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.

Lightweight high-precision SAR ship detection method based on YOLOv7-LDS

by Shiliang Zhu, Min Miao

The current challenges in Synthetic Aperture Radar (SAR) ship detection tasks revolve around handling significant variations in target sizes and managing high computational expenses, which hinder practical deployment on satellite or mobile airborne platforms. In response to these challenges, this research presents YOLOv7-LDS, a lightweight yet highly accurate SAR ship detection model built upon the YOLOv7 framework. In the core of YOLOv7-LDS’s architecture, we introduce a streamlined feature extraction network that strikes a delicate balance between detection precision and computational efficiency. This network is founded on Shufflenetv2 and incorporates Squeeze-and-Excitation (SE) attention mechanisms as its key elements. Additionally, in the Neck section, we introduce the Weighted Efficient Aggregation Network (DCW-ELAN), a fundamental feature extraction module that leverages Coordinate Attention (CA) and Depthwise Convolution (DWConv). This module efficiently aggregates features while preserving the ability to identify small-scale variations, ensuring top-quality feature extraction. Furthermore, we introduce a lightweight Spatial Pyramid Dilated Convolution Cross-Stage Partial Channel (LSPHDCCSPC) module. LSPHDCCSPC is a condensed version of the Spatial Pyramid Pooling Cross-Stage Partial Channel (SPPCSPC) module, incorporating Dilated Convolution (DConv) as a central component for extracting multi-scale information. The experimental results show that YOLOv7-LDS achieves a remarkable Mean Average Precision (mAP) of 99.1% and 95.8% on the SAR Ship Detection Dataset (SSDD) and the NWPU VHR-10 dataset with a parameter count (Params) of 3.4 million, a Giga Floating Point Operations Per Second (GFLOPs) of 6.1 and an Inference Time (IT) of 4.8 milliseconds. YOLOv7-LDS effectively strikes a fine balance between computational cost and detection performance, surpassing many of the current state-of-the-art object detection models. As a result, it offers a more resilient solution for maritime ship monitoring.

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.

Kinetics and mechanical work done to move the body centre of mass along a curve

by Raphael M. Mesquita, Patrick A. Willems, Arthur H. Dewolf, Giovanna Catavitello

When running on a curve, the lower limbs interact with the ground to redirect the trajectory of the centre of mass of the body (CoM). The goal of this paper is to understand how the trajectory of the CoM and the work done to maintain its movements relative to the surroundings (W_com) are modified as a function of running speed and radius of curvature. Eleven participants ran at different speeds on a straight line and on circular curves with a 6 m and 18 m curvature. The trajectory of the CoM and W_com were calculated using force-platforms measuring the ground reaction forces and infrared cameras recording the movements of the pelvis. To follow a circular path, runners overcompensate the rotation of their trajectory during contact phases. The deviation from the circular path increases when the radius of curvature decreases and speed increases. Interestingly, an asymmetry between the inner and outer lower limbs emerges as speed increases. The method to evaluate W_com on a straight-line was adapted using a referential that rotates at heel strike and remains fixed during the whole step cycle. In an 18 m radius curve and at low speeds on a 6 m radius, W_com changes little compared to a straight-line run. Whereas at 6 m s^-1 on a 6 m radius, W_com increases by ~25%, due to an augmentation in the work to move the CoM laterally. Understanding these adaptations provides valuable insight for sports sciences, aiding in optimizing training and performance in sports with multidirectional movements.

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.

Hepatitis E virus infections among patients with acute febrile jaundice in two regions of Cameroon: First molecular characterization of hepatitis E virus genotype 4

by Abdou Fatawou Modiyinji, Lange Tchamba Amorgathe Tankeu, Chavely Gwladys Monamele, Moise Henri Yifomnjou Moumbeket, Paul Alain Tagnouokam Ngoupo, Huguette Tchetgna Simo, Abanda Njei Ngu, Kazanji Mirdad, Richard Njouom

Background

Febrile jaundice is a common indicator of certain infectious diseases, including hepatitis E. In Cameroon, the yellow fever virus is the only pathogen that is monitored in patients who present with this symptom. However, more than 90% of the samples received as part of this surveillance are negative for yellow fever. This study aimed to describe the prevalence and hepatitis E virus (HEV) genotype among yellow fever-negative patients in the Far North and West regions of Cameroon.

Methods

In a cross-sectional study, yellow fever surveillance-negative samples collected between January 2021 and January 2023 were retrospectively analyzed. Anti-HEV IgM and IgG antibodies were tested using commercially available ELISA kits. Anti-HEV IgM and/or IgG positive samples were tested for HEV RNA by real-time RT-PCR, followed by nested RT-PCR, sequencing and phylogenetic analysis.

Results

Overall, 121 of the 543 samples (22.3%, 95% CI: 19.0% - 26.0%) were positive for at least one anti-HEV marker. Amongst these, 8.1% (44/543) were positive for anti-HEV IgM, 5.9% (32/543) for anti-HEV IgG, and 8.3% (45/544) for both markers. A total of 15.2% (12/79) samples were positive for HEV RNA real-time RT-PCR and 8 samples were positive for HEV RNA by nested RT-PCR. Phylogenetic analysis showed that the retrieved sequences clustered within HEV genotypes/subtypes 1/1e, 3/3f and 4/4b.

Conclusion

Our results showed that HEV is one of the causes of acute febrile jaundice in patients enrolled in the yellow fever surveillance program in two regions of Cameroon. We described the circulation of three HEV genotypes, including two zoonotic genotypes. Further studies will be important to elucidate the transmission routes of these zoonotic HEV genotypes to humans in Cameroon.

Comprehensive analysis of single cell and bulk data develops a promising prognostic signature for improving immunotherapy responses in ovarian cancer

by Huanfei Ding, Bowen Hu, Ruixia Guo

The tumor heterogeneity is an important cause of clinical therapy failure and yields distinct prognosis in ovarian cancer (OV). Using the advantages of integrated single cell RNA sequencing (scRNA-seq) and bulk data to decode tumor heterogeneity remains largely unexplored. Four public datasets were enrolled in this study, including E-MTAB-8107, TCGA-OV, GSE63885, and GSE26193 cohorts. Random forest algorithm was employed to construct a multi-gene prognostic panel and further evaluated by receiver operator characteristic (ROC), calibration curve, and Cox regression. Subsequently, molecular characteristics were deciphered, and treatments strategies were explored to deliver precise therapy. The landscape of cell subpopulations and functional characteristics, as well as the dynamic of macrophage cells were detailly depicted at single cell level, and then screened prognostic candidate genes. Based on the expression of candidate genes, a stable and robust cell characterized gene associated prognosis signature (CCIS) was developed, which harbored excellent performance at prognosis assessment and patient stratification. The ROC and calibration curves, and Cox regression analysis elucidated CCIS could serve as serve as an independent factor for predicting prognosis. Moreover, a promising clinical tool nomogram was also constructed according to stage and CCIS. Through comprehensive investigations, patients in low-risk group were charactered by favorable prognosis, elevated genomic variations, higher immune cell infiltrations, and superior antigen presentation. For individualized treatment, patients in low-risk group were inclined to better immunotherapy responses. This study dissected tumor heterogeneity and afforded a promising prognostic signature, which was conducive to facilitating clinical outcomes for patients with OV.

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.

Therapeutic interventions on human breast cancer xenografts promote systemic dissemination of oncogenes

by Gorantla V. Raghuram, Kavita Pal, Gaurav Sriram, Afzal Khan, Ruchi Joshi, Vishalkumar Jadhav, Sushma Shinde, Alfina Shaikh, Bhagyeshri Rane, Harshada Kangne, Indraneel Mittra

Metastatic dissemination following successful treatment of the primary tumour remains a common cause of death. There is mounting evidence that therapeutic interventions themselves may promote development of metastatic disease. We earlier reported that cell-free chromatin particles (cfChPs) released from dying cancer cells are potentially oncogenic. Based on this observation we hypothesized that therapeutic interventions may lead to the release of cfChPs from therapy induced dying cancer cells which could be carried via the blood stream to distant organs to transform healthy cells into new cancers that would masquerade as metastasis. To test this hypothesis, we generated xenografts of MDA-MB-231 human breast cancer cells in severe combined immune-deficient mice, and using immuno-fluorescence and FISH analysis looked for cfChPs in their brain cells. We detected multiple human DNA signals representing cfChPs in nuclei of brain cells of mice which co-localized with eight human onco-proteins. No intact MDA-MB-231 cells were detected. The number of co-localizing human DNA and human c-Myc signals increased dramatically following treatment with chemotherapy, localized radiotherapy or surgery, which could be prevented by concurrent treatment with three different cfChPs deactivating agents. These results suggest that therapeutic interventions lead to the release cfChPs from therapy induced dying cancer cells carrying oncogenes and are transported via the blood stream to brain cells to potentially transform them to generate new cancers that would appear as metastases. cfChPs induced metastatic spread of cancer is preventable by concurrent treatment with agents that deactivate cfChPs.

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.

Cost-effectiveness analysis of olaparib maintenance therapy for BRCA mutation ovarian cancer in the public sector in Malaysia

by Chee Meng Yong, Prathepamalar A. P. Yehgambaram, Shaun Wen Huey Lee

Introduction

Ovarian cancer is one of the most common cancer among women in Malaysia. Patients with ovarian cancer are often diagnosed at an advanced stage. Despite initial response to surgery and chemotherapy, most patients will experience a relapse. Olaparib has been reported have promising effects among BRCA mutated ovarian cancer patients. This study aimed to evaluate the cost–effectiveness of olaparib as a maintenance therapy for BRCA ovarian cancer in Malaysia.

Methods

We developed a four-state partitioned survival model which compared treatment with olaparib versus routine surveillance (RS) from a Malaysian healthcare perspective. Mature overall survival (OS) data from the SOLO-1 study were used and extrapolated using parametric models. Medication costs and healthcare resource usage costs were derived from local inputs and publications. Deterministic and probabilistic sensitivity analyses (PSA) were performed to explore uncertainties.

Results

In Malaysia, treating patients with olaparib was found to be more costly compared to RS, with an incremental cost of RM149,858 (USD 33,213). Patients treated with olaparib increased life years by 3.05 years and increased quality adjusted life years (QALY) by 2.76 (9.45 years vs 6.40 years; 7.62 vs 4.86 QALY). This translated to an incremental cost-effectiveness ratio (ICER) of RM 49,159 (USD10,895) per life year gained and RM54,357 (USD 12,047) per QALY gained, respectively. ICERs were most sensitive to time horizon of treatment, discount rate for outcomes, cost of treatment and health state costs, but was above the RM53,770/QALY threshold.

Conclusion

The use of olaparib is currently not a cost-effective strategy compared to routine surveillance based upon the current price in Malaysia for people with ovarian cancer with BRCA mutation, despite the improvement in overall survival.

Pharmacogenomics of poor drug metabolism in greyhounds: Canine P450 oxidoreductase genetic variation, breed heterogeneity, and functional characterization

by Stephanie E. Martinez, Amit V. Pandey, Tania E. Perez Jimenez, Zhaohui Zhu, Michael H. Court

Greyhounds metabolize cytochrome P450 (CYP) 2B11 substrates more slowly than other dog breeds. However, CYP2B11 gene variants associated with decreased CYP2B11 expression do not fully explain reduced CYP2B11 activity in this breed. P450 oxidoreductase (POR) is an essential redox partner for all CYPs. POR protein variants can enhance or repress CYP enzyme function in a CYP isoform and substrate dependent manner. The study objectives were to identify POR protein variants in greyhounds and determine their effect on coexpressed CYP2B11 and CYP2D15 enzyme function. Gene sequencing identified two missense variants (Glu315Gln and Asp570Glu) forming four alleles, POR-H1 (reference), POR-H2 (570Glu), POR-H3 (315Gln, 570Glu) and POR-H4 (315Gln). Out of 68 dog breeds surveyed, POR-H2 was widely distributed across multiple breeds, while POR-H3 was largely restricted to greyhounds and Scottish deerhounds (35% allele frequencies), and POR-H4 was rare. Three-dimensional protein structure modelling indicated significant effects of Glu315Gln (but not Asp570Glu) on protein flexibility through loss of a salt bridge between Glu315 and Arg519. Recombinant POR-H1 (reference) and each POR variant (H2-H4) were expressed alone or with CYP2B11 or CYP2D15 in insect cells. No substantial effects on POR protein expression or enzyme activity (cytochrome c reduction) were observed for any POR variant (versus POR-H1) when expressed alone or with CYP2B11 or CYP2D15. Furthermore, there were no effects on CYP2B11 or CYP2D15 protein expression, or on CYP2D15 enzyme kinetics by any POR variant (versus POR-H1). However, V_max values for 7-benzyloxyresorufin, propofol and bupropion oxidation by CYP2B11 were significantly reduced by coexpression with POR-H3 (by 34–37%) and POR-H4 (by 65–72%) compared with POR-H1. K_m values were unaffected. Our results indicate that the Glu315Gln mutation (common to POR-H3 and POR-H4) reduces CYP2B11 enzyme function without affecting at least one other major canine hepatic P450 (CYP2D15). Additional in vivo studies are warranted to confirm these findings.

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.

Maternal and perinatal outcomes of hypertensive disorders in pregnancy: Insights from the National Hospital of Obstetrics and Gynecology in Vietnam

by Nguyen Thi Huyen Anh, Nguyen Manh Thang, Truong Thanh Huong

Introduction

Hypertension is the common disorder encountered during pregnancy, complicating 5% to 10% of all pregnancies. Hypertensive disorders in pregnancy (HDP) are also a leading cause of maternal and perinatal morbidity and mortality. The majority of feto-maternal complications due to HPD have occurred in the low- and middle-income countries. However, few studies have been done to assess the feto-maternal outcomes and the predictors of adverse perinatal outcome among women with HDP in these countries.

Methods

A prospective cohort study was conducted on women with HDP who were delivered at National Hospital of Obstetrics and Gynecology, Vietnam from March 2023 to July 2023. Socio-demographic and obstetrics characteristics, and feto-maternal outcomes were obtained by trained study staff from interviews and medical records. Statistical analysis was performed using SPSS version 26.0. Bivariate and multiple logistic regressions were done to determine factors associated with adverse perinatal outcome. A 95% confidence interval not including 1 was considered statically significant.

Results

A total of 255 women with HDP were enrolled. Regarding adverse maternal outcomes, HELLP syndrome (3.9%), placental abruption (1.6%), and eclampsia (1.2%) were three most common complications. There was no maternal death associated with HDP. The most common perinatal complication was preterm delivery developed in 160 (62.7%) of neonates. Eight stillbirths (3.1%) were recorded whereas the perinatal mortality was 6.3%. On bivariate logistic regression, variables such as residence, type of HDP, highest systolic BP, highest diastolic BP, platelet count, severity symptoms, and birth weight were found to be associated with adverse perinatal outcome. On multiple logistic regression, highest diastolic BP, severity symptoms, and birth weight were found to be independent predictors of adverse perinatal outcome.

Conclusion

Our study showed lower prevalence of stillbirth, perinatal mortality, and maternal complication compared to some previous studies. Regular antenatal care and early detection of abnormal signs during pregnancy help to devise an appropriate monitoring and treatment strategies for each women with HDP.

Interactions of plumbagin with five common antibiotics against <i>Staphylococcus aureus in vitro</i>

by Songtao Bie, Qiuyue Mo, Chen Shi, Hui Yuan, Chunshuang Li, Tong Wu, Wenlong Li, Heshui Yu

Staphylococcus aureus is the main culprit, causing a variety of severe clinical infections. At the same time, clinics are also facing the severe situation of antibiotic resistance. Therefore, effective strategies to address this problem may include expanding the antimicrobial spectrum by exploring alternative sources of drugs or delaying the development of antibiotic resistance through combination therapy so that existing antibiotics can continue to be used. Plumbagin (PLU) is a phytochemical that exhibits antibacterial activity. In the present study, we investigated the in vitro antibacterial activity of PLU. We selected five antibiotics with different mechanisms and inhibitory activities against S. aureus to explore their interaction with the combination of PLU. The interaction of combinations was evaluated by the Bliss independent model and visualized through response surface analysis. PLU exhibited potent antibacterial activity, with half maximal inhibitory concentration (IC₅₀) and minimum inhibitory concentration (MIC) values against S. aureus of 1.73 μg/mL and 4 μg/mL, respectively. Synergism was observed when PLU was combined with nitrofurantoin (NIT), ciprofloxacin (CPR), mecillinam (MEC), and chloramphenicol (CHL). The indifference of the trimethoprim (TMP)-PLU pairing was demonstrated across the entire dose-response matrix, but significant synergy was observed within a specific dose region. In addition, no antagonistic interactions were indicated. Overall, PLU is not only a promising antimicrobial agent but also has the potential to enhance the growth-inhibitory activity of some antibiotics against S. aureus, and the use of the interaction landscape, along with the dose-response matrix, for analyzing and quantifying combination results represents an improved approach to comprehending antibacterial combinations.

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

Inter- and intra-rater reproducibility of quantitative T1 measurement using semiautomatic region of interest placement in myometrium

by Sadahiro Nakagawa, Takahiro Uno, Shunta Ishitoya, Eriko Takabayashi, Akiko Oya, Wakako Kubota, Atsutaka Okizaki

Purpose

This study aimed to investigate the inter- and intraobserver reproducibility of quantitative T1 (qT1) measurements using manual and semiautomatic region of interest (ROI) placements. We hypothesized the usefulness of the semiautomatic method, which utilizes a three-dimensional (3D) anatomical relationship between the myometrium and other tissues, for minimizing ROI placement variation, thereby improving qT1 reproducibility compared to the manual approach. The semiautomatic approach, which considered anatomical relationships, was expected to enhance reproducibility by reducing ROI placement variabilities.

Materials and methods

This study recruited 23 healthy female volunteers. Data with variable flip angle (VFA) and inversion recovery were acquired using 3D-spoiled gradient echo and spin echo sequences, respectively. T1 maps were generated with VFA. Manual and semiautomatic ROI placements were independently conducted. Mean qT1 values were calculated from the T1 maps using the corresponding pixel values of the myometrial ROI. Inter- and intraobserver reproducibility of qT1 values was investigated. The inter- and intraobserver reproducibility of qT1 values was evaluated by calculating the coefficient of variation (CoV). Further, reproducibility was evaluated with inter- and intraobserver errors and intraclass correlation coefficients (ICCs). Bland–Altman analysis was utilized to compare the results, estimate bias, and determine the limits of agreement.

Results

The mean inter- and intraobserver CoV of the qT1 values for semiautomatic ROI placement was significantly lower than those for manual ROI placement (p p p p Conclusion

Semiautomatic ROI placement demonstrated high reproducibility of qT1 measurements compared with manual methods. Semiautomatic ROI placement may be useful for evaluating uterine qT1 with high reproducibility.

Authenticity: Effective emotional labor strategies on teaching efficacy of university teachers in China

by Jiuhua Zheng, Yuqing Geng, Juan Gao, Qinjun Xiang

Based on the job demands-resources model, this study explored the relationships among emotional labor strategies, job demands of teaching, job resources, and teaching efficacy for university teachers. The results, based on a sample of 316 university teachers from China, showed that the teachers preferred to convey authenticity by expressing deep acting and naturally felt emotion. Furthermore, deep acting and naturally felt emotions were found to have a significant positive effect on teaching efficacy, whereas surface acting did not have any significant relationship with teaching efficacy. As organizational variables, job demands significantly positively affected surface acting, deep acting, and naturally felt emotion. In contrast, job resources positively affected surface and deep acting, but no significant relationship with naturally felt emotions was found. These results highlight that university teachers from China could benefit from adopting authentic emotional labor strategies, specifically deep acting and naturally felt emotions, as the most effective strategies in teaching. Based on the above findings, this paper concludes with recommendations for university administrators to alleviate the emotional labor of college faculty. For example, universities should pay more attention to teachers’ emotional state, provide resources to support them, and give more space and support to college teachers in teaching.

Safety and efficacy of bempedoic acid among patients with statin intolerance and those without: A meta-analysis and a systematic randomized controlled trial review

by Yi Li, Hongyu Gao, Jinghui Zhao, Liqing Ma, Dan Hu

Objective

Bempedoic acid, an innovative oral medication, has garnered significant interest in recent times due to its potential as a therapeutic intervention for hypercholesterolemia. Nonetheless, the outcomes of the initial investigations might have been more definitive and coherent. Our objective was to perform a quantitative meta-analysis in order to evaluate bempedoic acid’s safety and effectiveness.

Methods

A search was conducted on ClinicalTrials.gov, and PubMed from the time of inception until September 28, 2023. Randomized controlled trials comparing the safety and efficacy of bempedoic acid among patients with statin intolerance and those without were included in our analysis. The trial outcomes were summarized using a random effects model and were provided as mean differences or odds ratios (ORs) with a confidence interval of 95%. Additionally, trial heterogeneity and the possibility of bias were evaluated and investigated.

Results

Bempedoic acid treatment reduced low-density lipoprotein cholesterol levels more than placebo (mean difference -2.97%, 95% CI -5.89% to -0.05%), according to a pooled analysis of 16 eligible trials. The risk of death (OR 1.18, 95% CI 0.70 to 1.98) and muscle-associated occurrences (OR 1.00, 95% CI 0.77 to 1.31) was not impacted by bempedoic acid. In contrast, discontinuation of treatment was more frequently caused by adverse events in the bempedoic acid group (OR 1.13, 95% CI 1.01 to 1.27).

Conclusions

In patients with statin intolerance as well as those without, bempedoic acid is a safe and efficacious lipid-lowering agent, according to findings from randomized controlled trials.