Nevin Manimala

Am J Physiol Heart Circ Physiol. 2022 Dec 23. doi: 10.1152/ajpheart.00483.2022. Online ahead of print.

ABSTRACT

The use of digital image analysis and count regression models contributes to the reproducibility and rigor of histological studies in cardiovascular research. The use of formalized computer-based quantification strategies of histological images essentially removes potential researcher bias, allows for higher analysis throughput, and enables easy sharing of formalized quantification tools, contributing to research transparency and data transferability. Moreover, the use of count regression models rather than ratios in statistical analysis of cell population data incorporates the extent of sampling into analysis and acknowledges the non-gaussian nature of count distributions. Using quantification of proliferating cardiomyocytes in embryonic murine hearts as an example, we describe how these improvements can be implemented using open-source artificial intelligence-based image analysis tools and novel count regression models to efficiently analyze real-life data.

PMID:36563012 | DOI:10.1152/ajpheart.00483.2022

Environ Sci Pollut Res Int. 2022 Dec 23. doi: 10.1007/s11356-022-24803-x. Online ahead of print.

ABSTRACT

To investigate correlations between environmental and meteorological factors and frequency of presentation for coronary heart disease (CHD) in Beijing. Daily measurements of levels of six atmospheric pollutants were made, data relating to meteorological conditions collected, and CHD-related outpatient visits recorded from January 2015 to December 2019 in Beijing. A time-series analysis was made, using a generalized additive model with Poisson distribution, and R 3.6.3 software was used to estimate relationships among levels of atmospheric pollutants, ambient temperature, and visits occasioned by CHD. Results were controlled for time-dependent trend, other weather variables, day of the week, and holiday effects. Lag-response curves were plotted for specific and incremental cumulative effects of relative risk (RR). The aim was to correlate meteorological-environmental factors and the daily number of CHD-related hospital visits and to quantify the degree of correlation to identify any pathological associations. Response diagrams and three-dimensional diagrams of predicted exposure lag effects were constructed in order to evaluate relationships among the parameters of air pollution, temperature, and daily CHD visits. The fitted model was employed to predict the lag RR and 95% confidence interval (95% CI) for specific and incremental cumulative effects of random air pollutants at random concentrations. This model may then be used to predict effects on the outcome variable at any concentration of any defined pollutant, giving flexibility for public health purposes. The overall lag-response RR curves for the specific cumulative effects of the pollutants, particulate matter (PM)2.5, PM10, SO₂, CO, and NO₂, were statistically significant and for PM2.5, PM10, CO, and NO₂, the overall lag-response RR curves for the incremental cumulative effect were statistically significant. When PM2.5, PM10, SO₂, CO, and NO₂ concentrations were above threshold values and the temperature was below 45 °F (reference value 70 °F), the number of CHD-related hospital visits increased with a time lag effect. The outpatient volume of CHD was predicted by the model to guide the flexible distribution of medical resources. Elevated PM2.5, PM10, SO₂, CO, and NO₂ concentrations in the atmosphere combined and low ambient temperature increased the risk of CHD with a time lag effect.

PMID:36562963 | DOI:10.1007/s11356-022-24803-x

Probiotics Antimicrob Proteins. 2022 Dec 23. doi: 10.1007/s12602-022-10024-8. Online ahead of print.

ABSTRACT

Hepcidin antimicrobial peptide (hamp) is active in teleosts against invading pathogens and plays important roles in the stress and immune responses of finfish. The response of hamp gene was studied in yellow perch (yp) (Perca flavescens) challenged with lipopolysaccharides to understand if this immunity response is sex-specifically different. The cloned hamp gene consists of an open-reading frame of 273 bp and encodes a deduced protein of 90 amino acids (a.a.), which includes a signal peptide of 24 a.a., a pro-domain of 40 a.a. and a mature peptide of 26 a.a. Yp hamp involves 8 cysteine residues with 4 disulfide bonds, and a protein with an internal alpha helix flanked with C- and N-terminal random coils was modeling predicted. RT-qPCR was used to analyze the relative abundances (RAs) of hamp mRNA in the livers of juvenile female and male yellow perch challenged with lipopolysaccharide. The expression levels of hamp were significantly elevated by 3 h (RA = 7.3) and then peaked by 6 h (RA = 29.4) post-treatment in females but the peak was delayed to 12 h (RA = 65.4) post-treatment in males. The peak mRNA level of challenged males was shown 7.6-fold higher than females. The post-treatment responses in both genders decreased to their lowest levels by 24 h and 48 h. Overall, female perch had an earlier but less-sensitive response to the lipopolysaccharide challenge than male.

PMID:36562953 | DOI:10.1007/s12602-022-10024-8

Drug Saf. 2022 Dec 23. doi: 10.1007/s40264-022-01266-0. Online ahead of print.

ABSTRACT

INTRODUCTION: Little is known about the role played by anticoagulants in COVID-19.

OBJECTIVE: The aim of this study was to assess the impact of previous anticoagulant treatment on risk of hospitalization due to COVID-19, progression to severe COVID-19 and susceptibility to COVID-19 infection.

METHODS: We conducted a multiple population-based case-control study in northwest Spain, in 2020, to assess (1) risk of hospitalization: cases were all patients admitted due to COVID-19 with PCR confirmation, and controls were a random matched sample of subjects without a positive PCR; (2) progression: cases were hospitalized COVID-19 subjects, and controls were all non-hospitalized COVID-19 patients; and (3) susceptibility: cases were patients with a positive PCR (hospitalized and non-hospitalized), and the controls were the same as for the hospitalization model. Adjusted odds ratios (ORs) and 95% confidence intervals (95% CIs) were calculated using a generalized linear mixed model.

RESULTS: The consumption of antivitamin K and direct-acting anticoagulants apparently was not associated with the risk of progression to severe COVID-19 (OR 0.93 [95% CI 0.74-1.17] and OR 1.04 [95% CI 0.79-1.36], respectively). Antivitamin K anticoagulants were associated with a significantly lower risk of hospitalization (OR 0.77 [95% CI 0.64-0.93]), which, in part, can be explained by a decreased risk of susceptibility to infection (OR 0.83 [95% CI 0.74-0.92]). The use of direct-acting anticoagulants was not associated with the risk of hospitalization, although it also seems to decrease susceptibility (OR 0.85 [95% CI 0.74-0.98]). It has also been observed that low-molecular-weight heparins were associated with an increased risk of progression to severe COVID-19 (OR 1.25 [95% CI 1.01-1.55]).

CONCLUSION: The results of this study have shown that antivitamin K anticoagulants and direct-acting anticoagulants do not increase the risk of progression to more severe stages. Antivitamin K consumption was associated with a lower risk of hospitalization and susceptibility to infection.

PMID:36562942 | DOI:10.1007/s40264-022-01266-0

Mol Cell Biochem. 2022 Dec 23. doi: 10.1007/s11010-022-04624-9. Online ahead of print.

ABSTRACT

Although 2,4-DNP is claimed to promote fast weight reduction, it is also related with an intolerable high risk of serious side effects to various tissues. On the other hand, it is known to have neuroprotective effects. These different effects of 2,4-DNP may be due to the administration conditions. For this reason, in this study, it was aimed for the first time to clarify the oxidative changes that occur in the brain during the use of 2,4-DNP, depending on the dose, time and gender. For this purpose, 60 Wistar rats (30 male, 30 female) were divided into ten groups: control groups, short-term/long-term groups and low dose/high dose groups. Except for the control groups, 2,4-DNP was administered to the other groups by oral gavage. End of the experiment, thiobarbituric acid-reactive substances (TBARs), glutathione (GSH), nitric oxide (NOx) and ascorbic acid (AA) levels were measured in the brain tissues of sacrificed animals. 2,4-DNP administration showed attenuation impact on oxidative stress depending on both dose, time and gender. It can be said that it is more beneficial in terms of neuroprotection, especially in the short-term and male groups. In conclusion, our findings suggest that, depending on the dose, time, and gender, 2,4-DNP may be beneficial in the treatment of neurodegenerative disorders.

PMID:36562917 | DOI:10.1007/s11010-022-04624-9

Can J Public Health. 2022 Dec 23. doi: 10.17269/s41997-022-00728-3. Online ahead of print.

ABSTRACT

OBJECTIVES: Female marriage before age 18 is a global health issue related to gender inequality, but it is understudied in Canada. This study examined marriage trends among mothers aged < 18 versus older mothers and the sociodemographic correlates of marriage among adolescent mothers aged < 18 and older adolescent mothers.

METHODS: Using the Canadian Vital Statistics – Birth Database, marriage prevalence was estimated by maternal age groups (< 18-year, 18-19-year, 20-24-year, and 25-49-year) between 1989-1990 and 2017-2018 (n = 10,399,250). Multivariable logistic regression was then used to examine the sociodemographic characteristics associated with marriage within adolescent maternal age group (< 18-year, 18-19-year, and 20-24-year) among births registered between 2000 and 2018.

RESULTS: From 1989-1990 to 2017-2018, marriage prevalence declined 80.5%, 60.2%, 47.3%, and 16.0% in the < 18-year, 18-19-year, 20-24-year, and 25-49-year groups, respectively. Within the < 18-year, 18-19-year, and 20-24-year adolescent maternal age groups, older maternal age, larger parental age gap, foreign-born parents, rurality, and earlier birth period were associated with higher adjusted odds of marriage. Higher maternal neighbourhood income was associated with marriage among births to mothers aged 18-19 and 20-24 years but not among those to mothers aged < 18 years.

CONCLUSION: Marriage prevalence declined among mothers of all ages, but the shifts away from marriage appear stronger among younger mothers. The sociodemographic correlates of marriage are generally similar among mothers below age 18 and slightly older adolescent mothers.

PMID:36562916 | DOI:10.17269/s41997-022-00728-3

Breast Cancer Res Treat. 2022 Dec 23. doi: 10.1007/s10549-022-06844-5. Online ahead of print.

ABSTRACT

PURPOSE: A 4-weekly schedule of pegylated liposomal doxorubicin (PLD) has been approved for the treatment of metastatic breast cancer (MBC). Phase II trials have suggested interest in a 2-weekly regimen. This study aimed to compare the efficacy and safety of these two schedules.

METHODS: Data from MBC patients treated with PLD between 2011 and 2021 were retrospectively collected. The objective was to demonstrate the noninferiority of the 2-weekly versus the 4-weekly schedule in terms of 6-month progression-free survival (PFS). The prespecified noninferiority margin was calculated as 1.20. A propensity score to receive either schedule was estimated using a gradient boosting algorithm. Survival analyses using Cox regression models weighted by the propensity score were performed to compare the schedules.

RESULTS: Among the 192 patients included, 96 (50%) underwent each schedule. The median number of previous systemic therapies was 4 (IQR, 3 to 6). Anthracyclines were previously given in early breast cancer in 63.9% of patients. The median follow-up was 10.0 months (IQR, 5.0 to 20.1). A comparable distribution of adverse events was observed. The median PFS was 3.2 months (95% CI, 2.9 to 3.9), and the median overall survival was 12.1 months (95% CI, 10.8 to 14.9). The weighted hazard ratio for PFS was 1.12 (90% CI, 0.82 to 1.54), including the noninferiority boundaries.

CONCLUSION: PLD appeared to be a well-tolerated drug in this heavily pretreated MBC population. The efficacy and safety of the 2-weekly schedule did not provide any advantage, suggesting no interest in changing the registered regimen.

PMID:36562910 | DOI:10.1007/s10549-022-06844-5

Radiol Med. 2022 Dec 23. doi: 10.1007/s11547-022-01577-3. Online ahead of print.

ABSTRACT

PURPOSE: The aim of this multicentric study was to assess which imaging method has the best inter-reader agreement for glenoid bone loss quantification in anterior shoulder instability. A further aim was to calculate the inter-method agreement comparing bilateral CT with unilateral CT and MR arthrography (MRA) with CT measurements. Finally, calculations were carried out to find the least time-consuming method.

METHOD: A retrospective evaluation was performed by 9 readers (or pairs of readers) on a consecutive series of 110 patients with MRA and bilateral shoulder CT. Each reader was asked to calculate the glenoid bone loss of all patients using the following methods: best fit circle area on both MRA and CT images, maximum transverse glenoid width on MRA and CT, CT PICO technique, ratio of the maximum glenoid width to height on MRA and CT, and length of flattening of the anterior glenoid curvature on MRA and CT. Using Pearson’s correlation coefficient (PCC), the following agreement values were calculated: the inter-reader for each method, the inter-method for MRA with CT quantifications and the inter-method for CT best-fit circle area and CT PICO. Statistical analysis was carried out to compare the time employed by the readers for each method.

RESULTS: Inter-reader agreement PCC mean values were the following: 0.70 for MRA and 0.77 for CT using best fit circle diameter, 0.68 for MRA and 0.72 for CT using best fit circle area, 0.75 for CT PICO, 0.64 for MRA and 0.62 for CT anterior straight line and 0.49 for MRA and 0.43 for CT using length-to-width ratio. CT-MRA inter-modality PCC mean values were 0.9 for best fit circle diameter, 0.9 for best fit circle area, 0.62 for anterior straight line and 0.94 for length-to-width methods. PCC mean value comparing unilateral CT with PICO CT methods was 0.8. MRA best fit circle area method was significantly faster than the same method performed on CT (p = 0.031), while no significant difference was seen between CT and MRA for remaining measurements.

CONCLUSIONS: CT PICO is the most reliable imaging method, but both CT and MRA can be reliably used to assess glenoid bone loss. Best fit circle area CT and MRA methods are valuable alternative measurement techniques.

PMID:36562906 | DOI:10.1007/s11547-022-01577-3

Lifetime Data Anal. 2022 Dec 23. doi: 10.1007/s10985-022-09585-1. Online ahead of print.

ABSTRACT

For discrete-time survival data, conditional likelihood inference in Cox’s hazard odds model is theoretically desirable but exact calculation is numerical intractable with a moderate to large number of tied events. Unconditional maximum likelihood estimation over both regression coefficients and baseline hazard probabilities can be problematic with a large number of time intervals. We develop new methods and theory using numerically simple estimating functions, along with model-based and model-robust variance estimation, in hazard probability and odds models. For the probability hazard model, we derive as a consistent estimator the Breslow-Peto estimator, previously known as an approximation to the conditional likelihood estimator in the hazard odds model. For the hazard odds model, we propose a weighted Mantel-Haenszel estimator, which satisfies conditional unbiasedness given the numbers of events in addition to the risk sets and covariates, similarly to the conditional likelihood estimator. Our methods are expected to perform satisfactorily in a broad range of settings, with small or large numbers of tied events corresponding to a large or small number of time intervals. The methods are implemented in the R package dSurvival.

PMID:36562895 | DOI:10.1007/s10985-022-09585-1

Dig Dis Sci. 2022 Dec 23. doi: 10.1007/s10620-022-07793-1. Online ahead of print.

ABSTRACT

BACKGROUND: Acute pancreatitis (AP) is a common gastrointestinal disease in which infection is a serious complication. Understanding its bacterial spectrum and antibiotic resistance is of great significance for treatment.

OBJECTIVE: This retrospective study analyzed the Medical Information Mart for Intensive Care database with the aim of identifying the distribution characteristics of pathogenic bacteria in AP patients.

METHODS: First, 2089 AP patients were classified and analyzed statistically according to culture results. Second, the bacterial profile, antibiotic resistance, and antibiotic-use data of positive culture group were analyzed. Third, logistic regression analysis was used to identify the rick factors of culture results, and culture results correlations with mortality.

RESULTS: This study included 1486 patients in negative culture group, 603 patients in positive cultures. Enterococcus spp. (71%), Enterococcus faecium (61%), and Staphylococcus aureus coagulase-positive (54%) exhibited the highest proportions of drug resistance. Logistic regression revealed five factors related to positive culture (the number of antibiotics, length of stay in hospital, length of stay in intensive care unit, mechanical ventilation, and parenteral nutrition) and four factors related to distribution of multidrug-resistant bacterial infection (age, hemoglobin, length of stay in hospital, and duration on antibiotics).

CONCLUSIONS: This study found that enteric bacteria were the most common source of infection (26.7%). Carbapenems, penicillins containing enzyme inhibitors, fifth-generation cephalosporins, oxazolidinones, and some of the aminoglycoside antibiotics had high sensitivity, which can guide the use of clinical empiric antibiotics. Positive culture was an independent risk factor for in-hospital all-cause mortality of AP patients.

PMID:36562889 | DOI:10.1007/s10620-022-07793-1