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Objective The study aim was to evaluate the prevalence and predictors of hypertension among an urban adult population in Mbarara city, Western Uganda. Methods We evaluated blood pressure measurements, social demographic and clinical parameters of adults living in Mbarara city, Uganda. These parameters were extracted from medical records of adults who participated in the Uganda World Kidney Day 2020 health screening activities. A total of 302 adults were evaluated for hypertension using the American College of Cardiology/American Heart Association 2017 (blood pressure threshold 130/80 mmHg) and International Society of Hypertension 2020 guidelines (threshold 140/90 mmHg). Results The mean age of the participants was 42.5 years (standard deviation: 15.1) and majority were male 195/302 (64.6%). Using American College of Cardiology/American Heart Association 2017 guidelines, 156/302 (51.7%) adults were newly diagnosed with hypertension compared to 68/302 (22.5%) newly diagnosed with hypertension using International Society of Hypertension 2020 guidelines. Only 23/302 (7.6%) were on treatment. Based on American College of Cardiology/American Heart Association 2017 guidelines, age ≥40 years and overweight/obesity were statistically significant predictors of hypertension (p Discussion The prevalence of hypertension is high among this urban adult population irrespective of the guidelines used, highlighting the need for hypertension prevention interventions.

Decision-making errors such as present bias (PB) can have important consequences for health behaviors, but have been largely studied in the financial domain. We conducted a mixed-method study on PB in the context of ART adherence among clinic-enrolled adults in Uganda (n = 39). Specifically, we quantified PB by asking about preferences between medication available sooner to minimize headaches versus available later to cure headaches. We describe demographic similarities among PB participants and qualitatively explored how participants reflected on their PB (or absence thereof) in the context of health. Participants reporting PB were predominantly male, single/unmarried, older, had higher levels of education and income and more advanced HIV progression. Three common reasons for more present-biased choices provided were: (1) wanting to avoid pain, (2) wanting to return to work, and (3) fear of one's health worsening if s/he did not address their illness immediately. While PB in the financial domain often suggests that poorer individuals are more likely to prefer immediate rewards over their wealthier counterparts, our results suggest poor health is potentially a driving factor of PB. Further research is needed to build on these finding and inform how programs can frame key messages regarding ART adherence to patients displaying PB.Trial registration: ClinicalTrials.gov identifier: NCT03494777.

Cleidocranial dysplasia (CCD) is an autosomal dominant hereditary disease associated with the gene RUNX2. Disease-specific induced pluripotent stem cells (iPSCs) have emerged as a useful resource to further study human hereditary diseases such as CCD. In this study, we identified a novel CCD-specific RUNX2 mutation and established iPSCs with this mutation. Biopsies were obtained from familial CCD patients and mutation analyses were performed through Sanger sequencing and next generation sequencing. CCD-specific human iPSCs (CCD-hiPSCs) were established and maintained under completely defined serum, feeder, and integration-free condition using a non-integrating replication-defective Sendai virus vector. We identified the novel mutation RUNX2_c.371C>G and successfully established CCD-hiPSCs. The CCD-hiPSCs inherited the same mutation, possessed pluripotency, and showed the ability to differentiate the three germ layers. We concluded that RUNX2_c.371C>G was likely pathogenic because our results, derived from next generation sequencing, are supported by actual clinical evidence, familial tracing, and genetic data. Thus, we concluded that hiPSCs with a novel CCD-specific RUNX2 mutation are viable as a resource for future studies on CCD.

Glioblastoma is a glioma characterized by highly malignant features. Numerous studies conducted on the relationship between glioblastoma and the microenvironment have indicated the significance of tumor-associated macrophages/microglia (TAMs) in glioblastoma progression. Since interleukin (IL)-1β secreted by TAMs has been suggested to promote glioblastoma growth, we attempted to elucidate the detailed mechanisms of IL-1β in glioblastoma growth in this study. A phospho-receptor tyrosine kinase array and RNA-sequencing studies indicated that IL-1β induced the activation of signal transducer and activator of transcription-3 and nuclear factor-kappa B signaling. Glioblastoma cells stimulated by IL-1β induced the production of IL-6 and CXCL8, which synergistically promoted glioblastoma growth via signal transducer and activator of transcription-3 and nuclear factor-kappa B signaling. By immunohistochemistry, IL-1β expression was seen on TAMs, especially in perinecrotic areas. These results suggest that IL-1β might be a useful target molecule for anti-glioblastoma therapy.

People living with HIV (PLWHIV) need family planning (FP) services to avert the spread of HIV and eliminate mother to child transmission (MTCT). Besides, family planning services greatly reduce the incidence of vertical transmission reducing new cases of pediatric infections. The aim of this study was to establish the factors influencing the utilization of FP services among PLWHIV affiliated to The AIDS Service Organization (TASO) Masaka responsible for the unmet need for FP utilization. A cross-sectional study with quantitative data analysis was used. A structured questionnaire was used to collect data in line with the set objectives. Categorical data were presented as frequency percent and continuous data as a mean ±standard deviation. The data were analyzed with the statistical software called Medcalc software v. 19.5.6. Analysis was done using the test of proportion at 95% confidence interval and a P

We previously reported that there was a subgroup of IDH-mutated astrocytomas harboring only 19q-loss showing oligodendroglioma-like morphology and significantly longer overall survival (OS) compared with 19q-intact astrocytomas. The aim of this study was to further explore the biological characteristics of this possible subgroup and obtain insight into the mechanism of their relatively benign clinical behavior. We compared gene expression pattern between five 19q-loss and five 19q-intact IDH-mutated astrocytomas by microarray analysis. By comparing expression levels of genes of 19q-loss astrocytomas to those of 19q-intact astrocytomas, 102 up-regulated genes and 162 down-regulated genes were extracted. The down-regulated genes clustered heavily to 19q and 4p while the up-regulated genes clustered to 4q. It was noteworthy that fibroblast growth factor 1 associated with stem cell maintenance and multiple genes associated with glioma progression were down-regulated in 19q-loss astrocytomas, and these results were validated with the independent TCGA data set. On t-SNE analysis of the 19q-loss astrocytomas with other IDH-mutant glioma subgroups from the TCGA datasets, the expression pattern of the 19q-loss astrocytomas showed no shift toward oligodendrogliomas with 1p/19q codeletion but rather constituted a subgroup of astrocytoma. These findings suggested that 19q-loss in astrocytomas is more likely acquired event rather than an early event in oncogenesis like the 1p/19q-codeletion in oligodendrogliomas, and that the biological features of 19q-loss astrocytomas are possibly related to differentially expressed genes associated with stem cell maintenance and glioma progression.

OBJECTIVE Traumatic brain injury (TBI) is a major cause of mortality and morbidity in Uganda and other low- and middle-income countries (LMICs). Due to the difficulty of long-term in-person follow-up, there is a paucity of literature on longitudinal outcomes of TBI in LMICs. Using a scalable phone-centered survey, this study attempted to investigate factors associated with both mortality and quality of life in Ugandan patients with TBI. METHODS A prospective registry of adult patients with TBI admitted to the neurosurgical ward at Mulago National Referral Hospital was assembled. Long-term follow-up was conducted between 10.4 and 30.5 months after discharge (median 18.6 months). Statistical analyses included univariable and multivariable logistic regression and Cox proportional hazards regression to elucidate factors associated with mortality and long-term recovery. RESULTS A total of 1274 adult patients with TBI were included, of whom 302 (23.7%) died as inpatients. Patients who died as inpatients received surgery less frequently (p < 0.001), had more severe TBI at presentation (p < 0.001), were older (p < 0.001), and were more likely to be female (p < 0.0001). Patients presenting with TBI resulting from assault were at reduced risk of inpatient death compared with those presenting with TBI caused by road traffic accidents (OR 0.362, 95% CI 0.128–0.933). Inpatient mortality and postdischarge mortality prior to follow-up were 23.7% and 9%, respectively. Of those discharged, 60.8% were reached through phone interviews. Higher Glasgow Coma Scale score at discharge (continuous HR 0.71, 95% CI 0.53–0.94) was associated with improved long-term survival. Tracheostomy (HR 4.38, 95% CI 1.05–16.7) and older age (continuous HR 1.03, 95% CI 1.009–1.05) were associated with poor long-term outcomes. More than 15% of patients continued to suffer from TBI sequelae years after the initial injury, including seizures (6.1%) and depression (10.0%). Despite more than 60% of patients seeking follow-up healthcare visits, mortality was still 9% among discharged patients, suggesting a need for improved longitudinal care to monitor recovery progress. CONCLUSIONS Inpatient and postdischarge mortality remain high following admission to Uganda’s main tertiary hospital with the diagnosis of TBI. Furthermore, posttraumatic sequelae, including seizures and depression, continue to burden patients years after discharge. Effective scalable solutions, including phone interviews, are needed to elucidate and address factors limiting in-hospital capacity and access to follow-up healthcare.

Introduction: Malaria remains the world’s leading vector-born cause of mortality and morbidity, and Eastern Uganda contains some of the country’s highest prevalence rates. Though academic societies, such as universities, may be prone to high malaria transmission, the extent of the burden and risk factors in university communities of Eastern Uganda are poorly understood. The aim in this study was to examine malaria prevalence, preventive strategies, and risk factors, among University communities in Eastern Uganda; to inform targeted malaria eradication efforts in academic settings. Methods: A mixed methods approach was applied. A case study of Islamic University in Uganda (IUIU), located in Eastern Uganda, was selected. A retrospective approach was used to determine malaria prevalence in IUIU from August to December 2019. Stratified random sampling was used to select IUIU community members; these were subjected to semi-structured questionnaires and Key informant Interviews (KII) to examine the preventive approaches and risk factors. An observational survey was also conducted to identify barriers to malaria prevention. Data was analyzed using descriptive statistics, graphs, Chi-square, and pictures; with STATA version-15.0. Results: The study involved 255 respondents (204, 80% students, 51, 20% staff); 130, 51% were males, 125, 49% were females. Malaria prevalence was; 12.9%, 11.7% and 12.7% for students, staff, and the general study population respectively. Lowest prevalence was registered in November (8.3% for students, 0% for staff), and the highest in December (18.4% for students, 6.7% for staff). Overall malaria prevalence in IUIU was significantly greater than Uganda’s national prevalence (χ2=182.009; p

Background Carbon monoxide causes electrical, functional, and morphological changes in the heart. It is unclear, however, whether the indicators of myocardial damage can predict the patient’s prognosis after carbon monoxide poisoning. This retrospective study aimed to investigate the relationship between the carboxyhemoglobin level and electrocardiographic (ECG) changes and whether the ECG changes and troponin I levels are related to the patient’s prognosis after carbon monoxide poisoning. Methods Carboxyhemoglobin, troponin I, and ECG parameters were measured in 70 patients with carbon monoxide poisoning. The QT and RR intervals were measured for each ECG lead in all patients, and the corrected QT interval and corrected QT dispersion were calculated. Results The correlation between the maximum corrected QT interval and the carboxyhemoglobin level was significant (P = 0.0072, R2 = 0.1017), as were the relationships between QT dispersion and carboxyhemoglobin (P R2 = 0.2358) and the corrected QT dispersion and carboxyhemoglobin (P R2 = 0.2613). The multivariate logistic analysis showed that the significant predictors of sequential disability were corrected QT dispersion (P = 0.0042), and troponin I level (P = 0.0021). Conclusions Patients’ prognosis following carbon monoxide poisoning can be predicted based on corrected QT dispersion and the troponin I level. Patients with myocardial damage should be monitored not only for their cardiovascular outcome but also for their neurological outcome and their prognosis.

Objective We describe a case of intracranial and extracranial multiple arterial dissecting aneurysms in rheumatoid arthritis (RA). Case Presentation A 29-year-old man with a medical history of RA since 18 years of age was admitted to our hospital for vomiting, dysarthria, and conscious disturbance. At 23, he underwent ligation of the left internal carotid artery (ICA) with superficial temporal artery to middle cerebral artery anastomosis because of acute infarct of the left hemisphere caused by arterial dissection of the left ICA. During the current admission, computed tomography (CT) revealed subarachnoid hemorrhage, and digital subtraction angiography (DSA) demonstrated dissecting aneurysms of the left intracranial vertebral artery (VA) and right extracranial VA. We diagnosed him with a ruptured dissecting aneurysm of the left intracranial VA and performed endovascular parent artery occlusion on the left VA. For the right unruptured VA aneurysm, we performed coil embolization simultaneously. At 2 weeks after the endovascular treatment, follow-up DSA revealed that multiple de novo dissecting aneurysms developed on the origin of the left VA and left and right internal thoracic arteries. Those aneurysms were treated with coil embolization. Other remaining aneurysms on the left thyrocervical trunk, right transverse cervical artery, and both common iliac arteries were treated by conservative therapy. While continuing medical treatment for RA, the patient recovered and was discharged to a rehabilitation hospital. Conclusion Considering that RA-induced vasculitis can be a potential risk of vascular complications including multiple arterial dissections, physicians should carefully perform endovascular interventional procedures for patients with long-term RA.

Erdheim-Chester disease (ECD) is a non-Langerhans form of histiocytosis that occurs in systemic organs, such as bone, the central nervous system, cardiovascular system, lungs, and kidneys. We report the case of a 68-year-old woman with a cranial pharyngeal tumor and a bone lesion in the tibia. The case was diagnosed as ECD. Pathological analysis showed the typical feature of foamy macrophage accumulation. The macrophages were positive for CD68, and negative for CD1a and S100. The BRAF V600E mutation was identified. In addition, immunohistochemistry was performed for the detailed characterization of the macrophages. The macrophages had low proliferative activity and an M2-like phenotype, and they expressed colony-stimulating factor-1 receptor (CSF1R) on the cell surface.

Background Following initiation of MDR-TB treatment, patients have a choice to receive follow up DOT supervision at either the central initiating facility or at a peripheral facility. Objectives We describe the adherence patterns of MDR-TB patients undergoing DOT supervision at the two health facility categories during intensive phase of treatment. Methods We used a retrospective cohort of patients initiated on MDR TB treatment at Mulago National Referral Hospital between 2014 and 2016. We extracted data from the National Tuberculosis and Leprosy Program records and analysed these using STATA V14. Result Majority (84.01%) of the patients received their DOT supervision from the peripheral facilities. Males made up 62.1% of patients, and 91.2% had had their household contacts screened for MDR-TB. 26.5% of the patients on peripheral DOT supervision had good adherence to treatment protocol compared to 0% among patients on central initiating health facility DOT supervision. Among the patients with good adherence, 24.1% had contacts screened for MDR-TB as compared to 3.6% with poor adherence. Conclusion More patients preferred MDR-TB DOT supervision at peripheral facilities, which had better adherence to the treatment protocol compared to the central initiating facility. Younger people and those with household contacts screened had better adherence to the treatment protocol, highlighting areas for targeted interventional programs for MDR-TB in resource limited settingsMore patients preferred MDR-TB DOT supervision at peripheral facilities, which had better adherence to the treatment protocol compared to the central initiating facility. Younger people and those with household contacts screened had better adherence to the treatment protocol, highlighting areas for targeted interventional programs for MDR-TB in resource limited settings.

Background and Aims: Children in contact with adults having pulmonary Tuberculosis (TB) are vulnerable to TB infection and hence contact tracing and screening is important for early detection of infection. However, there are few contacts traced and the prevalence and risk factors for transmission are not well studied. The objective of this study was to determine the prevalence of infection and risk factors associated with TB transmission among under five children in household contact with adult pulmonary TB patients. Materials and Methods: A cross sectional study was carried out in three health facilities with a high TB burden in Mbale District, Eastern Uganda involving all under five household contacts of adults with pulmonary tuberculosis recorded in the TB register from October 2018 to March 2019 and still on treatment. Structured questionnaires were administered to the index clients to obtain their demographic and clinical data about TB, HIV as well as information on the children. Children were screened using the intensive case finding forms to identify presumptive cases. Results: The total number of index TB Clients line listed were 70. Number of clients traced was 38, 21 (%) of whom had children under five years and a total of 33 children were identified. The number of presumptive cases was 9/33 (27.27%). 77.8% of the presumptive cases were living in poorly ventilated houses. Conclusion: The study identified children with presumptive TB and various risk factors for TB transmission. Intensive contact tracing can therefore help reduce TB transmission within the communities. It is recommended to undertake studies aiming at improving contact tracing and strategies to eliminate the risk factors to TB transmission.

This study aimed to explore the genetic alterations and to identify good responders in the experimental arm in the tumor samples from newly diagnosed glioblastoma (GBM) patients enrolled in JCOG0911; a randomized phase II trial was conducted to compare the efficacy of interferonβ (IFNβ) plus temozolomide (TMZ) with that of TMZ alone. Of 122 tumors, we performed deep targeted sequencing to determine the somatic mutations, copy number variations, and tumor mutation burden; pyrosequencing for O6-methylguanine-DNA methyltransferase (MGMT) promoter methylation; Sanger sequencing for the telomerase reverse transcriptase (TERT) promoter; and microsatellite instability (MSI) testing in 95, 91, 91 and 72 tumors, respectively. We performed a multivariable Cox regression analysis using backward stepwise selection of variables including clinical factors (sex, age, performance status, residual tumor after resection, tumor location) and genetic alterations. Deep sequencing detected an IDH1 mutation in 13 tumors (14%). The MGMT promoter methylation by quantitative pyrosequencing was observed in 41% of the tumors. A mutation in the TERT promoter was observed in 69% of the tumors. While high tumor mutation burden (> 10 mutations per megabase) was seen in four tumors, none of the tumors displayed MSI-high. The clinical and genetic factors considered as independent favorable prognostic factors were gross total resection (hazard ratio [HR]: 0.49, 95% confidence interval, 0.30–0.81, P = 0.0049) and MGMT promoter methylation (HR: 0.43, 0.21–0.88, P = 0.023). However, tumor location at the temporal lobe (HR: 1.90, 1.22–2.95, P = 0.0046) was an independent unfavorable prognostic factor. No predictive factors specific to the TMZ + IFNβ + Radiotherapy (RT) group were found. This additional sub-analytical study of JCOG0911 among patients with newly diagnosed GBM showed that tumor location at the temporal lobe, gross total resection, and MGMT promoter methylation were significant prognostic factors, although no factors specific to IFNβ addition were identified.

Glioblastoma multiforme (GBM), a lethal brain tumor developing in the white matter of the adult brain, contains a small population of GBM stem cells (GSCs), which potentially cause chemotherapeutic resistance and tumor recurrence. However, the mechanisms underlying the pathogenesis and maintenance of GSCs remain largely unknown. A recent study reported that incorporation of ribosomes and ribosomal proteins into somatic cells promoted lineage trans‐differentiation toward multipotency. This study aimed to investigate the mechanism underlying stemness acquisition in GBM cells by focusing on 40S ribosomal protein S6 (RPS6). RPS6 was significantly upregulated in high‐grade glioma and localized at perivascular, perinecrotic, and border niches in GBM tissues. siRNA‐mediated RPS6 knock‐down significantly suppressed the characteristics of GSCs, including their tumorsphere potential and GSC marker expression; STAT3 was downregulated in GBM cells. RPS6 overexpression enhanced the tumorsphere potential of GSCs and these effects were attenuated by STAT3 inhibitor (AG490). Moreover, RPS6 expression was significantly correlated with SOX2 expression in different glioma grades. Immunohistochemistry data herein indicated that RPS6 was predominant in GSC niches, concurrent with the data from IVY GAP databases. Furthermore, RPS6 and other ribosomal proteins were upregulated in GSC‐predominant areas in this database. The present results indicate that, in GSC niches, ribosomal proteins play crucial roles in the development and maintenance of GSCs and are clinically associated with chemoradioresistance and GBM recurrence., We evaluated ribosomal protein S6 (RPS6) that has important roles in developing glioblastoma stem‐like cells. RPS6‐positive cells were highly expressed in glioblastoma stem‐like cell dominant areas. Also, we tested the RPS6 regulated stem cell properties of glioblastoma stem‐like cells. These findings are a break‐through in targeting therapy for ribosomal proteins to downregulate stem cell properties in glioblastoma.

Spinal arteriovenous (AV) shunts are rare conditions that sometimes present with myelopathy symptoms. The progression of the symptoms is usually gradual; however, some cases show rapid deterioration. We retrospectively investigated the factors that induced the rapid deterioration of myelopathy symptoms in patients with spinal AV shunts. We treated 33 patients with myelopathy with spinal AV shunts at our institutions, eight of whom experienced rapid deterioration (within 24 hours: 24.2%). Of these, three were related to the body movement or particular postures associated with playing golf, 30 minutes of Japanese straight sitting, and massage care. One patient showed deterioration after embolization for a tracheal aneurysm. The remaining four patients received steroid pulse therapy (high-dose steroid infusion) shortly before the rapid deterioration. These symptoms stopped progressing after cessation of steroid use. While positional or physical factors contributing to myelopathy deterioration might exist, we could not identify specific factors in this study. Nevertheless, rapid deterioration was frequently observed after high-dose steroid use. We must take care not to administer high-dose steroids for myelopathy caused by spinal AV shunt disease.

Background Central nervous system (CNS) germ cell tumors (GCTs) are neoplasms predominantly arising in pediatric and young adult populations. While germinomas generally respond to chemotherapy and radiation, non-germinomatous GCTs (NGGCTs) require more intensive treatment. This study aimed to determine whether 12p gain could predict the prognosis of CNS GCTs. Methods Eighty-two CNS GCTs were included in this study. The 12p gain was defined by an additional 12p in the background of potential polyploidy or polysomy. Cases were analyzed using an Illumina methylation 450K array for copy number investigations and validated by fluorescence in situ hybridization (FISH). Results A 12p gain was found in 25-out-of-82 cases (30%) and was more frequent in NGGCTs (12% of germinoma cases and 50% of NGGCT cases), particularly in cases with malignant components, such as immature teratoma, yolk sac tumor, choriocarcinoma, and embryonal carcinoma. 12p gain and KIT mutation were mutually exclusive events. The presence of 12p gain correlated with shorter progression-free (PFS) and overall survival (OS) (10-year OS: 59% vs. 94%, with and without 12p gain, respectively, P = 0.0002), even with histology and tumor markers incorporated in the multivariate analysis. Among NGGCTs, 12p gain still had prognostic significance for PFS and OS (10-year OS: 47% vs. 90%, respectively, P = 0.02). The 12p copy number status was shared among histological components in mixed GCTs. Conclusions 12p gain may predict the presence of malignant components of NGGCTs, and poor prognosis of the patients. It may be associated with early tumorigenesis of CNS GCT.

Background Gender differences among patients with drug resistant tuberculosis (DRTB) and HIV co-infection could affect treatment outcomes. We compared characteristics and treatment outcomes of DRTB/HIV co-infected men and women in Uganda. Methods We conducted a retrospective chart review of patients with DRTB from 16 treatment sites in Uganda. Eligible patients were aged ≥ 18 years, had confirmed DRTB, HIV co-infection and a treatment outcome registered between 2013 and 2019. We compared socio-demographic and clinical characteristics and tuberculosis treatment outcomes between men and women. Potential predictors of mortality were determined by cox proportional hazard regression analysis that controlled for gender. Statistical significance was set at p Results Of 666 DRTB/HIV co-infected patients, 401 (60.2%) were men. The median (IQR) age of men and women was 37.0 (13.0) and 34.0 (13.0) years respectively (p 3 increment). Conclusion Mortality was higher among men than women with DRTB/HIV co-infection which could be explained by several sociodemographic and clinical differences.

Background Germinoma preferentially occurs in pediatric and young adult age groups. Although they are responsive to treatment with chemotherapy and radiation, the treatment may cause long-term sequelae in their later lives. Here, we searched for clinical and histopathological features to predict the prognosis of germinoma and affect treatment response. Methods A total of 114 germinoma cases were included in the analysis. We investigated the association between clinical factors, tumor cell content, and progression-free survival (PFS). Results The tumor cell content was widely distributed from Conclusions We found that tumor cell content significantly affected the prognosis of germinomas. Although validation of these results using an independent and larger cohort is necessary, this potentially opens the possibility of leveraging this pathological factor in future clinical trials when stratifying the treatment intensity.

Background The epidemiology of hepatitis B virus (HBV) in the general population in east Africa is not well documented. In this meta-analysis, we examined 37 full published research articles to synthesise up-to-date data on the prevalence and predictors of the HBV burden for the effective prevention and management of the virus in our region. Methods We examined 37 full published research articles found using PubMed, Scopus, African Journal Online (AJOL), and Google Scholar between May and October 2020. Dichotomous data on HBV prevalence and predictors of infection were extracted from the individual studies. The HBV prevalence, test of proportion, relative risk, and I2 statistics for heterogeneity were calculated using MedCalc software version 19.1.3. Begg’s tests was used to test for publication bias. Sources of heterogeneity were analysed through sensitivity analysis, meta-regression, and sub-group analysis at 95% CI. P Results The prevalence of HBV was generally high (6.025%), with publications from Kenya (8.54%), Uganda (8.454%) and those from between 2011 and 2015 (8.759%) reporting the highest prevalence (P P P > 0.05). Omitting the study with the largest sample size slightly increased pooled HBV prevalence to 6.149%, suggesting that the studies are robust. Begg’s test showed no evidence of publication bias for overall meta-analysis (p > 0.05). Conclusion The burden of HBV is still high, with the male sex, blood transfusion, body scarification, and HIV seropositivity being potential predictors of infection. Thus, it is important to scale up control and prevention measures targeting persons at high risk.

Background Many HIV-positive patients do not appropriately adhere to their antiretroviral medication (ART). This leads to higher viral loads and greater probability of HIV transmission. Present bias—a tendency to give in to short-term temptations at the expense of long-term outcomes—is a potential driver of low adherence. In this study we test a novel intervention rooted in behavioral economics that is designed to overcome present bias and increase ART adherence. Methods/design We will enroll 330 HIV-positive patients at Mildmay Hospital in Kampala, Uganda, into a 2-year randomized controlled trial. Participants will be randomized to one of three groups. The first intervention group (T1, n = 110) will be eligible for small lottery prizes based on timely clinic visits and demonstration of viral suppression. Group 2 (T2, n = 110) will be eligible for the same lottery prizes conditional on high adherence measured by a medication event management system (MEMS) cap. The control group (n = 110) will receive the usual standard of care. Adherence will be measured continuously throughout the intervention period and for 12 months post-intervention to evaluate effect persistence. Surveys will be conducted at baseline and then every 6 months. Viral loads will be measured annually. Primary outcomes are whether the viral load is detectable and MEMS-measured adherence. Secondary outcomes are the log-transformed viral load as a continuous measure and a binary measure for whether the person took at least 90% of their ART pills. Discussion Our study is one of the first to investigate the effectiveness of lottery incentives for improving ART adherence, and in addition, it compares the relative efficacy of using electronically measured adherence versus viral load to determine lottery eligibility. MEMS caps are relatively costly, whereas viral load testing is now part of routine clinical care in Uganda. BEST will test whether directly incentivizing viral suppression (which can be implemented using readily available clinic data) is as effective as incentivizing electronically measured adherence. Cost-effectiveness analyses of the two implementation modes will also be performed. Trial registration ClinicalTrials.gov, NCT03494777. Registered on 11 April 2018.

As a result of rapid progress in genome medicine technologies, such as the evolution of DNA sequencing and the development of molecular targeted drugs, the era of precision cancer medicine has begun. In 2019, a nationwide genome medicine system was established and cancer gene panel sequencing began being covered by national health insurance in Japan. However, patients with brain tumors have not benefited much from genome medicine, even though gliomas contain many potential molecular targets, such as alterations in EGFR, IDH1/2, BRAF, and Histone H3K27. Targeted therapies for these molecules are currently under enthusiastic development; however, such attempts have not yet achieved remarkable success. To date, only a limited number of targeted drugs for brain tumors such as immune checkpoint, neurotrophic tyrosine receptor kinase (NTRK), and Bruton tyrosine kinase (BTK) inhibitors are available, and only in limited cases. Several obstacles remain in the development of drugs to treat brain tumors, including the difficulties in conducting clinical trials because of the relatively rare incidence and in drug delivery through the blood-brain barrier (BBB). Furthermore, general problems for numerous types of cancer, such as tumor heterogeneity, also exist for brain tumors. We hope that overcoming these issues could enable precision genome medicine to be more beneficial for patients with brain tumors such as malignant gliomas. In addition, careful consideration of ethical, legal, and social issues (ELSIs) is important as it is indispensable for maintaining good relationships with patients, which is one of the keys for genome medicine promotion.

Maffucci syndrome (MS) and Ollier disease (OD) are nonhereditary congenital diseases characterized by multiple enchondromas and/or chondrosarcomas. Recent studies have implicated somatic mosaic mutations of isocitrate dehydrogenase 1 or 2 (IDH1/2) as contributing to the pathogenesis of MS and OD. Occasionally, patients with these disorders may also present with central nervous system (CNS) tumors; however, detailed genetic analyses are limited. In this article, the authors report on a male patient with MS, harboring three CNS tumors that share a common genetic alteration. Over a 9-year period, three separate tumor resections were conducted for sellar, intraparenchymal brainstem, and osseous clival tumors. The histopathological diagnoses were pituitary adenoma, diffuse astrocytoma, and chondrosarcoma, respectively. Sanger sequencing revealed a common IDH1 R132C mutation among all three CNS tumors but not in blood DNA. Administering chemotherapy (nimustine) and subsequent radiation therapy to the brainstem glioma and the residual lesion in the clivus have kept the patient progression free for 18 months. This is the first report demonstrating an IDH1 mutation shared among three different CNS tumors in a single patient with MS. The findings support the hypothesis that in MS and OD, a single common IDH1 mutation triggers tumorigenesis in cells of different origins and locations in a somatic mosaic fashion.

The poor prognosis of subarachnoid hemorrhage (SAH) might be associated with sympathetic nerve activation (catecholamine surge) initiated by hypothalamic injury. As renal denervation (RD) has been shown to exert protective effects on cardiovascular dysfunction by suppressing increased central sympathetic nerve activation, we examined whether RD improved the experimental SAH prognosis in this study. Two hundred thirty-eight male Sprague-Dawley rats were divided into sham-operated and SAH-operated groups, and then each rat was further separated into Sham-operated and RD-operated groups. Bilateral RD was performed approximately 45 min after SAH induction. We examined the effect of RD on early brain injury (EBI) and delayed cerebral ischemia (DCI) as a primary endpoint, and also explored the effect on cerebral vasospasm (CVS) as a secondary endpoint. Although RD did not exert significant effects on primary endpoint, RD significantly prevented CVS and reduced SAH-induced increases in the number of phosphorylated extracellular signal-regulated kinase (ERK)-positive endothelial cells, cyclooxygenase-2 expression, and macrophage infiltration in major cerebral arteries. Moreover, RD significantly decreased the areas displaying dopamine β-hydroxylase and glial fibrillary acidic protein immunopositivity in the paraventricular nucleus of the hypothalamus and serum angiotensin II levels, all of which were increased by SAH. Although RD decreased systolic blood pressure, significant changes in cerebral blood flow were not observed compared with SAH + Sham group. Based on the findings, RD improved CVS by reducing endothelial cell damage and the effects were associated with the stabilization of central sympathetic nerve activation in a SAH model.

Although Alzheimer's disease (AD) is associated with an increased risk of intracerebral hemorrhage (ICH) caused by hypertension and cerebral amyloid angiopathy, the precise clinical course after hypertensive ICH in AD patients is still unknown. In this study, we investigated how striatal ICH, a frequent site for hypertensive ICH, affected the prognosis of AD. We employed 17- and 18-month-old male 5XFAD (5X) mice and littermate (LT) controls, and striatal ICH was induced by collagenase injection. First, to address the acute effects of ICH on 5X mice, hemorrhagic volume and brain edema were evaluated 3 days after ICH. Next, to address the long-term effects of ICH on 5X mice, morbidity, mortality, neurological function (beam-walking and rotarod tests), and cognitive function (Y-maze and nest-building tests) were monitored. Twenty-eight days later, the animals were euthanized, their brains were isolated, and the cytotoxic alterations were investigated. The results revealed that the acute effects of ICH were not significantly different between 5X and LT mice. In contrast, 5X mice showed significantly higher morbidity and mortality in response to ICH, as well as delayed neurological function recovery, compared to LT mice through 28 days. ICH did not affect cognitive function in either group. Infiltrated macrophages in the perihemorrhagic cortex, gp91phox , p67phox , and COX-2 were significantly increased in 5X mice in response to ICH. We demonstrated that striatal ICH deteriorated prognosis and delayed neurofunctional recovery in 5X mice, which might be associated with enhanced oxidative stress in the presence of AD-like pathology.

Summary 2-Methylthio-N6-isopentenyl modification of adenosine (ms2i6A) is an evolutionally conserved modification found in mitochondrial (mt)-tRNAs. Cdk5 regulatory subunit-associated protein 1 (CDK5RAP1) specifically converts N6-isopentenyladenosine (i6A) to ms2i6A at position A37 of four mt-DNA-encoded tRNAs, and the modification regulates efficient mitochondrial translation and energy metabolism in mammals. Here, we report that the ms2 conversion mediated by CDK5RAP1 in mt-tRNAs is required to sustain glioma-initiating cell (GIC)-related traits. CDK5RAP1 maintained the self-renewal capacity, undifferentiated state, and tumorigenic potential of GICs. This regulation was not related to the translational control of mt-proteins. CDK5RAP1 abrogated the antitumor effect of i6A by converting i6A to ms2i6A and protected GICs from excessive autophagy triggered by i6A. The elevated activity of CDK5RAP1 contributed to the amelioration of the tumor-suppressive effect of i6A and promoted GIC maintenance. This work demonstrates that CDK5RAP1 is crucial for the detoxification of endogenous i6A and that GICs readily utilize this mechanism for survival., Graphical Abstract, Highlights • CDK5RAP1 is required to sustain the growth of GICs through ms2 modification of i6A • Deficit of CDK5RAP1 inhibits the growth of GIC through i6A accumulation • CDK5RAP1 detoxifies i6A by conversion into ms2i6A in the mitochondria of GICs • Mitochondria serve as antidotal machinery against i6A in GICs, Biological Sciences; Molecular Biology; Cell Biology; Stem Cells Res earch; Cancer

A series of recent evidences suggested activated macrophages have broadly two distinct forms that possess opposite functions for the process of inflammation: classically activated macrophages (M1/kill macrophages) and alternatively activated macrophages (M2/repair macrophages) according to their functions and expression markers. To elucidate what roles those two phenotypes of macrophages play in the evolution of cerebral aneurysm, the presence of macrophages inside the aneurysm walls was assessed with an immunohistochemical approach. The portions of the aneurysm domes deflated after neck clipping were utilized for the further histological examinations, including immunostainings with five antibodies to identify macrophage subpopulations. In this study, contrary to the previous reports, the following various ratios of subtypes were observed in the aneurysm walls: M1 M2 (2 cases), M1 M2 (2 cases), M1 = M2 (3 cases). While M1-like macrophages have been typically regarded as a main driver of the degenerating process, these surprisingly richer presences of M2-like macrophages in the aneurysm walls suggests that an unrecognized biological process might be in play in aneurysm development.

Background Uganda has one of the largest unmet neurosurgical needs in the world, but has seen major improvements in neurosurgery—largely centered at Mulago National Referral Hospital (MNRH). This study implements the first long-term follow-up and outcomes analysis of central nervous system tumor patients in Uganda. Methods Inpatient data were collected using a prospective database of patients presenting to the MNRH neurosurgical ward between 2014 and 2015. Follow-up health care status was assessed in the patient's language using phone surveys. Analysis was performed to identify which factors were associated with patient outcomes. Results The MNRH neurosurgical ward saw 112 patients with central nervous system tumors (adult N = 87, female: 70%, median age: 37 years). Meningiomas (21%) comprised the most common tumor diagnosis. In-hospital mortality (18%), 30-day mortality (22%), and 1-year mortality (35%) were high. Thirty percent of patients underwent tumor resection in-patient and had greater median overall survival (66.5 months vs. 5.1 months for nonsurgical patients, P = 0.025). For those with known pathologic diagnoses, patients with glioblastomas had decreased median overall survival (0.83 months vs. 59 months for meningiomas, P = 0.02). Phone interviews yielded an 85% response rate. Of the survivors at the time of follow-up, 55% reported a subjective return to normalcy, and 75% received follow-up care for their tumor with most returning to MNRH. Conclusions We show evidence for improved overall survival with surgical care at MNRH. In addition, phone interviews as a method of measuring health outcomes provided an effective means of follow-up, showing that most patients do seek follow-up care.

Aims Alterations in microenvironments are a hallmark of cancer, and these alterations in germinomas are of particular significance. Germinoma, the most common subtype of central nervous system germ cell tumours, often exhibits massive immune cell infiltration intermingled with tumour cells. The role of these immune cells in germinoma, however, remains unknown. Methods We investigated the cellular constituents of immune microenvironments and their clinical impacts on prognosis in 100 germinoma cases. Results Patients with germinomas lower in tumour cell content (i.e. higher immune cell infiltration) had a significantly longer progression-free survival time than those with higher tumour cell contents (P = 0.03). Transcriptome analyses and RNA in-situ hybridization indicated that infiltrating immune cells comprised a wide variety of cell types, including lymphocytes and myelocyte-lineage cells. High expression of CD4 was significantly associated with good prognosis, whereas elevated nitric oxide synthase 2 was associated with poor prognosis. PD1 (PDCD1) was expressed by immune cells present in most germinomas (93.8%), and PD-L1 (CD274) expression was found in tumour cells in the majority of germinomas examined (73.5%). Conclusions The collective data strongly suggest that infiltrating immune cells play an important role in predicting treatment response. Further investigation should lead to additional categorization of germinoma to safely reduce treatment intensity depending on tumour/immune cell balance and to develop possible future immunotherapies.

Neurofibromatosis type 1 (NF1) is a rare disease with an incidence of approximately one in every 3000 births. NF1 is mainly recognized as a tumor suppressor. Vasculopathy in NF1 is well described in the literature, but the association between NF1 and cerebral aneurysm has not been determined. We report a case of a 67-year-old female with NF1 accompanied by 8 cerebral aneurysms. Two of the patient's unruptured aneurysms, the large distal anterior cerebral artery (ACA) aneurysm and anterior communicating artery aneurysm, were initially treated with microsurgical clipping. The peripheral ACA aneurysm gradually increased in size and ruptured after 5 years. Coil embolization was performed for the ruptured aneurysm. Four of the 5 remaining unruptured aneurysms were treated surgically. The patient is currently well, without neurological deficit, and coil embolization is scheduled for the last remaining aneurysm. NF1 is a probable risk factor for multiple cerebral aneurysms due to vessel wall vulnerability. Therapeutic indications for patients with NF1 who show multiple cerebral aneurysms include strict follow-up and aggressive treatment to avoid subarachnoid hemorrhage.

Glioblastoma is one of the most devastating human malignancies for which a novel efficient treatment is urgently required. This pre–clinical study shows that eribulin, a specific inhibitor of telomerase reverse transcriptase (TERT)‐RNA‐dependent RNA polymerase, is an effective anticancer agent against glioblastoma. Eribulin inhibited the growth of 4 TERT promoter mutation‐harboring glioblastoma cell lines in vitro at subnanomolar concentrations. In addition, it suppressed the growth of glioblastoma cells transplanted subcutaneously or intracerebrally into mice, and significantly prolonged the survival of mice harboring brain tumors at a clinically equivalent dose. A pharmacokinetics study showed that eribulin quickly penetrated brain tumors and remained at a high concentration even when it was washed away from plasma, kidney or liver 24 hours after intravenous injection. Moreover, a matrix‐assisted laser desorption/ionization mass spectrometry imaging analysis revealed that intraperitoneally injected eribulin penetrated the brain tumor and was distributed evenly within the tumor mass at 1 hour after the injection whereas only very low levels of eribulin were detected in surrounding normal brain. Eribulin is an FDA‐approved drug for refractory breast cancer and can be safely repositioned for treatment of glioblastoma patients. Thus, our results suggest that eribulin may serve as a novel therapeutic option for glioblastoma. Based on these data, an investigator‐initiated registration‐directed clinical trial to evaluate the safety and efficacy of eribulin in patients with recurrent GBM (UMIN000030359) has been initiated.

Background Sixth-nerve palsy often develops as a result of trauma, neoplasm, or vascular disease affecting the pons. Less commonly, this palsy can be caused by pathology of the internal carotid artery in the cavernous sinus region. Here, we describe a rare case of spontaneous dissection of the internal carotid artery in the cavernous sinus accompanied by acute sixth nerve palsy that was successfully treated with surgery. Case Description An 18-year-old man presented suddenly and spontaneously with isolated abducent nerve palsy. His magnetic resonance angiography identified a dissection of the right internal carotid artery in the cavernous sinus. We successfully treated it with high-flow bypass and ligation of the internal carotid artery (ICA). Conclusions Intracavernous ICA dissection is a possible cause of sixth nerve palsy. While most cases likely result from compromised arterial blood supply to the affected nerve, compression of the cranial nerves by the expanded artery can occur in some cases. Surgical treatment is a safe and effective option for relieving nerve compression after intracavernous ICA dissection.

Background Standard sampling methods to evaluate the proliferative ability of meningioma have not been established. Methods This prospective study was conducted to evaluate the effectiveness of intraoperative rapid flow cytometry (iFC) using raw samples for the quantitative assessment of proliferative ability in meningioma cells and to investigate intratumoral heterogeneity. Proliferation index (PI) was defined as the ratio of aneuploid cells with an abnormal number of chromosomes to the total cells. Results From 50 patients, 118 specimens were analyzed. There was a statistically significant correlation between the postoperative MIB‐1 labeling index (LI) and PI (R = 0.59, P

Purpose of the report This study aimed to determine the most effective metabolic index of FDG-PET and MET-PET to differentiate high- and low-grade gliomas, and then to characterize tumor metabolism according to the 2016 WHO classification. We also developed a new calculation method of potential infiltrative tumor volume to overcome the current limitations of tumor evaluation according to metabolic index, which focuses solely on tumor core area. Materials and methods Patients who underwent both FDG-PET and MET-PET, as well as surgical treatment, were retrospectively identified. All tumors were diagnosed histologically and included 44 high-grade and 19 low-grade gliomas. Metabolic indices of tumor-to-normal (T/N) ratio and maximum value within the tumor itself were compared between high- and low-grade tumors. A calculation method for potential infiltrative tumor volume was developed and compared between these 2 grades. Results T/N, calculated as tumor value divided by normal cortex value, was the most effective (area under the curve, 0.800 for FDG-PET; area under the curve, 0.773 for MET-PET) for differentiating high- and low-grade gliomas. Potential infiltrative volume effectively distinguished between high- and low-grade glioma (43.8 ± 30.2 mL vs 14.0 ± 12.6 mL; P = 0.005 [t test]). A combination of T/N, with a cutoff value of 0.9 or higher on FDG-PET and/or 3.0 or higher on MET-PET, and potential infiltrative volume, with a cutoff value of 20.0 mL or higher, provided a diagnostic accuracy of 89% in distinguishing high- from low-grade gliomas. Conclusions Evaluation of potential infiltrative volume surrounding the tumor core area, in addition to the T/N ratio of the tumor core, may help distinguish between high- and low-grade gliomas.

The Saving Mothers, Giving Life initiative employed 2 key strategies to improve the ability of pregnant women to reach maternal care: (1) increase the number of emergency obstetric and newborn care facilities, including upgrading existing health facilities, and (2) improve accessibility to such facilities by renovating and constructing maternity waiting homes, improving communication and transportation systems, and supporting community-based savings groups. These interventions can be adapted in low-resource settings to improve access to maternity care services., Background: Between June 2011 and December 2016, the Saving Mothers, Giving Life (SMGL) initiative in Uganda and Zambia implemented a comprehensive approach targeting the persistent barriers that impact a woman's decision to seek care (first delay), ability to reach care (second delay), and ability to receive adequate care (third delay). This article addresses how SMGL partners implemented strategies specifically targeting the second delay, including decreasing the distance to facilities capable of managing emergency obstetric and newborn complications, ensuring sufficient numbers of skilled birth attendants, and addressing transportation challenges. Methods: Both quantitative and qualitative data collected by SMGL implementing partners for the purpose of monitoring and evaluation were used to document the intervention strategies and to describe the change in outputs and outcomes related to the second delay. Quantitative data sources included pregnancy outcome monitoring data in facilities, health facility assessments, and population-based surveys. Qualitative data were derived from population-level verbal autopsy narratives, programmatic reports and SMGL-related publications, and partner-specific evaluations that include focus group discussions and in-depth interviews. Results: The proportion of deliveries in any health facility or hospital increased from 46% to 67% in Uganda and from 63% to 90% in Zambia between baseline and endline. Distance to health facilities was reduced by increasing the number of health facilities capable of providing basic emergency obstetric and newborn care services in both Uganda and Zambia—a 200% and 167% increase, respectively. Access to facilities improved through integrated transportation and communication services efforts. In Uganda there was a 6% increase in the number of health facilities with communication equipment and a 258% increase in facility deliveries supported by transportation vouchers. In Zambia, there was a 31% increase in health facilities with available transportation, and the renovation and construction of maternity waiting homes resulted in a 69% increase in the number of health facilities with associated maternity waiting homes. Conclusion: The collective SMGL strategies addressing the second delay resulted in increased access to delivery services as seen by the increase in the proportion of facility deliveries in SMGL districts, improved communication and transportation services, and an increase in the number of facilities with associated maternity waiting homes. Sustaining and improving on these efforts will need to be ongoing to continue to address the second delay in Uganda and Zambia.

Background: Movement disorders are rare in brain tumors. We describe a 45-year-old woman with hemichorea, a concomitant contralateral sphenoid ridge meningioma. Case Description: The meningioma enlarged as her hemichorea worsened, and after meningioma resection, the hemichorea gradually subsided. N-isopropyl-p-[123I]-iodoamphetamine single-photon emission computed tomography performed preoperatively showed decreased regional cerebral blood flow (CBF) to the basal ganglia circuit ipsilateral to the tumor and, when repeated postoperatively, confirmed improved regional CBF. Conclusion: We propose that the enlarging sphenoid ridge meningioma had a remote effect on regional CBF and the thalamocortical motor center and that complex changes in the basal ganglia output may have caused the hemichorea.

Background: The incidence of disseminated tuberculosis (DTB) is increasing worldwide yet its epidemiological characteristics in Uganda are not known. The purpose of this study was to determine the prevalence, associated factors, and treatment outcomes of DTB among patients at a national tuberculosis (TB) treatment center in Uganda.Methodology: The study took place at the TB unit of Mulago National Referral Hospital in Kampala, Uganda. We conducted a retrospective chart review of TB patients who were enrolled in care between January 2015 and December 2019. Eligible charts were for patients with pulmonary bacteriologically confirmed TB enrolled into care in the period under study. DTB was defined as TB at two or more non-contiguous sites.Results: Overall, 400 patient charts were eligible, of whom 240(60.0%) were aged 15 – 34 years and 205 (51.3%) were female. The prevalence of DTB was 8.5% (34/400) (95% CI: 6.0% – 11.7%). Patients with DTB were more likely to be casual laborers (44.1% vs 21.3%, p = 0.023), from Bantu ethnic group (67.7% vs. 40.5%, p = 0.0021), and had at least one comorbidity (82.4% vs 37.2%, p Conclusion: Our findings highlight the need for early detection of TB before dissemination and greater use of TB preventive therapies in HIV-infected individuals to counter the observed high mortality of DTB.

Simple Summary Black patients are diagnosed and die earlier of endometrial cancer in comparison with their White counterparts. Factors that have been implicated in this racial disparity, such as socioeconomic status, increased frequencies of more aggressive tumor histology, and comorbid conditions, do not account for all of the disparity. Molecular defects in the endometrial tumors likely also contribute to the more aggressive tumor biology and the patient disparities. In this study, we reviewed the published data of molecular characteristics of endometrial cancer in different races. The majority of the publications compare Black and White patients, and identify molecules and pathways that can be targeted with existing drugs. These findings encourage molecular profile studies comparing additional races and ethnicities, and development of race-specific treatments. Abstract In contrast to the decline in incidence and mortality of most other cancers, these rates are rising for endometrial cancer. Black women with endometrial cancer have earlier diagnosis, more aggressive histology, advanced stage and worse outcomes compared with their White counterparts. Socioeconomic status, a higher incidence of aggressive histology, and comorbid conditions are known factors leading to racial disparity in patients with endometrial cancer; nevertheless, they do not account for the entire racial disparity; which emphasizes the roles of molecular, histopathological and genetic factors. We performed a comprehensive review of all published scientific literature up to January 2021 reporting histopathologic, genetic and molecular factors associated with racial disparities in patients with endometrial cancer. The interactions and pathways of molecules reported to have significant differential expression in endometrial cancers from Black and White patients were identified with Ingenuity Pathway Analysis. The majority of studies compared Black and White patients; however, limited data are available for other racial and ethnic groups. Reported differences that could account for the worse survival of Black endometrial cancer patients include more aggressive histopathologies and molecular alterations, including upregulation of molecules driving cell cycle progression, and p53 and HER2/NEU signaling. Several of these molecules are targeted by existing pharmaceuticals. These findings encourage further study and the development of race-specific treatment strategies.

Objectives: During 2010-2018, the Arkansas Department of Health reported 21 genotype-matched cases of tuberculosis (TB) among residents of a rural county in Arkansas with a low incidence of TB and in nearby counties. The Arkansas Department of Health and the Centers for Disease Control and Prevention investigated to determine the extent of TB transmission and provide recommendations for TB control. Methods: We reviewed medical and public health records, interviewed patients, and reviewed patients’ social media posts to describe patient characteristics, identify epidemiologic links, and establish likely chains of transmission. Results: We identified 21 cases; 11 reported during 2010-2013 and 10 during 2016-2018. All case patients were US-born non-Hispanic Black people. Eighteen case patients had the outbreak genotype, and 3 clinically diagnosed (non–culture-confirmed) case patients had epidemiologic links to patients with the outbreak genotype. Social media reviews revealed epidemiologic links among 10 case patients not previously disclosed during interviews. Eight case patients (38%) had ≥1 health care visit during their infectious period, and 7 patients had estimated infectious periods of >12 months. Conclusions: Delayed diagnoses and prolonged infectiousness led to TB transmission in this rural community. TB education and awareness is critical to reducing transmission, morbidity, and mortality, especially in areas where health care providers have limited TB experience. Use of social media can help elucidate people at risk, especially when traditional TB investigation techniques are insufficient.

Background: African countries have the highest number of people living with HIV (PWH). The continent is home to 12% of the global population, but accounts for 71% of PWH globally. Antiretroviral therapy has played an important role in the reduction of the morbidity and mortality rates for HIV, which necessitates increased surveillance of the threats from pernicious risks to which PWH who live longer remain exposed. This includes cardiopulmonary comorbidities, which pose significant public health and economic challenges. A significant contributor to the cardiopulmonary comorbidities is tobacco smoking. Indeed, globally, PWH have a 2–4-fold higher utilization of tobacco compared to the general population, leading to endothelial dysfunction and atherogenesis that result in cardiopulmonary diseases, such as chronic obstructive pulmonary disease and coronary artery disease. In the context of PWH, we discuss (1) the current trends in cigarette smoking and (2) the lack of geographically relevant data on the cardiopulmonary conditions associated with smoking; we then review (3) the current evidence on chronic inflammation induced by smoking and the potential pathways for cardiopulmonary disease and (4) the multifactorial nature of the syndemic of smoking, HIV, and cardiopulmonary diseases. This commentary calls for a major, multi-setting cohort study using a syndemics framework to assess cardiopulmonary disease outcomes among PWH who smoke. Conclusion: We call for a parallel program of implementation research to promote the adoption of evidence-based interventions, which could improve health outcomes for PWH with cardiopulmonary diseases and address the health inequities experienced by PWH in African countries.

Background Much effort is required to dissect the adhesion in the surgical trajectory in reoperation via the lateral suboccipital retrosigmoid approach. Lumbar drainage is a standard procedure in neurosurgical practice; its usefulness during reoperation has not been reported. The purpose of this study is to elucidate whether pretreatment with lumbar drainage is effective in enabling a more straightforward lateral suboccipital approach during reoperation. Methods There were 13 reoperations among 115 lateral suboccipital craniotomies performed by a single surgeon between April 2016 and March 2018 at our institution. Lumbar drainage was performed prior to reoperations when tight adhesion was anticipated by preoperative neuroimaging. We retrospectively inspected 11 reoperations in which the video recordings were available. Results After lumber drainage, the cerebellum was slack by the start of the dural incision. The total approach time, defined as the time between starting dural incision and reaching the cerebellopontine cistern, in the group with lumbar drainage (47 min. 45 sec., n = 6) was 13 min. 46 sec. shorter than that of the group without drainage (61 min. 31 sec., n = 5) (p = 0.09). The number of times hemostasis was required in the group with drainage (4 ± 1.4) was significantly lower than that of the group without drainage (7 ± 1.4) (p Conclusions Lumbar drainage assisted in a smooth and safe dissection of the surgical trajectory for the reoperation via lateral suboccipital retrosigmoid craniotomy. Our results suggest a usefulness of lumbar drainage prior to reoperation.

Background: Malaria remains the world’s leading vector-born cause of mortality and morbidity, and Eastern Uganda contains some of the country’s highest prevalence rates. Though academic societies, such as universities, may be prone to high malaria transmission, the extent of the burden and risk factors in university communities of Eastern Uganda are poorly understood. The aim in this study was to examine malaria prevalence, preventive strategies, and risk factors, among University communities in Eastern Uganda; to inform targeted malaria eradication efforts in academic settings. Methods: A mixed methods approach was applied. A case study of Islamic University in Uganda (IUIU), located in Eastern Uganda, was selected. A retrospective approach was used to determine malaria prevalence in IUIU from August to December 2019. Stratified random sampling was used to select IUIU community members; these were subjected to semi-structured questionnaires and Key informant Interviews (KII) to examine the preventive approaches and risk factors. An observational survey was also conducted to identify barriers to malaria prevention. Data was analyzed using descriptive statistics, graphs, Chi-square, and pictures; with STATA version-15.0. Results: The study involved 255 respondents (204, 80% students, 51, 20% staff); 130, 51% were males, 125, 49% were females. Malaria prevalence was; 12.9%, 11.7% and 12.7% for students, staff, and the general study population respectively. Lowest prevalence was registered in November (8.3% for students, 0% for staff), and the highest in December (18.4% for students, 6.7% for staff). Overall malaria prevalence in IUIU was significantly greater than Uganda’s national prevalence (χ2=182.009; pConclusion: The overall prevalence of malaria in IUIU community was 12.7%; and was significantly higher than Uganda’s national prevalence (7%). Usage of insecticide-treated bed-nets was the commonest intervention, but showed no statistically significant association with malaria non-prevalence. Awareness programs should be enhanced to address inappropriate use of malaria control methods/tools, because the widespread adoption of these interventions alone did not effectively curb the burden.

Simple Summary Neurofibromatosis type 2 (NF2) is a rare genetic hereditary disease characterized by multiple central nervous system tumors, most frequently bilateral vestibular schwannomas (VSs). No chemotherapeutic agents are available for clinical use, and surgery and radiotherapy are the only therapeutic options available now. Still, neither treatment option alleviates hearing loss in patients with NF2 and VS; they may even exacerbate it. However, bevacizumab has been reported to be effective in suppressing the tumor’s growth and has shown unprecedented efficacy in improving hearing. We describe a new ongoing and novel clinical trial, BeatNF2, a randomized, double-blinded, placebo-controlled, multicenter trial to assess bevacizumab’s efficacy and safety in patients with NF2. The study’s primary endpoint is improved hearing function 24 weeks after the beginning of the treatment protocol. Abstract Neurofibromatosis type 2 (NF2) causes bilateral vestibular schwannomas (VSs), leading to deafness. VS is treated by surgery or radiation, but neither treatments prevent hearing loss. Bevacizumab was found to be effective in suppressing the tumor’s growth and may help to improve hearing. We are conducting a randomized, double-blind, multicenter clinical trial to verify the efficacy and safety of bevacizumab in NF2-related VS. The primary objective is to evaluate the efficacy of bevacizumab in improving hearing in the affected ear. One of the secondary objectives is to evaluate bevacizumab’s efficacy in rechallenge treatment in relapsed cases. Sixty patients will randomly receive either bevacizumab or a placebo and will be clinically observed for 48 weeks in the initial intervention phase. In the first half (24 weeks), they will receive either 5 mg/kg of bevacizumab or a placebo drug. In the second half, all patients will receive 5 mg/kg of bevacizumab. If hearing function deteriorated in a patient who had shown improvement during the first phase, a rechallenge dose with bevacizumab would be offered.

BackgroundYouth living with HIV (YLHIV) in Sub-Saharan African (SSA) are less likely to adhere to antiretroviral therapy (ART) and other health-related regimens. As a consequence, YLHIV are not only at risk for health problems and mental health comorbidities, but are also at risk for cognitive deficits, including in areas of memory and executive functioning. The Suubi+Adherence study followed 702 adolescents (10-16 years of age) receiving bolstered standard of care and a family economic empowerment intervention comprising an incentivized youth financial savings account (YSA) augmented with financial literacy training (FLT) and peer mentorship. The study findings pointed to superior short-term viral suppression and positive adolescent health and mental health functioning among participants receiving the intervention. The original group of adolescents who received Suubi+Adherence are now transitioning into young adulthood. This paper presents a protocol for the follow-up phase titled Suubi+Adherence Round 2.MethodsThe original cohort in Suubi+Adherence will be tracked for an additional five years (2020-2025). Specifically, the long term follow-up will allow to: 1) ascertain the extent to which the short term outcomes identified in the first 6 years of the intervention are maintained as the same group transitions through young adulthood; and 2) address new scientific questions regarding ART adherence; HIV care engagement; protective health behaviors; and the potential of FEE to mitigate the development of HIV-associated neurocognitive disorders in YLHIV. Additionally, the team examines the potential mechanisms through which the observed long-term outcomes happen. Moreover, the Suubi+Adherence-Round 2 adds a qualitative component and extends the cost effectiveness component.DiscussionGuided by asset and human development theories, Suubi+Adherence-R2 will build on the recently concluded Suubi+Adherence study to conduct one of the largest and longest running studies of YLHIV in SSA as they transition into young adulthood. The study will address new scientific questions regarding long-term ART adherence, HIV care engagement, protective health behaviors, and the potential of FEE to mitigate the development of HIV-associated neurocognitive disorders in YLHIV. The findings may inform efforts to improve HIV care among Uganda’s YLHIV, with potential replicability in other low-resource countries.Trial registrationClinicalTrials.gov, ID:NCT01790373