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The vast majority of human genes encode multiple isoforms through alternative splicing, and the temporal and spatial regulation of those isoforms is critical for organismal development and function. The spliceosome, which regulates and executes splicing reactions, is primarily composed of small nuclear ribonucleoproteins (snRNPs) that consist of small nuclear RNAs (snRNAs) and protein subunits. snRNA gene transcription is initiated by the snRNA-activating protein complex (SNAPc). Here, we report ten individuals, from eight families, with bi-allelic, deleterious SNAPC4 variants. SNAPC4 encoded one of the five SNAPc subunits that is critical for DNA binding. Most affected individuals presented with delayed motor development and developmental regression after the first year of life, followed by progressive spasticity that led to gait alterations, paraparesis, and oromotor dysfunction. Most individuals had cerebral, cerebellar, or basal ganglia volume loss by brain MRI. In the available cells from affected individuals, SNAPC4 abundance was decreased compared to unaffected controls, suggesting that the bi-allelic variants affect SNAPC4 accumulation. The depletion of SNAPC4 levels in HeLa cell lines via genomic editing led to decreased snRNA expression and global dysregulation of alternative splicing. Analysis of available fibroblasts from affected individuals showed decreased snRNA expression and global dysregulation of alternative splicing compared to unaffected cells. Altogether, these data suggest that these bi-allelic SNAPC4 variants result in loss of function and underlie the neuroregression and progressive spasticity in these affected individuals.
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Processamento Alternativo , Proteínas de Ligação a DNA , Paraparesia Espástica , Fatores de Transcrição , Paraparesia Espástica/genética , Humanos , Proteínas de Ligação a DNA/genética , Fatores de Transcrição/genética , Células HeLa , Isoformas de Proteínas/genética , RNA-Seq , Masculino , Feminino , Linhagem , Alelos , Lactente , Pré-Escolar , Criança , Adolescente , Estrutura Secundária de Proteína , RNA Nuclear Pequeno/genéticaRESUMO
Metachromatic leukodystrophy (MLD) is a fatal, progressive neurodegenerative disorder caused by biallelic pathogenic mutations in the ARSA (Arylsulfatase A) gene. With the advent of presymptomatic diagnosis and the availability of therapies with a narrow window for intervention, it is critical to define a standardized approach to diagnosis, presymptomatic monitoring, and clinical care. To meet the needs of the MLD community, a panel of MLD experts was established to develop disease-specific guidelines based on healthcare resources in the United States. This group developed a consensus opinion for best-practice recommendations, as follows: (i) Diagnosis should include both genetic and biochemical testing; (ii) Early diagnosis and treatment for MLD is associated with improved clinical outcomes; (iii) The panel supported the development of newborn screening to accelerate the time to diagnosis and treatment; (iv) Clinical management of MLD should include specialists familiar with the disease who are able to follow patients longitudinally; (v) In early onset MLD, including late infantile and early juvenile subtypes, ex vivo gene therapy should be considered for presymptomatic patients where available; (vi) In late-onset MLD, including late juvenile and adult subtypes, hematopoietic cell transplant (HCT) should be considered for patients with no or minimal disease involvement. This document summarizes current guidance on the presymptomatic monitoring of children affected by MLD as well as the clinical management of symptomatic patients. Future data-driven evidence and evolution of these recommendations will be important to stratify clinical treatment options and improve clinical care.
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Leucodistrofia Metacromática , Humanos , Recém-Nascido , Cerebrosídeo Sulfatase/genética , Consenso , Terapia Genética/métodos , Leucodistrofia Metacromática/terapia , Leucodistrofia Metacromática/diagnóstico , Leucodistrofia Metacromática/genética , Triagem Neonatal/métodos , Estados UnidosRESUMO
BACKGROUND: There is some evidence of an association between inflammation in the pathogenesis of mental disorders. Soluble urokinase plasminogen activator receptor (suPAR) is a biomarker of chronic inflammation, which provides a more stable index of systemic inflammation than more widely used biomarkers. This review aims to synthesise studies that measured suPAR concentrations in individuals with a psychiatric disorder, to determine if these concentrations are altered in comparison to healthy participants. METHOD: Comprehensive literature searches from inception to October 2023 were conducted of five relevant databases (PubMed, Web of Science, Embase, Scopus, APA PsychInfo). Random-effects meta-analyses were performed to compare the standardised mean difference of blood suPAR levels (i.e. plasma or serum) for individuals with any psychiatric disorder relative to controls. Separate meta-analyses of suPAR levels were conducted for individuals with schizophrenia or other psychotic disorder and depressive disorder. Risk of bias was assessed using the Newcastle Ottawa Scale. Post-hoc sensitivity analyses included excluding studies at high risk of bias, and analyses of studies that measured suPAR concentrations either in serum or in plasma separately. RESULTS: The literature search identified 149 records. Ten full-text studies were screened for eligibility and 9 studies were included for review. Primary analyses revealed no significant difference in suPAR levels between individuals with any psychiatric disorder compared to controls (k = 7, SMD = 0.42, 95 % CI [-0.20, 1.04]). However, those with depressive disorder had elevated suPAR levels relative to controls (k = 3, SMD = 0.61, 95 % CI [0.34, 0.87]). Similarly, secondary analyses showed no evidence of a significant difference in suPAR levels in individuals with any psychiatric disorder when studies at high risk of bias were excluded (k = 6, SMD = 0.54, 95 % CI [-0.14, 1.22]), but elevated suPAR concentrations for those with schizophrenia or other psychotic disorder were found (k = 3, SMD = 0.98, 95 % CI [0.39, 1.58]). Furthermore, studies that analysed plasma suPAR concentrations found elevated plasma suPAR levels in individuals with any psychiatric disorder relative to controls (k = 5, SMD = 0.84, 95 % CI [0.38, 1.29]), while studies measuring serum suPAR levels in any psychiatric disorder did not find a difference (k = 2, SMD = -0.61, 95 % CI [-1.27, 0.04]). For plasma, elevated suPAR concentrations were also identified for those with schizophrenia or other psychotic disorder (k = 3, SMD = 0.98, 95 % CI [0.39, 1.58]). DISCUSSION: When studies measuring either only serum or only plasma suPAR were considered, no significant difference in suPAR levels were observed between psychiatric disorder groups, although significantly elevated suPAR levels were detected in those with moderate to severe depressive disorder. However, plasma suPAR levels were significantly elevated in those with any psychiatric disorder relative to controls, while no difference in serum samples was found. A similar finding was reported for schizophrenia or other psychotic disorder. The plasma findings suggest that chronic inflammatory dysregulation may contribute to the pathology of schizophrenia and depressive disorder. Future longitudinal studies are required to fully elucidate the role of this marker in the psychopathology of these disorders.
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Biomarcadores , Receptores de Ativador de Plasminogênio Tipo Uroquinase , Esquizofrenia , Humanos , Receptores de Ativador de Plasminogênio Tipo Uroquinase/sangue , Biomarcadores/sangue , Esquizofrenia/sangue , Transtornos Mentais/sangue , Inflamação/sangue , Inflamação/metabolismo , Transtornos Psicóticos/sangue , Transtornos Psicóticos/metabolismoRESUMO
The COVID-19 pandemic has exerted a global impact on both physical and mental health, and clinical populations have been disproportionally affected. To date, however, the mechanisms underlying the deleterious effects of the pandemic on pre-existing clinical conditions remain unclear. Here we investigated whether the onset of the pandemic was associated with an increase in brain/blood levels of inflammatory markers and MRI-estimated brain age in patients with chronic low back pain (cLBP), irrespective of their infection history. A retrospective cohort study was conducted on 56 adult participants with cLBP (28 'Pre-Pandemic', 28 'Pandemic') using integrated Positron Emission Tomography/ Magnetic Resonance Imaging (PET/MRI) and the radioligand [11C]PBR28, which binds to the neuroinflammatory marker 18 kDa Translocator Protein (TSPO). Image data were collected between November 2017 and January 2020 ('Pre-Pandemic' cLBP) or between August 2020 and May 2022 ('Pandemic' cLBP). Compared to the Pre-Pandemic group, the Pandemic patients demonstrated widespread and statistically significant elevations in brain TSPO levels (P =.05, cluster corrected). PET signal elevations in the Pandemic group were also observed when 1) excluding 3 Pandemic subjects with a known history of COVID infection, or 2) using secondary outcome measures (volume of distribution -VT- and VT ratio - DVR) in a smaller subset of participants. Pandemic subjects also exhibited elevated serum levels of inflammatory markers (IL-16; P <.05) and estimated BA (P <.0001), which were positively correlated with [11C]PBR28 SUVR (r's ≥ 0.35; P's < 0.05). The pain interference scores, which were elevated in the Pandemic group (P <.05), were negatively correlated with [11C]PBR28 SUVR in the amygdala (r = -0.46; P<.05). This work suggests that the pandemic outbreak may have been accompanied by neuroinflammation and increased brain age in cLBP patients, as measured by multimodal imaging and serum testing. This study underscores the broad impact of the pandemic on human health, which extends beyond the morbidity solely mediated by the virus itself.
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COVID-19 , Dor Crônica , Adulto , Humanos , Pandemias , Dor Crônica/metabolismo , Estudos Retrospectivos , Encéfalo/diagnóstico por imagem , Encéfalo/metabolismo , Tomografia por Emissão de Pósitrons/métodos , Envelhecimento , Receptores de GABA/metabolismoRESUMO
DESCRIPTION: In May 2022, leadership within the U.S. Department of Veterans Affairs (VA) and U.S. Department of Defense (DoD) approved a joint clinical practice guideline for the use of opioids when managing chronic pain. This synopsis summarizes the recommendations that the authors believe are the most important to highlight. METHODS: In December 2020, the VA/DoD Evidence-Based Practice Work Group assembled a team to update the 2017 VA/DoD Clinical Practice Guideline for Opioid Therapy for Chronic Pain. The guideline development team included clinical stakeholders and conformed to the National Academy of Medicine's tenets for trustworthy clinical practice guidelines. The guideline team developed key questions to guide a systematic evidence review that was done by an independent third party and distilled 20 recommendations for care using the GRADE (Grading of Recommendations Assessment, Development and Evaluation) system. The guideline team also created 3 one-page algorithms to help guide clinical decision making. This synopsis presents the recommendations and highlights selected recommendations on the basis of clinical relevance. RECOMMENDATIONS: This guideline is intended for clinicians who may be considering opioid therapy to manage patients with chronic pain. This synopsis reviews updated recommendations for the initiation and continuation of opioid therapy; dose, duration, and taper of opioids; screening, assessment, and evaluation; and risk mitigation. New additions are highlighted, including recommendations about the use of buprenorphine instead of full agonist opioids; assessing for behavioral health conditions and factors associated with higher risk for harm, such as pain catastrophizing; and the use of pain and opioid education to reduce the risk for prolonged opioid use for postsurgical pain.
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Dor Crônica , Veteranos , Humanos , Estados Unidos , Dor Crônica/tratamento farmacológico , Analgésicos Opioides/efeitos adversos , United States Department of Veterans AffairsRESUMO
OBJECTIVE: To evaluate a range of pathologically proven malignant bone tumours, including primary bone sarcoma and metastatic bone lesions, referred to a tertiary referral centre for the presence of the flow-void sign on MR imaging. MATERIALS AND METHODS: A retrospective search was performed using the radiology information system and oncology database in our institution to identify patients over the age of 40 years referred with a solitary bone lesion. Patients with a range of pathologically proven malignant bone tumours, including primary bone tumours and metastatic bone lesions, were included in the study. MRI images were reviewed for the presence of the flow-void sign. The presence and type of the flow-void sign were correlated with lesion size. RESULTS: Two hundred and sixty-six cases were included in the study. Overall, the flow-void sign was identified in 40.9% of cases. The flow-void sign was most frequently seen in renal cell carcinoma metastasis (90.0%). The sign is highly sensitive (90%) for renal cell carcinoma metastases with a high negative predictive value (98.09%). When the flow-void sign is identified, the lesion is almost three times more likely to represent a renal cell carcinoma metastasis than any other malignant tumour in patients over the age of 40 years with a solitary bone lesion. CONCLUSION: The flow-void sign is highly sensitive for renal cell carcinoma bone metastases and could negate the need for biopsy in patients with a known history of renal cell carcinoma or in whom an occult renal cell carcinoma is subsequently identified.
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Neoplasias Ósseas , Carcinoma de Células Renais , Doenças das Cartilagens , Neoplasias Renais , Humanos , Adulto , Carcinoma de Células Renais/patologia , Estudos Retrospectivos , Neoplasias Ósseas/secundário , Imageamento por Ressonância Magnética/métodos , Neoplasias Renais/patologiaRESUMO
Chondroblastoma is a rare benign tumor, typically presenting in the first two decades. Systemic metastases in chondroblastoma are extremely rare and it is the rarity of these metastases which lead the World Health Organisation to re-classify this lesion from "intermediate" to "benign" in its updated classification of bone tumors in 2020. We present an unusual case of a 55 year-old male patient who presented with multiple FDG-avid bone lesions on a background of conventional chondroblastoma of the rib excised at another institution 11-years previously. Two of these lesions were also histologically-proven as conventional chondroblastoma at biopsy. This case highlights that, although rare, metastases can be seen in patients with chondroblastoma. To our knowledge, this is the only case with an unusual pattern of metastases limited to bone.
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Neoplasias Ósseas , Condroblastoma , Masculino , Adulto , Humanos , Pessoa de Meia-Idade , Condroblastoma/diagnóstico por imagem , Condroblastoma/cirurgia , Condroblastoma/patologia , Neoplasias Ósseas/diagnóstico por imagem , Neoplasias Ósseas/patologia , BiópsiaRESUMO
Alterations in interoception have been linked to psychopathology. Recent findings suggest that both the attention to and the accuracy of, interoceptive perceptions may be oppositely related to subclinical symptomatology. Thus, providing well-validated tools that tap into these interoceptive processes is crucial for understanding the relation between interoceptive processing and subclinical psychopathology. In the current study (N = 642), we aimed to (1) validate the German version of the Interoceptive Attention Scale (IATS; Gabriele et al., 2022), and (2) test the differential association of self-reported interoceptive attention and accuracy with subclinical symptomatology, including alexithymia, depressive, and anxious symptomatology. We observed that a one-factor solution is a well-fitting model for the IATS. Further, the IATS showed good internal consistency, convergent, and divergent validity, but poor test-retest reliability. Self-reported interoceptive attention and accuracy were unrelated to each other. However, IATS scores were positively related to all measures of psychopathology (except depressive symptomatology), whereas self-reported interoceptive accuracy scores showed negative or nonsignificant relations with these. Our data suggest that the IATS is a good instrument to measure self-report interoceptive attention in the German population. Further, we highlight the need to distinguish between constructs of interoception to better understand the relation between interoception and psychopathology.
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Every day we constantly observe other people receiving rewards. Theoretical accounts posit that vicarious reward processing might be linked to people's sensitivity to internal body states (interoception) and facilitates a tendency to act prosocially. However, the neural processes underlying the links between vicarious reward processing, interoception, and prosocial behaviour are poorly understood. Previous research has linked vicarious reward processing to the anterior cingulate gyrus (ACCg) and the anterior insula (AI). Can we predict someone's propensity to be prosocial or to be aware of interoceptive signals from variability in how the ACCg and AI process rewards? Here, participants monitored rewards being delivered to themselves or a stranger during functional magnetic resonance imaging. Later, they performed a task measuring their willingness to exert effort to obtain rewards for others, and a task measuring their propensity to be aware and use interoceptive respiratory signals. Using multivariate similarity analysis, we show that people's willingness to be prosocial is predicted by greater similarity between self and other representations in the ACCg. Moreover, greater dissimilarity in self-other representations in the AI is linked to interoceptive propensity. These findings highlight that vicarious reward is linked to bodily signals in AI, and foster prosocial tendencies through the ACCg.
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Altruísmo , Interocepção , Humanos , Recompensa , Giro do Cíngulo , Conscientização , Imageamento por Ressonância MagnéticaRESUMO
PURPOSE: The NIH Undiagnosed Diseases Program (UDP) aims to provide diagnoses to patients who have previously received exhaustive evaluations yet remain undiagnosed. Patients undergo procedural anesthesia for deep phenotyping for analysis with genomic testing. METHODS: A retrospective chart review was performed to determine the safety and benefit of procedural anesthesia in pediatric patients in the UDP. Adverse perioperative events were classified as anesthesia-related complications or peri-procedural complications. The contribution of procedures performed under anesthesia to arriving at a diagnosis was also determined. RESULTS: From 2008 to 2020, 249 pediatric patients in the UDP underwent anesthesia for diagnostic procedures. The majority had a severe systemic disease (American Society for Anesthesiology status III, 79%) and/or a neurologic condition (91%). Perioperative events occurred in 45 patients; six of these were attributed to anesthesia. All patients recovered fully without sequelae. Nearly half of the 249 patients (49%) received a diagnosis, and almost all these diagnoses (88%) took advantage of information gleaned from procedures performed under anesthesia. CONCLUSIONS: The benefits of anesthesia involving multiple diagnostic procedures in a well-coordinated, multidisciplinary, research setting, such as in the pediatric UDP, outweigh the risks.
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Anestesia , Anestesiologia , Doenças não Diagnosticadas , Criança , Humanos , Estados Unidos/epidemiologia , Doenças não Diagnosticadas/etiologia , Estudos Retrospectivos , Anestesia/efeitos adversos , Medição de Risco , Difosfato de UridinaRESUMO
Glycogen storage disease type IV (GSD IV) is an ultra-rare autosomal recessive disorder caused by pathogenic variants in GBE1 which results in reduced or deficient glycogen branching enzyme activity. Consequently, glycogen synthesis is impaired and leads to accumulation of poorly branched glycogen known as polyglucosan. GSD IV is characterized by a remarkable degree of phenotypic heterogeneity with presentations in utero, during infancy, early childhood, adolescence, or middle to late adulthood. The clinical continuum encompasses hepatic, cardiac, muscular, and neurologic manifestations that range in severity. The adult-onset form of GSD IV, referred to as adult polyglucosan body disease (APBD), is a neurodegenerative disease characterized by neurogenic bladder, spastic paraparesis, and peripheral neuropathy. There are currently no consensus guidelines for the diagnosis and management of these patients, resulting in high rates of misdiagnosis, delayed diagnosis, and lack of standardized clinical care. To address this, a group of experts from the United States developed a set of recommendations for the diagnosis and management of all clinical phenotypes of GSD IV, including APBD, to support clinicians and caregivers who provide long-term care for individuals with GSD IV. The educational resource includes practical steps to confirm a GSD IV diagnosis and best practices for medical management, including (a) imaging of the liver, heart, skeletal muscle, brain, and spine, (b) functional and neuromusculoskeletal assessments, (c) laboratory investigations, (d) liver and heart transplantation, and (e) long-term follow-up care. Remaining knowledge gaps are detailed to emphasize areas for improvement and future research.
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Doença de Depósito de Glicogênio Tipo IV , Doença de Depósito de Glicogênio , Doenças Neurodegenerativas , Pré-Escolar , Humanos , Doença de Depósito de Glicogênio Tipo IV/diagnóstico , Doença de Depósito de Glicogênio Tipo IV/genética , Doença de Depósito de Glicogênio Tipo IV/terapia , Doença de Depósito de Glicogênio/diagnóstico , Doença de Depósito de Glicogênio/genética , Doença de Depósito de Glicogênio/terapia , GlicogênioRESUMO
OBJECTIVES: Innovations to improve public sanitation facilities, especially in healthcare facilities (HCFs) in low-income countries, are limited. SaTo pans represent novel, largely untested, modifications to reduce odour and flies and improve acceptability of HCF sanitation facilities. We conducted a pilot project to evaluate acceptability, cleanliness, flies and odour within latrines in 37 HCFs in Kisumu, Kenya, randomised into intervention (SaTo pan modifications) and control arms by sub-county and HCF level. METHODS: At baseline (pre-intervention) and endline (>3 months after completion of SaTo pan installations in latrines in intervention HCFs), we surveyed users, cleaners and in-charges, observed odour and cleanliness, and assessed flies using fly tape. Unadjusted difference-in-difference analysis compared changes from baseline to endline in patient-reported acceptability and observed latrine conditions between intervention and control HCFs. A secondary assessment compared patient-reported acceptability following use of SaTo pan versus non-SaTo pan latrines within intervention HCFs. RESULTS: Patient-reported acceptability of latrines was higher following the intervention (baseline: 87%, endline: 96%, p = 0.05). However, patient-reported acceptability was also high in the control arm (79%, 86%, p = 0.34), and the between-arm difference-in-difference was not significant. Enumerator-observed odour declined in intervention latrines (32%-14%) compared with controls (36%-51%, difference-in-difference ratio: 0.32, 95% confidence interval: 0.12-0.84), but changes in flies, puddling of urine and visible faeces did not differ between arms. In the secondary assessment, fewer intervention than control latrines had patient-reported flies (0% vs. 26%) and odour (18% vs. 50%), and reported satisfaction was greater. Most cleaners reported dropholes and floors were easier to clean in intervention versus controls; limited challenges with water for flushing were reported. CONCLUSIONS: Our results suggest SaTo pans may be acceptable by cleaners and users and reduce odour in HCF sanitation facilities, though challenges exist and further evaluation with larger sample sizes is needed.
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Dípteros , Banheiros , Animais , Humanos , Atenção à Saúde , Quênia , Projetos Piloto , Saneamento , TecnologiaRESUMO
Hydrogen peroxide is a primary atmospheric oxidant significant in terminating gas-phase chemistry and sulfate formation in the condensed phase. Laboratory experiments have shown an unexpected oxidation acceleration by hydrogen peroxide in grain boundaries. While grain boundaries are frequent in natural snow and ice and are known to host impurities, it remains unclear how and to which extent hydrogen peroxide enters this reservoir. We present the first experimental evidence for the diffusive uptake of hydrogen peroxide into grain boundaries directly from the gas phase. We have machined a novel flow reactor system featuring a drilled ice flow tube that allows us to discern the effect of the ice grain boundary content on the uptake. Further, adsorption to the ice surface for temperatures from 235 to 258 K was quantified. Disentangling the contribution of these two uptake processes shows that the transfer of hydrogen peroxide from the atmosphere to snow at temperatures relevant to polar environments is considerably more pronounced than previously thought. Further, diffusive uptake to grain boundaries appears to be a novel mechanism for non-acidic trace gases to fill the highly reactive impurity reservoirs in snow's grain boundaries.
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Peróxido de Hidrogênio , Gelo , Neve/química , Gases , TemperaturaRESUMO
We report aircraft observations of extreme levels of HCl and the dihalogens Cl2, Br2, and BrCl in an industrial plume near the Great Salt Lake, Utah. Complete depletion of O3 was observed concurrently with halogen enhancements as a direct result of photochemically produced halogen radicals. Observed fluxes for Cl2, HCl, and NOx agreed with facility-reported emissions inventories. Bromine emissions are not required to be reported in the inventory, but are estimated as 173 Mg year-1 Br2 and 949 Mg year-1 BrCl, representing a major uncounted oxidant source. A zero-dimensional photochemical box model reproduced the observed O3 depletions and demonstrated that bromine radical cycling was principally responsible for the rapid O3 depletion. Inclusion of observed halogen emissions in both the box model and a 3D chemical model showed significant increases in oxidants and particulate matter (PM2.5) in the populated regions of the Great Salt Lake Basin, where winter PM2.5 is among the most severe air quality issues in the U.S. The model shows regional PM2.5 increases of 10%-25% attributable to this single industrial halogen source, demonstrating the impact of underreported industrial bromine emissions on oxidation sources and air quality within a major urban area of the western U.S.
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Poluentes Atmosféricos , Poluição do Ar , Perda de Ozônio , Ozônio , Poluentes Atmosféricos/análise , Halogênios , Ozônio/análise , Bromo , Lagos , Poluição do Ar/análise , Material Particulado/análise , OxidantesRESUMO
PURPOSE: Low-density lipoprotein cholesterol (LDL-C) recommendations differ between the 2018 American College of Cardiology/American Heart Association (ACC/AHA) and 2019 European Society of Cardiology/European Atherosclerosis Society (ESC/EAS) guidelines for patients with atherosclerotic cardiovascular disease (ASCVD) (< 70 vs. < 55 mg/dl, respectively). In the DA VINCI study, residual cardiovascular risk was predicted in ASCVD patients. The extent to which relative and absolute risk might be lowered by achieving ACC/AHA versus ESC/EAS LDL-C recommended approaches was simulated. METHODS: DA VINCI was a cross-sectional observational study of patients prescribed lipid-lowering therapy (LLT) across 18 European countries. Ten-year cardiovascular risk (CVR) was predicted among ASCVD patients receiving stabilized LLT. For patients with LDL-C ≥ 70 mg/dl, the absolute LDL-C reduction required to achieve an LDL-C of < 70 or < 55 mg/dl (LDL-C of 69 or 54 mg/dl, respectively) was calculated. Relative and absolute risk reductions (RRRs and ARRs) were simulated. RESULTS: Of the 2039 patients, 61% did not achieve LDL-C < 70 mg/dl. For patients with LDL-C ≥ 70 mg/dl, median (interquartile range) baseline LDL-C and 10-year CVR were 93 (81-115) mg/dl and 32% (25-43%), respectively. Median LDL-C reductions of 24 (12-46) and 39 (27-91) mg/dl were needed to achieve an LDL-C of 69 and 54 mg/dl, respectively. Attaining ACC/AHA or ESC/EAS goals resulted in simulated RRRs of 14% (7-25%) and 22% (15-32%), respectively, and ARRs of 4% (2-7%) and 6% (4-9%), respectively. CONCLUSION: In ASCVD patients, achieving ESC/EAS LDL-C goals could result in a 2% additional ARR over 10 years versus the ACC/AHA approach.
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Aterosclerose , Doenças Cardiovasculares , Inibidores de Hidroximetilglutaril-CoA Redutases , Estados Unidos/epidemiologia , Humanos , LDL-Colesterol , Inibidores de Hidroximetilglutaril-CoA Redutases/uso terapêutico , Estudos Transversais , Aterosclerose/diagnóstico , Aterosclerose/tratamento farmacológico , Aterosclerose/epidemiologia , Comportamento de Redução do Risco , Doenças Cardiovasculares/diagnóstico , Doenças Cardiovasculares/epidemiologia , Doenças Cardiovasculares/prevenção & controle , Fatores de RiscoRESUMO
BACKGROUND: The present study aimed at (1) providing further validity and reliability evidence for the Italian version of the cognitive section of the ALS Cognitive Behavioral Screen (ALS-CBS™) and (2) testing its diagnostics within an Italian ALS cohort, as well as at (3) exploring its capability to discriminate patients from healthy controls (HCs). METHODS: N = 293 non-demented ALS patients were administered the cognitive sections of the ALS-CBS™ and Edinburgh Cognitive and Behavioural ALS Screen (ECAS). N = 96 HCs demographically matched with N = 96 patients were also administered the cognitive section of the ALS-CBS™. In patients, factorial and construct validity, internal reliability, and diagnostics against a defective score on the cognitive section of the ECAS were tested. Case-control discrimination was assessed via a logistic regression. RESULTS: ALS-CBS™ cognitive subscales were underpinned by a simple, unidimensional structure, internally reliable (McDonald's ω = 0.74), and mostly related with ECAS executive and fluency scores (rs = 0.54-0.71). Both raw and age- and education-adjusted scores on the cognitive section of the ALS-CBS™ accurately detected ECAS-defined cognitive impairment (AUC = 0.80 and .88, respectively), yielding optimal error-based, information-based and unitary diagnostics. A cut-off of < 15.374 was identified on adjusted scores. The test was able to discriminate patients from HCs (p < 0.001). DISCUSSION: The cognitive section of the Italian ALS-CBS™ is a valid, reliable, and diagnostically sound ALS-specific screener for detecting frontotemporal, executive-/attentive-based cognitive inefficiency in non-demented ALS patients, being also able to discriminate them from normotypical individuals.
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Esclerose Lateral Amiotrófica , Transtornos Cognitivos , Disfunção Cognitiva , Humanos , Transtornos Cognitivos/diagnóstico , Transtornos Cognitivos/etiologia , Esclerose Lateral Amiotrófica/complicações , Esclerose Lateral Amiotrófica/diagnóstico , Esclerose Lateral Amiotrófica/psicologia , Reprodutibilidade dos Testes , Testes Neuropsicológicos , Disfunção Cognitiva/diagnóstico , Itália , Cognição/fisiologiaRESUMO
BACKGROUND: Expectations for psychological responses to exercise are not well characterized, particularly in people at risk for anxiety-related illnesses. Given the substantial evidence for salutary effects of exercise on anxiety symptoms and emerging recognition for expectations as a critical mechanism of placebo/nocebo effects, this study explored the interplay between expectations and physical activity in young adults with and without analogue generalized anxiety disorder. METHODS: Participants (N=470, 23.2±4.8 years, 63% female) completed a physical activity and mood survey, including a 7-day physical activity recall questionnaire, and a 20-item questionnaire designed to measure positive and negative expectations for psychological and perceptual responses to exercise, particularly expectations for symptoms in the generalized anxiety disorder symptom profile. Analogue generalized anxiety disorder status was determined using the Generalized Anxiety Disorder subscale of the Psychiatric Diagnostic Screening Questionnaire. RESULTS: For select outcomes, expected exercise-induced changes significantly differed according to analogue generalized anxiety disorder (whole-body pain, sleep quality, psychological well-being, stress, relaxation) and active versus inactive (anxious mood, depressed mood, concentration, physical function, psychological well-being, relaxation) status. However, these findings did not survive corrections for multiple comparisons and the magnitude of these differences was small, approximating 0.25 standard deviations. Expectations for anxious (Spearman's ρ=-0.14, p≤0.002) and depressed mood (ρ=-0.15, p≤0.002), and psychological well-being (ρ=0.15, p≤0.001) were significantly associated with higher physical activity levels. Exercise expectations for anxious mood explained a significant, but small (+1.5%, p≤0.03), amount of variance in physical activity. CONCLUSIONS: Expectations for exercise-induced improvements did not significantly differ between young adults based on analogue generalized anxiety disorder or physical activity status.
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Transtornos de Ansiedade , Depressão , Adulto Jovem , Humanos , Feminino , Masculino , Estudos Transversais , Exercício Físico , Ansiedade , Inquéritos e QuestionáriosRESUMO
BACKGROUND: The aim of this year-long mixed methods research was to examine the intersection between health, health literacy and local government to identify ways to better connect people to place-based primary health care (PHC). METHODS: Four local government areas located within the Perth metropolitan geographic area provided the setting for the current research. Researchers were co-located into the four local governments over a 10-month period to engage with community stakeholders and services. Two methodologies were used to achieve the objective: eight group model building (GMB) workshops were conducted with N = 148 participants to create causal loop diagrams of the barriers and enablers to people being healthy and well in each of the LGAs and develop potential action ideas from these. Surveys were used to collect health service use and health literacy, as measured using a validated Health Literacy Questionnaire (HLQ), across the four LGAs (N = 409, approximately 100 respondents/area). RESULTS: The causal loop diagram themes common across LGAs included: (1) mental health; (2) access to services; (3) health system capacity; (4) economics; and (5) physical wellbeing. Health literacy was relatively high for all nine domains of the HLQ. In the five domains rated from one to four the lowest score was 2.8 for 'appraisal of information' and the highest was 3.2 for 'feeling understood and supported by healthcare providers'. In the four domains rated from one to five; the lowest score was 3.7 for 'navigating the healthcare system' and the highest was 4.1 for 'understand health information well enough to know what to do'. Prioritised action ideas recommended increases in practitioners to meet local needs and training General Practitioners and other health staff in culturally sensitive and trauma informed health care. The survey findings and field notes from the GMB were used to construct personas embodied in vignettes highlighting general themes identified in the workshops including those relevant to local areas. CONCLUSIONS: There are many possibilities for health care and local governments to work together to bring services to community members disengaged from the health system. Bringing together people from diverse backgrounds and organisations created synergies that resulted in novel and feasible potential strategies to improve community health.
Assuntos
Letramento em Saúde , Humanos , Austrália Ocidental , Governo Local , Atenção à Saúde , Atenção Primária à Saúde , Inquéritos e QuestionáriosRESUMO
Two factors that decrease the replicability of studies in the scientific literature are publication bias and studies with underpowered desgins. One way to ensure that studies have adequate statistical power to detect the effect size of interest is by conducting a-priori power analyses. Yet, a previous editorial published in the Journal of Sports Sciences reported a median sample size of 19 and the scarce usage of a-priori power analyses. We meta-analysed 89 studies from the same journal to assess the presence and extent of publication bias, as well as the average statistical power, by conducting a z-curve analysis. In a larger sample of 174 studies, we also examined a) the usage, reporting practices and reproducibility of a-priori power analyses; and b) the prevalence of reporting practices of t-statistic or F-ratio, degrees of freedom, exact p-values, effect sizes and confidence intervals. Our results indicate that there was some indication of publication bias and the average observed power was low (53% for significant and non-significant findings and 61% for only significant findings). Finally, the usage and reporting practices of a-priori power analyses as well as statistical results including test statistics, effect sizes and confidence intervals were suboptimal.
Assuntos
Projetos de Pesquisa , Humanos , Viés de Publicação , Reprodutibilidade dos Testes , Tamanho da Amostra , ViésRESUMO
Counselor turnover is a serious problem for substance use disorder (SUD) treatment programs, especially in rural areas. This study examined the relationship between workload, workplace environment, and emotional exhaustion on turnover intentions among SUD treatment counselors in rural Pennsylvania. An online, anonymous survey was administered to rural SUD treatment counselors in Pennsylvania between October and December 2020. Completed surveys from 206 counselors were used for analysis. Variables included multi-dimensional measures of emotional exhaustion, intention to quit, workload, and workplace environment. Results showed age, perceptions of distributive justice, and management communication to be inversely related to emotional exhaustion and intention to quit. A subsequent analysis showed that the direct effects of these variables on intention to quit were reduced with the inclusion of emotional exhaustion in modeling, suggesting a potential mediation effect. Findings indicated that higher levels of emotional exhaustion were directly related to a greater intention to quit. A statistically significant indirect relationship was also found for distributive justice on intention to quit through emotional exhaustion, indicating a significant mediating effect. While counseling is a stressful occupation with high potential for burnout, these results show that organizations can adopt practices that help lower emotional exhaustion and turnover intentions for their counselors which could improve retention in the SUD treatment field. This is especially important for rural areas, where there is a high demand for SUD services and not enough treatment workers to meet that demand.
Rural SUD counselors experience high levels of burnout and turnover.Emotional exhaustion ("burnout") is the strongest predictor of intent to quit.Management communication and distributive justice can improve counselor retention.