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La calidad del agua está relacionada con parámetros biológicos, químicos y físicos y el grado de concentración de estos componentes presentes en el agua y que, de acuerdo a su nivel de presencia, afectan el consumo del recurso hídrico. Por ello, es necesario analizar la presencia de estos elementos en el agua del Estero El Macho en la ciudad de Machala, Ecuador a través de la aplicabilidad del método estadístico. El diseño de la investigación es correlacional con el apoyo de métodos estadísticos, regresión lineal múltiple y análisis de componentes principales presentes en las aguas. Los resultados evidenciaron la presencia de agentes tales como: Coliformes fecales, demanda bioquímica de oxígeno, demanda química de oxígeno, hierro y oxígeno disuelto fuera de los límites permitidos para un agua de calidad, por consiguiente, el agua del estuario de El Macho no cumple los criterios de calidad para poder ser consumida sin problemas. Se concluye que se deben desarrollar políticas para mitigar la presencia e impacto de estos componentes identificados, que afectan la calidad del agua.

El secado del maíz permite reducir el contenido de humedad presente en el grano a niveles que permitan un almacenamiento seguro. El objetivo de esta investigación permite analizar los sistemas de secado de maíz empleados en el Cantón Quevedo, Provincia de Los Ríos. Para alcanzar nuestro objetivo se realizaron visitas de campo en la zona objeto de estudio, por lo que se consideraron factores relacionados con la tecnología empleada y período de cosecha de maíz, características de la región costera del Ecuador. Se determinó que el secado estacionario o de lecho fijo es el sistema de secado ampliamente empleado para el secado de maíz, el cual emplea como combustible el gas licuado de petróleo subsidiado para su funcionamiento. La humedad de recibo de maíz en las plantas de secado presenta niveles de humedad por encima del 30 %, en los dos periodos de cosecha del producto, situación que repercute en los tiempos de proceso y en la calidad del producto. La demanda de combustible para secar una masa promedio de producto, 60,2 Ton, entre el primer período de cosecha que va de Marzo – Junio, y el segundo período, Septiembre – Noviembre, presenta una diferencia de 300,77 Kg de GLP con relación a la primera cosecha, siendo la humedad de recibo un factor clave a tomar en cuenta.

Abstract St. John's wort (SJW) extract, a herbal medicine with antidepressant effects, is a potent inducer of intestinal and/or hepatic cytochrome P450 (CYP) enzymes and P‐glycoprotein (P‐gp), which can cause clinically relevant drug interactions. It is currently not known whether SJW can also induce P‐gp activity at the human blood–brain barrier (BBB), which may potentially lead to decreased brain exposure and efficacy of certain central nervous system (CNS)‐targeted P‐gp substrate drugs. In this study, we used a combination of positron emission tomography (PET) imaging and cocktail phenotyping to gain a comprehensive picture on the effect of SJW on central and peripheral P‐gp and CYP activities. Before and after treatment of healthy volunteers (n = 10) with SJW extract with a high hyperforin content (3–6%) for 12–19 days (1800 mg/day), the activity of P‐gp at the BBB was assessed by means of PET imaging with the P‐gp substrate [11C]metoclopramide and the activity of peripheral P‐gp and CYPs was assessed by administering a low‐dose phenotyping cocktail (caffeine, omeprazole, dextromethorphan, and midazolam or fexofenadine). SJW significantly increased peripheral P‐gp, CYP3A, and CYP2C19 activity. Conversely, no significant changes in the peripheral metabolism, brain distribution, and P‐gp‐mediated efflux of [11C]metoclopramide across the BBB were observed following the treatment with SJW extract. Our data suggest that SJW does not lead to significant P‐gp induction at the human BBB despite its ability to induce peripheral P‐gp and CYPs. Simultaneous intake of SJW with CNS‐targeted P‐gp substrate drugs is not expected to lead to P‐gp‐mediated drug interactions at the BBB.

Tumbo fruit has potential for industrialization due to its nutritional and functional properties, but scientific knowledge of this species is still limited compared to other species of the same genus, Passiflora. This review compiles the latest scientific advances on Tumbo, which cover the food technological aspects of Tumbo fruit, its uses and its potential as a source of bioactives for different industries, especially food, pharmaceutical, and cosmetics. The products (nectar, jellies, jams, wines, others) and by-products of the processing of the Tumbo fruit have various nutritional, sensory, and composition attributes for developing new food and non-food products. The potential applications of the fruit and its derivatives are broad, such as cosmetics, drugs, functional foods, and additives; these applications are due to its technological properties and its content of bioactive molecules. The Tumbo biorefinery presents an important perspective, especially for its bioactivity of high biological value for different industries.

Summary: Hypoxia-inducible factor 1 (HIF-1) is a transcriptional activator that mediates cellular adaptation to decreased oxygen availability. HIF-1 recruits chromatin-modifying enzymes leading to changes in histone acetylation, citrullination, and methylation at target genes. Here, we demonstrate that hypoxia-inducible gene expression in estrogen receptor (ER)-positive MCF7 and ER-negative SUM159 human breast cancer cells requires the histone H2A/H2B chaperone facilitates chromatin transcription (FACT) and the H2B ubiquitin ligase RING finger protein 20/40 (RNF20/40). Knockdown of FACT or RNF20/40 expression leads to decreased transcription initiation and elongation at HIF-1 target genes. Mechanistically, FACT and RNF20/40 are recruited to hypoxia response elements (HREs) by HIF-1 and stabilize binding of HIF-1 (and each other) at HREs. Hypoxia induces the monoubiquitination of histone H2B at lysine 120 at HIF-1 target genes in an HIF-1-dependent manner. Together, these findings delineate a cooperative molecular mechanism by which FACT and RNF20/40 stabilize multiprotein complex formation at HREs and mediate histone ubiquitination to facilitate HIF-1 transcriptional activity.

Abstract Background Cervical cancer is the leading cause of cancer death in Kenyan women. Integrating cervical cancer screening into family planning (FP) clinics is a promising strategy to improve health for reproductive-aged women. The objective of this cluster randomized trial was to test the efficacy of an implementation strategy, the Systems Analysis and Improvement Approach (SAIA), as a tool to increase cervical cancer screening in FP clinics in Mombasa County, Kenya. Methods Twenty FP clinics in Mombasa County were randomized 1:1 to SAIA versus usual procedures. SAIA has five steps: (1) cascade analysis tool to understand the cascade and identify inefficiencies, (2) sequential process flow mapping to identify bottlenecks, (3) develop and implement workflow modifications (micro-interventions) to address identified bottlenecks, (4) assess the micro-intervention in the cascade analysis tool, and (5) repeat the cycle. Prevalence ratios were calculated using Poisson regression with robust standard errors to compare the proportion of visits where women were screened for cervical cancer in SAIA clinics compared to control clinics. Results In the primary intent-to-treat analysis in the last quarter of the trial, 2.5% (37/1507) of visits with eligible FP clients at intervention facilities included cervical cancer screening compared to 3.7% (66/1793) in control clinics (prevalence ratio [PR] 0.67, 95% CI 0.45–1.00). When adjusted for having at least one provider trained to perform cervical cancer screening at baseline, there was no significant difference between screening in intervention clinics compared to control clinics (adjusted PR 1.14, 95% CI 0.74–1.75). Conclusions The primary analysis did not show an effect on cervical cancer screening. However, the COVID-19 pandemic and a healthcare worker strike likely impacted SAIA’s implementation with significant disruptions in FP care delivery during the trial. While SAIA’s data-informed decision-making and clinic-derived solutions are likely important, future work should directly study the mechanisms through which SAIA operates and the influence of contextual factors on implementation. Trial registration ClinicalTrials.gov, NCT03514459. Registered on April 19, 2018.

Abstract Background Epithelial trauma is a risk factor of HIV infection in men who have sex with men (MSM) and female sex workers (FSWs). Painful intercourse may be indicative of epithelial tissue disruption. Previous studies on a cohort of Kenyan FSWs established an association between prolonged sexual abstinence and late HIV seroconversion. Our research objective was to establish whether there is a relationship between HIV serostatus and signs of epithelial disruption and between HIV serostatus and sexual abstinence behaviour. Methods Participants were selected from a Nairobi health facility. A structured questionnaire was administered to 322 FSWs, who provided data on HIV status, sexual behaviour, abstinence intervals and the level of sexual dysfunction. Sexual dysfunction scores were created using parts of the Female Sexual Function Index (FSFI-19). Additional questions addressed epithelial trauma signs. Descriptive data analysis, bivariate and multivariate logistic regression were used to describe the study population and determine factors associated with living with HIV. Potential factors influencing sexual dysfunction were assessed by FSWs via self-rating. Results 36% of FSWs reported discomfort or pain during vaginal penetration half the time. 44% noticed genital bleeding half the time. Vaginal tenderness was experienced by 70.6% half the time during or after intercourse. Variables predictive of living with HIV on multivariate analysis included a medium and high score of discomfort or pain during and following vaginal penetration (medium: AOR 2.288, p-value 0.032, 95% CI 1.075–4.871; high: AOR 3.044, p-value 0.031, 95% CI 1.110–8.348). No significant association of HIV status with past abstinence durations as reported by participants could be established in the multivariate analysis. A majority of FSWs agreed that steady partnerships (81% agreement), regularity of intercourse (74%), foreplay (72%) and lubricants (65%) alleviated dyspareunia. Conclusions Recurrent exposure to blood during sex was highly prevalent in FSWs, as was sexual dysfunction. Complaint levels were associated with living with HIV, providing evidence that reducing sexual dysfunctions may prevent HIV transmission. Preventive initiatives may be created that address sexual dysfunction in key populations and general populations with a high HIV prevalence. Subjective assessments indicate that prevention may include the promotion of sexual intercourse regularity, foreplay, and lubricant use.

Abstract Background Mobile Health (“mHealth”) interventions have shown promise in improving HIV treatment outcomes for stigmatized populations. This paper presents the findings from a randomized controlled trial to assess the efficacy, participant-level feasibility and acceptability of a theory-informed mHealth intervention, Motivation Matters!, designed to improve viral suppression and ART adherence among HIV-seropositive women who engage in sex work in Mombasa, Kenya. Methods A total of 119 women were randomized between the intervention and standard of care control. The primary outcome examined viral suppression (≤ 30 copies/mL) six months following ART initiation. ART adherence was assessed monthly using a visual analogue scale. Participant-level feasibility was measured through response rates to study text messages. Acceptability was assessed through qualitative exit interviews. Results Six months following treatment initiation, 69% of intervention and 63% of control participants were virally suppressed (Risk Ratio [RR] = 1.09, 95% Confidence Interval [95% CI] (0.83, 1.44). Among women who were viremic at baseline and endorsed engagement in sex work, 74% of women in the intervention arm compared with 46% of women in the control arm achieved viral suppression at month six RR = 1.61, 95% CI (1.02, 2.55). Adherence was higher in intervention versus control participants every month. All participants responded to at least one message, and there was a 55% overall response rate to intervention text messages. Qualitative exit interviews suggested high acceptability and perceived impact of the intervention. Conclusion The improvements in ART adherence and viral suppression, combined with encouraging data on feasibility and acceptability, provides preliminary evidence that Motivation Matters! could support ART adherence and viral suppression in women who engage in sex work. Trial registration This trial was registered with ClinicalTrials.gov (NCT02627365, 10/12/2015; http://clinicaltrials.gov ).

Abstract Background Current advances in biomedical research have introduced new ethical challenges in obtaining informed consent in low and middle-income settings. For example, there are controversies about the use of broad consent in the collection of biological samples for use in future biomedical research. However, few studies have explored preferred informed consent models for future use of biological samples in Malawi and South Africa. Therefore, we conducted an empirical study to understand preferred consent models among key stakeholders in biomedical studies that involve collection of biological samples in Malawi and South Africa. The main objective of the study was to explore views of key stakeholders on current policies on informed consent in Malawi and South Africa. Methods This was a qualitative study involving in-depth interviews and focus group discussions. Thirty-four in-depth interviews and 6 focus group discussions were conducted with REC members, Funders, Policymakers, CAB members and Research Participants in Malawi and South Africa to gather their views on models of informed consent. The study was conducted in Cape Town, South Africa, and Blantyre and Lilongwe in Malawi. Results Most key stakeholders preferred broad consent and tiered consent to specific consent. Some participants expressed a strong preference for specific consent to other models of informed consent in biomedical research. Few participants did not have any preference for a consent model, opting for any consent model which provides adequate information about the proposed research and what their national consent regulations require. Finally, very few participants preferred blanket consent to other informed consent models. Conclusions This study aimed to help fill the gap in the scientific literature on key stakeholder views on consent models for future use of biological samples in Malawi and South Africa. The findings of the study have provided some evidence that may support policies on permissible consent models for future use of biological samples in sub-Saharan Africa considering the differences in informed consent regulations and guidelines. Finally, the findings can inform ongoing discussions on permissible consent models to be used for future use of biological samples.

Abstract Background Cervical cancer is the most common cancer in sub-Saharan Africa. With appropriate screening and treatment, cervical cancer can be prevented. In Kenya, cervical cancer screening is recommended for all women of reproductive age who visit a health facility. In particular, the Kenyan Ministry of Health has tasked family planning clinics and HIV clinics with implementing cervical cancer screening as part of the overall cervical cancer screening strategy. A cross-sectional survey was conducted to understand cervical cancer screening practices and explore clinic-level barriers and facilitators to screening in family planning clinics (FP) in Mombasa County, Kenya. Methods Structured interviews were conducted with randomly sampled FP clinic managers to collect information about clinic size, location, type, management support, infrastructure, screening practices, and availability of screening commodities. Data were abstracted from FP registers for a 15-month period from October 1, 2017 until December 31, 2018 to understand cervical cancer screening prevalence. Generalized linear models were used to calculate prevalence ratios (PR) and identify clinic-level correlates of reporting any cervical cancer screening. Results A total of 70 clinics were sampled, 54% (38) were urban and 27% (19) were public facilities. The median number of staff in a clinic was 4 (interquartile range [IQR] 2–6) with a median of 1 provider trained to perform screening (IQR 0–3). Fifty-four percent (38/70) of clinic managers reported that their clinics performed cervical cancer screening. Of these, only 87% (33) and 71% (27) had dependable access to speculums and acetic acid, respectively. Being a public FP clinic was associated with higher prevalence of reported screening (14/38 [37%] vs 6/32 [16%]; prevalence rate ratio [PR] 1.57, 95%CI 1.05–2.33). Clinics that reported cervical cancer screening were much more likely to have at least one provider trained to perform cervical cancer screening (84%, 32/38) compared to clinics that did not report screening (28%, 9/32; PR 3.77, 95%CI 1.82–7.83). Conclusion Integration of cervical cancer screening into FP clinics offers great potential to reach large numbers of reproductive-aged women. Increasing training of healthcare providers and ensuring adequate commodity supplies in FP clinics offer concrete solutions to increase screening in a largely unscreened population.

Abstract Background Although HIV testing in family planning (FP) clinics is a promising approach for engaging women in HIV treatment and prevention services, HIV testing rates are low in FP clinics in Kenya. In 2018, a cluster randomized trial was implemented in Mombasa, Kenya applying the Systems Analysis and Improvement Approach (SAIA) to integrate HIV testing into FP services (1K24HD088229-01). We estimated the incremental costs and explored cost drivers of the FP HIV SAIA implementation in Mombasa, Kenya. Methods We conducted a costing evaluation from the payer perspective for the FP HIV SAIA randomized control trial. We identified relevant activities for the intervention including start-up, training, research and FP HIV SAIA. We estimated activity time burden using a time-and motion study. We derived unit costs through staff interviews and programmatic budgets. We present cost estimates for two different scenarios: as-implemented including research and projected costs for a Ministry of Health-supported intervention. All costs are reported in 2018 USD. Results For an annual program output of 36,086 HIV tests administered to new FP clients, we estimated the total annual program cost to be $91,994 with an average cost per new FP client served of $2.55. Personnel and HIV rapid testing kits comprised 55% and 21% of programmatic costs, respectively. Assuming no changes to program outputs and with efficiency gains under the MOH scenario, the estimated cost per new FP client served decreased to $1.30 with a programmatic cost reduction of 49%. Conclusion FP HIV SAIA is a low-cost and flexible implementation strategy for facilitating integrated delivery of HIV testing alongside FP services. Although cost implications of the FP HIV SAIA intervention must continue to be evaluated over time, these findings provide context-specific cost data useful for budget planning and decision-making regarding intervention delivery and expansion. Trial registration The trial was registered on December 15, 2016, with clinicaltrials.gov (NCT02994355).

Abstract Background In Kenya, HIV incidence is highest among reproductive-age women. A key HIV mitigation strategy is the integration of HIV testing and counseling (HTC) into family planning services, but successful integration remains problematic. We conducted a cluster-randomized trial using the Systems Analysis and Improvement Approach (SAIA) to identify and address bottlenecks in HTC integration in family planning clinics in Mombasa County, Kenya. This trial (1) assessed the efficacy of this approach and (2) examined if SAIA could be sustainably incorporated into the Department of Health Services (DOHS) programmatic activities. In Stage 1, SAIA was effective at increasing HTC uptake. Here, we present Stage 2, which assessed if SAIA delivery would be sustained when implemented by the Mombasa County DOHS and if high HTC performance would continue to be observed. Methods Twenty-four family planning clinics in Mombasa County were randomized to either the SAIA implementation strategy or standard care. In Stage 1, the study staff conducted all study activities. In Stage 2, we transitioned SAIA implementation to DOHS staff and compared HTC in the intervention versus control clinics 1-year post-transition. Study staff provided training and minimal support to DOHS implementers and collected quarterly HTC outcome data. Interviews were conducted with family planning clinic staff to assess barriers and facilitators to sustaining HTC delivery. Results Only 39% (56/144) of planned SAIA visits were completed, largely due to the COVID-19 pandemic and a prolonged healthcare worker strike. In the final study quarter, 81.6% (160/196) of new clients at intervention facilities received HIV counseling, compared to 22.4% (55/245) in control facilities (prevalence rate ratio [PRR]=3.64, 95% confidence interval [CI]=2.68–4.94). HIV testing was conducted with 60.5% (118/195) of new family planning clients in intervention clinics, compared to 18.8% (45/240) in control clinics (PRR=3.23, 95% CI=2.29–4.55). Interviews with family planning clinic staff suggested institutionalization contributed to sustained HTC delivery, facilitated by low implementation strategy complexity and continued oversight. Conclusions Intervention clinics demonstrated sustained improvement in HTC after SAIA was transitioned to DOHS leadership despite wide-scale healthcare disruptions and incomplete delivery of the implementation strategy. These findings suggest that system interventions may be sustained when integrated into DOHS programmatic activities. Trial registration ClinicalTrials.gov (NCT02994355) registered on 16 December 2016.

Abstract Background Significant gaps remain in HIV testing and counseling (HTC) in family planning (FP) clinics. To address these gaps, our group tested an implementation strategy called the Systems Analysis and Improvement Approach (SAIA), an evidenced-based multi-component implementation strategy focused on improving entire care cascades. In a cluster randomized trial of 24 FP clinics in Mombasa County, Kenya, SAIA led to a significant increase in HTC in intervention clinics compared to control clinics. The objective of this manuscript was to evaluate SAIA using the Consolidated Framework for Implementation Research (CFIR) and assess the Implementation Outcomes Framework outcomes of acceptability, appropriateness, and feasibility. Methods This qualitative assessment was nested within the cluster-randomized trial. Data collection included questionnaires to assess modifiable and non-modifiable health system factors related to HTC and in-depth interviews to query clinic norms, priorities, communication strategies, and readiness for change. The primary outcomes of interest were feasibility, appropriateness, and acceptability of SAIA. Data on inner setting and structural characteristics of FP clinics were collected to inform how context may impact outcomes. All interviews were recorded and analyzed using a rapid assessment approach. Results Of the 12 intervention clinics, 6 (50%) were public facilities. Availability of resources varied by clinic. Most clinics had a positive implementation climate, engaged leadership, and access to resources and information. While not all clinics identified HTC as a clinic priority, most reported a strong culture of embracing change and recognition of the importance of HIV testing within FP clinics. Interviews highlighted very high acceptability, appropriateness, and feasibility of SAIA. The implementation strategy was not complicated and fit well into existing clinic processes. In particular, staff appreciated that SAIA allowed clinic staff to generate contextually relevant solutions that they implemented. Conclusions SAIA was implemented in FP clinics of varying sizes, capacity, and management support and was found to be acceptable, appropriate, and feasible. The agency that clinic staff felt in proposing and implementing their own solutions was likely part of SAIA’s success. We anticipate this will continue to be a mechanism of SAIA’s success when it is scaled up to more clinics in future trials. Trial registration ClinicalTrials.gov (NCT02994355) registered 16 December 2016.

The movements of humans have a significant impact on population health. While studies of such movements are as old as public health itself, the COVID-19 pandemic has raised the profile of mobility research using digital technologies to track transmission routes and calculate the effects of health policies, such as lockdowns. In sub-Saharan Africa, the high prevalence of cell phone and smartphone use is a source of potentially valuable mobility data for public health purposes. Researchers can access call data records, passively collected in real time from millions of clients by cell phone companies, and associate these records with other data sets to generate insights, make predictions or draw possible policy implications. The use of mobility data from this source could have a range of significant benefits for society, from better control of infectious diseases, improved city planning, more efficient transportation systems and the optimisation of health resources. We discuss key ethical issues raised by public health studies using mobility data from cell phones in sub-Saharan Africa and identify six key ethical challenge areas: autonomy, including consent and individual or group privacy; bias and representativeness; community awareness, engagement and trust; function creep and accountability; stakeholder relationships and power dynamics; and the translation of mobility analyses into health policy. We emphasise the ethical importance of narrowing knowledge gaps between researchers, policymakers and the general public. Given that individuals do not really provide valid consent for the research use of phone data tracking their movements, community understanding and input will be crucial to the maintenance of public trust. Significance: • Mobility data derived from cell phones are being increasingly used for health research and public health purposes in sub-Saharan Africa, with minimal individual consent and largely without public awareness. • While such data can have significant potential public health benefits, risks and concerns related to their collection and use in sub-Saharan African contexts have not been widely discussed. • Innovative community engagement initiatives, which are appropriate and responsive to sub-Saharan African contexts, need to be developed to address ethical challenge areas and help warrant public trust in mobility research.

Abstract Background Periodontitis has been associated with adverse pregnancy outcomes. Little is known about the burden and risk factors for periodontitis among reproductive age women in sub-Saharan Africa. This analysis aimed to determine the prevalence and correlates of periodontitis among Kenyan women planning to conceive. Methods HIV-seronegative, reproductive-age women who were planning to conceive were enrolled and underwent a periodontal examination. Following the US Centers for Disease Control and Prevention clinical case definitions, the presence and severity of periodontitis was determined by establishing the level of clinical periodontal attachment loss and graded in three categories: no/mild, moderate, and severe. Secondary outcomes included the scores on the Gingival Index and Decayed, Missing, and Filled Teeth (DMFT) Index. Correlates of periodontitis were examined using univariable and multivariable logistic regression. Results Of the 647 women in the study, 84% (n = 541) had no/mild periodontitis, 15% (n = 97) had moderate periodontitis, and 1% (n = 9) had severe periodontitis. Mild gingivitis was present in 61% (n = 396) of women, while 27% (n = 176) had moderate gingivitis, and 1% (n = 9) had severe gingivitis. The majority (75%, n = 487) of women had a DMFT index in the very low range (score

Nanomaterials are present in a wide variety of health products, drugs and medical devices and their use is constantly increasing, varying in terms of diversity and quantity. The topic is vast because it covers nanodrugs, but also excipients (that includes varying proportions of NMs) and medical devices (with intended or not-intended (by-products of wear) nanoparticles). Although researchers in the field of nanomedicines in clinical research and industry push for clearer definitions and relevant regulations, the endeavor is challenging due to the enormous diversity of NMs in use and their specific properties. In addition, regulatory hurdles and discrepancies are often cited as obstacles to the clinical development of these innovative products. The scientific council of the Agence Nationale de Sécurité du Médicament et des produits de santé (ANSM) undertook a multidisciplinary analysis encompassing fundamental, environmental and societal dimensions with the aim of identifying topics of interest for regulatory assessment and surveillance. This analysis allowed for proposing some recommendations for approximation and harmonization of international regulatory practices for the assessment of the risk/benefit balance of these products, considering as well the public expectations as regards efficacy and safety of nanomaterials used in Health products, in terms of human and environmental health.

Summary: Intratumoral hypoxia is a microenvironmental feature that promotes breast cancer progression and is associated with cancer mortality. Plexin B3 (PLXNB3) is highly expressed in estrogen receptor-negative breast cancer, but the underlying mechanisms and consequences have not been thoroughly investigated. Here, we report that PLXNB3 expression is increased in response to hypoxia and that PLXNB3 is a direct target gene of hypoxia-inducible factor 1 (HIF-1) in human breast cancer cells. PLXNB3 expression is correlated with HIF-1α immunohistochemistry, breast cancer grade and stage, and patient mortality. Mechanistically, PLXNB3 is required for hypoxia-induced MET/SRC/focal adhesion kinase (FAK) and MET/SRC/STAT3/NANOG signaling as well as hypoxia-induced breast cancer cell migration, invasion, and cancer stem cell specification. PLXNB3 knockdown impairs tumor formation and lung metastasis in orthotopic breast cancer mouse models.

Most cervicovaginal microbiome-immunology studies to date have relied on 16S rDNA microbial profiling which does not resolve the molecular subgroups of Gardnerella, believed to be central to the pathogenesis of bacterial vaginosis (BV) and subsequent risk of HIV acquisition. Here we used the cpn60 universal target which in addition to other microbial taxa, resolves four Gardnerella subgroups, for cervicovaginal microbial profiling in a longitudinal cohort of Kenyan women to examine associations with cellular and soluble markers of inflammation and HIV susceptibility. Participants (N = 41) were sampled, contributing 362 samples for microbiome analysis. All non-Lactobacillus dominant microbial communities were associated with high pro-inflammatory cytokine levels. Divergent associations were observed among different Gardnerella subgroup dominated communities with respect to the chemokine IP-10. Specifically, Gardnerella subgroup A dominant and polymicrobial communities were associated with reduced concentrations of IP-10 in adjusted linear mixed models (p

Abstract Background The number of older women living with HIV in Africa is growing, and their health outcomes may be adversely impacted by social frailty, which reflects deficits in social resources that accumulate over the lifespan. Our objective was to adapt a Social Vulnerability Index (SVI) originally developed in Canada for use in a study of older women living with or without HIV infection in Mombasa, Kenya. Methods We adapted the SVI using a five-step process: formative qualitative work, translation into Kiswahili, a Delphi procedure, exploration of potential SVI items in qualitative work, and a rating and ranking exercise. Four focus group discussions (FGD) were conducted (three with women living with HIV and one with HIV-negative women), and two expert panels were constituted for this process. Results Themes that emerged in the qualitative work were physical impairment with aging, decreased family support, a turn to religion and social groups, lack of a financial safety net, mixed support from healthcare providers, and stigma as an added burden for women living with HIV. Based on the formative FGD, the expert panel expanded the original 19-item SVI to include 34 items. The exploratory FGD and rating and ranking exercise led to a final 16-item Kenyan version of the SVI (SVI-Kenya) with six domains: physical safety, support from family, group participation, instrumental support, emotional support, and financial security. Conclusions The SVI-Kenya is a holistic index to measure social frailty among older women in Kenya, incorporating questions in multiple domains. Further research is needed to validate this adapted instrument.

The Sup35 prion protein of budding yeast has been reported to undergo phase separation to form liquid droplets both at low pH in vitro and when energy depletion decreases the intracellular pH in vivo. It also has been shown using purified proteins that this phase separation is driven by the prion domain of Sup35 and does not re-quire its C-terminal domain. In contrast, we now find that a Sup35 fragment consisting of only the N-terminal prion domain and the M-domain does not phase separate in vivo; this phase separation of Sup35 requires the C-terminal domain, which binds Sup45 to form the translation termination complex. The phase-separated Sup35 not only colocalizes with Sup45 but also with Pub1, a stress granule marker protein. In addition, like stress granules, phase separation of Sup35 appears to require mRNA since cycloheximide treatment, which inhibits mRNA release from ribosomes, prevents phase separation of Sup35. Finally, unlike Sup35 in vitro, Sup35 condensates do not disassemble in vivo when the intracellular pH is increased. These results suggest that, in energy-depleted cells, Sup35 forms supramolecular assemblies that differ from the Sup35 liquid droplets that form in vitro.

Bioconcentration and bioaccumulation levels of lead, zinc, iron and arsenic in Scirpus californicus of the Paca and Tragadero Lagoons, Jauja, Peru, were evaluated. Water, sediment and Scirpus californicus samples were collected from each lagoon, which were transported to the laboratory for the analytical determination of lead, iron, zinc and arsenic, which was performed by atomic absorption spectrophotometry based on the methodology recommended by FAO. The results obtained reveal the current status of the quality of the aquatic environment of natural wetlands in the central region of Peru in terms of heavy metals and arsenic, which provide an important source of water for the populations of large cities in the central region of Peru. The presence of heavy metals and arsenic with great impact on the quality of these water bodies may be due to the pressure exerted by anthropogenic activities such as mining, agriculture, industrial and domestic wastewater. The sediments of Paca and Tragadero Lagoons showed high concentrations of Fe, exceeding international standards. Aquatic vegetation represented by Scirpus californicus in both lagoons bio accumulated mainly Zn, without exceeding international standards.

Introduction Prevalence of lifetime-induced abortion in female sex workers (FSWs) in Kenya was previously estimated between 43% and 86%. Our analysis aimed at assessing lifetime prevalence and correlates, and incidence and predictors of induced abortions among FSWs in Kenya.Methods This is a secondary prospective cohort analysis using data collected as part of the WHISPER or SHOUT cluster-randomised trial in Mombasa, assessing effectiveness of an SMS-intervention to reduce incidence of unintended pregnancy. Eligible participants were current FSWs, 16–34 years and not pregnant or planning pregnancy. Baseline data on self-reported lifetime abortion, correlates and predictors were collected between September 2016 and May 2017. Abortion incidence was measured at 6-month and 12-month follow-up. A multivariable logistic regression model was used to assess correlates of lifetime abortion and discrete-time survival analysis was used to assess predictors of abortions during follow-up.Results Among 866 eligible participants, lifetime abortion prevalence was 11.9%, while lifetime unintended pregnancy prevalence was 51.2%. Correlates of lifetime abortions were currently not using a highly effective contraceptive (adjusted OR (AOR)=1.76 (95% CI=1.11 to 2.79), p=0.017) and having ever-experienced intimate partner violence (IPV) (AOR=2.61 (95% CI=1.35 to 5.06), p=0.005). Incidence of unintended pregnancy and induced abortion were 15.5 and 3.9 per 100 women-years, respectively. No statistically significant associations were found between hazard of abortion and age, sex work duration, partner status, contraceptive use and IPV experience.Conclusion Although experience of unintended pregnancy remains high, lifetime prevalence of abortion may have decreased among FSW in Kenya. Addressing IPV could further decrease induced abortions in this population.Trial registration number ACTRN12616000852459.

Objectives: To understand the public’s perceptions around rapid SARS-CoV-2 antigen self-testing in Kenya, including the drivers of acceptability, willingness to pay, and adherence to hygiene and prevention recommendations following a positive self-test.Methods: A household-based, cross-sectional survey, using a 35-item questionnaire, was conducted in Mombasa and Taita–Taveta counties, Kenya, during August 2021. Individuals aged ≥18 years were enrolled using a stratified sampling approach.Results: There were 419 participants (mean age 35.7 years). A minority (10.5%) had ever tested for SARS-CoV-2. If SARS-CoV-2 self-testing were available, 39.9% and 41.5% would be likely and very likely, respectively, to use it. If unavailable free-of-charge, 63.01% would pay for it. Multivariate analyses suggested that people in rural areas (Coefficient 0.30, 95%CI: 0.11–0.48, p = 0.002), aged 36–55 (Coefficient 0.21, 95%CI: 0.03–0.40, p = 0.023), and employed full time (Coefficient 0.32, 95%CI: 0.06–0.58, p = 0.016) would have more odds to adhere to recommended hygiene and prevention actions.Conclusion: SARS-CoV-2 self-testing was considered acceptable. Availability of self-testing could expand access to COVID-19 testing in Kenya, particularly among rural communities who have limited access to testing, and among mildly symptomatic individuals.

Patients with high-grade serous ovarian cancer (HGSOC) have a very poor overall survival. Current therapeutic approaches do not bring benefit to all patients. Although genetic alterations and molecular mechanisms are well characterized, the molecular pathological conditions are poorly investigated. Solute carrier organic anion transporter family member 4A1 (SLCO4A1) encodes OATP4A1, which is an uptake membrane transporter of metabolic products. Its expression may influence various signaling pathways associated with the molecular pathophysiological conditions of HGSOC and consequently tumor progression. RNA sequencing of 33 patient-derived HGSOC cell lines showed that SLCO4A1 expression was diverse by individual tumors, which was further confirmed by RT-qPCR, Western blotting and immunohistochemistry. Gene Set Enrichment Analysis revealed that higher SLCO4A1 level was associated with inflammation-associated pathways including NOD-like receptor, adipocytokine, TALL1, CD40, NF-κB, and TNF-receptor 2 signaling cascades, while low SLCO4A1 expression was associated with the mitochondrial electron transport chain pathway. The overall gene expression pattern in all cell lines was specific to each patient and remained largely unchanged during tumor progression. In addition, genes encoding ABCC3 along with SLCO4A1-antisense RNA 1, were associated with higher expression of the SLCO4A1, indicating their possible involvement in inflammation-associated pathways that are downstream to the prostaglandin E2/cAMP axis. Taken together, increased SLCO4A1/OATP4A1 expression is associated with the upregulation of specific inflammatory pathways, while the decreased level is associated with mitochondrial dysfunction. These molecular pathophysiological conditions are tumor specific and should be taken into consideration by the development of therapies against HGSOC.

Hepatocellular carcinoma (HCC) is a major cause of cancer mortality worldwide and available therapies, including immunotherapies, are ineffective for many patients. HCC is characterized by intratumoral hypoxia, and increased expression of hypoxia-inducible factor 1α (HIF-1α) in diagnostic biopsies is associated with patient mortality. Here we report the development of 32-134D, a low-molecular-weight compound that effectively inhibits gene expression mediated by HIF-1 and HIF-2 in HCC cells, and blocks human and mouse HCC tumor growth. In immunocompetent mice bearing Hepa1-6 HCC tumors, addition of 32-134D to anti-PD1 therapy increased the rate of tumor eradication from 25% to 67%. Treated mice showed no changes in appearance, behavior, body weight, hemoglobin, or hematocrit. Compound 32-134D altered the expression of a large battery of genes encoding proteins that mediate angiogenesis, glycolytic metabolism, and responses to innate and adaptive immunity. This altered gene expression led to significant changes in the tumor immune microenvironment, including a decreased percentage of tumor-associated macrophages and myeloid-derived suppressor cells, which mediate immune evasion, and an increased percentage of CD8+ T cells and natural killer cells, which mediate antitumor immunity. Taken together, these preclinical findings suggest that combining 32-134D with immune checkpoint blockade may represent a breakthrough therapy for HCC.

The Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) virus has been causing the COVID-19 pandemic since December 2019, with over 600 million infected persons worldwide and over six million deaths. We investigated the anti-viral effects of polyphenolic green tea ingredients and the synthetic resveratrol analogue 3,3′,4,4′,5,5′-hexahydroxy-trans-stilbene (HHS), a compound with antioxidant, antitumor and anti-HIV properties. In the TCID50 assay, four out of nine green tea constituents showed minor to modest cell protective effects, whereas HHS demonstrated the highest reduction (1103-fold) of the TCID50, indicating pronounced inhibition of virus replication. HHS was also a highly effective inhibitor of SARS-CoV-2 proliferation in VeroE6 cells with an IC50 value of 31.1 µM. HSS also inhibited the binding of the receptor-binding domain (RBD) of the spike protein to the human angiotensin-converting enzyme 2 (ACE2) receptor (RBD-ACE2) binding with 29% at 100 µM and with 9.2% at 50 µM indicating that the SARS-CoV-2 inhibitory effect might at least in part be attributed to the inhibition of virus binding to ACE2. Based on the chemical similarity to other polyphenols, the oral bioavailability of HHS is likely also very low, resulting in blood levels far below the inhibitory concentration of EGCG against SARS-CoV-2 observed in vitro. However, administration of HHS topically as a nose or throat spray would increase concentrations several-fold above the minimal inhibitory concentration (MIC) in the mucosa and might reduce virus load when administered soon after infection. Due to these promising tissue culture results, further preclinical and clinical studies are warranted to develop HHS as an additional treatment option for SARS-CoV-2 infection to complement vaccines, which is and will be the main pillar to combat the COVID-19 pandemic.

The use of fungicides from the strobilurin and carboxamide groups demonstrates an effect on photosynthetic efficiency by increasing CO2 assimilation and, consequently, plant productivity, due to better a physiological performance. The objective was to evaluate the effect of the application of these fungicides on the physiology and yield of tomato plants. A randomized block design was used with six treatments and five blocks: control, azoxystrobin (75 g ha−1), boscalid (75 g ha−1), pyraclostrobin (75 g ha−1), fluxapyroxad (75 g ha−1) and fluxapyroxad + pyraclostrobin (50.1 g and 99.9 g ha−1). Different physiological, biochemical and antioxidant enzymatic parameters were evaluated. The application of fungicides increased the CO2 assimilation by 64% and the production per plant by 91%. The activity of the nitrate reductase enzyme increased by 1.69 times, the antioxidant system by 3.68 times and photosynthetic pigments by 1.16 times under the action of the studied fungicides with respect to the control. Therefore, the application of fungicides favored the development of the tomato plant, especially with the use of Pyraclostrobin (75 g ha−1).

Inherited retinal dystrophies (IRDs) are a global problem that is largely unaddressed, especially in Africa. Black indigenous Africans are rarely represented in research that develops genetic tests and genetic therapies for IRDs, yet their genomes are more diverse. The aim of this literature review is to synthesize information on the IRD genetic research conducted among indigenous black Africans to identify challenges and opportunities for progress. PubMed was searched to identify empirical publications reporting the genetic analysis of IRDs among indigenous Africans. A total of 11 articles were selected for the review. Based on the information in the articles, the main genetic testing methods in use include next-generation, whole exome, and Sanger sequencing. The main IRDs characterized by the genetic tests include retinitis pigmentosa, Leber Congenital Amaurosis, Stagardt disease, and cone dystrophy. Examples of implicated genes include MERTK, GUCY2D, ABCA4, and KCNV2 for the four IRDs, respectively. Research activities on the genetics of IRDs are generally scanty in Africa. Even in South Africa and North Africa where some research activities were noted, only a few indigenous black Africans were included in the study cohorts. There is an urgent need for genetic research on IRDs, especially in East, Central, and West Africa.

This study presents qualitative results from a mixed-method investigation conducted between May and August 2012 into the prevalence and consequences of four forms of intimate partner violence among women living with HIV who attended the Comprehensive Care Clinic at the Kenyatta National Hospital in Nairobi. As a part of the research, a quantitative survey found that among 600 sexually active women living with HIV aged 18–69, all reported experiencing emotional abuse; 20%, 17%, and 15% experienced controlling behavior, physical violence, and sexual violence, respectively. Qualitative research using focus group discussions with 19 women from the quantitative survey sought to contextualize these experiences and place them within a larger social structure where institutionalized gender inequality sets the tone for intimate partner violence against women in households. Participants reported that intimate partner violence led to their exposure to the virus and made them leery of disclosing their positive status or seeking support from a male partner for fear of a violent reaction. This fear and the socio-structural conditions in Kenya limit their ability to actively pursue comprehensive care, the stress of which can exacerbate symptoms and make managing the disease more difficult.

The phytosorption potential of metals of Hydrocotyle ranunculoides was evaluated for the mitigation of water pollution in the high Andean wetlands of Peru. The plants were selected from 10 wetland sites in the community of Pomachaca- Tarma and were washed with potable water, dried, ground, weighed, chemically digested and read with Varian AA 240 atomic absorption equipment. The plant showed copper concentrations in the root (12.08 ± 1.67 mg/kg) greater than the stem (7.37 ± 1.00 mg/kg), followed by the leaves (7.37 ± 1.56 mg/kg). Lead concentration in the root was 0.228 ± 0.711 mg/kg, but was not found in the stem or leaves. The highest zinc concentration was in the root (67.52 ± 12.57 mg/kg) to the stem (53.30 ± 0.61 mg/kg), followed by the leaves (43.99 ± 8.49 mg/kg). Finally, iron was higher in the root (5571.28 ± 693.94 mg/kg) than in the leaves (342.76 ±122.09 mg/kg), followed by the stem (291.94 ± 54.84 mg/kg). Surrounding water had pH between 7.2 and 7.6; no copper and lead were found, zinc was 0.005 ± 0.012 mg/L and iron was 0.009± 0.007 mg/L. In the sediment, copper was 26.12 ± 0.65 mg/kg, lead 28.25 ± 2.41 mg/kg, zinc 85.98 ± 11.38 mg/kg and iron 26111.89 ± 614.37 mg/kg. These results indicate that this plant absorbs metals in the order of Fe>Zn>Cu>Pb and is an alternative for the development of phytotechnology, oriented to the treatment of effluents with metals that contaminate water in wetlands.

BackgroundEmerging evidence suggests that after completion of treatment for tuberculosis (TB) a significant proportion of patients experience sequelae. However, there is limited synthesized evidence on this from low-income countries, from Sub-Saharan Africa, and in HIV infected individuals. We seek to provide an updated comprehensive systematic review and meta-analysis on the magnitude and factors associated with post-TB lung disease (PTLD) in low- and middle-income countries (LMICs).MethodsWe searched PubMed, Embase and CINAHL for studies from LMICs with data on post-TB lung health in patients who had previously completed treatment for pulmonary TB. Data on study characteristics, prevalence of PTLD-specifically abnormal lung function (spirometry), persisting respiratory symptoms and radiologic abnormalities were abstracted. Statistical analysis was performed using Microsoft Excel and R version 4.1 software, and random effects meta-analysis conducted to compute pooled prevalence of PTLD, evaluate heterogeneity, and assess factors associated with PTLD.ResultsWe identified 32 eligible studies with 6225 participants. Twenty-one studies were from Africa, 16 included HIV infected participants, spirometry was conducted in 20 studies, symptom assessment in 16 and chest imaging in eight. Pooled prevalence of abnormal lung function was 46.7%, persistent respiratory symptoms 41.0%, and radiologic abnormalities 64.6%. Magnitude of any type of PTLD varied by HIV status (HIV- 66.9%, HIV+ 32.8%, p = 0.0013), across geographic setting (SE Asia 57.5%, Southern America 50.8%, and Africa 38.2%, p = 0.0118), and across urban-rural settings (symptom prevalence: rural 68.8%, urban 39.1%, mixed settings 27.9%, p = 0.0035), but not by income settings, sex or age-group.ConclusionsThere is high burden of post-TB persistent respiratory symptoms, functional lung impairment and radiologic structural abnormalities in individuals living in LMICs. Burden varies across settings and by HIV status. This evidence may be valuable to advocate for and inform implementation of structured health care specific to the needs of this vulnerable population of individuals.

BackgroundThe microbiota of the lower female genital tract plays an important role in women's health. Microbial profiling using the chaperonin60 (cpn60) universal target (UT) improves resolution of vaginal species associated with negative health outcomes compared to the more commonly used 16S ribosomal DNA target. However, the choice of DNA extraction and PCR product purification methods may bias sequencing-based microbial studies and should be optimized for the sample type and molecular target used. In this study, we compared two commercial DNA extraction kits and two commercial PCR product purification kits for the microbial profiling of cervicovaginal samples using the cpn60 UT.MethodsDNA from cervicovaginal secretions and vaginal lavage samples as well as mock community standards were extracted using either the specialized QIAamp DNA Microbiome Kit, or the standard DNeasy Blood & Tissue kit with enzymatic pre-treatment for enhanced lysis of gram-positive bacteria. Extracts were PCR amplified using well-established cpn60 primer sets and conditions. Products were then purified using a column-based method (QIAquick PCR Purification Kit) or a gel-based PCR clean-up method using the QIAEX II Gel Extraction Kit. Purified amplicons were sequenced with the MiSeq platform using standard procedures. The overall quality of each method was evaluated by measuring DNA yield, alpha diversity, and microbial composition.ResultsDNA extracted from cervicovaginal samples using the DNeasy Blood and Tissue kit, pre-treated with lysozyme and mutanolysin, resulted in increased DNA yield, bacterial diversity, and species representation compared to the QIAamp DNA Microbiome kit. The column-based PCR product purification approach also resulted in greater average DNA yield and wider species representation compared to a gel-based clean-up method. In conclusion, this study presents a fast, effective sample preparation method for high resolution cpn60 based microbial profiling of cervicovaginal samples.

Background. Active case finding (ACF) for tuberculosis (TB) is a key strategy to reduce diagnostic delays, expedite treatment, and prevent transmission. Objective. Our objective was to identify the populations, settings, screening and diagnostic approaches that optimize coverage (proportion of those targeted who were screened) and yield (proportion of those screened who had active TB) in ACF programs. Methods. We performed a comprehensive search to identify studies published from 1980-2016 that reported the coverage and yield of different ACF approaches. For each outcome, we conducted meta-analyses of single proportions to produce estimates across studies, followed by meta-regression to identify predictors. Findings. Of 3,972 publications identified, 224 met criteria after full-text review. Most individuals who were targeted successfully completed screening, for a pooled coverage estimate of 93.5%. The pooled yield of active TB across studies was 3.2%. Settings with the highest yield were internally-displaced persons camps (15.6%) and healthcare facilities (6.9%). When compared to symptom screening as the reference standard, studies that screened individuals regardless of symptoms using microscopy, culture, or GeneXpert®MTB/RIF (Xpert) had 3.7% higher case yield. In particular, microbiological screening (usually microscopy) as the initial test, followed by culture or Xpert for diagnosis had 3.6% higher yield than symptom screening followed by microscopy for diagnosis. In a model adjusted for use of Xpert testing, approaches targeting persons living with HIV (PLWH) had a 4.9% higher yield than those targeting the general population. In all models, studies targeting children had higher yield (4.8%-5.7%) than those targeting adults. Conclusion. ACF activities can be implemented successfully in various populations and settings. Screening yield was highest in internally-displaced person and healthcare settings, and among PLWH and children. In high-prevalence settings, ACF approaches that screen individuals with laboratory tests regardless of symptoms have higher yield than approaches focused on symptomatic individuals.

Methods: A priority-setting process (PSP) was launched to define priorities for patient-centered antimicrobial resistance (AMR) surveillance and research in low- and middle-income countries (LMICs). A list of uncertainties related to AMR surveillance in human health was generated using an online survey of stakeholders in LMICs, which asked for unanswered questions about diagnosis, treatment, or prevention of antibiotic resistance. Results: A total of 445 respondents generated 1076 questions that were mapped to a final shortlist of 107 questions. The most common theme was the treatment of drug-resistant infections, followed by diagnosis, then prevention, and requests for local AMR data. The most asked question was a request for local AMR data, revealing the lack of basic information in many LMICs to guide actions to tackle AMR. The steering group recommended three research areas to be prioritized for funding in the next five years: infection prevention and control in LMICs, improved electronic patient records, starting with laboratory information management systems, and sustainable behavior change among doctors and other health care professionals with a focus on diagnostic stewardship.

Abstract Background Infection and sepsis are a main cause of acute-on-chronic liver failure (ACLF). Adequate dosing of antimicrobial therapy is of central importance to improve outcome. Liver failure may alter antibiotic drug concentrations via changes of drug distribution and elimination. We studied the pharmacokinetics of meropenem in critically ill patients with ACLF during continuous veno-venous hemodialysis (CVVHD) and compared it to critically ill patients without concomitant liver failure (NLF). Methods In this prospective cohort study, patients received meropenem 1 g tid short-term infusion (SI). Meropenem serum samples were analyzed by high-performance liquid chromatography. A population pharmacokinetic analysis was performed followed by Monte Carlo simulations of (A) meropenem 1 g tid SI, (B) 2 g loading plus 1 g prolonged infusion tid (C) 2 g tid SI, and (D) 2 g loading and continuous infusion of 3 g/day on days 1 and 7. Probability of target attainment (PTA) was assessed for 4× the epidemiological cut-off values for Enterobacterales (4 × 0.25 mg/L) and Pseudomonas spp. (4 × 2 mg/L). Results Nineteen patients were included in this study. Of these, 8 patients suffered from ACLF. A two-compartment model with linear clearance from the central compartment described meropenem pharmacokinetics. The peripheral volume of distribution (V 2) was significantly higher in ACLF compared to NLF (38.6L versus 19.7L, p = .05). PTA for Enterobacterales was achieved in 100% for all dosing regimens. PTA for Pseudomonas spp. in ACLF on day 1/7 was: A: 18%/80%, B: 94%/88%, C: 85%/98% D: 100%/100% and NLF: A: 48%/65%, B: 91%/83%, C: 91%/93%, D: 100%/100%. Conclusion ALCF patients receiving CVVHD had a higher V 2 and may require a higher loading dose of meropenem. For Pseudomonas, high doses or continuous infusion are required to reach PTA in ACLF patients.

Endometrial cancer (EC) is the most common gynecological malignancy in resource-abundant countries. The majority of EC cases are estrogen dependent but the mechanisms of estrogen biosynthesis and oxidative metabolism and estrogen action are not completely understood. Here, we evaluated formation of estrogens in models of moderately and poorly differentiated EC: RL95-2 and KLE cells, respectively. Results revealed high expression of estrone-sulfate (E1-S) transporters (SLCO1A2, SLCO1B3, SLCO1C1, SLCO3A1, SLC10A6, SLC22A9), and increased E1-S uptake in KLE vs RL95-2 cells. In RL95-2 cells, higher levels of sulfatase and better metabolism of E1-S to E1 were confirmed compared to KLE cells. In KLE cells, disturbed balance in expression of HSD17B genes led to enhanced activation of E1 to E2, compared to RL95-2 cells. Additionally, increased CYP1B1 expression and down-regulation of genes encoding phase II metabolic enzymes: COMT, NQO1, NQO2, and GSTP1 suggested decreased detoxification of carcinogenic metabolites in KLE cells. Results indicate that in model cell lines of moderately and poorly differentiated EC, estrogens can be formed via the sulfatase pathway.

La profilaxis antibiótica mediante infiltración periincisional consiste en infiltrar el antibiótico en la zona en donde se va a realizar la incisión antes de la intervención, lo que permite niveles hísticos del antibiótico muy elevados y mantenidos durante la intervención (4). La apendicitis aguda por ser una cirugía estandarizada y un proceso con riesgo infeccioso, es un buen modelo para estudiar la utilidad de la vía para la prevención de la infección postoperatoria (32). Se presentan los resultados de un estudio cuasiexperimental de tipo clínico controlado, de 35 apendicectomías con profilaxis periincisional antibiótica con cloranfenicol, y 35 apendicectomías sin profilaxis (26). El grupo que recibió profilaxis presentó la infección de la herida operatoria en el 2.8l% de los casos y ningún caso de infección intraabdominal; en el grupo control, se observó infección de la herida operatoria en el 14% de los casos operados, e infección intraabdominal en el 2.8%. Los resultados con profilaxis periincisional son semejantes e incluso superiores a los informados en la literatura con el uso de profilaxis por vía intravenosa.

Genetic analysis of the F8 gene can play a vital role in the diagnosis and management of people with hemophilia A (PWH). Knowing the causative mutation can assist treating clinicians in predicting the risk of inhibitor formation and a person’s response to treatment. It is also a vital tool for genetic counselors in assisting PWH with family planning. Mutational analysis has been limited in developing countries, mainly due to resource constraints; however, with the development of more cost-effective screening tools, these assays are becoming more common in developing countries. Unfortunately, the clinical utility of these assays remain unclear in some of these underresourced countries, resulting in a lack of clinician buy-in. We aimed to highlight the wide-ranging impact mutational analysis potentially has on PWH and their extended families in a developing country. We used a gel-based in-house method to determine the inversion 22 (Inv22) mutation in a family where a young boy, without a family history, was recently diagnosed with hemophilia A. Inv22 was detected in the proband and his mother, but not in any other direct family member. Therefore, we concluded that the mutation was a de novo mutation in the mother. Subsequently, this result has bearing on at least 23 direct blood-relatives. Genetic screening extends far wider than the treatment of PWH and is vital in the management of PWH and their extended families. With the availability of cost-effective genetic screening assays this should also be the case in developing countries.

The majority of Kenya’s > 3 million camels have antibodies against Middle East respiratory syndrome coronavirus (MERS-CoV), although human infection in Africa is rare. We enrolled 243 camels aged 0–24 months from 33 homesteads in Northern Kenya and followed them between April 2018 to March 2020. We collected and tested camel nasal swabs for MERS-CoV RNA by RT-PCR followed by virus isolation and whole genome sequencing of positive samples. We also documented illnesses (respiratory or other) among the camels. Human camel handlers were also swabbed, screened for respiratory signs, and samples were tested for MERS-CoV by RT-PCR. We recorded 68 illnesses among 58 camels, of which 76.5% (52/68) were respiratory signs and the majority of illnesses (73.5% or 50/68) were recorded in 2019. Overall, 124/4692 (2.6%) camel swabs collected from 83 (34.2%) calves in 15 (45.5%) homesteads between April–September 2019 screened positive, while 22 calves (26.5%) recorded reinfections (second positive swab following ≥ 2 consecutive negative tests). Sequencing revealed a distinct Clade C2 virus that lacked the signature ORF4b deletions of other Clade C viruses. Three previously reported human PCR positive cases clustered with the camel infections in time and place, strongly suggesting sporadic transmission to humans during intense camel outbreaks in Northern Kenya.

Abstract With expanded HIV treatment and prevention programmes, most infants born to HIV‐positive women are uninfected, but the patterns and determinants of their growth are not well described. This study aimed to assess growth patterns in a cohort of HIV‐exposed uninfected (HEU) infants who participated in an experimental HIV vaccine trial and to test for associations with maternal and infant factors, including in‐utero exposure to antiretroviral therapy (ART), mode of delivery, exclusive breastfeeding, mother's education and receipt of the vaccine. Infants in the trial were seen at regular clinic visits from birth to 48 weeks of age. From the anthropometric measurements at these visits, weight‐for‐age z‐scores (WAZ), weight‐for‐length z‐scores (WLZ) and length‐for‐age z‐scores (LAZ) were computed using World Health Organization (WHO) software and reference tables. Growth patterns were investigated with respect to maternal and infant factors, using linear mixed regression models. From 94 infants included at birth, growth data were available for 75.5% at 48 weeks. The determinants of infant growth in this population are multifactorial: infant LAZ during the first year was significantly lower among infants delivered by caesarean section (p = 0.043); both WAZ and LAZ were depressed among infants with longer exposure to maternal ART (WAZ: p = 0.015; LAZ: p < 0.0001) and among infants of mothers with lower educational level (WAZ: p = 0.038; LAZ: p < 0.0001); the effect of maternal education was modified by breastfeeding practice, with no differences seen in exclusively breastfed infants. These findings inform intervention strategies to preserve growth in this vulnerable infant population.

During the COVID-19 (coronavirus disease 2019) pandemic, universities had to shift from face-to-face to emergency remote education. Students were forced to study online, with limited access to facilities and less contact with peers and teachers, while at the same time being exposed to more autonomy. This study examined how students adapted to emergency remote learning, specifically focusing on students’ resource-management strategies using an individual differences approach. One thousand eight hundred university students completed a questionnaire on their resource-management strategies and indicators of (un)successful adaptation to emergency remote learning. On average, students reported being less able to regulate their attention, effort, and time and less motivated compared to the situation before the crisis started; they also reported investing more time and effort in their self-study. Using a k-means cluster analysis, we identified four adaptation profiles and labeled them according to the reported changes in their resource-management strategies: the overwhelmed, the surrenderers, the maintainers, and the adapters. Both the overwhelmed and surrenderers appeared to be less able to regulate their effort, attention, and time and reported to be less motivated to study than before the crisis. In contrast, the adapters appreciated the increased level of autonomy and were better able to self-regulate their learning. The resource-management strategies of the maintainers remained relatively stable. Students’ responses to open-answer questions on their educational experience, coded using a thematic analysis, were consistent with the quantitative profiles. Implications about how to support students in adapting to online learning are discussed.

Abstract Background A high proportion of African women utilize family planning (FP) services. Accordingly, incorporating HIV testing into FP services may strategically target the first WHO 90–90-90 goal of 90% of people living with HIV knowing their status. Methods The objective of this analysis was to determine the proportion of new FP clients counseled and tested for HIV, as well as correlates of HIV testing, in a random sample of 58 FP clinics in Mombasa County, Kenya. Structured interviews of FP clinic managers collected data on characteristics of FP clinics and staff. Study staff performed a 3-month review of FP registers, summarizing new client HIV testing and counseling (HTC). Because overall rates of HTC were quite low, a binary variable was created comparing clinics performing any HIV counseling and/or testing to clinics performing none. Generalized linear models were used to calculate prevalence ratios (PR) and identify correlates of HTC. Factors associated with any HTC with a p-value

In the original article [...]

INTRODUCTION: Opportunistic fungal infections due to immunosuppression coupled with antifungal drug resistance are an emerging challenge globally. The present study examined the antifungal susceptibility of yeasts and molds from sputum of tuberculosis retreatment and relapse patients at selected reference facilities in Kenya. METHODS: a total of 340 sputa samples from patients who gave written informed consent were examined. Fungal culture was done on sabouraud dextrose agar (SDA). Molds were identified by macroscopic and microscopic features while yeasts were inoculated on CHROMTMagar Candida and confirmed using API 20C AUXTM. Itraconazole (ICZ), voriconazole (VCZ), fluconazole (FCZ) and amphotericin B (AMB) were tested using broth micro-dilution methods according to Clinical and Laboratory Standards Institute (CLSI). RESULTS: out of the 340 samples, 14.4% (n=49) and 15.6% (n=53) were positive for yeasts and molds respectively. Candida albicans and C. krusei were the most predominant isolates constituting 49.0% (n=24) and 20.4% (n=10) of the total yeasts respectively. Aspergillus spp. were the most frequent (22.6%) molds and isolates with MICs 4μg/ml on the antifungal agents were noted. All the molds except two (n=2) isolates of Scedosporium aspiopermum exhibited MICs 4μg/ml for fluconazole. Overall, molds were more sensitive to AMB and VCZ.Candida albicans had MIC50 0.06μg/ml, and MIC 904μg/ml. There was a statistically significant difference (F=3.7, P=0.004=0.05) in the overall sensitivity pattern of molds for the four antifungal agents while there was no significant difference (F=1.7, P=0.154=0.05) in sensitivity exhibited by the yeasts. CONCLUSION: the study demonstrates the significance of fungal colonization in presumptive tuberculosis retreatment or relapse with evidence of triazole resistance. There is need to strengthen fungal diagnostic and clinical management capabilities in susceptible populations.

IntroductionEvidence that supports the use of COVID-19 convalescent plasma (CCP) for treatment of COVID-19 is increasingly emerging. However, very few African countries have undertaken the collection and processing of CCP. The aim of this study was to assess the feasibility of collecting and processing of CCP, in preparation for a randomized clinical trial of CCP for treatment of COVID-19 in Uganda.MethodsIn a cross-sectional study, persons with documented evidence of recovery from COVID-19 in Uganda were contacted and screened for blood donation via telephone calls. Those found eligible were asked to come to the blood donation centre for further screening and consent. Whole blood collection was undertaken from which plasma was processed. Plasma was tested for transfusion transmissible infections (TTIs) and anti-SARS CoV-2 antibody titers. SARS-CoV-2 testing was also done on nasopharyngeal swabs from the donors.Results192 participants were contacted of whom 179 (93.2%) were eligible to donate. Of the 179 eligible, 23 (12.8%) were not willing to donate and reasons given included: having no time 7(30.4%), fear of being retained at the COVID-19 treatment center 10 (43.5%), fear of stigma in the community 1 (4.3%), phobia for donating blood 1 (4.3%), religious issues 1 (4.4%), lack of interest 2 (8.7%) and transport challenges 1 (4.3%). The median age was 30 years and females accounted for 3.7% of the donors. A total of 30 (18.5%) donors tested positive for different TTIs. Antibody titer testing demonstrated titers of more than 1:320 for all the 72 samples tested. Age greater than 46 years and female gender were associated with higher titers though not statistically significant.ConclusionCCP collection and processing is possible in Uganda. However, concerns about stigma and lack of time, interest or transport need to be addressed in order to maximize donations.

IntroductionThe postpartum period can be challenging for women living with HIV. Understanding how the postpartum period impacts ART adherence and condomless sex could inform the development of comprehensive sexual and reproductive health and HIV services tailored to the needs of women living with HIV during this critical interval.MethodsIn a longitudinal cohort study of HIV-seropositive Kenyan women, late ART refills and self-reported condomless sex were compared between the woman's pregnancy and the postpartum period. Analyses were conducted using generalized estimating equations and adjusted for alcohol use, depressive symptoms, intimate partner violence (IPV), and having a recent regular partner. Effect modification was explored for selected variables.Results and discussion151 women contributed visits. Late ART refills occurred at 7% (32/439) of pregnancy visits compared to 18% (178/1016) during the postpartum period (adjusted relative risk [aRR] 2.44, 95% confidence interval [CI] 1.62-3.67). This association differed by women's education level. Women with ≥8 years of education had late ART refills more during the postpartum period than pregnancy (aRR 3.00, 95%CI 1.95-4.62). In contrast, in women with ConclusionImproved support for ART adherence during the postpartum period and addressing IPV to limit condomless sex could improve HIV treatment and prevention outcomes for HIV-seropositive women as well as their infants and sexual partners.

A prerequisite for the design of an HIV vaccine that elicits protective antibodies is understanding the developmental pathways that result in desirable antibody features. The development of antibodies that mediate antibody-dependent cellular cytotoxicity (ADCC) is particularly relevant because such antibodies have been associated with HIV protection in humans. We reconstructed the developmental pathways of six human HIV-specific ADCC antibodies using longitudinal antibody sequencing data. Most of the inferred naive antibodies did not mediate detectable ADCC. Gain of antigen binding and ADCC function typically required mutations in complementarity determining regions of one or both chains. Enhancement of ADCC potency often required additional mutations in framework regions. Antigen binding affinity and ADCC activity were correlated, but affinity alone was not sufficient to predict ADCC potency. Thus, elicitation of broadly active ADCC antibodies may require mutations that enable high-affinity antigen recognition along with mutations that optimize factors contributing to functional ADCC activity.