Cellular and molecular mechanisms underlying plasma membrane functionality and integrity.

The plasma membrane not only protects the cell from the extracellular environment, acting as a selective barrier, but also regulates cellular events that originate at the cell surface, playing a key role in various biological processes that are essential for the preservation of cell homeostasis. Therefore, elucidation of the mechanisms involved in the maintenance of plasma membrane integrity and functionality is of utmost importance. Cells have developed mechanisms to ensure the quality of proteins that inhabit the cell surface, as well as strategies to cope with injuries inflicted to the plasma membrane. Defects in these mechanisms can lead to the development or onset of several diseases. Despite the importance of these processes, a comprehensive and holistic perspective of plasma membrane quality control is still lacking. To tackle this gap, in this Review, we provide a thorough overview of the mechanisms underlying the identification and targeting of membrane proteins that are to be removed from the cell surface, as well as the membrane repair mechanisms triggered in both physiological and pathological conditions. A better understanding of the mechanisms underlying protein quality control at the plasma membrane can reveal promising and unanticipated targets for the development of innovative therapeutic approaches.

Peripheral Nerve Stimulation for Painful Mononeuropathy Secondary to Leprosy: A 12-Month Follow-Up Study.

OBJECTIVE: Leprosy affects approximately 10-15 million patients worldwide and remains a relevant public health issue. Chronic pain secondary to leprosy is a primary cause of morbidity, and its treatment remains a challenge. We evaluated the feasibility and safety of peripheral nerve stimulation (PNS) for painful mononeuropathy secondary to leprosy that is refractory to pharmacological therapy and surgical intervention (decompression). METHODS: Between 2011 and 2013 twenty-three patients with painful mononeuropathy secondary to leprosy were recruited to this prospective case series. All patients were considered to be refractory to optimized conservative treatment and neurosurgical decompression. Pain was evaluated over the course of the study using the neuropathic pain scale and the visual analog scale for pain. In the first stage, patients were implanted with a temporary electrode that was connected to an external stimulator, and were treated with PNS for seven days. Patients with 50% or greater pain relief received a definitive implantation in the second stage. Follow-ups in the second stage were conducted at 1, 3, 6, and 12 months. RESULTS: After seven days of trial in the first stage, 10 patients showed a pain reduction of 50% or greater. At 12-month follow-up in the second stage, 6 of the 10 patients who underwent permanent device implantation showed a pain reduction of 50% or greater (75% reduction on average), and two patients showed a 30% reduction in pain. Two patients presented with electrode migration that required repositioning during the 12-month follow-up period. CONCLUSIONS: Our data suggest that PNS might have significant long-term utility for the treatment of painful mononeuropathy secondary to leprosy. Future studies should be performed in order to corroborate our findings in a larger population and encourage the clinical implementation of this technique.

Interactive virtual assistance for mental health promotion and self-care management in elderly with type 2 diabetes (IVAM-ED): study protocol and statistical analysis plan for a randomized controlled trial.

BACKGROUND: With one in five individuals aged 65 or older living with type 2 diabetes worldwide, it is crucial to acknowledge and address the challenges faced by this population. In this context, our study aims to evaluate the efficacy of a behavioral intervention model delivered through a smart speaker on mental health and diabetes self-care in the elderly with diabetes. METHODS: This is a single-center, pragmatic, parallel two-arm open randomized clinical trial involving elderly patients with type 2 diabetes. We plan to enroll a total of 112 individuals who will be randomized 1:1 to receive the Smart Speaker EchoDot 3rd Gen device (Amazon Echo®) for home use (intervention arm) or to maintain usual care (control arm). The primary outcome is mental distress, assessed using the 20-item Self Reporting Questionnaire (SRQ-20) after a 12-week intervention period. Secondary outcomes include quality of life, adherence to diabetes self-care behaviors, perception of stress, glycemic control, blood pressure, and lipid profile. Analysis of covariance (ANCOVA) will be used to evaluate the effects of the intervention on the outcomes. DISCUSSION: This study assesses the effectiveness of an interactive virtual assistance system for enhancing mental health and glycemic control among elderly individuals with type 2 diabetes. The findings may introduce smart speakers as a valuable tool for promoting diabetes-related self-care in this population. TRIAL REGISTRATION: ClinicalTrials.gov NCT05329376. Registered on 15 April 2022. Enrollment began on 20 June 2023 and the last update of protocol was on 13 December 2023.

"She has become my best friend": a qualitative study on the perspective of elderly with type 2 diabetes regarding the use of an interactive virtual assistant device for diabetes care and mental health promotion.

AIMS: To qualitatively evaluate the experiences and emotional responses of elderly individuals with type 2 diabetes regarding the use of an interactive virtual assistant device. METHODS AND RESULTS: This qualitative study included elderly individuals who were diagnosed with type 2 diabetes and who had been using the Smart Speaker EchoDot 3rd Gen (Amazon Echo®) device for three months. A structured face-to-face interview with open-ended questions was conducted to evaluate their experiences and emotional responses associated with the device. Data analysis was performed using inductive thematic content analysis with deductive coding followed by narrative synthesis to present the overall perceptions of the participants. Thirty individuals with a mean diabetes duration of 17.1 ± 9.45 years and a mean age of 71.9 ± 5.1 years were interviewed to ensure saturation of responses. Three major themes were identified through response analysis: (1) Emotional response to user experience; (2) Humanization feelings in human-device interactions; (3) Diabetes-related self-care. Overall, participants experienced a wide range of feelings regarding the use of the interactive virtual assistant device, predominantly with positive connotations, highlighting aspects of humanization of technology and its use, and experiencing assistance in self-care related to diabetes. CONCLUSION: Our results highlight the overwhelmingly positive emotional responses and strong sense of humanization expressed by elderly individuals with diabetes toward an interactive virtual assistant device. This underscores its potential to improve mental health and diabetes care, although further studies are warranted to fully explore its impact.

Family accommodation in obsessive-compulsive disorder: An updated systematic review and meta-analysis.

Family accommodation might play a crucial role in obsessive-compulsive disorder (OCD). Previous systematic reviews on family accommodation in OCD have focused on specific populations or variables or are outdated. We conducted a preregistered systematic review and meta-analysis on family accommodation in adults, children, and adolescents with OCD (CRD42021264461). We searched PubMed, Scopus, and Web of Science using the keywords "family accommodation" and "obsessive-compulsive disorder. One hundred-eight studies involving 8928 individuals with OCD were included. Our results indicate that levels of family accommodation in OCD are moderate, that there is a significant positive correlation between family accommodation and OCD severity (r = 0.42), that baseline family accommodation does not predict pre- to post-treatment change in OCD severity (g = -0.03), and that family accommodation decreases as a result of both individual and family-focused cognitive behavioral therapy for OCD (g = 2.00 and g = 1.17, respectively). Our findings highlight the relevance of family accommodation in OCD and may help guide assessment and treatment.

Pediatric inflammatory multisystemic syndrome in Brazil: sociodemographic characteristics and risk factors to death.

OBJECTIVE: To determine the incidence of MIS-C in Brazil, describe the clinical and sociodemographic characteristics of the pediatric population affected by MIS-C and compare mortality and lethality outcomes with isolated Covid-19 and MIS-C cases. METHODS: Observational and retrospective cohort study of cases of MIS-C associated with Covid-19 in the Brazilian population between 04/01/2020 and 04/17/2021. Data from the Ministry of Health's epidemiological bulletin up to the 15th epidemiological week of 2021, were used. The analyzes were descriptive through absolute and relative frequencies. The significance level is 5% in Stata 16.0 package. RESULTS: Between 04/01/2020 and 04/07/2021, 903 cases of MIS-C associated with Covid-19 were notified in Brazil, of which, the largest part (55.26%) were male, between 0 and 4 years old (45.29%), from the Southeast region (38.76%). The deaths (61; 6.7%) were higher in the female gender, between 0 and 4 years old (47.54%) and in the Southeast region (34.43%). It was identified that the risk of death by MIS-C related to Covid-19 is 5.29 (CI = 2.83; 9.87 and P-value = <0.001) times higher in adolescents from 15-19 years old than in other age groups when compared to 0-4 years old children. Also, the residency in North region was as risk factor to death (RR = 3.72, IC = 1.29; 10.74 e P-value = 0.008). CONCLUSION: In this study, despite the numbers showing more deaths from zero to 4 years old, the risk for teenagers is notably higher. In addition, Brazil's Northern region is a risk factor that reaffirms social inequality and poor access to health.

Transient receptor potential ankyrin 1 mediates headache-related cephalic allodynia in a mouse model of relapsing-remitting multiple sclerosis.

ABSTRACT: Primary headache conditions are frequently associated with multiple sclerosis (MS), but the mechanism that triggers or worsens headaches in patients with MS is poorly understood. We previously showed that the proalgesic transient receptor potential ankyrin 1 (TRPA1) mediates hind paw mechanical and cold allodynia in a relapsing-remitting experimental autoimmune encephalomyelitis (RR-EAE) model in mice. Here, we investigated the development of periorbital mechanical allodynia (PMA) in RR-EAE, a hallmark of headache, and if TRPA1 contributed to this response. RR-EAE induction by injection of the myelin oligodendrocyte peptide fragment35-55 (MOG35-55) and Quillaja A adjuvant (Quil A) in C57BL/6J female mice elicited a delayed and sustained PMA. The PMA at day 35 after induction was reduced by the calcitonin gene-related peptide receptor antagonist (olcegepant) and the serotonin 5-HT1B/D receptor agonist (sumatriptan), 2 known antimigraine agents. Genetic deletion or pharmacological blockade of TRPA1 attenuated PMA associated with RR-EAE. The levels of oxidative stress biomarkers (4-hydroxynonenal and hydrogen peroxide, known TRPA1 endogenous agonists) and superoxide dismutase and NADPH oxidase activities were increased in the trigeminal ganglion of RR-EAE mice. Besides, the treatment with antioxidants (apocynin or α-lipoic acid) attenuated PMA. Thus, the results of this study indicate that TRPA1, presumably activated by endogenous agonists, evokes PMA in a mouse model of relapsing-remitting MS.

How to get away with murder: The multiple strategies employed by pathogenic protozoa to avoid complement killing.

Parasitic protozoa are eukaryotic unicellular organisms that depend on a variety of living organisms and can develop intra- and extracellularly inside their hosts. In humans, these parasites cause diseases with a significant impact on public health, such as malaria, toxoplasmosis, Chagas disease, leishmaniasis and amebiasis. The ability of a parasite in establishing a successful infection depends on a series of intricate evolutionarily selected adaptations, which include the development of molecular and cellular strategies to evade the host immune system effector mechanisms. The complement system is one of the main effector mechanisms and the first humoral shield of hosts innate immunity against pathogens. For unicellular pathogens, such as protozoa, bacteria and fungi, the activation of the complement system may culminate in the elimination of the invader mainly via 1- the formation of a pore that depolarizes the plasma membrane of the parasite, causing cell lysis; 2- opsonization and killing by phagocytes; 3- increasing vascular permeability while also recruiting neutrophils to the site of activation. Numerous strategies to avoid complement activation have been reported for parasitic protozoa, such as 1- sequestration of complement system regulatory proteins produced by the host, 2- expression of complement system regulatory proteins, 3- proteolytic cleavage of different complement effector molecules, 4- formation of a physical glycolipid barrier that prevents deposition of complement molecules on the plasma membrane, and 5- removal, by endocytosis, of complement molecules bound to plasma membrane. In this review, we revisit the different strategies of blocking various stages of complement activation described for the main species of parasitic protozoa, present the most recent discoveries in the field and discuss new perspectives on yet neglected strategies and possible new evasion mechanisms.

The Benefits of Dog-Assisted Therapy as Complementary Treatment in a Children's Mental Health Day Hospital.

Dog-assisted therapy (DAT) has shown benefits in people with mental health disorders. A child psychiatric day hospital would be a suitable setting to implement DAT and evaluate the benefits in a pediatric population. METHODS: Mixed methods research in a naturalistic setting was considered in this pre-post quantitative study including 23 children under 13 treated in a day hospital over 2 years. Quantitative analysis included the number of emotional and behavioral outbursts and attendance rate and self-control and social impairment questionnaires completed by family members and therapists. In the qualitative study, the experiences of 12 mental health professionals involved in DAT were documented through semi-structured interviews. RESULTS: On DAT days, there were fewer emotional and behavioral outbursts and higher attendance. Significant differences were obtained between pre- and post-test scores on the SCRS and the SRS-2 completed by the therapists, while no significant differences were obtained on the questionnaires completed by the parents. Observations based on the qualitative study were as follows: (1) DAT improves emotional self-regulation; (2) DAT could facilitate the work of therapists in day hospitals; (3) health professionals displayed uncertainty due to a lack of familiarity with DAT. CONCLUSIONS: DAT improved emotional self-regulation, attendance rate and self-control and social response in children with mental disorders attending a day hospital.

Peripheral nerve entrapments-rare causes of a common condition: case series.

Compressive syndromes of peripheral nerves both in the upper and lower limbs are part of daily clinical practice; however, the etiological diagnosis can be challenging and impact on the outcome of the patient. We report five cases with rare etiologies of nerve entrapments: one in the lower limb and four in the upper limbs with the final diagnosis made only during the operation. The patients evolved without post-operative complications and had good outcomes. This series includes the first report of sciatic compression by a lipoma in the popliteal fossa, two lipomas one with compression of infraclavicular brachial plexus and another with compressing the posterior interosseous nerve, and two reports of vascular lesions due to blunt traumas, which are also uncommon. This series adds to the literature more hypotheses of differential diagnoses in nerve entrapments, which is fundamental to surgical decisions and pre-operative planning-and perhaps most importantly prevents wrong diagnosis of idiopathic compressions, which would lead to a completely wrong approach and unfavorable outcomes.

Pediatric inflammatory multisystemic syndrome in Brazil: sociodemographic characteristics and risk factors to death

Abstract Objective: To determine the incidence of MIS-C in Brazil, describe the clinical and sociodemographic characteristics of the pediatric population affected by MIS-C and compare mortality and lethality outcomes with isolated Covid-19 and MIS-C cases. Methods: Observational and retrospective cohort study of cases of MIS-C associated with Covid-19 in the Brazilian population between 04/01/2020 and 04/17/2021. Data from the Ministry of Health's epidemiological bulletin up to the 15th epidemiological week of 2021, were used. The analyzes were descriptive through absolute and relative frequencies. The significance level is 5% in Stata 16.0 package. Results: Between 04/01/2020 and 04/07/2021, 903 cases of MIS-C associated with Covid-19 were notified in Brazil, of which, the largest part (55.26%) were male, between 0 and 4 years old (45.29%), from the Southeast region (38.76%). The deaths (61; 6.7%) were higher in the female gender, between 0 and 4 years old (47.54%) and in the Southeast region (34.43%). It was identified that the risk of death by MIS-C related to Covid-19 is 5.29 (CI = 2.83; 9.87 and P-value = <0.001) times higher in adolescents from 15-19 years old than in other age groups when compared to 0-4 years old children. Also, the residency in North region was as risk factor to death (RR = 3.72, IC = 1.29; 10.74 e P-value = 0.008). Conclusion: In this study, despite the numbers showing more deaths from zero to 4 years old, the risk for teenagers is notably higher. In addition, Brazil's Northern region is a risk factor that reaffirms social inequality and poor access to health.

[Vulnerability of men who have sex with men in the context of AIDS]. / Vulnerabilidade de homens que fazem sexo com homens no contexto da AIDS.

The number of AIDS cases in men who have sex with men (MSM) decreased in the initial years of the epidemic, but the percentage of cases in this group has remained unaltered in the last five years. This study, aimed to improve knowledge on the impact of AIDS in the daily lives of MSM, was conducted in Campo Grande, Mato Grosso do Sul State, Brazil, using a questionnaire and interviews. The results show that MSM perceive their vulnerability to HIV infection, referring to inconsistent condom use and multiple sex partners, given that 65% of homosexuals, 75% of bisexuals, and 33% of transvestites reported up to 5 partners in the previous month and emphasizing that 59% of the group reported more than 11 partners during the same period. The susceptibility of certain groups and the identification and understanding of their specificities pose a major challenge in any geographic context where such conditions are present.

Peripheral nerve entrapments - rare causes of a common condition: case series

Compressive syndromes of peripheral nerves both in the upper and lower limbs are part of daily clinical practice; however, the etiological diagnosis can be challenging and impact on the outcome of the patient. We report five cases with rare etiologies of nerve entrapments: one in the lower limb and four in the upper limbs with the final diagnosis made only during the operation. The patients evolved without post-operative complications and had good outcomes. This series includes the first report of sciatic compression by a lipoma in the popliteal fossa, two lipomas one with compression of infraclavicular brachial plexus and another with compressing the posterior interosseous nerve, and two reports of vascular lesions due to blunt traumas, which are also uncommon. This series adds to the literature more hypotheses of differential diagnoses in nerve entrapments, which is fundamental to surgical decisions and pre-operative planning—and perhaps most importantly prevents wrong diagnosis of idiopathic compressions, which would lead to a completely wrong approach and unfavorable outcomes.

Interação universidade e comunidade através dos movimentos sociais dos bairros Santa Luzia e Ipiranga de Juiz de Fora-MG / University and community interaction through social movements of Santa Luzia and Ipiranga neighborhoods of Juiz de Fora-MG

Este artigo fez parte do projeto de extensão Movimentos Sociais e Educação Popular: Construindo Interação entre Universidade e Comunidade, cujo objetivo era a aproximação dos discentes dos cursos de Enfermagem e Medicina da UFJF com a comunidade local, através da interação comos movimentos sociais dos bairros Santa Luzia e Ipiranga, na região Sul de Juiz de Fora. A pesquisa exploratória, de natureza quanti-qualitativa, teve como objetivos: levantar os movimentos sociais atuantes nessa região; identificar a articulação desses movimentos sociais com a população e realizar diagnóstico da atuação desses movimentos. Foram aplicados questionários semiestruturados aos 14 líderes dos movimentos sociais. Os resultados evidenciaram que os principais objetivos dos movimentos são: realização de ações de natureza assistencialista e de promoção humana;desenvolvimento de ações de lazer e cultura, doações de alimentos e artigos diversos. Eles gostariam de ampliar as ações assistencialistas, os cursos profissionalizante oferecidos e as atividades culturais. Possuem boa inserção na comunidade e recebem apoio de instituições religiosas e educacionais.

This article was part of the Social Movements and Popular Education extension project: Building Interaction between University and Community, that aimed to liaise nursing and medicine undergraduates with the local community,through an interaction with the social movements of Santa Luzia and Ipiranga neighborhoods, in the southern region of Juiz de Fora, MG, Brazil. This exploratory, quantitative qualitative study aimed to survey the social movements active in the area, identify the articulation of these social movements with the population, and diagnose the activityof these movements. Semi-structured questionnaires were applied to 14 leaders of diverse social movements. The results showed that the main objectives of the movements were: human development and assistentialism actions;leisure and cultural activities and food and goods donations. They would like to increase assistentialism actions, professional courses and cultural activities. They are well integrated into the community and receive support from religious and educational institutions.

Vulnerabilidade de homens que fazem sexo com homens no contexto da AIDS / Vulnerability of men who have sex with men in the context of AIDS / Vulnerability of men who have sex with men in the context of AIDS

O número de casos de AIDS entre homens que fazem sexo com homens (HSH) diminuiu nos primeiros anos da epidemia, mas nos últimos cinco anos os percentuais de casos de AIDS nessa população permanecem inalterados. A pesquisa, que teve por objetivo aprofundar a compreensão sobre o impacto da AIDS no cotidiano dos HSH, foi realizada em Campo Grande, Mato Grosso do Sul, Brasil, utilizando-se questionário e entrevistas. Os resultados mostram que os HSH percebem-se como vulneráveis à infecção pelo HIV, referem uso inconsistente do preservativo e ocorrência de múltiplas parcerias, visto que 65 por cento dos homossexuais, 75 por cento dos bissexuais e 33 por cento dos travestis tiveram até cinco parceiros no último mês, destacando-se que 59 por cento deste grupo tiveram mais de 11 parceiros no mesmo período. A suscetibilidade de determinados grupos e a identificação e compreensão de suas particularidades constituem o grande desafio a ser enfrentado em qualquer espaço geográfico em que essas condições se façam presentes.

The number of AIDS cases in men who have sex with men (MSM) decreased in the initial years of the epidemic, but the percentage of cases in this group has remained unaltered in the last five years. This study, aimed to improve knowledge on the impact of AIDS in the daily lives of MSM, was conducted in Campo Grande, Mato Grosso do Sul State, Brazil, using a questionnaire and interviews. The results show that MSM perceive their vulnerability to HIV infection, referring to inconsistent condom use and multiple sex partners, given that 65 percent of homosexuals, 75 percent of bisexuals, and 33 percent of transvestites reported up to 5 partners in the previous month and emphasizing that 59 percent of the group reported more than 11 partners during the same period. The susceptibility of certain groups and the identification and understanding of their specificities pose a major challenge in any geographic context where such conditions are present.

Impacto da nefrite sobre os resultados gestacionais de mulheres com lúpus eritematoso sistêmico / The impact of nephritis on gestational results in women with systemic lupus erythematosus

OBJETIVO: avaliar o impacto da nefrite lúpica e suas complicacões nos resultados gestacionais. MÉTODOS: avaliamos retrospectivamente 76 gestacões em 63 pacientes com lúpus eritematoso sistêmico (LES). RESULTADOS: a hipertensão arterial estava presente como complicacão clínica em 23 (30 por cento) gestacões. Vinte e sete (36 por cento) gestacões ocorreram em 19 pacientes com nefrite. Encontramos um número significativamente mais elevado de óbitos fetais quando avaliamos todas as pacientes com nefrite em comparacão com aquelas sem nefrite (37 por cento e 12,2 por cento, respectivamente [p=0,019]). CONCLUSÕES: além da atividade de nefrite e do diagnóstico de nefrite propriamente dito, tiveram relacão com pior sobrevida fetal a associacão da síndrome do anticorpo antifosfolipídeo ou deteccão de um dos anticorpos relacionados, a presenca HAS e insuficiência renal (mesmo em suas fases iniciais).