Hypertension Related Co-Morbidities and Complications in Women of Sub-Saharan Africa: A Brief Review.

Hypertension is the leading cause of cardiovascular disease in women, and sub-Saharan African (SSA) countries have some of the highest rates of hypertension in the world. Expanding knowledge of causes, management, and awareness of hypertension and its co-morbidities worldwide is an effective strategy to mitigate its harms, decrease morbidities and mortality, and improve individual quality of life. Hypertensive disorders of pregnancy (HDPs) are a particularly important subset of hypertension, as pregnancy is a major stress test of the cardiovascular system and can be the first instance in which cardiovascular disease is clinically apparent. In SSA, women experience a higher incidence of HDP compared with other African regions. However, the region has yet to adopt treatment and preventative strategies for HDP. This delay stems from insufficient awareness, lack of clinical screening for hypertension, and lack of prevention programs. In this brief literature review, we will address the long-term consequences of hypertension and HDP in women. We evaluate the effects of uncontrolled hypertension in SSA by including research on heart disease, stroke, kidney disease, peripheral arterial disease, and HDP. Limitations exist in the number of studies from SSA; therefore, we will use data from countries across the globe, comparing and contrasting approaches in similar and dissimilar populations. Our review highlights an urgent need to prioritize public health, clinical, and bench research to discover cost-effective preventative and treatment strategies that will improve the lives of women living with hypertension in SSA.

Hoslundia opposita vahl; a potential source of bioactive compounds with antioxidant and antibiofilm activity for wound healing.

BACKGROUND: Biofilms and oxidative stress retard wound healing. The resistance of biofilms to antibiotics has led to a search for alternative approaches in biofilm elimination. Antioxidants work synergistically with antibacterial agents against biofilms. Hence recent research has suggested plants as candidates in the development of new alternatives in biofilm treatments and as antioxidants due to the presence of phytocompounds which are responsible for their bioactivities. Hoslundia opposita Vahl is one of the plants used by traditional healers to treat wounds and other infections, this makes it a potential candidate for drug discovery hence, in this study, we investigate the antibiofilm and antioxidant activity of methanolic extract of hoslundia opposita Vahl from Uganda. We also identify phytochemicals responsible for its bioactivity. METHOD: the plant was extracted by maceration using methanol, and the extract was investigated for antioxidant activity using 2,2-diphenyl-1-picrylhydrazyl radical (DPPH) assay. The antibiofilm activity using microtiter plate assay (MTP) assay where the Minimum biofilm inhibitory concentration required to inhibit 50% or 90% of the biofilm (MBIC50 and MBIC90) and Minimum biofilm eradication concentration required to remove 50% or 90% of the biofilm (MBEC50 and MBEC90) were measured. It was further analysed for its phytochemical composition using quantitative screening, as well as Gas chromatography-mass spectrometry (GC-MS) and Liquid chromatography mass-spectrometry (LC-MS). RESULTS: H. Opposita Vahl extract showed good antioxidant activity with of 249.6 mg/mL. It inhibited the growth of P. aeruginosa and S. aureus biofilms with MBIC50 of 28.37 mg/mL and 10 mg/mL, respectively. It showed the ability to eradicate P. aeruginosa and S. aureus biofilms with MBEC50 of 23.85 and 39.01 mg/mL respectively. Phytochemical analysis revealed the presence of alkaloids, tannins, flavonoids, and phenols. GC-MS analysis revealed 122 compounds in the extract of which, 23 have evidence of antioxidant or antibiofilm activity in literature. The most abundant compounds were; 1,4- Citric acid, Tetracontane-1,40-diol (43.43.3%, 1, Olean-12-en-28-oic acid, 3-hydroxy-, methyl ester, (3.beta) (15.36%) 9-Octadecenamide (12.50%), Squalene (11.85%) Palmitic Acid 4TMS (11.28%), and alpha Amyrin (11.27%). The LC-MS identified 115 and 57 compounds in multiple reaction mode (MRM) and scan modes respectively. CONCLUSION: H. opposita Vahl showed antibiofilm and antioxidant activity due to bioactive compounds identified, hence the study justifies its use for wound healing. It can be utilised in further development of new drugs as antibiofilm and antioxidants.

Review of Herbal Medicinal Plants Used in the Management of Cancers in the East Africa Region from 2019 to 2023.

BACKGROUND: In the East African region, herbal plants are essential in the treatment and control of cancer. Given the diverse ecological and cultural makeup of the regional states, it is likely that different ethnic groups will use the same or different plants for the same or different diseases. However, since 2019, this has not been compiled into a single study. PURPOSE: The study aimed to compile and record the medicinal plants utilized in East Africa from April 2019 to June 2023 to treat various cancer types. MATERIALS AND METHODS: The study examined 13 original studies that included ethnobotanical research conducted in East Africa. They were retrieved from several internet databases, including Google Scholar, Scopus, PubMed/Medline, Science Direct, and Research for Life. The study retrieved databases on plant families and species, plant parts used, preparation methods and routes of administration, and the country where the ethnobotanical field surveys were conducted. Graphs were produced using the GraphPad Prism 8.125 program (GraphPad Software, Inc., San Diego, CA). Tables and figures were used to present the data, which had been condensed into percentages and frequencies. RESULTS: A total of 105 different plant species from 45 different plant families were identified, including Asteraceae (14), Euphorbiaceae (12), Musaceae (8), and Apocynaceae (7). Uganda registered the highest proportion (46% of the medicinal plants used). The most commonly mentioned medicinal plant species in cancer management was Prunus africana. Herbs (32%), trees and shrubs (28%), and leaves (45%) constituted the majority of herbal remedies. Most herbal remedies were prepared by boiling (decoction) and taken orally (57%). CONCLUSION: East Africa is home to a wide variety of medicinal plant species that local populations and herbalists, or TMP, frequently use in the treatment of various types of cancer. The most frequently used families are Asteraceae and Euphorbiaceae, with the majority of species being found in Uganda. The most frequently utilized plant species is Prunus africana. Studies on the effectiveness of Prunus africana against other malignancies besides prostate cancer are required.

A di-electrophoretic simulation procedure of iron-oxide micro-particle drug attachment system for leukemia treatment using COMSOL software: a potential treatment reference for LMICs.

Background: Leukemia encompasses various subtypes, each with unique characteristics and treatment approaches. The challenge lies in developing targeted therapies that can effectively address the specific genetic mutations or abnormalities associated with each subtype. Some leukemia cases may become resistant to existing treatments over time making them less susceptible to chemotherapy or other standard therapies. Objective: Developing new treatment strategies to overcome resistance is an ongoing challenge particularly in Low and Middle Income Countries (LMICs). Computational studies using COMSOL software could provide an economical, fast and resourceful approach to the treatment of complicated cancers like leukemia. Methods: Using COMSOL Multiphysics software, a continuous flow microfluidic device capable of delivering anti-leukemia drugs to early-stage leukemia cells has been computationally modeled using dielectrophoresis (DEP). Results: The cell size difference enabled the micro-particle drug attachment to the leukemia cells using hydrodynamic focusing from the dielectrophoretic force. This point of care application produced a low voltage from numerically calculated electrical field and flow speed simulations. Conclusion: Therefore, such a dielectrophoretic low voltage application model can be used as a computational treatment reference for early-stage leukemia cells with an approximate size of 5 µm.

Autologous adipose-derived stromal vascular fraction (SVF) in scar treatment among patients with keloids and hypertrophic scars: a systematic review and meta-analysis of current practices and outcomes.

BACKGROUND: Keloids and hypertrophic scars are some of the most common skin conditions globally, associated with poor treatment response and high recurrence rates. Autologous adipose-derived stromal vascular fraction (SVF) is increasingly recognized as an emerging therapy albeit limited literature on its outcome in scar treatment. This review aimed to describe the current practices and outcomes of adipose-derived stromal Vascular Fraction in scar treatment. METHODS: This systematic review assessed articles describing the use of SVF in scar treatment published between 2000 and 2023. Article searches of Medline/PubMed, Cochrane Library, and Embase databases using Mesh terms and the Boolean operators ("AND", "OR") by two independent researchers were done whilst following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. Clinical studies assessing SVF in scar treatment with a primary outcome measure being an improvement in scar characteristics including the thickness, scar assessment scores were included. RESULTS: Among the 1425 studies identified in the search, 20 studies met the inclusion criteria with a total of 493 patients included. Eight of these were clinical trials with the rest being observational studies. Follow-up ranged from 3 months to 24 months. In all studies, there was an improvement in scar characteristics following single-dose treatment with SVF or its equivalent. All studies reported SVF to be safe. CONCLUSION: The review found that autologous adipose-derived SVF is a clinically effective therapy for keloids and scar treatment.

Efficacy of nano encapsulated herbal extracts in the treatment of induced wounds in animal models: a systematic review protocol.

BACKGROUND: Wounds inflict pain and affect human health causing high expenditure on treatment and management. Herbal crude extracts are used in traditional medicine as a treatment for wounds and other illnesses. However, the progress in the use of plants has been deterred due to their poor solubility and poor bioavailability requiring administration at high doses. It has been established that nanoencapsulation of herbal products in nanocarriers (size 1 nm to 100 nm) such as nanofibers, nanoparticles, nanospheres, and nanoliposomes greatly improves their efficacy. Due to their small and large surface area, nanocarriers are more biologically active, improve bioavailability, protect the drug from deterioration, and release it to the targeted site in a sustainable manner. AIM: The review aims to collate and appraise evidence on the efficacy of nano encapsulated herbal extracts in the treatment of induced wounds in animal models. METHODS: The review will be protocol-driven and conducted according to the Preferred Reporting Items for Systematic Reviews and Meta-analysis for Protocols (PRISMA-P) and protocol guidelines for systematic review and meta-analysis for animal intervention studies. The final review will be conducted and reported with reference to PRISMA 2020 statement. Studies will be searched in Pub Med, ProQuest, Web of Science, Medline Ovid, EMBASE, and Google Scholar. The PRISMA flow criteria will be followed in screening the articles for inclusion. Data extraction form will be designed in Excel spreadsheet 2013 and data extracted based on the primary and secondary outcomes. Risk of bias assessment will be done using SYRCLE's risk of bias tool for animal studies. Data analysis will be done using narrative and quantitative synthesis. EXPECTED RESULTS: We hope to make meaningful comparisons between the effectiveness of the herb-loaded nanomaterials and other interventions (controls) in the selected studies, based on the primary and secondary outcome measures. We expect that these findings to inform clinical practice on whether preclinical studies show enough quality evidence on the efficacy and safety of herbal-loaded nanomaterials that can be translated into clinical trials and further research. SYSTEMIC REVIEW REGISTRATION: PROSPERO 330330. The protocol was submitted on the 11th of May 2022.

Safety and feasibility of autologous adipose-derived stromal vascular fraction in the treatment of keloids: a phase one randomized controlled pilot trial.

INTRODUCTION: Autologous adipose-derived stromal vascular fraction (SVF) has been described to have therapeutic benefits in the treatment of keloids. However, most of the evidence on its efficacy is based on observational studies the majority of which are conducted in high-income countries and yet the highest burden of keloids is in low- and middle-income countries (LMICs). OBJECTIVES: We set out to determine the safety and feasibility of using autologous adipose derived stromal vascular fraction in the treatment of keloids in LMICs. METHODS: In this phase II randomized controlled pilot clinical trial conducted in the Plastic Surgery Unit of Kirruddu National Referral Hospital in Kampala Uganda, 8 patients were assigned a 1:1 ratio to either SVF or triamcinolone acetonide (TAC) arms. In the SVF arm, a median (Inter quartile range) amount of stromal cell infiltration of 2.7×106 (11×106) was administered, while the controls received 10 mg/ml TAC at a ratio of 1:1 TAC to keloid volume. Primary endpoints were adverse event development based on the Common Terminology Criteria for Adverse Events (CTCAE) v5.0 tool and feasibility assessment based on ≥ 70% recruitment feasibility and ≥ 80% interventional feasibility rates. RESULTS: The participants' mean age was 27.9 (±6.5) years, with a female predilection of 5 (63%). Overall, no adverse events were reported in the SVF arm, while ulceration in a single patient in the TAC arm, which was a grade II adverse event, was reported. Recruitment feasibility of 80% and interventional feasibility with 100% completion were reported. CONCLUSION: Based on our findings, an autologous adipose-derived stromal vascular fraction is feasible and safe for the treatment of keloids in LMICs.

Glycocalyx-Sodium Interaction in Vascular Endothelium.

The glycocalyx generally covers almost all cellular surfaces, where it participates in mediating cell-surface interactions with the extracellular matrix as well as with intracellular signaling molecules. The endothelial glycocalyx that covers the luminal surface mediates the interactions of endothelial cells with materials flowing in the circulating blood, including blood cells. Cardiovascular diseases (CVD) remain a major cause of morbidity and mortality around the world. The cardiovascular risk factors start by causing endothelial cell dysfunction associated with destruction or irregular maintenance of the glycocalyx, which may culminate into a full-blown cardiovascular disease. The endothelial glycocalyx plays a crucial role in shielding the cell from excessive exposure and absorption of excessive salt, which can potentially cause damage to the endothelial cells and underlying tissues of the blood vessels. So, in this mini review/commentary, we delineate and provide a concise summary of the various components of the glycocalyx, their interaction with salt, and subsequent involvement in the cardiovascular disease process. We also highlight the major components of the glycocalyx that could be used as disease biomarkers or as drug targets in the management of cardiovascular diseases.

Medicinal plants used in the management of cancers by residents in the Elgon Sub-Region, Uganda.

BACKGROUND: In Uganda, medicinal plants have been utilized to treat a variety of ailments, including cancer. However, there is little information available about the medicinal plants used to treat cancer in the Elgon subregion. As a result, the current study documented the plant species used in the management of cancer in the Elgon sub-region. METHODS: Data were gathered by observation, self-administered questionnaires, interview guides, and guided field trips. Analyzing descriptive statistics and creating graphs were done using SPSS (version 21.0) and GraphPad Prism® version 9.0.0, respectively. Well-established formulae were used to calculate quantitative indices. The narratives were interpreted using major theories and hypotheses in ethnobotany. RESULTS: A total of 50 plant species from 36 families were documented, and herbal knowledge was mainly acquired through inheritance. Fabaceae and Asteraceae comprised more plant species used in herbal preparation. Most plants were collected from forest reserves (63%); herbal therapies were made from herbs (45%); and leaves were primarily decocted (43%). The most frequently used plants were Tylosema fassoglensis, Hydnora abyssinica, Azidarachata indica, Prunus Africana, Kigelia africana, Syzygium cumini, Hydnora africana, Rhoicissus tridentata, Albizia coriaria, and Plectranthus cuanneus. All the most commonly used plants exhibited a high preference ranking (60-86%) and reliability level (74.1-93.9%). Generally, the ICF for all the cancers treated by medicinal plants was close to 1 (0.84-0.95). CONCLUSIONS: The ten most commonly utilized plants were favored, dependable, and most important for treating all known cancers. As a result, more investigation is required to determine their phytochemistry, toxicity, and effectiveness in both in vivo and in vitro studies. This could be a cornerstone for the pharmaceutical sector to develop new anticancer medications.

Dietary intake, body composition and micronutrient profile of patients on maintenance hemodialysis attending Kiruddu National Referral Hospital, Uganda: A cross sectional study.

Patients on maintenance hemodialysis are at a great risk for altered nutritional status, characterized by protein energy wasting and micronutrient deficiency due to medication interactions and dietary restrictions. This study determined the dietary intake, micronutrient profile and body composition of patients on maintenance hemodialysis at Kiruddu National referral hospital (KNRH), Uganda. A cross sectional study was done among adult CKD patients on maintenance hemodialysis therapy at KNRH. Data concerning patients' demographics, clinical history and dietary intake was obtained using interactive and quantitative food frequency questionnaires. Body composition was obtained using the TANITA BC-351, Japan weighing Bathroom scale and anthropometric measurements using standard methods and procedures. Serum micronutrient profile assessment was done using the COBAS Auto analyzer. Data analysis was done using the SPSS software version 20. T-test was used to make comparisons and logistic regression analysis was done to check for any correlations. A P-value of < 0.05 was considered statistically significant. Among the 63 hemodialysis patients, 38% were female, with a median duration of hemodialysis of 12 months and the overall age range of patients was 31-40 years. Majority (92.1%) of the patients had hypertension. Carbohydrates like maize flour were highly consumed, in addition to eggs among the proteins on the daily basis. Fruits and vegetables were not highly consumed. Regarding body composition; 75% of the study participants had normal Body mass Index (BMI), the mean muscle mass was 51.94±8.68, body fat was 15.25±7.35, bone mass was 2.77±0.46 and body water was 62.04±9.06. Patients had deranged micronutrient levels especially for Vitamin D, Potassium and phosphorus. In conclusion, hemodialysis patients at KNRH, have altered nutritional status as evidenced by altered body weight for some patients and deranged micronutrient levels. We recommend that hemodialysis patients should be regularly assessed for nutritional status, appropriately treated and educated about their nutritional status.

Green synthesis and characterization of iron-oxide nanoparticles using Moringa oleifera: a potential protocol for use in low and middle income countries.

OBJECTIVE: Green synthesized iron(III) oxide (Fe3O4) nanoparticles are gaining appeal in targeted drug delivery systems because of their low cost, fast processing and nontoxicity. However, there is no known research work undertaken in the production of green synthesized nano-particles from the Ugandan grown Moringa Oleifera (MO). This study aims at exploring and developing an optimized protocol aimed at producing such nanoparticles from the Ugandan grown Moringa. RESULTS: While reducing ferric chloride solution with Moringa oleifera leaves, Iron oxide nanoparticles (Fe3O4-NPs) were synthesized through an economical and completely green biosynthetic method. The structural properties of these Fe3O4-NPs were investigated by Ultra Violet-visible (UV-Vis) spectrophotometry, X-ray diffraction (XRD), energy dispersive X-ray spectroscopy (EDX) and scanning electron microscopy (SEM). These nanoparticles exhibited UV-visible absorption peaks at 225 nm (nm) for the sixth dilution and 228 nm for the fifth dilution which indicated that the nanoparticles were photosensitive and the SEM study confirmed the spherical nature of these nanoparticles. The total synthesis time was approximately 5 h after drying the moringa leaves, and the average particle size was approximately 16 nm. Such synthesized nanoparticles can potentially be useful for drug delivery, especially in Low and Middle Income Countries (LMICs).

Clinical presentation and outcomes in children with retinoblastoma managed at the Uganda Cancer Institute.

Background: The majority of patients with retinoblastoma, the most common intraocular cancer of childhood, are found in low-and middle-income countries (LMICs), with leukocoria being the most common initial presenting sign and indication for referral. Findings from the current study serve to augment earlier findings on the clinical presentation and outcomes of children with retinoblastoma in Uganda. Methods: This was a retrospective study in which we reviewed records of children admitted with a diagnosis of retinoblastoma at the Uganda Cancer Institute from January 2009 to February 2020. From the electronic database, using admission numbers, files were retrieved. Patient information was recorded in a data extraction tool. Results: A total of 90 retinoblastoma patients were studied, with a mean age at the first Uganda Cancer Institute (UCI) presentation of 36.7 months. There were more males (57.8%) than females, with a male to female ratio of 1.37 : 1. The majority (54.4%) had retinoblastoma treatment prior to UCI admission. The most common presenting symptoms were leukocoria (85.6%), eye reddening (64.4%), and eye swelling (63.3%). At 3 years of follow-up after index admission at UCI, 36.7% of the patients had died, 41.1% were alive, and 22.2% had been lost to follow-up. The median 3-year survival for children with retinoblastoma in our study was 2.18 years. Significant predictors of survival in the multivariate analysis were follow-up duration ( P ¯ < 0.001 ), features of metastatic spread (P = 0.001), history of eye swelling (P = 0.012), and bilateral enucleation (P = 0.011). Conclusions: The majority of children who presented to the Uganda Cancer Institute were referred with advanced retinoblastoma, and there was a high mortality rate. Retinoblastoma management requires a multidisciplinary team that should include paediatric ophthalmologists, paediatric oncologists, ocular oncologists, radiation oncologists, and nurses.

Unique circulating microRNA profiles in epidemic Kaposi's sarcoma.

Background: Human herpesvirus 8 (HHV-8) causes Kaposi's sarcoma (KS). Kaposi sarcoma in HIV/AIDS patients is referred to as epidemic KS and is the most common HIV-related malignancy worldwide. The lack of a diagnostic assay to detect latent and early-stage disease has increased disease morbidity and mortality. Serum miRNAs have previously been used as potential biomarkers of normal physiology and disease. In the current study, we profiled unique serum miRNAs in patients with epidemic KS to generate baseline data to aid in developing a miRNA-based noninvasive biomarker assay for epidemic KS. Methods: This was a comparative cross-sectional study involving 27 patients with epidemic KS and 27 HIV-positive adults with no prior diagnosis or clinical manifestation of KS. DNA and RNA were isolated from blood and serum collected from study participants. Nested PCR for circulating HHV-8 DNA was performed on the isolated DNA, whereas miRNA library preparation and sequencing for circulating miRNA were performed on the RNA samples. The miRge2 pipeline and EdgeR were used to analyse the sequencing data. Results: Fifteen out of the 27 epidemic KS-positive subjects (55.6%) tested positive for HHV-8 DNA, whereas only 3 (11.1%) out of the 27 HIV-positive, KS-negative subjects tested positive for HHV-8 DNA. Additionally, we found a unique miRNA expression signature in 49 circulating miRNAs in epidemic KS subjects compared to subjects with no epidemic KS, with 41 miRNAs upregulated and 8 miRNAs downregulated. Subjects with latent KS infection had a differential upregulation of circulating miR-193a compared to HIV-positive, KS-negative subjects for whom circulating HHV-8 DNA was not detected. Further analysis of serum from epidemic KS patients revealed a miRNA signature according to KS tumor status and time since first HIV diagnosis. Conclusions: This study reveals unique circulating miRNA profiles in the serum of patients with epidemic KS versus HIV-infected subjects with no KS, as well as in subjects with latent KS. Many of the dysregulated miRNAs in epidemic KS patients were previously reported to have crucial roles in KS infection and latency, highlighting their promising roles as potential biomarkers of latent or active KS infection.

Adipose-derived stromal vascular fraction (SVF) in scar treatment: a systematic review protocol.

BACKGROUND: Autologous adipose-derived stromal vascular fraction (SVF) is an emerging therapy that is being pioneered as a potential treatment for keloids and hypertrophic scars. Up to this point, there isn't a cure for keloids and hypertrophic scars yet they comprise the commonest benign skin disorders. Despite published studies reporting potential therapeutic benefits of SVF, their use and efficacy on scar improvement are not clearly described. The aim of this review is to describe the clinical practice involved in harvesting, processing, utilization of SVF, and associated efficacy in scar treatment. METHODS: We shall include published clinical articles evaluating the efficacy of SVF on improving scar characteristics and assessment scores among adults with keloids or hypertrophic scars. Article search of Medline/PubMed, Cochrane Library and Embase using Mesh terms of "scars" and "stromal vascular fraction" combined with the Boolean operators ("AND", "OR") will be performed by two independent researchers following the Preferred Reporting Items for Systematic Review and Meta-Analysis Protocols (PRISMA-P) statement. The primary outcome measure will be the mean difference in the Scar characteristics including Scar assessment scores, scar thickness among others. DATA SYNTHESIS: Descriptive data synthesis and mean differences between treatment arms will be calculated for the primary outcome of the scar assessment scores. In case more than three studies provide consistent characteristics of the scar assessment scores, a meta-analysis will be conducted. DISCUSSION: Evidence obtained from the systematic review will form the foundation upon which further clinical trials research will be conducted in evaluating the efficacy of autologous adipose-derived stromal vascular fraction in keloid and hypertrophic scar. The systematic review has been submitted to the PROSPERO database and is currently under review.

A descriptive prospective study of sports medicine practices for athletes in Uganda.

BACKGROUND: Many international sporting organizations have recommended practices to reduce the risk of injury. These practices include screening for injury, having appropriate emergency medical care, and protocols for managing injury before return-to-play. The extent of the uptake of these practices in a developing country such as Uganda, is unknown. METHODOLOGY: Using a descriptive case study approach, this investigation focused on a sample of injured athletes (n = 75) in Uganda from four main sports associations (football, athletics, basketball and rugby). The data were collected through observations and interviews after the injury. Using a best medical practice framework the phases of emergency, intermediate, rehabilitative, and return-to-sports participation were described. RESULT: Nine conditions/types of injury were included. The results revealed a lack of specific pre-season screening or return-to-play readiness for all the injured athletes. Further, there was a lack of application of best practice principles for most of the injury types. For athletes who received medical care, the results show inconsistencies and inadequacies from the acute stage of the injury to return-to-sports participation. CONCLUSION: This study identified barriers such as up-to-date knowledge among the sports resource providers; the gaps for appropriate and adequate specific facilities for managing injured athletes, and policies to mandate care of injured athletes. These barriers detract from applying best medical practices.

A systematic review of modeling and simulation approaches in designing targeted treatment technologies for Leukemia Cancer in low and middle income countries.

Virtual experimentation is a widely used approach for predicting systems behaviour especially in situations where resources for physical experiments are very limited. For example, targeted treatment inside the human body is particularly challenging, and as such, modeling and simulation is utilised to aid planning before a specific treatment is administered. In such approaches, precise treatment, as it is the case in radiotherapy, is used to administer a maximum dose to the infected regions while minimizing the effect on normal tissue. Complicated cancers such as leukemia present even greater challenges due to their presentation in liquid form and not being localised in one area. As such, science has led to the development of targeted drug delivery, where the infected cells can be specifically targeted anywhere in the body. Despite the great prospects and advances of these modeling and simulation tools in the design and delivery of targeted drugs, their use by Low and Middle Income Countries (LMICs) researchers and clinicians is still very limited. This paper therefore reviews the modeling and simulation approaches for leukemia treatment using nanoparticles as an example for virtual experimentation. A systematic review from various databases was carried out for studies that involved cancer treatment approaches through modeling and simulation with emphasis to data collected from LMICs. Results indicated that whereas there is an increasing trend in the use of modeling and simulation approaches, their uptake in LMICs is still limited. According to the review data collected, there is a clear need to employ these tools as key approaches for the planning of targeted drug treatment approaches.

Mice depleted for Exchange Proteins Directly Activated by cAMP (Epac) exhibit irregular liver regeneration in response to partial hepatectomy.

The exchange proteins directly activated by cAMP 1 and 2 (Epac1 and Epac2) are expressed in a cell specific manner in the liver, but their biological functions in this tissue are poorly understood. The current study was undertaken to begin to determine the potential roles of Epac1 and Epac2 in liver physiology and disease. Male C57BL/6J mice in which expression of Epac1 and/or Epac2 are deleted, were subjected to partial hepatectomy and the regenerating liver was analyzed with regard to lipid accumulation, cell replication and protein expression. In response to partial hepatectomy, deletion of Epac1 and/or Epac2 led to increased hepatocyte proliferation 36 h post surgery, and the transient steatosis observed in wild type mice was virtually absent in mice lacking both Epac1 and Epac2. The expression of the protein cytochrome P4504a14, which is implicated in hepatic steatosis and fibrosis, was substantially reduced upon deletion of Epac1/2, while a number of factors involved in lipid metabolism were significantly decreased. Moreover, the number of Küpffer cells was affected, and Epac2 expression was increased in the liver of wild type mice in response to partial hepatectomy, further supporting a role for these proteins in liver function. This study establishes hepatic phenotypic abnormalities in mice deleted for Epac1/2 for the first time, and introduces Epac1/2 as regulators of hepatocyte proliferation and lipid accumulation in the regenerative process.

Deletion of exchange proteins directly activated by cAMP (Epac) causes defects in hippocampal signaling in female mice.

Previous studies demonstrate essential roles for the exchange proteins directly activated by cAMP 1 and 2 (Epac1 and Epac2; here collectively referred to as Epac) in the brain. In the hippocampus, Epac contributes to the control of neuronal growth and differentiation and has been implicated in memory and learning as well as in anxiety and depression. In the present study we address the hypothesis that Epac affects hippocampal cellular responses to acute restraint stress. Stress causes activation of the hypothalamus-pituitary-adrenal (HPA)-axis, and glucocorticoid receptor (GR) signaling is essential for proper feedback regulation of the stress response, both in the brain and along the HPA axis. In the hippocampus, GR expression is regulated by cAMP and the brain enriched micro RNA miR-124. Epac has been associated with miR-124 expression in hippocampal neurons, but not in regulation of GR. We report that hippocampal expression of Epac1 and Epac2 increased in response to acute stress in female wild type mice. In female mice genetically deleted for Epac, nuclear translocation of GR in response to restraint stress was significantly delayed, and moreover, miR-124 expression was decreased in these mice. Male mice lacking Epac also showed abnormalities in miR-124 expression, but the phenotype was less profound than in females. Serum corticosterone levels were slightly altered immediately after stress in both male and female mice deleted for Epac. The presented data indicate that Epac1 and Epac2 are involved in controlling cellular responses to acute stress in the mouse hippocampus and provide novel insights into the underlying transcriptional and signaling networks. Interestingly, we observe sex specific differences when Epac is deleted. As the incidence and prevalence of stress-related diseases are higher in women than in men, the Epac knockout models might serve as genetic tools to further elucidate the cellular mechanisms underlying differences between male and female with regard to regulation of stress.

Nutritional supplement practices of professional Ugandan athletes: a cross-sectional study.

BACKGROUND: The use of nutritional supplements (NS) places athletes at great risk for inadvertent doping. Due to the paucity of data on supplement use, this study aimed to determine the proportion of Ugandan athletes using nutritional supplements and to investigate the athletes' motivation to use these supplements. METHODS: A cross-sectional study was conducted in which an interviewer-administered questionnaire was used to collect data from 359 professional athletes participating in individual (boxing, cycling, athletics) and team (basketball, rugby, football, netball, and volleyball) sports. The data were categorized, and a Chi-square test was used for statistical analysis. RESULTS: Of the 359 athletes, 48 (13.4%) used nutritional supplements. Carbohydrate supplements, energy drinks, vitamin and mineral supplements, fish oils, and protein supplements were the most common supplements used by athletes. NS use was significantly more common among athletes who played rugby and basketball (X2 = 61.101, p < 0.0001), athletes who had played the sport for 5-10 years (X2 = 7.460, p = 0.024), and athletes who had attained a tertiary education (X2 = 33.377, p < 0.0001). The athletes' occupation had no bearing on whether they used supplements. Nutritionists/dieticians, retail stores and pharmacies were the most common sources of NS products, whereas health practitioners, online media and teammates were the most common sources of information regarding NS. Most athletes used NS to improve their physical performance and health. CONCLUSIONS: Compared to NS use by athletes elsewhere, NS use among Ugandan athletes was low. However, determinants of athlete NS use in the current study (category of sport and duration of time spent playing the sport) are similar to those reported elsewhere.

Doping knowledge, attitudes, and practices of Ugandan athletes': a cross-sectional study.

BACKGROUND: Despite the development of advanced drug testing systems, both deliberate and inadvertent doping in sports is increasing in elite, amateur and school sports. As a result, alternative approaches that seek to influence an athlete's attitudes are needed to address the growing doping concerns that threaten both the health and well being of the athlete as well as the legitimacy of the sport. Therefore, the current study set out to establish the doping attitudes, knowledge and practices of professional Ugandan athletes, gathering information that may guide the design of more efficient doping prevention programs. METHODS: This was a cross-sectional study of 384 professional Ugandan athletes from four contact team sports (basketball, football, handball and rugby) and two individual sports (athletics and cycling). An Interviewer administered questionnaire used contained; questions about the doping behavior, the performance enhancement attitude scale (PEAS), and doping use belief (DUB) statements. RESULTS: Approximately 60 % of the athletes reported familiarity with information on doping and that most of this information came from fellow colleagues (41.9 %), individual or team coaches (29.7 %) or the media (15.6 %). However, nearly 80 % of these athletes could not correctly define doping. The overall mean PEAS score, a measure of doping attitudes, for all study participants was 39.8 ± 14.8. Female athletes (PEAS: 41.1 ± 15.1), athletes with a prior doping history (PEAS: 44.1 ± 15.6) and athletes from the sport of athletics (PEAS: 56.6 ± 17.4) had higher mean PEAS scores than their respective counterparts. Regarding doping behaviors/practices, 9.3 % of the study participants had been offered a doping agent at some point, although only 3.9 % of the athletes acknowledged recent use. CONCLUSIONS: The confessed use of doping agents in this study was low, which may suggest that fewer athletes use doping agents in Uganda. However, there is still an urgent need for educational anti-doping programs to address the knowledge gaps observed amongst athletes in this study. Modifying the existing Physical education curriculum for inclusion of more content about doping in sport could provide the basis for doping prevention programs amongst amateur athletes in Ugandan primary and secondary schools.