Novel B-cell subsets as potential biomarkers in idiopathic inflammatory myopathies: insights into disease pathogenesis and disease activity.

Idiopathic inflammatory myopathies are a heterogeneous group of rare autoimmune disorders characterized by progressive muscle weakness and the histopathologic findings of inflammatory infiltrates in muscle tissue. Although their pathogenesis remains indefinite, the association of autoantibodies with clinical manifestations and the evidence of high effectiveness of depleting therapies suggest that B cells could be implicated. Therefore, we explored the landscape of peripheral B cells in this disease by multiparametric flow cytometry, finding significant numerical decreases in memory and double-negative subsets, as well as an expansion of the naive compartment relative to healthy controls, that contribute to defining disease-associated B-cell subset signatures and correlating with different clinical features of patients. Additionally, we determined the potential value of these subsets as diagnostic biomarkers, thus positioning B cells as neglected key elements possibly participating in idiopathic inflammatory myopathy onset or development.

Inflammatory myopathies and beyond: The dual role of neutrophils in muscle damage and regeneration.

Skeletal muscle is one of the most abundant tissues of the human body and is responsible for the generation of movement. Muscle injuries can lead to severe disability. Skeletal muscle is characterized by an important regeneration capacity, which is possible due to the interaction between the myoblasts and immune cells. Neutrophils are fundamental as inducers of muscle damage and as promoters of the initial inflammatory response which eventually allows the muscle repair. The main functions of the neutrophils are phagocytosis, respiratory burst, degranulation, and the production of neutrophil extracellular traps (NETs). An overactivation of neutrophils after muscle injuries may lead to an expansion of the initial damage and can hamper the successful muscle repair. The importance of neutrophils as inducers of muscle damage extends beyond acute muscle injury and recently, neutrophils have become more relevant as part of the immunopathogenesis of chronic muscle diseases like idiopathic inflammatory myopathies (IIM). This heterogeneous group of systemic autoimmune diseases is characterized by the presence of muscle inflammation with a variable amount of extramuscular features. In IIM, neutrophils have been found to have a role as biomarkers of disease activity, and their expansion in peripheral blood is related to certain clinical features like interstitial lung disease (ILD) and cancer. On the other hand, low density granulocytes (LDG) are a distinctive subtype of neutrophils characterized by an enhanced production of NETs. These cells along with the NETs have also been related to disease activity and certain clinical features like ILD, vasculopathy, calcinosis, dermatosis, and cutaneous ulcers. The role of NETs in the immunopathogenesis of IIM is supported by an enhanced production and deficient degradation of NETs that have been observed in patients with dermatomyositis and anti-synthetase syndrome. Finally, new interest has arisen in the study of other phenotypes of LDG with a phenotype corresponding to myeloid-derived suppressor cells, which were also found to be expanded in patients with IIM and were related to disease activity. In this review, we discuss the role of neutrophils as both orchestrators of muscle repair and inducers of muscle damage, focusing on the immunopathogenesis of IIM.

Novel clinical and immunological features associated with persistent post-acute sequelae of COVID-19 after six months of follow-up: a pilot study.

BACKGROUND: Currently, there is scant information regarding the features associated to the persistence of post-COVID-19 syndrome, which is the main aim of the present study. METHODS: A cohort study of 102 COVID-19 patients was conducted. The post-COVID-19 symptoms were assessed by a standardised questionnaire. Lymphocyte immunophenotyping was performed by flow cytometry and chemokines/cytokines, neutrophil extracellular traps, the tripartite motif 63, anti-cellular, and anti-SARS-CoV-2 IgG antibodies were addressed in serum. The primary outcome was the persistence of post-COVID-19 syndrome after six months follow-up. RESULTS: Thirteen patients (12.7%) developed the primary outcome and had a more frequent history of post-COVID-19 syndrome 3 months after infection onset (p = .044), increased levels of IL-1α (p = .011) and IP-10 (p = .037) and increased CD57 expression in CD8+ T cells (p = .003). There was a trend towards higher levels of IFN-γ (p = .051), IL-1ß (p = .062) and IL-6 (p = .087). The history of post COVID-19 in the previous 3 months, obesity, baseline serum MIP-1α and IP-10, and CD57 expression in CD8+ T cells were independently associated with the persistence of post-COVID-19 syndrome. CONCLUSION: Our data suggest an important relationship between a pro-inflammatory state mediated through metabolic pathways related to obesity and increased cellular senescence as a key element in the persistence of post-COVID-19 syndrome at six months of follow-up.

Clinical and immunological features associated to the development of a sustained immune humoral response in COVID-19 patients: Results from a cohort study.

Background: Until now, most of the research addressing long-term humoral responses in coronavirus disease 2019 (COVID-19) had only evaluated the serum titers of anti-severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) IgGs, without the assessment of the baseline antiviral clinical and immune profile, which is the aim of this study and may be the key factor leading to a broad and sustained antibody response. Methods: We included 103 patients with COVID-19. When the patients sought medical attention (baseline), a blood sample was drawn to perform immunophenotype of lymphocytes by flow cytometry. The patients were assessed 15 days after baseline and then every month until the third month, followed by a last visit 6 months after recruitment. We evaluated the anti-SARS-COV-2 IgG at all time points, and the serum levels of cytokines, chemokines, anti-cellular (AC) antibodies and neutrophil extracellular traps were also assessed during the follow-up. The primary outcome of the study was the presence of a sustained immune humoral response, defined as an anti-SARS-CoV-2 IgG titer >4.99 arbitrary units/mL in at least two consecutive measures. We used generalized lineal models to assess the features associated with this outcome and to assess the effect of the changes in the cytokines and chemokines throughout time on the development of a sustained humoral immune response. Results: At baseline the features associated to a sustained immune humoral response were the diagnosis of critical disease, absolute number of lymphocytes, serum IP-10, IL-4, IL-2, regulatory T cells, CD8+ T cells, and positive AC antibodies. Critical illness and the positivity of AC antibodies were associated with a sustained humoral immune response after 3 months, whilst critical illness and serum IL-13 were the explanatory variables after 6 months. Conclusion: A sustained immune humoral response is strongly related to critical COVID-19, which is characterized by the presence of AC antibodies, quantitative abnormalities in the T cell compartment, and the serum cytokines and chemokines during acute infection and throughout time.

Neutrophil Extracellular Traps Contribute to COVID-19 Hyperinflammation and Humoral Autoimmunity.

The coronavirus disease 2019 (COVID-19) is related to enhanced production of NETs, and autoimmune/autoinflammatory phenomena. We evaluated the proportion of low-density granulocytes (LDG) by flow cytometry, and their capacity to produce NETs was compared with that of conventional neutrophils. NETs and their protein cargo were quantified by confocal microscopy and ELISA. Antinuclear antibodies (ANA), anti-neutrophil cytoplasmic antibodies (ANCA) and the degradation capacity of NETs were addressed in serum. MILLIPLEX assay was used to assess the cytokine levels in macrophages' supernatant and serum. We found a higher proportion of LDG in severe and critical COVID-19 which correlated with severity and inflammatory markers. Severe/critical COVID-19 patients had higher plasmatic NE, LL-37 and HMGB1-DNA complexes, whilst ISG-15-DNA complexes were lower in severe patients. Sera from severe/critical COVID-19 patients had lower degradation capacity of NETs, which was reverted after adding hrDNase. Anti-NET antibodies were found in COVID-19, which correlated with ANA and ANCA positivity. NET stimuli enhanced the secretion of cytokines in macrophages. This study unveils the role of COVID-19 NETs as inducers of pro-inflammatory and autoimmune responses. The deficient degradation capacity of NETs may contribute to the accumulation of these structures and anti-NET antibodies are related to the presence of autoantibodies.

Values, Environmental Beliefs, and Connection With Nature as Predictive Factors of the Pro-environmental Vote in Spain.

This research analyzes the predictive capacity of psychosocial variables that can influence the decision to vote for political parties that include pro-environmental measures in their program. To this end, a study was carried out with a sample of 414 people of legal age who could exercise their right to vote (mean age = 26.92, SD = 10.53). The participants were divided into two groups: (1) Pro-environmental voters, those who during the last elections in Spain based their voting decision on whether the political party included pro-environment measures in its electoral program (n = 190), and (2) Non-pro-environmental voters, those other people who voted for a political party without considering whether pro-environment measures were included in its electoral program (even if such environmental protection measures had been included) (n = 224). The results indicate that, in comparison with their counterparts who do not vote for pro-environmental parties, those who voted for political parties during the last elections by considering the inclusion of pro-environment measures in their electoral program showed the highest scores on the biospheric and socio-altruistic values of ecocentrism, anthropocentrism, connectivity with nature and environmental concern, and scored lower on self-centered values. With the exception of connectivity with nature, biospheric values and beliefs were good predictors of pro-environmental voting behavior.

Western diet-induced obesity disrupts the diurnal rhythmicity of hippocampal core clock gene expression in a mouse model.

Western diet (WD) feeding disrupts core clock gene expression in peripheral tissues and contributes to WD-induced metabolic disease. The hippocampus, the mammalian center for memory, is also sensitive to WD feeding, but whether the WD disrupts its core clock is unknown. To this end, male mice were maintained on a WD for 16 weeks and diurnal metabolism, gene expression and memory were assessed. WD-induced obesity disrupted the diurnal rhythms of whole-body metabolism, markers of inflammation and hepatic gene expression, but did not disrupt diurnal expression of hypothalamic Bmal1, Npas2 and Per2. However, all measured core clock genes were disrupted in the hippocampus after WD feeding and the expression pattern of genes implicated in Alzheimer's disease and synaptic function were altered. Finally, WD feeding disrupted hippocampal memory in a task- and time-dependent fashion. Our results implicate WD-induced alterations in the rhythmicity of hippocampal gene expression in the etiology of diet-induced memory deficits.

Estilos de afrontamiento y nivel de estrés de madres adolescentes con hijos hospitalizados en la unidad de cuidados intensivos neonatales, Chiapas, México / Coping styles and stress level of adolescent mothers with hospitalized children in neonatal intensive care unit Chiapas, México

Introdución: el embarazo en adolescentes se considera un problema de salud pública por los efectos adversos que pueden tener la madre y el niño durante todo el embarazo. Entre los principales problemas para el niño se destaca prematurez, retraso en el crecimiento y síndrome de dificultad respiratoria. La adolescente tiene que asumir el nuevo rol, y practicar el afrontamiento (COPING); simultáneamente las madres experimentan estrés. Objetivo: analizar los estilos de afrontamiento y nivel de estrés de madres adolescentes con hijos hospitalizados en la unidad de cuidados intensivos neonatales UCIN. Material y métodos: estudio cuantitativo, transversal, observacional, prolectivo. Muestreo a conveniencia con 80 adolescentes seleccionadas en un hospital de segundo nivel; se aplicó un cuestionario de autoinforme en escala tipo Likert integrado por datos sociodemográficos, escala de afrontamiento en adolescentes y escala de estrés parental ambos instrumentos adaptados por López, Carmona y Ponce en 2016. Tipo de análisis: SPSS 23, y estadística descriptiva, estadística inferencial. Resultados: respecto a los estilos de afrontamiento se encontró que las adolescentes se dirigen al estilo improductivo, la estrategia autoinculparse. En relación al análisis del estrés percibido, se encontró en niveles altos, la subescala correspondiente a la relación con el niño y el rol materno, muestra el estrés medio, en la subdimensión se tienen los aspectos y sonidos de la unidad y la apariencia y conducta del niño. Conclusiones: las madres adolescentes se dirigen al estilo de afrontamiento improductivo suelen desconfiar de sus capacidades, provocando sentimientos de inseguridad, de esta manera la hospitalización del recién nacido en la UCIN y la relación con el niño y el rol materno para ellas es en extremo estresante. Por lo tanto, se requieren de una intervención educativa y de capacitación para direccionar sus conductas hacía un afrontamiento positivo y de esta manera mejorar la actuación respecto al cuidado de su hijo en una terapia intensiva neonatal.

[Gait, balance and independence rehabilitation program in elderly adults in a primary care unit]. / Programa para la rehabilitación funcional del adulto mayor. Mejorar la marcha, el equilibrio y la independencia.

OBJECTIVE: to evaluate the effect of a supervised rehabilitation program to improve gait, balance and independence in elderly patients attending a family medicine unit. METHODS: we conducted a quasi-experimental study over a period of four weeks in a group of 72 patients older than 65 years. INTERVENTION: a supervised program regarding the risk factors for falling, and balance, gait, coordination and oculovestibular system, the modalities to be done two or three times a week in the primary care unit or at home. An analysis of both tests was performed by "up and go," Tinetti scale and the Katz index. ANALYSIS: "intention to treat" and "by protocol." RESULTS: mean age was 72 ± 5 years, 67.8% were female and 81.9% of the patients completed the program. A significant clinical improvement with statistical level were evident for gait and balance (p = 0.001), independence showed only clinical improvement (p = 0.083). The efficacy for periodicity (two or three times/week) and performance place showed same clinical improvement and statistical level for gait and balance (p = 0.001 to 0.003) and independence showed only clinical improvement (p = 0.317 to 0.991). CONCLUSIONS: an integral rehabilitation program improved gait, balance and clinical independence significantly. The supervised program is applicable and can be reproduced at primary care unit or home for geriatric care and preventive actions.

Objetivo: evaluar un programa de rehabilitación de la marcha, equilibrio e independencia supervisado para adultos mayores en el primer nivel de atención. Métodos: estudio cuasiexperimental de 72 adultos mayores de 65 años de edad que recibieron orientación de factores de riesgo de caída, entrenamiento de marcha, equilibrio e independencia, dos o tres veces por semana en la unidad médica o en el domicilio por cuatro semanas. Se aplicó prueba levántate y anda, escala de Tinetti e índice de Katz. Análisis estadístico: intención a tratar y por protocolo. Resultados: 81.9 % completó el programa, la edad promedio fue de 72 ± 5 años; 67.8 % fue del sexo femenino. Se demostró mejoría estadísticamente significativa en la marcha y el equilibrio (p = 0.001) y sin significación estadística para independencia (p = 0.083). En los subgrupos que acudieron a la unidad médica adversus domicilio se observó mejoría con significación estadística solo en la marcha y el equilibrio (p = 0.001-0.003) y solo mejoría con relevancia clínica en la independencia (p = 0.317 a 1.000). Conclusiones: el programa es aplicable con resultados significativos en el primer nivel de atención.

[Contribution of electroneuromyography to the evaluation of neuropathy in diabetic patients]. / Utilidad de la electroneuromiografía para evaluar neuropatía en pacientes diabéticos.

OBJECTIVE: To determine the type and the frequency of diabetic neuropathy, diagnosed by electroneuromyography, in patients with type 2 diabetes mellitus, and the correlation between the neuropathy diagnosis and clinical symptoms. DESIGN: Cross-sectional descriptive and correlative of patients with diagnosis of type 2 diabetes mellitus, sent for electroneuromyography study in 2000. Study place: Laboratory of electrodiagnosis of the Unidad de Medicina Física y Rehabilitación Región Norte. Measuring: Electroneuromyography was performed, and the type and frequency of the diabetic neuropathy, as well as the presence of clinical systematization, according to the initial diagnosis, were assessed. Furthermore, sex, occupation, and medical unit of reference were identified. ANALYSIS: Measures of central tendency and dispersion, as well as association by means of quadruple correlation ratio were considered. RESULTS: 219 electrodiagnostic studies were carried out in patients with type 2 diabetes mellitus, of which 152 were males. The age average was of 54.3 +/- 8.9 years old. The prevailing occupation was that of housewives with 128. The references of the Hospital General de Zona 24 were 39; those of Unidad de Medicina Física y Rehabilitación Región Norte were 32, and those of the Hospital General de Zona 98 were 28. There was a presence of clinical systematization in 186 (84.9%) patients. The electroneuromyography diagnosed diabetic neuropathy in 174 patients, of which 89 correspond to neuropathy due to segmental demyelination, and 85 to mixed neuropathy; in 21 patients, the electroneuromyography was normal. Of the 186 patients with clinical systematization, the electroneuromyography was positive in 170, with r = 0.70. CONCLUSIONS: The prevalence of diabetic neuropathy in patients with type 2 diabetes mellitus is of 80%, the type of variety is of segmental demyelination in 51% and of mixed type in 49%. There is a high correlation between the clinical diagnosis of diabetic neuropathy and the confirmation by electroneuromyography.

[Clinical guidelines for the prevention of falls in elderly people]. / Guia de práctica clínica para la prevencion de caídas en el adulto mayor.

Demographic changes in our population are focusing on the health providers to prevent or minimize functional impairments resulting from the various chronic and multiple illnesses to which the elderly are prone. Because of that, we developed strategies that can help us to take decisions in order to identify the risk factors, and to prescribe preventive and rehabilitation programs. With this background, we organized an expert team to develop this guideline with evidence based on medicine methodology, and focus on the first level treatment prescribed by the general practitioner, with the participation of the health team and the support networks.