Schizophrenia in Malaysian families: A study on factors associated with quality of life of primary family caregivers

<p>Abstract</p> <p>Background</p> <p>Schizophrenia is a chronic illness which brings detrimental effects in the caregivers' health. This study was aimed at highlighting the socio-demographic, clinical and psychosocial factors associated with the subjective Quality of Life (QOL) of Malaysian of primary family caregivers of subjects with schizophrenia attending an urban tertiary care outpatient clinic in Malaysia.</p> <p>Methods</p> <p>A cross-sectional study was performed to study patient, caregiver and illness factors associated with the QOL among 117 individuals involved with caregiving for schizophrenia patients. The study used WHOQOL-BREF to assess caregivers' QOL and Brief Psychiatric Rating Scale (BPRS) to assess the severity of patients' symptoms. Social Readjustment Rating Scale (SRRS) assessed the stress level due to life events.</p> <p>Results</p> <p>The mean scores of WHOQOL-BREF in physical, psychological, social and environmental domains were 66.62 (14.36), 61.32 (15.52), 62.77 (17.33), 64.02 (14.86) consecutively. From multiple regression analysis, factors found to be significantly associated with higher QOL were higher educational level among caregivers in social and environmental domains; caregivers not having medical problem/s in physical and psychological domains; later onset and longer illness duration of illness in social domains; patients not attending day care program in environmental domain; lower BPRS score in physical and environmental domains. SRRS score of caregivers was also found to have a significant negative correlation with QOL in environmental and psychological domains. Other factors were not significantly associated with QOL.</p> <p>Conclusion</p> <p>Caregivers with more social advantages such as higher educational level and physically healthier and dealing with less severe illness had significantly higher QOL in various aspects. Supporting the caregivers in some of these modifiable factors in clinical practice is important to achieve their higher level QOL.</p

The role of head-up cardiopulmonary resuscitation in sudden cardiac arrest: a systematic review and meta-analysis

BACKGROUND: Head-up cardiopulmonary resuscitation (HU-CPR) is an experimental treatment for sudden cardiac arrest (SCA), where cardiopulmonary resuscitation (CPR) is performed in a ramped position. We evaluated whether HU-CPR improved survival and surrogate outcomes as compared to standard CPR (S-CPR). METHODS: Studies reporting on HU-CPR in SCA were searched for in PubMed, Embase and Cochrane Library from inception to May 1st 2021. Outcomes included neurologically-intact survival, 24-hour-survival, intracranial pressure (ICP), cerebral perfusion pressure (CerPP) and brain blood flow (BBF). Risk of bias was assessed using the GRADE assessment tool and Newcastle Ottawa Scale. Fixed- and random-effects models were used to estimate the pooled effects of HU-CPR at 30 degrees. RESULTS: Thirteen articles met the criteria for inclusion (11 animal-only studies, one before-and-after human-only study, one study that utilized human- and animal-cadavers). Among animal studies, the most common implementation of HU-CPR was a 30-degree upward tilt of the head and thorax (n=7), while four studies investigated controlled sequential elevation (CSE). Two animal studies reported improved cerebral performance category (CPC) scores at 24-hour. The pooled effect on 24-hour survival was not statistically significant (P=0.37). The lone human study reported doubled return of spontaneous circulation (ROSC) (17.9% versus 34.2%, P<0.0001). The pooled effect on ROSC in three porcine studies was OR =3.63 (95% CI: 0.72–18.39). Pooled effects for surrogate physiological outcomes of intracranial cranial pressure (MD −14.08, 95% CI: −23.21 to −4.95, P=0.003), CerPP (MD 14.39, 95% CI: 3.07–25.72, P=0.01) and BBF (MD 0.14, 95% CI: 0.02–0.27, P=0.03), showed statistically significant benefit. DISCUSSION: Overall, HU-CPR improved neurologically-intact survival at 24-hour, ROSC and physiological surrogate outcomes in animal models. Despite promising preclinical data, and one human observational study, clinical equipoise remains surrounding the role of HU-CPR in SCA, necessitating clarification with future randomized human trials

Efficacy and safety results from IMblaze370, a randomised Phase III study comparing atezolizumab+cobimetinib and atezolizumab monotherapy vs regorafenib in chemotherapy-refractory metastatic colorectal cancer

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Co-administration With the Pharmacological Chaperone AT1001 Increases Recombinant Human α-Galactosidase A Tissue Uptake and Improves Substrate Reduction in Fabry Mice

Fabry disease is an X-linked lysosomal storage disorder (LSD) caused by mutations in the gene (GLA) that encodes the lysosomal hydrolase α-galactosidase A (α-Gal A), and is characterized by pathological accumulation of the substrate, globotriaosylceramide (GL-3). Regular infusion of recombinant human α-Gal A (rhα-Gal A), termed enzyme replacement therapy (ERT), is the primary treatment for Fabry disease. However, rhα-Gal A has low physical stability, a short circulating half-life, and variable uptake into different disease-relevant tissues. We hypothesized that coadministration of the orally available, small molecule pharmacological chaperone AT1001 (GR181413A, 1-deoxygalactonojirimycin, migalastat hydrochloride) may improve the pharmacological properties of rhα-Gal A via binding and stabilization. AT1001 prevented rhα-Gal A denaturation and activity loss in vitro at neutral pH and 37 °C. Coincubation of Fabry fibroblasts with rhα-Gal A and AT1001 resulted in up to fourfold higher cellular α-Gal A and ~30% greater GL-3 reduction compared to rhα-Gal A alone. Furthermore, coadministration of AT1001 to rats increased the circulating half-life of rhα-Gal A by >2.5-fold, and in GLA knockout mice resulted in up to fivefold higher α-Gal A levels and fourfold greater GL-3 reduction than rhα-Gal A alone. Collectively, these data highlight the potentially beneficial effects of AT1001 on rhα-Gal A, thus warranting clinical investigation

Purification and bioactivity of exendin-4, a peptide analogue of GLP-1, expressed in Pichia pastoris

Exendin-4, a peptide analogue of glucagon-like peptide-1 (GLP-1), has been developed for treatment of type 2 diabetes. Herein, the secretive exendin-4 fusion protein, expressed by methanol induction in Pichia pastoris system, was purified to homogeneity by chromatography followed by enterokinase cleavage of the fusion protein and subsequent purification of the recombinant exendin-4. Purity of the recombinant exendin-4 was 95.6%. Bioactivity assay revealed that it had glucose-lowering and insulin-releasing action in vivo

Resolving the ancestry of Austronesian-speaking populations

There are two very different interpretations of the prehistory of Island Southeast Asia (ISEA), with genetic evidence invoked in support of both. The “out-of-Taiwan” model proposes a major Late Holocene expansion of Neolithic Austronesian speakers from Taiwan. An alternative, proposing that Late Glacial/postglacial sea-level rises triggered largely autochthonous dispersals, accounts for some otherwise enigmatic genetic patterns, but fails to explain the Austronesian language dispersal. Combining mitochondrial DNA (mtDNA), Y-chromosome and genome-wide data, we performed the most comprehensive analysis of the region to date, obtaining highly consistent results across all three systems and allowing us to reconcile the models. We infer a primarily common ancestry for Taiwan/ISEA populations established before the Neolithic, but also detected clear signals of two minor Late Holocene migrations, probably representing Neolithic input from both Mainland Southeast Asia and South China, via Taiwan. This latter may therefore have mediated the Austronesian language dispersal, implying small-scale migration and language shift rather than large-scale expansion

Constitutively decreased TGFBR1 allelic expression is a common finding in colorectal cancer and is associated with three TGFBR1 SNPs

Purpose: Constitutively decreased TGFBR1 allelic expression is emerging as a potent modifier of colorectal cancer risk in mice and humans. This phenotype was first observed in mice, then in lymphoblastoid cell lines from patients with microsatellite stable colorectal tumors. Patients and Methods: We assessed the frequency of constitutively decreased TGFBR1 allelic expression and association with SNPs covering the TGFBR1 locus using RNA and DNA extracted from the peripheral blood lymphocytes of 118 consecutive patients with biopsy-proven adenocarcinoma of the colon or the rectum. Results: We found that 11(9.3%) of 118 patients exhibited decreased TGFBR1 allelic expression (TGFBR1 ASE). TGFBR1 ASE was strongly associated with three SNPs in linkage disequilibrium with each other: rs7034462 (p = 7.2 × 10-4), TGFBR1*6A (p = 1.6 × 10-4) and rs11568785 (p = 1.4 × 10-4). Conclusion: These results confirm the high prevalence of constitutively decreased TGFBR1 allelic expression among patients with colorectal cancer. The association of this phenotype with TGFBR1*6A, rs7034462 and rs1156875 suggests an association between TGFBR1 SNPs and colorectal cancer, which warrants additional studies