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Dynamics of the Vaginal Microflora during the Menstrual Cycle of HIV-positive and HIV-negative Women in a Sub-urban Community in Kenya
No full textIntroduction: Normal vaginal microflora is usually dominated by Lactobacillus species, which play an important role in the maintenance of vaginal health. The dynamism of the vaginal microflora is especially notable as changes that occur during menses. The vaginal micro-environment is dynamic and undergoes changes during the menstrual cycle in women of reproductive age. These changes correlate with the accompanying hormonal changes. Indeed, the vagina is a highly dynamic ecosystem. Studies show that changes occur in the vaginal microflora during the normal menstrual cycle.
The recurrent imbalance that occurs in the equilibrium of vaginal microflora favors the overgrowth of bacterial vaginosis (BV)-associated bacteria. The relative depletion of the resident Lactobacilli has been shown to be most profound at the time of menses, indicating that the vaginal microflora become less stable during this event. This phenomenon has generally been attributed to the premenstrual decline in circulating levels of estrogen, which in turn affects the colonisation strength of the vaginal Lactobacilli, for example by limiting their capacity for epithelial adherence. The vaginal Lactobacillus microflora are probably further challenged by the menstrual flooding of the vagina, which is accompanied by a sharply rising pH, further exacerbating the unfavorable conditions for epithelial adherence of the Lactobacilli. Under such conditions, the colonisation resistance offered to BV-associated anaerobes can easily be overcome. Menses possibly also induces a wash-out of Lactobacilli through haemagglutination. These mechanisms might explain why BV is less prevalent in pregnant and postmenopausal women, despite the relative estrogen deficiency, especially in the latter group. To further demonstrate the important role that hormones might play in maintaining the balance in the vaginal ecosystem, a recent longitudinal study found women using hormonal contraceptives to have less prevalence due to greater remission of BV. The objective of this study was to characterize and explore the changes in the vaginal microflora during the menstrual cycle of HIV positive (HIV+) and HIV negative (HIV-) women in a sub-urban population of Kenya.
Methods: In a longitudinal study of 38 premenopausal women, 20 HIV+ and 18 HIV-, high vaginal swabs were taken for genomic DNA extraction. Gram stains were prepared at each of the six visits for each woman. Nugent scores were performed, and quantification of three Lactobacillus spp. (L. crispatus, L. jensenii and L. iners) and Gardnerella vaginalis and Atopobium vaginae carried out by real-time or quantitative PCR (qPCR) technique.
Results: Results based on Gram stain category showed a high concentration of L. iners in the normal vaginal microflora. This increases during bacterial vaginosis (BV). There were high levels of L. jensenii in half of the women with BV, while L. Crispatus was absent in BV cases. Concentration of G. vaginalis increased progressively from normal to BV microflora while A. vaginae was absent in normal microflora but was detectable in intermediate gram stain and increased progressively during the BV phase.
Analysis based on HIV status showed a high concentration of L. iners and G. vaginalis in both the HIV+ and HIV- groups. Condom use was significantly higher in HIV+ women, but the number of those harbouring the protective L. crispatus was less than in the HIV- group. The concentration of L. crispatus was remarkably lower in the HIV+ group. Atopobium vaginae was present in both groups but L. jensenii was not detectable in the HIV+ women.
Based on the phase of the menstrual cycle, analysis showed a high concentration of L. iners and G. vaginalis throughout the cycle. Concentration of L. crispatus increased while concentration of A. vaginae decreased throughout the menstrual cycle. At the initial phase of the menstrual cycle, L. jensenii was comparatively low and not detectable thereafter.
Conclusions: The predominant species in normal vaginal microflora in this Kenyan population of women is L. iners, and which increased during BV. Both HIV+ and HIV- groups had high concentrations of L. iners and G. vaginalis. Throughout the menstrual cycle, concentration of L. crispatus increased while concentration of A. vaginae decreased. At the initial phase of the menstrual cycle, L. jensenii was comparatively low and not detectable thereafter
Team objective structured bedside assessment (TOSBA) in paediatric undergraduate students
No full textObjective: To develop a team objective structured bedside assessment (TOSBA) tool for assessing the paediatric undergraduate students\u27 clinical skills at the bedside. Study design: A validation, cross-sectional study. Place and Duration of the Study: Department of Paediatrics, Ziauddin Medical University Hospital, Karachi, Pakistan, from March to June, 2023. Methodology: Three groups of 4th-year students (n = 61) at Ziauddin Medical University underwent this formative assessment process 4-5 times during a 4-week rotation. Psychometric analysis for reliability was done by calculating the internal consistency and item-total correlation of TOSBA scores. At the same time, validity was determined by correlating TOSBA scores with the end-of-rotation objective structured clinical evaluation (OSCE) scores. Results: The TOSBA tool\u27s overall reliability was good, with Cronbach\u27s alpha values \u3e0.7 for all clinical skills assessed. Spearman\u27s correlation revealed r2 \u3e0.4 (p \u3c 0.001) for history taking and clinical reasoning. Item-total correlation varied across stations, occasionally falling below 0.7. Strong correlations (0.46 to 0.73, p \u3c 0.001) were observed between similar constructs. The multi-trait-multi-method matrix highlighted divergent validity, showing no or negative correlations within the same method (TOSBA or OSCE), except for physical examination, which differed from OSCE. Conclusion: The TOSBA tool developed for formative assessment of undergraduate paediatric students is a reliable and moderately valid tool for formative assessment of undergraduate students
Towards rabies elimination in Pakistan: Barriers, facilitators, and the role of one health
No full textBackground: Rabies is a neglected zoonotic disease with an estimated 59,000 deaths annually, disproportionately affecting low- and middle-income countries. Pakistan remains a high-burden setting due to weak surveillance, poor intersectoral coordination, and limited public awareness. Therefore, this study aimed to examine the barriers and facilitators to rabies control in Pakistan through the One Health approach, integrating perspectives from both community members and institutional stakeholders.Methods: This mixed-methods study design was conducted in Karachi, where 385 household respondents completed a structured Knowledge, Attitudes, and Practices (KAP) survey, and 10 stakeholders (out of 14 approached) were interviewed across human, animal, and environmental sectors. The survey tool was adapted from previously validated instruments and pilot-tested. Thematic analysis was conducted using a deductive framework based on One Health principles. The quantitative data were analyzed descriptively using IBM SPSS Statistics 21, whereas the qualitative data were analyzed using Atlas.ti.Results: The average knowledge score was 5.54 out of 13 (42.6%), indicating substantial knowledge gaps among community members. Key barriers identified included limited vaccine availability, inadequate surveillance systems, fragmented dog population control, and weak multisectoral collaboration. Enabling factors included stakeholder willingness, local Trap-Neuter-Vaccinate-Release (TNVR) initiatives, and existing collaborative frameworks. Stakeholder awareness of the One Health approach was present but lacked institutional translation.Conclusion: A coordinated, One Health-based strategy for rabies elimination is urgently needed in Pakistan that addresses both systemic and community-level gaps through sustained advocacy, stronger intersectoral coordination, expansion of TNVR initiatives, and establishment of centralized surveillance for bite incidents and post-exposure management
Enhancing health workforce capacity through life skills-based interventions: Evidence from Pakistan on reducing gender-based violence
No full textBackground: Gender-based violence is a pervasive issue in Pakistan, necessitating effective interventions to enhance the responsiveness of healthcare workers\u27 capacity to respond effectively to Gender-based violence. This study aims to strengthen the health system\u27s response to Gender-based violence by implementing a need-based Life Skills-Based Training program for healthcare providers in Pakistan.Method: A quasi-experimental pre-post study design was employed. The intervention, i.e., Life Skills-Based Training program was implemented across four diverse districts Matiari and Shadadkot (Sindh), Chitral (Khyber Pakhtunkhwa), and Gilgit (Gilgit-Baltistan) to ensure geographic and sociocultural variation. A total of 84 healthcare providers and 78 stakeholders were purposively selected based on their roles in patient care or Gender-based violence-related policymaking. Life Skills-Based Training was delivered over six days at each site, including tailored modules for healthcare providers and stakeholders, focusing on Gender-based violence concepts, screening, counseling, referral pathways, and system-level advocacy. A pre- and post-test assessment was administered to measure changes in knowledge, competencies, and attitudes using structured questionnaires adapted from UNHCR and UNICEF tools. Quantitative analysis of score improvements and qualitative feedback were used to evaluate training effectiveness.Results: A comparative analysis of pre- and post-test assessments demonstrated significant improvements in participants\u27 Gender-based violence knowledge, awareness, and case management skills, with high satisfaction reported in Life Skills-Based Training evaluations. Feedback highlighted themes such as the effectiveness of training, the need for competent professionals, involving community leaders, replicating sessions, government health system responses, and integrating Gender-based violence education into curricula. Follow-up results demonstrated the sustainability of interventions, with participants actively applying their knowledge and leading community education.Conclusion: The study highlights the need for continuous capacity-building and integrating Gender-based violence education into healthcare and educational systems to improve support for survivors. Strengthening the health workforce with targeted training and protocols is essential for addressing Gender-based violence effectively, offering a framework for similar efforts in other regions to foster equitable and responsive healthcare
AI fragment based optimization of saffron and chamomile phytochemicals as aryl hydrocarbon receptor inhibitors for dementia therapy an integrated computational approach
No full textDementia represents a rapidly rising global health challenge as a progressive neurodegenerative disease with few options for disease-modifyingtreatments. The present studyaimed to explore the leading phytochemicals from Crocus sativus (saffron) and Matricaria chamomilla (chamomile) and apply AI fragmentation on lead phytochemicals to target the aryl hydrocarbon receptor (AHR), an expertized target for dementia therapy. Bioactive compounds were screened from ISO 3632-2-2010 (E) specified for saffron and GC-MS specified for chamomile. Protein Network mapping, Density Functional Theory, Molecular docking, and molecular dynamics simulations were performed to determine thebinding affinity and interactions stability of key phytochemicals with AHR, such as safranal and bisabolone oxide A. In-silico ADMET predictions of pharmacokinetics and toxicity showed good properties for these molecules. In addition, their structuraland pharmacological properties were optimized to enhance drug-like features by using artificial intelligence (AI) generative model. Collectively, our findings highlight these AI-enhanced phytochemicals as promising AHR modulators with potentially therapeutic activities in pathological pathways that lead toneuroinflammation and oxidative stress involved in the pathogenesis of dementia. They offer an avenue for additional experimental validation and encourage further investigation of these leads as sources of new therapeutic modalities to treat neurodegenerativediseases
Lack of HIV suppression is associated with plasma aflatoxin B1 in Kenyan women living with HIV and receiving anti-retroviral therapy
No full textBackground
Aflatoxins are carcinogenic and immunosuppressive compounds found in Aspergillus-contaminated corn. Kenyan women living with HIV (WLWH) receiving antiretroviral therapy (ART) were studied to examine associations of aflatoxin exposure and HIV immune control.
Methods
Sixty WLWH were enrolled; 56 completed the Month-12 visit. Blood samples were collected for aflatoxin, CD4 cell counts and HIV viral load. Logistic regression and linear regression models were fitted to examine factors associated with (1) detectable HIV viral load, and (2) HIV viral load in copies/mL.
Results
All WLWH were receiving ART (mean 9.9 years). Eight women (14.3%) had a detectable HIV viral load (mean 12,439 copies/mL). Aflatoxin B1 was detected in 23 of 56 WLWH (41.7%); 17 of 48 (35.4%) with an undetectable HIV viral load, and 6 of 8 (75.0%) with a detectable HIV viral load (p = 0.053). The mean plasma aflatoxin B1 concentration for all WLWH was 0.0403 pg/μL; 0.0341 pg/μL and 0.0771 pg/μL for WLWH with undetectable or detectable HIV viral loads, respectively (p = 0.039).
Conclusions
Aflatoxin B1 detection is associated with lack of HIV viral load suppression, defined as a detectable HIV viral load, among a cohort of Kenyan WLWH, all receiving ART. Studies are needed to determine the mechanisms involved
Using the observational medical outcomes partnership common data model for a multi-registry intensive care unit benchmarking federated analysis: lessons learned
Full text linkObjective: Federated analysis is a method that allows data analysis to be performed on similar datasets without exchanging any data, thus facilitating international research collaboration while adhering to strict privacy laws. This study aimed to evaluate the feasibility of using federated analysis to benchmark mortality in 2 critical care quality registry databases converted to the Observational Medical Outcomes Partnership (OMOP) Common Data Model (CDM), describing challenges to and recommendations for performing federated analysis on data transformed to OMOP CDM.
Materials and Methods: To identify as many challenges as possible and to be able to complete the benchmarking phase, a 2-step approach was taken during implementation. The first step was a naive implementation to allow challenges to surface naturally; the second step was developing solutions for the encountered challenges. Expected patient mortality risk was calculated by applying the Acute Physiology and Chronic Health Evaluation II (APACHE II) model to data from OMOP CDM databases containing adult ICU encounters between July 1, 2019 and December 31, 2022. An analysis script was developed to calculate comparable, registry level standardized mortality ratios. Challenges were recorded and categorized into predefined categories: “data preparation,” “data analysis plan,” and “data interpretation.” Challenges specific to the OMOP CDM were further categorized using published steps from an existing generic harmonization process.
Results: A total of 7 challenges were identified, 4 of which were related to data preparation, 1 to data analysis, and 1 to data interpretation. Out of all 7 challenges, 4 stemmed from decisions made during the implementation of OMOP CDM. Several recommended solutions were distilled from the naive approach.
Discussion: Federated analysis facilitated by a CDM is a feasible option for critical care quality registries. However, future analysis is influenced by decisions made during the CDM implementation process. Thus, prior publication of data dictionaries and the use of metadata to communicate data handling and data source classification during CDM implementation will improve the efficiency and accuracy of subsequent analysis
INSPIRE : Vol 8 Issue 7
No full textMessage from the Chair Medicine at National & International Forums Dr. Amna Subhan Elected to APASL Executive Committee Dean Adil Haider\u27s Farewell Dr Ali Zubairi AKU visit Histopathology Workshop at DUHS Mango Fiesta Poem | My cup overflows In-depth featuring Dr Sadia Masood Featured faculty | Dr Asad Habibi What academics are readinghttps://ecommons.aku.edu/inspire/1091/thumbnail.jp
Higher plasma AFB1 concentration is associated with increased risk of HPV 16 and HPV 18 detection and persistence among Ugandan women
Full text linkIntroduction: Aflatoxins are environmental hazards; potent carcinogenic and immunosuppressive agents that contaminates corn and other crops. A high proportion of hepatocellular carcinoma cases are caused by exposure to dietary aflatoxins. Cervical cancer is common among Ugandan women; this malignancy is caused by persistent infection with oncogenic HPV types. An analysis was performed to examine associations between plasma aflatoxin B1 (AFB1) detection and oncogenic HPV detection (HPV types 16, 18, 31, 33, 35, 39, 45, 51, 52, 56, 58, 59, 66, and 68) and persistence among Ugandan women.
Methods: Ugandan women were enrolled in a prospective cohort study. Annual cervical swabs (Enrollment, Month 12 and Month 24) were tested for oncogenic HPV. Plasma AFB1 concentration was measured (as AFB1-lysine conjugate, or AFB1-lys) at Enrollment and Month 12. Multivariable regression models were fitted to examine associations of plasma AFB1-lys concentrations and oncogenic HPV controlling for demographic and behavioral characteristics.
Results: The analytical sample consisted of 114 women with a mean age of 33.2 years; 60 women were living with HIV; 59 were receiving antiretroviral therapy (ART) at enrollment. AFB1-lysine adducts (AFB1-lys) was detected in plasma from all 114 women. Multivariable regression models showed that plasma AFB1-lys concentration was associated with a higher risk of detection of HPV 16 (OR = 2.64, 95% CI = 1.42–4.90, p = 0.002) and HPV 18 (OR = 2.24, 95% CI = 1.27–3.96, p = 0.005), and persistence of HPV 16 (OR = 3.16, 95% CI = 1.59–6.26, p = 0.001) and HPV 18 (OR = 2.06, 95% CI = 1.09–3.90, p = 0.025), controlling for age, marital status, years of education, home ownership, distance to health care, number of lifetime sex partners, age of first sex, and HIV status.
Conclusions: AFB1 is an environmental hazard that is prevalent among Ugandan women. Higher plasma AFB1-lys concentration was associated with detection and persistence of HPV 16 and HPV 18; this association was independent of HIV status. As a result, these women may be at increased risk of cervical cancer. Further studies are needed to determine the mechanisms involved