Catechin Protects against Lipopolysaccharide-induced Depressive-like Behaviour in Mice by Regulating Neuronal and Inflammatory Genes.

BACKGROUND: Many studies have suggested that tea has antidepressant effects; however, the underlying mechanism is not fully studied. As the main anti-inflammatory polyphenol in tea, catechin may contribute to the protective role of tea against depression. OBJECTIVE: The objective of this study is to prove that catechin can protect against lipopolysaccharide (LPS)-induced depressive-like behaviours in mice, and then explore the underlying molecular mechanisms. METHODS: Thirty-one C57BL/6J mice were categorized into the normal saline (NS) group, LPS group, catechin group, and amitriptyline group according to their treatments. Elevated Plus Maze (EPM), Tail Suspension Test (TST), and Open Field Test (OFT) were employed to assess depressive- like behaviours in mice. RNA sequencing (RNA-seq) and subsequent Bioinformatics analyses, such as differential gene analysis and functional enrichment, were performed on the four mouse groups. RESULTS: In TST, the mice in the LPS group exhibited significantly longer immobility time than those in the other three groups, while the immobility times for the other three groups were not significantly different. Similarly in EPM, LPS-treated mice exhibited a significantly lower percentage in the time/path of entering open arms than the mice in the other three groups, while the percentages of the mice in the other three groups were not significantly different. In OFT, LPS-treated mice exhibited significantly lower percentages in the time/path of entering the centre area than those in the other three groups. The results suggested that the LPS-induced depression models were established successfully and catechin can reverse (LPS)-induced depressive-like behaviours in mice. Finally, RNA-seq analyses revealed 57 differential expressed genes (DEGs) between LPS and NS with 19 up-regulated and 38 down-regulated. Among them, 13 genes were overlapped with the DEGs between LPS and cetechin (in opposite directions), with an overlapping p-value < 0.001. The 13 genes included Rnu7, Lcn2, C4b, Saa3, Pglyrp1, Gpx3, Lyz2, S100a8, S100a9, Tmem254b, Gm14288, Hbb-bt, and Tmem254c, which might play key roles in the protection of catechin against LPS-induced depressive-like behaviours in mice. The 13 genes were significantly enriched in defense response and inflammatory response, indicating that catechin might work through counteracting changes in the immune system induced by LPS. CONCLUSION: Catechin can protect mice from LPS-induced depressive-like behaviours through affecting inflammatory pathways and neuron-associated gene ontologies.

The characteristics of intratumoral microbial community reflect the development of lung adenocarcinoma.

Introduction: An increasing number of studies have demonstrated the pivotal role of microbiota changes in the onset, progression, diagnosis, treatment, and prognosis of lung adenocarcinoma (LUAD). However, a comprehensive analysis of intratumoral microbiome variation across distinct LUAD stages has not been performed. The aim of this study was to identify the microbial markers that significantly vary during tumor stage of LUAD. Methods: Here, we used the cancer genome atlas (TCGA) database to comprehensively compare and analyze the differences in microbial composition between 267 patients with early and 224 patients with advanced LUAD. In order to determine the best biomarkers, we used the random forest (RF) model and found that the microbial markers have a certain ability in predicting the stage of LUAD. Results: We found that there were certain differences in the microbiome of patients with LUAD at different stages, especially in the tumor tissues of patients with advanced LUAD, whose co-abundance network was significantly more complex. We also found that five bacterial biomarkers (Pseudoalteromonas, Luteibacter, Caldicellulosiruptor, Loktanella, and Serratia) were correlated with LUAD stage, among which Pseudoalteromonas, Luteibacter, Caldicellulosiruptor, and Serratia were significantly overexpressed in patients with advanced LUAD. In particular, after integrating the biomarkers of mRNA, we achieved an area under the curve (AUC) of 0.70. Discussion: Our study revealed the microbial profile of patients with LUAD and the intrinsic pathogenic mechanism between the microbiome and the disease, and established a multi-omics model to determine LUAD tumor stage.

Unveiling the Genetic Secrets of Chinese Indigenous Pigs from Guizhou Province: Diversity, Evolution and Candidate Genes Affecting Pig Coat Color.

The local pig breeds in Guizhou possess exceptional meat quality, robust adaptability, and resilience to harsh feeding conditions, making them ideal for producing high-quality pork. With over 10 local pig breeds in the region, we focused on 7 specific breeds: Baixi pigs (BX), Congjiang Xiang pigs (CJX), Guanling pigs (GL), Jianhe White Xiang pigs (JHBX), Jiangkou Luobo pigs (JKLB), Kele pigs (KL), and Qiandong Hua pigs (QDH). Unfortunately, these breeds face threats such as introduced species and inbreeding, resulting in a decline in population size and numbers. To better protect and utilize these breeds, we employed genome-wide single-nucleotide polymorphism (SNP) markers to investigate the population structure, genetic diversity, and selection characteristics of 283 pigs across these seven breeds. Our findings revealed distinct ancestral sources between Chinese and Western pig breeds, as demonstrated by principal component analysis, adjacent tree analysis, and ADMIXTURE analysis. Notably, JHBX exhibited a distant genetic relationship from the other six local pig breeds in Guizhou province, showcasing unique genetic characteristics. While the genetic diversity of the six Chinese native pig populations, excluding JHBX, was generally moderate in Guizhou province, the JHBX population displayed low genetic diversity. Therefore, it is imperative to intensify selection efforts to prevent inbreeding decline in JHBX while further enhancing the protection measures for the other six pig populations. Additionally, we identified candidate genes influencing the size disparity among pigs in Guizhou province through signal selection. Our study outcomes serve as a reference for developing effective conservation and utilization plans for pig breeds in Guizhou province and deepen our understanding of the genetic mechanisms underlying pig body size.

Mending the gap: Measurement needs to address policy implementation through a health equity lens.

Policies represent a key opportunity to improve the health outcomes of populations, and if implemented well, can reduce disparities affecting marginalized populations. Many policies are only evaluated on whether they elicit their intended health outcome. However, a lack of understanding regarding if and how they are implemented may hinder the intended impact overall and on addressing health disparities. Implementation science offers an array of frameworks and methodological approaches for assessing policy delivery, yet few examples exist that meaningfully include health equity as a core focus. This commentary describes the importance of equity-informed implementation measurement by providing case examples and implications for assessment. In addition, we highlight examples of emerging work in policy implementation grounded in health equity with suggested steps for moving the field forward. The ultimate goal is to move toward open-access measurement approaches that can be adapted to study implementation of a variety of policies at different stages of implementation, driven by input from marginalized populations and implementation practitioners, to move the needle on addressing health disparities.

This article talks about the need to include health equity as a major focus when understanding if and how policies are being implemented. We talk about gaps in the implementation science field and how equity-informed measurement tools can help to bridge this gap. Finally, we give some examples of efforts in place and where others can add to the growing resources to improve policy delivery.

Service readiness for the management of non-communicable diseases in publicly financed facilities in Malawi: findings from the 2019 Harmonised Health Facility Assessment census survey.

INTRODUCTION: Non-communicable diseases (NCDs) are rising in low-income and middle-income countries, including Malawi. To inform policy-makers and planners on the preparedness of the Malawian healthcare system to respond to NCDs, we estimated NCD service readiness in publicly financed healthcare facilities in Malawi. METHODS: We analysed data from 564 facilities surveyed in the 2019 Harmonised Health Facility Assessment, including 512 primary healthcare (PHC) and 52 secondary and tertiary care (STC) facilities. To characterise service readiness, applying the law of minimum, we estimated the percentage of facilities with functional equipment and unexpired medicines required to provide NCD services. Further, we estimated permanently unavailable items to identify service readiness bottlenecks. RESULTS: Fewer than 40% of PHC facilities were ready to deliver services for each of the 14 NCDs analysed. Insulin and beclomethasone inhalers had the lowest stock levels at PHC facilities (6% and 8%, respectively). Only 17% of rural and community hospitals (RCHs) have liver and kidney diagnostics. STC facilities had varying service readiness, ranging from 27% for managing acute diabetes complications to 94% for chronic type 2 diabetes management. Only 38% of STC facilities were ready to manage chronic heart failure. Oral pain medicines were widely available at all levels of health facilities; however, only 22% of RCHs and 29% of STCs had injectable morphine or pethidine. Beclomethasone was never available at 74% of PHC and 29% of STC facilities. CONCLUSION: Publicly financed facilities in Malawi are generally unprepared to provide NCD services, especially at the PHC level. Targeted investments in PHC can substantially improve service readiness for chronic NCD conditions in local communities and enable STC to respond to acute NCD complications and more complex NCD cases.

Lifting all boats: strategies to promote equitable bidirectional research training opportunities to enhance global health reciprocal innovation.

Inequities in global health research are well documented. For example, training opportunities for US investigators to conduct research in low-income and middle-income countries (LMIC) have exceeded opportunities for LMIC investigators to train and conduct research in high-income countries. Reciprocal innovation addresses these inequities through collaborative research across diverse global settings.The Fogarty International Center of the US National Institutes of Health (NIH) promotes research capacity building in LMICs. Fogarty K-grants for mentored career development in global health are available for both US and LMIC investigators, whereas the D43 is the standard grant to support institutional training programmes in LMIC. Other NIH institutes fund T32 training grants to support biomedical research training in the USA, but very few have any global health component. Most global health training partnerships have historically focused on research conducted solely in LMIC, with few examples of bidirectional training partnerships. Opportunities may exist to promote global health reciprocal innovation (GHRI) research by twinning K-awardees in the USA with those from LMIC or by intentionally creating partnerships between T32 and D43 training programmes.To sustain independent careers in GHRI research, trainees must be supported through the path to independence known as the K (mentored grantee)-to-R (independent grantee) transition. Opportunities to support this transition include comentorship, research training at both LMIC and US institutions and protected time and resources for research. Other opportunities for sustainability include postdoctoral training before and after the K-award period, absorption of trained researchers into home institutions, South-South training initiatives and innovations to mitigate brain drain.

Cost savings in male circumcision post-operative care using two-way text-based follow-up in rural and urban South Africa.

INTRODUCTION: Voluntary medical male circumcision (VMMC) clients are required to attend multiple post-operative follow-up visits in South Africa. However, with demonstrated VMMC safety, stretched clinic staff in SA may conduct more than 400,000 unnecessary reviews for males without complications, annually. Embedded into a randomized controlled trial (RCT) to test safety of two-way, text-based (2wT) follow-up as compared to routine in-person visits among adult clients, the objective of this study was to compare 2wT and routine post-VMMC care costs in rural and urban South African settings. METHODS: Activity-based costing (ABC) estimated the costs of post-VMMC care, including counselling, follow-ups, and tracing in $US dollars. Transportation for VMMC and follow-up was provided for rural clients in outreach settings but not for urban clients in static sites. Data were collected from National Department of Health VMMC forms, RCT databases, and time-and-motion surveys. Sensitivity analysis presents different follow-up scenarios. We hypothesized that 2wT would save per-client costs overall, with higher savings in rural settings. RESULTS: VMMC program costs were estimated from 1,084 RCT clients: 537 in routine care and 547 in 2wT. On average, 2wT saved $3.56 per client as compared to routine care. By location, 2wT saved $7.73 per rural client and increased urban costs by $0.59 per client. 2wT would save $2.16 and $7.02 in follow-up program costs if men attended one or two post-VMMC visits, respectively. CONCLUSION: Quality 2wT follow-up care reduces overall post-VMMC care costs by supporting most men to heal at home while triaging clients with potential complications to timely, in-person care. 2wT saves more in rural areas where 2wT offsets transportation costs. Minimal additional 2wT costs in urban areas reflect high care quality and client engagement, a worthy investment for improved VMMC service delivery. 2wT scale-up in South Africa could significantly reduce overall VMMC costs while maintaining service quality.

Evaluating the implementation of a dynamic digital application to enable community-based decentralisation of rheumatic heart disease case management in Uganda: protocol for a hybrid type III effectiveness-implementation study.

INTRODUCTION: Rheumatic heart disease (RHD) affects over 39 million people worldwide, the majority in low-income and middle-income countries. Secondary antibiotic prophylaxis (SAP), given every 3-4 weeks can improve outcomes, provided more than 80% of doses are received. Poor adherence is strongly correlated with the distance travelled to receive prophylaxis. Decentralising RHD care has the potential to bridge these gaps and at least maintain or potentially increase RHD prophylaxis uptake. A package of implementation strategies was developed with the aim of reducing barriers to optimum SAP uptake. METHODS AND ANALYSIS: A hybrid implementation-effectiveness study type III was designed to evaluate the effectiveness of a package of implementation strategies including a digital, cloud-based application to support decentralised RHD care, integrated into the public healthcare system in Uganda. Our overarching hypothesis is that secondary prophylaxis adherence can be maintained or improved via a decentralisation strategy, compared with the centralised delivery strategy, by increasing retention in care. To evaluate this, eligible patients with RHD irrespective of their age enrolled at Lira and Gulu hospital registry sites will be consented for decentralised care at their nearest participating health centre. We estimated a sample size of 150-200 registrants. The primary outcome will be adherence to secondary prophylaxis while detailed implementation measures will be collected to understand barriers and facilitators to decentralisation, digital application tool adoption and ultimately its use and scale-up in the public healthcare system. ETHICS AND DISSEMINATION: This study was approved by the Institutional Review Board (IRB) at Cincinnati Children's Hospital Medical Center (IRB 2021-0160) and Makerere University School of Medicine Research Ethics Committee (Mak-SOMREC-2021-61). Participation will be voluntary and informed consent or assent (>8 but <18) will be obtained prior to participation. At completion, study findings will be communicated to the public, key stakeholders and submitted for publication.

Associations of genome-wide structural variations with phenotypic differences in cross-bred Eurasian pigs.

BACKGROUND: During approximately 10,000 years of domestication and selection, a large number of structural variations (SVs) have emerged in the genome of pig breeds, profoundly influencing their phenotypes and the ability to adapt to the local environment. SVs (≥ 50 bp) are widely distributed in the genome, mainly in the form of insertion (INS), mobile element insertion (MEI), deletion (DEL), duplication (DUP), inversion (INV), and translocation (TRA). While studies have investigated the SVs in pig genomes, genome-wide association studies (GWAS)-based on SVs have been rarely conducted. RESULTS: Here, we obtained a high-quality SV map containing 123,151 SVs from 15 Large White and 15 Min pigs through integrating the power of several SV tools, with 53.95% of the SVs being reported for the first time. These high-quality SVs were used to recover the population genetic structure, confirming the accuracy of genotyping. Potential functional SV loci were then identified based on positional effects and breed stratification. Finally, GWAS were performed for 36 traits by genotyping the screened potential causal loci in the F2 population according to their corresponding genomic positions. We identified a large number of loci involved in 8 carcass traits and 6 skeletal traits on chromosome 7, with FKBP5 containing the most significant SV locus for almost all traits. In addition, we found several significant loci in intramuscular fat, abdominal circumference, heart weight, and liver weight, etc. CONCLUSIONS: We constructed a high-quality SV map using high-coverage sequencing data and then analyzed them by performing GWAS for 25 carcass traits, 7 skeletal traits, and 4 meat quality traits to determine that SVs may affect body size between European and Chinese pig breeds.

'I understood the texting process well'. Participant perspectives on usability and acceptability of SMS-based telehealth follow-up after voluntary medical male circumcision in South Africa.

Background: Voluntary medical male circumcision (MC) is a biomedical HIV prevention method that requires post-operative follow-up for healing confirmation. Recent research found that a two-way texting (2wT) app providing SMS-based telehealth for MC patients was safe and reduced provider workload. We evaluated 2wT usability among MC clients in South Africa assigned the 2wT intervention within a larger randomized controlled trial (RCT) of 2wT safety and workload. Methods: This quantitative usability study is within an RCT where 547 men used 2wT to interact with an MC provider via SMS. The sub-study involved the first 100 men assigned to 2wT who completed a usability survey 14 days after surgery. Acceptability was assessed through 2wT response rates of the 547 men. Regression models analyzed associations between age, wage, location, potential adverse events (AEs), and 2wT responses. Results: Men assigned to 2wT found it safe, comfortable, and convenient, reporting time and cost savings. High response rates (88%) to daily messages indicated acceptability. Age, wage, and location didn't affect text responses or potential AEs. Conclusion: 2wT for post-MC follow-up was highly usable and acceptable, suggesting its viability as an alternative to in-person visits. It enhanced confidence in wound self-management. This SMS-based telehealth can enhance MC care quality and be adapted to similar contexts for independent healing support, particularly for men.

Effect of eIF2α in Neuronal Injury Induced by High Glucose and the Protective Mechanism of Resveratrol.

Diabetes mellitus (DM) is a type of metabolic disease characterized by chronic hyperglycemia, which can lead to different degrees of cognitive decline. Therefore, it is crucial to explore the molecular biological mechanisms of neuronal injury. In this study, we investigated the effect of high glucose on eIF2α expression and the mechanism of neuronal injury, and on this basis, the protective mechanism of resveratrol is explored. Treatment with 50 mM high glucose in cortical neurons increased the levels of eIF2α phosphorylation; the expressions of ATF4 and CHOP increased. ISRIB alleviated high glucose-induced neuronal injury by reducing eIF2α phosphorylation when neurons were pretreated with ISRIB before high glucose treatment. Compared with the high glucose-treated group, resveratrol pretreatment reduced eIF2α phosphorylation, the levels of its downstream molecules ATF4 and CHOP, and LDH release. Resveratrol reduced the level of cortical eIF2α phosphorylation and the expression of its downstream molecules in DM mice and improved the ability of spatial memory and learning in DM mice without affecting anxiety and motor performance. Meanwhile, resveratrol modulated the expression of Bcl-2 protein and also effectively decreased the DM-induced up-regulation of Bax, caspase-3, p53, p21, and p16. Taken together, these results suggested that high glucose caused neuronal injury through the eIF2α/ATF4/CHOP pathway which was inhibited by ISRIB and resveratrol. The present study indicates that eIF2α is the new target for the treatment of high glucose-induced neuronal injury, and resveratrol is a potential new medicine to treat diabetes encephalopathy.

A 4D Theoretical Framework for Measuring Topic-Specific Influence on Twitter: Development and Usability Study on Dietary Sodium Tweets.

BACKGROUND: Social media has emerged as a prominent approach for health education and promotion. However, it is challenging to understand how to best promote health-related information on social media platforms such as Twitter. Despite commercial tools and prior studies attempting to analyze influence, there is a gap to fill in developing a publicly accessible and consolidated framework to measure influence and analyze dissemination strategies. OBJECTIVE: We aimed to develop a theoretical framework to measure topic-specific user influence on Twitter and to examine its usability by analyzing dietary sodium tweets to support public health agencies in improving their dissemination strategies. METHODS: We designed a consolidated framework for measuring influence that can capture topic-specific tweeting behaviors. The core of the framework is a summary indicator of influence decomposable into 4 dimensions: activity, priority, originality, and popularity. These measures can be easily visualized and efficiently computed for any Twitter account without the need for private access. We demonstrated the proposed methods by using a case study on dietary sodium tweets with sampled stakeholders and then compared the framework with a traditional measure of influence. RESULTS: More than half a million dietary sodium tweets from 2006 to 2022 were retrieved for 16 US domestic and international stakeholders in 4 categories, that is, public agencies, academic institutions, professional associations, and experts. We discovered that World Health Organization, American Heart Association, Food and Agriculture Organization of the United Nations (UN-FAO), and World Action on Salt (WASH) were the top 4 sodium influencers in the sample. Each had different strengths and weaknesses in their dissemination strategies, and 2 stakeholders with similar overall influence, that is, UN-FAO and WASH, could have significantly different tweeting patterns. In addition, we identified exemplars in each dimension of influence. Regarding tweeting activity, a dedicated expert published more sodium tweets than any organization in the sample in the past 16 years. In terms of priority, WASH had more than half of its tweets dedicated to sodium. UN-FAO had both the highest proportion of original sodium tweets and posted the most popular sodium tweets among all sampled stakeholders. Regardless of excellence in 1 dimension, the 4 most influential stakeholders excelled in at least 2 out of 4 dimensions of influence. CONCLUSIONS: Our findings demonstrate that our method not only aligned with a traditional measure of influence but also advanced influence analysis by analyzing the 4 dimensions that contribute to topic-specific influence. This consolidated framework provides quantifiable measures for public health entities to understand their bottleneck of influence and refine their social media campaign strategies. Our framework can be applied to improve the dissemination of other health topics as well as assist policy makers and public campaign experts to maximize population impact.

The water extract of Potentilla discolor Bunge (PDW) ameliorates high-sugar diet-induced type II diabetes model in Drosophila melanogaster via JAK/STAT signaling.

ETHNOPHARMACOLOGICAL RELEVANCE: Potentilla discolor Bunge (PD) is a member of the Rosaceae family. It has been traditionally used in folk medicine for the treatment of diabetes. Additionally, people in folk also eat fresh and tender PD stems as vegetables or brew them as tea. AIM OF THE STUDY: The aim of this study was to explore the antidiabetic effects and underlying mechanisms of the water extract of Potentilla discolor (PDW) in a fruit fly model of high-sugar diet-induced type 2 diabetes. MATERIALS AND METHODS: The antidiabetic efficacy of PDW was evaluated in a fruit fly model of diabetes induced by a high-sugar diet (HSD). Various physiological parameters were tested to evaluate the anti-diabetic effect of PDW. Gene expression levels related to insulin signaling pathways, glucose metabolism, lipid metabolism, and JAK/STAT signaling pathways were primarily analyzed using RT-qPCR to investigate the therapeutic mechanisms. RESULTS: In this study, we found that the water extract of Potentilla discolor (PDW) can ameliorate type II diabetes phenotypes induced by the HSD in fruit flies. These phenotypes include growth rate, body size, hyperglycemia, glycogen metabolism, fat storage, and intestinal microflora homeostasis. PDW also improved the body size of s6k and rheb knockdown flies, suggesting its potential to activate the downstream insulin pathway and alleviate insulin resistance. Furthermore, we demonstrated that PDW reduced the expression of two target genes of the JAK/STAT signaling pathway, namely the insulin antagonist Impl2 and insulin receptor inhibitor Socs36E, which act as regulators inhibiting the activation of the insulin signaling pathway. CONCLUSIONS: This study provides evidence for the anti-diabetic activity of PDW and suggests that its underlying mechanism may involve the improvement of insulin resistance by inhibiting the JAK/STAT signaling pathway.

Expanding the Evidence on the Safety and Efficiency of 2-Way Text Messaging-Based Telehealth for Voluntary Medical Male Circumcision Follow-up Compared With In-Person Reviews: Randomized Controlled Trial in Rural and Urban South Africa.

BACKGROUND: There is a dearth of high-quality evidence from digital health interventions in routine program settings in low- and middle-income countries. We previously conducted a randomized controlled trial (RCT) in Zimbabwe, demonstrating that 2-way texting (2wT) was safe and effective for follow-up after adult voluntary medical male circumcision (VMMC). OBJECTIVE: To demonstrate the replicability of 2wT, we conducted a larger RCT in both urban and rural VMMC settings in South Africa to determine whether 2wT improves adverse event (AE) ascertainment and, therefore, the quality of follow-up after VMMC while reducing health care workers' workload. METHODS: A prospective, unblinded, noninferiority RCT was conducted among adult participants who underwent VMMC with cell phones randomized in a 1:1 ratio between 2wT and control (routine care) in North West and Gauteng provinces. The 2wT participants responded to a daily SMS text message with in-person follow-up only if desired or an AE was suspected. The control group was requested to make in-person visits on postoperative days 2 and 7 as per national VMMC guidelines. All participants were asked to return on postoperative day 14 for study-specific review. Safety (cumulative AEs ≤day 14 visit) and workload (number of in-person follow-up visits) were compared. Differences in cumulative AEs were calculated between groups. Noninferiority was prespecified with a margin of -0.25%. The Manning score method was used to calculate 95% CIs. RESULTS: The study was conducted between June 7, 2021, and February 21, 2022. In total, 1084 men were enrolled (2wT: n=547, 50.5%, control: n=537, 49.5%), with near-equal proportions of rural and urban participants. Cumulative AEs were identified in 2.3% (95% CI 1.3-4.1) of 2wT participants and 1.0% (95% CI 0.4-2.3) of control participants, demonstrating noninferiority (1-sided 95% CI -0.09 to ∞). Among the 2wT participants, 11 AEs (9 moderate and 2 severe) were identified, compared with 5 AEs (all moderate) among the control participants-a nonsignificant difference in AE rates (P=.13). The 2wT participants attended 0.22 visits, and the control participants attended 1.34 visits-a significant reduction in follow-up visit workload (P<.001). The 2wT approach reduced unnecessary postoperative visits by 84.8%. Daily response rates ranged from 86% on day 3 to 74% on day 13. Among the 2wT participants, 94% (514/547) responded to ≥1 daily SMS text messages over 13 days. CONCLUSIONS: Across rural and urban contexts in South Africa, 2wT was noninferior to routine in-person visits for AE ascertainment, demonstrating 2wT safety. The 2wT approach also significantly reduced the follow-up visit workload, improving efficiency. These results strongly suggest that 2wT provides quality VMMC follow-up and should be adopted at scale. Adaptation of the 2wT telehealth approach to other acute follow-up care contexts could extend these gains beyond VMMC. TRIAL REGISTRATION: ClinicalTrials.gov NCT04327271; https://www.clinicaltrials.gov/ct2/show/NCT04327271.

Cost savings in male circumcision post-operative care using two-way text-based follow-up in rural and urban South Africa.

Introduction: Voluntary medical male circumcision (VMMC) clients are required to attend multiple post-operative follow-up visits in South Africa. However, with demonstrated VMMC safety, stretched clinic staff in SA may conduct more than 400,000 unnecessary reviews for males without complications, annually. Embedded into a randomized controlled trial (RCT) to test safety of two-way, text-based (2wT) follow-up as compared to routine in-person visits among adult clients, the objective of this study was to compare 2wT and routine post-VMMC care costs in rural and urban South African settings. Methods: Activity-based costing (ABC) estimated the costs of post-VMMC care, including counselling, follow-ups, and tracing in $US dollars. Transportation for VMMC and follow-up was provided for rural clients in outreach settings but not for urban clients in static sites. Data were collected from National Department of Health VMMC forms, RCT databases, and time-and-motion surveys. Sensitivity analysis presents different follow-up scenarios. We hypothesized that 2wT would save per-client costs overall, with higher savings in rural settings. Results: VMMC program costs were estimated from 1,084 RCT clients: 537 in routine care and 547 in 2wT. On average, 2wT saved $3.56 per client as compared to routine care. By location, 2wT saved $7.73 per rural client and increased urban costs by $0.59 per client. 2wT would save $2.16 and $7.02 in follow-up program costs if men attended one or two post-VMMC visits, respectively. Conclusion: Quality 2wT follow-up care reduces overall post-VMMC care costs by supporting most men to heal at home while triaging clients with potential complications to timely, in-person care. 2wT saves more in rural areas where 2wT offsets transportation costs. Minimal additional 2wT costs in urban areas reflect high care quality and client engagement, a worthy investment for improved VMMC service delivery. 2wT scale-up in South Africa could significantly reduce overall VMMC costs while maintaining service quality.

MAD2B Blunts Chronic Unpredictable Stress and Corticosterone Stimulation-Induced Depression-Like Behaviors in Mice.

BACKGROUND: Depression is a prevalent and recurrent psychiatric disorder. Aberrant neural structure and activity play fundamental roles in the occurrence of depression. Mitotic arrest deficient protein (MAD2B) is highly expressed in neurons and may be implicated in synaptic plasticity in the central nervous system. However, the effect of MAD2B in depression, as well as the related molecular mechanism, is uncertain. METHODS: Here, we employed mouse models of depression induced by chronic unpredictable stress exposure or corticosterone (CORT) stimulation. Depression-like behaviors in mice were evaluated by sucrose preference, forced swimming, and tail suspension tests. Hippocampal MAD2B overexpression was mediated by adeno-associated virus 8 containing enhanced green fluorescent protein. In vitro primary neuronal cells were obtained from the hippocampus of rat embryos and were treated with CORT, and MAD2B overexpression was performed using lentivirus. MAD2B and glutamate metabotropic receptor 4 (GRM4) levels were evaluated by western blots and quantitative PCR. Primary neuronal miR-29b-3p expression was detected by quantitative PCR. RESULTS: MAD2B expression was reduced in the hippocampus in mice exhibiting depressive-like behaviors. However, hippocampal MAD2B overexpression protected mice from developing either chronic unpredictable stress- or CORT-induced depression-like behaviors, an effect associated with reduced expression of GRM4, a presynaptic receptor involved in depression. Moreover, MAD2B overexpression in primary neuronal cells also decreased GRM4 expression while enhancing the level of miR-29b-3p; this phenomenon was also observed under CORT stimulation. CONCLUSIONS: Our results suggest an important role of neuronal MAD2B in the pathogenesis of depression via the miR-29b-3p/GRM4 signaling pathway. MAD2B could be a potential therapeutic target for depressive disorders.

Projecting Long-Term Care Costs for Home and Community-Based Services in China from 2005 to 2050.

OBJECTIVES: The aim of this study was to estimate and project the trend in long-term care (LTC) costs for home and community-based services as a percentage of gross domestic product in China between 2005 and 2050. DESIGN: Longitudinal. SETTING AND PARTICIPANTS: We used 61,249 observations from 37,702 adults age ≥65 years from waves 2005, 2008, 2011, 2014, and 2018 of the Chinese Longitudinal Healthy Longevity Surveys. METHODS: LTC costs for home and community-based services consisted of the monetary value of time spent on LTC and the direct LTC cost. We used the age-sex-residence-specific weights provided by the Chinese Longitudinal Healthy Longevity Surveys to estimate the LTC costs from 2005 to 2018. We used a component-based model to project LTC costs, in which the 2-part model was used to estimate the average LTC costs and the multi-state Markov model approach was used to project the future population by age, sex, and disability state. RESULTS: The percentage of older adults with disabilities was projected to increase from 6.1% in 2005 to 7.5% in 2020 and 9.6% in 2050. The total LTC cost for home and community-based services were projected to increase from 0.3% of gross domestic product in 2005 to 0.7% in 2020 and to 6.4% in 2050. CONCLUSIONS AND IMPLICATIONS: Policymakers in China should take urgent actions to delay the onset of disabilities among older adults, which would curb the increasing LTC costs and maintain the sustainability of the LTC policies.

Conditional deletion of MAD2B in forebrain neurons enhances hippocampus-dependent learning and memory in mice.

Mitotic arrest deficient 2-like protein 2 (MAD2B) is not only a DNA damage repair agent but also a cell cycle regulator that is widely expressed in the hippocampus and the cerebral cortex. However, the functions of MAD2B in hippocampal and cerebral cortical neurons are poorly understood. In this study, we crossed MAD2B flox/flox and calcium/calmodulin-dependent protein kinase II alpha (Camk2a)-Cre mice to conditionally knock out MAD2B in the forebrain pyramidal neurons by the Cre/loxP recombinase system. First, RNA sequencing suggested that the differentially expressed genes in the hippocampus and the cerebral cortex between the WT and the MAD2B cKO mice were related to learning and memory. Then, the results of behavioral tests, including the Morris water maze test, the novel object recognition test, and the contextual fear conditioning experiment, suggested that the learning and memory abilities of the MAD2B cKO mice had improved. Moreover, conditional knockout of MAD2B increased the number of neurons without affecting the number of glial cells in the hippocampal CA1 and the cerebral cortex. At the same time, the number of doublecortin-positive (DCX+) cells was increased in the dentate gyrus (DG) of the MAD2B cKO mice. In addition, as shown by Golgi staining, the MAD2B cKO mice had more mushroom-like and long-like spines than the WT mice. Transmission electron microscopy (TEM) revealed that spine synapses increased and shaft synapses decreased in the CA1 of the MAD2B cKO mice. Taken together, our findings indicated that MAD2B plays an essential role in regulating learning and memory.

Delayed diagnosis of complex glycerol kinase deficiency in a Chinese male infant: a case report.

BACKGROUND: Xp21 contiguous gene deletion syndrome is a rare genetic metabolic disorder with poor prognosis in infants, involving deletions of one or more genes in Xp21. When deletions of adrenal hypoplasia (AHC), Duchenne muscular dystrophy (DMD), and chronic granulomatosis (CGD) loci are included, complex glycerol kinase deficiency (CGKD) can be diagnosed. We present a case of CGKD that was initially misdiagnosed and died during treatment in our hospital in terms of improving our understanding of the clinical features and diagnosis of this disease, as well as highlighting the need for more precise dosing of corticosteroid replacement therapy. CASE PRESENTATION: A 48-day-old full-term male infant was transferred to our medical center with global growth delay and persistent vomiting. Routine laboratory tests revealed hyperkalemia, hyponatremia, and a high level of creatine kinase. The initial diagnosis was adrenal cortical hyperplasia (ACH), then revised to adrenocortical insufficiency with a normal level of ACTH detected. After supplementing the routine lipid test and urinary glycerol test, CGKD was diagnosed clinically due to positive triglyceridemia and urinary glycerol, and the follow-up gene screening further confirmed the diagnosis. The boy kept thriving after corticosteroid replacement and salt supplementation. While levels of serum ACTH and cortisol decreased and remained low after corticosteroid replacement was administered. The patient died of acute type 2 respiratory failure and hypoglycemia after an acute upper respiratory tract infection, which may be the result of adrenal crisis after infection. Infants with CGKD have a poor prognosis, so physicians should administer regular follow-ups, and parents counseling during treatment to improve the survival of patients. CONCLUSIONS: Overall, CGKD, although rare, cannot be easily excluded in children with persistent vomiting. Extensive blood tests can help to detect abnormal indicators. Adrenal crisis needs to be avoided as much as possible during corticosteroid replacement therapy.