Nevin Manimala

J Phys Chem B. 2022 Nov 11. doi: 10.1021/acs.jpcb.2c04610. Online ahead of print.

ABSTRACT

By analyzing the Kubo-cluster-cumulant expansion of the potential of mean force of polypeptide chains corresponding to backbone-local interactions averaged over the rotation of the peptide groups about the C^α···C^α virtual bonds, we identified two important kinds of “along-chain” correlations that pertain to extended chain segments bordered by turns (usually the β-strands) and to the folded spring-like segments (usually α-helices), respectively, and are expressed as multitorsional potentials. These terms affect the positioning of structural elements with respect to each other and, consequently, contribute to determining their packing. Additionally, for extended chain segments, the correlation terms contribute to propagating the conformational change at one end to the other end, which is characteristic of allosteric interactions. We confirmed both findings by statistical analysis of the virtual-bond geometry of 77 950 proteins. Augmenting coarse-grained and, possibly, all-atom force fields with these correlation terms could improve their capacity to model protein structure and dynamics.

PMID:36367920 | DOI:10.1021/acs.jpcb.2c04610

PLoS One. 2022 Nov 11;17(11):e0277542. doi: 10.1371/journal.pone.0277542. eCollection 2022.

ABSTRACT

BACKGROUND: Metabolic syndromes (MetS) and diabetes mellitus (DM) comorbidity is a growing major global public health problem with huge morbidity and mortality. It is a pro-inflammatory and prothrombotic disorder characterized by alteration of platelet indices and increased platelet activation, however, the tendency to use them in diagnosis is not yet fully evaluated in our context and there is limited evidence on the role of platelet indices in predicting and differentiating DM+MetS comorbidity in Ethiopia. Thus, this study aimed to evaluate platelet indices in HC, DM, and DM+MetS, and to determine their role in the prediction of DM+MetS comorbidity risk and the distinction between DM+MetS and DM or healthy persons in southwest Ethiopia.

METHOD AND MATERIALS: A comparative cross-sectional study was conducted in Wolkite University specialized hospital from March to August 2021. A total of 336 study participants (112 healthy controls (HC), 112 DM, 112 DM+MetS) was included in this study. Anthropmetric data were measured and the venous blood sample was collected to determine platelet indices, lipid profiles, and blood glucose levels. The SPSS version 21 statistical software was used to perform receiver operating curve (ROC), one-way ANOVA, and independent T-test analysis. The p-value for statistical significance was set at <0.05.

RESULT: In the present study, we found a significant difference in the mean value of PLT, MPV, and PDW between DM+MetS, DM, and HC. A statistically significant difference in the mean value of MPV and PDW was observed between HC and DM+MetS as well as DM and DM+MetS (p-value<0.001). At the cutoff value of 9.65fl with a sensitivity of 81.3% and a specificity of 67.9%, MPV differentiates DM+MetS from HC with an AUC of 0.859. MPV can differentiate DM+MetS from DM at a cutoff value of 10.05fl with sensitivity, specificity, and an AUC of 67.9%, 65.2%, and 0.675, respectively. At the cutoff value of 9.65fl with a sensitivity of 69.6% and a specificity of 67.9%, MPV differentiates DM from HC with an AUC of 0.747. The best platelet parameter identified in this study for predicting the presence of DM+MetS comorbidity was MPV (AUC=0.859; 95%CI=0.81-0.90).

CONCLUSION: In this study, a significant difference in the mean value of PLT, MPV, and PDW was found between DM+MetS, DM, and HC. The mean value of platelet indices showed significant increases in DM+MetS patients in comparison to HC and DM. MPV has been identified as a good potential marker to predict DM+MetS comorbidity and to differentiate DM+MetS comorbidity from the HC or DM. Our results show that MPV could be a good hematological marker to differentiate DM+MetS comorbidity from the HC or DM, and may offer supportive information for early diagnosis, prevention, and control. Thus, the findings of this study should be taken into account for the prevention and control of DM+MetS comorbidity.

PMID:36367899 | DOI:10.1371/journal.pone.0277542

PLoS One. 2022 Nov 11;17(11):e0277456. doi: 10.1371/journal.pone.0277456. eCollection 2022.

ABSTRACT

In 1919, the European bison population became extinct in the wild. The rescue of the lowland subspecies and the whole species was achieved mainly thanks to individuals from the Białowieża Forest (Polish-Belarusian border). There are currently two breeding lines-the lowland (purebred B. b. Bonasus) founded by 7 individuals and the lowland-Caucasian (hybrids of B. b. Bonasus and B. b. caucasicus) founded by 12 individuals. This genealogical study was conducted on 15,071 individuals recorded in the pedigree book between 1881 and 2020. Its objective was to determine the level of genetic variability and inbreeding almost 100 years after the rescue measures were initiated. The completeness of the pedigree of the reference population was 77% in the fifth generation backwards. A maximum of 23 generations can be traced back in the pedigree. The average inbreeding coefficient and the mean average relatedness of the reference population were very high, about 17% and 16% respectively. No significant amount of new inbreeding was discovered. The reference population has lost 9.11% of the total genetic diversity compared to the population of founders. A male of the Caucasian subspecies Kaukasus was discovered among the ancestors of the lowland lineage reference population. The effective population size calculated based on the increase in inbreeding was 23.93 individuals, based on complete generations equivalent it was 16.1 individuals. Wright’s F-statistics showed very small differences in genotypic frequencies between individuals within the two lineages in the reference population (FIS = 0.10), between individuals and the total population (FIT = 0.04) and low differentiation between lineages (FST = 0.06). The population of the European bison from the Białowieża Forest is generally very uniform but still shows good fitness.

PMID:36367897 | DOI:10.1371/journal.pone.0277456

Diabetes Care. 2022 Nov 11:dc212305. doi: 10.2337/dc21-2305. Online ahead of print.

ABSTRACT

OBJECTIVE: There is limited evidence on the association of sustained low-income status, income changes, and all-cause mortality risk in individuals with type 2 diabetes (T2D).

RESEARCH DESIGN AND METHODS: Using the Korean Health Insurance Service database, we studied 1,923,854 adults with T2D (aged ≥30 years) without cardiovascular disease and cancer, who were enrolled from 2009 through 2012 and followed to the end of 2020 (median 10.8 years of follow-up). We defined income levels based on the amount of health insurance premiums and categorized them into quartiles, the first being the low-income group, and assessed the income status annually in the preceding 5 years. Cox proportional hazards models were used to quantify the association of low-income status and income changes with mortality, with adjustment for sociodemographic factors, comorbidities, and diabetes duration and treatment.

RESULTS: Participants who consecutively had low income showed a higher risk of mortality (hazard ratio [HR] 1.19; 95% CI 1.16-1.22), compared with those who had never been in the low-income group. This association was much stronger for consecutive recipients of Medical Aid, reflecting very-low-income status (HR 2.26; 95% CI 2.16-2.36), compared with those who had never been Medical Aid beneficiaries. Sustained low- and very-low-income status was associated with increased risk of mortality, specifically for younger adults (aged<40 years) and males. Those who experienced declines in income between the first (preceding 5 years) and the last (baseline) time points had an increased risk of mortality, regardless of baseline income status.

CONCLUSIONS: Among Korean adults with T2D, sustained low-income status and declines in income were associated with increased risk of mortality.

PMID:36367896 | DOI:10.2337/dc21-2305

PLoS One. 2022 Nov 11;17(11):e0271397. doi: 10.1371/journal.pone.0271397. eCollection 2022.

ABSTRACT

Collaboration across sectors is critical to address complex health problems, particularly during the current COVID-19 pandemic. We examined the ability to collaborate during the pandemic as part of a baseline evaluation of an intersectoral network of healthcare and community organizations established to improve the collective response to transgender (trans) persons who have been sexually assaulted (the trans-LINK Network). A validated social network analysis survey was sent to 119 member organizations in Ontario, Canada. Survey respondents were asked, ‘Has COVID-19 negatively affected your organization’s ability to collaborate with other organizations on the support of trans survivors of sexual assault?’ and ‘How has COVID-19 negatively affected your organization’s ability to collaborate within the trans-LINK Network?’. Data were analyzed using descriptive statistics. Seventy-eight member organizations participated in the survey (response rate = 66%). Most organizations (79%) indicated that the pandemic had affected their ability to collaborate with others in the network, citing most commonly, increased workload (77%), increased demand for services (57%), and technical and digital challenges (50%). Survey findings were shared in a stakeholder consultation with 22 representatives of 21 network member organizations. Stakeholders provided suggestions to prevent and address the challenges, barriers, and disruptions in serving trans survivors experienced during the pandemic, which were organized into themes. Seven themes were generated and used as a scaffold for the development of recommendations to advance the network, including: increase communication and knowledge exchange among member organizations through the establishment of a network discussion forum and capacity building group workshops; enhance awareness of network organizations by developing a member-facing directory of member services, their contributions, and ability to provide specific supports; strengthen capacity to provide virtual and in-person services and programs through enhanced IT support and increased opportunities for knowledge sharing and skill development; and adopt a network wide syndemic approach that addresses co-occurring epidemics (COVID-19 + racism, housing insecurity, transphobia, xenophobia) that impact trans survivors of sexual assault.

PMID:36367864 | DOI:10.1371/journal.pone.0271397

PLoS One. 2022 Nov 11;17(11):e0277359. doi: 10.1371/journal.pone.0277359. eCollection 2022.

ABSTRACT

The use of virtual laboratory simulations in various disciplines, which provide important educational benefits, has increased. Several studies show that laboratory activities, including scenario-based virtual laboratory simulation (SB-VLS), stimulate cognitive and non-cognitive skills. However, the effects of the SB-VLS when integrated into molecular biology courses, on the development of cognitive skills, such as scientific report writing skills, remain unexplored. A pre-post-test, randomized, quasi-experimental design was used. Thirty-five female students were randomly assigned to experimental or control groups. The control group (n = 17) attended a traditional lecture and video lab demonstration (VLD), while the experimental group (n = 18) participated in SB-VLS on molecular cloning. Findings revealed statistically significant differences, with large effects sizes in the SB-VLS group between pre- and post-test in intrinsic motivation (2.9 vs 3.86, p = 0.042, Cohen’s d = 4.17), self-efficacy (3.31 vs 3.85, p = 0.002, Cohen’s d = 1.071), and knowledge gain scales (50.93 vs 75.93, p = 0.001, Cohen’s d = 1.46). Moreover, between-group effect sizes of the experimental and control groups were also large for intrinsic motivation (dppc2 = 1.441), self-efficacy (dppc2 = 0.766), and knowledge (dppc2 = 1.147), indicating that the effect of the SB-VLS was significant, which may be due to the activities and techniques used in SB-VLS to develop learning outcomes. Additionally, the SB-VLS group had statistically better lab report scores as compared to the control group (3.92 vs. 4.72, p < 0.0001). Collectively, our data show that SB-VLS is an innovative teaching strategy and an effective tool for developing non-cognitive and cognitive skills, especially scientific report writing skills.

PMID:36367856 | DOI:10.1371/journal.pone.0277359

PLoS One. 2022 Nov 11;17(11):e0277060. doi: 10.1371/journal.pone.0277060. eCollection 2022.

ABSTRACT

OBJECTIVE: To compare diagnostic values between the 40 keV virtual monoenergetic plus (40 keV VMI+) dual source dual energy computed tomography (DSDECT) pulmonary angiography images and the standard mixed (90 and 150 kV) images for the detection of acute pulmonary embolism (PE).

METHODS: Chest DSDECTs of 64 patients who were suspected of having acute PE were retrospectively reviewed by two independent reviewers. The assessments of acute PE of all patients on a per-location basis were compared between the 40 keV VMI+ and the standard mixed datasets (reference standard) with a two-week interval.

RESULTS: This study consisted of 64 patients (33 women and 31 men; mean age, 60.2 years; range 18-90 years), with a total of 512 locations. The interobserver agreement (Kappa) for detection of acute PE using the 40 keV VMI+ images and the standard mixed CT images were 0.7478 and 0.8750 respectively. The area under receiver operating characteristics (AuROC) for diagnosis of acute PE using the 40 keV VMI+ was 0.882. Four locations (0.78%) revealed a false negative result. Hypodense filling defects were identified in twelve locations (1.95%) in the 40 keV VMI+ images but had been interpreted as a negative study in the standard mixed CT images. The repeated reviews revealed that each location contained a hypodense filling defect but was overlooked on the standard mixed CT images.

CONCLUSIONS: Low-energy VMI + DSDECT images have beneficial in improving the diagnostic value of acute PE in doubtful or disregarded standard mixed images.

PMID:36367855 | DOI:10.1371/journal.pone.0277060

J Bone Joint Surg Am. 2022 Oct 27. doi: 10.2106/JBJS.22.00404. Online ahead of print.

ABSTRACT

BACKGROUND: Irrigation is commonly used as an adjuvant treatment during the intralesional curettage of bone tumors. The goal of the present study was to analyze the in vitro cytotoxicity of commonly used irrigation solutions on chondrosarcoma and giant cell tumor (GCT) cells as there is no consensus on which solution leads to the greatest amount of cell death.

METHODS: An in vitro evaluation was performed by exposing human GCT and human chondrosarcoma cell lines to 0.9% saline solution, sterile water, 70% ethanol, 3% hydrogen peroxide, 0.05% chlorhexidine gluconate (CHG), and 0.3% povidone iodine solutions independently for 2 and 5 minutes. A low-cytotoxicity control (LCC) and a high-cytotoxicity control (HCC) were established to determine the mean cytotoxicity of each solution and each solution’s superiority to LCC and non-inferiority to HCC.

RESULTS: The present study demonstrated that 0.05% CHG was non-inferior to the HCC when chondrosarcoma was exposed for 5 minutes and when GCT was exposed for 2 and 5 minutes (mean cytotoxicity, 99% to 102%) (p < 0.003 for all). Sterile water was superior to the LCC when chondrosarcoma was exposed for 5 minutes and when GCT was exposed for 2 minutes (mean, 28% to 37%) (p < 0.05). Sterile water (mean, 18% to 38%) (p < 0.012) and 3% hydrogen peroxide (mean, 7% to 16%) (p < 0.001) were both inferior to the HCC. The 3 other solutions were non-superior to the LCC (mean, -24% to -5%) (p < 0.023).

CONCLUSIONS: In vitro irrigation in 0.05% CHG provided high cytotoxicity, comparable with the HCC. Therefore, the use of a 0.05% CHG solution clinically could serve as a potential chemical adjuvant during intralesional curettage of chondrosarcoma and GCT.

CLINICAL RELEVANCE: In an effort to reduce the burden of residual tumor cells, irrigation solutions are often utilized as adjuvant local therapy. Use of a 0.05% CHG solution clinically could serve as a potential chemical adjuvant to intralesional curettage of chondrosarcoma and GCT. Further in vivo studies may be indicated to assess clinical outcomes and safety associated with the use of 0.05% CHG in the treatment of chondrosarcoma and GCT.

PMID:36367764 | DOI:10.2106/JBJS.22.00404

JAMA Health Forum. 2022 Nov 4;3(11):e224039. doi: 10.1001/jamahealthforum.2022.4039.

ABSTRACT

IMPORTANCE: The 2021 expanded Child Tax Credit provided advance monthly payments to many US families with children from July through December 2021 and was associated with a reduction in food insufficiency. Less is known about the effect of the discontinuation of monthly payments.

OBJECTIVE: To assess whether the discontinuation of monthly Child Tax Credit payments was associated with subsequent changes in food insufficiency among lower-income US households with children.

DESIGN, SETTING, AND PARTICIPANTS: This population-based cross-sectional study used data from the Household Pulse Survey, a recurring online survey of US households conducted by the US Census Bureau, from January 2021 to March 2022. This study estimated difference-in-differences regression models for households making less than $50 000, less than $35 000, and less than $25 000 annually, adjusting for demographic characteristics and state of residence. The estimation sample of households making less than $50 000/y included 114 705 responses, representing a weighted population size of 27 342 296 households.

EXPOSURES: Receipt of monthly Child Tax Credit payments, as measured by living in a household with children during the period of monthly payments from July through December 2021.

MAIN OUTCOMES AND MEASURES: Household food insufficiency, as measured by a respondent indicating that there was sometimes or often not enough food to eat in the household in the previous 7 days.

RESULTS: Among 114 705 households making less than $50 000/y, respondents were predominantly female (57%); White (71%); not of Hispanic, Latino, or Spanish origin (79%); had high school or equivalent education (38%); and were unmarried (70%). Following the discontinuation of monthly Child Tax Credit payments, food insufficiency in US households with children increased by 3.5 percentage points (95% CI, 1.4-5.7 percentage points) among households making less than $50 000/y, 4.9 percentage points (95% CI, 2.6-7.3 percentage points) among households making less than $35 000/y, and 6.2 percentage points (95% CI, 3.3-9.3 percentage points) among households making less than $25 000/y. These estimates represent a relative increase in food insufficiency of approximately 16.7% among households making less than $50 000/y, 20.8% among households making less than $35 000/y, and 23.2% among households making less than $25 000/y.

CONCLUSIONS AND RELEVANCE: In this population-based cross-sectional study, discontinuation of monthly Child Tax Credit payments in December 2021 was associated with a statistically significant increase in household food insufficiency among lower-income households, with the greatest increase occurring in the lowest-income households.

PMID:36367738 | DOI:10.1001/jamahealthforum.2022.4039

JAMA Netw Open. 2022 Nov 1;5(11):e2241505. doi: 10.1001/jamanetworkopen.2022.41505.

ABSTRACT

IMPORTANCE: Metformin is often used as a first-line therapy for type 2 diabetes; however, frequent discontinuation with reduced kidney function and increased disease severity indicates that a comparison with any other group (eg, nonusers or insulin users) must address significant residual confounding concerns.

OBJECTIVES: To examine the potential for residual confounding in a commonly used observational study design applied to metformin and to propose a more robust study design for future observational studies of metformin.

DESIGN, SETTING, AND PARTICIPANTS: This retrospective cohort study with a prevalent user design was conducted using an administrative claims database for Medicare Advantage beneficiaries in the US. Participants were categorized into 2 distinct cohorts: 404 458 individuals with type 2 diabetes and 81 791 individuals with prediabetes. Clinical history was observed in 2018, and end points were observed in 2019. Statistical analyses were conducted between May and December 2021.

EXPOSURES: Prevalent use (recent prescription and history of use on at least 90 of the preceding 365 days) of metformin or insulin but not both at the start of the observation period.

MAIN OUTCOMES AND MEASURES: Total inpatient admission days in 2019 and total medical spending (excluding prescription drugs) in 2019. Each of these measures was treated as a binary outcome (0 vs >0 inpatient days and top 10% vs bottom 90% of medical spending).

RESULTS: The study included 404 458 adults with type 2 diabetes (mean [SD] age, 74.5 [7.5] years; 52.7% female). A strong metformin effect estimate was associated with reduced inpatient admissions (odds ratio, 0.60; 95% CI, 0.58-0.62) and reduced medical expenditures (odds ratio, 0.57; 95% CI, 0.55-0.60). However, implementation of additional robust design features (negative control outcomes and a complementary cohort) revealed that the estimated beneficial effect was attributable to residual confounding associated with individuals’ overall health, not metformin itself.

CONCLUSIONS AND RELEVANCE: These findings suggest that common observational study designs for studies of metformin in a type 2 diabetes population are at risk for consequential residual confounding. By performing 2 additional validation checks, the study design proposed here exposes residual confounding that nullifies the initially favorable claim derived from a common study design.

PMID:36367726 | DOI:10.1001/jamanetworkopen.2022.41505