Electrochemical detection of selected heavy metals in water: a case study of African experiences

The safety of water resources throughout the globe has been compromised by various human activities and climate change over the last decades. Consequently, the world is currently confronted with a severe shortage of water supply and a water safety crisis, amidst a growing population. With poor environmental regulations, indiscriminate budding of urban slums, poverty, and a lack of basic knowledge of hygiene and sanitation, the African water supply has been critically threatened by different organic and inorganic contaminants, which results in several health issues. Inorganic pollutants such as heavy metals are particularly of interest because they are mostly stable and non-biodegradable. Therefore, they are not easily removed from water. In different parts of the continent, the concentration of heavy metals in drinking water far exceeds the permissible level recommended by the World Health Organization (WHO). Worse still, this problem is expected to increase with growing population, industrialization, urbanization, and, of course, corruption of government and local officials. Most of the African population is ignorant of the standards of safe water. In addition, the populace lack access to affordable and reliable technologies and tools that could be used in the quantification of these pollutants. This problem is not only applicable to domestic, but also to commercial, communal, and industrial water sources. Hence, a global campaign has been launched to ensure constant assessment of the presence of these metals in the environment and to promote awareness of dangers associated with unsafe exposure to them. Various conventional spectroscopic heavy metal detection techniques have been used with great success across the world. However, such techniques suffer from some obvious setbacks, such as the cost of procurement and professionalism required to operate them, which have limited their applications. This paper, therefore, reviews the condition of African water sources, health implications of exposure to heavy metals, and the approaches explored by various indigenous electrochemists, to provide a fast, affordable, sensitive, selective, and stable electrochemical sensors for the quantification of the most significant heavy metals in our water bodies.

The safety of water resources throughout the globe has been compromised by various human activities and climate change over the last decades.     

Chitosan from Crabs (Scylla serrata) Represses Hyperlipidemia-Induced Hepato-Renal Dysfunctions in Rats: Modulation of CD43 and p53 Expression

Hepato-renal dysfunctions associated with hyperlipidemia necessitates a continuous search for natural remedies. This study thus evaluated the effect of dietary chitosan on diet-induced hyperlipidemia in rats. A total of 30 male Wistar rats (90 ± 10) g were randomly allotted into six (6) groups (n = 5): Normal diet, High-fat diet (HFD), and Normal diet + 5% chitosan. The three other groups received HFD, supplemented with 1%, 3%, and 5% of chitosan. The feeding lasted for 6 weeks, after which the rats were sacrificed. The liver and kidneys were harvested for analyses. Hepatic alanine aminotransferase (ALT), aspartate aminotransferase (AST), alkaline phosphatase (ALP) activity, and renal biomarkers (ALT, AST, urea, and creatinine) were assayed spectrophotometrically. Additionally, expression of hepatic and renal CD43 and p53 was estimated immunohistochemically. The HFD group had elevated bodyweight compared to normal which was reversed in the chitosan-supplemented groups. Hyperlipidemia caused a significant (p < 0.05) decrease in the hepatic (AST, ALT, and ALP) and renal (AST and ALT) activities, while renal urea and creatinine increased. Furthermore, the HFD group showed an elevated level of hepatic and renal CD43 while p53 expression decreased. However, groups supplemented with chitosan showed improved hepatic and renal biomarkers, as well as corrected the aberrations in the expressions of p53 and CD43. Conclusively, dietary chitosan inclusion in the diet (between 3% and 5%) could effectively improve kidney and liver functionality via abatement of inflammatory responses.     

What are the recommendations for returning athletes who have experienced long term COVID-19 symptoms?

Currently, there is limited research reporting the symptoms of long COVID among athletes, and the recommendations for athletes returning to competition/training who have experienced long COVID symptoms. Therefore, the aim of this systematic review is to synthesise the recommendations for returning athletes who have experienced long COVID symptoms. The protocol was registered in PROSPERO under CRD42021265939. Two authors searched the electronic databases PubMed, Embase, Scopus, the Cochrane Library, Web of Science, CINAHL, PsycINFO, and SPORTDiscus from August 2019-July 2021. Search terms included words related to “long COVID”, “athlete” and “return”. Data extraction was completed for each study by two independent investigators for: (1) first author name; (2) year of publication; (3) journal; (4) Definition of athlete (i.e. elite or non-elite) (5) Recommendations reported. A total of 220 records were found. Following title and abstract screening, 61 studies were eligible for full text screening. Overall, no studies, commentaries, editorials or reviews provided specific recommendations for “long COVID” defined as COVID-19 signs and symptoms lasting for over 4 weeks as a result of COVID-19 infection. In addition, we found no studies which reported symptoms of athletes suffering from long COVID. Despite the lack of evidence, we did find eight separate professional recommendations for managing “long-term effects” and “ongoing” or “prolonged” symptoms and COVID-19 complications among athletes. Practitioners should be aware of both mental and physical symptoms of long COVID, and additional considerations may be required for athletes who have undergone intensive care. The present review provides a list of recommendations based on existing literature that may be followed and implemented for returning athletes.

Key Messages

• Further research, including longitudinal research of athletes who have tested positive for COVID-19, is required to develop evidenced-based guidelines for athletes with ongoing COVID-19 symptoms.
• Prior to returning to play after COVID-19 infection, a thorough medical history, physical and psychological examination should be conducted by a medical professional.
• Athletes should continue to monitor and record their own physical and psychological markers of health.

     

Rapid vascular glucose uptake via enzyme-assisted subcutaneous infusion: Enzyme-Assisted Subcutaneous Infusion Access Study

Background

Enzyme-assisted subcutaneous infusion (EASI), with subcutaneous human recombinant hyaluronidase pretreatment, may offer an alternative to standard intravenous (IV) access.

Objectives

This study's objectives were to assess paramedic (Emergency Medical Technician–Paramedic [EMTP])-placed EASI access in volunteers to determine (1) feasibility of EMTP EASI access placement; (2) subject/EMTP ratings of placement ease, discomfort, and overall EASI vs IV preference; and (3) speed of intravascular uptake of EASI infusate.

Methods

Twenty adults underwent 20-gauge IV placement by 4 EMTPs, receiving a 250-mL maximal-rate IV bolus of normal saline. Next, each subject received in the other arm a 20-gauge EASI access line (with 1-mL injection of 150 U of human recombinant hyaluronidase), through which was infused 250 mL D5NS (1 g glucose was labeled with stable tracer 13C). Blood draws enabled gas chromatography/mass spectrometry (GC/MS) assessment of 13C-glucose uptake. Intravenous access and EASI access were compared for time parameters and subject/EMTP ratings. Data were analyzed with median and interquartile range, Kruskal-Wallis testing, Fisher exact test, and regression (GC/MS data).

Results

Intravenous access and EASI access were successful in all 20 subjects. Compared with EASI access (all placed in <15 seconds), IV access took longer; but the 250-mL bolus was given more quickly via IV access. EMTPs rated EASI easier to place than IV; pain ratings were similar for IV and EASI. The GC/MS showed intravascular uptake at all time points.

Conclusions

Enzyme-assisted subcutaneous infusion is faster and easier to initiate than IV access; intravascular absorption of EASI-administered fluids begins within minutes.     

Pharmacodynamics of TD-1792, a novel glycopeptide-cephalosporin heterodimer antibiotic used against Gram-positive bacteria, in a neutropenic murine thigh model

TD-1792 is a novel glycopeptide-cephalosporin heterodimer investigational antibiotic that displays potent bactericidal effects against clinically relevant Gram-positive organisms in vitro. The present studies evaluated the in vivo pharmacokinetics (PK) and pharmacodynamics (PD) of TD-1792 in the neutropenic murine thigh infection animal model. TD-1792, dosed subcutaneously (SC), produced dose-dependent reduction in the thigh bacterial burden of several organisms, including methicillin-susceptible and -resistant strains of Staphylococcus aureus and Staphylococcus epidermidis (MSSA, MRSA, MSSE, MRSE, respectively), penicillin-susceptible strains of Streptococcus pneumoniae (PSSP), Streptococcus pyogenes, and vancomycin-intermediate-susceptible Staphylococcus aureus (VISA). In single-dose efficacy studies, the 1-log(10) CFU kill effective dose (ED(1-log kill)) estimates for TD-1792 ranged from 0.049 to 2.55 mg/kg of body weight administered SC, and the bacterial burden was reduced by up to 3 log(10) CFU/g from pretreatment values. Against S. aureus ATCC 33591 (MRSA), the total 24-h log(10) stasis dose (ED(stasis)) and ED(1-logkill) doses for TD-1792 were 0.53 and 1.11 mg/kg/24 h, respectively, compared to 23.4 and 54.6 mg/kg/24 h for vancomycin, indicating that TD-1762 is 44- to 49-fold more potent than vancomycin. PK-PD analysis of data from single-dose and dose-fractionation studies for MRSA (ATCC 33591) demonstrated that the total-drug 24-h area under the concentration-time curve-to-MIC ratio (AUC/MIC ratio) was the best predictor of efficacy (r(2) = 0.826) compared to total-drug maximum plasma concentration of drug-to-MIC ratio (Cmax/MIC ratio; r(2) = 0.715) and percent time that the total-drug plasma drug concentration remains above the MIC (%Time>MIC; r(2) = 0.749). The magnitudes of the total-drug AUC/MIC ratios associated with net bacterial stasis, a 1-log(10) CFU reduction from baseline and near maximal effect, were 21.1, 37.2, and 51.8, respectively. PK-PD targets based on such data represent useful inputs for analyses to support dose selection decisions for clinical studies of patients.     

Population Pharmacokinetics of Fusidic Acid: Rationale for Front-Loaded Dosing Regimens Due to Autoinhibition of Clearance

The objectives of this analysis were to develop a population pharmacokinetic (PK) model to describe the absorption and disposition of fusidic acid after single and multiple doses and to determine the effect of food on the rate and extent of bioavailability. Plasma PK data from three phase 1 studies (n = 75; n = 14 with and without food) in which healthy subjects received sodium fusidate (500 to 2,200 mg) as single or multiple oral doses every 8 h (q8h) or q12h for up to 7 days were modeled using S-ADAPT (MCPEM algorithm). Accumulation of fusidic acid after multiple doses was more than that predicted based on single-dose data. The PK of fusidic acid was best described using a time-dependent mixed-order absorption process, two disposition compartments, and a turnover process to describe the autoinhibition of clearance. The mean total clearance (% coefficient of variation) was 1.28 liters/h (33%) and the maximum extent of autoinhibition was 71.0%, with a 50% inhibitory concentration (IC₅₀) of 46.3 mg/liter (36%). Food decreased the extent of bioavailability by 18%. As a result of the autoinhibition of clearance, steady state can be achieved earlier with dosing regimens that contain higher doses (after 8 days for 750 mg q12h and 1 day for 1,500 mg q12h on day 1 followed by 600 mg q12h versus 3 weeks for 500 mg q12h). Given that large initial doses autoinhibit the clearance of fusidic acid, this characteristic provides a basis for the administration of front-loaded dosing regimens of sodium fusidate which would allow for effective concentrations to be achieved early in therapy.