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1.
Europace ; 26(2)2024 Feb 01.
Artigo em Inglês | MEDLINE | ID: mdl-38366154

RESUMO

AIMS: Common to adult electrophysiology studies (EPSs), intracardiac echocardiography (ICE) use in paediatric and congenital heart disease (CHD) EPS is limited. The purpose of this study was to assess the efficacy of ICE use and incidence of associated complications in paediatric and CHD EPS. METHODS AND RESULTS: This single-centre retrospective matched cohort study reviewed EPS between 2013 and 2022. Demographics, CHD type, and EPS data were collected. Intracardiac echocardiography cases were matched 1:1 to no ICE controls to assess differences in complications, ablation success, fluoroscopy exposure, procedure duration, and arrhythmia recurrence. Cases and controls with preceding EPS within 5 years were excluded. Intracardiac echocardiography cases without an appropriate match were excluded from comparative analyses but included in the descriptive cohort. We performed univariable and multivariable logistic regression to assess associations between variables and outcomes. A total of 335 EPS were reviewed, with ICE used in 196. The median age of ICE cases was 15 [interquartile range (IQR) 12-17; range 3-47] years, and median weight 57 [IQR 45-71; range 15-134] kg. There were no ICE-related acute or post-procedural complications. There were 139 ICE cases matched to no ICE controls. Baseline demographics and anthropometrics were similar between cases and controls. Fluoroscopy exposure (P = 0.02), procedure duration (P = 0.01), and arrhythmia recurrence (P = 0.01) were significantly lower in ICE cases. CONCLUSION: Intracardiac echocardiography in paediatric and CHD ablations is safe and reduces procedure duration, fluoroscopy exposure, and arrhythmia recurrence. However, not every arrhythmia substrate requires ICE use. Thoughtful selection will ensure the judicious and strategic application of ICE to enhance outcomes.


Assuntos
Ablação por Cateter , Cardiopatias Congênitas , Adulto , Humanos , Criança , Estudos Retrospectivos , Estudos de Coortes , Resultado do Tratamento , Arritmias Cardíacas/diagnóstico por imagem , Arritmias Cardíacas/cirurgia , Ecocardiografia/métodos , Fluoroscopia , Ablação por Cateter/efeitos adversos , Cardiopatias Congênitas/diagnóstico por imagem , Cardiopatias Congênitas/cirurgia
2.
FEMS Microbiol Ecol ; 100(2)2024 01 24.
Artigo em Inglês | MEDLINE | ID: mdl-38200713

RESUMO

The discharge of hydrothermal vents on the seafloor provides energy sources for dynamic and productive ecosystems, which are supported by chemosynthetic microbial populations. These populations use the energy gained by oxidizing the reduced chemicals contained within the vent fluids to fix carbon and support multiple trophic levels. Hydrothermal discharge is ephemeral and chemical composition of such fluids varies over space and time, which can result in geographically distinct microbial communities. To investigate the foundational members of the community, microbial growth chambers were placed within the hydrothermal discharge at Axial Seamount (Juan de Fuca Ridge), Magic Mountain Seamount (Explorer Ridge), and Kama'ehuakanaloa Seamount (Hawai'i hotspot). Campylobacteria were identified within the nascent communities, but different amplicon sequence variants were present at Axial and Kama'ehuakanaloa Seamounts, indicating that geography in addition to the composition of the vent effluent influences microbial community development. Across these vent locations, dissolved iron concentration was the strongest driver of community structure. These results provide insights into nascent microbial community structure and shed light on the development of diverse lithotrophic communities at hydrothermal vents.


Assuntos
Fontes Hidrotermais , Microbiota , Água do Mar/microbiologia , Biodiversidade , Fontes Hidrotermais/microbiologia , Processos Autotróficos , Filogenia
3.
Front Cell Infect Microbiol ; 13: 1253670, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37965264

RESUMO

Tick serine protease inhibitors (serpins) play crucial roles in tick feeding and pathogen transmission. We demonstrate that Ixodes scapularis (Ixs) nymph tick saliva serpin (S) 41 (IxsS41), secreted by Borrelia burgdorferi (Bb)-infected ticks at high abundance, is involved in regulating tick evasion of host innate immunity and promoting host colonization by Bb. Recombinant (r) proteins were expressed in Pichia pastoris, and substrate hydrolysis assays were used to determine. Ex vivo (complement and hemostasis function related) and in vivo (paw edema and effect on Bb colonization of C3H/HeN mice organs) assays were conducted to validate function. We demonstrate that rIxsS41 inhibits chymase and cathepsin G, pro-inflammatory proteases that are released by mast cells and neutrophils, the first immune cells at the tick feeding site. Importantly, stoichiometry of inhibition analysis revealed that 2.2 and 2.8 molecules of rIxsS41 are needed to 100% inhibit 1 molecule of chymase and cathepsin G, respectively, suggesting that findings here are likely events at the tick feeding site. Furthermore, chymase-mediated paw edema, induced by the mast cell degranulator, compound 48/80 (C48/80), was blocked by rIxsS41. Likewise, rIxsS41 reduced membrane attack complex (MAC) deposition via the alternative and lectin complement activation pathways and dose-dependently protected Bb from complement killing. Additionally, co-inoculating C3H/HeN mice with Bb together with rIxsS41 or with a mixture (rIxsS41 and C48/80). Findings in this study suggest that IxsS41 markedly contributes to tick feeding and host colonization by Bb. Therefore, we conclude that IxsS41 is a potential candidate for an anti-tick vaccine to prevent transmission of the Lyme disease agent.


Assuntos
Borrelia burgdorferi , Ixodes , Doença de Lyme , Serpinas , Camundongos , Animais , Ixodes/fisiologia , Quimases , Ninfa , Catepsina G , Saliva/metabolismo , Camundongos Endogâmicos C3H , Inflamação , Serpinas/metabolismo , Proteínas do Sistema Complemento , Edema
4.
Eur J Appl Physiol ; 2023 Nov 11.
Artigo em Inglês | MEDLINE | ID: mdl-37950762

RESUMO

PURPOSE: This study examined the acute effects of interrupting sitting with light-intensity walking on postprandial cardiometabolic risk markers in South Asian adults. METHODS: South Asians with overweight/obesity (n = 19; body mass index [BMI] > 23 kg·m-2) and normal-weight (n = 8; BMI 18.0-22.9 kg·m-2) aged 48.8 ± 5.6 years completed two, 5-h conditions: (1) prolonged sitting (SIT), and (2) interrupted sitting with 5-min bouts of light-intensity walking every 30-min (INT-SIT). Blood samples and resting expired air samples were collected throughout each condition. Statistical analyses were completed using linear mixed models. RESULTS: In participants with overweight/obesity, postprandial glucose, triglycerides (TAG) and metabolic load index (MLI) over time were lower, whereas resting substrate utilisation and resting energy expenditure (REE) were higher, in INT-SIT than SIT (all p ≤ 0.05). Compared with SIT (0.18 [95% CI 0.13, 0.22] kcal.min-1), INT-SIT (0.23 [95% CI 0.18, 0.27] kcal.min-1) increased postprandial REE iAUC in participants with overweight/obesity (p = 0.04, d = 0.51). Postprandial TAG concentrations over time were lower in INT-SIT versus SIT (p = 0.01, d = 30) in normal-weight participants, with no differences in any other outcomes for this sample group. CONCLUSION: These findings suggest that interrupting sitting with 5-min bouts of light walking every 30-min acutely attenuates cardiometabolic risk markers among South Asians living with overweight/obesity, whereas limited effects may be seen in individuals with normal-weight.

5.
Front Vet Sci ; 10: 1240227, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37818390

RESUMO

Many dairy operations uses a Brix refractometer to assess the quality of first-milking colostrum. This study investigated whether a digital Brix refractometer could be used in a model to predict colostrum IgG concentration and whether more than one %Brix threshold could be used for different colostrum IgG concentrations. Colostrum from 182 animals was tested using a digital Brix refractometer and by single radial immunodiffusion. Statistical analysis, using simple linear regression to relate %Brix results with corresponding colostral IgG concentration, and receiver operating characteristic (ROC) analysis were used to identify %Brix cutoffs that had no false positive results. Colostral IgG concentrations from digital Brix refractometry had a R2 value of 0.818 and a S-value of 21.7 g/L. The large S-value shows that a digital Brix refractometer should not be used in a model to predict colostrum IgG concentration. However, %Brix scores of 19.0, 22.0, 25.0 and 30.0 percent can be used to estimate minimum colostral IgG concentrations of 25, 50, 75 and 100 g/L. These four cutoffs can be used to strategically feed smaller volumes of colostrum to newborn calves. Smaller volumes may reduce unwanted side effects and shorten the time interval in which calves refuse to nurse, while still delivering an adequate mass of IgG to have successful transfer of passive immunity.

6.
Heart Rhythm ; 20(12): 1752-1758, 2023 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-37648183

RESUMO

BACKGROUND: Guidelines addressing magnetic resonance imaging (MRI) in patients with cardiac implantable electronic devices (CIEDs) provide algorithms for imaging pediatric and congenital heart disease (CHD) patients. Guideline acceptance varies by institution. Guidelines also do not support routine MRI scans in patients with epicardial or abandoned leads, common in pediatric and CHD patients. OBJECTIVE: The purpose of this study was to determine the incidence of MRI-related complications in pediatric and CHD patients with CIEDs, including epicardial and/or abandoned leads. METHODS: A multicenter retrospective review included patients with CIEDs who underwent any MRI between 2007 and 2022 at congenital cardiac centers. The primary outcome was any patient adverse event or clinically significant CIED change after MRI, defined as pacing lead capture threshold increase >0.5 V with output change, P- or R- wave amplitude decrease >50% with sensitivity change, or impedance change >50%. RESULTS: Across 14 institutions, 314 patients (median age 18.8 [1.3; 31.4] years) underwent 389 MRIs. There were 288 pacemakers (74%) and 87 implantable cardioverter-defibrillators (22%); 52% contained epicardial leads, and 14 (4%) were abandoned leads only. Symptoms or CIED changes occurred in 4.9% of MRI scans (6.1% of patients). On 9 occasions (2%), warmth or pain occurred. Pacing capture threshold or lead impedance changes occurred in 1.4% and 2.0% of CIEDs post-MRI and at follow-up. CONCLUSION: Our data provide evidence that MRIs can be performed in pediatric and CHD patients with CIEDs, including non-MRI-conditional CIEDs and epicardial and/or abandoned leads, with rare minor symptoms or CIED changes but no other complications.


Assuntos
Desfibriladores Implantáveis , Cardiopatias Congênitas , Marca-Passo Artificial , Adolescente , Criança , Humanos , Cardiopatias Congênitas/diagnóstico , Cardiopatias Congênitas/terapia , Imageamento por Ressonância Magnética/métodos , Estudos Retrospectivos , Lactente , Pré-Escolar , Adulto Jovem , Adulto
7.
Gerontologist ; 2023 Aug 07.
Artigo em Inglês | MEDLINE | ID: mdl-37549891

RESUMO

BACKGROUND AND OBJECTIVES: State regulating agencies use 350 different licenses and certifications to govern assisted living (AL), resulting in significant variation in regulations governing health services, the scope of practice, and capacity. This lack of standardization makes it difficult to compare and contrast AL operations and residents' outcomes across similarly regulated communities. RESEARCH DESIGN AND METHODS: We used qualitative and quantitative methods to empirically develop and describe a typology of state AL regulations that captures inter and intra-state variation. Based on the rules governing health services, we created regulatory specificity scores for five thematic dimensions: medication administration, third-party care, skilled nursing, medication review, and licensed nurse staffing. With these scores, we conducted a K-means cluster analysis to identify groups of AL license types. To differentiate the regulatory types, we calculated standardized mean differences across structure, process, outcome, and resident characteristics of the AL communities licensed under each type. RESULTS: We identified six types of AL differentiated by the regulatory provisions governing health services: Housing, Holistic, Hybrid, Hospitality, Healthcare, and Health Support. The types align with previous work and reflect tangible differences in resident characteristics, health service structures, processes, and outcomes. DISCUSSION AND IMPLICATIONS: This typology effectively captures differences across regulated dimensions and can inform and support quality of care. Researchers, policymakers, and consumers may benefit from using this typology and acknowledging these differences in AL licensure when designing research studies, developing policies, and selecting an AL community.

8.
Mod Pathol ; 36(10): 100285, 2023 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-37474003

RESUMO

We have developed an artificial intelligence (AI)-based digital pathology model for the evaluation of histologic features related to eosinophilic esophagitis (EoE). In this study, we evaluated the performance of our AI model in a cohort of pediatric and adult patients for histologic features included in the Eosinophilic Esophagitis Histologic Scoring System (EoEHSS). We collected a total of 203 esophageal biopsy samples from patients with mucosal eosinophilia of any degree (91 adult and 112 pediatric patients) and 10 normal controls from a prospectively maintained database. All cases were assessed by a specialized gastrointestinal (GI) pathologist for features in the EoEHSS at the time of original diagnosis and rescored by a central GI pathologist (R.K.M.). We subsequently analyzed whole-slide image digital slides using a supervised AI model operating in a cloud-based, deep learning AI platform (Aiforia Technologies) for peak eosinophil count (PEC) and several histopathologic features in the EoEHSS. The correlation and interobserver agreement between the AI model and pathologists (Pearson correlation coefficient [rs] = 0.89 and intraclass correlation coefficient [ICC] = 0.87 vs original pathologist; rs = 0.91 and ICC = 0.83 vs central pathologist) were similar to the correlation and interobserver agreement between pathologists for PEC (rs = 0.88 and ICC = 0.91) and broadly similar to those for most other histologic features in the EoEHSS. The AI model also accurately identified PEC of >15 eosinophils/high-power field by the original pathologist (area under the curve [AUC] = 0.98) and central pathologist (AUC = 0.98) and had similar AUCs for the presence of EoE-related endoscopic features to pathologists' assessment. Average eosinophils per epithelial unit area had similar performance compared to AI high-power field-based analysis. Our newly developed AI model can accurately identify, quantify, and score several of the main histopathologic features in the EoE spectrum, with agreement regarding EoEHSS scoring which was similar to that seen among GI pathologists.

9.
J Am Med Dir Assoc ; 24(10): 1513-1517.e3, 2023 10.
Artigo em Inglês | MEDLINE | ID: mdl-37268016

RESUMO

OBJECTIVE: Present an updated approach to identifying Medicare beneficiaries residing in licensed assisted living (AL) settings in the United States. DESIGN: Retrospective cohort study using a national list of licensed AL settings, US Postal Service (USPS) data, and enrollment, claims, and assessment data from the Centers for Medicare and Medicaid Services. SETTING AND PARTICIPANTS: A total of 403,326 beneficiaries residing in 29,905 licensed AL settings. METHODS: We identified every ZIP+4 code affiliated with each AL address. We then identified all of the Medicare beneficiaries with that ZIP+4 on January 1, 2019, and excluded beneficiaries in nursing homes and hospitals on that date. We identified beneficiaries who were "definitively" and "very likely AL residents" according to the number of addresses corresponding to the ZIP+4 in the USPS data, the capacity of the AL setting, and the presence of a claim or assessment indicating services were delivered in AL. We compared beneficiaries excluded during our new capacity restriction step (ie, "possibly neighbors") to those included as being "definitively" and "very likely AL residents" using standardized mean differences. RESULTS: The cohort excluded (ie, "possibly neighbors") using our new step in the identification process appears to be younger and healthier than the cohorts we include as being "definitively" and "very likely AL residents." In addition, the cohort we identified through our added step of supplementing with claims and assessment data have similar demographics to the other cohorts we include, although they appear to be in poorer health. CONCLUSIONS AND IMPLICATIONS: Leveraging licensed capacity information and supplementing with claims and assessment data produce greater confidence in the ability to accurately identify AL residents using ZIP+4 codes reported in Medicare administrative data.


Assuntos
Medicare , Casas de Saúde , Idoso , Humanos , Estados Unidos , Estudos Retrospectivos
10.
Histopathology ; 83(4): 512-525, 2023 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-37387193

RESUMO

AIMS: Reticulin stain is used routinely in the histological evaluation of hepatocellular carcinoma (HCC). The goal of this study was to assess whether the histological reticulin proportionate area (RPA) in HCCs predicts tumour-related outcomes. METHODS AND RESULTS: We developed and validated a supervised artificial intelligence (AI) model that utilises a cloud-based, deep-learning AI platform (Aiforia Technologies, Helsinki, Finland) to specifically recognise and quantify the reticulin framework in normal livers and HCCs using routine reticulin staining. We applied this reticulin AI model to a cohort of consecutive HCC cases from patients undergoing curative resection between 2005 and 2015. A total of 101 HCC resections were included (median age = 68 years, 64 males, median follow-up time = 49.9 months). AI model RPA reduction of > 50% (compared to normal liver tissue) was predictive of metastasis [hazard ratio (HR) = 3.76, P = 0.004, disease-free survival (DFS, HR = 2.48, P < 0.001) and overall survival (OS), HR = 2.80, P = 0.001]. In a Cox regression model, which included clinical and pathological variables, RPA decrease was an independent predictor of DFS and OS and the only independent predictor of metastasis. Similar results were found in the moderately differentiated HCC subgroup (WHO grade 2), in which reticulin quantitative analysis was an independent predictor of metastasis, DFS and OS. CONCLUSION: Our data indicate that decreased RPA is a strong predictor of various HCC-related outcomes, including within the moderately differentiated subgroup. Reticulin, therefore, may represent a novel and important prognostic HCC marker, to be further explored and validated.


Assuntos
Carcinoma Hepatocelular , Neoplasias Hepáticas , Masculino , Humanos , Idoso , Carcinoma Hepatocelular/diagnóstico , Carcinoma Hepatocelular/patologia , Neoplasias Hepáticas/diagnóstico , Neoplasias Hepáticas/patologia , Reticulina , Inteligência Artificial , Biomarcadores Tumorais/análise , Prognóstico , Estudos Retrospectivos
11.
Lab Invest ; 103(9): 100200, 2023 09.
Artigo em Inglês | MEDLINE | ID: mdl-37331629

RESUMO

Currently, the precise evaluation of tissue hepatic iron content (HIC) requires laboratory testing using tissue-destructive methods based on colorimetry or spectrophotometry. To maximize the use of routine histologic stains in this context, we developed an artificial intelligence (AI) model for the recognition and spatially resolved measurement of iron in liver samples. Our AI model was developed using a cloud-based, supervised deep learning platform (Aiforia Technologies). Using digitized Pearl Prussian blue iron stain whole slide images representing the full spectrum of changes seen in hepatic iron overload, our training set consisted of 59 cases, and our validation set consisted of 19 cases. The study group consisted of 98 liver samples from 5 different laboratories, for which tissue quantitative analysis using inductively coupled plasma mass spectrometry was available, collected between 2012 and 2022. The correlation between the AI model % iron area and HIC was Rs = 0.93 for needle core biopsy samples (n = 73) and Rs = 0.86 for all samples (n = 98). The digital hepatic iron index (HII) was highly correlated with HII > 1 (area under the curve [AUC] = 0.93) and HII > 1.9 (AUC = 0.94). The percentage area of iron within hepatocytes (vs Kupffer cells and portal tract iron) identified patients with any hereditary hemochromatosis-related mutations (either homozygous or heterozygous) (AUC = 0.65, P = .01) with at least similar accuracy than HIC, HII, and any histologic iron score. The correlation between the Deugnier and Turlin score and the AI model % iron area for all patients was Rs = 0.87 for total score, Rs = 0.82 for hepatocyte iron score, and Rs = 0.84 for Kupffer cell iron score. Iron quantitative analysis using our AI model was highly correlated with both detailed histologic scoring systems and tissue quantitative analysis using inductively coupled plasma mass spectrometry and offers advantages (related to the spatial resolution of iron analysis and the nontissue-destructive nature of the test) over standard quantitative methods.


Assuntos
Hemocromatose , Sobrecarga de Ferro , Humanos , Ferro , Inteligência Artificial , Fígado/patologia , Hemocromatose/genética , Hemocromatose/patologia , Sobrecarga de Ferro/genética , Sobrecarga de Ferro/patologia
12.
Health Place ; 82: 103046, 2023 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-37257251

RESUMO

Despite the advances in person-based approaches to studying food environments, most studies using these approaches have relied on individual-centered activity space measures and largely ignored cohabiting household members who play crucial roles in shaping an individual's food access, food behaviors, and diet. This can be problematic for completely capturing food environments relevant to an individual and add uncertainties to explorations of how individuals' food environments relate to their food behaviors. This viewpoint discusses the need for, and implications of, considering household members when measuring food access and disentangling the behavioral pathways connecting the food environment to diet. Ultimately, a conceptual framework and potential questions are proposed to integrate household members into food environment research.


Assuntos
Dieta , Alimentos , Humanos , Preferências Alimentares , Características da Família , Comportamento do Consumidor , Abastecimento de Alimentos
13.
Curr Cardiol Rep ; 25(6): 543-551, 2023 06.
Artigo em Inglês | MEDLINE | ID: mdl-37115433

RESUMO

PURPOSE OF REVIEW: With increased electrocardiogram screening, asymptomatic preexcitation has become more prevalent. Historically, the asymptomatic-symptomatic dichotomy has directed management. This approach warrants scrutiny, as asymptomatic Wolff-Parkinson-White (WPW) syndrome is not without risk. Children may be unreliable symptom reporters, have atypical arrhythmia symptoms, yet have years to become symptomatic. RECENT FINDINGS: In a large WPW study, symptomatic patients were more likely to undergo ablation than asymptomatic patients, yet, except for symptoms, there were no differences in clinical or electrophysiology study (EPS) characteristics. Present data confirm real risk in asymptomatic WPW-sudden death can be the first symptom. Although malignant arrhythmias correlate better with EPS risk stratification than with symptoms, EPS data are imperfect predictors. Unlike adults with WPW, children have yet to prove survivorship. Asymptomatic children must be treated differently than adults. Sudden death risk is low but front-loaded in the young. An aggressive approach to asymptomatic WPW is warranted in this era of highly successful, low-risk catheter ablations.


Assuntos
Ablação por Cateter , Síndrome de Wolff-Parkinson-White , Criança , Adulto , Humanos , Síndrome de Wolff-Parkinson-White/complicações , Síndrome de Wolff-Parkinson-White/diagnóstico , Síndrome de Wolff-Parkinson-White/terapia , Arritmias Cardíacas , Morte Súbita , Eletrocardiografia
14.
Pediatr Neurol ; 143: 34-43, 2023 06.
Artigo em Inglês | MEDLINE | ID: mdl-36996759

RESUMO

BACKGROUND: Neurofibromatosis type 1 (NF1) is a genetic neurocutaneous disorder commonly associated with motor and cognitive symptoms that greatly impact quality of life. Transcranial magnetic stimulation (TMS) can quantify motor cortex physiology, reflecting the basis for impaired motor function as well as, possibly, clues for mechanisms of effective treatment. We hypothesized that children with NF1 have impaired motor function and altered motor cortex physiology compared to typically developing (TD) control children and children with attention-deficit/hyperactivity disorder (ADHD). METHODS: Children aged 8-17 years with NF1 (n = 21) were compared to children aged 8-12 years with ADHD (n = 59) and TD controls (n = 88). Motor development was assessed using the Physical and Neurological Examination for Subtle Signs (PANESS) scale. The balance of inhibition and excitation in motor cortex was assessed using the TMS measures short-interval cortical inhibition (SICI) and intracortical facilitation (ICF). Measures were compared by diagnosis and tested using bivariate correlations and regression for association with clinical characteristics. RESULTS: In NF1, ADHD severity scores were intermediate between the ADHD and TD cohorts, but total PANESS scores were markedly elevated (worse) compared to both (P < 0.001). Motor cortex ICF (excitatory) was significantly lower in NF1 than in TD and ADHD (P < 0.001), but SICI (inhibitory) did not differ. However, in NF1, better PANESS scores correlated with lower SICI ratios (more inhibition; ρ = 0.62, P = 0.003) and lower ICF ratios (less excitation; ρ = 0.38, P = 0.06). CONCLUSIONS: TMS-evoked SICI and ICF may reflect processes underlying abnormal motor function in children with NF1.


Assuntos
Inibição Neural , Neurofibromatose 1 , Criança , Humanos , Adolescente , Inibição Neural/fisiologia , Neurofibromatose 1/complicações , Qualidade de Vida , Potencial Evocado Motor/fisiologia , Eletromiografia , Estimulação Magnética Transcraniana
15.
Cell Chem Biol ; 30(3): 308-320.e5, 2023 03 16.
Artigo em Inglês | MEDLINE | ID: mdl-36882060

RESUMO

RNA oxidation has been implicated in neurodegeneration, but the underlying mechanism for such effects is unclear. Extensive RNA oxidation occurs within the neurons in multiple sclerosis (MS) brains. Here, we identified selectively oxidized mRNAs in neuronal cells that pertained to neuropathological pathways. N-acetyl aspartate transferase 8 like (NAT8L) is one such transcript, whose translation product enzymatically synthesizes N-acetyl aspartic acid (NAA), a neuronal metabolite important for myelin synthesis. We reasoned that impediment of translation of an oxidized NAT8L mRNA will result in a reduction in its cognate protein, thus lowering the NAA level. This hypothesis is supported by our studies on cells, an animal model, and postmortem human MS brain. Reduced brain NAA level hampers myelin integrity making neuronal axons more susceptible to damage, which contributes to MS neurodegeneration. Overall, this work provides a framework for a mechanistic understanding of the link between RNA oxidation and neurodegeneration.


Assuntos
Esclerose Múltipla , Animais , Humanos , Esclerose Múltipla/metabolismo , Esclerose Múltipla/patologia , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , Neurônios/metabolismo , Encéfalo/metabolismo , RNA/metabolismo , Acetiltransferases/metabolismo
16.
J Am Med Dir Assoc ; 24(6): 821-826, 2023 06.
Artigo em Inglês | MEDLINE | ID: mdl-36870364

RESUMO

OBJECTIVES: Limitations to admission play a critical role in shaping the composition of residents residing within licensed assisted living (AL) communities. DESIGN: We document variation across 165 licensure classifications in how state agencies limit who AL communities may admit and what assessments are required to make those determinations. SETTING AND PARTICIPANTS: AL regulations and licensed AL communities across all 50 states in 2018. METHODS: We estimated the proportion of all licensed AL communities regulated by admission limitations and identified groups consisting of those that limit admission based on a health-related condition, specified behavior, mental health condition, and/or cognitive impairment as well as those that impose no limitations to admission. We also estimated the proportion of all licensed AL communities required to conduct assessments at time of admission. RESULTS: The largest group of ALs (29% nationally) is governed by regulations limiting the admission of persons with a health condition. The next largest group of AL communities (23.6%) limit admissions based on health, specified behavior, mental health conditions, and cognitive impairment. In contrast, 11.1% of licensed AL communities have no regulations restricting admissions. We also found that more than 8 of every 10 licensed communities were required to have residents complete a health assessment at admission, but less than half were required to complete a cognitive assessment. CONCLUSIONS AND IMPLICATIONS: The variation we observe implies that state agencies have created multiple licensure classifications that serve as a mechanism for sorting types of residents into settings based on their need (eg, health, mental health, cognitive). Although future research should investigate the implications of this regulatory diversity, the categories outlined here may be helpful to clinicians, consumers, and policy makers to better understand the options in their state and how various AL licensure classifications compare to one another.


Assuntos
Moradias Assistidas , Disfunção Cognitiva , Humanos , Estados Unidos , Hospitalização
17.
JAMA Health Forum ; 4(2): e225338, 2023 02 03.
Artigo em Inglês | MEDLINE | ID: mdl-36735249

RESUMO

This cross-sectional study examines different levels of state Medicaid financing for assisted living and the association with the number of beneficiaries with dual Medicare and Medicaid eligibility who live in assisted living facilities.


Assuntos
Medicaid , Medicare , Idoso , Humanos , Estados Unidos , Hospitalização , Definição da Elegibilidade
18.
J Palliat Med ; 26(6): 757-767, 2023 06.
Artigo em Inglês | MEDLINE | ID: mdl-36580545

RESUMO

Background: Potentially burdensome transitions at the end of life (e.g., repeated hospitalizations toward the end of life and/or health care transitions in the last three days of life) are common among residential care/assisted living (RC/AL) residents, and are associated with lower quality of end-of-life care reported by bereaved family members. We examined the association between state RC/AL regulations relevant to end-of-life care delivery and the likelihood of residents experiencing potentially burdensome transitions. Methods: Retrospective cohort study combining RC/AL registries of states' regulations with Medicare claims data for residents in large RC/ALs (i.e., 25+ beds) in the United States on the 120th day before death (N = 129,153), 2017-2019. Independent variables were state RC/AL regulations relevant to end-of-life care, including third-party services, staffing, and medication management. Analyses included: (1) separate logistic regression models for each RC/AL regulation, adjusting for sociodemographic covariates; (2) separate logistic regression models with a Medicare fee-for-service (FFS) subgroup to control for comorbidities, and (3) multivariable regression analysis, including all regulations in both the overall sample and the Medicare FFS subgroup. Results: We found a lack of associations between potentially burdensome transitions and regulations regarding third-party services and staffing. There were small associations found between regulations related to medication management (i.e., requiring regular medication reviews, permitting direct care workers for injections, requiring/not requiring licensed nursing staff for injections) and potentially burdensome transitions. Conclusions: In this cross-sectional study, the associations of RC/AL regulations with potentially burdensome transitions were either small or not statistically significant, calling for more studies to explain the wide variation observed in end-of-life outcomes among RC/AL residents.


Assuntos
Transição para Assistência do Adulto , Idoso , Humanos , Estados Unidos , Estudos Retrospectivos , Estudos Transversais , Medicare , Morte
20.
Time Soc ; 31(4): 480-507, 2022 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-36339032

RESUMO

Understanding how coupled adults arrange food-related labor in relation to their daily time allocation is of great importance because different arrangements may have implications for diet-related health and gender equity. Studies from the time-use perspective argue that daily activities such as work, caregiving, and non-food-related housework can potentially compete for time with foodwork. However, studies in this regard are mostly centered on individual-level analyses. They fail to consider cohabiting partners' time spent on foodwork and non-food-related activities, a factor that could be helpful in explaining how coupled partners decide to allocate time to food activities. Using 108 daily time-use logs from seventeen opposite-gender couples living in Toronto, Canada, this paper examines how male and female partners' time spent on non-food-related activities impact the total amount of time spent on foodwork by coupled adults and the difference in time spent on foodwork between coupled women and men. Results show that both male and female partners took a higher portion of foodwork when their partner worked longer. When men worked for additional time, the couple-level duration of foodwork decreased. Without a significant impact on the gender difference in foodwork duration, women's increased caregiving duration was associated with a reduction of total time spent on foodwork by couples. An increase in caregiving and non-food-related chores by men was associated with an increased difference in duration of foodwork between women and men, which helped secure a constant total amount of foodwork at the couple level. These behavioral variations between men and women demonstrate the gender differences in one's responsiveness to the change of partners' non-food-related tasks. The associations found among non-food-related activities and foodwork are suggestive of a need to account for partners' time allocation when studying the time-use dynamics of foodwork and other daily activities.

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