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1.
J Pathol ; 2024 Jul 18.
Artigo em Inglês | MEDLINE | ID: mdl-39022853

RESUMO

Metabolic dysfunction-associated steatotic liver disease (MASLD) is a chronic liver condition that often progresses to more advanced stages, such as metabolic dysfunction-associated steatohepatitis (MASH). MASH is characterized by inflammation and hepatocellular ballooning, in addition to hepatic steatosis. Despite the relatively high incidence of MASH in the population and its potential detrimental effects on human health, this liver disease is still not fully understood from a pathophysiological perspective. Deregulation of polyamine levels has been detected in various pathological conditions, including neurodegenerative diseases, inflammation, and cancer. However, the role of the polyamine pathway in chronic liver disorders such as MASLD has not been explored. In this study, we measured the expression of liver ornithine decarboxylase (ODC1), the rate-limiting enzyme responsible for the production of putrescine, and the hepatic levels of putrescine, in a preclinical model of MASH as well as in liver biopsies of patients with obesity undergoing bariatric surgery. Our findings reveal that expression of ODC1 and the levels of putrescine, but not spermidine nor spermine, are elevated in hepatic tissue of both diet-induced MASH mice and patients with biopsy-proven MASH compared with control mice and patients without MASH, respectively. Furthermore, we found that the levels of putrescine were positively associated with higher aspartate aminotransferase concentrations in serum and an increased SAF score (steatosis, activity, fibrosis). Additionally, in in vitro assays using human HepG2 cells, we demonstrate that elevated levels of putrescine exacerbate the cellular response to palmitic acid, leading to decreased cell viability and increased release of CK-18. Our results support an association between the expression of ODC1 and the progression of MASLD, which could have translational relevance in understanding the onset of this disease. © 2024 The Pathological Society of Great Britain and Ireland.

2.
Cell Mol Life Sci ; 81(1): 304, 2024 Jul 15.
Artigo em Inglês | MEDLINE | ID: mdl-39009859

RESUMO

The autophagy-lysosomal pathway plays a critical role in the clearance of tau protein aggregates that deposit in the brain in tauopathies, and defects in this system are associated with disease pathogenesis. Here, we report that expression of Tau35, a tauopathy-associated carboxy-terminal fragment of tau, leads to lipid accumulation in cell lines and primary cortical neurons. Our findings suggest that this is likely due to a deleterious block of autophagic clearance and lysosomal degradative capacity by Tau35. Notably, upon induction of autophagy by Torin 1, Tau35 inhibited nuclear translocation of transcription factor EB (TFEB), a key regulator of lysosomal biogenesis. Both cell lines and primary cortical neurons expressing Tau35 also exhibited changes in endosomal protein expression. These findings implicate autophagic and endolysosomal dysfunction as key pathological mechanisms through which disease-associated tau fragments could lead to the development and progression of tauopathy.


Assuntos
Autofagia , Endossomos , Metabolismo dos Lipídeos , Lisossomos , Neurônios , Proteínas tau , Proteínas tau/metabolismo , Proteínas tau/genética , Lisossomos/metabolismo , Humanos , Neurônios/metabolismo , Animais , Endossomos/metabolismo , Tauopatias/metabolismo , Tauopatias/patologia , Fatores de Transcrição de Zíper de Leucina e Hélice-Alça-Hélix Básicos/metabolismo , Fatores de Transcrição de Zíper de Leucina e Hélice-Alça-Hélix Básicos/genética , Camundongos
3.
Sleep Med ; 121: 196-202, 2024 Jul 10.
Artigo em Inglês | MEDLINE | ID: mdl-39002328

RESUMO

BACKGROUND: The prevalence of sleep-related issues among older adults is a significant concern, with half of the older population reporting these problems. Consequently, strategies to improve sleep are needed for this population. This study aims to assess the effects of a health educational program on sleep behaviour among pre-frail or frail older adults residing in the community and to explore possible associations with frailty. METHODS: This randomised controlled trial (NCT05610605) included a total of 197 community-dwelling older adults with frailty/pre-frailty, divided into control (n = 88) and educational (n = 109) groups, were assessed at baseline, after the 6-month educational program (6 months), and 6 months after the intervention (12 months). The intervention comprised four group sessions and six follow-up phone calls, focusing on frailty, physical activity, dietary habits, and cognitive training. Sleep quality was measured using the Pittsburgh Sleep Quality Index (PSQI) and wrist-worn accelerometry. RESULTS: At 6 months, a significant time-by-group interaction was found for self-reported [ß = -0.449, 95%CI (-0.844, -0.053), p = 0.026] and accelerometer-measured [ß = 0.505, 95%CI (0.085, 0.926), p = 0.019] sleep efficiency, showing improved sleep efficiency in the intervention group vs. controls. A significant time-by-group interaction at 6 months was noted for sleep awakenings [ß = -0.402, 95%CI (-0.825, -0.020), p = 0.047]. The educational program led to a significant decrease in awakenings, while the control group experienced an increase. The change in the number of awakenings (Rs = 0.183, p = 0.020) at 6 months was significantly associated with changes in frailty. Moreover, a significant time-by-group interaction was reported at the 12-month assessment [ß = -0.449, 95%CI (-0.844, -0.053), p = 0.026] for self-reported sleep quality, indicating better results in the intervention group compared to controls. CONCLUSION: The educational program improved sleep quality and sleep efficiency while reducing the number of awakenings per night among community-dwelling frail older adults, offering a practical approach to addressing sleep-related challenges in this demographic.

4.
Cogn Emot ; : 1-9, 2024 Jul 11.
Artigo em Inglês | MEDLINE | ID: mdl-38992967

RESUMO

Previous research has demonstrated the influence of emotions during linguistic processing, indicating the interactivity of both processes in the brain. However, little is known regarding such interplay in a second language (L2). This study addressed this question by examining the reading effects of syntactic violations while processing L2 emotional and neutral statements. Forty-six Spanish-English bilinguals with various levels of L2 proficiency and emotional resonance (i.e. capability for emotional experience in L2) were presented with a self-paced sentence reading task. Sentences contained positive (16), neutral (16) and negative (16) verbs, half of them presented in agreement and half in disagreement with the preceding pronoun. Analysis of verb reading times using linear mixed effects modelling revealed a significant interaction between syntactic violation, verb valence and emotional resonance, suggesting that stronger emotional L2 experience results in a higher saliency of negative verbs, reducing the impact of syntactic violations.

5.
Front Med (Lausanne) ; 11: 1407812, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38983363

RESUMO

Objective: In patients with iron deficiency anaemia (IDA), the diagnostic yield of gastroscopy and colonoscopy (bidirectional endoscopy) in detecting neoplastic lesions is low. This study aimed to develop and validate a faecal immunochemical test (FIT)-based model to optimise the work-up of patients with IDA. Methods: Outpatients with IDA were enrolled in a prospective, multicentre study from April 2016 to October 2019. One FIT was performed before bidirectional endoscopy. Significant gastrointestinal lesions were recorded and a combined model developed with variables that were independently associated with significant colorectal lesions in the multivariate analysis. The model cut-off was selected to provide a sensitivity of at least 95% for colorectal cancer (CRC) detection, and its performance was compared to different FIT cut-offs. The data set was randomly split into two groups (developed and validation cohorts). An online calculator was developed for clinical application. Results: The development and validation cohorts included 373 and 160 patients, respectively. The developed model included FIT value, age, and sex. In the development and validation cohorts, a model cut-off of 0.1375 provided a negative predictive value of 98.1 and 96.7% for CRC and 90.7 and 88.3% for significant colorectal lesions, respectively. This combined model reduced the rate of missed significant colorectal lesions compared to FIT alone and could have avoided more than one-fourth of colonoscopies. Conclusion: The FIT-based combined model developed in this study may serve as a useful diagnostic tool to triage IDA patients for early endoscopic referral, resulting in considerable reduction of unnecessary colonoscopies.

6.
Front Psychiatry ; 15: 1244694, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-39026525

RESUMO

Background: Language disturbances are a core feature of schizophrenia, often studied as a formal thought disorder. The neurobiology of language in schizophrenia has been addressed within the same framework, that language and thought are equivalents considering symptoms and not signs. This review aims to systematically examine published peer-reviewed studies that employed neuroimaging techniques to investigate aberrant brain-language networks in individuals with schizophrenia in relation to linguistic signs. Methods: We employed a language model for automatic data extraction. We selected our studies according to the PRISMA recommendations, and we conducted the quality assessment of the selected studies according to the STROBE guidance. Results: We analyzed the findings from 37 studies, categorizing them based on patient characteristics, brain measures, and language task types. The inferior frontal gyrus (IFG) and superior temporal gyrus (STG) exhibited the most significant differences among these studies and paradigms. Conclusions: We propose guidelines for future research in this field based on our analysis. It is crucial to investigate larger networks involved in language processing, and language models with brain metrics must be integrated to enhance our understanding of the relationship between language and brain abnormalities in schizophrenia.

8.
Heliyon ; 10(11): e32330, 2024 Jun 15.
Artigo em Inglês | MEDLINE | ID: mdl-38961931

RESUMO

The evaluation of the university experience of students is an increasingly frequent field of analysis among the academic community, as they represent one of the most important groups in universities and it is essential to know their opinion and satisfaction with the different services and resources that the university institution makes available to them. In this sense, the two objectives of the study were the following: 1) To analyse the undergraduate university experience of the different groups of students (graduates, students, drop-outs). 2) To identify which aspects of the academic training received predict each of the student groups. To this end, a study was carried out specifically aimed at undergraduate education students at the University of Granada (Spain), distinguishing between graduates, students, and those who had dropped out of their studies. A total of 292 students participated (82 female and 210 male), of whom 123 were graduates, 98 were still students and 71 were drop-outs. After the application of three questionnaires, it was found that the three aforementioned groups of participants coincided in particularly valuing characteristic dimensions of the formal teaching-learning scenario in the university experience. In addition, the linear regression analysis carried out identified the personalised attention factor as having the highest predictive value as regards student type. Thus, the results of the study point to an assessment of academic training focused on the need on the part of all three groups of participants for teacher support and individualised guidance. The study may be useful in providing universities with new data to help improve the teaching performance of Education degree teaching staff concerning students; for example, by encouraging their participation in tutorial action programmes.

9.
Rev Esp Enferm Dig ; 2024 Jul 03.
Artigo em Inglês | MEDLINE | ID: mdl-38958154

RESUMO

INTRODUCTION: The early diagnosis of achalasia requires a high degree of clinical suspicion, and delays in diagnosis are frequent. High-resolution oesophageal manometry (HRM) is the gold standard for its diagnostic confirmation. There are two HRM systems, perfusion and solid-state, which allow its classification into three subtypes: I, or classical; II, or with pan-oesophageal pressurization; and III, or spastic. OBJECTIVE: To determine the clinical and manometric characteristics of the three subtypes with high-resolution perfusion and solid-state equipment and the time of evolution until diagnosis. METHODS: This was a multicentre, observational, retrospective study of patients from the INTEGRA database of the Spanish Association of Neurogastroenterology and Motility who were diagnosed with primary achalasia confirmed by HRM, who fell under the Chicago Classification v3.0, and who had not been treated. RESULTS: The study included 110 patients (subtype I, N = 14; subtype II, N = 73; subtype III, N = 23). The HRM equipment was perfusion for 49 and solid-state for 61. The mean age was 61.8 ± 14 years (age range 44-81), the age was lower in subtype II, and the sex distribution was similar. The time of clinical evolution until diagnosis was > 12 months (51.6%), subtype II being the one that was diagnosed earlier and the most often (66.3%). Dysphagia was the most frequent symptom (90.5%). According to the comparative analysis by high-resolution perfusion and solid-state oesophageal manometry equipment, the baseline pressure of the lower oesophageal sphincter was higher in the solid-state oesophagus, but the difference was not statistically significant. The median integrated relaxation pressure at 4 seconds (IRP4) was similar (21 mmHg) between the perfusion and solid-state measurements. We describe the ranges of IRP4 in achalasia patients with both systems and confirm the possibility of achalasia even when IRP4 is within the normal range. CONCLUSIONS: Achalasia in our environment has a significant diagnostic delay. No significant differences were observed in the oesophagogastric junction between the two groups diagnosed with perfusion and solid-state equipment.

10.
Rev Esp Enferm Dig ; 2024 Jul 05.
Artigo em Inglês | MEDLINE | ID: mdl-38967269

RESUMO

Acute pancreatitis is a common condition in Gastroenterology. Among its possible etiologies are ampullary tumors, rare neoplasms whose growth can hinder pancreatic drainage. Although they are usually epithelial, adenomas and adenocarcinomas, less commonly other histological types have been reported, such as neuroendocrine tumors. They constitute a small percentage of both ampullary tumors and neuroendocrine tumors of the digestive tract, classified into three histological grades based on mitotic count and Ki-67. Although the diagnosis is usually incidental, its main form of presentation is clinical or analytical cholestasis, with acute pancreatitis being an exceptional initial presentation. Endoscopic resection is the treatment of choice for well-differentiated tumors without evidence of local infiltration of the duodenal wall or intraductal growth greater than 10mm, with endoscopic ultrasound playing a key role in this assessment. We present the case of a 45-year-old cholecystectomized woman who was admitted to our service with a condition compatible with acute pancreatitis, initially suspected to be of biliary origin. After several radiological and endoscopic studies, an enlargement of the duodenal papilla suggestive of ampulloma was detected. Histological examination demonstrated a well-differentiated neuroendocrine tumor of the duodenal papilla which, lacking evidence of local duodenal infiltration or intraductal growth, was successfully resected endoscopically.

11.
Drug Deliv ; 31(1): 2372285, 2024 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-38952133

RESUMO

In this study, chitosan low molecular weight (LCH) and chitosan medium molecular weight (MCH) were employed to encapsulate a yarrow extract rich in chlorogenic acid and dicaffeoylquinic acids (DCQAs) that showed antiproliferative activity against colon adenocarcinoma cells. The design of CH micro/nanoparticles to increase the extract colon delivery was carried out by using two different techniques: ionic gelation and spray drying. Ionic gelation nanoparticles obtained were smaller and presented higher yields values than spray-drying microparticles, but spray-drying microparticles showed the best performance in terms of encapsulation efficiency (EE) (> 94%), also allowing the inclusion of a higher quantity of extract. Spray-drying microparticles designed using LCH with an LCH:extract ratio of 6:1 (1.25 mg/mL) showed a mean diameter of 1.31 ± 0.21 µm and EE values > 93%, for all phenolic compounds studied. The release profile of phenolic compounds included in this formulation, at gastrointestinal pHs (2 and 7.4), showed for most of them a small initial release, followed by an increase at 1 h, with a constant release up to 3 h. Chlorogenic acid presented the higher release values at 3 h (56.91% at pH 2; 44.45% at pH 7.4). DCQAs release at 3 h ranged between 9.01- 40.73%, being higher for 1,5- and 3,4-DCQAs. After gastrointestinal digestion, 67.65% of chlorogenic and most DCQAs remained encapsulated. Therefore, spray-drying microparticles can be proposed as a promising vehicle to increase the colon delivery of yarrow phenolics compounds (mainly chlorogenic acid and DCQAs) previously described as potential agents against colorectal cancer.


Assuntos
Achillea , Proliferação de Células , Quitosana , Ácido Clorogênico , Neoplasias Colorretais , Nanopartículas , Tamanho da Partícula , Extratos Vegetais , Quitosana/química , Humanos , Extratos Vegetais/farmacologia , Extratos Vegetais/administração & dosagem , Extratos Vegetais/química , Achillea/química , Ácido Clorogênico/farmacologia , Ácido Clorogênico/administração & dosagem , Ácido Clorogênico/química , Nanopartículas/química , Proliferação de Células/efeitos dos fármacos , Neoplasias Colorretais/tratamento farmacológico , Linhagem Celular Tumoral , Ácido Quínico/análogos & derivados , Ácido Quínico/farmacologia , Ácido Quínico/química , Ácido Quínico/administração & dosagem , Liberação Controlada de Fármacos , Sistemas de Liberação de Medicamentos/métodos , Antineoplásicos Fitogênicos/farmacologia , Antineoplásicos Fitogênicos/administração & dosagem , Antineoplásicos Fitogênicos/química , Colo/efeitos dos fármacos , Colo/metabolismo , Portadores de Fármacos/química , Peso Molecular
12.
Ticks Tick Borne Dis ; 15(6): 102382, 2024 Jul 19.
Artigo em Inglês | MEDLINE | ID: mdl-39032307

RESUMO

Cholesterol is a molecule vital for tick physiology, but ticks cannot synthesize it and rely on dietary cholesterol. Therefore, tick proteins involved in cholesterol absorption and transport, such as the Niemann-Pick type C1 domain-containing (NPC1) proteins, are promising targets for anti-tick vaccine development. The aim of this study was to assess the structure, function, and protective efficacy of the NPC1 orthologues identified previously in the midgut transcriptomes of argasid ticks Ornithodoros erraticus and Ornithodoros moubata. For this purpose, their corresponding cDNA coding sequences were cloned and sequenced, their secondary and 3D structures were predicted, and their function was evaluated through RNAi-mediated gene knockdown and in vitro feeding on blood supplemented with ezetimibe, which inhibits cholesterol binding by NPC1 proteins. Subsequently, the protective efficacy of a recombinant form of NPC1 from O. moubata (rOmNPC1) was tested in a rabbit vaccine trial. While inhibiting cholesterol absorption with ezetimibe resulted in up to 77 % mortality in adult O. moubata, NPC1 gene knockdown and vaccination with rOmNPC1 decreased female reproductive performance in terms of the number and fertility of laid eggs. This study presents the initial molecular and functional insights into NPC1 proteins in soft ticks and supports the hypothesis that disrupting cholesterol metabolism diminishes tick viability and reproduction, rendering Niemann-Pick type C1 domain-containing proteins promising targets for drugs or vaccines.

13.
bioRxiv ; 2024 Jul 01.
Artigo em Inglês | MEDLINE | ID: mdl-39005434

RESUMO

Amphibians represent a diverse group of tetrapods, marked by deep divergence times between their three systematic orders and families. Studying amphibian biology through the genomics lens increases our understanding of the features of this animal class and that of other terrestrial vertebrates. The need for amphibian genomics resources is more urgent than ever due to the increasing threats to this group. Amphibians are one of the most imperiled taxonomic groups, with approximately 41% of species threatened with extinction due to habitat loss, changes in land use patterns, disease, climate change, and their synergistic effects. Amphibian genomics resources have provided a better understanding of ontogenetic diversity, tissue regeneration, diverse life history and reproductive modes, antipredator strategies, and resilience and adaptive responses. They also serve as critical models for understanding widespread genomic characteristics, including evolutionary genome expansions and contractions given they have the largest range in genome sizes of any animal taxon and multiple mechanisms of genetic sex determination. Despite these features, genome sequencing of amphibians has significantly lagged behind that of other vertebrates, primarily due to the challenges of assembling their large, repeat-rich genomes and the relative lack of societal support. The advent of long-read sequencing technologies, along with computational techniques that enhance scaffolding capabilities and streamline computational workload is now enabling the ability to overcome some of these challenges. To promote and accelerate the production and use of amphibian genomics research through international coordination and collaboration, we launched the Amphibian Genomics Consortium (AGC) in early 2023. This burgeoning community already has more than 282 members from 41 countries (6 in Africa, 131 in the Americas, 27 in Asia, 29 in Australasia, and 89 in Europe). The AGC aims to leverage the diverse capabilities of its members to advance genomic resources for amphibians and bridge the implementation gap between biologists, bioinformaticians, and conservation practitioners. Here we evaluate the state of the field of amphibian genomics, highlight previous studies, present challenges to overcome, and outline how the AGC can enable amphibian genomics research to "leap" to the next level.

14.
Int J Telerehabil ; 16(1): e6605, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-39022433

RESUMO

Given Colombia's status as a middle-income country with healthcare challenges, leveraging telemedicine could significantly benefit hard-to-reach regions, under-resourced and underserved communities. This study provides a comprehensive overview of the country's telerehabilitation landscape, exploring the clinicians' and patients' perspectives during the COVID-19 pandemic through systematic review and qualitative analysis. Sixteen therapists and three patients were identified via snowball sampling. The literature review was scarce and scattered across various topics in the country; some studies delved into specific aspects like legislative frameworks and patient outcomes from different medical specialties. The qualitative analysis demonstrates that despite the learning curve, telerehabilitation strengthens therapeutic support, enhances patient autonomy, fosters a positive patient-provider relationship, achieves treatment goals, promotes family involvement, reduces time and costs, and ensures continuity of therapy services. This study identified research gaps, challenges, and opportunities in telerehabilitation in a Latin American country. Adopting telemedicine technologies in low- and middle-income countries could significantly enhance their healthcare systems.

16.
J Clin Nurs ; 2024 Jun 26.
Artigo em Inglês | MEDLINE | ID: mdl-38932443

RESUMO

BACKGROUND: The coexistence of frailty and type 2 diabetes mellitus in the older population heightens the risk of adverse events. However, research on functional and wellness factors associated with frailty in this population is limited. PURPOSE: To investigate the associations of physical performance, functional dependency, physical activity, nutritional status, sleep, self-perceived health and depression with frailty in community-dwelling older adults with coexisting frailty and type 2 diabetes mellitus. DESIGN: Cross-sectional. METHODS: The study included 123 community-dwelling older adults (73.7 ± 6.0 years) with pre-frailty/frailty and type 2 diabetes mellitus. Physical performance (Short Physical Performance Battery), functional dependency (Barthel Index and Lawton & Brody), physical activity and inactivity (GeneActiv wrist-worn accelerometer), malnutrition risk (Mini Nutritional Assessment), sleep (Pittsburgh Sleep Quality Index), self-perceived health (EuroQoL 5-Dimension 3-Level) and depression (Yesavage 15-item-Geriatric-Depression-Scale) were evaluated through personal interviews. Principal component analysis (PCA) was performed to categorize the variables into components, and logistic regressions were used to propose the best-fitted model for each component. RESULTS: The PCA identified four components: (i) physical performance, with gait speed and leg mean velocity as the main variables associated with frailty; (ii) balance, showing significant associations with monopodal balance; (iii) daily activities, with moderate to vigorous physical activity and the Lawton and Brody score as the main variables associated with frailty within this component; and (iv) wellness factors, with nutritional status, self-perceived health and depression score as the primary variables associated with frailty. CONCLUSIONS: This research underscores the significance of physical function and daily activities as protective factors against frailty in community-dwelling older adults with coexisting frailty and type 2 diabetes mellitus. The health dimension contributes both protective and risk factors, emphasizing the need for comprehensive assessments in managing frailty in this population. REPORTING METHOD: The study adhered to the STROBE checklist. PATIENT OR PUBLIC CONTRIBUTION: No patient or public contribution.

18.
Adv Lab Med ; 5(2): 189-196, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38939205

RESUMO

Objectives: Despite clinical guidelines do not recommend the use of point-of-care testing (POCT) glucometers for diagnostic purposes yet, the analytical performance is continuously improving. Thus, we evaluate the technical accuracy and clinical concordance of POCT glucometers during an oral glucose tolerance test (OGTT) in children for prediabetes and diabetes diagnosis in a comparison study. Methods: Pediatric patients with an OGTT indication who attended the Diabetes Unit between December 2020 and September 2021 were recruited for this prospective observational study. During the functional test, glycaemia was immediately measured in venous blood using two glucometers (unconnected and connected) and sent to the central laboratory. Results: The study included 98 patients. There was a high correlation between the glucometers and the central laboratory (Pearson correlation coefficient=0.912 and 0.950, for unconnected and connected glucometer, respectively). The median OGTT turnaround time (TAT) was significantly decreased (connected glucometer: 2.02 h [interquartile range, 2.00-2.07], central laboratory: 11.63 h [6.09-25.80]), with similar overall cost. The diagnostic concordance between connected glucometer and the central laboratory was 71.1 % (95 % confidence interval (CI) 61.5-79.2). The clinical decision would have been the same in the 92.8 % of the cases, but treatment would have not been indicated in 4 patients (4.1 %). Conclusions: POCT glucometers have demonstrated a high correlation and an acceptable diagnostic concordance with the central laboratory during an OGTT, as well the connected device offers a significant decrease in TAT, without increasing costs. However, as severe clinical impact could happen, POCT glucometers may not be used for diagnosis yet.

19.
Genes (Basel) ; 15(6)2024 May 26.
Artigo em Inglês | MEDLINE | ID: mdl-38927623

RESUMO

HELIX syndrome (Hypohidrosis-Electrolyte disturbances-hypoLacrimia-Ichthyosis-Xerostomia) (MIM#617671) (ORPHA:528105), described in 2017, is due to an abnormal claudin 10 b protein, secondary to pathogenic CLDN10 variants. So far, only ten families have been described. We aim to describe the phenotype in the first Spanish family identified, highlight the skin anomalies as an important clue, and expand the genotypic spectrum. Two adult brothers from consanguineous parents with suspected ectodermal dysplasia (ED) since early childhood were re-evaluated. A comprehensive phenotypic exam and an aCGH + SNP4 × 180 K microarray followed by Sanger sequencing of the CLDN10 gene were performed. They presented hypohidrosis, xerosis, mild ichthyosis, plantar keratosis, palm hyperlinearity, alacrima, and xerostomia. In adulthood, they also developed a salt-losing nephropathy with hypokalemia and hypermagnesemia. The molecular study in both patients revealed a novel pathogenic homozygous deletion of 8 nucleotides in exon 2 of the CLDN10 gene [CLDN10 (NM_0006984.4): c.322_329delGGCTCCGA, p.Gly108fs*] leading to a premature truncation of the protein. Both parents were heterozygous carriers. Hypohidrosis, ichthyosis, and plantar keratosis associated with alacrima and xerostomia should raise suspicion for HELIX syndrome, which also includes nephropathy and electrolyte disturbances in adults. Given the potential for ED misdiagnosis in infancy, it is important to include the CLDN10 gene in a specific genodermatosis next-generation sequencing (NGS) panel to provide early diagnosis, accurate management, and genetic counseling.


Assuntos
Claudinas , Humanos , Masculino , Claudinas/genética , Adulto , Ictiose/genética , Ictiose/patologia , Hipo-Hidrose/genética , Displasia Ectodérmica/genética , Displasia Ectodérmica/patologia , Linhagem , Fenótipo
20.
Mult Scler Relat Disord ; 88: 105732, 2024 Jun 17.
Artigo em Inglês | MEDLINE | ID: mdl-38936324

RESUMO

BACKGROUND: The treatment landscape for neuromyelitis optica spectrum disorder (NMOSD) has changed in recent years with the approval of therapies with different efficacy, safety and administration profiles. OBJECTIVE: The aim of this study was to assess neurologists' preferences for different NMOSD treatment attributes using conjoint analysis (CA). METHODS: We conducted an online, non-interventional, cross-sectional study in collaboration with the Spanish Society of Neurology. Our CA assessed five drugs' attributes: prevention of relapse, prevention of disability accumulation, safety risk, management during pregnancy, and route and frequency of administration. Participants were presented with eight hypothetical treatment scenarios to rank based on their preferences from the most preferred to the least. An ordinary least squares method was selected to estimate weighted preferences. RESULTS: A total of 104 neurologists were included. Mean age (standard deviation-SD) was 37.7 (10.3) years, 52.9 % were male, and median time (interquartile range) of experience managing NMOSD was 5.0 (2.9, 10.8) years. Neurologists placed the greatest importance on efficacy attributes, time to relapse (44.1 %) being the most important, followed by preventing disability accumulation (36.8 %). In contrast, route and frequency of administration (4.6 %) was the least important characteristic. Participants who prioritised efficacy attributes felt more comfortable in decision-making, had fewer past experiences of care-related regret and a lower attitude to risk taking than their counterparts. CONCLUSION: Neurologists' treatment preferences in NMOSD were mainly driven by efficacy attributes. These results may be useful to design policy decisions and treatment guidelines for this condition.

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