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AnteayerPLOS ONE Medicine&Health

Perceptions of diabetes risk and prevention in Nairobi, Kenya: A qualitative and theory of change development study

by Anthony Muchai Manyara, Elizabeth Mwaniki, Jason M. R. Gill, Cindy M. Gray

Background

Type 2 diabetes is increasing in Kenya, especially in urban settings, and prevention interventions based on local evidence and context are urgently needed. Therefore, this study aimed to explore diabetes risk and co-create a diabetes prevention theory of change in two socioeconomically distinct communities to inform future diabetes prevention interventions.

Methods

In-depth interviews were conducted with middle-aged residents in two communities in Nairobi (one low-income (n = 15), one middle-income (n = 14)), and thematically analysed. The theory of change for diabetes prevention was informed by analysis of the in-depth interviews and the Behaviour Change Wheel framework, and reviewed by a sub-set (n = 13) of interviewees.

Results

The key factors that influenced diabetes preventive practices in both communities included knowledge and skills for diabetes prevention, understanding of the benefits/consequences of (un)healthy lifestyle, social influences (e.g., upbringing, societal perceptions), and environmental contexts (e.g., access to (un)healthy foods and physical activity facilities). The proposed strategies for diabetes prevention included: increasing knowledge and understanding about diabetes risk and preventive measures particularly in the low-income community; supporting lifestyle modification (e.g., upskilling, goal setting, action planning) in both communities; identifying people at high risk of diabetes through screening in both communities; and creating social and physical environments for lifestyle modification (e.g., positive social influences on healthy living, access to healthy foods and physical activity infrastructure) particularly in the low-income community. Residents from both communities agreed that the strategies were broadly feasible for diabetes prevention but proposed the addition of door-to-door campaigns and community theatre for health education. However, residents from the low-income community were concerned about the lack of government prioritisation for implementing population-level interventions, e.g., improving access to healthy foods and physical activity facilities/infrastructure.

Conclusion

Diabetes prevention initiatives in Kenya should involve multicomponent interventions for lifestyle modification including increasing education and upskilling at individual level; promoting social and physical environments that support healthy living at population level; and are particularly needed in low-income communities.

Institutional capacity assessment in the lens of implementation research: Capacity of the local institutions in delivering WASH services at Cox’s Bazar district, Bangladesh

by Mahbubur Rahman, Mahbub-Ul Alam, Sharmin Khan Luies, Sharika Ferdous, Zahidul Mamun, Musarrat Jabeen Rahman, Debashish Biswas, Tazrina Ananya, Asadullah, Abul Kamal, Ritthick Chowdhury, Eheteshamul Russel Khan, Dara Johnston, Martin Worth, Umme Farwa Daisy, Tanvir Ahmed

Background

The influx of Forcibly Displaced Myanmar Nationals (FDMNs) has left the Southwest coastal district of Cox’s Bazar with one of the greatest contemporary humanitarian crises, stressing the existing water, sanitation, and hygiene (WASH) resources and services. This study aimed to assess the existing capacity of local institutions involved in delivering WASH services and identify relevant recommendations for intervention strategies.

Methods

We used a qualitative approach, including interviews and capacity assessment workshops with institutions engaged in WASH service delivery. We conducted five key informant interviews (KII) with sub-district level officials of the Department of Public Health Engineering (DPHE), Directorate General of Health Services (DGHS), Directorate of Primary Education (DPE) and Bangladesh Rural Advancement Committee (BRAC) to have a general idea of WASH service mechanisms. Seven capacity assessment workshops were organized with the relevant district and sub-district level stakeholders from August 2019 to September 2019. These workshops followed three key areas: i) knowledge of policy, organizational strategy, guidelines, and framework; ii) institutional arrangements for service delivery such as planning, implementation, coordination, monitoring, and reporting; and iii) availability and management of human, financial and infrastructural resources. Data were categorized using thematic content analysis.

Results

The majority of stakeholders lacked awareness of national WASH policies. Furthermore, the top-down planning approaches resulted in activities that were not context-specific, and lack of coordination between multiple institutions compromised the optimal WASH service delivery at the local level. Shortage of human resources in delivering sustainable WASH services, inadequate supervision, and inadequate evaluation of activities also required further improvement, as identified by WASH stakeholders.

Conclusion

Research evidence suggests that decision-makers, donors, and development partners should consider learning from the WASH implementers and stakeholders about their existing capacity, gaps, and opportunities before planning for any WASH intervention in any particular area.

Estimating infection prevalence using the positive predictive value of self-administered rapid antigen diagnostic tests: An exploration of SARS-CoV-2 surveillance data in the Netherlands from May 2021 to April 2022

by Koen M.F. Gorgels, Senna C.J.L. van Iersel, Sylvia F.A. Keijser, Christian J.P.A. Hoebe, Jacco Wallinga, Albert J. van Hoek

Measuring the severity of the disease of SARS-CoV-2 is complicated by the lack of valid estimations for the prevalence of infection. Self-administered rapid antigen diagnostic tests (Ag-RDTs) were available in the Netherlands since March 2021, requiring confirmation by reverse-transcription polymerase chain reaction (RT-PCR) for positive results. We explored the possibility of utilizing the positive predictive value (PPV) of Ag-RDTs to estimate SARS-CoV-2 prevalence. We used data from all Public Health service testing facilities between 3 May 2021 and 10 April 2022. The PPV was calculated by dividing the number of positive RT-PCR results by the total number of confirmation tests performed, and used to estimate the prevalence and compared with the number of COVID-19 hospital admissions. In total 3,599,894 cases were included. The overall PPV was 91.8% and 88.8% were symptomatic. During our study period, the estimated prevalence ranged between 2–22% in symptomatic individuals and 2–14% in asymptomatic individuals, with a correlation between the estimated prevalence and hospital admissions two weeks later (r = 0.68 (p

Caffeinated beverages intake and risk of deep vein thrombosis: A Mendelian randomization study

by Tong Lin, Haiyan Mao, Yuhong Jin

This study aimed to explore the potential link between coffee and tea consumption and the risk of deep vein thrombosis (DVT) through Mendelian randomization (MR) analysis. Employing the MR, we identified 33 single nucleotide polymorphisms (SNPs) as instrumental variables (IVs) for coffee intake and 38 SNPs for tea intake. The investigation employed the inverse-variance weighted (IVW) method to evaluate the causal impact of beverage consumption on DVT risk. Additionally, MR-Egger and MR-PRESSO tests were conducted to assess pleiotropy, while Cochran’s Q test gauged heterogeneity. Robustness analysis was performed through a leave-one-out approach. The MR analysis uncovered a significant association between coffee intake and an increased risk of DVT (odds ratio [OR] 1.008, 95% confidence interval [CI] = 1.001–1.015, P = 0.025). Conversely, no substantial causal effect of tea consumption on DVT was observed (OR 1.001, 95% CI = 0.995–1.007, P = 0.735). Importantly, no significant levels of heterogeneity, pleiotropy, or bias were detected in the instrumental variables used. In summary, our findings suggest a modestly heightened risk of DVT associated with coffee intake, while tea consumption did not exhibit a significant impact on DVT risk.

Potential efficacy of caffeine ingestion on balance and mobility in patients with multiple sclerosis: Preliminary evidence from a single-arm pilot clinical trial

by Afsoon Dadvar, Melika Jameie, Mehdi Azizmohammad Looha, Mohammadamin Parsaei, Meysam Zeynali Bujani, Mobina Amanollahi, Mahsa Babaei, Alireza Khosravi, Hamed Amirifard

Objectives

Caffeine’s potential benefits on multiple sclerosis (MS), as well as on the ambulatory performance of non-MS populations, prompted us to evaluate its potential effects on balance, mobility, and health-related quality of life (HR-QoL) of persons with MS (PwMS).

Methods

This single-arm pilot clinical trial consisted of a 2-week placebo run-in and a 12-week caffeine treatment (200 mg/day) stage. The changes in outcome measures during the study period (weeks 0, 2, 4, 8, and 12) were evaluated using the Generalized Estimation Equation (GEE). The outcome measures were the 12-item Multiple Sclerosis Walking Scale (MSWS-12) for self-reported ambulatory disability, Berg Balance Scale (BBS) for static and dynamic balance, Timed Up and Go (TUG) for dynamic balance and functional mobility, Multiple Sclerosis Impact Scale (MSIS-29) for patient’s perspective on MS-related QoL (MS-QoL), and Patients’ Global Impression of Change (PGIC) for subjective assessment of treatment efficacy. GEE was also used to evaluate age and sex effect on the outcome measures over time. (Iranian Registry of Clinical Trials, IRCT2017012332142N1).

Results

Thirty PwMS were included (age: 38.89 ± 9.85, female: 76.7%). Daily caffeine consumption significantly improved the objective measures of balance and functional mobility (BBS; P-value Conclusions

Caffeine may enhance balance, functional mobility, and QoL in PwMS. Being male was associated with a sharper increase in self-reported ambulatory disability over time. The effects of aging on balance get more pronounced over time.

Trial registration

This study was registered with the Iranian Registry of Clinical Trials (Registration number: IRCT2017012332142N1), a Primary Registry in the WHO Registry Network.

Downregulation of the CD151 protects the cardiac function by the crosstalk between the endothelial cells and cardiomyocytes via exosomes

by Luying Jiang, Jingbo Liu, Zhenjia Yang, Jianyu Wang, Wenkai Ke, Kaiyue Zhang, Chunran Zhang, Houjuan Zuo

Background

Heart failure (HF) is the last stage in the progression of various cardiovascular diseases. Although it is documented that CD151 contributes to regulate the myocardial infarction, the function of CD151 on HF and involved mechanisms are still unclear.

Method and results

In the present study, we found that the recombinant adeno-associated virus (rAAV)-mediated endothelial cell-specific knockdown of CD151-transfected mice improved transverse aortic constriction (TAC)-induced cardiac function, attenuated myocardial hypertrophy and fibrosis, and increased coronary perfusion, whereas overexpression of the CD151 protein aggravated cardiac dysfunction and showed the opposite effects. In vitro, the cardiomyocytes hypertrophy induced by PE were significantly improved, while the proliferation and migration of cardiac fibroblasts (CFs) were significantly reduced, when co-cultured with the CD151-silenced endothelial cells (ECs). To further explore the mechanisms, the exosomes from the CD151-silenced ECs were taken by cardiomyocyte (CMs) and CFs, verified the intercellular communication. And the protective effects of CD151-silenced ECs were inhibited when exosome inhibitor (GW4869) was added. Additionally, a quantitative proteomics method was used to identify potential proteins in CD151-silenced EC exosomes. We found that the suppression of CD151 could regulate the PPAR signaling pathway via exosomes.

Conclusion

Our observations suggest that the downregulation of CD151 is an important positive regulator of cardiac function of heart failure, which can regulate exosome-stored proteins to play a role in the cellular interaction on the CMs and CFs. Modulating the exosome levels of ECs by reducing CD151 expression may offer novel therapeutic strategies and targets for HF treatment.

The application of flipped learning to a gross anatomy dissection course

by Eun-Kyung Chung, Heoncheol Yun, Kwang-Il Nam, Young-Suk Cho, Eui-Ryoung Han

We implemented flipped learning for a gross anatomy dissection course and compared its effects on students’ motivation and academic achievement with those of traditional dissection methods. We invited 142 first-year medical students at Chonnam National University Medical School to participate in this study. All participants engaged in traditional dissection methods in the first part of the study and flipped learning in the latter part. Medical students’ motivation to learn anatomy by cadaveric dissection was measured using the ARCS (Attention, Relevance, Confidence, and Satisfaction) model. Thereafter, all students completed a written examination consisting of 96 multiple-choice questions. The students’ mean motivational score regarding attention was significantly higher in association with flipped learning than with traditional learning. However, the students’ mean motivational scores regarding relevance, confidence, and satisfaction were not significantly different between the methods. Additionally, the mean anatomy practice test score was significantly higher in association with flipped learning than with traditional learning. The students’ motivational scores and anatomy practice test scores associated with flipped learning positively correlated with the extent of learning material completion. The students’ responses indicated that flipped learning helped enhance the learning process, improve time management, reduce confusion during practice, and promote independent practice. The application of flipped learning to a cadaveric dissection course increased individual learning motivation, which improved learning activities both in and out of class, as well as academic achievement.

Physical activity and cognitive function in adults born very preterm or with very low birth weight–an individual participant data meta-analysis

by Kristina Anna Djupvik Aakvik, Silje Dahl Benum, Marjaana Tikanmäki, Petteri Hovi, Katri Räikkönen, Sarah L. Harris, Lianne J. Woodward, Brian A. Darlow, Marit S. Indredavik, Stian Lydersen, Paul Jarle Mork, Eero Kajantie, Kari Anne I. Evensen

Objective

Individuals born very preterm ( Study design

Cohorts with data on physical activity and cognitive function in adults born very preterm/very low birth weight and term-born controls were recruited from the Research on European Children and Adults Born Preterm, and the Adults Born Preterm International Collaboration Consortia. A systematic literature search was performed in PubMed and Embase.

Results

Five cohorts with 1644 participants aged 22–28 years (595 very preterm/very low birth weight and 1049 controls) were included. Adults born very preterm/very low birth weight reported 1.11 (95% CI: 0.68 to 1.54) hours less moderate to vigorous physical activity per week than controls, adjusted for cohort, age and sex. The difference between individuals born very preterm/very low birth weight and controls was larger among women than among men. Neither intelligence quotient nor self-reported executive function mediated the association between very preterm/very low birth weight and moderate to vigorous physical activity. Results were essentially the same when we excluded individuals with neurosensory impairments.

Conclusion

Adults born very preterm/very low birth weight, especially women, reported less moderate to vigorous physical activity than their term-born peers. Cognitive function did not mediate this association. Considering the risk of adverse health outcomes among individuals born preterm, physical activity could be a target for intervention.

Developing a PRogram to Educate and Sensitize Caregivers to Reduce the Inappropriate Prescription Burden in the Elderly with Alzheimer’s Disease (D-PRESCRIBE-AD): Trial protocol and rationale of an open-label pragmatic, prospective randomized controlled

by Sonal Singh, Noelle M. Cocoros, Xiaojuan Li, Kathleen M. Mazor, Mary T. Antonelli, Lauren Parlett, Mark Paullin, Thomas P. Harkins, Yunping Zhou, Paula A. Rochon, Richard Platt, Inna Dashevsky, Carly Massino, Cassandra Saphirak, Sybil L. Crawford, Jerry H. Gurwitz

Context

Potentially inappropriate prescribing of medications in older adults, particular those with dementia, can lead to adverse drug events including falls and fractures, worsening cognitive impairment, emergency department visits, and hospitalizations. Educational mailings from health plans to patients and their providers to encourage deprescribing conversations may represent an effective, low-cost, “light touch”, approach to reducing the burden of potentially inappropriate prescription use in older adults with dementia.

Objectives

The objective of the Developing a PRogram to Educate and Sensitize Caregivers to Reduce the Inappropriate Prescription Burden in Elderly with Alzheimer’s Disease (D-PRESCRIBE-AD) trial is to evaluate the effect of a health plan based multi-faceted educational outreach intervention to community dwelling patients with dementia who are currently prescribed sedative/hypnotics, antipsychotics, or strong anticholinergics.

Methods

The D-PRESCRIBE-AD is an open-label pragmatic, prospective randomized controlled trial (RCT) comparing three arms: 1) educational mailing to both the health plan patient and their prescribing physician (patient plus physician arm, n = 4814); 2) educational mailing to prescribing physician only (physician only arm, n = 4814); and 3) usual care (n = 4814) among patients with dementia enrolled in two large United States based health plans. The primary outcome is the absence of any dispensing of the targeted potentially inappropriate prescription during the 6-month study observation period after a 3-month black out period following the mailing. Secondary outcomes include dose-reduction, polypharmacy, healthcare utilization, mortality and therapeutic switching within targeted drug classes.

Conclusion

This large pragmatic RCT will contribute to the evidence base on promoting deprescribing of potentially inappropriate medications among older adults with dementia. If successful, such light touch, inexpensive and highly scalable interventions have the potential to reduce the burden of potentially inappropriate prescribing for patients with dementia.ClinicalTrials.gov Identifier: NCT05147428.

Unraveling implicit human behavioral effects on dynamic characteristics of Covid-19 daily infection rates in Taiwan

by Ting-Li Chen, Elizabeth P. Chou, Min-Yi Chen, Fushing Hsieh

We investigate the dynamic characteristics of Covid-19 daily infection rates in Taiwan during its initial surge period, focusing on 79 districts within the seven largest cities. By employing computational techniques, we extract 18 features from each district-specific curve, transforming unstructured data into structured data. Our analysis reveals distinct patterns of asymmetric growth and decline among the curves. Utilizing theoretical information measurements such as conditional entropy and mutual information, we identify major factors of order-1 and order-2 that influence the peak value and curvature at the peak of the curves, crucial features characterizing the infection rates. Additionally, we examine the impact of geographic and socioeconomic factors on the curves by encoding each of the 79 districts with two binary characteristics: North-vs-South and Urban-vs-Suburban. Furthermore, leveraging this data-driven understanding at the district level, we explore the fine-scale behavioral effects on disease spread by examining the similarity among 96 age-group-specific curves within urban districts of Taipei and suburban districts of New Taipei City, which collectively represent a substantial portion of the nation’s population. Our findings highlight the implicit influence of human behaviors related to living, traveling, and working on the dynamics of Covid-19 transmission in Taiwan.

Knowledge, attitudes, and practices regarding antibiotic use in Bangladesh: Findings from a cross-sectional study

by Md. Abu Raihan, Md. Saiful Islam, Shariful Islam, A. F. M. Mahmudul Islam, Khandaker Tanveer Ahmed, Tania Ahmed, Md. Nahidul Islam, Shamsunnahar Ahmed, Mysha Samiha Chowdhury, Dipto Kumar Sarker, Anika Bushra Lamisa

Background

Escalating antibiotic resistance presents a notable worldwide dilemma, pointing a large involvement of general population. The objective of this study was to assess knowledge, attitudes, and practices regarding the utilization of antibiotics among Bangladeshi residents.

Methods

A cross-sectional study, conducted from January 01 to April 25, 2022, included 1,947 Bangladeshi adults with a history of antibiotic use, via online surveys and face-to-face interviews using a pretested semi-structured questionnaire. Descriptive statistics, Chi-square tests, and multivariate linear regression models were employed.

Results

Mean scores for knowledge, attitudes, and practices were 6.59±1.20, 8.34±1.19, and 12.74±2.59, with correct rates of 73.22%, 92.67%, and 57.91%. Positive predictors for knowledge included being unmarried (β = 0.10, p = 0.001), higher education (College: β = 0.09, p = 0.025; Bachelor: β = 0.22, p Conclusions

Participants exhibited adequate knowledge and positive attitudes but lagged behind in proper practice of antibiotic use. Proper initiatives should be tailored to enhance prudent antibiotic use and mitigate the risk of antimicrobial resistance.

Allogeneic limbo-deep anterior lamellar keratoplasty (Limbo-DALK)—A novel surgical technique in corneal stromal disease and limbal stem cell deficiency

by Verena Schöneberger, Volkan Tahmaz, Mario Matthaei, Sigrid Roters, Simona L. Schlereth, Friederike Schaub, Claus Cursiefen, Björn O. Bachmann

Purpose

To describe a novel corneal surgical technique combining Deep Anterior Lamellar Keratoplasty (DALK) with grafting of allogeneic limbus (Limbo-DALK) for the treatment of eyes with corneal stromal pathology and limbal stem cell deficiency (LSCD).

Methods

Clinical records of six Limbo-DALKs performed in five patients diagnosed with LSCD and corneal stromal pathology requiring keratoplasty were retrospectively reviewed. All patients were diagnosed with LSCD due to various pathologies including thermal and chemical burns, congenital aniridia or chronic inflammatory ocular surface disease. Parameters analysed included demographics, diagnoses, clinical history, thickness measurements using anterior segment OCT, visual acuity, and epithelial status. Regular follow-up visits were scheduled at 6 weeks as well as 3, 6, 9, and 12 and 18 months postoperatively. Main outcome measures were time to graft epithelialisation and the occurrence of corneal endothelial decompensation.

Results

Two grafts showed complete epithelial closure at 2 days, two at 14 days. In one eye, complete epithelial closure was not achieved after the first Limbo-DALK, but was achieved one month after the second Limbo-DALK. No endothelial decompensation occurred except in one patient with silicone oil associated keratopathy. Endothelial graft rejection was not observed in any of the grafts.

Conclusion

Based on the data from this pilot series, limbo-DALK appears to be a viable surgical approach for eyes with severe LSCD and corneal stromal pathology, suitable for emergency situations (e.g. corneal ulceration with impending corneal perforation), while minimising the risk of corneal endothelial decompensation.

Multimodality radiomics for tumor prognosis in nasopharyngeal carcinoma

by Sararas Khongwirotphan, Sornjarod Oonsiri, Sarin Kitpanit, Anussara Prayongrat, Danita Kannarunimit, Chakkapong Chakkabat, Chawalit Lertbutsayanukul, Sira Sriswasdi, Yothin Rakvongthai

Background

The prognosis of nasopharyngeal carcinoma (NPC) is challenging due to late-stage identification and frequently undetectable Epstein-Barr virus (EBV) DNA. Incorporating radiomic features, which quantify tumor characteristics from imaging, may enhance prognosis assessment.

Purpose

To investigate the predictive power of radiomic features on overall survival (OS), progression-free survival (PFS), and distant metastasis-free survival (DMFS) in NPC.

Materials and methods

A retrospective analysis of 183 NPC patients treated with chemoradiotherapy from 2010 to 2019 was conducted. All patients were followed for at least three years. The pretreatment CT images with contrast medium, MR images (T1W and T2W), as well as gross tumor volume (GTV) contours, were used to extract radiomic features using PyRadiomics v.2.0. Robust and efficient radiomic features were chosen using the intraclass correlation test and univariate Cox proportional hazard regression analysis. They were then combined with clinical data including age, gender, tumor stage, and EBV DNA level for prognostic evaluation using Cox proportional hazard regression models with recursive feature elimination (RFE) and were optimized using 20 repetitions of a five-fold cross-validation scheme.

Results

Integrating radiomics with clinical data significantly enhanced the predictive power, yielding a C-index of 0.788 ± 0.066 to 0.848 ± 0.079 for the combined model versus 0.745 ± 0.082 to 0.766 ± 0.083 for clinical data alone (pp Conclusions

The combination of multimodality radiomic features from CT and MR images could offer superior predictive performance for OS, PFS, and DMFS compared to relying on conventional clinical data alone.

Infiltration of CD3+ and CD8+ lymphocytes in association with inflammation and survival in pancreatic cancer

by Gerik W. Tushoski-Alemán, Kelly M. Herremans, Patrick W. Underwood, Ashwin Akki, Andrea N. Riner, Jose G. Trevino, Song Han, Steven J. Hughes

Background

Pancreatic ductal adenocarcinomas (PDAC) have heterogeneous tumor microenvironments relatively devoid of infiltrating immune cells. We aimed to quantitatively assess infiltrating CD3+ and CD8+ lymphocytes in a treatment-naïve patient cohort and assess associations with overall survival and microenvironment inflammatory proteins.

Methods

Tissue microarrays were immunohistochemically stained for CD3+ and CD8+ lymphocytes and quantitatively assessed using QuPath. Levels of inflammation-associated proteins were quantified by multiplexed, enzyme-linked immunosorbent assay panels on matching tumor and tissue samples.

Results

Our findings revealed a significant increase in both CD3+ and CD8+ lymphocytes populations in PDAC compared with non-PDAC tissue, except when comparing CD8+ percentages in PDAC versus intraductal papillary mucinous neoplasms (IPMN) (p = 0.5012). Patients with quantitatively assessed CD3+ low tumors (lower 50%) had shorter survival (median 273 days) compared to CD3+ high tumors (upper 50%) with a median overall survival of 642.5 days (p = 0.2184). Patients with quantitatively assessed CD8+ low tumors had significantly shorter survival (median 240 days) compared to CD8+ high tumors with a median overall survival of 1059 days (p = 0.0003). Of 41 proteins assessed in the inflammation assay, higher levels of IL-1B and IL-2 were significantly associated with decreased CD3+ infiltration (r = -0.3704, p = 0.0187, and r = -0.4275, p = 0.0074, respectively). Higher levels of IL-1B were also significantly associated with decreased CD8+ infiltration (r = -0.4299, p = 0.0045), but not IL-2 (r = -0.0078, p = 0.9616). Principal component analysis of the inflammatory analytes showed diverse inflammatory responses in PDAC.

Conclusion

In this work, we found a marked heterogeneity in infiltrating CD3+ and CD8+ lymphocytes and individual inflammatory responses in PDAC. Future mechanistic studies should explore personalized therapeutic strategies to target the immune and inflammatory components of the tumor microenvironment.

Effect of antiplatelet therapy after COVID-19 diagnosis: A systematic review with meta-analysis and trial sequential analysis

by Hong Duo, Mengying Jin, Yanwei Yang, Rewaan Baheti, Yujia Feng, Zirui Fu, Yuyue Jiang, Lanzhuoying Zheng, Jing Wan, Huaqin Pan

Background

Coronavirus disease 2019 (COVID-19) may predispose patients to thrombotic disease in the venous and arterial circulations.

Methods

Based on the current debate on antiplatelet therapy in COVID-19 patients, we performed a systematic review and meta-analysis to investigate the effect of antiplatelet treatments. We searched PubMed, EMBASE, Cochrane Central Register of Controlled Trials, and Web of Science on February 1, 2023, and only included Randomized clinical trials. The study followed PRISMA guidelines and used Random-effects models to estimate the pooled percentage and its 95% CI.

Results

Five unique eligible studies were included, covering 17,950 patients with COVID-19. The result showed no statistically significant difference in the relative risk of all-cause death in antiplatelet therapy versus non-antiplatelet therapy (RR 0.94, 95% CI, 0.83–1.05, P = 0.26, I2 = 32%). Compared to no antiplatelet therapy, patients who received antiplatelet therapy had a significantly increased relative risk of major bleeding (RR 1.81, 95%CI 1.09–3.00, P = 0.02, I2 = 16%). The sequential analysis suggests that more RCTs are needed to draw more accurate conclusions. This systematic review and meta-analysis revealed that the use of antiplatelet agents exhibited no significant benefit on all-cause death, and the upper bound of the confidence interval on all-cause death (RR 95% CI, 0.83–1.05) suggested that it was unlikely to be a substantiated harm risk associated with this treatment. However, evidence from all RCTs suggested a high risk of major bleeding in antiplatelet agent treatments.

Conclusion

According to the results of our sequential analysis, there is not enough evidence available to support or negate the use of antiplatelet agents in COVID-19 cases. The results of ongoing and future well-designed, large, randomized clinical trials are needed.

Characterization and comparison of human and mouse milk cells

by Rose Doerfler, Saigopalakrishna Yerneni, Alexandra Newby, Namit Chaudhary, Ashley Shu, Katherine Fein, Juliana Hofstatter Azambuja, Kathryn A. Whitehead

Recent data has characterized human milk cells with unprecedented detail and provided insight into cell populations. While such analysis of freshly expressed human milk has been possible, studies of cell functionality within the infant have been limited to animal models. One commonly used animal model for milk research is the mouse; however, limited data are available describing the composition of mouse milk. In particular, the maternal cells of mouse milk have not been previously characterized in detail, in part due to the difficulty in collecting sufficient volumes of mouse milk. In this study, we have established a method to collect high volumes of mouse milk, isolate cells, and compare the cell counts and types to human milk. Surprisingly, we found that mouse milk cell density is three orders of magnitude higher than human milk. The cell types present in the milk of mice and humans are similar, broadly consisting of mammary epithelial cells and immune cells. These results provide a basis of comparison for mouse and human milk cells and will inform the most appropriate uses of mouse models for the study of human phenomena.

Performance comparison of stress hyperglycemia ratio for predicting fatal outcomes in patients with thrombolyzed acute ischemic stroke

by Sarawut Krongsut, Chatchon Kaewkrasaesin

Background

The stress hyperglycemia ratio (SHR), a newly developed metric, is used to assess adverse outcomes in patients with acute ischemic stroke (AIS). However, the relationship between SHR and fatal outcomes (in-hospital mortality [IHM], malignant cerebral edema [MCE], symptomatic intracerebral hemorrhage [sICH], 3-month mortality, and poor functional outcome) in AIS patients receiving recombinant tissue plasminogen activator (rt-PA) treatment is unclear, and determining the optimal threshold remains incomplete.

Materials and methods

We retrospectively enrolled a total of 345 AIS patients treated with rt-PA during 2015–2022 and collected data on various glucose metrics, including different types of SHR, glycemic gap (GG), random plasma glucose (RPG), fasting plasma glucose (FPG), and hemoglobin A1c (HbA1c). SHR and GG were calculated using these equations: SHR1, [FPG]/[HbA1c]; SHR2, [admission RPG]/[HbA1c]; SHR3, FPG/[(1.59 × HbA1c)−2.59]; SHR4, [admission RPG]/[(1.59 × HbA1c)−2.59]; GG, admission RPG − [(1.59 × HbA1c)−2.59]. We used multivariable logistic regression analysis (MVLR) to identify the association between different glucose metrics and outcomes while comparing their predictive values.

Results

SHR1 had the greatest predictive power and a more significant correlation with fatal outcomes than other continuous glucose metrics. The area under the curve of the SHR1 for IHM, MCE, and sICH, 3-month mortality, and poor functional outcome were 0.75, 0.77, 0.77, 0.76, and 0.73, respectively. SHR1 (per 1-point increases) was independently associated with IHM (Odds ratios [ORs] = 5.80; 95% CI [1.96, 17.17]; p = 0.001), MCE (ORs = 4.73; 95% CI [1.71, 13.04]; p = 0.003), sICH (ORs = 4.68, 95% CI [1.48–14.82]; p = 0.009), 3-month mortality (ORs = 10.87; 95% CI [3.56, 33.21]; p Conclusion

SHR1 demonstrates an independent association with fatal outcomes in AIS patients treated with rt-PA, exhibiting superior predictive ability over other glucose metrics.

Relationship between rumination, self-compassion, and psychological health among Japanese university students: A cross-sectional study

by Kaho Yamasaki, Ayaka Sampei, Hiromitsu Miyata

Objectives

Rumination is suggested to exacerbate psychological health, but there is room for investigating the potential protecting factors for individuals with high ruminative tendencies against psychological symptoms. The present cross-sectional study aimed to uncover the associations between rumination as a maladaptive dimension of self-focus, self-compassion, and psychological health, and whether and how components of self-compassion may moderate the associations between rumination and psychological health in Japanese undergraduate students.

Methods

A questionnaire survey was conducted by using both an online platform and a paper-based questionnaire. The survey included established Japanese versions of psychological scales on rumination, self-compassion, perceived stress, trait anxiety, and depression.

Results

The results revealed statistically significant positive correlations between rumination and negative dimensions of self-compassion, and rumination and psychological symptoms. Positive dimensions of self-compassion were significantly negatively correlated with both rumination and psychological symptoms. Reflection as a positive dimension of self-focus did not show significant correlations with most psychological variables. Furthermore, hierarchical multiple regression analyses involving subscales of self-compassion and their interactions with rumination as predictors revealed that the interactions between rumination and components of self-compassion, i.e., over-identification and mindfulness, significantly predicted trait anxiety. Higher rumination predicted higher anxiety when over-identification was high, but not when over-identification was low. Also, lower rumination predicted lower anxiety when mindfulness was high, but not when mindfulness was low.

Conclusions

The results suggest significant associations between rumination, components of self-compassion, and psychological health in a population of Japanese undergraduate students. The data also suggest that components of self-compassion play moderating roles in the relationship between rumination and psychological health, potentially serving as aggravating/protective factors for psychological health. Longitudinal studies and comparisons between different cultures should be conducted in the future quest.

Real-world prescription of anti-COVID-19 drugs in hospitalized patients with COVID-19 in Japan

by Haruka Shida, Maki Komamine, Kazuhiro Kajiyama, Takashi Waki, Hotaka Maruyama, Yoshiaki Uyama

Objective

Prescription trends and patterns of anti-COVID-19 drugs in hospitalized patients were examined based on real world data to understand the use of anti-COVID-19 drugs in clinical practice in Japan.

Design

The longitudinal and cross-sectional study was conducted utilizing data from January 1, 2019 to December 31, 2021 of the MID-NET® medical information database, which stored the electronic medical records, administrative claim data, and diagnosis procedure combination data of patients in Japan.

Participants

Hospitalized patients with a COVID-19-related diagnosis who received at least one anti-COVID-19 drug between April 1, 2020 and December 31, 2021.

Exposures

The following 14 drugs were included in this study: remdesivir, baricitinib, combination product of casirivimab and imdevimab, favipiravir, dexamethasone, ivermectin, azithromycin, nafamostat mesylate, camostat mesylate, ciclesonide, tocilizumab, sarilumab, combination product of lopinavir and ritonavir, and hydroxychloroquine.

Results

We identified 5,717 patients hospitalized with COVID-19 and prescribed at least one anti-COVID-19 drug. The entire cohort generally included patients over 41–50 years and more males. The most common prescription pattern was dexamethasone monotherapy (22.9%), followed by the concomitant use of remdesivir and dexamethasone (15.0%), azithromycin monotherapy (15.0%), remdesivir monotherapy (10.2%), and nafamostat mesylate monotherapy (8.5%). However, an often prescribed anti-COVID-19 drug differed depending on the period.

Conclusions and relevance

This study revealed the real-world situation of anti-COVID-19 drug prescriptions in hospitalized COVID-19 patients in Japan. A prescribed drug would depend on the latest scientific evidence, such as efficacy, safety, and approval status, at the time of prescription. Understanding the prescription of anti-COVID-19 drugs will be important for providing the most up-to-date treatments to patients and evaluating the benefit and/or risk of anti-COVID-19 drugs based on the utilization of an electronic medical record database.

Jagged 2 inhibition attenuates hypoxia-induced mitochondrial damage and pulmonary hypertension through Sirtuin 1 signaling

by Hanhan Liu, Zhou Pan, Xiaofeng Wu, Cheng Gong, Junbo Hu

Notch pathway has played a significant role in the pathophysiology of pulmonary hypertension (PH). However, the role of Jagged 2 (Jag2), one ligand of Notch, remains to be elucidated.Therefore, determining the contribution of Jag2 to PH and its impact on pulmonary artery smooth muscle cells (PASMCs) was the aim of this investigation. Adeno-associated virus-mediated Jag2 inhibition was used to explore the role of Jag2 in peripheral pulmonary vascular remodeling assessed in a rat model of chronic hypoxia (10% O2, 4 weeks) induced pulmonary hypertension. In vitro, the effect of Jag2 silencing on hypoxia (1% O2, 24h) induced rat PASMCs was determined. Group differences were assessed using a 2-sided unpaired Student’s t-test for two groups and one-way ANOVA for multiple groups. Jag2 upregulation was first confirmed in rats with sustained hypoxia-induced PH using publicly available gene expression data, experimental PH rat models and hypoxia induced rat PASMCs. Jag2 deficiency decreased oxidative stress injury, peripheral pulmonary vascular remodeling (0.276±0.020 vs. 0.451±0.033 μm, PPJag2 knockdown decreased proliferation (1.227±0.051 vs. 1.45±0.07, P = 0.012), increased apoptosis (16.733%±0.724% vs. 6.56%±0.668%, P
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