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The placenta is crucial for fetal development, yet the impact of environmental stressors such as arsenic exposure remains poorly understood. We apply single-cell RNA sequencing to analyze the response of the mouse placenta to arsenic, revealing cell-type-specific gene expression, function, and pathological changes. Notably, the Prap1 gene, which encodes proline-rich acidic protein 1 (PRAP1), is significantly upregulated in 26 placental cell types including various trophoblast cells. Our study shows a female-biased increase in PRAP1 in response to arsenic and localizes it in the placenta. In vitro and ex vivo experiments confirm PRAP1 upregulation following arsenic treatment and demonstrate that recombinant PRAP1 protein reduces arsenic-induced cytotoxicity and downregulates cell cycle pathways in human trophoblast cells. Moreover, PRAP1 knockdown differentially affects cell cycle processes, proliferation, and cell death depending on the presence of arsenic. Our findings provide insights into the placental response to environmental stress, offering potential preventative and therapeutic approaches for environment-related adverse outcomes in mothers and children.
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Arsênio , Placenta , Análise de Célula Única , Trofoblastos , Feminino , Gravidez , Placenta/metabolismo , Placenta/efeitos dos fármacos , Animais , Humanos , Camundongos , Trofoblastos/metabolismo , Trofoblastos/efeitos dos fármacos , Trofoblastos/citologia , Arsênio/toxicidade , Análise de Sequência de RNA , Estresse Fisiológico/genética , Ciclo Celular/efeitos dos fármacos , Ciclo Celular/genética , Proliferação de Células/efeitos dos fármacos , Regulação para Cima/efeitos dos fármacos , Camundongos Endogâmicos C57BLRESUMO
Psoriatic arthritis (PsA) is a complex inflammatory disease that challenges diagnosis and complicates the rational selection of effective therapies. Although T cells are considered active effectors in psoriasis and PsA, the role of CD8+ T cells in pathogenesis is not well understood. We selected the humanized mouse model NSG-SGM3 transgenic strain to examine psoriasis and PsA endotypes. Injection of PBMCs and sera from patients with psoriasis and PsA generated parallel skin and joint phenotypes in the recipient mouse. The transfer of human circulating memory T cells was followed by migration and accumulation in the skin and synovia of these immunodeficient mice. Unexpectedly, immunoglobulins were required for recapitulation of the clinical phenotype of psoriasiform lesions and PsA domains (dactylitis, enthesitis, bone erosion). Human CD8+ T cells expressing T-bet, IL-32 and CXCL14 were detected by spatial transcriptomics in murine synovia and by immunofluorescence in the human PsA synovia. Importantly, depletion of human CD8+ T cells prevented skin and synovial inflammation in mice humanized with PsA peripheral blood cells. The humanized model of psoriasis and PsA represents a valid platform for accelerating the understanding of disease pathogenesis, improving the design of personalized therapies, and revealing psoriatic disease targets.
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Artrite Psoriásica , Linfócitos T CD8-Positivos , Modelos Animais de Doenças , Animais , Artrite Psoriásica/imunologia , Artrite Psoriásica/patologia , Humanos , Camundongos , Linfócitos T CD8-Positivos/imunologia , Linfócitos T CD8-Positivos/metabolismo , Camundongos Transgênicos , Pele/patologia , Pele/imunologia , Feminino , Masculino , Fenótipo , Psoríase/imunologia , Psoríase/patologiaRESUMO
The present work describes a quick, simple, and efficient method based on the use of layered double hydroxides (LDH) coupled to dispersive solid phase micro-extraction (DSPME) to remove α-naphthol (α-NAP) and ß-naphthol (ß-NAP) isomers from water samples. Three different LDHs (MgAl-LDH, NiAl-LDH, and CoAl-LDH) were used to study how the interlayer anion and molar ratio affected the removal performance. The critical factors in the DSPME procedure (pH, LDH amount, contact time) were optimized by the univariate method under the optimal conditions: pH, 4-8; LDH amount, 5 mg; and contact time, 2.5 min. The method can be successfully applied in real sample waters, removing NAP isomers even in ultra-trace concentrations. The large volume sample stacking (LVSS-CE) technique provides limits of detections (LODs) of 5.52 µg/L and 6.36 µg/L for α-naphthol and ß-naphthol, respectively. The methodology's precision was evaluated on intra- and inter-day repeatability, with %RSD less than 10% in all cases. The MgAl/Cl--LDH selectivity was tested in the presence of phenol and bisphenol A, with a removal rate of >92.80%. The elution tests suggest that the LDH MgAl/Cl--LDH could be suitable for pre-concentration of α-naphthol and ß-naphthol in future works.
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Eletroforese Capilar , Limite de Detecção , Naftóis , Microextração em Fase Sólida , Poluentes Químicos da Água , Naftóis/química , Naftóis/análise , Naftóis/isolamento & purificação , Poluentes Químicos da Água/análise , Poluentes Químicos da Água/isolamento & purificação , Poluentes Químicos da Água/química , Eletroforese Capilar/métodos , Microextração em Fase Sólida/métodos , Hidróxidos/química , Isomerismo , Reprodutibilidade dos Testes , Concentração de Íons de HidrogênioRESUMO
Age-related macular degeneration (AMD) and diabetic retinopathy (DR) are common retinal diseases responsible for most blindness in working-age and elderly populations. Oxidative stress and mitochondrial dysfunction play roles in these pathogenesis, and new therapies counteracting these contributors could be of great interest. Some molecules, like coenzyme Q10 (CoQ10), are considered beneficial to maintain mitochondrial homeostasis and contribute to the prevention of cellular apoptosis. We investigated the impact of adding CoQ10 (Q) to a nutritional antioxidant complex (Nutrof Total®; N) on the mitochondrial status and apoptosis in an in vitro hydrogen peroxide (H2O2)-induced oxidative stress model in human retinal pigment epithelium (RPE) cells. H2O2 significantly increased 8-OHdG levels (p < 0.05), caspase-3 (p < 0.0001) and TUNEL intensity (p < 0.01), and RANTES (p < 0.05), caspase-1 (p < 0.05), superoxide (p < 0.05), and DRP-1 (p < 0.05) levels, and also decreased IL1ß, SOD2, and CAT gene expression (p < 0.05) vs. control. Remarkably, Q showed a significant recovery in IL1ß gene expression, TUNEL, TNFα, caspase-1, and JC-1 (p < 0.05) vs. H2O2, and NQ showed a synergist effect in caspase-3 (p < 0.01), TUNEL (p < 0.0001), mtDNA, and DRP-1 (p < 0.05). Our results showed that CoQ10 supplementation is effective in restoring/preventing apoptosis and mitochondrial stress-related damage, suggesting that it could be a valid strategy in degenerative processes such as AMD or DR.
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Apoptose , Peróxido de Hidrogênio , Estresse Oxidativo , Epitélio Pigmentado da Retina , Ubiquinona , Humanos , Ubiquinona/análogos & derivados , Ubiquinona/farmacologia , Epitélio Pigmentado da Retina/metabolismo , Epitélio Pigmentado da Retina/efeitos dos fármacos , Estresse Oxidativo/efeitos dos fármacos , Apoptose/efeitos dos fármacos , Peróxido de Hidrogênio/metabolismo , Peróxido de Hidrogênio/farmacologia , Mitocôndrias/metabolismo , Mitocôndrias/efeitos dos fármacos , Antioxidantes/farmacologia , Células Epiteliais/metabolismo , Células Epiteliais/efeitos dos fármacos , Linhagem Celular , Suplementos NutricionaisRESUMO
Casein kinase 1 δ (CK1δ) controls essential biological processes including circadian rhythms and Wnt signaling, but how its activity is regulated is not well understood. CK1δ is inhibited by autophosphorylation of its intrinsically disordered C-terminal tail. Two CK1 splice variants, δ 1 and δ 2 , are known to have very different effects on circadian rhythms. These variants differ only in the last 16 residues of the tail, referred to as the extreme C-termini (XCT), but with marked changes in potential phosphorylation sites. Here we test if the XCT of these variants have different effects in autoinhibition of the kinase. Using NMR and HDX-MS, we show that the δ 1 XCT is preferentially phosphorylated by the kinase and the δ 1 tail makes more extensive interactions across the kinase domain. Mutation of δ1 -specific XCT phosphorylation sites increases kinase activity both in vitro and in cells and leads to changes in circadian period, similar to what is reported in vivo. Mechanistically, loss of the phosphorylation sites in XCT disrupts tail interaction with the kinase domain. δ1 autoinhibition relies on conserved anion binding sites around the CK1 active site, demonstrating a common mode of product inhibition of CK1δ . These findings demonstrate how a phosphorylation cycle controls the activity of this essential kinase.
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BACKGROUND AND OBJECTIVES: The aging population is growing faster than all other demographic strata. With older age comes a greater risk of health conditions such as obesity and high blood pressure (BP). These cardiometabolic risk factors (CMRs) exhibit prominent sex differences in midlife and aging, yet their influence on brain health in females vs males is largely unexplored. In this study, we investigated sex differences in relationships between BP, body mass index (BMI), and brain age over time and tested for interactions with APOE ε4 genotype (APOE4), a known genetic risk factor of Alzheimer disease. METHODS: The sample included participants from 2 United Kingdom-based longitudinal birth cohorts, the Lothian Birth Cohort (1936) and Insight 46 (1946). Participants with MRI data from at least 1 time point were included to evaluate sex differences in associations between CMRs and brain age. The open-access software package brainageR 2.1 was used to estimate brain age for each participant. Linear mixed-effects models were used to assess the relationships between brain age, BMI, BP, and APOE4 status (i.e., carrier vs noncarrier) in males and females over time. RESULTS: The combined sample comprised 1,120 participants (48% female) with a mean age (SD) of 73 (0.72) years in the Lothian Birth Cohort and 71 (0.68) years in Insight 46 at the time point 1 assessment. Approximately 30% of participants were APOE4 carriers. Higher systolic and diastolic BP was significantly associated with older brain age in females only (ß = 0.43-0.56, p < 0.05). Among males, higher BMI was associated with older brain age across time points and APOE4 groups (ß = 0.72-0.77, p < 0.05). In females, higher BMI was linked to older brain age among APOE4 noncarriers (ß = 0.68-0.99, p < 0.05), whereas higher BMI was linked to younger brain age among carriers, particularly at the last time point (ß = -1.75, p < 0.05). DISCUSSION: This study indicates sex-dependent and time-dependent relationships between CMRs, APOE4 status, and brain age. Our findings highlight the necessity of sex-stratified analyses to elucidate the role of CMRs in individual aging trajectories, providing a basis for developing personalized preventive interventions.
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Envelhecimento , Apolipoproteína E4 , Índice de Massa Corporal , Encéfalo , Caracteres Sexuais , Humanos , Masculino , Feminino , Apolipoproteína E4/genética , Idoso , Estudos Longitudinais , Encéfalo/metabolismo , Encéfalo/diagnóstico por imagem , Encéfalo/crescimento & desenvolvimento , Envelhecimento/genética , Pressão Sanguínea/fisiologia , Imageamento por Ressonância Magnética , Estudos de Coortes , Reino Unido/epidemiologia , Fatores de Risco CardiometabólicoRESUMO
OBJECTIVE: Our objective was to identify systemic sclerosis (SSc) patients with a high burden of autonomic symptoms and to determine whether they have a distinct clinical phenotype, gastrointestinal (GI) transit or extraintestinal features. METHODS: In a prospective cohort of SSc patients with GI disease, clinical data were systematically obtained at routine visits. Dysautonomia was identified by the Composite Autonomic Symptom Score (COMPASS)-31questionnaire. GI transit was measured by whole-gut scintigraphy. Associations between total COMPASS-31 scores and clinical features, GI symptoms, and transit were evaluated. Comparisons between patients with global autonomic dysfunction [(GAD); ≥5 positive COMPASS-31 subdomains] and those with limited autonomic dysfunction [(LAD); <5 positive subdomains] were also studied. RESULTS: 91 patients with SSc and GI involvement were included [mean age 57, 90% female, 74% limited cutaneous disease, 83% significant GI disease (Medsger score ≥2)]. The mean COMPASS-31 score in SSc was higher than controls (38.8 vs. 7.2). 33% had GAD, 67% had LAD. Patients with GAD were more likely to have limited SSc (93% vs. 65%; p<0.01) and have sicca symptoms (100% vs. 77%; p=0.01). Gastric and colonic transit were faster in patients with GAD (p<0.05). Upper GI involvement (Medsger GI score of 1 or 2) was associated with higher total COMPASS-31 scores (p=0.02). CONCLUSION: Symptoms of global dysautonomia are seen in up to one-third of patients with SSc and GI involvement. Identifying specific clinical characteristics associated with GAD in SSc will help to identify a population that may benefit from therapies that modulate the autonomic nervous system.
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BACKGROUND AND OBJECTIVES: Factors associated with cerebral small vessel disease (SVD) progression, including incident infarcts, are unclear. We aimed to determine the frequency of incident infarcts over 1 year after minor stroke and their relation to baseline SVD burden, vascular risks, and recurrent stroke and cognitive outcomes. METHODS: We recruited patients with lacunar or nondisabling cortical stroke. After diagnostic imaging, we repeated structural MRI at 3-6 monthly intervals for 12 months, visually assessing incident infarcts on diffusion-weighted imaging or FLAIR. We used logistic regression to determine associations of baseline vascular risks, SVD score, and index stroke subtype with subsequent incident infarcts. We assessed cognitive and functional outcomes at 1 year using Montreal Cognitive Assessment (MoCA) and modified Rankin scale (mRS), adjusting for baseline age, mRS, MoCA, premorbid intelligence, and SVD score. RESULTS: We recruited 229 participants, mean age 65.9 (SD 11.1). Over half of all participants, 131 of 229 (57.2%) had had an index lacunar stroke. From baseline to 1-year MRI, we detected 117 incident infarcts in n = 57/229 (24.8%) participants. Incident infarcts were mainly of the small subcortical (86/117 [73.5%] in n = 38/57 [66.7%]) vs cortical infarct subtype (n = 19/57 [33.3%]). N = 39/57 participants had incident infarcts at 1 visit; 18 of 57 at 2 or more visits; and 19 of 57 participants had multiple infarcts at a single visit. Only 7 of 117 incident infarcts corresponded temporally to clinical stroke syndromes. The baseline SVD score was the strongest predictor of incident infarcts (adjusted odds ratio [OR] 1.87, 95% CI 1.39-2.58), while mean arterial pressure was not associated. All participants with incident infarcts were prescribed an antiplatelet or anticoagulant. Lower 1-year MoCA was associated with lower baseline MoCA (ß 0.47, 95% CI 0.33-0.61), lower premorbid intelligence, and older age. Higher 1-year mRS was associated with higher baseline mRS only (OR 5.57 [3.52-9.10]). Neither outcome was associated with incident infarcts. DISCUSSION: In the year after stroke in a population enriched for lacunar stroke, incident infarcts occurred in one-quarter and were associated with worse baseline SVD. Most incident infarcts detected on imaging did not correspond to clinical stroke/transient ischemic attack. Worse 1-year cognition and function were not associated with incident infarcts.
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Doenças de Pequenos Vasos Cerebrais , Acidente Vascular Cerebral , Humanos , Masculino , Idoso , Feminino , Doenças de Pequenos Vasos Cerebrais/diagnóstico por imagem , Doenças de Pequenos Vasos Cerebrais/epidemiologia , Doenças de Pequenos Vasos Cerebrais/complicações , Pessoa de Meia-Idade , Acidente Vascular Cerebral/epidemiologia , Acidente Vascular Cerebral/diagnóstico por imagem , Imageamento por Ressonância Magnética , Acidente Vascular Cerebral Lacunar/diagnóstico por imagem , Acidente Vascular Cerebral Lacunar/epidemiologia , Incidência , Infarto Encefálico/epidemiologia , Infarto Encefálico/diagnóstico por imagemRESUMO
Bronchiolitis obliterans syndrome (BOS) after hematopoietic cell transplantation (HCT) is associated with substantial morbidity and mortality. Quantitative CT (qCT) can help diagnose advanced BOS meeting National Institutes of Health (NIH) criteria (NIH-BOS) but has not been used to diagnose early, often asymptomatic BOS (early BOS), limiting the potential for early intervention and improved outcomes. Using Pulmonary Function Tests (PFT) to define NIH-BOS, early BOS, and mixed BOS (NIH-BOS with restrictive lung disease) in patients from two large cancer centers, we applied qCT to identify early BOS and distinguish between types of BOS. Patients with transient impairment or healthy lungs were included for comparison. PFT were done at month 0, 6, and 12. Analysis was performed with association statistics, principal component analysis, conditional inference trees (CIT), and machine learning (ML) classifier models. Our cohort included 84 allogeneic HCT recipients -- 66 BOS (NIH-defined, early, or mixed) and 18 without BOS. All qCT metrics had moderate correlation with Forced Expiratory Volume in 1 second, and each qCT metric differentiated BOS from those without BOS (non-BOS) (P < 0.0001). CIT's distinguished 94% of participants with BOS versus non-BOS, 85% early BOS versus non-BOS, 92% early BOS versus NIH-BOS. ML models diagnosed BOS with area under the curve (AUC) 0.84 (95% confidence interval [CI] 0.74-0.94) and early BOS with AUC 0.84 (95% CI 0.69 - 0.97). Quantitative CT metrics can identify individuals with early BOS, paving the way for closer monitoring and earlier treatment in this vulnerable population.
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Antígeno CD47 , Neoplasias , Receptores Imunológicos , Humanos , Antígeno CD47/metabolismo , Antígeno CD47/antagonistas & inibidores , Neoplasias/tratamento farmacológico , Neoplasias/metabolismo , Receptores Imunológicos/metabolismo , Receptores Imunológicos/antagonistas & inibidores , Animais , Transdução de Sinais/efeitos dos fármacos , Antineoplásicos/uso terapêutico , Terapia de Alvo Molecular/métodos , Antígenos de DiferenciaçãoRESUMO
Introduction: This study investigated a remotely delivered, therapist-facilitated, personalized music listening intervention for community-dwelling older adults experiencing loneliness during the Covid-19 pandemic. We assessed its feasibility and individuals' experiences of social connection and emotional well-being during the intervention. Methods: Ten cognitively unimpaired older adults who endorsed loneliness completed eight weekly sessions with a board-certified music therapist via Zoom. Participants were guided in developing two online personalized music playlists and were asked to listen to playlists for at least one hour daily. Feasibility metrics were attendance, accessibility, and compliance rates. Post-study interview responses were analyzed using a rapid qualitative methodology. Exploratory pre- and post-study measures of loneliness and other aspects of psychological well-being were obtained using validated questionnaires. Results: Ten participants (mean age 75.38 [65 to 85] years, 80% women) were enrolled from March to August 2021. Attendance and compliance rates were 100% and the accessibility rate was 90%. Most participants associated music with positive memories before the program and many reported that the intervention prompted them to reconnect with music or listen to music with greater intention. They cited increased connection from interacting with the music therapist and the music itself, as well as specific positive emotional impacts from integrating music into their daily lives. Median pre- to post-questionnaire measures of psychological function all changed in an improved direction. Discussion: Remotely delivered music therapy may be a promising intervention to promote regular music listening and socioemotional well-being in lonely older adults.
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COVID-19 , Solidão , Musicoterapia , Humanos , Musicoterapia/métodos , Idoso , Feminino , Masculino , COVID-19/psicologia , Solidão/psicologia , Projetos Piloto , Idoso de 80 Anos ou mais , Estudos de Viabilidade , SARS-CoV-2RESUMO
BACKGROUND: stevia and D-tagatose have shown a reduction in total calorie and carbohydrate intake as a substitute for sucrose, demonstrating a stabilizing effect on pH and bacterial proliferation. OBJECTIVE: to evaluate the effect of D-tagatose, stevia and sucrose on salivary pH and bacterial activity in odontology students. METHODOLOGY: a controlled study of parallel and randomized groups with a single blind, whose sample considered three groups subjected to a mouthwash of D-tagatose (n = 10), stevia (n = 10) and sucrose (n = 10). These solutions were administered over 1 minute in a single 6.4 % concentrated dose. Data collection and analysis considered the recording of salivary pH 5 min before exposure to the sweetener, immediately after expulsion of the mouthwash and 15 min later, 30 min, 45 min and 48 hours. The counting of the final number of colony-forming units per mL (CFU/mL) was counted using the salivary samples obtained immediately after exposure of the sweetener together with the sample obtained 30 minutes later, with the cultures performed on agar plates. RESULTS: D-tagatose, stevia and sucrose presented significant differences in total CFU/mL at 30 minutes (p < 0.001), while salivary pH showed significant differences at 48 hours after administration (p < 0.001). CONCLUSION: D-tagatose, stevia and sucrose present significant differences in total CFU/mL and salivary pH, these findings being a possible indication of a partial inhibitory effect on bacterial metabolism.
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The dataset provides data obtained with eye-tracking while 55 volunteers solved 3 distinct neuropsychological tests on a screen inside a closed room. Among the 55 volunteers, 22 were women and 33 were men, all with ages ranging between 9 and 50, and 5 of whom were diagnosed with Attention Deficit Hyperactivity Disorder (ADHD) [1]. The eye-tracker used for the collection of the data was an EyeTribe, which has a sampling rate of 60 Hz and an average visual angle between 0.5 and 1, which correspond to an on-screen error between 0.5 and 1cm (0.1969 to 0.393 inches aprox) respectively, when the distance to the user is around 60cm (23.62 in) [2], which was the case during the collection of these data. The neuropsychological tests were implemented in a software named NEURO-INNOVA KIDS® [3], which are the following: a domino test adapted from the D-48 intelligence test [4], an adaptation of the MASMI test consisting of unfolded cubes [5], the figures series completion test adapted from [6], and the Poppelreuter figures test [7]. Before each of the tests, a calibration process was performed, ensuring that the visual angle error was less than or equal to 0.5 cm (0.1969 in), which is considered an acceptable calibration. The collective mean duration of the four administered tests amounted to 20 minutes. This dataset exhibits significant promise for potential utilization due to the extensive prevalence of these neuropsychological assessments among healthcare practitioners for evaluating diverse cognitive faculties in individuals. Moreover, it has been empirically established that poor performance on these tests is associated with attention deficits [8].
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Ovarian cancer (OC) is the leading cause of death in women with gynecological cancers. Its diagnosis is more likely in advanced ages, with the older population being the most seen in consultations. Poly(ADP-ribose) inhibitors (PARPi) have changed OC clinical practice and evolution, showing great benefit. However, there is a lack of evidence of PARPi in elderly population that can impact the therapeutic decision and the safety/efficacy. It is necessary to avoid age as limiting factor in PARPis prescription. We conducted a review of the most relevant randomized phase III trials of maintenance PARPi after first-line treatment of advanced OC. We observed the lack of a single criterion for considering older patients, varying among trials. There is a benefit of PARPis in different populations. However, PARPi effect on quality of life is not reported, something of great relevance considering their vulnerability. Measures are needed to benefit older patients to better adapt PARPi treatment.
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Children are highly vulnerable to mild traumatic brain injury (mTBI). Blood biomarkers can help in their management. This study evaluated the performances of biomarkers, in discriminating between children with mTBI who had intracranial injuries (ICIs) on computed tomography (CT+) and (1) patients without ICI (CT-) or (2) both CT- and in-hospital-observation without CT patients. The aim was to rule out the need of unnecessary CT scans and decrease the length of stay in observation in the emergency department (ED). Newborns to teenagers (≤16 years old) with mTBI (Glasgow Coma Scale > 13) were included. S100b, glial fibrillary acidic protein (GFAP), and heart fatty-acid-binding protein (HFABP) performances to identify patients without ICI were evaluated through receiver operating characteristic curves, where sensitivity was set at 100%. A total of 222 mTBI children sampled within 6 h since their trauma were reported. Nineteen percent (n = 43/222) underwent CT scan examination, whereas the others (n = 179/222) were kept in observation at the ED. Sixteen percent (n = 7/43) of the children who underwent a CT scan had ICI, corresponding to 3% of all mTBI-included patients. When sensibility (SE) was set at 100% to exclude all patients with ICI, GFAP yielded 39% specificity (SP), HFABP 37%, and S100b 34% to rule out the need of CT scans. These biomarkers were even more performant: 52% SP for GFAP, 41% for HFABP, and 39% for S100b, when discriminating CT+ versus both in-hospital-observation and CT- patients. These markers can significantly help in the management of patients in the ED, avoiding unnecessary CT scans, and reducing length of stay for children and their families.
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PURPOSE: To synthesize the evidence and generate a combined weighted measure on the frequency of ocular manifestations of mucous membrane pemphigoid (OMMP). METHODS: Systematic literature review and meta-analysis, searching PubMed, Embase, VHL, and Google Scholar. Articles reporting patients with mucous membrane pemphigoid and ocular involvement were included. At least, two reviewers independently and in parallel participated in all the following phases; preliminary screening, full-text review, risk of bias assessment by validated tools, and data extraction. Qualitative analysis and meta-analysis were conducted. This study was previously registered in PROSPERO (CRD42023451844). RESULTS: Thirty-five studies met the inclusion criteria, comprising 1,439 patients and 1,040 eyes summarized in qualitative analysis. Twenty-eight studies were included in the meta-analysis. Ages included ranged from 60.4 to 75 years. Women were reported with more frequency. The mean time for diagnosis was 55.1 months, usually with bilateral ocular disease in 90% (95% CI 78%; 96%). Trichiasis and entropion were the most frequent manifestations in up to 92%, followed by symblepharon and punctate keratitis. Ankyloblepharon, persistent epithelial defects, and visual impairment were less frequent complications. Direct immunofluorescence positivity in conjunctival biopsies was 54% (95% CI 43%; 64%). Extraocular involvement was highly frequent, being oral and skin involvement the most frequently reported. CONCLUSIONS: Our systematic review and meta-analysis evidenced that patients around 60 years of age are the most affected population with a female preponderance, usually with bilateral ocular involvement. Trichiasis and entropion were the most frequent findings; although visual impairment and persistent epithelial defects were less reported, they should not be overlooked in suspected OMMP.
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Examining underlying neurostructural correlates of specific cognitive abilities is practically and theoretically complicated by the existence of the positive manifold (all cognitive tests positively correlate): if a brain structure is associated with a cognitive task, how much of this is uniquely related to the cognitive domain, and how much is due to covariance with all other tests across domains (captured by general cognitive functioning, also known as general intelligence, or 'g')? We quantitatively address this question by examining associations between brain structural and diffusion MRI measures (global tissue volumes, white matter hyperintensities, global white matter diffusion fractional anisotropy and mean diffusivity, and FreeSurfer processed vertex-wise cortical volumes, smoothed at 20mm fwhm) with g and cognitive domains (processing speed, crystallised ability, memory, visuospatial ability). The cognitive domains were modelled using confirmatory factor analysis to derive both hierarchical and bifactor solutions using 13 cognitive tests in 697 participants from the Lothian Birth Cohort 1936 study (mean age 72.5 years; SD = .7). Associations between the extracted cognitive factor scores for each domain and g were computed for each brain measure covarying for age, sex and intracranial volume, and corrected for false discovery rate. There were a range of significant associations between cognitive domains and global MRI brain structural measures (r range .008 to .269, p < .05). Regions implicated by vertex-wise regional cortical volume included a widespread number of medial and lateral areas of the frontal, temporal and parietal lobes. However, at both global and regional level, much of the domain-MRI associations were shared (statistically accounted for by g). Removing g-related variance from cognitive domains attenuated association magnitudes with global brain MRI measures by 27.9-59.7% (M = 46.2%), with only processing speed retaining all significant associations. At the regional cortical level, g appeared to account for the majority (range 22.1-88.4%; M = 52.8% across cognitive domains) of regional domain-specific associations. Crystallised and memory domains had almost no unique cortical correlates, whereas processing speed and visuospatial ability retained limited cortical volumetric associations. The greatest spatial overlaps across cognitive domains (as denoted by g) were present in the medial and lateral temporal, lateral parietal and lateral frontal areas.
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BACKGROUND: Despite significant progress in cardiovascular disease (CVD) management, it remains a public health priority and a global challenge. Within the disease process, health care after a cardiovascular event (secondary prevention) is essential to prevent recurrences. Nonetheless, evidence has suggested the existence of gender disparities in CVD management, leaving women in a vulnerable situation. The objective of this study is to identify all available evidence on the existence of gender differences in health care attention after a major adverse cardiovascular event. METHODS: A scoping review following the structure of PRISMA-ScR was conducted. To define the inclusion criteria, we used Joanna Briggs Institute (JBI) population, concept, context framework for scoping reviews. A systematic search was performed in MEDLINE (PubMed), EMBASE and Cochrane. The methods of this review are registered in the International Platform of Registered Systematic Review and Meta-Analysis Protocols (INPLASY) (INPLASY202350084). RESULTS: The initial search retrieved 3,322 studies. 26 articles were identified manually. After the reviewing process, 93 articles were finally included. The main intervention studied was the pharmacological treatment received (n = 61, 66%), distantly followed by guideline-recommended care (n = 26, 28%) and cardiac rehabilitation (CR) referral (n = 16)". Literature described gender differences in care and management of secondary prevention of CVD. Women were less frequently treated with guideline-recommended medications and seem more likely to be non-adherent. When analysing guideline recommendations, women were more likely to make dietary changes, however, men were more likely to increase physical activity. Studies also showed that women had lower rates of risk factor testing and cholesterol goals attainment. Female sex was associated with lower rates of cardiac rehabilitation referral and participation. CONCLUSIONS: This review allowed us to compile knowledge on the existence of gender inequalities on the secondary prevention of CVD. Additional research is required to delve into various factors influencing therapeutic disparities, referral and non-participation in CR programs, among other aspects, in order to improve existing knowledge about the management and treatment of CVD in men and women. This approach is crucial to ensure the most equitable and effective attention to this issue.
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Doenças Cardiovasculares , Prevenção Secundária , Humanos , Doenças Cardiovasculares/prevenção & controle , Prevenção Secundária/métodos , Feminino , Masculino , Fatores Sexuais , Disparidades em Assistência à Saúde/estatística & dados numéricosRESUMO
Metabolic syndrome (MetS) is a group of clinical traits directly linked to type 2 diabetes mellitus and cardiovascular diseases, whose prevalence has been rising nationally and internationally. We aimed to evaluate ten known and novel surrogate markers of insulin resistance and obesity to identify MetS in Mexican adults. The present cross-sectional study analyzed 10575 participants from ENSANUT-2018. The diagnosis of MetS was based on the Adult Treatment Panel III (ATP III) criteria and International Diabetes Federation (IDF) criteria, stratified by sex and age group. According to ATP III, the best biomarker was the metabolic score for insulin resistance (METS-IR) in men aged 20-39 and 40-59 years and lipid accumulation product (LAP) in those aged ≥60 years. The best biomarker was LAP in women aged 20-39 and triglyceride-glucose index (TyG) in those aged 40-59 and ≥60 years. Using the IDF criteria, the best biomarker was LAP in men of all ages. TyG gave the best results in women of all ages. The best biomarker for diagnosis of MetS in Mexican adults depends on the criteria, including sex and age group. LAP and TyG are easy to obtain, inexpensive, and especially useful at the primary care level.