Search

IntroductionAn 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.MethodsHere, 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.ResultsWe 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.DiscussionOur 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.

Abstract 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.

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.

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

Abstract 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.

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.

BackgroundSocial 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. ObjectiveWe 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. MethodsWe 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. ResultsMore 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. ConclusionsOur 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.

Abstract Background Aconitum carmichaelii, the mother root of Aconitum, has a long‐applied history for treating many diseases in China. Increased use of it has prompted significant concerns regarding its extensive cardiotoxicity and neurotoxicity. The molecular mechanisms underlying A. carmichaelii‐induced neurotoxicity are poorly understood. Methods We took advantage of the zebrafish model to investigate the neurotoxic mechanism of A. carmichaelii. In addition to the behavior and neuronal activity testing, gene expression of neuronal oxidative stress, and apoptosis levels were also analyzed. Results In contrast to the excitatory effect of low‐dose A. carmichaelii decoction, hypoactivity of locomotor behavior, and neural activity, especially telencephalon, were detected in the 20 mg/mL group. High doses of A. carmichaelii induced excessive ROS by downregulating DJ‐1 and activating Nox5, and further triggered cell apoptosis through the bax/bcl2a‐caspase‐9 pathway in zebrafish larva. Mitochondrial protection‐related genes PinK1 and Parkin were upregulated to protect against mitochondrial dysfunction during cellular stress. The ROS scavenger‐NAC significantly alleviated neurotoxicity in the 20 mg/mL group. Conclusion The study reveals the potential mechanism of A. carmichaelii‐induced neurotoxicity and provides new insights into a significant risk marker of A. carmichaelii poisoning.

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.

BackgroundThere 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). ObjectiveTo 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. MethodsA 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. ResultsThe 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

IntroductionVoluntary 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.MethodsActivity-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.ResultsVMMC 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.ConclusionQuality 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.

Parkinson's disease is the second most prevalent neurodegenerative disease after Alzheimer's disease, mostly happened in the elder population and the prevalence gradually increased with age. Parkinson’s disease is a movement disorder that severely affects patients’ daily life. The mechanism of Parkinson’s disease still remains unknown, however, studies already proved that the damage or absence of dopaminergic neurons located in the substantia nigra and the decreased dopamine in the striatum are significantly related to Parkinson’s disease. To date, the mainstream treatment of Parkinson's disease has been achieved by alleviating its associated morbid symptoms, such as the use of levodopa, carbidopa, dopamine receptor agonists, monoamine oxidase type B inhibitors, anticholinergic drugs, etc. However, strong side effects, even toxicity, have been reported after using these drugs, with reduced effectiveness over time. Plant compounds have shown good therapeutic effects in neurodegenerative diseases as a less toxic treatment. In this review, we have compiled several natural plant compounds and classified the currently reported compounds for therapeutic use based on their structural parent nuclei and constituent elements. We wish to inspire new ideas for the treatment of Parkinson's disease by summarizing their mechanisms.

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 MAD2Bflox/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.

BackgroundRoad traffic injury is a pressing public health issue in Tanzania. Increasing helmet use among motorcycle drivers can help reduce the burden due to road traffic injuries in the country. Helmet adherence can be supported through mobile health interventions. ObjectiveThe aim of this study is to evaluate the comparative impact of two different types of SMS text messaging reminders on motorcycle helmet use. MethodsParticipants were 391 commercial motorcycle taxi drivers in Dar es Salaam, Tanzania. Participants were randomized into three groups, each receiving a different set of messages: (1) social norming messages aimed at emphasizing society’s positive stance on helmet wearing, (2) fear appeal messages that emphasized the dangers of riding without a helmet, and (3) control group messages, which included basic road safety messages unrelated to helmet use. Every participant received the control messages. Adherence to helmet use was evaluated by self-report through surveys conducted at baseline, 3 weeks, and 6 weeks. ResultsAt 6 weeks, the odds of self-reporting consistent helmet use were estimated to be 1.58 times higher in the social norming group than in the control group (P=.04), though this difference was not significant after accounting for multiple testing. There was little difference between fear appeal and control group recipients (odds ratio 1.03, P=.47). Subgroup analysis suggests that both fear appeal and social norming message types might have been associated with increased helmet use among participants who did not consistently wear helmets at baseline (odds ratio 1.66 and odds ratio 1.84, respectively), but this was not significant (P=.11 and P=.07, respectively). Among those who were consistent wearers at baseline, the social norming messages performed better than the fear appeal messages, and this difference reached traditional significance (P=.03), but was not significant after accounting for multiple testing. ConclusionsThe use of SMS text messaging reminders may improve helmet use among motorcycle drivers when framed as social norming messages. Given that nearly half of the drivers in our sample did not consistently wear their helmets on every trip, strategies to increase consistent usage could greatly benefit public safety. Trial RegistrationClinicalTrials.gov NCT02120742; https://clinicaltrials.gov/ct2/show/NCT02120742

Abstract Background Microcephalic osteodysplastic primordial dwarfism type II (MOPD II) is a rare autosomal recessive disorder characterized by severe pre‐ and postnatal growth restrictions, microcephaly, skeletal dysplasia, severe teeth deformities, and typical facial features. Previous studies have shown that MOPD II is associated with mutations in the pericentrin (PCNT) gene. Methods We evaluated the clinical features of a 10‐year and 7‐month‐old Chinese girl with MOPD II. Subsequently, next‐generation sequencing and flow cytometry were performed to investigate genetic characteristics and the expression of PCNT protein respectively. Results The patient presented with short stature, microcephaly, typical craniofacial features, teeth deformity, thrombocytosis, and a delayed bone age (approximately 7 years). No abnormality in growth hormone or insulin‐like growth factor 1 was detected. Notably, the patient was found to carry a novel homozygous PCNT mutation (c.6157G>T, p.Glu2053Ter), which was inherited from her healthy heterozygous parents. Meanwhile, significant deficiency of PCNT expression was identified in the patient. Conclusion Our study identified a novel PCNT mutation associated with MOPD II, expanded the mutation spectrum of the PCNT gene and improved our understanding of the molecular basis of MOPD II.

Introduction As the world responds to COVID-19 and aims for the Sustainable Development Goals, the potential for primary healthcare (PHC) is substantial, although the trends and effectiveness of PHC expenditure are unknown. We estimate PHC expenditure for each low-income and middle-income country between 2000 and 2017 and test which health outputs and outcomes were associated with PHC expenditure.Methods We used three data sources to estimate PHC expenditures: recently published health expenditure estimates for each low-income and middle-income country, which were constructed using 1662 country-reported National Health Accounts; proprietary data from IQVIA to estimate expenditure of prescribed pharmaceuticals for PHC; and household surveys and costing estimates to estimate inpatient vaginal delivery expenditures. We employed regression analyses to measure the association between PHC expenditures and 15 health outcomes and intermediate health outputs.Results PHC expenditures in low-income and middle-income countries increased between 2000 and 2017, from $41 per capita (95% uncertainty interval $33–$49) to $90 ($73–$105). Expenditures for low-income countries plateaued since 2014 at $17 per capita ($15–$19). As national income increased, the proportion of health expenditures on PHC generally decrease; however, the fraction of PHC expenditures spent via ambulatory care providers grew. Increases in the fraction of health expenditures on PHC was associated with lower maternal mortality rate (p value≤0.001), improved coverage of antenatal care visits (p value≤0.001), measles vaccination (p value≤0.001) and an increase in the Health Access and Quality index (p value≤0.05). PHC expenditure was not systematically associated with all-age mortality, communicable and non-communicable disease (NCD) burden.Conclusion PHC expenditures were associated with maternal and child health but were not associated with reduction in health burden for other key causes of disability, such as NCDs. To combat changing disease burdens, policy-makers and health professionals need to adapt primary healthcare to ensure continued impact on emerging health challenges.

Background: Rheumatic heart disease (RHD) has declined dramatically in wealthier countries in the past three decades, but it remains endemic in many lower-resourced regions and can have significant costs to households. The objective of this study was to quantify the economic burden of RHD among Ugandans affected by RHD.Methods: This was a cross-sectional cost-of-illness study that randomly sampled 87 participants and their households from the Uganda National RHD registry between December 2018 and February 2020. Using a standardized survey instrument, we asked participants and household members about outpatient and inpatient RHD costs and financial coping mechanisms incurred over the past 12 months. We used descriptive statistics to analyze levels and distributions of costs and the frequency of coping strategies. Multivariate Poisson regression models were used to assess relationships between socioeconomic characteristics and utilization of financial coping mechanisms.Results: Most participants were young or women, demonstrating a wide variation in socioeconomic status. Outpatient and inpatient costs were primarily driven by transportation, medications, and laboratory tests, with overall RHD direct and indirect costs of $78 per person-year. Between 20 and 35 percent of households experienced catastrophic healthcare expenditure, with participants in the Northern and Western Regions 5–10 times more likely to experience such hardship and utilize financial coping mechanisms than counterparts in the Central Region, a wealthier area. Increases in total RHD costs were positively correlated with increasing use of coping behaviors.Conclusion: Ugandan households affected by RHD, particularly in lower-income areas, incur out-of-pocket costs that are very high relative to income, exacerbating the poverty trap. Universal health coverage policy reforms in Uganda should include mechanisms to reduce or eliminate out-of-pocket expenditures for RHD and other chronic diseases.

Abstract Background Bone damage is a condition that affects the quality of life of patients. Mesenchymal stem cells (MSCs) are important for bone repair. Osteoking is a natural compound in traditional Chinese Medicine used to treat bone diseases; however, the effect of Osteoking on the differentiation of MSCs has not been reported. In this study, we aimed to investigate the effect of Osteoking on the osteogenic and adipogenic differentiation potential of rat bone marrow mesenchymal stem cells (rbMSCs). Methods The effects of Osteoking on the proliferation and differentiation of rbMSCs were investigated. Different concentrations of Osteoking were prepared, and its cytotoxicity was evaluated by CCK-8 assay. The expression of osteogenic and adipogenic genes were determined, and several staining methods were used to reveal the osteogenic and adipogenic differentiation potential of rbMSCs. Results Our results show that appropriate concentrations of Osteoking can enhance osteogenic differentiation of rbMSCs and reduce adipogenic differentiation without any effect on proliferation. This may be related to the changes in related gene expression. Conclusion Osteoking enhances osteogenic differentiation and inhibits adipogenic differentiation of rbMSCs. Therefore, Osteoking may have a therapeutic potential for treating bone disease caused by changes in differentiation function of MSCs.

Modulator of apoptosis protein1 (MOAP1), also known as MAP1 and PNMA4, belongs to the PNMA gene family consisting of at least 15 genes located on different chromosomes. MOAP1 interacts with the BAX protein, one of the most important apoptosis regulators. Due to its critical role in a few of disease-associated pathways, MOAP1 is associated with many diseases such as cancers and neurological diseases. In this study, we introduced MOAP1 and its biological functions and reviewed the associations between MOAP1 and a few diseases including cancers, neurological diseases, and other diseases such as inflammation and heart diseases. We also explained possible biological mechanisms underlying the associations between MOAP1 and these diseases, and discussed a few future directions regarding MOAP1, especially its potential roles in neurodegenerative disorders. In summary, MOAP1 plays a critical role in the development and progression of cancers and neurological diseases by regulating a few genes related to cellular apoptosis such as BAX and RASSF1A and interacting with disease-associated miRNAs, including miR-25 and miR1228.

A 3D finite element (FE) model is built to numerically analyze heating parameters on temperature during brazing diamond grains by the pulsed laser spot heating. A pulsed Nd:YAG laser is used for experimental validation. The results show that during laser heating, the temperature varies periodically because of the pulsed heat flux. Four key thermal indices, the maximum temperature Tmax, the minimum temperature Tmin, the average temperature Tav and the temperature fluctuation amplitude ΔT are addressed. The primary factor affecting Tmax, ΔT and Tav is the pulse power and on Tmin is the pulse frequency. The secondary effect factor on Tmax, Tav and ΔT is the pulse width and on Tmin is the pulse power. For engineering practice, the order of designing heating parameters is recommended as: pulse power, second frequency and last width.

ObjectiveWith a quasi-experimental design, this study aims to assess whether the Zero-markup Policy for Essential Drugs (ZPED) reduces the medical expense for patients at county hospitals, the major healthcare provider in rural China.MethodsData from Ningshan county hospital and Zhenping county hospital, China, include 2014 outpatient records and 9239 inpatient records. Quantitative methods are employed to evaluate ZPED. Both hospital-data difference-in-differences and individual-data regressions are applied to analyze the data from inpatient and outpatient departments.ResultsIn absolute terms, the total expense per visit reduced by 19.02 CNY (3.12 USD) for outpatient services and 399.6 CNY (65.60 USD) for inpatient services. In relative terms, the expense per visit was reduced by 11% for both outpatient and inpatient services. Due to the reduction of inpatient expense, the estimated reduction of outpatient visits is 2% among the general population and 3.39% among users of outpatient services. The drug expense per visit dropped by 27.20 CNY (4.47 USD) for outpatient services and 278.7 CNY (45.75 USD) for inpatient services. The proportion of drug expense out of total expense per visit dropped by 11.73 percentage points in outpatient visits and by 3.92 percentage points in inpatient visits.ConclusionImplementation of ZPED is a benefit for patients in both absolute and relative terms. The absolute monetary reduction of the per-visit inpatient expense is 20 times of that in outpatient care. According to cross-price elasticity, the substitution between inpatient and outpatient due to the change in inpatient price is small. Furthermore, given that the relative reductions are the same for outpatient and inpatient visits, according to relative thinking theory, the incentive to utilize outpatient or inpatient care attributed to ZPED is equivalent, regardless of the 20-times price difference in absolute terms.

This article explores the need to reevaluate policy implementation science in a global context, particularly in low-resource settings in the Global South. It highlights the limitations of existing frameworks, which are often based on Global North perspectives and may not be applicable to diverse settings. The article suggests incorporating traditional implementation science and political science theories to develop more effective frameworks that consider power dynamics and stakeholder collaboration. It also emphasizes the importance of adapting universal health coverage policies to fit different governance structures and resource contexts. The text includes case studies from Pakistan and Rwanda to illustrate the importance of tailoring policies to local contexts. The authors argue for refining policy implementation science frameworks to address these issues and promote evidence-based policymaking in global health. The article provides a list of references that offer valuable insights and research findings for library patrons conducting research on related topics. [Extracted from the article]

The glycolytic enzyme cytoplasmic glyceraldehyde-3-phosphate dehydrogenase (GAPC3) is involved in multiple biological processes in plants, including transcriptional regulation, and material metabolism. However, the relationship between OsGAPC3 and the quality traits of rice is poorly understood. Here we identify OsGAPC3 mutations that enhance the protein content and grain nutritional quality of rice by regulating the OsAAP6 gene expression. The number and volume of type-II protein bodies in the endosperm of the OsGAPC3 mutants, and GPC increase significantly. We report significant increases in chalkiness area and degree, and decreases for starch content, gel consistency, and taste value. Results of proteomic detection and analysis reveal that OsGAPC3 affects the major storage substances (proteins and starch) metabolism in rice, and the accumulation of proteins and starch in the endosperm. Additionally, the OsGAPC3 mutation significantly decreases the rice-seedling salt tolerance. Therefore, OsGAPC3 affects multiple quality traits of rice, participates in regulating rice-seedling salt-stress response. These data can be used to design better-quality and stronger salt-resistant rice varieties.

This study aimed to investigate the interfacial behaviour of caseins in different micelle content and its effect on the stability of emulsions, including micellar casein concentrate (MCN), calcium caseinate (CaC) and sodium caseinate (NaC). Results revealed that at high protein concentrations (0.5 %–2.5 %), MCN, CaC and NaC exhibited similar interfacial behaviour as well as unfolding rate constants (k1) of 3.11–3.41 × 10−4 (s−1), 2.96–3.35 × 10−4 (s−1) and 2.75–3.27 × 10−4 (s−1), respectively. The interfacial layer formed was dominated by non-micelles, and microscopic images revealed the thickness of the interfacial layer to be 10–20 nm. By contrast, at low concentrations, the differences in the slope of E–π curves and k1 indicated that the micelle content of casein affects protein interfacial behaviour and properties and that micellar casein is involved in the formation of the interfacial layer. The formation of large numbers of droplets during emulsion preparation results in a similar low concentration environment. Cryo-TEM showed adsorption of micellar casein in all three casein-stabilised emulsions, and the amount of adsorption was proportional to the micelle content. NaC has faster adsorption and rearrangement rates due to fewer micelles and more non-micelles, so that NaC forms smaller droplets and more stable emulsions than those formed by MCN and CaC within the range of 0.5 % to 2.0 %.

ABSTRACT Loquat (Eriobotrya japonica Lindl.) is a kind of subtropical fruit cultivated in many countries. This study aimed to evaluate the changes in the content of total phenol, total flavonoid, and 1,1-Diphenyl-2-picrylhydrazyl (DPPH), scavenging activity during the seven developmental stages and to determine the optimum harvesting time of loquat fruits by using chlorophyll fluorescence and Red Green Blue (RGB) intensity detection. Our results revealed a high correlation between chlorophyll fluorescence parameters and the internal chemical parameters (total phenol, total flavonoid, and DPPH scavenging activity) in loquat. The best prediction model from ST1 to ST5 for total flavonoid with variable fluorescence (Fv) and Fv / maximum fluorescence (Fm), R 2 = 0.79, and for DPPH scavenging activity with Fm, Fv, and Fv/Fm, R 2 = 0.92 was achieved, respectively. Total phenol correlated with minimum fluorescence (Fo) and Fv from ST4 to ST7, with R 2 = 0.99. Red Green Blue (RGB) intensity is also highly correlated with the internal chemical parameters. Both total phenol and DPPH radical scavenging activities had the best correlations with the B intensity value (R 2 = 0.998, R 2 = 0.970) in the ST1-ST4 period, respectively. Total phenols and total flavonoids had the best correlation with the G intensity value (R 2 = 0.909, R 2 = 0.986) in the ST5-ST7 period, respectively. In conclusion, developmental stage ST5 is the optimum harvesting time for loquat fruit, and chlorophyll fluorescence and RGB intensity are both noninvasive measurements for quality assessment during the loquat development period and for the prediction of the optimal time for harvesting loquat fruit.