Adverse hematological profiles associated with chlorpromazine antipsychotic treatment in male rats: Preventive and reversal mechanisms of taurine and coenzyme-Q10.

Chlorpromazine (CPZ) is one of the most effective antipsychotic drugs used for managing psychotic related disorders owing to its dopamine receptor blocking action. However, pharmacological investigations against CPZ's cytotoxic effect have remained scarce. Hence, this study investigated the preventive and reversal effects of taurine and coenzyme-Q10 (COQ-10), which are compounds with proven natural antioxidant properties, against CPZ-induced hematological impairments in male rats. In the preventive study, rats received oral saline (10 ml/kg), taurine (150 mg/kg/day), COQ-10 (10 mg/kg/day) or in combination for 56 days, alongside CPZ (30 mg/kg, p.o.) between days 29-56. In the reversal protocol, rats had CPZ repeatedly for 56 days before taurine and COQ-10 treatments or their combination from days 29-56. Rats were also given taurine (150 mg/kg/day), and COQ-10 (10 mg/kg/day) alone for 56 days. Serums were extracted and assayed for hematological, with oxidative and inflammatory markers. CPZ induced decreased red/white blood cells, erythropoietin, platelet count, packed cell volume and hemoglobin, neutrophil, and lymphocyte, which were prevented and reversed by taurine and COQ-10, or their combination. Taurine and COQ-10 improved mean corpuscular volume, hemoglobin concentration, with increased erythropoietin levels relative to CPZ groups. CPZ-induced increased malondialdehyde, tumor necrosis factor-alpha and interleukin-6 levels with decreased interleukin-10, glutathione, and superoxide-dismutase were prevented and reversed by taurine and COQ-10 in comparison with CPZ groups. Taurine and COQ-10 alone notably improved the antioxidant/anti-inflammatory status relative to controls. Among other mechanisms, taurine and COQ-10 abated CPZ-induced hematological deficiencies, via decreased serum levels of oxidative stress, and pro-inflammatory cytokines release, with increased antioxidants and anti-inflammation function.

Ginkgo biloba modulates ET-I/NO signalling in Lead Acetate induced rat model of endothelial dysfunction: Involvement of oxido-inflammatory mediators.

This study investigated the modulatory effect of Ginkgo biloba extract on lead acetate-induced endothelial dysfunction. Animals were administered GBE (50 mg/kg and 100 mg/kg orally) after exposures to lead acetate (25 mg/kg orally) for 14 days. Aorta was harvested after euthanasia, the tissue was homogenised, and supernatants were decanted after centrifuging. Oxidative, nitrergic, inflammatory, and anti-apoptotic markers were assayed using standard biochemical procedure, ELISA, and immunohistochemistry, respectively. GBE reduced lead-induced oxidative stress by increasing SOD, GSH, and CAT as well as reducing MDA levels in endothelium. Pro-inflammatory cytokines (TNF-α and IL-6) were reduced while increasing Bcl-2 protein expression. GBE lowered endothelin-I and raised nitrite levels. Histological changes caused by lead acetate were normalised by GBE. Our findings suggest that Ginkgo biloba extract restored endothelin-I and nitric oxide functions by increasing Bcl-2 protein expression and reducing oxido-inflammatory stress in endothelium.

Enhancing ESL students' academic achievement in expository essay writing using digital graphic organisers: A mixed-methods research.

Students in Nigerian English language classrooms encounter difficulty in writing. However, the utilisation of metacognitive strategies has the potential to aid students in organising their thoughts during writing for better achievement. Therefore, this study aims to examine the effect of digital graphic organisers on secondary school students' achievement in expository essay writing and the students' perceptions of writing challenges and the impact of the strategy. The study adopted a mixed-methods research design consisting of a within-group experimental design and focus group interview. Five research questions and one hypothesis are formulated to guide the study. An intact class size of 38 students is the subject of the study, while an expository essay writing achievement test and a focus group interview were used for data collection. Percentage, mean and standard deviation, and thematic analysis were used in answering the research questions, while a paired sample t-test was used to test the null hypothesis at 0.05 significance. The study found a statistically significant difference between students' mean achievement scores before and after exposure to digital graphic organiser charts when writing expository essays.

Comparative Analysis of Fasting Blood Glucose and Salivary Electrolytes Concentrations among Individuals with Type II Diabetes: A Randomized Controlled Hospital Based Study.

Salivary gland dysfunction is common in people with diabetes. This study aimed to compare the measurements of salivary electrolytes (SE); Na+, K+, Cl- and HCO3 - between diabetes and an age matched control group, and assess the relationship between fasting blood glucose (FBG) and salivary electrolytes, and salivary glucose (SG). Eighty-five human participants [diabetes group, n = 45 (23 males and 22 females) and control group, n = 40 (20 males and 20 females)] aged between 25 and 65years were tested. Saliva samples were taken between 7.00 am and 8.00 am after an overnight fast and SG and SE concentrations were analysed. Diabetes mellitus was defined using FBG ≥ 126 mg/dl. SG and SE concentrations were analysed using t-test and Pearson Correlation Coefficient tested the relationship between FBG and Salivary electrolytes and glucose. The participants were matched in their baseline demographic characteristics with a mean age of 49 years (standard deviation SD, 11 years), body mass index (25.7 kg/m2 (SD, 3.6). Half of them were males (50.6 %) and predominantly traders (30.6 %). However, the mean values for the salivary sodium, potassium, chloride and bicarbonate electrolytes were significantly higher in the diabetes group compared with the control group (P < 0.05). Of the salivary electrolytes, only the bicarbonate was significantly correlated with FBG (r = -0.594, p = 0.004) in female participants. This study found that people with diabetes have elevated salivary electrolytes which were not dependent on their age and gender. Although this study suggests some potential for saliva as an alternative in monitoring of diabetes mellitus, extensive research is required before we can reach any firm conclusion.

Development and formulation of antidiabetic property of Anarcadium occidantale-based solid lipid microparticles.

Anacardium occidentale (AO) possesses potent anti-diabetic properties, owing to its high phytochemicals content. This study attempted to maximise the efficacy of AO by encapsulating it in a solid lipid microparticle (SLMs) formulation. Leaves of AO were extracted with water and formulated into SLMs using a lipid matrix composed of P90H and Dika fat. Characterisation of the SLMs include morphology, particle size, pH, encapsulation efficiency percentage, in vitro release and anti-diabetic properties. SLMs were spherical with sizes ranging from 16.7 ± 0.8 µm to 40.12 ± 2.34 µm and had a fairly stable pH over time. Highest drug entrapment was 87%. Batch A2 exhibited an even release of 89%, sustained over time, and a mean percentage reduction in glucose of 25.9% at 12 h after oral administration to study animals. Anacardium occidentale-loaded SLMs exhibited a good hypoglycaemic effect and can be used in the management of diabetes.

Proinflammatory and Anti-inflammatory Cytokine Response to Isometric Handgrip Exercise and the Effects of Duration and Intensity of the Isometric Efforts in Prehypertensive Participants.

Objective: The purpose of this study was to investigate the responses of selected inflammatory cytokines to isometric handgrip exercise and identify possible effects of intensity and duration of the isometric effort on these variables. Methods: A total of 192 sedentary prehypertensive Nigerian participants aged between 30 and 50 years were recruited into the study and randomly distributed into 3 groups of 64 participants each. The participants performed 24 consecutive days of isometric handgrip exercise at 30% maximum voluntary contraction. At the end of the 24 days, group 1 discontinued the exercise protocol, while group 2 continued the exercise protocol for another 24 consecutive days, and group 3 continued with the exercise protocol for another 24 consecutive days but at 50% maximum voluntary contraction. The parameters used to assess the inflammatory cytokine variables included interleukin-6 (IL-6), interleukin-10 (IL-10), and tumor necrosis factor-alpha (TNF-α). Results: There was an increase in the resting values of IL-10 across the 3 groups, while the resting values of IL-6 and TNF-α were reduced significantly across groups. Generally, the exercise-induced changes in the levels of these cytokines (TNF-α, IL-6, and IL-10) should improve inflammatory and metabolic abnormalities. Conclusion: The isometric handgrip exercise protocols in this study resulted in elevation of anti-inflammatory cytokine (IL-10) and reductions in the values of proinflammatory cytokines TNF- α and IL-6.

Therapeutic efficacy of N-acetylcysteine and zinc sulphate against di-(2-ethylhexyl) phthalate-induced testicular oxido-nitrergic stress in male Wistar rat.

The therapeutic efficacy of N-acetylcysteine (NAC) and zinc sulphate on di-(2-ethylhexyl) phthalate (DEHP)-induced testicular oxido-nitrergic stress in rats was investigated in 36 male Wistar rats (170 ± 10 g) randomly assigned into one of six groups (n = 6). Group 1 (control) received 2.5 ml/kg of distilled water for 42 days, while group 2 (vehicle) received 2.5 ml/kg of corn oil for 42 days. Groups 3,4,5, and 6 were administered DEHP (750 mg/kg/day) for 21 days, after which groups 4, 5, and 6 received zinc sulphate (0.5 mg/kg/day), NAC (100 mg/kg/day), and zinc sulphate (0.5 mg/kg/day) + NAC (100 mg/kg/day) for an additional 21 days respectively. After the experimental period, the animals were euthanized by light thiopental sodium, and their testes were carefully dissected out for histological and biochemical assays. The result shows a significant alteration in testicular levels of malondialdehyde, nitric oxide, antioxidant enzymes, total antioxidant capacity, sulphydryl levels, dehydrogenases and testicular architecture following the administration of DEHP. These effects were reversed by coadministration of NAC and zinc sulphate in the study. We therefore concluded that the combined effects of NAC and ZnSO4 effectively improved testicular antioxidant status and reduced testicular nitregic stress, thus improving testicular architecture and functions.

Up-regulation of B-cell lymphoma factor-2 expression, inhibition of oxidative stress and down-regulation of pro-inflammatory cytokines are involved in the protective effect of cabbage (Brassica oleracea) juice in lead-induced endothelial dysfunction in rats.

BACKGROUND: Oxido-inflammatory stress and dysregulation of nitric oxide (NO) system has been implicated in lead toxicity. Cabbage is an antioxidant-rich household vegetable with plethora of therapeutic potentials. The present study investigated the anti-oxido-inflammatory activity of cabbage in lead-induced endothelial dysfunction. METHODS: Twenty (20) male Wistar rats were selected into four groups (n = 5) and treated with distilled water (1 mL/100 g b.wt), lead acetate (25 mg/kg b.wt), cabbage juice (1 mL/100 g b.wt) and lead acetate (25 mg/kg b.wt) plus cabbage juice (1 mL/100 g b.wt) respectively. Treatment was done orally for 28 days, thereafter, oxidative stress (SOD, CAT, GSH, and MDA), inflammatory (TNF-α and IL-6) and apoptotic (Bcl-2) markers were assayed using standard biochemical assays as well as histoarchitectural study of the endothelium. RESULTS: The results showed that they were significant increase in MDA, ET-1, TNF-α and IL-6 while SOD, GSH, CAT, NO and Bcl-2 protein expression were decreased in Lead exposed animals. Endothelial histoarchitecture was also altered. Following Cabbage juice treatment, MDA, ET-I, TNF-α and IL-6 were down-regulated while SOD, GSH, CAT, NO and Bcl-2 protein expression were up-regulated. Histoarchitecture was significantly recovered. CONCLUSION: The study suggests that cabbage juice could mitigates Lead-induced endothelial dysfunction by modulating oxido-inflammatory and anti-apoptotic mediators. DATA AVAILABILITY: All data are available upon request.

Vaccine Efficacy in Adults in a Respiratory Syncytial Virus Challenge Study.

BACKGROUND: Although human respiratory syncytial virus (RSV) is an important cause of illness and death in older adults, no RSV vaccine has been licensed. METHODS: In a phase 2a study, we randomly assigned healthy adults (18 to 50 years of age), in a 1:1 ratio, to receive a single intramuscular injection of either bivalent prefusion F (RSVpreF) vaccine or placebo. Approximately 28 days after injection, participants were inoculated intranasally with the RSV A Memphis 37b challenge virus and observed for 12 days. The per-protocol prespecified primary end points were the following: reverse-transcriptase-quantitative polymerase-chain-reaction (RT-qPCR)-confirmed detectable RSV infection on at least 2 consecutive days with at least one clinical symptom of any grade from two categories or at least one grade 2 symptom from any category, the total symptom score from day 1 to discharge, and the area under the curve (AUC) for the RSV viral load in nasal-wash samples measured by means of RT-qPCR from day 2 after challenge to discharge. In addition, we assessed immunogenicity and safety. RESULTS: After participants were inoculated with the challenge virus, vaccine efficacy of 86.7% (95% CI, 53.8 to 96.5) was observed for symptomatic RSV infection confirmed by any detectable viral RNA on at least 2 consecutive days. The median AUC for the RSV viral load (hours × log10 copies per milliliter) as measured by RT-qPCR assay was 0.0 (interquartile range, 0.0 to 19.0) in the vaccine group and 96.7 (interquartile range, 0.0 to 675.3) in the placebo group. The geometric mean factor increase from baseline in RSV A-neutralizing titers 28 days after injection was 20.5 (95% CI, 16.6 to 25.3) in the vaccine group and 1.1 (95% CI, 0.9 to 1.3) in the placebo group. More local injection-site pain was noted in the vaccine group than in the placebo group. No serious adverse events were observed in either group. CONCLUSIONS: RSVpreF vaccine was effective against symptomatic RSV infection and viral shedding. No evident safety concerns were identified. These findings provide support for further evaluation of RSVpreF vaccine in a phase 3 efficacy study. (Funded by Pfizer; EudraCT number, 2020-003887-21; ClinicalTrials.gov number, NCT04785612.).

PEGylated aceclofenac solid lipid microparticles homolipid-based solidified reverse micellar solutions for drug delivery.

Aceclofenac is a non-steroidal anti-inflammatory drug with poor aqueous solubility and a short half-life resulting in low bioavailability. Aceclofenac-loaded solid lipid microparticles based solidified reverse micellar solution (SLMs-SRMS) for oral drug delivery was investigated to improve the bioavailability and control drug release. Hot homogenization method was adopted to prepare the SLMs using a homolipid irvingia fat and Phospholipon® 90H with or without propylene glycol 6000 (PEGylation) in different ratios and characterized in vitro. The in vivo anti-inflammatory activity of the drug was determined on mice inflamed with carrageenan as phlogistic agent. Results showed that the morphology and particle sizes of the SLMs were spherical and smooth and ranged between 5.24 ± 0.01-97.44 ± 0.18 µm. EE % ranged between 67 - 81 %. A significant (p < 0.05) viscosity of 490 mPasec-1 was obtained. FTIR spectra indicated compatibility amongst the constituents. DSC showed a broad peak which depicted an imperfect matrix resulting in a deformation of crystal arrangement creating many spaces for drug entrapment. Delayed drug release was observed in almost all the formulations in SIF (pH, 6.8). Anti-inflammatory activity showed a significant inhibitory effect (p < 0.05, up to 90 %). Hence, the aceclofenac-loaded SLMs-SRMS showed desirable characteristics and could be used for controlled delivery of aceclofenac and thus alternative to conventional aceclofenac oral formulation.

Immune system response to isometric handgrip exercise and effects of duration and intensity of the exercise protocol on selected immune system parameters in prehypertensives.

BACKGROUND: Recent studies have shown that physical exercise significantly modulates immunocyte dynamics and possibly plays a significant role on immune function. This study examined the responses of some selected immune system parameters to isometric handgrip exercise and identified possible effects of intensity and duration of the exercise protocols. METHODS: One hundred and ninety-two (N=192) sedentary pre-hypertensive subjects, aged between 30-50 years were recruited into the study. They were randomly distributed into three groups of 64 subjects each. A detailed explanation and a demonstration of the exercise protocol were given to the subjects and they were asked to report at the Exercise Physiology unit of the Physiotherapy department, Federal Medical Centre, Asaba, Delta State at 4.00 pm daily for the exercise practice. The training session for each day took place between the hours of 4.00 pm and 8.00 pm daily (FMC/ASB/A81.VOL.XII/101). The subjects performed a 24 consecutive day's isometric handgrip exercise at 30% Maximum Voluntary Contraction (MVC). At the end of the 24 days, group one (GP1) discontinued with the exercise protocol, while group two (GP2) and group three (GP3) continued with the exercise protocol for another 24 consecutive days nevertheless GP3 performed at an increased intensity of 50% MVC. The clinical trial was registered with Nigeria Clinical Trial Registry, Federal Ministry of Health, Abuja Nigeriawith Trial No: 1216582 (https://www.nctr.nhrec.net/viewTrials.php?TID=1216582). RESULTS: At the end of the study, the result shows thatthe number of CD4 cells and CD4/CD8 ratio significantly (P<0.05) increased while the CD8 cell decreased in GP2 and GP3. It was further shown that increase in duration produced a more significant change compared to an increase in intensity of the isometric effort. CONCLUSION: The study established that isometric handgrip exercise alters the circulating levels of the immune system parameters which could have positive beneficial effects on the prehypertensive individuals as the number of CD4 cells and CD4/CD8 ratio increased especially when practiced over a longer duration.

EDP-938, a Respiratory Syncytial Virus Inhibitor, in a Human Virus Challenge.

BACKGROUND: Respiratory syncytial virus (RSV) infection causes substantial morbidity and mortality among infants, older adults, and immunocompromised adults. EDP-938, a nonfusion replication inhibitor of RSV, acts by modulating the viral nucleoprotein. METHODS: In a two-part, phase 2a, randomized, double-blind, placebo-controlled challenge trial, we assigned participants who had been inoculated with RSV-A Memphis 37b to receive EDP-938 or placebo. Different doses of EDP-938 were assessed. Nasal-wash samples were obtained from day 2 until day 12 for assessments. Clinical symptoms were assessed by the participants, and pharmacokinetic profiles were obtained. The primary end point was the area under the curve (AUC) for the RSV viral load, as measured by reverse-transcriptase-quantitative polymerase-chain-reaction assay. The key secondary end point was the AUC for the total symptom score. RESULTS: In part 1 of the trial, 115 participants were assigned to receive EDP-938 (600 mg once daily [600-mg once-daily group] or 300 mg twice daily after a 500-mg loading dose [300-mg twice-daily group]) or placebo. In part 2, a total of 63 participants were assigned to receive EDP-938 (300 mg once daily after a 600-mg loading dose [300-mg once-daily group] or 200 mg twice daily after a 400-mg loading dose [200-mg twice-daily group]) or placebo. In part 1, the AUC for the mean viral load (hours × log10 copies per milliliter) was 204.0 in the 600-mg once-daily group, 217.7 in the 300-mg twice-daily group, and 790.2 in the placebo group. The AUC for the mean total symptom score (hours × score, with higher values indicating greater severity) was 124.5 in the 600-mg once-daily group, 181.8 in the 300-mg twice-daily group, and 478.8 in the placebo group. The results in part 2 followed a pattern similar to that in part 1: the AUC for the mean viral load was 173.9 in the 300-mg once-daily group, 196.2 in the 200-mg twice-daily group, and 879.0 in the placebo group, and the AUC for the mean total symptom score was 99.3, 89.6, and 432.2, respectively. In both parts, mucus production was more than 70% lower in each EDP-938 group than in the placebo group. The four EDP-938 regimens had a safety profile similar to that of placebo. Across all dosing regimens, the EDP-938 median time to maximum concentration ranged from 4 to 5 hours, and the geometric mean half-life ranged from 13.7 to 14.5 hours. CONCLUSIONS: All EDP-938 regimens were superior to placebo with regard to lowering of the viral load, total symptom scores, and mucus weight without apparent safety concerns. (ClinicalTrials.gov number, NCT03691623.).

Prevention of Respiratory Syncytial Virus Infection in Healthy Adults by a Single Immunization of Ad26.RSV.preF in a Human Challenge Study.

BACKGROUND: Respiratory syncytial virus (RSV) is a significant cause of severe lower respiratory tract disease in children and older adults, but has no approved vaccine. This study assessed the potential of Ad26.RSV.preF to protect against RSV infection and disease in an RSV human challenge model. METHODS: In this double-blind, placebo-controlled study, healthy adults aged 18-50 years were randomized 1:1 to receive 1 × 1011 vp Ad26.RSV.preF or placebo intramuscularly. Twenty-eight days postimmunization, volunteers were challenged intranasally with RSV-A (Memphis 37b). Assessments included viral load (VL), RSV infections, clinical symptom score (CSS), safety, and immunogenicity. RESULTS: Postchallenge, VL, RSV infections, and disease severity were lower in Ad26.RSV.preF (n = 27) vs placebo (n = 26) recipients: median VL area under the curve (AUC) quantitative real-time polymerase chain reaction: 0.0 vs 236.0 (P = .012; predefined primary endpoint); median VL-AUC quantitative culture: 0.0 vs 109; RSV infections 11 (40.7%) vs 17 (65.4%); median RSV AUC-CSS 35 vs 167, respectively. From baseline to 28 days postimmunization, geometric mean fold increases in RSV A2 neutralizing antibody titers of 5.8 and 0.9 were observed in Ad26.RSV.preF and placebo, respectively. Ad26.RSV.preF was well tolerated. CONCLUSIONS: Ad26.RSV.preF demonstrated protection from RSV infection through immunization in a human challenge model, and therefore could potentially protect against natural RSV infection and disease. CLINICAL TRIALS REGISTRATION: NCT03334695; CR108398, 2017-003194-33 (EudraCT); VAC18193RSV2002.

Computational, chemical profiling and biochemical evaluation of antidiabetic potential of Parkia biglobosa stem bark extract in type 2 model of rats.

The present study investigated the antidiabetic and antioxidant capacity of hydromethanol extract from Parkia biglobosa stem bark (PBSBHM) in fructose-streptozotocin induced type 2 diabetic rats after 28 days of oral administration. Simultaneously, evaluated the phenolic profiles and mineral compositions of crude extract. Molecular docking analysis of protocatechuic acid, the most abundant phenolic acid with potential downstream partners protein kinase A (PKA), protein kinase C (PKC), and Ca2+/calmodulin-dependent protein kinase II (CaMK II), was investigated. The preliminary results showed that PBSBHM crude extract contained 225.2 ± 18.25 mg GAE/g of total phenolic and 99.28 ± 12.3 mg QE/g of total flavonoid. Both protocatechuic and gallic acids were identified as a prominent phenolic compound through HPLC analysis, while vanillic acid was not detected. High mineral composition of K, Mg, P, Ca while Mn and Cr as trace elements were found in PBSBHM by plasma optical emission spectroscopy. PBSBHM extracts showed a significant radical scavenging activity from a therapeutic point of view, a moderate antioxidant potential and improved glucose tolerance after 30 min of glucose loading. PBSBHM extracts significantly attenuated serum glucose level and glycosylated haemoglobin at the tested dosage. However, it elevated the hepatic hexokinase activity and glycogen level compared with the diabetic untreated rats. PBSBHM ameliorates the decreased activity of pancreatic superoxide dismutase, catalase and reduced glutathione but decreased the MDA level. Docking analysis of protocatechuic acid showed a moderate affinity for the target enzymes compared to the standard drugs. Our data showed that the stem bark extract of this botanical has antidiabetic potential and at least in part substantiates its traditional use in the management of diabetes, possibly due to the synergistic interactions of protocatechuic acid with other biologically active components.

In Vivo Attenuation of Alcohol- and Cadmium Chloride-Induced Testicular Toxicity Modulated by Silymarin in Male Wistar Rat.

The aim of the study is to investigate the in vivo attenuation of alcohol- and cadmium chloride-induced testicular toxicity modulated by Silymarin in male Wistar rats. A total of fifty-six (56) Wistar rats were used for this study and they were randomized into seven (7) groups of eight (8) rats each. Group 1 was control rats; Groups 2-7 served as the experimental groups. After 6 weeks treatment duration, the rats were euthanized, semen was collected for semen analysis, blood samples for testosterone, and FSH and LH assay determination, and left testes was harvested for histological analysis. One-way ANOVA was used to compare means at p-level < 0.05 was considered significant. Findings from this study have shown that alcohol and cadmium chloride adversely affected semen parameters, testosterone, and FSH and LH hormone milieu. Data also showed that Silymarin administration attenuated the adverse effect of alcohol and cadmium chloride on semen quality and hormones associated with reproductive functions. Hence, Silymarin mopped the effect of in vivo attenuation of alcohol and cadmium chloride testicular damage. The findings of this study have further established that alcohol and cadmium chloride adversely affected semen parameters, testicular alterations, and serum hormonal milieu. However, the effect was more significantly deleterious in rats exposed to cadmium chloride when compared to rats exposed to alcohol, subsequently alcohol- and cadmium chloride-induced degeneration of testicular tissues. Furthermore, Silymarin administration attenuated the adverse effect of alcohol on semen quality and hormones associated with reproductive functions.

The current epidemiological status of urogenital schistosomiasis among primary school pupils in Katsina State, Nigeria: An imperative for a scale up of water and sanitation initiative and mass administration of medicines with Praziquantel.

INTRODUCTION: Human schistosomiasis, a debilitating and chronic disease, is among a set of 17 neglected tropical infectious diseases of poverty that is currently posing a threat to the wellbeing of 2 billion people in the world. The SHAWN/WASH and MAM programmes in the study area require epidemiological data to enhance their effectiveness. We therefore embarked on this cross-sectional study with the aim of investigating the prevalence, intensity and risk factors of urogenital schistosomiasis. METHODOLOGY/ PRINCIPAL FINDINGS: Interviewed 484 respondents produced terminal urine samples (between 10.00h - 14.00h) which were analyzed with Medi ─Test Combi 10 and centrifuged at 400 r.p.m for 4 minutes using C2 series Centurion Scientific Centrifuge. Eggs of S. haematobium were identified with their terminal spines using Motic Binocular Microscope. Data were analyzed with Epi Info 7. In this study, the overall prevalence and arithmetic mean intensity of the infection were 8.68% (6.39─ 11.64) and 80.09 (30.92─129.28) eggs per 10ml of urine respectively. Urogenital schistosomiasis was significantly associated with knowledge about the snail host (χ2 = 4.23; P = 0.0398); water contact activities (χ2 = 25.788; P = 0.0001), gender (χ2 = 16.722; P = 0.0001); age (χ2 = 9.589; P = 0.0019); economic status of school attended (χ2 = 4.869; P = 0.0273); residence distance from open water sources (χ2 = 10.546; P = 0.0012); mothers' occupational (χ2 = 6.081; P = 0.0137) and educational status (χ2 = 4.139; P = 0.0419). CONCLUSION/ SIGNIFICANCE: The overall prevalence obtained in this survey shows that the study area was at a low-risk degree of endemicity for urogenital schistosomiasis. Beneath this is a subtle, latent and deadly morbidity-inducing heavy mean intensity of infection, calling for urgent implementation of WHO recommendation that MAM with PZQ be carried out twice for School-Age Children (enrolled or not enrolled) during their primary schooling age (once each at the point of admission and graduation). The criteria for classifying endemic areas for schistosomiasis should also be reviewed to capture the magnitude of mean intensity of infection rather than prevalence only as this may underplay its epidemiological severity.

Correction: Accelerating Influenza Research: Vaccines, Antivirals, Immunomodulators and Monoclonal Antibodies. The Manufacture of a New Wild-Type H3N2 Virus for the Human Viral Challenge Model.

[This corrects the article DOI: 10.1371/journal.pone.0145902.].

Accelerating Influenza Research: Vaccines, Antivirals, Immunomodulators and Monoclonal Antibodies. The Manufacture of a New Wild-Type H3N2 Virus for the Human Viral Challenge Model.

BACKGROUND: Influenza and its associated diseases are a major cause of morbidity and mortality. The United States Advisory Committee on Immunization Practices recommends influenza vaccination for everyone over 6 months of age. The failure of the flu vaccine in 2014-2015 demonstrates the need for a model that allows the rapid development of novel antivirals, universal/intra-seasonal vaccines, immunomodulators, monoclonal antibodies and other novel treatments. To this end we manufactured a new H3N2 influenza virus in compliance with Good Manufacturing Practice for use in the Human Viral Challenge Model. METHODS AND STRAIN SELECTION: We chose an H3N2 influenza subtype, rather than H1N1, given that this strain has the most substantial impact in terms of morbidity or mortality annually as described by the Centre for Disease Control. We first subjected the virus batch to rigorous adventitious agent testing, confirmed the virus to be wild-type by Sanger sequencing and determined the virus titres appropriate for human use via the established ferret model. We built on our previous experience with other H3N2 and H1N1 viruses to develop this unique model. HUMAN CHALLENGE AND CONCLUSIONS: We conducted an initial safety and characterisation study in healthy adult volunteers, utilising our unique clinical quarantine facility in London, UK. In this study we demonstrated this new influenza (H3N2) challenge virus to be both safe and pathogenic with an appropriate level of disease in volunteers. Furthermore, by inoculating volunteers with a range of different inoculum titres, we established the minimum infectious titre required to achieve reproducible disease whilst ensuring a sensitive model that can be translated to design of subsequent field based studies. TRIAL REGISTRATION: ClinicalTrials.gov NCT02525055.