Ecological and seasonal variations and other factors associated with clinical malaria in the Central Region of Ghana: A cross-sectional study.

BACKGROUND: This study investigated malaria transmission under various contrasting settings in the Central Region, a malaria endemic region in Ghana. METHODS: This cross-sectional study was carried out in five randomly selected districts in the Central Region of Ghana. Three of the districts were forested, while the rest was coastal. Study participants were selected to coincide with either the regular rainy or dry season. From each study site, hospital attendees were randomly selected with prior consent. Consciously, study participants were selected in both rainy (September and October, 2020) and dry (November and December, 2020) seasons. Clinical data for each patient was checked for clinical malaria suspicion and microscopic confirmation of malaria. Using SPSS Version 24 (Chicago, IL, USA), bivariate analysis was done to determine the association of independent variables (ecological and seasonal variations) with malaria status. When the overall analysis did not yield significant association, further statistical analysis was performed after stratification of variables (into age and gender) to determine whether any or both of them would significantly associate with the dependent variable. RESULTS: Of the 3993 study participants, 62.5% were suspected of malaria whereas 38.2% were confirmed to have clinical falciparum malaria. Data analysis revealed that in both rainy and dry seasons, malaria cases were significantly higher in forested districts ) than coastal districts (x2 = 217.9 vs x2 = 50.9; p < 0.001). Taken together, the risk of malaria was significantly higher in the dry season (COR = 1.471, p < 0.001) and lower in coastal zones (COR = 0.826, p = 0.007). There was significant reduced risk of participants aged over 39 years of malaria (COR=0.657, p < 0.001). Whereas, in general patients between 10 and 19 years were insignificantly less likely to have malaria (COR = 0.911, p = 0.518) compared to participants aged less than< 10 years, the reverse was observed in coastal districts where patients less than 10 years of age in coastal districts were less likely to have malaria (COR=2.440, p = 0.003). In general, gender did not associate with malaria, but when stratified by study district, the risk of female gender to malaria was significantly higher in Agona Swedru (COR = 5.605, p < 0.001), Assin central (COR = 2.172, p < 0.001), Awutu Senya (COR = 2.410, p < 0.001) and Cape Coast (COR = 3.939, p < 0.001) compared to Abura-Asebu-Kwamankese. CONCLUSION: This study demonstrated that the predictors of malaria differ from one endemic area to another. Therefore, malaria control interventions such as distribution of long-lasting insecticide treated bed nets, residual spraying with insecticide and mass distribution of antimalaria prophylaxis must be intensified in forested districts in all seasons with particular attention on females.

The Embryological Landscape of Mayer-Rokitansky-Kuster-Hauser Syndrome: Genetics and Environmental Factors.

Mayer-Rokitansky-Küster-Hauser (MRKH) syndrome is a disorder caused by Müllerian ducts dysgenesis affecting 1 in 5000 women with a typical 46,XX karyotype. The etiology of MRKH syndrome is complex and largely unexplained. Familial clustering suggests a genetic component and the spectrum of clinical presentations seems consistent with an inheritance pattern characterized by incomplete penetrance and variable expressivity. Mutations of several candidate genes have been proposed as possible causes based on genetic analyses of human patients and animal models. In addition, studies of monozygotic twins with discordant phenotypes suggest a role for epigenetic changes following potential exposure to environmental compounds. The spectrum of clinical presentations is consistent with intricate disruptions of shared developmental pathways or signals during early organogenesis. However, the lack of functional validation and translational studies have limited our understanding of the molecular mechanisms involved in this condition. The clinical management of affected women, including early diagnosis, genetic testing of MRKH syndrome, and the implementation of counseling strategies, is significantly impeded by these knowledge gaps. Here, we illustrate the embryonic development of tissues and organs affected by MRKH syndrome, highlighting key pathways that could be involved in its pathogenesis. In addition, we will explore the genetics of this condition, as well as the potential role of environmental factors, and discuss their implications to clinical practice.

Sterilizing Immunity against COVID-19: Developing Helper T cells I and II activating vaccines is imperative.

Six months after the publication of the severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) sequence, a record number of vaccine candidates were listed, and quite a number of them have since been approved for emergency use against the novel coronavirus disease 2019 (COVID-19). This unprecedented pharmaceutical feat did not only show commitment, creativity and collaboration of the scientific community, but also provided a swift solution that prevented global healthcare system breakdown. Notwithstanding, the available data show that most of the approved COVID-19 vaccines protect only a proportion of recipients against severe disease but do not prevent clinical manifestation of COVID-19. There is therefore the need to probe further to establish whether these vaccines can induce sterilizing immunity, otherwise, COVID-19 vaccination would have to become a regular phenomenon. The emergence of SARS-CoV-2 variants could further affect the capability of the available COVID-19 vaccines to prevent infection and protect recipients from a severe form of the disease. These notwithstanding, data about which vaccine(s), if any, can confer sterilizing immunity are unavailable. Here, we discuss the immune responses to viral infection with emphasis on COVID-19, and the specific adaptive immune response to SARS-CoV-2 and how it can be harnessed to develop COVID-19 vaccines capable of conferring sterilizing immunity. We further propose factors that could be considered in the development of COVID-19 vaccines capable of stimulating sterilizing immunity. Also, an old, but effective vaccine development technology that can be applied in the development of COVID-19 vaccines with sterilizing immunity potential is reviewed.

Alkaloidal extract from Carica papaya seeds ameliorates CCl4-induced hepatocellular carcinoma in rats.

BACKGROUND: Hepatocellular carcinoma (HCC) is the third cause of cancer-related mortality globally. However, available treatments are expensive and are associated with adverse effects or poor treatment outcomes in advanced disease. Meanwhile, plants like Carica papaya have demonstrated various biological activities that further studies may lead to the identification of newer and safer treatment options for HCC. AIM: To evaluate the anticancer activity of an alkaloidal extract derived from Carica papaya seeds using rodent models of HCC. EXPERIMENTAL PROCEDURE: Carica Papaya fruits were collected and authenticated. The seeds were isolated and air-dried. Alkaloidal extract was prepared from a 70% ethanol soxhlet crude extract and referred to as Carica papaya alkaloidal extract (CPAE). HCC was induced in 68 out of 84 healthy male Sprague Dawley rats by intraperitoneal injection of carbon tetrachloride (CCl4) for 16 weeks. These rats were put into five groups of 10; Carica papaya alkaloidal extract [(CPAE) (50, 100, and 200 mg/kg), Lenvatinib (4 mg/kg)], 1% dimethyl sulphoxide (DMSO), and 2 untreated groups (control and model). A prophylaxis study was performed with 10 rats by co-administration of CPAE (200 mg/kg) and CCl4 six hours apart for 16 weeks. Rats were sacrificed after a twelve-week treatment program under anesthesia for histological, hematological, and biochemical analyses. RESULTS AND CONCLUSION: CPAE (100 and 200 mg/kg) significantly restored weight loss (48.44 and 51.75% respectively), reduced tumor multiplicity, and dose-dependently reversed liver histomorphological changes induced by CCl4 compared to the model group. The CPAE (100 and 200 mg/kg) further reduced bleeding time, improved prothrombin time and restored platelet count (p < 0.01) compared to the model. The CPAE (200 mg/kg) again significantly (p < 0.0001) reduced serum alpha-fetoprotein levels compared to the model group and prevented the establishment of HCC in rats when concerrently administered with CCl4 in 16 weeks prophylactic study.

Alkaloidal extract from Zanthoxylum zanthoxyloides stimulates insulin secretion in normoglycemic and nicotinamide/streptozotocin-induced diabetic rats.

INTRODUCTION: Increase in the prevalence of type-2 diabetes in Sub-Sahara Africa has created the need for robust treatment and management programs. However, an effective diabetes management program requires a high annual budget that most countries in this region cannot afford. That said, various plants and plant products in this region have either been confirmed and/or ethnopharmacologically used for the management of type-2 diabetes. AIM: To investigate the antidiabetic and insulin secretory effects of an alkaloidal extract derived from Zanthoxylum zanthoxyloides in normoglycemic and experimental diabetic rats. MATERIALS AND METHODS: Alkaloidal extract was prepared from leaves of Z anthoxylum zanthoxyloides (ZZAE). Nicotinamide/streptozotocin-induced type-2 diabetes was modeled in male Sprague Dawley rats weighing between 130 to 150 g. The experimental diabetic rats were grouped into six treatment groups [Model, 20% Tween20, chlorpropamide, and ZZAE (50, 100, and 150 mg/kg)], and one control group. Fasting blood glucose (FBG), and body weight were measured weekly. Rats were sacrificed 2 days after treatment under chloroform anesthesia to collect blood samples and to isolate major organs for biochemical, and histological analyses respectively. Islets of Langerhans were isolated from normoglycemic rats and co-cultured with ZZAE and chlorpropamide (10 µg/mL) to assess the insulin secretory effect of ZZAE. RESULTS: ZZAE improved glucose kinetics curve in normoglycemic (p < 0.001) and experimental diabetic rats (p < 0.05) compared to the model. ZZAE (100 and 150 mg/kg) restored islets population, and improved kidney, and liver, histoarchitecture. ZZAE (150 mg/kg) improved post-treatment serum insulin levels compared to the model group (p < 0.001) and the Chlorpropamide group (p < 0.05). ZZAE also restored glycogen synthesis in skeletal muscles of experimental diabetic rats and stimulated insulin secretion in pancreatic islets of Langerhans isolated from normoglycemic rats. CONCLUSION: These results showed that ZZAE has active alkaloids that can be explored for diabetes management.

GREB1L as a candidate gene of Mayer-Rokitansky-Küster-Hauser Syndrome.

Mayer-Rokitansky-Küster-Hauser (MRKH) Syndrome is a sex development disorder that affects 1 in every 4500 46, XX live births. At least a subset of MRKH syndrome is genetically related to which various candidate genes have been identified. The growth regulation by estrogen in breast cancer 1-like gene (GREB1L) is an androgen-regulated gene reported to be a co-activator of the retinoic acid receptor gene (RAR). Thus expression levels of GREB1L have implications on renal system cellular differentiation, morphogenesis, and homeostasis in vertebrates. Variants of GREB1L have been reported in familial and sporadic MRKH Syndrome and more importantly, in a three-generation family ofMRKH syndrome propositae. Much the same way, Mutants of GREB1L have also been identified in isolated bilateral renal agenesis and deafness both of which are extra-genital tract anomalies in MRKH type 2. Again, renal agenesis transgenic mice have been produced from an E13.5 CRISPR/cas9 GREB1L mutagenesis. Though no GREB1L mutation has been reported in cardiac malformation, there is evidence that GREB1L is involved in ventricular development. Here, we intorigate evidence that projects GREB1L as a candidate gene of Mayer-Rokitansky-Küster-Hauser Syndrome and propose that functional validation analysis to that effect is imparative.

Prospect of reprogramming replication licensing for cancer drug development.

Eukaryotic chromosomal DNA replication is preceded by replication licensing which involves the identification of the origin of replication by origin recognition complex (ORC). The ORC loads pre-replication complexes (pre-RCs) through a series of tightly regulated mechanisms where the ORC interacts with Cdc6 to recruit cdt1-MCM2-7 complexes to the origin of replication. In eukaryotes, adherence to regulatory mechanisms of the replication program is required to ensure that all daughter cells carry the exact copy of genetic material as the parent cell. Failure of which leads to the development of genome instability syndromes like cancer, diabetes, etc. In an event of such occurrence, preventing cells from carrying the defaulted genetic material and passing it to other cells hinges on the regulation of chromosomal DNA replication. Thus, understanding the mechanisms underpinning chromosomal DNA replication and particularly replication licensing can expose druggable enzymes, effector molecules, and secondary messengers that can be targeted for diagnosis and therapeutic purposes. Effectively drugging these molecular markers to reprogram pre-replication events can be used to control the fate of chromosomal DNA replication for the treatment of genome instability disorders and in this case, cancer. This review discusses available knowledge of replication licensing in the contest of molecular drug discovery for the treatment of cancer.