Collagen Based Multicomponent Interpenetrating Networks as Promising Scaffolds for 3D Culture of Human Neural Stem Cells, Human Astrocytes, and Human Microglia

This work describes for the first time the fabrication and characterization of multicomponent interpenetrating networks composed of collagen I, hyaluronic acid, and poly(ethylene glycol) diacrylate for the 3D culture of human neural stem cells, astrocytes, and microglia. The chemical composition of the scaffolds can be modulated while maintaining values of complex moduli within the range of the mechanical performance of brain tissue (∼6.9 kPa) and having cell viability exceeding 84%. The developed scaffolds are a promising new family of biomaterials that can potentially serve as 3D in vitro models for studying the physiology and physiopathology of the central nervous system

Micro-Ethical Decision Making Among Baccalaureate Nursing Students: A Qualitative Investigation

Nursing students frequently encounter micro-ethical nursing practice problems during their clinical experience. The purpose of this study was to understand the lived experiences of senior-level baccalaureate students faced with making micro-ethical clinical decisions in practice settings. A descriptive qualitative design was used, and five central themes emerged. A dominant finding was the experience of unapplied and forgotten ethics education revealing a mismatch between what faculty perceived was taught and students’ experiences of that education. When faced with micro-ethical decisions, participants trusted and deferred to staff nurse recommendations, even if the advice contradicted best-practice standards. Contextual naivete was brought out of concealment, contributing to the experience of moral disequilibrium (i.e., students felt conflicted about what they learned in school as best practice and what they observed being role modeled in the clinical environment). This study resulted in theory-guided implications for nursing education and recommendations for future study

Psychiatric disorders and urbanization in Germany

<p>Abstract</p> <p>Background</p> <p>Epidemiological studies over the last decade have supplied growing evidence of an association between urbanization and the prevalence of psychiatric disorders. Our aim was to examine the link between levels of urbanization and 12-month prevalence rates of psychiatric disorders in a nationwide German population study, controlling for other known risk factors such as gender, social class, marital status and the interaction variables of these factors with urbanization.</p> <p>Methods</p> <p>The Munich Composite International Diagnostic Interview (M-CIDI) was used to assess the prevalence of mental disorders (DSM-IV) in a representative sample of the German population (N = 4181, age: 18–65). The sample contains five levels of urbanization based on residence location.</p> <p>The epidemiological study was commissioned by the German Ministry of Research, Education and Science (BMBF) and approved by the relevant Institutional Review Board and ethics committee. Written informed consent was obtained for both surveys (core survey and Mental Health Supplement). Subjects did not get any financial compensation for their study participation.</p> <p>Results</p> <p>Higher levels of urbanization were linked to higher 12-month prevalence rates for almost all major psychiatric disorders (with the exception of substance abuse and psychotic disorders). The weighted prevalence percentages were highest in the most urbanized category. Alongside urbanization, female gender, lower social class and being unmarried were generally found to be associated with higher levels of psychopathology. The impact of urbanization on mental health was about equal (for almost all major psychiatric disorders) in young people and elderly people, men and women, and in married and single people. Only people from a low social class in the most urbanized settings had more somatoform disorders, and unmarried people in the most urbanized settings had more anxiety disorders.</p> <p>Conclusion</p> <p>Psychiatric disorders are more prevalent among the inhabitants of more urbanized areas. probably because of environmental stressors.</p

FoxQ1 Overexpression Influences Poor Prognosis in Non-Small Cell Lung Cancer, Associates with the Phenomenon of EMT

BACKGROUND: We determined the expression of forkhead box Q1 (FoxQ1), E-cadherin (E-cad), Mucin 1 (MUC1), vimentin (VIM) and S100 calcium binding protein A4 (S100A4), all epithelial-mesenchymal transition (EMT) indicator proteins in non-small cell lung cancer (NSCLC) tissue samples. We also investigated the relationship between these five proteins expression and other clinicopathologic factors in NSCLC. Finally, we assessed the potential value of these markers as prognostic indicators of survival in NSCLC's patients. METHODS: Quantitative real-time PCR and immunohistochemistry were used to characterize the expression of the FoxQ1 mRNA and protein in NSCLC. Expression of transcripts and translated products for the other four EMT indicator proteins was assessed by immunohistochemistry in the same clinical NSCLC samples. RESULTS: FoxQ1 mRNA and protein were up-regulated in NSCLC compared with normal tissues (P = 0.015 and P<0.001, respectively). Expression of FoxQ1 in adenocarcinoma was higher than in squamous cell carcinoma (P = 0.005), and high expression of FoxQ1 correlated with loss of E-cad expression (P = 0.012), and anomalous positivity of VIM (P = 0.024) and S100A4 (P = 0.004). Additional survival analysis showed that high expression of FoxQ1 (P = 0.047) and E-cad (P = 0.021) were independent prognostic factors. CONCLUSION: FoxQ1 maybe plays a specific role in the EMT of NSCLC, and could be used as a prognostic factor for NSCLC

Analysis of arterial intimal hyperplasia: review and hypothesis

which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. Background: Despite a prodigious investment of funds, we cannot treat or prevent arteriosclerosis and restenosis, particularly its major pathology, arterial intimal hyperplasia. A cornerstone question lies behind all approaches to the disease: what causes the pathology? Hypothesis: I argue that the question itself is misplaced because it implies that intimal hyperplasia is a novel pathological phenomenon caused by new mechanisms. A simple inquiry into arterial morphology shows the opposite is true. The normal multi-layer cellular organization of the tunica intima is identical to that of diseased hyperplasia; it is the standard arterial system design in all placentals at least as large as rabbits, including humans. Formed initially as one-layer endothelium lining, this phenotype can either be maintained or differentiate into a normal multi-layer cellular lining, so striking in its resemblance to diseased hyperplasia that we have to name it &quot;benign intimal hyperplasia&quot;. However, normal or &quot;benign &quot; intimal hyperplasia, although microscopically identical to pathology, is a controllable phenotype that rarely compromises blood supply. It is remarkable that each human heart has coronary arteries in which a single-layer endothelium differentiates earl

Impact of primary kidney disease on the effects of empagliflozin in patients with chronic kidney disease: secondary analyses of the EMPA-KIDNEY trial

Background: The EMPA KIDNEY trial showed that empagliflozin reduced the risk of the primary composite outcome of kidney disease progression or cardiovascular death in patients with chronic kidney disease mainly through slowing progression. We aimed to assess how effects of empagliflozin might differ by primary kidney disease across its broad population. Methods: EMPA-KIDNEY, a randomised, controlled, phase 3 trial, was conducted at 241 centres in eight countries (Canada, China, Germany, Italy, Japan, Malaysia, the UK, and the USA). Patients were eligible if their estimated glomerular filtration rate (eGFR) was 20 to less than 45 mL/min per 1·73 m2, or 45 to less than 90 mL/min per 1·73 m2 with a urinary albumin-to-creatinine ratio (uACR) of 200 mg/g or higher at screening. They were randomly assigned (1:1) to 10 mg oral empagliflozin once daily or matching placebo. Effects on kidney disease progression (defined as a sustained ≥40% eGFR decline from randomisation, end-stage kidney disease, a sustained eGFR below 10 mL/min per 1·73 m2, or death from kidney failure) were assessed using prespecified Cox models, and eGFR slope analyses used shared parameter models. Subgroup comparisons were performed by including relevant interaction terms in models. EMPA-KIDNEY is registered with ClinicalTrials.gov, NCT03594110. Findings: Between May 15, 2019, and April 16, 2021, 6609 participants were randomly assigned and followed up for a median of 2·0 years (IQR 1·5–2·4). Prespecified subgroupings by primary kidney disease included 2057 (31·1%) participants with diabetic kidney disease, 1669 (25·3%) with glomerular disease, 1445 (21·9%) with hypertensive or renovascular disease, and 1438 (21·8%) with other or unknown causes. Kidney disease progression occurred in 384 (11·6%) of 3304 patients in the empagliflozin group and 504 (15·2%) of 3305 patients in the placebo group (hazard ratio 0·71 [95% CI 0·62–0·81]), with no evidence that the relative effect size varied significantly by primary kidney disease (pheterogeneity=0·62). The between-group difference in chronic eGFR slopes (ie, from 2 months to final follow-up) was 1·37 mL/min per 1·73 m2 per year (95% CI 1·16–1·59), representing a 50% (42–58) reduction in the rate of chronic eGFR decline. This relative effect of empagliflozin on chronic eGFR slope was similar in analyses by different primary kidney diseases, including in explorations by type of glomerular disease and diabetes (p values for heterogeneity all &gt;0·1). Interpretation: In a broad range of patients with chronic kidney disease at risk of progression, including a wide range of non-diabetic causes of chronic kidney disease, empagliflozin reduced risk of kidney disease progression. Relative effect sizes were broadly similar irrespective of the cause of primary kidney disease, suggesting that SGLT2 inhibitors should be part of a standard of care to minimise risk of kidney failure in chronic kidney disease. Funding: Boehringer Ingelheim, Eli Lilly, and UK Medical Research Council