Search

Objective Despite current diagnostic systems distinguishing schizophrenia ( SZ) and bipolar disorder ( BD) as separate diseases, emerging evidence suggests they share a number of clinical and epidemiological features, such as increased cardiovascular disease ( CVD) risk. It is not well understood if poor cardiac autonomic nervous system regulation, which can be indexed non-invasively by the calculation of heart rate variability ( HRV), contributes to these common CVD risk factors in both diseases. Method We calculated HRV in 47 patients with SZ, 33 patients with BD and 212 healthy controls. Measures of symptom severity were also collected from the patient groups. Results Heart rate variability was significantly reduced in both these disorders in comparison with the healthy participants; however, there were no HRV differences between disorders. Importantly, these reductions were independent of the medication, age or body mass index effects. There was also preliminary evidence that patients with reduced HRV had increased overall and negative psychosis symptom severity regardless of SZ or BD diagnosis. Conclusion We suggest that HRV may provide a possible biomarker of CVD risk and symptom severity in severe mental illness. Thus, our results highlight the importance of cardiometabolic screening across SZ and bipolar spectrum disorders. [ABSTRACT FROM AUTHOR]

Recruitment issues are common in couple relationship education ( CRE). Hence, learning more about factors shaping attitudes toward CRE could aid with these efforts. This study used dyadic data techniques to assess how common recruitment barriers are associated with attitudes toward CRE. The study also investigated differences by gender and income in a sample of 99 couples. Results show that time pressure influenced attitudes toward CRE differently for male and female partners, and time and vocational stressors were more impactful for those with higher incomes. The findings underscore the need to implement CRE marketing efforts reflective of the attitudes and needs of the audience. [ABSTRACT FROM AUTHOR]

Aim: The aim of this study was to test the hypothesis that IL-6 regulates exercise-induced gene responses in subcutaneous adipose tissue in mice. Methods: Four-month-old male IL-6 whole body knockout (KO) mice and C57B wild-type (WT) mice performed 1 h of treadmill exercise, where subcutaneous adipose tissue (AT) was removed either immediately after, 4 h or 10 h after exercise as well as from mice not running acutely. Moreover, AT was sampled at resting conditions after 5 weeks of exercise training. Results: AT leptin mRNA decreased immediately after a single running exercise bout in both genotypes and returned to baseline within 10 h of recovery in IL-6 KO mice, but not WT mice. Leptin mRNA content decreased in WT and increased in IL-6 KO mice with training, but without significant alterations in leptin protein. Acute exercise induced a decrease in the AT TNFα mRNA content in WT, but not in IL-6-KO mice, while training lowered resting levels of TNFα mRNA in both genotypes. In addition, an exercise-induced decline in AT PPARγ mRNA content was absent in IL-6 KO mice and in line training increased PPARγ mRNA only in IL-6 KO mice. Conclusion: The present findings indicate a role of IL-6 in regulating exercise- and training-induced leptin and PPARγ expression in adipose tissue. In addition, while IL-6 is required for TNF-α mRNA reduction in response to acute exercise, IL-6 does not appear to be mandatory for anti-inflammatory effects of exercise training in adipose tissue. [ABSTRACT FROM AUTHOR]

Bennouna-Greene V, Kremer S, Stoetzel C, Christmann D, Schuster C, Durand M, Verloes A, Sigaudy S, Holder-Espinasse M, Godet J, Brandt C, Marion V, Danion A, Dietemann J-L, Dollfus H. Hippocampal dysgenesis and variable neuropsychiatric phenotypes in patients with Bardet-Biedl syndrome underline complex CNS impact of primary cilia. The Bardet-Biedl syndrome (BBS) is a rare ciliopathy clinically defined by the association of retinitis pigmentosa, polydactyly, obesity, kidney disease and cognitive impairment. The cognitive functioning, behavioral phenotype, prevalence of psychiatric diseases and memory performances of a cohort of 34 patients with BBS were evaluated and a systemic brain magnetic resonance imaging (MRI) was performed. The patients' cognitive functioning was of marked variable efficiency ranging from normal to disabling performances. Neuropsychological disorders such as slow thought process, attention difficulties and obsessive-compulsive traits were observed. Our main finding was hippocampal dysgenesis, diagnosed by MRI, found in 42.31% of the patients in this cohort. Moreover, we show that BBS proteins are expressed in the human hippocampus and in the human brain in the normal subject. Recent literature in the murine model shows that hippocampal neurogenesis, in particular in the adult mouse, requires an intact primary cilia. These results encourage us to further investigate the possible role of BBS proteins in the hippocampus and related central nervous system structures. [ABSTRACT FROM AUTHOR]

Summary Most emerging infectious diseases are zoonotic, yet recent commissions have highlighted deficiencies in their surveillance. We conducted a survey to understand the needs of state agencies for zoonotic disease surveillance. The findings will hopefully support the development of biomedical informatics applications that can link animal and human data for surveillance. [ABSTRACT FROM AUTHOR]

In order to produce components in optical quality in ultra-precision cutting processes it is very important to have a highly balanced system. Achieving the best possible balancing state is a time consuming process. Therefore, the prediction of the influence of the balancing state on the surface quality of the component is desirable. On the other hand, such a model should enable us to predict a necessary balancing state for a desired surface quality and thus save time in the balancing process. In this paper we present a model of an ultra-precision cutting experimental platform that determines vibrations and displacements of the platform caused by unbalances and forces from the cutting process. The actual cutting parameters are described by a second model. Since they depend on the unbalance displacements, both models have to be coupled to an interaction model. To compute balancing weights from vibrational measurements, regularization techniques for the solution of inverse and ill-posed problems are employed and presented. [ABSTRACT FROM AUTHOR]

Background Cardiovascular disease is an increasing concern among HIV-infected persons and their providers. We determined if fatty liver disease is a marker for underlying coronary atherosclerosis among HIV-infected persons. Methods We performed a cross-sectional study in HIV-infected adults to evaluate the prevalence of and factors, including fatty liver disease, associated with subclinical coronary atherosclerosis. All participants underwent computed tomography for determination of coronary artery calcium (CAC; positive defined as a score >0) and fatty liver disease (defined as a liver-to-spleen ratio <1.0). Factors associated with CAC were determined using multivariate logistic regression models. Results We included in the study 223 HIV-infected adults with a median age of 43 years [interquartile range (IQR) 36-50 years]; 96% were male and 49% were Caucasian. The median CD4 count was 586 cells/μL and 83% were receiving antiretroviral medications. Seventy-five (34%) had a positive CAC score and 29 (13%) subjects had fatty liver disease. Among those with CAC scores of 0, 1-100 and >100, the percentage with concurrent fatty liver disease was 8, 18 and 41%, respectively ( P=0.001). In the multivariate model, CAC was associated with increasing age [odds ratio (OR) 4.3 per 10 years; P<0.01], hypertension (OR 2.6; P<0.01) and fatty liver disease (OR 3.8; P<0.01). Conclusions Coronary atherosclerosis as detected using CAC is prevalent among young HIV-infected persons. The detection of fatty liver disease among HIV-infected adults should prompt consideration of assessment for underlying cardiovascular disease and risk factor reduction. [ABSTRACT FROM AUTHOR]

Zoonotic diseases are infectious diseases transmittable between animals and humans and outbreaks of these diseases in animals can signify that humans are also infected (or vice versa). Thus, communication between animal and human health agencies is critical for surveillance. Understanding how these agencies conduct surveillance and share information is important for the development of successful automated zoonotic monitoring systems. Individual interviews were conducted with 13 professionals who perform animal or human zoonotic disease surveillance in one of the New England states. Questions centred on existing surveillance methods, collaborations between animal and human health agencies, and technological and data needs. The results showed that agencies routinely communicate over suspected zoonotic disease cases, yet there are barriers preventing automated electronic linking of health data of animals and humans. These include technological barriers and barriers due to sensitivity and confidentiality of information. Addressing these will facilitate the development of electronic systems for integrating animal and human zoonotic disease surveillance data. [ABSTRACT FROM AUTHOR]

Background: Atopic dermatitis (AD) is a T cell dependent chronic relapsing inflammatory skin disorder successfully treated with cyclosporine A (CsA). Clinical observations indicate that even low-dose CsA therapy is successful in severely affected AD patients. We studied the impact of low-dose CsA therapy on the ability of T helper cells to be activated, and examined whether regulatory T (Treg) cells are increased in these patients. Methods: Peripheral T cells were activated in a whole blood sample and interleukin-2 producing cells were measured by intracellular cytokine staining. Regulatory T cells were analyzed by intracellular FoxP3 staining. Regulatory T cells (CD4+CD25+CD127low) and effector T cells (CD4+CD25−CD127+) were sorted by flow cytometry and used for suppression assays. Results: A group of AD patients treated with low-dose CsA had a significantly larger Treg cell population than a healthy control subject group. In individual patients, onset of low-dose CsA therapy reduced the ability of T cells to be activated to 42 ± 18% ( P < 0.005) and significantly increased Treg cells, both in absolute numbers (1.6-fold change) and frequencies (1.7-fold change). Treg cells from AD patients showed similar suppressive capacities as Treg cells from healthy donors. Furthermore, Treg cells from AD patients had skin homing properties. Conclusion: Our results indicate that the therapeutic effect of low-dose CsA therapy in AD patients might be not only mediated by the inhibition of T cell hyperactivity but also by an increased population of Treg cells. [ABSTRACT FROM AUTHOR]

Background Epilepsy has a pervasive impact on the lives of people with intellectual disability and their carers. The delivery of high-quality care is impacted on by the complexity and diversity of epilepsy in this population. This article presents the results of a consensus clinical guideline process. Results A Delphi process identified a list of priority areas for the development of evidence-based guidelines. All guidelines were graded and consensus on scoring was achieved across the guideline group. Conclusion There is a dearth of high-quality evidence from well-constructed studies on which to base guidance. However, the development of internationally derived consensus guidelines may further support the management of epilepsy in adults with an intellectual disability. [ABSTRACT FROM AUTHOR]

In this article we describe some of the benefits and challenges of using self ratings and ratings of the partner to measure empathy and similar terms in couple research. If both members of the dyad are assessed, there will be four measures of the same variable. How to use these 4 measures in research and clinical work is a central question in this paper. We demonstrate 3 different latent models that can be used to analyze these ratings based on different theoretical premises. Using empathy as the independent variable with a longitudinal sample of 275 couples, structural equation models are used to evaluate the strength of these models in predicting relationship satisfaction. The findings indicate that the model that is consistent with the social constructionist perspective that focuses on the perceptions within the same person is a good fit to the data. Other models that compare ratings between members of the dyad do not fit the data well. The results demonstrate that perceptions of empathy do have a significant influence on relationship satisfaction across time, especially for females. However, it is largely males' perceptions of empathy of the self and the partner that influence relationship satisfaction for females. [ABSTRACT FROM AUTHOR]

This study investigates the utility of the family of origin parachute model in predicting longitudinal outcomes for couples in romantic relationships. This conceptual model contains common family variables that are theoretically and empirically related to later adult functioning and are believed to influence attitudes that adult children develop regarding romantic relationships as well as self-esteem. Data from two samples were used to analyze this model. The results support the model and demonstrate its ability to predict membership in relationship satisfaction groups. Suggestions are presented for integrating the family of origin in applied work. [ABSTRACT FROM AUTHOR]

Interest in change interventions that are common to different models of relationship therapy has spurred investigation of enactments as one such candidate. In change-focused enactments, therapists structure and coach couple/family interaction, as opposed to channeling interaction through the therapist. Still, varying levels of couple/family distress, volatility, and reactivity mean that readiness for enactment intervention varies along a broad continuum and changes over the course of therapy. This suggests the need for differentiated enactments. Currently, however, no model exists for adapting enactments to changing relationship conditions. We propose a five-stage developmental model of clinical operations in couple therapy that adapts the process and structure of enactments to changing levels of relationship distress, interactional volatility, and emotional reactivity. The model increases the possibility for therapists to use enactments successfully over the entire course of couple therapy. Issues to be considered in using the couple enactments model as a template for the development of enactment models for other relationship systems are noted. [ABSTRACT FROM AUTHOR]

Beta-haemolytic streptococci are important human and animal pathogens: their genetic traits that are associated with the ability to infect human hosts remain, however, unclear. The surface protein, Lmb, mediates the adherence of Streptococcus agalactiae to human laminin. For further analysis of the corresponding gene, the adjacent genomic regions were sequenced. Lmb is localized on a putative composite transposon of 16 kb and is flanked by two copies of a novel insertion sequence element (ISSag2). It harbours the genes scpB and lmb, which are 98% identical with the respective genes of Streptococcus pyogenes. Analysis of the distribution of these genes and ISSag2 among 131 streptococcal strains revealed that all of the human isolates, but only 20% (12 of 61) of the animal isolates, contained scpB and lmb or their homologues. To investigate if the putative transposon can be mobilized, an erythromycin resistance marker was incorporated into the lmb gene of S. agalactiae. Screening for mutant strains with a regained susceptibility for erythromycin identified strains with a deletion of scpB, lmb, and one copy of ISSag2. We hypothesize that a horizontal gene transfer caused the exchange of scpB and lmb and that the ability of S. pyogenes, S. agalactiae and group C and G streptococcal strains to colonize or infect human hosts is dependent on their presence. [ABSTRACT FROM AUTHOR]

For religious couples, the spiritual domain stands alongside biological, psychological, and systemic domains as an influence upon interaction and mechanism for change. A qualitative methodology consisting of structured interviews of religious spouses was used to investigate effects of prayer on couple interaction during conflict. A reliable description of the dynamics of prayer across spouse interviews was extracted by four analysts using a group interpretive procedure. Findings suggest that prayer invokes a couple-God system, which significantly influences couple interaction during conflict. Overall, prayer appears to be a significant ‘softening’ event for religious couples, facilitating reconciliation and problem solving. Prayer 1) invokes an experience of relationship with Deity; 2) deescalates hostile emotions and reduces emotional reactivity; 3) enhances relationship and partner orientation and behavior; 4) facilitates empathy and unbiased perspective; 5) increases self-change focus; and 6) encourages couple responsibility for reconciliation and problem solving. Therapists' support of religious couples' use of prayer as a change mechanism is considered. [ABSTRACT FROM AUTHOR]

Rabbit anti-T-helper factor (anti-THF) was prepared by immunization with affinity-purified timothy antigen B (AgB)-specific helper factor. The rabbit anti-THF and an anti-IgE fraction (anti-Eid) purified by a pharosc-AgB&equirv;timothy IgE affinity adsorbent were evaluated for the resence of antiidiotypic antibodies. Both antibodies (anti-THF and anti-Eid), (i) specifically induce [³H]-thymidine incorporation of AgB-primed T cells at optimum concentrations; (ii) specifically block antigen-induced lymphocyte proliferation when preincubated with AgB-primed T cells at an excess concentration; and (iii) specifically stimulate in vivo IgE formation when preincubated with AgB-primed B or T cells and injected into syngeneic X-irradiated recipients. AntiTHF and anti-Eid purified by an AgB-specific T suppressor factor (TSF) affi-gel adsorbent retain their ability to specifically initiate ³H]-thymidine incorporation of AgB-primed T cells. The data indicate that both anti-THF, and anti-Eid recognize unique determinants present on AgB-specific T-helper, T-suppressor and B cells, and suggest that the receptors on AgB-specific T and B cells share cross-reactive idiotypic determinants. [ABSTRACT FROM AUTHOR]

Spleen cells from LAF1 mice primed with photo-oxidized antigen B exhibit helper T-ten activity when assayed in an adoptive transfer system with spleen cells from mice primed with timothy pollen extract and treated with anti-thy 1.2 serum and complement. These helper cells, when placed in culture with antigen B, secrete a soluble antigen B-specific helper factor (THF) that requires the presence of normal spleen cells or cells that do not adhere to nylon wool in order to exhibit T cell-replacing activity. The THF has been partially purified over an immobilized antigen adsorbent. The eluted THF exhibits a mol. wt of 65,000 by sodium dodecyl sulphate-polyacrylamide gel electrophoresis (SDS-PAGE), and contains 5% carbohydrate by weight. The THF is I-Ak-positive and Ig-negative. [ABSTRACT FROM AUTHOR]

We studied the early events in athymic immunoincompetent rats after implantation with cultured thymic fragments (CIT) under the kidney capsule, with special emphasis on the settlement of lymphocytes and non-lymphoid RT1 class II elements. At 2 weeks alter grafting, tissue under the kidney capsule comprises strands of keratin-positive epithelial cells from the graft, without immigrant cells. At 3 weeks, the CTF graft is populated with lymphocytes and with non-lymphoid RT1 class II-positive cells expressing the recipient haplotype (allogeneic combinations). Part of these cells bear determinants recognized by an anti-rat dendritic cell antibody. At 4 weeks the graft exhibits a completely restored thymic architecture. At the periphery, the first indications of T-cell competence generated after CTF implantation are observed 6 weeks after implantation. At 18 weeks, the peripheral thymus-dependent immune system is almost completely developed. This includes in vitro alloreactivity, even to the donor RT1 haplotype of the graft. But skin grafts of the allogeneic CTF donor haplotype are not rejected. Thus, a state of in vivo tolerance is induced under the influence of grafted epithelium. which is not due to a specific deletion of alloreactive cells. We conclude that CTF regain their original thymic architecture between 2 and 4 weeks after implantation in (allogencic) athymic nude recipients, and that only after this restoration does peripheral thymus-dependent immune competence start to develop. [ABSTRACT FROM AUTHOR]

We have extended our previous study of induction of T-lymphocyte immunocompetent in athymic nude rats by cultured epithelium (CTE) of syngeneic origin to that by CTE of allogeneic origin. Immune responsiveness (IgG-class antibody and delayed-type hypersensitivity) after ovalbumin immunization is detectable by 4–6 weeks after transplantation. However, the antibody appears at a slower rate when compared with heterozygous immunocompetent littermates. Seven weeks after transplantation phytohaemagglutinin responsiveness of spleen cells is detectable, and in T-dependent areas of lymphoid organs lymphocytes with helper and non-helper T-cell phenotype are present, but at lower levels than those in heterozygous immunocompetent littermates. Levels comparable to that of immunocompetent rats are reached about 20 weeks after transplantation. Since CTE contains thymocytes, control experiments consisted of transplantation with high numbers of allogeneic freshly isolated thymocytes in athymic nude rats. These animals showed IgG-class antibody formation after ovalbumin immunization, but at lower levels than CTE-treated rats, and were almost negative in T-cell immunocompetence assessed in the other assays. We conclude that CTE of allogeneic origin induces T-cell immunocompetence in athymic nude rats to the level of heterozygous immunocompetent littermates. This study adds to the rationale of CTE transplantation applied in treatment of thymic dysfunction. [ABSTRACT FROM AUTHOR]

When a partially purified dog liver phosphorylase phosphatase preparation was incubated with ATP and Mg ions, ks activity increased several fold. A slower activation was observed in the presence of Mg ions only. When the same preparation was preincubated with ATP alone. complete inactivation was obtained. The ATP pretreated enzyme could then be reactivated by Mg++, as well as by ATP and Mg++. The activation and the inactivation of the phosphorylase phosphatase, were shown to be dependent on time, temperature and the concentration of ATP and Mg ions. Neither on the activation nor on the inactivation of the phosphorylase phosphatase could an effect of cyclic 3':5'-AMP be observed. [ABSTRACT FROM AUTHOR]

This article focuses on the identification and treatment of a Clostridium and Vibrio infection in South African abalone, Haliotis midae L. Tissue samples obtained from affected abalone, were plated onto the agar surface and incubated at a temperature of 37 degree celsius for 24 hours. As there was no growth, they were reincubated for a further 24 hours which also produced no cultures. A tissue sample was then placed in tryptone soya broth and incubated overnight. The sample was then plated out as described previously and incubated for 24 hours.

We describe a two-tier screening methodology used to select receptorspecies for an ecological risk assessment of the Columbia River at the Hanford Site in south-central Washington state. This approach wasdeveloped and implemented under the guidance of the Columbia River Comprehensive Impact Assessment Management Team (CRCIA Team), a pubic steering committee comprised of members of regulatory agencies, native American tribes and other stakeholders. Three hundred sixty-eight species that occur in the riverine and riparian communities of the Columbia River were reduced to 52 using criteria identified by an independent panel of biologists (tier I) and by scoring and ranking species based on their potential exposure to contaminated media (tier II).This two-tier screening methodology could be implemented at other locations where the number of species present must be reduced for an ecological risk assessment and where receptor species with relatively high potential contaminant exposures need to be evaluated. Participation of the CRCIA Team in the species selection process facilitated agreement between risk assessors, regulators, and stakeholders as to the number and kinds of organisms to be evaluated in our risk assessment. It is critical that regulators and stakeholders be involved in theselection of receptors to ensure that species of public interest as well as ecologically relevant species are evaluated in ecological risk assessments. This approach will increase the likelihood that such risk assessments will be used in management decisions. [ABSTRACT FROM AUTHOR]

Objectives: Cenobamate is an antiseizure medication (ASM) approved in Europe as adjunctive therapy for adults with inadequately controlled focal seizures. This post hoc analysis reports onset of efficacy and characterizes time to onset, duration, and severity of the most common treatment-emergent adverse events (TEAEs) during cenobamate titration., Materials & Methods: Adult patients with uncontrolled focal seizures taking 1 to 3 concomitant ASMs were randomized to receive adjunctive cenobamate or placebo (double-blind studies C013 and C017) or cenobamate (open-label study C021). Outcome assessments included efficacy (median percentage change in seizure frequency and onset [studies C013 and C017]) and safety (onset, duration, and severity of TEAEs [all studies])., Results: Onset of efficacy was observed by Weeks 1 to 4 of titration in studies C013 and C017 which used a faster titration schedule than study CO21. In study C013, the median percentage seizure frequency reduction was 36.7% in patients receiving cenobamate versus 16.3% in those taking placebo (p = .002); in study C017, significant differences in seizure frequency emerged in Week 1 and continued throughout titration between all cenobamate groups and placebo (p < .001). The most commonly reported TEAEs were somnolence, dizziness, fatigue, and headache, with first onset of each reported as early as Week 1; however, the majority resolved., Conclusions: Reductions in seizure frequency occurred during titration with initial efficacy observed prior to reaching the target dose. These reductions were regarded as clinically meaningful because they may indicate early efficacy at lower doses than previously expected and had a considerable impact on patient quality of life. Long-term treatment with adjunctive cenobamate was generally safe and well-tolerated., (© 2022 The Authors. Acta Neurologica Scandinavica published by John Wiley & Sons Ltd.)

Objectives: To assess tolerability and efficacy of lacosamide in adults with cerebrovascular epilepsy etiology (CVEE)., Materials and Methods: Exploratory post hoc analyses of a double-blind, initial monotherapy trial of lacosamide vs carbamazepine-controlled release (carbamazepine-CR) (SP0993; NCT01243177); a double-blind conversion to lacosamide monotherapy trial (SP0902; NCT00520741); and an observational study of adjunctive lacosamide added to one antiepileptic drug (SP0973 VITOBA; NCT01098162). Patients with CVEE were identified based on epilepsy etiology recorded at baseline., Results: In the initial monotherapy trial, 61 patients had CVEE (lacosamide: 27; carbamazepine-CR: 34). 20 (74.1%) patients on lacosamide (27 [79.4%] on carbamazepine-CR) reported treatment-emergent adverse events (TEAEs), most commonly (≥10%) headache, dizziness, and fatigue (carbamazepine-CR: headache, dizziness). A numerically higher proportion of patients on lacosamide than carbamazepine-CR completed 6 months (22 [81.5%]; 20 [58.8%]) and 12 months (18 [66.7%]; 17 [50.0%]) treatment without seizure at last evaluated dose. In the conversion to monotherapy trial, 26/30 (86.7%) patients with CVEE reported TEAEs, most commonly (≥4 patients) dizziness, convulsion, fatigue, headache, somnolence, and cognitive disorder. During lacosamide monotherapy, 17 (56.7%) patients were 50% responders and six (20.0%) were seizure-free. In the observational study, 36/83 (43.4%) patients with CVEE reported TEAEs, most commonly (≥5%) fatigue and dizziness. Effectiveness was assessed for 75 patients. During the last 3 months, 60 (80%) were 50% responders and 42 (56.0%) were seizure-free., Conclusions: These exploratory post hoc analyses suggested lacosamide was generally well tolerated and effective in patients with CVEE, with data from the initial monotherapy trial suggesting numerically better efficacy than carbamazepine-CR., (© 2020 The Authors. Acta Neurologica Scandinavica published by John Wiley & Sons Ltd.)

Background Acute psychological stress and negative emotions are known risk factors for atrial fibrillation (AF). Whether exposure to chronic stress syndromes, such as posttraumatic stress disorder (PTSD), also increases susceptibility to AF is unknown. Methods and Results We prospectively assessed the incidence of AF over a 13-year period among 988 090 young and middle-aged veterans (mean age, 30.29±9.19 years; 87.8% men, 64.5% white) who first accessed care through the Veterans Health Administration from October 2001 to November 2014 and were free of AF, atrial flutter, or atrial tachycardia at baseline. Time-varying, multivariate Cox proportional hazard models were used to examine the independent contribution of PTSD to new AF. We also tested for effect modification by sex and controlled for healthcare use. During a mean follow-up of 4.8 years, 2491 patients were diagnosed with AF. Patients with PTSD had a higher overall incidence of AF ( P <0.0001) and were more likely to develop AF at a younger age than those without PTSD ( P =0.004). PTSD was significantly associated with incident AF in unadjusted models (hazard ratio, 1.31; 95% CI, 1.19-1.43) and models that adjusted for demographics, lifestyle factors, cardiovascular risk factors, and depression (hazard ratio, 1.13; 95% CI, 1.02-1.24). The interaction with sex was nonsignificant ( P =0.93). Conclusions PTSD was associated increased risk for early incident AF after adjustment for established AF risk factors and depression in this cohort of young and middle-aged veterans. Findings from this study require validation in more diverse populations to determine their generalizability.

Background & Aims: Infections with multidrug-resistant gram-negative bacteria are significantly impairing the prognosis of patients with liver disease. In particular, carbapenem resistance further narrows therapeutic options. This study investigates the impact of carbapenem-resistant gram-negative bacteria on the outcome of patients with liver disease and cirrhosis., Methods: Between January 2011 and July 2015, 132 patients treated at the tertiary liver transplant centre at University Hospital Frankfurt, Germany, were tested positive for carbapenem-resistant gram-negative bacteria and retrospectively analysed in this study. Risk factors for fatal outcome were evaluated using multivariate regression analysis. Competing-risk analysis was performed on patients tested positive for Enterobacteriaceae or non-fermenting species, for example, Pseudomonas aeruginosa, Acinetobacter baumannii, Stenotrophomonas maltophilia. Subgroup analysis of cirrhotic patients was performed on a matched cohort of cirrhotic patients, comparable model for end-stage liver disease and tested negative for carbapenem-resistant gram-negative bacteria., Results: 97 (73.5%) and 35 (26.5%) patients were infected or colonised with carbapenem-resistant gram-negative bacteria respectively. Within the observation period, 61/132 (46.2%) patients died, with sepsis being the leading cause (38/61, 62.3%). Decompensated liver disease, sepsis and admission to intensive care unit were independent risk factors for fatal outcome. Lethal sepsis in patients positive for non-fermenting bacteria was significantly more frequent than in those positive for Enterobacteriaceae, independently from liver function. Subgroup analysis of cirrhotic patients showed that sepsis (54.9% vs 13%) and lethal sepsis were significantly more frequent after detection of carbapenem-resistant gram-negative bacteria, independently from localisation of pathogen detection., Conclusions: Patients with advanced liver disease are prone to fatal infections caused by carbapenem-resistant gram-negative bacteria., (© 2017 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Objectives: Due to demographic change and high incidence of epilepsy in elderly, the number of elderly with epilepsies is increasing. However, only few studies investigated the impact of epilepsy on quality of life (QoL). We investigated how epilepsy affects different aspects of QoL dependent on the age of the patients and the age of onset of epilepsy., Materials and Methods: In a multicenter, cross-sectional study, three patient groups were recruited from five centers: Group A1: 45 elderly (≥65 years.) with late onset of epilepsy (≥65 years), group A2: 51 elderly (≥65 years.) with early-onset, long-lasting epilepsy (≤50 years), group B: 41 young adults (≤50 years) with epilepsy. Statistical analysis of differences between groups was performed using generalized linear models., Results: Elderly with late-onset epilepsy (group A1) had a significantly lower seizure frequency, were treated with less anti-epileptic drugs (AEDs), and reported a better tolerability of AED treatment, but had more comorbidities compared with groups A2 and B. After adjusting for seizure frequency, tolerability of AEDs and comorbidity, young adults (group B) reported the highest overall QoL, whereas patients of group A1 and A2 did not differ significantly. Epilepsy-related fears, especially fears of stigmatization, were significantly higher in elderly with long-lasting epilepsy compared with groups A1 and B., Conclusion: Seizure-related variables, tolerability of AEDs and comorbidity have a stronger impact on QoL and on restrictions due to epilepsy than age, age at onset of epilepsy or duration of epilepsy. However, some results indicate group-specific patterns of impairment and epilepsy-related fears., (© 2014 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

The prevalence and incidence of epilepsies in elderly is high. Due to demographic development, the portion of elderly patients with epilepsy will continue to rise over the next decades. In this study, we aimed to investigate seizure semiology, etiology, comorbidity, and therapy in elderly patients dependent on onset of epilepsy and in comparison with younger patients. In a prospective multicentre study, 202 epilepsy patients were included in a consecutive manner and subdivided into three groups (group A1: >65 years, onset of epilepsy after the age of 65 years; group A2: >65 years with early onset epilepsy, seizure onset before the age of 50 years; and group B: <50 years with epilepsy). Clinical data with respect to epilepsy, seizures, comorbidity, etiology, and anti-epileptic drug (AED) therapy were assessed using a questionnaire developed especially for these patient groups and filled out by the physicians. The clinical profile with regard to etiology, postictal conditions, and comorbidities clearly depends on the age of the patients and age of onset of epilepsy. Patients with an epilepsy onset after 65 years need lower doses of AEDs, gain better seizure control and have more concomitant diseases than younger patients or elderly epilepsy patients with early-onset epilepsy., (© 2014 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

The diuretic bumetanide, which acts by blocking the Na-K-Cl cotransporter (NKCC), is widely used to inhibit neuronal NKCC1, particularly when NKCC1 expression is abnormally increased in brain diseases such as epilepsy. However, bumetanide poorly penetrates into the brain and, in rodents, is rapidly eliminated because of extensive oxidation of its N-butyl sidechain, reducing the translational value of rodent experiments. Inhibition of oxidation by piperonyl butoxide (PBO) has previously been reported to increase the half-life and diuretic activity of bumetanide in rats. Here we studied whether inhibition of bumetanide metabolism by PBO also increases brain levels of bumetanide in rats, and whether this alters pharmacodynamic effects in the kindling model of epilepsy. Furthermore, we studied the effects of PBO in mice. Mice eliminated bumetanide less rapidly than rats (elimination half-life 47 min vs. 13 min). Pretreatment with PBO increased the half-life in mice to average values (70 min) previously determined in humans, and markedly elevated brain levels of bumetanide. In rats, the increase in plasma and brain levels of bumetanide by PBO was less marked than in mice. PBO significantly increased the diuretic activity of bumetanide in rats and, less effectively, in mice. In epileptic mice, bumetanide (with PBO) did not suppress spontaneous seizures. In the rat kindling model, bumetanide (with or without PBO) did not exert anticonvulsant effects on fully kindled seizures, but dose-dependently altered kindling development. These data indicate that PBO offers a simple means to enhance the translational properties of rodent experiments with bumetanide, particularly when using mice., (© 2013 Federation of European Neuroscience Societies and John Wiley & Sons Ltd.)

In patients at risk of developing epilepsy after an initial precipitating injury to the brain, the epileptogenic latent period may offer a window of opportunity for initiating potential antiepileptogenic therapy in an attempt to prevent epilepsy from developing. One potential target for antiepileptogenesis is the development of neuronal hyperexcitability during the latent period. Surprisingly, some recent studies in models of temporal lobe epilepsy (TLE) have suggested that proconvulsant drugs could have favourable effects on epileptogenesis, resulting in the proposal of pursuing proconvulsant prophylaxis for epileptogenesis. In the present study, we evaluated this provocative hypothesis by experiments with the GABA(A) receptor antagonist pentylenetetrazole (PTZ) in two TLE models, the intrahippocampal kainate model and the lithium-pilocarpine model in rats. First, we repeatedly determined the PTZ seizure threshold by i.v. infusion of the convulsant during the latent period following intrahippocampal kainate. In line with recent experiments in the lithium-pilocarpine model, the PTZ seizure threshold was significantly decreased over several days following status epilepticus. We then studied whether prolonged infusion of a proconvulsant dose of PTZ at different times after kainate or pilocarpine affected the development of epilepsy. PTZ did not prevent the development of spontaneous recurrent seizures and did not decrease their frequency or severity, but exerted only a moderate disease-modifying effect in that spontaneous seizures in the kainate model were significantly shortened. These data indicate that administration of proconvulsant drugs such as PTZ during the latent period following SE is not a promising strategy for preventing epilepsy., (© 2012 The Authors. European Journal of Neuroscience © 2012 Federation of European Neuroscience Societies and Blackwell Publishing Ltd.)

A standard oral glucose tolerance test (OGTT) was administered to 28 adults with Williams syndrome (WS). Three quarters of the WS subjects showed abnormal glucose curves, meeting diagnostic criteria for either diabetes or the pre-diabetic state of impaired glucose tolerance. Fasting mean glucose and median insulin levels did not differ significantly in the total WS cohort versus age-gender-BMI matched controls, though the glucose area under the curve was greater in the WS subjects. HbA1c levels were not as reliable as the OGTT in diagnosing the presence of diabetes. Given the high prevalence of impaired glucose regulation, adults with WS should be screened for diabetes, and when present should be treated in accordance with standard medical practice. Hemizygosity for a gene mapping to the Williams syndrome chromosome region (WSCR) is likely the major factor responsible for the high frequency of diabetes in WS. Syntaxin-1A is a prime candidate gene based on its location in the WSCR, its role in insulin release, and the presence of abnormal glucose metabolism in mouse models with aberrantly expressed Stx-1a.

Aims: International guidelines on ethics in biomedical research require that the informed consent of all enrolled participants is obtained. A written document describing the research, the informed consent (IC) document, must be given to all participants by the investigator. Most IC documents are long, containing much information. The aim of the present study was to determine whether the modification of the IC document by a working group or systematic improvement in its lexicosyntactic readability can improve comprehension of the written information given to patients participating in biomedical research., Methods: One hundred and fifty-nine patients were randomized to read one of the three versions of the IC document: unchanged document, document modified using systematic improvement of lexicosyntactic readability and document modified by a working group., Results: Neither the improvement in the lexicosyntactic readability, nor the intervention of the working group significantly improved the score of objective comprehension for the subjects included in this study: it was 66.6 (95% confidence interval 64.0, 69.2) for the control group, 68.8 (66.2, 71.4) for the group with the document improved for lexicosyntactic readability and 69.2 (66.0, 72.4) for the group who read the document improved by the working group (P= 0.38)., Conclusions: We failed to show that improving IC document comprehension through a lexicosyntactic approach or by a working group leads to better comprehension.

Familial haemophagocytic lymphohistiocytosis (HLH) is considered an autosomal recessive disease, although the putative gene responsible for the disease has not yet been localized. Identification of the involved gene may elucidate the pathogenesis of the disease and is essential for prenatal testing in affected families. We present an infant with HLH and constitutional inversion 9 (p23q31) in cells from bone marrow, lymphocytes and fibroblasts. The parents had normal karyotypes. It may be speculated that one of the parents was a carrier of HLH and a de novo inversion occurred in chromosome 9 from the non-carrier parent. This would imply that the putative HLH-related gene is located at one of the two breakpoints on chromosome 9.