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Abstract It is not uncommon for malicious sellers to collude with fake reviewers (also called spammers) to write fake reviews for multiple products to either demote competitors or promote their products’ reputations, forming a gray industry chain. To detect spammer groups in a heterogeneous network with rich semantic information from both buyers and sellers, researchers have conducted extensive research using Frequent Item Mining-based and graph-based methods. However, these methods cannot detect spammer groups with cross-product attacks and do not jointly consider structural and attribute features, and structure-attribute correlation, resulting in poorer detection performance. Therefore, we propose a collaborative training-based spammer group detection algorithm by constructing a heterogeneous induced sub-network based on the target product set to detect cross-product attack spammer groups. To jointly consider all available features, we use the collaborative training method to learn the feature representations of nodes. In addition, we use the DBSCAN clustering method to generate candidate groups, exclude innocent ones, and rank them to obtain spammer groups. The experimental results on real-world datasets indicate that the overall detection performance of the proposed method is better than that of the baseline methods.

Data envelopment analysis (DEA) has been used for decades to investigate utility efficiency- and management-specific features. DEA has been extended in various industries with different models that consume different types of production variables to meet industry-specific efficiencies. However, the discernment of production variables and proper DEA models is still a problem in the water industry. Ratio information has been used in DEA for absolute data to assess utility efficiency- and management-specific features; using ratios in DEA for absolute data produces wrong efficiency results because the convexity axiom of DEA for absolute data is not satisfied. This study presents a collection of information and an assessment of DEA for absolute and ratio data to identify the strengths of the production variables and the DEA model that are appropriate for assessing utility efficiency- and management-specific features. The analysis shows that the use of ratio variables in DEA for ratios improves utility economics, the working environment, and the social trust dimension. HIGHLIGHTS DEA models and production variable selection.; Proper utility benchmarking and DEA model choices.; Efficient utility benchmarking.; Using performance indicators as production variables in DEA.; Efficiency comparison.;

Urban water utility (UWU) regulation has been a potential practice in the water industry for years. This is because UWUs operate in an environment without competitors, and regulating them in a competitive scenario under sunshine regulation helps UWUs simulate the best management strategies. During efficiency assessment, the selection of the best, intermediate and least performing UWUs involves averaging scores of many efficiency assessment criteria analysed separately. This study expands a UWU efficiency assessment based on attaining service-level-benchmark and agreed target-level criteria using network data envelopment analysis (NDEA) for ratios. The assessment shows that the average of efficiencies of the two criteria identify a UWU with the best and worst performance in selected key indicators. HIGHLIGHTS Utility benchmarking in a competitive scenario using DEA for ratios.; Regulation with performance improvement.; Employment of service benchmark approach to analyze a utility's efficiency.; Selection of the most efficient utility using non-parametric method.; Application of Network DEA in regulation of a water utility.;

This study examined the effects of Spaceteam ESL, a digital shouting game, on the development of oral reading fluency (ORF) among 71 English as a second language (ESL) students in three primary and secondary schools in Mombasa, Kenya. Following a mixed-methods approach for data collection and analysis, we pre-tested and post-tested the participants on their ability to read aloud efficiently (speed) and accurately (accuracy) in three tasks: (1) phrases extracted from the game; (2) phrases not related to the game; and (3) a short anecdote. Paired-samples t-tests results revealed that, as hypothesized, participants who played Spaceteam ESL improved their ORF on measures of speed on all tasks, possibly because of the fast-paced nature of the game. However, no significant differences were observed in terms of accuracy due to a ceiling effect: the participants had already mastered the intricacies of the letter-to-sound rules of English orthography. Overall, these findings corroborate our hypothesis that some of the affordances of Spaceteam ESL (e.g., focus on speed reading, multiple and varied opportunities for practice) could contribute to the development of some aspects of oral reading fluency.

Short-form video platforms have become an important marketing channel for library resources and services. However, such promotions’ actual performance is not as good as expected. This research examined the performance of library marketing on the dominant short-form video platform in China, Douyin (aka TikTok worldwide), with social media analytics, including topic and correlation analysis. Results indicated that the number of fans of an account is positively correlated with the number of likes (p < 0.001) and independent of the number of videos (p > 0.05). Libraries post videos most often on the topic of “Reading Promotion”(31%), but the marketing performance on this topic is average (Mean DMI = 90.27). The most popular topics for patrons are “Hot Topics” and “Knowledge Quiz” (Mean DMI = 207.00). Using short-form videos for library marketing is a new practice, and scant studies have evaluated such performance, especially in Asia. Our results strengthen library practitioners’ awareness and reflections on conducting new media services and short-form video promotion, especially for the newer generation.

The world is witnessing an unpredictable COVID-19 pandemic that has impacted all levels of online education, shaping future trends. However, this shift was so sudden and drastic that unrevealed puzzles exist regarding the public’s authentic opinion towards online classes, even though three years have passed. Many experts and policymakers have conducted qualitative and quantitative research to explore effective pedagogies, the satisfaction of different stakeholders, and factors influential on learners’ performance. However, scant studies have examined personal opinions and concerns toward online classes hidden behind people’s anonymous posts on social media. This research investigates the sentiments, concerns, and their variance with time regarding online classes by learners and educators on Reddit, which is a dominant social network among them. Data were collected via the official API from identified relevant subreddits and keyword search results across Reddit. Sentiment analysis was applied to reveal their emotions and their changes. Topic modeling was conducted to discover the concerns hidden in the posts. The results revealed the concerns about online classes, such as severe cheating behaviors, and showed doubts about previous strategies to solve disadvantages in online classes. In addition, the results verified the habitual difference and motivations of social media usage between educators and learners.

Cervical cancer has become the most frequent female malignancy and presents as a general health challenge in many countries undergoing economic development. Various human papillomaviruses (HPV) types have appeared as one of the most critically identifiable causes of widespread cervical cancers. Conventional cervical cytological inspection has limitations of variable sensitivity according to cervical cytology. Glycobiology has been fundamental in related exploration in various gynecologic and reproductive fields and has contributed to our understanding of cervical cancer. It is associated with altered expression of N-linked glycan as well as abnormal expression of terminal glycan structures. The analytical approaches available to determine serum and tissue glycosylation, as well as potential underlying molecular mechanisms involved in the cellular glycosylation alterations, are monitored. Moreover, cellular glycosylation influences various aspects of cervical cancer biology, ranging from cell surface expressions, cell-cell adhesion, cancer signaling, cancer diagnosis, and management. In general, discoveries in glycan profiling make it technically reproducible and affordable to perform serum glycoproteomic analyses and build on previous work exploring an expanded variety of glycosylation markers in the majority of cervical cancer patients.

BackgroundHyperthermia treatment has been explored as a strategy to overcome biological barriers that hinder effective drug delivery in solid tumors. Most studies have used mild hyperthermia treatment (MHT) to target the delivery of thermo-sensitive liposomes carriers. Others have studied its application to permeabilize tumor vessels and improve tumor interstitial transport. However, the role of MHT in altering tumor vessel interfacial and adhesion properties and its relationship to improved delivery has not been established. In the present study, we evaluated effects of MHT treatment on tumor vessel flow dynamics and expression of adhesion molecules and assessed enhancement in particle localization using mesoporous silicon vectors (MSVs). We also determined the optimal time window at which maximal accumulation occur.ResultsIn this study, using intravital microscopy analyses, we showed that temporal mild hyperthermia (∼1 W/cm(2)) amplified delivery and accumulation of MSVs in orthotopic breast cancer tumors. The number of discoidal MSVs (1000×400 nm) adhering to tumor vasculature increased 6-fold for SUM159 tumors and 3-fold for MCF-7 breast cancer tumors. By flow chamber experiments and Western blotting, we established that a temporal increase in E-selectin expression correlated with enhanced particle accumulation. Furthermore, MHT treatment was shown to increase tumor perfusion in a time-dependent fashion.ConclusionsOur findings reveal that well-timed mild hyperthermia treatment can transiently elevate tumor transport and alter vascular adhesion properties and thereby provides a means to enhance tumor localization of non-thermally sensitive particles such as MSVs. Such enhancement in accumulation could be leveraged to increase therapeutic efficacy and reduce drug dosing in cancer therapy.

We report cell mechanical changes in response to alteration of expression of the human equilibrative nucleoside transporter-1 (hENT1), a most abundant and widely distributed plasma membrane nucleoside transporter in human cells and/or tissues. Modulation of hENT1 expression level altered the stiffness of pancreatic cancer Capan-1 and Panc 03.27 cells, which was analyzed by atomic force microscopy (AFM) and correlated to microfluidic platform. The hENT1 knockdown induced reduction of cellular stiffness in both of cells up to 70%. In addition, cellular phenotypic changes such as cell morphology, migration, and expression level of epithelial-mesenchymal transition (EMT) markers were observed after hENT1 knockdown. Cells with suppressed hENT1 became elongated, migrated faster, and had reduced E-cadherin and elevated N-cadherin compared to parental cells which are consistent with epithelial-mesenchymal transition (EMT). Those cellular phenotypic changes closely correlated with changes in cellular stiffness. This study suggests that hENT1 expression level affects cellular phenotype and cell elastic behavior can be a physical biomarker for quantify hENT1 expression and detect phenotypic shift. Furthermore, cell mechanics can be a critical tool in detecting disease progression and response to therapy.

Abstract Background Rotavirus has a significant morbidity and mortality in children under two years. The burden of rotavirus diarrhea 4 years post introduction of rotavirus vaccine in Uganda is not well established. This study aimed to determine the prevalence, severity of dehydration and factors associated with rotavirus diarrhea among children aged 3 to 24 months after the introduction of the vaccine at Fort Portal Regional Referral hospital. Methods This was a cross-sectional hospital-based study in which children with acute watery diarrhea were included. A rectal tube was used to collect a stool sample for those unable to provide samples. Stool was tested for rotavirus using rapid immunochromatographic assay. Data was analysed using SPSS version 22 with logistic regression done to determine the factors. Results Out of 268 children with acute watery diarrhea, 133 (49.6%) were females. Rotavirus test was positive in 42 (15.7%), majority of whom had some dehydration 28(66.7%). The factors that were independently associated with rotavirus diarrhea were; age

Inflammatory bowel disease (IBD), a condition of the digestive tract and one of the autoimmune diseases, is becoming a disease of significant global public health concern and substantial clinical burden. Various signaling pathways have been documented to modulate IBD, but the exact activation and regulatory mechanisms have not been fully clarified; thus, a need for constant exploration of the molecules and pathways that play key roles in the development of IBD. In recent years, several protein post-translational modification pathways, such as ubiquitination, phosphorylation, methylation, acetylation, and glycolysis, have been implicated in IBD. An aberrant ubiquitination in IBD is often associated with dysregulated immune responses and inflammation. Mesenchymal stem cells (MSCs) play a crucial role in regulating ubiquitination modifications through the ubiquitin-proteasome system, a cellular machinery responsible for protein degradation. Specifically, MSCs have been shown to influence the ubiquitination of key signaling molecules involved in inflammatory pathways. This paper reviews the recent research progress in MSC-regulated ubiquitination in IBD, highlighting their therapeutic potential in treating IBD and offering a promising avenue for developing targeted interventions to modulate the immune system and alleviate inflammatory conditions.

Abstract Background Chronic obstructive pulmonary disease (COPD) is the third leading cause of death worldwide among people over 40 years of age, and erythrocytosis is one of the major complications associated with increased mortality among COPD patients. The study aimed to determine the proportion of COPD, associated factors, and the burden of erythrocytosis among COPD participants. Methods and materials A descriptive cross-sectional study design was used. A consecutive sampling technique was used to obtain study participants at the Fort Portal Regional Referral Hospital outpatient clinic. Focused history and physical examination were carried out to select eligible participants. Participants were screened using the COPD population screener for spirometry after consenting to participate. The study enrolled all adults at risk of having COPD based on the COPD population screener and able to undergo spirometry. Spirometry was carried out according to the Global Chronic Obstructive Lung Disease and European Respiratory Society guidelines, and haemoglobin concentration was measured. Results One hundred eighty participants were enrolled in the study, most of whom were females. The modal and mean age of participants was 60 years with 139 (77.2%) females and primary as the highest education level 149(82.8%). The proportion of COPD was 25% (45) [95% CI 18.9 – 32] and highest among females (68.9%) and those aged 60 years and above (70%). The combined COPD assessment tool groups had a proportion of 55.6%, 37.8%, 4.4%, and 2.2% for groups A, B, C, and D, respectively. Age

ABSTRACTInflammatory bowel disease (IBD) is a chronic and debilitating condition of relapsing and remitting inflammation in the gastrointestinal tract. Conventional therapeutic approaches for IBD have shown limited efficacy and detrimental side effects, leading to the quest for novel and effective treatment options for the disease. Bacterial membrane vesicles (MVs) are nanosized lipid particles secreted by lysis or blebbing processes from both Gram-negative and Gram-positive bacteria. These vesicles, known to carry bioactive components, are facsimiles of the parent bacterium and have been implicated in the onset and progression, as well as in the amelioration of IBD. This review discusses the overview of MVs and their impact in the pathogenesis, diagnosis, and treatment of IBD. We further discuss the technical challenges facing this research area and possible research questions addressing these challenges. We summarize recent advances in the diverse relationship between IBD and MVs, and the application of this knowledge as a viable and potent therapeutic strategy for IBD.

Abstract Background Inflammatory bowel disease (IBD) is a global disease with a growing public health concern and is associated with a complex interplay of factors, including the microbiota and immune system. Resveratrol, a natural anti-inflammatory and antioxidant agent, is known to relieve IBD but the mechanism involved is largely unexplored. Methods This study examines the modulatory effect of resveratrol on intestinal immunity, microbiota, metabolites, and related functions and pathways in the BALB/c mice model of IBD. Mouse RAW264.7 macrophage cell line was used to further explore the involvement of the macrophage-arginine metabolism axis. The treatment outcome was assessed through qRT-PCR, western blot, immunofluorescence, immunohistochemistry, and fecal 16S rDNA sequencing and UHPLC/Q-TOF–MS. Results Results showed that resveratrol treatment significantly reduced disease activity index (DAI), retained mice weight, repaired colon and spleen tissues, upregulated IL-10 and the tight junction proteins Occludin and Claudin 1, and decreased pro-inflammatory cytokines IL-1β, IL-6, and TNF-α. Resveratrol reduced the number of dysregulated metabolites and improved the gut microbial community structure and diversity, including reversing changes in the phyla Bacteroidetes, Proteobacteria, and Firmicutes, increasing ‘beneficial’ genera, and decreasing potential pathogens such as Lachnoclostridium, Acinobacter, and Serratia. Arginine–proline metabolism was significantly different between the colitis-treated and untreated groups. In the colon mucosa and RAW264.7 macrophage, resveratrol regulated arginine metabolism towards colon protection by increasing Arg1 and Slc6a8 and decreasing iNOS. Conclusion This uncovers a previously unknown mechanism of resveratrol treatment in IBD and provides the microbiota-macrophage-arginine metabolism axis as a potential therapeutic target for intestinal inflammation.

Mesenchymal stem cells (MSCs) have shown great potential in the treatment of several inflammatory diseases due to their immunomodulatory ability, which is mediated by exosomes secreted by MSCs (MSC-Exs). The incidence of inflammatory bowel disease (IBD) is increasing globally, but there is currently no long-term effective treatment. As an emerging therapy, MSC-Exs have proven to be effective in alleviating IBD experimentally, and the specific mechanism continues to be explored. The gut microbiota plays an important role in the occurrence and development of IBD, and MSCs and MSC-Exs can effectively regulate gut microbiota in animal models of IBD, but the mechanism involved and whether the outcome can relieve the characteristic dysbiosis necessary to alleviate IBD still needs to be studied. This review provides current evidence on the effective modulation of the gut microbiota by MSC-Exs, offering a basis for further research on the pathogenic mechanism of IBD and MSC-Ex treatments through the improvement of gut microbiota.

Kenyan farmers' Deposit-taking Savings and Credit Co operatives (DT-SACCOs) have seen a drop in credit provision, from 9.6 % in 2022 to 5.2 % in 2023. Additionally, 52 % of these SACCOs have been declared illiquid due to imprudent lending practices. This has led to the closure or license revocation of 33 % of farmers-based DT-SACCOs. To address this issue, the study aimed to assess the moderating effect of SACCO size on the relationship between lending decisions and liquidity of farmers-based DT-SACCOs. The study employed an explanatory research design and utilized self administered questionnaires. The study findings indicate that SACCO size significantly moderates the relationship between lending decisions and liquidity of farmers-based DT-SACCOs. As a recommendation, SACCOs should consider their size when making lending decisions, allowing larger SACCOs to manage more risk in loans to farmers, while smaller SACCOs may need to exercise more caution.

The review discusses students’ challenges as they move between educational levels and the labor market, mainly due to the lack of effective, efficient, and timely career guidance. The review suggests that using ontologies can improve career guidance delivery by providing a structured approach to representing and organizing career-related data. The study conducted a systematic literature review and found that ontologies have not been extensively applied in the career guidance domain. The review highlights the unique advantages of using ontologies for career guidance (CG), such as formal representation, interoperability, and knowledge representation and reasoning. The review also points out the loopholes in the few studies that attempted to use ontologies in CG. A systematic literature review was carried out to assess the extent to which ontologies have been applied in CG. Four reviewers performed a systematic search in IEEE, Scopus, Web of Science, and google scholar independently using agreed-upon criteria. To eliminate the bias of leaving out important studies, abstracts from selected conferences were carefully screened and reference scanning of the search results was performed. Out of 307 studies, 11 were found to match the search parameters and were included in the study.

Abstract Background Ferroptosis, a unique form of non-apoptotic cell death, is dependent on iron and lipoperoxidation, and has been shown to be associated with the pathogenesis of inflammatory bowel disease (IBD). Human umbilical cord mesenchymal stem cell-derived exosomes (hucMSC-Ex) are involved in cell survival, immune conditioning, and damage repair. However, the relationship between hucMSC-Ex, IBD, and ferroptosis is unknown. This paper explores the role of hucMSC-Ex in the repair of IBD through the regulation of the ferroptosis signaling pathway. Results In this study, we used small RNA sequencing to find that miR-129-5p was highly expressed in hucMSC-Ex, and by predicting its targeting to ACSL4, we verified the effect of miR-129-5p on mice IBD in vitro and human colonic epithelial cells (HCoEpiC) in vivo. We found that miR-129-5p reduces ferroptosis in intestinal epithelial cells by targeting ACSL4 to repair IBD, which provides new strategies for the prevention and treatment of IBD. Conclusion In conclusion, our results demonstrate that hucMSC-Ex relieves IBD by targeting ACSL4 with miR-129-5p to inhibit lipid peroxidation (LPO) and ferroptosis, reducing intestinal inflammation and repairing damages. Graphic abstract Mechanism of hucMSC-Ex inhibiting ferroptosis in intestinal epithelial cells. System Xc− mediates the transport of extracellular cystine into the cell, which gets reduced to cysteine to participate in GSH-mediated metabolism. GPX4 strongly inhibits ferroptosis by helping scavenge reactive oxygen species. The depletion of GSH correlates with decreased GPX4, and the imbalance of the antioxidant system leads to the formation of toxic phospholipid hydroperoxide, which promotes the occurrence of ferroptosis with the participation of irons. HucMSC-Ex has the ability to relieve GSH and GPX4 depletion and repair the intracellular antioxidant system. Ferric ions enter the cytosol through DMT1 and participate in lipid peroxidation. HucMSC-Ex can reduce the expression of DMT1 and alleviate this process. HucMSC-Ex-derived miR-129-5p targets ACSL4 and reduces the expression of ACSL4, an enzyme that mediates the conversion of PUFAs into phospholipids in intestinal epithelial cells, and is a positive regulator of lipid peroxidation. Abbreviations: GSH, glutathione; GPX4, glutathione peroxidase 4; GSSG, oxidized glutathione; DMT1, divalent metal transporter 1; ACSL4, acyl-CoA synthetase long-chain family member 4; PUFAs, polyunsaturated fatty acids; ALOXs, lipoxygenases; CoA, coenzyme A; PL, phospholipid; PLOOH, hydroperoxides, LOH, phospholipid alcohols; LPO, lipid peroxidation.

Inflammatory bowel disease (IBD), which encompasses Crohn’s disease (CD) and ulcerative colitis (UC), is a complicated illness whose exact cause is yet unknown. Necroptosis is associated with IBD pathogenesis, leading to intestinal barrier abnormalities and uncontrolled inflammation. Molecules involved in necroptosis, however, exhibit different expression levels in IBD and its associated colorectal cancer. Multiple studies have shown that inhibiting these molecules alleviates necroptosis-induced IBD. Moreover, due to the severe scarcity of clinical medications for treating IBD caused by necroptosis, we review the various functions of crucial necroptosis molecules in IBD, the stimuli regulating necroptosis, and the current emerging therapeutic strategies for treating IBD-associated necroptosis. Eventually, understanding the pathogenesis of necroptosis in IBD will enable the development of additional therapeutic approaches for the illness.

Iron deficiency anaemia is still a global public health concern with the highest burden among children 6 to 23 months due to their rapid growth spurt exceeding breastmilk supply. Therefore, nutritional supply is a key source of iron to attain the required nutrients for better growth and development. This was a cross-sectional descriptive study done at Ishaka Adventist Hospital (IAH) and Kampala International University Teaching Hospital (KIUTH) from April to July 2022. Participants were consecutively enrolled in the study. Structured questionnaires, 24-hour dietary recall, and clinical assessment were used to obtain data. Data analysis was done using the statistical package for social scientists (SPSS) V22.0. Bivariable and multivariable analyses were done using logistic regression for associations with significance set at P value < 0.05. A total of 364 participants were enrolled, with the majority being males (198, 54.4%) and born at term (333, 91.5%). The modal age was 12-17 months [163(44.8%)] with a mean age of 14.1 months (SD 5.32). The overall prevalence of IDA was 151/364 (41.5%). The factors associated with IDA included male sex (aOR 1.61), current episode of diarrhoea (aOR 1.71), poor meal frequency (aOR 1.78), no vegetable consumption (aOR 2.47), and consuming fruits once (aOR 1.97) in 7 days preceding the study. The study finds a high prevalence of IDA among infants 6-23 months with at least four in 10 being affected. Screening for IDA should be recommended in male children with current diarrhoea, poor intake of fruits and vegetables, and poor meal frequency. The Mentzer index is an equally good alternative screening test for IDA.

ABSTRACTThe gut microbiome serves as a signaling hub that integrates environmental inputs with genetic and immune signals to influence the host’s metabolism and immunity. Gut bacteria are intricately connected with human health and disease state, with specific bacteria species driving the characteristic dysbiosis found in gastrointestinal conditions such as inflammatory bowel disease (IBD); thus, gut bacteria changes could be harnessed to improve IBD diagnosis, prognosis, and treatment. The advancement in next-generation sequencing techniques such as 16S rRNA and whole-genome shotgun sequencing has allowed the exploration of the complexity of the gut microbial ecosystem with high resolution. Current microbiome data is promising and appears to perform better in some studies than the currently used fecal inflammation biomarker, calprotectin, in predicting IBD from healthy controls and irritable bowel syndrome (IBS). This study reviews current data on the differential potential of gut bacteria within IBD cohorts, and between IBD and other gastrointestinal diseases.

# Background Poverty is a barrier to health equity. While it is believed that tuberculosis (TB) and Human Immunodeficiency Virus (HIV) care is free in Kenya, this is only partially true. Co-morbidities such as diabetes mellitus (DM), which are not currently subsidized, triple the risk of contracting TB and contribute to poor outcomes such as drug-resistant TB (DR-TB), while also increasing the cost of care. After TB treatment, there is a three-fold risk of death, with cardiovascular disease being a major contributor, and diabetes is directly correlated with cardiovascular risk. The lack of costing data on co-morbidities in TB/HIV care has made it challenging to define a subsidized care package for patients. # Methods This cross-sectional, mixed methods, nested design study aimed to determine the cost of managing TB patients, with or without HIV, in addition to diabetes or prediabetes, from a health system perspective using a bottom-up (BU) approach. The study aimed to propose a minimum care package as part of efforts towards universal health coverage in Kenya. STATA was used to randomly sample 36 health facilities within Nairobi County, Kenya, representing 10 of the 17 sub-counties. # Results The average health system costs for screening, diagnosis, and risk counseling of TB patients were USD (\$) 27.26 in public and USD ($) 44.70 in private health facilities, averaging USD (\$) 35.98. The costs for managing TB and HIV, TB and DM, and TB, DM, and HIV in public and private facilities respectively were USD (\$) 28.17 and USD (\$) 51.75, USD (\$) 31.75 and USD (\$) 47.93, and USD (\$) 32.67 and USD (\$) 54.98. # Conclusions The cost of managing dysglycemia in TB and HIV patients is incremental, and subsidies can improve access to care. The proposed minimum care package, which includes dysglycemia care (self-monitoring, cardiovascular and ophthalmology screening, and foot care), is almost ten times less than what the health system currently pays for TB complications like DR-TB.

This study assessed the relationship between dividend yield and financial performance of the listed companies at Nairobi Securities Exchange. Bird in hand theory anchored the study. An explanatory research design was adopted where all the 62 firms listed in Nairobi Securities Exchange (NSE) participated in the study. Secondary data collected from the published financial statements for the years from 2018 to 2020 by use of a data collection sheet was analysed using descriptive statistics and regression analysis. The results indicated that dividend yield had a positive and significant relationship with the performance of the listed firms at NSE. The study recommended that the listed firms should strive to have a sizable amount of the profits accrued by the firm be paid as dividends and that the listed firms should strive to be consistent in their dividend payments.

Inflammatory bowel disease (IBD) has been referred to as the “green cancer,” and its progression to colorectal cancer (CRC) poses a significant challenge for the medical community. A common factor in their development is glycolysis, a crucial metabolic mechanism of living organisms, which is also involved in other diseases. In IBD, glycolysis affects gastrointestinal components such as the intestinal microbiota, mucosal barrier function, and the immune system, including macrophages, dendritic cells, T cells, and neutrophils, while in CRC, it is linked to various pathways, such as phosphatidylinositol-3-kinase (PI3K)/AKT, AMP-activated protein kinase (AMPK), mammalian target of rapamycin (mTOR), and transcription factors such as p53, Hypoxia-inducible factor (HIF), and c-Myc. Thus, a comprehensive study of glycolysis is essential for a better understanding of the pathogenesis and therapeutic targets of both IBD and CRC. This paper reviews the role of glycolysis in diseases, particularly IBD and CRC, via its effects on the intestinal microbiota, immunity, barrier integrity, signaling pathways, transcription factors and some therapeutic strategies targeting glycolytic enzymes.

Epigenetic modification is a complex process of reversible and heritable alterations in gene function, and the combination of epigenetic and metabolic alterations is recognized as an important causative factor in diseases such as inflammatory bowel disease (IBD), osteoarthritis (OA), systemic lupus erythematosus (SLE), and even tumors. Mesenchymal stem cell (MSC) and MSC-derived exosome (MSC-EXO) are widely studied in the treatment of inflammatory diseases, where they appear to be promising therapeutic agents, partly through the potent regulation of epigenetic modifications such as DNA methylation, acetylation, phosphorylation, and expression of regulatory non-coding RNAs, which affects the occurrence and development of inflammatory diseases. In this review, we summarize the current research on the role of MSC-EXO in inflammatory diseases through their modulation of epigenetic modifications and discuss its potential application in the treatment of inflammatory diseases.

Abstract Background Despite global interventions to prevent and control diarrhea, it still remains a public health problem leading to childhood morbidity and mortality majorly in developing countries. In Uganda, diarrhea is amongst the five leading causes of under-five mortality, contributing to more than 140,000 deaths every year and this accounts for 7.1% of all under-five mortalities in Uganda. Efforts to prevent and lower diarrheal diseases need to be informed by data on determinants of diarrhea. The study assessed factors associated with diarrheal diseases among children below five years in selected slum settlements in Entebbe municipality, Wakiso District, Uganda. Methods The study employed a cross-sectional study design covering 384 randomly selected households having children

Abstract Inflammatory bowel disease (IBD), a chronic gut immune dysregulation and dysbiosis condition is rapidly increasing in global incidence. Regardless, there is a lack of ideal diagnostic markers, while conventional treatment provides scarce desired results, thus, the exploration for better options. Changes in the gut microbial composition and metabolites either lead to or are caused by the immune dysregulation that characterizes IBD. This study examined the fecal metagenomics and metabolomic changes in IBD patients. A total of 30 fecal samples were collected from 15 IBD patients and 15 healthy controls for 16S rDNA gene sequencing and UHPLC/Q-TOF-MS detection of metabolomics. Results showed that there was a severe perturbation of gut bacteria community composition, diversity, metabolites, and associated functions and metabolic pathways in IBD. This included a significantly decreased abundance of Bacteroidetes and Firmicutes, increased disease-associated phyla such as Proteobacteria and Actinobacteria, and increased Escherichia coli and Klebsiella pneumoniae in IBD. A total of 3146 metabolites were detected out of which 135 were differentially expressed between IBD and controls. Metabolites with high sensitivity and specificity in differentiating IBD from healthy individuals included 6,7,4′-trihydroxyisoflavone and thyroxine 4′-o-.beta.-d-glucuronide (AUC = 0.92), normorphine and salvinorin a (AUC = 0.90), and trichostachine (AUC = 0.91). Moreover, the IBD group had significantly affected pathways including primary bile acid biosynthesis, vitamin digestion and absorption, and carbohydrate metabolism. This study reveals that the combined evaluation of metabolites and fecal microbiome can be useful to discriminate between healthy subjects and IBD patients and consequently serve as therapeutic and diagnostic targets.

Abstract Background Between 2000 and 2019, more than 1.8 billion long-lasting insecticidal nets (LLINs) were distributed in Africa. While the insecticidal durability of LLINs is around 3 years, nets are commonly discarded 2 years post distribution. This study investigated the factors associated with the decision of users to discard LLINs. Methods A mixed-method sequential explanatory approach using a structured questionnaire followed by focus group discussions (FGDs) to collect information on experiences, views, reasons, how and when LLINs are discarded. Out of 6,526 households that responded to the questionnaire of LLINs durability trial, 160 households were randomly selected from the households in four villages in Bagamoyo Tanzania for FGDs but only 155 households participated in the FGDs. Five of the household representatives couldn’t participate due to unexpected circumstances. A total of sixteen FGDs each comprising of 8–10 adults were conducted; older women (40–60 years), older men (40–60 years), younger women (18–39 years), younger men (18–39 years). During the FGDs, participants visually inspected seven samples of LLINs that were “too-torn” based on Proportionate Hole Index recommended by the World Health Organization (WHO) guidelines on LLIN testing, the nets were brought to the discussion and participants had to determine if such LLINs were to be kept or discarded. The study assessed responses from the same participants that attended FGD and also responded to the structured questionnaire, 117 participants fulfilled the criteria, thus data from only 117 participants are analysed in this study. Results In FGDs, integrity of LLIN influenced the decision to discard or keep a net. Those of older age, women, and householders with lower income were more likely to classify a WHO “too-torn” net as “good”. The common methods used to discard LLINs were burning and burying. The findings were seen in the quantitative analysis. For every additional hole, the odds of discarding a WHO “too-torn” LLIN increased [OR = 1.05 (95%CI (1.04–1.07)), p

Background. Intestinal fibrosis, one of the complications of inflammatory bowel disease (IBD), is associated with fistula and intestinal stricture formation. There are currently no treatments for fibrosis. Mesenchymal stem cell-derived exosomes have been proven to exert inhibitory and reversal effects in IBD and other organ fibrosis. In this study, we explored the role of human umbilical cord mesenchymal stem cell-derived exosomes (hucMSC-Ex) in IBD-related fibrosis and its associated mechanism to provide new ideas for the prevention and treatment of IBD-related intestinal fibrosis. Methods. We established a DSS-induced mouse IBD-related intestinal fibrosis model and observed the effect of hucMSC-Ex on the mouse model. We also used the TGF-induced human intestinal fibroblast CCD-18Co to observe the role of hucMSC-Ex in the proliferation, migration, and activation of intestinal fibroblasts. Having observed that the extracellular-signal-regulated kinase (ERK) pathway in intestinal fibrosis can be inhibited by hucMSC-Ex, we treated intestinal fibroblasts with an ERK inhibitor to emphasize the potential target of ERK phosphorylation in the treatment of IBD-associated intestinal fibrosis. Results. In the animal model of IBD-related fibrosis, hucMSC-Ex alleviated inflammation-related fibrosis as evident in the thinning of the mice’s intestinal wall and decreased expression of related molecules. Moreover, hucMSC-Ex inhibited TGF-β-induced proliferation, migration, and activation of human intestinal fibroblasts, and ERK phosphorylation played a key role in IBD-associated fibrosis. The inhibition of ERK decreased the expression of fibrosis-related indicators such as α-SMA, fibronectin, and collagen I. Conclusion. hucMSC-Ex alleviates DSS-induced IBD-related intestinal fibrosis by inhibiting profibrotic molecules and intestinal fibroblast proliferation and migration by decreasing ERK phosphorylation.

IntroductionDuring the peak of the COVID-19 pandemic, nearly all educational institutions globally had to eventually embrace the maneuver of transferring to nearly 100% online learning as a new routine for different curricula. Although many students in developing countries such as Kenya are only experiencing the exclusive online learning approach for the first time, research on students’ experience and satisfaction with COVID-19-imposed online learning is largely lacking. Thus, this study examined the effect of online-learning experiences on satisfaction in the setting of the COVID-19 pandemic in Kenya. The mediating role of students’ preference on the relationship between online-learning experience and satisfaction was also examined.MethodsA web-based survey involving 501 respondents was analyzed using IBM® SPSS® and AMOS software platforms. A structural equation model (SEM) was used to analyze the relationships.Results and DiscussionResults showed that 80% of participants indicated their preference for in-person learning as against 20% for online learning. Students’ satisfaction-SS had a significant positive correlation with online classroom perceived quality-OCPQ, acquisition of self-confidence-ASC, teaching performance and engagement-TPE, and preference for online learning-POL but a negative correlation with internet access and cost-IAC. Moreover, while POL positively correlated with OCPQ, ASC, and TPE, it negatively correlated with IAC. Both the structural model for the main effect and the mediation model provided a good fit and confirmed these relationships. Student preference had a significant effect on satisfaction and played a significant mediating role in the relationship between online-learning experience and satisfaction. These findings shed light on the underlying factors that explain students’ online learning satisfaction and provide guidelines for universities and policymakers to make better decisions that enhance students’ online-learning experience and satisfaction.

Gastrointestinal tumours are the most common solid tumours, with a poor prognosis and remain a major challenge in cancer treatment. Mesenchymal stem cells (MSC) are multipotent stromal cells with the potential to differentiate into multiple cell types. Several studies have shown that MSC-derived exosomes have become essential regulators of intercellular communication in a variety of physiological and pathological processes. Notably, MSC-derived exosomes support or inhibit tumour progression in different cancers through the delivery of proteins, RNA, DNA, and bioactive lipids. Herein, we summarise current advances in MSC-derived exosomes in cancer research, with particular reference to their role in gastrointestinal tumour development. MSC-derived exosomes are expected to be a novel potential strategy for the treatment of gastrointestinal cancers.

Farnesoid-X receptor (FXR), as a nuclear receptor activated by bile acids, is a vital molecule involved in bile acid metabolism. Due to its expression in immune cells, FXR has a significant effect on the function of immune cells and the release of chemokines when immune cells sense changes in bile acids. In addition to its regulation by ligands, FXR is also controlled by post-translational modification (PTM) activities such as acetylation, SUMOylation, and methylation. Due to the high expression of FXR in the liver and intestine, it significantly influences intestinal homeostasis under the action of enterohepatic circulation. Thus, FXR protects the intestinal barrier, resists bacterial infection, reduces oxidative stress, inhibits inflammatory reactions, and also acts as a tumor suppressor to impair the multiplication and invasion of tumor cells. These potentials provide new perspectives on the treatment of intestinal conditions, including inflammatory bowel disease (IBD) and its associated colorectal cancer (CRC). Moreover, FXR agonists on the market have certain organizational heterogeneity and may be used in combination with other drugs to achieve a greater therapeutic effect. This review summarizes current data on the role of FXR in bile acid metabolism, regulation of immune cells, and effects of the PTM of FXR. The functions of FXR in intestinal homeostasis and potential application in the treatment of IBD and CRC are discussed.

Abstract Background Human umbilical cord mesenchymal stem cell (hucMSC)-derived exosomes are recognized as novel cell-free therapeutic agents for inflammatory bowel disease (IBD), a condition caused by dysregulated intestinal mucosal immunity. In this event, macrophage pyroptosis, a process of cell death following the activation of NLRP3 (NOD-like receptor family, pyrin domain-containing 3) inflammasomes, is believed to partially account for inflammatory reactions. However, the role of macrophage pyroptosis in the process of hucMSC-derived exosomes alleviating colitis remains unknown. This study aimed at exploring the therapeutic effect and mechanism of hucMSC-derived exosomes on colitis repair. Methods In vivo, we used BALB/c mice to establish a dextran sulfate sodium (DSS)-induced colitis model and administrated hucMSC-derived exosomes intravenously to estimate its curative effect. Human myeloid leukemia mononuclear (THP-1) cells and mouse peritoneal macrophages (MPMs) were stimulated with lipopolysaccharides (LPS) and Nigericin to activate NLRP3 inflammasomes, which simulated an inflammation environment in vitro. A microRNA mimic was used to verify the role of miR-378a-5p/NLRP3 axis in the colitis repair. Results hucMSC-derived exosomes inhibited the activation of NLRP3 inflammasomes in the mouse colon. The secretion of interleukin (IL)-18, IL-1β, and Caspase-1 cleavage was suppressed, resulting in reduced cell pyroptosis. The same outcome was observed in the in vitro cell experiments, where the co-culture of THP-1 cells and MPMs with hucMSC-derived exosomes caused decreased expression of NLRP3 inflammasomes and increased cell survival. Furthermore, miR-378a-5p was highly expressed in hucMSC-derived exosomes and played a vital function in colitis repair. Conclusion hucMSC-derived exosomes carrying miR-378a-5p inhibited NLRP3 inflammasomes and abrogated cell pyroptosis to protect against DSS-induced colitis.

In an effort to reduce agency problems the members of Deposit Taking Savings and Credit Co-operatives elect board of directors to offer governance in attaining their economic, social and cultural needs. Nevertheless, governance costs have increased by 36 percent since 2014 to 2019 leading to reduction in surpluses which have rendered an aggregate of 47.32 percent of the Deposit Taking Savings and Credit Co-operatives financially unsound, thus putting 341-billion-member savings at risk. This necessitated the assessment of the moderating effect of SACCO size on governance costs and financial soundness. A descriptive cross-sectional survey design was adopted where data collection sheet was used in secondary data collection. A binary logistic regression results established that with presence of a moderator in the nexus between predictor and response variable, the strength of relationship between variables registered a significant change (15.6 percent to 18.3 percent) as well as with introduction of interaction term (15.6 percent to 19.3 percent). The study concluded that SACCO size portrayed a statistically significant moderating effect between predictor variable and response variable. The study recommends that small size Deposit Taking Savings and Credit Co-operatives should merge with other Deposit Taking Savings and Credit Co-operatives who are of a similar common bond or interest to form larger Deposit Taking Savings and Credit Co-operatives in term of Size so as to achieve financial soundness.

Abstract Background Recent studies reporting the intricate crosstalk between cellular and molecular mediators and the lymphatic endothelium in the development of inflammatory bowel diseases (IBD) suggest altered inflammatory cell drainage and lymphatic vasculature, implicating the lymphatic system as a player in the occurrence, development, and recurrence of intestinal diseases. This article aims to review recent data on the modulatory functions of cellular and molecular components of the IBD microenvironment on the lymphatic system, particularly lymphangiogenesis. It serves as a promising therapeutic target for IBD management and treatment. The interaction with gut microbiota is also explored. Main text Evidence shows that cells of the innate and adaptive immune system and certain non-immune cells participate in the complex processes of inflammatory-induced lymphangiogenesis through the secretion of a wide spectrum of molecular factors, which vary greatly among the various cells. Lymphangiogenesis enhances lymphatic fluid drainage, hence reduced infiltration of immunomodulatory cells and associated-inflammatory cytokines. Interestingly, some of the cellular mediators, including mast cells, neutrophils, basophils, monocytes, and lymphatic endothelial cells (LECs), are a source of lymphangiogenic molecules, and a target as they express specific receptors for lymphangiogenic factors. Conclusion The effective target of lymphangiogenesis is expected to provide novel therapeutic interventions for intestinal inflammatory conditions, including IBD, through both immune and non-immune cells and based on cellular and molecular mechanisms of lymphangiogenesis that facilitate inflammation resolution.

Aim: To develop an extraction protocol and determine stability for antimicrobial peptide (AMP) Kn2-7 and its d-enantiomer dKn2-7 in human serum. Materials & methods: We compared use of ethanol, acetonitrile, RapiGest SF Surfactant and 1% formic acid in ethanol for AMP recovery from serum prior to liquid chromatography-mass spectrometry quantification. Results: Precipitation of samples with 1% formic acid in ethanol caused the least amount of AMP loss during extraction from serum. Time-course experiments revealed dKn2-7 was significantly more stable than Kn2-7 in 25% serum, with 78.5% of dKn2-7 and only 1.0% of Kn2-7 remaining after 24 h at 37°C. Conclusion: The optimized method significantly increased peptide recovery and allowed more accurate and consistent quantification of Kn2-7 and dKn2-7 serum stability.

Intestinal fibrosis is an important complication of inflammatory bowel disease (IBD). In the course of the development of fibrosis, certain parts of the intestine become narrowed, significantly destroying the structure and function of the intestine and affecting the quality of life of patients. Chronic inflammation is an important initiating factor of fibrosis. Unfortunately, the existing anti-inflammatory drugs cannot effectively prevent and alleviate fibrosis, and there is no effective anti-fibrotic drug, which makes surgical treatment the mainstream treatment for intestinal fibrosis and stenosis. Mesenchymal stem cells (MSCs) are capable of tissue regeneration and repair through their self-differentiation, secretion of cytokines, and secretion of extracellular vesicles. MSCs have been shown to play an important therapeutic role in the fibrosis of many organs. However, the role of MSC in intestinal fibrosis largely remained unexplored. This review summarizes the mechanism of intestinal fibrosis, including the role of immune cells, TGF-β, and the gut microbiome and metabolites. Available treatment options for fibrosis, particularly, MSCs are also discussed.

In semi-arid rural Kenya, most households travel long distances to access food markets. This has negative effects on food consumption and the use of market facilities. Over70 % of farmers in Tharaka Constituency lack access to formal markets often relying on contracted middlemen who buy at farm gate for traders in major urban centres. Studies on intra-variation in accessibility to market services remains scanty, yet market purchases account for most food consumed across urban and rural areas. Distance defines accessibility and performance of market facilities in most areas where food insecurity and malnutrition are common. This study used Geographic Information Systems (GIS) to measure physical accessibility to open air markets within semi-arid Tharaka, a constituency where vulnerability to acute food shortage is comparatively high. Normative, administrative and geospatial datasets were used in the analysis. Results showed that geographic accessibility to local market centres vary spatially across the villages. In terms of market accessibility, 40.4% of the total population live in areas with high inaccessibility risks while 36.1% are found in places with low inaccessibility risks and only 23.5% of the population exists in areas with moderate inaccessibility risks. This means a large proportion of deprived population live in villages within high to very high inaccessibility risk areas. This spatial inequity has implications on household food security and explains the chronic problems of hunger and malnutrition experienced in the area. Therefore, markets within high inaccessibility risk areas should be upgraded and infrastructure thereof improved to enable food mobility across these areas.

Abstract Background Long-lasting insecticidal nets (LLINs) are the most sustainable and effective malaria control tool currently available. Global targets are for 80% of the population living in malaria endemic areas to have access to (own) and use a LLIN. However, current access to LLINs in endemic areas is 56% due to system inefficiencies and budget limitations. Thus, cost-effective approaches to maximize access to effective LLINs in endemic areas are required. This study evaluated whether LLINs that had been stored for 5 years under manufacturer’s recommended conditions may be optimally effective against Anopheles mosquitoes, to inform malaria control programmes and governments on the periods over which LLINs may be stored between distributions, in an effort to maximize use of available LLINs. Methods Standard World Health Organization (WHO) bioassays (cone and tunnel test) were used to evaluate the bio-efficacy and wash resistance of Olyset® and DawaPlus® 2.0 (rebranded Tsara® Soft) LLINs after 5 years of storage at 25 °C to 33.4 °C and 40% to 100% relative humidity. In addition, a small scale Ifakara Ambient Chamber test (I-ACT) was conducted to compare the bio-efficacy of one long stored LLINs to one new LLIN of the same brand, washed or unwashed. LLINs were evaluated using laboratory reared fully susceptible Anopheles gambiae sensu stricto (s.s.) (Ifakara strain) and pyrethroid resistant Anopheles arabiensis (Kingani strain). Results After 5 years of storage, both unwashed and washed, Olyset® and DawaPlus® 2.0 (Tsara® Soft) LLINs passed WHO bio-efficacy criteria on knockdown (KD60) ≥ 95%, 24-h mortality ≥ 80% and ≥ 90% blood-feeding inhibition in WHO assays against susceptible An. gambiae s.s. DawaPlus® 2.0 LLINs also passed combined WHO bioassay criteria against resistant An. arabiensis. Confirmatory I-ACT tests using whole nets demonstrated that long-stored LLINs showed higher efficacy than new LLINs on both feeding inhibition and mortality endpoints against resistant strains. Conclusions Even after long-term storage of around 5 years, both Olyset® and DawaPlus® 2.0 LLINs remain efficacious against susceptible Anopheles mosquitoes at optimal storage range of 25 °C to 33.4 °C for temperature and 40% to 100% relative humidity measured by standard WHO methods. DawaPlus® 2.0 (Tsara® Soft) remained efficacious against resistant strain.

Abstract Background Mesenchymal stromal cells (MSCs) have attracted intense interest due to their powerful intrinsic properties of self-regeneration, immunomodulation and multi-potency, as well as being readily available and easy to isolate and culture. Notwithstanding, MSC based therapy suffers reduced efficacy due to several challenges which include unfavorable microenvironmental factors in vitro and in vivo. Body In the quest to circumvent these challenges, several modification techniques have been applied to the naïve MSC to improve its inherent therapeutic properties. These modification approaches can be broadly divided into two groups to include genetic modification and preconditioning modification (using drugs, growth factors and other molecules). This field has witnessed great progress and continues to gather interest and novelty. We review these innovative approaches in not only maintaining, but also enhancing the inherent biological activities and therapeutics of MSCs with respect to migration, homing to target site, adhesion, survival and reduced premature senescence. We discuss the application of the improved modified MSC in some selected human diseases. Possible ways of yet better enhancing the therapeutic outcome and overcoming challenges of MSC modification in the future are also elaborated. Conclusion The importance of prosurvival and promigratory abilities of MSCs in their therapeutic applications can never be overemphasized. These abilities are maintained and even further enhanced via MSC modifications against the inhospitable microenvironment during culture and transplantation. This is a turning point in MSC-based therapy with promising preclinical studies and higher future prospect.

Egyptian rousette bats (ERBs) are natural reservoirs for Marburg virus (MARV), but these bats have not been linked to the MARV Angola strain that caused the largest and deadliest outbreak on record. Here, Amman et al., in a multi-institutional surveillance effort, identify and isolate Angola-like MARV in ERBs in West Africa.

Community-based screening for tuberculosis (TB) could improve detection but is resource intensive. We set out to evaluate the accuracy of computer-aided TB screening using digital chest X-ray (CXR) to determine if this approach met target product profiles (TPP) for community-based screening. CXR images from participants in the 2016 Kenya National TB Prevalence Survey were evaluated using CAD4TBv6 (Delft Imaging), giving a probabilistic score for pulmonary TB ranging from 0 (low probability) to 99 (high probability). We constructed a Bayesian latent class model to estimate the accuracy of CAD4TBv6 screening compared to bacteriologically-confirmed TB across CAD4TBv6 threshold cut-offs, incorporating data on Clinical Officer CXR interpretation, participant demographics (age, sex, TB symptoms, previous TB history), and sputum results. We compared model-estimated sensitivity and specificity of CAD4TBv6 to optimum and minimum TPPs. Of 63,050 prevalence survey participants, 61,848 (98%) had analysable CXR images, and 8,966 (14.5%) underwent sputum bacteriological testing; 298 had bacteriologically-confirmed pulmonary TB. Median CAD4TBv6 scores for participants with bacteriologically-confirmed TB were significantly higher (72, IQR: 58-82.75) compared to participants with bacteriologically-negative sputum results (49, IQR: 44-57, p

Community-based screening for tuberculosis (TB) could improve detection but is resource intensive. We set out to evaluate the accuracy of computer-aided TB screening using digital chest X-ray (CXR) to determine if this approach met target product profiles (TPP) for community-based screening. CXR images from participants in the 2016 Kenya National TB Prevalence Survey were evaluated using CAD4TBv6 (Delft Imaging), giving a probabilistic score for pulmonary TB ranging from 0 (low probability) to 99 (high probability). We constructed a Bayesian latent class model to estimate the accuracy of CAD4TBv6 screening compared to bacteriologically-confirmed TB across CAD4TBv6 threshold cut-offs, incorporating data on Clinical Officer CXR interpretation, participant demographics (age, sex, TB symptoms, previous TB history), and sputum results. We compared model-estimated sensitivity and specificity of CAD4TBv6 to optimum and minimum TPPs. Of 63,050 prevalence survey participants, 61,848 (98%) had analysable CXR images, and 8,966 (14.5%) underwent sputum bacteriological testing; 298 had bacteriologically-confirmed pulmonary TB. Median CAD4TBv6 scores for participants with bacteriologically-confirmed TB were significantly higher (72, IQR: 58–82.75) compared to participants with bacteriologically-negative sputum results (49, IQR: 44–57, p

Abstract Background Several investigations affirm that, patients with inflammatory bowel disease (IBD) exhibit dysbiosis characterized by restricted biodiversity and imbalanced bacterial composition intertwined with immune dysregulation. The interaction between stem cells and gut microbiota is a novel and highly promising field that could add up to a better understanding of the gut physiology, as well as therapeutic improvement towards diseases like IBD. Through direct contact or release of products and/or metabolites, gut bacteria regulate gut homeostasis, damage repair, regeneration and differentiation of stem cells. In the same way, mesenchymal stem cells (MSCs) produce similar effects including restoration of gut–microbiome composition. Body We reviewed the anti-inflammatory, antimicrobial, pathogenic bacterial clearance, proliferation and tissue remodeling effects of mesenchymal stem cells (MSCs) and fecal microbiota transplantation (FMT) as separate transplants in IBD, and the outcome of the interaction between MSCs and gut microbiota. Conclusion The two therapies share several points of connection in therapeutics with enhanced functionalities in their interaction with each other. Focused investigations of MSC–gut bacteria interactions could lead to a novel discovery in therapeutics. We also anticipate an improved clinical remission rate in a combined FMT–MSC transplantation approach in IBD than the current single FMT or MSC approach.

Inflammatory bowel disease (IBD) is characterized by intense immune dysregulation, gut microbiota imbalance, and intestinal epithelium destruction. Among the factors that contribute to the pathogenesis of IBD, lymphatics have received less attention, hence less studied, characterized, and explored. However, in recent years, the role of the lymphatic system in gastrointestinal pathophysiology continues to be highlighted. This paper examines the implications of lymphatic changes in IBD pathogenesis related to immune cells, gut microbiota, intestinal and mesenteric epithelial barrier integrity, and progression to colorectal cancer (CRC). Therapeutic targets of lymphatics in IBD studies are also presented. Available studies indicate that lymph nodes and other secondary lymphatic tissues, provide highly specialized microenvironments for mounting effective immune responses and that lymphatic integrity plays a significant role in small intestine homeostasis, where the lymphatic vasculature effectively controls tissue edema, leukocyte exit, bacterial antigen, and inflammatory chemokine clearance. In IBD, there are functional and morphological alterations in intestinal and mesenteric lymphatic vessels (more profoundly in Crohn's disease [CD] compared to ulcerative colitis [UC]), including lymphangiogenesis, lymphangiectasia, lymphadenopathy, and lymphatic vasculature blockade, affecting not only immunity but gut microbiota and epithelial barrier integrity. While increased lymphangiogenesis is primarily associated with a good prognosis of IBD, increased lymphangiectasia, lymphadenopathy, and lymphatic vessel occlusion correlate with poor prognosis. IBD therapies that target the lymphatic system seek to increase lymphangiogenesis via induction of lymphangiogenic factors and inhibition of its antagonists. The resultant increased lymphatic flow coupled with other anti-inflammatory activities restores gut homeostasis.

Tumor cells express a high quantity of exosomes packaged with unique cargos under hypoxia, an important characteristic feature in solid tumors. These hypoxic tumor-derived exosomes are, crucially, involved in the interaction of cancer cells with their microenvironment, facilitating not only immune evasion, but increased cell growth and survival, enhanced angiogenesis, epithelial–mesenchymal transition (EMT), therapeutic resistance, autophagy, pre-metastasis, and metastasis. This paper explores the tumor microenvironment (TME) remodeling effects of hypoxic tumor-derived exosome towards facilitating the tumor progression process, particularly, the modulatory role of these factors on tumor cell immune evasion through suppression of immune cells, expression of surface recognition molecules, and secretion of antitumor soluble factor. Tumor-expressed exosomes educate immune effector cells, including macrophages, monocytes, T cells, natural killer (NK) cells, dendritic cells (DCs), γδ T lymphocytes, regulatory T cells (Tregs), myeloid-derived suppressor cells (MDSCs), mast cells, and B cells, within the hypoxic TME through the release of factors that regulate their recruitment, phenotype, and function. Thus, both hypoxia and tumor-derived exosomes modulate immune cells, growth factors, cytokines, receptor molecules, and other soluble factors, which, together, collaborate to form the immune-suppressive milieu of the tumor environment. Exploring the contribution of exosomal cargos, such as RNAs and proteins, as indispensable players in the cross-talk within the hypoxic tumor microenvironmental provides a potential target for antitumor immunity or subverting immune evasion and enhancing tumor therapies.

Abstract Background Many people living with HIV would like to have children but family planning (FP) services often focus on only contraception. Availability of safer conception services is still very low in most low income countries. In this study we assessed the knowledge and use of safer conception methods (SCM) among HIV infected women in HIV care in Uganda to inform integration of safer conception in existing FP services. Methods Data were accrued from a nationally representative cross-sectional survey of 5198 HIV+ women aged 15–49 years from 245 HIV clinics in Uganda. Knowledge and use of safer conception methods and associated factors were determined. The measure of association was prevalence ratio (PR) with corresponding 95% confidence intervals, obtained using a modified Poisson regression via generalized linear models. All the analyses were conducted using STATA version 12.0. Results Overall knowledge of any safer conception method was 74.1% (3852/5198). However only 13.2% knew 3 to 4 methods, 18.9% knew only 2 methods and 42% knew only one method. Knowledge of specific SCM was highest for timed unprotected intercourse (TUI) at 39% (n = 2027) followed by manual self-insemination (MSI) at 34.8% (n = 1809), and pre-exposure prophylaxis (PrEP) at 24.8% (n = 1289). Knowledge of SCM was higher in the Eastern region (84.8%, P

Germinal matrix-intraventricular hemorrhage (GM-IVH) is a common intracranial complication in preterm infants, especially those born before 32 weeks of gestation and very-low-birth-weight infants. Hemorrhage originates in the fragile capillary network of the subependymal germinal matrix of the developing brain and may disrupt the ependymal lining and progress into the lateral cerebral ventricle. GM-IVH is associated with increased mortality and abnormal neurodevelopmental outcomes such as posthemorrhagic hydrocephalus, cerebral palsy, epilepsy, severe cognitive impairment, and visual and hearing impairment. Most affected neonates are asymptomatic, and thus, diagnosis is usually made using real-time transfontanellar ultrasound. The present review provides a synopsis of the pathogenesis, grading, incidence, risk factors, and diagnosis of GM-IVH in preterm neonates. We explore brief literature related to outcomes, management interventions, and pharmacological and nonpharmacological prevention strategies for GM-IVH and posthemorrhagic hydrocephalus.

Research on mesenchymal stem cells (MSCs) starts from the earliest assumption that cells derived from the bone marrow have the ability to repair tissues. Several scientists have since documented the crucial role of bone marrow-derived MSCs (BM-MSCs) in processes such as embryonic bone and cartilage formation, adult fracture and tissue repair, and immunomodulatory activities in therapeutic applications. In addition to BM-MSCs, several sources of MSCs have been reported to possess tissue repair and immunoregulatory abilities, making them potential treatment options for many diseases. Therefore, the therapeutic potential of MSCs in various diseases including autoimmune conditions has been explored. In addition to an imbalance of T cell subsets in most patients with autoimmune diseases, they also exhibit complex disease manifestations, overlapping symptoms among diseases, and difficult treatment. MSCs can regulate T cell subsets to restore their immune homeostasis toward disease resolution in autoimmune conditions. This review summarizes the role of MSCs in relieving autoimmune diseases via the regulation of T cell phenotypes.

BackgroundAdolescent girls and young women (AGYW) are at increased risk of sexually transmitted infections (STIs). We assessed sexual-risk behaviours and HIV and syphilis prevalence among AGYW in Uganda to inform the design of target-specific risk-reduction interventions.MethodsThis analysis utilizes data from 8,236 AGYW aged 10-24 years, collected in 20 districts, between July and August 2018. AGYW engaged in sexual-risk behaviour if they: a) reported a history of STIs; or b) had their sexual debut before age 15; or c) engaged in sex with 2+ partners in the past 12 months; or c) did not use or used condoms inconsistently with their most recent partners. We diagnosed HIV using DetermineTM HIV-1/2, Stat-PakTM HIV-1/2 and SD Bioline. We used SD Bioline Syphilis test kits to diagnose syphilis and Treponema Pallidum Hemagglutination Assay for confirmatory syphilis testing. Comparison of proportions was done using Chi-square (χ2) tests. Data were analysed using STATA (version 14.1).ResultsOf 4,488 AGYW (54.5%) that had ever had sex, 12.9% (n = 581) had their sexual debut before age 15; 19.1% (n = 858) reported a history of STIs. Of those that had ever had sex, 79.6% (n = 3,573) had sex in the 12 months preceding the survey; 75.6% (n = 2,707) with one (1) and 24.2% (n = 866) with 2+ partners. Condom use with the most recent sexual partner was low, with only 20.4% (n = 728) reporting consistent condom use while 79.6% (n = 2,842) reported inconsistent or no condom use. In-school AGYW were significantly less likely to have ever had sex (35.6% vs. 73.6%, PConclusionIn-school AGYW engaged in more protective sexual behaviors and had less HIV and syphilis than their out-of-school counterparts. These findings suggest a need for target-specific risk-reduction interventions stratified by schooling status.