Category: Nevin Manimala

Int J Surg Pathol. 2023 Mar 3:10668969231152242. doi: 10.1177/10668969231152242. Online ahead of print.

ABSTRACT

Transmural fibrosis and stricture formation are key pathogenic processes for Crohn’s disease that underlies clinical refractoriness, resulting in severe morbidity. The mechanisms for fibroplasia in Crohn’s are not fully elucidated. In this study, we identified a cohort of refractory Crohn’s disease with surgically resected bowel specimens including cases with bowel stricture and age-/sex-matched refractory disease without bowel stricture. Via immunohistochemistry, density and distribution of IgG4+ plasma cells in resected cases were analyzed. The histologic severity of fibrosis and association with gross evidence of stricture formation and IgG4+ plasma cells were comprehensively analyzed. Our results showed that density of IgG4+ plasma cells/high-power field (IgG4+ PCs/HPF) was significantly associated with increasing histologic fibrosis score (15 IgG4+ PCs/HPF in specimens with fibrosis score 0 vs 31 IgG4+ PC/HPF in fibrosis score 2 and 3, P = .039). Patients with gross evidence of stricture had significantly higher fibrosis scores compared to those without gross evidence of stricture (P = .044). There was a trend that mean IgG4+ plasma cell count was higher in Crohn’s disease with gross stricture formation (P = .26), although it did not reach statistical significance (likely due to multiple pathogenesis events involved in bowel stricture formation besides IgG4+ plasma cells; such as transmural fibrosis, muscular hypertrophy, transmural ulcer/scar formation, and muscular-neural dysfunction). Our findings indicate IgG4+ plasma cells are associated with increasing histologic fibrosis in Crohn’s. Further research is needed to establish a role for IgG4+ plasma cells in fibroplasia with an eye toward potential medical therapies targeting IgG4+ plasma cells to prevent transmural fibrosis.

PMID:36866568 | DOI:10.1177/10668969231152242

Chem Asian J. 2023 Mar 3:e202300067. doi: 10.1002/asia.202300067. Online ahead of print.

ABSTRACT

Halogen⋯halogen interaction is a highly debated and important topic in crystal engineering and supramolecular chemistry. There are controversies about the nature and geometry of these interactions. F, Cl, Br and I are the four halogens that involve in these interactions. Very often the lighter and the heavier halogens behave differently. The nature of the interactions also depends upon the nature of the atom which is covalently bonded to the halogens. In this review different homo-halogen⋯halogen, hetero-halogen⋯halogen, halogen⋯halide interactions, their natures, and preferred geometries have been discussed. Different motifs of halogen⋯halogen interactions, interchangeability of the halogen⋯halogen interactions with other supramolecular synthons and interchangeability between different halogens and other functional groups also have been discussed. Some of the important applications, in which halogen⋯halogen interactions have been successfully employed, are mentioned.

PMID:36866564 | DOI:10.1002/asia.202300067

Front Biosci (Landmark Ed). 2023 Feb 20;28(2):30. doi: 10.31083/j.fbl2802030.

ABSTRACT

BACKGROUND: Obesity results from a chronic imbalance between energy intake and energy expenditure. Total energy expenditure for all physiological functions combined can be measured approximately by calorimeters. These devices assess energy expenditure frequently (e.g., in 60-second epochs), resulting in massive complex data that are nonlinear functions of time. To reduce the prevalence of obesity, researchers often design targeted therapeutic interventions to increase daily energy expenditure.

METHODS: We analyzed previously collected data on the effects of oral interferon tau supplementation on energy expenditure, as assessed with indirect calorimeters, in an animal model for obesity and type 2 diabetes (Zucker diabetic fatty rats). In our statistical analyses, we compared parametric polynomial mixed effects models and more flexible semiparametric models involving spline regression.

RESULTS: We found no effect of interferon tau dose (0 vs. 4 μg/kg body weight/day) on energy expenditure. The B-spline semiparametric model of untransformed energy expenditure with a quadratic term for time performed best in terms of the Akaike information criterion value.

CONCLUSIONS: To analyze the effects of interventions on energy expenditure assessed with devices that collect data at frequent intervals, we recommend first summarizing the high dimensional data into epochs of 30 to 60 minutes to reduce noise. We also recommend flexible modeling approaches to account for the nonlinear patterns in such high dimensional functional data. We provide freely available R codes in GitHub.

PMID:36866554 | DOI:10.31083/j.fbl2802030

Front Biosci (Landmark Ed). 2023 Feb 22;28(2):31. doi: 10.31083/j.fbl2802031.

ABSTRACT

BACKGROUND: The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is responsible for the COVID-19 pandemic and so it is crucial the right evaluation of viral infection. According to the Centers for Disease Control and Prevention (CDC), the Real-Time Reverse Transcription PCR (RT-PCR) in respiratory samples is the gold standard for confirming the disease. However, it has practical limitations as time-consuming procedures and a high rate of false-negative results. We aim to assess the accuracy of COVID-19 classifiers based on Arificial Intelligence (AI) and statistical classification methods adapted on blood tests and other information routinely collected at the Emergency Departments (EDs).

METHODS: Patients admitted to the ED of Careggi Hospital from April 7th-30th 2020 with pre-specified features of suspected COVID-19 were enrolled. Physicians prospectively dichotomized them as COVID-19 likely/unlikely case, based on clinical features and bedside imaging support. Considering the limits of each method to identify a case of COVID-19, further evaluation was performed after an independent clinical review of 30-day follow-up data. Using this as a gold standard, several classifiers were implemented: Logistic Regression (LR), Quadratic Discriminant Analysis (QDA), Random Forest (RF), Support Vector Machine (SVM), Neural Networks (NN), K-nearest neighbor (K-NN), Naive Bayes (NB).

RESULTS: Most of the classifiers show a ROC >0.80 on both internal and external validation samples but the best results are obtained applying RF, LR and NN. The performance from the external validation sustains the proof of concept to use such mathematical models fast, robust and efficient for a first identification of COVID-19 positive patients. These tools may constitute both a bedside support while waiting for RT-PCR results, and a tool to point to a deeper investigation, by identifying which patients are more likely to develop into positive cases within 7 days.

CONCLUSIONS: Considering the obtained results and with a rapidly changing virus, we believe that data processing automated procedures may provide a valid support to the physicians facing the decision to classify a patient as a COVID-19 case or not.

PMID:36866553 | DOI:10.31083/j.fbl2802031

Front Biosci (Landmark Ed). 2023 Feb 16;28(2):29. doi: 10.31083/j.fbl2802029.

ABSTRACT

BACKGROUND: The Apoptotic protease activating factor 1 (Apaf-1) protein, as one of the factors involved in the activation of the mitochondrial apoptotic pathway, plays an important role in cancer biology. Apaf-1 expression in tumour cells has been shown to be downregulated, with significant implications for tumour progression. Hence, we investigated the expression of Apaf-1 protein in the Polish population of patients with colon adenocarcinoma without any therapy prior to radical surgery. Moreover, we assessed the relation between Apaf-1 protein expression and the clinicopathological factors. The prognostic activity of this protein was analyzed in relation to 5-year survival of patients. In order to show the localization of Apaf-1 protein at the cellular level, the immunogold labelling method was used.

METHODS: The study was conducted using the colon tissue material from patients with histopathologically confirmed colon adenocarcinoma. Immunohistochemical expression of Apaf-1 protein was performed using Apaf-1 antibody at dilution 1:600. The associations between the immunohistochemistry (IHC) expression of Apaf-1 and clinical parameters were analyzed using the Chi2 test and Chi2Yatesa test. Kaplan-Meier analysis and the log-rank test were used to verify the relationship between the intensity of Apaf-1 expression and 5-year survival rate of patients. The results were considered statistically significant when p < 0.05.

RESULTS: Apaf-1 expression was evaluated by immunohistochemical staining in whole tissue sections. Thirty-nine (33.23%) samples had strong Apaf-1 protein expression and 82 (67.77%) samples were characterized by low expression. The high expression of Apaf-1 was clearly correlated with the histological grade of the tumour (p = 0.001), proliferating cell nuclear antigen (PCNA) immunohistochemical expression (p = 0.005), age (p = 0.015), depth of invasion (p < 0.001) and angioinvasion (p < 0.001). The 5-year survival rate was significantly higher in the group of patients with high expression of this protein (log-rank, p < 0.001).

CONCLUSIONS: We can conclude that Apaf-1 expression is positively correlated with reduced survival of colon adenocarcinoma patients.

PMID:36866552 | DOI:10.31083/j.fbl2802029

J Phycol. 2023 Mar 3. doi: 10.1111/jpy.13326. Online ahead of print.

ABSTRACT

Viet Nam has a coastline of 3,200 km with thousands of islands providing diverse habitats for benthic harmful algal species including species of Gambierdiscus. Some of these species produce ciguatera toxins, which may accumulate in large carnivore fish potentially posing major threats to public health. This study reports five species of Gambierdiscus from Vietnamese waters, notably G. australes, G. caribaeus, G. carpenteri, G. pacificus, and G. vietnamensis sp. nov. All species are identified morphologically by LM and SEM, and identifications are supported by molecular analyses of nuclear rDNA (D1-D3 and D8-D10 domains of LSU, SSU, and ITS1-5.8S-ITS2 region) based on cultured material collected during 2010-2021. Statistical analyses of morphometric measurements may be used to differentiate some species if a sufficiently large number of cells are examined. Gambierdiscus vietnamensis sp. nov. is morphologically similar to other strongly reticulated species, such as G. belizeanus and possibly G. pacificus; the latter species is morphologically indistinguishable from G. vietnamensis sp. nov., but they are genetically distinct, and molecular analysis is deemed necessary for proper identification of the new species. This study also revealed that strains denoted G. pacificus from Hainan Island (China) should be included in G. vietnamensis sp. nov.

PMID:36866508 | DOI:10.1111/jpy.13326

Cytometry A. 2023 Mar 3. doi: 10.1002/cyto.a.24728. Online ahead of print.

ABSTRACT

Förster resonance energy transfer (FRET) is a radiationless interaction between a donor and an acceptor whose distance dependence makes it a sensitive tool for studying the oligomerization and the structure of proteins. When FRET is determined by measuring the sensitized emission of the acceptor, a parameter characterizing the ratio of detection efficiencies of an excited acceptor vs. an excited donor is invariably involved in the formalism. For FRET measurements involving fluorescent antibodies or other external labels, this parameter, designated by α, is usually determined by comparing the intensity of a known number of donors and acceptors in two independent samples leading to a large statistical variability if the sample size is small. Here, we present a method that improves precision by applying microbeads with a calibrated number of antibody binding sites and a donor-acceptor mixture in which donors and acceptors are present in a certain, experimentally determined ratio. A formalism is developed for determining α and the superior reproducibility of the proposed method compared to the conventional approach is demonstrated. Since the novel methodology does not require sophisticated calibration samples or special instrumentation, it can be widely applied for the quantification of FRET experiments in biological research.

PMID:36866503 | DOI:10.1002/cyto.a.24728

Gerontologist. 2023 Mar 2:gnad021. doi: 10.1093/geront/gnad021. Online ahead of print.

ABSTRACT

BACKGROUND AND OBJECTIVES: The Veterans RAND 12-Item Health Survey (VR-12) is a generic patient-reported outcome measure of physical and mental health status. An adapted version of the VR-12 was developed for use with older adults living in long-term residential care (LTRC) homes in Canada: VR-12 (LTRC-C). This study aimed to evaluate the psychometric validity of the VR-12 (LTRC-C).

RESEARCH DESIGN AND METHODS: Data for this validation study were collected via in-person interviews for a province-wide survey of adults living in LTRC homes across British Columbia (N = 8,657). Three analyses were conducted to evaluate validity and reliability: 1) confirmatory factor analyses (CFA) were conducted to validate the measurement structure, 2) correlations with measures of depression, social engagement and daily activities were examined to evaluate convergent and discriminant validity and 3) Cronbach’s alpha (r) statistics were obtained to evaluate internal consistency reliability.

RESULTS: A measurement model with two correlated latent factors (representing physical health and mental health), four cross-loadings, and four correlated items resulted in acceptable fit (Root Mean Square Error of Approximation = .07; Comparative Fit Index = .98). Physical and mental health were correlated in expected directions with measures of depression, social engagement, and daily activities, though magnitudes of the correlations were quite small. Internal consistency reliability was acceptable for physical and mental health (r >0.70).

DISCUSSION AND IMPLICATIONS: This study supports the use of the VR-12 (LTRC-C) to measure perceived physical and mental health among older adults living in LTRC homes.

PMID:36866495 | DOI:10.1093/geront/gnad021

Lancet Glob Health. 2023 Mar;11 Suppl 1:S5. doi: 10.1016/S2214-109X(23)00090-6.

ABSTRACT

BACKGROUND: A high prevalence of excess weight in children younger than 5 years suggests the involvement of early-life risk factors. The preconception and pregnancy periods are crucial stages for the implementation of interventions to prevent childhood obesity. Most studies so far have evaluated the effects of early-life factors separately, with only a few investigating the combined effect of parental lifestyle factors. Our objective was to fill the literature gap regarding parental lifestyle factors in the preconception and pregnancy periods and to study their association with the risk of overweight in children after the age of 5 years.

METHODS: We harmonised and interpreted data from four European mother-offspring cohorts (EDEN [comprising 1900 families], Elfe [comprising 18 000 families], Lifeways [comprising 1100 families], and Generation R [comprising 9500 families]). Written informed consent was obtained from parents of all involved children. Lifestyle factor data collected through questionnaires comprised parental smoking, BMI, gestational weight gain, diet, physical activity, and sedentary behaviour. We applied principal component analyses to identify multiple lifestyle patterns in preconception and pregnancy. Their association with child BMI z-score and risk of overweight (including obesity, overweight and obesity, as defined by the International Task Force reference) between the ages of 5 and 12 years were assessed using cohort-specific multivariable linear and logistic regression models (adjusted for confounders including parental age, education level, employment status, geographic origin, parity, and household income).

FINDINGS: Among the various lifestyle patterns identified in all cohorts, the two that better explained variance were high parental smoking plus low maternal diet quality or high maternal sedentary behaviour, and high parental BMI plus low gestational weight gain. Overall, we observed that patterns characterised by high parental BMI, smoking, low-quality diet, or sedentary lifestyle before or during pregnancy were associated with higher BMI z-scores and risk of overweight and obesity in children aged 5-12 years.

INTERPRETATION: Our data contribute to a better understanding of how parental lifestyle factors might be associated with the risk of childhood obesity. These findings are valuable to inform future family-based and multi-behavioural child obesity prevention strategies in early life.

FUNDING: European Union’s Horizon 2020 under the ERA-NET Cofund action (reference 727565) and European Joint Programming Initiative “A Healthy Diet for a Healthy Life” (JPI HDHL, EndObesity).

PMID:36866482 | DOI:10.1016/S2214-109X(23)00090-6

Lancet Glob Health. 2023 Mar;11 Suppl 1:S16. doi: 10.1016/S2214-109X(23)00099-2.

ABSTRACT

BACKGROUND: 70% of children with obesity and overweight live in low-income and middle-income countries. Several interventions have been done to reduce the prevalence of childhood obesity and prevent incident cases. Hence, we did a systematic review and meta-analysis to determine the effectiveness of these interventions in reducing and preventing childhood obesity.

METHODS: We conducted a search for randomised controlled trials and quantitative non-randomised studies published on MEDLINE, Embase, Web of Science, and PsycINFO databases between Jan 1, 2010, and Nov 1, 2022. We included interventional studies on the prevention and control of obesity in children up to age 12 years in low-income and middle-income countries. Quality appraisal was performed using Cochrane’s risk-of-bias tools. We did three-level random-effects meta-analyses and explored the heterogeneity of studies included. We excluded critical risk-of-bias studies from primary analyses. We assessed the certainty of evidence using the Grading of Recommendations Assessment, Development, and Evaluation.

FINDINGS: The search generated 12 104 studies, of which eight studies were included involving 5734 children. Six studies were based on obesity prevention, most of which targeted behavioural changes with a focus on counselling and diet, and a significant reduction in BMI was observed (standardised mean difference 2·04 [95% CI 1·01-3·08]; p<0·001). In contrast, only two studies focused on the control of childhood obesity; the overall effect of the interventions in these studies was not significant (p=0·38). The combined studies of prevention and control had a significant overall effect, with study-specific estimates ranging between 0·23 and 3·10, albeit with a high statistical heterogeneity (I²>75%).

INTERPRETATION: Preventive interventions, such as behavioural change and diet modification, are more effective than control interventions in reducing and preventing childhood obesity.

FUNDING: None.

PMID:36866473 | DOI:10.1016/S2214-109X(23)00099-2