Miracle-dz/UniFAR-FTUs huggingface dataset:
Barriers and facilitators to accessing psychological therapies for severe mental health difficulties in later life

Abstract Background: The number of people growing older with severe mental illness (SMI) is rising, reflecting societal trends towards an ageing population. Evidence suggests that older people are less likely to seek help, be referred for and receive psychological therapy compared with younger people, but past research has focused on those with mild to moderate mental health needs. Aims: This research aims to identify the specific barriers faced by older people with SMI. Method: We interviewed 53 participants (22 service users with SMI aged over 50 years, 11 carers of people with SMI, and 20 health care professionals) about their views and experiences of accessing therapy for SMI in later life. Results: Thematic analysis revealed five themes: organizational and resource issues; myths about therapy and attitudinal barriers; stigma; encouraging access to therapy; and meeting age-specific needs. Conclusions: Barriers faced by older people with SMI are not only age-related, but also reflect specific issues associated with having a SMI over many years. Improving awareness of the benefits of psychological therapies is important not only for older people with SMI themselves, but also for their carers and staff who work with them.
Anatomical, histological and computed tomography comparisons of the eye and adnexa of crab-eating fox (Cerdocyon thous) to domestic dogs

An understanding of species' morphological and physiological parameters is crucial to developing conservation strategies for wild animals kept in human care. Detailed information is lacking for crab-eating fox (Cerdocyon thous) eyes and adnexa. Therefore, the aim of this study was to describe anatomical, histological and computed tomography (CT) features of the eye and adnexa in crab-eating fox, compared to domestic dogs. CT of the eye and adnexa of one live animal and a frozen specimen was performed for anatomical identification. In addition, the heads of five animals of each species were fixed in 10% buffered formalin for gross anatomical description of the eye and adnexa using topographic dissection and exenteration techniques. All steps were photographed and features such as location, shape, and distances and relationships between structures were described. For histological evaluation, two eyes of each species were fixed in 10% buffered formalin, processed by routine paraffin inclusion technique and stained with hematoxylin and eosin. The CT scan was difficult to evaluate, mainly that of the frozen head, which did not provide good definition of the soft tissues; nevertheless, it demonstrated the potential for structure visualization and description. The gross anatomical and histological evaluations showed the presence of eyelashes on the upper eyelid and of upper and lower lacrimal points, an incomplete orbit with supraorbital ligament, slightly exposed sclera with discretely pigmented limbus and pigmentation throughout the conjunctiva, and a slit-shaped pupil. Hematoxylin and eosin staining demonstrated structural similarities between the crab-eating fox and domestic dog. Thus, the possibility of using the domestic dog as a study model for the preventive and therapeutic management of wild dogs kept in human care is demonstrated.
A randomized evaluation of on-site monitoring nested in a multinational randomized trial

Background: Evidence from prospectively designed studies to guide on-site monitoring practices for randomized trials is limited. A cluster randomized study, nested within the Strategic Timing of AntiRetroviral Treatment (START) trial, was conducted to evaluate on-site monitoring. Methods: Sites were randomized to either annual on-site monitoring or no on-site monitoring. All sites were centrally monitored, and local monitoring was carried out twice each year. Randomization was stratified by country and projected enrollment in START. The primary outcome was a participant-level composite outcome including components for eligibility errors, consent violations, use of antiretroviral treatment not recommended by protocol, late reporting of START primary and secondary clinical endpoints (defined as the event being reported more than 6 months from occurrence), and data alteration and fraud. Logistic regression fixed effect hierarchical models were used to compare on-site versus no on-site monitoring for the primary composite outcome and its components. Odds ratios and 95% confidence intervals comparing on-site monitoring versus no on-site monitoring are cited. Results: In total, 99 sites (2107 participants) were randomized to receive annual on-site monitoring and 97 sites (2264 participants) were randomized to be monitored only centrally and locally. The two monitoring groups were well balanced at entry. In the on-site monitoring group, 469 annual on-site monitoring visits were conducted, and 134 participants (6.4%) in 56 of 99 sites (57%) had a primary monitoring outcome. In the no on-site monitoring group, 85 participants (3.8%) in 34 of 97 sites (35%) had a primary monitoring outcome (odds ratio = 1.7; 95% confidence interval: 1.1–2.7; p = 0.03). Informed consent violations accounted for most outcomes in each group (56 vs 41 participants). The largest odds ratio was for eligibility violations (odds ratio = 12.2; 95% confidence interval: 1.8–85.2; p = 0.01). The number of participants with a late START primary endpoint was similar for each monitoring group (23 vs 16 participants). Late START grade 4 and unscheduled hospitalization events were found for 34 participants in the on-site monitoring group and 19 participants in the no on-site monitoring group (odds ratio = 2.0; 95% confidence interval: 1.1–3.7; p = 0.02). There were no cases of data alteration or fraud. Based on the travel budget for on-site monitoring and the hours spent conducting on-site monitoring, the estimated cost of on-site monitoring was over US$2 million. Conclusion: On-site monitoring led to the identification of more eligibility and consent violations and START clinical events being reported more than 6 months from occurrence as compared to no on-site monitoring. Considering the nature of the excess monitoring outcomes identified at sites receiving on-site monitoring, as well as the cost of on-site monitoring, the value to the START study was limited.
In Situ Quantification of Silver Nanoparticle Dissolution Kinetics in Simulated Sweat Using Linear Sweep Stripping Voltammetry.

Linear sweep stripping voltammetry (LSSV) is demonstrated as a sensitive, rapid, and cost-efficient analytical technique for the quantification of silver nanoparticle (AgNP) dissolution rates in simulated sweat. LSSV does not require the extensive sample preparation (e.g., ultrafiltration or centrifugation) needed by more commonly employed techniques, such as atomic spectroscopy. The limit of detection (LOD) of Ag(I)(aq) was 14 ± 6 μg L-1 and measured dissolution rate constants, kdissolution, varied from 0.0168 - 0.1524 h-1, depending on solution conditions. These values are comparable and agree well with those determined by others in the literature using atomic spectroscopy. Importantly, LSSV had the necessary sensitivity to distinguish the effects of SSW solution conditions on AgNP dissolution rates. Specifically, enhanced dissolution rates were observed with decreased pH and with increased NaCl concentration. The colloidal stability of AgNPs in SSW solutions was also characterized using dynamic light scattering (DLS), zeta potential, and quantitative UV-vis spectroscopy measurements. An increase in AgNP aggregation rate was observed with increased NaCl concentration in SSW, suggesting that the enhancement in AgNP dissolution is driven by the large Cl/Ag ratio and is independent of AgNP aggregation.
Impact of circadian rhythms on female reproduction and infertility treatment success.

PURPOSE OF REVIEW In recent years, new studies have investigated the role and influence of sleep on female fertility and early pregnancy outcomes, providing a growing body of knowledge demonstrating how regulation by sleep of hormones are important to reproduction, and how disruptions in sleep, circadian rhythms, and genes regulating circadian rhythmicity can negatively impact fertility and early pregnancy outcomes. This review aims to summarize the most recent research on the relationship among circadian rhythms, fertility, and early pregnancy outcomes in women, and to explore possible fertility interventions. RECENT FINDINGS Recent studies have found altered levels of FSH, LH, and prolactin with sleep disturbance or circadian dysrhythmia. Disruption of circadian rhythms in the form of shift work, jet lag, and daylight savings time changes have been associated with poorer fertility and early pregnancy outcomes. Alterations in the expression of circadian rhythm-regulating circadian locomotor output cycles kaput (CLOCK) genes have been associated with decreased fertility and increased rates of miscarriage. SUMMARY Overall, undisrupted sleep and circadian rhythmicity appear to optimize fertility and early pregnancy outcomes and may play an important role in the success of fertility treatment.
Does self-reported pregnancy loss identify women at risk of an adverse cardiovascular phenotype in later life? Insights from UK Biobank

Introduction Cardiovascular disease (CVD) is more common in women who have had pregnancy complications such as spontaneous pregnancy loss. We used cross-sectional data from the UK Biobank Imaging Enhancement Study to determine whether pregnancy loss is associated with cardiac or vascular remodelling in later life, which might contribute to this increased risk. Methods Pregnancy history was reported by women participating in UK Biobank between 2006 and 2010 at age 40–69 years using a self-completed touch-screen questionnaire. Associations between self-reported spontaneous pregnancy loss and cardiovascular measures, collected in women who participated in the Imaging Enhancement Study up to the end of 2015, were examined. Cardiac structure and function were assessed by magnetic resonance (CMR) steady-state free precession imaging at 1.5 Tesla. Carotid intima-media thickness (CIMT) measurements were taken for both common carotid arteries using a CardioHealth Station. Statistical associations with CMR and carotid measures were adjusted for age, BMI and other cardiovascular risk factors. Results Data were available on 2660 women of whom 111 were excluded because of pre-existing cardiovascular disease and 30 had no pregnancy information available. Of the remaining 2519, 446 were nulligravid and 2073 had a history of pregnancies, of whom 622 reported at least one pregnancy loss (92% miscarriages and 8% stillbirths) and 1451 reported no pregnancy loss. No significant differences in any cardiac or carotid parameters were evident in women who reported pregnancy loss compared to other groups (Table 1). Conclusion Women who self-report pregnancy loss do not have significant differences in cardiac structure, cardiac function, or carotid structure in later life to explain their increased cardiovascular risk. This suggests any cardiovascular risks associated with pregnancy loss operate through other disease mechanisms. Alternatively, other characteristics of pregnancy loss, which we were not able to take account of, such as timing and number of pregnancy losses may be required to identify those at greatest cardiovascular risk.
Periodic Event-Triggered Output-Feedback Stabilization for Stochastic Systems

This article is devoted to explore the periodic event-triggered stabilization for continuous-time stochastic systems, and to develop analysis tools/methods for stochastic periodic event-triggered control. Notably, without real-time monitoring of system behavior as in the scenario with continuous event evaluation, it is critical to delicately estimate and govern the execution/sampling error to achieve the desired system performance. This, under stochastic effects, would be substantially challenging, since the behavior of the stochastic system is hard to predict and is disparate between trials even with the same initial conditions. In this article, a framework of global stabilization via periodic event-triggered output-feedback is established: 1) a criterion condition based on the ISS-Lyapunov function is presented for the feasibility of the desired event-triggered stabilization; 2) both the asymptotic stabilization and exponential stabilization are achieved for the systems, with delicately specifying the periodic event-triggering mechanism; and 3) the involved analysis, without applying the well-known Lyapunov theorems, can serve as a pattern from estimating sampling and execution errors to assess the closed-loop stability for stochastic periodic event-triggered control. Moreover, based on the established framework, we contribute the stabilizing controller design via periodic event-triggered output-feedback for a class of stochastic nonlinear systems.
The independent roles of mindfulness and distress tolerance in treatment outcomes in dialectical behavior therapy skills training.

Despite research supporting the effectiveness of dialectical behavior therapy (DBT) for borderline personality disorder (BPD), few studies have examined how DBT leads to clinical change. DBT is theorized to lead to improved clinical outcomes by enhancing the capacity for emotion regulation, including improvement in skills (e.g., mindfulness and distress tolerance) for managing emotional distress and impulsive behaviors. Therefore, the aim of this study was to test whether improvements in mindfulness and distress tolerance indirectly affect the relationship between DBT skills training and clinical outcomes. The sample consists of 84 patients diagnosed with BPD who were enrolled in a randomized controlled trial comparing 20 weeks of DBT-skills group (DBT-S) to an active waitlist control. Mindfulness and distress tolerance were assessed at baseline and at the end of the 20 weeks. BPD symptoms, general psychiatric symptoms, and social adjustment were assessed at the end of 20 weeks and combined into a latent variable representing a broad assessment of general psychopathology. Relative to the waitlist control group, improvements in mindfulness and distress tolerance each independently indirectly affected the relationship between DBT-S and posttreatment general psychopathology. Findings suggest that DBT-S exerts its effects on outcomes through improvements in mindfulness and distress tolerance. These findings support the significance of mindfulness and distress tolerance in DBT-S for BPD. Limitations, future directions, and clinical implications are discussed. (PsycINFO Database Record (c) 2019 APA, all rights reserved).
Yck1 casein kinase I regulates the activity and phosphorylation of Pah1 phosphatidate phosphatase from Saccharomyces cerevisiae

The PAH1-encoded phosphatidate phosphatase in Saccharomyces cerevisiae plays a major role in triacylglycerol synthesis and the control of phospholipid synthesis. For its catalytic function on the nuclear/endoplasmic reticulum membrane, Pah1 translocates to the membrane through its phosphorylation/dephosphorylation. Pah1 phosphorylation on multiple serine/threonine residues is complex and catalyzed by diverse protein kinases. In this work, we demonstrate that Pah1 is phosphorylated by the YCK1-encoded casein kinase I (CKI), regulating Pah1 catalytic activity and phosphorylation. Phosphoamino acid analysis coupled with phosphopeptide mapping of the CKI-phosphorylated Pah1 indicated that it is phosphorylated mainly on multiple serine residues. Using site-directed mutagenesis and phosphorylation analysis of Pah1, we identified eight serine residues (i.e. Ser-114, Ser-475, Ser-511, Ser-602, Ser-677, Ser-705, Ser-748, and Ser-774) as the target sites of CKI. Of these residues, Ser-475 and Ser-511 were specific for CKI, whereas the others were shared by casein kinase II (Ser-705), Cdc28–cyclin B (Ser-602), Pho85–Pho80 (Ser-114, Ser-602, and Ser-748), protein kinase A (Ser-667 and Ser-774), and protein kinase C (Ser-677). CKI-mediated phosphorylation of Pah1 stimulated both its phosphatidate phosphatase activity and its subsequent phosphorylation by casein kinase II. However, the CKI-mediated phosphorylation of Pah1 strongly inhibited its subsequent phosphorylation by Pho85–Pho80, protein kinase A, and protein kinase C. In a reciprocal analysis, Pah1 phosphorylation by Pho85–Pho80 inhibited subsequent phosphorylation by CKI. CKI-mediated Pah1 phosphorylation was also inhibited by a peptide containing the Pah1 residues 506–517, including the kinase-specific Ser-511 residue. These findings advance our understanding of how Pah1 catalytic activity and phosphorylation are regulated by multiple protein kinases.
Challenges and solutions in the development of vaccines against emerging and neglected infectious diseases

ABSTRACT Emerging and emergent infectious diseases (EIDs) represent a significant and growing cause of morbidity and mortality with increased potential for pandemics due to globalization and international trade. Challenges remain to the approach toward vaccine development for EIDs. This Special Feature explores areas related to vaccine development and testing, including unique challenges posed in the developing world. Vaccines against multiple pathogens spanning a number of viral families are explored with respect to past activities through to future commercialization. Cost drivers balanced against clinical need are discussed and unique challenges posed by rare diseases are considered.
Estatus Eléctrico durante el sueño lento y factores de Riesgo Neurológico: Diferentes manifestaciones de un mismo sindrome

RESUMEN Este estudio se realizo para conocer las caracteristicas de un grupo de pacientes con estatus electrico en sueno lento evaluados en la Fundacion Liga Central Contra la Epilepsia, entre los anos 2003 a 2013. Se buscaron factores asociados al desarrollo del sindrome, asi como la respuesta al tratamiento. De los pacientes detectados que cumplieron con los criterios segun ILAE 2010, se tomaron datos sobre antecedentes, sintomas y respuesta terapeutica. En ese periodo de tiempo fueron diagnosticados 15 pacientes, 60% varones; 11 iniciaron con epilepsia y 4 por alteraciones del neurodesarrollo o del aprendizaje. Todos presentaron alteraciones comportamentales y 12 epilepsia, manifestada por diferentes tipos de crisis, que en un 66% fue de dificil control pese a recibir diferentes esquemas antiepilepticos. La mayoria de ellos presentaron antecedentes de riesgo pre, peri o posnatales, considerando que estos explican la dificultad en el diagnostico inicial y las dificultades posteriores en el tratamiento. ABSTRACT ELECTRICAL STATUS EPILEPTICUS DURING SLOW SLEEP AND NEUROLOGICAL RISK FACTORS: DIFFERENT EXPRESSIONS OF SAME SYNDROME This study was carried out to elucidate the characteristics of patients with electrical status epilepticus during slow sleep or ESES syndrome, that were evaluated at Central League Against Epilepsy, between 2003 and 2013. A search was conducted to find associated risk factors for developing this syndrome as well as treatment outcomes and initial symptoms. Patients detected met the 2010 ILAE criteria. 15 patients were found; 60% were males, 11 had epilepsy as initial presentation, 4 had learning difficulties or neurodevelopmental delay. All patients had behavioral alterations and 12 had epilepsy, which presented with multiple types of crisis. 66% had refractory epilepsy. Most patients had prenatal, perinatal and postnatal risk factors; this is probably why making an initial diagnosis is a difficult task and a source of further treatment difficulties.
The Route from the Folded to the Amyloid State: Exploring the Potential Energy Surface of a Drug‐Like Miniprotein

Abstract The amyloid formation of the folded segment of a variant of Exenatide (a marketed drug for type‐2 diabetes mellitus) was studied by electronic circular dichroism (ECD) and NMR spectroscopy. We found that the optimum temperature for E5 protein amyloidosis coincides with body temperature and requires well below physiological salt concentration. Decomposition of the ECD spectra and its barycentric representation on the folded‐unfolded‐amyloid potential energy surface allowed us to monitor the full range of molecular transformation of amyloidogenesis. We identified points of no return (e.g.; T=37 °C, pH 4.1, c E5=250 μm, c NaCl=50 mm, t>4–6 h) that will inevitably gravitate into the amyloid state. The strong B‐type far ultraviolet (FUV)‐ECD spectra and an unexpectedly strong near ultraviolet (NUV)‐ECD signal (Θ ≈275–285 nm) indicate that the amyloid phase of E5 is built from monomers of quasi‐elongated backbone structure (φ≈−145°, ψ≈+145°) with strong interstrand Tyr↔Trp interaction. Misfolded intermediates and the buildup of “toxic” early‐stage oligomers leading to self‐association were identified and monitored as a function of time. Results indicate that the amyloid transition is triggered by subtle misfolding of the α‐helix, exposing aromatic and hydrophobic side chains that may provide the first centers for an intermolecular reorganization. These initial clusters provide the spatial closeness and sufficient time for a transition to the β‐structured amyloid nucleus, thus the process follows a nucleated growth mechanism.
Polyneuropathien bei HIV-Infektion

In approximately 10-16% of the cases, diseases of the peripheral nerves occur in the fully developed stage of AIDS, more seldom, however, in the stage of ARC. Some cases have been described in the stage of seroconversion or lymphadenopathy. At this stage cranial neuropathies can show up in connection with aseptic meningitis. The peripheral nerve diseases are present as distal symmetric sensomotory neuropathy, as chronic demyelinating polyradiculoneuropathy, as acute polyradiculoneuritis and as mononeuropathy multiplex. Frequently Varicella-zoster-radiculitis is observed. Cranial neuropathies are noted especially together with atypical aseptic meningitis, as a syndrome of the above mentioned polyneuropathies, with intracranial lymphomas and meningitides and meningoencephalitides caused by opportunistic infections. The morphological findings of the roots and nerves are variable: axonal degeneration and/or demyelination, infiltration of lymphocytes and microvasculitis. The pathogenesis varies: amongst others, direct infection by HIV, immunopathological changes and opportunistic infections are considered. The spontaneous development frequently leads to a remission. Treatment with corticosteroids and/or plasma exchange is only partially successful.
Gene Expression Analysis to Investigate Biological Networks Underlying Nasal Inflammatory Dysfunctions Induced by Diesel Exhaust Particles Using an In Vivo System

Objectives: Diesel exhaust particles (DEP)s are notorious ambient pollutants composed of a complex mixture of a carbon core and diverse chemical irritants. Several studies have demonstrated significant relationships between DEP exposure and serious nasal inflammatory response in vitro, but available information regarding underlying networks in terms of gene expression changes has not sufficiently explained potential mechanisms of DEP-induced nasal damage, especially in vivo. Methods: In the present study, we identified DEP-induced gene expression profiles under short-term and long-term exposure, and identified signaling pathways based on microarray data for understanding effects of DEP exposure in the mouse nasal cavity. Results: Alteration in gene expression due to DEP exposure provokes an imbalance of the immune system via dysregulated inflammatory markers, predicted to disrupt protective responses against harmful exogenous substances in the body. Several candidate markers were identified after validation using qRT-PCR, including S100A9, CAMP, IL20, and S100A8. Conclusions: Although further mechanistic studies are required for verifying the utility of the potential biomarkers suggested by the present study, our in vivo results may provide meaningful suggestions for understanding the complex cellular signaling pathways involved in DEP-induced nasal damages.