Search

Abstract Background Herbal medicines used for male sexual disorders are widespread across the globe and have been noted as likely candidates for adulteration. To assure access to safe and quality herbal products, this study aimed at sampling some herbal capsules indicated for male vitality for quality analytical checks. Methods Herbal capsules sampled from two regions were subjected to physicochemical assessment, using pharmacopeial and regulatory standards. Microbial quality analysis was also performed on the selected products. A validated HPLC method for simultaneous analysis of sildenafil citrate and tadalafil was used to detect and quantify the possible presence of phosphodiesterase inhibitors in the selected products. Results Out of a total of 57 herbal capsules, 19 were indicated for male sexual related illnesses of which only 8 fulfilled the inclusion criteria of being used exclusively for male vitality. The majority (62.5%) of the herbal products failed the weight uniformity test but all of them disintegrated within the acceptable limit of 30 min. The moisture and heavy metal contents were within limits of acceptability. Majority (87.5%) of the herbal products failed the test for the aerobic bacteria count; however, none of the isolated bacteria was pathogenic. Sildenafil citrate was detected in the majority (87.5%) of the herbal products in concentrations of 0.98–33.95 mg/g. Two products contained both sildenafil and tadalafil. High batch-to-batch variability was recorded in some physicochemical parameters and pharmaceutical adulterants. Conclusion High incidence of quality fails and adulteration of herbal capsules for sexual disorders observed means there is a real risk of unintended dosing with phosphodiesterase inhibitors. This represents a public health issue and necessitates tighter monitoring of production standards by the regulator.

Abstract Background Little is known about the nexus between online gambling and psychological distress among youth, especially in Ghana. This study aimed to investigate the effects of online sports betting on psychological distress, focusing on depression, anxiety, and stress among young individuals in the Volta region of Ghana. Methods A cross-sectional study was carried out at various betting centers in the Volta region of Ghana. Four hundred and three (403) participants were selected using a multi-stage sampling method. The study used a standardized questionnaire to assess psychological distress with the Depression, Anxiety, and Stress Scale (DASS 21) and problematic gambling with the Problem Gambling Severity Index (PGSI). The analysis included both descriptive and inferential methods. These include the implementation of the bootstrap technique within multiple regression models using the current versions of Jeffreys’s Amazing Statistics Program (JASP) [0.18.2], Statistical Package for the Social Sciences (SPSS) [29.0.2], and Microsoft Excel (2019). Results The study found a prevalence of 40% for problematic gambling and 44% for moderate gambling problems among participants, resulting in an overall gambling prevalence of 84%. Regarding psychological distress, the estimated prevalence of depression among participants was 43.6%, with stress reported at 31.1% and anxiety at 68.8%. The overall prevalence of psychological distress was 48%. When analyzing the link between gambling and psychological distress, the study noted that males were more prone to gambling-related psychological distress than females (β = 2.036, p = 0.025). Furthermore, individuals with problem gambling showed the highest probability of experiencing more significant psychological distress compared to other groups (β = 9.228, p = 0.002), followed by those with moderate gambling levels (β = 3.283, p = 0.002). Conclusion We recommend that the mental health unit of the Ghana Health Service, in collaboration with the Gaming Commission of Ghana, should develop youth-friendly interventions to address the prevalence and onset of problematic gambling among the youth, especially males. This could, in turn, reduce the prevalence of psychological distress among youth engaged in online gambling in Ghana.

Faced with challenges like resource depletion and climate change, the cement industry needs sustainable solutions. This study explores the potential of geologically-delinaeated black shale from Apersua, Ghana, as a supplementary cementitious material (SCM) to reduce reliance on traditional methods. The researchers analysed the shale's chemical composition and mineralogy, then created laboratory cement formulations with varying black shale content. These were compared to standard formulations without shale. The results show cement with black shale has comparable compressive strength, meeting standard requirements. Even a formulation with only black shale (excluding limestone, a common ingredient) passed strength tests. Overall, the black shale demonstrated good potential as a SCM based on strength, chemical makeup, setting time, and its possible contribution to durability. This research suggests that black shales from Apersua are worth exploring further as a sustainable and potentially cost-effective alternative in cement production.

Introduction: The demand and consumption of vegetables are significantly increasing worldwide, which has resulted in urban farming on anthropogenic sites. This study assessed the concentrations of some selected heavy metals in lettuce and spring onion in line with the WHO/FAO required standard and its implications on human health. Methods: The study was carried out in Kumasi, within moist semi-deciduous forest vegetation, Ghana. The digested samples were analyzed for heavy metals (Cu, Cr, Fe, Mg, Ni, and Zn) using atomic absorption spectrophotometer (AAS Model AA 400p). Analysis of variance was used to test the level of significance at α = .05. Results: The study found mean concentrations of chromium and iron in lettuce and spring onion to be below detection level (BDL) in all study sites based on WHO/FAO permissible level. Also, while copper in lettuce was BDL at all the sites, there were higher mean concentration of copper in spring onion at BSGS (131.5 ± 0.31 mg/kg) and BSG (120.8 ± 0.01 mg/kg). The mean concentration of nickel in lettuce (137.15 ± 0.0231) and spring onion (173.55 ± 0.02 mg/kg) at BSGS were higher than WHO/FAO permissible level. Mean concentration of zinc in both lettuce and spring onion were higher than WHO/FAO permissible level in all the study sites, except zinc in spring onion at KT. The ANOVA test statistics showed no significant difference among the concentrations of heavy metals in all sites, except zinc in lettuce and nickel in spring onion. The study found cancer risk factor for nickel, which exceeded the benchmark of 1 × 10 −6 for both lettuce and spring onion, indicating that long-term consumption could increase the risk of cancer in consumers. Conclusion: The study’s findings call for strict regulation and regular monitoring of heavy metals in vegetables cultivated at anthropogenic sites in urban areas to ensure food safety and consumer health.

Various parts of the plant, Sterculia setigera Delile, from the Malvaceae family are largely used in most African countries for medicinal purposes. In African traditional medicine, the plant is used to treat fever, bacterial infection, diarrhoea, epilepsy, anaemia, and hypertension. Due to its high therapeutic properties, it has become a highly sought-after plant by researchers for pharmacological properties aimed at validating or providing scientific backing for its traditional use. Additionally, efforts to obtain small natural molecules from the plant as scaffolds for the development of new drugs have been explored. Although it is extensively used in traditional medicine and its phytochemical composition and biological activity are widely studied, there is no review paper that systematically analyses its biological activities and phytochemical composition. Hence, this review provides a systematic overview of the biological activities, phytochemical constituents, and ethnomedicinal properties of the plant. The data show S. setigera is a promising medicinal plant with pharmacological potential and thus can be useful for the development of novel therapeutic agents.

Background Globally, one of the measures of high performing healthcare facilities is the compliance of patient safety culture, which encompasses the ability of health institutions to avoid or drastically reduce patient harm or risks. These risks or harm is linked with numerous adverse patient outcomes such as medication error, infections, unsafe surgery and diagnosis error.Objectives The general objective of this study was to investigate into the impact of patient safety culture practices experienced on patient satisfaction among patients who attend the Kwesimintsim Government Hospital in the Takoradi municipality.Methods This study was a descriptive cross-sectional study and a consecutive sampling technique was used to select 336 respondents for the study. Data was collected using a structured questionnaire and processed using Statistical Package for Social Sciences, V.21. Both descriptive and inferential statistics were carried out and result were presented using figures and tables.Results The study found that the overall patient safety compliance level observed by the respondents was poor (29.2%). The prevalence of adverse events experienced among the respondents was high (58%). The leading adverse events mentioned were medication errors, followed by wrong prescriptions and infections. The consequences of these adverse events encountered by the respondents were mentioned as increased healthcare costs (52%), followed by hospitalisation (43%), worsening of health conditions (41%) and contraction of chronic health conditions (22%). Patient safety cultural practices such as teamwork (β=0.17, p=0.03), response to error (β=0.16, p=0.005), communication openness (β=0.17, p=0.003) and handoffs and information exchange (β=0.17, p=0.002) were found to positively influence patient satisfaction.Conclusion The poor general compliance of the patient safety culture in the facility is unfortunate, and this can affect healthcare outcomes significantly. The study therefore entreats facility managers and various stakeholders to see patient safety care as an imperative approach to delivering quality essential healthcare and to act accordingly to create an environment that supports it.

Lenacapavir (LEN) is a highly potent, long-acting antiretroviral medication for treating people infected with muti-drug-resistant HIV-1 phenotypes. The inhibitor targets multifaceted functions of the viral capsid protein (CA) during HIV-1 replication. Previous studies have mainly focused on elucidating LEN's mode of action during viral ingress. Additionally, the inhibitor has been shown to interfere with mature capsid assembly during viral egress. However, the mechanism for how LEN affects HIV-1 maturation is unknown. Here, we show that pharmacologically relevant LEN concentrations do not impair proteolytic processing of Gag in virions. Instead, we have elucidated the primary mechanism for highly potent inhibition of HIV-1 maturation by sub-stoichiometric LEN:CA ratios. The inhibitor exerts opposing effects on formation of CA pentamers versus hexamers, the key capsomere intermediates in mature capsid assembly. LEN impairs formation of pentamers, whereas it induces assembly of hexameric lattices by imposing an opened CA conformation and stabilizing a dimeric form of CA. Consequently, LEN treatment results in morphologically atypical virus particles containing malformed, hyper-stable CA assemblies, which fail to infect target cells. Moreover, we have uncovered an inverse correlation between inhibitor potency and CA levels in cell culture assays, which accounts for LEN's ability to potently (with pM EC 50 values) inhibit HIV-1 maturation at clinically relevant drug concentrations., Author Summary: Lenacapavir (LEN) is the first-in-class HIV-1 capsid targeting antiretroviral that exhibits multimodal modality to inhibit both early and late steps of viral replication. Our studies here have elucidated previously undescribed structural and mechanistic bases for a highly potent antiviral activity of LEN during viral egress. These findings will inform clinical applications of LEN as a potent HIV-1 maturation inhibitor and aid the development of second-generation inhibitors targeting assembly of the mature viral capsid.

Lenacapavir (LEN) is the first in class viral capsid protein (CA) targeting antiretroviral for treating multi-drug-resistant HIV-1 infection. Clinical trials and cell culture experiments have identified resistance associated mutations (RAMs) in the vicinity of the hydrophobic CA pocket targeted by LEN. The M66I substitution conferred by far the highest level of resistance to the inhibitor compared to other RAMs. Here we investigated structural and mechanistic bases for how the M66I change affects LEN binding to CA and viral replication. The high-resolution X-ray structure of the CA(M66I) hexamer revealed that the β-branched side chain of Ile66 induces steric hindrance specifically to LEN thereby markedly reducing the inhibitor binding affinity. By contrast, the M66I substitution did not affect binding of Phe-Gly (FG)-motif-containing cellular cofactors CPSF6, NUP153, or SEC24C, which engage the same hydrophobic pocket of CA. In cell culture the M66I variant did not acquire compensatory mutations or replicate in the presence of LEN. Analysis of viral replication intermediates revealed that HIV-1 (M66I CA) predominantly formed correctly matured viral cores, which were more stable than their wildtype counterparts. The mutant cores stably bound to the nuclear envelope but failed to penetrate inside the nucleus. Furthermore, the M66I substitution markedly altered HIV-1 integration targeting. Taken together, our findings elucidate mechanistic insights for how the M66I change confers remarkable resistance to LEN and affects HIV-1 replication. Moreover, our structural findings provide powerful means for future medicinal chemistry efforts to rationally develop second generation inhibitors with a higher barrier to resistance., Importance: Lenacapavir (LEN) is a highly potent and long-acting antiretroviral that works by a unique mechanism of targeting the viral capsid protein. The inhibitor is used in combination with other antiretrovirals to treat multi-drug-resistant HIV-1 infection in heavily treatment-experienced adults. Furthermore, LEN is in clinical trials for preexposure prophylaxis (PrEP) with interim results indicating 100 % efficacy to prevent HIV-1 infections. However, one notable shortcoming is a relatively low barrier of viral resistance to LEN. Clinical trials and cell culture experiments identified emergent resistance mutations near the inhibitor binding site on capsid. The M66I variant was the most prevalent capsid substitution identified in patients receiving LEN to treat muti-drug resistant HIV-1 infections. The studies described here elucidate the underlying mechanism by which the M66I substitution confers a marked resistance to the inhibitor. Furthermore, our structural findings will aid future efforts to develop the next generation of capsid inhibitors with enhanced barriers to resistance.

HIV-1 integration favors nuclear speckle (NS)-proximal chromatin and viral infection induces the formation of capsid-dependent CPSF6 condensates that colocalize with nuclear speckles (NSs). Although CPSF6 displays liquid-liquid phase separation (LLPS) activity in vitro, the contributions of its different intrinsically disordered regions, which includes a central prion-like domain (PrLD) with capsid binding FG motif and C-terminal mixed-charge domain (MCD), to LLPS activity and to HIV-1 infection remain unclear. Herein, we determined that the PrLD and MCD both contribute to CPSF6 LLPS activity in vitro. Akin to FG mutant CPSF6, infection of cells expressing MCD-deleted CPSF6 uncharacteristically arrested at the nuclear rim. While heterologous MCDs effectively substituted for CPSF6 MCD function during HIV-1 infection, Arg-Ser domains from related SR proteins were largely ineffective. While MCD-deleted and wildtype CPSF6 proteins displayed similar capsid binding affinities, the MCD imparted LLPS-dependent higher-order binding and co-aggregation with capsids in vitro and in cellulo. NS depletion reduced CPSF6 puncta formation without significantly affecting integration into NS-proximal chromatin, and appending the MCD onto a heterologous capsid binding protein partially restored virus nuclear penetration and integration targeting in CPSF6 knockout cells. We conclude that MCD-dependent CPSF6 condensation with capsids underlies post-nuclear incursion for viral DNA integration and HIV-1 pathogenesis., (© The Author(s) 2024. Published by Oxford University Press on behalf of Nucleic Acids Research.)

HIV-1 infection requires passage of the viral core through the nuclear pore of the cell, a process that depends on functions of the viral capsid. Recent studies have shown that HIV-1 cores enter the nucleus prior to capsid disassembly. Interactions of the viral capsid with the nuclear pore complex are necessary but not sufficient for nuclear entry, and the mechanism by which the viral core traverses the comparably sized nuclear pore is unknown. Here we show that the HIV-1 core is highly elastic and that this property is linked to nuclear entry and infectivity. Using atomic force microscopy-based approaches, we found that purified wild type cores rapidly returned to their normal conical morphology following a severe compression. Results from independently performed molecular dynamic simulations of the mature HIV-1 capsid also revealed its elastic property. Analysis of four HIV-1 capsid mutants that exhibit impaired nuclear entry revealed that the mutant viral cores are brittle. Adaptation of two of the mutant viruses in cell culture resulted in additional substitutions that restored elasticity and rescued infectivity and nuclear entry. We also show that capsid-targeting compound PF74 and the antiviral drug Lenacapavir reduce core elasticity and block HIV-1 nuclear entry at concentrations that preserve interactions between the viral core and the nuclear envelope. Our results indicate that elasticity is a fundamental property of the HIV-1 core that enables nuclear entry, thereby facilitating infection. These results provide new insights into the role of the capsid in HIV-1 nuclear entry and the antiviral mechanisms of HIV-1 capsid inhibitors., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Deshpande et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)