Prediction models in first-episode psychosis: systematic review and critical appraisal

Background: People presenting with first-episode psychosis (FEP) have heterogenous outcomes. More than 40% fail to achieve symptomatic remission. Accurate prediction of individual outcome in FEP could facilitate early intervention to change the clinical trajectory and improve prognosis. Aims: We aim to systematically review evidence for prediction models developed for predicting poor outcome in FEP. Method: A protocol for this study was published on the International Prospective Register of Systematic Reviews, registration number CRD42019156897. Following Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidance, we systematically searched six databases from inception to 28 January 2021. We used the Checklist for Critical Appraisal and Data Extraction for Systematic Reviews of Prediction Modelling Studies and the Prediction Model Risk of Bias Assessment Tool to extract and appraise the outcome prediction models. We considered study characteristics, methodology and model performance. Results: Thirteen studies reporting 31 prediction models across a range of clinical outcomes met criteria for inclusion. Eleven studies used logistic regression with clinical and sociodemographic predictor variables. Just two studies were found to be at low risk of bias. Methodological limitations identified included a lack of appropriate validation, small sample sizes, poor handling of missing data and inadequate reporting of calibration and discrimination measures. To date, no model has been applied to clinical practice. Conclusions: Future prediction studies in psychosis should prioritise methodological rigour and external validation in larger samples. The potential for prediction modelling in FEP is yet to be realised

MÉTODOS NÃO FARMACOLÓGICOS PARA MANEJO DA DOR NA UTI NEONATAL

The intention of this study was to analyze the effectiveness of comfortable carrying and swaddling in reducing pain in premature babies. A quantitative approach was carried out, according to the hypotheses of an experimental study of the randomized and crossover clinical trial type. considering the analyzes based on the duration of the painful intervention, changes in heart rate, respiratory rate, and oxygen saturation, as well as the organization according to the subsystems of autonomic, motor and behavioral development of the newborn, it was evident that there were no statistically significant differences between the facilitated restraint and diaper interventions. However, faster physiological and behavioral stability was noted during the application of facilitating restraint compared to bandaging, promoting reorganization and reducing agitation and hemodynamic changes. Facilitated support is achieved by positioning the hands simulating the fetal position. Although swaddling the newborn involves keeping the newborn's limbs flexed and the hands close to the face, an adequate thoracic excursion must be ensured, a position that must be maintained by wrapping the premature baby's body in padding or diapers, which have the function of offering greater safety during the painful procedure. This study demonstrated the effectiveness of non-pharmacological interventions, restraint and swaddling in pain management during procedures that cause distress in neonates.A intenção deste estudo foi analisar a eficácia do transporte confortável e do enfaixamento na redução da dor em bebês prematuros. Foi realizada uma abordagem quantitativa, segundo as hipóteses de um estudo experimental do tipo ensaio clínico randomizado e cruzado. levando em consideração as análises baseadas na duração da intervenção dolorosa, nas alterações da frequencia cardíaca, na frequencia respiratória e na saturação de oxigênio, bem como na organização de acordo com os subsistemas de desenvolvimento autonômico, motor e comportamental do recém-nascido ficou evidente que houve não houve diferenças estatisticamente significativos entre as intervenções de contenção facilitada e fralda. Porém, foi notada estabilidade fisiológica e comportamental mais rápida durante a aplicação da contenção facilitadora em comparação ao enfaixamento, promovendo reorganização e reduzindo a agitação e as alterações hemodinâmicas. A sustentação facilitada é obtida pelo posicionamento das mãos simulando a posição fetal. Embora envolver o recém-nascido envolva manter os membros do recém-nascido flexionados e as mãos próximos ao rosto deve-se garantir uma adequada excursão torácica, posição que deve ser mantida envolvendo o corpo do prematuro em estofos, fossas ou fraldas, que têm a função de oferecer maior segurança durante o procedimento dolorido. Este estudo demonstrou a eficácia de intervenções não farmacológicas, contenção e enfaixamento no manejo da dor durante procedimentos que causam sofrimento em neonatos. &nbsp

Smaller total and subregional cerebellar volumes in posttraumatic stress disorder:a mega-analysis by the ENIGMA-PGC PTSD workgroup

Although the cerebellum contributes to higher-order cognitive and emotional functions relevant to posttraumatic stress disorder (PTSD), prior research on cerebellar volume in PTSD is scant, particularly when considering subregions that differentially map on to motor, cognitive, and affective functions. In a sample of 4215 adults (PTSD n = 1642; Control n = 2573) across 40 sites from the ENIGMA-PGC PTSD working group, we employed a new state-of-the-art deep-learning based approach for automatic cerebellar parcellation to obtain volumetric estimates for the total cerebellum and 28 subregions. Linear mixed effects models controlling for age, gender, intracranial volume, and site were used to compare cerebellum volumes in PTSD compared to healthy controls (88% trauma-exposed). PTSD was associated with significant grey and white matter reductions of the cerebellum. Compared to controls, people with PTSD demonstrated smaller total cerebellum volume, as well as reduced volume in subregions primarily within the posterior lobe (lobule VIIB, crus II), vermis (VI, VIII), flocculonodular lobe (lobule X), and corpus medullare (all p -FDR &lt; 0.05). Effects of PTSD on volume were consistent, and generally more robust, when examining symptom severity rather than diagnostic status. These findings implicate regionally specific cerebellar volumetric differences in the pathophysiology of PTSD. The cerebellum appears to play an important role in higher-order cognitive and emotional processes, far beyond its historical association with vestibulomotor function. Further examination of the cerebellum in trauma-related psychopathology will help to clarify how cerebellar structure and function may disrupt cognitive and affective processes at the center of translational models for PTSD.</p

Smaller total and subregional cerebellar volumes in posttraumatic stress disorder:a mega-analysis by the ENIGMA-PGC PTSD workgroup

Although the cerebellum contributes to higher-order cognitive and emotional functions relevant to posttraumatic stress disorder (PTSD), prior research on cerebellar volume in PTSD is scant, particularly when considering subregions that differentially map on to motor, cognitive, and affective functions. In a sample of 4215 adults (PTSD n = 1642; Control n = 2573) across 40 sites from the ENIGMA-PGC PTSD working group, we employed a new state-of-the-art deep-learning based approach for automatic cerebellar parcellation to obtain volumetric estimates for the total cerebellum and 28 subregions. Linear mixed effects models controlling for age, gender, intracranial volume, and site were used to compare cerebellum volumes in PTSD compared to healthy controls (88% trauma-exposed). PTSD was associated with significant grey and white matter reductions of the cerebellum. Compared to controls, people with PTSD demonstrated smaller total cerebellum volume, as well as reduced volume in subregions primarily within the posterior lobe (lobule VIIB, crus II), vermis (VI, VIII), flocculonodular lobe (lobule X), and corpus medullare (all p -FDR &lt; 0.05). Effects of PTSD on volume were consistent, and generally more robust, when examining symptom severity rather than diagnostic status. These findings implicate regionally specific cerebellar volumetric differences in the pathophysiology of PTSD. The cerebellum appears to play an important role in higher-order cognitive and emotional processes, far beyond its historical association with vestibulomotor function. Further examination of the cerebellum in trauma-related psychopathology will help to clarify how cerebellar structure and function may disrupt cognitive and affective processes at the center of translational models for PTSD.</p

Nesting and fate of transplanted stem cells in hypoxic/ischemic injured tissues: The role of HIF1α /sirtuins and downstream molecular interactions

International audienceOxidative stress (OS) plays a pivotal role in diabetes mellitus (DM) onset, progression, and chronic complications. Hyperglycemia-induced reactive oxygen species (ROS) have been shown to reduce insulin secretion from pancreatic β-cells, to impair insulin sensitivity and signaling in insulin-responsive tissues, and to alter endothelial cells function in both type 1 and type 2 DM. As a powerful antioxidant without side effects, astaxanthin (ASX), a xanthophyll carotenoid, has been suggested to contribute to the prevention and treatment of DM-associated pathologies. ASX reduces inflammation, OS, and apoptosis by regulating different OS pathways though the exact mechanism remains elusive. Based on several studies conducted on type 1 and type 2 DM animal models, orally or parenterally administrated ASX improves insulin resistance and insulin secretion; reduces hyperglycemia; and exerts protective effects against retinopathy, nephropathy, and neuropathy. However, more experimental support is needed to define conditions for its use. Moreover, its efficacy in diabetic patients is poorly explored. In the present review, we aimed to identify the up-to-date biological effects and underlying mechanisms of ASX on the ROS-induced DM-associated metabolic disorders and subsequent complications. The development of an in-depth research to better understand the biological mechanisms involved and to identify the most effective ASX dosage and route of administration is deemed necessary

Impact of Astaxanthin on Diabetes Pathogenesis and Chronic Complications.

International audienceOxidative stress (OS) plays a pivotal role in diabetes mellitus (DM) onset, progression, and chronic complications. Hyperglycemia-induced reactive oxygen species (ROS) have been shown to reduce insulin secretion from pancreatic β-cells, to impair insulin sensitivity and signaling in insulin-responsive tissues, and to alter endothelial cells function in both type 1 and type 2 DM. As a powerful antioxidant without side effects, astaxanthin (ASX), a xanthophyll carotenoid, has been suggested to contribute to the prevention and treatment of DM-associated pathologies. ASX reduces inflammation, OS, and apoptosis by regulating different OS pathways though the exact mechanism remains elusive. Based on several studies conducted on type 1 and type 2 DM animal models, orally or parenterally administrated ASX improves insulin resistance and insulin secretion; reduces hyperglycemia; and exerts protective effects against retinopathy, nephropathy, and neuropathy. However, more experimental support is needed to define conditions for its use. Moreover, its efficacy in diabetic patients is poorly explored. In the present review, we aimed to identify the up-to-date biological effects and underlying mechanisms of ASX on the ROS-induced DM-associated metabolic disorders and subsequent complications. The development of an in-depth research to better understand the biological mechanisms involved and to identify the most effective ASX dosage and route of administration is deemed necessary

Contributions of trauma and economic insecurity to psychological distress in response to the COVID‐19 pandemic

Abstract Racially minoritized women with limited socioeconomic resources are at increased risk for adverse psychological outcomes in response to the coronavirus disease 2019 (COVID‐19) pandemic. Disproportionate rates of trauma exposure and economic insecurity likely heighten risk for these outcomes among socioeconomically vulnerable individuals, but the unique contributions of these factors are poorly understood. As such, we examined trauma and economic factors as predictors of pandemic‐related psychological distress and symptoms. Ninety‐six women recruited for a trauma research study (91.7% Black, Mage = 38.3 years, SDage = 11.8 years) completed measures of trauma exposure, economic insecurity, and several items assessing psychological distress and symptoms related to the COVID‐19 pandemic. We examined concern for mental and physical health impacts of COVID‐19 as well as changes in self‐reported levels of anxiety and anhedonia from the 3 months before the pandemic to the previous 2 weeks. Linear regression analyses were used to assess contributions of trauma exposure and economic insecurity to COVID‐19‐related distress. Childhood maltreatment and lifetime trauma exposure did not predict COVID‐19‐related distress; however, financial concern significantly contributed to concern for the physical health impact of COVID‐19 (B = 0.30, p < 0.05). Food insecurity emerged as the only significant predictor of concern for the mental health impact of COVID‐19 (B = 0.91, p < 0.01). Housing instability was the only significant predictor of COVID‐19‐related increases in anhedonia (B = −0.30, p < 0.05). Economic insecurity, namely, self‐reported financial concern, food insecurity, and housing instability, was related to COVID‐19‐related psychological distress and symptoms in a sample of predominately Black American women living in under‐resourced communities. Findings may help identify populations at risk for COVID‐19‐related psychological distress and symptoms and appropriate interventions, such as expanding access to nutritious food sources and housing support, for minoritized community members

Experimental Type 2 Diabetes Differently Impacts on the Select Functions of Bone Marrow-Derived Multipotent Stromal Cells

International audienceBone marrow-derived multipotent stromal cells (BMMSCs) represent an attractive therapeutic modality for cell therapy in type 2 diabetes mellitus (T2DM)-associated complications. T2DM changes the bone marrow environment; however, its effects on BMMSC properties remain unclear. The present study aimed at investigating select functions and differentiation of BMMSCs harvested from the T2DM microenvironment as potential candidates for regenerative medicine. BMMSCs were obtained from Zucker diabetic fatty (ZDF; an obese-T2DM model) rats and their lean littermates (ZL; controls), and cultured under normoglycemic conditions. The BMMSCs derived from ZDF animals were fewer in number, with limited clonogenicity (by 2-fold), adhesion (by 2.9-fold), proliferation (by 50%), migration capability (by 25%), and increased apoptosis rate (by 2.5-fold) compared to their ZL counterparts. Compared to the cultured ZL-BMMSCs, the ZDF-BMMSCs exhibited (i) enhanced adipogenic differentiation (increased number of lipid droplets by 2-fold; upregulation of the Pparg, AdipoQ, and Fabp genes), possibly due to having been primed to undergo such differentiation in vivo prior to cell isolation, and (ii) different angiogenesis-related gene expression in vitro and decreased proangiogenic potential after transplantation in nude mice. These results provided evidence that the T2DM environment impairs BMMSC expansion and select functions pertinent to their efficacy when used in autologous cell therapies

GAELIC/SALIT Interlending Project 2005

The GAELIC Interlending and Document Supply Project was the fortunate recipient of a SALI Trust grant of R15 000 to investigate the performance levels of the ten GAELIC member libraries in supplying and requesting books and articles within the interlending system of South Africa. The duration of the project was from January to September 2005. The Project was led by Heidi Visser of the Academic Information Services at the University of Pretoria

Modular one-pot assembly of CRISPR arrays enables library generation and reveals factors influencing crRNA biogenesis.

CRISPR-Cas systems inherently multiplex through CRISPR arrays—whether to defend against different invaders or mediate multi-target editing, regulation, imaging, or sensing. However, arrays remain difficult to generate due to their reoccurring repeat sequences. Here, we report a modular, one-pot scheme called CRATES to construct CRISPR arrays and array libraries. CRATES allows assembly of repeat-spacer subunits using defined assembly junctions within the trimmed portion of spacers. Using CRATES, we construct arrays for the single-effector nucleases Cas9, Cas12a, and Cas13a that mediated multiplexed DNA/RNA cleavage and gene regulation in cell-free systems, bacteria, and yeast. CRATES further allows the one-pot construction of array libraries and composite arrays utilized by multiple Cas nucleases. Finally, array characterization reveals processing of extraneous CRISPR RNAs from Cas12a terminal repeats and sequence- and context-dependent loss of RNA-directed nuclease activity via global RNA structure formation. CRATES thus can facilitate diverse multiplexing applications and help identify factors impacting crRNA biogenesis