The autophagy protein RUBCNL/PACER represses RIPK1 kinase-dependent apoptosis and necroptosis.

Mesenchymal stem cells (MSCs) are used in cell therapy; nonetheless, their application is limited by their poor survival after transplantation in a proinflammatory microenvironment. Macroautophagy/autophagy activation in MSCs constitutes a stress adaptation pathway, promoting cellular homeostasis. Our proteomics data indicate that RUBCNL/PACER (RUN and cysteine rich domain containing beclin 1 interacting protein like), a positive regulator of autophagy, is also involved in cell death. Hence, we screened MSC survival upon various cell death stimuli under loss or gain of function of RUBCNL. MSCs were protected from TNF (tumor necrosis factor)-induced regulated cell death when RUBCNL was expressed. TNF promotes inflammation by inducing RIPK1 kinase-dependent apoptosis or necroptosis. We determine that MSCs succumb to RIPK1 kinase-dependent apoptosis upon TNF sensing and necroptosis when caspases are inactivated. We show that RUBCNL is a negative regulator of both RIPK1-dependent apoptosis and necroptosis. Furthermore, RUBCNL mutants that lose the ability to regulate autophagy, retain their function in negatively regulating cell death. We also found that RUBCNL forms a complex with RIPK1, which disassembles in response to TNF. In line with this finding, RUBCNL expression limits assembly of RIPK1-TNFRSF1A/TNFR1 complex I, suggesting that complex formation between RUBCNL and RIPK1 represses TNF signaling. These results provide new insights into the crosstalk between the RIPK1-mediated cell death and autophagy machineries and suggest that RUBCNL, due to its functional duality in autophagy and apoptosis/necroptosis, could be targeted to improve the therapeutic efficacy of MSCs. Abbreviations: BAF: bafilomycin A1; CASP3: caspase 3; Caspases: cysteine-aspartic proteases; cCASP3: cleaved CASP3; CQ: chloroquine; CHX: cycloheximide; cPARP: cleaved poly (ADP-ribose) polymerase; DEPs: differential expressed proteins; ETO: etoposide; MEF: mouse embryonic fibroblast; MLKL: mixed lineage kinase domain-like; MSC: mesenchymal stem cell; MTORC1: mechanistic target of rapamycin kinase complex 1; Nec1s: necrostatin 1s; NFKB/NF-kB: nuclear factor of kappa light polypeptide gene enhancer in B cells; PLA: proximity ligation assay; RCD: regulated cell death; RIPK1: receptor (TNFRSF)-interacting serine-threonine kinase 1; RIPK3: receptor-interacting serine-threonine kinase 3; RUBCNL/PACER: RUN and cysteine rich domain containing beclin 1 interacting protein like; siCtrl: small interfering RNA nonsense; siRNA: small interfering RNA; TdT: terminal deoxynucleotidyl transferase; Tm: tunicamycin; TNF: tumor necrosis factor; TNFRSF1A/TNFR1: tumor necrosis factor receptor superfamily, member 1a.

Online scientific research on placentophagy: a bibliometric analysis.

Objective: To classify the bibliometric indicators of online scientific research on placentophagy. Methods: A bibliometric study was conducted to quantify the scientific production of authors and institutions with the aim of highlighting the growth and impact of these publications nationally and internationally. The Bradford Law, network maps, and textual statistics were used, with searches conducted in libraries and databases in October 2021. Results: The sample consisted of 64 articles, whose primary authors were associated with 49 institutions, and mostly with degrees in anthropology. The United States of America was the country that published the most papers on the theme, and most studies were reviews with individual production. Through the term analysis, it was found that the predominant themes regarding placentophagy were the following: Alternative therapy for women's health, methodologies used for research in this area, period of placenta ingestion (postpartum period), and its benefits. Conclusion: The bibliometric indicators found are essential for the development of future research.

Online scientific research on placentophagy: a bibliometric analysis

Abstract Objective: To classify the bibliometric indicators of online scientific research on placentophagy. Methods: A bibliometric study was conducted to quantify the scientific production of authors and institutions with the aim of highlighting the growth and impact of these publications nationally and internationally. The Bradford Law, network maps, and textual statistics were used, with searches conducted in libraries and databases in October 2021. Results: The sample consisted of 64 articles, whose primary authors were associated with 49 institutions, and mostly with degrees in anthropology. The United States of America was the country that published the most papers on the theme, and most studies were reviews with individual production. Through the term analysis, it was found that the predominant themes regarding placentophagy were the following: Alternative therapy for women's health, methodologies used for research in this area, period of placenta ingestion (postpartum period), and its benefits. Conclusion: The bibliometric indicators found are essential for the development of future research.

The autophagy protein Def8 is altered in Alzheimer's disease and Aß42-expressing Drosophila brains.

Alzheimer's disease (AD) is the most common neurodegenerative disorder, characterized by protein accumulation in the brain as a main neuropathological hallmark. Among them, Aß42 peptides tend to aggregate and create oligomers and plaques. Macroautophagy, a form of autophagy characterized by a double-membrane vesicle, plays a crucial role in maintaining neuronal homeostasis by degrading protein aggregates and dysfunctional organelles as a quality control process. Recently, DEF8, a relatively uncharacterized protein, has been proposed as a participant in vesicular traffic and autophagy pathways. We have reported increased DEF8 levels in lymphocytes from mild cognitive impairment (MCI) and early-stage AD patients and a neuronal profile in a murine transgenic AD model. Here, we analyzed DEF8 localization and levels in the postmortem frontal cortex of AD patients, finding increased levels compared to healthy controls. To evaluate the potential function of DEF8 in the nervous system, we performed an in silico assessment of its expression and network profiles, followed by an in vivo evaluation of a neuronal Def8 deficient model using a Drosophila melanogaster model of AD based on Aß42 expression. Our findings show that DEF8 is an essential protein for maintaining cellular homeostasis in the nervous system, and it is upregulated under stress conditions generated by Aß42 aggregation. This study suggests DEF8 as a novel actor in the physiopathology of AD, and its exploration may lead to new treatment avenues.

Integrative and complementary practices to control nausea and vomiting in pregnant women: a systematic review.

OBJECTIVE: to synthesize the evidence available in the literature on the effects of integrative and complementary practices in nausea and vomiting treatment in pregnant women. METHOD: a systematic review, reported according to PRISMA and registered in PROSPERO. The search for studies was carried out in 11 databases. To assess risk of bias in randomized clinical trials, the Cochrane Collaboration Risk of Bias Tool (RoB 2) was used. RESULTS: the final sample consisted of 31 articles, divided into three categories: aromatherapy, phytotherapy and acupuncture. It was observed that aromatherapy with lemon essential oil, ginger capsules, pericardial 6 point acupressure were the interventions that proved to be effective. Less than half of studies reported adverse effects, with mild and transient symptoms predominating. Most articles were classified as "some concern" in risk of bias assessment. CONCLUSION: the three most effective interventions to control gestational nausea and vomiting were aromatherapy, herbal medicine and acupuncture, with significant results in the assessment of individual studies.

Neuronal Rubicon Represses Extracellular APP/Amyloid ß Deposition in Alzheimer's Disease.

Alzheimer's disease (AD) is the most prevalent age-associated neurodegenerative disease. A decrease in autophagy during aging contributes to brain disorders by accumulating potentially toxic substrates in neurons. Rubicon is a well-established inhibitor of autophagy in all cells. However, Rubicon participates in different pathways depending on cell type, and little information is currently available on neuronal Rubicon's role in the AD context. Here, we investigated the cell-specific expression of Rubicon in postmortem brain samples from AD patients and 5xFAD mice and its impact on amyloid ß burden in vivo and neuroblastoma cells. Further, we assessed Rubicon levels in human-induced pluripotent stem cells (hiPSCs), derived from early-to-moderate AD and in postmortem samples from severe AD patients. We found increased Rubicon levels in AD-hiPSCs and postmortem samples and a notable Rubicon localization in neurons. In AD transgenic mice lacking Rubicon, we observed intensified amyloid ß burden in the hippocampus and decreased Pacer and p62 levels. In APP-expressing neuroblastoma cells, increased APP/amyloid ß secretion in the medium was found when Rubicon was absent, which was not observed in cells depleted of Atg5, essential for autophagy, or Rab27a, required for exosome secretion. Our results propose an uncharacterized role of Rubicon on APP/amyloid ß homeostasis, in which neuronal Rubicon is a repressor of APP/amyloid ß secretion, defining a new way to target AD and other similar diseases therapeutically.

Cuidados paliativos e comunicação: uma reflexão à luz da teoria do final de vida pacífico / Palliative care and communication: a reflection in the light of the peaceful end of life theory / Cuidados paliativos y comunicación: una reflexión a la luz de la teoría del final pacífico de la vida

RESUMO Objetivo: analisar a contribuição do cuidado de enfermagem, com ênfase na comunicação, para o paciente sob cuidados paliativos na fase terminal e seus familiares. Método: estudo qualitativo, realizado em um Hospital Filantrópico da cidade de João Pessoa-PB, Brasil, em 2019, desenvolvido com 15 familiares de pacientes em cuidados paliativos, por meio de entrevistas semiestruturadas. Os dados foram submetidos à análise de conteúdo, proposta por Bardin, à luz da Teoria do Final de Vida Pacífico. Resultados: emergiram duas categorias: 'A comunicação dos profissionais de enfermagem como estratégia para promover conforto, paz, dignidade e respeito para pacientes e familiares em cuidados paliativos'; 'A presença e o diálogo de pessoas importantes para o paciente sob cuidados paliativos são fundamentais para um final de vida pacífico.' Conclusão: espera-se que, através desse estudo, seja possível aprimorar a assistência à família acerca da comunicação nos cuidados paliativos.

ABSTRACT Objective: to analyze the contribution of nursing care, with emphasis on communication, for the patient under palliative care in the terminal phase and their families. Method: qualitative study, conducted in a Philanthropic Hospital in the city of João Pessoa-PB, Brazil, in 2019, developed with 15 family members of patients in palliative care, through semi-structured interviews. The data were submitted to content analysis, proposed by Bardin, in the light of the Pacific End of Life Theory. Results: two categories emerged: 'Communication by nursing professionals as a strategy to promote comfort, peace, dignity and respect for patients and families in palliative care'; 'The presence and dialogue of people important to the patient under palliative care are fundamental for a peaceful end of life.' Conclusion: it is hoped that, through this study, it will be possible to improve assistance to the family about communication in palliative care.

RESUMEN Objetivo: analizar la contribución de los cuidados de enfermería, con énfasis en la comunicación, para el paciente en cuidados paliativos en fase terminal y sus familias. Método: estudio cualitativo, realizado en un Hospital Filantrópico de la ciudad de João Pessoa-PB, Brasil, en 2019, desarrollado con 15 familiares de pacientes en cuidados paliativos, a través de entrevistas semiestructuradas. Los datos fueron sometidos a un análisis de contenido, propuesto por Bardin, a la luz de la Teoría del Final Tranquilo de la Vida. Resultados: surgieron dos categorías: "La comunicación de los profesionales de enfermería como estrategia para promover el confort, la paz, la dignidad y el respeto a los pacientes y familiares en los cuidados paliativos"; "La presencia y el diálogo de las personas importantes para el paciente en los cuidados paliativos son fundamentales para un final de vida tranquilo". Conclusión: se espera que, a través de este estudio, sea posible mejorar la asistencia a la familia sobre la comunicación en los cuidados paliativos.

Effects of low-power laser auriculotherapy on chronic spinal pain: Randomized clinical trial.

AIMS AND OBJECTIVES: To evaluate the effect of laser auriculotherapy on chronic spinal pain. It is a randomized controlled clinical trial. METHODS: Volunteers with chronic spinal pain underwent three evaluations: an initial evaluation, a final evaluation immediately after the last intervention session, and a 15-day follow-up. Pain intensity, nociceptive threshold in relation to mechanical stimulus, and degree of pain (the greatest and least pain) in the last seven days were the assessed variables. The experimental group (EG, n = 24) underwent 10 sessions of laser auriculotherapy twice a week, while the control group (CG, n = 23) did not receive any intervention. RESULTS: The EG showed great clinical improvement in relation to the variable pain intensity between pre- and post-interventions (65.2%) and pre-intervention and follow-up (58.62%) compared to the CG. There was a significant increase in the nociceptive threshold for the EG. In contrast, the CG showed a significant reduction in the nociceptive threshold. The intergroup analysis indicated an improvement in pain intensity for the EG (0.006). This result remained at the follow-up (0.012). The nociceptive threshold increased over time for the EG (0.016). In contrast, the CG showed a reduction in this variable with a significant difference over time (<0.001). CONCLUSION: The results of this clinical trial suggest that the proposed intervention may be effective in reducing pain intensity and increasing the nociceptive threshold. The effect of the intervention remained 15 days after the end of the treatment, when the volunteers were re-evaluated.

Contribution of Autophagy-Lysosomal Pathway in the Exosomal Secretion of Alpha-Synuclein and Its Impact in the Progression of Parkinson's Disease.

Parkinson's disease (PD) is caused by the degeneration of dopaminergic neurons due to an accumulation of intraneuronal abnormal alpha-synuclein (α-syn) protein aggregates. It has been reported that the levels of exosomal α-syn of neuronal origin in plasma correlate significantly with motor dysfunction, highlighting the exosomes containing α-syn as a potential biomarker of PD. In addition, it has been found that the selective autophagy-lysosomal pathway (ALP) contributes to the secretion of misfolded proteins involved in neurodegenerative diseases. In this review, we describe the evidence that supports the relationship between the ALP and α-syn exosomal secretion on the PD progression and its implications in the diagnosis and progression of this pathology.

Insulin-like growth factor 2 and autophagy gene expression alteration arise as potential biomarkers in Parkinson's disease.

Insulin-like growth factor 2 (IGF2) and autophagy-related genes have been proposed as biomolecules of interest related to idiopathic Parkinson's disease (PD). The objective of this study was to determine the IGF2 and IGF1 levels in plasma and peripheral blood mononuclear cells (PBMCs) from patients with moderately advanced PD and explore the potential correlation with autophagy-related genes in the same blood samples. IGF1 and IGF2 levels in patients' plasma were measured by ELISA, and the IGF2 expression levels were determined by real-time PCR and Western blot in PBMCs. The expression of autophagy-related genes was evaluated by real-time PCR. The results show a significant decrease in IGF2 plasma levels in PD patients compared with a healthy control group. We also report a dramatic decrease in IGF2 mRNA and protein levels in PBMCs from PD patients. In addition, we observed a downregulation of key components of the initial stages of the autophagy process. Although IGF2 levels were not directly correlated with disease severity, we found a correlation between its levels and autophagy gene profile expression in a sex-dependent pattern from the same samples. To further explore this correlation, we treated mice macrophages cell culture with α-synuclein and IGF2. While α-synuclein treatment decreased levels Atg5, IGF2 treatment reverted these effects, increasing Atg5 and Beclin1 levels. Our results suggest a relationship between IGF2 levels and the autophagy process in PD and their potential application as multi-biomarkers to determine PD patients' stages of the disease.

Integrative and complementary practices to control nausea and vomiting in pregnant women: a systematic review / Prácticas integradoras y complementarias para el control de náuseas y vómitos en gestantes: una revisión sistemática / Práticas integrativas e complementares para controle de náuseas e vômitos em gestantes: revisão sistemática

ABSTRACT Objective: to synthesize the evidence available in the literature on the effects of integrative and complementary practices in nausea and vomiting treatment in pregnant women. Method: a systematic review, reported according to PRISMA and registered in PROSPERO. The search for studies was carried out in 11 databases. To assess risk of bias in randomized clinical trials, the Cochrane Collaboration Risk of Bias Tool (RoB 2) was used. Results: the final sample consisted of 31 articles, divided into three categories: aromatherapy, phytotherapy and acupuncture. It was observed that aromatherapy with lemon essential oil, ginger capsules, pericardial 6 point acupressure were the interventions that proved to be effective. Less than half of studies reported adverse effects, with mild and transient symptoms predominating. Most articles were classified as "some concern" in risk of bias assessment. Conclusion: the three most effective interventions to control gestational nausea and vomiting were aromatherapy, herbal medicine and acupuncture, with significant results in the assessment of individual studies.

RESUMEN Objetivo: sintetizar las evidencias disponibles en la literatura sobre los efectos de las prácticas integradoras y complementarias en el tratamiento de náuseas y vómitos en gestantes. Método: revisión sistemática, reportada según PRISMA y registrada en PROSPERO. La búsqueda de estudios se realizó en 11 bases/bases de datos. Para evaluar el riesgo de sesgo en los ensayos clínicos aleatorios, se utilizó la herramienta Cochrane Collaboration Risk of Bias Tool (RoB 2). Resultados: la muestra final estuvo compuesta por 31 artículos, divididos en tres categorías: aromaterapia, fitoterapia y acupuntura. Se observó que la aromaterapia con aceite esencial de limón, las cápsulas de jengibre, la acupresión en el punto 6 del pericardio fueron las intervenciones que demostraron ser efectivas. Menos de la mitad de los estudios reportaron efectos adversos, predominando los síntomas leves y transitorios. La mayoría de los artículos se clasificaron como "cierta preocupación" en la evaluación del riesgo de sesgo. Conclusión: las tres intervenciones más efectivas para controlar las náuseas y los vómitos gestacionales fueron la aromaterapia, la fitoterapia y la acupuntura, con resultados significativos en la evaluación de los estudios individuales.

RESUMO Objetivo: sintetizar as evidências disponíveis na literatura sobre os efeitos das práticas integrativas e complementares no tratamento de náusea e vômito em gestantes. Método: revisão sistemática, relatada conforme o PRISMA e registrada no PROSPERO. A busca pelos estudos foi realizada em 11 bases/bancos de dados. Para avaliação do risco de viés dos ensaios clínicos randomizados, utilizou-se a ferramenta Cochrane Collaboration Risk of Bias Tool (RoB 2). Resultados: a amostra final foi composta por 31 artigos, divididos em três categorias: aromaterapia, fitoterapia e acupuntura. Observou-se que a aromaterapia com óleo essencial de limão, cápsulas de gengibre, acupressão no ponto pericárdio 6 foram as intervenções que se provaram eficazes. Menos da metade dos estudos relatou efeitos adversos, sendo que predominaram sintomas de leve intensidade e transitórios. A maioria dos artigos foi classificada como "alguma preocupação" na avaliação do risco de viés. Conclusão as três intervenções mais eficazes para controle de náusea e vômito gestacional foram aromaterapia, fitoterapia e acupuntura, com resultados significativos na avaliação dos estudos individuais.

Cuidados paliativos e comunicação: uma reflexão à luz da teoria do final de vida pacífico / Palliative care and communication: a reflection in the light of the peaceful end of life theory / Cuidados paliativos y comunicación: una reflexión a la luz de la teoría del final pacífico de la vida

RESUMO Objetivo: analisar a contribuição do cuidado de enfermagem, com ênfase na comunicação, para o paciente sob cuidados paliativos na fase terminal e seus familiares. Método: estudo qualitativo, realizado em um Hospital Filantrópico da cidade de João Pessoa-PB, Brasil, em 2019, desenvolvido com 15 familiares de pacientes em cuidados paliativos, por meio de entrevistas semiestruturadas. Os dados foram submetidos à análise de conteúdo, proposta por Bardin, à luz da Teoria do Final de Vida Pacífico. Resultados: emergiram duas categorias: 'A comunicação dos profissionais de enfermagem como estratégia para promover conforto, paz, dignidade e respeito para pacientes e familiares em cuidados paliativos'; 'A presença e o diálogo de pessoas importantes para o paciente sob cuidados paliativos são fundamentais para um final de vida pacífico.' Conclusão: espera-se que, através desse estudo, seja possível aprimorar a assistência à família acerca da comunicação nos cuidados paliativos.

ABSTRACT Objective: to analyze the contribution of nursing care, with emphasis on communication, for the patient under palliative care in the terminal phase and their families. Method: qualitative study, conducted in a Philanthropic Hospital in the city of João Pessoa-PB, Brazil, in 2019, developed with 15 family members of patients in palliative care, through semi-structured interviews. The data were submitted to content analysis, proposed by Bardin, in the light of the Pacific End of Life Theory. Results: two categories emerged: 'Communication by nursing professionals as a strategy to promote comfort, peace, dignity and respect for patients and families in palliative care'; 'The presence and dialogue of people important to the patient under palliative care are fundamental for a peaceful end of life.' Conclusion: it is hoped that, through this study, it will be possible to improve assistance to the family about communication in palliative care.

RESUMEN Objetivo: analizar la contribución de los cuidados de enfermería, con énfasis en la comunicación, para el paciente en cuidados paliativos en fase terminal y sus familias. Método: estudio cualitativo, realizado en un Hospital Filantrópico de la ciudad de João Pessoa-PB, Brasil, en 2019, desarrollado con 15 familiares de pacientes en cuidados paliativos, a través de entrevistas semiestructuradas. Los datos fueron sometidos a un análisis de contenido, propuesto por Bardin, a la luz de la Teoría del Final Tranquilo de la Vida. Resultados: surgieron dos categorías: "La comunicación de los profesionales de enfermería como estrategia para promover el confort, la paz, la dignidad y el respeto a los pacientes y familiares en los cuidados paliativos"; "La presencia y el diálogo de las personas importantes para el paciente en los cuidados paliativos son fundamentales para un final de vida tranquilo". Conclusión: se espera que, a través de este estudio, sea posible mejorar la asistencia a la familia sobre la comunicación en los cuidados paliativos.

DEF8 and Autophagy-Associated Genes Are Altered in Mild Cognitive Impairment, Probable Alzheimer's Disease Patients, and a Transgenic Model of the Disease.

BACKGROUND: Disturbances in the autophagy/endolysosomal systems are proposed as early signatures of Alzheimer's disease (AD). However, few studies are available concerning autophagy gene expression in AD patients. OBJECTIVE: To explore the differential expression of classical genes involved in the autophagy pathway, among them a less characterized one, DEF8 (Differentially expressed in FDCP 8), initially considered a Rubicon family member, in peripheralblood mononuclear cells (PBMCs) from individuals with mild cognitive impairment (MCI) and probable AD (pAD) and correlate the results with the expression of DEF8 in the brain of 5xFAD mice. METHOD: By real-time PCR and flow cytometry, we evaluated autophagy genes levels in PBMCs from MCI and pAD patients. We evaluated DEF8 levels and its localization in brain samples of the 5xFAD mice by real-time PCR, western blot, and immunofluorescence. RESULTS: Transcriptional levels of DEF8 were significantly reduced in PBMCs of MCI and pAD patients compared with healthy donors, correlating with the MoCA and MoCA-MIS cognitive tests scores. DEF8 protein levels were increased in lymphocytes from MCI but not pAD, compared to controls. In the case of brain samples from 5xFAD mice, we observed a reduced mRNA expression and augmented protein levels in 5xFAD compared to age-matched wild-type mice. DEF8 presented a neuronal localization. CONCLUSION: DEF8, a protein proposed to act at the final step of the autophagy/endolysosomal pathway, is differentially expressed in PBMCs of MCI and pAD and neurons of 5xFAD mice. These results suggest a potential role for DEF8 in the pathophysiology of AD.

Implications of Selective Autophagy Dysfunction for ALS Pathology.

Amyotrophic lateral sclerosis (ALS) is a lethal neurodegenerative disorder that progressively affects motor neurons in the brain and spinal cord. Due to the biological complexity of the disease, its etiology remains unknown. Several cellular mechanisms involved in the neurodegenerative process in ALS have been found, including the loss of RNA and protein homeostasis, as well as mitochondrial dysfunction. Insoluble protein aggregates, damaged mitochondria, and stress granules, which contain RNA and protein components, are recognized and degraded by the autophagy machinery in a process known as selective autophagy. Autophagy is a highly dynamic process whose dysregulation has now been associated with neurodegenerative diseases, including ALS, by numerous studies. In ALS, the autophagy process has been found deregulated in both familial and sporadic cases of the disease. Likewise, mutations in genes coding for proteins involved in the autophagy machinery have been reported in ALS patients, including selective autophagy receptors. In this review, we focus on the role of selective autophagy in ALS pathology.

Validação de um protocolo de auriculoterapia com laser para dor crônica na coluna vertebral / Validación de un protocolo de auriculoterapia láser para el dolor crónico en la columna vertebral / Validation of a laser auriculotherapy protocol for chronic spinal pain

RESUMO Objetivo: validar um protocolo de auriculoterapia com laser para dor crônica na coluna vertebral. Método: estudo metodológico realizado a partir de uma revisão sistemática, baseada no PRISMA Statement; validação de conteúdo por 21 experts e validação clínica do protocolo desenvolvido em pessoas com dor. Resultados: a partir da análise de 13 artigos foi observado o efeito positivo da acupuntura no alívio da dor e foi possível construir o seguinte protocolo: auriculoterapia com laser, em cinco sessões, com a proporção de uma sessão por semana, aplicação bilateral com alternância do pavilhão auricular nos pontos Shenmen, rim, simpático, bexiga, fígado, subcórtex e vértebras cervical, torácica e/ ou lombar, dependendo do local da dor. A avaliação desse conteúdo assumindo nível de concordância de 80% interavaliadores resultou em aprovação de todos os itens do protocolo. Na avaliação clínica, ao ser administrado em pessoas com dor na coluna vertebral, o protocolo desenvolvido demonstrou reduzir a média de dor, aumentar o limiar de tolerância e diminuir o impacto da dor nas atividades de vida diária. Conclusão: a acupuntura auricular, realizada com laser de baixa potência infravermelho no protocolo estudado, provou ser capaz de tratar com efetividade a dor crônica na coluna vertebral.

RESUMEN Objetivo: validar un protocolo de auriculoterapia láser para el dolor crónico en la columna vertebral. Método: estudio metodológico realizado a partir de una revisión sistemática, en base a la declaración PRISMA; validación de contenido por 21 expertos y validación clínica del protocolo de tratamiento en personas con dolor. Resultados: del análisis de 13 artículos se observó el efecto positivo de la acupuntura en el alivio del dolor y se pudo construir el siguiente protocolo: auriculoterapia láser, en cinco sesiones, con una sesión por semana, aplicación bilateral con alternancia de pabellón auricular en los puntos Shen Men, Riñón, Nervio simpático, Vejiga, Hígado, Subcórtex y vértebras cervicales, torácicas y / o lumbares, dependiendo de la localización del dolor. La evaluación de este contenido, asumiendo un nivel de acuerdo del 80% entre evaluadores, resultó en la aprobación de todos los ítems del protocolo. En la evaluación clínica, cuando se administró a personas con dolor en la columna, el protocolo de tratamiento demostró reducir el promedio de dolor, aumentar el umbral de tolerancia y disminuir el impacto del dolor en las actividades de la vida diaria. Conclusión: la acupuntura auricular, realizada con láser infrarrojo de baja potencia en el protocolo estudiado, demostró ser capaz de tratar eficazmente el dolor crónico de columna vertebral.

ABSTRACT Objective: to validate a laser auriculotherapy protocol for chronic spinal pain. Method: methodological study carried from a systematic review based on the PRISMA Statement; content validation carried out by 21 specialists and pilot test with clinical validation of the protocol developed in people with pain. Results: from the analysis of 13 articles, a positive effect of acupuncture on pain relief was noted and it was possible to develop the following protocol: laser auriculotherapy, in 5 sessions, with the proportion of one session a week, bilateral application with alternation of the auricular pavilion at Shenmen points, Kidney, Sympathetic Nervous System, Urinary Bladder, Liver, Subcortex and Cervical, Thoracic and/or Lumbar Vertebrae, depending on the location of the pain. The evaluation of this content, assuming a level of agreement of 80% interobserver, resulted in the approval of all items in the protocol. In the clinical evaluation, when it was administered in people with spinal pain, the protocol developed showed a reduction in the pain average, an improvement in the tolerance threshold and a reduction in the pain impact on daily activities. Conclusion: the auricular acupuncture, carried out using an infrared low-level laser, in the studied protocol, proved to be capable of effectively treating chronic spinal pain.

Down syndrome and Alzheimer's disease: common molecular traits beyond the amyloid precursor protein.

Alzheimer's disease (AD) is the most prevalent type of dementia. Down syndrome (DS) is the leading genetic risk factor for Early-Onset AD, prematurely presenting the classic pathological features of the brain with AD. Augmented gene dosage, including the APP gene, could partially cause this predisposition. Recent works have revealed that alterations in chromosome location due to the extra Chromosome 21, as well as epigenetic modifications, could promote changes in gene expression other than those from Chromosome 21. As a result, similar pathological features and cellular dysfunctions in DS and AD, including impaired autophagy, lysosomal activity, and mitochondrial dysfunction, could be controlled beyond APP overexpression. In this review, we highlight some recent data regarding the origin of the shared features between DS and AD and explore the mechanisms concerning cognitive deficiencies in DS associated with dementia, which could shed some light into the search for new therapeutic targets for AD treatment.

Outside in: Unraveling the Role of Neuroinflammation in the Progression of Parkinson's Disease.

Neuroinflammation is one of the most important processes involved in the pathogenesis of Parkinson's disease (PD). The current concept of neuroinflammation comprises an inflammation process, which occurs in the central nervous system due to molecules released from brain-resident and/or blood-derived immune cells. Furthermore, the evidence of the contribution of systemic delivered molecules to the disease pathogenesis, such as the gut microbiota composition, has been increasing during the last years. Under physiological conditions, microglia and astrocytes support the well-being and well-function of the brain through diverse functions, including neurotrophic factor secretion in both intact and injured brain. On the other hand, genes that cause PD are expressed in astrocytes and microglia, shifting their neuroprotective role to a pathogenic one, contributing to disease onset and progression. In addition, growth factors are a subset of molecules that promote cellular survival, differentiation and maturation, which are critical signaling factors promoting the communication between cells, including neurons and blood-derived immune cells. We summarize the potential targeting of astrocytes and microglia and the systemic contribution of the gut microbiota in neuroinflammation process archived in PD.

Unraveling the role of motoneuron autophagy in ALS.

In recent years, the role of autophagy in the pathogenesis of most neurodegenerative diseases has transitioned into a limbo of protective or detrimental effects. Genetic evidence indicates that mutations in autophagy-regulatory genes can result in the occurrence of amyotrophic lateral sclerosis (ALS), suggesting a physiological role of the pathway to motoneuron function. However, experimental manipulation of autophagy in ALS models led to conflicting results depending on the intervention strategy and the disease model used. A recent work by the Maniatis group systematically explored the role of cell-specific autophagy in motoneurons at different disease stages, revealing surprising and unexpected findings. Autophagy activity at early stages may contribute to maintaining the structure and function of neuromuscular junctions, whereas at later steps of the disease it has a pathogenic activity possibly involving cell-nonautonomous mechanisms related to glial activation. This new study adds a new layer of complexity in the field, suggesting an intricate interplay between proteostasis alterations, the time-differential function of autophagy in neurons, and muscle innervation in ALS.

Disulfide cross-linked multimers of TDP-43 and spinal motoneuron loss in a TDP-43A315T ALS/FTD mouse model.

Tar DNA binding protein 43 (TDP-43) is the principal component of ubiquitinated protein inclusions present in nervous tissue of most cases of both amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD). Previous studies described a TDP-43A315T transgenic mouse model that develops progressive motor dysfunction in the absence of protein aggregation or significant motoneuron loss, questioning its validity to study ALS. Here we have further characterized the course of the disease in TDP-43A315T mice using a battery of tests and biochemical approaches. We confirmed that TDP-43 mutant mice develop impaired motor performance, accompanied by progressive body weight loss. Significant differences were observed in life span between genders, where females survived longer than males. Histopathological analysis of the spinal cord demonstrated a significant motoneurons loss, accompanied by axonal degeneration, astrogliosis and microglial activation. Importantly, histopathological alterations observed in TDP-43 mutant mice were similar to some characteristic changes observed in mutant SOD1 mice. Unexpectedly, we identified the presence of different species of disulfide-dependent TDP-43 aggregates in cortex and spinal cord tissue. Overall, this study indicates that TDP-43A315T transgenic mice develop key features resembling key aspects of ALS, highlighting its relevance to study disease pathogenesis.