Category: Nevin Manimala

Indian J Pathol Microbiol. 2024 Feb 19. doi: 10.4103/ijpm.ijpm_582_23. Online ahead of print.

ABSTRACT

BACKGROUND: Coronavirus disease 2019 (COVID-19) emerged as a global pandemic, threatening millions of lives worldwide. Everyone was overwhelmed by the plethora of information from different sources, creating confusion, misconceptions, and panic in the community.

AIMS: This study aimed to estimate the knowledge, attitudes, and practices (KAP) among medical and dental students toward COVID-19 and to identify factors influencing them.

MATERIALS AND METHODS: A cross-sectional study was conducted among undergraduate students enrolled in MBBS and BDS courses, and KAP scores were calculated using a self-administered questionnaire. The statistical analysis was done by unpaired t test and one-way analysis of variance.

RESULTS: MBBS students had higher KAP scores when compared with BDS students. Knowledge gaps were discovered in the areas of COVID-19 transmission through blood, World Health Organization (WHO)-designated variants of concern, disinfectant usage, and mandatory vaccination. A majority (91.33%) of the students had a positive attitude toward COVID-19. Better knowledge and practice scores were significantly associated with vaccinated students and those who trusted government website resources.

CONCLUSION: Curriculum modifications and creative teaching strategies can fill the lacunae in the KAP scores. Medical and dental students, as torchbearers of the healthcare fraternity, can play a critical role in raising awareness during public health emergencies.

PMID:38427767 | DOI:10.4103/ijpm.ijpm_582_23

Indian J Pathol Microbiol. 2024 Feb 19. doi: 10.4103/ijpm.ijpm_361_23. Online ahead of print.

ABSTRACT

BACKGROUND: Prostate cancer is a common cancer in males, frequently leading to mortality. Multiple genetic factors play roles in prostate cancer pathogenesis. Demonstration of pathological pathways and customised treatment options have been possible with next-generation sequencing.

AIM: In this study, we aimed to evaluate the relationships of the changes in the prostate cancer pathways genes with the pathological, immunohistochemical and the clinical parameters.

STUDY DESIGN: Retrospective cross-sectional study. Materials and Methods: Among the prostate needle biopsy materials investigated in Adnan Menderes University Faculty of Medicine, Department of Pathology, thirty-one cases, who had been analysed using the next-generation sequencing system, were included in this study.

RESULTS: As a result of statistical analysis, a significant relationship was found between the pathogenic mutation detected in androgen receptor and Breast Cancer Gene 2 genes and tumour volume. In all cases with a pathogenic mutation in the androgen receptor gene, a pathogenic mutation in the Protein Tyrosine Phosphatase and Tensin Homolog gene was also observed and a significant relationship was found between them. Castration resistance was observed in cases with high tumour volume, and a statistically significant difference was found. A statistically significant relationship was found between tumour volume and Ki-67 expression. In addition, a significant relationship was observed between the castration resistance and Ki-67, c-erbB2 expressions. A statistically significant relationship was found between Ki-67 and c-erbB2.

CONCLUSION: Regarding prognosis prediction and treatment, identifying the molecular changes in genes playing roles in prostate cancer with next-generation sequencing is very important.

PMID:38427749 | DOI:10.4103/ijpm.ijpm_361_23

Indian J Pathol Microbiol. 2024 Feb 19. doi: 10.4103/ijpm.ijpm_351_23. Online ahead of print.

ABSTRACT

BACKGROUND: The red cell distribution width (RDW) has been recognized as a new prognostic factor in various pathophysiological states including breast cancers. The aim of this study was to compare the RDW values between patients diagnosed with benign and malignant breast tumors and to evaluate the potential of elevated RDW as a biomarker for breast cancer activity.

MATERIALS AND METHODS: A cross-sectional study compared RDW values in age-matched cohorts diagnosed with benign and malignant breast lesions and correlated them with prognostic factors for malignant breast tumors. The study excluded individuals with inflammatory disorders, pre-neoplastic disease, hematological disorders, or those taking immunosuppressive or anti-inflammatory medications. The RDW values were measured using an automated hematology analyzer. The study’s statistical analysis was conducted using SPSS software at a significance level of 0.05.

RESULTS: RDW demonstrated a statistically significant elevation in the cohort of patients with malignant breast tumors, those with metastatic breast tumors, a greater number of infiltrated axillary lymph nodes, larger tumor diameter, and a higher grade of the primary tumor mass.

CONCLUSIONS: The findings of this study suggest that RDW has the potential to serve as a biomarker for assessing breast cancer activity and could offer substantial advantages in clinical contexts. The present study is not without limitations, and the authors suggest that a larger multicenter prospective study be conducted to further validate it’s efficacy over an extended duration.

PMID:38427746 | DOI:10.4103/ijpm.ijpm_351_23

Sci Adv. 2024 Mar;10(9):eadg2636. doi: 10.1126/sciadv.adg2636. Epub 2024 Mar 1.

ABSTRACT

Human genome-wide association studies (GWAS) suggest a functional role for central glutamate receptor signaling and plasticity in body weight regulation. Here, we use UK Biobank GWAS summary statistics of body mass index (BMI) and body fat percentage (BF%) to identify genes encoding proteins known to interact with postsynaptic α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) and N-methyl-d-aspartate (NMDA) receptors. Loci in/near discs large homolog 4 (DLG4) and protein interacting with C kinase 1 (PICK1) reached genome-wide significance (P < 5 × 10^–8) for BF% and/or BMI. To further evaluate the functional role of postsynaptic density protein-95 (PSD-95; gene name: DLG4) and PICK1 in energy homeostasis, we used dimeric PSD-95/disc large/ZO-1 (PDZ) domain-targeting peptides of PSD-95 and PICK1 to demonstrate that pharmacological inhibition of PSD-95 and PICK1 induces prolonged weight-lowering effects in obese mice. Collectively, these data demonstrate that the glutamate receptor scaffolding proteins, PICK1 and PSD-95, are genetically linked to obesity and that pharmacological targeting of their PDZ domains represents a promising therapeutic avenue for sustained weight loss.

PMID:38427737 | DOI:10.1126/sciadv.adg2636

J Phys Chem A. 2024 Mar 1. doi: 10.1021/acs.jpca.3c07732. Online ahead of print.

ABSTRACT

The Δδ regression approach of Blade et al. [ J. Phys. Chem. A 2020, 124(43), 8959-8977] for accurately discriminating between solid forms using a combination of experimental solution- and solid-state NMR data with density functional theory (DFT) calculation is here extended to molecules with multiple conformational degrees of freedom, using furosemide polymorphs as an exemplar. As before, the differences in measured ¹H and ¹³C chemical shifts between solution-state NMR and solid-state magic-angle spinning (MAS) NMR (Δδ_experimental) are compared to those determined by gauge-including projector augmented wave (GIPAW) calculations (Δδ_calculated) by regression analysis and a t-test, allowing the correct furosemide polymorph to be precisely identified. Monte Carlo random sampling is used to calculate solution-state NMR chemical shifts, reducing computation times by avoiding the need to systematically sample the multidimensional conformational landscape that furosemide occupies in solution. The solvent conditions should be chosen to match the molecule’s charge state between the solution and solid states. The Δδ regression approach indicates whether or not correlations between Δδ_experimental and Δδ_calculated are statistically significant; the approach is differently sensitive to the popular root mean squared error (RMSE) method, being shown to exhibit a much greater dynamic range. An alternative method for estimating solution-state NMR chemical shifts by approximating the measured solution-state dynamic 3D behavior with an ensemble of 54 furosemide crystal structures (polymorphs and cocrystals) from the Cambridge Structural Database (CSD) was also successful in this case, suggesting new avenues for this method that may overcome its current dependency on the prior determination of solution dynamic 3D structures.

PMID:38427685 | DOI:10.1021/acs.jpca.3c07732

PLoS One. 2024 Mar 1;19(3):e0290132. doi: 10.1371/journal.pone.0290132. eCollection 2024.

ABSTRACT

BACKGROUND: Bone mineral density is an important indicator of osteoporosis, and its variation with volatile organic compounds exposure has rarely been studied. However, the relationship between chloroform (an essential volatile organic compounds component) and bone mineral density remains unclear. Consequently, we aimed to explore the relationship between chloroform alone and bone mineral density or bone mineral content.

METHODS: Herein, 2,553 individuals aged 18 and above from the National Health and Nutrition Examination Surveys (NHANES) in 2009-2010, 2013-2014, and 2017-2020, were included. We employed two independent t-tests and multi-linear regression models to statistically assess the relationship between chloroform exposure and BMD/BMC in the spine and femoral area.

RESULTS: A “V”-shaped correlation between chloroform exposure and bone mineral density or bone mineral content (BMD/BMC) was observed in the unadjusted model, particularly in the Ward’s triangle and femoral neck as a whole. A negative correlation was specifically observed for the Ward’s triangle BMD/BMC and L4 BMD/BMC. On the other hand, in the adjusted model, a dominantly negative correlation between the L4 BMC and chloroform exposure was observed over a range of exposure levels. The subgroup analysis revealed a negative correlation between chloroform concentrations and BMC in the femur and spine, especially in women and the 65-80 age population.

CONCLUSION: Our study revealed a “V” shaped correlation between chloroform and BMD/BMC of the femur and spine in U.S. adults. This finding highlights the fact that prolonged exposure to chloroform may cause the changes in BMD/BMC.

PMID:38427675 | DOI:10.1371/journal.pone.0290132

Stem Cell Rev Rep. 2024 Mar 1. doi: 10.1007/s12015-024-10705-7. Online ahead of print.

ABSTRACT

BACKGROUND: The Coronavirus disease-2019 (COVID-19) pandemic continues, and the death toll continues to surge. This meta-analysis aimed to determine the efficacy of mesenchymal stem cells (MSCs) on mortality in patients with COVID-19.

METHODS: A systematic search was made of PubMed, Embase, Cochrane Library, and clinicaltrials.gov, without language restrictions. Randomized controlled trials (RCTs) on treatment of COVID-19 with MSCs, compared with placebo or blank, were reviewed. Studies were pooled to risk ratios (RRs), with 95% confidence intervals (CIs).

RESULTS: Seventeen RCTs (enrolling 1019 participants) met the inclusion criteria. MSCs showed significant effect on 28-day mortality (RR 0.76, 95% CI 0.62 to 0.93; P = 0.008). There was no statistically significant difference in 60-day mortality (RR 0.87, 95% CI 0.70 to 1.09; P = 0.22), and 90-day mortality (RR 0.91, 95% CI 0.72 to 1.15; P = 0.44) between the two groups.

CONCLUSIONS: MSCs significantly reduced 28-day mortality in patients with COVID-19. The long-term effect of MSCs on mortality require further study.

PMID:38427315 | DOI:10.1007/s12015-024-10705-7

J Nephrol. 2024 Mar 1. doi: 10.1007/s40620-023-01874-8. Online ahead of print.

ABSTRACT

BACKGROUND: IgA nephropathy (IgAN) is a common primary glomerular disease. The O-glycosylation status of IgA1 plays a crucial role in disease pathophysiology. The level of poorly-O-galactosylated IgA1, or galactose-deficient IgA1 (Gd-IgA1), has also been identified as a potential biomarker in IgAN. We sought to examine the value of serum Gd-IgA1 as a biomarker in IgAN, by investigating its association with clinical, laboratory, and histopathological features of IgAN.

METHODS: The review followed Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) recommendations and was registered in PROSPERO (CRD42021287423). The literature search was conducted in PubMed, Web of Science, Cochrane, and Scopus, and the selected articles were evaluated for eligibility based on predefined criteria. The methodological quality of the studies was assessed using the Newcastle-Ottawa Scale. Statistical analysis was performed to calculate effect sizes and assess heterogeneity among the studies.

RESULTS: This review analyzed 29 out of 1,986 studies, conducted between 2005 and 2022, with participants from multiple countries. Gd-IgA1 levels were not associated with age and gender, while associations with hypertension, hematuria, and proteinuria were inconsistent. In the meta-analyses, a correlation between serum Gd-IgA1 and estimated glomerular filtration rate was identified, however, the relationships between Gd-IgA1 levels and chronic kidney disease (CKD) stage and progression to kidney failure were inconsistent.

CONCLUSIONS: Serum Gd-IgA1 levels were not associated with validated prognostic risk factors, but were negatively correlated with kidney function. Further research in larger studies using standardized assays are needed to establish the value of Gd-IgA1 as a prognostic risk factor in IgAN.

PMID:38427309 | DOI:10.1007/s40620-023-01874-8

J Nephrol. 2024 Mar 1. doi: 10.1007/s40620-023-01856-w. Online ahead of print.

ABSTRACT

INTRODUCTION: Interstitial fibrosis and tubular atrophy are leading causes of renal allograft failure. Shear wave elastography could be a promising noninvasive method for providing information on the state of the kidney, with specific regard to fibrosis but currently available data in the literature are controversial. Our study aimed to analyze the correlation between shear wave elastography and various kidney dysfunction measures.

METHODS: This review was registered on PROSPERO (CRD42021283152). We systematically searched three major databases (MEDLINE, Embase, and CENTRAL) for articles concerning renal transplant recipients, shear wave elastography, fibrosis, and kidney dysfunction. Meta-analytical calculations for pooled Pearson and Spearman correlation coefficients (r) were interpreted with 95% confidence intervals (CIs). Heterogeneity was tested with Cochran’s Q test. I² statistic and 95% CI were reported as a measurement of between-study heterogeneity. Study quality was assessed with the QUADAS2 tool.

RESULTS: In total, 16 studies were included in our meta-analysis. Results showed a moderate correlation between kidney stiffness and interstitial fibrosis and tubular atrophy, graded according to BANFF classification, on biopsy findings for pooled Pearson (r = 0.48; CI: 0.20, 0.69; I² = 84%) and Spearman correlations (r = 0.57; CI: 0.35, 0.72; I² = 74%). When compared to kidney dysfunction parameters, we found a moderate correlation between shear wave elastography and resistive index (r = 0.34 CI: 0.13, 0.51; I² = 67%) and between shear wave elastography and estimated Glomerular Filtration Rate (eGFR) (r = -0.65; CI: – 0.81, – 0.40; I² = 73%). All our outcomes had marked heterogeneity.

CONCLUSION: Our results showed a moderate correlation between kidney stiffness measured by shear wave elastography and biopsy results. While noninvasive assessment of kidney fibrosis after transplantation is an important clinical goal, there is insufficient evidence to support the use of elastography over the performance of a kidney biopsy.

PMID:38427308 | DOI:10.1007/s40620-023-01856-w

Qual Life Res. 2024 Mar 1. doi: 10.1007/s11136-024-03605-3. Online ahead of print.

ABSTRACT

PURPOSE: Statistical power for response shift detection with structural equation modeling (SEM) is currently underreported. The present paper addresses this issue by providing worked-out examples and syntaxes of power calculations relevant for the statistical tests associated with the SEM approach for response shift detection.

METHODS: Power calculations and related sample-size requirements are illustrated for two modelling goals: (1) to detect misspecification in the measurement model, and (2) to detect response shift. Power analyses for hypotheses regarding (exact) overall model fit and the presence of response shift are demonstrated in a step-by-step manner. The freely available and user-friendly R-package lavaan and shiny-app ‘power4SEM’ are used for the calculations.

RESULTS: Using the SF-36 as an example, we illustrate the specification of null-hypothesis (H₀) and alternative hypothesis (H₁) models to calculate chi-square based power for the test on overall model fit, the omnibus test on response shift, and the specific test on response shift. For example, we show that a sample size of 506 is needed to reject an incorrectly specified measurement model, when the actual model has two-medium sized cross loadings. We also illustrate power calculation based on the RMSEA index for approximate fit, where H₀ and H₁ are defined in terms of RMSEA-values.

CONCLUSION: By providing accessible resources to perform power analyses and emphasizing the different power analyses associated with different modeling goals, we hope to facilitate the uptake of power analyses for response shift detection with SEM and thereby enhance the stringency of response shift research.

PMID:38427288 | DOI:10.1007/s11136-024-03605-3