Potential for Maternally Administered Vaccine for Infant Group B Streptococcus.

BACKGROUND: Natural history studies have correlated serotype-specific anti-capsular polysaccharide (CPS) IgG in newborns with a reduced risk of group B streptococcal disease. A hexavalent CPS-cross-reactive material 197 glycoconjugate vaccine (GBS6) is being developed as a maternal vaccine to prevent invasive group B streptococcus in young infants. METHODS: In an ongoing phase 2, placebo-controlled trial involving pregnant women, we assessed the safety and immunogenicity of a single dose of various GBS6 formulations and analyzed maternally transferred anti-CPS antibodies. In a parallel seroepidemiologic study that was conducted in the same population, we assessed serotype-specific anti-CPS IgG concentrations that were associated with a reduced risk of invasive disease among newborns through 89 days of age to define putative protective thresholds. RESULTS: Naturally acquired anti-CPS IgG concentrations were associated with a reduced risk of disease among infants in the seroepidemiologic study. IgG thresholds that were determined to be associated with 75 to 95% reductions in the risk of disease were 0.184 to 0.827 µg per milliliter. No GBS6-associated safety signals were observed among the mothers or infants. The incidence of adverse events and of serious adverse events were similar across the trial groups for both mothers and infants; more local reactions were observed in the groups that received GBS6 containing aluminum phosphate. Among the infants, the most common serious adverse events were minor congenital anomalies (umbilical hernia and congenital dermal melanocytosis). GBS6 induced maternal antibody responses to all serotypes, with maternal-to-infant antibody ratios of approximately 0.4 to 1.3, depending on the dose. The percentage of infants with anti-CPS IgG concentrations above 0.184 µg per milliliter varied according to serotype and formulation, with 57 to 97% of the infants having a seroresponse to the most immunogenic formulation. CONCLUSIONS: GBS6 elicited anti-CPS antibodies against group B streptococcus in pregnant women that were transferred to infants at levels associated with a reduced risk of invasive group B streptococcal disease. (Funded by Pfizer and the Bill and Melinda Gates Foundation; C1091002 ClinicalTrials.gov number, NCT03765073.).

Seroprevalence of hepatitis C, hepatitis B, hiv and syphilis among blood donors at a tertiary care hospital in Mogadishu-Somalia in 2020-2022: a retrospective study.

BACKGROUND: The safety of blood donation requires screening for transfusion-transmitted infections, including human immunodeficiency virus (HIV), syphilis, hepatitis B virus (HBV) and hepatitis C virus (HCV). This study aimed to determine the seroprevalence of HIV, HBV, HCV and syphilis in blood donors of Mogadishu Tertiary Care Hospital, Somalia from 2020 to 2022. METHODS: The records of 109,385 blood donors who attended our blood center in Mogadishu-Somalia between 2020 and 2022 were examined retrospectively. Serum samples of donors; HBsAg, anti-HCV, anti-HIV and syphilisscreening tests were studied using the microparticleEnzyme-Linked ImmunoSorbent Assay (ELISA)(Vitros, Ortho-Clinical Diagnostics, U.S) method.The distribution of HBsAg, anti-HCV, anti-HIV and syphilis positivity rates of 109,385 blood donors according to years, gender and age were examined. Kolmogorov Smirnov, Skewness, Kurtosis tests and histogram were used for normality analysis. Chi-squared test (χ2) and Fisher Exact test were used to analyze categorical data. Categorical variables were expressed as frequency (percentage). Analysis of continuous data was performed with the Mann Whitney U test. P < 0.05 value was considered statistically significant. RESULTS: HBsAg positivity was found in 0.6% of the donors, anti-HCV positivity in 0.01%, anti-HIV positivity in 0.03% and syphilispositivity in 0.3%. The results showed that among the blood donors, the prevalence of syphilis, HIV, Hepatitis B, and Hepatitis Cwas notably low. CONCLUSION: The prevalence of HBV, HCV, HIV, and syphilis among blood donors in Somalia was found to be quite low. Even if our found seroprevalence rates are low, to guarantee the safety of blood for recipients, strict selection of blood donors and thorough screening of donors' blood using accepted procedures are strongly advised.

Combining In Vitro, In Vivo, and Network Pharmacology Assays to Identify Targets and Molecular Mechanisms of Spirulina-Derived Biomolecules against Breast Cancer.

The current research employed an animal model of 7,12-dimethylbenz(a)anthracene (DMBA)-induced mammary gland carcinogenesis. The estrogen receptor-positive human breast adenocarcinoma cell line (MCF-7) was used for in vitro analysis. This was combined with a network pharmacology-based approach to assess the anticancer properties of Spirulina (SP) extract and understand its molecular mechanisms. The results showed that the administration of 1 g/kg of SP increased the antioxidant activity by raising levels of catalase (CAT) and superoxide dismutase (SOD), while decreasing the levels of malonaldehyde (MDA) and protein carbonyl. A histological examination revealed reduced tumor occurrence, decreased estrogen receptor expression, suppressed cell proliferation, and promoted apoptosis in SP protected animals. In addition, SP disrupted the G2/M phase of the MCF-7 cell cycle, inducing apoptosis and reactive oxygen species (ROS) accumulation. It also enhanced intrinsic apoptosis in MCF-7 cells by upregulating cytochrome c, Bax, caspase-8, caspase-9, and caspase-7 proteins, while downregulating Bcl-2 production. The main compounds identified in the LC-MS/MS study of SP were 7-hydroxycoumarin derivatives of cinnamic acid, hinokinin, valeric acid, and α-linolenic acid. These substances specifically targeted three important proteins: ERK1/2 MAPK, PI3K-protein kinase B (AKT), and the epidermal growth factor receptor (EGFR). Network analysis and molecular docking indicated a significant binding affinity between SP and these proteins. This was verified by Western blot analysis that revealed decreased protein levels of p-EGFR, p-ERK1/2, and p-AKT following SP administration. SP was finally reported to suppress MCF-7 cell growth and induce apoptosis by modulating the PI3K/AKT/EGFR and MAPK signaling pathways suggesting EGFR as a potential target of SP in breast cancer (BC) treatment.

Zirconium-based hydrophobic-MOFs as innovative electrode modifiers for flibanserin determination: Exploring the electrooxidation mechanism using a comprehensive spectroelectrochemical study.

Three different types of Zr-based MOFs derived from benzene dicarboxylic acid (BDC) and naphthalene dicarboxylic acid as organic linkers (ZrBDC, 2,6-ZrNDC, and 1,4-ZrNDC) were synthesized. They were characterized using X-ray diffraction analysis (XRD), X-ray photoelectron spectroscopy (XPS), Fourier-transform IR spectroscopy (FT-IR), and Transmission electron microscopy (TEM). Their hydrophilic/hydrophobic nature was investigated via contact angle measurements; ZrBDC MOF was hydrophilic and the other two (ZrNDC) MOFs were hydrophobic. The three MOFs were combined with MWCNTs as electrode modifiers for the determination of a hydrophobic analyte, flibanserin (FLB), as a proof-of-concept analyte. Under the optimized experimental conditions, a significant enhancement in the oxidation peak current of FLB was observed when utilizing 2,6-ZrNDC and 1,4-ZrNDC, being the highest when using 1,4-ZrNDC. Furthermore, a thorough investigation of the complex oxidation pathway of FLB was performed by carrying out simultaneous spectroelectrochemical measurements. Based on the obtained results, it was verified that the piperazine moiety of FLB is the primary site for electrochemical oxidation. The fabricated sensor based on 1,4-ZrNDC/MW/CPE showed an oxidation peak of FLB at 0.8 V vs Ag/AgCl. Moreover, it showed excellent linearity for the determination of FLB in the range 0.05 to 0.80 µmol L-1 with a correlation coefficient (r) = 0.9973 and limit of detection of 3.0 nmol L-1. The applicability of the developed approach was demonstrated by determination of FLB in pharmaceutical tablets and human urine samples with acceptable repeatability (% RSD values were below 1.9% and 2.1%, respectively) and reasonable recovery values (ranged between 97 and 103% for pharmaceutical tablets and between 96 and 102% for human urine samples). The outcomes of the suggested methodology can be utilized for the determination of other hydrophobic compounds of pharmaceutical or biological interest with the aim of achieving low detection limits of these compounds in various matrices.

Evaluation of masticatory performance and patient satisfaction for conventional and 3D-printed implant overdentures: a randomized crossover study.

BACKGROUND: This crossover clinical study aimed to evaluate and compare masticatory performance and patient satisfaction for patients rehabilitated with conventional heat-cured acrylic resin and 3D-printed mandibular implant overdentures retained with bar attachment. MATERIALS AND METHODS: Sixteen completely edentulous healthy participants received new conventional dentures. In the mandible, four interforaminal implants were inserted. Following the stage of osseointegration, the bar was constructed in a trapezoidal configuration. Each patient randomly received the following overdentures using a crossover design: (1) conventional heat-cured acrylic resin overdenture and (2) 3D-printed overdenture (developed by scanning of mandibular conventional overdenture). The masticatory performance was assessed by conducting a two-colour mixing ability test at 5, 10, 20, 30, and 50 masticatory cycles. Moreover, the McGill Denture Satisfaction Questionnaire (MDSQ) was employed to assess patient satisfaction. Evaluation was performed after 3 months of using each overdenture. Paired sample t tests were used to compare the masticatory performance and MDSQ scores of patients for both prostheses. RESULTS: No significant difference in masticatory performance was reported between the two types of overdentures. Regarding patient satisfaction, only the esthetic aspect was significantly better for conventionally processed overdentures than for printed overdentures. Insignificant differences were observed regarding other MDSQ items between the two overdentures. CONCLUSION: Within this clinical study, 3D-printed implant overdentures showed promising results in terms of chewing efficiency and patient satisfaction compared to conventionally fabricated implant overdentures. TRIAL REGISTRATION: Retrospectively registered at www. CLINICALTRIALS: gov : NCT06148727.(28/11/2023).

Evaluating systematic targeted universal testing for tuberculosis in primary care clinics of South Africa: A cluster-randomized trial (The TUTT Trial).

BACKGROUND: The World Health Organization (WHO) recommends systematic symptom screening for tuberculosis (TB). However, TB prevalence surveys suggest that this strategy does not identify millions of TB patients, globally. Undiagnosed or delayed diagnosis of TB contribute to TB transmission and exacerbate morbidity and mortality. We conducted a cluster-randomized trial of large urban and rural primary healthcare clinics in 3 provinces of South Africa to evaluate whether a novel intervention of targeted universal testing for TB (TUTT) in high-risk groups diagnosed more patients with TB per month compared to current standard of care (SoC) symptom-directed TB testing. METHODS AND FINDINGS: Sixty-two clinics were randomized; with initiation of the intervention clinics over 6 months from March 2019. The study was prematurely stopped in March 2020 due to clinics restricting access to patients, and then a week later due to the Coronavirus Disease 2019 (COVID-19) national lockdown; by then, we had accrued a similar number of TB diagnoses to that of the power estimates and permanently stopped the trial. In intervention clinics, attendees living with HIV, those self-reporting a recent close contact with TB, or a prior episode of TB were all offered a sputum test for TB, irrespective of whether they reported symptoms of TB. We analyzed data abstracted from the national public sector laboratory database using Poisson regression models and compared the mean number of TB patients diagnosed per clinic per month between the study arms. Intervention clinics diagnosed 6,777 patients with TB, 20.7 patients with TB per clinic month (95% CI 16.7, 24.8) versus 6,750, 18.8 patients with TB per clinic month (95% CI 15.3, 22.2) in control clinics during study months. A direct comparison, adjusting for province and clinic TB case volume strata, did not show a significant difference in the number of TB cases between the 2 arms, incidence rate ratio (IRR) 1.14 (95% CI 0.94, 1.38, p = 0.46). However, prespecified difference-in-differences analyses showed that while the rate of TB diagnoses in control clinics decreased over time, intervention clinics had a 17% relative increase in TB patients diagnosed per month compared to the prior year, interaction IRR 1.17 (95% CI 1.14, 1.19, p < 0.001). Trial limitations were the premature stop due to COVID-19 lockdowns and the absence of between-arm comparisons of initiation and outcomes of TB treatment in those diagnosed with TB. CONCLUSIONS: Our trial suggests that the implementation of TUTT in these 3 groups at extreme risk of TB identified more TB patients than SoC and could assist in reducing undiagnosed TB patients in settings of high TB prevalence. TRIAL REGISTRATION: South African National Clinical Trials Registry DOH-27-092021-4901.

Psychological legacies of intergenerational trauma under South African apartheid: Prenatal stress predicts greater vulnerability to the psychological impacts of future stress exposure during late adolescence and early adulthood in Soweto, South Africa.

BACKGROUND: South Africa's rates of psychiatric morbidity are among the highest in sub-Saharan Africa and are foregrounded by the country's long history of political violence during apartheid. Growing evidence suggests that in utero stress exposure is a potent developmental risk factor for future mental illness risk, yet the extent to which the psychiatric effects of prenatal stress impact the next generation are unknown. We evaluate the intergenerational effects of prenatal stress experienced during apartheid on psychiatric morbidity among children at ages 17-18 and also assess the moderating effects of maternal age, social support, and past household adversity. METHODS: Participants come from Birth-to-Twenty, a longitudinal birth cohort study in Soweto-Johannesburg, South Africa's largest peri-urban township which was the epicentre of violent repression and resistance during the final years of the apartheid regime. Pregnant women were prospectively enrolled in 1990 and completed questionnaires assessing social experiences, and their children's psychiatric morbidity were assessed at ages 17-18. RESULTS: Full data were available from 304 mother-child pairs in 2007-8. Maternal prenatal stress in 1990 was not directly associated greater psychiatric morbidity during at ages 17-18. Maternal age and past household adversity moderated the intergenerational mental health effects of prenatal stress such that children born to younger mothers and late adolescent/young adult children experiencing greater household adversity exhibited worse psychiatric morbidity at ages 17-18. Social support did not buffer against the long-term psychiatric impacts of prenatal stress. CONCLUSIONS: Greater prenatal stress from apartheid predicted adverse psychiatric outcomes among children born to younger mothers and adolescents/young adults who experienced greater concurrent stress. Our findings suggest that prenatal stress may affect adolescent mental health, have stress-sensitising effects, and represent possible intergenerational effects of trauma experienced under apartheid in this sample.

In vitro assessment of PEG-6000 coated-ZnO nanoparticles: modulating action to the resisted antibiotic activity against APEC.

BACKGROUND: Avian pathogenic Escherichia coli (APEC) are considered a growing health problem to both poultry and the public, particularly due to its multi-drug resistance. Zinc oxide nanoparticles (ZnO-NPs) are a promising multi-benefit candidate. This study focused on boosting the antimicrobial effect of the chemically synthesized ZnO-NPs using Polyethylene glycol-6000 (PEG-6000) and evaluating their potential to recover the sensitivity of Florfenicol and Streptomycin-resistant APEC to these drugs in a concentration range of 0.1-0.4 mg/mL. Four samples of ZnO-NPs were formulated and tested microbiologically. RESULTS: The physicochemical characterization showed well-crystallized spherical in situ synthesized ZnO-NPs using PEG-6000 (surfactant) and ethanol (co-surfactant) of ∼19-67 nm particle size after coating with PEG-6000 molecules. These ZnO-NPs demonstrated a strong concentration-dependent antibacterial effect against multidrug-resistant APEC strains, with a minimum inhibitory concentration of 0.1 mg/mL, Combining PEG-6000 coated in situ synthesized ZnO-NPs and Florfenicol induced 60% high sensitivity (30 mm inhibitory-zone), 30% intermediate sensitivity, and 10% resistance against APEC strains. The combination with Streptomycin revealed 50% high sensitivity, 30% intermediate sensitivity, and 20% resistance with a 20 mm maximum zone of inhibition using agar well diffusion test. CONCLUSION: In situ preparation of ZnO-NPs using PEG-6000 and ethanol followed by coating with PEG-6000 enhanced its antibacterial activity in minimum inhibitory concentration and regained the efficacy of Florfenicol and Streptomycin against APEC, referring to a non-antibiotic antimicrobial alternative and an effective combination regimen against multidrug-resistant APEC E. coli in veterinary medicine.

Valuation of environmental influence of recently invented high-performance liquid chromatographic method for hypoglycemic mixtures of gliflozins and metformin in the presence of melamine impurities: Application of molecular modeling simulation approach.

Molecular modeling is the science of representing molecular structures numerically and simulating their behavior with the equations of quantum and classical physics. Coupling molecular modeling and simulation with chromatographic resolution for pharmaceutical products constitutes a new technique in pharmaceutical analysis. An innovative high-performance liquid chromatographic (HPLC) methodology was developed for the quantification of metformin hydrochloride (MET), empagliflozin (EMP), and canagliflozin (CAN) in bulk, laboratory-developed combinations, pharmaceutical tablets, and in the presence of melamine. Chromatographic separation was accomplished using a Symmetry column with 0.03 M potassium dihydrogen phosphate buffer and 0.02 M heptane sulphonic acid: acetonitrile as the mobile phase. Molecular modeling using molecular operating environment software was applied to properly select the stationary phase suitable for the developed HPLC method. Additionally, molecular modeling estimates and validates binding between the studied analytes and the stationary phase to clarify and explain the chromatographic separation and elution order. In accordance with the International Conference of Harmonization recommendations, the method was validated in terms of linearity, accuracy, precision, and selectivity. The linearity ranges (µg/ml) were 200-1500 (MET), 2-15 (EMP), and 20-150 (CAN) and the limit of detection values were in the ranges of 0.17-54.58 µg/ml. Analysis of pharmaceutical tablets using the suggested approach yielded satisfactory outcomes. As a result, it might be used in quality control laboratories to analyze the aforementioned medications.

Infection, nutritional status, and body composition: Associations at birth and 6 months postnatally in Soweto, South Africa.

INTRODUCTION: The impact of infection on infant nutritional status, body size, and growth is well documented. However, research into the impact of infection on infant body composition is limited. Greater understanding is, therefore, needed on the effects of infection in early life. METHODS: Associations between a composite morbidity index consisting of the sum of the cumulative tallies for a range of symptoms representing infection and morbidity in the infants and nutritional status (height-for-age (HAZ), and weight-for-height (WHZ)), and body composition (fat-free mass (FFM), fat mass (FM), fat-free mass index (FFMI), and fat mass index (FMI)) at 6 months of age were investigated using hierarchical regression analysis. RESULTS: The sample comprised data between birth and 6 months postnatally, of 156 infants who were a priori born healthy in Soweto, South Africa. Morbidity, over the cumulative period of birth to 6 months, was associated with lower FMI (ß = -1.77) and lower FM (ß = -0.61), and conversely with higher FFM (ß = 0.94), in infants at 6 months. No associations were found between the morbidity index and FFMI, HAZ, and WHZ. Increased birthweight was associated with a higher FFM (ß = 0.66), HAZ (ß = 1.14), and WHZ (ß = 0.87). Finally, safely managed sanitation facilities, representative of reduced environmental exposure to fecal-oral transmission pathways were associated with a higher HAZ (ß = 1.21). DISCUSSION: Reduction in FMI and FM and exposure to inflammatory cytokines associated with mounting an immune response could alter phenotypic trajectories during to this period of plasticity. From a public health perspective, these results imply that it is important to intensify efforts to prevent infection in infants in the first 6 months postnatally, and that these efforts should concentrate on access to safely managed sanitation facilities.