Microbiological quality of fermented Cassava (Gari) sold in Ota Ogun State Nigeria

Thirty six gari samples (eighteen each of white and yellow types) were subjected to microbial analysis. Samples were serially diluted to 104 and appropriate dilutions inoculated by spread plate method onto Nutrient agar, MacConkey agar and Potato- Dextrose agar plates for Total aerobic plate count (TAPC), Coliform count (CC) and Fungal count respectively. TAPC for white gari ranged from 2.0x102 to 1.1x104, coliform count ranged from no growth (NG) to 7.1x103 while fungal count ranged from no growth to 6.0x102. The microbial load of yellow gari ranged from 1.0x102 to 5.0x103 for TAPC, NG to 6.0x103 for coliform count and NG to 3.0x103 for fungal count. The bacteria isolates from the various samples include Bacillus spp Enterobacter spp, Pseudomonas, Staphylococcus and Klebsiella spp. Fungi isolated includes Aspergillus niger, Aspergillus fumigatus, Fusarium, Rhizopus and Penicillium spp. The pH of the samples ranged from 4.76 to 4.94 in the yellow type and 4.78 to 4.91 in the white type. The moisture content was 6 to 8 percent in yellow type and 4 to 7 percent in the white type. Application of good manufacturing practices (GMP) and HACCP in gari production is imperative

Ex-vivo evaluation of crab shell chitosan as absorption enhancer in ciprofloxacin tablet formulation

This study was aimed at evaluating crab shell chitosan as absorption enhancer in ciprofloxacin tablet formulation using the ex-vivo model. Six batches of ciprofloxacin tablets containing varying concentrations of crab shell-derived chitosan ranging from 0 to 5% w/w at 1% w/w intervals were produced. Batch CTS-0 containing no chitosan served as the control. The crushing strength, friability, disintegration time, dissolution profile and permeation profile of all the batches were determined. Friability was not significantly affected but the crushing strength and disintegration time of tablets decreased with increase in concentration of chitosan. There was no significant difference in the cumulative percent drug released in 1 h but the cumulative percent drug permeated in 4 h increased with increase in the concentration of chitosan. It increased from 68% (when no chitosan was added) to 81.8% (when 5% w/w chitosan was incorporated). The polymer caused a faster onset of drug release but the eventual total drug released was not significantly influenced. It also improved the permeation of the released drug. This study correlates with in-vivo bioavailability study because the usual oral bioavailability of ciprofloxacin without absorption enhancer is 70%. Hence, crab shell chitosan at concentration of 5% w/w could increase the absorption of ciprofloxacin from 70 to 82%. The study suggests the use of the chitosan at this concentration to improve the absorption of ciprofloxacin.Key words: Crab shell chitosan, ciprofloxacin, dissolution, permeation, absorption

Blindness in Tuberous Sclerosis: A Case Report

Tuberous sclerosis (TS) is inherited as an autosomal dominant trait with variable penetrance characterised by glial cell tumor which arises from the cerebral and the retina. Blindness in association with Tuberous sclerosis (TS) is rare. When visual loss occurs it may be associated with hamartomas from retinal or optic nerve involvement or from intracranial (brain) tumours that affect either the part of the brain that processes visual information or from optic nerve damage following raised intracranial pressure. Very few cases of TS with blindness have been reported globally. Deterioration in academic performance might be the first pointer to the visual impairment. We report a case of a 13 year old girl who presented with increasing number of facial rash over an 11 years period, recurrent headache and deteriorating academic performance of 1 year and loss of vision of 6 months with a recent episode of convulsion. Similar skin rashes without other associated symptoms were noticed on the mother and one of the younger siblings. She was a Tanner stage one in development. She had facial angio fibromas, shagreen patches over the left hypochondria, back regions and face. Ophthalmic evaluation showed a visual acuity of being able to count fingers at not more than one meter from the face and only perception of light in the right and left eye respectively, both eyes had brisk pupillary activities, good mydriasis and clear media. The retinal and optic nerve head appeared normal in the right eye whereas in the left eye was a huge tuberous hamartoma of the optic disc and macular as well as generalised vascular occlusion and subretinal fluid. The Computerized tomography (CT) scan showed an Intraventricular tumour, with calcification within the tumours and subependymal. There was associated obstructive hydrocephalus. Patient was managed by a multi disciplinary team of ophthalmologists, neurosurgeons and radiologists, coordinated by a paediatrician.Conclusion: The diagnosis of tuberous sclerosis complex (TSC) was based on the lesions found on clinical examination, imaging, and pathologic studies. The blindness was multi-factorial in cause including intracranial, retinal and optic nerve tumours. Comprehensive medical history, detailed physical examinations and neuroimaging study are essential in making a diagnosis of TSC. Our patient was mis-diagnosed at various health facilities for many years. This delay in making appropriate diagnosis and instituting treatment could have contributed to the eventual outcome.Keywords: Tuberous Sclerosis, Blindness, Deteriorating Academic Performanc

Pulverized Calcined Clay and Carbide Waste as Alternative Binder in Concrete and Mortar Applications for Sustainable Construction

Portland cement (PC) based concrete is the world’s most consumed man-made material and this consequently puts lots of demand on cement as a binder. The CO2 gas emission during cement clinker production has placed this important material into non-environmental-friendly classification with quest for greener alternatives being on the rise. A recent study showed combination of Pulverized Calcined Clay (PCC) and Calcium Carbide Waste (CCW) as possible alternative for total PC replacement with resulting appreciable mortar strength but delayed setting times and lower strength than PC mortars. This paper reports on effects of PCC-CCW as alternative binder on strength properties of mortars. The mortar mixes had superplasticizers added to reduce water/binder ratio while the CCW was treated to reduce impurities with a view to improving the strength development and a bid to mitigate the observed setbacks of earlier study. The pozzolanic activity indices of the PCC was determined via X-Ray Fluorescence(XRF) and strength determination (strength activity index). The PCC was combined with Purified CCW to determine the binder’s strengths at varying PCC:CCW replacements to determine the prescribed mix combination for optimum strength. Improved optimised mortar strength of 13.11MPa was achieved compared to 11.89MPa in the previous stud

11β-HSD1 inhibition in men mitigates prednisolone-induced adverse effects in a proof-of-concept randomised double-blind placebo-controlled trial

Glucocorticoids prescribed to limit inflammation, have significant adverse effects. As 11β-hydroxysteroid dehydrogenase type 1 (11β-HSD1) regenerates active glucocorticoid, we investigated whether 11β-HSD1 inhibition with AZD4017 could mitigate adverse glucocorticoid effects without compromising their anti-inflammatory actions. We conducted a proof-of-concept, randomized, double-blind, placebo-controlled study at Research Unit, Churchill Hospital, Oxford, UK (NCT03111810). 32 healthy male volunteers were randomized to AZD4017 or placebo, alongside prednisolone treatment. Although the primary endpoint of the study (change in glucose disposal during a two-step hyperinsulinemic, normoglycemic clamp) wasn’t met, hepatic insulin sensitivity worsened in the placebo-treated but not in the AZD4017-treated group. Protective effects of AZD4017 on markers of lipid metabolism and bone turnover were observed. Night-time blood pressure was higher in the placebo-treated but not in the AZD4017-treated group. Urinary (5aTHF+THF)/THE ratio was lower in the AZD4017-treated but remained the same in the placebo-treated group. Most anti-inflammatory actions of prednisolone persisted with AZD4017 co-treatment. Four adverse events were reported with AZD4017 and no serious adverse events. Here we show that co-administration of AZD4017 with prednisolone in men is a potential strategy to limit adverse glucocorticoid effects

Global burden of 288 causes of death and life expectancy decomposition in 204 countries and territories and 811 subnational locations, 1990–2021: a systematic analysis for the Global Burden of Disease Study 2021

BACKGROUND Regular, detailed reporting on population health by underlying cause of death is fundamental for public health decision making. Cause-specific estimates of mortality and the subsequent effects on life expectancy worldwide are valuable metrics to gauge progress in reducing mortality rates. These estimates are particularly important following large-scale mortality spikes, such as the COVID-19 pandemic. When systematically analysed, mortality rates and life expectancy allow comparisons of the consequences of causes of death globally and over time, providing a nuanced understanding of the effect of these causes on global populations. METHODS The Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) 2021 cause-of-death analysis estimated mortality and years of life lost (YLLs) from 288 causes of death by age-sex-location-year in 204 countries and territories and 811 subnational locations for each year from 1990 until 2021. The analysis used 56 604 data sources, including data from vital registration and verbal autopsy as well as surveys, censuses, surveillance systems, and cancer registries, among others. As with previous GBD rounds, cause-specific death rates for most causes were estimated using the Cause of Death Ensemble model-a modelling tool developed for GBD to assess the out-of-sample predictive validity of different statistical models and covariate permutations and combine those results to produce cause-specific mortality estimates-with alternative strategies adapted to model causes with insufficient data, substantial changes in reporting over the study period, or unusual epidemiology. YLLs were computed as the product of the number of deaths for each cause-age-sex-location-year and the standard life expectancy at each age. As part of the modelling process, uncertainty intervals (UIs) were generated using the 2·5th and 97·5th percentiles from a 1000-draw distribution for each metric. We decomposed life expectancy by cause of death, location, and year to show cause-specific effects on life expectancy from 1990 to 2021. We also used the coefficient of variation and the fraction of population affected by 90% of deaths to highlight concentrations of mortality. Findings are reported in counts and age-standardised rates. Methodological improvements for cause-of-death estimates in GBD 2021 include the expansion of under-5-years age group to include four new age groups, enhanced methods to account for stochastic variation of sparse data, and the inclusion of COVID-19 and other pandemic-related mortality-which includes excess mortality associated with the pandemic, excluding COVID-19, lower respiratory infections, measles, malaria, and pertussis. For this analysis, 199 new country-years of vital registration cause-of-death data, 5 country-years of surveillance data, 21 country-years of verbal autopsy data, and 94 country-years of other data types were added to those used in previous GBD rounds. FINDINGS The leading causes of age-standardised deaths globally were the same in 2019 as they were in 1990; in descending order, these were, ischaemic heart disease, stroke, chronic obstructive pulmonary disease, and lower respiratory infections. In 2021, however, COVID-19 replaced stroke as the second-leading age-standardised cause of death, with 94·0 deaths (95% UI 89·2-100·0) per 100 000 population. The COVID-19 pandemic shifted the rankings of the leading five causes, lowering stroke to the third-leading and chronic obstructive pulmonary disease to the fourth-leading position. In 2021, the highest age-standardised death rates from COVID-19 occurred in sub-Saharan Africa (271·0 deaths [250·1-290·7] per 100 000 population) and Latin America and the Caribbean (195·4 deaths [182·1-211·4] per 100 000 population). The lowest age-standardised death rates from COVID-19 were in the high-income super-region (48·1 deaths [47·4-48·8] per 100 000 population) and southeast Asia, east Asia, and Oceania (23·2 deaths [16·3-37·2] per 100 000 population). Globally, life expectancy steadily improved between 1990 and 2019 for 18 of the 22 investigated causes. Decomposition of global and regional life expectancy showed the positive effect that reductions in deaths from enteric infections, lower respiratory infections, stroke, and neonatal deaths, among others have contributed to improved survival over the study period. However, a net reduction of 1·6 years occurred in global life expectancy between 2019 and 2021, primarily due to increased death rates from COVID-19 and other pandemic-related mortality. Life expectancy was highly variable between super-regions over the study period, with southeast Asia, east Asia, and Oceania gaining 8·3 years (6·7-9·9) overall, while having the smallest reduction in life expectancy due to COVID-19 (0·4 years). The largest reduction in life expectancy due to COVID-19 occurred in Latin America and the Caribbean (3·6 years). Additionally, 53 of the 288 causes of death were highly concentrated in locations with less than 50% of the global population as of 2021, and these causes of death became progressively more concentrated since 1990, when only 44 causes showed this pattern. The concentration phenomenon is discussed heuristically with respect to enteric and lower respiratory infections, malaria, HIV/AIDS, neonatal disorders, tuberculosis, and measles. INTERPRETATION Long-standing gains in life expectancy and reductions in many of the leading causes of death have been disrupted by the COVID-19 pandemic, the adverse effects of which were spread unevenly among populations. Despite the pandemic, there has been continued progress in combatting several notable causes of death, leading to improved global life expectancy over the study period. Each of the seven GBD super-regions showed an overall improvement from 1990 and 2021, obscuring the negative effect in the years of the pandemic. Additionally, our findings regarding regional variation in causes of death driving increases in life expectancy hold clear policy utility. Analyses of shifting mortality trends reveal that several causes, once widespread globally, are now increasingly concentrated geographically. These changes in mortality concentration, alongside further investigation of changing risks, interventions, and relevant policy, present an important opportunity to deepen our understanding of mortality-reduction strategies. Examining patterns in mortality concentration might reveal areas where successful public health interventions have been implemented. Translating these successes to locations where certain causes of death remain entrenched can inform policies that work to improve life expectancy for people everywhere. FUNDING Bill & Melinda Gates Foundation

Re-current Epizootics of Highly Pathogenic Avian Influenza in Nigeria: Status of Vaccination as Alternate control

Epizootic of Highly Pathogenic Avian Influenza subtype H5N1 in Nigeria was successfully contained during the first wave that lasted from 2006 to 2008 without the use of vaccine. Re-current and more severe outbreak was witnessed in 2015 and there are suspicions that some farmers may have resorted to vaccination to prevent infections in their flocks. We investigate evidence of vaccination in farms and the status of vaccination as alternate control for HPAI in Nigeria. The study was carried out in a cross section of 24 commercial poultry farms in four States in South West and North Central Nigeria. Five hundred and one sera collected randomly were screened by agar gel immunodiffusion (AGID) assay for antibody to group specific influenza A nucleoprotein. One hundred and eight sera obtained from five H5N1 infected poultry farms were also concurrently screened. Reactive sera were further analysed by Hemagglutinin Inhibition (HI) test against H5 antigen using 1% suspension of pooled washed chicken red blood cells. Only 8 out of 501 sera (1.6%) had evidence of influenza A antibody. All of the 8 samples were from one farm with 20 samples collected representing 40% seroconversion at farm level. Three out of those sera were positive for H5 at HI titer of 3log2. All other sera including those obtained from HPAI infected farms were negative for influenza antibody. This study confirms limited antibody response to avian influenza  subtype H5 most likely due to vaccination in one commercial flock. Vaccination against avian influenza by farmers desperate to protect their investments may lead to unregulated and suboptimal application of vaccines requiring farmers’ and stakeholders’ engagement to forestall negative impact. Keywords: Avian influenza; Control measures; Recurrent outbreaks; Vaccination status

Biopharmaceutics and clinical outcomes of emerging dosage forms of insulin: A systematic review

Background: Many works are ongoing with the aim of obtaining a more convenient way than the parenteral injection for administering insulin. Purpose: To review the biopharmaceutics and clinical outcomes of the various emerging dosage forms of insulin so as to identify the promising formulations. Method: A systematic literature search with analysis was carried out to obtain information on the biopharmaceutics and clinical outcomes of the emerging dosage forms. Results: Intraperitoneal insulin was found to be characterized by direct drug delivery through the portal vein to the liver having bioavailability of 60%, but its clinical application is limited by the high risk of infection. The bioavailability of transdermal insulin has been enhanced using electrical, mechanical and physical techniques; and such formulations could achieve up to 39.5% blood glucose reduction. Oral insulin, known to be the most convenient, has its bioavailability limited to 1% by enzymatic degradation and poor absorption. Its challenges however, have been addressed by various interventions to achieve different levels of bioavailability up to 73.1%. Buccal insulin has shown potentials in managing postprandial hyperglycaemia without posing hypoglycaemic risk but its clinical applicability has not been established; whereas the long transit time, lower levels of peptidases and incorporation of permeation-enhancers have been shown to be responsible for the good treatment outcome of colon-targeted insulin. Rectal insulin with bioavailability of 11% has been shown to be considerably safe but not cost-effective while the ocular insulin is limited by poor absorption. Nasal tolerance and high rate of treatment failures were shown to be limiting intranasal insulin while the pulmonary insulin is being limited by peripheral drug retention and insulin resistance. Conclusion: The biopharmaceutical profiles and clinical outcomes of transdermal, oral and colon-targeted insulin are superior to those of the other dosage forms. Further research works could be done towards the full development of these promising formulations