Prevalence, characteristics, and impact of adverse events in 34 Madrid hospitals. The ESHMAD study

Introduction: Adverse Events (AE) are one of the main problems in healthcare. Therefore, many policies have been developed worldwide to mitigate their im pact. The Patient Safety Incident Study in Hospitals in the Community of Madrid (ESHMAD) measures the results of them in the region. Methods: Cross-sectional study, conducted in May 2019, in hospitalised patients in 34 public hospitals using the Harvard Medical Practice Study methodology. A logistic regression model was carried out to study the association of the variables with the presence of AE, calibrated and adjusted by patient. Results: A total of 9975 patients were included, estimating a prevalence of AE of 11.9%. A higher risk of AE was observed in patients with surgical procedures (OR[CI95%]: 2.15[1.79 to 2.57], vs. absence), in Intensive Care Units (OR[CI95%]: 1.60[1.17 to 2.17], vs. Medical) and in hospitals of medium complexity (OR[CI95%]: 1.45[1.12 to 1.87], vs. low complexity). A 62.6% of AE increased the length of the stay or it was the cause of admission, and 46.9% of AE were considered prevent able. In 11.5% of patients with AE, they had contributed to their death. Conclusions: The prevalence of AE remains similar to the previously estimated one in studies developed with the same methodology. AE keep leading to longer hospital stays, contributing to patient's death, showing that it is necessary to put focus on patient safety again. A detailed analysis of these events has enabled the detection of specific areas for improvement according to the type of care, centre and patient

System Dynamics of Cognitive Vulnerabilities and Family Support Among Latina Children and Adolescents

The paper describes an approach to developing a data-driven development of a feedback theory of cognitive vulnerabilities and family support focused on understanding the dynamics experienced among Latina children, adolescents, and families. Family support is understood to be a response to avoidant and maladaptive behaviors that may be characteristic of cognitive vulnerabilities commonly associated depression and suicidal ideation. A formal feedback theory is developed, appraised, and analyzed using a combination of secondary analysis of qualitative interviews (N = 30) and quantitative analysis using system dynamics modeling and simulation. Implications for prevention practice, treatment, and future research are discussed

SOSIALISASI BANK SAMPAH DI KELURAHAN PANDAN KASTURI

Pola hidup sehat merupakan aspek yang sangat penting dalam kehidupan manusia apalagi didalam masa pandemi covid-19 ini. Salah satu cara penerapan pola hidup sehat adalah dengan menjaga kebersihan lingkungan. Sampah tentunya menjadi acuan besar dalam mempengaruhi lingkungan, untuk itu pentingnya pengelolahan sampah sangat di perlukan untuk masyarakat. Tujuan PKM ini adalah untuk memberikan pemahaman tentang pentingnya pengelolahan sampah dengan adanya bank sampah. Kegiatan ini melibatkan ketua-ketua RT/RW yang berada Kelurahan Pandan Kasturi, Kecamatan Sirimau,Kota Ambon dan juga Team Green Mollucas Ambon sebagai narasumber. Metode yang digunakan dalam kegiatan ini adalah Ceramah dan Diskusi. Ceramah yang diberikan dalam bentuk penjelasan powerpoint oleh team Green Mollucas Ambon dan dilanjutkan dengan sesi diskusi atau tanya jawab. Hasil dari kegiatan ini adalah Ketua-Ketua RT/RW Kelurahan Pandan Kasturi ,Kecamatan Sirimau,Kota Ambon dapat menerima pengetahuan tentang penting pengelolah sampah dengan adanya Bank Sampah dan bahkan memiliki tekad untuk membangun bank sampah di Kelurahan Pandan Kasturi,Kecamatan Sirimau ,Kota Ambon serta meminta pendampingan lebih lanjut dari Green Moluccas mengenai pembangunan Bank Sampah

Detailed Regulatory Mechanism of the Interaction between ZO-1 PDZ2 and Connexin43 Revealed by MD Simulations

The gap junction protein connexin43 (Cx43) binds to the second PDZ domain of Zonula occludens-1 (ZO-1) through its C-terminal tail, mediating the regulation of gap junction plaque size and dynamics. Biochemical study demonstrated that the very C-terminal 12 residues of Cx43 are necessary and sufficient for ZO-1 PDZ2 binding and phosphorylation at residues Ser (-9) and Ser (-10) of the peptide can disrupt the association. However, only a crystal structure of ZO-1 PDZ2 in complex with a shorter 9 aa peptide of connexin43 was solved experimentally. Here, the interactions between ZO-1 PDZ2 and the short, long and phosphorylated Cx43 peptides were studied using molecular dynamics (MD) simulations and free energy calculation. The short peptide bound to PDZ2 exhibits large structural variations, while the extension of three upstream residues stabilizes the peptide conformation and enhanced the interaction. Phosphorylation at Ser(-9) significantly weakens the binding and results in conformational flexibility of the peptide. Glu210 of ZO-1 PDZ2 was found to be a key regulatory point in Cx43 binding and phosphorylation induced dissociation

Pair-Wise Regulation of Convergence and Extension Cell Movements by Four Phosphatases via RhoA

Various signaling pathways regulate shaping of the main body axis during early vertebrate development. Here, we focused on the role of protein-tyrosine phosphatase signaling in convergence and extension cell movements. We identified Ptpn20 as a structural paralogue of PTP-BL and both phosphatases were required for normal gastrulation cell movements. Interestingly, knockdowns of PTP-BL and Ptpn20 evoked similar developmental defects as knockdown of RPTPα and PTPε. Co-knockdown of RPTPα and PTP-BL, but not Ptpn20, had synergistic effects and conversely, PTPε and Ptpn20, but not PTP-BL, cooperated, demonstrating the specificity of our approach. RPTPα and PTPε knockdowns were rescued by constitutively active RhoA, whereas PTP-BL and Ptpn20 knockdowns were rescued by dominant negative RhoA. Consistently, RPTPα and PTP-BL had opposite effects on RhoA activation, both in a PTP-dependent manner. Downstream of the PTPs, we identified NGEF and Arhgap29, regulating RhoA activation and inactivation, respectively, in convergence and extension cell movements. We propose a model in which two phosphatases activate RhoA and two phosphatases inhibit RhoA, resulting in proper cell polarization and normal convergence and extension cell movements

Mortality Risk of Hypnotics: Strengths and Limits of Evidence

Sleeping pills, more formally defined as hypnotics, are sedatives used to induce and maintain sleep. In a review of publications for the past 30 years, descriptive epidemiologic studies were identified that examined the mortality risk of hypnotics and related sedative-anxiolytics. Of the 34 studies estimating risk ratios, odds ratios, or hazard ratios, excess mortality associated with hypnotics was significant (p < 0.05) in 24 studies including all 14 of the largest, contrasted with no studies at all suggesting that hypnotics ever prolong life. The studies had many limitations: possibly tending to overestimate risk, such as possible confounding by indication with other risk factors; confusing hypnotics with drugs having other indications; possible genetic confounders; and too much heterogeneity of studies for meta-analyses. There were balancing limitations possibly tending towards underestimates of risk such as limited power, excessive follow-up intervals with possible follow-up mixing of participants taking hypnotics with controls, missing dosage data for most studies, and over-adjustment of confounders. Epidemiologic association in itself is not adequate proof of causality, but there is proof that hypnotics cause death in overdoses; there is thorough understanding of how hypnotics euthanize animals and execute humans; and there is proof that hypnotics cause potentially lethal morbidities such as depression, infection, poor driving, suppressed respiration, and possibly cancer. Combining these proofs with consistent evidence of association, the great weight of evidence is that hypnotics cause huge risks of decreasing a patient's duration of survival

PDZ domains and their binding partners: structure, specificity, and modification

PDZ domains are abundant protein interaction modules that often recognize short amino acid motifs at the C-termini of target proteins. They regulate multiple biological processes such as transport, ion channel signaling, and other signal transduction systems. This review discusses the structural characterization of PDZ domains and the use of recently emerging technologies such as proteomic arrays and peptide libraries to study the binding properties of PDZ-mediated interactions. Regulatory mechanisms responsible for PDZ-mediated interactions, such as phosphorylation in the PDZ ligands or PDZ domains, are also discussed. A better understanding of PDZ protein-protein interaction networks and regulatory mechanisms will improve our knowledge of many cellular and biological processes

Discovery and Characterization of Novel Vascular and Hematopoietic Genes Downstream of Etsrp in Zebrafish

The transcription factor Etsrp is required for vasculogenesis and primitive myelopoiesis in zebrafish. When ectopically expressed, etsrp is sufficient to induce the expression of many vascular and myeloid genes in zebrafish. The mammalian homolog of etsrp, ER71/Etv2, is also essential for vascular and hematopoietic development. To identify genes downstream of etsrp, gain-of-function experiments were performed for etsrp in zebrafish embryos followed by transcription profile analysis by microarray. Subsequent in vivo expression studies resulted in the identification of fourteen genes with blood and/or vascular expression, six of these being completely novel. Regulation of these genes by etsrp was confirmed by ectopic induction in etsrp overexpressing embryos and decreased expression in etsrp deficient embryos. Additional functional analysis of two newly discovered genes, hapln1b and sh3gl3, demonstrates their importance in embryonic vascular development. The results described here identify a group of genes downstream of etsrp likely to be critical for vascular and/or myeloid development

ICF, An Immunodeficiency Syndrome: DNA Methyltransferase 3B Involvement, Chromosome Anomalies, and Gene Dysregulation

The immunodeficiency, centromeric region instability, and facial anomalies syndrome (ICF) is the only disease known to result from a mutated DNA methyltransferase gene, namely, DNMT3B. Characteristic of this recessive disease are decreases in serum immunoglobulins despite the presence of B cells and, in the juxtacentromeric heterochromatin of chromosomes 1 and 16, chromatin decondensation, distinctive rearrangements, and satellite DNA hypomethylation. Although DNMT3B is involved in specific associations with histone deacetylases, HP1, other DNMTs, chromatin remodelling proteins, condensin, and other nuclear proteins, it is probably the partial loss of catalytic activity that is responsible for the disease. In microarray experiments and real-time RT-PCR assays, we observed significant differences in RNA levels from ICF vs. control lymphoblasts for pro- and anti-apoptotic genes (BCL2L10, CASP1, and PTPN13); nitrous oxide, carbon monoxide, NF-κB, and TNFa signalling pathway genes (PRKCH, GUCY1A3, GUCY1B3, MAPK13; HMOX1, and MAP4K4); and transcription control genes (NR2F2 and SMARCA2). This gene dysregulation could contribute to the immunodeficiency and other symptoms of ICF and might result from the limited losses of DNA methylation although ICF-related promoter hypomethylation was not observed for six of the above examined genes. We propose that hypomethylation of satellite 2at1qh and 16qh might provoke this dysregulation gene expression by trans effects from altered sequestration of transcription factors, changes in nuclear architecture, or expression of noncoding RNAs