Organochlorine and Organophosphorus Pesticides Residues in Commercial Poultry Feed Samples in Lagos State, Nigeria

Pesticides are among Persistent Organic Pollutants (POP) used in agricultural practices to increase production efficiency. They enter the food chain, bioaccumulate and are toxic to human, animals and the environment. The presence of pesticide residues in animal feeds has been rarely monitored and reported in Nigeria. This study evaluated the levels of pesticide residues in different brands and types of poultry feeds that are produced, marketed and used in Lagos, Nigeria. Five types of five commonly used commercial brands (25 samples) of poultry feeds were purchased from animal feed markets in Lagos, Nigeria. Simultaneous detection and quantitation of selected thirteen (13) OCPs and eight (8) OPs residues in the feeds was carried out using Gas ChromatographyElectron Capture Detector (GC-ECD) and Gas Chromatography-Flame Ionization Detector (GC-FID) respectively. Results revealed that all the feed samples had multiple pesticide residues levels which ranged from 0.10 - 1.83 mg/kg for OCPs and 0.25 - 6.04 mg/kg for OPs. These values were above the Maximum Residual Limit (MRL). The detected pesticide residues order of violation of the MRL was Methoxychlor > Dieldrin >Endrin ketone for OCPs, and Trichlorfon > Malathion > Diazinon for OPs. There was no significant (p>0.05) differences in the pesticide residues levels among the brands and types of the samples. Present study indicates extensive and unwholesome use of pesticides in the agro industry in Nigeria suggesting need to enforce Good Agricultural Practices (GAP), Good Storage Practices (GSP), Good Manufacturing Practices (GMP) and constant monitoring of pesticide residues thereby implementing the Good health and Wellbeing (Goal 3) of the 2030 Sustainable Development Goal

How Unsafe is Myomectomy at Caesarean Section?

Objective: To provide evidence on the safety or otherwise of the practice of myomectomy during Caesarean section.Methods: This was a prospective, randomized, case controlled study conducted at the Obio Cottage Hospital, Port Harcourt, Nigeria, between November 2011 and October 2012. 42 Caesarean section patients, who also had myomectomy, were compared with those who had Caesarean section alone. The Caesarean myomectomy cases also had the number, location and size of the fibroids removed analyzed.Results: 446 women were delivered by Caesarean section and 42 of these had Caesarean myomectomy. The mean ages were similar. Between 1 and 23, uterine fibroids were removed. The mean blood loss from the  Caesarean myomectomy and Caesarean section was 584.72 and  695.71mls respectively. There was no statistical difference in the blood loss, Hematocrit deficit and length of hospital stay (p values of 0.053, 0.299 and 0.334 respectively) while the duration of surgery and number of sutures used were statistically different between the two groups (p value < 0.001 in both). The post-operative complications were similar.Conclusions: This study found that Caesarean myomectomy is a safe procedure in experienced hands and has obvious advantages to the patient.Keywords: Caesarean section, Myomectomy, Blood loss, Port Harcourt

Risk factors, pre-presentation management and clinical state of children with diarrhoea presenting in a community cottage hospital

Diarrhoael disease ranks second as the cause of under -five mortality worldwide and is particularly important in the developing world. Risk factors include water source, poor human and domestic waste disposal, poor hand washing and breastfeeding practices. Outcome depends on appropriate oral rehydration therapy, continued feeding and rational use of drugs. This work was designed to identify ongoing risk factors for diarrhoae presenting in a Cottage Hospital serving a well-defined catchment community in the Niger Delta region of Nigeria. It also aimed at identifying modalities of treatment before presentation at the hospital, clinical state at presentation and outcome of treatment on the children. A prospective study recruiting all children admitted for diarrhoae disease in the hospital between January and June 2016. Sociodemographic data, risk factors, place and modalities of prepresentation management, clinical state on admission and outcome were recorded. Simple proportions, percentages and tables were used to analyze the data using stata 10 (stata corp. Texas). Fifty-four children representing 11.11% of 468 paediatric admissions to the hospital in the period were admitted into the study. The age range was 3 – 96months (median 11 months; 1QR 6 – 18 months). Identified risk factors were lack of Exclusive Breastfeeding (85.19%), use of feeding bottles (20.37%), questionable or poor sources of water (92.59%), poor hand washing practices with; 33.62% not washing hands always before feeding child and 35.91%, not always washing hands after cleaning infant/child’s faeces. Most of the children (35 or 64.82%) first presented at Patent Medicine Stores and 38 or 70.37% had some oral fluids. While 9 (16.67%) had dysentery 31(57.41) had anti-microbials and 18 (33.33%) had anti-emetics. Twelve (33.33%) of the children had severe dehydration and 2(3.70%) had extrapyramidal crisis from use of anti-emetics. None died, but one child developed cortical damage from hypoglycaemia. Diarrhoae is an important children problem in this catchment community. Major risk factors are lack of exclusive breastfeeding, unsatisfactory hand washing practices, questionable water sources and use of feeding bottles. These children are largely mismanaged at patent medicine stores before presentation at hospital. Provision of potable water should be a priority in this and similar communities. Good hygiene practices and Exclusive Breast Feeding(EBF) should be consistently taught in ante-natal clinics and immunization centres. Training and retraining of patent medicine dealers is essential

Crystallization and preliminary X-ray analysis of mycophenolic acid-resistant and mycophenolic acid-sensitive forms of IMP dehydrogenase from the human fungal pathogen Cryptococcus

Fungal human pathogens such as Cryptococcus neoformans are becoming an increasingly prevalent cause of human morbidity and mortality owing to the increasing numbers of susceptible individuals. The few antimycotics available to combat these pathogens usually target fungal-specific cell-wall or membrane-related components; however, the number of these targets is limited. In the search for new targets and lead compounds, C. neoformans has been found to be susceptible to mycophenolic acid through its target inosine monophosphate dehydrogenase (IMPDH); in contrast, a rare subtype of the related C. gattii is naturally resistant. Here, the expression, purification, crystallization and preliminary crystallographic analysis of IMPDH complexed with IMP and NAD+ is reported for both of these Cryptococcus species. The crystals of IMPDH from both sources had the symmetry of the tetragonal space group I422 and diffracted to a resolution of 2.5 A for C. neoformans and 2.6 A for C. gattii

A Screening Pipeline for Antiparasitic Agents Targeting Cryptosporidium Inosine Monophosphate Dehydrogenase

Persistent diarrhea is a leading cause of illness and death among impoverished children, and a growing share of this disease burden can be attributed to the parasite Cryptosporidium. There are no vaccines to prevent Cryptosporidium infection, and the treatment options are limited and unreliable. Critically, no effective treatment exists for children or adults suffering from AIDS. Cryptosporidium presents many technical obstacles for drug discovery; perhaps the most important roadblock is the difficulty of monitoring drug action. Here we have developed a set of methods to accelerate the drug discovery process for cryptosporidiosis. We exploit the opportunities for experimental manipulation in the related parasite Toxoplasma to genetically engineer a Cryptosporidium model. This new model parasite mirrors the metabolism of Cryptosporidium for a particularly promising drug target that supplies the building blocks for DNA and RNA. Drug effectiveness can be assayed through simple fluorescence measurements for many candidates. Using this assay as an initial filter, and adapting other assays to a high throughput format, we identify several novel chemical compounds that exhibit markedly improved anti-cryptosporidial activity and excellent selectivity

Identification of Novel Mt-Guab2 Inhibitor Series Active against M. tuberculosis

Tuberculosis (TB) remains a leading cause of mortality worldwide. With the emergence of multidrug resistant TB, extensively drug resistant TB and HIV-associated TB it is imperative that new drug targets be identified. The potential of Mycobacterium tuberculosis inosine monophosphate dehydrogenase (IMPDH) as a novel drug target was explored in the present study. IMPDH exclusively catalyzes the conversion of inosine monophosphate (IMP) to xanthosine monophosphate (XMP) in the presence of the cofactor nicotinamide adenine dinucleotide (NAD+). Although the enzyme is a dehydrogenase, the enzyme does not catalyze the reverse reaction i.e. the conversion of XMP to IMP. Unlike other bacteria, M. tuberculosis harbors three IMPDH-like genes, designated as Mt-guaB1, Mt-guaB2 and Mt-guaB3 respectively. Of the three putative IMPDH's, we previously confirmed that Mt-GuaB2 was the only functional ortholog by characterizing the enzyme kinetically. Using an in silico approach based on designed scaffolds, a series of novel classes of inhibitors was identified. The inhibitors possess good activity against M. tuberculosis with MIC values in the range of 0.4 to 11.4 µg mL−1. Among the identified ligands, two inhibitors have nanomolar Kis against the Mt-GuaB2 enzyme

The Cryptosporidium parvum Kinome

<p>Abstract</p> <p>Background</p> <p>Hundreds of millions of people are infected with cryptosporidiosis annually, with immunocompromised individuals suffering debilitating symptoms and children in socioeconomically challenged regions at risk of repeated infections. There is currently no effective drug available. In order to facilitate the pursuit of anti-cryptosporidiosis targets and compounds, our study spans the classification of the <it>Cryptosporidium parvum </it>kinome and the structural and biochemical characterization of representatives from the CDPK family and a MAP kinase.</p> <p>Results</p> <p>The <it>C</it>. <it>parvum </it>kinome comprises over 70 members, some of which may be promising drug targets. These <it>C. parvum </it>protein kinases include members in the AGC, Atypical, CaMK, CK1, CMGC, and TKL groups; however, almost 35% could only be classified as OPK (other protein kinases). In addition, about 25% of the kinases identified did not have any known orthologues outside of <it>Cryptosporidium spp</it>. Comparison of specific kinases with their <it>Plasmodium falciparum </it>and <it>Toxoplasma gondii </it>orthologues revealed some distinct characteristics within the <it>C. parvum </it>kinome, including potential targets and opportunities for drug design. Structural and biochemical analysis of 4 representatives of the CaMK group and a MAP kinase confirms features that may be exploited in inhibitor design. Indeed, screening <it>Cp</it>CDPK1 against a library of kinase inhibitors yielded a set of the pyrazolopyrimidine derivatives (PP1-derivatives) with IC₅₀values of < 10 nM. The binding of a PP1-derivative is further described by an inhibitor-bound crystal structure of <it>Cp</it>CDPK1. In addition, structural analysis of <it>Cp</it>CDPK4 identified an unprecedented Zn-finger within the CDPK kinase domain that may have implications for its regulation.</p> <p>Conclusions</p> <p>Identification and comparison of the <it>C. parvum </it>protein kinases against other parasitic kinases shows how orthologue- and family-based research can be used to facilitate characterization of promising drug targets and the search for new drugs.</p

Effects of antibiotic resistance, drug target attainment, bacterial pathogenicity and virulence, and antibiotic access and affordability on outcomes in neonatal sepsis: an international microbiology and drug evaluation prospective substudy (BARNARDS)

Background Sepsis is a major contributor to neonatal mortality, particularly in low-income and middle-income countries (LMICs). WHO advocates ampicillin–gentamicin as first-line therapy for the management of neonatal sepsis. In the BARNARDS observational cohort study of neonatal sepsis and antimicrobial resistance in LMICs, common sepsis pathogens were characterised via whole genome sequencing (WGS) and antimicrobial resistance profiles. In this substudy of BARNARDS, we aimed to assess the use and efficacy of empirical antibiotic therapies commonly used in LMICs for neonatal sepsis. Methods In BARNARDS, consenting mother–neonates aged 0–60 days dyads were enrolled on delivery or neonatal presentation with suspected sepsis at 12 BARNARDS clinical sites in Bangladesh, Ethiopia, India, Pakistan, Nigeria, Rwanda, and South Africa. Stillborn babies were excluded from the study. Blood samples were collected from neonates presenting with clinical signs of sepsis, and WGS and minimum inhibitory concentrations for antibiotic treatment were determined for bacterial isolates from culture-confirmed sepsis. Neonatal outcome data were collected following enrolment until 60 days of life. Antibiotic usage and neonatal outcome data were assessed. Survival analyses were adjusted to take into account potential clinical confounding variables related to the birth and pathogen. Additionally, resistance profiles, pharmacokinetic–pharmacodynamic probability of target attainment, and frequency of resistance (ie, resistance defined by in-vitro growth of isolates when challenged by antibiotics) were assessed. Questionnaires on health structures and antibiotic costs evaluated accessibility and affordability. Findings Between Nov 12, 2015, and Feb 1, 2018, 36 285 neonates were enrolled into the main BARNARDS study, of whom 9874 had clinically diagnosed sepsis and 5749 had available antibiotic data. The four most commonly prescribed antibiotic combinations given to 4451 neonates (77·42%) of 5749 were ampicillin–gentamicin, ceftazidime–amikacin, piperacillin–tazobactam–amikacin, and amoxicillin clavulanate–amikacin. This dataset assessed 476 prescriptions for 442 neonates treated with one of these antibiotic combinations with WGS data (all BARNARDS countries were represented in this subset except India). Multiple pathogens were isolated, totalling 457 isolates. Reported mortality was lower for neonates treated with ceftazidime–amikacin than for neonates treated with ampicillin–gentamicin (hazard ratio [adjusted for clinical variables considered potential confounders to outcomes] 0·32, 95% CI 0·14–0·72; p=0·0060). Of 390 Gram-negative isolates, 379 (97·2%) were resistant to ampicillin and 274 (70·3%) were resistant to gentamicin. Susceptibility of Gram-negative isolates to at least one antibiotic in a treatment combination was noted in 111 (28·5%) to ampicillin–gentamicin; 286 (73·3%) to amoxicillin clavulanate–amikacin; 301 (77·2%) to ceftazidime–amikacin; and 312 (80·0%) to piperacillin–tazobactam–amikacin. A probability of target attainment of 80% or more was noted in 26 neonates (33·7% [SD 0·59]) of 78 with ampicillin–gentamicin; 15 (68·0% [3·84]) of 27 with amoxicillin clavulanate–amikacin; 93 (92·7% [0·24]) of 109 with ceftazidime–amikacin; and 70 (85·3% [0·47]) of 76 with piperacillin–tazobactam–amikacin. However, antibiotic and country effects could not be distinguished. Frequency of resistance was recorded most frequently with fosfomycin (in 78 isolates [68·4%] of 114), followed by colistin (55 isolates [57·3%] of 96), and gentamicin (62 isolates [53·0%] of 117). Sites in six of the seven countries (excluding South Africa) stated that the cost of antibiotics would influence treatment of neonatal sepsis

Influence of Comorbidities and Socioeconomic Factors on the Association Between Anemia and Mortality in Adults with Heart Failure: A Population Based Study

Objective: The objective of this dissertation was to examine the effects of biological (comorbidities) and non-biological (socioeconomic status, SES) factors on the association between anemia and mortality in adults with heart failure (HF) using a nationally representative population-based data. Five highly prevalent and serious comorbidities, namely coronary artery disease (CAD), chronic kidney disease (CKD), chronic obstructive pulmonary disease (COPD), hypertension and diabetes, were selected and their modifying effect on the association between anemia and mortality in adults with HF determined. Also, the excess risk due to socioeconomic factors such as health insurance, education level and family income on the association between anemia and mortality was calculated. Methods: This was a retrospective cohort study using the population-based National Health and Nutrition Examination Survey (NHANES) survey data from 1999-2010. Our cohort was made up of subjects who self-reported as having been diagnosed with HF and specific comorbidities (hypertension, CAD, COPD, CKD, and diabetes). Demographic, clinical and laboratory variables collected from survey participants were used for analysis. Of the 62,160 subjects included in NHANES during the study period, only participants who provided self-reported data and health measurements at the mobile examination center (MEC) (n=59,367) were selected. After applying all inclusion and exclusion criteria, the final sample size was 926. We conducted multiple Cox regression analysis to estimate the relative risk of mortality using anemia as the main exposure variable. Further analysis examined the interaction between anemia and specific-comorbidities on the additive and multiplicative scales. Also, the excess risk of mortality attributable to socioeconomic factor was derived. Results: The study sample included 926 subjects who self-reported they had been diagnosed with HF. The prevalence of anemia in the cohort was 23%, whereas the overall crude mortality rate was 40%. Findings suggest significant modifying effects of Diabetes the additive scale; indicating the effect of diabetes and anemia on mortality is greater than the sum of the effect of these exposures and anemia taken separately. We did not observe excess additive risk of mortality for any other comorbidities along with anemia. Also, none of the comorbidities studied revealed any meaningful modifying effects on the multiplicative scale. Furthermore, the joint effect of anemia with family annual income, and anemia with health insurance type were significantly associated with the risk of mortality in adults with HF. Conclusion: Select comorbidities modify the association between anemia and mortality in HF on additive and multiplicative scales, albeit in different directions. Greater focus should be given to the treatment of patients with anemia in HF coexisting with diabetes, to achieve improved survival outcomes. In addition, mortality in HF varied by income group or health insurance type. Therefore standardizing clinical care for HF patients irrespective of income or health insurance type will reduce the disparities along socioeconomic status in HF population