Loyola Generativity Scale e Generative Behavior Checklist: Um estudo psicométrico com idosos espanhóis LGBT+ / Loyola Generativity Scale and Generative Behavior Checklist: A Psychometric Study with Spanish LGBT+ Older Adults / Loyola Generativity Scale y Generative Behavior Checklist: Un estudio psicométrico con personas mayores españolas LGBT+

Resumo Enquadramento: A generatividade tem sido associada à resiliência e à satisfação com a vida na velhice, incluindo entre a população lésbica, gay, bissexual e transgénero (LGBT+) mais velha. Objetivo: Analisar as propriedades psicométricas da Loyola Generativity Scale (LGS) e da Generative Behavior Checklist (GBC) para idosos espanhóis LGBT + (com mais de 50 anos). Metodologia: Foi realizado um estudo psicométrico com 141 idosos espanhóis LGBT+ com o objetivo de examinar a validade de construto (análise fatorial exploratória), a validade convergente e a fiabilidade (consistência interna) da LGS e da GBC. Resultados: Os métodos de análise paralela e a análise fatorial exploratória sugeriram um modelo de dois fatores para ambos os instrumentos com boa adequação da amostra. A LGS explicou 45,1% da variância e apresentou uma consistência interna de 0,78. O GBC explicou 41,76% da variância e apresentou uma consistência interna de 0,879. Foi encontrada uma correlação positiva e estatisticamente significativa entre a satisfação com a vida e as escalas generativas. Foi também observada uma correlação positiva e significativa (rs = 0,310) entre os dois instrumentos. Conclusão: Ambos os instrumentos demonstraram ser válidos e fiáveis para medir a generatividade em idosos espanhóis LGBT+.

Abstract Background: Generativity has been associated with resilience and life satisfaction in older age, including among lesbian, gay, bisexual, and transgender (LGBT+) older adults. Objective: To examine the psychometric properties of the Loyola Generativity Scale (LGS) and Generative Behavior Checklist (GBC) for Spanish LGBT+ older adults (over the age of 50). Methodology: A psychometric study was conducted with 141 Spanish LGBT+ older adults to examine the construct validity (exploratory factor analysis), convergent validity, and reliability (internal consistency) of the LGS and the GBC. Results: Parallel and exploratory factor analyses suggested a two-factor model with good sample adequacy for both scales. The LGS explained 45.1% of the variance and had an internal consistency of 0.78. The GBC explained 41.76 % of the variance and had an internal consistency of 0.879. A positive and statistically significant correlation was found between life satisfaction and the generative scales. A positive and significant correlation (rs = 0.310) was also observed between both instruments. Conclusion: Both instruments proved valid and reliable for measuring generativity in Spanish LGBT+ older adults.

Resumen Marco contextual: La generatividad se asocia con la resiliencia y la satisfacción con la vida en la vejez, incluidas las de las personas adultas lesbianas, gays, bisexuales y transexuales (LGBT+). Objetivo: Examinar las propiedades psicométricas de la Loyola Generativity Scale (LGS) y la Generative Behavior Checklist (GBC) en adultos mayores LGBT+ españoles (mayores de 50 años). Metodología: Estudio psicométrico con 141 adultos mayores LGBT+. Se analizó la validez de constructo (análisis factorial exploratorio), la validez convergente y la consistencia interna de cada escala. Resultado: Los análisis factoriales paralelos y exploratorios sugieren un modelo bifactorial para ambas escalas con una buena adecuación a la muestra. La LGS explica el 45,1% de la varianza y tiene una consistencia interna de 0,78. La GBC explica el 41,76% de la varianza y tiene una consistencia interna de 0,879. Se encontró una correlación positiva estadísticamente significativa entre la satisfacción con la vida y las escalas de generatividad. Las dos escalas mostraron una correlación positiva y significativa (rs = 0,310). Conclusión: Ambas escalas han demostrado ser válidas y fiables para medir la generatividad en adultos mayores LGBT+ españoles.

Solitude in old age: a scoping review of conceptualisations, associated factors and impacts.

OBJECTIVE: This study aimed to map the existing scientific research about solitude in older adults, focusing on its conceptualizations, associated factors, and impacts. METHOD: A scoping review was conducted, searching Scopus, Web of Science, PubMed, and Academic Search Complete databases for publications from 1985 until December 2023. RESULTS: Twenty-four studies were included. The main findings suggest a wide-ranging conceptualisation of solitude, with most studies (n = 16) adopting neutral definitions such as "being alone, without communicating with others"; and a subset of studies adopting definitions that alluded to "positive solitude" (as the choice of being with oneself, underscoring potential benefits). Individual characteristics were identified as key associated factors of solitude. Both positive impacts and negative impacts were reported. CONCLUSION: The variability in conceptualisation and impacts likely stems from methodological and theoretical differences in approaching solitude. This underscores the need for additional research to establish a widely accepted conceptual framework. Such consensus could enhance the understanding of the conditions contributing to positive and negative impacts associated with solitude and inform targeted interventions.

Identification of a pathogenic mutation in ARPP21 in patients with amyotrophic lateral sclerosis.

BACKGROUND AND OBJECTIVE: Between 5% and 10% of amyotrophic lateral sclerosis (ALS) cases have a family history of the disease, 30% of which do not have an identifiable underlying genetic cause after a comprehensive study of the known ALS-related genes. Based on a significantly increased incidence of ALS in a small geographical region from Spain, the aim of this work was to identify novel ALS-related genes in ALS cases with negative genetic testing. METHODS: We detected an increased incidence of both sporadic and, especially, familial ALS cases in a small region from Spain compared with available demographic and epidemiological data. We performed whole genome sequencing in a group of 12 patients with ALS (5 of them familial) from this unique area. We expanded the study to include affected family members and additional cases from a wider surrounding region. RESULTS: We identified a shared missense mutation (c.1586C>T; p.Pro529Leu) in the cyclic AMP regulated phosphoprotein 21 (ARPP21) gene that encodes an RNA-binding protein, in a total of 10 patients with ALS from 7 unrelated families. No mutations were found in other ALS-causing genes. CONCLUSIONS: While previous studies have dismissed a causal role of ARPP21 in ALS, our results strongly support ARPP21 as a novel ALS-causing gene.

Diagnostic performance of plasma pTau217, pTau181, Aß1-42 and Aß1-40 in the LUMIPULSE automated platform for the detection of Alzheimer disease.

BACKGROUND: Recently developed blood markers for Alzheimer's disease (AD) detection have high accuracy but usually require ultra-sensitive analytic tools not commonly available in clinical laboratories, and their performance in clinical practice is unknown. METHODS: We analyzed plasma samples from 290 consecutive participants that underwent lumbar puncture in routine clinical practice in a specialized memory clinic (66 cognitively unimpaired, 130 participants with mild cognitive impairment, and 94 with dementia). Participants were classified as amyloid positive (A +) or negative (A-) according to CSF Aß1-42/Aß1-40 ratio. Plasma pTau217, pTau181, Aß1-42 and Aß1-40 were measured in the fully-automated LUMIPULSE platform. We used linear regression to compare plasma biomarkers concentrations between A + and A- groups, evaluated Spearman's correlation between plasma and CSF and performed ROC analyses to assess their diagnostic accuracy to detect brain amyloidosis as determined by CSF Aß1-42/Aß1-40 ratio. We analyzed the concordance of pTau217 with CSF amyloidosis. RESULTS: Plasma pTau217 and pTau181 concentration were higher in A + than A- while the plasma Aß1-42/Aß1-40 ratio was lower in A + compared to A-. pTau181 and the Aß1-42/Aß1-40 ratio showed moderate correlation between plasma and CSF (Rho = 0.66 and 0.69, respectively). The areas under the ROC curve to discriminate A + from A- participants were 0.94 (95% CI 0.92-0.97) for pTau217, and 0.88 (95% CI 0.84-0.92) for both pTau181 and Aß1-42/Aß1-40. Chronic kidney disease (CKD) was related to increased plasma biomarker concentrations, but ratios were less affected. Plasma pTau217 had the highest fold change (× 3.2) and showed high predictive capability in discriminating A + from A-, having 4-7% misclassification rate. The global accuracy of plasma pTau217 using a two-threshold approach was robust in symptomatic groups, exceeding 90%. CONCLUSION: The evaluation of blood biomarkers on an automated platform exhibited high diagnostic accuracy for AD pathophysiology, and pTau217 showed excellent diagnostic accuracy to identify participants with AD in a consecutive sample representing the routine clinical practice in a specialized memory unit.

"There's Still Time to be Happy": The Life Trajectories of Portuguese Transgender Women Who Transitioned at 50+ Years.

The process of transitioning involves making changes to align one's life with their authentic gender identity. This study explores the life trajectories of three Portuguese transgender women who transitioned later in life (50+ years old) by identifying key chapters in their life courses. Through inductive thematic analysis, six chapters were identified from the participants' interviews: (1) awareness of "something different in me," (2) locked into suffering, (3) finding comfort in something that is socially recognized, (4) "it is enough": it is time to recognize and embrace the woman I am, (5) living my life as a woman, and (6) building and leaving a legacy. Aging and the process of self-discovery played pivotal roles in participants' process of transitioning. The perception of finitude and the limitations associated with the time of life led them to realize that there was no time to waste and a sense of urgency to live authentically.

O processo de transição envolve mudanças para alinhar a vida com a identidade de género autêntica. Este estudo explora as trajetórias de vida de três mulheres transgénero portuguesas que fizeram a transição mais tardia (depois dos 50 anos), identificando capítulos-chave nos seus percursos de vida. Através da análise temática indutiva, foram identificados seis capítulos a partir das entrevistas dos participantes: (1) consciência de "algo diferente em mim," (2) fechada no sofrimento, (3) encontrar conforto em algo que é socialmente reconhecido, (4) "já chega:" é altura de reconhecer a mulher que sou, (5) viver a minha vida como mulher, e (6) construir e deixar um legado. O envelhecimento e o processo de autodescoberta desempenharam papéis fundamentais no processo de transição das participantes. A perceção da finitude e das limitações associadas ao tempo de vida levou-as a perceber que não havia tempo a perder, dando um sentido de urgência para viver de forma autêntica.

Next-generation sequencing reveals remarkable genetic stability in primary and corresponding recurrent intestinal-type sinonasal adenocarcinoma.

BACKGROUND: Recurrent intestinal-type sinonasal adenocarcinoma (ITAC) can occur several years after primary treatment and with different histology. We aimed to clarify if such recurrences could be second primary tumors and to identify actionable mutations as targets for personalized treatment of recurrent ITAC. METHODS: Twelve pairs of primary and recurrent ITAC were histologically examined and analyzed by next-generation sequencing. RESULTS: Histological differences between primary and recurrent tumor pairs were observed in five cases. Frequent mutations included TP53, APC, TSC2, ATM, EPHA2, BRCA2, LRP1B, KRAS, and KMT2B. There was 86% concordance of somatic mutations between the tumor pairs, while four cases carried additional mutations in the recurrence. CONCLUSIONS: We found all cases to be clonal recurrences and not second primary tumors. Moreover, tumor pairs showed a remarkable genomic stability, suggesting that personalized treatment of a recurrence may be based on actionable molecular genetic targets observed in the primary tumor.

Clinicopathological correlates in the frontotemporal lobar degeneration-motor neuron disease spectrum.

Amyotrophic lateral sclerosis (ALS) is a devastating motor neuron disease (MND) that shares a common clinical, genetic and pathologic spectrum with frontotemporal dementia (FTD). It is highly heterogeneous in its presentation and features. Up to 50% of patients with MND develop cognitive-behavioural symptoms during the course of the disease, meeting criteria for FTD in 10%-15% of cases. In the absence of a precise biomarker, neuropathology is still a valuable tool to understand disease nosology, reach a definite diagnostic confirmation and help define specific subgroups of patients with common phenotypic, genetic and biomarker profiles. However, few neuropathological series have been published, and the frequency of frontotemporal lobar degeneration (FTLD) in MND is difficult to estimate. In this work we describe a large clinicopathological series of MND patients, analysing the frequency of concurrent FTLD changes and trying to define specific subgroups of patients based on their clinical, genetic and pathological characteristics. We performed an observational, retrospective, multicentre case study. We included all cases meeting neuropathological criteria for MND from the Neurological Tissue Bank of the FRCB-IDIBAPS-Hospital Clínic Barcelona Biobank between 1994 and 2022, regardless of their last clinical diagnosis. While brain donation is encouraged in all patients, it is performed in very few, and representativeness of the cohort might not be precise for all patients with MND. We retrospectively reviewed clinical and neuropathological data and describe the main clinical, genetic and pathogenic features, comparing neuropathologic groups between MND with and without FTLD changes and aiming to define specific subgroups. We included brain samples from 124 patients, 44 of whom (35.5%) had FTLD neuropathologic features (i.e. FTLD-MND). Pathologic TDP-43 aggregates were present in 93.6% of the cohort and were more extensive (higher Brettschneider stage) in those with concurrent FTLD (P < 0.001). Motor symptom onset was more frequent in the bulbar region in FTLD-MND cases than in those with isolated MND (P = 0.023), with no differences in survival. We observed a better clinicopathological correlation in the MND group than in the FTLD-MND group (93.8% versus 61.4%; P < 0.001). Pathogenic genetic variants were more common in the FTLD-MND group, especially C9orf72. We describe a frequency of FTLD of 35.5% in our series of neuropathologically confirmed cases of MND. The FTLD-MND spectrum is highly heterogeneous in all aspects, especially in patients with FTLD, in whom it is particularly difficult to define specific subgroups. In the absence of definite biomarkers, neuropathology remains a valuable tool for a definite diagnosis, increasing our knowledge in disease nosology.

Clinical dimensions along the non-fluent variant primary progressive aphasia spectrum.

It is debated whether primary progressive apraxia of speech (PPAOS) and progressive agrammatic aphasia (PAA) belong to the same clinical spectrum, traditionally termed non-fluent/agrammatic variant primary progressive aphasia (nfvPPA), or exist as two completely distinct syndromic entities with specific pathologic/prognostic correlates. We analysed speech, language and disease severity features in a comprehensive cohort of patients with progressive motor speech impairment and/or agrammatism to ascertain evidence of naturally occurring, clinically meaningful non-overlapping syndromic entities (e.g. PPAOS and PAA) in our data. We also assessed if data-driven latent clinical dimensions with aetiologic/prognostic value could be identified. We included 98 participants, 43 of whom had an autopsy-confirmed neuropathological diagnosis. Speech pathologists assessed motor speech features indicative of dysarthria and apraxia of speech (AOS). Quantitative expressive/receptive agrammatism measures were obtained and compared with healthy controls. Baseline and longitudinal disease severity was evaluated using the Clinical Dementia Rating Sum of Boxes (CDR-SB). We investigated the data's clustering tendency and cluster stability to form robust symptom clusters and employed principal component analysis to extract data-driven latent clinical dimensions (LCD). The longitudinal CDR-SB change was estimated using linear mixed-effects models. Of the participants included in this study, 93 conformed to previously reported clinical profiles (75 with AOS and agrammatism, 12 PPAOS and six PAA). The remaining five participants were characterized by non-fluent speech, executive dysfunction and dysarthria without apraxia of speech or frank agrammatism. No baseline clinical features differentiated between frontotemporal lobar degeneration neuropathological subgroups. The Hopkins statistic demonstrated a low cluster tendency in the entire sample (0.45 with values near 0.5 indicating random data). Cluster stability analyses showed that only two robust subgroups (differing in agrammatism, executive dysfunction and overall disease severity) could be identified. Three data-driven components accounted for 71% of the variance [(i) severity-agrammatism; (ii) prominent AOS; and (iii) prominent dysarthria]. None of these data-driven LCDs allowed an accurate prediction of neuropathology. The severity-agrammatism component was an independent predictor of a faster CDR-SB increase in all the participants. Higher dysarthria severity, reduced words per minute and expressive and receptive agrammatism severity at baseline independently predicted accelerated disease progression. Our findings indicate that PPAOS and PAA, rather than exist as completely distinct syndromic entities, constitute a clinical continuum. In our cohort, splitting the nfvPPA spectrum into separate clinical phenotypes did not improve clinical-pathological correlations, stressing the need for new biological markers and consensus regarding updated terminology and clinical classification.

Sox2 and ßIII-Tubulin as Biomarkers of Drug Resistance in Poorly Differentiated Sinonasal Carcinomas.

Poorly differentiated sinonasal carcinomas (PDCs) are tumors that have a poor prognosis despite advances in classical treatment. Predictive and prognostic markers and new personalized treatments could improve the oncological outcomes of patients. In this study, we analyzed SOX2 and ßIII-tubulin as biomarkers that could have prognostic and therapeutic impacts on these tumors. The cohort included 57 cases of PDCs: 36 sinonasal undifferentiated carcinoma (SNUC) cases, 13 olfactory neuroblastoma (ONB) cases, and 8 sinonasal neuroendocrine carcinoma (SNEC) cases. Clinical follow-up data were available for 26 of these cases. Sox2 expression was detected using immunohistochemistry in 6 (75%) SNEC cases, 19 (53%) SNUC cases, and 6 (46%) ONB cases. The absence of Sox2 staining correlated with a higher rate of recurrence (p = 0.015), especially distant recurrence. The majority of cases showed ßIII-tubulin expression, with strong positivity in 85%, 75%, and 64% of SNEC, ONB, and SNUC cases, respectively. Tumors with stronger ßIII-tubulin expression demonstrated longer disease-free survival than those with no expression or low expression (p = 0.049). Sox2 and ßIII-tubulin expression is common in poorly differentiated sinonasal tumors and has prognostic and therapeutic utility.

Signaling Pathways mTOR and ERK as Therapeutic Targets in Sinonasal Intestinal-Type Adenocarcinoma.

Despite advances in surgery and radiotherapy, the overall prognosis of sinonasal intestinal-type adenocarcinoma (ITAC) is poor, and new treatment options are needed. Recent studies have indicated alterations in cellular signaling pathways that may serve as targets for modern inhibitors. Our aim was to evaluate the frequency of mTOR and ERK pathway upregulation in a retrospective series of 139 ITAC and to test the efficacy and mechanism of action of candidate targeted inhibitors in cell line ITAC-3. An immunohistochemical analysis on p-AKT, p-mTOR, p-S6, p-4E-BP1, and p-ERK indicated, respectively, a 68% and 57% mTOR and ERK pathway activation. In vitro studies using low doses of mTOR inhibitor everolimus and ERK inhibitor selumetinib showed significant growth inhibition as monotherapy and especially as combined therapy. This effect was accompanied by the downregulation of mTOR and ERK protein expression. Our data open a new and promising possibility for personalized treatment of ITAC patients.

Effects of storage conditions on the stability of blood-based markers for the diagnosis of Alzheimer's disease.

OBJECTIVES: Alzheimer's disease (AD) is considered the most common cause of dementia in older people. Recently, blood-based markers (BBM) Aß1-42, Aß1-40, and phospho Tau181 (p-Tau181) have demonstrated the potential to transform the diagnosis and prognostic assessment of AD. Our aim was to investigate the effect of different storage conditions on the quantification of these BBM and to evaluate the interchangeability of plasma and serum samples. METHODS: Forty-two individuals with some degree of cognitive impairment were studied. Thirty further patients were retrospectively selected. Aß1-42, Aß1-40, and p-Tau181 were quantified using the LUMIPULSE-G600II automated platform. To assess interchangeability between conditions, correction factors for magnitudes that showed strong correlations were calculated, followed by classification consistency studies. RESULTS: Storing samples at 4 °C for 8-9 days was associated with a decrease in Aß fractions but not when stored for 1-2 days. Using the ratio partially attenuated the pre-analytical effects. For p-Tau181, samples stored at 4 °C presented lower concentrations, whereas frozen samples presented higher ones. Concerning classification consistency in comparisons that revealed strong correlations (p-Tau181), the percentage of total agreement was greater than 90 % in a large number of the tested cut-offs values. CONCLUSIONS: Our findings provide relevant information for the standardization of sample collection and storage in the analysis of AD BBM in an automated platform. This knowledge is crucial to ensure their introduction into clinical settings.

Leaving a Mark and Passing the Torch: Intended Legacies of Older Lesbian and Gay Spanish Activists.

Aging paradigms should entail all individuals. More research on older LGBT+ adults is needed since the literature has been mainly built on heteronormative and cisgender standards. The creation and shaping of the kind of legacy an individual would like to leave behind when he/she dies is key in aging well. This study explores the intended legacies of older lesbian and gay adults (50+ years old) who were activists in social movements in Spain. Eighteen participants (12 gay men) participated in a semi-structured interview on their intended legacies. Thematic analysis was used to analyze the interviews. The main findings showed that all participants reported intended legacies: i) personal, to transmit their lived knowledge and to be remembered as good and committed persons; ii) broader, to contribute to LGBT+ rights, and to a better society; iii) composite, the desire that younger generations recognize their contributions, and to know they helped to protect new generations. The participants in this study lived a life of intense involvement in social movements, and currently their intended legacies involve leaving a mark and passing the torch to younger generations. This understanding will help us to develop adequate practices that promote well-being in older LGBT+ adults.

A Novel External Auditory Canal Squamous Cell Carcinoma Cell Line Sensitive to CDK4/6 Inhibition.

OBJECTIVE: To characterize cell line CAE606 derived from a squamous cell carcinoma (SCC) of the external auditory canal (EAC) and to show its usefulness as a model for testing candidate therapeutic agents. STUDY DESIGN: Preclinical translational research. SETTING: Biomedical research institute. METHODS: The cell line was initiated from a moderately differentiated T2N0M0 EAC SCC. We studied its histologic and genetic features as well as growth and invasion parameters. Sensitivity to cell CDK4/6 cell cycle inhibitor palbociclib was analyzed. RESULTS: CAE606 cells expressed heavy molecular weight cytokeratin, p63, and vimentin. The population doubling time was 25.8 hours, and the cells showed fast collective cell migration in a wound-healing assay. Short tandem repeat analysis confirmed it to be derived from the primary tumor of the patient. Next-generation sequencing revealed alterations in cell cycle regulation genes, including inactivating mutations in CDKN2A and TP53 and high-level amplification of CCND1 and EGFR. CAE606 showed a strong decrease of phospo-Rb expression upon exposure to the CDK4/6 inhibitor palbociclib, causing significant growth inhibition with an IC50 of 0.46 µM. CONCLUSION: This is the first report of a stable EAC SCC cell line. Its genetic features make it a useful tool for preclinical testing of new therapeutic agents for EAC SCC, particularly those targeting cell cycle regulation in combination with radio- and chemotherapy or other specific signaling pathway inhibitors.

Neuroinflammation-Related Proteins NOD2 and Spp1 Are Abnormally Upregulated in Amyotrophic Lateral Sclerosis.

BACKGROUND AND OBJECTIVES: Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disease of unknown etiology and poorly understood pathophysiology. There is no specific biomarker either for diagnosis or prognosis. The aim of our study was to investigate differentially expressed proteins in the CSF and serum from patients with ALS to determine their role in the disease process and evaluate their utility as diagnostic or prognostic biomarkers. METHODS: We performed mass spectrometry in the CSF from 3 patients with ALS and 3 healthy controls (HCs). The results were compared with motor cortex dysregulated transcripts obtained from 11patients with sporadic ALS and 8 HCs. Candidate proteins were tested using ELISA in the serum of 123 patients with ALS, 30 patients with Alzheimer disease (AD), 28 patients with frontotemporal dementia (FTD), and 102 HCs. Patients with ALS, AD, and FTD were prospectively recruited from January 2003 to December 2020. A group of age-matched HCs was randomly selected from the Sant Pau Initiative on Neurodegeneration cohort of the Sant Pau Memory Unit. RESULTS: Nucleotide-binding oligomerization domain-containing protein 2 (NOD2) and osteopontin (Spp1) were differentially expressed in the CSF and the motor cortex transcriptome of patients with ALS compared with that in HCs (p < 0.05). NOD2 and Spp1 levels were significantly higher in sera from patients with ALS than in HCs (p < 0.001). Receiver operating characteristic analysis showed an area under the curve of 0.63 for NOD2 and 0.81 for Spp1. NOD2 levels were significantly lower in patients with AD and FTD than in patients with ALS (p < 0.0001), but we found no significant differences in Spp1 levels between patients with ALS, AD (p = 0.51), and FTD (p = 0.42). We found a negative correlation between Spp1 levels and ALS functional rating scale (r = -0.24, p = 0.009). DISCUSSION: Our discovery-based approach identified NOD2 as a novel biomarker in ALS and adds evidence to the contribution of Spp1 in the disease process. Both proteins are involved in innate immunity and autophagy and are increased in the serum from patients with ALS. Our data support a relevant role of neuroinflammation in the pathophysiology of the disease and may identify targets for disease-modifying treatments in ALS. Further longitudinal studies should investigate the diagnostic and prognostic value of NOD2 and Spp1 in clinical practice.

Hypoechogenicity of the raphe nuclei as a biomarker of migraine: A case-control study, review, and meta-analysis.

BACKGROUND AND PURPOSE: Hypoechogenicity of the raphe nuclei (hR) has been related to major depression. Comorbidity between migraine and depression is bidirectional postulating a common mechanism of serotonergic dysfunction. We aimed to investigate the association between migraine and hR and its role as biomarker of migraine-associated depression and disease severity. METHODS: This is a single-center cross-sectional descriptive study. We included consecutive patients with episodic (EM) and chronic migraine (CM). We collected their comorbidities, analgesic consumption, hospital anxiety and depression scale (HADS), disability, and impact on quality of life associated with migraine. We also included a group of control subjects, matched for age and sex with the patients. In both groups, hR was assessed by means of transcranial sonography. We performed a meta-analysis of the studies investigating the association between migraine and hR. RESULTS: A total of 107 subjects were included (57 cases and 50 controls). hR rate was lower in controls than in migraine patients (22.2% vs. 42.9%, p = .02) with a progressive increase in EM and CM groups respect to the control group (33.3% and 50% vs. 22.2%, respectively; p = .03). Among patients, hR was not associated with depression, higher HADS score, greater migraine-related disability, or higher consumption of analgesic medication. The meta-analysis showed a significant association between migraine and hR (odds ratio = 2.16; 95% confidence interval: 1.42-3.29). CONCLUSION: hR is more prevalent in migraine patients than in controls and, in our population, its prevalence increases in a stepwise manner in patients with EM and CM. These findings support the role of raphe nuclei in migraine pathophysiology.

Diagnostic performance of plasma pTau 217, pTau 181, Aß 1-42 and Aß 1-40 in the LUMIPULSE automated platform for the detection of Alzheimer disease.

BACKGROUND: Recently developed blood markers for Alzheimer's disease (AD) detection have high accuracy but usually require ultra-sensitive analytic tools not commonly available in clinical laboratories, and their performance in clinical practice is unknown. METHODS: We analyzed plasma samples from 290 consecutive participants that underwent lumbar puncture in routine clinical practice in a specialized memory clinic (66 cognitively unimpaired, 130 participants with mild cognitive impairment, and 94 with dementia). Participants were classified as amyloid positive (A+) or negative (A-) according to CSF Aß1-42/Aß1-40 ratio. Plasma pTau217, pTau181, Aß1-42 and Aß1-40 were measured in the fully-automated LUMIPULSE platform. We used linear regression to compare plasma biomarkers concentrations between A + and A- groups, evaluated Spearman's correlation between plasma and CSF and performed ROC analyses to assess their diagnostic accuracy to detect brain amyloidosis as determined by CSF Aß1-42/Aß1-40 ratio. We analyzed the potential of pTau217 to predict amyloidosis in CSF. RESULTS: Plasma pTau217 and pTau181 concentration were higher in A + than A- while the plasma Aß1-42/Aß1-40 ratio was lower in A + compared to A-. pTau181 and the Aß1-42/Aß1-40 ratio showed moderate correlation between plasma and CSF (Rho = 0.66 and 0.69, respectively). The areas under the ROC curve to discriminate A + from A- participants were 0.94 (95% CI 0.92-0.97) for pTau217, and 0.88 (95% CI 0.84-0.92) for both pTau181 and Aß1-42/Aß1-40. Chronic kidney disease (CKD) was related to increased plasma biomarker concentrations, but ratios were less affected. Plasma pTau217 had the highest fold change (x4.2) and showed high predictive capability in discriminating A + from A-, having 4-7% misclassification rate. The global accuracy of plasma pTau217 using a two-threshold approach was robust in symptomatic groups, exceeding 90%. CONCLUSION: The evaluation of blood biomarkers on an automated platform exhibited high diagnostic accuracy for AD pathophysiology, and pTau217 showed excellent diagnostic accuracy to identify participants with AD in a consecutive sample representing the routine clinical practice in a specialized memory unit.

Characterization of a Preclinical In Vitro Model Derived from a SMARCA4-Mutated Sinonasal Teratocarcinosarcoma.

Sinonasal teratocarcinosarcoma (TCS) is a rare tumor that displays a variable histology with admixtures of epithelial, mesenchymal, neuroendocrine and germ cell elements. Facing a very poor prognosis, patients with TCS are in need of new options for treatment. Recently identified recurrent mutations in SMARCA4 may serve as target for modern therapies with EZH1/2 and CDK4/6 inhibitors. Here, we present the first in vitro cell line TCS627, established from a previously untreated primary TCS originating in the ethmoid sinus with invasion into the brain. The cultured cells expressed immunohistochemical markers, indicating differentiation of epithelial, neuroepithelial, sarcomatous and teratomatous components. Whole-exome sequencing revealed 99 somatic mutations including SMARCA4, ARID2, TET2, CDKN2A, WNT7A, NOTCH3 and STAG2, all present both in the primary tumor and in the cell line. Focusing on mutated SMARCA4 as the therapeutic target, growth inhibition assays showed a strong response to the CDK4/6 inhibitor palbociclib, but much less to the EZH1/2 inhibitor valemetostat. In conclusion, cell line TCS627 carries both histologic and genetic features characteristic of TCS and is a valuable model for both basic research and preclinical testing of new therapeutic options for treatment of TCS patients.

A Sexologia e Seus Especialistas na Mídia Durante a Pandemia da Covid-19 / Sexology and Its Media Experts During the Covid-19 Pandemic / Sexología y Sus Expertos en Medios Durante la Pandemia del Covid-19

No escopo de uma pesquisa de abrangência nacional sobre práticas sexuais e gestão de risco, nos chamou atenção, na procura por materiais de mídia relacionando sexo e sexualidades com a pandemia de Covid-19, a presença majoritária de um grupo de "especialistas" ligados ao campo heterogêneo da Sexologia, tais como psicólogas, psiquiatras, urologistas, sexólogas, educadoras sexuais, associadas/os aos infectologistas. Por meio da pesquisa de palavras-chave, via buscador do Google, inventariamos um número de 44 matérias oriundas de sites de grupos jornalísticos grandes e alternativos, bem como de clínicas, associações profissionais e blogs particulares, publicadas entre março de 2020 a julho de 2021. Dessas, concentramos nossa análise em 30 matérias correspondentes àquelas veiculadas pelos grupos jornalísticos grandes e alternativos. A leitura realizada foi inspirada pela problemática da produção de objetos via práticas enunciativas e materiais, mediante as quais associações entre elementos diversos, perguntas e respostas explicitadas vão estabilizando não só os sentidos, mas os próprios objetos em disputa, no caso aqui observado, as práticas sexuais. Ao final de nosso estudo, percebeu-se que o sexo e a sexualidade produzidos pelos "especialistas" através dos canais de mídia tendem à generalização dos corpos e a descontextualização das práticas.

In the scope of a nationwide survey on sexual practices and risk management, what caught our attention, in the search for media materials relating sex and sexualities to the Covid-19 pandemic, the majority presence of a group of "specialists" linked to the heterogeneous field of Sexology, such as psychologists, psychiatrists, urologists, sexologists, sex educators, associated with infectologists. Through keyword research, via google search, we inventoried a number of 44 articles from large and alternative journalistic groups websites, as well as clinics, professional associations and private blogs, published between March 2020 and July 2021. From these, we focused our analysis on 30 articles corresponding to those published by large and alternative journalistic groups. The reading performed was inspired by the problematic of the production of objects via enunciative and material practices, through which associations between different elements, questions and explicit answers, stabilize not only the senses, but the objects in dispute, in the case observed here, sexual practices. At the end of our study, it was noticed that the sex and sexuality produced by the "specialists" through the media channels tends to the generalization of bodies and the decontextualization of practices.

En el ámbito de una encuesta a nivel nacional sobre prácticas sexuales y gestión de riesgos, lo que llamó nuestra atención, en la búsqueda de materiales mediáticos que relacionan el sexo con la pandemia de la Covid-19, destaca la presencia mayoritaria de un grupo de especialistas vinculados al heterogéneo campo de la Sexología, como psicólogos, psiquiatras, urólogos, sexólogos, y otra. A través de una investigación de palabras clave, a través de una búsqueda en Google, inventariamos una serie de 44 artículos de sitios web de grupos periodísticos grandes y alternativos, así como clínicas, asociaciones profesionales y blogs privados, publicados entre marzo de 2020 y julio de 2021. Enfocamos nuestro análisis en 30 artículos publicados por grandes y alternativos grupos periodísticos. La lectura realizada se inspiró en el problema de la producción de objetos a través de prácticas enunciativas y materiales, a través de las cuales asociaciones entre diferentes elementos, preguntas y respuestas explícitas, estabilizan no sólo los sentidos, sino los objetos en disputa, en el caso, prácticas sexuales. Al final de nuestro estudio, se percibió que el sexo y la sexualidad producidos por los especialistas tienden a la generalización de los cuerpos ya la descontextualización de las prácticas.

Current Evidence Involving WALANT Surgery.

Wide-awake local anesthesia no-tourniquet (WALANT) surgery is an attractive option for hand surgeons, particularly during resource-scarce periods, as it eliminates dependence on main operating rooms or hospital-based procedures. The limited prepping or draping used for WALANT field sterility is as effective, if not more effective, than standard sterile prepping or draping. Patient anxiety surrounding WALANT surgery is similar to or less than that of general or local anesthesia with or without tourniquet. Patients use the same or lower amounts of postoperative narcotics after WALANT as compared to after the other anesthetic methods. Wide-awake local anesthesia no-tourniquet surgery saves significant costs for the same surgeries when performed under general or local anesthesia with or without tourniquet. There are very few complications associated with the WALANT method of anesthesia; rare case reports include vasovagal syncope and cardiac arrhythmia due to inadvertent intravascular injection of epinephrine.

DNA methylation-based classification of sinonasal tumors.

The diagnosis of sinonasal tumors is challenging due to a heterogeneous spectrum of various differential diagnoses as well as poorly defined, disputed entities such as sinonasal undifferentiated carcinomas (SNUCs). In this study, we apply a machine learning algorithm based on DNA methylation patterns to classify sinonasal tumors with clinical-grade reliability. We further show that sinonasal tumors with SNUC morphology are not as undifferentiated as their current terminology suggests but rather reassigned to four distinct molecular classes defined by epigenetic, mutational and proteomic profiles. This includes two classes with neuroendocrine differentiation, characterized by IDH2 or SMARCA4/ARID1A mutations with an overall favorable clinical course, one class composed of highly aggressive SMARCB1-deficient carcinomas and another class with tumors that represent potentially previously misclassified adenoid cystic carcinomas. Our findings can aid in improving the diagnostic classification of sinonasal tumors and could help to change the current perception of SNUCs.