Impact of Complete Intermittent Blood Flow Restriction in Upper Limbs Strength and Neural Function.

Purpose: We aimed to investigate the chronic effects of low-load strength training (LT) with complete intermittent blood flow restriction (IBFR) on neural adaptations and strength in biceps brachii. Methods: Nineteen volunteers were randomly assigned into two different 9-week training protocols consisting of three assessment weeks and six training weeks: (a) LT with complete IBFR (LT-IBFR; n = 10) and (b) LT without complete IBFR (LT; n = 9). Strength was evaluated by predicted 1 repetition maximum (1RM) at weeks 1, 5, and 9 and neural function by root mean square (RMS) and median frequency (MDF) at sessions 1, 7, and 12 during the first three and last three repetitions. Both groups performed three sets of Scott curl with 20% of predicted 1RM interspersed with 90s rest twice a week. Results: No changes were found in predicted 1RM throughout the training protocols nor between groups. LT-IBFR group showed lower RMS in the first set than LT for the first three repetitions and higher RMS in all sets for the last three repetitions with decreases in this value across the sets with no longitudinal changes for both groups. MDF in the first three repetitions did not differentiate between groups, however, in the last three repetitions, MDF were lower for LTIBFR group in all sets and it increased across the sets for this condition with no chronical changes for both groups in both repetitions zones. These results suggest that LT-IBFR may be ineffective for increasing Q5 strength and it did not promote chronic neural adaptations.

Entre "centrado na pessoa" e "freestyle": a abordagem do sofrimento mental comum em residências de medicina de família e comunidade / The "patient-centered" or "freestyle" method: the approach to common mental suffering in family and community medicine residency programs / Entre "centrado en la persona" y "freestyle": el abordaje del sufrimiento mental común en residencias de medicina de familia y comunidad

Este trabalho apresenta um estudo qualitativo sobre a abordagem do sofrimento mental comum (SMC) em programas de residência de Medicina de Família e Comunidade de Minas Gerais. Foram realizadas entrevistas semiestruturadas com 16 participantes de três programas de residência, entre março e maio de 2022. A interpretação dos dados seguiu os princípios da Análise Temática de Braun e Clarke. Para os participantes, o SMC é uma demanda frequente na Atenção Primária que deve ser abordada, principalmente com intervenções psicossociais. Contudo, os participantes reconhecem que não têm aplicado essas intervenções nos moldes recomendados pela literatura. Os entrevistados relatam conhecer diversas técnicas de intervenção, mas só sabem aplicar algumas, com destaque para os componentes do "método clínico centrado na pessoa". Esse fato contribui para despertar emoções negativas, como angústia e frustração, e aumentar o número de referenciamentos desnecessários para outros profissionais.

This work presents a qualitative study of the approach to common mental suffering (CMS) in family and community medicine residency programs in the state of Minas Gerais, Brazil. Semi-structured interviews were conducted with 16 participants from three residency programs between March and May 2022. The data were interpreted drawing on the principles of Braun and Clarke's thematic analysis method. According to the participants, CMS is a frequent demand in primary care and should be approached using mainly psychosocial interventions. However, the participants recognize that they have not applied these interventions in the manner recommended by the literature. The interviewees reported that despite being aware of a diverse range of intervention techniques, they only know how to apply some, with emphasis on the components of the "patient-centered clinical method". This fact has contributed to the awakening of negative emotions, such as anguish and frustration, and increased the number of unnecessary referrals to other professionals.

Este trabajo presenta un estudio cualitativo sobre el abordaje del sufrimiento mental común (SMC) en programas de residencia de Medicina de Familia y Comunidad del estado de Minas Gerais. Se realizaron entrevistas semiestructuradas con 16 participantes de tres programas de residencia, entre marzo y mayo de 2022. La interpretación de los datos siguió los principios del Análisis Temático de Braun y Clarke. Para los participantes, el SMC es una demanda frecuente en la atención primaria que hay que abordar, principalmente, con intervenciones psicosociales. No obstante, los participantes reconocen que no han aplicado esas intervenciones en los estándares recomendados por la literatura. Los entrevistados relatan que conocen diversas técnicas de intervención, pero que solo saben aplicar algunas, con destaque para los componentes del método clínico centrado en la persona?. Este hecho contribuye para despertar emociones negativas, tales como angustia y frustración, y para aumentar el número de derivaciones innecesarias para otros profesionales.

Fructose biphosphate aldolase: A new cassava allergen.

Background: Food allergy has considerably increased in recent years and this situation has been aggravated mainly by the consumption of more processed and complex foods, since minor or potentially allergenic foods are not required to be labeled. Manihot esculenta (cassava) is a widely consumed food in South America, Africa, and Asia and can be used in the production of flour and starch, as well as several other products. This root can cause allergic reactions with symptoms ranging from mild to severe. Methods: Thus, the aim of this study was the characterization of the immunogenic cassava proteins responsible for sensitizing patients allergic to it. Using a 2D-SDS-PAGE based proteomic approach, six proteins were identified, including Fructose Bisphosphate Aldolase (FBA). Recombinant FBA was produced in Expi293 cells and evaluated by immunoblotting with the serum of 10 individual study subjects. Results: Our results showed six cassava IgE-reactive proteins. From those, recombinant fructose bisphosphate aldolase (FBA) showed a positivity of 80% among tested sera, proving to be a highly sensitizing protein. Conclusion: The recombinant FBA molecule obtained in this study can be important for in vivo diagnostic assays, by producing more accurate results, and for desensitization protocols, in which the use of the isolated molecule produces more precise results by avoiding secondary sensitization. Trial registration: All patients signed a consent form approved by the internal ethics committee CAPPesq, Comissão de Ética para Análise de Projetos de Pesquisa do HC FMUSP (CAAE: 10420619.6.0000.0068).

Augmented action observation: Theory and practical applications in sensorimotor rehabilitation.

Sensory feedback is a fundamental aspect of effective motor learning in sport and clinical contexts. One way to provide this is through sensory augmentation, where extrinsic sensory information are associated with, and modulated by, movement. Traditionally, sensory augmentation has been used as an online strategy, where feedback is provided during physical execution of an action. In this article, we argue that action observation can be an additional effective channel to provide augmented feedback, which would be complementary to other, more traditional, motor learning and sensory augmentation strategies. Given these similarities between observing and executing an action, action observation could be used when physical training is difficult or not feasible, for example during immobilization or during the initial stages of a rehabilitation protocol when peripheral fatigue is a common issue. We review the benefits of observational learning and preliminary evidence for the effectiveness of using augmented action observation to improve learning. We also highlight current knowledge gaps which make the transition from laboratory to practical contexts difficult. Finally, we highlight the key areas of focus for future research.

Digital Platform for Continuous Monitoring of Patients Using a Smartwatch: Longitudinal Prospective Cohort Study.

BACKGROUND: Since the COVID-19 pandemic, there has been a boost in the digital transformation of the human society, where wearable devices such as a smartwatch can already measure vital signs in a continuous and naturalistic way; however, the security and privacy of personal data is a challenge to expanding the use of these data by health professionals in clinical follow-up for decision-making. Similar to the European General Data Protection Regulation, in Brazil, the Lei Geral de Proteção de Dados established rules and guidelines for the processing of personal data, including those used for patient care, such as those captured by smartwatches. Thus, in any telemonitoring scenario, there is a need to comply with rules and regulations, making this issue a challenge to overcome. OBJECTIVE: This study aimed to build a digital solution model for capturing data from wearable devices and making them available in a safe and agile manner for clinical and research use, following current laws. METHODS: A functional model was built following the Brazilian Lei Geral de Proteção de Dados (2018), where data captured by smartwatches can be transmitted anonymously over the Internet of Things and be identified later within the hospital. A total of 80 volunteers were selected for a 24-week follow-up clinical trial divided into 2 groups, one group with a previous diagnosis of COVID-19 and a control group without a previous diagnosis of COVID-19, to measure the synchronization rate of the platform with the devices and the accuracy and precision of the smartwatch in out-of-hospital conditions to simulate remote monitoring at home. RESULTS: In a 35-week clinical trial, >11.2 million records were collected with no system downtime; 66% of continuous beats per minute were synchronized within 24 hours (79% within 2 days and 91% within a week). In the limit of agreement analysis, the mean differences in oxygen saturation, diastolic blood pressure, systolic blood pressure, and heart rate were -1.280% (SD 5.679%), -1.399 (SD 19.112) mm Hg, -1.536 (SD 24.244) mm Hg, and 0.566 (SD 3.114) beats per minute, respectively. Furthermore, there was no difference in the 2 study groups in terms of data analysis (neither using the smartwatch nor the gold-standard devices), but it is worth mentioning that all volunteers in the COVID-19 group were already cured of the infection and were highly functional in their daily work life. CONCLUSIONS: On the basis of the results obtained, considering the validation conditions of accuracy and precision and simulating an extrahospital use environment, the functional model built in this study is capable of capturing data from the smartwatch and anonymously providing it to health care services, where they can be treated according to the legislation and be used to support clinical decisions during remote monitoring.

From rubber hands to neuroprosthetics: Neural correlates of embodiment.

Our interaction with the world rests on the knowledge that we are a body in space and time, which can interact with the environment. This awareness is usually referred to as sense of embodiment. For the good part of the past 30 years, the rubber hand illusion (RHI) has been a prime tool to study embodiment in healthy and people with a variety of clinical conditions. In this paper, we provide a critical overview of this research with a focus on the RHI paradigm as a tool to study prothesis embodiment in individuals with amputation. The RHI relies on well-documented multisensory integration mechanisms based on sensory precision, where parietal areas are involved in resolving the visuo-tactile conflict, and premotor areas in updating the conscious bodily representation. This mechanism may be transferable to prosthesis ownership in amputees. We discuss how these results might transfer to technological development of sensorised prostheses, which in turn might progress the acceptability by users.

Distúrbios do olfato, uma revisão narrativa do diagnóstico ao tratamento / Olfactory dysfunction: a narrative review from diagnosis to treatment

Os distúrbios do olfato (DO) impactam de forma significativa na qualidade de vida dos indivíduos, e o conhecimento teórico a respeito do assunto deve ser de domínio dos alergologistas e imunologistas clínicos, possibilitando, assim, o seu diagnóstico e implementação de intervenções. Suas causas podem ser variadas, entre elas estão: rinite alérgica, rinossinusite crônica com ou sem pólipos, infecções de vias aéreas superiores, exposição a substâncias químicas, doenças neurológicas, drogas, traumas e o próprio envelhecimento. O olfato pode ser avaliado e mensurado através de testes com metodologias diferentes, cujo objetivo é avaliar parâmetros como a identificação de odores, limiar e discriminação olfativa. Esses testes são de fundamental importância para caracterizar objetivamente a queixa do paciente, como também avaliar o olfato antes e após determinada aplicação terapêutica. O tratamento das desordens olfativas é baseado em sua etiologia, portanto determinar a sua causa é indispensável para uma melhor eficácia no manejo. Entre as principais opções estão os corticoides tópicos, com impacto significativo nos pacientes com doença sinusal associada, treinamento olfatório e outras intervenções como ômega 3, vitamina A intranasal, e terapias que ainda requerem mais estudos.

Olfactory dysfunction significantly impacts quality of life, and allergists and clinical immunologists must be informed about it for diagnostic and interventional purposes. The causes are varied: allergic rhinitis, chronic rhinosinusitis with or without polyps, upper airway infections, exposure to chemicals, neurological diseases, drugs, trauma, and aging itself. Olfactory function can be evaluated and measured by several tests that use different methodologies to evaluate and identify odors, olfactory threshold, and olfactory discrimination. These tests are fundamental for objectively characterizing patient complaints and evaluating olfactory function before and after therapeutic interventions. Olfactory disorders are treated according to their etiology, so determining their cause is a major factor in treatment efficacy. The main options include topical corticosteroids, which have a significant impact on patients with sinus disease, olfactory training, other therapies (such as omega 3 and intranasal vitamin A), in addition to therapies that require further research.

Vocal singing skills by cochlear implanted children without formal musical training: Familiar versus unfamiliar songs.

OBJECTIVES: Vocal singing skills in pediatric CI users are not much known due to the limited number of studies. The principal aim of the present study was to evaluate vocal singing skills in Italian pediatric CI users. A further aim was to investigate factors that may significantly influence their performance. METHODS: The participants were twenty-two implanted children and twenty-two hearing peers. Their vocal singing skills for familiar ("Happy Birthday to You") and unfamiliar songs ("Baton Twirler" from Pam Pam 2- Tribute to Gordon) were evaluated in relation to their music perception (the Gordon test). Acoustic analysis was performed using Praat and MATLAB software. Nonparametric statistical tests and principal component analysis (PCA) were used to analyze the data. RESULTS: Hearing children outperformed implanted peers in both music perception and vocal singing tasks (all measures regarding intonation, vocal range, melody, and memory for the familiar song versus measures regarding intonation and overall melody production for the unfamiliar song). Music perception and vocal singing performances revealed strong correlations. For the familiar and unfamiliar songs, age-appropriate vocal singing was observed in 27.3% versus 45.4% of children, all implanted within 24 months of age. Age at implantation and duration of CI experience were moderately correlated with the total score obtained from the Gordon test. CONCLUSION: Implanted children show limited vocal singing skills in comparison to their hearing peers. However, some children implanted within 24 months of age seem to achieve vocal singing skills as good as their hearing peers. Future research could be useful to better understand the role of brain plasticity to implement specific training programs for both music perception and vocal singing.

IgE and IgG4 Epitopes of Dermatophagoides and Blomia Allergens before and after Sublingual Immunotherapy.

Sublingual immunotherapy (SLIT) is used worldwide to treat house dust mites (HDM) allergy. Epitope specific immunotherapy with peptide vaccines is used far less, but it is of great interest in the treatment of allergic reactions, as it precludes the drawbacks of allergen extracts. The ideal peptide candidates would bind to IgG, blocking IgE-binding. To better elucidate IgE and IgG4 epitope profiles during SLIT, sequences of main allergens, Der p 1, 2, 5, 7, 10, 23 and Blo t 5, 6, 12, 13, were included in a 15-mer peptide microarray and tested against pooled sera from 10 patients pre- and post-1-year SLIT. All allergens were recognized to some extent by at least one antibody isotype and peptide diversity was higher post-1-year SLIT for both antibodies. IgE recognition diversity varied among allergens and timepoints without a clear tendency. Der p 10, a minor allergen in temperate regions, was the molecule with more IgE-peptides and might be a major allergen in populations highly exposed to helminths and cockroaches, such as Brazil. SLIT-induced IgG4 epitopes were directed against several, but not all, IgE-binding regions. We selected a set of peptides that recognized only IgG4 or were able to induce increased ratios of IgG4:IgE after one year of treatment and might be potential targets for vaccines.

Automated prostate multi-regional segmentation in magnetic resonance using fully convolutional neural networks.

OBJECTIVE: Automatic MR imaging segmentation of the prostate provides relevant clinical benefits for prostate cancer evaluation such as calculation of automated PSA density and other critical imaging biomarkers. Further, automated T2-weighted image segmentation of central-transition zone (CZ-TZ), peripheral zone (PZ), and seminal vesicle (SV) can help to evaluate clinically significant cancer following the PI-RADS v2.1 guidelines. Therefore, the main objective of this work was to develop a robust and reproducible CNN-based automatic prostate multi-regional segmentation model using an intercontinental cohort of prostate MRI. METHODS: A heterogeneous database of 243 T2-weighted prostate studies from 7 countries and 10 machines of 3 different vendors, with the CZ-TZ, PZ, and SV regions manually delineated by two experienced radiologists (ground truth), was used to train (n = 123) and test (n = 120) a U-Net-based model with deep supervision using a cyclical learning rate. The performance of the model was evaluated by means of dice similarity coefficient (DSC), among others. Segmentation results with a DSC above 0.7 were considered accurate. RESULTS: The proposed method obtained a DSC of 0.88 ± 0.01, 0.85 ± 0.02, 0.72 ± 0.02, and 0.72 ± 0.02 for the prostate gland, CZ-TZ, PZ, and SV respectively in the 120 studies of the test set when comparing the predicted segmentations with the ground truth. No statistically significant differences were found in the results obtained between manufacturers or continents. CONCLUSION: Prostate multi-regional T2-weighted MR images automatic segmentation can be accurately achieved by U-Net like CNN, generalizable in a highly variable clinical environment with different equipment, acquisition configurations, and population. KEY POINTS: • Deep learning techniques allows the accurate segmentation of the prostate in three different regions on MR T2w images. • Multi-centric database proved the generalization of the CNN model on different institutions across different continents. • CNN models can be used to aid on the diagnosis and follow-up of patients with prostate cancer.

In-vitro NLRP3 functional test assists the diagnosis of cryopyrin-associated periodic syndrome (CAPS) patients: A Brazilian cooperation.

OBJECTIVE: To report our five-years experience on the use of NLRP3 inflammasome functional assays in the differential diagnosis of Brazilian patients with a clinical suspicion of CAPS. PATIENTS AND METHODS: The study included 9 patients belonging to 2 families (I, II) and 7 unrelated patients with a clinical suspicion of AID according to Eurofever/PRINTO classification, recruited between 2017 and 2022. The control group for the NLRP3 functional assay consisted of 10 healthy donors and for the CBA cytokines measurement of 19 healthy controls. Patients underwent clinical evaluation, genetic and functional analysis. RESULTS: All members of the family I received the diagnosis of Muckle-Wells Syndrome (MWS), carried the NLRP3 Thr348Met variant and resulted positive for the functional assay. The 2 patients of the family II resulted negative for the mutational screening but positive for the functional assay compatible with a MWS clinical phenotype. In 2 unrelated patients with NLRP3 mutations, including a novel mutation (Gly309Val, Asp303His), a positive functional test confirmed the clinical diagnosis of NOMID. 3 unrelated MWS and 1 FCAS patients resulted negative to the genetic screening and positive for the functional test. One patient with a FCAS-like phenotype harbored the NLRP12 His304Tyr variant confirming the diagnosis of FCAS2. CONCLUSION: The NLRP3 inflammasome functional assay can assist the clinical diagnosis of CAPS even in patients with unknown genetic defects.

Strength training with and without arteriovenous blood flow restriction improves performance, regardless of changes in muscle hypertrophy, in Wistar rats.

Strength training (ST) with blood flow restriction (BFR) is known to promote increases in hypertrophy and strength sometimes similar to traditional ST despite the effects of the arterial BFR on muscle adaptations and safety are not well established. The aim of this study was to assess whether ST with arterial BFR is able to improve muscular adaptations, performance and its safety in Wistar rats. Animals aging 8 weeks were divided in four groups: sedentary sham (S/S), sedentary with arterial BFR (S/BFR), trained sham (T/S), and trained with arterial BFR (T/BFR). Training protocol consisted of four weeks of ST composed by six sets of 10 ladder climbing with 50% of 1 maximal voluntary contraction. Body weight, epididymal fat, maximum loaded weight, manual grip strength, muscular hypertrophy index, systolic blood pressure, enzyme activity of superoxide dismutase, nitrite/nitrate concentration and tumor necrosis factor alpha were analyzed. The BFR rate was between 36% and 38%. T/BRF was effective to promote strength and hypertrophy. T/S is an alternative to improve strength, but it did not promote hypertrophy. Furthermore, we found no significant cardiac and metabolic changes. Thus, T/BFR is able to improve muscle adaptations and performance in rats, without causing cardiovascular and metabolic damage.

Low load strength training, associated with or without blood flow restriction increased NO production and decreased production of reactive oxygen species in rats aorta.

Studies have shown that strength training (ST) with blood flow restriction (BFR) in which low load is used (20-50% of 1 maximum voluntary contraction - MVC) can produce positive adaptations similar to ST with loads equal to or greater than 70% 1 MVC. Furthermore, recent studies have investigated the effects of STBFR on muscle adaptations, but few studies investigated the effects of STBFR on vascular function. This study aimed to evaluate the effects of the STBFR program on the vascular reactivity of the abdominal aorta of Wistar rats with femoral arteriovenous blood flow restriction. Male rats were divided into four groups: sedentary sham (S/S), sedentary with blood flow restriction (S/BFR), trained sham (T/S), and trained with blood flow restriction (T/BFR). The animals in the S/BFR and T/BFR groups underwent surgery to BFR in the femoral artery and vein. After one week, the trained groups started the ST which consisted of climbing ladder, six sets of 10 repetitions with 50% of 1 MVC assessed by maximum loaded weight (MLW) carried out for four weeks. Concentration-response curves to Acetylcholine (ACh: 10 nM - 100 µM) and Phenylephrine (PHE: 1 nM - 30 µM) were performed in aortic rings with intact endothelium. The production of nitric oxide (NO) and reactive oxygen species (ROS) in situ and the vascular remodeling marker (MMP-2) were also measured. The ST increased the strength of the T/S and T/BFR groups in MLW tests. The S/BFR group showed a 22% reduction in relaxation to acetylcholine, but exercise prevented this reduction in the T/BFR group. In animals without BFR, ST did not alter the response to acetylcholine. An increase in NO production was seen in T/S and T/BFR showed a reduction in ROS production (62% and 40%, respectively). In conclusion low load ST with BFR promotes similar vascular function responses to ST without BFR. Low load ST with and without BFR is interventions that can improve performance with similar magnitudes. Both training methods could have some benefits for vascular health due to NO production in the aorta increased in the T/S group and decreased production of reactive oxygen species in the T/BFR group.

Recessive NLRC4-Autoinflammatory Disease Reveals an Ulcerative Colitis Locus.

PURPOSE: NLRC4-associated autoinflammatory disease (NLRC4-AID) is an autosomal dominant condition presenting with a range of clinical manifestations which can include macrophage activation syndrome (MAS) and severe enterocolitis. We now report the first homozygous mutation in NLRC4 (c.478G > A, p.A160T) causing autoinflammatory disease with immune dysregulation and find that heterozygous carriers in the general population are at increased risk of developing ulcerative colitis. METHODS: Circulating immune cells and inflammatory markers were profiled and historical clinical data interrogated. DNA was extracted and sequenced using standard procedures. Inflammasome activation assays for ASC speck formation, pyroptosis, and IL-1ß/IL-18 secretion confirmed pathogenicity of the mutation in vitro. Genome-wide association of NLRC4 (A160T) with ulcerative colitis was examined using data from the IBD exomes portal. RESULTS: A 60-year-old Brazilian female patient was evaluated for recurrent episodes of systemic inflammation from six months of age. Episodes were characterized by recurrent low-grade fever, chills, oral ulceration, uveitis, arthralgia, and abdominal pain, followed by diarrhea with mucus and variable skin rash. High doses of corticosteroids were somewhat effective in controlling disease and anti-IL-1ß therapy partially controlled symptoms. While on treatment, serum IL-1ß and IL-18 levels remained elevated. Genetic investigations identified a homozygous mutation in NLRC4 (A160T), inherited in a recessive fashion. Increased ASC speck formation and IL-1ß/IL-18 secretion confirmed pathogenicity when NLRC4 (A160T) was analyzed in human cell lines. This allele is significantly enriched in patients with ulcerative colitis: OR 2.546 (95% 1.778-3.644), P = 0.01305. CONCLUSION: NLRC4 (A160T) can either cause recessively inherited autoinflammation and immune dysregulation, or function as a heterozygous risk factor for the development of ulcerative colitis.

O estado da arte das síndromes autoinflamatórias associadas à criopirina / The state of the art of cryopyrin-associated periodic syndromes

As síndromes autoinflamatórias associadas à criopirina (CAPS) compreendem um grupo espectral de doenças raras autoinflamatórias. Todas estas doenças estão relacionadas ao inflamassoma NLRP3, sendo que de 50-60% dos pacientes apresentam mutações ao longo do gene NLRP3. Clinicamente, febre recorrente associada à urticária neutrofílica e outros sintomas sistêmicos são o grande marco clínico, comum a todo o espectro. O bloqueio da interleucina-1 trouxe grande alívio ao tratamento destas desordens, mas variações na resposta clínica podem ser observadas, principalmente nos espectros mais graves. Neste trabalho os autores trazem uma revisão do estado da arte das doenças autoinflamatórias CAPS. Foi realizado levantamento de literatura e, ao final, 49 artigos restaram como base para construção do texto final. O trabalho traz de forma narrativa os principais pontos relacionados a imunofisiopatologia, manifestação clínica, diagnóstico, tratamento, complicações e novas armas diagnósticas, e terapia gênica.

Cryopyrin-associated periodic syndromes (CAPS) comprise a spectrum of rare autoinflammatory disorders. They are all related to the NLRP3 inflammasome, and 50-60% of the patients harbor mutations along the NLRP3 gene. Clinically, recurrent fever associated with neutrophilic urticaria and other systemic symptoms are a hallmark of all the disorders in the spectrum. Biologic drugs that can block interleukin-1 were a milestone for the treatment of such rare diseases, although variability in clinical response to this therapeutic intervention were observed, especially in those affected by severe phenotypes. In this paper, the authors provide a state-of-the-art review of CAPS. A literature search was performed and, finally, 49 articles remained for the construction of the final manuscript. The article presents a narrative review focused on the topics related to immune pathophysiology, clinical manifestations, diagnosis, treatment, complications and new therapeutic options, and gene therapy.

Immunological repertoire linked to PSTPIP1-associated myeloid-related inflammatory (PAMI) syndrome.

BACKGROUND: Mutations along PSTPIP1 gene are associated to two specific conditions, PAPA syndrome and PAMI syndrome, both autoinflammatory disorders associated to disturbances in cytoskeleton formation. Immunological aspects of PAMI syndrome has not yet been reported neither the clinical impact on therapeutical decisions. METHODS: Clinical data of patients records were retrospectively accessed. Genomic DNA were extracted and sequenced following standard procedures. Peripheral lymphocytes were quantified in T, B e FOXP3 phenotypes. RESULTS: We describe two related patients with PAMI syndrome harboring the usual E250K mutation. Anti-IL1 therapy could partially control the disease in the index patient. A broad spectrum of immunological effects as well as an aberrant expression of FOXP3 could be observed. CONCLUSIONS: Here we report two related brazilian patients with PAMI syndromes harboring the E250K mutation in PSTPIP1, their immunological aspects and the therapeutical response to canakinumab.

Mathematical modeling of the transmission of SARS-CoV-2-Evaluating the impact of isolation in São Paulo State (Brazil) and lockdown in Spain associated with protective measures on the epidemic of CoViD-19.

Coronavirus disease 2019 (CoViD-19), with the fatality rate in elder (60 years old or more) being much higher than young (60 years old or less) patients, was declared a pandemic by the World Health Organization on March 11, 2020. A mathematical model considering young and elder subpopulations under different fatality rates was formulated based on the natural history of CoViD-19 to study the transmission of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). The model considered susceptible, exposed, asymptomatic, pre-symptomatic, mild CoViD-19, severe CoViD-19, and recovered compartments, besides compartments of isolated individuals and those who were caught by test. This model was applied to study the epidemiological scenario resulting from the adoption of quarantine (isolation or lockdown) in many countries to control the rapid propagation of CoViD-19. We chose as examples the isolation adopted in São Paulo State (Brazil) in the early phase but not at the beginning of the epidemic, and the lockdown implemented in Spain when the number of severe CoViD-19 cases was increasing rapidly. Based on the data collected from São Paulo State and Spain, the model parameters were evaluated, and we obtained a higher estimation for the basic reproduction number R0 (9.24 for São Paulo State, and 8 for Spain) compared to the currently accepted estimation of R0 around 2 using the SEIR (susceptible, exposed, infectious, and recovered compartments) model. In comparison with the lockdown in Spain, the relatively early adoption of the isolation in São Paulo State resulted in enlarging the period of the first wave of the epidemic and delaying its peak. The model allowed to explain the flattening of the epidemic curves by quarantine when associated with the protective measures (face mask, washing hands with alcohol and gel, and social distancing) adopted by the population. The description of the epidemic under quarantine and protections can be a background to foreseen the epidemiological scenarios from the release strategies, which can help guide public health policies by decision-makers.

Sonification of combined action observation and motor imagery: Effects on corticospinal excitability.

Action observation and motor imagery are valuable strategies for motor learning. Their simultaneous use (AOMI) increases neural activity, with related benefits for motor learning, compared to the two strategies alone. In this study, we explored how sonification influences AOMI. Twenty-five participants completed a practice block based on AOMI, motor imagery and physical execution of the same action. Participants were divided into two groups: An experimental group that practiced with sonification during AOMI (sAOMI), and a control group, which did not receive any extrinsic feedback. Corticospinal excitability at rest and during action observation and AOMI was assessed before and after practice, with and without sonification sound, to test the development of an audiomotor association. The practice block increased corticospinal excitability in all testing conditions, but sonification did not affect this. In addition, we found no differences in action observation and AOMI, irrespective of sonification. These results suggest that, at least for simple tasks, sonification of AOMI does not influence corticospinal excitability; In these conditions, sonification may have acted as a distractor. Future studies should further explore the relationship between task complexity, value of auditory information and action, to establish whether sAOMI is a valuable for motor learning.

Case Report: Expanding Clinical, Immunological and Genetic Findings in Sideroblastic Anemia With Immunodeficiency, Fevers and Development Delay (SIFD) Syndrome.

Since the first description of the syndrome of sideroblastic anemia with immunodeficiency, fevers and development delay (SIFD), clinical pictures lacking both neurological and hematological manifestations have been reported. Moreover, prominent skin involvement, such as with relapsing erythema nodosum, is not a common finding. Up to this moment, no genotype and phenotype correlation could be done, but mild phenotypes seem to be located in the N or C part. B-cell deficiency is a hallmark of SIFD syndrome, and multiple others immunological defects have been reported, but not high levels of double negative T cells. Here we report a Brazilian patient with a novel phenotype of SFID syndrome, carrying multiple immune defects and harboring a novel mutation on TRNT1 gene.

Does sonification of action simulation training impact corticospinal excitability and audiomotor plasticity?

Sonification is a sensory augmentation strategy whereby a sound is associated with, and modulated by, movement. Evidence suggests that sonification could be a viable strategy to maximize learning and rehabilitation. Recent studies investigated sonification of action observation, reporting beneficial effects, especially in Parkinson's disease. However, research on simulation training-a training regime based on action observation and motor imagery, in which actions are internally simulated, without physical execution-suggest that action observation alone is suboptimal, compared to the combined use of action observation and motor imagery. In this study, we explored the effects of sonified action observation and motor imagery on corticospinal excitability, as well as to evaluate the extent of practice-dependent plasticity induced by this training. Nineteen participants were recruited to complete a practice session based on combined and congruent action observation and motor imagery (AOMI) and physical imitation of the same action. Prior to the beginning, participants were randomly assigned to one of two groups, one group (nine participants) completed the practice block with sonified AOMI, while the other group (ten participants) completed the practice without extrinsic auditory information and served as control group. To investigate practice-induced plasticity, participants completed two auditory paired associative stimulation (aPAS) protocols, one completed after the practice block, and another one completed alone, without additional interventions, at least 7 days before the practice. After the practice block, both groups significantly increased their corticospinal excitability, but sonification did not exert additional benefits, compared to non-sonified conditions. In addition, aPAS significantly increased corticospinal excitability when completed alone, but when it was primed by a practice block, no modulatory effects on corticospinal excitability were found. It is possible that sonification of combined action observation and motor imagery may not be a useful strategy to improve corticospinal, but further studies are needed to explore its relationship with performance improvements. We also confirm the neuromodulatory effect of aPAS, but its interaction with audiomotor practice remain unclear.