Nevin Manimala

J Infect Dev Ctries. 2023 Feb 28;17(2):260-267. doi: 10.3855/jidc.15493.

ABSTRACT

INTRODUCTION: The present study evaluated the characteristics of the initial dengue outbreaks in the Jaffna peninsula, a region without dengue prior to mid-2009 in dengue-endemic Sri Lanka, a tropical island nation.

METHODOLOGY: This is a cross-sectional study conducted using a total of 765 dengue patients’ clinical data and samples collected from the Teaching Hospital, Jaffna during the initial dengue outbreaks. Clinical, non-specific, and specific virological laboratory characteristics including the platelet count, NS1 antigen, and anti-DENV IgM/IgG were evaluated as correlates of dengue virus (DENV) infection in the two initial outbreaks of 2009/2010 and 2011/2012 in Northern Sri Lanka.

RESULTS: Firstly, affected age and clinical characteristics were significantly different between the outbreaks (p < 0.005). Secondly, NS1 antigen detection in patients with fever days < 5 was statistically significant (p < 0.005). Thirdly, platelet count, detection of NS1 antigen, and anti-DENV IgM/IgG profiles were adequate to diagnose 90% of the patients; hepatomegaly and platelet count of < 25,000/mm3 were identified as predictors of severe disease. Fourthly, secondary DENV infections were detected in the early stages of the illness in many patients. Finally, infecting DENV serotypes were different between the two outbreaks.

CONCLUSIONS: Clinical and non-specific laboratory characteristics and the infecting DENV serotypes between the two initial outbreaks in Northern Sri Lanka were significantly different. NS1 antigen, anti-DENV IgM/IgG, and platelet counts were identified 90% of the dengue patients. Hepatomegaly and platelet count of < 25,000/mm3 were able to predict the disease severity in this study.

PMID:36897909 | DOI:10.3855/jidc.15493

ESC Heart Fail. 2023 Mar 10. doi: 10.1002/ehf2.14284. Online ahead of print.

ABSTRACT

BACKGROUND: Recent heart failure (HF) guidelines have re-classified HF patients with left ventricular ejection fraction (LVEF) between 41% and 49% as HF with mildly reduced ejection fraction (HFmrEF). HFmrEF treatment is often considered a grey zone as no randomized controlled trials (RCTs) were conducted exclusively on these patients.

AIMS: A network meta-analysis (NMA) was performed to compare treatment effect of mineralocorticoid receptor antagonists (MRA), angiotensin receptor neprilysin inhibitor (ARNi), angiotensin receptor blockers (ARB), angiotensin-converting-enzyme inhibitors (ACEi), sodium-glucose cotransporter-2 inhibitors (SGLT2i), and beta-blockers (BB) in HFmrEF cardiovascular (CV) outcomes.

METHODS AND RESULTS: RCTs sub-analyses evaluating the efficacy of pharmacological treatment in HFmrEF patients were searched. Hazard ratios (HRs) and their variance were extracted from each RCT for (i) composite of CV death or HF hospitalizations, (ii) CV death, and (iii) HF hospitalizations. A random-effects NMA was performed to compare and assess the treatment efficiency. Six RCTs with subgroup analysis according to participants’ ejection fraction, a patient-level pooled meta-analysis of two RCTs, and an individual patient-level analysis of eleven BB RCTs were included, totalling 7966 patients. To our primary endpoint, SGLT2i vs. placebo was the only comparison with significant results, with a 19% risk reduction in the composite of CV death or HF hospitalizations [HR 0.81, 95% confidence interval (CI) 0.67-0.98]. In HF hospitalizations, the impact of the pharmacological therapies was more notorious, and ARNi reduced in 40% the risk of HF hospitalizations (HR 0.60, 95% CI 0.39-0.92), SGLT2i in 26% (HR 0.74, 95% CI 0.59-0.93) and renin-angiotensin system inhibition (RASi) with ARB and ACEi in 28% (HR 0.72, 95% CI 0.53-0.98). Although BBs were globally less beneficial, they were the only class that supported a reduced risk of CV death (HR vs. placebo: 0.48, 95% CI 0.24-0.95). We did not observe a statistically significant difference in any comparison between active treatments. There was a sound reduction with ARNi on the primary endpoint (HR vs. BB: 0.81, 95% CI 0.47-1.41; HR vs. MRA 0.94, 95% CI 0.53-1.66) and on HF hospitalizations (HR vs. RASi 0.83, 95% CI 0.62-1.11; HR vs. SGLT2i 0.80, 95% CI 0.50-1.30).

CONCLUSIONS: In addition to SGLT2i, pharmacological treatment recommended for HF with reduced LVEF, namely, ARNi, MRA, and BB, can also be effective in HFmrEF. This NMA did not show significant superiority over any pharmacological class.

PMID:36896801 | DOI:10.1002/ehf2.14284

Psychol Med. 2023 Mar 10:1-9. doi: 10.1017/S0033291723000429. Online ahead of print.

ABSTRACT

BACKGROUND: Patients with remitted psychosis face a dilemma between the wish to discontinue antipsychotics and the risk of relapse. We test if an operationalized guided-dose-reduction algorithm can help reach a lower effective dose without increased risks of relapse.

METHODS: A 2-year open-label randomized prospective comparative cohort trial from Aug 2017 to Sep 2022. Patients with a history of schizophrenia-related psychotic disorders under stable medications and symptoms were eligible, randomized 2:1 into guided dose reduction group (GDR) v. maintenance treatment group (MT1), together with a group of naturalistic maintenance controls (MT2). We observed if the relapse rates would be different between 3 groups, to what extent the dose could be reduced, and if GDR patients could have improved functioning and quality of life.

RESULTS: A total of 96 patients, comprised 51, 24, and 21 patients in GDR, MT1, and MT2 groups, respectively. During follow-up, 14 patients (14.6%) relapsed, including 6, 4, and 4 from GDR, MT1, and MT2, statistically no difference between groups. In total, 74.5% of GDR patients could stay well under a lower dose, including 18 patients (35.3%) conducting 4 consecutive dose-tapering and staying well after reducing 58.5% of their baseline dose. The GDR group exhibited improved clinical outcomes and endorsed better quality of life.

CONCLUSIONS: GDR is a feasible approach as the majority of patients had a chance to taper antipsychotics to certain extents. Still, 25.5% of GDR patients could not successfully decrease any dose, including 11.8% experienced relapse, a risk comparable to their maintenance counterparts.

PMID:36896797 | DOI:10.1017/S0033291723000429

Mol Ecol. 2023 Mar 10. doi: 10.1111/mec.16912. Online ahead of print.

ABSTRACT

Deforestation threatens the integrity of the Amazon biome and the ecosystem services it provides, including greenhouse gas mitigation. Forest-to-pasture conversion has been shown to alter the flux of methane gas (CH₄ ) in Amazonian soils, driving a switch from acting as a sink to a source of atmospheric CH₄ . This study aimed to better understand this phenomenon by investigating soil microbial metagenomes, focusing on the taxonomic and functional structure of methane-cycling communities. Metagenomic data from forest and pasture soils were combined with in situ CH₄ fluxes and soil edaphic factors measurements and analysed using multivariate statistical approaches. We found a significantly higher abundance and diversity of methanogens in pasture soils. As inferred by co-occurrence networks, these microorganisms seem to be less interconnected within the soil microbiota in pasture soils. Metabolic traits were also different between land uses, with increased hydrogenotrophic and methylotrophic pathways of methanogenesis in pasture soils. Land-use change also induced shifts in taxonomic and functional traits of methanotrophs, with bacteria harboring genes encoding the soluble form of methane monooxygenase enzyme (sMMO) depleted in pasture soils. Redundancy analysis and multimodel inference revealed that the shift in methane-cycling communities was associated with high pH, organic matter, soil porosity, and micronutrients in pasture soils. These results comprehensively characterize the effect of forest-to-pasture conversion on the microbial communities driving the methane-cycling microorganisms in the Amazon rainforest, which will contribute to the efforts to preserve this important biome.

PMID:36896778 | DOI:10.1111/mec.16912

Minim Invasive Ther Allied Technol. 2023 Mar 10:1-8. doi: 10.1080/13645706.2023.2186181. Online ahead of print.

ABSTRACT

BACKGROUND: To compare the models obtained with classical statistical methods and machine learning (ML) algorithms to predict postoperative infective complications (PICs) after retrograde intrarenal surgery (RIRS).

MATERIAL AND METHODS: Patients who underwent RIRS between January 2014 and December 2020 were retrospectively screened. Patients who did not develop PICs were classified as Group 1 and patients who developed as Group 2.

RESULTS: Three-hundred and twenty-two patients were included in the study; 279 patients (86.6%) who did not develop PICs were classified as Group 1, and 43 patients (13.3%) who developed PICs were classified as Group 2. In multivariate analysis, the presence of diabetes mellitus, preoperative nephrostomy, and stone density were determined to be factors that significantly predicted the development of PICs. The area under the curve (AUC) of the model obtained by classical Cox regression analysis was 0.785, and the sensitivity and specificity were 74% and 67%, respectively. With the Random Forest, K- Nearest Neighbour, and Logistic Regression methods, the AUC was calculated as 0.956, 0.903, and 0.849, respectively. RF’s sensitivity and specificity were calculated as 87% and 92%, respectively.

CONCLUSION: With ML, more reliable and predictive models can be created than with classical statistical methods.

PMID:36896768 | DOI:10.1080/13645706.2023.2186181

Hum Brain Mapp. 2023 Mar 10. doi: 10.1002/hbm.26257. Online ahead of print.

ABSTRACT

Brain wiring redundancy counteracts aging-related cognitive decline by reserving additional communication channels as a neuroprotective mechanism. Such a mechanism plays a potentially important role in maintaining cognitive function during the early stages of neurodegenerative disorders such as Alzheimer’s disease (AD). AD is characterized by severe cognitive decline and involves a long prodromal stage of mild cognitive impairment (MCI). Since MCI subjects are at high risk of converting to AD, identifying MCI individuals is essential for early intervention. To delineate the redundancy profile during AD progression and enable better MCI diagnosis, we define a metric that reflects redundant disjoint connections between brain regions and extract redundancy features in three high-order brain networks-medial frontal, frontoparietal, and default mode networks-based on dynamic functional connectivity (dFC) captured by resting-state functional magnetic resonance imaging (rs-fMRI). We show that redundancy increases significantly from normal control (NC) to MCI individuals and decreases slightly from MCI to AD individuals. We further demonstrate that statistical features of redundancy are highly discriminative and yield state-of-the-art accuracy of up to 96.8 ± 1.0% in support vector machine (SVM) classification between NC and MCI individuals. This study provides evidence supporting the notion that redundancy serves as a crucial neuroprotective mechanism in MCI.

PMID:36896755 | DOI:10.1002/hbm.26257

Hum Brain Mapp. 2023 Mar 10. doi: 10.1002/hbm.26259. Online ahead of print.

ABSTRACT

Statistical effects of cortical metrics derived from standard T1- and T2-weighted magnetic resonance imaging (MRI) images, such as gray-white matter contrast (GWC), boundary sharpness coefficient (BSC), T1-weighted/T2-weighted ratio (T1w/T2w), and cortical thickness (CT), are often interpreted as representing or being influenced by intracortical myelin content with little empirical evidence to justify these interpretations. We first examined spatial correspondence with more biologically specific microstructural measures, and second compared between-marker age-related trends with the underlying hypothesis that different measures primarily driven by similar changes in myelo- and microstructural underpinnings should be highly related. Cortical MRI markers were derived from MRI images of 127 healthy subjects, aged 18-81, using cortical surfaces that were generated with the CIVET 2.1.0 pipeline. Their gross spatial distributions were compared with gene expression-derived cell-type densities, histology-derived cytoarchitecture, and quantitative R1 maps acquired on a subset of participants. We then compared between-marker age-related trends in their shape, direction, and spatial distribution of the linear age effect. The gross anatomical distributions of cortical MRI markers were, in general, more related to myelin and glial cells than neuronal indicators. Comparing MRI markers, our results revealed generally high overlap in spatial distribution (i.e., group means), but mostly divergent age trajectories in the shape, direction, and spatial distribution of the linear age effect. We conclude that the microstructural properties at the source of spatial distributions of MRI cortical markers can be different from microstructural changes that affect these markers in aging.

PMID:36896711 | DOI:10.1002/hbm.26259

Biometrics. 2023 Mar 10. doi: 10.1111/biom.13853. Online ahead of print.

ABSTRACT

The Dirichlet-multinomial (DM) distribution plays a fundamental role in modern statistical methodology development and application. Recently, the DM distribution and its variants have been used extensively to model multivariate count data generated by high-throughput sequencing technology in omics research due to its ability to accommodate the compositional structure of the data as well as overdispersion. A major limitation of the DM distribution is that it is unable to handle excess zeros typically found in practice which may bias inference. To fill this gap, we propose a novel Bayesian zero-inflated DM model for multivariate compositional count data with excess zeros. We then extend our approach to regression settings and embed sparsity-inducing priors to perform variable selection for high-dimensional covariate spaces. Throughout, modeling decisions are made to boost scalability without sacrificing interpretability or imposing limiting assumptions. Extensive simulations and an application to a human gut microbiome data set are presented to compare the performance of the proposed method to existing approaches. We provide an accompanying R package with a user-friendly vignette to apply our method to other data sets. This article is protected by copyright. All rights reserved.

PMID:36896642 | DOI:10.1111/biom.13853

J Clin Endocrinol Metab. 2023 Mar 10:dgad108. doi: 10.1210/clinem/dgad108. Online ahead of print.

ABSTRACT

CONTEXT: Liver function abnormalities (LFA) have been described in patients with Turner Syndrome (TS). Although a high risk of cirrhosis has been reported, there is a need to assess the severity of liver damage in a large cohort of adult patients with TS.

OBJECTIVE: Evaluate the types of LFA and their respective prevalence, search for their risk factors and evaluate the severity of liver impairment by using a non-invasive fibrosis marker.

DESIGN AND SETTINGS: A monocentric retrospective cross-sectional study.

PATIENTS AND INTERVENTION: Data were collected during a day hospital.

MAIN OUTCOME MEASURES: Liver enzymes (ALT, AST, GGT, ALP), FIB-4 score, liver ultrasound imaging, elastography and liver biopsies, when available.

RESULTS: 264 patients with TS were evaluated at a mean age of 31.15 ± 11.48 years. The overall prevalence of LFA was 42.8%. Its risk factors were age, BMI, insulin resistance and an X isochromosome (Xq). The mean FIB-4 sore of the entire cohort was 0.67 ± 0.41. Less than 10% of patients were at risk of developing fibrosis. Cirrhosis was observed in 2/19 liver biopsies. There was no significant difference in the prevalence of LFA between premenopausal patients with natural cycles and those receiving hormone replacement therapy (HRT) (p = 0.063). A multivariate analysis adjusted for age showed no statistically significant correlation between HRT and abnormal GGT levels (p = 0.12).

CONCLUSION: Patients with TS have a high prevalence of LFA. However, 10% are at high risk of developing fibrosis. The FIB-4 score is useful and should be part of the routine screening strategy. Longitudinal studies and better interactions with hepatologists should improve our knowledge of liver disease in patients with TS.

PMID:36896592 | DOI:10.1210/clinem/dgad108

Ann Med. 2023 Dec;55(1):898-907. doi: 10.1080/07853890.2023.2184859.

ABSTRACT

BACKGROUND: The purpose of this study was to explore the changes in blood cellular and biochemical parameters of rats in a natural environment of low pressure and low oxygen on the plateau.

METHODS: Male Sprague-Dawley rats in two groups were raised in different environments from 4 weeks of age for a period of 24 weeks. They were raised to 28 weeks of age and then transported to the plateau medical laboratory of Qinghai University. Blood cellular and biochemical parameters were measured and the data of the two groups were statistically analyzed.

RESULTS: 1. RBC in the HA group was higher than that in the Control group, but there was no significant difference between the two groups (p > 0.05), Compared with the Control group, HGB, MCV, MCH, MCHC and RDW in the HA group were significantly higher (p < 0.05). 2. Compared with the Control group, WBC, LYMP, EO, LYMP% and EO% in the HA group decreased significantly (p < 0.05), and ANC% increased significantly (p < 0.05). 3. In the platelet index, compared with the Control group, PLT in the HA group was significantly reduced (p < 0.05), PDW, MRV, P-LCR were significantly increased (p < 0.05). 4. In blood biochemical indicators, compared with the Control group, AST, TBIL, IBIL, LDH in the HA group decreased significantly (p < 0.05), CK in the HA group increased significantly (p < 0.05).

CONCLUSIONS: 1. The indexes related to red blood cells, white blood cells, platelets and some biochemical indexes in the blood of rats at high altitude have changed. 2. Under the high altitude environment, the oxygen carrying capacity of SD rats is improved, the resistance to disease may be reduced, the coagulation and hemostasis functions may be affected, and there is a risk of bleeding. The liver function, renal function, heart function and skeletal muscle energy metabolism may be affected. 3. This study can provide an experimental basis for the research on the pathogenesis of high-altitude diseases from the perspective of blood.KEY MESSAGESIn this study, red blood cells, white blood cells, platelets and blood biochemical indicators were included in the real plateau environment to comprehensively analyze the changes of blood cellular and biochemical parameters in rats under the chronic plateau hypobaric hypoxia environment.From the perspective of blood, this study can provide an experimental basis for research on the pathogenesis of high-altitude diseases.Explore the data support of oxygen-carrying capacity, disease resistance and energy metabolism of the body in the natural environment at high altitude.

PMID:36896573 | DOI:10.1080/07853890.2023.2184859