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Background: Urogenital schistosomiasis caused by Schistosoma haematobium affects approximately 110 million people globally, with the majority of cases in low- and middle-income countries. Schistosome infections have been shown to impact the host immune system, gene expression, and microbiome composition. Studies have demonstrated variations in pathology between schistosome subspecies. In the case of S. haematobium, infection has been associated with HIV acquisition and bladder cancer. However, the underlying pathophysiology has been understudied compared to other schistosome species. This systematic review comprehensively investigates and assimilates the effects of S. haematobium infection on systemic and local host mucosal immunity, cellular gene expression and microbiome. Methods: We conducted a systematic review assessing the reported effects of S. haematobium infections and anthelmintic treatment on the immune system, gene expression and microbiome in humans and animal models. This review followed PRISMA guidelines and was registered prospectively in PROSPERO (CRD42022372607). Randomized clinical trials, cohort, cross-sectional, case-control, experimental ex vivo, and animal studies were included. Two reviewers performed screening independently. Results: We screened 3,177 studies and included 94. S. haematobium was reported to lead to: (i) a mixed immune response with a predominant type 2 immune phenotype, increased T and B regulatory cells, and select pro-inflammatory cytokines; (ii) distinct molecular alterations that would compromise epithelial integrity, such as increased metalloproteinase expression, and promote immunological changes and cellular transformation, specifically upregulation of genes p53 and Bcl-2; and (iii) microbiome dysbiosis in the urinary, intestinal, and genital tracts. Conclusion: S. haematobium induces distinct alterations in the host's immune system, molecular profile, and microbiome. This leads to a diverse range of inflammatory and anti-inflammatory responses and impaired integrity of the local mucosal epithelial barrier, elevating the risks of secondary infections. Further, S. haematobium promotes cellular transformation with oncogenic potential and disrupts the microbiome, further influencing the immune system and genetic makeup. Understanding the pathophysiology of these interactions can improve outcomes for the sequelae of this devastating parasitic infection. Author summary: The parasitic trematode S. haematobium affects 110 million people worldwide. Many studies have described the effects of schistosome infections on humans and animals, but data focusing solely on S. haematobium infections, which cause urogenital schistosomiasis are scarce. Our goal was to evaluate, in a systematic manner, how S. haematobium infection affects the immune system, gene expression and microbiome of the host. These effects are important because they could lead to increased risk of infections, such as HIV, and bladder cancer. We screened 3,179 studies for potential relevance and included 94 of them in this review. Our analysis showed that S. haematobium infection profoundly alters the immune system with a mixed pro-inflammatory and anti-inflammatory response, though with a predominant type 2 immune phenotype and increased regulatory cells. We further found consistent evidence that it impairs local mucosal epithelial barrier integrity, promotes cellular transformation with pro-oncogenic changes in the host, and is associated with microbial alterations in urine, stool, and genital tracts. We discuss how these findings might be interpreted, and the additional research needed, to improve our understanding of S. haematobium pathophysiology and ameliorate the potential sequelae of S. haematobium infection, such as increased viral infections and cancer. [ABSTRACT FROM AUTHOR]

Background: There is an increasing emphasis on promoting women's autonomy in reproductive decision-making, particularly given global efforts to increase contraceptive access and uptake. Scales to quantify autonomy have inconsistently included the effect of external influences and focused primarily on influences of partners. Objectives: This study aimed to gain greater depth in understanding how influences including and beyond a woman's partner affect her contraceptive decision-making, as well as how external influences can overlap and further complicate contraceptive decision-making. Design: A phenomenological, qualitative study in which in-depth interviews were conducted in three phases from May 2021 to February 2022 with women living in northwest Tanzania who had varying histories of contraceptive use or non-use. Methods: One-on-one, in-depth interviews were conducted in Swahili, the national language of Tanzania, by trained female interviewers. Interviews were digitally recorded, transcribed, translated into English, and independently coded by three investigators. Analysis was conducted using NVivo. The codes developed from the transcripts were grouped into overarching themes with supporting illustrative quotes. Results: A total of 72 women were interviewed. Partners were the most influential in women's family planning decision-making, followed by friends, relatives, community religious leaders, and healthcare providers. Out of the 52 women with a partner who had ever used family planning, 76.9% had discussed their desire to use family planning with their partner and nearly all reported strong pressures to use or not to use family planning from partners, family, and friends. Rarely, participants stated that they were devoid of any influence. Conclusion: In rural Tanzania, women's decision-making about family planning was highly impacted by external influences, including not only partners but also family, friends, and community. Indicators of women's reproductive autonomy and measurements of interventions to promote contraceptive use should incorporate measures of these external influences. [ABSTRACT FROM AUTHOR]

A laboratory-based lateral flow (LF) test that utilizes up-converting reporter particles (UCP) for ultrasensitive quantification of Schistosoma circulating anodic antigen (CAA) in urine is a well-accepted test to identify active infection. However, this UCP-LF CAA test requires sample pre-treatment steps not compatible with field applications. Flow, a new low-cost disposable, allows integration of large-volume pre-concentration of urine analytes and LF detection into a single field-deployable device. We assessed a prototype Flow-Schistosoma (Flow-S) device with an integrated UCP-LF CAA test strip, omitting all laboratory-based steps, to enable diagnosis of active Schistosoma infection in the field using urine. Flow-S is designed for large-volume (5–20 mL) urine, applying passive paper-based filtration and antibody-based CAA concentration. Samples tested for schistosome infection were collected from women of reproductive age living in a Tanzania region where S. haematobium infection is endemic. Fifteen negative and fifteen positive urine samples, selected based on CAA levels quantified in paired serum, were analyzed with the prototype Flow-S. The current Flow-S prototype, with an analytical lower detection limit of 1 pg CAA/mL, produced results correlated with the laboratory-based UCP-LF CAA test. Urine precipitates occurred in frozen banked samples and affected accurate quantification; however, this should not occur in fresh urine. Based on the findings of this study, Flow-S appears suitable to replace the urine pre-treatment required for the laboratory-based UCP-LF CAA test, thus allowing true field-based applications with fresh urine samples. The urine precipitates observed with frozen samples, though less important given the goal of testing fresh urines, warrant additional investigation to evaluate methods for mitigation. Flow-S devices permit testing of pooled urine samples with applications for population stratified testing. A field test with fresh urine samples, a further optimized Flow-S device, and larger statistical power has been scheduled. [ABSTRACT FROM AUTHOR]

Background Reasons for the high prevalence of Kaposi sarcoma–associated herpesvirus (KSHV) in sub-Saharan Africa, and risk factors leading to viral reactivation and shedding, remain largely undefined. Preliminary studies have suggested that schistosome infection, which has been associated with impaired viral control, is associated with KSHV. In this study we sought to determine the relationship between active Schistosoma mansoni or Schistosoma haematobium infection and KSHV shedding. Methods We quantified KSHV DNA in saliva and cervical swabs from 2 cohorts of women living in northwestern Tanzanian communities endemic for S mansoni or S haematobium by real-time polymerase chain reaction. χ2 and Fisher exact tests were used to determine differences in clinical and demographic factors between those who were and were not shedding KSHV. Results Among 139 total women, 44.6% were KSHV seropositive. Six percent of those with S mansoni and 17.1% of those with S haematobium were actively shedding KSHV in saliva and none in cervical samples. Women from the S mansoni cohort who were shedding virus reported infertility more frequently (80% vs 19.5%, P =.009). There was no difference in frequency of KSHV salivary shedding between schistosome-infected and -uninfected women. Conclusions In an area with high KSHV seroprevalence and endemic schistosome infections, we provide the first report with data demonstrating no association between schistosome infection and salivary or cervical herpesvirus shedding. KSHV salivary shedding was associated with infertility, a known effect of another herpesvirus, human herpesvirus 6. [ABSTRACT FROM AUTHOR]

Schistosoma haematobium, the parasite that causes urogenital schistosomiasis, is widely prevalent in Tanzania. In addition to well-known effects on the urinary tract, S. haematobium also causes clinically- evident damage to the reproductive tract in approximately half of infected women, which is known as female genital schistosomiasis (FGS). FGS has major gynecologic and social consequences on women's reproductive health, yet little information is available regarding FGS in Tanzania. To cover that gap, we conducted the present scoping review to examine the epidemiology of FGS in Tanzania (both in the mainland and Zanzibar island) and to make recommendations for future work in this area. The available evidence from community-based and hospital-based retrospective studies indicates that FGS is a significant health problem in the country. Very few community-based studies have been reported from mainland Tanzania, and Zanzibar. Our review highlights the scarcity of efforts to address FGS in Tanzania and the need for additional community-based studies. The studies will help us understand the true burden of the disease nationwide, to assess the impact of praziquantel on FGS lesions, and to address social and mental health in relation to FGS. This review emphasizes integration of delivery of FGS related services in primary health care systems through the reproductive health clinics which covers sexually transmitted infections, HIV and cervical cancer screening. These actions are essential if this neglected gynecological disease is to be addressed in Tanzania. Author summary: Female genital schistosomiasis (FGS) caused by Schistosoma haematobium affects mostly the reproductive tract of girls and women in rural and marginalized communities. This disease has been largely neglected by the schistosomiasis endemic communities and public health professionals. The present review aimed at assessing the evidence/epidemiology of FGS among women/girls in Tanzania. Furthermore, the review assessed the availability of information, published literature on FGS including comorbidities that address FGS in Tanzania mainland and Zanzibar islands. The evidence generated was important to inform the need to address FGS key gaps among researchers, healthcare workers and communities. Overall, the findings indicated that the knowledge of FGS was lacking among the endemic communities and healthcare workers. Findings from this review have shown the available gaps in literature on FGS in Tanzania, from very few community-and-hospitals based studies reported from mainland Tanzania, and Zanzibar. To address this gap, further research is essential to understanding the true burden of disease-associated morbidity, to assessing the impact of single dose praziquantel in FGS lesions, to understanding mental health in relation to FGS, and to integrating delivery of FGS related services in primary health care systems. [ABSTRACT FROM AUTHOR]

Problem In the United Republic of Tanzania, the incidence of non-neonatal circumcision-related tetanus is probably underreported. Approach We analysed charts and extracted information on outcome and wound location for non-neonatal cases of tetanus admitted to the intensive care unit of Bugando Medical Centre between 2001 and 2016. Local setting Bugando Medical Centre, which is one of four teaching referral hospitals in the United Republic of Tanzania, has a 13-bed intensive care unit that manages all admitted patients with tetanus. Within the United Republic of Tanzania, formal programmes of tetanus immunization are targeted at infants or women. Relevant changes From our inpatient logs, we identified six patients with non- neonatal tetanus among male patients with a recent history of circumcision. Only one of these patients had been circumcised within a subnational programme of voluntary medical male circumcision. The other five had been circumcised outside of the programme--e.g. at small rural dispensaries or by a traditional provider with no formal medical training. The six patients were aged 11-55 years and five (83%) of them died in hospital--all of overwhelming sepsis. Lessons learnt Within the Tanzanian programme of voluntary medical male circumcision, education on wound hygiene probably helps to reduce the incidence of non-neonatal circumcision-related tetanus. The corresponding incidence among the boys and men who are circumcised beyond this subnational programme is probably higher. The training of all circumcision providers in wound care and a vaccination programme to ensure that male Tanzanians receive tetanus immunization post- infancy are recommended. Probleme En Republique-Unie deTanzanie, l'incidence du tetanos non neonatal lie a la circoncision est probablement sous-estimee. Approche Nous avons analyse des tableaux et extrait des informations concernant les suites et l'emplacement de la plaie des cas de tetanos non neonatal admis dans le service de soins intensifs du centre medical Bugando entre 2001 et 2016. Environnement local Le centre medical Bugando, l'un des quatre hopitaux centraux d'enseignement de la Republique-Unie de Tanzanie, dispose d'un service de soins intensifs dote de 13 lits qui prend en charge tous les patients admis avec le tetanos. Dans la Republique-Unie de Tanzanie, les programmes formels de vaccination contre le tetanos ciblent les nourrissons ou les femmes. Changements significatifs Nous avons releve, dans nos registres d'hospitalisation, six patients atteints de tetanos non neonatal parmi les patients masculins ayant recemment subi une circoncision. Seul un de ces patients avait ete circoncis dans le cadre d'un programme infranational de circoncision masculine medicale volontaire. Les cinq autres avaient ete circoncis en-dehors de ce programme, par exemple dans de petits dispensaires ruraux ou par un praticien traditionnel sans formation medicale formelle. Ces six patients etaient ages de 11 a 55 ans et cinq (83%) d'entre eux sont decedes a l'hopital, tous de septicemie. Lecons tirees Dans le cadre du programme tanzanien de circoncision masculine medicale volontaire, l'education a l'hygiene de la plaie contribue probablement a reduire l'incidence du tetanos non neonatal lie a la circoncision. L'incidence correspondante chez les garcons et les hommes qui sont circoncis en-dehors de ce programme infranational est probablement plus importante. La formation en matiere de soin des plaies de toutes les personnes qui pratiquent des circoncisions et la mise en place d'un programme de vaccination permettant aux Tanzaniens de beneficier de vaccins contre le tetanos apres la petite enfance sont recommandees. Problema En la Republica Unida de Tanzania, es posible que no se comunique la incidencia del tetanos relacionado con la circuncision no neonatal. Enfoque Hemos analizado graficos y extraido informacion sobre las consecuencias y la localizacion de la herida para los casos no neonatales de tetanos ingresados en la unidad de cuidados intensivos del Bugando Medical Centre entre 2001 y 2016. Marco regional El Bugando Medical Centre, uno de los cuatro hospitales de referencia en la Republica Unida de Tanzania, cuenta con una unidad de cuidados intensivos de 13 camas que se ocupa de todos los pacientes ingresados con tetanos. En la Republica Unida de Tanzania, los programas oficiales de vacunacion contra el tetanos estan orientados a infantes o mujeres. Cambios relevantes A partir de los registros de pacientes hospitalizados, se identificaron a seis pacientes con tetanos no neonatal entre los pacientes varones con un historial reciente de circuncision. Solo uno de estos pacientes habia sido circuncidado dentro de un programa subnacional para la circuncision masculina voluntarla medica. Los otros cinco habian sido circuncidados fuera del programa, por ejemplo, en pequenos dispensarlos rurales o atendidos por un proveedor tradicional sin formacion medica oficial. Los seis pacientes tenian entre 11 y 55 anos de edad y cinco (83%) de ellos murieron en el hospital, todos a causa de una sepsis Incontenible. Lecciones aprendidas Dentro del programa de Tanzania para la circuncision masculina voluntaria medica, probablemente la educacion sobre la higiene de las heridas ayude a reducir la Incidencia del tetanos relacionado con la circuncision no neonatal. Es probable que la Incidencia correspondiente entre los ninos y hombres circuncidados fuera de este programa subnacional sea mayor. Se recomienda la formacion de todos los proveedores de circuncision en el cuidado de heridas y un programa de vacunacion para asegurar que los varones de Tanzania sean vacunados contra el tetanos despues de la Infancia., Introduction By 2012, 14 countries in eastern and southern Africa--including the United Republic of Tanzania--had been prioritized for the scale-up of voluntary medical male circumcision. (1) The goal of the [...]

Background: Globally, helminth infections and cardiometabolic diseases often overlap in populations and individuals. Neither the causal relationship between helminth infections and cardiometabolic diseases nor the effect of helminth eradication on cardiometabolic risk have been reviewed systematically in a large number of human and animal studies. Methods: We conducted a systematic review assessing the reported effects of helminth infections and anthelmintic treatment on the development and/or severity of cardiometabolic diseases and risk factors. The search was limited to the most prevalent human helminths worldwide. This study followed PRISMA guidelines and was registered prospectively in PROSPERO (CRD42021228610). Searches were performed on December 10, 2020 and rerun on March 2, 2022 using Ovid MEDLINE ALL (1946 to March 2, 2022), Web of Science, Cochrane Library, Global Index Medicus, and Ovid Embase (1974 to March 2, 2022). Randomized clinical trials, cohort, cross-sectional, case-control, and animal studies were included. Two reviewers performed screening independently. Results: Eighty-four animal and human studies were included in the final analysis. Most studies reported on lipids (45), metabolic syndrome (38), and diabetes (30), with fewer on blood pressure (18), atherosclerotic cardiovascular disease (11), high-sensitivity C-reactive protein (hsCRP, 5), and non-atherosclerotic cardiovascular disease (4). Fifteen different helminth infections were represented. On average, helminth-infected participants had less dyslipidemia, metabolic syndrome, diabetes, and atherosclerotic cardiovascular disease. Eleven studies examined anthelmintic treatment, of which 9 (82%) reported post-treatment increases in dyslipidemia, metabolic syndrome, and diabetes or glucose levels. Results from animal and human studies were generally consistent. No consistent effects of helminth infections on blood pressure, hsCRP, or cardiac function were reported except some trends towards association of schistosome infection with lower blood pressure. The vast majority of evidence linking helminth infections to lower cardiometabolic diseases was reported in those with schistosome infections. Conclusions: Helminth infections may offer protection against dyslipidemia, metabolic syndrome, diabetes, and atherosclerotic cardiovascular disease. This protection may lessen after anthelmintic treatment. Our findings highlight the need for mechanistic trials to determine the pathways linking helminth infections with cardiometabolic diseases. Such studies could have implications for helminth eradication campaigns and could generate new strategies to address the global challenge of cardiometabolic diseases. Author summary: Helminth infections are caused by parasitic worms and affect over 1.5 billion people worldwide. Helminth infections and cardiometabolic diseases are both common and overlap with one another in many parts of the world. Studies have separately examined the relationship between helminth infections and various cardiometabolic diseases, but the relationships overall, as well as the impact of treatment of parasitic worms, have not been studied systematically. The authors conducted a systematic review to assess the impact of helminth infections, and treatment of helminth infections, on cardiometabolic diseases and risk factors. Eighty-four total studies were analyzed and included in the final review. People and animals infected with helminths were generally found to have fewer cardiometabolic disease risk factors including better overall cholesterol profiles, less diabetes, and less atherosclerotic heart disease than uninfected study participants. After treatment of helminth infections, participants frequently experienced worsening in those cardiometabolic measurements. There were no consistent effects of helminth infections on blood pressure, high-sensitivity CRP (an inflammatory marker), or other cardiac function. In summary, helminth infections may offer protection against certain cardiometabolic diseases and risk factors. More studies are needed to elucidate the pathways linking helminth infections with cardiometabolic diseases as it may impact how we treat both disease processes in regions where both are prevalent. [ABSTRACT FROM AUTHOR]

Schistosoma mansoni infection may impair genital mucosal antiviral immunity, but immune cell populations have not been well characterized. We characterized mononuclear cells from cervical brushings of women with and without S mansoni infection. We observed lower frequencies of natural killer T cells and higher frequencies of CD14+ monocytes in infected women. [ABSTRACT FROM AUTHOR]

Background: Cryptococcal meningitis is a leading cause of death among HIV‐infected individuals in sub‐Saharan Africa. Recent developments include the availability of intravenous fluconazole, cryptococcal antigen assays and new data to support fluconazole pre‐emptive treatment. In this study, we describe the impact of screening HIV‐positive adult inpatients with serum cryptococcal antigen (CRAG) at a Tanzanian referral hospital. Methods: All adults admitted to the medical ward of Bugando Medical Centre are counseled and tested for HIV. In this prospective cohort study, we consecutively enrolled HIV‐positive patients admitted between September 2009 and January 2010. All patients were interviewed, examined and screened with serum CRAG. Patients with positive serum CRAG or signs of meningitis underwent lumbar puncture. Patients were managed according to standard World Health Organization treatment guidelines. Discharge diagnoses and in‐hospital mortality were recorded. Results: Of 333 HIV‐infected adults enrolled in our study, 15 (4.4%) had confirmed cryptococcal meningitis and 10 of these 15 (66%) died. All patients with cryptococcal meningitis had at least two of four classic symptoms and signs of meningitis: fever, headache, neck stiffness and altered mental status. Cryptococcal meningitis accounted for a quarter of all in‐hospital deaths. Conclusions: Despite screening of all HIV‐positive adult inpatients with the serum CRAG at the time of admission and prompt treatment with high‐dose intravenous fluconazole in those with confirmed cryptococcal meningitis, the in‐hospital mortality rate remained unacceptably high. Improved strategies for earlier diagnosis and treatment of HIV, implementation of fluconazole pre‐emptive treatment for high‐risk patients and acquisition of better resources for treatment of cryptococcal meningitis are needed., Background Cryptococcal meningitis is one of the most common and severe opportunistic infections among people infected with HIV: there are an estimated 720, 000 cases and 500, 000 deaths per [...]

The photolysis of CpW(CO)(sub 3)Me is demonstrated to produce methyl radicals and to cleave DNA in a single-stranded manner, and preliminary evidence implicated a carbon-centered radical in this process. The mechanism of strand scission in this reaction was determined to occur by hydrogen atom abstraction from the 4'- and 5'-positions of the deoxyribose moiety of the backbone of DNA.

Acetoacetanilide and 4'-chloroacetoacetanilide were trilithiated with excess lithium diisopropylamide and condensed with several aromatic esters, followed by neutralization, separate acid cyclization, and rearrangements. After C-acylation of trilithiated acetoacetanilides and cyclization to 4H-pyran-4-ones, these compounds underwent multistep rearrangements to 4-anilino-6-aryl-2H-pyran-2-ones. Key words: pyranones, trianions, Claisen-type condensations, rearrangements.

* Early diagnosis of infants infected perinatally with HIV in sub-Saharan Africa depends on completion of multiple steps for results to reach an infant's caregivers in a timely manner. * This project, designed by a pediatric HIV nurse in Tanzania, applied sequential quality improvement interventions to reduce the lengthy turnaround time between dried blood collection from exposed infants and return of test results. * Low-cost interventions successfully reduced the turnaround time from 55 to 38 days, and increased the number of results given to caregivers to >90%. * This work can serve as a model for implementation to improve identification of HIV-infected infants in other resource-poor settings., Introduction Newborns infected with HIV before, during, or shortly after delivery have high mortality, with 50% dying before one year of age, and 20% of these early deaths occurring between [...]

Background Hypertension is a growing public health emergency in rural sub-Saharan Africa. Based on the known influence of religious leaders in rural sub-Saharan Africa and our prior research, we explored perspectives of religious leaders on hypertension and potential strategies to improve hypertension control in their communities. Methods We conducted 31 in-depth interviews with Christian (n = 17) and Muslim (n = 14) religious leaders in rural Tanzania. Interviews focused on religious leaders' perceptions of hypertension and how they could play a role in promoting blood pressure reduction. We used interpretative phenomenological analysis, a qualitative research method, to understand religious leaders' perspectives on, and experiences with, hypertension. Results Three main themes emerged during analysis. First, we found that perceptions about causes, treatment, and complications of hypertension are influenced by religious beliefs. Second, religious beliefs can enable engagement with hypertension care through religious texts that support the use of biomedical care. Third, religious leaders are enthusiastic potential partners for promoting hypertension control in their communities. These themes were consistent between religion and gender of the religious leaders. Conclusions Religious leaders are eager to learn about hypertension, to share this knowledge with others and to contribute to improved health in their communities. [ABSTRACT FROM AUTHOR]

Background: For patients with sentinel lymph node (SLN)-positive cutaneous melanoma, the Second Multicenter Selective Lymphadenectomy trial demonstrated equivalent disease-specific survival (DSS) with active surveillance using nodal ultrasound versus completion lymph node dissection (CLND). Adoption and outcomes of active surveillance in clinical practice and in adjuvant therapy recipients are unknown.Methods: In a retrospective cohort of SLN-positive adults treated at 21 institutions in Australia, Europe, and the United States from June 2017 to November 2019, the authors evaluated the impact of active surveillance and adjuvant therapy on all-site recurrence-free survival (RFS), isolated nodal RFS, distant metastasis-free survival (DMFS), and DSS using Kaplan-Meier curves and Cox proportional hazard models.Results: Among 6347 SLN biopsies, 1154 (18%) were positive and had initial negative distant staging. In total, 965 patients (84%) received active surveillance, 189 (16%) underwent CLND. Four hundred thirty-nine patients received adjuvant therapy (surveillance, 38%; CLND, 39%), with the majority (83%) receiving anti-PD-1 immunotherapy. After a median follow-up of 11 months, 220 patients developed recurrent disease (surveillance, 19%; CLND, 22%), and 24 died of melanoma (surveillance, 2%; CLND, 4%). Sixty-eight patients had an isolated nodal recurrence (surveillance, 6%; CLND, 4%). In patients who received adjuvant treatment without undergoing prior CLND, all isolated nodal recurrences were resectable. On risk-adjusted multivariable analyses, CLND was associated with improved isolated nodal RFS (hazard ratio [HR], 0.36; 95% CI, 0.15-0.88), but not all-site RFS (HR, 0.68; 95% CI, 0.45-1.02). Adjuvant therapy improved all-site RFS (HR, 0.52; 95% CI, 0.47-0.57). DSS and DMFS did not differ by nodal management or adjuvant treatment.Conclusions: Active surveillance has been adopted for most SLN-positive patients. At initial assessment, real-world outcomes align with randomized trial findings, including in adjuvant therapy recipients.Lay Summary: For patients with melanoma of the skin and microscopic spread to lymph nodes, monitoring with ultrasound is an alternative to surgically removing the remaining lymph nodes. The authors studied adoption and real-world outcomes of ultrasound monitoring in over 1000 patients treated at 21 centers worldwide, finding that most patients now have ultrasounds instead of surgery. Although slightly more patients have cancer return in the lymph nodes with this strategy, typically, it can be removed with delayed surgery. Compared with up-front surgery, ultrasound monitoring results in the same overall risk of melanoma coming back at any location or of dying from melanoma. [ABSTRACT FROM AUTHOR]

Background: Internationally, pediatric depression and suicide are significant issues. Additionally, in the context of the COVID-19 pandemic, pediatric mental health needs are rising astronomically. In light of Child & Adolescent Psychiatrist (CAP) subspecialist shortages in the United States (US), there is an increasing call for primary care physicians in Family Medicine and Pediatrics to address an increasingly broad variety of patient needs. Here we report on the development and preliminary evaluation of medical student and resident perceptions on the "INteractive Virtual Expert-led Skills Training" (INVEST) medical education curriculum, a virtual synchronous CAP curriculum employing active learning strategies, including expert-led discussion and video modeling, and discussion designed to meet those priorities. Methods: In a standardized 60-min training format, our curriculum leverages audience response system polling, video modeling of key clinical skills, and interactive discussion with an expert subspecialist, over a virtual video conferencing platform. The primary educational strategy relies on use of video modeling to demonstrate best practice with CAP led group discussion to solidify and explain important concepts. Five waves of medical students and residents (N = 149) participated in the INVEST curriculum and completed pre- and post-training surveys regarding knowledge and comfort in the management of pediatric patients with depression and suicidality. Results: Trainee participants reported significant positive gains in perceived likelihood of encountering pediatric suicidality as well as knowledge/comfort with depression screening and suicidality assessment in a primary care setting. Across some competency areas, there was an effect of medical learner level. Learners at lower levels generally reported the highest benefit. Medical students reported significant increases in their comfort interpreting and discussing positive depression screens and evidenced the greatest relative benefit in comfort with discussing suicidality. Conclusion: To our knowledge, INVEST is the first fully virtual, multimodal curriculum led by expert CAP subspecialists. Our findings suggest that INVEST shows promise for equipping medical learners with baseline knowledge for caring for patients with pediatric depression and suicidality. This synchronous, virtually delivered curriculum allows for critical training delivered to diverse medical learners regardless of geographic location, a particular benefit during the current COVID-19 pandemic. [ABSTRACT FROM AUTHOR]

Although a growing number of studies suggest interactions between Schistosoma parasites and viral infections, the effects of schistosome infections on the host response to viruses have not been evaluated comprehensively. In this systematic review, we investigated how schistosomes impact incidence, virulence, and prevention of viral infections in humans and animals. We also evaluated immune effects of schistosomes in those coinfected with viruses. We screened 4,730 studies and included 103. Schistosomes may increase susceptibility to some viruses, including HIV and Kaposi's sarcoma-associated herpesvirus, and virulence of hepatitis B and C viruses. In contrast, schistosome infection may be protective in chronic HIV, Human T-cell Lymphotropic Virus-Type 1, and respiratory viruses, though further research is needed. Schistosome infections were consistently reported to impair immune responses to hepatitis B and possibly measles vaccines. Understanding the interplay between schistosomes and viruses has ramifications for anti-viral vaccination strategies and global control of viral infections. Author summary: Many studies have described the effects of parasitic Schistosoma worm infections on the way that humans and animals respond to a variety of viral infections. Our goal was to evaluate, in a systematic manner, how having a schistosome parasitic infection affects a host's susceptibility to viral infections, the clinical disease course of viral infections, and prevention of viral infections by vaccines. We also assessed the effects of schistosome infection on the host immune response to viruses. We screened 4,730 studies for potential relevance and included 103 of them in this review. Overall, our analysis showed that schistosome infection impairs the host response to many viruses. This includes increasing host susceptibility to HIV and possibly Kaposi's sarcoma-associated herpesvirus, worsening the severity of clinical disease in hepatitis B and C infections, and decreasing immune responses to vaccines for hepatitis B and possibly measles. The studies that we analyzed also suggested that schistosome infection may protect the host against poor clinical outcomes from some viral infections including Human T-cell Lymphotropic Virus-Type 1, respiratory viruses, and chronic HIV. We discuss how these findings might be interpreted, and the additional research needed, in order to improve anti-viral vaccination strategies and control of viral infections globally. [ABSTRACT FROM AUTHOR]

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Background: Detection of subclinical cryptococcal disease using cryptococcal antigen screening among HIV‐positive individuals presents a potential opportunity for prevention of both clinical disease and death if patients with detectable cryptococcal antigen are identified and treated pre‐emptively. Recently developed point‐of‐care cryptococcal antigen tests may be useful for screening, particularly in resource‐limiting settings, but few studies have assessed their utility. Methodology: The objectives of this study were to determine the prevalence and factors associated with cryptococcal antigenemia in HIV‐positive patients with CD4[sup.+] T‐cell counts ≤200 cells/µL who were initiating ART, and also to evaluate the utility of the point‐of‐care urine lateral flow assay (LFA) cryptococcal antigen test using two different diluents, compared to gold standard serum antigen testing, as a screening tool. Urine and serum of outpatients initiating antiretroviral therapy at two hospitals in Mwanza were tested for cryptococcal antigen, and demographic and clinical characteristics were obtained using structured questionnaires and patients’ files. Patients with asymptomatic cryptococcal antigenemia received oral fluconazole in accordance with World Health Organization recommendations. Results: Among 140 patients screened, 10 (7.1%) had asymptomatic cryptococcal antigenemia with a positive serum cryptococcal antigen. Four of these ten patients had CD4 counts between 100 and 200 cells/µL. The prevalence of cryptococcal antigen detected in urine using a standard (older) and a test (newer) diluent were 44 (31.4%) and 19 (13.6%), with Kappa coefficients compared to serum of 0.28 and 0.51 (p Conclusions: Our findings suggest that HIV‐positive outpatients with CD4 counts, Introduction Cryptococcus neoformans is one of the leading opportunistic infections in people living with HIV/AIDS in sub‐Saharan Africa [1–4]. It is estimated that 3% of HIV‐positive individuals in sub‐Saharan Africa [...]