Targeted variant prevalence of FBXW7 gene mutation in colorectal carcinoma propagation. The first systematic review and meta-analysis.

FBXW7 is a tumour suppressor gene that functions as E3-ubiquitin-ligase, targeting numerous oncoproteins for degradation, i.e., Cyclin-E, c-Myc, and Notch. FBXW7 performs a pivotal role in regulating cell cycle progression. FBXW7 mutation is frequently implicated in various cancers. Methodology: A systematic review and meta-analysis done on several studies using "Preferred Reporting Items for Systemmatic Reviews and Meta-Analysis (PRISMA)" criteria and registered with PROSPERO (registration-number-CRD42023388845). The preliminary search comprises 1182 articles; however, 58 studies were subsequently chosen after eliminating non-eligible studies. To explore the prevalence of FBXW7 mutation among colorectal cancer patients, data were analysed using "OpenMeta Analyst and comprehensive meta-analysis-3.0 (CMA-3.0)" software. Results: This meta-analysis involves 13,974 respondents; most were males 7825/13,974, (56.0 %). Overall prevalence of FBXW7 mutations was 10.3 %, (95%CI: 8.6-12.4), I2 = 90.5 %, (P < 0.001). The occurrence of FBXW7 mutations was highest in Russia [19.0 %, (95%CI: 9.8-33.7)] and Taiwan [18.8 %, (95%CI: 8.7-35.9)], P-values< 0.05 while the least prevalence was reported in Netherland (4 %) and Italy (5 %), both P-values< 0.001. Overall prevalence of FBXW7 abberation was greatest amongst male gender: "53.9 %, (95%CI: 8.3-62.0 %)", Tumour location (colon): 59.8 %, (95%CI: 53.9-65), tumour site (left): 61.6 %, (95%CI: 53.8-68.9), Tumour-grade (Moderate): 65.9 %, (95%CI: 54.9-75.4 %), and Tumour late-stage: 67.9 %, (95%CI: 49.7-84.3 %), all P-values< 0.001. When stratified according to study-period, an increasing trend was noted from 2018 till present with the highest mutation rate recorded in 2022 (15.3 %). Conclusion: Overall prevalence of FBXW7 mutations was 10.3 % with male gender, left side, and late-stage being most mutated, and these outcomes conform with severally published articles on FBXW7 mutation.

Effects of combined aerobic and resistance training on glycemic control, blood pressure, inflammation, cardiorespiratory fitness and quality of life in patients with type 2 diabetes and overweight/obesity: a systematic review and meta-analysis.

Background: Structured aerobic or resistance training alone seems to be a beneficial tool for improving glucose homeostasis, chronic systemic inflammation, resting cardiovascular function, and mental health in people with obesity and type 2 diabetes mellitus (T2DM). The aim of the present study was to synthesize the available data on the effectiveness of combined aerobic and resistance training (CART) on glycemic control, blood pressure, inflammation, cardiorespiratory fitness (CRF), and quality of life (QoL) in overweight and obese individuals with T2DM. Methods: A database search was carried out in PubMed, Web of Science, Scopus, Science Direct, Cochrane Library, and Google Scholar from inception up to May 2023. The Cochrane risk of bias tool was used to assess eligible studies, and the GRADE method to evaluate the reliability of evidence. A random-effects model was used, and data were analyzed using standardized mean differences and 95% confidence intervals. The study protocol was registered in the International Prospective Register of Systematic Reviews (ID: CRD42022355612). Results: A total of 21,612 studies were retrieved; 20 studies were included, and data were extracted from 1,192 participants (mean age: 57 ± 7 years) who met the eligibility criteria. CART demonstrated significant improvements in body mass index, glycated hemoglobin, systolic and diastolic blood pressure, C-reactive protein, tumor necrosis factor-alpha, interleukin-6, CRF, and QoL compared to ST. These findings highlight the significance of exercise interventions such as CART as essential elements within comprehensive diabetes management strategies, ultimately enhancing overall health outcomes in individuals with T2DM and overweight/obesity.No differences were found in resting heart rate between CART and ST. An uncertain risk of bias and poor quality of evidence were found among the eligible studies. Conclusion: These outcomes show clear evidence considering the positive role of CART in inducing beneficial changes in various cardiometabolic and mental health-related indicators in patients with T2DM and concurrent overweight/obesity. More studies with robust methodological design are warranted to examine the dose-response relationship, training parameters configuration, and mechanisms behind these positive adaptations.

Psychophysiological Adaptations to Exercise Training in COVID-19 Patients: A Systematic Review.

Introduction: Many COVID-19 patients display adverse symptoms, such as reduced physical ability, poor quality of life, and impaired pulmonary function. Therefore, this systematic review is aimed at evaluating the effectiveness of physical exercise on various psychophysiological indicators among COVID-19 patients who may be at any stage of their illness (i.e., critically ill, hospitalized, postdischarge, and recovering). Methods: A systematic search was conducted in PubMed, Scopus, ScienceDirect, Web of Science, and Google Scholar from 2019 to 2021. Twenty-seven studies, which assessed a total of 1525 patients, were included and analysed. Results: Overall, data revealed significant improvements in the following parameters: physical function, dyspnoea, pulmonary function, quality of life (QOL), lower limb endurance and strength, anxiety, depression, physical activity level, muscle strength, oxygen saturation, fatigue, C-reactive protein (CRP), interleukin 6 (IL-6), tumour necrosis factor-alpha (TNF-α), lymphocyte, leukocytes, and a fibrin degradation product (D-dimer). Conclusions: Physical training turns out to be an effective therapy that minimises the severity of COVID-19 in the intervention group compared to the standard treatment. Therefore, physical training could be incorporated into conventional treatment of COVID-19 patients. More randomized controlled studies with follow-up evaluations are required to evaluate the long-term advantages of physical training. Future research is essential to establish the optimal exercise intensity level and assess the musculoskeletal fitness of recovered COVID-19 patients. This trial is registered with CRD42021283087.

International AIDS society conference 2023 summary.

AIM: This article summarizes key research presented at the International AIDS Society (IAS) Conference in Brisbane, held in July 2023. CO-MORBIDITIES: The REPRIEVE Trial as a conference highlight, demonstrating significantly fewer major cardiovascular events amongst people with HIV who were randomized to pitavastatin compared to placebo. Key data on weight, hypertension and incident diabetes are also summarized. ANTIRETROVIRAL THERAPY: Novel data on doravirine and islatravir are described as are trials demonstrating efficacy dolutegravir/lamivudine first-line in people without baseline resistance testing and in suppressed switch amongst people with historic lamivudine resistance. HIV CURE: The sixth case of HIV cure secondary to stem cell transplantation is summarized, as are new insights into the central nervous system as an HIV reservoir.

Enablers and barriers to effective HIV self-testing in the private sector among sexually active youths in Nigeria: A qualitative study using journey map methodology.

BACKGROUND: HIV is a public health burden in Nigeria. HIV self-testing is one of the approaches to testing, which is the first of the 95:95:95 cascade of a coherent response to the epidemic. The ability to self-test HIV is influenced by various factors that can either serve as enablers or barriers. Exploring these enablers and barriers to the uptake of HIVST will help achieve optimal HIV self-testing and provide a deeper understanding of the HIVST kits users' journey. OBJECTIVE: The purpose of the study was to identify enablers and barriers to the uptake of HIV self-testing among sexually active youth in Nigeria using journey map methodology. METHODS: We conducted a qualitative exploratory study between January 2021 to October 2021 to understand the journey map for taking up and using HIVST in the private health delivery systems which include the pharmacies and PPMVs. 80 youths in Lagos, Anambra and Kano states were interviewed using IDIs and in-person FGDs. Their responses were audio-recorded, transcribed and analyzed using a qualitative software package (Nvivo software). RESULTS: A journey map for taking up and effectively using HIVST using the private sector among sexually active youths using key enablers and barriers at the attract, purchase, use, confirmation, linkage, and reporting stage was developed. The major enablers among participants were privacy and confidentiality, bundling purchases with other health products, easy-to-use instructions, and past experience with other self-testing kits. The major barriers were fear of discrimination, big packaging, high price, lack of confidence from user error and fear of status disclosure. CONCLUSIONS: Sexually active young people's perspectives enhance our understanding of the barriers and enablers of using HIVST through the private sector. Optimizing the enablers such as improved confidentiality that may be seen in e-pharmacy, reducing barriers and factoring sexually young people's perspectives will enhance the market and the uptake of HIVST towards ensuring sustainability and accelerating progress towards the 95-95-95 targets.

Stakeholders' perception of a total market approach to HIV self-testing (HIVST) for the private sector in Nigeria.

BACKGROUND: The continuous supply of affordable and quality HIV self-test (HIVST) is a key pillar toward achieving the global HIV 95-95-95 target in Nigeria. This was a descriptive qualitative study that explored private sector stakeholders' perceptions of the enablers and barriers of the HIVST market in Nigeria. METHODS: A total of 29 In-depth interviews (IDIs) were conducted with HIVST supply chain stakeholders and private sector providers (PPMVs and Community Pharmacies). Responses were analyzed using Nvivo software and we systematically developed a total market approach analysis for supply chain stakeholders and archetypes for community Pharmacies and PPMVs based on insights gathered from their journey map. RESULTS: Challenges to the supply side dynamics include forecasting, point of care service delivery, the availability of free and subsidized HIVST kits in the market, neglect of private sector providers (Community Pharmacists and PPMVs) in the healthcare delivery system, limited demand for HIVST, and regulatory bottlenecks influences the overall market dynamics. High cost of the HIVST kit, which triggers low availability, accessibility and affordability from the demand side, depicts the need to understand the market dynamics. Addressing the barriers and optimizing the enablers of the three-model pharmacist and PPMV's will change the market dynamic and service delivery to generate demand. CONCLUSION: To address challenges which already exist, the government need to revise the process guidelines for introducing new HIVST products in the Nigerian market, developing contingency plans to ensure the supply of HIVST remains sufficient when experiencing economic shocks, and create a sustainable roadmap toward optimizing the market for HIVST kits.

A Nanoplex PCR Assay for the Simultaneous Detection of Vancomycin- and Linezolid-Resistant Genes in Enterococcus.

BACKGROUND: Enterococci are Gram-positive cocci found in the guts of humans and animals. The goal of this research is to develop a multiplex PCR assay that can detect the Enterococcus genus, four VRE genes, and three LZRE genes simultaneously. METHODS: Primers used in this study were specifically designed for the detection of 16S rRNA of Enterococcus genus, vanA-vanB-vanC-vanD for vancomycin, cfr methyltransferase, and optrA, and poxtA, as well as an adenosine triphosphate-binding cassette (ABC) transporter for linezolid. A Vibrio cholerae ctxA (internal amplification control) was included. Optimization of primer concentrations and PCR components was also done. This was followed by evaluating the sensitivity and specificity of the optimized multiplex PCR. RESULTS: Final Primer concentrations were optimized as follows: 16S rRNA is 1.0 pmol/µL, vanA is 1.0 pmol/µL, optrA is 1.0 pmol/µL, cfr is 1.0 pmol/µL, poxtA is 0.1 pmol/µL, vanB is 0.08 pmol/µL, ctxA is 0.07 pmol/µL, vanC is 0.8 pmol/µL, and vanD is 0.1 pmol/µL. Further, the optimized concentrations for MgCl2, dNTPs and Taq DNA polymerase were 2.5 mM, 0.16 mM, and 0.75 units respectively, and an annealing temperature of 64.5 °C. CONCLUSIONS: The developed multiplex PCR is sensitive and species-specific. The development of a multiplex PCR assay that will take into account all known VRE genes and linezolid mutation is highly recommended.

A GNAS Gene Mutation's Independent Expression in the Growth of Colorectal Cancer: A Systematic Review and Meta-Analysis.

Globally, colorectal carcinoma CRC is the third most common cancer and the third most common reason for cancer-associated mortality in both genders. The GNAS mutations are significantly linked with poor prognosis and failed treatment outcomes in CRC. A systematic review and meta-analysis of multiple studies executed following Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) criteria and registered with PROSPERO (registration number: CRD42021256452). The initial search includes a total of 271 publications; however, only 30 studies that merit the eligibility criteria were eventually chosen. Data analysis via OpenMeta Analyst and comprehensive meta-analysis 3.0 (CMA 3.0) software were used to investigate the prevalence of GNAS gene mutation among CRC patients. The meta-analysis consisted of 10,689 participants with most being males 6068/10,689 (56.8%). Overall, prevalence of GNAS mutations was 4.8% (95% CI: 3.1−7.3) with I2 = 94.39% and (p < 0.001). In 11/30 studies, the frequency of GNAS gene mutations was majorly in codons R201C [40.7% (95% CI: 29.2−53.2%)] and in codon R201H [39.7% (95% CI = 27.1−53.8)]. Overall prevalence of GNAS mutations was highest among the male gender: 53.9% (95% CI: 48.2−59.5%: I2 = 94.00%, (p < 0.001), tumour location (colon): 50.5% (95% CI: 33.2−67.6%: I2 = 97.93%, (p < 0.001), tumour grade (Well): 57.5% (95% CI: 32.4−79.2%: I2 = 98.10%, (p < 0.001) and tumour late stage: 67.9% (95% CI: 49.7−84.3%: I2 = 98.%, (p < 0.001). When stratified according to study location, a higher prevalence was observed in Japan (26.8%) while Italy has the lowest (0.4%). Overall prevalence of GNAS gene mutations was 4.8% with codons R201C and R201H being the most mutated, and the results conformed with numerous published studies on GNAS mutation.

Impact of traditional healers in the provision of mental health services in Nigeria.

Mental health remains one of the most overlooked issues in Nigeria. The burden posed by traditional healers in the provision of mental health services is becoming a public health concern in the country. This article presents a review of the present situation on the mental health service provision in Nigeria by traditional healers and highlights way forward actions for policy makers, government, and other stakeholders. These include the need for a policy direction on the need for establishing an improved system of psychiatric and mental health services in hospitals that will drive cultural acceptability, accessibility, and affordability. Further, there is a need for policy measures to be in place towards creating long term directions and sustainability of documentations of traditional healer's activities, harmful avoidance and improved mental health services in primary health centers. The fact that traditional healers are indispensable in provision of mental health services, call for collaborative effort to improve services such as behavioral change, capacity building and referral practice that could save more lives and reduce severity of complications.

The Prediction of Survival Outcome and Prognosis Factor in Association with Comorbidity Status in Patients with Colorectal Cancer: A Research-Based Study.

Colorectal carcinoma (CRC) is rising exponentially in Asia, representing 11% of cancer worldwide. This study analysed the influence of CRC on patients' life expectancy (survival and prognosis factors) via clinicopathology data and comorbidity status of CRC patients. Methodology: A retrospective study performed in HUSM using clinical data from the Surgery unit from 2015 to 2020. The demographic and pertinent clinical data were retrieved for preliminary analyses (data cleansing and exploration). Demographics and pathological characteristics were illustrated using descriptive analysis; 5-year survival rates were calculated using Kaplan−Meier methods; potential prognostic variables were analysed using simple and multivariate logistic regression analysis conducted via the Cox proportional hazards model, while the Charlson Comorbidity Scale was used to categorize patients' disease status. Results: Of a total of 114 CRC patients, two-thirds (89.5%) were from Malay tribes, while Indian and Chinese had 5.3% each. The 50−69.9 years were the most affected group (45.6%). Overall, 40.4% were smokers (majorly male (95.7%)), 14.0% ex-smokers, and 45.6% non-smokers (p-value = 0.001). The Kaplan−Meier overall 5-year median survival time was 62.5%. From the outcomes, patients who were male and >70 years had metastasis present, who presented with per rectal bleeding and were classified as Duke C; and who has tumour in the rectum had the lowest survival rate. Regarding the prognosis factors investigated, "Gender" (adjusted hazard ratio (HR): 2.62; 95% CI: 1.56−7.81, p-value = 0.040), "Presence of metastases" (HR: 3.76; 95% CI: 1.89−7.32, p-value = 0.010), "Metastasis site: Liver" (HR: 5.04; 95% CI: 1.71−19.05, p-value = 0.039), "Lymphovascular permeation" (HR: 2.94; 95% CI: 1.99−5.92, p-value = 0.021), and "CEA-level" (HR: 2.43; 95% CI: 1.49−5.80, p-value = 0.001) remained significant in the final model for multiple Cox proportional hazard regression analyses. There was a significant mean association between tumour grades and the patient's comorbidity status. Conclusions: Histopathological factors (gender, metastases presence, site of metastases, CEA level, and lymphovascular permeation) showed the best prognosis-predicting factors in CRC.

A Systematic Review and Meta-analysis on the Occurrence of Biomarker Mutation in Colorectal Cancer among the Asian Population.

Globally, colorectal carcinoma (CRC) is the third most common cancer and the third major cause of cancer-related death in both sexes. KRAS and BRAF mutations are almost mutually exclusively involved in the pathogenesis of CRC. Both are major culprits in treatment failure and poor prognosis for CRC. Method. A systematic review and meta-analysis of various research was done following the Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) guidelines. This trial is registered with PROSPERO CRD42021256452. The initial search included 646 articles; after the removal of noneligible studies, a total of 88 studies was finally selected. Data analysis was carried out using OpenMeta Analyst and Comprehensive Meta-Analysis 3.0 (CMA 3.0) software to investigate the prevalence of KRAS and BRAF mutations among patients with CRC in Asia. Results. The meta-analysis comprises of 25,525 sample sizes from Asia with most being male 15,743/25525 (61.7%). Overall prevalence of KRAS mutations was (59/88) 36.3% (95% CI: 34.5-38.2) with I 2 = 85.54% (P value < 0.001). In 43/59 studies, frequency of KRAS mutations was majorly in codon 12 (76.6% (95% CI: 74.2-78.0)) and less in codon 13 (21.0% (95% CI: 19.1-23.0)). Overall prevalence of BRAF mutations was 5.6% (95% CI: 3.9-8.0) with I 2 = 94.00% (P value < 0.001). When stratified according to location, a higher prevalence was observed in Indonesia (71.8%) while Pakistan has the lowest (13.5%). Conclusion. Total prevalence of KRAS and BRAF mutations in CRC was 36.6% and 5.6%, respectively, and the results conformed with several published studies on KRAS and BRAF mutations.

Prevalence of EBV infection in 1157 diseased cohorts in Nigeria: A systematic review and meta-analysis.

BACKGROUND: Epstein-Barr virus (EBV) is a member of the herpesvirus family that is known to ubiquitously infect people worldwide. However, the actual prevalence of EBV infection in diseased patients in Nigeria, remains unknown. This study was thus conducted to ascertain the true prevalence. METHODS: A systematic review and meta-analysis of published data was conducted according to the guidelines of Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA). Electronic databases including PubMed, Scopus, ScienceDirect, and Google Scholar were searched for studies reporting the occurrence of EBV infection among patients with established diseases. Studies were included if they assessed EBV infection in diseased patients in Nigeria. Data were extracted and subsequently analysed using R software. Funnel plot and Egger's regression test was used to assess publication bias, while JBI prevalence tool was used to assess study quality. RESULTS: A total of 13 studies covering 228 cases of EBV infection among 1157 diseased patients were included. Summary estimates were computed using random-effects model. The pooled prevalence of EBV infection was 20.3% (95% CI: 10.8-34.9, I2 â€‹= â€‹92.26, p â€‹< â€‹0.001). When stratified according to the type of disease, higher estimates were obtained for patients suffering from Kaposi's sarcoma (98.7%, 95% CI: 82.2-99.9) and Nasopharyngeal malignancy (85.7%, 95% CI: 70.0-93.9). A prevalence of 13.4% (95% CI: 6.0-27.4) and 12.2% (95% CI: 4.8-27.8) was derived for the most reported patient populations, lymphoma and HIV, respectively. CONCLUSION: This first meta-analysis on the prevalence of EBV among Nigerian patients suffering from various diseases reveals a prevalence that emphasises the need to routinely monitor EBV infection in all EBV-associated diseases in Nigeria.

Prevalence of Nasopharyngeal Carcinoma in Patients with Dermatomyositis: A Systematic Review and Meta-Analysis.

For more than 50 years, nasopharyngeal carcinoma (NPC) has been associated with dermatomyositis (DM), a rare idiopathic inflammatory disorder that mainly affects the skin and muscles. Although the association between these rare diseases is well-documented, the actual prevalence of NPC in DM patients remains unknown. Here, a systematic review and meta-analysis of published data was conducted in accordance with the guidelines of Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA). Electronic databases including PubMed, Scopus, ScienceDirect, and Google Scholar were searched without year or language restrictions for studies reporting the occurrence of NPC in DM patients. The study protocol was lodged with PROSPERO (CRD42021225335). A total of 95 studies covering 303 cases of NPC among 16,010 DM patients was included. Summary estimates were calculated using the random-effects model. The pooled prevalence of NPC in DM was 3.3% (95% CI, 2.5-4.3). When stratified according to study location, higher prevalence estimates were obtained for Hong Kong (36.5%), Malaysia (27.7%), and Singapore (11.9%). There was a predominance of cases among male DM patients compared with females, and most patients were aged 40 and above. Many of the NPC cases were found to be diagnosed after the diagnosis of DM. It is therefore pertinent to screen for NPC in DM patients, especially among older DM patients in the Asian region.