Bivalent Omicron BA.4/BA.5 BNT162b2 Vaccine in 6-Month- to <12-Year-Olds.

BACKGROUND: With the future epidemiology and evolution of SARS-CoV-2 uncertain, use of safe and effective COVID-19 vaccines in pediatric populations remains important. METHODS: We report data from two open-label substudies of an ongoing phase 1/2/3 master study (NCT05543616) investigating safety and immunogenicity of a variant-adapted bivalent COVID-19 vaccine encoding ancestral and Omicron BA.4/BA.5 spike proteins (bivalent BNT162b2). The open-label groups presented here evaluate dose 4 with bivalent BNT162b2 in 6-month-<12-year-olds who previously received three original (monovalent) BNT162b2 doses. In 6-month-<5-year-olds, primary immunogenicity objectives were to demonstrate superiority (neutralizing titer) and noninferiority (seroresponse rate) to Omicron BA.4/BA.5 and noninferiority (neutralizing titer and seroresponse rate) to SARS-CoV-2 ancestral strains in participants who received bivalent BNT162b2 dose 4 compared with a matched group who received three doses of original BNT162b2 in the pivotal pediatric study (NCT04816643). In 5-<12-year-olds, primary immunogenicity comparisons were descriptive. Reactogenicity and safety following vaccination were evaluated. RESULTS: In 6-month-<5-year-olds, dose 4 with bivalent BNT162b2 met predefined immunogenicity superiority and noninferiority criteria against Omicron BA.4/BA.5 and ancestral strains when compared with dose 3 of original BNT162b2. In 5-<12-year-olds, bivalent BNT162b2 induced robust Omicron BA.4/BA.5 and ancestral strain neutralizing titers comparable to dose 3 of original BNT162b2. The safety profile for dose 4 of bivalent BNT162b2 given as dose 4 was consistent with that of original BNT162b2 in 6 month-<12-year-olds. Reactogenicity events were generally mild-to-moderate. No adverse events led to discontinuation. CONCLUSIONS: These safety and immunogenicity data support a favorable benefit-risk profile for a variant-adapted BNT162b2 in children <12 years old.

Occurrence, ecological risk assessment and source apportionment of pharmaceuticals, steroid hormones and xenoestrogens in the Ghanaian aquatic environments.

Elevated levels of pharmaceuticals, steroid hormones and xenoestrogens (PSHXEs) in the aquatic environment pose a serious threat to the ecological balance. The endocrine disrupting PSHXEs in aquatic systems are linked to several adverse effects like reproductive health impairment, feminization, high mortality rate, decreased biodiversity etc. This study, therefore, sought to investigate the occurrence and the ecological risks posed by some selected PSHXEs and also conduct source apportionment of the PSHXEs in the Ghanaian aquatic environments. A total of 48 samples comprising 24 sediments and water each were taken from six waterbodies in Ghana. The samples were extracted using SPE cartridges for water and QuEChERS-dSPE for sediments. The analyses were done using Shimadzu Prominence UFLC 20A series. Ecological risk assessments were also conducted with the aid of USEPA T.E.S.T., whereas source apportionments were conducted using the APCS-MLR receptor model. Elevated mean total levels of PSHXEs ranging between 12,187 and 52,117 ng/L and 2,022-6,047 ng/g for water and sediment samples respectively were found. The risk quotients (RQ > 1) suggested a high risk posed by PSHXEs in water to organisms at the three trophic levels and also to benthic organisms in sediments of the Ghanaian aquatic environments for a short-term period. The APCS-MLR receptor model suggested three statistically significant sources (p < 0.05) designated by signature PSHXEs as domestic (major), mix hospital and industrial and agricultural waste sources. The source apportionment suggested increased use of steroid estrogens and anabolic drugs among the Ghana populace.

Physical distancing and risk of COVID-19 in small-scale fisheries: a remote sensing assessment in coastal Ghana.

The novel coronavirus is predicted to have dire implications on global food systems including fisheries value chains due to restrictions imposed on human movements in many countries. In Ghana, food production, both agriculture and fisheries, is exempted from restrictions as an essential service. The enforcement of COVID-19 prevention protocols, particularly social distancing, has been widely reported in Ghana's agricultural markets whereas casual observations and media reports on fish landing sites suggest no such enforcements are in place. This study aimed to provide sound scientific evidence as a basis for informed policy direction and intervention for the artisanal fishing sector in these challenging times. We employed an unmanned aerial vehicle in assessing the risk of artisanal fishers to the pandemic using physical distancing as a proxy. From analysis of cumulative distribution function (G-function) of the nearest-neighbour distances, this study underscored crowding at all surveyed fish landing beaches, and identified potential "hotspots" for disease transmission. Aerial measurements taken at times of peak landing beach activity indicated that the highest proportion of people, representing 56%, 48%, 39% and 78% in Elmina, Winneba, Apam and Mumford respectively, were located at distances of less than one metre from their nearest neighbour. Risk of crowding was independent of the population at the landing beaches, suggesting that all categories of fish landing sites along the coast would require equal urgency and measured attention towards preventing and mitigating the spread of the disease.

Assessment of surface water quality status of the Aby Lagoon System in the Western Region of Ghana.

The pollution status of the Tendo Lagoon, the upstream section of the Aby Lagoon System, was investigated. The water temperature, pH, turbidity, dissolved oxygen (DO), electrical conductivity (EC), nitrates (NO3 -), and phosphate (PO4 3-) levels were evaluated using samples taken during the wet and dry seasons to assess the variabilities in water quality in the area. The water quality data was subjected to paired t-test, One-way ANOVA, Factor Analysis, Cluster analysis (CA) as well as a Water Quality Index (WQI) evaluation using the Canadian Council of Ministers of the Environment (CCME) model. The paired sample t-test confirmed that the surface water quality varies significantly between the wet and dry season samples (p < 0.05) except for phosphate loads which may be contributed largely by year-round municipal waste discharges. The results of the ANOVA showed that the variation of the water quality parameters among sampling stations was not statistically significant except for turbidity which was relatively higher in the upstream sections where the Tano River enters the lagoon. The results of FA indicated that three significant factors-relating to the degradation of organic materials, suspended solids (turbidity) and nutrients- accounted for 73.65% of spatio-temporal variations in the water quality. The CA showed that the eight sampling stations can be grouped into four distinct clusters based on their water quality. The source of pollution in the demarcated sections of the Aby Lagoon was concluded to be largely due to the result of localized anthropogenic inputs of domestic waste and sediments carried from the upstream in the Tano River. An evaluation of the CCME WQI for the sampling stations revealed that all the sampling stations showed marginal water quality relative to the target water quality range recommended by the Water Resources Commission (WRC) of Ghana for domestic use and protection of aquatic life. Monitoring programs were recommended with effective management measures instituted and implemented for the sustainability of the lagoon and the Tano River Basin.

Antimicrobial and Antibiofilm Activities of Helical Antimicrobial Peptide Sequences Incorporating Metal-Binding Motifs.

Antimicrobial peptides (AMPs) represent alternative strategies to combat the global health problem of antibiotic resistance. However, naturally occurring AMPs are generally not sufficiently active for use as antibiotics. Optimized synthetic versions incorporating additional design principles are needed. Here, we engineered amino-terminal Cu(II) and Ni(II) (ATCUN) binding motifs, which can enhance biological function, into the native sequence of two AMPs, CM15 and citropin1.1. The incorporation of metal-binding motifs modulated the antimicrobial activity of synthetic peptides against a panel of carbapenem-resistant enterococci (CRE) bacteria, including carbapenem-resistant Klebsiella pneumoniae (KpC+) and Escherichia coli (KpC+). Activity modulation depended on the type of ATCUN variant utilized. Membrane permeability assays revealed that the in silico selected lead template, CM15, and its ATCUN analogs increased bacterial cell death. Mass spectrometry, circular dichroism, and molecular dynamics simulations indicated that coordinating ATCUN derivatives with Cu(II) ions did not increase the helical tendencies of the AMPs. CM15 ATCUN variants, when combined with Meropenem, streptomycin, or chloramphenicol, showed synergistic effects against E. coli (KpC+ 1812446) biofilms. Motif addition also reduced the hemolytic activity of the wild-type AMP and improved the survival rate of mice in a systemic infection model. The dependence of these bioactivities on the particular amino acids of the ATCUN motif highlights the possible use of size, charge, and hydrophobicity to fine-tune AMP biological function. Our data indicate that incorporating metal-binding motifs into peptide sequences leads to synthetic variants with modified biological properties. These principles may be applied to augment the activities of other peptide sequences.

The Relationship between Firefighters' Work Demand and Work-related Musculoskeletal Disorders: The Moderating Role of Task Characteristics.

BACKGROUND: Emergency workers such as firefighters are cataloged within the most demanding and injurious professions globally. Considering the health and safety implications in firefighting, a lot of research needs to be conducted to examine how firefighters' task characteristics and their work demand influence the development of work-related musculoskeletal disorders (WMSDs). This study therefore examines how the task characteristics of firefighters moderates the relationship between their work demand and the development of WMSDs. METHODS: Convenient sampling was employed to select 320 firefighters in the Greater Accra region of Ghana. Data were analyzed using descriptive statistics, correlation, and regression. RESULTS: The findings revealed that work demand and task characteristics have significant positive effects on WMSDs. Again, the task characteristics of firefighters moderates the relationship between their work demand and WMSDs. CONCLUSION: Since the study shows that task characteristics influences the relationship between work demand and WMSDs, it is vital for managers to constantly modify the nature of tasks performed by and work demand of emergency workers to minimize the development of WMSDs and other industrial health complications.

The Relationship between Firefighters' Work Demand and Work-related Musculoskeletal Disorders: The Moderating Role of Task Characteristics

BACKGROUND: Emergency workers such as firefighters are cataloged within the most demanding and injurious professions globally. Considering the health and safety implications in firefighting, a lot of research needs to be conducted to examine how firefighters' task characteristics and their work demand influence the development of work-related musculoskeletal disorders (WMSDs). This study therefore examines how the task characteristics of firefighters moderates the relationship between their work demand and the development of WMSDs. METHODS: Convenient sampling was employed to select 320 firefighters in the Greater Accra region of Ghana. Data were analyzed using descriptive statistics, correlation, and regression. RESULTS: The findings revealed that work demand and task characteristics have significant positive effects on WMSDs. Again, the task characteristics of firefighters moderates the relationship between their work demand and WMSDs. CONCLUSION: Since the study shows that task characteristics influences the relationship between work demand and WMSDs, it is vital for managers to constantly modify the nature of tasks performed by and work demand of emergency workers to minimize the development of WMSDs and other industrial health complications.

IFN-γ and IL-5 whole blood response directed against mycolactone polyketide synthase domains in patients with Mycobacterium ulcerans infection.

BACKGROUND: Buruli ulcer is a disease of the skin and soft tissues caused by infection with a slow growing pathogen, Mycobacterium ulcerans. A vaccine for this disease is not available but M. ulcerans possesses a giant plasmid pMUM001 that harbours the polyketide synthase (PKS) genes encoding a multi-enzyme complex needed for the production of its unique lipid toxin called mycolactone, which is central to the pathogenesis of Buruli ulcer. We have studied the immunogenicity of enzymatic domains in humans with M. ulcerans disease, their contacts, as well as non-endemic areas controls. METHODS: Between March 2013 and August 2015, heparinized whole blood was obtained from patients confirmed with Buruli ulcer. The blood samples were diluted 1 in 10 in Roswell Park Memorial Institute (RPMI) medium and incubated for 5 days with recombinant mycolactone PKS domains and mycolyltransferase antigen 85A (Ag85A). Blood samples were obtained before and at completion of antibiotic treatment for 8 weeks and again 8 weeks after completion of treatment. Supernatants were assayed for interferon-γ (IFN-γ) and interleukin-5 (IL-5) by enzyme-linked immunosorbent assay. Responses were compared with those of contacts and non-endemic controls. RESULTS: More than 80% of patients and contacts from endemic areas produced IFN-γ in response to all the antigens except acyl carrier protein type 3 (ACP3) to which only 47% of active Buruli ulcer cases and 71% of contacts responded. The highest proportion of responders in cases and contacts was to load module ketosynthase domain (Ksalt) (100%) and enoylreductase (100%). Lower IL-5 responses were induced in a smaller proportion of patients ranging from 54% after ketoreductase type B stimulation to only 21% with ketosynthase type C (KS C). Among endemic area contacts, the, highest proportion was 73% responding to KS C and the lowest was 40% responding to acyltransferase with acetate specificity type 2. Contacts of Buruli ulcer patients produced significantly higher IFN-γ and IL-5 responses compared with those of patients to PKS domain antigens and to mycolyltransferase Ag85A of M. ulcerans. There was low or no response to all the antigens in non-endemic areas controls. IFN-γ and IL-5 responses of patients improved after treatment when compared to baseline results. DISCUSSION: The major response to PKS antigen stimulation was IFN-γ and the strongest responses were observed in healthy contacts of patients living in areas endemic for Buruli ulcer. Patients elicited lower responses than healthy contacts, possibly due to the immunosuppressive effect of mycolactone, but the responses were enhanced after antibiotic treatment. A vaccine made up of the most immunogenic PKS domains combined with the mycolyltransferase Ag85A warrants further investigation.

Tapering Practices of Strongman Athletes.

Winwood, PW, Dudson, MK, Wilson, D, Mclaren-Harrison, JKH, Redjkins, V, Pritchard, HJ, and Keogh, JWL. Tapering practices of strongman athletes. J Strength Cond Res 32(5): 1181-1196, 2018-This study provides the first empirical evidence of how strongman athletes taper for strongman competitions. Strongman athletes (n = 454) (mean ± SD: 33.2 ± 8.0 years, 178.1 ± 10.6 cm, 108.6 ± 27.9 kg, 12.6 ± 8.9 years general resistance training, 5.3 ± 5.0 years strongman implement training) completed a self-reported 4-page internet survey on tapering practices. Analysis by sex (male and female), age (≤30 and >30 years), body mass (≤105 and >105 kg), and competitive standard (local/regional amateur, national amateur and professional) was conducted. Eighty-seven percent (n = 396) of strongman athletes reported that they used a taper. Athletes stated that their typical taper length was 8.6 ± 5.0 days, with the step taper the most commonly performed taper (52%). Training volume decreased during the taper by 45.5 ± 12.9%, and all training ceased 3.9 ± 1.8 days out from competition. Typically, athletes reported that training frequency and training duration stayed the same or decreased and training intensity decreased to around 50% in the last week. Athletes generally stated that tapering was performed to achieve recovery, rest, and peak performance; the deadlift, yoke walk, and stone lifts/work took longer to recover from than other lifts; assistance exercises were reduced or removed in the taper; massage, foam rolling, nutritional changes, and static stretching were strategies used in the taper; and, poor tapering occurred when athletes trained too heavy/hard or had too short a taper. These data will assist strongman athletes and coaches in the optimization of tapering variables leading to more peak performances. Future research could investigate the priming and preactivation strategies strongman athletes use on competition day.

In utero exposure to malaria is associated with metabolic traits in adolescence: The Agogo 2000 birth cohort study.

OBJECTIVES: Malaria in pregnancy (MiP) contributes to fetal undernutrition and adverse birth outcomes, and may constitute a developmental origin of metabolic diseases in the offspring. In a Ghanaian birth cohort, we examined the relationships between MiP-exposure and metabolic traits in adolescence. METHODS: MiP at delivery was assessed in 155 mother-child pairs. Among the now teenaged children (mean age, 14.8 years; 53% male), we measured fasting plasma glucose (FPG), body mass index (BMI), and systolic and diastolic blood pressure (BP). Associations of MiP with the adolescents' FPG, BMI, and BP were examined by linear regression. RESULTS: At delivery, 45% were MiP-exposed, which increased FPG in adolescence, adjusted for mother's age at delivery, parity and familial socio-economic status (infected vs. uninfected: mean ΔFPG = 0.20 mmol/L; 95% confidence interval (CI): 0.01, 0.39; p = 0.049). As a trend,this was discernible for BP, particularly for microscopic infections (mean Δsystolic BP = 5.43 mmHg; 95% CI: 0.00, 10.88; p = 0.050; mean Δdiastolic BP = 3.67 mmHg; 95% CI: -0.81, 8.14; p = 0.107). These associations were largely independent of birth weight, gestational age and teenage BMI. Adolescent BMI was not related to MiP. CONCLUSIONS: In rural Ghana, exposure to malaria during fetal development contributes to metabolic conditions in young adulthood.

Adolescent health in rural Ghana: A cross-sectional study on the co-occurrence of infectious diseases, malnutrition and cardio-metabolic risk factors.

In sub-Saharan Africa, infectious diseases and malnutrition constitute the main health problems in children, while adolescents and adults are increasingly facing cardio-metabolic conditions. Among adolescents as the largest population group in this region, we investigated the co-occurrence of infectious diseases, malnutrition and cardio-metabolic risk factors (CRFs), and evaluated demographic, socio-economic and medical risk factors for these entities. In a cross-sectional study among 188 adolescents in rural Ghana, malarial infection, common infectious diseases and Body Mass Index were assessed. We measured ferritin, C-reactive protein, retinol, fasting glucose and blood pressure. Socio-demographic data were documented. We analyzed the proportions (95% confidence interval, CI) and the co-occurrence of infectious diseases (malaria, other common diseases), malnutrition (underweight, stunting, iron deficiency, vitamin A deficiency [VAD]), and CRFs (overweight, obesity, impaired fasting glucose, hypertension). In logistic regression, odds ratios (OR) and 95% CIs were calculated for the associations with socio-demographic factors. In this Ghanaian population (age range, 14.4-15.5 years; males, 50%), the proportions were for infectious diseases 45% (95% CI: 38-52%), for malnutrition 50% (43-57%) and for CRFs 16% (11-21%). Infectious diseases and malnutrition frequently co-existed (28%; 21-34%). Specifically, VAD increased the odds of non-malarial infectious diseases 3-fold (95% CI: 1.03, 10.19). Overlap of CRFs with infectious diseases (6%; 2-9%) or with malnutrition (7%; 3-11%) was also present. Male gender and low socio-economic status increased the odds of infectious diseases and malnutrition, respectively. Malarial infection, chronic malnutrition and VAD remain the predominant health problems among these Ghanaian adolescents. Investigating the relationships with evolving CRFs is warranted.

High prevalence of multidrug-resistant tuberculosis among patients with rifampicin resistance using GeneXpert Mycobacterium tuberculosis/rifampicin in Ghana.

OBJECTIVE/BACKGROUND: Drug-resistant strains of tuberculosis (TB) represent a major threat to global TB control. In low- and middle-income countries, resource constraints make it difficult to identify and monitor cases of resistance using drug susceptibility testing and culture. Molecular assays such as the GeneXpert Mycobacterium tuberculosis/rifampicin may prove to be a cost-effective solution to this problem in these settings. The objective of this study is to evaluate the use of GeneXpert in the diagnosis of pulmonary TB since it was introduced into two tertiary hospitals in Ghana in 2013. METHODS: A 2-year retrospective audit of clinical cases involving patients who presented with clinically suspected TB or documented TB not improving on standard therapy and had samples sent for GeneXpert testing. RESULTS: GeneXpert identified 169 cases of TB, including 17 cases of rifampicin-resistant TB. Of the seven cases with final culture and drug susceptibility testing results, six demonstrated further drug resistance and five of these were multidrug-resistant TB. CONCLUSION: These findings call for a scale-up of TB control in Ghana and provide evidence that the expansion of GeneXpert may be an optimal means to improve case finding and guide treatment of drug-resistant TB in this setting.

Recovery and banking: allograft bone.

Orthopedic surgeries often require bone grafts to replace lost bone. When using the patients own bone is not an option--by choice or dictated by the type or quantity of preferred graft material--bone from a tissue bank may be the answer. A call is made and the order is placed. However, bone grafts are not manufactured like metal implants; they were once a part of a living human being. This article explains the special role tissue banks perform in providing bone and connective tissue grafts.

Octreotide reverses hyperinsulinemia and prevents hypoglycemia induced by sulfonylurea overdoses.

Emergency therapy of sulfonylurea overdoses with glucose is often unsatisfactory because glucose stimulates insulin release and initiates a need for escalating quantities of hypertonic glucose to maintain normoglycemia. We tested the hypothesis that octreotide, an analog of somatostatin, would reverse hyperinsulinemia induced by a sulfonylurea overdose. Eight normal subjects received glipizide (1.45 mg/kg) on three occasions. Within 3 h, all subjects became hypoglycemic (< 50 mg/dL) and were initially treated with 50% dextrose followed by 1) dextrose infusion, 2) octreotide (30 ng/kg.min, iv), or 3) diazoxide (300 mg, iv, every 4 h). Euglycemia (85 mg/dL) was maintained with supplementary dextrose in treatment limbs 2 and 3. Insulin concentrations were 4-5 times greater with dextrose alone or in combination with diazoxide than with octreotide (P < 0.01). Dextrose requirements during diazoxide or dextrose alone were not different, but were both greater than those during octreotide treatment (P < 0.0001). All therapies were stopped at 13 h. Glucose levels remained above 3.6 mmol/L (65 mg/dL) in six of eight subjects receiving octreotide for the remaining 4 h. Glucose fell to below 3.6 mmol/L within 1.5 h of stopping either dextrose or diazoxide in each subject. Overall, octreotide reduced and in four of eight subjects entirely eliminated the need for exogenous glucose after a large overdose of glipizide. We conclude that octreotide is safe and effective and should be strongly considered as a logical therapeutic alternative for this metabolic emergency.

Successful treatment of severe refractory sulfonylurea-induced hypoglycemia with octreotide.

OBJECTIVE: To test the clinical use of octreotide in the treatment of sulfonylurea-induced hypoglycemia. RESEARCH DESIGN AND METHODS: A case is reported of sulfonylurea-induced hypoglycemic coma in a nondiabetic subject, which was complicated by relapse of hypoglycemia after resuscitation with intravenous dextrose. Subcutaneous octreotide, 50 micrograms 12 hourly, suppressed stimulated endogenous insulin secretion, thereby preventing a further recurrence of hypoglycemia. RESULTS: No adverse effects of treatment were observed. CONCLUSIONS: These results suggest a significant role for octreotide as an adjunct to intravenous dextrose in the management of severe and refractory cases of sulfonylurea-induced hypoglycemia.