginosa (P wound is colonised by multiple bacterial species and that once they are established many of them persist in the wound. Our results suggest that the presence...... of P. aeruginosa in venous leg ulcers can induce ulcer enlargement and/or cause delayed healing....

Repeated Muscle Injury as a Presumptive Trigger for Chronic Masticatory Muscle Pain

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Dean Dessem

2011-01-01

Full Text Available skeletal muscles sustain a significant loss of maximal contractile force after injury, but terminally damaged fibers can eventually be replaced by the growth of new muscle (regeneration, with full restoration of contractile force over time. After a second injury, limb muscles exhibit a smaller reduction in maximal force and reduced inflammation compared with that after the initial injury (i.e., repeated bout effect. In contrast, masticatory muscles exhibit diminished regeneration and persistent fibrosis, after a single injury; following a second injury, plasma extravasation is greater than after a single injury and maximal force is decreased more than after the initial injury. Thus, masticatory muscles do not exhibit a repeated bout effect and are instead increasingly damaged by repeated injury. We propose that the impaired ability of masticatory muscles to regenerate contributes to chronic muscle pain by leading to an accumulation of tissue damage, fibrosis, and a persistent elevation and prolonged membrane translocation of nociceptive channels such as P2X3 as well as enhanced expression of neuropeptides including CGRP within primary afferent neurons. These transformations prime primary afferent neurons for enhanced responsiveness upon subsequent injury thus triggering and/or exacerbating chronic muscle pain.

Decreased MORF leads to prolonged endoplasmic reticulum stress in periodontitis-associated chronic inflammation.

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Xue, Peng; Li, Bei; An, Ying; Sun, Jin; He, Xiaoning; Hou, Rui; Dong, Guangying; Fei, Dongdong; Jin, Fang; Wang, Qintao; Jin, Yan

2016-11-01

The association between inflammation and endoplasmic reticulum (ER) stress has been described in many diseases. However, if and how chronic inflammation governs the unfolded protein response (UPR) and promotes ER homeostasis of chronic inflammatory disease remains elusive. In this study, chronic inflammation resulted in ER stress in mesenchymal stem cells in the setting of periodontitis. Long-term proinflammatory cytokines induced prolonged ER stress and decreased the osteogenic differentiation of periodontal ligament stem cells (PDLSCs). Interestingly, we showed that chronic inflammation decreases the expression of lysine acetyltransferase 6B (KAT6B, also called MORF), a histone acetyltransferase, and causes the upregulation of a key UPR sensor, PERK, which lead to the persistent activation of the UPR in PDLSCs. Furthermore, we found that the activation of UPR mediated by MORF in chronic inflammation contributes to the PERK-related deterioration of the osteogenic differentiation of PDLSCs both in vivo and in vitro. Taken together, our results suggest that chronic inflammation compromises UPR function through MORF-mediated-PERK transcription, which is a previously unrecognized mechanism that contributes to impaired ER function, prolonged ER stress and defective osteogenic differentiation of PDLSCs in periodontitis.

Chronic disease as risk multiplier for disadvantage.

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Stutzin Donoso, Francisca

2018-03-06

This paper starts by establishing a prima facie case that disadvantaged groups or individuals are more likely to get a chronic disease and are in a disadvantaged position to adhere to chronic treatment despite access through Universal Health Coverage. However, the main aim of this paper is to explore the normative implications of this claim by examining two different but intertwined argumentative lines that might contribute to a better understanding of the ethical challenges faced by chronic disease health policy. The paper develops the argument that certain disadvantages which may predispose to illness might overlap with disadvantages that may hinder self-management, potentially becoming disadvantageous in handling chronic disease. If so, chronic diseases may be seen as disadvantages in themselves, describing a reproduction of disadvantage among the chronically ill and a vicious circle of disadvantage that could both predict and shed light on the catastrophic health outcomes among disadvantaged groups-or individuals-dealing with chronic disease. © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2018. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

ON THE ROLE OF BACTERIAL MICROFLORA IN ETIOLOGY OF CHRONIC ADENOIDITIS IN CHILDREN

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D. A. Tulupov

2014-01-01

Full Text Available A review of the results of clinical studies on the role of pathogenic bacterial microflora in etiology of chronic adenoiditis in children is shown in this article. According to the literature data the main cause of the development of chronic diseases of the nasopharynx in children is viral infection. The role of the bacterial microflora is secondary, but nevertheless significant. The main bacterial pathogens isolated from the nasopharynx of children with chronic adenoiditis are Staphylococcus aureus, Haemophilus influenzae and Streptococcus pneumonia. However there is significant dissociation in the prevalence of these bacterial agents according to the data of different scientists. Ability of the bacteria to produce biomembranes plays significant role in formation of persistence of the above-mentioned pathogens in the nasopharynx in chronic adenoiditis. Bacterial biomembranes as well as the revealing of the large amounts of bacteria within the tissues of adenoids determines discussions on possibilities of systemic and topical antibacterial treatment. 

From acute to persistent low back pain: a longitudinal investigation of somatosensory changes using quantitative sensory testing-an exploratory study.

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Marcuzzi, Anna; Wrigley, Paul J; Dean, Catherine M; Graham, Petra L; Hush, Julia M

2018-03-01

Chronic low back pain (LBP) is commonly associated with generalised pain hypersensitivity. It is suggested that such somatosensory alterations are important determinants for the transition to persistent pain from an acute episode of LBP. Although cross-sectional research investigating somatosensory function in the acute stage is developing, no longitudinal studies designed to evaluate temporal changes have been published. This exploratory study aimed to investigate the temporal development of somatosensory changes from the acute stage of LBP to up to 4 months from onset. Twenty-five people with acute LBP (testing with the assessor blinded to group allocation, and again at 2 and 4 months. Psychological variables were concurrently assessed. People with acute LBP were classified based on their average pain severity over the previous week at 4 months as recovered (≤1/10 numeric rating scale) or persistent (≥2/10 numeric rating scale) LBP. In the persistent LBP group, (1) there was a significant decrease in pressure pain threshold between 2 and 4 months ( P psychological variables were significantly higher in those with persistent LBP compared with the recovered LBP group at all time points ( P importance of concurrent evaluation of psychological contributors in acute LBP.

Persistent cough in an adolescent.

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Stein, M T; Harper, G; Chen, J

1999-12-01

Jessica, a 14-year-old girl with a history of asthma, went to her pediatrician's office because of a persistent cough. She had been coughing for at least 3 months with occasional cough-free periods of less than a few days. The cough was nonproductive and was not accompanied by fever, rhinorrhea, or facial or chest pain. Jessica and her mother observed that the cough increased with exercise and typically was not present during sleep. She has used two metered-dose inhalers--albuterol and cromolyn--without any change in the cough pattern. For the past 5 years, Jessica has had mild asthma responsive to albuterol. She enjoys running on the cross-country team, soccer, and dancing. She is an average student and denies any change in academic performance. She has never been hospitalized or had an emergency department visit for asthma or pneumonia. There has been no recent travel or exposure to a person with a chronic productive cough, tobacco smoke, or a live-in pet. Jessica lives with her mother and younger sister in a 10-year-old, carpeted apartment without any evidence of mold or recent renovation. In the process of taking the history, the pediatrician noticed that Jessica coughed intermittently, with two or three coughs during each episode. At times, the cough was harsh; at other times, it was a quiet cough, as if she were clearing her throat. She was cooperative, without overt anxiety or respiratory distress. After a complete physical examination with normal findings, the pediatrician interviewed Jessica and her mother alone. Jessica's parents had been divorced for the past 6 years. She lived with her mother but visited her father, and his new family with two young children, every weekend. She spoke about this arrangement comfortably and said that she loved her father and mother but didn't like the tension she experienced at her father's home. "I don't like adults arguing when kids are around." When asked why she thought the cough persisted so long, she commented in a

Does underwater flash photography affect the behaviour, movement and site persistence of seahorses?

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Harasti, D; Gladstone, W

2013-11-01

The effect of flash photography on seahorse species has never been tested. An experiment was established to test the effect of flash photography and the handling of Hippocampus whitei, a medium-sized seahorse species endemic to Australia, on their behavioural responses, movements and site persistence. A total of 24 H. whitei were utilized in the experiment with eight in each of the three treatments (flash photography, handling and control). The effect of underwater flash photography on H. whitei movements was not significant; however, the effect of handling H. whitei to take a photograph had a significant effect on their short-term behavioural responses to the photographer. Kaplan-Meier log-rank test revealed that there was no significant difference in site persistence of H. whitei from each of the three treatments and that flash photography had no long-term effects on their site persistence. It is concluded that the use of flash photography by divers is a safe and viable technique with H. whitei, particularly if photographs can be used for individual identification purposes. © 2013 The Fisheries Society of the British Isles.

Assessment of immunological changes in Epstein-Barr virus co-infection in Egyptian chronic HCV patients

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Sahar Shoman

2014-09-01

Full Text Available Epstein-Barr virus (EBV plays a major role in liver pathology. Similar to other members of the herpesvirus family, EBV establishes a persistent infection in more than 90% of adults. The aim of this study was to evaluate the impact of EBV and chronic hepatitis C co-infection (HCV on biochemical and immunological responses in patients. The study was conducted in 62 patients and 33 apparently healthy controls. Patients were divided into three groups: group I, consisting of 31 patients with chronic hepatitis C infection (CHC, group II, consisting of eight patients with EBV infection and without HCV infection and group III, consisting of 23 patients with EBV and chronic HCV. The percentage of CD3+ cells, helper CD4+ cells and CD19+ B-cells was measured by flow cytometry. Human interferon-γ (IFN-γ and interleukin (IL-15 levels were measured by an ELISA. The levels of liver alanine aminotransferase and aspartate aminotransferase enzymes were higher in EBV/HCV patients compared to that in EBV and HCV mono-infected patients. EBV/HCV patients had significantly reduced percentages of CD3+ and CD4+ cells compared to EBV patients. Serum IFN-γ levels were significantly reduced in EBV/HCV patients (3.86 pg/mL compared to CHC patients (6.76 pg/mL and normal controls (4.69 pg/mL. A significant increase in serum IL-15 levels was observed in EBV/HCV patients (67.7 pg/mL compared to EBV patients (29.3 pg/mL. Taken together, these observations suggest that HCV and EBV co-infection can potentiate immune response dampening in patients.

Traumatization and chronic pain: a further model of interaction

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Egloff N

2013-11-01

Full Text Available Niklaus Egloff,1 Anna Hirschi,2 Roland von Känel1 1Department of General Internal Medicine, Division of Psychosomatic Medicine, Inselspital, University Hospital, Bern, Switzerland; 2Outpatient Clinic for Victims of Torture and War, Swiss Red Cross, Bern-Wabern, Switzerland Abstract: Up to 80% of patients with severe posttraumatic stress disorder are suffering from “unexplained” chronic pain. Theories about the links between traumatization and chronic pain have become the subject of increased interest over the last several years. We will give a short summary about the existing interaction models that emphasize particularly psychological and behavioral aspects of this interaction. After a synopsis of the most important psychoneurobiological mechanisms of pain in the context of traumatization, we introduce the hypermnesia–hyperarousal model, which focuses on two psychoneurobiological aspects of the physiology of learning. This hypothesis provides an answer to the hitherto open question about the origin of pain persistence and pain sensitization following a traumatic event and also provides a straightforward explanatory model for educational purposes. Keywords: posttraumatic stress disorder, chronic pain, hypermnesia, hypersensitivity, traumatization

Environmental Burkholderia cenocepacia Strain Enhances Fitness by Serial Passages during Long-Term Chronic Airways Infection in Mice

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Alessandra Bragonzi

2017-11-01

Full Text Available Burkholderia cenocepacia is an important opportunistic pathogen in cystic fibrosis (CF patients, and has also been isolated from natural environments. In previous work, we explored the virulence and pathogenic potential of environmental B. cenocepacia strains and demonstrated that they do not differ from clinical strains in some pathogenic traits. Here, we investigated the ability of the environmental B. cenocepacia Mex1 strain, isolated from the maize rhizosphere, to persist and increase its virulence after serial passages in a mouse model of chronic infection. B. cenocepacia Mex1 strain, belonging to the recA lineage IIIA, was embedded in agar beads and challenged into the lung of C57Bl/6 mice. The mice were sacrificed after 28 days from infection and their lungs were tested for bacterial loads. Agar beads containing the pool of B. cenocepacia colonies from the four sequential passages were used to infect the mice. The environmental B. cenocepacia strain showed a low incidence of chronic infection after the first passage; after the second, third and fourth passages in mice, its ability to establish chronic infection increased significantly and progressively up to 100%. Colonial morphology analysis and genetic profiling of the Mex1-derived clones recovered after the fourth passage from infected mice revealed that they were indistinguishable from the challenged strain both at phenotypic and genetic level. By testing the virulence of single clones in the Galleria mellonella infection model, we found that two Mex1-derived clones significantly increased their pathogenicity compared to the parental Mex1 strain and behaved similarly to the clinical and epidemic B. cenocepacia LMG16656T. Our findings suggest that serial passages of the environmental B. cenocepacia Mex1 strain in mice resulted in an increased ability to determine chronic lung infection and the appearance of clonal variants with increased virulence in non-vertebrate hosts.

Assessment of persistency and bioaccumulation in pesticide registration frameworks within the Organization for Economic Cooperation and Development.

NARCIS (Netherlands)

Montforts, Mark H M M

This article describes the results of a survey conducted in 2003 on methods used by different member countries within the Organization for Economic Cooperation and Development (OECD) to evaluate persistent and bioaccumulative pesticides. The objectives were to establish the differences in taking

Isolation mediates persistent founder effects on zooplankton colonisation in new temporary ponds

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Badosa, Anna; Frisch, Dagmar; Green, Andy J.; Rico, Ciro; Gómez, Africa

2017-03-01

Understanding the colonisation process in zooplankton is crucial for successful restoration of aquatic ecosystems. Here, we analyzed the clonal and genetic structure of the cyclical parthenogenetic rotifer Brachionus plicatilis by following populations established in new temporary ponds during the first three hydroperiods. Rotifer populations established rapidly after first flooding, although colonisation was ongoing throughout the study. Multilocus genotypes from 7 microsatellite loci suggested that most populations (10 of 14) were founded by few clones. The exception was one of the four populations that persisted throughout the studied hydroperiods, where high genetic diversity in the first hydroperiod suggested colonisation from a historical egg bank, and no increase in allelic diversity was detected with time. In contrast, in another of these four populations, we observed a progressive increase of allelic diversity. This population became less differentiated from the other populations suggesting effective gene flow soon after its foundation. Allelic diversity and richness remained low in the remaining two, more isolated, populations, suggesting little gene flow. Our results highlight the complexity of colonisation dynamics, with evidence for persistent founder effects in some ponds, but not in others, and with early immigration both from external source populations, and from residual, historical diapausing egg banks.

Structural Relationships among Self-Regulated Learning, Learning Flow, Satisfaction, and Learning Persistence in Cyber Universities

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Joo, Young Ju; Joung, Sunyoung; Kim, Jiyeon

2014-01-01

Learning persistence in a cyber-learning environment is not only an index determining the success or failure of individual learners but also a source of important information to establish the management direction of educational programs in an organization. Accordingly, learners need to be motivated to continue to grow in order to ensure both…

Species-level persistence probabilities for recovery and conservation status assessment.

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Che-Castaldo, Judy P; Neel, Maile C

2016-12-01

Recovery planning for species listed under the U.S. Endangered Species Act has been hampered by a lack of consistency and transparency, which can be improved by implementing a standardized approach for evaluating species status and developing measurable recovery criteria. However, managers lack an assessment method that integrates threat abatement and can be used when demographic data are limited. To help meet these needs, we demonstrated an approach for evaluating species status based on habitat configuration data. We applied 3 established persistence measures (patch occupancy, metapopulation capacity, and proportion of population lost) to compare 2 conservation strategies (critical habitat designated by the U.S. Fish and Wildlife Service and the Forest Service's Carbonate Habitat Management Strategy) and 2 threat scenarios (maximum limestone mining, removal of all habitat in areas with mining claims; minimum mining, removal of habitat only in areas with existing operations and high-quality ore) against a baseline of existing habitat for 3 federally listed plant species. Protecting all area within the designated critical habitat maintained a similar level (83.9-99.9%) of species persistence as the baseline, whereas maximum mining greatly reduced persistence (0.51-38.4% maintained). The 3 persistence measures provided complementary insights reflecting different aspects of habitat availability (total area, number of patches, patch size, and connectivity). These measures can be used to link recovery criteria developed following the 3 R principles (representation, redundancy, and resilience) to the resulting improvements in species viability. By focusing on amount and distribution of habitat, our method provides a means of assessing the status of data-poor species to inform decision making under the Endangered Species Act. © 2016 Society for Conservation Biology.

Strain-specific outcomes of repeated social defeat and chronic fluoxetine treatment in the mouse.

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Razzoli, Maria; Carboni, Lucia; Andreoli, Michela; Michielin, Francesca; Ballottari, Alice; Arban, Roberto

2011-01-01

Social stress is a risk factor for affective disorders in vulnerable individuals. Although the biological nature of stress susceptibility/resilience remains to be elucidated, genetic variation is considered amongst the principal contributors to brain disorders. Furthermore, genetic predisposition may be determinant for the therapeutic outcome, as proposed for antidepressant treatments. In the present studies we compared the inherently diverse genetic backgrounds of 2 mouse strains by assessing the efficacy of a chronic antidepressant treatment in a repeated social stress procedure. C57BL/6J and BalbC mice underwent 10-day social defeats followed by 28-day fluoxetine treatment (10 mg/kg/mL, p.o.). In C57BL/6J, most of the social defeat-induced changes were of metabolic nature including persistently altered feed efficiency and decreased abdominal fat stores that were ameliorated by fluoxetine. BalbC mouse behavior was persistently affected by social defeat both in the social avoidance and the forced swim tests, and in either procedure it was restored by chronic fluoxetine, whereas their endocrine parameters were mostly unaffected. The highlighted strain-specific responsivity to the metabolic and behavioral consequences of social defeat and to the chronic antidepressant treatment offers a promising research tool to further explore the underlying neural mechanisms and genetic basis of stress susceptibility and treatment response. Copyright © 2010 Elsevier Inc. All rights reserved.

Direct evaluation of Pseudomonas aeruginosa biofilm mediators in a chronic infection model.

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Byrd, Matthew S; Pang, Bing; Hong, Wenzhou; Waligora, Elizabeth A; Juneau, Richard A; Armbruster, Chelsie E; Weimer, Kristen E D; Murrah, Kyle; Mann, Ethan E; Lu, Haiping; Sprinkle, April; Parsek, Matthew R; Kock, Nancy D; Wozniak, Daniel J; Swords, W Edward

2011-08-01

Biofilms contribute to Pseudomonas aeruginosa persistence in a variety of diseases, including cystic fibrosis, burn wounds, and chronic suppurative otitis media. However, few studies have directly addressed P. aeruginosa biofilms in vivo. We used a chinchilla model of otitis media, which has previously been used to study persistent Streptococcus pneumoniae and Haemophilus influenzae infections, to show that structures formed in vivo are biofilms of bacterial and host origin within a matrix that includes Psl, a P. aeruginosa biofilm polysaccharide. We evaluated three biofilm and/or virulence mediators of P. aeruginosa known to affect biofilm formation in vitro and pathogenesis in vivo--bis-(3',5')-cyclic dimeric GMP (c-di-GMP), flagella, and quorum sensing--in a chinchilla model. We show that c-di-GMP overproduction has a positive impact on bacterial persistence, while quorum sensing increases virulence. We found no difference in persistence attributed to flagella. We conclude from these studies that a chinchilla otitis media model provides a means to evaluate pathogenic mediators of P. aeruginosa and that in vitro phenotypes should be examined in multiple infection systems to fully understand their role in disease.

Chronic widespread musculoskeletal pain, fatigue, depression and disordered sleep in chronic post-SARS syndrome; a case-controlled study.

Science.gov (United States)

Moldofsky, Harvey; Patcai, John

2011-03-24

The long term adverse effects of Severe Acute Respiratory Syndrome (SARS), a viral disease, are poorly understood. Sleep physiology, somatic and mood symptoms of 22 Toronto subjects, 21 of whom were healthcare workers, (19 females, 3 males, mean age 46.29 yrs.+/- 11.02) who remained unable to return to their former occupation (mean 19.8 months, range: 13 to 36 months following SARS) were compared to 7 healthy female subjects. Because of their clinical similarities to patients with fibromyalgia syndrome (FMS) these post-SARS subjects were similarly compared to 21 drug free female patients, (mean age 42.4 +/- 11.8 yrs.) who fulfilled criteria for fibromyalgia. Chronic post-SARS is characterized by persistent fatigue, diffuse myalgia, weakness, depression, and nonrestorative sleep with associated REM-related apneas/hypopneas, an elevated sleep EEG cyclical alternating pattern, and alpha EEG sleep anomaly. Post- SARS patients had symptoms of pre and post-sleep fatigue and post sleep sleepiness that were similar to the symptoms of patients with FMS, and similar to symptoms of patients with chronic fatigue syndrome. Both post-SARS and FMS groups had sleep instability as indicated by the high sleep EEG cyclical alternating pattern rate. The post-SARS group had a lower rating of the alpha EEG sleep anomaly as compared to the FMS patients. The post-SARS group also reported less pre-sleep and post-sleep musculoskeletal pain symptoms. The clinical and sleep features of chronic post-SARS form a syndrome of chronic fatigue, pain, weakness, depression and sleep disturbance, which overlaps with the clinical and sleep features of FMS and chronic fatigue syndrome.

The role of metabolism in bacterial persistence

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Stephanie M. Amato

2014-03-01

Full Text Available Bacterial persisters are phenotypic variants with extraordinary tolerances toward antibiotics. Persister survival has been attributed to inhibition of essential cell functions during antibiotic stress, followed by reversal of the process and resumption of growth upon removal of the antibiotic. Metabolism plays a critical role in this process, since it participates in the entry, maintenance, and exit from the persister phenotype. Here, we review the experimental evidence that demonstrates the importance of metabolism to persistence, highlight the successes and potential for targeting metabolism in the search for anti-persister therapies, and discuss the current methods and challenges to understand persister physiology.

Type D personality and cardiac mortality in patients with chronic heart failure

DEFF Research Database (Denmark)

Schiffer, Angélique A; Smith, Otto R F; Pedersen, Susanne S.

2010-01-01

Clinical predictors of cardiac mortality in chronic heart failure (CHF) are established, but less is known about chronic psychological predictors. Therefore, we examined the prognostic value of Type D personality (tendency to experience negative feelings and inhibit self-expression) in CHF patients....

Introduction: Persistent Modelling

DEFF Research Database (Denmark)

Ayres, Phil

2012-01-01

This introduction to 'Persistent Modelling – an extended role for architectural representation' identifies how the book probes the relationship between representation and the represented, in an architectural context. It discusses how the book presents an examination and discussion of historical......, familiar contemporary and, perhaps, not so familiar emerging manifestations of this relation. What persists from this probing, fully intact, is that representation and the represented remain inextricably related in our contemporary and emerging practices. What comes into focus is that the nature...

Contribution of stone size to chronic kidney disease in kidney stone formers.

Science.gov (United States)

Ahmadi, Farrokhlagha; Etemadi, Samira Motedayen; Lessan-Pezeshki, Mahbob; Mahdavi-Mazdeh, Mitra; Ayati, Mohsen; Mir, Alireza; Yazdi, Hadi Rokni

2015-01-01

To determine whether stone burden correlates with the degree of chronic kidney disease in kidney stone formers. A total of 97 extracorporeal shockwave lithotripsy candidates aged 18 years and older were included. Size, number and location of the kidney stones, along with cumulative stone size, defined as the sum of diameters of all stones) were determined. Estimated glomerular filtration rate was determined using the Chronic Kidney Disease Epidemiology Collaboration cystatin C/creatinine equation, and chronic kidney disease was defined as estimated glomerular filtration rate chronic kidney disease. The relationship persisted even after adjustment for age, sex, body mass index, C-reactive protein, fasting plasma glucose, thyroid stimulating hormone, presence of microalbuminuria, history of renal calculi, history of extracorporeal shockwave lithotripsy, number and location of the stones (odds ratio 1.24, 95% confidence interval 1.02-1.52). The same was not observed for individuals with a cumulative stone size ≥ 20 mm. In kidney stone formers with a cumulative stone size up to 20 mm, estimated glomerular filtration rate linearly declines with increasing cumulative stone size. Additionally, cumulative stone size is an independent predictor of chronic kidney disease in this group of patients. © 2014 The Japanese Urological Association.

Zika Virus Persistently Infects and Is Basolaterally Released from Primary Human Brain Microvascular Endothelial Cells

Directory of Open Access Journals (Sweden)

Megan C. Mladinich

2017-07-01

Full Text Available Zika virus (ZIKV is a mosquito-borne Flavivirus that has emerged as the cause of encephalitis and fetal microencephaly in the Americas. ZIKV uniquely persists in human bodily fluids for up to 6 months, is sexually transmitted, and traverses the placenta and the blood-brain barrier (BBB to damage neurons. Cells that support persistent ZIKV replication and mechanisms by which ZIKV establishes persistence remain enigmatic but central to ZIKV entry into protected neuronal compartments. The endothelial cell (EC lining of capillaries normally constrains transplacental transmission and forms the BBB, which selectively restricts access of blood constituents to neurons. We found that ZIKV (strain PRVABC59 persistently infects and continuously replicates in primary human brain microvascular ECs (hBMECs, without cytopathology, for >9 days and following hBMEC passage. ZIKV did not permeabilize hBMECs but was released basolaterally from polarized hBMECs, suggesting a direct mechanism for ZIKV to cross the BBB. ZIKV-infected hBMECs were rapidly resistant to alpha interferon (IFN-α and transiently induced, but failed to secrete, IFN-β and IFN-λ. Global transcriptome analysis determined that ZIKV constitutively induced IFN regulatory factor 7 (IRF7, IRF9, and IFN-stimulated genes (ISGs 1 to 9 days postinfection, despite persistently replicating in hBMECs. ZIKV constitutively induced ISG15, HERC5, and USP18, which are linked to hepatitis C virus (HCV persistence and IFN regulation, chemokine CCL5, which is associated with immunopathogenesis, as well as cell survival factors. Our results reveal that hBMECs act as a reservoir of persistent ZIKV replication, suggest routes for ZIKV to cross hBMECs into neuronal compartments, and define novel mechanisms of ZIKV persistence that can be targeted to restrict ZIKV spread.

Interacting influences of gender and chronic pain status on parasympathetically mediated heart rate variability in adolescents and young adults.

Science.gov (United States)

Walker, Lynn S; Stone, Amanda L; Smith, Craig A; Bruehl, Stephen; Garber, Judy; Puzanovova, Martina; Diedrich, André

2017-08-01

Considerable research links chronic pain to autonomic nervous system (ANS) dysfunction, specifically low heart rate variability (HRV) mediated by reduced parasympathetic activity. However, little is known about factors that influence ANS function in chronic pain. The ANS is the primary pathway for brain-gut communication, making it of particular interest in gastrointestinal disorders, such as irritable bowel syndrome, characterized by functional abdominal pain (FAP). We evaluated the relation of sex, pain severity, and psychological stress to ANS function in adolescents/young adults from a database of pediatric FAP and control participants enrolled 8 years earlier in a prospective study of pain. At follow-up in adolescence/young adulthood (Mean age = 19.46, SD = 3.48), we classified participants as Pain-Remit (n = 130), Pain-Persist (n = 96), and pain-free controls (n = 123). We recorded electrocardiogram data at rest and during laboratory stressors. Results demonstrated significantly lower HRV in Pain-Persist females compared with Pain-Remit females, female controls, and all males regardless of pain category. Spectral analysis of electrocardiogram showed that Pain-Persist females had reduced power in the high frequency domain of cardiac activity, ie, reduced parasympathetic "braking" of sympathetic activity, both at rest and during stress. Pain-Remit females exhibited levels of autonomic imbalance intermediate between those of females with persistent FAP and all other participants. Parasympathetically mediated low HRV in young women with persistent FAP may reflect a peripheral mechanism (eg, gut dysfunction) or a central nervous system mechanism (eg, pain amplification or poor emotion self-regulation) involving prolonged sympathetic activation.

Multiple FNH-Like Lesions in a Patient with Chronic Budd-Chiari Syndrome: Gd-EOB-Enhanced MRI and BR1 CEUS Findings