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Sex and age are major risk factors for chronic diseases. Recent studies examining age-related molecular changes in plasma provided insights into age-related disease biology. Cerebrospinal fluid (CSF) proteomics can provide additional insights into brain aging and neurodegeneration. By comprehensively examining 7,006 aptamers targeting 6,139 proteins in CSF obtained from 660 healthy individuals aged from 43 to 91 years old, we subsequently identified significant sex and aging effects on 5,097 aptamers in CSF. Many of these effects on CSF proteins had different magnitude or even opposite direction as those on plasma proteins, indicating distinctive CSF-specific signatures. Network analysis of these CSF proteins revealed not only modules associated with healthy aging but also modules showing sex differences. Through subsequent analyses, several modules were highlighted for their proteins implicated in specific diseases. Module 2 and 6 were enriched for many aging diseases including those in the circulatory systems, immune mechanisms, and neurodegeneration. Together, our findings fill a gap of current aging research and provide mechanistic understanding of proteomic changes in CSF during a healthy lifespan and insights for brain aging and diseases.
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The Knight-Alzheimer Disease Research Center (Knight-ADRC) at Washington University in St. Louis has pioneered and led worldwide seminal studies that have expanded our clinical, social, pathological, and molecular understanding of Alzheimer Disease. Over more than 40 years, research volunteers have been recruited to participate in cognitive, neuropsychologic, imaging, fluid biomarkers, genomic and multi-omic studies. Tissue and longitudinal data collected to foster, facilitate, and support research on dementia and aging. The Genetics and high throughput -omics core (GHTO) have collected of more than 26,000 biological samples from 6,625 Knight-ADRC participants. Samples available include longitudinal DNA, RNA, non-fasted plasma, cerebrospinal fluid pellets, and peripheral blood mononuclear cells. The GHTO has performed deep molecular profiling (genomic, transcriptomic, epigenomic, proteomic, and metabolomic) from large number of brain (n = 2,117), CSF (n = 2,012) and blood/plasma (n = 8,265) samples with the goal of identifying novel risk and protective variants, identify novel molecular biomarkers and causal and druggable targets. Overall, the resources available at GHTO support the increase of our understanding of Alzheimer Disease.
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Doença de Alzheimer , Doença de Alzheimer/genética , Humanos , Genômica , Biomarcadores , Demência/genética , Proteômica , MultiômicaRESUMO
INTRODUCTION: Membranous nephropathy (MN) is the most common cause of primary nephrotic syndrome in adults (20-30%). Light microscopy shows thickening of glomerular basement membrane with appearance of spikes. These histological findings are not evident in early forms, in which case the granular deposition pattern of IgG and/or C3 in the basement membrane by immunofluorescence (IF) constitutes the diagnostic tool that allows to differentiate it from minimal change disease (MCD). Complement system plays a key role in the pathophysiology of MN. C4d is a degradation product and a marker of the complement system activation. C4d labelling by immunohistochemical (HI) technique can help in the differential diagnosis between both glomerulopathies NM and MCD when the material for IF is insufficient and light microscopy is normal. Our objective was to explore the discrimination power of C4d to differentiate between MN and MCD in renal biopsy material. METHODS: Paraffin-embedded samples were recovered from renal biopsies with a diagnosis of MN and MCD performed between 1/1/2008 and 4/1/2019. IH staining was performed by immunoperoxidase technique using a rabbit anti-human C4d polyclonal antibody. RESULTS: In all cases with MN (n = 27, 15 males) with a median age of 63 (range: 18-87) years, C4d deposits were detected. In 21 cases with MCD (12 males) with a median age of 51 (range: 18-87) years, the C4d marking was negative in every samples. CONCLUSION: The results indicate that the marking of the renal biopsy with C4d is a useful tool for the differential diagnosis between NM and MCD.
Introducción: La nefropatía membranosa (NM) es la causa más frecuente de síndrome nefrótico primario en adultos (20-30%). En la microscopia óptica se observa engrosamiento de membrana basal glomerular con aparición de espigas. Estos hallazgos histológicos no son evidentes en formas tempranas, en cuyo caso el patrón de depósito granular de IgG y/o C3 en la membrana basal por inmunofluorescencia (IF) permite diferenciarla de enfermedad por cambios mínimos (ECM). El sistema del complemento juega un papel central en la fisiopatología de la NM. C4d es producto de degradación y un marcador de la activación del complemento. La marcación con C4d en muestras de biopsias renales, por técnica de inmunohistoquímica (IH) puede colaborar en el diagnóstico diferencial entre ambas glomerulopatías. Nuestro objetivo fue explorar el poder de discriminación del C4d para diferenciar NM de ECM en material de biopsias renales. Métodos: Se recuperaron muestras en parafina de biopsias renales con diagnóstico de NM y ECM realizados entre 1/1/2008 y 1/4/2019. Se realizaron tinciones de IH por técnica de inmunoperoxidasa con C4d usando un anticuerpo policlonal antihumano de conejo. Resultados: En todos los casos con NM (n = 27, 15 hombres) con mediana de edad de 63 (rango: 18-86) años se detectaron depósitos de C4d. En los 21 casos con ECM (12 hombres) con mediana de edad de 51 (rango: 18-87) años la marcación de C4d fue negativa. Conclusión: Los resultados indican que la marcación de la biopsia renal con C4d es una herramienta útil para el diagnóstico diferencial entre NM y ECM.
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Complemento C4b , Glomerulonefrite Membranosa , Glomerulonefrite Membranosa/diagnóstico , Glomerulonefrite Membranosa/patologia , Glomerulonefrite Membranosa/imunologia , Humanos , Masculino , Adulto , Pessoa de Meia-Idade , Feminino , Idoso , Complemento C4b/análise , Adulto Jovem , Diagnóstico Diferencial , Idoso de 80 Anos ou mais , Adolescente , Biópsia , Biomarcadores/análise , Nefrose Lipoide/patologia , Nefrose Lipoide/diagnóstico , Fragmentos de Peptídeos/análise , Estudos RetrospectivosRESUMO
There is a need for affordable, scalable, and specific blood-based biomarkers for Alzheimer's disease that can be applied to a population level. We have developed and validated disease-specific cell-free transcriptomic blood-based biomarkers composed by a scalable number of transcripts that capture AD pathobiology even in the presymptomatic stages of the disease. Accuracies are in the range of the current CSF and plasma biomarkers, and specificities are high against other neurodegenerative diseases.
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Although the prevalence of pediatric obesity is rising, understanding of the perceptions, attitudes, behaviors, and barriers to effective obesity care among Spanish adolescents living with obesity (ALwO), their caregivers, and healthcare professionals (HCPs) is lacking. In 2021, the cross-sectional ACTION Teens survey study was conducted in 10 countries; results from the Spanish cohort are presented herein. The survey was completed by 648 ALwO, 644 caregivers, and 251 HCPs in Spain. A total of 25% of ALwO and 43% of caregivers thought that their/their child's weight was normal, and more caregivers than ALwO perceived the ALwO's health to be at least good (95% vs. 59%, respectively). Only 53% of ALwO and 9% of caregivers reported receiving an obesity diagnosis, despite HCPs reporting they provide diagnoses to 87% of ALwO/caregivers. Although 65% of HCPs felt that ALwO may not be comfortable discussing weight, only 26% of ALwO who had discussed weight with an HCP (n = 488) reported not feeling comfortable. Inability to control hunger was a key barrier to ALwO losing weight identified by ALwO/caregivers, but not HCPs. Improved communication between the three groups, a better understanding of barriers to weight loss, and improved health education on obesity are needed in order to enhance obesity care in Spain.
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Cuidadores , Obesidade Infantil , Criança , Humanos , Adolescente , Espanha/epidemiologia , Estudos Transversais , Obesidade Infantil/epidemiologia , Obesidade Infantil/terapia , Pessoal de Saúde , Atitude , Atenção à SaúdeRESUMO
Genetic studies of Alzheimer disease (AD) have prioritized variants in genes related to the amyloid cascade, lipid metabolism, and neuroimmune modulation. However, the cell-specific effect of variants in these genes is not fully understood. Here, we perform single-nucleus RNA-sequencing (snRNA-seq) on nearly 300,000 nuclei from the parietal cortex of AD autosomal dominant (APP and PSEN1) and risk-modifying variant (APOE, TREM2 and MS4A) carriers. Within individual cell types, we capture genes commonly dysregulated across variant groups. However, specific transcriptional states are more prevalent within variant carriers. TREM2 oligodendrocytes show a dysregulated autophagy-lysosomal pathway, MS4A microglia have dysregulated complement cascade genes, and APOEε4 inhibitory neurons display signs of ferroptosis. All cell types have enriched states in autosomal dominant carriers. We leverage differential expression and single-nucleus ATAC-seq to map GWAS signals to effector cell types including the NCK2 signal to neurons in addition to the initially proposed microglia. Overall, our results provide insights into the transcriptional diversity resulting from AD genetic architecture and cellular heterogeneity. The data can be explored on the online browser ( http://web.hararilab.org/SNARE/ ).
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Doença de Alzheimer , Humanos , Doença de Alzheimer/genética , Doença de Alzheimer/metabolismo , Heterozigoto , Microglia/metabolismo , Lobo Parietal/metabolismo , RNA/metabolismoRESUMO
INTRODUCTION: Genetic associations with Alzheimer's disease (AD) age at onset (AAO) could reveal genetic variants with therapeutic applications. We present a large Colombian kindred with autosomal dominant AD (ADAD) as a unique opportunity to discover AAO genetic associations. METHODS: A genetic association study was conducted to examine ADAD AAO in 340 individuals with the PSEN1 E280A mutation via TOPMed array imputation. Replication was assessed in two ADAD cohorts, one sporadic early-onset AD study and four late-onset AD studies. RESULTS: 13 variants had p<1×10-7 or p<1×10-5 with replication including three independent loci with candidate associations with clusterin including near CLU. Other suggestive associations were identified in or near HS3ST1, HSPG2, ACE, LRP1B, TSPAN10, and TSPAN14. DISCUSSION: Variants with suggestive associations with AAO were associated with biological processes including clusterin, heparin sulfate, and amyloid processing. The detection of these effects in the presence of a strong mutation for ADAD reinforces their potentially impactful role.
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Doença de Alzheimer , Clusterina , Humanos , Clusterina/genética , Colômbia , Doença de Alzheimer/diagnóstico , Mutação/genética , Amiloide , Presenilina-1/genética , Idade de InícioRESUMO
INTRODUCTION: The identification of multiple genetic risk factors for Alzheimer's disease (AD) suggests that many pathways contribute to AD onset and progression. However, the metabolomic and lipidomic profiles in carriers of distinct genetic risk factors are not fully understood. The metabolome can provide a direct image of dysregulated pathways in the brain. METHODS: We interrogated metabolomic signatures in the AD brain, including carriers of pathogenic variants in APP, PSEN1, and PSEN2 (autosomal dominant AD; ADAD), APOE É4, and TREM2 risk variant carriers, and sporadic AD (sAD). RESULTS: We identified 133 unique and shared metabolites associated with ADAD, TREM2, and sAD. We identified a signature of 16 metabolites significantly altered between groups and associated with AD duration. DISCUSSION: AD genetic variants show distinct metabolic perturbations. Investigation of these metabolites may provide greater insight into the etiology of AD and its impact on clinical presentation. HIGHLIGHTS: APP/PSEN1/PSEN2 and TREM2 variant carriers show distinct metabolic changes. A total of 133 metabolites were differentially abundant in AD genetic groups. ß-citrylglutamate is differentially abundant in autosomal dominant, TREM2, and sporadic AD. A 16-metabolite profile shows differences between Alzheimer's disease (AD) genetic groups. The identified metabolic profile is associated with duration of disease.
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Doença de Alzheimer , Humanos , Doença de Alzheimer/genética , Doença de Alzheimer/patologia , Precursor de Proteína beta-Amiloide/genética , Encéfalo/patologia , Heterozigoto , Lipidômica , Mutação , Presenilina-1/genéticaRESUMO
Alzheimer's disease (AD), the leading cause of dementia, has an estimated heritability of approximately 70%1. The genetic component of AD has been mainly assessed using genome-wide association studies, which do not capture the risk contributed by rare variants2. Here, we compared the gene-based burden of rare damaging variants in exome sequencing data from 32,558 individuals-16,036 AD cases and 16,522 controls. Next to variants in TREM2, SORL1 and ABCA7, we observed a significant association of rare, predicted damaging variants in ATP8B4 and ABCA1 with AD risk, and a suggestive signal in ADAM10. Additionally, the rare-variant burden in RIN3, CLU, ZCWPW1 and ACE highlighted these genes as potential drivers of respective AD-genome-wide association study loci. Variants associated with the strongest effect on AD risk, in particular loss-of-function variants, are enriched in early-onset AD cases. Our results provide additional evidence for a major role for amyloid-ß precursor protein processing, amyloid-ß aggregation, lipid metabolism and microglial function in AD.
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Transportador 1 de Cassete de Ligação de ATP , Adenosina Trifosfatases , Doença de Alzheimer , Exossomos , Humanos , Adenosina Trifosfatases/genética , Doença de Alzheimer/genética , Transportador 1 de Cassete de Ligação de ATP/genética , Estudo de Associação Genômica Ampla , Fatores de Risco , Exossomos/genéticaRESUMO
BACKGROUND: In fewer than 1% of patients, AD is caused by autosomal dominant mutations in either the presenilin 1 (PSEN1), presenilin 2 (PSEN2), or amyloid precursor protein (APP) genes. The full extent of familial AD and frequency of these variants remains understudied in Latin American (LatAm) countries. Due to the rare nature of these variants, determining the pathogenicity of a novel variant in these genes can be challenging. Here, we use a systematic approach to assign the likelihood of pathogenicity in variants from densely affected families in Latin American populations. METHODS: Clinical data was collected from LatAm families at risk for DIAD. Symptomatic family members were identified and assessed by local clinicians and referred for genetic counseling and testing. To determine the likelihood of pathogenicity among variants of unknown significance from LatAm populations, we report pedigree information, frequency in control populations, in silico predictions, and cell-based models of amyloid-beta ratios. RESULTS: We identified five novel variants in the presenilin1 (PSEN1) gene from Brazilian and Mexican families. The mean age at onset in newly identified families was 43.5 years (range 36-54). PSEN1 p.Val103_Ser104delinsGly, p.Lys395Ile, p.Pro264Se, p.Ala275Thr, and p.Ile414Thr variants have not been reported in PubMed, ClinVar, and have not been reported in dominantly inherited AD (DIAD) families. We found that PSEN1 p.Val103_Ser104delinsGly, p.Lys395Ile, p.Pro264Se, and p.Ala275Thr produce Aß profiles consistent with known AD pathogenic mutations. PSEN1 p.Ile414Thr did not alter Aß in a manner consistent with a known pathogenic mutation. CONCLUSIONS: Our study provides further insights into the genetics of AD in LatAm. Based on our findings, including clinical presentation, imaging, genetic, segregations studies, and cell-based analysis, we propose that PSEN1 p.Val103_Ser104delinsGly, p.Lys395Ile, p.Pro264Se, and p.Ala275Thr are likely pathogenic variants resulting in DIAD, whereas PSEN1 p.Ile414Thr is likely a risk factor. This report is a step forward to improving the inclusion/engagement of LatAm families in research. Family discovery is of great relevance for the region, as new initiatives are underway to extend clinical trials and observational studies to families living with DIAD.
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Doença de Alzheimer , Adulto , Doença de Alzheimer/genética , Precursor de Proteína beta-Amiloide/genética , Humanos , América Latina , Pessoa de Meia-Idade , Mutação/genética , Presenilina-1/genéticaRESUMO
BACKGROUND: Autosomal-dominant Alzheimer's disease (ADAD) is caused by pathogenic mutations in APP, PSEN1, and PSEN2, which usually lead to an early age at onset (< 65). Circular RNAs are a family of non-coding RNAs highly expressed in the nervous system and especially in synapses. We aimed to investigate differences in brain gene expression of linear and circular transcripts from the three ADAD genes in controls, sporadic AD, and ADAD. METHODS: We obtained and sequenced RNA from brain cortex using standard protocols. Linear counts were obtained using the TOPMed pipeline; circular counts, using python package DCC. After stringent quality control (QC), we obtained the counts for PSEN1, PSEN2 and APP genes. Only circPSEN1 passed QC. We used DESeq2 to compare the counts across groups, correcting for biological and technical variables. Finally, we performed in-silico functional analyses using the Circular RNA interactome website and DIANA mirPath software. RESULTS: Our results show significant differences in gene counts of circPSEN1 in ADAD individuals, when compared to sporadic AD and controls (ADAD = 21, AD = 253, Controls = 23-ADADvsCO: log2FC = 0.794, p = 1.63 × 10-04, ADADvsAD: log2FC = 0.602, p = 8.22 × 10-04). The high gene counts are contributed by two circPSEN1 species (hsa_circ_0008521 and hsa_circ_0003848). No significant differences were observed in linear PSEN1 gene expression between cases and controls, indicating that this finding is specific to the circular forms. In addition, the high circPSEN1 levels do not seem to be specific to PSEN1 mutation carriers; the counts are also elevated in APP and PSEN2 mutation carriers. In-silico functional analyses suggest that circPSEN1 is involved in several pathways such as axon guidance (p = 3.39 × 10-07), hippo signaling pathway (p = 7.38 × 10-07), lysine degradation (p = 2.48 × 10-05) or Wnt signaling pathway (p = 5.58 × 10-04) among other KEGG pathways. Additionally, circPSEN1 counts were able to discriminate ADAD from sporadic AD and controls with an AUC above 0.70. CONCLUSIONS: Our findings show the differential expression of circPSEN1 is increased in ADAD. Given the biological function previously ascribed to circular RNAs and the results of our in-silico analyses, we hypothesize that this finding might be related to neuroinflammatory events that lead or that are caused by the accumulation of amyloid-beta.
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Doença de Alzheimer , Humanos , Doença de Alzheimer/metabolismo , Precursor de Proteína beta-Amiloide/genética , Precursor de Proteína beta-Amiloide/metabolismo , Encéfalo/metabolismo , Mutação , Presenilina-1/genética , Presenilina-1/metabolismo , RNA Circular/genéticaRESUMO
Bullying is a severe public health problem, and bystanders' reactions are a key variable in its perpetration and maintenance. This study aimed to assess the level of secondary victimization of bullying victims as a function of the student's sex and the victim's category (nonnormative vs. normative) in three experimental conditions (feminine, masculine, and ethnicity) from a socioecological perspective. Specifically, two dimensions of secondary victimization were evaluated: avoidance and devaluation/blaming of the victim. A sequence of mixed-design ANOVAs was performed with a sample of 553 Spanish (53.3%) and Portuguese (46.7%) students, aged between 14 and 19 years. Results show that nonnormative victims, those who transgress feminine and masculine gender stereotypes, and those who belong to a minority ethnic group (gypsies) are avoided more than normative victims; and that boys perpetrate more secondary victimization than girls. These results reveal the situation of vulnerability suffered by adolescents who transgress the gender norm as well as those who belong to minority ethnic groups, and highlight that the motivations concealed by the secondary victimization of bullying victims originate in the group processes of identity construction and categorization that configure the boundaries of "legitimacy" and are strongly influenced by social beliefs about normative and nonnormative identities. This socioecological approach could guide prevention strategies, so generic antibullying policies that do not explicitly address biases about gender, sexual, and cultural identity can be overcome to reduce the high levels of stigma occurring in the schools through critical and culturally responsive pedagogy.
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Bullying , Vítimas de Crime , Adolescente , Adulto , Etnicidade , Feminino , Humanos , Masculino , Instituições Acadêmicas , Estudantes , Adulto JovemRESUMO
Background: The process of transition to adult life of youth with a record of protection is crucial to overcome the difficulties to achieve an independent life. Objective: This research aims to analyze the conditions under which protected youth are emancipated, as well as the factors that facilitate emancipation. Method: A qualitative study was performed with three samples: longitudinal follow-ups with youths when they exit the system and during 12 months (N = 24); life stories of youths who have exited the child welfare system at least 2 years ago and a maximum of 5 years ago (N = 22); interviews with professionals conducting their intervention in adolescent protection resources (N = 18). Results: The results indicate that protective action is not enabling youths' learning in normalized contexts, which negatively affects the conditions under which emancipation occurs. The experience of the protective action conditions the tendency to benefit from the post-majority socio-educational accompaniment. Conclusions: The importance of socio-educational intervention continuing during the first moments of emancipation, providing professional accompaniment to the entire collective, is highlighted.
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Resumen Introducción/objetivo: El acoso sexual es una de las violencias que más debe preocupar a la comunidad educativa, por ello, el objetivo de este estudio consiste en analizar los conocimientos, las percepciones y las actitudes de los y las estudiantes universitarios hacia el acoso sexual. Método: Desde un enfoque cualitativo se han realizado diez entrevistas individuales a estudiantes (seis alumnas y cuatro alumnos) y ocho grupos de discusión heterogéneos formados por 67 estudiantes. Todos pertenecientes a una universidad de carácter público situada en el noroeste de España. Resultados: El alumnado tiene pocos conocimientos sobre el acoso sexual y, además, no recibe formación que le otorgue las herramientas que le permitan identificarlo y combatirlo. Asimismo, la mayoría de los/as participantes expresa que el acoso sexual es habitual en el entorno académico, pero que está invisibilizado. A través de sus propias palabras se identifica que perciben actitudes permisivas hacia el acoso sexual por parte de los/as docentes y de la universidad, considerando que no hay una verdadera implicación para intervenir en las situaciones de acoso. Conclusiones: Es necesario que la universidad se comprometa a implementar estrategias de prevención e intervención, con el propósito de identificar, sancionar y erradicar todas y cada una de las formas de violencia, incluido el acoso sexual.
Abstract Introduction/objective: Sexual harassment is one of the types of violence that should most concern the educational community, consequently, the objective of this study is to analyze the knowledge, perceptions and attitudes of university students towards sexual harassment. Method: From a qualitative approach, ten individual interviews were carried out with students (six female students and four male students) and eight heterogeneous discussion groups made up of 67 students. All of them belong to a public university located in the northwest of Spain. Results: The students have little knowledge about sexual harassment and, in addition, they do not receive training that gives them the tools that allow them to identify and combat it. Likewise, most of the participants express that sexual harassment is common in the academic environment, but that it is invisible. Through their own words, it is identified that they perceive permissive attitudes towards sexual harassment on the part of teachers and the university, considering that there is no real implication to intervene in harassment situations. Conclusions: It is necessary for the university to commit to implement prevention and intervention strategies, in order to identify, punish and eradicate each and every one of the forms of violence, including sexual harassment.
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Alzheimer's disease (AD) has become a common disease of the elderly for which no cure currently exists. After over 30 years of intensive research, we have gained extensive knowledge of the genetic and molecular factors involved and their interplay in disease. These findings suggest that different subgroups of AD may exist. Not only are we starting to treat autosomal dominant cases differently from sporadic cases, but we could be observing different underlying pathological mechanisms related to the amyloid cascade hypothesis, immune dysfunction, and a tau-dependent pathology. Genetic, molecular, and, more recently, multi-omic evidence support each of these scenarios, which are highly interconnected but can also point to the different subgroups of AD. The identification of the pathologic triggers and order of events in the disease processes are key to the design of treatments and therapies. Prevention and treatment of AD cannot be attempted using a single approach; different therapeutic strategies at specific disease stages may be appropriate. For successful prevention and treatment, biomarker assays must be designed so that patients can be more accurately monitored at specific points during the course of the disease and potential treatment. In addition, to advance the development of therapeutic drugs, models that better mimic the complexity of the human brain are needed; there have been several advances in this arena. Here, we review significant, recent developments in genetics, omics, and molecular studies that have contributed to the understanding of this disease. We also discuss the implications that these contributions have on medicine.
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Doença de Alzheimer/genética , Doença de Alzheimer/metabolismo , Doença de Alzheimer/terapia , Peptídeos beta-Amiloides/metabolismo , Biomarcadores/metabolismo , HumanosRESUMO
This article aims to break with two social stereotypes often held about Latinas in Spain. Authors analyze Latinas' main strengths from a resilient and intersectional approach, to consider them holistically within social work interventions. Rather than focusing on Latinas' difficulties, authors point to their multiple strengths and the ability to move forward. The study took place in the province of Tarragona, Catalonia (Spain). A qualitative approach was used. Participants included Latinas living in Tarragona and social workers from the Tarragona social services. The techniques used were nine life stories and 59 semi-open questionnaires with Latinas, and 14 interviews with social workers. The authors identified a fighting attitude and an entrepreneurial and creative spirit as both individual and collective strengths, especially within Latinas' social networks. Latinas did not recognize themselves as victims, nor did they claim to assume that identity. The social workers' interventions are implemented in a weak welfare system based on a model characterized by a paternalistic and victim-based viewpoint. Adopting approaches such as intersectionality and resilience would allow for the creation of fairer policies, programs, and projects targeted for Latinas, not just in Spain, but in other countries, too.
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Hispânico ou Latino , Serviço Social , Atitude , Humanos , Espanha , Inquéritos e QuestionáriosRESUMO
Understanding the tissue-specific genetic controls of protein levels is essential to uncover mechanisms of post-transcriptional gene regulation. In this study, we generated a genomic atlas of protein levels in three tissues relevant to neurological disorders (brain, cerebrospinal fluid and plasma) by profiling thousands of proteins from participants with and without Alzheimer's disease. We identified 274, 127 and 32 protein quantitative trait loci (pQTLs) for cerebrospinal fluid, plasma and brain, respectively. cis-pQTLs were more likely to be tissue shared, but trans-pQTLs tended to be tissue specific. Between 48.0% and 76.6% of pQTLs did not co-localize with expression, splicing, DNA methylation or histone acetylation QTLs. Using Mendelian randomization, we nominated proteins implicated in neurological diseases, including Alzheimer's disease, Parkinson's disease and stroke. This first multi-tissue study will be instrumental to map signals from genome-wide association studies onto functional genes, to discover pathways and to identify drug targets for neurological diseases.
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Doença de Alzheimer , Encéfalo/metabolismo , Líquido Cefalorraquidiano/metabolismo , Plasma/metabolismo , Locos de Características Quantitativas , Idoso , Doença de Alzheimer/genética , Doença de Alzheimer/metabolismo , Feminino , Regulação da Expressão Gênica , Ensaios de Triagem em Larga Escala/métodos , Humanos , Masculino , Pessoa de Meia-Idade , Proteoma , Proteômica/métodosRESUMO
Adolescence, a period of physical, social, cognitive and emotional development, represents a target population for sexual health promotion and education when it comes to achieving the 2030 Agenda goals for sustainable and equitable societies. The aim of this study is to provide an overview of what is known about the dissemination and effectiveness of sex education programs and thereby to inform better public policy making in this area. Methodology: We carried out a systematic review based on international scientific literature, in which only peer-reviewed papers were included. To identify reviews, we carried out an electronic search of the Cochrane Database Reviews, ERIC, Web of Science, PubMed, Medline, Scopus and PsycINFO. This paper provides a narrative review of reviews of the literature from 2015 to 2020. Results: 20 reviews met the inclusion criteria (10 in school settings, 9 using digital platforms and 1 blended learning program): they focused mainly on reducing risk behaviors (e.g., VIH/STIs and unwanted pregnancies), whilst obviating themes such as desire and pleasure, which were not included in outcome evaluations. The reviews with the lowest risk of bias are those carried out in school settings and are the ones that most question the effectiveness of sex education programs. Whilst the reviews of digital platforms and blended learning show greater effectiveness in terms of promoting sexual and reproductive health in adolescents (ASRH), they nevertheless also include greater risks of bias. Conclusion: A more rigorous assessment of the effectiveness of sexual education programs is necessary, especially regarding the opportunities offered by new technologies, which may lead to more cost-effective interventions than with in-person programs. Moreover, blended learning programs offer a promising way forward, as they combine the best of face-to-face and digital interventions, and may provide an excellent tool in the new context of the COVID-19 pandemic.