Targeting the contact system in a rabbit model of extracorporeal membrane oxygenation.

Previous studies suggested that contact pathway factors drive thrombosis in mechanical circulation. We used a rabbit model of veno-arterial extracorporeal circulation (VA-ECMO) to evaluate the role of factors XI and XII in ECMO-associated thrombosis and organ damage. Factors XI and XII (FXI, FXII) were depleted using established antisense oligonucleotides before placement on a blood-primed VA-ECMO circuit. Decreasing FXII or FXI to < 5% of baseline activity significantly prolonged ECMO circuit lifespan, limited the development of coagulopathy, and prevented fibrinogen consumption. Histological analysis suggested that FXII depletion mitigated interstitial pulmonary edema and hemorrhage whereas heparin and FXI depletion did not. Neither FXI nor FXII depletion was associated with significant hemorrhage in other organs. In vitro analysis showed that membrane oxygenator fibers (MOFs) alone are capable of driving significant thrombin generation in a FXII- and FXI-dependent manner. MOFs also augment thrombin generation triggered by low (1 pM) or high (5 pM) tissue factor concentrations. However, only FXI elimination completely prevented the increase in thrombin generation driven by MOFs, suggesting MOFs augment thrombin-mediated FXI activation. Together, these results suggest that therapies targeting FXII or FXI limit thromboembolic complications associated with ECMO. Further studies are needed to determine the contexts wherein targeting FXI and FXII, either alone or in combination, would be most beneficial in ECMO. Moreover, studies are also needed to determine the potential mechanisms coupling FXII to end-organ damage in ECMO.

Mental Wellbeing and Social Resilience of Eritrean Refugees Living in Germany.

Mental health and social resilience play a significant role in refugees' adaptation during the resettlement process in the host country. Maintaining good mental wellbeing helps the refugees to respond to stressful experiences with healthy life choices. This study aimed to explore the mental wellbeing and social resilience of Eritrean refugees living in Germany and to identify social conditions and enablers to foster adaptation. This study employs a qualitative approach with a semi-structured, in-depth interview data collection method. Informants were identified among mostly young adult refugees living in Heidelberg, Germany, with a migration history of 3-6 years. In total, 15 informants were recruited through snowball sampling. Data were sorted and analyzed using the five pillars of the Adaptation and Development after Persecution and Trauma (ADAPT) model. The findings suggest that Eritrean refugees experienced psychological distress after resettlement in Germany; however, with time, their mental health improved. The study revealed conditions that were experienced as hindrances, as well as ones that were considered to be resources of positive mental wellbeing and social resilience for resettled refugees. Resettlement challenges described by the participants were the language barrier, discrimination, unemployment, insecure residence status, loss of family and friends, conflict within the diaspora community, and isolation. The main sources of mental wellbeing and social resilience include the feeling of being welcomed by local communities, access to social services, adopting new relationships, and educational opportunities. These experiences encouraged refugees to have a favorable view of their lives and futures and were also found to facilitate better integration and adaptation. Understanding refugee mental wellbeing and social resilience requires a multidimensional perspective. Eritrean refugees living in Germany have experienced and are still experiencing resettlement challenges, such as, for example, loss of family and friends, negative perception of the German system, loss of past achievements, or unemployment. However, they have developed adaptive and resilience mechanisms, as well, such as seeing an opportunity for a better life, adopting new roles, and accepting Germany as a "second home". In addressing those issues reported by the refugees as hindrances, these could be turned into sources of mental wellbeing and resilience.

Urinary 11-dehydrothromboxane B2 aspirin efficacy testing is sensitive to perioperative inflammation in pediatric solid-organ transplant patients.

BACKGROUND: Evidence for aspirin efficacy testing in pediatrics is limited, especially outside of cardiology, yet thrombotic events have high morbidity in other areas such as pediatric transplant surgery. Debates about whether thromboembolic events while on aspirin represent "aspirin resistance" or "high on-treatment platelet reactivity" persist, given the poor intertest agreement between testing platforms. PROCEDURE: This prospective observational study involved measuring aspirin efficacy using ex vivo testing of platelet aggregation (VerifyNow-Aspirin, VN) and urine 11-dehydrothromboxane B2 (AsprinWorks, UTxB2) contemporaneously at up to three time points after major noncardiac organ transplant surgery. The collection days (CD) were the second and seventh days after stable aspirin dosing and then a convalescent time point 2-9 months later. RESULTS: Fifty-five participants (age range, 0-21 years) were enrolled, having undergone total pancreatectomy with islet autotransplantation (N = 36), orthotopic liver transplantation (N = 18), and combined liver-kidney transplantation (N = 1). Platelet reactivity measured by VN remained unchanged, whereas UTxB2, which was elevated postoperatively, decreased significantly from CD1 to CD2 and CD3. Discordance in therapeutic efficacy was noted per manufacturer cutoffs, with therapeutic VN results in 86% of tests, whereas 12% of UTxB2 were therapeutic. Age-based stratification of UTxB2 results using previously published pediatric median levels increased overall UTxB2 therapeutic rates (80%) and intertest concordance (67% vs 27% if using adult range). No thrombotic events were observed. CONCLUSIONS: Our data suggest that urine thromboxane production may be an underappreciated reflection of postoperative inflammation. Validation of pediatric normal ranges for UTxB2 is a critical next step.

Eritrean Refugees' and Asylum-Seekers' Attitude towards and Access to Oral Healthcare in Heidelberg, Germany: A Qualitative Study.

Oral health concerns in Eritrean refugees have been an overlooked subject. This qualitative study explored the access of Eritrean refugees and asylum-seekers (ERNRAS) to oral health care services in Heidelberg, Germany, as well as their perceptions and attitudes towards oral health care. It involved 25 participants. We employed online semi-structured interviews (n = 15) and focus group discussions (n = 2). The data was recorded, transcribed, and analysed, using thematic analysis. The study found out that most of the participants have a relatively realistic perception and understanding of oral health. However, they have poor dental care practices, whilst a few have certain misconceptions of the conventional oral hygiene tools. Along with the majority's concerns regarding psychosocial attributes of poor oral health, some participants are routinely consuming Berbere (a traditional spice-blended pepper) to prevent bad breath. Structural or supply-side barriers to oral healthcare services included: communication hurdles; difficulty in identifying and navigating the German health system; gaps in transculturally, professionally, and communicationally competent oral health professionals; cost of dental treatment; entitlement issues (asylum-seekers); and appointment mechanisms. Individual or demand-side barriers comprised: lack of self-sufficiency; issue related to dental care beliefs, trust, and expectation from dentists; negligence and lack of adherence to dental treatment follow-up; and fear or apprehension of dental treatment. To address the oral health burdens of ERNRAS, it is advised to consider oral health education, language-specific, inclusive, and culturally and professionally appropriate healthcare services.

Experiences of psychotherapists working with refugees in Germany: a qualitative study.

BACKGROUND: Despite a high burden of mental health problems among refugees, there is limited knowledge about effective mental health care provision for this group. Although substantial efforts in understanding the complexity of cross-cultural psychotherapy - which in the context of this study we use to refer to therapy with client and therapist of different cultural backgrounds - have been made, there remains a dearth of research exploring barriers for effective cross-cultural psychotherapy. This study aimed at narrowing this gap in knowledge by exploring major challenges encountered by psychotherapists in cross-cultural psychotherapy and strategies which have proven useful in overcoming such challenges. METHODS: We employed a qualitative study design, conducting semi-structured in-depth interviews with 10 purposely selected psychotherapists working with refugees in Germany. Respondents were from varying theoretical background and had varying levels of experience. Data were analyzed using a thematic approach, following a mix of deductive and inductive coding. RESULTS: Respondents reported three main challenges in their cross-cultural practice: different or unrealistic expectations of clients towards what psychotherapy would offer them; challenges grounded in different illness explanatory models; and communication challenges. In dealing with these challenges, respondents recommended psychoeducation to overcome issues related to problematic expectations towards psychotherapy; "imagining the real", identifying "counter magic" and other client-appropriate resources to deal with issues related to clients' foreign illness attributions; and translators in dealing with communication barriers, though the latter not univocally. CONCLUSIONS: Results show that psychotherapy with refugees can be very successful, at least from the psychotherapist perspective, but also poses significant challenges. Our findings underline the importance of developing, testing, and institutionalizing structured and structural approaches to training psychotherapists in cross-cultural therapy at scale, to accommodate the rising mental health care need of refugees as a client group.

A Novel Transgenic Mouse Model to Investigate the Cell-Autonomous Effects of torsinA(ΔE) Expression in Striatal Output Neurons.

Dystonia is a disabling neurological syndrome characterized by abnormal movements and postures that result from intermittent or sustained involuntary muscle contractions; mutations of DYT1/TOR1A are the most common cause of childhood-onset, generalized, inherited dystonia. Patient and mouse model data strongly support dysregulation of the nigrostriatal dopamine neurotransmission circuit in the presence of the DYT1-causing mutation. To determine striatal medium spiny neuron (MSN) cell-autonomous and non-cell autonomous effects relevant to dopamine transmission, we created a transgenic mouse in which expression of mutant torsinA in forebrain is restricted to MSNs. We assayed electrically evoked and cocaine-enhanced dopamine release and locomotor activity, dopamine uptake, gene expression of dopamine-associated neuropeptides and receptors, and response to the muscarinic cholinergic antagonist, trihexyphenidyl. We found that over-expression of mutant torsinA in MSNs produces complex cell-autonomous and non-cell autonomous alterations in nigrostriatal dopaminergic and intrastriatal cholinergic function, similar to that found in pan-cellular DYT1 mouse models. These data introduce targets for future studies to identify which are causative and which are compensatory in DYT1 dystonia, and thereby aid in defining appropriate therapies.

Genetic mechanisms of electroconvulsive therapy response in depression.

Electroconvulsive therapy (ECT) is known to be one of the most effective treatments for managing depression and other severe mental illnesses. Nevertheless, the exact mechanisms underlying response to ECT remain uncertain. This mini-review presents clinical findings regarding the role of genetic factors in the aetiology of the ECT response. Studies on the role of variation in the catechol-O-methyltransferase (COMT) gene; other dopamine-, serotonin-, and G-protein-related genes; brain-derived neurotrophic factor (BDNF); apolipoprotein E (APOE); angiotensin I-converting enzyme (ACE) and vascular endothelial growth factor (VEGF) genes in mediating response to ECT are summarized. The existing data support the notion that some genetic factors-particularly the functional COMT val158met polymorphism-may play a role in the magnitude of clinical response to ECT, and thus could serve as potential biomarkers for future personalized treatment approaches. However, much of the work to date is preliminary, and large-scale confirmatory studies are still needed. Copyright © 2016 John Wiley & Sons, Ltd.

A Survey of the Practice of Electroconvulsive Therapy in South Africa.

OBJECTIVES: The aim of this study was to describe the contemporary practice of electroconvulsive therapy (ECT) in South Africa. METHODS: A 36-item questionnaire was sent to all hospitals that practiced ECT in a 12-month period between 2011 and 2012. RESULTS: Forty-two institutions had an ECT machine on site, but 13 institutions reported nonuse. Electroconvulsive therapy services were available in only 6 of the 9 provinces. Questionnaires were sent to the 29 active sites. Twenty-four units (82.8%) responded, and of these, 20 institutions (68.9%) responded to question on the number of patients treated with ECT. Pre-ECT procedures commonly involved informed consent, a physical examination, and basic blood investigations. Bilateral, unilateral, and bifrontal electrode placements were used, whereas dose titration methods and seizure monitoring were used by most respondents. The number of persons treated with ECT per 10,000 persons per year was 0.22, whereas the number of ECT procedures performed per 10,000 persons per year was 1.19. The most common indication for ECT was depression, with most patients being between the ages of 18 and 59 years. CONCLUSIONS: The characteristics and rate of ECT utilization in South Africa have been determined and generally emulated international guidelines and trends. However, accessibility to services and aspects such as training and accreditation could be improved.

The Young's modulus of fetal preterm and term amniotic membranes.

OBJECTIVE: To examine the Young's modulus of the human amniotic membranes, as well as its relationship to gestational age. To determine whether cellular and material-related parameters affect this modulus. STUDY DESIGN: In a prospective study at the Obstetric outpatient clinic of the University Hospital Zurich Young's modulus, thickness and mesenchymal:epithelial cell ratio of amniotic membranes of preterm (N=23) and term (N=40) placentae were examined. Significance (P<0.05) was calculated with the Mann-Whitney two-sample rank sum test and Wilcoxon signed rank test, while correlations were made using the Spearman's correlation. RESULTS: The Young's modulus of preterm amniotic membranes was significantly higher than that of term membranes. It varied within the same amniotic membrane. The thickness of the amnion in both preterm and term membranes did not differ significantly. The thinner the preterm and term amniotic membranes, the higher the Young's modulus was. There was no relation to the mesenchymal:epithelial cell ratio in the amnion. CONCLUSIONS: Preterm amniotic membranes are stiffer than term amniotic membranes. Tentatively, we hypothesise that there may be a correlation between the extracellular matrix components and the elastic properties of the membrane.

The JIL-1 kinase regulates the structure of Drosophila polytene chromosomes.

The JIL-1 kinase localizes to interband regions of Drosophila polytene chromosomes and phosphorylates histone H3 Ser10. Analysis of JIL-1 hypomorphic alleles demonstrated that reduced levels of JIL-1 protein lead to global changes in polytene chromatin structure. Here we have performed a detailed ultrastructural and cytological analysis of the defects in JIL-1 mutant chromosomes. We show that all autosomes and the female X chromosome are similarly affected, whereas the defects in the male X chromosome are qualitatively different. In polytene autosomes, loss of JIL-1 leads to misalignment of interband chromatin fibrils and to increased ectopic contacts between nonhomologous regions. Furthermore, there is an abnormal coiling of the chromosomes with an intermixing of euchromatic regions and the compacted chromatin characteristic of banded regions. In contrast, coiling of the male X polytene chromosome was not observed. Instead, the shortening of the male X chromosome appeared to be caused by increased dispersal of the chromatin into a diffuse network without any discernable banded regions. To account for the observed phenotypes we propose a model in which JIL-1 functions to establish or maintain the parallel alignment of interband chromosome fibrils as well as to repress the formation of contacts and intermingling of nonhomologous chromatid regions.

Update on pediatric perfusion practice in North America: 2005 survey.

The devices and techniques used for pediatric cardiopulmonary bypass (CPB) undergo continuous change. New techniques and clinical comparisons of devices are frequently reported in the literature; however, information about the extent to which these techniques and devices are adopted into clinical practice at pediatric heart centers are not well described. We conducted a mail survey of North American pediatric cardiac surgery centers to gain perspective on the extent to which various devices and techniques were used for CPB along with program demographic data. In January 2005, surveys were mailed to 180 North American open heart centers. The survey was nearly identical in format and content to three earlier surveys completed in 1989, 1994, and 1999, with the exception that new questions were added to address new techniques and devices that have emerged over the years. Responses were received from 76 hospitals, for an overall response rate of 42%. Of the responding centers, 53 were performing pediatric open heart surgery and 23 were not. Twenty centers performed only pediatric open heart surgery, and 33 performed both pediatric and adult open heart surgery. The mean pediatric annual caseload of responding centers was 195 procedures/yr (range, 20-650 procedures/yr; median, 154 procedures/yr). A total of 9943 pediatric open heart procedures were performed at responding centers in 2004. Most of the centers surveyed reported use of an open venous reservoir system (88%), use of roller pumps (90%), and use of arterial line filtration (98%). Most centers used circuits that have surface treatments with heparin or some other surface-modifying agent (74%). There has been an increase in the use of all types of safety devices. Modified ultrafiltration is used at 75% of the centers surveyed. Centers reported an increase in the availability of all types of cardiac support devices including extracorporeal membrane oxygenation for postcardiotomy cardiac support (90%). This survey provides an overview of clinical practice in 2004. The series of surveys document the historical progression of clinical practice over the past 16 years. Practice surveys may also be useful for identifying gaps between evidence-based knowledge and clinical practice. These surveys document the diffusion of innovation related to CPB during the past 16 years and areas of variation in practice that need further study.

Effects of lorazepam and oxazepam on perceptual and procedural memory functions.

RATIONALE: Lorazepam has been found to consistently impair performance on both episodic and perceptual priming tasks, whereas other benzodiazepines have shown perceptual priming to be preserved. However, it has recently been postulated that benzodiazepines may exert time-dependent effects on implicit memory processes after research findings indicated some benzodiazepines, other than lorazepam, impair performance on priming tasks when tested at the time of peak plasma concentration level after benzodiazepine administration. OBJECTIVES: To compare time-dependent effects of lorazepam and oxazepam on implicit memory tasks, specifically perceptual priming and procedural learning. METHODS: Thirty-three healthy female undergraduates were randomised to one of three time groups (pre-peak, peak, post-peak) and administered placebo, 2.5 mg lorazepam, and 30 mg oxazepam, in counterbalanced order, at 1-week intervals. Assessments included word-stem completion (perceptual priming) and rotary pursuit (procedural learning) tasks. RESULTS: At all time intervals, lorazepam but not oxazepam significantly impaired perceptual priming but procedural learning was preserved under both drugs. CONCLUSIONS: These findings are consistent with previous research showing a differential effect of lorazepam in impairing perceptual memory but the notion that benzodiazepines exert time-dependent effects on implicit memory processes was not supported.