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1.
J Women Aging ; : 1-16, 2024 May 05.
Artigo em Inglês | MEDLINE | ID: mdl-38704816

RESUMO

This article investigates the impact of demographic and socioeconomic inequalities on wellness, composed of both physical health and subjective well-being. We examine how gender inequality moderates the joint effects of aging and income on wellness in China. Utilizing generalized linear mixed model (GLMM), we analyze data from the Chinese General Social Survey (CGSS) spanning from 2003 to 2021. Our results reveal that income inequality disproportionately affects physical health among older, underweight, lower-class females; males are more susceptible to negative impacts on subjective well-being, particularly among lower-class, middle-aged males. These gendered patterns are situated in the contemporary Chinese society and are explained in relation to intra-household distributional inequality and the gender role expectations in the Confucian culture. We also discussed the policy implications of how to reduce the gaps in wellness across social classes, age cohorts, and genders.

2.
Epilepsia ; 2024 Apr 18.
Artigo em Inglês | MEDLINE | ID: mdl-38634858

RESUMO

OBJECTIVE: Determination of the real-world performance of a health care system in the treatment of status epilepticus (SE). METHODS: Prospective, multicenter population-based study of SE in Auckland, New Zealand (NZ) over 1 year, with data recorded in the EpiNet database. Focus on treatment patterns and determinants of SE duration and 30-day mortality. The incidence, etiology, ethnic discrepancies, and seizure characteristics of this cohort have been published previously. RESULTS: A total of 365 patients were included in this treatment cohort; 326 patients (89.3%) were brought to hospital because of SE, whereas 39 patients (10.7%) developed SE during a hospital admission for another reason. Overall, 190 (52.1%) had a known history of epilepsy and 254 (70.0%) presented with SE with prominent motor activity. The mean Status Epilepticus Severity Score (STESS) was 2.15 and the mean SE duration of all patients was 44 min. SE self-terminated without any treatment in 84 patients (22.7%). Earlier administration of appropriately dosed benzodiazepine in the pre-hospital setting was a major determinant of SE duration. Univariate analysis demonstrated that mortality was significantly higher in older patients, patients with longer durations of SE, higher STESS, and patients who developed SE in hospital, but these did not maintain significance with multivariate analysis. There was no difference in the performance of the health care system in the treatment of SE across ethnic groups. SIGNIFICANCE: When SE was defined as 10 continuous minutes of seizure, overall mortality was lower than expected and many patients had self-limited presentations for which no treatment was required. Although there were disparities in the incidence of SE across ethnic groups there was no difference in treatment or outcome. The finding highlights the benefit of a health care system designed to deliver universal health care.

3.
J Neurol Sci ; 460: 122987, 2024 May 15.
Artigo em Inglês | MEDLINE | ID: mdl-38579412

RESUMO

Neuronal intranuclear inclusion disease, caused by a GGC repeat expansion in the 5'-untranslated region of NOTCH2NLC, is a rare neurodegenerative condition with highly variable clinical manifestations. In recent years, the number of reported cases have increased dramatically in East Asia. We report the first four genetically confirmed cases of neuronal intranuclear inclusion disease in New Zealand, all having Polynesian ancestry (three New Zealand Maori and one Cook Island Maori). Phenotypically, they resemble cases reported from recent large East Asian cohorts.


Assuntos
Corpos de Inclusão Intranuclear , Doenças Neurodegenerativas , Humanos , Nova Zelândia , Corpos de Inclusão Intranuclear/patologia , Corpos de Inclusão Intranuclear/genética , Doenças Neurodegenerativas/genética , Doenças Neurodegenerativas/patologia , Masculino , Feminino , Pessoa de Meia-Idade , Idoso , Receptor Notch2/genética
4.
Palliat Med ; 38(4): 492-497, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38444061

RESUMO

BACKGROUND: Seizures are an important palliative symptom, the management of which can be complicated by patients' capacity to swallow oral medications. In this setting, and the wish to avoid intravenous access, subcutaneous infusions may be employed. Options for antiseizure medications that can be provided subcutaneously may be limited. Subcutaneous sodium valproate may be an additional management strategy. AIM: To evaluate the published experience of subcutaneous valproate use in palliative care, namely with respect to effectiveness and tolerability. DESIGN: A systematic review was registered (PROSPERO CRD42023453427), conducted and reported according to PRISMA reporting guidelines. DATA SOURCES: The databases PubMed, EMBASE and Scopus were searched for publications until August 11, 2023. RESULTS: The searches returned 429 results, of which six fulfilled inclusion criteria. Case series were the most common study design, and most studies included <10 individuals who received subcutaneous sodium valproate. There were three studies that presented results on the utility of subcutaneous sodium valproate for seizure control, which described it to be an effective strategy. One study also described it as an effective treatment for neuropathic pain. The doses were often based on presumed 1:1 oral to subcutaneous conversion ratios. Only one study described a local site adverse reaction, which resolved with a change of administration site. CONCLUSIONS: There are limited data on the use of subcutaneous sodium valproate in palliative care. However, palliative symptoms for which subcutaneous sodium valproate have been used successfully are seizures and neuropathic pain. The available data have described few adverse effects, supporting its use with an appropriate degree of caution.


Assuntos
Neuralgia , Ácido Valproico , Humanos , Ácido Valproico/efeitos adversos , Cuidados Paliativos , Convulsões/induzido quimicamente , Convulsões/tratamento farmacológico , Neuralgia/tratamento farmacológico
6.
Elife ; 122024 Feb 29.
Artigo em Inglês | MEDLINE | ID: mdl-38420996

RESUMO

An animal entering a new environment typically faces three challenges: explore the space for resources, memorize their locations, and navigate towards those targets as needed. Here we propose a neural algorithm that can solve all these problems and operates reliably in diverse and complex environments. At its core, the mechanism makes use of a behavioral module common to all motile animals, namely the ability to follow an odor to its source. We show how the brain can learn to generate internal "virtual odors" that guide the animal to any location of interest. This endotaxis algorithm can be implemented with a simple 3-layer neural circuit using only biologically realistic structures and learning rules. Several neural components of this scheme are found in brains from insects to humans. Nature may have evolved a general mechanism for search and navigation on the ancient backbone of chemotaxis.


Assuntos
Algoritmos , Objetivos , Animais , Humanos , Aprendizagem , Odorantes
7.
Ophthalmol Glaucoma ; 7(1): 47-53, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-37558051

RESUMO

PURPOSE: To compare early vs. delayed use of aqueous suppressants on Ahmed glaucoma valve (AGV) outcomes. DESIGN: Single-center retrospective comparative case series. PARTICIPANTS: Patients who underwent AGV surgery at Wills Eye Hospital in the period between 2016 and 2021. METHODS: Retrospective review of AGV surgery at Wills Eye Hospital 2016 to 2021 for refractory glaucoma. Two groups were created: group 1 or those who received early aqueous suppressant therapy in the first 2 weeks postoperatively whenever the intraocular pressure (IOP) was > 10 mmHg, and group 2 or those who received delayed treatment after 2 weeks whenever the IOP exceeded the target pressure. Aqueous suppressant therapy included topical beta blockers, carbonic anhydrase inhibitors, and/or alpha agonists. MAIN OUTCOME MEASURES: The primary outcome measures were the frequency of hypertensive phase (HP) defined as IOP > 21 mmHg in first 3 months after an initial reduction to 21 mmHg or less in the first postoperative week not caused by tube obstruction or retraction, and month-12 surgical failure defined as 5 ≥ IOP > 21 mmHg on 2 consecutive visits, vision decline to no light perception (NLP), or glaucoma reoperation. Secondary outcome measures included changes in visual acuity (VA), IOP, and glaucoma medications at 12 months. Predictive factors for surgical failure were also identified. RESULTS: A total of 407 eyes of 391 patients (260 in group 1, 147 in group 2) with similar baseline characteristics were included. Hypertensive phase was more common in group 2 than 1 (41.5% vs. 18.5%; P < 0.001). At month 12 (N = 303 eyes), group 1 was less likely to fail than group 2 (21.2% vs. 36.8%, P = 0.003). Multivariate regression analysis showed that HP (odds ratio [OR] = 10.47, P < 0.001), delayed aqueous suppression use (OR = 2.17, P = 0.003), and lower baseline VA (OR = 1.56, P = 0.015) were the strongest predictors of month-12 failure. CONCLUSIONS: Early use of aqueous suppressants may lower the risk of HP and improve AGV outcomes. FINANCIAL DISCLOSURE(S): Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.


Assuntos
Implantes para Drenagem de Glaucoma , Glaucoma , Humanos , Estudos Retrospectivos , Resultado do Tratamento , Seguimentos
9.
J Occup Health Psychol ; 28(5): 325-342, 2023 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-37768590

RESUMO

Previous research examining differences in levels of well-being between leaders and nonleaders has yielded mixed results. To explain the inconsistencies, we compare levels of well-being among nonleaders, mid-level leaders, and high-level leaders. Drawing from the job demands-resources model (Bakker & Demerouti, 2007, 2017) and the expanded version proposed by Crawford et al. (2010), we anticipate mid-level leaders will have lower levels of well-being compared to senior leaders and nonleaders, and females will be more vulnerable than males in mid-level leadership. In Study 1, we use multilevel models and propensity score matching (N = 24,067) and find mid-level leaders have worse general health conditions compared to nonleaders and high-level leaders, and that this effect is more pronounced among females. In Study 2, we collect experience sampling data from workers (N = 86; 1,634 observations) who completed a short survey four times daily for five consecutive working days. Mid-level leaders report more end-of-day negative emotions than high-level leaders and nonleaders, mediated by higher job demands and lower levels of job control to combat the negative effects of job demands; an effect that is particularly pronounced among female respondents. In Study 3, we use a two-wave time-lagged survey study (N = 330) and find middle managers have more challenge and hindrance job demands than nonleaders, and insufficient job control to offset the negative effects of job demands. Female middle managers report the most physical health symptoms and enjoy less eudaemonic well-being than their male counterparts. We conclude that leadership levels and gender have important and overlooked impacts on well-being. (PsycInfo Database Record (c) 2023 APA, all rights reserved).


Assuntos
Emoções , Liderança , Humanos , Feminino , Masculino , Bases de Dados Factuais , Análise Multinível
10.
Ann Clin Transl Neurol ; 10(11): 2166-2170, 2023 11.
Artigo em Inglês | MEDLINE | ID: mdl-37726939

RESUMO

Circannual status epilepticus (SE) patterns in communities near Earth's poles best test the hypothesis that SE susceptibility varies with light exposure because these communities are routinely subject to large changes in annual light exposure, which may result in changes to daily sleep time. We compared northern hemispheric circannual SE occurrence in Kivalliq, Canada (latitude-62.8° N) to southern hemispheric Auckland, New Zealand (latitude-36.9° S). Instead of peaking at a similar calendar time, SE peaked at a similar solar time during the increasing daylight phase after each region's respective winter solstice. This demonstrates that cumulative effects of increasing light exposure can mediate SE susceptibility.


Assuntos
Convulsões , Estado Epiléptico , Humanos , Convulsões/diagnóstico , Estações do Ano , Sono , Nova Zelândia
13.
Elife ; 102021 07 01.
Artigo em Inglês | MEDLINE | ID: mdl-34196271

RESUMO

Animals learn certain complex tasks remarkably fast, sometimes after a single experience. What behavioral algorithms support this efficiency? Many contemporary studies based on two-alternative-forced-choice (2AFC) tasks observe only slow or incomplete learning. As an alternative, we study the unconstrained behavior of mice in a complex labyrinth and measure the dynamics of learning and the behaviors that enable it. A mouse in the labyrinth makes ~2000 navigation decisions per hour. The animal explores the maze, quickly discovers the location of a reward, and executes correct 10-bit choices after only 10 reward experiences - a learning rate 1000-fold higher than in 2AFC experiments. Many mice improve discontinuously from one minute to the next, suggesting moments of sudden insight about the structure of the labyrinth. The underlying search algorithm does not require a global memory of places visited and is largely explained by purely local turning rules.


Assuntos
Comportamento Exploratório/fisiologia , Aprendizagem em Labirinto/fisiologia , Algoritmos , Animais , Feminino , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Gravação em Vídeo
14.
Nucleic Acids Res ; 49(10): 5623-5636, 2021 06 04.
Artigo em Inglês | MEDLINE | ID: mdl-34019669

RESUMO

Iron-sulfur clusters (4Fe-4S) exist in many enzymes concerned with DNA replication and repair. The contribution of these clusters to enzymatic activity is not fully understood. We identified the MET18 (MMS19) gene of Saccharomyces cerevisiae as a strong mutator on GC-rich genes. Met18p is required for the efficient insertion of iron-sulfur clusters into various proteins. met18 mutants have an elevated rate of deletions between short flanking repeats, consistent with increased DNA polymerase slippage. This phenotype is very similar to that observed in mutants of POL3 (encoding the catalytic subunit of Pol Î´) that weaken binding of the iron-sulfur cluster. Comparable mutants of POL2 (Pol ϵ) do not elevate deletions. Further support for the conclusion that met18 strains result in impaired DNA synthesis by Pol Î´ are the observations that Pol Î´ isolated from met18 strains has less bound iron and is less processive in vitro than the wild-type holoenzyme.


Assuntos
DNA Polimerase III/metabolismo , Reparo do DNA , Replicação do DNA , Proteínas Ferro-Enxofre/metabolismo , Proteínas de Saccharomyces cerevisiae/metabolismo , Saccharomyces cerevisiae/genética , Fatores de Transcrição/metabolismo , Domínio Catalítico , DNA Polimerase Dirigida por DNA/metabolismo , Ligação Proteica
15.
Med Drug Discov ; 5: 100036, 2020 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-32292908

RESUMO

This paper provides an overview of the current global market and manufacturing landscape for hydroxychloroquine (HCQ). The capacity and capabilities of global producers to meet the potential demand for treating patients inflicted with COVID-19 by the novel corona virus SARS-CoV-2, should HCQ's efficacy be established by more definitive clinical trials, is also assessed. Given the large existing manufacturing base and abundance of raw materials for HCQ, the supply challenge can be met with considerable efforts and international cooperation. Preemptive and coordinated emergency efforts among global governments, regulatory agencies, chemical and pharmaceutical industries are imperative for meeting the potential surge in demand.

16.
Org Biomol Chem ; 17(11): 3056-3065, 2019 03 13.
Artigo em Inglês | MEDLINE | ID: mdl-30834400

RESUMO

Our annulation strategy utilized for the synthesis of 2-azaspiro[3.4]octane is explained. Three successful routes for the synthesis were developed. One of the approaches involved annulation of the cyclopentane ring and the remaining two approaches involved annulation of the four membered ring. All three approaches employ readily available starting materials with conventional chemical transformations and minimal chromatographic purifications to afford the title compound. The merits and limitations of the three approaches are also discussed.

17.
Neurohospitalist ; 9(1): 22-25, 2019 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-30671160

RESUMO

The therapeutic window for acute ischemic stroke with intravenous recombinant tissue plasminogen activator (IV rt-PA) is brief and crucial. The American Heart Association/American Stroke Association Target: Stroke Best Practice Strategies (TSBPS) aim to improve intravenous thrombolysis door-to-needle (DTN) time. We assessed the efficacy of implementation of selected TSBPS to reduce DTN time in a large tertiary care hospital. A multidisciplinary DTN committee assessed causes of delayed DTN time and implemented focused TSBPS in our urban academic medical center. We analyzed door-to-CT time, DTN time, and CT to IV rt-PA time in consecutive patients treated with IV rt-PA over 27 months preimplementation and 13 months postimplementation. One hundred forty-eight patients were included in the preimplementation and 126 in the postimplementation group. We found no significant difference between the groups in demographics, comorbidities, anticoagulation status, prethrombolysis hypertension treatment, arrival by EMS, after-hours arrival, or in stroke etiology. After implementation, median DTN time improved from 59 (interquartile range [IQR]: 52-80) to 29 (IQR: 20-41) minutes (P < .001). Door-to-CT time decreased from 17 (14-21) to 16 (12-19) minutes (P = .016), and CT-to-IV rt-PA time improved from 43 (IQR: 31-59) to 13 (IQR: 6-23) minutes (P < .001). Rates of symptomatic intracranial hemorrhage (2.7% vs 3.2%, P = .82) and treatment of stroke mimics (9% vs 13%, P = .31) were similar in both the groups. Individualized hospital gap analysis identifies targeted interventions that lead to rapid and sustained improvement in treatment times.

18.
Proc (Bayl Univ Med Cent) ; 31(1): 12-19, 2018 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-29686545

RESUMO

Ventricular dysfunction is common among patients with repaired cyanotic congenital heart disease. To date, no pharmacologic intervention has been demonstrated to be beneficial in this setting. To begin addressing this knowledge gap, we conducted a single-center prospective, randomized, open-label pilot study to investigate the effects of eplerenone on serologic markers of collagen turnover and inflammation, 6-minute walk distance, and quality of life in patients with tetralogy of Fallot (TOF) or transposition of the great arteries with a systemic right ventricle (transposition of the great arteries [TGA]). Patients were randomized to a 3-month drug-free period at the beginning of the treatment period or at the end. All patients received 12 months of eplerenone therapy during the treatment period. Twenty-six patients were enrolled in the trial; 17 completed the study protocol: 8 with TOF and 9 with TGV. Eplerenone had no effect on serum levels of procollagen 1 N-terminal peptide (PINP), procollagen 3 N-terminal peptide (PIIINP), or galectin-3 (G3). Similarly, eplerenone had no effect on 6-minute walk distance or quality of life. In conclusion, PINP and PIIINP levels are as high as or higher in patients with TOF and TGA than in patients with normal cardiac anatomy and heart failure, whereas G3 levels are lower. Eplerenone is well tolerated by adults born with congenital heart disease.

19.
Circ Arrhythm Electrophysiol ; 11(4): e005689, 2018 04.
Artigo em Inglês | MEDLINE | ID: mdl-29654127

RESUMO

BACKGROUND: This study was designed to estimate the costs of index hospitalizations after cardiac arrest in the United States. METHODS AND RESULTS: We used the US Nationwide Inpatient Sample (2003-2012) to identify patients with cardiac arrest. Log transformation of inflation-adjusted cost was determined for care to patient outcomes. Overall, an estimated 1 387 396 patients were hospitalized after cardiac arrest. The mean age of the cohort was 66 years, 45% were women, and the majority were white. Inpatient procedures included coronary angiography (15%), percutaneous coronary intervention (7%), intra-aortic balloon pump (4.4%), therapeutic hypothermia (1.1%), and mechanical circulatory support (0.1%). The rates of therapeutic hypothermia increased from zero in 2003 to 2.7% in 2012 (P<0.001). Both hospital charges and inflation-adjusted cost increased linearly over time. In a multivariate analysis, predictors of inflation-adjusted cost included large hospital size, urban teaching hospital, and length of stay. Among comorbidities, atrial fibrillation or fluid and electrolytes imbalance was most associated with cost. Among selected interventions, the cost was significantly increased with automatic implantable cardioverter defibrillators (odds ratio, 1.83; P<0.001), intra-aortic balloon pump (odds ratio, 1.50; P<0.001), hypothermia (odds ratio, 1.28; P<0.001), and extracorporeal membrane oxygenation (odds ratio, 2.38; P<0.001). CONCLUSIONS: In the period between 2003 and 2012, postcardiac arrest hospitalizations resulted in a steady rise in associated health care cost, likely related to increased length of stay, medical procedures, and systems of care. Although targeted cost containment for postarrest interventions may reduce the finance burden, there is an increasing need for funding research into prediction and prevention of cardiac arrest, which offers greater societal benefit.


Assuntos
Parada Cardíaca/economia , Parada Cardíaca/terapia , Custos Hospitalares , Hospitalização/economia , Avaliação de Processos e Resultados em Cuidados de Saúde/economia , Idoso , Bases de Dados Factuais , Feminino , Parada Cardíaca/diagnóstico , Parada Cardíaca/epidemiologia , Custos Hospitalares/tendências , Hospitalização/tendências , Humanos , Masculino , Avaliação de Processos e Resultados em Cuidados de Saúde/tendências , Fatores de Tempo , Resultado do Tratamento , Estados Unidos/epidemiologia
20.
J Neurosurg ; 128(2): 511-514, 2018 02.
Artigo em Inglês | MEDLINE | ID: mdl-28298012

RESUMO

OBJECTIVE Thyroid disorder has been known to affect vascular function and has been associated with aortic aneurysm formation in some cases; however, the connection has not been well studied. The authors hypothesized that hypothyroidism is associated with the formation of cerebral aneurysms. METHODS The authors performed a retrospective case-control study of consecutive patients who had undergone cerebral angiography at an academic, tertiary care medical center in the period from April 2004 through April 2014. Patients with unruptured aneurysms were identified from among those who had undergone 3-vessel catheter angiography. Age-matched controls without cerebral aneurysms on angiography were also identified from the same database. Patients with previous subarachnoid hemorrhage or intracranial hemorrhage were excluded. History of hypothyroidism and other risk factors were recorded. RESULTS Two hundred forty-three patients with unruptured cerebral aneurysms were identified and age matched with 243 controls. Mean aneurysm size was 9.6 ± 0.8 mm. Hypothyroidism was present in 40 patients (16.5%) and 9 matched controls (3.7%; adjusted OR 3.2, 95% CI 1.3-7.8, p = 0.01). Subgroup analysis showed that men with hypothyroidism had higher odds of an unruptured cerebral aneurysm diagnosis than the women with hypothyroidism, with an adjusted OR of 12.7 (95% CI 1.3-121.9) versus an OR of 2.5 (95% CI 1.0-6.4) on multivariate analysis. CONCLUSIONS Hypothyroidism appears to be independently associated with unruptured cerebral aneurysms, with a higher effect seen in men. Given the known pathophysiological associations between hypothyroidism and vascular dysfunction, this finding warrants further exploration.


Assuntos
Hipotireoidismo/complicações , Aneurisma Intracraniano/complicações , Idoso , Angiografia Digital , Estudos de Casos e Controles , Angiografia Cerebral , Feminino , Humanos , Hipotireoidismo/epidemiologia , Aneurisma Intracraniano/diagnóstico por imagem , Aneurisma Intracraniano/epidemiologia , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Fatores de Risco , Ruptura , Fatores Sexuais
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