The effects of exposure to multiple stressors of Lead (Pb) and Cypermethrin on biochemical profiles of African catfish, Clarias gariepinus

The African catfish ( Clarias gariepinus ) is a widely cultured fish species in many African countries because of its rich nutritional quality. In this study, the impacts of exposure to common environmental contaminants; a heavy metal (Lead) and a pyrethroid insecticide (Cypermethrin) on the biochemical contents of C. gariepinus was investigated. Juveniles of C. gariepinus were exposed to borehole water (control), 2 mg/L Pb, 0.5 \ub5g/L cypermethrin or 2 mg/L Pb + 0.5 \ub5g/L cypermethrin for 96 h after which the total protein levels, glycogen contents and total cholesterol in the liver and muscle were determined. Fish exposure to cypermethrin and a mixture of cypermethrin and Pb resulted in a significant decrease in glycogen and protein levels but a significant increase in the cholesterol levels in liver and muscle (p < 0.05). There was no significant difference between the control and the group exposed to 2 mg/L Pb. The glycogen and total cholesterol levels were significantly higher in the liver in groups exposed to cypermethrin and the mixture of cypermethrin and Pb (p < 0.05) while the total protein levels were higher in the muscle, although this difference was not statistically significant. The results of this study suggest that environmental pollution of aquatic environments have adverse effects on the health of resident fish as well as other aquatic life

Oxidative damage and changes in Glutathione S-transferase activity in juvenile African catfish, Clarias gariepinus exposed to cypermethrin and chlorpyrifos

Cypermethrin and chlorpyrifos are broad-spectrum insecticides routinely used as household and agricultural insecticides. Since aquatic environments serve as sinks for numerous environmental pollutants, the effects of these substances on the resident aquatic organisms can be quite serious. In this study, we investigated the effects of exposure of African catfish to cypermethrin and chlorpyrifos on oxidative damage and the activity of glutathione S-transferase (GST). Juvenile African catfish were exposed to 1.25 \ub5g/L cypermethrin, 1.25 \ub5g/L chlorpyrifos, 2.5 \ub5g/L cypermethrin or 2.5 \ub5g/L chlorpyrifos for 96 h. Control fish were maintained in borehole water. At the end of the 96 h exposure, tissue lipid peroxidation (LPO), protein carbonylation and GST activities were determined. Contaminant exposure resulted in a significant increase (p < 0.05) in the levels of LPO and protein carbonylation and the activity of GST in the gills, liver and muscle of exposed fish compared to the controls. Oxidative damage was more serious in the groups exposed to chlorpyrifos compared to those exposed to cypermethrin, thus implying that chlorpyrifos is more toxic to these fish than cypermethrin. The results of this study indicate that the pollution of aquatic ecosystems with cypermethrin and chlorpyrifos may cause oxidation of biomolecules (lipids and proteins) that are involved in essential physiological and biochemical activities in animals

Dynamics in the murine norovirus capsid revealed by high-resolution cryo-EM

Icosahedral viral capsids must undergo conformational rearrangements to coordinate essential processes during the viral life cycle. Capturing such conformational flexibility has been technically challenging yet could be key for developing rational therapeutic agents to combat infections. Noroviruses are nonenveloped, icosahedral viruses of global importance to human health. They are a common cause of acute gastroenteritis, yet no vaccines or specific antiviral agents are available. Here, we use genetics and cryo-electron microscopy (cryo-EM) to study the high-resolution solution structures of murine norovirus as a model for human viruses. By comparing our 3 structures (at 2.9- to 3.1-Å resolution), we show that whilst there is little change to the shell domain of the capsid, the radiating protruding domains are flexible, adopting distinct states both independently and synchronously. In doing so, the capsids sample a range of conformational space, with implications for maintaining virion stability and infectivity

Effects of State of Boar on Nutrients Digestibility, Nitrogen Balance, Backfat Measurements, Cut-up Parts and Organ Weights of Finishing Pigs

A study was conducted to determine the nutrients digestibility, backfat composition, cut-up parts and organ weights of intact and castrated finishing pigs. Forty eight Large White male pigs with initial average weight of 36.82±0.45 kg were randomly assigned to two treatments with each treatment consisting of three replicates of eight pigs each. Twenty four of the experimental animals were castrated while the remaining twenty four were left intact. Four pigs per replicate were selected and housed in metabolic cages to determine nutrient digestibility and carcass evaluation was performed when the pigs in each experimental group attained an average weight of 70 kg in order to verify the backfat composition, cut-up parts and organ weights. The experiment was arranged in a Completely Randomised Design. Dry matter intake, excreted faeces/dry matter intake, dry matter digestibility, crude protein digestibility, nitrogen intake, absorption and retention were significantly (P<0.05) influenced by state of boar. Castrated boars had higher mean values in these parameters except in excreted faeces/dry matter. Intact boars had higher significant (P<0.05) mean values in liver (1.98%), kidney (0.20%) and heart (0.22%) weights in comparison with the corresponding values (1.57, 0.12 and 0.12%, respectively) recorded for castrated boars. Subcutaneous fat depth and fat free index were significantly (P<0.05) influenced by state of boars. Intact boar recorded better value (49.07) for fat free index when compared to 43.46 obtained by the castrated boar. It was concluded that state of boar had effect on nutrient digestibilities, organ weights (liver, kidney and heart weights) and backfat deposits (subcutaneous fat depth and fat free index) of finishing pigs

Computational screening of phytochemicals from three medicinal plants as inhibitors of transmembrane protease serine 2 implicated in SARS-CoV-2 infection

Background: SARS-CoV-2 infection or COVID-19 is a major global public health issue that requires urgent attention in terms of drug development. Transmembrane Protease Serine 2 (TMPRSS2) is a good drug target against SARS-CoV-2 because of the role it plays during the viral entry into the cell. Virtual screening of phytochemicals as potential inhibitors of TMPRSS2 can lead to the discovery of drug candidates for the treatment of COVID-19. Purpose: The study was designed to screen 132 phytochemicals from three medicinal plants traditionally used as antivirals; Zingiber officinalis Roscoe (Zingiberaceae), Artemisia annua L. (Asteraceae), and Moringa oleifera Lam. (Moringaceae), as potential inhibitors of TMPRSS2 for the purpose of finding therapeutic options to treat COVID19. Methods: Homology model of TMPRSS2 was built using the ProMod3 3.1.1 program of the SWISS-MODEL. Binding affinities and interaction between compounds and TMPRSS2 model was examined using molecular docking and molecular dynamics simulation. The drug-likeness and ADMET (absorption, distribution, metabolism, excretion, and toxicity) properties of potential inhibitors of TMPRSS2 were also assessed using admetSAR web tool. Results: Three compounds, namely, niazirin, quercetin, and moringyne from M. oleifera demonstrated better molecular interactions with binding affinities ranging from -7.1 to -8.0 kcal/mol compared to -7.0 kcal/mol obtained for camostat mesylate (a known TMPRSS2 inhibitor), which served as a control. All the three compounds exhibited good drug-like properties by not violating the Lipinski rule of 5. Niazirin and moringyne possessed good ADMET properties and were stable in their interactions with the TMPRSS2 based on the molecular dynamics simulation. However, the ADMET tool predicted the potential hepatotoxic and mutagenic effects of quercetin. Conclusion: This study demonstrated the potentials of niazirin, quercetin, and moringyne from M. oleifera, to inhibit the activities of human TMPRSS2, thus probably being good candidates for further development as new drugs for the treatment or management of COVID-19

Public Health Surveillance for Adverse Events Following COVID-19 Vaccination in Africa

Local, national, and international health agencies have advocated multi-pronged public health strategies to limit infections and prevent deaths. The availability of safe and effective vaccines is critical in the control of a pandemic. Several adverse events have been reported globally following reception of different vaccines, with limited or no data from Africa. This cross-sectional epidemiological study investigated adverse events following COVID-19 vaccination in Africans from April–June, 2021 using a structured online questionnaire. Out of 1200 participants recruited, a total of 80.8% (n = 969) respondents from 35 countries, including 22 African countries and 13 countries where Africans live in the diaspora, reported adverse events. Over half of the vaccinees were male (53.0%) and frontline healthcare workers (55.7%), respectively. A total of 15.6% (n = 151) reported previous exposure to SARS-CoV-2, while about one-fourth, 24.8% (n = 240), reported different underlying health conditions prior to vaccination. Fatal cases were 5.1% (n = 49), while other significant heterogenous events were reported in three categories: very common, common, and uncommon, with the latter including enlarged lymph nodes 2.4% (n = 23), menstrual disorder 0.5% (n = 5), and increased libido 0.2% (n = 2). The study provided useful data for concerned authorities and institutions to prepare plans that will address issues related to COVID-19 vaccines

The evolving SARS-CoV-2 epidemic in Africa: insights from rapidly expanding genomic surveillance

Investment in SARS-CoV-2 sequencing in Africa over the past year has led to a major increase in the number of sequences generated, now exceeding 100,000 genomes, used to track the pandemic on the continent. Our results show an increase in the number of African countries able to sequence domestically, and highlight that local sequencing enables faster turnaround time and more regular routine surveillance. Despite limitations of low testing proportions, findings from this genomic surveillance study underscore the heterogeneous nature of the pandemic and shed light on the distinct dispersal dynamics of Variants of Concern, particularly Alpha, Beta, Delta, and Omicron, on the continent. Sustained investment for diagnostics and genomic surveillance in Africa is needed as the virus continues to evolve, while the continent faces many emerging and re-emerging infectious disease threats. These investments are crucial for pandemic preparedness and response and will serve the health of the continent well into the 21st century

A novel formulation of inhaled sodium cromoglicate (PA101) in idiopathic pulmonary fibrosis and chronic cough: a randomised, double-blind, proof-of-concept, phase 2 trial

Background Cough can be a debilitating symptom of idiopathic pulmonary fibrosis (IPF) and is difficult to treat. PA101 is a novel formulation of sodium cromoglicate delivered via a high-efficiency eFlow nebuliser that achieves significantly higher drug deposition in the lung compared with the existing formulations. We aimed to test the efficacy and safety of inhaled PA101 in patients with IPF and chronic cough and, to explore the antitussive mechanism of PA101, patients with chronic idiopathic cough (CIC) were also studied. Methods This pilot, proof-of-concept study consisted of a randomised, double-blind, placebo-controlled trial in patients with IPF and chronic cough and a parallel study of similar design in patients with CIC. Participants with IPF and chronic cough recruited from seven centres in the UK and the Netherlands were randomly assigned (1:1, using a computer-generated randomisation schedule) by site staff to receive PA101 (40 mg) or matching placebo three times a day via oral inhalation for 2 weeks, followed by a 2 week washout, and then crossed over to the other arm. Study participants, investigators, study staff, and the sponsor were masked to group assignment until all participants had completed the study. The primary efficacy endpoint was change from baseline in objective daytime cough frequency (from 24 h acoustic recording, Leicester Cough Monitor). The primary efficacy analysis included all participants who received at least one dose of study drug and had at least one post-baseline efficacy measurement. Safety analysis included all those who took at least one dose of study drug. In the second cohort, participants with CIC were randomly assigned in a study across four centres with similar design and endpoints. The study was registered with ClinicalTrials.gov (NCT02412020) and the EU Clinical Trials Register (EudraCT Number 2014-004025-40) and both cohorts are closed to new participants. Findings Between Feb 13, 2015, and Feb 2, 2016, 24 participants with IPF were randomly assigned to treatment groups. 28 participants with CIC were enrolled during the same period and 27 received study treatment. In patients with IPF, PA101 reduced daytime cough frequency by 31·1% at day 14 compared with placebo; daytime cough frequency decreased from a mean 55 (SD 55) coughs per h at baseline to 39 (29) coughs per h at day 14 following treatment with PA101, versus 51 (37) coughs per h at baseline to 52 (40) cough per h following placebo treatment (ratio of least-squares [LS] means 0·67, 95% CI 0·48–0·94, p=0·0241). By contrast, no treatment benefit for PA101 was observed in the CIC cohort; mean reduction of daytime cough frequency at day 14 for PA101 adjusted for placebo was 6·2% (ratio of LS means 1·27, 0·78–2·06, p=0·31). PA101 was well tolerated in both cohorts. The incidence of adverse events was similar between PA101 and placebo treatments, most adverse events were mild in severity, and no severe adverse events or serious adverse events were reported. Interpretation This study suggests that the mechanism of cough in IPF might be disease specific. Inhaled PA101 could be a treatment option for chronic cough in patients with IPF and warrants further investigation