Chronic adiponectin deficiency leads to Alzheimer’s disease-like cognitive impairments and pathologies through AMPK inactivation and cerebral insulin resistance in aged mice

(a) Immunoblotting analysis of IRβ in the hippocampus and frontal cortex of 18-month old wildtype and APN-KO mice. (b) Densitometric analysis of the ratio of IRβ. Mean ± S.E.M.; ***p < 0.001, n.s. statistically not significant; Scale bar: 100 μm. (JPG 30 kb

Effects of Phosphodiesterase-5 Inhibitors in Patients with Chronic Obstructive Pulmonary Disease: A Systematic Review and Meta-Analysis

Chronic obstructive pulmonary disease (COPD) is a major burden of healthcare worldwide. We aimed to determine the effects of PDE-5 inhibitors on clinical outcomes and haemodynamic parameters in patients with COPD. A PROSPERO-registered systematic review and meta-analysis (identification number CRD42021227578) were performed to analyse the effects of PDE-5 inhibitors in patients with COPD. Data were sourced from MEDLINE, EMBASE, Cochrane Register of Controlled Trials and "ClinicalTrials.gov." Randomised controlled trials (RCTs) comparing PDE-5 inhibitors with control in patients with COPD were included. Quality assessment was carried out using the Cochrane Collaboration's tool for assessing the risk of bias in randomised trials. The pooled mean difference of 6-minute walk distance (6MWD) and mean pulmonary arterial pressure based on inverse variance estimation were analysed with a fixed-effect model or random-effects model meta-analysis. Nine RCTs involving 414 patients were included in the review. There was no significant difference in 6MWD (mean difference = 22.06 metres, 95% confidence interval (CI), -5.80 to 49.91). However, there was a statistically significant difference between PDE-5 inhibitor and control groups in mean pulmonary artery pressure (mean difference = -3.83 mmHg, 95% CI, -5.93 to -1.74). Headaches were the most common adverse event, occurring significantly in the PDE-5 inhibitor intervention group (odds ratio 3.83, 95% CI, 1.49 to 9.86). This systematic review indicates that PDE-5 inhibitors do not improve exercise capacity despite some possible improvements in haemodynamic parameters in COPD patients

Risk of self-harm and the use of leukotriene receptor antagonists and inhaled corticosteroids:a population-based study

Background Whether leukotriene receptor antagonists (LTRAs) or inhaled corticosteroids (ICS) use can increase the risk of self-harm remains unclear. Objective To evaluate the association between self-harm and use of LTRA and ICS among patients with asthma. Methods This self-controlled case series (SCCS) study used data from the UK Clinical Practice Research Datalink linked to hospital and mortality records. We included patients with asthma aged ≥10 years who had at least one prescription of LTRA, one prescription of ICS, and an incident self-harm during 2005-2020. Incidence rate ratios (IRRs) of self-harm during periods of (presented in order of precedence if they overlapped): pre-LTRA, pre-ICS, LTRA-alone, ICS-alone, and combination use of LTRA and ICS, versus non-use, were calculated using conditional Poisson regression model. Additional analyses using SCCS extension, case-case-time-control, and cohort study designs were used to examine robustness of results. Results Among 313,943 individuals prescribed LTRA and ICS, 2,900 had incident self-harm. IRRs were 0.77 (95%CI=0.58-1.01) during pre-LTRA, 0.68 (95%CI=0.57-0.82) during LTRA-alone, and 0.70 (95%CI=0.56-0.86) during combination use. Further analysis suggested the self-harm incidence was lower during the first 90 days of LTRA use (IRR=0.74; 95%CI=0.58-0.95), before returning to non-use level (IRR=0.93; 95%CI=0.74-1.17). Comparable incidence to non-use was observed during pre-ICS (IRR=0.99; 95%CI=0.71-1.39) and ICS-alone (IRR=0.88; 95%CI=0.75-1.04). The results were robust across sensitivity analyses and study designs, which did not suggest increased risk of self-harm with LTRA/ICS use. Conclusion Using the SCCS design, which was based on comparisons within a population with both the outcome and exposure of interest, our study does not support an association between self-harm and LTRA or ICS in patients with asthma

Identification of microbial community in the urban environment: The concordance between conventional culture and nanopore 16S rRNA sequencing

IntroductionMicrobes in the built environment have been implicated as a source of infectious diseases. Bacterial culture is the standard method for assessing the risk of exposure to pathogens in urban environments, but this method only accounts for &lt;1% of the diversity of bacteria. Recently, full-length 16S rRNA gene analysis using nanopore sequencing has been applied for microbial evaluations, resulting in a rise in the development of long-read taxonomic tools for species-level classification. Regarding their comparative performance, there is, however, a lack of information.MethodsHere, we aim to analyze the concordance of the microbial community in the urban environment inferred by multiple taxonomic classifiers, including ARGpore2, Emu, Kraken2/Bracken and NanoCLUST, using our 16S-nanopore dataset generated by MegaBLAST, as well as assess their abilities to identify culturable species based on the conventional culture results.ResultsAccording to our results, NanoCLUST was preferred for 16S microbial profiling because it had a high concordance of dominant species and a similar microbial profile to MegaBLAST, whereas Kraken2/Bracken, which had similar clustering results as NanoCLUST, was also desirable. Second, for culturable species identification, Emu with the highest accuracy (81.2%) and F1 score (29%) for the detection of culturable species was suggested.DiscussionIn addition to generating datasets in complex communities for future benchmarking studies, our comprehensive evaluation of the taxonomic classifiers offers recommendations for ongoing microbial community research, particularly for complex communities using nanopore 16S rRNA sequencing

Phenomic analysis of chronic granulomatous disease reveals more severe integumentary infections in X-Linked compared with autosomal recessive chronic granulomatous disease

BACKGROUND : Chronic granulomatous disease (CGD) is an inborn error of immunity (IEI), characterised by recurrent bacterial and fungal infections. It is inherited either in an Xlinked (XL) or autosomal recessive (AR) mode. Phenome refers to the entire set of phenotypes expressed, and its study allows us to generate new knowledge of the disease. The objective of the study is to reveal the phenomic differences between XL and AR-CGD by using Human Phenotype Ontology (HPO) terms. METHODS : We collected data on 117 patients with genetically diagnosed CGD from Asia and Africa referred to the Asian Primary Immunodeficiency Network (APID network). Only 90 patients with sufficient clinical information were included for phenomic analysis. We used HPO terms to describe all phenotypes manifested in the patients. RESULTS : XL-CGD patients had a lower age of onset, referral, clinical diagnosis, and genetic diagnosis compared with AR-CGD patients. The integument and central nervous system were more frequently affected in XL-CGD patients. Regarding HPO terms, perianal abscess, cutaneous abscess, and elevated hepatic transaminase were correlated with XL-CGD. A higher percentage of XL-CGD patients presented with BCGitis/BCGosis as their first manifestation. Among our CGD patients, lung was the most frequently infected organ, with gastrointestinal system and skin ranking second and third, respectively. Aspergillus species, Mycobacterium bovis, and Mycobacteirum tuberculosis were the most frequent pathogens to be found. CONCLUSION : Phenomic analysis confirmed that XL-CGD patients have more recurrent and aggressive infections compared with AR-CGD patients. Various phenotypic differences listed out can be used as clinical handles to distinguish XL or AR-CGD based on clinical features.The Society for Relief of Disabled Children and Jeffrey Modell Foundation.https://www.frontiersin.org/journals/immunologydm2022Paediatrics and Child Healt

Translation and validation of the Pharmacy Services Questionnaire (PSQ) in a Chinese population

BackgroundThe Pharmacy Services Questionnaire (PSQ) was developed to measure patient satisfaction with pharmaceutical care. However, it has not been translated into Cantonese-Chinese and validated in the Hong Kong population. To develop and validate a Cantonese-Chinese-translated PSQ among native Chinese patients who have used pharmacy services at community pharmacies in Hong Kong.MethodsThe PSQ was developed and translated into Cantonese-Chinese using iterative forward-backwards translation. Subjects were recruited by convenience sampling at three community pharmacies. Internal consistency, construct validity, discriminant validity, known-group comparison and Confirmatory Factor Analysis (CFA) were performed to confirm that the Cantonese-Chinese-translated PSQ is a valid measure of its intended constructs. Qualitative think-aloud interviews were carried out to test for comprehension and content validity. The subjects' views and interpretation of each questionnaire item were also explored to determine the relevance, comprehensiveness, and adequacy of the response options.ResultsA total of 236 adult subjects were recruited to complete the Cantonese-Chinese PSQ and the Chinese 5-Level EuroQol 5-Dimension (EQ-5D-5L HK) questionnaire. Additionally, think-aloud interviews were carried out with 15 subjects. Most subjects were able to understand and interpret the Cantonese-Chinese PSQ with relative ease. The internal consistency of Cantonese-Chinese PSQ was excellent (Cronbach's α > 0.96) for the full-scale, Friendly explanation (FE) subscale and Managing therapy (MT) subscale. CFA confirmed the hypothesised two-factor structure of the Cantonese-Chinese PSQ. Individuals with higher education levels showed statistically significantly higher satisfaction levels in the overall PSQ score and MT scale score compared to those with lower levels of education. Additionally, there was no statistically significant correlation between the Cantonese-Chinese PSQ and EQ-5D-5L HK scores, demonstrating discriminant validity.ConclusionThe Cantonese-Chinese translation of the PSQ is a validated, reliable, and semantically equivalent instrument used to assess satisfaction towards services provided by community pharmacies

Robust estimation of bacterial cell count from optical density

Optical density (OD) is widely used to estimate the density of cells in liquid culture, but cannot be compared between instruments without a standardized calibration protocol and is challenging to relate to actual cell count. We address this with an interlaboratory study comparing three simple, low-cost, and highly accessible OD calibration protocols across 244 laboratories, applied to eight strains of constitutive GFP-expressing E. coli. Based on our results, we recommend calibrating OD to estimated cell count using serial dilution of silica microspheres, which produces highly precise calibration (95.5% of residuals &lt;1.2-fold), is easily assessed for quality control, also assesses instrument effective linear range, and can be combined with fluorescence calibration to obtain units of Molecules of Equivalent Fluorescein (MEFL) per cell, allowing direct comparison and data fusion with flow cytometry measurements: in our study, fluorescence per cell measurements showed only a 1.07-fold mean difference between plate reader and flow cytometry data

Ultralight vector dark matter search using data from the KAGRA O3GK run

Among the various candidates for dark matter (DM), ultralight vector DM can be probed by laser interferometric gravitational wave detectors through the measurement of oscillating length changes in the arm cavities. In this context, KAGRA has a unique feature due to differing compositions of its mirrors, enhancing the signal of vector DM in the length change in the auxiliary channels. Here we present the result of a search for U(1)B−L gauge boson DM using the KAGRA data from auxiliary length channels during the first joint observation run together with GEO600. By applying our search pipeline, which takes into account the stochastic nature of ultralight DM, upper bounds on the coupling strength between the U(1)B−L gauge boson and ordinary matter are obtained for a range of DM masses. While our constraints are less stringent than those derived from previous experiments, this study demonstrates the applicability of our method to the lower-mass vector DM search, which is made difficult in this measurement by the short observation time compared to the auto-correlation time scale of DM