Immunological Response against Breast Lineage Cells Transfected with Human Papillomavirus (HPV).

Breast cancer is the most common neoplasm worldwide. Viral infections are involved with carcinogenesis, especially those caused by oncogenic Human Papillomavirus (HPV) genotypes. Despite the detection of HPV in breast carcinomas, the virus's activity against this type of cancer remains controversial. HPV infection promotes remodeling of the host's immune response, resulting in an immunosuppressive profile. This study assessed the individual role of HPV oncogenes in the cell line MDA-MB-231 transfected with the E5, E6, and E7 oncogenes and co-cultured with peripheral blood mononuclear cells. Immunophenotyping was conducted to evaluate immune system modulation. There was an increase in CD4+ T cell numbers when compared with non-transfected and transfected MDA-MB-231, especially in the Treg profile. Pro-inflammatory intracellular cytokines, such as IFN-γ, TNF-α, and IL-17, were impaired by transfected cells, and a decrease in the cytolytic activity of the CD8+ and CD56+ lymphocytes was observed in the presence of HPV oncogenes, mainly with E6 and E7. The E6 and E7 oncogenes decrease monocyte expression, activating the expected M1 profile. In the monocytes found, a pro-inflammatory role was observed according to the cytokines released in the supernatant. In conclusion, the MDA-MB-231 cell lineage transfected with HPV oncogenes can downregulate the number and function of lymphocytes and monocytes.

Localised erythema nodosum leprosum-A rare entity managed with thalidomide.

Leprosy is caused by Mycobacterium leprae. The condition primarily affects the skin and peripheral nerves. There are two types of leprosy reactions, Type 1 and Type 2 or erythema nodosum leprosum (ENL). ENL is a severe multi-system, immune-mediated complication of lepromatous leprosy. It is characterised by widespread painful cutaneous nodules, fever and peripheral oedema. This report discusses the unusual case of a 29-year-old woman who developed a localised form of ENL which required thalidomide to induce remission.

Hymenaea rubriflora Ducke stem bark extract has vasorelaxant and contractile inhibition capacity

Abstract We investigated the vasodilatory effects of Hymenaea rubriflora Ducke stem bark extract (HRHAc). Vascular reactivity of the aortic rings of Wistar rats was tested by in vitro cumulative doses (0.1 - 729 µg/mL). Rats (n=5) were treated with 25 (G25), 50 (G50) and 100 (G100) mg/ kg of HR-HAc or saline (control group - CG) for four weeks. An in vitro assay resulted in dose-dependent relaxation of the aortic rings with functional endothelium, which was inhibited in the presence of L-NAME. Rings of the treated animals increased acetylcholine relaxing potency at all doses, with a greater effect on G50 (pD2 = 7.8±0.1, Emax = 95.6±1.1) and a decreased contractile potency to phenylephrine in G25 (pD2 = 6.9±0.06, Emax = 61.5±6.0%) and G50 (pD2= 6.6±0.06, Emax = 71.0±8.5%) when compared to the CG in the presence and absence of endothelium (pD2= 6.4± 0.1, 6.4±0.1 and 6.9±0.1, respectively). Cumulative doses of nitroprusside resulted in increased relaxing potency in all treated groups and maintained Emax at 100%. It is concluded that HR-HAc has vasorelaxant capacity and inhibitory vascular contraction activity applied either directly to aortic rings or after treatment with in vivo supplementation, which places this extract as a potential nutraceutical or pharmacological agent for treating diseases associated with vascular dysfunction.

COVID-19 vaccination and leprosy-A UK hospital-based retrospective cohort study.

BACKGROUND: Individuals with leprosy are at risk of leprosy reactions, T-cell mediated immunological complications, which lead to nerve function impairment. Leprosy reactions require systemic immunosuppression which is a risk factor for severe COVID-19. Vaccination for SARS-CoV-2 infection is recommended in the UK and became widely available in 2021 with individuals at increased risk of severe disease, including the immunosuppressed, prioritised. Vaccines for SARS-CoV-2 may provoke a T cell response. The latter poses a theoretical risk of provoking an immunological response to latent Mycobacterium leprae infection leading to clinical disease or in those with clinical disease triggering a leprosy reaction. BCG vaccination is associated with the development of leprosy in a small proportion of healthy contacts of people with leprosy within twelve weeks of administration. BCG causes a Th1 immune response. METHODOLOGY/PRINCIPAL FINDINGS: We performed a retrospective cohort study to determine the SARS-CoV-2 vaccination status of individuals diagnosed with leprosy attending the Leprosy Clinic in 2021 and whether any had developed leprosy or experienced a new leprosy reaction within twelve weeks of receiving a dose of a SARS-CoV-2 vaccine. The electronic patient records were used to retrieve data. Fifty-two individuals with leprosy attended the clinic in 2021 of which five people were newly diagnosed with leprosy. Thirty-seven (71%) were male and the median age was 48.5 years old (Range 27-85 years). Eight (15.4%) individuals were taking multi-drug therapy (MDT) and eight (15.4%) had completed MDT within three years of the study. Twenty-two (41.5%) individuals were prescribed a systemic immunosuppressant drug during 2021. Ten (18.9%) individuals have one or more risk factors for severe COVID-19. The SARS-CoV-2 vaccination status of fifty (96%) were recorded of which forty-nine were vaccinated (98%). One individual had declined vaccination. One individual was diagnosed with borderline tuberculoid (BT) leprosy having developed red skin lesions with reduced sensation (which increased in size and number) and thickened peripheral nerves one week after a second dose of BNT162b2 vaccine. Another individual who had completed MDT more than three years earlier developed red plaques and tender thickened nerves consistent with a leprosy Type 1 reaction eight weeks after a single dose of BNT162b2 vaccine (having received two doses of CoronaVac vaccine three months earlier). CONCLUSIONS/SIGNIFICANCE: The development of BT leprosy and a Type 1 reaction in another individual shortly after a dose of BNT162b2 vaccine may be associated with vaccine mediated T cell responses. The benefits of vaccination to reduce the risk of severe COVID-19 outweigh these unwanted events but data from leprosy endemic countries may provide further information about potential adverse effects of augmented T cell responses in individuals with leprosy or latent M. leprae infection.

Whole Yeast Vaccine Displaying ZIKV B and T Cell Epitopes Induces Cellular Immune Responses in the Murine Model.

Improving antigen presentation is crucial for the success of immunization strategies. Yeasts are classically used as biofactories to produce recombinant proteins and are efficient vehicles for antigen delivery, in addition to their adjuvant properties. Despite the absence of epidemic outbreaks, several vaccine approaches continue to be developed for Zika virus infection. The development of these prophylactic strategies is fundamental given the severity of clinical manifestations, mainly due to viral neurotropism. The present study aimed to evaluate in vivo the immune response induced by P. pastoris recombinant strains displaying epitopes of the envelope (ENV) and NS1 ZIKV proteins. Intramuscular immunization with heat-attenuated yeast enhanced the secretion of IL-6, TNF-α, and IFN-γ, in addition to the activation of CD4+ and CD8+ T cells, in BALB/c mice. P. pastoris displaying ENV epitopes induced a more robust immune response, increasing immunoglobulin production, especially IgG isotypes. Both proposed vaccines showed the potential to induce immune responses without adverse effects, confirming the safety of administering P. pastoris as a vaccine vehicle. Here, we demonstrated, for the first time, the evaluation of a vaccine against ZIKV based on a multiepitope construct using yeast as a delivery system and reinforcing the applicability of P. pastoris as a whole-cell vaccine.

Healthcare workers exposed to COVID-19 patients present an inflammatory status and Th2/Th17/Th22 immune profile: findings from before vaccine application in Brazil.

Healthcare workers present an increased risk of contagion for the SARS-CoV-2 virus due to their labor exposure. Here, we describe the clinical, laboratory, and immunological characteristics of healthcare workers, before vaccine application, exposed to SARS-CoV-2-infected patients. We collected sociodemographic, clinical, and laboratory information from 50 professionals who worked during the COVID-19 pandemic at the Clinical Hospital of the Northwest in Brazil. The results showed that most workers are women, over 50 years old, and worked as nursing technicians. Approximately 56% of workers were positive for a previous infection by RT-PCR and/or anti-SARS-CoV-2-immunoglobulin tests. Increased levels of hematocrit, neutrophils, NK lymphocytes, and fibrinogen, were found in positive healthcare workers, suggesting a light inflammatory status. The immunological findings showed an increase in IL-17 production and a Th2/Th17/Th22 profile followed by high serology for anti-SARS-CoV-2 IgM and IgG. Those data reveal the importance of studies with healthcare workers to investigate if the continuous exposition to the virus may result in chronic activation of the immune system and/or pulmonary inflammation in this target group.

Percepções e conhecimentos médicos sobre limitação de suporte de vida / Physician perceptions and knowledge about limiting life support / Percepciones y conocimientos médicos sobre la limitación del soporte vital

Resumo Este estudo descritivo e qualitativo identificou percepções e conhecimentos de médicos de unidades de terapia intensiva sobre a limitação do suporte de vida. Os resultados revelaram diferentes compreensões e estímulos acerca do uso da limitação do suporte de vida: tomadas de decisão isoladas e compartilhadas; empecilhos como família, profissionais, questões jurídicas e imprevisibilidade da morte; e relatos de casos específicos com benefícios, dilemas e especificidades por quadro e faixa etária. Existe consenso quanto à necessidade de limitação do suporte de vida, mas falta preparo na formação e persistem divergências de compreensão. Os diferentes estímulos para seu uso e as dificuldades para tomada de decisão e definição de condutas são permeados por conflitos éticos, culturais e pessoais e demonstram a necessidade de educar sobre o tema em diferentes níveis de formação de profissionais de saúde.

Abstract This qualitative, descriptive study identified perceptions and knowledge of intensive care unit physicians about limiting life support. Results revealed different understandings and reasons for limiting life support: shared and isolated decision-making; obstacles such as family, professionals, legal issues and unpredictability of death; and specific case reports with benefits, dilemmas, and specificities by clinical picture and age group. Physicians agree on the need to limit life support but lack training on the topic and differences in understanding remain. The multiple reasons for its use and difficulties in decision-making and definition of conduct are permeated by ethical, cultural and personal conflicts, demonstrating the need for better education on the theme at different levels of health professional training.

Resumen Este estudio descriptivo y cualitativo identificó las percepciones y el conocimiento de los médicos en las unidades de cuidados intensivos sobre la limitación del soporte vital. Los resultados revelaron diferentes comprensiones y estímulos sobre el uso de la limitación del soporte vital: toma de decisiones aislada y compartida; obstáculos como la familia, los profesionales, las cuestiones legales y la imprevisibilidad de la muerte; e informes de casos específicos con beneficios, dilemas y especificidades por condición y grupo de edad. Existe consenso sobre la necesidad de limitar el soporte vital, pero carece de preparación y persisten las diferencias de comprensión. Los diferentes estímulos para su uso y las dificultades para la toma de decisiones y la definición de conductas están impregnados de conflictos éticos, culturales y personales, además de que demuestran la necesidad de discutir sobre el tema en los diferentes niveles de formación de los profesionales de la salud.

Síndrome de Fournier: implementação do processo de Enfermagem à luz da teoria de Wanda Horta / Fournier's syndrome: implementation of the Nursing process according to the theory of Wanda Horta / Síndrome de Fournier: implementación del proceso de Enfermería a la luz de la teoría de Wanda Horta

Objetivo: Descrever a experiência de discentes do curso de graduação em Enfermagem da Universidade Federal de Alagoas durante a implementação do Processo de Enfermagem a um indivíduo acometido pela Síndrome de Fournier. Métodos: Estudo descritivo, do tipo relato de experiência, baseado na vivência dos estudantes de enfermagem, durante a atividades curriculares de Estágio Supervisionado em uma Unidade de Terapia Intensiva de um hospital público alagoano. A experiência ocorreu ao longo do mês de outubro de 2019. A implementação do Processo de Enfermagem foi guiada à luz da Teoria das Necessidades Humanas Básicas, proposta por Wanda Aguiar Horta. Resultados: Foi implementado o Processo de Enfermagem, com base em suas seis fases, que identificou os problemas do indivíduo e possibilitou o levantamento das intervenções necessárias para efetivar o cuidado, conforme a teoria sugere. A implementação dessa ferramenta científica, de maneira dinâmica e inter-relacionada, proporcionou uma assistência hospitalar mais segura e humanizada ao indivíduo. Conclusão: O cumprimento das seis fases do Processo de Enfermagem permitiu aos enfermeirandos vivenciarem a experiência hospitalar de forma enriquecedora, pelo fato de ter contribuído não apenas com a evolução satisfatória do paciente assistido, mas também com o fortalecimento do trabalho em equipe e da Enfermagem enquanto ciência aplicada. (AU)

Objective: To describe the experience of undergraduate Nursing students at the Federal University of Alagoas during the implementation of the Nursing Process to an individual affected by Fournier's Syndrome. Methods: Descriptive study, of the experience report type, based on the experience of Nursing students, during the curricular activities of the Supervised Internship in an Intensive Care Unit of a public hospital in Alagoas. The experience occurred throughout the month of October, 2019. The implementation of the Nursing Process was guided according to the Theory of Basic Human Needs, proposed by Wanda Aguiar Horta. Results: The Nursing Process was implemented, based on its six phases, which identified the individual's problems and enabled the survey of the necessary interventions to carry out care, as the theory suggests. The implementation of this scientific tool, in a dynamic and interrelated way, provided safer and more humanized hospital care to the individual. Conclusion: The fulfillment of the six phases of the Nursing Process allowed the Nursing students to undergo the hospital experience in an enriching way, because it contributed not only to the satisfactory evolution of the assisted patient, but also to the strengthening of the teamwork and of Nursing as an applied science. (AU)

Objetivo: Describir la experiencia de estudiantes universitarios de Enfermería de la Universidad Federal de Alagoas durante la implementación del Proceso de Enfermería a una persona afectada por el Síndrome de Fournier. Metodos: Estudio descriptivo, tipo de informe de experiencia, basado en la experiencia de estudiantes de Enfermería durante las actividades curriculares de pasantías supervisadas, en una Unidad de Cuidados Intensivos de un hospital público en Alagoas. La experiencia ocurrió durante todo el mes de Octubre de 2019. La implementación del Proceso de Enfermería se guió a la luz de la Teoría de las Necesidades Humanas Básicas, propuesta por Wanda Aguiar Horta. Resultados: El proceso de enfermería se implementó, en base a sus seis fases, que identificaron los problemas del individuo y permitieron la encuesta de las intervenciones necesarias para llevar a cabo la atención, como sugiere la teoría. La implementación de esta herramienta científica, de manera dinámica e interrelacionada, brindó una atención hospitalaria más segura y humanizada al individuo. Conclusión: El cumplimiento de las seis fases del Proceso de Enfermería permitió a los estudiantes de Enfermería vivir la experiencia hospitalaria de manera enriquecedora, debido a que contribuyó no solo a la evolución satisfactoria del paciente asistido, sino también al fortalecimiento del trabajo en equipo y de la Enfermería como ciencia aplicada. (AU)

Supplementation with Spirulina platensis Prevents Damage to Rat Erections in a Model of Erectile Dysfunction Promoted by Hypercaloric Diet-Induced Obesity.

Erectile dysfunction (ED) is the inability to achieve and/or maintain a penile erection sufficient for sexual satisfaction. Currently, many patients do not respond to the pharmacotherapy. The effects of a supplementation with Spirulina platensis, were evaluated in a model of ED induced by hypercaloric diet consumption. Wistar rats were divided into groups fed with standard diet (SD) or hypercaloric diet (HD) and supplemented with this alga at doses of 25, 50 or 100 mg/kg. Experimental adiposity parameters and erectile function were analyzed. In SD groups, Spirulina platensis reduced food intake, final body mass and adiposity index, and increased the total antioxidant capacity (TAC) of adipose tissue. However, no change was observed in erectile function. In the HD group, without Spirulina supplementation, a decrease in food intake was observed, in addition to an increase of final body mass, weight gain, adipose reserves, and adiposity index. Additionally, reduction in the number and increase in the latency of penile erection and adipose malondialdehyde levels, as well as a reduction in TCA was noted. Furthermore, cavernous contractility was increased, and the relaxing response was decreased. Interestingly, these deleterious effects were prevented by the algae at doses of 25, 50 and/or 100 mg/kg. Therefore, the supplementation with S. platensis prevents damages associated to a hypercaloric diet consumption and emerges as an adjuvant the prevention of ED.

Understanding leprosy reactions and the impact on the lives of people affected: An exploration in two leprosy endemic countries.

BACKGROUND: Leprosy reactions, Type-1 and erythema nodosum leprosum, are immune-mediated complications of leprosy, which play a significant role in the morbidity associated with the disease. A considerable amount of literature has been published on the impact of leprosy in general but few studies focus specifically on leprosy reactions. This study aimed to investigate the impact of leprosy reactions on physical, psychological, and social aspects of the lives of people affected by analysing their life experiences and perspectives about leprosy reactions. METHODS/PRINCIPAL FINDINGS: This qualitative study involved people affected by leprosy reactions and their family members in two leprosy endemic countries. The data were collected through 66 interviews and 9 focus group discussions (4-6 participants each) in Surabaya, Indonesia, and Purulia, India. Content analysis and conversational analysis were performed. This study found that both types of leprosy reactions were perceived as an unpredictable and painful condition. Leprosy reactions restricted physical activities of the participants, such as going to bathroom, sleeping, eating, and cooking. In the interviews, the respondents expressed a range of emotions and feelings including confusion, sadness, anxiety, and anger. Some recounted that they felt stigmatized and lost opportunities to socialise and earn money. Differences between the two settings were identified. The majority of Indonesian participants preferred to stay at home, and some concealed the diagnosis of leprosy, while most of the Indian respondents continued working up to the time of hospitalization. CONCLUSION: Leprosy reactions are a distressing complication of leprosy and adversely affect the lives of those affected. Individuals reported physical discomfort, distress, anxiety, stigma, and financial hardship and these negative impacts in the physical, psychological, and social spheres reinforced each other. These findings provide important information about a need for early detection and sustained commitment to follow-up care for people with a history of leprosy reactions. More research on new drugs for reactional episodes, tools to measure knowledge, attitude, and practice, and costing study on leprosy reactions treatment are needed. We recommend the development and testing of holistic strategies to improve the management of leprosy reactions.

Memory elicitation, T-cell response and antibody production: an independent study of an inactivated entire virus vaccine (Coronavac).

Health professionals working to mitigate the COVID-19 pandemic are one of the main risk groups for the disease, being prioritized for vaccination. Considering this, the aim of this study was to analyze the immune response of these professionals immunized with CoronaVac in the first and second doses. Blood samples were collected after the first and second doses of the vaccine (CoronaVac) and used to investigate hematological and biochemical parameters, analysis of immunoglobulin production, cytokines, and gene expression profile, as well as the identification of subsets of immune cells. Post-first dose immunological phenotypic memory (CD27+) profiles (T CD4+, TCD8+ and CD19+) showed a significant increase, as did Monocyte APCs (CD80+HLA-DR+) in relation to the second dose. The cytokines IL-2, IL-6 and IFN-° showed increased values in relation to the other analyzed cytokines. The Th2/Th17 profile in the second dose was characterized by gene expression analysis. The production of IgM and IgG after vaccination showed statistically significant values in the comparison between doses. CoronaVac showed activation of APCs monocytes, memory response of T and B lymphocytes, with immunoglobulins production. This set of responses is characterized by the Th2/Th17 immunological profile.

An assessment of the reported impact of the COVID-19 pandemic on leprosy services using an online survey of practitioners in leprosy referral centres.

BACKGROUND: The coronavirus disease 2019 (COVID-19) pandemic has led to governments implementing a variety of public health measures to control transmission and has affected health services. Leprosy is a communicable neglected tropical disease caused by Mycobacterium leprae and is an important health problem in low- and middle-income countries. The natural history of leprosy means that affected individuals need long-term follow-up. The measures recommended to reduce transmission of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) can create barriers to health services. We evaluated the impact of the COVID-19 epidemic response on leprosy services and disease management. METHODS: We conducted a cross-sectional online survey with healthcare professionals in leprosy referral centres. RESULTS: Eighty percent of leprosy diagnostic services were reduced. All respondents reported that multidrug therapy (MDT) was available but two reported a reduced stock. Clinicians used alternative strategies such as telephone consultations to maintain contact with patients. However, patients were not able to travel to the referral centres. DISCUSSION: This study highlights the effects of the initial phase of the SARS-CoV-2 pandemic on leprosy services in a range of leprosy-endemic countries. Many services remained open, providing leprosy diagnosis, MDT and leprosy reaction medications. Centres developed innovative measures to counter the negative impacts of the COVID-19 pandemic.

Aprosopia/holoprosencephaly in a stillborn puppy: when the face predicts the brain.

In a litter of three puppies, one was stillborn and had facial and brain defects. Fusion of the maxilla and mandible and absence of the face were observed. The forebrain (telencephalon and the diencephalon) was reduced in size and fused, and the telencephalic longitudinal fissure, olfactory bulbs, and optic nerves were absent (Figures 6 and 7). Lissencephaly was observed in the telencephalon and cerebellum. A diagnosis of aprosopia/holoprosencephaly was made.

Evaluation of the In Vivo Acute Toxicity and In Vitro Hemolytic and Immunomodulatory Activities of the Moringa oleifera Flower Trypsin Inhibitor (MoFTI).

BACKGROUND: Protease inhibitors have been isolated from plants and present several biological activities, including immunomodulatory action. OBJECTIVE: This work aimed to evaluate a Moringa oleifera flower trypsin inhibitor (MoFTI) for acute toxicity in mice, hemolytic activity on mice erythrocytes and immunomodulatory effects on mice splenocytes. METHODS: The acute toxicity was evaluated using Swiss female mice that received a single dose of the vehicle control or MoFTI (300 mg/kg, i.p.). Behavioral alterations were observed 15-240 min after administration, and survival, weight gain, and water and food consumption were analyzed daily. Organ weights and hematological parameters were analyzed after 14 days. Hemolytic activity of MoFTI was tested using Swiss female mice erythrocytes. Splenocytes obtained from BALB/c mice were cultured in the absence or presence of MoFTI for the evaluation of cell viability and proliferation. Mitochondrial membrane potential (Δψm) and reactive oxygen species (ROS) levels were also determined. Furthermore, the culture supernatants were analyzed for the presence of cytokines and nitric oxide (NO). RESULTS: MoFTI did not cause death or any adverse effects on the mice except for abdominal contortions at 15-30 min after administration. MoFTI did not exhibit a significant hemolytic effect. In addition, MoFTI did not induce apoptosis or necrosis in splenocytes and had no effect on cell proliferation. Increases in cytosolic and mitochondrial ROS release, as well as Δψm reduction, were observed in MoFTI-treated cells. MoFTI was observed to induce TNF-α, IFN-γ, IL-6, IL-10, and NO release. CONCLUSION: These results contribute to the ongoing evaluation of the antitumor potential of MoFTI and its effects on other immunological targets.

Evaluation of cytotoxic, immunomodulatory effects, antimicrobial activities and phytochemical constituents from various extracts of Passiflora edulis F. flavicarpa (Passifloraceae).

The leaves of P. edulis were subjected to physicochemical analysis, such as ion content, extractives, and structural molecules. The hexanic, ethanolic and ethyl acetate extracts were submitted to phytochemical analyzes by GC-MS, HPLC-MS, and spectrophotometry. In addition, antioxidant (DPPH, ABTS and TAA methods) potential, antimicrobial (MIC method) action, cytotoxicity and immunostimulant activity (flow cytometry analysis) were performed. The extracts showed a moderate antioxidant capacity and revealed the presence of several metabolites, mainly phenols, such as caffeic acid, p-coumaric acid and luteolin. The ethyl acetate and ethanolic extracts showed antifungal activity. In addition, the extracts did not affect splenocytes viability at 12.5 µg/mL and promoted the production of IL-6, IL-10, IL-17 and TNF-α cytokines. P. edulis extracts showed antifungal and antioxidant activity and were able to induce immunostimulatory action in splenocyte cultures in vitro.

Methotrexate and prednisolone study in erythema nodosum leprosum (MaPs in ENL) protocol: a double-blind randomised clinical trial.

INTRODUCTION: Erythema nodosum leprosum (ENL) is an immunological complication of leprosy. ENL results in morbidity and disability and if it is not treated can lead to death. The current treatment consists of thalidomide or high doses of oral corticosteroids for prolonged periods. Thalidomide is not available in many leprosy endemic countries. The use of corticosteroids is associated with morbidity and mortality. Identifying treatment regimens that reduce the use of corticosteroids in ENL is essential. Methotrexate (MTX) is used to treat many inflammatory diseases and has been used successfully to treat patients with ENL not controlled by other drugs, including prednisolone and thalidomide. We present the protocol of the 'MTX and prednisolone study in ENL' (MaPs in ENL) a randomised controlled trial (RCT) designed to test the efficacy of MTX in the management of ENL. METHODS AND ANALYSIS: MaPs in ENL is an international multicentre RCT, which will be conducted in leprosy referral centres in Bangladesh, Brazil, Ethiopia, India, Indonesia and Nepal. Patients diagnosed with ENL who consent to participate will be randomly allocated to receive 48 weeks of weekly oral MTX plus 20 weeks of prednisolone or 48 weeks of placebo plus 20 weeks of prednisolone. Participants will be stratified by type of ENL into those with acute ENL and those with chronic and recurrent ENL. The primary objective is to determine whether MTX reduces the requirement for additional prednisolone. Patients' reported outcome measures will be used to assess the efficacy of MTX. Participants will be closely monitored for adverse events. ETHICS AND DISSEMINATION: Results will be submitted for publication in peer-reviewed journals. Ethical approval was obtained from the Observational/Interventions Research Ethics Committee of the London School of Hygiene & Tropical Medicine (15762); The Leprosy Mission International Bangladesh Institutional Research Board (in process); AHRI-ALERT Ethical Review Committee, Ethiopia; Ethics Committee of the Managing Committee of the Bombay Leprosy Project; and The Leprosy Mission Trust India Ethics Committee; the Nepal Health and Research Council and Health Research Ethics Committee Dr. Soetomo, Indonesia. This study is registered at www.clinicaltrials.gov. This is the first RCT of MTX for ENL and will contribute to the evidence for the management of ENL.Trial registration numberNCT 03775460.

Potential Therapeutic Role of Dietary Supplementation with Spirulina platensis on the Erectile Function of Obese Rats Fed a Hypercaloric Diet.

Spirulina platensis, an important source of bioactive compounds, is a multicellular, filamentous cyanobacterium rich in high-quality proteins, vitamins, minerals, and antioxidants. Due to its nutrient composition, the alga is considered a complete food and is recognized for its anti-inflammatory, antioxidant, antiobesity, and reproprotective effects. All of which are important for prevention and treatment of organic and metabolic disorders such as obesity and erectile dysfunction. The aim of this study was to investigate the modulatory role of Spirulina platensis food supplementation and the mechanisms of action involved in reversing the damage caused by a hypercaloric diet on the erectile function of rats. The animals were divided into a standard diet group (SD, n = 5); a hypercaloric diet group (HCD, n = 5); a hypercaloric diet group supplemented with S. platensis at doses of 25 (HCD+SP25, n = 5), 50 (HCD+SP50, n = 5), and 100 mg/kg (HCD+SP100, n = 5); and a hypercaloric diet group subsequently fed a standard diet (HCD+SD, n = 5). In the rats fed a hypercaloric diet, dietary supplementation with S. platensis effectively increased the number of erections while decreasing latency to initiate penile erection. Additionally, S. platensis increases NO bioavailability, reduces inflammation by reducing the release of contractile prostanoids, enhances the relaxation effect promoted by acetylcholine (ACh), restores contractile reactivity damage and cavernous relaxation, reduces reactive oxygen species (ROS), and increases cavernous total antioxidant capacity (TAC). Food supplementation with S. platensis thus restores erectile function in obese rats, reduces production of contractile prostanoids, reduces oxidative stress, and increases NO bioavailability. Food supplementation with S. platensis thus emerges as a promising new therapeutic alternative for the treatment of erectile dysfunction as induced by obesity.

Biologics in Leprosy: A Systematic Review and Case Report.

Tumor necrosis factor (TNF)-α inhibitors increase susceptibility to tuberculosis, but the effect of biologics on susceptibility to leprosy has not been described. Moreover, biologics may play a role in treating erythema nodosum leprosum (ENL). The objectives of this systematic review were to determine whether the development of clinical leprosy is increased in patients being treated with biologics and to assess the use of biologics in treating leprosy reactions. A systematic literature review was completed of patients with leprosy who received treatment with biologics either before or after a diagnosis of leprosy was confirmed. All studies and case reports were included for qualitative evaluation. The search yielded 10 cases (including one duplicate publication) of leprosy diagnosed after initiation of TNF-α inhibitors and four case reports of refractory ENL successfully treated with infliximab or etanercept. An unpublished case of persistent ENL responsive to infliximab is also presented. These data demonstrate that the use of TNF-α inhibitors may be a risk factor for developing leprosy or reactivating subclinical infections. Leprosy can present with skin lesions and arthritis, so leprosy should be considered in patients presenting with these signs before starting treatment with these agents. Leprosy should be considered in patients who develop worsening eruptions and neurologic symptoms during treatment with TNF-α inhibitors. Finally, TNF-α inhibitors appear effective in some cases of refractory ENL.