Knowledge and utilization of family planning services among tertiary students in Northern Ghana: The case of College of Nursing and Midwifery, Nalerigu.

Though tertiary students studying health-related programs are assumed knowledgeable about family planning, this does not always translate to increased use of family planning services. In a cross-sectional survey, this study assessed 411 nursing, midwifery and allied health students' knowledge of family planning, contraceptive use, perceptions, and factors affecting the utilisation of family planning services. Each student completed a 24-itemised questionnaire in a Computer-Assisted Personal Interviewing Survey. The data was analysed with Stata /IC version 16. Statistical significance was set at p<0.05. Overall knowledge of family planning was 99.7%, commonly gained in school (51.8%), followed by clinics and hospitals (41.4%). Only 21.7% of the students used family planning services. Menstrual cramps (57.9%), infertility (33.1%), and weight gain (32.5%) were the commonly perceived side effects of contraceptive use. The high proximity of participants to family planning service providers and lack of community, family, and partner acceptance of modern contraceptives were associated with underutilisation. Despite the high level of knowledge of family planning, the student's utilisation of family planning services was poor. To boost family planning service uptake among tertiary health students, it is essential to tackle barriers related to community, family, and partner acceptance. This can be achieved through educational programs that involve men in family planning discussions and by enhancing service accessibility.

Même si les étudiants du supérieur qui étudient dans des programmes liés à la santé sont censés connaître la planification familiale, cela ne se traduit pas toujours par une utilisation accrue des services de planification familiale. Dans le cadre d'une enquête transversale, cette étude a évalué les connaissances de 411 étudiants en soins infirmiers, obstétricaux et paramédicaux en matière de planification familiale, d'utilisation des contraceptifs, de perceptions et de facteurs affectant l'utilisation des services de planification familiale. Chaque étudiant a rempli un questionnaire en 24 points dans le cadre d'une enquête par entretien personnel assisté par ordinateur. Les données ont été analysées avec Stata/IC version 16. La signification statistique a été fixée à p<0,05. La connaissance globale de la planification familiale était de 99,7 %, généralement acquise à l'école (51,8 %), suivie par les cliniques et les hôpitaux (41,4 %). Seulement 21,7% des étudiants ont utilisé les services de planification familiale. Les crampes menstruelles (57,9 %), l'infertilité (33,1 %) et la prise de poids (32,5 %) étaient les effets secondaires couramment perçus de l'utilisation de contraceptifs. La grande proximité des participants avec les prestataires de services de planification familiale et le manque d'acceptation des contraceptifs modernes par la communauté, la famille et les partenaires étaient associés à la sous-utilisation. Malgré le niveau élevé de connaissances en matière de planification familiale, l'utilisation des services de planification familiale par les étudiants était faible. Pour stimuler le recours aux services de planification familiale parmi les étudiants de l'enseignement supérieur en santé, il est essentiel de s'attaquer aux obstacles liés à l'acceptation par la communauté, la famille et les partenaires. Cet objectif peut être atteint grâce à des programmes éducatifs qui impliquent les hommes dans les discussions sur la planification familiale et en améliorant l'accessibilité des services.

Bridging the Gap in Malaria Parasite Resistance, Current Interventions, and the Way Forward from in Silico Perspective: A Review.

The past decade has seen most antimalarial drugs lose their clinical potency stemming from parasite resistance. Despite immense efforts by researchers to mitigate this global scourge, a breakthrough is yet to be achieved, as most current malaria chemotherapies suffer the same fate. Though the etiology of parasite resistance is not well understood, the parasite's complex life has been implicated. A drug-combination therapy with artemisinin as the central drug, artemisinin-based combination therapy (ACT), is currently the preferred malaria chemotherapy in most endemic zones. The emerging concern of parasite resistance to artemisinin, however, has compromised this treatment paradigm. Membrane-bound Ca2+-transporting ATPase and endocytosis pathway protein, Kelch13, among others, are identified as drivers in plasmodium parasite resistance to artemisinin. To mitigate parasite resistance to current chemotherapy, computer-aided drug design (CADD) techniques have been employed in the discovery of novel drug targets and the development of small molecule inhibitors to provide an intriguing alternative for malaria treatment. The evolution of plasmepsins, a class of aspartyl acid proteases, has gained tremendous attention in drug discovery, especially the non-food vacuole. They are expressed at multi-stage of the parasite's life cycle and involve in hepatocytes' egress, invasion, and dissemination of the parasite within the human host, further highlighting their essentiality. In silico exploration of non-food vacuole plasmepsin, PMIX and PMX unearthed the dual enzymatic inhibitory mechanism of the WM382 and 49c, novel plasmepsin inhibitors presently spearheading the search for potent antimalarial. These inhibitors impose structural compactness on the protease, distorting the characteristic twist motion. Pharmacophore modeling and structure activity of these compounds led to the generation of hits with better affinity and inhibitory prowess towards PMIX and PMX. Despite these headways, the major obstacle in targeting PM is the structural homogeneity among its members and to human Cathepsin D. The incorporation of CADD techniques described in the study at early stages of drug discovery could help in selective inhibition to augment malaria chemotherapy.

Lipid-Embedded Molecular Dynamics Simulation Model for Exploring the Reverse Prostaglandin D2 Agonism of CT-133 towards CRTH2 in the Treatment of Type-2 Inflammation Dependent Diseases.

Chemoattractant receptor-homologous molecule expressed on Th2 cells (CRTH2) has been involved in several inflammation dependent diseases by mediating the chemotaxis of pro-inflammatory cells in response to allergy and other responses through PGD2 ligation. This CRTH2-PGD2 signaling pathway has become a target for treating allergic and type 2 inflammation dependent diseases, with many inhibitors developed to target the PGD2 binding pocket. One of such inhibitors is the ramatroban analog, CT-133, which exhibited therapeutic potency cigarette smoke-induced acute lung injury in patients. Nonetheless, the molecular mechanism and structural dynamics that accounts for its therapeutic prowess remain unclear. Employing computational tools, this study revealed that although the carboxylate moiety in CT-133 and the native agonist PGD2 aided in their stability within the CRTH2 binding pocket, the tetrahydrocarbazole group of CT-133 engaged in strong interactions with binding pocket residues which could have formed as the basis of the antagonistic advantage of CT-133. Tetrahydrocarbazole group interactions also enhanced the relative stability CT-133 within the binding pocket which consequently favored CT-133 binding affinity. CT-133 binding also induced an inactive or 'desensitized' state in the helix 8 of CRTH2 which could conversely favor the recruitment of arrestin. These revelations would aid in the speedy development of small molecule inhibitors of CRTH2 in the treatment of type 2 inflammation dependent diseases.

Assessment of urogenital schistosomiasis among basic school children in selected communities along major rivers in the central region of Ghana.

INTRODUCTION: urogenital schistosomiasis affects school-aged children with impacts on health, growth, and cognitive development. Basic schools along active water bodies have a possibility of a high infection among the children. METHODS: we performed a school-based cross-sectional assessment of urogenital schistosomiasis among children in four selected rural communities along major rivers in the central region of Ghana. Three hundred and nine (309) basic school children class 1 to junior high school (JHS) 3 were recruited. Sociodemographic data and information on behavioral influences were collected with a structured written questionnaire. Laboratory examinations were conducted on fresh urine samples. Descriptive statistics and cross-tabulations with measures of association between variables, adjusted and unadjusted logistic regression analysis were performed on measured variables. RESULTS: we recorded a 10.4% prevalence of urogenital schistosomiasis. Schools in communities along the Kakum river recorded the highest disease burden (65.6%). The odds of infection among pupils who engage in irrigation activities were 4 folds more than those who do not engage in irrigation activities (adjusted odds ratio (aOR) (95%CI): 4.3 (1.6-12.1), P-value=0.005). Pupils of caregivers who resort to self-medication using local herbal concoctions had 14-fold more odds of infection compared to those who visit the health facility (aOR (95%CI): 14.4 (1.4-143.1), P-value=0.006). CONCLUSION: poor health-seeking behaviors and lack of access to health facilities influenced the disease proportion among the children in these endemic communities.

Exploring the ring potential of 2,4-diaminopyrimidine derivatives towards the identification of novel caspase-1 inhibitors in Alzheimer's disease therapy.

Pro-inflammatory activation of caspase-1 in the neurodegenerative pathway has been associated with age-dependent cognitive impairment and Alzheimer's disease (AD) in humans. A recent report highlighted 2,4-diaminopyrimidine ring as an essential fragment in the inhibition of human caspase-1. However, the role of the ring and its enzyme inhibitory mechanism is not thoroughly investigated at the molecular level. The purpose of this study is therefore in twofold: (1) to understand the enzyme binding mechanism of the 2,4-diaminopyrimidine ring and (2) to search for more potent caspase-1 inhibitors that contain the ring, using integrative per-residue energy decomposition (PRED) pharmacophore modeling. Ligand interaction profile of a reference compound revealed a peculiar hydrogen formation of the amino group of 2,4-diaminopyrimidine with active site residue Arg341, possibly forming the bases for its inhibitory prowess against caspase-1. A generated pharmacophore model for structure-based virtual screening identified compounds, ZINC724667, ZINC09908119, and ZINC09933770, as potential caspase-1 inhibitors that possessed desirable pharmacokinetic and physiochemical properties. Further analyses revealed active site residues, Arg179, Ser236, Cys285, Gln283, Ser339, and Arg341, as crucial to inhibitor binding by stabilizing and forming hydrogen bonds, hydrophobic, and pi-pi interactions with the 2,4-diaminopyrimidine rings. Common interaction patterns of the hits could have accounted for their selective and high-affinity ligand binding, which was characterized by notable disruptions in caspase-1 structural architecture. These compounds could further be explored as potential leads in the development of novel caspase-1 inhibitors.

'Polymorphism-aided' Selective Targeting and Inhibition of Caspase-6 by a Novel Allosteric Inhibitor Towards Efficient Alzheimer's Disease Treatment.

The predominance of Alzheimer's disease (AD) among the aged remains a global challenge. As such, the search for alternative and effective therapeutic options continuous unabated. Among the therapeutic targets explored over the years toward impeding the progression of AD is caspase-6 (Casp6), although selectively targeting Casp6 remains a challenge due to high homology with other members of the caspase family. Methyl 3-[(2,3-dihydro-1-benzofuran-2-yl formamido) methyl]-5-(furan-2-amido) benzoate (C13), a novel allosteric inhibitor, is reportedly shown to exhibit selective inhibition against mutant human Casp6 variants (E35K). However, structural and atomistic insights accounting for the reported inhibitory prowess of C13 remains unresolved. In this study, we seek to unravel the mechanistic selectivity of C13 coupled with the complementary effects of E35K single-nucleotide polymorphism (SNP) relative to Casp6 inhibition. Analyses of binding dynamics revealed that the variant Lysine-35 mediated consistent high-affinity interactions with C13 at the allosteric site, possibly forming the molecular basis of the selectivity of C13 as well as its high binding free energy as estimated. Analysis of residue interaction network around Glu35 and Lys35 revealed prominent residue network distortions in the mutant Casp6 conformation evidenced by a decrease in node degree, reduced number of edges and an increase short in path length relative to a more compact conformation in the wild system. The relatively higher binding free energy of C13 coupled with the stronger intermolecular interactions elicited in the mutant conformation further suggests that the mutation E35K probably favours the inhibitory activity of C13. Further analysis of atomistic changes showed increased C-α atom deviations consistent with structural disorientations in the mutant Casp6. Structural Insights provided could open up a novel paradigm of structure-based design of selective allosteric inhibition of Casp6 towards the treatment of neurodegenerative diseases.

From the Explored to the Unexplored: Computer-Tailored Drug Design Attempts in the Discovery of Selective Caspase Inhibitors.

The pathophysiological roles of caspases have made them attractive targets in the treatment and amelioration of neurologic diseases. In normal conditions, the expression of caspases is regulated in the brain, while at the onset of neurodegeneration, such as in Alzheimer's disease, they are typically overexpressed. Till date, several therapeutic efforts that include the use of small endogenous binders have been put forward to curtail dysfunctionalities that drive aberrant death in neuronal cells. Caspases are highly homologous, both in structure and in sequence, which leaves us with the question: is it possible to specifically and individually target caspases, while multiple therapeutic attempts to achieve selective targeting have failed! Based on antecedent events, the use of Computer-Aided Drug Design (CADD) methods has significantly contributed to the design of small molecule inhibitors, especially with selective target ability and reduced off-target therapeutic effects. Interestingly, we found out that there still exists an enormous room for the integration of structure/ligand-based drug design techniques towards the development of highly specific reversible and irreversible caspase inhibitors. Therefore, in this review, we highlight drug discovery approaches that have been directed towards caspase inhibition in addition to an insightful focus on applicable CADD techniques for achieving selective targeting in caspase research.

Same Target, Different Therapeutic Outcomes: The Case of CAY10471 and Fevipiprant on CRTh2 Receptor in Treatment of Allergic Rhinitis and Asthma.

OBJECTIVE: Prostaglandin 2 (PGD2) mediated signalling of Chemoattractant Receptorhomologous molecule expressed on Th2 cells (CRTh2) receptor has been implicated in the recruitment of inflammatory cells. This explains the design of highly selective compounds with innate abilities to antagonize PGD2-CRTh2 interactions and prevent pro-inflammatory allergies such as rhinitis and uncontrolled asthma. The development of PGD2-competitive CRTh2 binders; CAY10471 and Fevipiprant represent remarkable therapeutic progress even though they elicit disparate pharmacological propensities despite utilizing the same binding pocket. METHODS & RESULTS: In this study, we seek to pinpoint the underlying phenomenon associated with differential CRTh2 therapeutic inhibition by CAY10471 and Fevipiprant using membraneembedded molecular dynamics simulation. Findings revealed that the common carboxylate group of both compounds elicited strong attractive charges with active site Arg170 and Lys210. Interestingly, a distinctive feature was the steady occurrence of high-affinity salt-bridges and an Arg170-mediated pi-cation interaction with the tetrahydrocarbozole ring of CAY10471. Further investigations into the active site motions of both ligands revealed that CAY10471 was relatively more stable. Comparative binding analyses also revealed that CAY10471 exhibited higher ΔG, indicating the cruciality of the ring stabilization role mediated by Arg170. Moreover, conformational analyses revealed that the inhibitory activity of CAY10471 was more prominent on CRTh2 compared to Fevipiprant. CONCLUSIONS: These findings could further advance the strategic design of novel CRTh2 binders in the treatment of diseases related to pro-inflammatory allergies.