Medical students experience in working in a public COVID-19 telehealth program: a descriptive study.

BACKGROUND: Given the health and social needs generated by the COVID-19 pandemic, the Telehealth Network of Minas Gerais, Brazil, implemented a teleconsultation and telemonitoring program to assist patients with suspected or confirmed COVID-19, the TeleCOVID-MG program. The telemonitoring service was conducted by medical students, under the supervision of a physician. The main goal of this study was to analyze the experience of the students while collaborating on the aforementioned telemonitoring program. METHODS: A questionnaire with 27 questions was developed to address the participation of the students in the telehealth program. The questionnaire included questions about the student's profile, the system usability, and the satisfaction in participating in such a telehealth program. The questionnaire was generated on Google Forms® platform and sent via email to each student who was part of the telemonitoring team. RESULTS: Sixty students were included in the analysis (median age 25 years-old [interquartile range 24-26], 70% women). Of those, 61.6% collaborated on the telehealth program for more than 6 months, 65.1% performed more than 100 telemonitoring calls, 95.2% reported difficulties in contacting the patient through phone calls; 60.3% believe some patients might have felt insecure about being approached by medical students and not by graduate professionals; and 39.6% reported eventual system instabilities. The main strengths reported by the students were related to the system usability and to the self-perception of the quality of healthcare delivered to the patients. Even though 68.3% of the students mentioned technical difficulties, 96.6% reported that they were promptly solved. Finally, 98.3% believed that the program was useful and would recommend it to an acquaintance. CONCLUSION: This study reports a successful experience of undergraduate medical students in a COVID-19 telemonitoring program. Overall, the medical students were satisfied with their participation, especially considering the continuity of clinical practice remotely during a period of classes suspension during the COVID-19 pandemic and their important role in the assistance of patients from low-income regions, which has minimized the health system burden in an emergency context.

Effect of a Structured Multilevel Telehealth Service on Hospital Admissions and Mortality During COVID-19 in a Resource-Limited Region in Brazil: Retrospective Cohort Study.

BACKGROUND: The COVID-19 pandemic represented a great stimulus for the adoption of telehealth and many initiatives in this field have emerged worldwide. However, despite this massive growth, data addressing the effectiveness of telehealth with respect to clinical outcomes remain scarce. OBJECTIVE: The aim of this study was to evaluate the impact of the adoption of a structured multilevel telehealth service on hospital admissions during the acute illness course and the mortality of adult patients with flu syndrome in the context of the COVID-19 pandemic. METHODS: A retrospective cohort study was performed in two Brazilian cities where a public COVID-19 telehealth service (TeleCOVID-MG) was deployed. TeleCOVID-MG was a structured multilevel telehealth service, including (1) first response and risk stratification through a chatbot software or phone call center, (2) teleconsultations with nurses and medical doctors, and (3) a telemonitoring system. For this analysis, we included data of adult patients registered in the Flu Syndrome notification databases who were diagnosed with flu syndrome between June 1, 2020, and May 31, 2021. The exposed group comprised patients with flu syndrome who used TeleCOVID-MG at least once during the illness course and the control group comprised patients who did not use this telehealth service during the respiratory illness course. Sociodemographic characteristics, comorbidities, and clinical outcomes data were extracted from the Brazilian official databases for flu syndrome, Severe Acute Respiratory Syndrome (due to any respiratory virus), and mortality. Models for the clinical outcomes were estimated by logistic regression. RESULTS: The final study population comprised 82,182 adult patients with a valid registry in the Flu Syndrome notification system. When compared to patients who did not use the service (n=67,689, 82.4%), patients supported by TeleCOVID-MG (n=14,493, 17.6%) had a lower chance of hospitalization during the acute respiratory illness course, even after adjusting for sociodemographic characteristics and underlying medical conditions (odds ratio [OR] 0.82, 95% CI 0.71-0.94; P=.005). No difference in mortality was observed between groups (OR 0.99, 95% CI 0.86-1.12; P=.83). CONCLUSIONS: A telehealth service applied on a large scale in a limited-resource region to tackle COVID-19 was related to reduced hospitalizations without increasing the mortality rate. Quality health care using inexpensive and readily available telehealth and digital health tools may be delivered in areas with limited resources and should be considered as a potential and valuable health care strategy. The success of a telehealth initiative relies on a partnership between the involved stakeholders to define the roles and responsibilities; set an alignment between the different modalities and levels of health care; and address the usual drawbacks related to the implementation process, such as infrastructure and accessibility issues.

Whole blood transcriptomics reveals the enrichment of neutrophil activation pathways during erythema nodosum leprosum reaction.

Introduction: Patients with the multibacillary form of leprosy can develop reactional episodes of acute inflammation, known as erythema nodosum leprosum (ENL), which are characterized by the appearance of painful cutaneous nodules and systemic symptoms. Neutrophils have been recognized to play a role in the pathogenesis of ENL, and recent global transcriptomic analysis revealed neutrophil-related processes as a signature of ENL skin lesions. Methods: In this study, we expanded this analysis to the blood compartment, comparing whole blood transcriptomics of patients with non-reactional lepromatous leprosy at diagnosis (LL, n=7) and patients with ENL before administration of anti-reactional treatment (ENL, n=15). Furthermore, a follow-up study was performed with patients experiencing an ENL episode at the time of diagnosis and after 7 days of thalidomide treatment (THAL, n=10). Validation in an independent cohort (ENL=8; LL=7) was performed by RT-qPCR. Results: An enrichment of neutrophil activation and degranulation-related genes was observed in the ENL group, with the gene for the neutrophil activation marker CD177 being the most enriched gene of ENL episode when compared to its expression in the LL group. A more pro-inflammatory transcriptome was also observed, with increased expression of genes related to innate immunity. Validation in an independent cohort indicated that S100A8 expression could discriminate ENL from LL. Supernatants of blood cells stimulated in vitro with Mycobacterium leprae sonicate showed higher levels of CD177 compared to the level of untreated cells, indicating that the leprosy bacillus can activate neutrophils expressing CD177. Of note, suggestive higher CD177 protein levels were found in the sera of patients with severe/moderate ENL episodes when compared with patients with mild episodes and LL patients, highlighting CD177 as a potential systemic marker of ENL severity that deserves future confirmation. Furthermore, a follow-up study was performed with patients at the time of ENL diagnosis and after 7 days of thalidomide treatment (THAL, n=10). Enrichment of neutrophil pathways was sustained in the transcriptomic profile of patients undergoing treatment; however, important immune targets that might be relevant to the effect of thalidomide at a systemic level, particularly NLRP6 and IL5RA, were revealed. Discussion: In conclusion, our study reinforces the key role played by neutrophils in ENL pathogenesis and shed lights on potential diagnostic candidates and novel therapeutic targets that could benefit patients with leprosy.

Living fruits of Psychotria brachyceras Müll. Arg. (Rubiaceae) as the main larval host of Zygothrica orbitalis (Sturtevant, 1916) (Diptera, Drosophilidae)

ABSTRACT Zygothrica is a genus of Drosophilidae (Diptera) whose species utilize flowers and fungi for breeding sites, with records of fungi being used as courtship arena. Due to this habit, its representation in Drosophilidae surveys using banana-baited traps is generally low. However, Zygothrica orbitalis was well represented in a few samples with these traps. In this study, we report for the first time the breeding site of Z. orbitalis in living fruits of Psychotria brachyceras (Rubiaceae), noting that the use of living fruits is rare among Drosophilidae. The fructification of the plant occurs in the area of study from May to August, with previous collection records of the species in the Restinga (sandbank or strand) forest. Additionally, the emergence of some individuals of the invasive species Drosophila suzukii was observed, which highlights the necessity for continuous study of this plant to understand the dynamics between a native and an exotic species. Besides the ecological importance, our results are relevant for understanding the evolution of trophic resource use by the Zygothrica genus.

Clinical and electrocardiographic outcomes evaluated by telemedicine of outpatients with clinical suspicion of COVID-19 treated with chloroquine compounds in Brazil†.

Aims: To evaluate clinical and electrocardiographic outcomes of patients with COVID-19, comparing those using chloroquine compounds (chloroquine) to individuals without specific treatment. Methods: Outpatients with suspected COVID-19 in Brazil who had at least one tele-electrocardiography (ECG) recorded in a telehealth system were enrolled in two arms (Group 1: chloroquine and Group 2: without specific treatment) and one registry (Group 3: other treatments). Outcomes were assessed through follow-up calls (phone contact, days 3 and 14) and linkage to national mortality and hospitalization databases. The primary outcome was composed of: hospitalization, intensive care admission, mechanical ventilation, and all-cause death, and the ECG outcome was the occurrence of major abnormalities by the Minnesota code. Significant variables in univariable logistic regression were included in 4 models: 1-unadjusted; 2-adjusted for age and sex; 3-model 2 + cardiovascular risk factors and 4-model 3 + COVID-19 symptoms. Results: In 303 days, 712 (10.2%) patients were allocated in group 1, 3,623 (52.1%) in group 2 and 2,622 (37.7%) in group 3; 1,969 had successful phone follow-up (G1: 260, G2: 871, and G3: 838). A late follow-up ECG was obtained for 917 (27.2%) patients [group 1: 81 (11.4%), group 2: 512 (14.1%), group 3: 334 (12.7%)]. In adjusted models, chloroquine was independently associated with greater chance of the composite clinical outcome: phone contact (model 4): OR = 3.24 (95% CI 2.31-4.54), p < 0.001. Chloroquine was also independently associated with higher mortality, assessed by phone + administrative data (model 3): OR = 1.67 (95% CI 1.20-2.28). However, chloroquine did not associate with the occurrence of major ECG abnormalities [model 3; OR = 0.80 (95% CI 0.63-1.02, p = 0.07)]. Abstracts with partial results of this work was accepted in the American Heart Association Scientific Sessions, November 2022, in Chicago, IL, USA. Conclusion: Chloroquine was associated with a higher risk of poor outcomes in patients suspected to have COVID-19 when compared to those who received standard care. Follow-up ECGs were obtained in only 13.2% of patients and did not show any significant differences in major abnormalities amongst the three groups. In the absence of early ECG changes, other side effects, late arrhythmias or deferral of care may be hypothesized to explain the worse outcomes.

COVID-19 Telehealth Service Can Increase Access to the Health Care System and Become a Cost-Saving Strategy.

Introduction: Data addressing the economic aspects of telehealth initiatives are incipient. This study aimed to evaluate the labor costs for running a COVID-19 telehealth system and its potential incremental access to health care service. Methods: From July 2020 to July 2021, data from a Brazilian teleconsultation service were analyzed. Labor costs were estimated by time-driven activity-based costing. A Generalized Reduced Gradient solving method was coded to maximize the mean incremental access rate and two scenarios were considered to compare the teleconsultation with the in-person consultation: (1) only the length of time that patients spent with a clinician in an in-person consultation was accounted and (2) in addition to the medical consultation, nursing screening was accounted. The mean incremental access rate of the teleconsultation service was defined as a maximization objective in the model. Results: Mean labor costs per medical and nursing teleconsultations are Int$ 24 and Int$ 10, based on data analyses from 25,258 patients. Telemonitoring a patient with a daily call for 7 days costs, on average, Int$ 14. COVID-19 teleconsultation service represents, on average, an incremental access to medical consultation rate of 35% to 52% (min 23% max 63%) for the scenarios (1) and (2), respectively, and considering the current consumed budget for this service. Discussion: A COVID-19 telehealth service contributes to increasing access to the health care system without increasing costs. These services can be included in the bundle of care strategies offered in a national public health care system that looks for more sustainable strategies to provide care.

Cobertura vacinal: uma análise comparativa entre os estados da região nordeste do Brasil com ênfase no estado do Maranhão / Vaccination coverage: a comparative analysis between the states of the northeast region of Brazil with emphasis on the state of Maranhão / Cobertura de vacunación: un análisis comparativo entre los estados de la región nordeste de Brasil con énfasis en el estado de Maranhão

Introdução: Devido à escassez de pesquisas voltadas para a situação da cobertura vacinal no Nordeste, sobretudo no Maranhão, apresenta-se a necessidade de realizar uma análise comparativa entre os estados da região nordeste do Brasil. Objetivo: Analisar a cobertura vacinal entre os estados na Região Nordeste do Brasil entre 2017 a 2021, por meio da análise de dados secundários provenientes de sistemas de informação em saúde. Metodologia: trata-se de estudo ecológico de série temporal, com uso de dados secundários provenientes de sistemas de informação em saúde. Foi realizado por meio da coleta de dados disponibilizados pelo TABNET do Departamento de Informação e Informática do SUS (DATASUS), referentes ao período entre 2017 e 2021, nos estados da Região Nordeste do Brasil. Resultados: No período de 2017 a 2021 a cobertura vacinal na Região Nordeste do Brasil foi de 64,48%, sendo uma das piores do país, perdendo apenas para Região Norte (63,30%). Cabe salientar que a média no país em todo o período analisado foi de 68,57%, estando bem abaixo do ideal (entorno de 90% a 95% a depender do imunizante). E entre os anos de 2019 a 2020 houve um declínio de 12,05% e em 2021 14,87% da cobertura vacinal na região nordeste do país. Conclusão: Este estudo permitiu realizar uma análise comparativa entre os estados da região nordeste do Brasil com ênfase no estado do maranhão quanto à cobertura vacinal, onde foi observado que, o estado do Maranhão apresenta umas das menores taxas de vacinação em comparação com outros estados da região nordeste.

Introduction: Due to the lack of research focused on the situation of vaccination coverage in the Northeast, especially in Maranhão, there is a need to carry out a comparative analysis between the states of the northeast region of Brazil. Objective: To analyze vaccination coverage among states in the Northeast Region of Brazil between 2017 and 2021, through the analysis of secondary data from health information systems. Methodology: this is an ecological time series study, using secondary data from health information systems. It was carried out by collecting data provided by the TABNET of the Department of Information and Informatics of the SUS (DATASUS), referring to the period between 2017 and 2021, in the states of the Northeast Region of Brazil. Results: In the period from 2017 to 2021, vaccination coverage in the Northeast Region of Brazil was 64.48%, being one of the worst in the country, second only to the North Region (63.30%). It should be noted that the average in the country throughout the analyzed period was 68.57%, well below the ideal (around 90% to 95% depending on the immunizer). And between the years 2019 to 2020 there was a decline of 12.05% and in 2021 14.87% of vaccination coverage in the northeast region of the country. Conclusion: This study made it possible to carry out a comparative analysis between the states of the northeast region of Brazil, with emphasis on the state of maranhão regarding vaccination coverage, where it was observed that the state of Maranhão has one of the lowest vaccination rates compared to other states in the region. northeast region.

Introducción: Debido a la falta de investigaciones centradas en la situación de las coberturas de vacunación en el Nordeste, especialmente en Maranhão, surge la necesidad de realizar un análisis comparativo entre los estados de la región Nordeste de Brasil. Objetivo: Analizar las coberturas de vacunación entre los estados de la Región Nordeste de Brasil entre 2017 y 2021, a través del análisis de datos secundarios de los sistemas de información en salud. Metodología: se trata de un estudio de series temporales ecológicas, utilizando datos secundarios de los sistemas de información en salud. Fue realizado a partir de la recopilación de datos facilitados por el TABNET del Departamento de Información e Informática del SUS (DATASUS), referentes al período comprendido entre 2017 y 2021, en los estados de la Región Nordeste de Brasil. Resultados: En el período de 2017 a 2021, la cobertura de vacunación en la Región Nordeste de Brasil fue del 64,48%, siendo una de las peores del país, superada solo por la Región Norte (63,30%). Cabe señalar que el promedio en el país durante todo el período analizado fue de 68,57%, muy por debajo del ideal (alrededor de 90% a 95% dependiendo del inmunizador). Y entre los años 2019 a 2020 hubo un descenso de 12,05% y en 2021 de 14,87% de las coberturas de vacunación en la región nororiental del país. región nordeste. PALABRAS CLAVE: Cobertura de Vacunación; Vacunas; Enfermedades Prevenibles por Vacunas.

Synchronous Teleconsultation and Monitoring Service Targeting COVID-19: Leveraging Insights for Postpandemic Health Care.

BACKGROUND: Although a great number of teleconsultation services have been developed during the COVID-19 pandemic, studies assessing usability and health care provider satisfaction are still incipient. OBJECTIVE: This study aimed to describe the development, implementation, and expansion of a synchronous teleconsultation service targeting patients with symptoms of COVID-19 in Brazil, as well as to assess its usability and health care professionals' satisfaction. METHODS: This mixed methods study was developed in 5 phases: (1) the identification of components, technical and functional requirements, and system architecture; (2) system and user interface development and validation; (3) pilot-testing in the city of Divinópolis; (4) expansion in the cities of Divinópolis, Teófilo Otoni, and Belo Horizonte for Universidade Federal de Minas Gerais faculty and students; and (5) usability and satisfaction assessment, using Likert-scale and open-ended questions. RESULTS: During pilot development, problems contacting users were solved by introducing standardized SMS text messages, which were sent to users to obtain their feedback and keep track of them. Until April 2022, the expanded system served 31,966 patients in 146,158 teleconsultations. Teleconsultations were initiated through chatbot in 27.7% (40,486/146,158) of cases. Teleconsultation efficiency per city was 93.7% (13,317/14,212) in Teófilo Otoni, 92.4% (11,747/12,713) in Divinópolis, and 98.8% (4981/5041) in Belo Horizonte (university campus), thus avoiding in-person assistance for a great majority of patients. In total, 50 (83%) out of 60 health care professionals assessed the system's usability as satisfactory, despite a few system instability problems. CONCLUSIONS: The system provided updated information about COVID-19 and enabled remote care for thousands of patients, which evidenced the critical role of telemedicine in expanding emergency services capacity during the pandemic. The dynamic nature of the current pandemic required fast planning, implementation, development, and updates in the system. Usability and satisfaction assessment was key to identifying areas for improvement. The experience reported here is expected to inform telemedicine strategies to be implemented in a postpandemic scenario.

Gene expression patterns associated with multidrug therapy in multibacillary leprosy.

Multidrug therapy (MDT) has been successfully used in the treatment of leprosy. However, although patients are cured after the completion of MDT, leprosy reactions, permanent disability, and occasional relapse/reinfection are frequently observed in patients. The immune system of multibacillary patients (MB) is not able to mount an effective cellular immune response against M. leprae. Consequently, clearance of bacilli from the body is a slow process and after 12 doses of MDT not all MB patients reduce bacillary index (BI). In this context, we recruited MB patients at the uptake and after 12-month of MDT. Patients were stratified according to the level of reduction of the BI after 12 doses MDT. A reduction of at least one log in BI was necessary to be considered a responder patient. We evaluated the pattern of host gene expression in skin samples with RNA sequencing before and after MDT and between samples from patients with or without one log reduction in BI. Our results demonstrated that after 12 doses of MDT there was a reduction in genes associated with lipid metabolism, inflammatory response, and cellular immune response among responders (APOBEC3A, LGALS17A, CXCL13, CXCL9, CALHM6, and IFNG). Also, by comparing MB patients with lower BI reduction versus responder patients, we identified high expression of CDH19, TMPRSS4, PAX3, FA2H, HLA-V, FABP7, and SERPINA11 before MDT. From the most differentially expressed genes, we observed that MDT modulates pathways related to immune response and lipid metabolism in skin cells from MB patients after MDT, with higher expression of genes like CYP11A1, that are associated with cholesterol metabolism in the group with the worst response to treatment. Altogether, the data presented contribute to elucidate gene signatures and identify differentially expressed genes associated with MDT outcomes in MB patients.

The Type I Interferon Pathway Is Upregulated in the Cutaneous Lesions and Blood of Multibacillary Leprosy Patients With Erythema Nodosum Leprosum.

In leprosy patients, acute inflammatory episodes, known as erythema nodosum leprosum (ENL), are responsible for high morbidity and tissue damage that occur during the course of Mycobacterium leprae infection. In a previous study, we showed evidence implicating DNA-sensing via TLR9 as an important inflammatory pathway in ENL. A likely important consequence of TLR9 pathway activation is the production of type I interferons (IFN-I) by plasmacytoid dendritic cells (pDCs), also implicated in the pathogenesis of several chronic inflammatory diseases. In this study, we investigated whether the IFN-I pathway is activated during ENL. Blood samples and skin lesions from multibacillary patients diagnosed with ENL were collected and the expression of genes of the IFN-I pathway and interferon-stimulated genes were compared with samples collected from non-reactional multibacillary (NR) patients. Whole blood RNAseq analysis suggested higher activation of the IFN-I pathway in ENL patients, confirmed by RT-qPCR. Likewise, significantly higher mRNA levels of IFN-I-related genes were detected in ENL skin biopsies when compared to NR patient lesions. During thalidomide administration, the drug of choice for ENL treatment, a decrease in the mRNA and protein levels of some of these genes both in the skin and blood was observed. Indeed, in vitro assays showed that thalidomide was able to block the secretion of IFN-I by peripheral blood mononuclear cells in response to M. leprae sonicate or CpG-A, a TLR9 ligand. Finally, the decreased frequencies of peripheral pDCs in ENL patients, along with the higher TLR9 expression in ENL pDCs and the enrichment of CD123+ cells in ENL skin lesions, suggest the involvement of these cells as IFN-I producers in this type of reaction. Taken together, our data point to the involvement of the pDC/type I IFN pathway in the pathogenesis of ENL, opening new avenues in identifying biomarkers for early diagnosis and new therapeutic targets for the better management of this reactional episode.

Arginase 1 is a marker of protection against illness in contacts of leprosy patients.

Leprosy household contacts are generally more prone to develop the disease compared to the general population. Previous studies have demonstrated that genes related to the alternative activation (M2) profile in macrophages are associated with the increased bacillary load in multibacillary leprosy patients (MB), and that contacts of MB patients have a higher risk of contracting the disease. In addition, positive serological responses to PGL-1 or LID-1 are associated with a higher risk of disease. We performed a 5-year follow-up of contacts of leprosy patients and evaluated the pattern of gene and protein expression in cells from contacts that developed leprosy during this period. Leprosy household contacts had decreased soluble CD163 and heme oxygenase 1 (HO-1) serum levels when compared with healthy donors and leprosy patients. In contrast, arginase 1 activities were higher in contacts when compared with both healthy donors and leprosy patients. Of the contacts, 33 developed leprosy during the follow-up. Gene expression analysis revealed reduced ARG1 expression in these contacts when compared with contacts that did not develop disease. Arginase activity was a good predictive marker of protection in contacts (sensitivity: 90.0%, specificity: 96.77%) and the association with serology for anti-PGL-1 and anti-LID-1 increased the sensitivity to 100%. Altogether, the data presented here demonstrate a positive role of arginase against leprosy and suggest that the evaluation of arginase activity should be incorporated into leprosy control programs in order to aid in the decision of which contacts should receive chemoprophylaxis.

Gene Expression Profile of Mycobacterium leprae Contribution in the Pathology of Leprosy Neuropathy.

Peripheral neuropathy is the main cause of physical disability in leprosy patients. Importantly, the extension and pattern of peripheral damage has been linked to how the host cell will respond against Mycobacterium leprae (M. leprae) infection, in particular, how the pathogen will establish infection in Schwann cells. Interestingly, viable and dead M. leprae have been linked to neuropathology of leprosy by distinct mechanisms. While viable M. leprae promotes transcriptional modifications that allow the bacteria to survive through the use of the host cell's internal machinery and the subvert of host metabolites, components of the dead bacteria are associated with the generation of a harmful nerve microenvironment. Therefore, understanding the pathognomonic characteristics mediated by viable and dead M. leprae are essential for elucidating leprosy disease and its associated reactional episodes. Moreover, the impact of the viable and dead bacteria in Schwann cells is largely unknown and their gene signature profiling has, as yet, been poorly explored. In this study, we analyzed the early differences in the expression profile of genes involved in peripheral neuropathy, dedifferentiation and plasticity, neural regeneration, and inflammation in human Schwann cells challenged with viable and dead M. leprae. We substantiated our findings by analyzing this genetic profiling in human nerve biopsies of leprosy and non-leprosy patients, with accompanied histopathological analysis. We observed that viable and dead bacteria distinctly modulate Schwann cell genes, with emphasis to viable bacilli upregulating transcripts related to glial cell plasticity, dedifferentiation and anti-inflammatory profile, while dead bacteria affected genes involved in neuropathy and pro-inflammatory response. In addition, dead bacteria also upregulated genes associated with nerve support, which expression profile was similar to those obtained from leprosy nerve biopsies. These findings suggest that early exposure to viable and dead bacteria may provoke Schwann cells to behave differentially, with far-reaching implications for the ongoing neuropathy seen in leprosy patients, where a mixture of active and non-active bacteria are found in the nerve microenvironment.

Oligomeric α-Synuclein induces skin degeneration in reconstructed human epidermis.

Aged and photoaged skin exhibit fine wrinkles that are signs of epidermal inflammation and degeneration. It has been shown that healthy elderly skin expresses amyloidogenic proteins, including α-Synuclein, which are known to oligomerize and trigger inflammation and neurodegeneration. However, little is known about their putative role in skin physiology and sensitivity. To unravel this possible role, we investigated the impact of oligomeric α-Synuclein (Oα-Syn) in 2D and 3D keratinocyte human models. Exogenous Oα-Syn caused degeneration of reconstructed human epidermis (RHE) by diminishing proliferation and thickness of the stratum basale. Oα-Syn also increased NF-kB nuclear translocation in keratinocytes and triggered inflammation in the RHE, by increasing expression of interleukin-1ß and tumor necrosis factor-alpha, and the release of tumor necrosis factor-alpha in a time-dependent manner. Dexamethasone and an IL-1ß inhibitor partially diminished RHE degeneration caused by Oα-Syn. These findings suggest that Oα-Syn induces epidermal inflammation and decreases keratinocyte proliferation, and therefore might contribute to epidermal degeneration observed in human skin aging.

Gene expression profile of Mycobacterium leprae contribution in the pathology of leprosy neuropathy

Peripheral neuropathy is the main cause of physical disability in leprosy patients.Importantly, the extension and pattern of peripheral damage has been linked to how the host cell will respond against Mycobacterium leprae (M. leprae) infection, in particular, how the pathogen will establish infection in Schwann cells. Interestingly, viable and dead M. leprae have been linked to neuropathology of leprosy by distinct mechanisms. While viable M. leprae promotes transcriptional modifications that allow the bacteria to survive through the use of the host cell's internal machinery and the subvert of host metabolites, components of the dead bacteria are associated with the generation of a harmful nerve microenvironment. Therefore, understanding the pathognomonic characteristics mediated by viable and dead M. leprae are essential for elucidating leprosy disease and its associated reactional episodes. Moreover, the impact of the viable and dead bacteria in Schwann cells is largely unknown and their gene signature profiling has, as yet, been poorly explored. In this study, we analyzed the early differences in the expression profile of genes involved in peripheral neuropathy, dedifferentiation and plasticity, neural regeneration, and inflammation in human Schwann cells challenged with viable and dead M. leprae. We substantiated our findings by analyzing this genetic profiling in human nerve biopsies of leprosy and non-leprosy patients, with accompanied histopathological analysis. We observed that viable and dead bacteria distinctly modulate Schwann cell genes, with emphasis to viable bacilli upregulating transcripts related to glial cell plasticity, dedifferentiation and anti-inflammatory profile, while dead bacteria affected genes involved in neuropathy and pro-inflammatory response. In addition, dead bacteria also upregulated genes associated with nerve support, which expression profile was similar to those obtained from leprosy nerve biopsies. These findings suggest that early exposure to viable and dead bacteria may provoke Schwann cells to behave differentially, with far-reaching implications for the ongoing neuropathy seen in leprosy patients, where a mixture of active and non-active bacteria are found in the nerve microenvironment.

Two new species and a new species group of Mycodrosophila Oldenberg, 1914 (Diptera: Drosophilidae) from the Amazon.

There are 130 described species in the genus Mycodrosophila Oldenberg, 1914, distributed across all biogeographic regions. Most of these species show essential mycophagy. Currently, ten species are known from the Neotropical Region, nine of which are found in the Amazon, Atlantic Forest, Cerrado and Pampa biomes of Brazil. In this study, we describe the adult external morphology and structures of male and/or female terminalia for two new species from the Amazon Biome of Brazil. In addition, we propose a new species group, the Mycodrosophila neoprojectans group, encompassing the two new species described here, together with three previously described species from the Neotropics.

A new paradigm for leprosy diagnosis based on host gene expression.

Transcriptional profiling is a powerful tool to investigate and detect human diseases. In this study, we used bulk RNA-sequencing (RNA-Seq) to compare the transcriptomes in skin lesions of leprosy patients or controls affected by other dermal conditions such as granuloma annulare, a confounder for paucibacillary leprosy. We identified five genes capable of accurately distinguishing multibacillary and paucibacillary leprosy from other skin conditions. Indoleamine 2,3-dioxygenase 1 (IDO1) expression alone was highly discriminatory, followed by TLR10, BLK, CD38, and SLAMF7, whereas the HS3ST2 and CD40LG mRNA separated multi- and paucibacillary leprosy. Finally, from the main differentially expressed genes (DEG) and enriched pathways, we conclude that paucibacillary disease is characterized by epithelioid transformation and granuloma formation, with an exacerbated cellular immune response, while multibacillary leprosy features epithelial-mesenchymal transition with phagocytic and lipid biogenesis patterns in the skin. These findings will help catalyze the development of better diagnostic tools and potential host-based therapeutic interventions. Finally, our data may help elucidate host-pathogen interplay driving disease clinical manifestations.

WIN 55,212-2 shows anti-inflammatory and survival properties in human iPSC-derived cardiomyocytes infected with SARS-CoV-2.

Coronavirus disease 2019 (COVID-19) is caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), which can infect several organs, especially impacting respiratory capacity. Among the extrapulmonary manifestations of COVID-19 is myocardial injury, which is associated with a high risk of mortality. Myocardial injury, caused directly or indirectly by SARS-CoV-2 infection, can be triggered by inflammatory processes that lead to damage to the heart tissue. Since one of the hallmarks of severe COVID-19 is the "cytokine storm", strategies to control inflammation caused by SARS-CoV-2 infection have been considered. Cannabinoids are known to have anti-inflammatory properties by negatively modulating the release of pro-inflammatory cytokines. Herein, we investigated the effects of the cannabinoid agonist WIN 55,212-2 (WIN) in human iPSC-derived cardiomyocytes (hiPSC-CMs) infected with SARS-CoV-2. WIN did not modify angiotensin-converting enzyme II protein levels, nor reduced viral infection and replication in hiPSC-CMs. On the other hand, WIN reduced the levels of interleukins six, eight, 18 and tumor necrosis factor-alpha (TNF-α) released by infected cells, and attenuated cytotoxic damage measured by the release of lactate dehydrogenase (LDH). Our findings suggest that cannabinoids should be further explored as a complementary therapeutic tool for reducing inflammation in COVID-19 patients.

Autophagy-Associated IL-15 Production Is Involved in the Pathogenesis of Leprosy Type 1 Reaction.

Leprosy reactional episodes are acute inflammatory events that may occur during the clinical course of the disease. Type 1 reaction (T1R) is associated with an increase in neural damage, and the understanding of the molecular pathways related to T1R onset is pivotal for the development of strategies that may effectively control the reaction. Interferon-gamma (IFN-γ) is a key cytokine associated with T1R onset and is also associated with autophagy induction. Here, we evaluated the modulation of the autophagy pathway in Mycobacterium leprae-stimulated cells in the presence or absence of IFN-γ. We observed that IFN-γ treatment promoted autophagy activation and increased the expression of genes related to the formation of phagosomes, autophagy regulation and function, or lysosomal pathways in M. leprae-stimulated cells. IFN-γ increased interleukin (IL)-15 secretion in M. leprae-stimulated THP-1 cells in a process associated with autophagy activation. We also observed higher IL15 gene expression in multibacillary (MB) patients who later developed T1R during clinical follow-up when compared to MB patients who did not develop the episode. By overlapping gene expression patterns, we observed 13 common elements shared between T1R skin lesion cells and THP-1 cells stimulated with both M. leprae and IFN-γ. Among these genes, the autophagy regulator Translocated Promoter Region, Nuclear Basket Protein (TPR) was significantly increased in T1R cells when compared with non-reactional MB cells. Overall, our results indicate that IFN-γ may induce a TPR-mediated autophagy transcriptional program in M. leprae-stimulated cells similar to that observed in skin cells during T1R by a pathway that involves IL-15 production, suggesting the involvement of this cytokine in the pathogenesis of T1R.

Case Report: SARS-CoV-2 Mother-to-Child Transmission and Fetal Death Associated With Severe Placental Thromboembolism.

SARS-CoV-2 infection during pregnancy is not usually associated with significant adverse effects. However, in this study, we report a fetal death associated with mild COVID-19 in a 34-week-pregnant woman. The virus was detected in the placenta and in an unprecedented way in several fetal tissues. Placental abnormalities (MRI and anatomopathological study) were consistent with intense vascular malperfusion, probably the cause of fetal death. Lung histopathology also showed signs of inflammation, which could have been a contributory factor. Monitoring inflammatory response and coagulation in high-risk pregnant women with COVID-19 may prevent unfavorable outcomes, as shown in this case.