Notes

Pseudomonas aeruginosa: a great anti-biotic sturdy virus along with environmental origin.
It examines their limitations, the blind spots that they create in terms of the questions asked, and the capacity for research to take account of contextual factors that drive practice. It draws on new work from heterodox economics which seeks to target anticorruption interventions at practices that have high impact and which are politically and economically feasible to address. We consider how such approaches can be adopted into health systems and what new questions need to be addressed by researchers to support the development of sustainable solutions to corruption. We present a short case study from Bangladesh to show how such an approach reveals new perspectives on actors and drivers of corruption practice. We conclude by considering the most important areas for research and policy.This paper introduces a framework for conducting and disseminating mixed methods research on positive outlier countries that successfully improved their health outcomes and systems. We provide guidance on identifying exemplar countries, assembling multidisciplinary teams, collecting and synthesising pre-existing evidence, undertaking qualitative and quantitative analyses, and preparing dissemination products for various target audiences. Through a range of ongoing research studies, we illustrate application of each step of the framework while highlighting key considerations and lessons learnt. We hope uptake of this comprehensive framework by diverse stakeholders will increase the availability and utilisation of rigorous and comparable insights from global health success stories.
In recognition of our increasingly globalised world, global health is now a required component of the medical school curriculum in the UK. We review the current provision of global health education (GHE) in UK medical schools to identify gaps in compulsory teaching.

We conducted a review of the literature to inform a two-part electronic survey of global health compulsory teaching, optional teaching and pre-elective training. Surveys were sent to all 33 UK medical schools for completion by the faculty lead on global health and the nominated final year student representative.

Surveys were returned by 29 (88%) medical school faculty and 15 (45%) medical student representatives; 24 (83%) faculty and 10 (67%) students reported including GHE in the core curriculum; however, there was wide variation in the learning outcomes covered. On average 75% of faculty and 82% of students reported covering recommended global health themes 'global burden of disease', 'socioeconomic and environmental determinants of healthmprove access to fundamental GHE for all medical students.Muscle-invasive bladder cancer (MIBC) frequently harbors mutations in the CDKN1A gene, which encodes the tumor suppressor protein p21, with the majority of alterations truncating the peptide. The effect of these mutations is poorly understood. We hypothesized that after DNA-damaging events, cells deficient in p21 would be unable to halt the cell cycle and efficiently repair DNA damage, thus proceeding down the apoptotic pathway. Bobcat339 in vivo We used synthetic CRISPR guide RNAs to ablate the whole peptide (sg12, targeting the 12th amino acid) or the C-terminal proliferating cell nuclear antigen (PCNA)-binding domain (sg109) to mimic different p21-truncating mutations compared with a negative control (sgGFP) in bladder cancer cell lines. Loss of detectable p21 and a stable truncated p21 peptide were identified in sg12 and sg109 single-cell clones, respectively. We found that p21-deficient cells (sg12) were sensitized to cisplatin, while cells harboring distally truncated p21 (sg12 clones) demonstrated enhanced cisplatin resistance. p21-deficient sg12 clones demonstrated less repair of DNA-platinum adducts and increased γ-H2AX foci after cisplatin exposure, suggesting there was persistent DNA damage after p21 loss. p21-deficient sg12 clones were also unable to prevent the activation of CDK1 after DNA damage, and therefore, continued through the cell cycle, resulting in replication fork collapse, potentially explaining the observed cisplatin sensitization. sg109 clones were neither unable to sequester PCNA nor localize p21 to the nucleus after DNA damage, potentially explaining the chemoresistant phenotype. Our findings suggest that different CDKN1A truncations have different and perhaps disparate biology, and that there may be a duality of effect on cisplatin sensitivity depending on mutation context. IMPLICATIONS Some truncating CDKN1A mutations generate a retained peptide that may have neomorphic functions and affect cisplatin sensitivity in patients with bladder cancer.As the most complex organ of the human body, the brain is composed of diverse regions, each consisting of distinct cell types and their respective cellular interactions. Human brain development involves a finely tuned cascade of interactive events. These include spatiotemporal gene expression changes and dynamic alterations in cell-type composition. However, our understanding of this process is still largely incomplete owing to the difficulty of brain spatiotemporal transcriptome collection. In this study, we developed a tensor-based approach to impute gene expression on a transcriptome-wide level. After rigorous computational benchmarking, we applied our approach to infer missing data points in the widely used BrainSpan resource and completed the entire grid of spatiotemporal transcriptomics. Next, we conducted deconvolutional analyses to comprehensively characterize major cell-type dynamics across the entire BrainSpan resource to estimate the cellular temporal changes and distinct neocortical areas across development. Moreover, integration of these results with GWAS summary statistics for 13 brain-associated traits revealed multiple novel trait-cell-type associations and trait-spatiotemporal relationships. In summary, our imputed BrainSpan transcriptomic data provide a valuable resource for the research community and our findings help further studies of the transcriptional and cellular dynamics of the human brain and related diseases.
Non-invasive cardiac output monitoring (NICOM) provides continuous estimation of cardiac output. This has potential for use in the delivery suite in the management of acutely depressed term infants. This study aims to measure cardiac output in term infants at delivery and in the first hours of life.

Parents of term infants due to be born by elective caesarean section or vaginal delivery at Cork University Maternity Hospital, Ireland were approached in the antenatal period to participate. Cardiac output was measured using a CHEETAH NICOM device, which uses electrical bioreactance technology, at birth and at 2 hours of life.

Forty-nine newborns were included. The median gestational age was 39 (IQR 39-40) weeks and the median birth weight was 3.50 (IQR 3.14-3.91) kg. Cardiac output measurements were obtained at a median of 8 (IQR 5-12) min of life. The mean (SD) cardiac output was 101 (24) mL/kg/min in the delivery room and 89 (22) mL/kg/min at 2 hours of life. There was a statistically significant decrease in cardiac output from birth to 2 hours of life (difference in mean (95% CI) 13.5 (9.2 to 17.9) mL/kg/min, p<0.001, n=47). There were no adverse effects associated with NICOM.

This technique is feasible and safe in the delivery room. Mean cardiac output measures using NICOM are lower than those found in studies which used echocardiography to determine cardiac output at birth.
This technique is feasible and safe in the delivery room. Mean cardiac output measures using NICOM are lower than those found in studies which used echocardiography to determine cardiac output at birth.The previous studies have shown that plasma chitotriosidase (CHIT) levels increase in many diseases with inflammation. However, there are no reported studies investigating the relationship between CHIT and chronic heart failure (CHF) which is an inflammatory process. Therefore, we aimed to investigate the role of CHIT in diagnosis and severity of CHF in this study. 36 patients (50% male, mean age 63.17±10.18 years) with left ventricular ejection fraction less then 40% and 27 controls (44% male, mean age 61.33±8.73 years) were included in this study. Patients with CHF were divided into two groups as ischemic heart failure (IHF) and non-ischemic heart failure (NIHF) according to the underlying etiology. Plasma CHIT and N-terminal pro brain natriuretic peptide (NT-proBNP) levels were measured by ELISA method. Plasma CHIT and NT-proBNP levels were higher in patients with CHF than in controls (CHIT 931.25±461.39 ng/mL, 232.79±61.28 ng/mL, p less then 0.001; NT-proBNP, 595.31±428.11 pg/mL vs 78.13±30.47 pg/L; p less then 0.001). Also, the levels of these parameters increased in IHF compared with NIHF (CHIT, 1139.28±495.22 ng/mL, 671.22±237.21 ng/mL, p=0.002; NT-proBNP, 792.87±461.26 pg/mL vs 348.36±202.61 pg/mL, p=0.001) and there was a strong correlation between NT-proBNP and CHIT (r=0.969, p less then 0.001). According to this study findings, plasma CHIT level increases in CHF and its increased levels are correlated with NT-proBNP which is used diagnosis and prognosis of HF.Overproduction of mucus and impaired clearance play important roles in the pathogenesis of muco-obstructive lung diseases (MOLDs). This study aims to evaluate the therapeutic effect and safety of nebulized hypertonic saline (HS) on MOLDs. Five electronic databases including PubMed, Excerpt Medica Database (EMBASE), Cochrane Central Register of Controlled Trials, ClinicalTrials.gov and International Standard Randomized Controlled Trial Number Register were searched until June 2019. Randomized controlled trials or randomized controlled crossover trials which investigated the therapeutic effect of HS versus non-HS for MOLDs were included. Twenty-one studies met the eligibility criteria. For cystic fibrosis (CF), although the forced expiratory volume in the first second and forced vital capacity did not improve significantly (mean difference (MD) -0.48, 95% CI -3.72 to 2.76), (MD 1.85, 95% CI -4.31 to 8.01), respectively), the clearance capability of lung and quality of life (QOL) improved significantly in the HS group ((standard mean difference 0.44, 95% CI 0.02 to 0.87), (MD -0.64, 95% CI -)1.14, to 0.13), respectively). However, the results of trial sequential analysis showed the evidence needed more researches to support. The effect of nebulized HS on non-CF bronchiectasis, chronic obstructive pulmonary disease, and primary ciliary dyskinesia also need more evidence to conclude, since current studies are limited and results are inconsistent. Most adverse events of nebulized HS were mild and transient. In summary, the current available evidence suggests that nebulized HS may increase the QOL in CF, but there was no significant improvement in lung function. However, it is not possible to draw firm conclusions for other MOLDs due to limited data.Claude Desplan is Silver Professor in the Department of Biology and Director of the Center for Developmental Genetics at New York University. A biochemist by training, Claude began working on Drosophila embryogenesis in the 1980s, and his work now focuses on how neural diversity is established during the development of the Drosophila visual system. In 2020, Claude was awarded the Society for Developmental Biology's Edwin G. Conklin Medal, which recognises both his outstanding contribution to developmental biology research and his excellence in mentorship. We recently met with Claude (via Zoom) to find out more about his career and his research.
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