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Repetitive behaviours are common manifestations of frontotemporal dementia (FTD). Patients with FTD exhibit various types of repetitive behaviours with unique behavioural and cognitive substrates, including compulsivity, lack of impulse control, stereotypy and hoarding. Other sources of repetitive behaviours, such as restrictive interests and insistence on sameness, may also be seen in FTD. Although repetitive behaviours are highly prevalent and potentially discriminatory in this population, their expression varies widely between patients, and the field lacks consensus about the classification of these behaviours. Terms used to describe repetitive behaviours in FTD are highly heterogeneous and may lack precise definitions. This lack of harmonization of the definitions for distinct forms of repetitive behaviour limits the ability to differentiate between pathological behaviours and impedes understanding of their underlying mechanisms. This review examines established definitions of well-characterized repetitive behaviours in other neuropsychiatric disorders and proposes operational definitions applicable to patients with FTD. Building on extant models of repetitive behaviours in non-human and lesion work and models of social behavioural changes in FTD, we describe the potential neurocognitive bases for the emergence of different types of repetitive behaviours in FTD and their potential perpetuation by a predisposition towards habit formation. Finally, examples of distinct therapeutic approaches for different forms of repetitive behaviours are highlighted, along with future directions to accurately classify, measure and treat these symptoms when they impair quality of life.
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Demência Frontotemporal , Doença de Pick , Humanos , Demência Frontotemporal/diagnóstico , Qualidade de Vida , Comportamento Compulsivo , CogniçãoRESUMO
French Guiana, located in the Guiana Shield, is a natural reservoir for many zoonotic pathogens that are of considerable medical or veterinary importance. Until now, there has been limited data available on the description of parasites circulating in this area, especially on protozoan belonging to the phylum Apicomplexa; conversely, the neighbouring countries describe a high parasitic prevalence in animals and humans. Epidemiological surveillance is necessary, as new potentially virulent strains may emerge from these forest ecosystems, such as Amazonian toxoplasmosis. However, there is no standard tool for detecting protozoa in wildlife. In this study, we developed Meat-Borne-Parasite, a high-throughput meta-barcoding workflow for detecting Apicomplexa based on the Oxford Nanopore Technologies sequencing platform using the 18S gene of 14 Apicomplexa positive samples collected in French Guiana. Sequencing reads were then analysed with MetONTIIME pipeline. Thanks to a scoring rule, we were able to classify 10 samples out of 14 as Apicomplexa positive and reveal the presence of co-carriages. The same samples were also sequenced with the Illumina platform for validation purposes. For samples identified as Apicomplexa positive by both platforms, a strong positive correlation at up to the genus level was reported. Overall, the presented workflow represents a reliable method for Apicomplexa detection, which may pave the way for more comprehensive biomonitoring of zoonotic pathogens.
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PURPOSE: Liver cancer incidence among American Indians/Alaska Natives has risen over the past 20 years. Peripheral blood DNA methylation may be associated with liver cancer and could be used as a biomarker for cancer risk. We evaluated the association of blood DNA methylation with risk of liver cancer. METHODS: We conducted a prospective cohort study in 2324 American Indians, between age 45 and 75 years, from Arizona, Oklahoma, North Dakota and South Dakota who participated in the Strong Heart Study between 1989 and 1991. Liver cancer deaths (n = 21) were ascertained using death certificates obtained through 2017. The mean follow-up duration (SD) for non-cases was 25.1 (5.6) years and for cases, 11.0 (8.8) years. DNA methylation was assessed from blood samples collected at baseline using MethylationEPIC BeadChip 850 K arrays. We used Cox regression models adjusted for age, sex, center, body mass index, low-density lipoprotein cholesterol, smoking, alcohol consumption, and immune cell proportions to examine the associations. RESULTS: We identified 9 CpG sites associated with liver cancer. cg16057201 annotated to MRFAP1) was hypermethylated among cases vs. non-cases (hazard ratio (HR) for one standard deviation increase in methylation was 1.25 (95% CI 1.14, 1.37). The other eight CpGs were hypomethylated and the corresponding HRs (95% CI) ranged from 0.58 (0.44, 0.75) for cg04967787 (annotated to PPRC1) to 0.77 (0.67, 0.88) for cg08550308. We also assessed 7 differentially methylated CpG sites associated with liver cancer in previous studies. The adjusted HR for cg15079934 (annotated to LPS1) was 1.93 (95% CI 1.10, 3.39). CONCLUSIONS: Blood DNA methylation may be associated with liver cancer mortality and may be altered during the development of liver cancer.
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Indígenas Norte-Americanos , Neoplasias Hepáticas , Humanos , Pessoa de Meia-Idade , Idoso , Indígena Americano ou Nativo do Alasca , Metilação de DNA , Estudos Prospectivos , Indígenas Norte-Americanos/genética , Neoplasias Hepáticas/epidemiologia , Neoplasias Hepáticas/genéticaRESUMO
Thiopurines, an effective therapy for Crohn's disease (CD), often lead to adverse events (AEs). Gene polymorphisms affecting thiopurine metabolism may predict AEs. This retrospective study in CD patients (n = 114) with TPMT activity > 5 Units/Red Blood Cells analyzed TPMT (c.238 G > C, c.460 G > A, c.719 A > G), ITPA (c.94 C > A, IVS2 + 21 A > C), and NUDT15 (c.415 C > T) polymorphisms. All patients received azathioprine (median dose 2.2 mg/kg) with 41.2% experiencing AEs, mainly myelotoxicity (28.1%). No NUDT15 polymorphisms were found, 7% had TPMT, and 31.6% had ITPA polymorphisms. AEs led to therapy modifications in 41.2% of patients. Multivariate analysis identified advanced age (OR 1.046, p = 0.007) and ITPA IVS2 + 21 A > C (OR 3.622, p = 0.015) as independent predictors of AEs. IVS2 + 21 A > C was also associated with myelotoxicity (OR 2.863, p = 0.021). These findings suggest that ITPA IVS2 + 21 A > C polymorphism and advanced age predict AEs during thiopurine therapy for CD with intermediate-normal TPMT activity.
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Azatioprina , Doença de Crohn , Metiltransferases , Pirofosfatases , Humanos , Doença de Crohn/genética , Doença de Crohn/tratamento farmacológico , Pirofosfatases/genética , Feminino , Masculino , Adulto , Estudos Retrospectivos , Azatioprina/efeitos adversos , Azatioprina/uso terapêutico , Metiltransferases/genética , Pessoa de Meia-Idade , Adulto Jovem , Imunossupressores/efeitos adversos , Imunossupressores/uso terapêutico , Adolescente , Variantes Farmacogenômicos/genética , Polimorfismo de Nucleotídeo Único/genética , Polimorfismo Genético/genética , Mercaptopurina/efeitos adversos , Mercaptopurina/uso terapêutico , Análise Multivariada , Idoso , Fatores de Risco , Nudix Hidrolases , Inosina TrifosfataseRESUMO
BACKGROUND: Parkinson's disease (PD) is the second most common neurodegenerative disease following Alzheimer's disease. Nearly 30 causative genes have been identified for PD and related disorders. However, most of these genes were identified in European-derived families, and little is known about their role in Latin American populations. OBJECTIVES: Our goal was to assess the spectrum and frequency of pathogenic variants in known PD genes in familial PD patients from Latin America. METHODS: We selected 335 PD patients with a family history of PD from the Latin American Research Consortium on the Genetics of PD. We capture-sequenced the coding regions of 26 genes related to neurodegenerative parkinsonism. Of the 335 PD patients, 324 had sufficient sequencing coverage to be analyzed. RESULTS: We identified pathogenic variants in 41 individuals (12.7%) in FBXO7, GCH1, LRRK2, PARK7, PINK1, PLA2G6, PRKN, SNCA, and TARDBP, GBA1 risk variants in 25 individuals (7.7%), and variants of uncertain significance in another 24 individuals (7.4%) in ATP13A2, ATP1A3, DNAJC13, DNAJC6, GBA1, LRKK2, PINK1, VPS13C, and VPS35. Of the 70 unique variants identified, 19 were more frequent in Latin Americans than in any other population. CONCLUSIONS: This is the first screening of known PD genes in a large cohort of patients with familial PD from Latin America. There were substantial differences in the spectrum of variants observed in comparison to previous findings from PD families of European origin. Our data provide further evidence that differences exist between the genetic architecture of PD in Latinos and European-derived populations. © 2024 The Author(s). Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.
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BACKGROUND: Epigenetic dysregulation has been proposed as a key mechanism for arsenic-related cardiovascular disease (CVD). We evaluated differentially methylated positions (DMPs) as potential mediators on the association between arsenic and CVD. METHODS: Blood DNA methylation was measured in 2321 participants (mean age 56.2, 58.6% women) of the Strong Heart Study, a prospective cohort of American Indians. Urinary arsenic species were measured using high-performance liquid chromatography coupled to inductively coupled plasma mass spectrometry. We identified DMPs that are potential mediators between arsenic and CVD. In a cross-species analysis, we compared those DMPs with differential liver DNA methylation following early-life arsenic exposure in the apoE knockout (apoE-/-) mouse model of atherosclerosis. RESULTS: A total of 20 and 13 DMPs were potential mediators for CVD incidence and mortality, respectively, several of them annotated to genes related to diabetes. Eleven of these DMPs were similarly associated with incident CVD in 3 diverse prospective cohorts (Framingham Heart Study, Women's Health Initiative, and Multi-Ethnic Study of Atherosclerosis). In the mouse model, differentially methylated regions in 20 of those genes and DMPs in 10 genes were associated with arsenic. CONCLUSIONS: Differential DNA methylation might be part of the biological link between arsenic and CVD. The gene functions suggest that diabetes might represent a relevant mechanism for arsenic-related cardiovascular risk in populations with a high burden of diabetes.
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Arsênio , Aterosclerose , Doenças Cardiovasculares , Animais , Apolipoproteínas E , Arsênio/toxicidade , Aterosclerose/induzido quimicamente , Aterosclerose/genética , Doenças Cardiovasculares/induzido quimicamente , Doenças Cardiovasculares/genética , Metilação de DNA , Feminino , Humanos , Masculino , Camundongos , Pessoa de Meia-Idade , Estudos ProspectivosRESUMO
BACKGROUND: The role of sodium-glucose cotransporter 2 inhibitors (SGLT2i) in the management glomerular/systemic autoimmune diseases with proteinuria in real-world clinical settings is unclear. METHODS: This is a retrospective, observational, international cohort study. Adult patients with biopsy-proven glomerular diseases were included. The main outcome was the percentage reduction in 24-h proteinuria from SGLT2i initiation to 3, 6, 9 and 12 months. Secondary outcomes included percentage change in estimated glomerular filtration rate (eGFR), proteinuria reduction by type of disease and reduction of proteinuria ≥30% from SGLT2i initiation. RESULTS: Four-hundred and ninety-three patients with a median age of 55 years and background therapy with renin-angiotensin system blockers were included. Proteinuria from baseline changed by -35%, -41%, -45% and -48% at 3, 6, 9 and 12 months after SGLT2i initiation, while eGFR changed by -6%, -3%, -8% and -10.5% at 3, 6, 9 and 12 months, respectively. Results were similar irrespective of the underlying disease. A correlation was found between body mass index (BMI) and percentage proteinuria reduction at last follow-up. By mixed-effects logistic regression model, serum albumin at SGLT2i initiation emerged as a predictor of ≥30% proteinuria reduction (odds ratio for albumin <3.5 g/dL, 0.53; 95% CI 0.30-0.91; P = .02). A slower eGFR decline was observed in patients achieving a ≥30% proteinuria reduction: -3.7 versus -5.3 mL/min/1.73 m2/year (P = .001). The overall tolerance to SGLT2i was good. CONCLUSIONS: The use of SGLT2i was associated with a significant reduction of proteinuria. This percentage change is greater in patients with higher BMI. Higher serum albumin at SGLT2i onset is associated with higher probability of achieving a ≥30% proteinuria reduction.
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Diabetes Mellitus Tipo 2 , Glomerulonefrite , Nefropatias , Adulto , Humanos , Pessoa de Meia-Idade , Estudos de Coortes , Nefropatias/complicações , Glomerulonefrite/tratamento farmacológico , Glomerulonefrite/complicações , Proteinúria/etiologia , Proteinúria/complicações , Albumina Sérica , Sódio , Glucose , Diabetes Mellitus Tipo 2/complicaçõesRESUMO
PURPOSE: We aimed to estimate the absolute (incidence) and relative (hazard ratio; HR) risk of agranulocytosis associated with metamizole in comparison with non-steroidal antiinflammatory drugs (NSAIDs). METHODS: A cohort study of new users of metamizole versus NSAIDs was performed with BIFAP (Pharmacoepidemiologic Research Database in Public Health Systems; Spain). Patients aged ≥ 2 years in 2005-2022 were followed up from the day after their first metamizole or NSAID dispensation till the end of the treatment period to identify patients hospitalized due to idiosyncratic agranulocytosis. Incidence rate (IR) and adjusted HR of agranulocytosis with metamizole versus NSAID were estimated assuming the onset date of agranulocytosis was the date of hospitalization sensitivity analysis or 7 days before (main analysis). In secondary analyses, we used (1) opioids-paracetamol as negative control and (2) any hospitalized neutropenia as outcome (assuming the onset was 7 days before). RESULTS: The cohorts included 444,972 new users of metamizole, 3,814,367 NSAID, and 3,129,221 opioids-paracetamol on continuous treatment during a median of 37-40 days. Overall, 26 hospitalized agranulocytosis occurred, 5 in the first week (and so removed in main analysis) and 21 thereafter. IR of agranulocytosis was 14.20 (N = 5 cases) and 8.52 (N = 3), 1.95 (N = 6) and 1.62 (N = 5), and 4.29 (N = 15) and 3.72 (N = 13)/107 person-weeks of continuous treatment using the date of hospitalization or 7 days before, respectively. Two, 0 and 2 of cases identified in both analyses had neoplasia in every cohort, respectively. HR of agranulocytosis associated with metamizole was 7.20 [95% CI: 1.92-26.99] and 4.40 [0.90-21.57] versus NSAID, and 3.31 [1.17-9.34] and 2.45 [0.68-8.83] versus opioid-paracetamol, respectively. HR of neutropenia with metamizole was 2.98 [1.57-5.65] versus NSAID. CONCLUSIONS: Agranulocytosis was very rare but more common (above 4 times more) with metamizole than other analgesics. The impact of the drug-induced agranulocytosis was less precise with metamizole than the comparators due to its lower use, which precluded to find statistical differences in main analysis. The increased risk of hospitalized neutropenias with metamizole supports the link with its severity although triggers unavailable during the follow-up (ex. cytotoxic medication) can not be discarded.
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BACKGROUND: It has been suggested that maternal satisfaction should be included as an additional and appropriate outcome indicator in relation to the breastfeeding process. The aim of this study was to analyze the psychometric properties of various existing versions of the Maternal Breastfeeding Evaluation Scale in a Spanish sample. METHODS: This was a longitudinal observational study, evaluated at three different time points: in the hospital after delivery, and then at five and 12 months after delivery in a Spanish sample. A total of 690 mother participated in this study. RESULTS: Confirmatory factor analysis results indicated an improved fit of the data to the original model (CFI = 0.984; TLI = 0.982; RMSEA = 0.079). All dimensions of the Maternal Breastfeeding Evaluation Scale are positively associated with breastfeeding rates and negatively associated with perceived difficulty in continuing to breastfeed after returning to work at five months postpartum. Moreover, the scale can predict breastfeeding behavior at 12 months postpartum. CONCLUSIONS: The results of this study indicate that the structure of the original version of the Maternal Breastfeeding Evaluation Scale mean it is a is valid and reliable tool for assessing maternal perceptions of the breastfeeding experience in Spain. This research enhances our understanding of maternal satisfaction with the breastfeeding experience and its potential implications for supporting breastfeeding practices. It is an opportunity for the academic, healthcare, and policy sectors to develop more effective interventions to improve breastfeeding rates and ensure a positive experience for mothers.
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Aleitamento Materno , Mães , Psicometria , Humanos , Aleitamento Materno/psicologia , Feminino , Adulto , Análise Fatorial , Estudos Longitudinais , Espanha , Mães/psicologia , Inquéritos e Questionários/normas , Reprodutibilidade dos Testes , Adulto Jovem , Período Pós-Parto/psicologiaRESUMO
Parental feeding practices and behaviours are closely related to a number of child outcomes, including eating behaviour and health. The Toddler Feeding Style Questionnaire (TFSQ) was developed to provide an accurate instrument for evaluating parental feeding practices for toddlers by assessing two dimensions: responsiveness and demandingness. As the initial validation study was conducted in a sample of mothers only, the aims of this study are: a) to validate the TFSQ in fathers, b) to analyse its measurement invariance as a function of gender and parenting experience and c) to explore associations between socio-demographic variables and both dimensions. The TFSQ was completed by 377 fathers and 583 mothers. CFA confirmed the two-factor structure within the same items as the initial validation study, with good model fit indices (X2=230.089; TLI=0.883; CFI=0.91; RMSEA=0.08 (90% CI 0.068-0.092), SRMR=0.070). Strict invariance measurement in terms of gender and parenting experience was achieved. Overall, fathers scored higher than mothers on demandingness, regardless of their parenting experience. Primiparous mothers scored higher than multiparous mothers and primiparous fathers on the responsiveness dimension. However, there were no gender-based differences on this dimension for parents with more than one child. These results confirm that the TFSQ is an adequate and validated instrument for assessing parenting dimensions, as it performs equally well for mothers and fathers, regardless of their parenting experience. There is also support for the notion that parental attitudes to feeding may be related to their socio-economic background.
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AIM: To identify scales that assess parental stress in the paediatric clinical population and to analyse their psychometric properties. METHODS: Four electronic databases (PubMed, Web of Science, PsycINFO, and Scopus) and metasearch engines (Google Scholar and Open Grey) were searched with no time period limitations. Methodological quality was assessed using the COnsensus-based Standards for the selection of health Measurement INstruments (COSMIN) and quality of evidence using the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) approach modified by COSMIN. Finally, recommendations were made for the instruments with the highest quality of evidence. RESULTS: A total of 38 studies reporting on 11 different instruments for assessing parental stress in the paediatric clinical setting were included. Six instruments were 'A' rated (recommended) in the final phase in line with COSMIN guidelines. The Paediatric Inventory for Parents was the instrument that evaluated the highest number of psychometric properties and obtained the highest methodological quality, global assessment, and quality of evidence for the different psychometric properties. CONCLUSIONS: This systematic review provides an overview of the measurement properties of the parental stress instruments used in the paediatric clinical setting. The Paediatric Inventory for Parents stands out as being one of the most robust instruments for measuring stress in parents with a hospitalised or sick child. Evidence needs to be generated for all the parental stress scales used in the clinical setting. IMPACT: Given that the psychometric properties of the existing parental stress scales used in paediatric health care settings have not been systematically assessed, the present review utilised comprehensive methods according to COSMIN. NO PATIENT OR PUBLIC CONTRIBUTION: REPORTING METHOD: PRISMA statement and COSMIN reporting guidelines for studies on measurement properties of patient-reported outcome measures.
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Atenção à Saúde , Medidas de Resultados Relatados pelo Paciente , Humanos , Criança , Psicometria , Consenso , Bases de Dados Factuais , Reprodutibilidade dos TestesRESUMO
OBJECTIVES: To explore the rate of NUPs and associated factors in the PED of the 'Hospital Universitario y Politécnico La Fe' in Valencia (Spain) using Andersen's Behavioural Model. METHODS: We conducted a descriptive cross-sectional study using Andersen's Behavioural Model in parents visiting the PED with their children at the 'Hospital Universitario y Politécnico La Fe' in Valencia (Spain). RESULTS: The study involved a total of 530 participants, of whom 419 (79%) had made an NUP. The predisposing factors identified were: (I) paediatric patients brought in by their fathers (OR = 0.460; p = 0.005), (II) lower educational attainment (OR = 3.841; p = 0.000), (III) first-time parenthood (OR = 2.335; p = 0.000) and (IV) higher parental stress (OR = 1.974; p = 0.023). The enabling factors included: (I) responsibility for a significant part of the childcare shared with others (OR = 0.348; p = 0.041) and (II) the perception that PEDs provide better care than primary care (PC) services (OR = 1.628; p = 0.005). The need factors were: (I) existing chronic illness in the child seeking care (OR = 0.343; p = 0.000) and (II) the perceived severity of the urgency (OR = 0.440; p = 0.031). CONCLUSIONS: The NUP rates found in this study are similar to those found internationally. In accordance with Andersen's Behavioural Model, we identify predisposing, enabling and need factors to explain the multifactorial nature of NUPs in PEDs. IMPLICATIONS FOR PRACTICE: Identifying the factors associated with NUPs enables interventions to be targeted at those groups most likely to engage in NUPs, thereby optimising the functioning of the PED and improving the well-being of children and families. These interventions should focus on improving parental health literacy, providing education on making appropriate decisions about accessing health services and recognising severe symptoms in children, as well as improving access to high-quality PC services. Providing support to parents during the transition to parenthood would also be beneficial. REPORTING METHOD: This paper adheres to the STROBE initiative guidelines. CONTRIBUTION FROM PATIENTS OR MEMBERS OF THE PUBLIC: Participants, who voluntarily agreed to take part, contributed to the study by completing a paper-based questionnaire containing all the study variables as prepared by the research team.
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Serviço Hospitalar de Emergência , Humanos , Estudos Transversais , Masculino , Feminino , Serviço Hospitalar de Emergência/estatística & dados numéricos , Espanha , Criança , Pré-Escolar , Pais/psicologia , Adulto , Lactente , Adolescente , Modelos PsicológicosRESUMO
Our aim was to develop an accurate, highly sensitive method for HBV genotype determination and detection of genotype mixtures. We examined the preS and 5' end of the HBV X gene (5X) regions of the HBV genome using next-generation sequencing (NGS). The 1852 haplotypes obtained were subjected to genotyping via the Distance-Based discrimination method (DB Rule) using two sets of 95 reference sequences of genotypes A-H. In clinical samples from 125 patients, the main genotypes were A, D, F and H in Caucasian, B and C in Asian and A and E in Sub-Saharan patients. Genotype mixtures were identified in 28 (22.40%) cases, and potential intergenotypic recombination was observed in 29 (23.20%) cases. Furthermore, we evaluated sequence conservation among haplotypes classified into genotypes A, C, D, and E by computing the information content. The preS haplotypes exhibited limited shared conserved regions, whereas the 5X haplotypes revealed two groups of conserved regions across the genotypes assessed. In conclusion, we developed an NGS-based HBV genotyping method utilizing the DB Rule for genotype classification. We identified two regions conserved across different genotypes at 5X, offering promising targets for RNA interference-based antiviral therapies.
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Genótipo , Haplótipos , Vírus da Hepatite B , Sequenciamento de Nucleotídeos em Larga Escala , Vírus da Hepatite B/genética , Humanos , Sequenciamento de Nucleotídeos em Larga Escala/métodos , Hepatite B/virologia , Hepatite B/genética , Técnicas de Genotipagem/métodos , Sequência Conservada , Coinfecção/virologia , Genoma Viral , Masculino , Feminino , Filogenia , DNA Viral/genética , AdultoRESUMO
The aims of this study were to: (a) determine the differences in external load quantification between arbitrary and individual speed thresholds over the weekly microcycle in professional soccer players, and (b) analyse the association between internal load and different external load quantification strategies (ELQSs). Ten professional outfield players were monitored during training sessions and official matches using 10 Hz GPS devices over a 6-week in-season period. The absolute and relative ("R" before the distance category) distances covered were calculated for the following external load variables: medium-intensity running distance (MIR), high-intensity running (HIR), sprint distance (SD), and very high-intensity running (VHIR). Individualized thresholds were determined based on maximal sprinting speed (MSS) and the last speed achieved during the 30-15 Intermittent Fitness Test (VIFT) of each player. In terms of match-day workload, significant differences (p < 0.05) were observed between arbitrary and individualized strategies (i.e., MSS and VIFT) for the distance covered in MIR, HIR, SD, VHIR, RHIR, RSD, and RVHIR. The MSS strategy compared to arbitrary thresholds revealed significant differences (p < 0.05) for distance covered in HIR, RHIR, and VHIR during all training sessions. The present results showed that arbitrary thresholds lead to underestimation of external load absolute and relative metrics compared to the MSS strategy throughout the microcycle. The VIFT strategy mainly revealed differences in external load quantification regarding MD compared to arbitrary thresholds. Individualized speed threshold strategies did not achieve better associations with internal load measures in comparison with arbitrary thresholds in professional soccer players.
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Materials are more easily damaged during accidents that involve rapid deformation. Here, a design strategy is described for electronic materials comprised of conducting polymers that defies this orthodox property, making their extensibility and toughness dynamically adaptive to deformation rates. This counterintuitive property is achieved through a morphology of interconnected nanoscopic core-shell micelles, where the chemical interactions are stronger within the shells than the cores. As a result, the interlinked shells retain material integrity under strain, while the rate of dissociation of the cores controls the extent of micelle elongation, which is a process that adapts to deformation rates. A prototype based on polyaniline shows a 7.5-fold increase in ultimate elongation and a 163-fold increase in toughness when deformed at increasing rates from 2.5 to 10 000% min-1 . This concept can be generalized to other conducting polymers and highly conductive composites to create "self-protective" soft electronic materials with enhanced durability under dynamic movement or deformation.
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To evaluate molecular assays for Mpox diagnosis available in various clinical microbiology services in Spain through a quality control (QC) approach. A total of 14 centers from across Spain participated in the study. The Reference Laboratory dispatched eight serum samples and eight nucleic acid extracts to each participating center. Some samples were spiked with Mpox or Vaccinia virus to mimic positive samples for Mpox or other orthopox viruses. Participating centers provided information on the results obtained, as well as the laboratory methods used. Among the 14 participating centers seven different commercial assays were employed, with the most commonly used kit being LightMix Modular Orthopox/Monkeypox (Mpox) Virus (Roche®). Of the 12 centers conducting Mpox determinations, concordance ranged from 62.5% (n = 1) to 100% (n = 11) for eluates and from 75.0% (n = 1) to 100% (n = 10) for serum. Among the 10 centers performing Orthopoxvirus determinations, a 100% concordance was observed for eluates, while for serum, concordance ranged from 87.5% (n = 6) to 100% (n = 4). Repeatedly, 6 different centers reported a false negative in serum samples for Orthopoxvirus diagnosis, particularly in a sample with borderline Ct = 39. Conversely, one center, using the TaqMan™ Mpox Virus Microbe Detection Assay (Thermo Fisher), reported false positives in Mpox diagnosis for samples spiked with vaccinia virus due to cross-reactions. We observed a positive correlation of various diagnostic assays for Mpox used by the participating centers with the reference values. Our results highlight the significance of standardization, validation, and ongoing QC in the microbiological diagnosis of infectious diseases, which might be particularly relevant for emerging viruses.
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Mpox , Orthopoxvirus , Humanos , Monkeypox virus/genética , Mpox/diagnóstico , Reação em Cadeia da Polimerase , Controle de Qualidade , Vaccinia virus/genética , DNARESUMO
BACKGROUND: Sex differences in Parkinson's disease (PD) risk are well-known. However, the role of sex chromosomes in the development and progression of PD is still unclear. OBJECTIVE: The objective of this study was to perform the first X-chromosome-wide association study for PD risk in a Latin American cohort. METHODS: We used data from three admixed cohorts: (1) Latin American Research consortium on the Genetics of Parkinson's Disease (n = 1504) as discover cohort, and (2) Latino cohort from International Parkinson Disease Genomics Consortium (n = 155) and (3) Bambui Aging cohort (n = 1442) as replication cohorts. We also developed an X-chromosome framework specifically designed for admixed populations. RESULTS: We identified eight linkage disequilibrium regions associated with PD. We replicated one of these regions (top variant rs525496; discovery odds ratio [95% confidence interval]: 0.60 [0.478-0.77], P = 3.13 × 10-5 replication odds ratio: 0.60 [0.37-0.98], P = 0.04). rs5525496 is associated with multiple expression quantitative trait loci in brain and non-brain tissues, including RAB9B, H2BFM, TSMB15B, and GLRA4, but colocalization analysis suggests that rs5525496 may not mediate risk by expression of these genes. We also replicated a previous X-chromosome-wide association study finding (rs28602900), showing that this variant is associated with PD in non-European populations. CONCLUSIONS: Our results reinforce the importance of including X-chromosome and diverse populations in genetic studies. © 2023 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.
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Cromossomos Humanos X , Doença de Parkinson , Feminino , Humanos , Masculino , Estudo de Associação Genômica Ampla , Hispânico ou Latino , América Latina , Doença de Parkinson/genética , Fatores Sexuais , Cromossomos Humanos X/genética , Desequilíbrio de Ligação/genéticaRESUMO
OBJECTIVE: A wide variety of neuropsychiatric symptoms are described during the acute phase of anti-N-methyl-d-aspartate receptor encephalitis (ANMDARE), including psychosis, mania, depression, and catatonia, but there are few reports on suicidal thought and behaviors in ANMDARE. To address this gap in the literature, the authors measured the presence of suicidal thoughts and behaviors among a large cohort of Mexican patients diagnosed with definite ANMDARE. METHODS: This observational and longitudinal study included patients with definite ANMDARE hospitalized at the National Institute of Neurology and Neurosurgery of Mexico between 2014 and 2021. Suicidal thoughts and behaviors were assessed before and after treatment by means of a clinical interview with relatives and a direct clinical assessment with each patient. Thoughts of engaging in suicide-related behavior and acts of suicidal and nonsuicidal self-directed violence before and during hospitalization were recorded. RESULTS: From a total sample of 120 patients who fulfilled the diagnostic criteria for definite ANMDARE, 15 patients (13%) had suicidal thoughts and behaviors during the acute phase of the disease. All 15 of these patients experienced psychosis and had suicidal ideation with intention. Three patients engaged in preparatory behaviors and seven carried out suicidal self-directed violence. Psychotic depression and impulsivity were more frequent among those patients with suicidal thoughts and behaviors than among those without any form of suicidality. Four patients engaged in self-directed violence during hospitalization. Remission was sustained in 14 of 15 patients, with suicidal ideation and self-directed violence persisting during follow-up in only one patient. CONCLUSIONS: Suicidal thoughts and behaviors are not uncommon during the acute phase of ANMDARE. On the basis of our sample, the persistence of these features after immunotherapy is rare but may be observed. A targeted assessment of suicidal risk should be strongly considered in this population.
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Erotomania (de Clérambault's syndrome) refers to the delusional belief that another person, usually socially unreachable, is in love with the holder of the delusion. The occurrence of erotomania in Frontotemporal Dementia has rarely been reported. We present the unique case of a 59-year-old woman with a strong family history of early-onset dementia in whom erotomania was the initial manifestation that led to a diagnosis of definite Behavioral Variant of Frontotemporal Dementia with a pathogenic missense mutation in the MAPT gene. Based on this case, we propose a hypothetical model for developing erotomania in patients with FTD.
Assuntos
Delusões , Demência Frontotemporal , Proteínas tau , Humanos , Demência Frontotemporal/genética , Demência Frontotemporal/psicologia , Pessoa de Meia-Idade , Feminino , Delusões/etiologia , Proteínas tau/genética , Amor , Mutação de Sentido IncorretoRESUMO
BACKGROUND: Hemodialysis (HD) techniques that best remove molecules in the middle to high molecular weight range are on-line hemodiafiltration (OL-HDF) and HD with medium cut-off (MCO) membranes. The aim of this study was to compare efficacy and safety of OL-HDF with FxCordiax HDF 800™, with HD with 2 MCO dialyzers: Theranova 500® and the new Elisio 21HX™ dialyzer. METHODS: Fourteen patients following treatment with OL-HDF using FxCordiax HDF 800™ were randomized to receive a consecutive 1-week HD treatment with Theranova 500® and Elisio 21HX™.The reduction rate (RR) of differently sized molecules was compared, as well as the variation rate in molecules smaller than 1000, detected by nuclear magnetic resonance based chemometrics (metabolomics). Albumin loss in dialysate was quantified. RESULTS: Lower RRs were found for molecules around 20 000 with Elisio 21HX™ compared to OL- HDF (RR prolactin 58.5% versus 66.7%, p = 0.034; RR Kappa light chain 63.1% versus 71.8%, p = 0.010). Albumin loss per session was higher with Theranova 500® than with OL-HDF and with Elisio 21HX™ (2249.9 ± 714.1 mg, 815.2 ± 474.0 mg, 442.9 ± 135.9 mg, p < 0.001, respectively). Metabolomic studies suggested, by semi-quantitative analysis, a greater depurative capacity of OL-HDF, followed by Elisio 21HX™, and then Theranova 500®. CONCLUSIONS: In this study, HD with Theranova 500® has proven to be very similar in efficacy to OL-HDF, although with a significantly higher albumin loss. HD with Elisio 21HX™ resulted in lower removal of molecules around 20 000 compared to OL-HDF, with no significant difference compared to Theranova 500®, and with less albumin loss than Theranova 500®.