Factors Associated with Leg Ulcers in Adults with Sickle Cell Disease in Brazil.

OBJECTIVE: To define the prevalence of leg ulcers and identify the clinical and laboratory factors associated with leg ulcers in adult participants. METHODS: The authors conducted a cross-sectional study of 1,109 patients who were 18 years or older with SS or Sß0-thalassemia genotypes from a Brazilian cohort. Investigators assessed the prevalence of factors associated with leg ulcers from 2013 to 2017. RESULTS: The prevalence of leg ulcers was 21%. Increasing age (odds ratio [OR], 1.07; range, 1.06-1.09), male sex (OR, 2.03; range, 1.44-2.87), treatment with chronic transfusion therapy (OR, 1.88; range, 1.15-3.03), higher indirect bilirubin levels (OR, 1.48; range, 1.02-2.16), and low hemoglobin levels (OR, 2.17; range, 1.52-3.11) were associated with leg ulcers. Participants who self-reported as Black (OR, 6.75; range, 2.63-21.32), mixed (OR, 3.91; range, 1.55-12.20), and other/unknown (OR, 3.84; range, 1.04-15.24) were more likely to have leg ulcers compared with those who self-reported as White. CONCLUSIONS: The prevalence of leg ulcers in this Brazilian cohort was higher than the prevalence reported in developed countries. Known factors such as age and male sex were corroborated. The increased bilirubin level and decreased hemoglobin levels among participants with leg ulcers support the hypothesis that hemolysis is correlated with leg ulcer pathogenesis. Self-reported black skin color was an independent predictor of leg ulcers and warrants further study to understand the etiology and implications of this finding.

Phenotypical characterization of regulatory T cells in acute Zika infection.

Zika virus (ZIKV), alongside Dengue virus (DENV), Chikungunya virus (CHIKV), and Yellow Fever Virus (YFV) are prevalent arboviruses in the Americas. Each of these infections is associated with the development of associated disease immunopathology. Immunopathological processes are an outcome of counter-balancing impacts between effector and regulatory immune mechanisms. In this context, regulatory T cells (Tregs) are key in modulating the immune response and, therefore, in tissue damage control. However, to date, Treg phenotypes and mechanisms during acute infection of the ZIKV in humans have not been fully investigated. The main aim of this work was to characterize Tregs and their immunological profile related to cytokine production and molecules that are capable of controlling the exacerbated inflammatory profile in acute Zika infected patients. Using whole blood analyses of infected patients, an ex vivo phenotypical characterization of Tregs, circulating during acute Zika virus infection, was conducted by flow cytometry. We found that though there are no differences in absolute Treg frequency between infected and healthy control groups. However, pro-inflammatory cytokine up-regulation such as IFN-γ and LAP was observed in the acute disease. Furthermore, acute ZIKV patients expressed increased levels of CD39/CD73, perforin/granzyme B, PD-1, and CTLA-4, all markers involved in mechanisms used by Tregs to attempt to control strong inflammatory responses. Thus, the data indicates a potential contribution of Tregs during the inflammatory ZIKV infection response.

Enlightening clinical and therapeutic heterogeneity in thoracic actinomycosis: A review in bronchiectasis and non-bronchiectasis patients.

Actinomycosis is a rare chronic infection triggered by species of Actinomyces. Although thoracic involvement represents about 15% of human actinomycosis, its true incidence may be underestimated, not only because of its challenging diagnosis, but also because it can be treated unintentionally with antibiotics for other diseases. In this sense, this work aims at providing an up-to-date literature review on thoracic actinomycoses, with particular emphasis on presentation, diagnostic and therapeutic approaches, also paving upcoming clinical interventions from findings obtained of a presentation of a case series. Data discussed here clearly denote the rarity, non-specificity and heterogeneity of clinical presentations of the disease, reinforcing the need for individualized therapeutic approaches.

Social and behavioral characteristics of male blood donors and their sexual partners: an analysis to define risk subsets.

BACKGROUND: Men who have sex with men in Brazil are deferred from donation for 1 year since their last sexual contact. Legal proceedings in front of the Brazilian Supreme Court could compel blood collection agencies to discontinue use of sexual orientation questions. METHODS: Data from male participants in a completed HIV risk factor case-control study were used to evaluate whether it is possible to differentiate donors at lower and higher risk for HIV using two analytical approaches: latent class and random forest analyses. RESULTS: Male blood donors were divided into three distinct risk profile classes. Class 1 includes donors who are heterosexual (96.4%), are HIV negative (88.7%), have a main partner (99.4%), and practice unprotected sex (77.8%). Class 2 includes donors who are men who have sex with men /bisexuals' (100.0%), are HIV positive (97.4%), and were not aware of their sexual partners' HIV status (80.3%). Class 3 includes donors who are heterosexual (84.1%), practice unprotected vaginal/anal heterosexual sex (66.8% vs. 40.9%), and were both HIV positive and HIV negative (49.5% vs. 50.5%). We also found that asking donors about their partner(s)' HIV serostatus could replace asking about donors' sexual orientation and types of partners with relatively minor shifts in sensitivity (0.76 vs. 0.58), specificity (0.89 vs. 0.94), and positive predictive value (0.85 vs. 0.88). CONCLUSION: Sexual orientation questions on the donor questionnaire could be replaced without great loss in the sensitivity, specificity, and positive predictive value. Social and sexual behaviors of donors and their partners are proxies for HIV risk and can help to develop modified questions that will need controlled trials to be validated.

Human CD8 T-cell activation in acute and chronic chikungunya infection.

There is a need for more detailed elucidation of T-cell immunity in chikungunya infection. CD8 T cells are one of main actors against viruses. Here, we analysed CD8+ T lymphocytes from patients in the acute and chronic phases of chikungunya disease (CHIKD). Our results demonstrate that CD8+ T cells expressed higher ex vivo granzyme B, perforin and CD107A expression in patients in the acute phase of CHIKD compared with healthy individuals and higher ex vivo expression of CD69, interleukin-17A, interleukin-10 and CD95 ligand, and co-expression of CD95/CD95 ligand. These results elucidate the importance of these lymphocytes, demonstrating immune mechanisms mediated in human chikungunya infection.

New cost-effective bioconversion process of palm kernel cake into bioinsecticides based on Beauveria bassiana and Isaria javanica.

The present study aimed to add value to palm oil by-products as substrates to efficiently produce conidia of Beauveria bassiana and Isaria javanica (Hypocreales: Cordycipitaceae) for biological control of the whitefly Bemisia tabaci (Hemiptera: Aleyrodidae), through a solid-state fermentation process using palm kernel cake and palm fiber as nutrient source and solid matrix, respectively. The optimum culture conditions yielded high concentrations of viable conidia after air-drying, when the fungi were grown on palm kernel cake (B. bassiana 7.65 × 109 and I. javanica 2.91 × 109 conidia g-1 dry substrate) after 6 days under optimal growth conditions set to 60% substrate moisture and 32 °C. Both fungal strains exhibited high efficacy against third-instar whitefly nymphs, inducing mortality up to 62.9 and 56.6% by B. bassiana and I. javanica, respectively, assessed after 9 days post-application in a screenhouse. Furthermore, we noted that insect mortality was strongly correlated with high atmospheric moisture, while B. bassiana appeared to require shorter accumulative hours under high moisture to kill whitefly nymphs compared to I. javanica. Our results underpin a feasible and cost-effective mass production method for aerial conidia, using palm kernel as the main substrate in order to produce efficacious fungal bioinsecticides against an invasive whitefly species in Brazil. Finally, our fermentation process may offer a sustainable and cost-effective means to produce eco-friendly mycoinsecticides, using an abundant agro-industrial by-product from Brazil that will ultimately assist in the integrated management of agricultural insect pests.

A pedunculated lesion on the foot: acquired fibrokeratoma.

Acquired fibrokeratomas are benign and uncommon lesions consisting of collagenous papules and nodules covered by hyperkeratotic epidermis. These tumors occur mainly on the fingers and toes and infrequently on the palms and soles. They may possibly be triggered by a reaction to a trauma and presents as small and solitary dome-shaped lesions with a collarete of slightly raised skin at the base. Several case reports have been published of this rare lesion, with only a few investigators describing lesions of the feet.

What Are We Looking for in Computer-Based Learning Interventions in Medical Education? A Systematic Review.

BACKGROUND: Computer-based learning (CBL) has been widely used in medical education, and reports regarding its usage and effectiveness have ranged broadly. Most work has been done on the effectiveness of CBL approaches versus traditional methods, and little has been done on the comparative effects of CBL versus CBL methodologies. These findings urged other authors to recommend such studies in hopes of improving knowledge about which CBL methods work best in which settings. OBJECTIVE: In this systematic review, we aimed to characterize recent studies of the development of software platforms and interventions in medical education, search for common points among studies, and assess whether recommendations for CBL research are being taken into consideration. METHODS: We conducted a systematic review of the literature published from 2003 through 2013. We included studies written in English, specifically in medical education, regarding either the development of instructional software or interventions using instructional software, during training or practice, that reported learner attitudes, satisfaction, knowledge, skills, or software usage. We conducted 2 latent class analyses to group articles according to platform features and intervention characteristics. In addition, we analyzed references and citations for abstracted articles. RESULTS: We analyzed 251 articles. The number of publications rose over time, and they encompassed most medical disciplines, learning settings, and training levels, totaling 25 different platforms specifically for medical education. We uncovered 4 latent classes for educational software, characteristically making use of multimedia (115/251, 45.8%), text (64/251, 25.5%), Web conferencing (54/251, 21.5%), and instructional design principles (18/251, 7.2%). We found 3 classes for intervention outcomes: knowledge and attitudes (175/212, 82.6%), knowledge, attitudes, and skills (11.8%), and online activity (12/212, 5.7%). About a quarter of the articles (58/227, 25.6%) did not hold references or citations in common with other articles. The number of common references and citations increased in articles reporting instructional design principles (P=.03), articles measuring online activities (P=.01), and articles citing a review by Cook and colleagues on CBL (P=.04). There was an association between number of citations and studies comparing CBL versus CBL, independent of publication date (P=.02). CONCLUSIONS: Studies in this field vary highly, and a high number of software systems are being developed. It seems that past recommendations regarding CBL interventions are being taken into consideration. A move into a more student-centered model, a focus on implementing reusable software platforms for specific learning contexts, and the analysis of online activity to track and predict outcomes are relevant areas for future research in this field.

IgG4-related disease: Case report and 6-year follow-up of an elusive diagnosis mimicking malignancy.

Key Clinical Message: IgG4-related disease is a rare and emerging pathology, characterized by the appearance of pseudotumors. Due to the ability to mimic other pathologies, it is essential to consider it as a differential diagnosis in multisystemic processes. The diagnosis is challenging, requiring a multidisciplinary approach, to minimize the associated morbidity and mortality. Abstract: IgG4-related disease (IgG4-RD) is a rare, emerging, systemic and chronic pathology, characterized by the appearance of pseudotumors resulting from tissue infiltration by IgG4-positive plasma cells that promote eosinophilic inflammation of the tissue with subsequent fibrosis. We present the case of a male, 45-year-old patient, with marked weight loss and skin pallor detected by his family doctor during a child health consultation of his daughter. When questioned, the patient referred complaints of postprandial discomfort in the left hypochondrium with a feeling of fullness, weight loss, chronic fatigue and hyperhidrosis that had lasted for a month. On physical examination, he was pale, and had pain at palpation of the left hypochondrium. Laboratory data showed increased inflammation markers, abdominal ultrasound and CT demonstrated numerous enlarged lymph nodes in the upper quadrants, raising concern for a malignant lymphoproliferative process. Serological, imaging, clinical and laparoscopic excisional biopsy revealed features of IgG4-related disease and excluded malignant lymphoproliferative disease. The immediate response to treatment with oral prednisolone 30 mg/day also contributed for diagnosis confirmation. Due to refractory disease after gradual prednisolone reduction, second-line therapy with rituximab was initiated. Over the 6 years of follow-up, the patient presented multiple exacerbations characterized by the emergence of systemic symptoms, being maintained under close clinical and imaging follow-up by reumathology, infectious diseases, and family medicine specialists.

Enhancing pulmonary delivery and immunomodulation of respiratory diseases through virus-mimicking nanoparticles.

This study introduces the nanobromhexine lipid particle (NBL) platform designed for effective pulmonary drug delivery. Inspired by respiratory virus transport mechanisms, NBL address challenges associated with mucus permeation and inflammation in pulmonary diseases. Composed of low molecular weight polyethylene glycol-coated lipid nanoparticles with bromhexine hydrochloride, NBL exhibit a size of 118 ± 24 nm, a neutral zeta potential, osmolarity of 358 ± 28 mOsmol/kg, and a pH of 6.5. Nebulizing without leakage and showing no toxicity to epithelial cells, NBL display mucoadhesive properties with a 60% mucin-binding efficiency. They effectively traverse the dense mucus layer of Calu-3 cultures in an air-liquid interface, as supported by a 55% decrease in MUC5AC density and a 29% increase in nanoparticles internalization compared to non-exposed cells. In assessing immunomodulatory effects, NBL treatment in SARS-CoV-2-infected lung cells leads to a 40-fold increase in anti-inflammatory MUC1 gene expression, a proportional reduction in pro-inflammatory IL-6 expression, and elevated anti-inflammatory IL-10 expression. These findings suggest a potential mechanism to regulate the excessive IL-6 expression triggered by virus infection. Therefore, the NBL platform demonstrates promising potential for efficient pulmonary drug delivery and immunomodulation, offering a novel approach to addressing mucus permeation and inflammation in pulmonary diseases.

Primary care in supplementary health: assessment of costs in the care of older adult patients with heart diseases.

OBJECTIVES: to identify whether implementing a supplementary Primary Health Care (PHC) system makes it possible to reduce care costs for older adults with heart diseases. METHODS: a retrospective cohort of 223 patients with heart disease aged ≥ 60 years. Data were obtained from medical records and cost databases, assessed for a period of one year before and after PHC implementation. The results were expressed as mean absolute frequencies for number of hospitalizations and as average annual expenses expressed in dollars (US$) in relation to cost data. RESULTS: there was a reduction in hospitalization expenses after implementing supplementary PHC (p=0.01) and a decrease in the frequency of hospitalizations for the entire sample (p=0.006). There was a reduction in the frequency of consultations at the Emergency Room among frail older adults (p=0.011). CONCLUSIONS: there was a reduction in hospitalization costs and frequency of visits to the Emergency Room after supplementary PHC.

Prevalence and Risk Factors for Human T-Cell Lymphotropic Virus (HTLV) in Blood Donors in Brazil-A 10-Year Study (2007-2016).

It is unknown whether HTLV-1/2 prevalence has been stable or changing with time in Brazil. We present a 10-year (2007-2016) analysis of HTLV-1/2 infection in first-time blood donors from four blood banks in Brazil. The Brazilian blood centers participating in this multicenter Recipient Epidemiology and Donor Evaluation Study (REDS) are located in Recife in the Northeast and in São Paulo, Rio de Janeiro and Belo Horizonte located in the Southeast of the country. A previous REDS study using the same database from 2007 to 2009 showed that the prevalence per 100,000 donors was 222 in Recife, 83 in Belo Horizonte and 101 in São Paulo. From 2007 to 2016, HTLV-1/2 prevalence was calculated by year, blood center and birth cohort. Covariates included age, gender, schooling, self-reported skin color and type of donation. From 1,092,174 first-blood donations, in the general analysis, HTLV-1/2 infection predominated in females, donors over 50 years of age, black skin color and less educated. The average prevalence was 228 per 100,000 donors in Recife, 222 in Rio de Janeiro, 104 in Belo Horizonte and 103 in São Paulo. In the 10-year analysis, HTLV-1/2 prevalence was stable, but a trend was observed toward an increase in HTLV-1/2 infection among younger people (p < 0.001), males (p = 0.049), those with white skin color (p < 0.001), and higher education (p = 0.014). Therefore, this 10-year surveillance of the infection showed stable HTLV-1/2 prevalence overall but a trend toward increased prevalence among the younger and more educated donors despite Brazilian policies to control sexually transmitted infections being in place for more than 10 years.

Downregulation of CD73 on CD4+ T cells from patients with chronic Chikungunya infection.

Chikungunya is an important mosquito-borne disease caused by the arthritogenic chikungunya virus, characterized by sporadic outbreaks all around the world. Although CD4+ T cells seem to have an important role in the pathogenesis of chikungunya, the mechanisms involved in this process are not yet fully elucidated. The ectoenzymes CD39 and CD73, also expressed by CD4 T lymphocytes, are involved in the hydrolysis of pro-inflammatory extracellular ATP and generation of immunosuppressive adenosine and seem to be modulated in some arthritogenic pathologies. However, their involvement in Chikungunya disease is unclear. Thus, using flow cytometry, we investigated peripheral CD4+ T cells from patients with acute and chronic chikungunya to assess the expression of ectonucleotidases CD39 and CD73 and coinhibitory receptors and production of cytokine and cytolytic granules. Patients in the acute phase displayed increased levels of PD-1, CTLA-4, IL-10, and IFN-γ compared to healthy individuals and patients in the chronic phase. Moreover, during chronic Chikungunya, analyses of Mean Fluorescent Intensity (MFI) demonstrated a reduced density of LAP, Perforin and Granzyme B compared to the healthy control. Finally, reduced levels of the ectoenzymes CD39 and CD73 expression was found during the chronic phase suggesting a possible modulation of extracellular ATP and adenosine by CD4+ T cells that may be involved in the persistence of arthritogenic symptoms.

Regulatory T cells in acute and chronic human Chikungunya infection.

Chikungunya virus (CHIKV) infection generates strong immune responses that are associated with the disease pathophysiology. Regulatory T cells (Treg-cluster of differentiation (CD)-4+CD25highforkhead box P3 (FOXP3+)) are essential for the induction and maintenance of peripheral tolerance. Thus, they play key roles in determining the patient prognosis by preventing excessive immune responses via different suppression immune mechanisms. However, the regulatory mechanisms involved in human CHIKV infection are still poorly understood. Here, we characterize for the first time the Treg cell molecule-associated-mechanism during acute and chronic human Chikungunya disease. Here, we assessed the Treg cell population and molecule-associated mechanism in the peripheral blood samples of acute and chronic patients with Chikungunya. Our results indicate that CHIKV infection is associated with reduced frequency of Tregs, along with the impaired expression and production of Treg functional markers, including CD39, CD73, perforin, granzyme, programmed death 1 (PD-1), cytotoxic T lymphocyte antigen (CTLA)-4, and transforming growth factor (TGF)-ß. This observation suggests that Treg cells possess the poor regulatory capacity in both acute and chronic phases of the disease. Taken together, these data provide significant evidence that the imbalanced response of Treg cells plays an essential role in establishing the pathogenesis of Chikungunya.

Lung cancer: atypical brain metastases mimicking neurocysticercosis.

The authors describe a case of a 47-year-old male smoker with a 3-month history of hearing loss, tinnitus and dizziness. Physical examination revealed neurosensory hearing loss. Small rounded hypodensities without mass effect were evident in a computed tomography scan of the head, confirmed by brain magnetic resonance imaging as multiple cystic lesions in both cerebral and cerebellar hemispheres, without perilesional edema or gadolinium enhancement, suggestive of neurocysticercosis. Extraparenchymal involvement was also noted. Albendazole and dexamethasone were started. As a chest radiograph showed a bilateral reticulonodular pattern, a bronchoscopy was performed showing normal results. However, transbronchial biopsy revealed lung adenocarcinoma. Thoracoabdominopelvic computed tomography scan showed secondary lung and bone lesions. Since brain lesions were not suggestive of secondary tumor lesions, a brain biopsy was performed confirming metastatic disease. This case illustrates some peculiar imagiological features of brain metastases in lung cancer, indicating that sometimes invasive procedures are required to establish a definitive diagnosis.

Duration of temporary catheter use for hemodialysis: an observational, prospective evaluation of renal units in Brazil.

BACKGROUND: For chronic hemodialysis, the ideal permanent vascular access is the arteriovenous fistula (AVF). Temporary catheters should be reserved for acute dialysis needs. The AVF is associated with lower infection rates, better clinical results, and a higher quality of life and survival when compared to temporary catheters. In Brazil, the proportion of patients with temporary catheters for more than 3 months from the beginning of therapy is used as an evaluation of the quality of renal units. The aim of this study is to evaluate factors associated with the time between the beginning of hemodialysis with temporary catheters and the placement of the first arteriovenous fistula in Brazil. METHODS: This is an observational, prospective non-concurrent study using national administrative registries of all patients financed by the public health system who began renal replacement therapy (RRT) between 2000 and 2004 in Brazil. Incident patients were eligible who had hemodialysis for the first time. Patients were excluded who: had hemodialysis reportedly started after the date of death (inconsistent database); were younger than 18 years old; had HIV; had no record of the first dialysis unit; and were dialyzed in units with less than twenty patients. To evaluate individual and renal unit factors associated with the event of interest, the frailty model was used (N = 55,589). RESULTS: Among the 23,824 patients (42.9%) who underwent fistula placement in the period of the study, 18.2% maintained the temporary catheter for more than three months until the fistula creation. The analysis identified five statistically significant factors associated with longer time until first fistula: higher age (Hazard-risk - HR 0.99, 95% CI 0.99-1.00); having hypertension and cardiovascular diseases (HR 0.94, 95% CI 0.9-0.98) as the cause of chronic renal disease; residing in capitals cities (HR 0.92, 95% CI 0.9-0.95) and certain regions in Brazil - South (HR 0.83, 95% CI 0.8-0.87), Midwest (HR 0.88, 95% CI 0.83-0.94), Northeast (HR 0.91, 95% CI 0.88-0.94), or North (HR 0.88, 95% CI 0.83-0.94) and the type of renal unit (public or private). CONCLUSION: Monitoring the provision of arteriovenous fistulas in renal units could improve the care given to patients with end stage renal disease.

Predictors and reference equations for augmentation index, an arterial stiffness marker, in healthy children and adolescents.

OBJECTIVES: To investigate predictors and propose reference equations for the augmentation index normalized to 75 bpm heart rate (AIx@75) in healthy children and adolescents. METHODS: This was a cross-sectional, observational study involving 134 healthy children and adolescents aged 9 to 19 years old. Participants were categorized into child (n=53) and adolescent (n=81) groups, as well as into male (n=69) and female (n=65) groups. We evaluated AIx@75, vascular and hemodynamic parameters, anthropometric data, physical activity profile, and quality of life (Peds-QL4.0; physical, emotional, social and school domains). RESULTS: The predictors of AIx@75 in the whole sample were age, peripheral diastolic blood pressure (pDBP), mean arterial pressure, pulse pressure amplification (PPA), systolic volume (SV), cardiac index (CI), and pulse wave velocity (PWV; R2=80.47%). In the male group, the predictors of AIx@75 were SV, CI, total vascular resistence (TVR), and PWV (R2=78.56%), while in the female group, they were pDBP, PPA, SV, and PWV (R2=82.45%). In the children, they were pDBP, PPA, SV, and PWV (R2=79.17%), while in the adolescents, they were body mass index, pDBP, PPA, SV, TVR, and PWV (R2=81.57%). CONCLUSION: In the present study, we used a representative sample from Belo Horizonte to establish normality values of AIx@75. We also identified, for the first time, independent predictors of AIx@75 in healthy children and adolescents categorized by sex and age. Determining AIx@75 reference equations may facilitate the early diagnosis of preclinical atherosclerosis and allow an objective measure of the vascular effects of therapeutic interventions aimed at modifying cardiovascular risk factors.

Partial Pulpotomy with Mineral Trioxide Aggregate in Permanent Incisors with Complicated Crown Fracture: 5-Year Follow-Up.

Traumatic dental injuries are highly prevalent among children. This article describes a case report of a patient who has experienced dental trauma at 8 years old, which has led to enamel-dentine fracture with pulp exposure in the left central incisor and crown-root fracture with pulp exposure in the right central incisor. Partial pulpotomy was performed with the aim of maintaining the neurovascular bundle, thus allowing normal radicular formation. During follow-up 5 years later, teeth were asymptomatic and with no evidence of radiolucent lesions in radiographic examinations. This report demonstrates that traumatic fractures with pulp exposure can be treated effectively by the described technique.

Patterns of Sexual Risk Behavior, HIV Infection, and Use of Health Services Among Sub-Saharan African Migrants in Portugal.

This study identified patterns of sexual risk behavior among a sub-Saharan African migrant (SAM) population in Portugal and examined its associations with human immunodeficiency virus (HIV) prevalence, sociodemographics, use of sexual health services, and HIV testing. A cross-sectional biobehavioral survey was conducted with a venue-based sample of 790 SAMs. Data were collected using questionnaires and rapid HIV tests. Cluster analysis identified five subgroups with differing levels of HIV infection (2.5% to 11.3%). In Cluster 1, most participants reported sexual abstinence over the past year and the remaining used condoms consistently; this cluster had the highest HIV prevalence (11.3%). In Cluster 2, most reported one sexual partner and all reported unprotected sex; all HIV-positive participants in this cluster were unaware of their HIV-positive status. In Clusters 3 and 4, most had four or more partners, yet all used condoms. In Cluster 3, 56.5% reported both regular and occasional partners. In Cluster 4, 74% had only occasional partners; all engaged in commercial sex. In Cluster 5, all reported four or more partners and condomless sex. In all subgroups we found low rates of HIV testing and high unawareness of HIV serostatus. Targeted prevention interventions are needed to reduce unprotected sexual relations and undiagnosed infection, as well as improve linkage to sexual health services.

The DNA Sensor AIM2 Protects against Streptozotocin-Induced Type 1 Diabetes by Regulating Intestinal Homeostasis via the IL-18 Pathway.

Pattern recognition receptors (PRRs), such as Nod2, Nlrp3, Tlr2, Trl4, and Tlr9, are directly involved in type 1 diabetes (T1D) susceptibility. However, the role of the cytosolic DNA sensor, AIM2, in T1D pathogenesis is still unknown. Here, we demonstrate that C57BL/6 mice lacking AIM2 (AIM2-/-) are prone to streptozotocin (STZ)-induced T1D, compared to WT C57BL/6 mice. The AIM2-/- mice phenotype is associated with a greater proinflammatory response in pancreatic tissues, alterations in gut microbiota and bacterial translocation to pancreatic lymph nodes (PLNs). These alterations are related to an increased intestinal permeability mediated by tight-junction disruption. Notably, AIM2-/- mice treated with broad-spectrum antibiotics (ABX) are protected from STZ-induced T1D and display a lower pancreatic proinflammatory response. Mechanistically, the AIM2 inflammasome is activated in vivo, leading to an IL-18 release in the ileum at 15 days after an STZ injection. IL-18 favors RegIIIγ production, thus mitigating gut microbiota alterations and reinforcing the intestinal barrier function. Together, our findings show a regulatory role of AIM2, mediated by IL-18, in shaping gut microbiota and reducing bacterial translocation and proinflammatory response against insulin-producing ß cells, which ultimately results in protection against T1D onset in an STZ-induced diabetes model.