Dynapenia and sarcopenia identify walking speed decline in women but not in men.

OBJECTIVE: To determine the best indicator of mobility decline between dynapenia, low skeletal muscle mass index (SMMI), and sarcopenia defined by the EWGSOP2 using different cutoff points for grip strength. METHODS: A longitudinal study was conducted with a follow-up of eight years, involving 2,680 individuals aged 60 and older who participated in the ELSA study with a walking speed greater than 0.8 m/s at baseline. Dynapenia was defined using different cutoff points for grip strength. SMMI was defined by the 20th percentile of the entire ELSA sample distribution and sarcopenia was defined based on the EWGSOP2, using different cutoff points for grip strength. Mobility was analysed using the walking speed test. RESULTS: Over time, the greatest decline in walking speed occurred in dynapenic women with grip strength < 17 kg (-0.005 m/s per year; 95 % CI: -0.01 to -0.001) and < 20 kg (-0.007 m/s per year; 95 % CI: -0.01 to -0.001). With regards to sarcopenia, the greatest walking speed decline occurred in women with probable sarcopenia when defined by grip strength < 17 kg [(-0.006 m/s per year; 95 % CI: -0.01 to -0.001) or grip strength < 20 kg (-0.007 m/s per year; 95 % CI: -0.01 to -0.001)]. Dynapenia in men as well as low SMMI and sarcopenia in men and women did not enable identifying the risk of mobility decline. CONCLUSION: Dynapenia and probable sarcopenia defined by grip strength < 17 kg and < 20 kg enabled identifying walking speed decline over time only in women.

A cascading model for nudging employees towards energy-efficient behaviour in tertiary buildings.

Energy-related occupant behaviour in the built environment is considered crucial when aiming towards Energy Efficiency (EE), especially given the notion that people are most often unaware and disengaged regarding the impacts of energy-consuming habits. In order to affect such energy-related behaviour, various approaches have been employed, being the most common the provision of recommendations towards more energy-efficient actions. In this work, the authors extend prior research findings in an effort to automatically identify the optimal Persuasion Strategy (PS), out of ten pre-selected by experts, tailored to a user (i.e., the context to trigger a message, allocate a task or providing cues to enact an action). This process aims to successfully influence the employees' decisions about EE in tertiary buildings. The framework presented in this study utilizes cultural traits and socio-economic information. It is based on one of the largest survey datasets on this subject, comprising responses from 743 users collected through an online survey in four countries across Europe (Spain, Greece, Austria and the UK). The resulting framework was designed as a cascade of sequential data-driven prediction models. The first step employs a particular case of matrix factorisation to rank the ten PP in terms of preference for each user, followed by a random forest regression model that uses these rankings as a filtering step to compute scores for each PP and conclude with the best selection for each user. An ex-post assessment of the individual steps and the combined ensemble revealed increased accuracy over baseline non-personalised methods. Furthermore, the analysis also sheds light on important user characteristics to take into account for future interventions related to EE and the most effective persuasion strategies to adopt based on user data. Discussion and implications of the reported results are provided in the text regarding the flourishing field of personalisation to motivate pro-environmental behaviour change in tertiary buildings.

Primary intraosseous papillary intralymphatic angioendothelioma of the distal femoral epiphysis: a case report with literature review.

INTRODUCTION: Papillary intralymphatic angioendothelioma (PILA) is an exceptionally rare metastasizing soft tissue tumor. It tends to arise in the subcutaneous tissues of distal extremities in children. Only four intraosseous PILA cases have been reported until now in English language literature. CASE REPORT: We present a case of PILA arising in the distal femoral epiphysis of a 50-year-old female patient. It started as a relentless pain in her left knee. A plain radiography revealed a radiolucent area in the left internal femoral condyle. Computerized tomography revealed a 1-cm lytic lesion with a sclerotic rim. Magnetic resonance images showed a significant bone marrow edema signal focused on a 1-cm subchondral lesion suggestive of an intraarticular osteoid osteoma. Histologically, the tumor contained vascular channels covered by a single endothelial layer with intraluminal papillary endothelial structures lined with hobnail cells. Immunohistochemically, the cells were positive for ERG, CD31, and D2-40. The tumor underwent cryoablation and 6 months later, after local recurrence or tumor persistence, a wide tumor resection was referred. After 7 years of follow-up, the patient displayed neither local recurrence nor distant metastases. CONCLUSION: Primary intraosseous PILAs are exceedingly rare tumors that should be considered in the differential diagnosis of vascular bone tumors.

Understanding the factors that affect households' investment decisions required by the energy transition.

In energy systems' economic models, people's behaviour is often underestimated, and they are generally unaware of how habits impact energy efficiency. Improving efficiency is challenging, and recommendations alone may not be sufficient. Changing behaviour requires understanding the direct impact of needs and habits on energy efficiency. This research introduces a methodology that retrieves human expert knowledge from four key aspects of the current energy transition: everyday appliances, buildings, mobility, flexibility, and energy efficiency. The aim is to examine the causal relationship between energy consumption and human behaviour, gaining a deeper understanding of the links among the factors that drive final energy consumers to change habits through the adoption of energy-saving measures. Working in collaboration with expert panels, this study provides a methodology for extracting expert human knowledge based on a set of future energy transition scenarios aligned with the achievement of the Paris Agreement, a taxonomy of 32 factors that have a strong influence on households' investment decisions, and the results of a survey that characterises the European population through the 32-factor taxonomy and some socioeconomic conditions. In addition, the survey included a sample of the Latin American population to analyse how socioeconomic conditions (region, education, gender, etc.) influence the prioritisation of these factors. We discuss the high priority given to competence and autonomy over financial factors by inhabitants of the European Union residential sector. We provide an analysis of the factors through which other similar projects are focused and on which we converge. In addition, we contribute by presenting the hierarchy of priorities assigned by people. This highlights the importance for policymakers to take these aspects seriously when implementing energy policy interventions that go beyond purely financial measures and fiscal incentives.

FTIR Spectroscopy and Blood-Derived Extracellular Vesicles Duo in Alzheimer's Disease.

Background: Alzheimer's disease (AD) diagnosis is difficult, and new accurate tools based on peripheral biofluids are urgently needed. Extracellular vesicles (EVs) emerged as a valuable source of biomarker profiles for AD, since their cargo is disease-specific and these can be easily isolated from easily accessible biofluids, as blood. Fourier Transform Infrared (FTIR) spectroscopy can be employed to analyze EVs and obtain the spectroscopic profiles from different regions of the spectra, simultaneously characterizing carbohydrates, nucleic acids, proteins, and lipids. Objective: The aim of this study was to identify blood-derived EVs (bdEVs) spectroscopic signatures with AD discriminatory potential. Methods: Herein, FTIR spectra of bdEVs from two biofluids (serum and plasma) and distinct sets of Controls and AD cases were acquired, and EVs' spectra analyzed. Results: Analysis of bdEVs second derivative peaks area revealed differences between Controls and AD cases in distinct spectra regions, assigned to carbohydrates and nucleic acids, amides, and lipids. Conclusions: EVs' spectroscopic profiles presented AD discriminatory value, supporting the use of bdEVs combined with FTIR as a screening or complementary tool for AD diagnosis.

Phosphoproteome Microarray Analysis of Extracellular Particles as a Tool to Explore Novel Biomarker Candidates for Alzheimer's Disease.

Phosphorylation plays a key role in Alzheimer's disease (AD) pathogenesis, impacting distinct processes such as amyloid-beta (Aß) peptide production and tau phosphorylation. Impaired phosphorylation events contribute to senile plaques and neurofibrillary tangles' formation, two major histopathological hallmarks of AD. Blood-derived extracellular particles (bdEP) can represent a disease-related source of phosphobiomarker candidates, and hence, in this pilot study, bdEP of Control and AD cases were analyzed by a targeted phosphoproteomics approach using a high-density microarray that featured at least 1145 pan-specific and 913 phosphosite-specific antibodies. This approach, innovatively applied to bdEP, allowed the identification of 150 proteins whose expression levels and/or phosphorylation patterns were significantly altered across AD cases. Gene Ontology enrichment and Reactome pathway analysis unraveled potentially relevant molecular targets and disease-associated pathways, and protein-protein interaction networks were constructed to highlight key targets. The discriminatory value of both the total proteome and the phosphoproteome was evaluated by univariate and multivariate approaches. This pilot experiment supports that bdEP are enriched in phosphotargets relevant in an AD context, holding value as peripheral biomarker candidates for disease diagnosis.

An electricity smart meter dataset of Spanish households: insights into consumption patterns.

Smart meters are devices that provide detailed information about the energy consumed by specific electricity supply points, such as homes, offices, and businesses. Data from smart meters are useful for modeling energy systems, predicting electricity consumption, and understanding human behavior. We present the first smart meter dataset from Spanish electricity supply points, expanding the geographic diversity of available data on energy consumption at the household level and reducing biases in existing data, which typically come from a limited number of countries. The dataset consists of 25,559 raw hourly time series with an average length of nearly three years, spanning from November 2014 to June 2022. It also includes three subsets obtained by segmenting and cleaning the raw time series data, each focusing on the periods before, during, and after the COVID-19 lockdowns in Spain. This dataset is a valuable resource for studying electricity consumption patterns and behaviors that emerge in response to different natural experiments, such as nationwide and regional lockdowns, nighttime curfews, and changes in electricity pricing.

Prognostic Impact of AGR3 Protein Expression in Breast Cancer: A Systematic Review and Meta-analysis.

OBJECTIVE: To investigate the clinicopathological significance and prognosis of the expression of the anterior gradient 3 (AGR3) protein in women with breast cancer. DATA SOURCES: The PubMed, CINAHL, EMBASE, Scopus, and Web of Science databases were searched for studies published in English and without restrictions regarding the year of publication. The search terms were: breast cancer AND anterior gradient 3 OR AGR3 expression. STUDY SELECTION: We included observational or interventional studies, studies on AGR3 protein expression by immunohistochemistry, and studies on invasive breast cancer. Case reports, studies with animals, and reviews were excluded. In total, 4 studies were included, containing 713 cases of breast cancer. DATA COLLECTION: Data were extracted on clinicopathological characteristics and survival. A meta-analysis of the prevalence of AGR3 expression was performed according to the clinicopathological characteristics, hazard ratios (HRs), and overall survival and disease-free survival. DATA SYNTHESIS: The expression of AGR3 was found in 62% of the cases, and it was associated with histological grade II, positivity of estrogen and progesterone receptors, low expression of ki67, recurrence or distant metastasis, and lumen subtypes. In patients with low and intermediate histological grades, AGR3 expression was associated with worse overall survival (HR: 2.39; 95% confidence interval [95%CI]: 0.628-4.159; p = 0.008) and worse disease-free survival (HR: 3.856; 95%CI: 1.026-6.686; p = 0.008). CONCLUSION: The AGR3 protein may be a biomarker for the early detection of breast cancer and predict prognosis in luminal subtypes. In addition, in patients with low and intermediate histological grades, AGR3 protein expression may indicate an unfavorable prognosis in relation to survival.

OBJETIVO: Investigar o significado clinicopatológico e prognóstico da expressão da proteína anterior gradient 3 (AGR3) em mulheres com câncer de mama. FONTES DE DADOS: Utilizamos as bases de dados PubMed, CINAHL, EMBASE, Scopus e Web of Science para pesquisar estudos em inglês, sem restrições quanto ao ano de publicação. Os termos buscados foram: breast cancer AND anterior gradient 3 OR AGR3 expression. SELEçãO DOS ESTUDOS: Foram incluídos estudos observacionais ou intervencionais, estudos sobre a expressão da proteína AGR3 por imuno-histoquímica, e estudos sobre câncer de mama invasivo. Excluíram-se relatos de casos, estudos com animais e revisões. Quatro estudos foram selecionados, que continham 713 casos de câncer de mama. COLETA DE DADOS: Foram extraídos dados relativos a características clinicopatológicas e sobrevida. A metanálise da prevalência da expressão de AGR3 foi realizada conforme as características clinicopatológicas, razões de risco (RRs) e sobrevida global (SG) e sobrevida livre de doença (SLD). SíNTESE DOS DADOS: Encontrou-se expressão de AGR3 em 62% dos casos, que se associou com grau histológico II, positividade de receptores de estrogênio e progesterona, baixa expressão de ki67, recorrência ou metástase à distância e subtipos luminais. Em pacientes com graus histológicos baixo e intermediário, a expressão de AGR3 conferiu pior SG (RR: 2,39; intervalo de confiança de 95% [IC95%]: 0,628­4,159; p = 0,008) e pior SLD (RR: 3,856; IC95%: 1,026­6,686; p = 0,008). CONCLUSãO: A AGR3 pode ser um biomarcador para a detecção precoce do câncer de mama e predizer o prognóstico em subtipos luminais. Em graus histológicos baixo e intermediário, a expressão da proteína AGR3 pode indicar um prognóstico desfavorável em relação à sobrevida.

Optimized Automated Analysis of Live Neuronal Mitochondria Homeostasis Modulation by Isoform-Specific Retinoic Acid Receptors.

The complex mitochondrial network makes it very challenging to segment, follow, and analyze live cells. MATLAB tools allow the analysis of mitochondria in timelapse files, considerably simplifying and speeding up the process of image processing. Nonetheless, existing tools produce a large output volume, requiring individual manual attention, and basic experimental setups have an output of thousands of files, each requiring extensive and time-consuming handling. To address these issues, a routine optimization was developed, in both MATLAB code and live-script forms, allowing for swift file analysis and significantly reducing document reading and data processing. With a speed of 100 files/min, the optimization allows an overall rapid analysis. The optimization achieves the results output by averaging frame-specific data for individual mitochondria throughout time frames, analyzing data in a defined manner, consistent with those output from existing tools. Live confocal imaging was performed using the dye tetramethylrhodamine methyl ester, and the routine optimization was validated by treating neuronal cells with retinoic acid receptor (RAR) agonists, whose effects on neuronal mitochondria are established in the literature. The results were consistent with the literature and allowed further characterization of mitochondrial network behavior in response to isoform-specific RAR modulation. This new methodology allowed rapid and validated characterization of whole-neuron mitochondria network, but it also allows for differentiation between axon and cell body mitochondria, an essential feature to apply in the neuroscience field. Moreover, this protocol can be applied to experiments using fast-acting treatments, allowing the imaging of the same cells before and after treatments, transcending the field of neuroscience.

Monitoring clusterin and fibrillar structures in aging and dementia.

Objective: Clusterin is involved in a variety of physiological processes, including proteostasis. Several clusterin polymorphisms were associated with an increased risk of developing Alzheimer's disease, the world-leading cause of dementia. Herein, the effect of a clusterin polymorphism, aging and dementia in the levels of clusterin in human plasma were analysed in a primary care-based cohort, and the association of this chaperone with fibrillar structures discussed. Methods: 64 individuals with dementia (CDR≥1) and 64 age- and sex-matched Controls from a Portuguese cohort were genotyped for CLU rs1136000 polymorphism, and the plasma levels of clusterin and fibrils were assessed. Results: An increased prevalence of the CC genotype was observed for the dementia group, although no significant robustness was achieved. CLU rs11136000 SNP did not significantly change plasma clusterin levels in demented individuals. Instead, clusterin levels decreased with aging and even more in individuals with dementia. Importantly, plasma clusterin levels correlated with the presence of fibrillar structures in Control individuals, but not in those with dementia. Conclusion: This study reveals a significant decrease in plasma clusterin in demented individuals with aging, which related to altered clusterin-fibrils dynamics. Potentially, plasma clusterin and its association with fibrillar structures can be used to monitor dementia progression along aging.

Primary aneurysmal bone cyst of hands and feet: A series of 14 cases.

Aneurysmal bone cyst (ABC) is a relatively rare, benign bone tumor that occurs exceptionally in the hands and feet. The objective of this article is to present clinical, radiological, histopathological features and management of a series of 14 primary ABC cases in these unusual locations. Eight cases occurred in hands and six in feet. We present the first reported subungual case to occur in the hand. The average age of the patients was 26 years (range 7 to 49), with half being over the age of twenty at diagnosis. The male to female ration was 9:5. In radiological terms, ABC appeared as an expansive lesion with internal septa and without cortical disruption. Twelve cases displayed the classic multicystic morphology and two cases were of the solid variant. "Blue bone" was detected in 50 % of the specimens. Treatment consisted of curettage, excision, or amputation in all cases. Recurrence rate was observed in 35 % of the cases, with the similar ABC morphology as the original samples. New therapeutic options have been proposed on their own or in combination with surgery to reduce local recurrence rates.

Bioinformatic analysis of the SPs and NFTs proteomes unravel putative biomarker candidates for Alzheimer's disease.

Aging is the main risk factor for the appearance of age-related neurodegenerative diseases, including Alzheimer's disease (AD). AD is the most common form of dementia, characterized by the presence of senile plaques (SPs) and neurofibrillary tangles (NFTs), the main histopathological hallmarks in AD brains. The core of these deposits are predominantly amyloid fibrils in SPs and hyperphosphorylated Tau protein in NFTs, but other molecular components can be found associated with these pathological lesions. Herein, an extensive literature review was carried out to obtain the SPs and NFTs proteomes, followed by a bioinformatic analysis and further putative biomarker validation. For SPs, 857 proteins were recovered, and, for NFTs, 627 proteins of which 375 occur in both groups and represent the common proteome. Gene Ontology (GO) enrichment analysis permitted the identification of biological processes and the molecular functions most associated with these lesions. Analysis of the SPs and NFTs common proteins unraveled pathways and molecular targets linking both histopathological events. Further, validation of a putative phosphotarget arising from the in silico analysis was performed in serum-derived extracellular vesicles from AD patients. This bioinformatic approach contributed to the identification of putative molecular targets, valuable for AD diagnostic or therapeutic intervention.

Accuracy of mortality indicators due sepsis-associated deaths in the Federal District / Acurácia dos indicadores de mortalidade devido a sepse dos óbitos ocorridos no Distrito Federal / Precisión de los indicadores de mortalidad por sepsis de las defunciones ocurridas en el Distrito Federal

Background: Sepsis currently represents a challenge for health systems, this fact may be related to the spread of bacterial resistance, the increase in the population of elderly, immunosuppressed individuals, and the improvement of emergency care, favoring the survival of critically ill patients. This article aimed to evaluate the accuracy of mortality indicators due to sepsis in 2018. Method: Validation study of death certificates that occurred in the Federal District in 2018. Declarations whose basic causes of death identified were classified as garbage codes were identified, which were investigated by a multidisciplinary team, capable of reclassifying them with codes that allow for the improvement of health data. In order to assess accuracy, sensitivity, specificity, positive and negative predictive values, positive and negative likelihood ratios of death certificates from sepsis were calculated, with 95% confidence intervals. Results: A total of 6.244 statements were evaluated, of which 233 (3.74%) presented sepsis as the underlying cause before being investigated and only 35 (0.56%) maintained it after the investigation. The filling of statements with sepsis as the underlying cause by physicians showed a sensitivity of 0.9% (95%CI: 0.6 to 1.3) and a specificity of 92.0% (95%CI: 90.9 to 93.1). Conclusion: The low accuracy of the declarations demonstrates the non-reliability of the underlying cause of death from sepsis, especially the completion of death certificates that occurred in the Federal District in 2018.(AU)

Justificativa: A sepse, atualmente, representa um desafio para os sistemas de saúde, tal fato pode estar relacionado com a disseminação da resistência bacteriana, o aumento da população de idosos, os indivíduos imunossuprimidos, e a melhoria do atendimento de emergência, favorecendo a sobrevivência de pacientes críticos. Este artigo teve por objetivo avaliar a acurácia dos indicadores de mortalidade devido à sepse em 2018. Método: Estudo de validação da causa básica dos óbitos ocorridos no Distrito Federal em 2018. Foram identificadas as declarações de óbito cujas causas básicas de morte apontadas foram classificadas como garbage code sepse, as quais foram investigadas por uma equipe multidisciplinar, capacitada para reclassificá-las com códigos que permitem o aprimoramento dos dados em saúde. A fim de avaliar a acurácia, foram calculados os valores de sensibilidade, especificidade, valores preditivos positivo e negativo, razões de verossimilhança positiva e negativa das declarações dos óbitos por sepse, com intervalos de confiança de 95%. Resultados: Um total de 6.244 declarações foram avaliadas, das quais 233 (3,74%) apresentavam a sepse como causa básica antes de serem investigadas e apenas 35 (0,56%) mantiveram-na após a investigação. O preenchimento das declarações com a sepse enquanto causa básica pelos médicos apresentou sensibilidade de 0,9% (IC95%: 0,6 a 1,3) e especificidade de 92,0% (IC95%: 90,9 a 93,1). Conclusão: A baixa acurácia das declarações demonstra a não fidedignidade da causa básica de óbito por sepse, sobretudo, do preenchimento das declarações dos óbitos ocorridos no Distrito Federal em 2018.(AU)

Justificación: Sepsis representa en la actualidad un desafío para los sistemas de salud, este hecho puede estar relacionado con propagación de resistencias bacterianas, aumento de la población de ancianos, inmunodeprimidos, y mejora de la atención de urgencias, favoreciendo la supervivencia de los pacientes críticos. Este artículo tuvo como objetivo evaluar la precisión de los indicadores de mortalidad por sepsis en 2018. Método: Estudio de validación de causa básica de muertes ocurridas en Distrito Federal en 2018. Se identificaron actas de defunción cuyas causas básicas de muerte fueron clasificadas como sepsis código basura y fueron investigadas por un equipo multidisciplinario capacitado para reclasificarlas con códigos que permitan la mejora de datos de salud. Para evaluar la precisión, se calcularon sensibilidad, especificidad, valores predictivos positivo y negativo y razones de verosimilitud positiva y negativa de certificados de defunción por sepsis, con intervalos de confianza del 95%. Resultados: se evaluaron 6.244 declaraciones, de las cuales 233 (3,74%) tenían como causa básica la sepsis antes de ser investigadas y solo 35 (0,56%) mantuvieron después de investigación. Realización de declaraciones con sepsis como causa subyacente por parte de los médicos mostró sensibilidad del 0,9% (95%IC: 0,6 a 1,3) y especificidad del 92,0% (95%IC: 90,9 a 93,1). Conclusión: Baja precisión de las declaraciones demuestra la poca confiabilidad de la causa subyacente de muerte por sepsis, especialmente la finalización de los certificados de defunción ocurridos en Distrito Federal en 2018.(AU)

Canadian Academy of Sport and Exercise Medicine Position Paper: The Clinician's Role in Addressing and Preventing Maltreatment in Sport-10-year Anniversary.

ABSTRACT: In 2011, the Canadian Academy of Sport and Exercise Medicine released their first position paper on Abuse, Harassment, and Bullying in Sport. Since this time, there have been significant advancements within the global sport landscape, including the emergence of regulatory bodies and initiatives aimed at prioritizing athletes' health and well-being. While the shift to a more proactive approach for safeguarding athletes is evident and promising, athletes continue to be affected by cases of maltreatment. To advance safe sport, it is critical that all supporters of safe and healthy performance are aware of their roles and responsibilities for preventing and addressing maltreatment, including the Canadian sport medicine community. In this updated position statement, recent advancements in research on issues of maltreatment are summarized and specific recommendations are provided on how the medical community can contribute to appropriately identifying, treating, and preventing harm in sport, as well as their role in advocating for the health and well-being of athletes in their care.

Nonredundant Dimethyl Sulfoxide Reductases Influence Salmonella enterica Serotype Typhimurium Anaerobic Growth and Virulence.

Facultative anaerobic enteric pathogens can utilize a diverse array of alternate electron acceptors to support anaerobic metabolism and thrive in the hypoxic conditions within the mammalian gut. Dimethyl sulfoxide (DMSO) is produced by methionine catabolism and can act as an alternate electron acceptor to support anaerobic respiration. The DMSO reductase complex consists of three subunits, DmsA, DmsB, and DmsC, and allows bacteria to grow anaerobically with DMSO as an electron acceptor. The genomes of nontyphoidal Salmonella enterica encode three putative dmsABC operons, but the impact of the apparent genetic redundancy in DMSO reduction on the fitness of nontyphoidal S. enterica during infection remains unknown. We hypothesized that DMSO reduction would be needed for S. enterica serotype Typhimurium to colonize the mammalian gut. We demonstrate that an S. Typhimurium mutant with loss of function in all three putative DMSO reductases (ΔdmsA3) poorly colonizes the mammalian intestine when the microbiota is intact and when inflammation is absent. DMSO reduction enhances anaerobic growth through nonredundant contributions of two of the DMSO reductases. Furthermore, DMSO reduction influences virulence by increasing expression of the type 3 secretion system 2 and reducing expression of the type 3 secretion system 1. Collectively, our data demonstrate that the DMSO reductases of S. Typhimurium are functionally nonredundant and suggest DMSO is a physiologically relevant electron acceptor that supports S. enterica fitness in the gut.

Giant thigh glomus tumor of uncertain malignant potential: Case report with pathologic-radiologic correlation.

INTRODUCTION: Glomus tumors (GT) are rare, benign tumors that arise from glomus bodies and usually develop in digital areas. Extradigital GT are exceptional and thigh location is infrequent. CASE REPORT: We report a case of a GT of the thigh in a 79-year-old male patient that measured 9.5 cm in maximum size. The GT lay above the muscular fascia without infiltrating it. Internal hypervascularity was seen by spectral Doppler ultrasound. Magnetic resonance image showed a heterogeneous mass with hyperintense and hypointense components and internal lobes with liquid-liquid levels. Histopathology revealed a monotonous round-cell proliferation with central nuclei without atypia or mitotic figures, around small-caliber vessels. These cells expressed smooth muscle actin and pericellular collagen IV. GT of uncertain malignant potential was diagnosed. The mass was completely removed. The patient did not experience local relapse nor distant metastasis. CONCLUSION: GT are rare soft tissue tumors whose diagnosis of unusual giant masses in uncommon locations may be delayed and misdiagnosed given the low suspicion.

Therapeutic tools for familial ALS.

Familial ALS (FALS) accounts for 10 to 15% of ALS cases. In more than 70% of FALS patients, a causal gene is identified and animal models have been developed for a subset of them, mainly for the most frequently mutated genes. Therapeutic tools to treat those patients are dominated by gene-specific therapy and the most advanced approaches target the SOD1 gene mutations. Either by direct delivery of antisense oligonucleotides (ASO) or using viral vectors such as adenoviruses (AAV) to deliver ASOs, gene specific therapies have shown promising results in animal models. The recent use of subpial injections of AAV9+anti SOD1 ASO now shows that the disease is completely prevented or stopped in the animal, depending on the moment of injection, e.g., before or after disease onset. However, the use of viral vectors in humans seems to be limited at least by their immunogenicity. Antibody-based therapies are also efficient to treat animal models, but to a lesser extent. Most of the experiments targeted the SOD1 protein in its misfolded conformation. This approach seems better tolerated than the AAV one, an important limit being the choice of the epitope. Unexpectedly, some advances in treating the C9ORF72 animal model have been obtained using a modulation of microbiota, and this strategy has the great advantage to have an easy route of administration and a good safety profile. The landscape of experimental FALS treatment is rapidly evolving and results are promising. This is an important unmet need for ALS patients and several human phase I, II and III trials are ongoing.