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Abstract Ischemic retinopathies including diabetic retinopathy are major causes of vision loss. Inner blood-retinal barrier (BRB) breakdown with retinal vascular hyperpermeability results in macular edema. Although dysfunction of the neurovascular unit including neurons, glia, and vascular cells is now understood to underlie this process, there is a need for fuller elucidation of the underlying events in BRB dysfunction in ischemic disease, including a systematic analysis of myeloid cells and exploration of cellular cross-talk. We used an approach for microglia depletion with the CSF-1R inhibitor PLX5622 (PLX) in the retinal ischemia-reperfusion (IR) model. Under non-IR conditions, PLX treatment successfully depleted microglia in the retina. PLX suppressed the microglial activation response following IR as well as infiltration of monocyte-derived macrophages. This occurred in association with reduction of retinal expression of chemokines including CCL2 and the inflammatory adhesion molecule ICAM-1. In addition, there was a marked suppression of retinal neuroinflammation with reduction in expression of IL-1b, IL-6, Ptgs2, TNF-a, and Angpt2, a protein that regulates BRB permeability. PLX treatment significantly suppressed inner BRB breakdown following IR, without an appreciable effect on neuronal dysfunction. A translatomic analysis of Müller glial-specific gene expression in vivo using the Ribotag approach demonstrated a strong suppression of Müller cell expression of multiple pro-inflammatory genes following PLX treatment. Co-culture studies of Müller cells and microglia demonstrated that activated microglia directly upregulates Müller cell-expression of these inflammatory genes, indicating Müller cells as a downstream effector of myeloid cells in retinal IR. Co-culture studies of these two cell types with endothelial cells demonstrated the ability of both activated microglia and Müller cells to compromise EC barrier function. Interestingly, quiescent Müller cells enhanced EC barrier function in this co-culture system. Together this demonstrates a pivotal role for myeloid cells in inner BRB breakdown in the setting of ischemia-associated disease and indicates that myeloid cells play a major role in iBRB dysregulation, through direct and indirect effects, while Müller glia participate in amplifying the neuroinflammatory effect of myeloid cells.

Purpose: Hyperglycemia is a major risk factor for early lesions of diabetic retinal disease (DRD). Updating the DRD staging system to incorporate relevant basic and cellular mechanisms pertinent to DRD is necessary to better address early disease, disease progression, the use of therapeutic interventions, and treatment effectiveness. Design: We sought to review preclinical and clinical evidence on basic and cellular mechanisms potentially pertinent to DRD that might eventually be relevant to update the DRD staging system. Participants: Not applicable. Methods: The Basic and Cellular Mechanisms Working Group (BCM-WG) of the Mary Tyler Moore Vision Initiative carefully and extensively reviewed available preclinical and clinical evidence through multiple iterations and classified these. Main Outcome Measures: Classification was made into evidence grids, level of supporting evidence, and anticipated future relevance to DRD. Results: A total of 40 identified targets based on pathophysiology and other parameters for DRD were grouped into concepts or evaluated as specific candidates. VEGFA, peroxisome proliferator-activated receptor-alpha related pathways, plasma kallikrein, and angiopoietin 2 had strong agreement as promising for use as biomarkers in diagnostic, monitoring, predictive, prognostic, and pharmacodynamic responses as well as for susceptibility/risk biomarkers that could underlie new assessments and eventually be considered within an updated DRD staging system or treatment, based on the evidence and need for research that would fit within a 2-year timeline. The BCM-WG found there was strong reason also to pursue the following important concepts regarding scientific research of DRD acknowledging their regulation by hyperglycemia: inflammatory/cytokines, oxidative signaling, vasoprotection, neuroprotection, mitophagy, and nutrients/microbiome. Conclusion: Promising targets that might eventually be considered within an updated DRD staging system or treatment were identified. Although the BCM-WG recognizes that at this stage little can be incorporated into a new DRD staging system, numerous potential targets and important concepts deserve continued support and research, as they may eventually serve as biomarkers and/or therapeutic targets with measurable benefits to patients with diabetes. Financial Disclosure(s): Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.

BackgroundPre-exposure prophylaxis (PrEP) prevention-effective adherence is of critical importance but challenging particularly among key populations where periods of high HIV risk are frequent. We assessed the use of PrEP with reference to periods of unprotected sex among female sex workers in the city of Tanga.MethodsThis was part of the pragmatic quasi-experimental trial for HIV PrEP rollout in Tanzania involving a control cohort of 313 female sex workers aged ≥18 years recruited by respondent-driven sampling and followed for 12 months. PrEP use and periods of condomless or unprotected sex were assessed at the 6th and 12th month of follow-up. Prevention-effective adherence was defined as PrEP use of ≥2 pills/week and ≥6 pills/week for anal and vaginal condomless sex. Multivariable modified Poisson regression was conducted to determine factors influencing PrEP use (≥2 pills/week).ResultsOverall, 59.2 and 45.9% of participants had unprotected anal and vaginal sex with a client, respectively. The prevention-effective adherence for anal sex ranged from 8.0% (months 6) to 10.0% (months 12) while that of vaginal sex was from 10.1% (month 6) to 3.8% (month 12). Participants who lived with friends were 25.5 times more likely to use ≥2 PrEP doses per week than those who lived alone (aPR = 25.5; 95%CI: 2.55–255.42, p = 0.006). Compared to self-reporting poor health status, self-reporting good health status significantly increased the use of ≥2 PrEP doses per week (aPR = 17.4; 95%CI: 3.01–101.02, p = 0.001). Refusing condomless sex with a steady partner increased the likelihood of using ≥2 PrEP doses per week than accepting condomless sex with a steady partner (aPR = 11.2; 95%CI: 1.55–80.48, p = 0.017). The prevalence of using ≥2 PrEP doses per week was less among participants accepting condomless sex at high pay than those who refused (aPR = 0.1; 95%CI: 0.03–0.26, p = 0.000).ConclusionUse of PrEP during periods of unprotected sex was rare among female sex workers. Living with friends, self-reporting good health status, and refusing condomless sex with steady partners were associated with increased use of ≥2 PrEP doses per week. However, accepting condomless sex for increased payment was associated with reduced use of ≥2 PrEP doses per week. This calls for an in-depth study to understand the perspectives and circumstances shaping poor adherence during periods of unprotected sex among female sex workers.

Purpose: To review the evidence for imaging modalities in assessing the vascular component of diabetic retinal disease (DRD), to inform updates to the DRD staging system. Design: Standardized narrative review of the literature by an international expert workgroup, as part of the DRD Staging System Update Effort, a project of the Mary Tyler Moore Vision Initiative. Overall, there were 6 workgroups: Vascular Retina, Neural Retina, Systemic Health, Basic and Cellular Mechanisms, Visual Function, and Quality of Life. Participants: The Vascular Retina workgroup, including 16 participants from 4 countries. Methods: Literature review was conducted using standardized evidence grids for 5 modalities: standard color fundus photography (CFP), widefield color photography (WFCP), standard fluorescein angiography (FA), widefield FA (WFFA), and OCT angiography (OCTA). Summary levels of evidence were determined on a validated scale from I (highest) to V (lowest). Five virtual workshops were held for discussion and consensus. Main Outcome Measures: Level of evidence for each modality. Results: Levels of evidence for standard CFP, WFCP, standard FA, WFFA, and OCTA were I, II, I, I, and II respectively. Traditional vascular lesions on standard CFP should continue to be included in an updated staging system, but more studies are required before they can be used in posttreatment eyes. Widefield color photographs can be used for severity grading within the area covered by standard CFPs, although these gradings may not be directly interchangeable with each other. Evaluation of the peripheral retina on WFCP can be considered, but the method of grading needs to be clarified and validated. Standard FA and WFFA provide independent prognostic value, but the need for dye administration should be considered. OCT angiography has significant potential for inclusion in the DRD staging system, but various barriers need to be addressed first. Conclusions: This study provides evidence-based recommendations on the utility of various imaging modalities for assessment of the vascular component of DRD, which can inform future updates to the DRD staging system. Although new imaging modalities offer a wealth of information, there are still major gaps and unmet research needs that need to be addressed before this potential can be realized. Financial Disclosure(s): Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.

Abstract BackgroundIncreasing access to smartphones in sub-Saharan Africa offers an opportunity to leverage mobile health (mHealth) technology to improve access to health care in underserved populations. In the domain of HIV prevention, mHealth interventions can potentially contribute to solving the challenges of suboptimal adherence to pre-exposure prophylaxis (PrEP) and low retention in PrEP services among populations most vulnerable to HIV acquisition. However, there is a gap in the knowledge about the use of such interventions in sub-Saharan Africa. ObjectiveThis study aims to evaluate the extent and predictors of retention in an mHealth app (Jichunge MethodsA prospective cohort of female sex workers residing in Dar es Salaam were recruited, using respondent-driven sampling. All participants were provided with the JichungeJichunge ResultsA total of 470 female sex workers were recruited. Nearly three-quarters of participants (206/284, 72.5%) who came to the 6-month follow-up interview no longer had the JichungePPP ConclusionsMost female sex workers (206/284, 72.5%) who were enrolled in PrEP care in Tanzania no longer used the Jichunge

Abstract Background There is evidence that pre-exposure prophylaxis (PrEP) is effective in preventing HIV transmission, and PrEP is recommended by the World Health organization (WHO) for use by individuals at high risk of HIV infection. However, low adherence has been reported to hamper its effectiveness. Some evidence indicates that mHealth interventions may be a promising way of promoting PrEP adherence. Nevertheless, evaluations of mHealth interventions in Africa, the region most affected by HIV, are scarce. This study aimed at identifying the extent of and predictors for use of a smartphone based mHealth application among female sex workers in Dar es Salaam, Tanzania. Methods As part of a quasi-experimental study in Tanzania, 470 female sex workers who were eligible for PrEP and who owned a smartphone were recruited using respondent driven sampling. All participants were provided with an mHealth application called Jichunge, a smartphone-based app designed to promote adherence to PrEP by offering users information, advise and support during start-up and use of PrEP. We collected data through structured interviews at baseline and extracted user data from the app for a period of 30 days. Modified Poisson regression model with robust standard errors was used to identify predictors for the optimal use of the Jichunge app. Results Overall, the optimal use of the Jichunge app was 46.4%. Optimal use was significantly higher among women who were older (aPR = 1.3, 95% CI: 1.10-1.65, p = 0.004 for age 25-34 years, and aPR = 1.6, 95% CI: 1.19-2.07, p = 0.001 for age at least 35 years), who had secondary education or higher (aPR = 1.8, 95% CI: 1.08-2.94, p = 0.023), who had suboptimal social support (aPR = 1.2, 95% CI: 1.02-1.48, p = 0.030), who had high awareness of PrEP (aPR = 1.3, 95% CI: 1.08-1.55, p = 0.005), and who had experience using common mainstream social media applications (aPR = 1.4, 95% CI: 1.08-1.71, p = 0.009). Conclusion Optimal use of the Jichunge app was substantially higher among women with higher age, higher education, higher PrEP awareness, less social support, and experience using common social media applications. Individual and interpersonal factors should be considered in planning mHealth interventions. Further studies to determine predictors of longer-term mHealth engagement are needed. Trial registration International Clinical Trials Registry Platform PACTR202003823226570 ; 04.03.2020.

Background Mobile health (mHealth) applications have been reported to be effective in promoting access and adherence to health services. However, knowledge about their effect on retention in HIV preventive services among at-risk populations in sub-Saharan Africa is limited. Objective We aimed to evaluate the effect of the Jichunge mHealth application on retention in HIV pre-exposure prophylaxis (PrEP) services among female sex workers in Dar es Salaam, Tanzania. Methods We used respondent-driven sampling to recruit female sex workers eligible for PrEP and who owned a smartphone. All study participants were provided with a smartphone application ( Jichunge app) aiming to promote PrEP use through medication reminders, easy access to PrEP information, online consultations with a doctor and/or peer educator, and online discussions between PrEP users. The effect of optimal use of the Jichunge app on retention in PrEP services at 1-month was modelled using log-binomial regression. Results A total of 470 female sex workers with a median age of 26 (interquartile range: 22–30) years were recruited. Overall, 27.7% of female sex workers were retained in PrEP services at 1 month. Retention was twice as high among optimal users of the app than among sub-optimal users (adjusted risk ratios = 2.00, 95% confidence interval (CI): 1.41–2.83, p

Abstract Background Esophageal squamous cell carcinoma (ESCC) is a major cause of cancer morbidity and mortality in Eastern Africa. The majority of patients with ESCC in Eastern Africa present with advanced disease at the time of diagnosis. Several palliative interventions for ESCC are currently in use within the region, including chemotherapy, radiation therapy with and without chemotherapy, and esophageal stenting with self-expandable metallic stents; however, the comparative effectiveness of these interventions in a low resource setting has yet to be examined. Methods This prospective, observational, multi-center, open cohort study aims to describe the therapeutic landscape of ESCC in Eastern Africa and investigate the outcomes of different treatment strategies within the region. The 4.5-year study will recruit at a total of six sites in Kenya, Malawi and Tanzania (Ocean Road Cancer Institute and Muhimbili National Hospital in Dar es Salaam, Tanzania; Kilimanjaro Christian Medical Center in Moshi, Tanzania; Tenwek Hospital in Bomet, Kenya; Moi Teaching and Referral Hospital in Eldoret, Kenya; and Kamuzu Central Hospital in Lilongwe, Malawi). Treatment outcomes that will be evaluated include overall survival, quality of life (QOL) and safety. All patients (≥18 years old) who present to participating sites with a histopathologically-confirmed or presumptive clinical diagnosis of ESCC based on endoscopy or barium swallow will be recruited to participate. Key clinical and treatment-related data including standardized QOL metrics will be collected at study enrollment, 1 month following treatment, 3 months following treatment, and thereafter at 3-month intervals until death. Vital status and QOL data will be collected through mobile phone outreach. Discussion This study will be the first study to prospectively compare ESCC treatment strategies in Eastern Africa, and the first to investigate QOL benefits associated with different treatments in sub-Saharan Africa. Findings from this study will help define optimal management strategies for ESCC in Eastern Africa and other resource-limited settings and will serve as a benchmark for future research. Trial registration This study was retrospectively registered with the ClinicalTrials.gov database on December 15, 2021, NCT05177393 .

PURPOSEClinical breast examination (CBE) is one of the most common methods used for early detection of breast cancer in low- and middle-income countries. CBE alone is limited by lack of specificity and may result in unnecessary diagnostic procedures. We evaluated the feasibility of integrating CBE, fine-needle aspiration biopsy (FNAB), and rapid on-site evaluation (ROSE) in triaging palpable breast masses for specialized cancer care.MATERIALS AND METHODSAn intensive breast cancer screening event was conducted at a national trade fair by a multidisciplinary team of care providers targeting a healthy population in Dar es Salaam, Tanzania. All adults age ≥ 18 years were invited to participate. CBE was performed by oncologists and/or pathologists. FNAB was performed by a pathologist on palpable masses that were then categorized as benign, indeterminate, or suspicious for malignancy or definitively malignant based on ROSE.RESULTSA total of 208 individuals (207 females, one male; median age, 36 years; range, 18-68 years) were screened. Most (90.8%, 189 of 208) had normal findings, whereas 7.2% (15 of 208), 1% (2 of 208), and 1% (2 of 208) had a palpable mass, breast pain, and nipple discharge, respectively. Two participants had lesions too small for palpation-guided biopsy and clinically consistent with fibroadenomas; the participants were counseled, and observation was recommended. FNAB was performed on 13 breast masses, with 9 of 13 (69%) categorized as benign and 4 of 13 (31%) suspicious for malignancy. Final cytopathologic review of referred patients confirmed one case to be breast adenocarcinoma, one was suggestive of fibroadenoma, and two showed inflammations.CONCLUSIONIntegration of CBE with ROSE and FNAB was feasible in a breast cancer screening program in Tanzania. In settings with constrained resources for cancer care, this may be an effective method for triaging patients with breast masses.

PURPOSEThe eastern corridor of Africa is affected by a high burden of esophageal cancer (EC), with > 90% of patients presenting with advanced disease. Self-expanding metal stents (SEMS) have been previously reported as safe and effective for palliation of malignant dysphagia in resource-limited settings; however, access is limited throughout Eastern Africa.METHODSIn response to demand for palliative interventions for patients with dysphagia because of EC, the African Esophageal Cancer Consortium (AfrECC) partnered with the Clinton Health Access Initiative to improve access to SEMS in Eastern Africa. We undertook a stepwise implementation approach to (1) identify barriers to SEMS access, (2) conduct a market analysis, (3) select an industry partner, (4) establish regulatory and procurement processes, (5) develop endoscopic training resources, (6) create a medical device registry, and (7) establish principles of accountability.RESULTSFollowing an evaluation of market demand and potential SEMS manufacturers, Boston Scientific Corporation announced its commitment to launch an access program to provide esophageal SEMS to patients in Tanzania, Kenya, Malawi, and Zambia at a subsidized price. Parallel regulatory and procurement processes were established in each participating country. Endoscopy training courses were designed and conducted, using the Training-of-Trainers model. A device registry was created to centralize data for quality control and to monitor channels of SEMS distribution. Principles of accountability were developed to guide the sustainability of this endeavor.CONCLUSIONThe AfrECC Stent Access Initiative is an example of a multisector partnership formed to provide an innovative solution to align regional needs with a supply chain for a high-priority medical device.

PURPOSEEastern Africa is one of several regions affected by high incidence rates of esophageal squamous cell carcinoma (ESCC). A unique epidemiologic feature of ESCC in Eastern Africa is the high incidence in young people, with one-third of cases diagnosed at age < 45 years. This study aimed to investigate risk factors for early-onset ESCC in Tanzania through a secondary analysis of a matched case-control study.MATERIALS AND METHODSFrom 2013 to 2015, ESCC cases were recruited at Muhimbili National Hospital and Ocean Road Cancer Institute in Dar es Salaam, Tanzania. Hospital controls were identified from patients with nonmalignant conditions and matched 1:1 for sex and age (± 10 years). Questionnaires were used to assess sociodemographic characteristics and environmental, dietary, and lifestyle risk exposures. Multivariate logistic regression models were used to estimate age-specific odds ratios of ESCC for exposures among participants age 30-44 and ≥ 45 years.RESULTSA total of 471 cases and 471 controls were enrolled. Among cases, 100 (21%) were < 45 years. Multiple exposures were identified as risk factors for early-onset ESCC, several of which were unique to this age group, including infrequent teeth cleaning, secondhand tobacco smoke exposure, and pest infestation of grain and/or nuts. Lower socioeconomic status, family history of ESCC, tobacco smoking, home-brewed alcohol consumption, home storage of grain and/or nuts, and use of firewood for cooking were associated in the older but not the younger age group. Hot beverage intake was associated with increased ESCC risk in both age groups.CONCLUSIONOur results suggest that ESCC risk factors in Tanzania vary between age groups. With the data currently available, environmental and behavioral risk factors appear to play an important role in the high incidence of ESCC among young people.

Fast metabolisms tend to shorten lifespans by increasing oxidative damage. This study identifies a gene mutation that keeps a key antioxidant response active, possibly allowing Neoaves bird species to avoid the tradeoff between rapid metabolism and longevity that challenges most mammals, including humans.

Abstract Background Despite recent international efforts to develop resource-stratified clinical practice guidelines for cancer, there has been little research to evaluate the best strategies for dissemination and implementation in low- and middle-income countries (LMICs). Guideline publication alone is insufficient. Extensive research has shown that structured, multifaceted implementation strategies that target barriers to guideline use are most likely to improve adherence; however, most of this research has been conducted in high-income countries. There is a pressing need to develop and evaluate guideline implementation strategies for cancer management in LMICs in order to address stark disparities in cancer outcomes. Methods In preparation for the launch of Tanzania’s first National Cancer Treatment Guidelines, we developed a theory-driven implementation strategy for guideline-based practice at Ocean Road Cancer Institute (ORCI). Here, we use the Intervention Mapping framework to provide a detailed stepwise description of our process. First, we conducted a needs assessment to identify barriers and facilitators to guideline-based practice at ORCI. Second, we defined both proximal and performance objectives for our implementation strategy. Third, we used the Capability, Opportunity, Motivation and Behavior/Behavior Change Wheel (COM-B/BCW) framework to categorize the barriers and facilitators, choose behavior change techniques most likely to overcome targeted barriers and leverage facilitators, and select a feasible mode of delivery for each technique. Fourth, we organized these modes of delivery into a phased implementation strategy. Fifth, we operationalized each component of the strategy. Sixth, we identified the indicators of the process, outcome, and impact of our intervention and developed an evaluation plan to measure them using a mixed methods approach. Discussion We developed a robust, multifaceted guideline implementation strategy derived from a prominent behavior change theory for use in Tanzania. The barriers and strategies we generated are consistent with those well established in the literature, enhancing the validity and generalizability of our process and results. Through our rigorous evaluation plan and systematic account of modifications and adaptations, we will characterize the transferability of “proven” guideline implementation strategies to LMICs. We hope that by describing our process in detail, others may endeavor to replicate it, meeting a widespread need for dedicated efforts to implement cancer guidelines in LMICs.

IntroductionPeople who inject drugs (PWID) in Sub-Saharan Africa have limited access to comprehensive HIV services. While it is important to inform programming, knowledge about factors influencing access to comprehensive HIV services is scarce. We assessed the proportions of PWID with access to HIV prevention services and associated socio-cognitive factors in Tanzania.MethodsA cross-sectional survey was conducted among PWID between October and December 2017 in Dar es Salaam, Tanzania. Data on access to HIV prevention services, demographics and selected socio-cognitive factors were collected through structured face-to-face interviews. Weighted descriptive and forward selection multivariable logistics regression analyses were done to assess independent associations between HIV prevention services and predictors of interest. The results were two tailed and a p-value of less than 0.05 was considered statistically significant.ResultsThe study included 611 PWID (males: 94.4%) with a median age of 34 years (Interquartile Range (IQR), 29-38). A large majority of participants reported to have access to condoms (87.8%), sterile needles/syringes (72.8%) and ever tested for HIV (66.0%). About half (52.0%) reported to have used condoms in the past one month and about a third (28.5%) accessed a peer educator. The odds of testing for HIV decreased among participants who perceived their HIV risk to be high (aOR = 0.29; 95%CI: 0.17-0.49) and those experienced sexual violence (aOR = 0.60; 95%CI 0.37-0.98). However, the odds of testing for HIV increased among participants with secondary level of education (aOR = 2.16; 95%CI: 1.06-5.55), and those who reported having correct comprehensive HIV knowledge (CCHK) (aOR = 1.63; 95%CI 1.12-2.41). The odds of access to condoms increased among females (aOR = 2.23; 95%CI: 1.04-5.02) but decreased among participants with secondary level of education (aOR = 0.41; 95%CI: 0.19-0.84), an income of >TZS 200,000 (aOR = 0.39; 95%CI: 0.23-0.66) and those who perceived their HIV risk to be high (aOR = 0.13; 95%CI: 0.03-0.36). The odds of access to peer educators was higher among participants with primary (aOR = 1.61; 95%CI: 1.01-2.26), and secondary (aOR = 2.71; 95%CI: 1.39-5.33) levels of education. The odds of access to sterile needle and syringe decreased among participants who perceived their HIV risk to be high (aOR = 0.11;95%CI 0.05-0.22), and low-medium (aOR = 0.25;95%CI 0.11-0.52) but increased among those with primary level of education (aOR = 1.72;95%CI 1.06-2.78).ConclusionAccess to condom, HIV testing, sterile needles and syringes were relatively high among PWID. However, condom use and access to peer educators was relatively low. HIV knowledge and risk perception, gender, education, and sexual violence influenced access to HIV prevention services. There is an urgent need to address the identified socio-cognitive factors and scale up all aspects of HIV prevention services to fast-track attainment of the 2025 UNAIDS goals and ending the HIV epidemic.

Ischemic retinopathies including diabetic retinopathy are major causes of blindness. Although neurons and Müller glia are recognized as important regulators of reparative and pathologic angiogenesis, the role of mononuclear phagocytes (MPs) — particularly microglia, the resident retinal immune cells — is unclear. Here, we found MP activation in human diabetic retinopathy, especially in neovessels from human neovascular membranes in proliferative retinopathy, including TNF-α expression. There was similar activation in the mouse oxygen-induced retinopathy (OIR) model of ischemia-induced neovascularization. Glucagon-like peptide-1 receptor (GLP-1R) agonists are in clinical use for glycemic control in diabetes and are also known to modulate microglia. Herein, we investigated the effect of a long-acting GLP-1R agonist, NLY01. Following intravitreal administration, NLY01 selectively localized to MPs in retina with OIR. NLY01 modulated MPs but not retinal endothelial cell viability, apoptosis, and tube formation in vitro. In OIR, NLY01 treatment inhibited MP infiltration and activation, including MP expression of cytokines in vivo. NLY01 significantly suppressed global induction of retinal inflammatory cytokines, promoted reparative angiogenesis, and suppressed pathologic retinal neovascularization. Collectively, these findings indicate the important role of mononuclear phagocytes in regulation of retinal vascularization in ischemia and suggest modulation of MPs as a potentially new treatment strategy for ischemic retinopathies.

Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) infects a broader range of mammalian species than previously predicted, binding a diversity of angiotensin converting enzyme 2 (ACE2) orthologs despite extensive sequence divergence. Within this sequence degeneracy, we identify a rare sequence combination capable of conferring SARS-CoV-2 resistance. We demonstrate that this sequence was likely unattainable during human evolution due to deleterious effects on ACE2 carboxypeptidase activity, which has vasodilatory and cardioprotective functions in vivo. Across the 25 ACE2 sites implicated in viral binding, we identify 6 amino acid substitutions unique to mouse-one of the only known mammalian species resistant to SARS-CoV-2. Substituting human variants at these positions is sufficient to confer binding of the SARS-CoV-2 S protein to mouse ACE2, facilitating cellular infection. Conversely, substituting mouse variants into either human or dog ACE2 abolishes viral binding, diminishing cellular infection. However, these same substitutions decrease human ACE2 activity by 50% and are predicted as pathogenic, consistent with the extreme rarity of human polymorphisms at these sites. This trade-off can be avoided, however, depending on genetic background; if substituted simultaneously, these same mutations have no deleterious effect on dog ACE2 nor that of the rodent ancestor estimated to exist 70 million years ago. This genetic contingency (epistasis) may have therefore opened the road to resistance for some species, while making humans susceptible to viruses that use these ACE2 surfaces for binding, as does SARS-CoV-2.

BackgroundThere is limited evidence in Africa on the design and development of mobile health (mHealth) applications to guide best practices and ensure effectiveness. A pragmatic trial for HIV pre-exposure prophylaxis roll-out among key populations in Tanzania is needed. ObjectiveWe present the results of the development of a mobile app (Jichunge) intended to promote adherence to pre-exposure prophylaxis (PrEP) among men who have sex with men (MSM) and female sex workers (FSW) in Tanzania. MethodsA participatory design approach was employed and guided by the information system research framework. MSM and FSW were the target populations. A total of 15 MSM and 15 FSW were engaged in the relevance and design cycles, while the piloting phase included 10 MSM and 20 FSW. ResultsThe relevance cycle enabled the description of the existing problem, provided the compatible app features for the target population, and identified the need to develop an mHealth app that provides health services in a stigmatizing and discriminating environment. User involvement in the app’s design and evaluation provided an opportunity to incorporate social, cultural, and community-specific features that ensured usability. In addition, the participants suggested valuable information to inform the app, text message services, medication registration, and chat platform designs. ConclusionsThe participatory design approach in the development of mHealth apps is useful in identifying and validating population-specific functional features, improve usability, and ensuring future health impacts. Through this participatory process, the Jichunge app took end-user needs, perspectives, and experiences into account, eliciting enthusiasm regarding its potential role in supporting pre-exposure prophylaxis adherence for HIV and related behavioral change promotion. Trial RegistrationInternational Clinical Trials Registry Platform PACTR202003823226570; https://trialsearch.who.int/Trial2.aspx?TrialID=PACTR202003823226570

Summary: As severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) spreads, variants with enhanced virulence and transmissibility have emerged. Although in vitro systems allow rapid characterization, they do not fully recapitulate the dynamic interaction of virions and neutralizing antibodies in the airway. Here, we demonstrate that the N501Y variant permits respiratory infection in unmodified mice. We utilize N501Y to survey in vivo pseudovirus infection dynamics and susceptibility to reinfection with the L452R (Los Angeles), K417N + E484K (South Africa), and L452R + K417N + E484Q (India) variants. Human coronavirus disease 2019 (COVID-19)+ or vaccinated antibody isotypes, titers, variant receptor binding domain (RBD) binding, and neutralization potential are studied, revealing numerous significant correlations. Immune escape of the K417N + E484K variant is observed because infection can be appreciated in the nasopharynx, but not lungs, of mice transferred with low-antibody-tier plasma. Conversely, near-complete protection is observed in animals receiving high-antibody-tier plasma, a phenomenon that can only be appreciated in vivo.

(1) Background: There is a dearth of data on the levels and determinants of testing for drug-related infectious diseases among people who use drugs (PWUD). We assessed the proportions and determinants of testing for drug-related infectious diseases to inform ongoing interventions for PWUD. (2) Methods: A cross-sectional study involving 599 PWUD was conducted in Dar es Salaam and Tanga between January and February 2019. Data were collected through a researcher-administered questionnaire using handheld tablets. Logistic regression models were used to identify independent testing determinants for drug-related infectious diseases. (3) Results: A majority (98.0%) of participants were males, with a mean age of 36.8 (SD = 7.8) years. 75.0%, 40.6%, 38.6%, and 8.2% reported having ever tested for HIV, tuberculosis (TB), sexually transmitted infections (STIs), and viral hepatitis, respectively. The likelihood of HIV testing was higher among those living with someone (AOR = 2.18, 95% CI: 1.09–4.68) compared with those who were homeless and perceived treatment was appropriate (AOR = 2.18, 95% CI: 1.05–4.46), but was lower among those who experienced mild to moderate (AOR = 0.44, 95% CI: 0.21–0.95) and severe internalized stigma (AOR = 0.44, 95% CI: 0.22–0.94) compared with those reporting no internalized stigma, and among those who experienced financial difficulties resulting from spending on health care services (AOR = 0.60, 95% CI: 0.40–0.89). Perception of treatment appropriateness (AOR = 2.29, 96% CI: 1.10–5.06) and severe enacted stigma (AOR = 1.90, 95% CI: 1.06–3.42) were associated with increased odds of TB testing. The odds of STIs testing increased among those who were married (AOR = 2.31, 95% CI: 1.45–3.72) compared with those who were single and those who had experienced mild (AOR = 2.39, 95% CI: 1.28–4.53) or severe (AOR = 6.20, 95% CI: 1.99–23.83) sexual violence, compared with those who had not experienced sexual violence. However, the odds decreased among those who had been remanded in the past month (AOR = 0.64, 95% CI: 0.43–0.95) compared with those who were not remanded and among those who had financial difficulties resulting from spending on health care services (AOR = 0.66, 95% CI: 0.47–0.94). The likelihood of testing for viral hepatitis testing increased among those who had heard about the comprehensive HIV intervention package (CHIP) (AOR = 2.59, 95% CI: 1.40–4.94); however, it decreased among those who had financial difficulties resulting from spending on health care services (AOR = 0.48, 95% CI: 0.24–0.92). (4) Conclusions: Except for HIV, PWUD had undergone limited testing for drug-related infectious diseases. The study findings highlight some factors influencing testing for the selected infectious diseases investigated, which should be targeted for tailored interventions to improve diagnosis and treatment.

# Background The burden of non-communicable diseases (NCDs), including cancer, in Africa is rising. Policymakers are charged with formulating evidence-based cancer control plans; however, there is a paucity of data on cancers generated from within Africa. As part of efforts to enhance cancer research training in East Africa, we performed a needs assessment and gap analysis of cancer-related research training resources in Tanzania. # Methods A mixed-methods study to evaluate existing individual, institutional, and national resources supporting cancer research training in Tanzania was conducted. Qualitative data were collected using in-depth interviews while quantitative data were collected using self-administered questionnaires and online surveys. The study also included a desk-review of policy and guidelines related to NCD research and training. Study participants were selected to represent five groups: (i) policymakers; (ii) established researchers; (iii) research support personnel; (iv) faculty members in degree training programs; and (v) post-graduate trainees. # Results Our results identified challenges in four thematic areas. First, there is a need for coordination and monitoring of the cancer research agenda at the national level. Second, both faculty and trainees identified the need for incorporation of rigorous training to improve research competencies. Third, sustained mentoring and institutional investment in development of mentorship resources is critical to empowering early career investigators. Finally, academic institutions can enhance research outputs by providing adequate research infrastructure, prioritizing protected time for research, and recognizing research accomplishments by trainees and faculty. # Conclusions As we look towards establishment of cancer research training programs in East Africa, investment in the development of rigorous research training, mentorship resources, and research infrastructure will be critical to empowering local health professionals to engage in cancer research activities.

Background: Fine-needle aspiration biopsy (FNAB) is a minimally invasive, cost-effective diagnostic tool that can be used in low-resource settings. However, adequacy and accuracy of FNAB is highly dependent on the skills of the operator and requires specialized training. Poor technique can preclude definitive diagnoses because of insufficient quality or quantity of FNAB samples. We evaluated the efficacy of an intensive training experience in Tanzania on improving ultrasound-guided FNAB techniques. Methods: A 2-day workshop offered didactic lectures, demonstrations, and hands-on practicum on fundamentals of ultrasound imaging and FNAB technique. A prospective interventional study design was used with pre- and postintervention surveys and assessments to measure the effect of the workshop on specific skills related to slide smearing and ultrasound-guidance among participants. Results: Twenty-six pathologists and radiologists, including trainees in each specialty, participated in the workshop. Pre- and postworkshop assessments demonstrated that most participants improved significantly in nearly all technical skills for slide smearing and ultrasound-guided FNAB. After the workshop, most participants demonstrated substantial improvements in ability to prepare the ultrasound equipment, measure the lesion in three dimensions by ultrasound, target lesions in one pass using both parallel and perpendicular approaches, and prepare high-quality aspirate smears. Conclusion: An in-country 2-day workshop in Tanzania was efficacious in transferring basic skills in FNAB smear preparation and ultrasound-guided FNAB, resulting in skills enhancement among participating pathologists and radiologists. Although mastery of skills was not the goal of this short workshop, participants demonstrated proficiency in most technical elements after workshop completion, and the workshop generated interest among select participants to pursue additional intensive training in cytopathology.

Purpose: Age-standardized incidence rates for esophageal cancer (EC) in East Africa have been reported as disproportionately high compared with the worldwide incidence of nine per 100,000 population. This study aimed to characterize EC cases seen at Muhimbili National Hospital and Ocean Road Cancer Institute in Dar es Salaam, Tanzania. Methods: Demographic, clinical, and treatment variables were abstracted from charts of patients who received care for a diagnosis of EC at one or both institutions between 2011 and 2013. Categorical data were summarized as frequency counts and percentages. Continuous data were presented as medians and ranges. To compare men and women, Pearson’s χ2 and two-sample t tests were applied. Results: Seven hundred thirty-eight unique cases of EC were identified, of whom 68% were men and the median age was 60 years (range, 19 to 95 years). Notably, 93 cases (13%) were ≤ 40 years old at diagnosis. Squamous cell carcinoma was the dominant histology, comprising 90% of cases with documented histopathology. However, 34% of cases with a diagnosis of EC were not pathologically confirmed. The stage was documented as locoregional in 4% of cases, locally advanced in 20% of cases, metastatic in 14% of cases, and unknown in 63% of cases. Of 430 patients who received treatment at Ocean Road Cancer Institute, 76% were treated with radiation, 44% were treated with chemotherapy, 3% underwent a cancer-related surgical procedure, and 10% of cases received no cancer-directed therapy. The median overall survival for all patients was 6.9 months (95% CI, 5.0 to 12.8), regardless of stage at presentation. Conclusion: Between 2011 and 2013, cases of EC represented a large clinical burden at both institutions.

Anaerobic digestion is a well-known technology with wide application in the treatment of high-strength organic wastes. The economic feasibility of this type of installation is usually attained thanks to the availability of fiscal incentives. In this review, an analysis of the different factors associated with this biological treatment and a description of alternatives available in literature for increasing performance of the process were provided. The possible integration of this process into a biorefinery as a way for producing energy and chemical products from the conversion of wastes and biomass also analyzed. The future outlook of anaerobic digestion will be closely linked to circular economy principles. Therefore, this technology should be properly integrated into any production system where energy can be recovered from organics. Digestion can play a major role in any transformation process where by-products need further stabilization or it can be the central core of any waste treatment process, modifying the current scheme by a concatenation of several activities with the aim of increasing the efficiency of the conversion. Thus, current plants dedicated to the treatment of wastewaters, animal manures, or food wastes can become specialized centers for producing bio-energy and green chemicals. However, high installation costs, feedstock dispersion and market distortions were recognized as the main parameters negatively affecting these alternatives.

Methicillin-resistant Staphylococcus aureus (MRSA) among health care workers (HCWs) increases the risk of spreading the organism in hospital settings. A cross-sectional study was conducted between June and October 2016 among HCWs in tertiary and regional hospitals in Dar es Salaam, Tanzania, to determine the MRSA nasal carriage rate. Nasal swabs were collected from HCWs and cultured on mannitol salt agar. S. aureus was identified based on colonial morphology, Gram staining, catalase, coagulase, and DNase test results. MRSA was detected using the cefoxitin disk. Among 379 HCWs enrolled, 157/379 (41.4%) were colonized with S. aureus, of whom 59 (37.6%) were MRSA carriers giving an overall prevalence of 59/379 (15.6%). MRSA carriage was high among HCWs in Temeke (56.9%) and Amana (37.5%) regional hospitals. A high proportion of MRSA carriage was detected among nurses (35, 45.5%). MRSA isolates showed high resistance toward kanamycin (83.7%), gentamicin (83.1%), ciprofloxacin (71.2%), and trimethoprim-sulphamethoxazole (46.8%) compared to methicillin-sensitive S. aureus isolates (p≤0.001). In conclusion, we found a high nasal carriage of MRSA and resistance to commonly prescribed antimicrobial agents among HCWs. Implementation of infection control measures including contact precautions, urgent reporting of MRSA laboratory results, and routine MRSA screening of HCWs is highly needed to reduce MRSA spreading.

Rossella Mazzilli, Norina Imbrogno, Jlenia Elia, Michele Delfino, Olimpia Bitterman, Angela Napoli, Fernando Mazzilli Department of Clinical and Molecular Medicine, Sant'Andrea Hospital, Unit of Diabetology and Endocrinology, University of Rome Sapienza, Rome, Italy Background: The aim of this work was to evaluate the impact of diabetes on female sexuality and to highlight any differences between sexuality in the context of type 1 and type 2 diabetes mellitus (DM). Methods: The subjects selected were 49 women with type 1 DM, 24 women with type 2 DM, and 45 healthy women as controls. Each participant was given the nine-item Female Sexual Function Index questionnaire to complete. The metabolic profile was evaluated by body mass index and glycosylated hemoglobin assay. Results: The prevalence of sexual dysfunction (total score ≤30) was significantly higher in the type 1 DM group (25/49, 51%; 95% confidence interval [CI] 18–31) than in the control group (4/45, 9%; 95% CI 3–5; P=0.00006); there were no significant variations in the type 2 DM group (4/24, 17%; 95% CI 3–4) versus the control group (P=0.630, not statistically significant). The mean total score was significantly lower in the type 1 DM group (30.2±6.9) versus the control group (36.5±4.9; P=0.0003), but there was no significant difference between the type 2 DM group and the control group (P=0.773). With regard to specific questionnaire items, the mean values for arousal, lubrication, dyspareunia, and orgasm were significantly lower only in the type 1 DM group versus the control group. The mean values for desire were reduced in type 1 and type 2 DM groups versus control group. Conclusion: Type 1 DM is associated with sexual dysfunction. This may be due to classic neurovascular complications or to the negative impact of the disease on psychosocial factors. Larger and ideally longitudinal studies are necessary to better understand the relationship between DM and sexual dysfunction. Keywords: diabetes mellitus, female sexuality, Female Sexual Function Index

BackgroundEsophageal squamous cell carcinoma (ESCC) comprises 90% of all esophageal cancer cases globally and is the most common histology in low-resource settings. Eastern Africa has a disproportionately high incidence of ESCC.MethodsWe describe the genomic profiles of 61 ESCC cases from Tanzania and compare them to profiles from an existing cohort of ESCC cases from Malawi. We also provide a comparison to ESCC tumors in The Cancer Genome Atlas (TCGA).ResultsWe observed substantial transcriptional overlap with other squamous histologies via comparison with TCGA PanCan dataset. DNA analysis revealed known mutational patterns, both genome-wide as well as in genes known to be commonly mutated in ESCC. TP53 mutations were the most common somatic mutation in tumors from both Tanzania and Malawi but were detected at lower frequencies than previously reported in ESCC cases from other settings. In a combined analysis, two unique transcriptional clusters were identified: a proliferative/epithelial cluster and an invasive/migrative/mesenchymal cluster. Mutational signature analysis of the Tanzanian cohort revealed common signatures associated with aging and cytidine deaminase activity (APOBEC) and an absence of signature 29, which was previously reported in the Malawi cohort.ConclusionsThis study defines the molecular characteristics of ESCC in Tanzania, and enriches the Eastern African dataset, with findings of overall similarities but also some heterogeneity across two unique sites.ImpactDespite a high burden of ESCC in Eastern Africa, investigations into the genomics in this region are nascent. This represents the largest comprehensive genomic analysis ESCC from sub-Saharan Africa to date.

El objetivo de este trabajo fue evaluar las propiedades psicométricas de la Escala de Activación Conductual para la Depresión (BADS) en una muestra de estudiantes universitarios de México. Para ello se aplicó la escala a 381 estudiantes de una universidad privada. Los resultados evidenciaron que, comparada tanto con la versión original en inglés como con la adaptación española desarrollada en España, es una escala válida y consistente. Las dimensiones del instrumento original se replicaron en el análisis factorial confirmatorio. La validez de criterio y discriminante se contrastó por medio de correlaciones con el BDI-II, que arrojaron puntuaciones de acuerdo con lo esperado tanto para el total de la escala como para las distintas dimensiones. Un análisis de regresión logística ordinal demostró que las puntuaciones de corte del BDI-II (depresión mínima, leve, moderada y severa) predicen adecuadamente las puntuaciones del BADS. Respecto a la consistencia interna, en esta muestra alcanzó un alfa de Cronbach de .89 para el total de la escala y de .77 a .85 para sus dimensiones.

Anaerobic digestion and bioelectrochemical systems have great potential to recover energy from waste streams and help overcome common hurdles associated with this process, as integrated technologies. In this study, the benefit of integrating an electrogen-enriched bioanode in a batch anaerobic digester was explored under ambient temperature conditions associated with organic overloading and reactor acidity. An increase in CH4 production was observed in the electrode-containing reactors (0.56 L CH4 kgVS−1 h−1) in comparison with the conventional anaerobic digester (0.14 L CH4 kgVS−1 h−1) during the initial stages of operation. In addition, the mere presence of electrodes operating in open circuit mode resulted in a delay in volatile fatty acid (VFA) build-up. This seems to be associated with the enhancement in VFA consumption due to biomass proliferation on the electrode surface, rather than on electrochemical activity.

* Context.--Rapid onsite evaluation (ROSE) is critical in determining sample adequacy and triaging cytology samples. Although fine-needle aspiration biopsy (FNAB) is the primary method of initial tissue sampling in Tanzania, ROSE is not practiced. Objective.--To investigate the performance of ROSE in determining cellular adequacy and providing preliminary diagnoses in breast FNAB in a low-resource setting. Design.--Patients with breast masses were recruited prospectively from the FNAB clinic at Muhimbili National Hospital. Each FNAB was evaluated by ROSE for overall specimen adequacy, cellularity, and preliminary diagnosis. The preliminary interpretation was compared to the final cytologic diagnosis and histologic diagnosis, when available. Results.--Fifty FNAB cases were evaluated, and all were adequate for diagnosis on ROSE and final interpretation. Overall percentage of agreement (OPA) between preliminary and final cytologic diagnosis was 84%, positive percentage of agreement (PPA) was 33%, and negative percentage of agreement (NPA) was 100% ([kappa] = 0.4, P Conclusions.--False-positive rates of ROSE diagnoses for breast FNAB are low. While preliminary cytologic diagnoses had a high false-negative rate, final cytologic diagnoses had overall high concordance with histologic diagnoses. Therefore, the role of ROSE for preliminary diagnosis should be considered carefully in low-resource settings, and it may need to be paired with additional interventions to improve pathologic diagnosis. doi: 10.5858/arpa.2022-0398-OA, Breast cancer (BC) is the second leading cause of cancer-related mortality among women in Tanzania, with a majority of patients (63%-84%) presenting with advanced disease. (1-4) Tanzania has a hierarchical [...]

The incidence of esophageal squamous cell carcinoma (ESCC) is disproportionately high in the eastern corridor of Africa and parts of Asia. Emerging research has identified a potential association between poor oral health and ESCC. One possible link between poor oral health and ESCC involves the alteration of the microbiome. We performed an integrated analysis of four independent sequencing efforts of ESCC tumors from patients from high- and low-incidence regions of the world. Using whole genome sequencing (WGS) and RNA sequencing (RNAseq) of ESCC tumors from 61 patients in Tanzania, we identified a community of bacteria, including members of the genera Fusobacterium, Selenomonas, Prevotella, Streptococcus, Porphyromonas, Veillonella and Campylobacter, present at high abundance in ESCC tumors. We then characterized the microbiome of 238 ESCC tumor specimens collected in two additional independent sequencing efforts consisting of patients from other high-ESCC incidence regions (Tanzania, Malawi, Kenya, Iran, China). This analysis revealed similar ESCC-associated bacterial communities in these cancers. Because these genera are traditionally considered members of the oral microbiota, we next explored whether there was a relationship between the synchronous saliva and tumor microbiomes of ESCC patients in Tanzania. Comparative analyses revealed that paired saliva and tumor microbiomes were significantly similar with a specific enrichment of Fusobacterium and Prevotella in the tumor microbiome. Together, these data indicate that cancer-associated oral bacteria are associated with ESCC tumors at the time of diagnosis and support a model in which oral bacteria are present in high abundance in both saliva and tumors of some ESCC patients.

BackgroundEsophageal squamous cell carcinoma (ESCC) is a major cause of cancer morbidity and mortality in Eastern Africa. The majority of patients with ESCC in Eastern Africa present with advanced disease at the time of diagnosis. Several palliative interventions for ESCC are currently in use within the region, including chemotherapy, radiation therapy with and without chemotherapy, and esophageal stenting with self-expandable metallic stents; however, the comparative effectiveness of these interventions in a low resource setting has yet to be examined.MethodsThis prospective, observational, multi-center, open cohort study aims to describe the therapeutic landscape of ESCC in Eastern Africa and investigate the outcomes of different treatment strategies within the region. The 4.5-year study will recruit at a total of six sites in Kenya, Malawi and Tanzania (Ocean Road Cancer Institute and Muhimbili National Hospital in Dar es Salaam, Tanzania; Kilimanjaro Christian Medical Center in Moshi, Tanzania; Tenwek Hospital in Bomet, Kenya; Moi Teaching and Referral Hospital in Eldoret, Kenya; and Kamuzu Central Hospital in Lilongwe, Malawi). Treatment outcomes that will be evaluated include overall survival, quality of life (QOL) and safety. All patients (≥18 years old) who present to participating sites with a histopathologically-confirmed or presumptive clinical diagnosis of ESCC based on endoscopy or barium swallow will be recruited to participate. Key clinical and treatment-related data including standardized QOL metrics will be collected at study enrollment, 1 month following treatment, 3 months following treatment, and thereafter at 3-month intervals until death. Vital status and QOL data will be collected through mobile phone outreach.DiscussionThis study will be the first study to prospectively compare ESCC treatment strategies in Eastern Africa, and the first to investigate QOL benefits associated with different treatments in sub-Saharan Africa. Findings from this study will help define optimal management strategies for ESCC in Eastern Africa and other resource-limited settings and will serve as a benchmark for future research.Trial registrationThis study was retrospectively registered with the ClinicalTrials.gov database on December 15, 2021,  NCT05177393 .

PurposeAge-related cataracts affect the majority of older adults and are a leading cause of blindness worldwide. Treatments that delay cataract onset or severity have the potential to delay cataract surgery, but require relevant animal models that recapitulate the major types of cataracts for their development. Unfortunately, few such models are available. Here, we report the lens phenotypes of aged mice lacking the critical antioxidant transcription factor Nfe2l2 (designated as Nrf2 -/-).MethodsThree independent cohorts of Nrf2 -/- and wild-type C57BL/6J mice were evaluated for cataracts using combinations of slit lamp imaging, photography of freshly dissected lenses, and histology. Mice were fed high glycemic diets, low glycemic diets, regular chow ad libitum, or regular chow with 30% caloric restriction.ResultsNrf2 -/- mice developed significant opacities between 11 and 15 months and developed advanced cortical, posterior subcapsular, anterior subcapsular, and nuclear cataracts. Cataracts occurred similarly in male mice fed high or low glycemic diets, and were also observed in 21-month male and female Nrf2 -/- mice fed ad libitum or 30% caloric restriction. Histological observation of 18-month cataractous lenses revealed significant disruption to fiber cell architecture and the retention of nuclei throughout the cortical region of the lens. However, fiber cell denucleation and initiation of lens differentiation was normal at birth, with the first abnormalities observed at 3 months.ConclusionsNrf2 -/- mice offer a tool to understand how defective antioxidant signaling causes multiple forms of cataract and may be useful for screening drugs to prevent or delay cataractogenesis in susceptible adults.

BACKGROUND:East Africa is one of the fastest growing regions in the world and faces a rising burden of cancer; however, few people are equipped to effectively conduct research in this area. MATERIALS AND METHODS:A 31-item questionnaire was distributed to current trainees and recent graduates of the Master in Medicine in Clinical Oncology Program at Muhimbili University of Health and Allied Sciences in Tanzania. Areas that were assessed included (a) demographic information, (b) prior research training, (c) prior and current research activities, (d) attitudes toward the importance of research, and (e) supports and barriers to inclusion of research in an oncology career path. RESULTS:A total of 30 individuals responded to the survey, of whom 53% (n = 16) were male and 70% (n = 21) identified as current trainees. Among the majority of respondents, attitudes toward research were strongly favorable. Although only 37% (n = 11) reported receiving any formal training in research methodology, 87% (n = 26) reported intentions to incorporate research into their careers. The absence of protected time for research and lack of access to research funding opportunities were identified by a majority of respondents as critical barriers. CONCLUSION:A majority of current or recent oncology trainees in Tanzania desire to incorporate research into their careers, but most also lack adequate training in research methodology and longitudinal mentorship. Our future collaboration will focus on creation of appropriate research training curriculums and fostering an environment that catalyzes interprofessional development and transforms and extends context-specific cancer research in East Africa. IMPLICATIONS FOR PRACTICE:Current and recent oncology trainees in East Africa expressed a high enthusiasm for research, driven by a sense of urgency related to the burden from cancer that the region faces. This highlights the need for cancer research training and mentorship in this setting. This work hypothesizes that African principal investigators can operate effectively if proper attention is given to selection and provision of high-quality foundational didactic training to learn the theory and implementation of research as well as to the development of an environment conducive to mentoring.

PurposeAge-standardized incidence rates for esophageal cancer (EC) in East Africa have been reported as disproportionately high compared with the worldwide incidence of nine per 100,000 population. This study aimed to characterize EC cases seen at Muhimbili National Hospital and Ocean Road Cancer Institute in Dar es Salaam, Tanzania.MethodsDemographic, clinical, and treatment variables were abstracted from charts of patients who received care for a diagnosis of EC at one or both institutions between 2011 and 2013. Categorical data were summarized as frequency counts and percentages. Continuous data were presented as medians and ranges. To compare men and women, Pearson's χ2 and two-sample t tests were applied.ResultsSeven hundred thirty-eight unique cases of EC were identified, of whom 68% were men and the median age was 60 years (range, 19 to 95 years). Notably, 93 cases (13%) were ≤ 40 years old at diagnosis. Squamous cell carcinoma was the dominant histology, comprising 90% of cases with documented histopathology. However, 34% of cases with a diagnosis of EC were not pathologically confirmed. The stage was documented as locoregional in 4% of cases, locally advanced in 20% of cases, metastatic in 14% of cases, and unknown in 63% of cases. Of 430 patients who received treatment at Ocean Road Cancer Institute, 76% were treated with radiation, 44% were treated with chemotherapy, 3% underwent a cancer-related surgical procedure, and 10% of cases received no cancer-directed therapy. The median overall survival for all patients was 6.9 months (95% CI, 5.0 to 12.8), regardless of stage at presentation.ConclusionBetween 2011 and 2013, cases of EC represented a large clinical burden at both institutions.

BackgroundFine-needle aspiration biopsy (FNAB) is a minimally invasive, cost-effective diagnostic tool that can be used in low-resource settings. However, adequacy and accuracy of FNAB is highly dependent on the skills of the operator and requires specialized training. Poor technique can preclude definitive diagnoses because of insufficient quality or quantity of FNAB samples. We evaluated the efficacy of an intensive training experience in Tanzania on improving ultrasound-guided FNAB techniques.MethodsA 2-day workshop offered didactic lectures, demonstrations, and hands-on practicum on fundamentals of ultrasound imaging and FNAB technique. A prospective interventional study design was used with pre- and postintervention surveys and assessments to measure the effect of the workshop on specific skills related to slide smearing and ultrasound-guidance among participants.ResultsTwenty-six pathologists and radiologists, including trainees in each specialty, participated in the workshop. Pre- and postworkshop assessments demonstrated that most participants improved significantly in nearly all technical skills for slide smearing and ultrasound-guided FNAB. After the workshop, most participants demonstrated substantial improvements in ability to prepare the ultrasound equipment, measure the lesion in three dimensions by ultrasound, target lesions in one pass using both parallel and perpendicular approaches, and prepare high-quality aspirate smears.ConclusionAn in-country 2-day workshop in Tanzania was efficacious in transferring basic skills in FNAB smear preparation and ultrasound-guided FNAB, resulting in skills enhancement among participating pathologists and radiologists. Although mastery of skills was not the goal of this short workshop, participants demonstrated proficiency in most technical elements after workshop completion, and the workshop generated interest among select participants to pursue additional intensive training in cytopathology.

Objectives To evaluate the effect of student-volunteer reproductive health educators (RHEs) on frequency of counseling about long acting reversible contraception (LARC) and uptake of more effective contraception. Methods This was a non-randomized intervention study conducted at a resident continuity clinic. Eligible patients were females aged 14-25. Participants met with an RHE during their visit in addition to the standard care team. Patients in the historical group met only with the standard care team. We compared counseling patterns and uptake of more effective contraceptive methods between the baseline historical comparison and intervention groups. Results Nearly all eligible patients in the intervention group received counseling about LARC during their visit, whereas less than half of patients seen in the baseline period received the same counseling. Approximately two-thirds of patients who had no contraceptive method at the beginning of the visit chose to initiate a short- or long-acting method in the intervention group, compared to less than half of patients who were using no method in the baseline group. Conclusions for Practice Integration of student-volunteer RHEs increased the frequency with which patients were counseled about LARC and also increased the number of patients who switched to more effective contraception during their visit compared to patients seen in the same clinic before RHEs were introduced. Student-volunteer RHEs are a potentially cost-effective way to provide comprehensive health education in busy clinical settings., Author(s): M. S. Tschann [sup.1] , J. Elia [sup.1] , J. L. Salcedo [sup.1] Author Affiliations: (1) grid.410445.0, 0000 0001 2188 0957, Department of Obstetrics, Gynecology and Women's Health, John [...]