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1.
J Affect Disord Rep ; 162024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38737194

RESUMO

Background: Family caregivers of persons living with dementia often experience increased depression and suicidal ideation (SI). However, the feasibility and impact of therapies on caregiver SI has remained largely unexplored. Mentalizing imagery therapy (MIT) helps reduce psychological symptoms through mindfulness and guided imagery. This pilot study examined the feasibility of participation by caregivers with SI in a randomized controlled trial (RCT) of MIT versus a psychosocial support group (SG), and the respective impact of group on SI, depression, and secondary outcomes. Methods: A secondary analysis of data from an RCT of 4-week MIT or SG for caregivers (n = 46) was performed, identifying SI (n = 23) and non-SI (n = 23) cohorts. Group attendance and home practice were compared between cohorts. In the SI cohort (total n = 23, MIT n = 11, SG n = 12), group differences in SI, depression, and secondary outcomes were evaluated post-group and at 4-month follow-up. Results: Attendance in both groups and home practice in MIT were similar between SI and non-SI cohorts. In the SI cohort, MIT evinced greater improvements relative to SG in SI (p=.02) and depression (p=.02) post-group, and other secondary outcomes at follow-up. Limitations: Limitations include small sample size and single-item assessments of SI from validated depression rating scales. Conclusions: Participation in an RCT was feasible for caregivers with SI. MIT resulted in important benefits for SI and depression, while SG showed no acute SI benefit. The role of MIT in improving SI should be confirmed with adequately powered trials, as effective therapies to address caregiver SI are critical.

2.
Artigo em Inglês | MEDLINE | ID: mdl-38736284

RESUMO

OBJECTIVE: To compare the maternal-fetal/neonatal outcome in patients with systemic lupus erythematosus (SLE) with and without lupus nephritis (LN) in remission or with active disease. METHODS: A prospective cohort of pregnant patients with SLE (ACR 1997 criteria) was studied from January 2009 to December 2021. Demographic, clinical, biochemical, and immunological variables as well as the usual maternal-fetal/neonatal complications were recorded. We compared four groups according to the status of SLE during pregnancy: patients with quiescent SLE without lupus nephritis, patients with active SLE without lupus nephritis, patients with quiescent lupus nephritis, and patients with active lupus nephritis. Statistical analysis included descriptive statistics, bivariate analysis, and Cox regression analysis. RESULTS: A total of 439 pregnancies were studied, with a median age of 28 ± 6, SLE duration of 60 months (interquartile range 36-120). A higher frequency of maternal and fetal/neonatal complications was observed in patients with active SLE with or without lupus nephritis. Multivariate analysis showed that active LN was a risk factor for gestational hypertension (hazard ratios [HR] 1.95; 95% confidence intervals [CI]: 1.01-6.39), premature rupture of membranes (HR 3.56; 95% CI: 1.79-16.05) and more frequent cesarean section (HR 1.82; 95% CI: 1.13-2.94). CONCLUSION: LN is associated with a higher frequency of maternal complications, especially in those patients with active disease during pregnancy, and those maternal complications had an impact on poor fetal/neonatal outcomes. Strict control and timely care of LN could improve the obstetric prognosis.

3.
Emerg Microbes Infect ; : 2348521, 2024 Apr 30.
Artigo em Inglês | MEDLINE | ID: mdl-38686548

RESUMO

AbstractA free-range organic broiler (Gallus gallus domesticus) premises in Staffordshire was infected by high pathogenicity avian influenza virus (HPAIV) H5N8 during the 2020-2021 epizootic in the United Kingdom (UK). Following initial confirmation of the infection in poultry, multiple wild bird species were seen scavenging on chicken carcasses. Detected dead wild birds were subsequently demonstrated to have been infected and succumbed to HPAIV H5N8. Initially, scavenging species, magpie (Pica pica) and raven (Corvus corax), were found dead on the premises but over the following days, buzzards (Buteo buteo) were also found dead within the local area with positive detection of HPAIV in submitted carcasses. The subacute nature of microscopic lesions within a buzzard was consistent with the timeframe of infection. Finally, a considerable number of free-living pheasants (Phasianus colchicus) were also found dead in the surrounding area, with carcasses having higher viral antigen loads compared to infected chickens. Limited virus dissemination was observed in the carcasses of the magpie, raven and buzzard. Further, an avirulent avian paramyxovirus type 1 (APMV-1) was detected within poultry samples as well as in the viscera of a magpie infected with HPAIV. Immunohistochemistry did not reveal colocalization of avian paramyxovirus antigens with lesions, supporting an avirulent APMV-1 infection. Overall, this case highlights scenarios in which bi-directional transmission of avian viral diseases between commercial and wild bird species may occur. It also underlines the importance of bio separation and reduced access when infection pressure from HPAIV is high.

4.
Dent J (Basel) ; 12(4)2024 Apr 18.
Artigo em Inglês | MEDLINE | ID: mdl-38668025

RESUMO

The microbial compositions from concurrent peri-implant and periodontal lesions were compared, since the results reported in the literature on the etiological relationship between these oral pathologies are contradictory. Microbial compositions from nine patients were evaluated using Illumina MiSeq sequencing of 16S rRNA gene amplicons and Principal Components Analysis. Comparisons between the use of curettes or paper points as collection methods and between bacterial composition in both pathologies were performed. Paper points allowed the recovery of a higher number of bacterial genera. A higher bacterial diversity was found in peri-implantitis compared to periodontal samples from the same patient, while a greater number of operational taxonomic units (OTUs) were present in the corresponding periodontal samples. A higher abundance of oral pathogens, such as Porphyromonas or Treponema, was found in peri-implantitis sites. The opposite trend was observed for Aggregatibacter abundance, which was higher in periodontal than in peri-implantitis lesions, suggesting that both oral pathologies could be considered different but related diseases. Although the analysis of a higher number of samples would be needed, the differences regarding the microbial composition provide a basis for further understating the pathogenesis of peri-implant infections.

5.
Rev Argent Microbiol ; 2024 Apr 16.
Artigo em Espanhol | MEDLINE | ID: mdl-38632019

RESUMO

Free-living amoebae (FLA) of the genus Acanthamoeba are ubiquitous and amphizoic protozoa that colonize aquatic and terrestrial habitats and can serve as reservoirs for other microorganisms. They are considered econoses that can cause severe and rare pathologies. Due to limited epidemiological data available, the objective of this study was to investigate the presence of Acanthamoeba in coastal wetlands of the southeast of Buenos Aires province and evaluate their association with bacteriological and environmental variables. From February 2021 to July 2022, 22 seawater samples were collected at different points along the coast of the city of Mar del Plata (Buenos Aires, Argentina). Environmental parameters were determined and physicochemical and bacteriological studies, morphological identification, cultures and molecular typification were conducted. Regardless of the environmental and bacteriological variables, the presence of Acanthamoeba spp. was molecularly confirmed in 54.54% of the samples, being the first report of these protozoa in seawater in Argentina.

6.
Front Psychol ; 15: 1335168, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38586293

RESUMO

This bibliometric study scrutinizes the corpus of scientific output within the Web of Science pertaining to familial satisfaction among parents raising children with intellectual disabilities, focusing specifically on the milieu of educational inclusion. The analysis discerns a discernible ascension in scholarly interest in this domain, encapsulating 77 papers emanating from 75 journals, incorporating an aggregate of 3,497 cited references. Our investigation delineated 354 researchers across 39 nations, underscoring the transnational purview of this scholarly endeavor. The United States emerged as the pre-eminent contributor, with Canada and the United Kingdom following suit. Collaboration on an international scale was notably led by the US, with the UK and Australia trailing in tandem. Prominent institutions were identified for their scholarly output; the University of Kansas led with four papers, followed closely by Monash University, University of California Los Angeles, and University of California Riverside, each contributing three papers. Of particular note, the University of Kansas accrued 250 global citations (TGCS). A total of 75 journals were encompassed in this study. The Journal of Intellectual Disability Research emerged as the vanguard with four published papers, closely trailed by Child Care Health and Development and Exceptional Children. Notably, the latter boasted the highest impact factor (JCR = 4.09; Q1). In summation, this review proffers a meticulous and expansive overview of extant scholarship concerning the experiences of families rearing children with disabilities within the inclusive education framework.

7.
J Diabetes Complications ; 38(5): 108742, 2024 05.
Artigo em Inglês | MEDLINE | ID: mdl-38581842

RESUMO

AIMS: To compare the efficacy and safety of basal-plus (BP) insulin regimen with or without sitagliptin in non-critically ill patients with type 2 diabetes (T2D). METHODS: This open-label, randomized clinical trial included inpatients with a previous diagnosis of T2D and blood glucose (BG) between 180 and 400 mg/dL. Participants received basal and correctional insulin doses (BP regimen) either with or without sitagliptin. The primary outcome was the difference in the mean daily BG among the groups. RESULTS: Seventy-six patients (mean age 60 years, 64 % men) were randomized. Compared with BP insulin therapy alone, the sitagliptin-BP combination led to a lower mean daily BG (158.8 vs 175.0 mg/dL, P = 0.014), a higher percentage of readings within a BG range of 70-180 mg/dL (75.9 % vs 64.7 %, P < 0.001), and a lower number of BG readings >180 mg/dL (P < 0.001). Sitagliptin-BP resulted in fewer basal and supplementary insulin doses (P = 0.024 and P = 0.017, respectively) and lower daily insulin injections (P = 0.023) than those with insulin alone. The proportion of patients with hypoglycemia was similar in the two groups. CONCLUSIONS: For inpatients with T2D and hyperglycemia, the sitagliptin and BP regimen combination is safe and more effective than insulin therapy alone. CLINICALTRIALS: gov identifier: NCT05579119.


Assuntos
Glicemia , Diabetes Mellitus Tipo 2 , Quimioterapia Combinada , Hipoglicemiantes , Fosfato de Sitagliptina , Humanos , Fosfato de Sitagliptina/administração & dosagem , Fosfato de Sitagliptina/uso terapêutico , Fosfato de Sitagliptina/efeitos adversos , Diabetes Mellitus Tipo 2/tratamento farmacológico , Diabetes Mellitus Tipo 2/sangue , Masculino , Pessoa de Meia-Idade , Feminino , Idoso , Hipoglicemiantes/administração & dosagem , Hipoglicemiantes/efeitos adversos , Hipoglicemiantes/uso terapêutico , Glicemia/efeitos dos fármacos , Glicemia/análise , Glicemia/metabolismo , Insulina/administração & dosagem , Insulina/efeitos adversos , Insulina/uso terapêutico , Hospitalização/estatística & dados numéricos , Resultado do Tratamento , Hipoglicemia/induzido quimicamente , Hipoglicemia/epidemiologia
8.
Am J Med ; 2024 Mar 14.
Artigo em Inglês | MEDLINE | ID: mdl-38490305

RESUMO

BACKGROUND: Heart rate variability, a marker of autonomic function, has shown promising prognostic results in specific populations, but has not been tested in a general medical population. We hypothesized that heart rate variability identifies high-risk medical patients early after admission to the hospital. METHODS: This was a single-center prospective cohort study of acutely admitted medical patients aged ≥18 years with a life expectancy ≥3 months, included between 2019-2023. Unstable patients needing direct admission to the intensive care unit were excluded. Heart rate variability was recorded within 24 hours of admission for 10 minutes. The standard deviation of normal-normal beats (SDNN) was the primary heart rate variability marker. Low SDNN was defined as the lowest tertile (≤22 ms). The primary outcome was 30-day all-cause mortality. The secondary outcome was 30-day readmission or mortality. RESULTS: Among 721 patients included, low SDNN carried an 8-fold greater risk of 30-day mortality in univariate analysis (hazard ratio [HR] 8.3; P = .001); in multivariate analyses a 4-fold greater risk (HR 3.8; P = .037). Low SDNN was associated with the combined outcome of 30-day mortality or readmission (HR 1.5; P = .03) in multivariate analysis. In receiver operating characteristics analyses, low SDNN improved the predictive accuracy of early warning score for 30-day mortality or readmission from 0.63 to 0.71 (P = .008) but did not improve the accuracy for 30-day mortality alone. CONCLUSIONS: In patients admitted due to acute medical illness, low heart rate variability predicted 30-day mortality and readmission, suggesting heart rate variability as a tool to identify patients at high and low risk of relevant endpoints.

9.
J Clin Med ; 13(6)2024 Mar 14.
Artigo em Inglês | MEDLINE | ID: mdl-38541894

RESUMO

Background: The objective of this study was to evaluate the pain and inflammatory response in soft tissues using healing and prosthetic abutments of different diameters and lengths. Methods: The study population was rehabilitated with Astra Tech EV single implants (Dentsply Sirona, Atlantis, Dentsply Sirona S.A., Barcelona, Spain) of 4.2 and 4.8 millimetres in diameter in the upper and lower maxilla and loaded with custom abutments digitally designed using Dentsply Sirona's Virtual Atlantis Design software (Atlantis WebOrder, Dentsply Sirona S.A., Barcelona, Spain), version 4.6.5. The custom abutments had a larger diameter than the healing abutments to evaluate for biomarkers through ELISA. Results: Rehabilitations in the mandible and with healing abutments with diameters less than 4.29 mm and rehabilitators with diameters less than 2.18 mm elicited a higher pain and inflammatory response and, in turn, higher interleukin-1ß values. Conclusions: Greater inflammation was evident in cases in which healing abutments with reduced diameter were used compared to the same subsequent rehabilitation with prosthetic abutments with larger diameters.

10.
Saf Health Work ; 15(1): 80-86, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38496278

RESUMO

Background: The Work Ability Index (WAI) is an instrument that measures work ability. The wide dispersion of the WAI internationally has led to its adaptation for use in different countries. This study aimed to evaluate the psychometric properties of the Spanish version of the WAI. Methods: A methodological design was used over an opportunistic sample of 233 workers in the aeronautical industry in Spain. Reliability was evaluated through internal consistency. Factorial validity, known groups, and convergent validity were tested. Results: The Cronbach's alpha and item-total correlation indicated an adequate internal consistency. The confirmatory factor analysis, performed to evaluate the factorial validity, found adequate fit indices for a two-factor solution with a high correlation between the factors. Factor 1, "Subjectively estimated work ability and resources", was composed of 3 subscales and factor 2, "Ill-health-related", of 2 subscales. Subscales 4 and 6 had loading in both factors. Workers under 45 years of age obtained higher significant scores than older ones. Convergent validity was also evidenced since WAI was highly correlated with self-assessment of health status. Conclusions: The Spanish version of the WAI has shown evidence of reliability and validity in this study, supporting its use in individual and collective health surveillance by occupational health professionals. The factorial solution that was found has previously been reported in another international context. However, further research is needed to resolve the discrepancies detected in the role of some subscales between other national and international studies.

11.
Clin Exp Rheumatol ; 42(2): 367-376, 2024 02.
Artigo em Inglês | MEDLINE | ID: mdl-38488092

RESUMO

OBJECTIVES: To assess nailfold video capillaroscopic (NVC) abnormalities and their association with clinical features, myositis-specific autoantibodies (MSA), and myositis-associated antibodies (MAA) in a large multi-ethnic cohort of patients with idiopathic inflammatory myopathies (IIM). METHODS: We recruited 155 IIM patients from three centres in Mexico, Spain, and the USA. We evaluated the clinical and laboratory features of the patients and performed semiquantitative and quantitative analyses of the NVC. Each NVC study was defined as having a normal, non-specific, early systemic sclerosis (SSc), active SSc, or late SSc pattern. Twenty-three patients had at least one follow-up NVC when disease control was achieved. Quantitative variables were expressed as medians and interquartile range (IQR) and were compared with the Kruskal-Wallis, the Mann-Whitney U-test, and the Wilcoxon test for paired medians. Associations between qualitative variables were assessed with the χ2 test. RESULTS: Most patients were women (68.3%), Hispanic (73.5%), and had dermatomyositis (DM) (61.2%). Fourteen patients (9%) had a normal NVC. A non-specific abnormality pattern was the most frequent (53.9%), and was associated with joint involvement, interstitial lung disease, Jo1 autoantibodies, anti-synthetase syndrome, and immune-mediated necrotising myopathy. The SSc pattern was observed mostly in DM and overlap myositis and was associated with cutaneous features and anti-TIF-1g autoantibodies. After treatment, there was a decrease in the capillaroscopic score, the capillary diameter, and the number of avascular areas, and an increase in capillary density and bushy capillary number. CONCLUSIONS: NVC abnormalities are related to the diagnosis, clinical features, disease activity, and autoantibodies of patients with IIM.


Assuntos
Miosite , Escleroderma Sistêmico , Humanos , Feminino , Masculino , Angioscopia Microscópica , Unhas/irrigação sanguínea , Miosite/complicações , Capilares , Autoanticorpos , Escleroderma Sistêmico/diagnóstico
12.
Methods Cell Biol ; 185: 35-48, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38556450

RESUMO

Childhood cancer is a major cause of death in developed countries, and while treatments and survival rates have improved, long-term side effects remain a challenge. The genetic component of pediatric tumors and their aggressive progression, makes the study of childhood cancer a complex area of research. Here, we introduce the fruit fly Drosophila melanogaster as study model. We emphasize its numerous advantages, including binary gene expression systems that enable precise control over the timing and location of gene expression manipulation, the capacity to combine multiple genes associated with cancer or the testing of human cancer variants within a live, intact animal. As an illustrative example, we focus on the Drosophila cancer paradigm which involves medically relevant genes, the Notch and PI3K/Akt signaling pathways. We describe how this cancer paradigm allows assessing two critical aspects of tumorigenesis during juvenile stages: (1) viability (do animals with particular cancer mutations survive into adulthood?), and (2) tumor burden (what percentage of animals bearing the cancer mutations actually develop cancer and what is the extent of the tumor?). We highlight the potential of Drosophila as a molecular therapeutic tool for drug screening and drug repurposing of medicines already approved to treat other diseases in children, thereby accelerating the potential translation of results into humans. This preclinical animal model sustains huge potential and is cost-effective. It allows screening of thousands of compounds and genes at a relatively low cost and human efforts, opening innovative venues to explore more effective and safer treatments of childhood cancer.


Assuntos
Drosophila melanogaster , Neoplasias , Criança , Animais , Humanos , Drosophila melanogaster/genética , Drosophila melanogaster/metabolismo , Neoplasias/tratamento farmacológico , Neoplasias/genética , Neoplasias/patologia , Fosfatidilinositol 3-Quinases/metabolismo , Drosophila , Modelos Animais
13.
Ann Med Surg (Lond) ; 86(3): 1251-1260, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38463101

RESUMO

Objectives: This study aimed to analyze the Vaccine Adverse Event Reporting System (VAERS) database and systematically review the literature to provide a comprehensive analysis of reversible cerebral vasoconstriction syndrome (RCVS) and posterior reversible encephalopathy syndrome (PRES) secondary to vaccination. Methods: The authors analyzed the VAERS database and conducted a systematic review following PRISMA guidelines. The inclusion criteria for VAERS data were a score of ≥3 on the RCVS2 score and/or radiographic findings consistent with the diagnosis of RCVS or PRES. The systematic review was registered with PROSPERO. Results: Our combined data set included 29 cases (9 RCVS and 20 PRES). Most cases were women (72.4%) with a mean age of 50.7 years (SD 19.4 years). Most cases were associated with COVID-19 mRNA vaccines (58.6% Moderna, 20.7% Pfizer). Hypertension (37.9%), hyperlipidemia (13.7%), chronic kidney disease (CKD) (10.3%), and end-stage renal disease (6.8%) were common comorbidities. Furthermore, 20.6% (6/29) of cases were on immunosuppression therapy for various reasons. The mean time to symptom onset was 10.49 days after vaccination (SD 18.60), and the mean duration of hospitalization was 7.42 days (SD 5.94). The symptoms reported the most frequently were headache (41.3%), elevated blood pressure (31.0%), and emesis (17.2%). Typical radiographic findings included T2/FLAIR hyperintensities affecting the parieto-occipital lobes, indicative of vasogenic and/or cytotoxic edema. Conclusions: This study provides a comprehensive analysis of postvaccine RCVS and PRES. Both disease states were seen most often in those with pre-existing risk factors such as female sex, age over 50, hypertension, renal disease, and immunosuppression. Vaccines and their associated immune response may cause endothelial dysfunction leading to cerebral vasospasm and loss of cerebral autoregulation. However, further research is required to understand the underlying pathophysiological mechanisms. Despite the associations found, the absolute risk of these syndromes remains extremely low compared to the immense benefits of vaccination.

14.
medRxiv ; 2024 Feb 28.
Artigo em Inglês | MEDLINE | ID: mdl-38463998

RESUMO

The dynamics of SARS-CoV-2 transmission are influenced by a variety of factors, including social restrictions and the emergence of distinct variants. In this study, we delve into the origins and dissemination of the Alpha, Delta, and Omicron variants of concern in Galicia, northwest Spain. For this, we leveraged genomic data collected by the EPICOVIGAL Consortium and from the GISAID database, along with mobility information from other Spanish regions and foreign countries. Our analysis indicates that initial introductions during the Alpha phase were predominantly from other Spanish regions and France. However, as the pandemic progressed, introductions from Portugal and the USA became increasingly significant. Notably, Galicia's major coastal cities emerged as critical hubs for viral transmission, highlighting their role in sustaining and spreading the virus. This research emphasizes the critical role of regional connectivity in the spread of SARS-CoV-2 and offers essential insights for enhancing public health strategies and surveillance measures.

15.
Ann Med Surg (Lond) ; 86(2): 720-725, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-38333271

RESUMO

Objectives: To analyze the symptoms and severity of coronavirus disease 2019 (COVID-19) in people with multiple sclerosis (pwMS) on disease-modifying therapies using data from the COVID-19 in multiple sclerosis (MS) Global Data Sharing Initiative dataset. Methods: The open-access COVID-19 in MS Global Data Sharing Initiative dataset was obtained through credentialed access using PhysioNet. The variables analyzed included BMI, symptoms of COVID-19, age, current use of disease-modifying therapy (DMT), efficacy of DMT, comorbidities, hospitalization status, and type of MS. A linear regression analysis was completed. Data analysis and visualization were completed using STATA v15, R-Studio v1.1.447, Python v3.8, and its associated libraries, including NumPy, Pandas, and Matplotlib. Results: A total of 1141 participants were included in the analysis. 904 women and 237 men were diagnosed with MS. Among the pwMS included in the study; 208 (19.54%) had a suspected infection with COVID-19 and only 49 (5.25%) were confirmed. Any COVID-19 symptom was present in 360 individuals. The commonly reported DMT agents included dimethyl fumarate (12.71%) and fingolimod (10.17%). 101 in total (8.85%) reported not using any DMT. Factors associated with hospitalization and/or admission to the ICU included having any comorbidity (P=0.01), neuromuscular disorder (P=0.046), hypertension (P=0.005), chronic kidney disease (P<0.001), and immunodeficiency (P=0.003). The type of MS, the duration of the disease, and high-efficacy DMT therapy did not have a statistically significant influence on hospitalization. Conclusion: This study underscores the importance of comorbidities, especially neuromuscular disorders, hypertension, chronic kidney disease, and immunodeficiencies, as possible prognostic indicators for worse outcomes of COVID-19 in pwMS. On the contrary, the type of MS, the duration of the disease, and the efficacy of disease-modifying therapy did not significantly affect the severity of the symptoms of COVID-19 in this cohort.

16.
medRxiv ; 2024 Jan 17.
Artigo em Inglês | MEDLINE | ID: mdl-38313303

RESUMO

Objectives: Myositis is a heterogeneous family of autoimmune muscle diseases. As myositis autoantibodies recognize intracellular proteins, their role in disease pathogenesis has been unclear. This study aimed to determine whether myositis autoantibodies reach their autoantigen targets within muscle cells and disrupt the normal function of these proteins. Methods: Confocal immunofluorescence microscopy was used to localize antibodies and other proteins of interest in myositis muscle biopsies. Bulk RNA sequencing was used to study the transcriptomic profiles of 668 samples from patients with myositis, disease controls, and healthy controls. Antibodies from myositis patients were introduced into cultured myoblasts by electroporation and the transcriptomic profiles of the treated myoblasts were studied by bulk RNA sequencing. Results: In patients with myositis autoantibodies, antibodies accumulated inside myofibers in the same subcellular compartment as the autoantigen. Each autoantibody was associated with effects consistent with dysfunction of its autoantigen, such as the derepression of genes normally repressed by Mi2/NuRD in patients with anti-Mi2 autoantibodies, the accumulation of RNAs degraded by the nuclear RNA exosome complex in patients with anti-PM/Scl autoantibodies targeting this complex, and the accumulation of lipids within myofibers of anti-HMGCR-positive patients. Internalization of patient immunoglobulin into cultured myoblasts recapitulated the transcriptomic phenotypes observed in human disease, including the derepression of Mi2/NuRD-regulated genes in anti-Mi2-positive dermatomyositis and the increased expression of genes normally degraded by the nuclear RNA exosome complex in anti-PM/Scl-positive myositis. Conclusions: In myositis, autoantibodies are internalized into muscle fibers, disrupt the biological function of their autoantigen, and mediate the pathophysiology of the disease.

17.
Children (Basel) ; 11(2)2024 Feb 02.
Artigo em Inglês | MEDLINE | ID: mdl-38397294

RESUMO

(1) Introduction. An analysis was made of posterior crossbites in deciduous dentition and their relation to the type of feeding received by the child, with the objective of determining the influence of the way in which the child is fed in the early stages of life on the development of posterior crossbites. (2) Material and methods. A total of 1401 preschool children between 3 and 6 years of age from Seville (Spain) were included in the study. An intraoral exploration was carried out to assess the presence of crossbites (uni- or bilateral, and functional or not). The study was completed with a parent or legal guardian questionnaire exploring the type of feeding received by the child in the first stages of life, as well as the presence of bad oral habits and their duration. (3) Results. A total of 276 children (19.7%) presented posterior crossbite in occlusion. Uponn centering the midlines, 197 were maintained, indicating that 79 were due to premature contacts (functional crossbites). There were no significant differences in crossbites among the children who had received breastfeeding, though bottle-feeding was seen to favor crossbite. (4) Conclusions. No statistically significant relationship was found between posterior crossbites and breastfeeding, though an association between posterior crossbites and bottle-feeding was observed, with the number of crossbites increasing with the duration of bottle-feeding.

18.
Rev. clín. med. fam ; 17(1): 77-79, Feb. 2024. ilus
Artigo em Espanhol | IBECS | ID: ibc-230610

RESUMO

Presentamos el caso de un paciente que padeció una reacción cutánea intensa tras el contacto con los frutos y las hojas de una higuera y posterior exposición solar. Se trata de una reacción no inmunológica llamada fitofotodermatosis. Es una erupción inflamatoria de la piel que se produce tras el contacto con sustancias fototóxicas (furocumarinas o psoralenos) y que puede llegar a ser de gran intensidad. Por ello requiere una anamnesis exhaustiva y su conocimiento por parte del equipo médico de Atención Primaria y pediatría, ya que su diagnóstico diferencial puede ser muy complejo.(AU)


We report the case of a patient who developed an intense skin reaction after contact with the fruits and leaves of a fig tree and subsequent sun exposure. This is a non-immunological reaction called phytophotodermatosis. It is an inflammatory skin rash that occurs after contact with phototoxic substances (furocoumarins or psoralens) and could be very intense. That is why it requires an in-depth history; its knowledge by primary care physicians and paediatricians, is important because the differential diagnosis could be very complex.(AU)


Assuntos
Humanos , Masculino , Pessoa de Meia-Idade , Dermatopatias , Hipersensibilidade , Pele/lesões , Vesícula/diagnóstico por imagem , Dermatite Fototóxica , Pacientes Internados , Exame Físico , Atenção Primária à Saúde , Furocumarinas
19.
Acta Neuropathol ; 147(1): 19, 2024 Jan 19.
Artigo em Inglês | MEDLINE | ID: mdl-38240888

RESUMO

Myotonic dystrophy type 2 (DM2) is an autosomal-dominant multisystemic disease with a core manifestation of proximal muscle weakness, muscle atrophy, myotonia, and myalgia. The disease-causing CCTG tetranucleotide expansion within the CNBP gene on chromosome 3 leads to an RNA-dominated spliceopathy, which is currently untreatable. Research exploring the pathophysiological mechanisms in myotonic dystrophy type 1 has resulted in new insights into disease mechanisms and identified mitochondrial dysfunction as a promising therapeutic target. It remains unclear whether similar mechanisms underlie DM2 and, if so, whether these might also serve as potential therapeutic targets. In this cross-sectional study, we studied DM2 skeletal muscle biopsy specimens on proteomic, molecular, and morphological, including ultrastructural levels in two separate patient cohorts consisting of 8 (explorative cohort) and 40 (confirmatory cohort) patients. Seven muscle biopsy specimens from four female and three male DM2 patients underwent proteomic analysis and respiratory chain enzymology. We performed bulk RNA sequencing, immunoblotting of respiratory chain complexes, mitochondrial DNA copy number determination, and long-range PCR (LR-PCR) to study mitochondrial DNA deletions on six biopsies. Proteomic and transcriptomic analyses revealed a downregulation of essential mitochondrial proteins and their respective RNA transcripts, namely of subunits of respiratory chain complexes I, III, and IV (e.g., mt-CO1, mt-ND1, mt-CYB, NDUFB6) and associated translation factors (TACO1). Light microscopy showed mitochondrial abnormalities (e.g., an age-inappropriate amount of COX-deficient fibers, subsarcolemmal accumulation) in most biopsy specimens. Electron microscopy revealed widespread ultrastructural mitochondrial abnormalities, including dysmorphic mitochondria with paracrystalline inclusions. Immunofluorescence studies with co-localization of autophagy (p62, LC-3) and mitochondrial marker proteins (TOM20, COX-IV), as well as immunohistochemistry for mitophagy marker BNIP3 indicated impaired mitophagic flux. Immunoblotting and LR-PCR did not reveal significant differences between patients and controls. In contrast, mtDNA copy number measurement showed a reduction of mtDNA copy numbers in the patient group compared to controls. This first multi-level study of DM2 unravels thus far undescribed functional and structural mitochondrial abnormalities. However, the molecular link between the tetranucleotide expansion and mitochondrial dysfunction needs to be further elucidated.


Assuntos
Doenças Mitocondriais , Distrofia Miotônica , Humanos , Masculino , Feminino , Distrofia Miotônica/genética , Distrofia Miotônica/metabolismo , Distrofia Miotônica/patologia , Estudos Transversais , Proteômica , RNA , DNA Mitocondrial/genética , Doenças Mitocondriais/genética
20.
Cornea ; 43(5): 644-647, 2024 May 01.
Artigo em Inglês | MEDLINE | ID: mdl-38265274

RESUMO

PURPOSE: This study aimed to report a case of persistent keratouveitis associated with mpox virus infection in an immunocompetent patient with a history of laser-assisted in situ keratomileusis (LASIK), leading to the need for flap removal. METHODS: A comprehensive literature review was conducted, and a detailed case report was presented. RESULTS: A 44-year-old immunocompetent male patient with a history of LASIK and HIV infection presented with conjunctival and corneal lesions indicative of mpox infection. Despite initial topical treatment, the condition worsened, leading to severe epithelial and stromal keratitis with anterior chamber inflammation. Polymerase chain reaction testing confirmed the presence of mpox virus in conjunctival, corneal, and aqueous humor samples. The patient underwent various treatments, including tecovirimat, oral and topical corticosteroids, and topical trifluridine, and eventually flap removal with amniotic membrane application. Subsequent polymerase chain reaction testing of the aqueous humor yielded negative results, and the cornea gradually reepithelialized without inflammation. After 8 months, the patient's eye remained stable, with a central stromal scar. CONCLUSIONS: This case highlights the rare occurrence of mpox-associated keratouveitis and emphasizes the challenges faced in its management. The successful outcome achieved through a combination of antiviral therapy, antiinflammatories, and surgical intervention underscores the importance of a multidisciplinary approach in managing such cases.


Assuntos
Infecções por HIV , Ceratite , Ceratomileuse Assistida por Excimer Laser In Situ , Mpox , Uveíte , Masculino , Humanos , Adulto , Ceratomileuse Assistida por Excimer Laser In Situ/efeitos adversos , Córnea , Ceratite/induzido quimicamente , Ceratite/diagnóstico , Ceratite/tratamento farmacológico , Uveíte/complicações , Inflamação
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