The frequency and function of nucleoprotein-specific CD8+ T cells are critical for heterosubtypic immunity against influenza virus infection.

Cytotoxic T lymphocytes (CTLs) mediate host defense against viral and intracellular bacterial infections and tumors. However, the magnitude of CTL response and their function needed to confer heterosubtypic immunity against influenza virus infection are unknown. We addressed the role of CD8+ T cells in the absence of any cross-reactive antibody responses to influenza viral proteins using an adenoviral vector expressing a 9mer amino acid sequence recognized by CD8+ T cells. Our results indicate that both CD8+ T cell frequency and function are crucial for heterosubtypic immunity. Low morbidity, lower viral lung titers, low to minimal lung pathology, and better survival upon heterosubtypic virus challenge correlated with the increased frequency of NP-specific CTLs. NP-CD8+ T cells induced by differential infection doses displayed distinct RNA transcriptome profiles and functional properties. CD8+ T cells induced by a high dose of influenza virus secreted significantly higher levels of IFN-γ and exhibited higher levels of cytotoxic function. The mice that received NP-CD8+ T cells from the high-dose virus recipients through adoptive transfer had lower viral titers following viral challenge than those induced by the low dose of virus, suggesting differential cellular programming by antigen dose. Enhanced NP-CD8+ T-cell functions induced by a higher dose of influenza virus strongly correlated with the increased expression of cellular and metabolic genes, indicating a shift to a more glycolytic metabolic phenotype. These findings have implications for developing effective T cell vaccines against infectious diseases and cancer. IMPORTANCE: Cytotoxic T lymphocytes (CTLs) are an important component of the adaptive immune system that clears virus-infected cells or tumor cells. Hence, developing next-generation vaccines that induce or recall CTL responses against cancer and infectious diseases is crucial. However, it is not clear if the frequency, function, or both are essential in conferring protection, as in the case of influenza. In this study, we demonstrate that both CTL frequency and function are crucial for providing heterosubtypic immunity to influenza by utilizing an Ad-viral vector expressing a CD8 epitope only to rule out the role of antibodies, single-cell RNA-seq analysis, as well as adoptive transfer experiments. Our findings have implications for developing T cell vaccines against infectious diseases and cancer.

Self-reported continuing professional development needs of medical laboratory professionals in Ghana.

BACKGROUND: Because of the essential nature of the work of medical laboratory professionals, continuing development in knowledge and skills is indispensable. The study aimed at identifying and prioritizing the development and training needs of medical laboratory professionals in Ghana. This is expected to help in developing focused continuing professional development (CPD) that meets the needs of practitioners as well as the changing medical trends. METHODS: An online cross-sectional survey in February 2022 using a structured questionnaire was conducted. Respondents were asked questions that collected demographic and work-related data about them, their participation, preference, and challenges in being part of CPDs. Finally, a list of topics based on (i) quality management systems, (ii) technical competence, (iii) laboratory management, leadership, and coaching, (iv) pathophysiology, and (iv) data interpretation and research were asked with the option to rate them on a 3-point scale (most, moderate, and least) in order of importance. RESULTS: A total of 316 medical laboratory professionals participated in the study. Overall, the most frequently selected topics for training based on domains for CPD training and ranking as most important were (i) quality management systems, (mean = 80.59 ± 9.024; 95% CI = 73.04-88.13); (ii) pathophysiology, data interpretation, and research (mean = 78.0 ± 6.973; 95% CI = 73.97-82.03); (iii) technical competence (mean = 73.97 ± 10.65; 95% CI = 66.35-81.59); and (iv) laboratory management, leadership, and coaching (mean = 72.82 ± 9.719; 95% CI = 67.44-78.2). The factors affecting the choice of training needs included the medical laboratory professionals' current place of work, years in service, the reason for attending CPD activities, the period for attending the last CPD, being in a supervisory role, and the number of staff being supervised. Face-to-face presentations, training workshops, and hands-on workshops were the most preferred modes of CPD delivery with financial implications and workload/time constraints being the main challenges impeding CPD participation. CONCLUSION: The identified needs will help in developing CPD programs that address what medical laboratory professionals prioritize as training needs. Stakeholders should incorporate these training needs into future programs and address the challenges highlighted in this study to have more relevant training for medical laboratory professionals.

Candidiasis profile at the outpatient department of the university of cape coast hospital in the central region of Ghana: a retrospective study.

INTRODUCTION: Vulvovaginal candidiasis (VVC) is a public health problem with an estimated 138 million women globally experiencing recurrent VVC annually. The microscopic diagnosis of VVC has low sensitivity, but it remains an essential tool for diagnosis as the microbiological culture methods are limited to advanced clinical microbiology laboratories in developing countries. The study retrospectively analyzed the presence of red blood cells (RBCs), epithelial cells (ECs), pus cells (PCs) and Candida albicans positive in wet mount preparation of urine or high vaginal swabs (HVS) samples to test for their sensitivity and specificity for the diagnosis of candidiasis. METHODS: The study is a retrospective analysis at the Outpatient Department of the University of Cape Coast between 2013 and 2020. All urine and high vagina swabs (HVS) cultures samples using Sabourauds dextrose agar with wet mount data were analyzed. 2 × 2 contingency diagnostic test was used to ascertain the diagnostic accuracy of red blood cells (RBCs), epithelial cells (ECs), pus cells (PCs), and Candida albicans positive in wet mount preparation of urine or high vaginal swabs (HVS) samples for the diagnosis of candidiasis. The association of candidiasis among patients' demographics was analyzed using relative risk (RR) analysis. RESULTS: The high prevalence of candida infection was among female subjects 97.1% (831/856) compared to males 2.9% (25/856). The microscopic profiles which characterized candida infection were pus cells 96.4% (825/856), epithelial cells 98.7% (845/856), red blood cells (RBCs) 7.6% (65/856) and Candida albicans positive 63.2% (541/856). There was a lower risk of Candida infections among male patients compared to female patients RR (95% CI) = 0.061 (0.041-0.088). The sensitivity (95%) for detecting Candida albicans positive and red blood cells (0.62 (0.59-0.65)), Candida albicans positive and pus cells (0.75 (0.72-0.78)) and Candida albicans positive and epithelial cells (0.95 (0.92-0.96)) with corresponding specificity (95% CI) of 0.63 (0.60-0.67), 0.69 (0.66-0.72) and 0.74 (0.71-0.76) were detected among the high vaginal swab samples. CONCLUSION: In conclusion, the study has shown that the presence of PCs, ECs, RBCs or ratio of RBCs/ECs and RBCs/PCs in the wet mount preparation from urine or HVS can enhance microscopic diagnosis of VVC cases.

Standard-Dose Intradermal Influenza Vaccine Elicits Cellular Immune Responses Similar to Those of Intramuscular Vaccine in Men With and Those Without HIV Infection.

BACKGROUND: Human immunodeficiency virus (HIV)-infected persons are at a higher risk of severe influenza. Although we have shown that a standard-dose intradermal influenza vaccine versus a standard-dose intramuscular influenza vaccine does not result in differences in hemagglutination-inhibition titers in this population, a comprehensive examination of cell-mediated immune responses remains lacking. METHODS: Serological, antigen-specific B-cell, and interleukin 2-, interferon γ-, and tumor necrosis factor α-secreting T-cell responses were assessed in 79 HIV-infected men and 79 HIV-uninfected men. RESULTS: The route of vaccination did not affect the immunoglobulin A and immunoglobulin G (IgG) plasmablast or memory B-cell response, although these were severely impaired in the group with a CD4+ T-cell count of <200 cells/µL. The frequencies of IgG memory B cells measured on day 28 after vaccination were highest in the HIV-uninfected group, followed by the group with a CD4+ T-cell count of ≥200 cells/µL and the group with a CD4+ T-cell count of <200 cells/µL. The route of vaccination did not affect the CD4+ or CD8+ T-cell responses measured at various times after vaccination. CONCLUSIONS: The route of vaccination had no effect on antibody responses, antibody avidity, T-cell responses, or B-cell responses in HIV-infected or HIV-uninfected subjects. With the serological and cellular immune responses to influenza vaccination being impaired in HIV-infected individuals with a CD4+ T-cell count of <200 cells/µL, passive immunization strategies need to be explored to protect this population. CLINICAL TRIALS REGISTRATION: NCT01538940.

An Adjuvanted A(H5N1) Subvirion Vaccine Elicits Virus-Specific Antibody Response and Improves Protection Against Lethal Influenza Viral Challenge in Mouse Model of Protein Energy Malnutrition.

Background: Protein energy malnutrition (PEM) increases susceptibility to infectious diseases, including influenza infection, but no studies have addressed the potential influences of PEM on the immunogenicity and protective efficacy of avian influenza A(H5N1) vaccine. Methods: We investigated the role of PEM on vaccine-mediated protection after a lethal challenge with recombinant A(H5N1) virus using isocaloric diets providing either adequate protein (AP; 18% protein) or very low protein (VLP; 2% protein) in an established murine model of influenza vaccination. Results: We demonstrated that mice maintained on a VLP diet succumb to lethal challenge at greater rates than mice maintained on an AP diet, despite comparable immunization regimens. Importantly, there was no virus-induced mortality in both VLP and AP groups of mice when either group was immunized with adjuvanted low-dose A(H5N1) subvirion vaccine. Conclusions: Our results suggest that adjuvanted vaccination in populations where PEM is endemic may be one strategy to boost vaccination-promoted immunity and improve outcomes associated with highly pathogenic A(H5N1).

RIG-I ligand enhances the immunogenicity of recombinant H7HA protein.

Avian H7N9 influenza virus infection with fatal outcomes continues to pose a pandemic threat and highly immunogenic vaccines are urgently needed. In this report we show that baculovirus-derived recombinant H7 hemagglutinin protein, when delivered with RIG-I ligand, induced enhanced antibody and T cell responses and conferred protection against lethal challenge with a homologous H7N9 virus. These findings indicate the potential utility of RIG-I ligands as vaccine adjuvants to increase the immunogenicity of recombinant H7 hemagglutinin.

High viral burden restricts short-lived effector cell number at late times postinfection through increased natural regulatory T cell expansion.

Generating and maintaining a robust CD8(+) T cell response in the face of high viral burden is vital for host survival. Further, balancing the differentiation of effectors along the memory precursor effector cell pathway versus the short-lived effector cell (SLEC) pathway may be critical in controlling the outcome of virus infection with regard to clearance and establishing protection. Although recent studies have identified several factors that have the capacity to regulate effector CD8(+) T cell differentiation-for example, inflammatory cytokines-we are far from a complete understanding of how cells choose the memory precursor effector cell versus SLEC fate following infection. In this study, we have modulated the infectious dose of the poxvirus vaccinia virus as an approach to modulate the environment present during activation and expansion of virus-specific effector cells. Surprisingly, in the face of a high virus burden, the number of SLECs was decreased. This decrease was the result of increased natural regulatory T cells (Tregs) generated by high viral burden, as depletion of these cells restored SLECs. Our data suggest Treg modulation of differentiation occurs via competition for IL-2 during the late expansion period, as opposed to the time of T cell priming. These findings support a novel model wherein modulation of the Treg response as a result of high viral burden regulates late-stage SLEC number.

Consumption and drinking frequency of alcoholic beverage among women in Ghana: a cross-sectional study.

BACKGROUND: The consumption and drinking frequency of alcoholic beverage are identified with various individual factors. The aim of this study was to identify background characteristics of women associated with the consumption and drinking frequency of alcoholic beverage. METHODS: Data was extracted from the 2008 Ghana Demographic and Health Survey. The data consisted of women's (aged 15-49 years) background characteristics and their reported history of consumption and drinking frequency of alcoholic beverage. A weighted sample size of 4916 women was used in the present study. Binary logistic regression and multinomial logistic regression were applied to examine the independent association between the covariates and the consumption and drinking frequency of alcoholic beverage respectively. RESULTS: Out of the 4916 women that were included in the study, 17.5% consumed alcoholic beverage in the past week. Factors that were found to be associated with women who consumed alcoholic beverage in a binary logistic regression model were age (15-19 years up to 45-49 years), region (Central, Greater Accra, Volta, Ashanti, Northern, Upper East, and Upper West), ethnicity (Ga or Dangme, Mole-Dagbani, Grussi, Gruma or Mande), wealth quintile (middle), and employment status [past 12 months] (those employed). In the multinomial logistic regression model, drinking frequency of alcoholic beverage was associated with women in the Central (none), Greater Accra Region (none and 4 or more times), Eastern (none and 2-3 times), Brong Ahafo (none), Upper East (none), those who attained primary education (4 or more times), Ga/Dangme ethnic group (none), those of middle wealth quintile (none), and those employed (4 or more times). CONCLUSIONS: In the country, about 2 in 10 women consume alcoholic beverage and the drinking frequency of alcoholic beverage varied among women in the country. Hence, the maintenance of moderate alcoholic beverage consumption among women, where applicable, should be encouraged.

Changes in functional but not structural avidity during differentiation of CD8+ effector cells in vivo after virus infection.

By the peak of the CD8(+) T cell response, the effector cell pool consists of a heterogeneous population of cells that includes both those with an increased propensity to become long-lived memory cells (memory precursor effector cells; MPEC) and those that are terminally differentiated cells (short-lived effector cells; SLEC). Numerous studies have established the critical role that functional avidity plays in determining the in vivo efficacy of CD8(+) effector cells. Currently, how functional avidity differs in MPEC versus SLEC and the evolution of this property within these two populations during the expansion and contraction of the response are unknown. The data presented in this study show that at the peak of the effector response generated after poxvirus infection, SLEC were of higher functional avidity than their MPEC counterpart. Over time, however, SLEC exhibited a decrease in peptide sensitivity. This is in contrast to MPEC, which showed a modest increase in peptide sensitivity as the response reached equilibrium. The decrease in functional avidity in SLEC was independent of CD8 modulation or the amount of Ag receptor expressed by the T cell. Instead, the loss in sensitivity was correlated with decreased expression and activation of ZAP70 and Lck, critical components of TCR membrane proximal signaling. These results highlight the potential contribution of avidity in the differentiation and evolution of the T cell effector response after viral infection.

Serum calcium and magnesium levels in women presenting with pre-eclampsia and pregnancy-induced hypertension: a case-control study in the Cape Coast metropolis, Ghana.

BACKGROUND: Hypertensive disorders of pregnancy are important causes of morbidity and mortality. The levels of calcium (Ca2+) and magnesium (Mg2+) in pregnancy may implicate their possible role in pregnancy-induced hypertension. This study assessed serum Ca2+ and Mg2+ levels in women with PIH (pregnancy-induced hypertension) and PE (pre-eclampsia), compared to that in normal pregnancy. METHODS: This case-control study was conducted on 380 pregnant women (≥20 weeks gestation) receiving antenatal care at three hospitals in the Cape Coast metropolis, Ghana. This comprised 120 women with PIH, 100 women with PE and 160 healthy, age-matched pregnant women (controls). Demographic, anthropometric, clinical and obstetric data were gathered using an interview-based questionnaire. Venous blood samples were drawn for the estimation of calcium and magnesium. RESULTS: Systolic blood pressure (SBP) and diastolic blood pressure (DBP) were significantly raised in women with PIH (p < 0.0001) and PE (p < 0.0001). Women with hypertensive disorders (PE and PIH) had significantly lower serum calcium and magnesium levels than those in the control group (p < 0.0001 each). Of those with PIH, SBP correlated positively with BMI (r = 0.575, p < 0.01) and Ca2+ correlated positively with Mg2+ (r = 0.494, p < 0.01). This was similar amongst the PE group for SBP and BMI as well as for Ca2+and Mg2+ but was not significant. Multivariate analysis showed that women aged ≥40 years were at a significant risk of developing PIH (OR = 2.14, p = 0.000). CONCLUSION: In this study population, serum calcium and magnesium levels are lower in PIH and PE than in normal pregnancy. Mineral supplementation during the antenatal period may influence significantly, the occurrence of hypertensive disorders in pregnancy.

A leukocyte immune-type receptor specific polyclonal antibody recognizes goldfish kidney leukocytes and activates the MAPK pathway in isolated goldfish kidney neutrophil-like cells.

Leukocyte immune-type receptors (LITRs) belong to a large family of teleost immunoregulatory receptors that share phylogenetic and syntenic relationships with mammalian Fc receptor-like molecules (FCRLs). Recently, several putative stimulatory Carassius auratus (Ca)-LITR transcripts, including CaLITR3, have been identified in goldfish. CaLITR3 has four extracellular immunoglobulin-like (Ig-like) domains, a transmembrane domain containing a positively charged histidine residue, and a short cytoplasmic tail region. Additionally, the calitr3 transcript is highly expressed by goldfish primary kidney neutrophils (PKNs) and macrophages (PKMs). To further investigate the immunoregulatory potential of CaLITR3 in goldfish myeloid cells, we developed and characterized a CaLITR3-epitope-specific polyclonal antibody (anti-CaL3.D1 pAb). We show that the anti-CaL3.D1 pAb stains various hematopoietic cell types within the goldfish kidney, as well as in PKNs and PKMs. Moreover, cross-linking of the anti-CaL3.D1-pAb on PKN membranes induces phosphorylation of p38 and ERK1/2, critical components of the MAPK pathway involved in controlling a wide variety of innate immune effector responses such as NETosis, respiratory burst, and cytokine release. These findings support the stimulatory potential of CaLITR3 proteins as activators of fish granulocytes and pave the way for a more in-depth examination of the immunoregulatory functions of CaLITRs in goldfish myeloid cells.

Analysis of land-use and livelihood transformations in peri-urban areas: Insights from North-Western Ghana.

This paper questions claims that peri-urbanization perpetuates the shrinking of livelihood opportunities. A critical analysis of the peri-urbanization process presents a more nuanced transformation of livelihood opportunities. Drawing on concurrent triangulation mixed-method, primary data was sourced from non-farm workers using survey questionnaires, informant interviews, and observation from 225 respondents in a Ghanaian peri-urban community -Bamahu. Digital image software, Erdas Imaging 2015 and Landsat satellite were used to acquire land use and land cover data to affirm spatial differences. Quantitative data were analyzed using descriptive statistics complemented with thematic analysis for qualitative data. The findings showed significant land use and land cover alterations from 2000 to 2019. These changes resulted in the springing up of non-farm livelihoods that populated formal and informal non-farm opportunities. The analysis provides evidence that supports two key contributions to peri-urbanization and livelihood transformation debates. Empirically, it brings in-depth insights from original fieldwork data to highlight specific contextual realities by not only revealing the spatial alterations but also peering into how emerging non-farm livelihoods trade-off with existing farm-based livelihoods. Theoretically, it extends the debate by reframing peri-urbanization as a process of transforming livelihoods that thrive due to infrastructural development, new skills, and a ready market for goods and services. These findings have important implications for opening up a theorization of the peri-urbanization phenomenon. This paper concludes that the emergence of these livelihoods is crucial and should be adequately integrated into urban policies and plans to ensure inclusive cities.

Current evidence and therapeutic implication of PANoptosis in cancer.

Regulated cell death (RCD) is considered a critical pathway in cancer therapy, contributing to eliminating cancer cells and influencing treatment outcomes. The application of RCD in cancer treatment is marked by its potential in targeted therapy and immunotherapy. As a type of RCD, PANoptosis has emerged as a unique form of programmed cell death (PCD) characterized by features of pyroptosis, apoptosis, and necroptosis but cannot be fully explained by any of these pathways alone. It is regulated by a multi-protein complex called the PANoptosome. As a relatively new concept first described in 2019, PANoptosis has been shown to play a role in many diseases, including cancer, infection, and inflammation. This study reviews the application of PCD in cancer, particularly the emergence and implication of PANoptosis in developing therapeutic strategies for cancer. Studies have shown that the characterization of PANoptosis patterns in cancer can predict survival and response to immunotherapy and chemotherapy, highlighting the potential for PANoptosis to be used as a therapeutic target in cancer treatment. It also plays a role in limiting the spread of cancer cells. PANoptosis allows for the elimination of cancer cells by multiple cell death pathways and has the potential to address various challenges in cancer treatment, including drug resistance and immune evasion. Moreover, active investigation of the mechanisms and potential therapeutic agents that can induce PANoptosis in cancer cells is likely to yield effective cancer treatments and improve patient outcomes. Research on PANoptosis is still ongoing, but it is a rapidly evolving field with the potential to lead to new treatments for various diseases, including cancer.

Unmasking the Risk Factors Associated with Undiagnosed Diabetes and Prediabetes in Ghana: Insights from Cardiometabolic Risk (CarMeR) Study-APTI Project.

INTRODUCTION: Undiagnosed diabetes poses significant public health challenges in Ghana. Numerous factors may influence the prevalence of undiagnosed diabetes among adults, and therefore, using a model that takes into account the intricate network of these relationships should be considered. Our goal was to evaluate fasting plasma levels, a critical indicator of diabetes, and the associated direct and indirect associated or protective factors. METHODS: This research employed a cross-sectional survey to sample 1200 adults aged 25-70 years who perceived themselves as healthy and had not been previously diagnosed with diabetes from 13 indigenous communities within the Cape Coast Metropolis, Ghana. Diabetes was diagnosed based on the American Diabetes Association (ADA) criteria for fasting plasma glucose, and lipid profiles were determined using Mindray equipment (August 2022, China). A stepwise WHO questionnaire was used to collect data on sociodemographic and lifestyle variables. We analyzed the associations among the exogenous, mediating, and endogenous variables using a generalized structural equation model (GSEM). RESULTS: Overall, the prevalence of prediabetes and diabetes in the Cape Coast Metropolis was found to be 14.2% and 3.84%, respectively. In the sex domain, females had a higher prevalence of prediabetes (15.33%) and diabetes (5.15%) than males (12.62% and 1.24%, respectively). Rural areas had the highest prevalence, followed by peri-urban areas, whereas urban areas had the lowest prevalence. In the GSEM results, we found that body mass index (BMI), triglycerides (TG), systolic blood pressure (SBP), gamma-glutamyl transferase (GGT), and female sex were direct predictive factors for prediabetes and diabetes, based on fasting plasma glucose (FPG) levels. Indirect factors influencing diabetes and prediabetes through waist circumference (WC) included childhood overweight status, family history, age 35-55 and 56-70, and moderate and high socioeconomic status. High density lipoprotein (HDL) cholesterol, childhood overweight, low physical activity, female sex, moderate and high socioeconomic status, and market trading were also associated with high BMI, indirectly influencing prediabetes and diabetes. Total cholesterol, increased TG levels, WC, age, low physical activity, and rural dwellers were identified as indirectly associated factors with prediabetes and diabetes through SBP. Religion, male sex, and alcohol consumption were identified as predictive factors for GGT, indirectly influencing prediabetes and diabetes. CONCLUSIONS: Diabetes in indigenous communities is directly influenced by blood lipid, BMI, SBP, and alcohol levels. Childhood obesity, physical inactivity, sex, socioeconomic status, and family history could indirectly influence diabetes development. These findings offer valuable insights for policymakers and health-sector stakeholders, enabling them to understand the factors associated with diabetes development and implement necessary public health interventions and personalized care strategies for prevention and management in Ghana.

Risk factors for cardiometabolic health in Ghana: Cardiometabolic Risks Study Protocol-APTI Project.

Introduction: Cardiometabolic diseases are rapidly becoming primary causes of death in developing countries, including Ghana. However, risk factors for these diseases, including obesity phenotype, and availability of cost-effective diagnostic criteria are poorly documented in an African-ancestry populations in their native locations. The extent to which the environment, occupation, geography, stress, and sleep habits contribute to the development of Cardiometabolic disorders should be examined. Purpose: The overall goal of this study is to determine the prevalence of undiagnosed diabetes, prediabetes, and associated cardiovascular risks using a multi-sampled oral glucose tolerance test. The study will also investigate the phenotype and ocular characteristics of diabetes and prediabetes subgroups, as well as determine if lifestyle changes over a one-year period will impact the progression of diabetes and prediabetes. Methods and analysis: The study employs a community-based quasi-experimental design, making use of pre- and post-intervention data, as well as a questionnaire survey of 1200 individuals residing in the Cape Coast metropolis to ascertain the prevalence and risk factors for undiagnosed diabetes and prediabetes. Physical activity, dietary habits, stress levels, sleep patterns, body image perception, and demographic characteristics will be assessed. Glucose dysregulation will be detected using oral glucose tolerance test, fasting plasma glucose, and glycated hemoglobin. Liver and kidney function will also be assessed. Diabetes and prediabetes will be classified using the American Diabetes Association criteria. Descriptive statistics, including percentages, will be used to determine the prevalence of undiagnosed diabetes and cardiovascular risks. Inferential statistics, including ANOVA, t-tests, chi-square tests, ROC curves, logistic regression, and linear mixed model regression will be used to analyze the phenotypic variations in the population, ocular characteristics, glycemic levels, sensitivity levels of diagnostic tests, etiological cause of diabetes in the population, and effects of lifestyle modifications, respectively. Additionally, t-tests will be used to assess changes in glucose regulation biomarkers after lifestyle modifications. Ethics and dissemination: Ethics approval was granted by the Institutional Review Board of the University of Cape Coast, Ghana (UCCIRB/EXT/2022/27). The findings will be disseminated in community workshops, online learning platforms, academic conferences and submitted to peer-reviewed journals for publication.

HBV Infection Is an Intermediate-Risk Disease, Whereas Anaemia Is a Mild-to-Moderate Public Health Problem in Young Ghanaian Adults: A Four-Year Retrospective Analysis of Students' Medical Records.

Background: In sub-Saharan Africa, malaria, chronic viral diseases, nutritional deficiencies, and haemoglobinopathies are common causes of anaemia. Continual surveillance data is required to situate the anaemia and infectious disease burden within a given population. This study determined the 4-year trends of anaemia, hepatitis B virus (HBV), and HCV infections and factors associated with anaemia in young Ghanaian adults. Methods: This retrospective study analysed the medical records of 21,716 fresh students at the University of Cape Coast. Data was presented as percentages and line graphs to show the yearly trends in anaemia, HBV, and HCV infections. Binary logistic regression was used to determine the increased odds of anaemia in participants. Results: Although the 4-year anaemia prevalence was 14.2% (95% CI: 0.1403-0.1498), anaemia prevalence in women and men were 24.1% (95% CI: 0.2387-0.2562) and 6.6% (95% CI:0.0616-0.0705), respectively. Anaemia prevalence consistently remained mild (males) and moderate (females) public health problem over the four-year period. Adolescents were more represented in the anaemic group (18.7% prevalence), 70.9% of them being females. The prevalence of HBV and HCV infections were 5.4% (95% CI:0.0506-0.0567) and 0.9% (95% CI: 0.0082-0.0108), respectively; only 0.1% of participants had HBV and HCV coinfection. Males were more represented in both HBV (71.2%) and HCV (63.7%) infection groups. Moreover, 15.8% of the participants who were seropositive for HBsAg self-reported having previously been vaccinated, suggesting a breakthrough infection and/or vaccine nonresponse. Furthermore, female (COR: 4.545; p < 0.001), teenagers (COR: 1.697; p < 0.001), 20-29 years (COR: 1.221; p = 0.035), and positive sickling slide test (COR: 1.176; p = 0.003) were statistically significantly associated with increased odds of anaemia. Conclusion: Intentional preventative public health campaigns regarding anaemia, HBV, and HCV infection should, respectively, target females and young adult males to increase chances of making real change in behavioural attitudes in these at-risk groups.

Mesenchymal stem cell-derived exosome mitigates colitis via the modulation of the gut metagenomics-metabolomics-farnesoid X receptor axis.

Inflammatory bowel disease (IBD) is associated with chronic gut immune dysregulation and altered microbiome and metabolite composition. Bile acids and their receptors such as the farnesoid X receptor (FXR) form a crucial component of the chemical communications between the intestinal microbiota and the host immune system; thus, alterations in the bile acid pool affect intestinal homeostasis and exacerbate IBD. Considering the promising therapeutic effect of mesenchymal stem cell-derived exosomes (MSC-Ex) on IBD, this study assessed the regulatory effect of MSC-Ex on the gut bacteria composition and diversity, metabolites, and their related functions and pathways, as well as key inflammatory and anti-inflammatory cytokines during the mitigation of IBD. The dextran sulfate sodium (DSS)-induced IBD model of BABL/C mice was established, consisting of three groups: control, DSS, and MSC-Ex groups. Post administration of MSC-Ex, the effect was evaluated via hematoxylin and eosin (H&E) staining, immunohistochemistry (IHC), qRT-PCR, and western blotting. Mice fecal samples were obtained for metagenomics and metabolomics analysis via 16S rRNA gene sequencing and UHPLC/Q-TOF-MS respectively. Results showed that MSC-Ex mitigated colitis by significantly relieving the macroscopic and microscopic features of inflammation, modulating the gut metagenomics and metabolomics profile, and increasing colonic FXR. MSC-Ex improved the gut microbiota composition by significantly restoring the structure of OTUs and colitis-induced reduction in α-diversity, increasing the abundance of 'healthy' bacteria, decreasing disease-associated bacteria, decreasing detrimental functions, and enhancing other vital cellular functions. For the first time, we demonstrate that MSC-Ex mitigates colitis in mice by modulating the gut metagenomics-metabolomics-FXR axis, thus providing potential therapeutic targets.

The gut metagenomics and metabolomics signature in patients with inflammatory bowel disease.

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.

Antibiotic-resistant pathogenic bacterial isolates from patients attending the outpatient department of university of Cape Coast hospital, Ghana: A retrospective study between 2013-2015.

Uropathogenic Escherichia coli (E. coli) is an important urinary tract infection (UTI) that has been associated with both complicated and uncomplicated disease conditions. The global emergence of multiple drug-resistant (MDR) and extended-spectrum ß-lactamase (ESBL) is of public health concern as the resistance limits the current treatment options. The objective of this study was to analyze the antibiotic-resistant patterns among the uropathogenic E. coli isolates at the University of Cape Coast (UCC) hospital between 2013 and 2015 as baseline data to understand the current antibiotic resistance situation within UCC and its environs. A retrospective cross-sectional study of bacteria isolates at UCC hospital from January 2013 to December 2015 were analyzed. A standard biochemical and antibiotic susceptibility tests were performed using Kirby-Bauer NCCLs modified disc diffusion technique. The network of interaction between pathogenic isolates and antibiotic resistance was performed using Cytoscape software. Statistical significance was tested using ANOVA and one-sample Wilcoxon test. The overall E. coli prevalence was 15.76% (32/203); females had the highest infection of 17.33% (26/150) compared to male subjects who had 11.32% (6/53) out of all the pathogenic infections. The E. coli prevalence among the age categories were 2/21 (9.52%), 27/154 (17.53%) and 4/21 (19.05%) among ≤20 years, 21-40 years and 41-60 years respectively. The isolated resistant pathogens exhibited different antibiotic resistance patterns. An interaction network of nodes connecting to other nodes indicating positive correlations between the pathogens and antibiotic resistance was established. Escherichia coli, Citrobacter spp, Klebsiella spp among other isolated pathogens formed higher centrality in the network of interaction with antibiotic resistance. The individual E. coli isolates showed a significant difference in the mean ± SD (95% CI) pattern of antibiotic resistance, 2.409±1.205 (1.828-2.990), χ2 = 36.68, p<0.0001. In conclusion, the study reports the interaction of E. coli isolates at UCC hospital and its antibiotic-resistant status between 2013 and 2015. This data forms the baseline information for assessing the current antibiotic status in UCC and its environs.

Self-amplifying mRNA SARS-CoV-2 vaccines raise cross-reactive immune response to variants and prevent infection in animal models.

The spike (S) protein of SARS-CoV-2 plays a crucial role in cell entry, and the nucleocapsid (N) protein is highly conserved among human coronavirus homologs. For potentially broad effectiveness against both original virus and emerging variants, we developed Alphavirus-based self-amplifying mRNA (sa-mRNA) SARS-CoV-2 vaccines: an sa-mRNA S encoding a full-length S protein stabilized in a prefusion conformation and an sa-mRNA S-N co-expressing S and N proteins for the original virus. We show that these sa-mRNA SARS-CoV-2 vaccines raised potent neutralizing antibody responses in mice against not only the original virus but also the Alpha, Beta, Gamma, and Delta variants. sa-mRNA S vaccines against the Alpha and Beta variants also raised robust cross-reactive neutralizing antibody responses against their homologous viruses and heterologous variants. sa-mRNA S and sa-mRNA S-N vaccines elicited Th1-dominant, antigen-specific CD4+ T cell responses to S and N proteins and robust and broad CD8+ T cell responses to S protein. Hamsters immunized with either vaccine were fully protected from lung infection and showed significant reduction of viral load in upper respiratory tract. Our findings demonstrate that sa-mRNA SARS-CoV-2 vaccines are potent in animal models with potential to be highly effective against SARS-CoV-2 infection in humans.