PLA2 G4E, a candidate gene for resilience in Alzheimer's disease and a new target for dementia treatment

Clinical studies revealed that some aged-individuals accumulate a significant number of histopathological Alzheimer´s disease (AD) lesions in their brain, yet without developing any signs of dementia. Animal models of AD represent suitable tools to identify genes that might promote cognitive resilience and hence, this study first set out to identify cognitively resilient individuals in the aged-Tg2576 mouse model. A transcriptomic analysis of these mice identified PLA2 G4E as a gene that might confer resistance to dementia. Indeed, a significant decrease in PLA2 G4E is evident in the brain of late-stage AD patients, whereas no such changes are observed in early stage patients with AD neuropathological lesions but no signs of dementia. We demonstrated that adeno-associated viral vector-mediated overexpression of PLA2 G4E in hippocampal neurons completely restored cognitive deficits in elderly APP/PS1 mice, without affecting the amyloid or tau pathology. These PLA2 G4E overexpressing APP/PS1 mice developed significantly more dendritic spines than sham-injected mice, coinciding with the cognitive improvement observed. Hence, these results support the idea that a loss of PLA2 G4E might play a key role in the onset of dementia in AD, highlighting the potential of PLA2 G4E overexpression as a novel therapeutic strategy to manage AD and other disorders that course with memory deficits

Informe da tuberculose en Galicia. Caracter?sticas dos casos de tuberculose de Galicia no ano 2021. Evoluci?n do per?odo 1996-2021

[GLG] Actualizaci?n do informe anual da tuberculose, editado polo Programa galego de prevenci?n e control da tuberculose, con datos do ano 2021 e a evoluci?n do per?odo 1996-2021.[ES] Actualizaci?n del informe anual de la tuberculosis, editado por el Programa gallego de prevenci?n y control de la tuberculosis, con datos del a?o 2021 y evoluci?n del per?odo 1996-2021

Implementation of a multidisciplinary psychoeducational intervention for Parkinson's disease patients and carers in the community: study protocol

Background: Parkinson’s disease progressively limits patients at different levels and as a result family members play a key role in their care. However, studies show lack of an integrative approach in Primary Care to respond to the difficulties and psychosocial changes experienced by them. The aim of this study is to evaluate the effects of a multidisciplinary psychoeducational intervention focusing on improving coping skills, the psychosocial adjustment to Parkinson’s disease and the quality of life in patients and family carers in a Primary Care setting. Methods: This quasi-experimental study with control group and mixed methods was designed to evaluate a multidisciplinary psychoeducational intervention. Based on the study power calculations, 100 people with Parkinson’s disease and 100 family carers will be recruited and assigned to two groups. The intervention group will receive the ReNACE psychoeducational intervention. The control group will be given a general educational programme. The study will be carried out in six community-based health centres. The results obtained from the two groups will be collected for evaluation at three time points: at baseline, immediately after the intervention and at 6 months post-intervention. The results will be measured with these instruments: the Quality of Life Scale PDQ39 for patients and the Scale of Quality of Life of Care-givers SQLC for family carers, and for all participants the Psychosocial Adjustment to Illness scale and the Brief COPE Inventory. Focus groups will be organised with some patients and family carers who will have received the ReNACE psychoeducational intervention and also with the healthcare professionals involved in its development. Discussion: An important gap exists in the knowledge and application of interventions with a psychosocial approach for people with PD and family carers as a whole. This study will promote this comprehensive approach in Primary Care, which will clearly contribute in the existing knowledge and could reduce the burden of PD for patients and family carers, and also in other long-term conditions

Elementos clave en el proceso de convivencia con la enfermedad de Parkinson de pacientes y familiares cuidadores

Fundamento. La enfermedad de Parkinson produce un impacto considerable en la vida de las personas. Es necesario identificar los elementos clave que influyen en el proceso de convivencia con la enfermedad de Parkinson para que los profesionales de la salud puedan ayudar a los pacientes y sus familias a convivir lo mejor posible con los cambios y limitaciones producidos por la enfermedad. Material y método. Se llevó a cabo un estudio cualitativo descriptivo. Este estudio se corresponde con la primera fase de un diseño exploratorio secuencial (Mixed-methods) que incluye a su vez una fase cuantitativa. Se realizó un proyecto multicéntrico. Para la recogida de datos se aplicó un muestreo de conveniencia y se utilizó una entrevista semi-estructurada realizada individualmente a pacientes y familiares cuidadores y dos cuestionarios para pacientes: la Escala de Hoehn & Yahr y el Cuestionario PDNMS. Se realizó un análisis de contenido de las entrevistas y estadístico descriptivo de los cuestionarios. Resultados. La muestra la constituyeron 46 participantes. Se identificaron tres elementos clave en el proceso de convivencia con la enfermedad de Parkinson: aceptación, adaptación y automanejo. Estos elementos condicionaron dos modos de convivencia con la enfermedad de Parkinson: una convivencia positiva, caracterizada por sentimientos de armonía, equilibrio, y naturalidad; y una convivencia negativa caracterizada por sentimientos de frustración, pérdida de control y autoestima. Conclusiones. Es esencial que los profesionales de la salud conozcan a fondo estos elementos, así como los factores que los favorecen o dificultan. En la medida que se propicie la investigación en este ámbito y se identifiquen intervenciones efectivas se mejorará la atención integral de la personas en consonancia con las nuevas directrices para la cronicidad.Background. Parkinson’s disease has a considerable impact on people’s lives. It is necessary to identify the key elements that influence the process of living with Parkinson’s disease so that health professionals can help patients and their relatives to live as well as possible with the changes and limitations produced by the disease. Material and methods. A qualitative descriptive study was realized. This study corresponded to the first phase of a sequential, exploratory design (mixed method) that in turn included a quantitative phase. A multicentre project was carried out. Convenience sampling was applied to collect data, a semi-structured interview was realized individually with patients and carer-relatives and two questionnaires with patients: the Hoehn & Yahr scale and the PDNMS questionnaire. Content analysis of the interviews and a statistical description of the questionnaires were used. Results. The sample was made up of 46 participants. Three key elements were identified in the process of living with Parkinson’s disease: acceptance, adaptation and self-management. These elements conditioned the modes of living with Parkinson’s disease: positive living, characterized by feelings of harmony, balance and naturalness; negative living characterized be feelings of frustration, loss of control and self-esteem. Conclusions. It is essential for health professionals to have a deep understanding of these elements, as well as of the factors that favor or hinder them. To the extent that research in this field progresses and effective interventions are identified, comprehensive patient care will be improved in consonance with the new directives for chronicity

“I don’t have to explain, people understand”: Acceptability and Cultural Relevance of a Mobile Health Lifestyle Intervention for Filipinos with Type 2 Diabetes

BackgroundFilipino Americans have the highest risk for obesity-related type 2 diabetes and related complications compared with all major Asian American subgroups. Identifying effective interventions to improve Filipino health outcomes are needed to reduce this health disparity.ObjectiveTo assess the acceptability and cultural relevance of the PilAm Go4Health program - a culturally adapted mobile health weight-loss lifestyle intervention including virtual social networking for Filipino Americans with type 2 diabetes.Design setting participantsQualitative semi-structured post-program interviews explored perceptions of 45 Filipino Americans with type 2 diabetes in Northern California regarding their perceptions of the acceptability and cultural relevance of PilAm Go4Health. Participants' mean age was 57.6 years. Sixty-seven interviews were recorded, transcribed, and thematically analyzed by four independent coders.ResultsOver half (n=26, 57.8%) of the respondents found that a culturally tailored intervention program enhanced their engagement. All (n=45) of the respondents felt that mobile health technology promoted their self-efficacy. A majority of the respondents (n=29, 64.4%) expressed that they progressed from despair to self-efficacy as a result of their participation in the intervention. More than one-fourth of the participants (n=13, 28.8%) discussed that the intervention needed further cultural tailoring.ConclusionsOverall, PilAm Go4Health - a mobile health weight-loss lifestyle intervention - was acceptable and culturally relevant for Filipino Americans with type 2 diabetes. Findings may help inform clinician and researchers on effective intervention strategies for diabetes self-management when designing interventions for diverse populations

"I don't have to explain, people understand": Acceptability and Cultural Relevance of a Mobile Health Lifestyle Intervention for Filipinos with Type 2 Diabetes.

BackgroundFilipino Americans have the highest risk for obesity-related type 2 diabetes and related complications compared with all major Asian American subgroups. Identifying effective interventions to improve Filipino health outcomes are needed to reduce this health disparity.ObjectiveTo assess the acceptability and cultural relevance of the PilAm Go4Health program - a culturally adapted mobile health weight-loss lifestyle intervention including virtual social networking for Filipino Americans with type 2 diabetes.Design setting participantsQualitative semi-structured post-program interviews explored perceptions of 45 Filipino Americans with type 2 diabetes in Northern California regarding their perceptions of the acceptability and cultural relevance of PilAm Go4Health. Participants' mean age was 57.6 years. Sixty-seven interviews were recorded, transcribed, and thematically analyzed by four independent coders.ResultsOver half (n=26, 57.8%) of the respondents found that a culturally tailored intervention program enhanced their engagement. All (n=45) of the respondents felt that mobile health technology promoted their self-efficacy. A majority of the respondents (n=29, 64.4%) expressed that they progressed from despair to self-efficacy as a result of their participation in the intervention. More than one-fourth of the participants (n=13, 28.8%) discussed that the intervention needed further cultural tailoring.ConclusionsOverall, PilAm Go4Health - a mobile health weight-loss lifestyle intervention - was acceptable and culturally relevant for Filipino Americans with type 2 diabetes. Findings may help inform clinician and researchers on effective intervention strategies for diabetes self-management when designing interventions for diverse populations

"I don't have to explain, people understand": Acceptability and Cultural Relevance of a Mobile Health Lifestyle Intervention for Filipinos with Type 2 Diabetes.

BackgroundFilipino Americans have the highest risk for obesity-related type 2 diabetes and related complications compared with all major Asian American subgroups. Identifying effective interventions to improve Filipino health outcomes are needed to reduce this health disparity.ObjectiveTo assess the acceptability and cultural relevance of the PilAm Go4Health program - a culturally adapted mobile health weight-loss lifestyle intervention including virtual social networking for Filipino Americans with type 2 diabetes.Design setting participantsQualitative semi-structured post-program interviews explored perceptions of 45 Filipino Americans with type 2 diabetes in Northern California regarding their perceptions of the acceptability and cultural relevance of PilAm Go4Health. Participants' mean age was 57.6 years. Sixty-seven interviews were recorded, transcribed, and thematically analyzed by four independent coders.ResultsOver half (n=26, 57.8%) of the respondents found that a culturally tailored intervention program enhanced their engagement. All (n=45) of the respondents felt that mobile health technology promoted their self-efficacy. A majority of the respondents (n=29, 64.4%) expressed that they progressed from despair to self-efficacy as a result of their participation in the intervention. More than one-fourth of the participants (n=13, 28.8%) discussed that the intervention needed further cultural tailoring.ConclusionsOverall, PilAm Go4Health - a mobile health weight-loss lifestyle intervention - was acceptable and culturally relevant for Filipino Americans with type 2 diabetes. Findings may help inform clinician and researchers on effective intervention strategies for diabetes self-management when designing interventions for diverse populations

Targeting RNA-mediated toxicity in C9orf72 ALS and/or FTD by RNAi-based gene therapy

A hexanucleotide GGGGCC expansion in intron 1 of chromosome 9 open reading frame 72 (C9orf72) gene is the most frequent cause of amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD). The corresponding repeat-containing sense and antisense transcripts cause a gain of toxicity through the accumulation of RNA foci in the nucleus and deposition of dipeptide-repeat (DPR) proteins in the cytoplasm of the affected cells. We have previously reported on the potential of engineered artificial anti-C9orf72-targeting miRNAs (miC) targeting C9orf72 to reduce the gain of toxicity caused by the repeat-containing transcripts. In the current study, we tested the silencing efficacy of adeno-associated virus (AAV)5-miC in human-derived induced pluripotent stem cell (iPSC) neurons and in an ALS mouse model. We demonstrated that AAV5-miC transduces different types of neuronal cells and can reduce the accumulation of repeat-containing C9orf72 transcripts. Additionally, we demonstrated silencing of C9orf72 in both the nucleus and cytoplasm, which has an added value for the treatment of ALS and/or FTD patients. A proof of concept in an ALS mouse model demonstrated the significant reduction in repeat-containing C9orf72 transcripts and RNA foci after treatment. Taken together, these findings support the feasibility of a gene therapy for ALS and FTD based on the reduction in toxicity caused by the repeat-containing C9orf72 transcripts