RESUMEN
Temporal lobe epilepsy (TLE) is one of the most common types of epilepsy, yet approximately one-third of patients are refractory to current anticonvulsive drugs, which target neurons and synapses. Astrocytic and microglial dysfunction is commonly found in epileptic foci and has been shown to contribute to neuroinflammation and hyperexcitability in chronic epilepsy. Accumulating evidence points to a key role for glial hemichannels in epilepsy, but inhibiting both connexin (Cx) gap junctions and hemichannels can lead to undesirable side effects because the former coordinate physiological functions of cell assemblies. It would be a great benefit to use an orally available small molecule to block hemichannels to alleviate epileptic symptoms. Here, we explored the effect of D4, a newly developed compound that inhibits the Cx hemichannels but not Cx gap junctions using the pilocarpine mouse model of TLE. In vitro application of D4 caused a near-complete reduction in the pilocarpine-induced cell membrane permeability associated with increased Cx hemichannel activity. Moreover, preadministration of D4 in vivo effectively reduced neuroinflammation and altered synaptic inhibition, which then enhanced the animal survival rate. Posttreatment with a single dose of D4 in vivo has prolonged effects on suppressing the activation of astrocytes and microglia and rescued the changes in neuroinflammatory and synaptic gene expression induced by pilocarpine. Collectively, these results indicate that targeting Cx hemichannels by D4 is an effective and promising strategy for treating epilepsy in which neuroinflammation plays a critical role.
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Epilepsia del Lóbulo Temporal , Epilepsia , Animales , Ratones , Conexinas/metabolismo , Epilepsia del Lóbulo Temporal/tratamiento farmacológico , Epilepsia del Lóbulo Temporal/metabolismo , Pilocarpina , Enfermedades NeuroinflamatoriasRESUMEN
Glial cells play relevant roles in neuroinflammation caused by epilepsy. Elevated hemichannel (HC) activity formed by connexins (Cxs) or pannexin1 (Panx1) largely explains brain dysfunctions commonly caused by neuroinflammation. Glia express HCs formed by Cxs 43, 30, or 26, while glia and neurons both express HCs formed by Panx1. Cx43 HCs allow for the influx of Ca2+, which promotes glial reactivity, enabling the release of the gliotransmitters that contribute to neuronal over-stimulation. Valproate (VPA), an antiseizure medication, has pleiotropic actions on neuronal molecular targets, and their action on glial cell HCs remains elusive. We used HeLa cells transfected with Cx43, Cx30, Cx26, or Panx1 to determine the effect of VPA on HC activity in the brain. VPA slightly increased HC activity under basal conditions, but significantly enhanced it in cells pre-exposed to conditions that promoted HC activity. Furthermore, VPA increased ATP release through Cx43 HCs. The increased HC activity caused by VPA was resistant to washout, being consistent with in silico studies, which predicted the binding site for VPA and Cx43, as well as for Panx1 HCs on the intracellular side, suggesting that VPA first enters through HCs, after which their activity increases.
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Anticonvulsivantes , Conexinas , Ácido Valproico , Ácido Valproico/farmacología , Humanos , Anticonvulsivantes/farmacología , Conexinas/metabolismo , Células HeLa , Encéfalo/metabolismo , Encéfalo/efectos de los fármacos , Conexina 43/metabolismo , Proteínas del Tejido Nervioso/metabolismo , Adenosina Trifosfato/metabolismo , Neuronas/efectos de los fármacos , Neuronas/metabolismo , Neuroglía/efectos de los fármacos , Neuroglía/metabolismo , Animales , Epilepsia/metabolismo , Epilepsia/tratamiento farmacológico , Epilepsia/inducido químicamenteRESUMEN
PURPOSE: We aimed to assess whether nativity differences in socioeconomic (SES) barriers and health literacy were associated with healthcare delays among US cancer survivors. METHODS: "All of Us" survey data were analyzed among adult participants ever diagnosed with cancer. A binary measure of healthcare delay (1+ delays versus no delays) was created. Health literacy was assessed using the Brief Health Literacy Screen. A composite measure of SES barriers (education, employment, housing, income, and insurance statuses) was created as 0, 1, 2, or 3+. Multivariable logistic regression model tested the associations of (1) SES barriers and health literacy with healthcare delays, and (2) whether nativity modified this relationship. RESULTS: Median participant age was 64 years (n = 10,020), with 8% foreign-born and 18% ethnic minorities. Compared to survivors with no SES barriers, those with 3+ had higher likelihood of experiencing healthcare delays (OR 2.18, 95% CI 1.84, 2.58). For every additional barrier, the odds of healthcare delays were greater among foreign-born (1.72, 1.43, 2.08) than US-born (1.27, 1.21, 1.34). For every 1-unit increase in health literacy among US-born, the odds of healthcare delay decreased by 9% (0.91, 0.89, 0.94). CONCLUSION: We found that SES barriers to healthcare delays have a greater impact among foreign-born than US-born cancer survivors. Higher health literacy may mitigate healthcare delays among US cancer survivors. Healthcare providers, systems and policymakers should assess and address social determinants of health and promote health literacy as a way to minimize healthcare delays among both foreign- and US-born cancer survivors.
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Supervivientes de Cáncer , Neoplasias , Salud Poblacional , Adulto , Humanos , Persona de Mediana Edad , Promoción de la Salud , Escolaridad , Atención a la Salud , Neoplasias/epidemiologíaRESUMEN
BACKGROUND: From October 2020 to October 2022, we conducted an implementation study to offer telemedicine (TM) across four HIV units of general public hospitals in Buenos Aires. The intervention used TM to provide a continuum of care to patients with HIV. METHODS AND SETTING: We used the RE-AIM framework to evaluate the strategy. The study started during a COVID-19 outbreak with strict lockdown policies and continued until return to normal practices. Implementation facilitation served as the core implementation strategy. RESULTS: We reached 4118 patients (58% of eligible individuals), and the main perceived benefits were the ability to avoid exposure to infectious diseases and reduced travel time and cost. After a median of 515 days of follow-up, 95.7% of participants with HIV were receiving antiretroviral therapy, and 87.8% were virally suppressed, with a median CD4+ count of 648 cells/µL. In total, 36.6% reported clinical events, and 20.4% presented with COVID-19 infection. The proportion of physicians adopting TM was 69.37%. After enrolment, 2406 of 5640 (43%) follow-up visits were conducted via TM. By the end of the study, 26.29% of appointments offered in the four centres were through TM, whereas 73.71% were in-person appointments. CONCLUSION: It was feasible to implement TM in the four centres in the public health sector in Buenos Aires, Argentina. It was acceptable for both patients and healthcare workers, and effectively reached a large proportion of the population served in these clinics. Both healthcare workers and patients consider it a model of care that will continue to be offered in the future.
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COVID-19 , Infecciones por VIH , SARS-CoV-2 , Telemedicina , Humanos , COVID-19/epidemiología , COVID-19/prevención & control , Argentina/epidemiología , Infecciones por VIH/tratamiento farmacológico , Infecciones por VIH/epidemiología , Masculino , Femenino , Adulto , Persona de Mediana Edad , Pandemias , Continuidad de la Atención al Paciente/organización & administraciónRESUMEN
BACKGROUND: Alcohol, a widely abused drug, significantly diminishes life quality, causing chronic diseases and psychiatric issues, with severe health, societal, and economic repercussions. Previously, we demonstrated that non-voluntary alcohol consumption increases the opening of Cx43 hemichannels and Panx1 channels in astrocytes from adolescent rats. However, whether ethanol directly affects astroglial hemichannels and, if so, how this impacts the function and survival of astrocytes remains to be elucidated. RESULTS: Clinically relevant concentrations of ethanol boost the opening of Cx43 hemichannels and Panx1 channels in mouse cortical astrocytes, resulting in the release of ATP and glutamate. The activation of these large-pore channels is dependent on Toll-like receptor 4, P2X7 receptors, IL-1ß and TNF-α signaling, p38 mitogen-activated protein kinase, and inducible nitric oxide (NO) synthase. Notably, the ethanol-induced opening of Cx43 hemichannels and Panx1 channels leads to alterations in cytokine secretion, NO production, gliotransmitter release, and astrocyte reactivity, ultimately impacting survival. CONCLUSION: Our study reveals a new mechanism by which ethanol impairs astrocyte function, involving the sequential stimulation of inflammatory pathways that further increase the opening of Cx43 hemichannels and Panx1 channels. We hypothesize that targeting astroglial hemichannels could be a promising pharmacological approach to preserve astrocyte function and synaptic plasticity during the progression of various alcohol use disorders.
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Alcoholismo , Conexina 43 , Ratones , Ratas , Animales , Conexina 43/metabolismo , Astrocitos/metabolismo , Etanol/toxicidad , Etanol/metabolismo , Alcoholismo/metabolismo , Células Cultivadas , Conexinas/metabolismo , Proteínas del Tejido Nervioso/metabolismoRESUMEN
Objective: Patients with digital disparity experience challenges with utilizing and accessing virtual care. This study implemented a digital coordination program for patients in outpatient psychiatry. Methods: Clinicians referred patients to a digital health coordinator who provided training to enhance virtual access. Outcomes were patient sociodemographics, barriers to digital health care utilization, change in completed video visits, and clinician satisfaction. Results: The patient cohort included 44 patients with a mean age of 59.8, 75% female, 73% Caucasian, and 84% non-Hispanic. The median household income was less than $25,000. The most common barrier to completing a video visit was difficulty using Zoom. The proportion of completed to scheduled video visits increased in 27% of patients. In such patients, the mean increase in completed visits was 32%. A majority of referring providers (64%) reported increased meaningfulness of work. Conclusion: This pilot proactively identified disparities in virtual care access and mitigated digital literacy barriers, boosting meaningfulness of work for clinicians.
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Accesibilidad a los Servicios de Salud , Telemedicina , Humanos , Femenino , Masculino , Telemedicina/organización & administración , Persona de Mediana Edad , Accesibilidad a los Servicios de Salud/organización & administración , Adulto , Disparidades en Atención de Salud , Anciano , Proyectos Piloto , Salud DigitalRESUMEN
CX3CL1 is one of the 50 up-to-date identified and characterized chemokines. While other chemokines are produced as small, secreted proteins, CX3CL1 (fractalkine) is synthetized as a transmembrane protein which also leads to a soluble form produced as a result of proteolytic cleavage. The membrane-bound protein and the soluble forms exhibit different biological functions. While the role of the fractalkine/CX3CR1 signaling axis was described in the nervous system and was also related to the migration of leukocytes to sites of inflammation, its actions are controversial in cancer progression and anti-tumor immunity. In the present review, we first describe the known biology of fractalkine concerning its action through its cognate receptor, but also its role in the activation of different integrins. The second part of this review is dedicated to its role in cancer where we discuss its role in anti-cancer or procarcinogenic activities.
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Quimiocina CX3CL1 , Neoplasias , Humanos , Quimiocina CX3CL1/metabolismo , Neoplasias/metabolismo , Neoplasias/patología , Animales , Transducción de Señal , Integrinas/metabolismo , Inflamación/metabolismoRESUMEN
BACKGROUND: The purpose of this study was to understand the experiences of Black patients with cancer in health care by comparing drivers of high and low ratings. METHODS: Semistructured in-depth interviews were conducted with 18 Black patients with cancer recruited from cancer survivorship support groups and Facebook between May 2019 and March 2020. Interviews were coded across all transcripts by using a thematic analysis approach before comparing low- and high-rating groups. RESULTS: There were three major themes that influenced whether patients rated their care as low or high, which included the patient-provider relationship, health care staff interactions, and cancer care coordination. For example, the high-rating group described good communication with the health care team as physicians listening to their needs, being responsive to their concerns, and providing recommendations on how to address side effects. In contrast, the low-rating group described poor communication with their health care team as their needs being dismissed and being excluded from decision-making processes. Additionally, there were two distinct themes that influenced patients' low ratings: insurance and financial toxicity issues and experiences of health care discrimination. CONCLUSIONS: In an effort to promote equitable cancer care experiences for Black patients, it is important that health systems work to prioritize patient interactions with health care providers and staff, comprehensive care management for patients with cancer, and reductions in the financial burden of caring for cancer.
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BACKGROUND: Congenital heart diseases are the most prevalent congenital malformations and cause greater morbi-mortality in newborns and infants. The aim of this study was to analyze the social determinants in families with children with the severity of congenital heart disease. METHODS: Analytical cross-sectional study in 140 families of children with congenital heart disease to whom a structured survey was applied addressing topics related to family structure, health, economic conditions, exposure factors, and other social conditions relevant to the study, during 1 year. RESULTS: In all, 53.7% of the studied population belonged to low socioeconomic levels. No association was found between the severity of the heart disease and the presence of pathological antecedents in the parents. The families resided in urban areas. Also, 28.3% of the mothers had four or fewer prenatal controls during pregnancy. Only 22% of heart diseases were diagnosed during pregnancy. It was found that exposure to cigarette and wood smoke during pregnancy, in addition to low socioeconomic status, was associated with greater severity of heart disease (RACHS-1 and STS-Score), when evaluated by pathophysiological groups (cyanotic/non-cyanotic/single ventricle). CONCLUSIONS: Exposure to cigarette smoke, wood smoke during pregnancy, and low socioeconomic status turned out to be social determinants associated with the severity of heart disease analyzed by pathophysiological groups. IMPACT: The social component has not been well characterized as a cause of congenital heart disease, especially in countries like ours, where the existence of gaps and social inequities have a high impact. The findings of this study could have an impact on public health to the extent that policies are implemented to reduce exposure to cigarettes, especially during pregnancy. Knowledge of these changes and their measurement in this type of pathology could open the door to the creation of policies aimed at their prevention, focusing on the local risk factors found, which can impact the disease.
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Cardiopatías Congénitas , Determinantes Sociales de la Salud , Lactante , Niño , Embarazo , Femenino , Humanos , Recién Nacido , Estudios Transversales , Cardiopatías Congénitas/epidemiología , Madres , Salud PúblicaRESUMEN
Biotic interactions are key processes that strongly affect the performance of seedlings in plant communities. In this work, we evaluated the effect of grazing and shrubs on the emergence and establishment of seedlings with different life-forms (dicotyledonous and monocotyledonous) in a sub-humid grassland community. We delimited five areas of 25 m2 in which we established four permanent plots of 1.0 m2. Two plots were centered at shrubs (beneath the canopy) and two in open spaces (without shrubs). Half of the shrubs and open plots were fenced to avoid grazing. During two consecutive years we marked all emerged seedlings and followed their fate. Grazing promoted dicotyledonous seedling emergence but reduced establishment. On the contrary, shrubs reduced dicotyledonous emergence but enhanced establishment. We did not detect any effect of shrubs or grazing on the emergence of monocotyledonous seedlings. Most seedlings emerged during fall and winter and died during spring and summer. Recruitment from seeds in this grassland is rare and complex, involving biotic and abiotic factors, with different responses to grazing and shrubs depending on seedling life-form and ontogeny.
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Ecosistema , Plantones , Pradera , Estaciones del Año , SemillasRESUMEN
BACKGROUND AND OBJECTIVES: Despite its efficacy, patients may still seek to voluntarily discontinue sublingual (SL) buprenorphine treatment, but little guidance exist on how to safely conduct a taper. We, therefore, report on the use of extended-release buprenorphine (XR-BUP) to facilitate voluntary treatment discontinuation. METHODS: A case series (n = 4). RESULTS: Four individuals interested in voluntary discontinuation of sublingual buprenorphine treatment were transitioned to varying durations of XR-BUP, after which all were able to discontinue buprenorphine with minimal withdrawal symptoms. One individual had a brief recurrence to illicit opioid use. All remained engaged in treatment. DISCUSSION AND CONCLUSIONS: The use of XR-BUP, given its long terminal half-life, may be a helpful option for individuals who are interested in voluntary buprenorphine discontinuation. Collaboration with the patient must include information about the risk of lapse to use and overdose following discontinuation. SCIENTIFIC SIGNIFICANCE: The cases reported here provide preliminary support for the use of XR-BUP to help individuals discontinue buprenorphine treatment. There is only one other case series showing the use of XR-BUP in helping individuals successfully discontinue buprenorphine treatment. Buprenorphine discontinuation is clinically relevant and there is little guidance in the current literature.
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Buprenorfina , Sobredosis de Droga , Trastornos Relacionados con Opioides , Humanos , Buprenorfina/uso terapéutico , Antagonistas de Narcóticos/uso terapéutico , Trastornos Relacionados con Opioides/tratamiento farmacológico , Administración Sublingual , Sobredosis de Droga/tratamiento farmacológico , Preparaciones de Acción Retardada/uso terapéutico , Analgésicos Opioides/uso terapéutico , Naltrexona/uso terapéuticoRESUMEN
BACKGROUND AND OBJECTIVES: Patients with opioid use disorder may be asked by their clinicians to discontinue maintenance buprenorphine treatment before surgical operations due to concerns that buprenorphine will interfere with acute pain management. However, discontinuation of buprenorphine may not be well tolerated or safe for all patients. We, therefore, administered a survey to better understand the experiences of patients on buprenorphine treatment who had previously undergone painful procedures and had their buprenorphine maintenance treatment either continued or discontinued before the procedure. METHODS: After this study received institutional review board approval, patients were invited to participate if they were being prescribed sublingual buprenorphine for treatment of opioid use disorder and had also previously undergone a painful procedure requiring treatment with full agonist opioids. Patients who were eligible and agreed to participate (n = 32) then completed a survey of basic demographics; medical, psychiatric, and substance use histories; and their experience and satisfaction with the treatment of pain and substance use in the perioperative period, including whether buprenorphine was continued or discontinued before their procedure. RESULTS: Compared with patients whose home dose of buprenorphine was continued (n = 15), patients whose buprenorphine was discontinued preoperatively (n = 17) reported less satisfaction with pain management and were more likely to be prescribed full agonist opioids upon discharge. DISCUSSION AND CONCLUSIONS: Consistent with prior studies, these survey findings suggest that discontinuation of buprenorphine before painful surgeries may be associated with poorer clinical outcomes. SCIENTIFIC SIGNIFICANCE: This survey study adds patients' perspective to a growing body of scientific literature suggesting that discontinuation of maintenance buprenorphine treatment before painful procedures may decrease patient satisfaction and increase clinical risk.
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Buprenorfina , Trastornos Relacionados con Opioides , Humanos , Buprenorfina/uso terapéutico , Analgésicos Opioides/uso terapéutico , Dolor/tratamiento farmacológico , Trastornos Relacionados con Opioides/tratamiento farmacológico , Combinación Buprenorfina y Naloxona/uso terapéuticoRESUMEN
OBJECTIVE: Anti-dementia medications such as acetylcholinesterase inhibitors are an important part of the management pathway for dementia. However, there are limited data in New Zealand that have examined the rates and patterns of use of funded anti-dementia medication and how use differs with ethnicity, age and sex. METHODS: This was a retrospective population-based descriptive study. Using the Integrated Data Infrastructure, we identified individuals of all ages coded for a diagnosis of dementia and estimated the proportion dispensed funded anti-dementia medication - donepezil tablets and rivastigmine patches - between 1 July 2016 and 30 June 2020. Rates of medication use in five main ethnic groups (Maori, Pacific peoples, Asian, European, and Middle Eastern, Latin American and African) in the <65, 65-79 and 80 and over (80+) age groups were compared and also between males and females in all sub-groups. Log-binomial models were used to calculate relative risks to determine any differences in anti-dementia medication use in the five ethnic groups and the three age groups and between males and females in each of the four study years. RESULTS: Overall, one-third of the dementia population received a funded anti-dementia medication in the total population (all ages) between 2016 and 2020. Donepezil tablets were dispensed in 31.6-34.0% and rivastigmine patches in 1.4-2.1% across the four study years. Compared to people of European ethnicity, Maori, Pacific peoples, and Middle Eastern, Latin American and African groups were less likely to be dispensed an anti-dementia medication (Maori: relative risk = 0.79-0.81, p < 0.0001; Pacific peoples: relative risk = 0.72-0.74, p < 0.0001; Middle Eastern, Latin American and African: relative risk = 0.73-0.78, p < 0.05). Compared to the age 80+ group, the 65-79 age group was more likely (relative risk = 1.50-1.54, p < 0.0001), while the age <65 group was less likely (relative risk = 0.67-0.71, p < 0.0001) to be dispensed an anti-dementia medication. There were no statistically significant differences in anti-dementia medication use between males and females. CONCLUSION: This study provides important information about funded anti-dementia medication use in New Zealand and how this differs by ethnicity, age and sex. Despite higher dementia prevalence in Maori and Pacific peoples, these groups were less likely to receive funded anti-dementia medication.
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Acetilcolinesterasa , Anciano de 80 o más Años , Femenino , Humanos , Masculino , Donepezilo , Pueblo Maorí , Nativos de Hawái y Otras Islas del Pacífico , Nueva Zelanda/epidemiología , Estudios Retrospectivos , Rivastigmina , Persona de Mediana Edad , Anciano , Pueblos Isleños del Pacífico , Asiático , Pueblo Europeo , Pueblos de Medio Oriente , Hispánicos o Latinos , Pueblo AfricanoRESUMEN
BACKGROUND: The adherence of the elderly to therapeutic programs, either they are pharmacological or psychosocial, is generally low. OBJECTIVE: Identifying predictive variables of adherence of a social program from elderly with multifunctional independence or mild dependence. METHOD: Prospective longitudinal design with 104 elderly participants in a social program. The inclusion criteria were: to participate in a social program for elderly, present functional independence or mild dependence, without depression clinically confirmed. Descriptive analyzes were performed with the study variables in addition to hypothesis testing and linear and logistic regression models to identify predictive variables of adherence. RESULTS: 22% of the participants met the minimum adherence, observing better compliance in younger people (p = 0.004), among those who had a better Health-Related Quality of Life (p = 0.036) and better health literacy levels (p = 0.017). According to a linear regression model, the variables associated with adherence were: social program of origin (OR = 5,122), perception of social support (OR = 1,170), cognitive status (OR = 2,537). CONCLUSION: The level of adherence of the older people of the study can be evaluated as low, which is consistent with the findings of the specialized literature. The variables identified with predictive capacity on adherence were social program of origin, a condition that can be incorporated into the design of the interventions in order to facilitate territorial equity. It is also important to highlight the importance of health literacy and the risk of dysphagia in the level of adherence.
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Alfabetización en Salud , Calidad de Vida , Humanos , Anciano , Estudios Prospectivos , Apoyo SocialRESUMEN
The anthology "Chicana Lesbians: the Girls Our Mothers Warned Us About" was instrumental to my writing as it bolstered my confidence to take control over my sexuality and sensuality. The text in this collection affirmed that exploring and expressing my sexuality through writing was an act of empowerment and defiance within a sexist, racist, heteronormative, and capitalist society.
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Homosexualidad Femenina , Minorías Sexuales y de Género , Femenino , Humanos , Conducta Sexual , Sexualidad , MadresRESUMEN
The BarA/UvrY two-component signal transduction system is widely conserved in γ-proteobacteria and provides a link between the metabolic state of the cells and the Csr posttranscriptional regulatory system. In Escherichia coli, the BarA/UvrY system responds to the presence of acetate and other short-chain carboxylic acids by activating transcription of the noncoding RNAs, CsrB and CsrC, which sequester the RNA-binding protein CsrA, a global regulator of gene expression. However, the state of the carboxyl group in the acetate molecule, which serves as the BarA stimulus, and the signal reception site of BarA remain unknown. In this study, we show that the deletion or replacement of the periplasmic domain of BarA and also the substitution of certain hydroxylated and hydrophobic amino acid residues in this region, result in a sensor kinase that remains unresponsive to its physiological stimulus, demonstrating that the periplasmic region of BarA constitutes a functional detector domain. Moreover, we provide evidence that the protonated state of acetate or formate serves as the physiological stimulus of BarA. In addition, modeling of the BarA sensor domain and prediction of the signal-binding site, by blind molecular docking, revealed a calcium channels and chemotaxis receptors domain with a conserved binding pocket, which comprised uncharged polar and hydrophobic amino acid residues. Based on the comparative sequence and phylogenetic analyses, we propose that, at least, two types of BarA orthologues diverged and evolved separately to acquire distinct signal-binding properties, illustrating the wide adaptability of the bacterial sensor kinase proteins.
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Acetatos/química , Proteínas de Escherichia coli/química , Escherichia coli/enzimología , Proteínas de la Membrana/química , Simulación del Acoplamiento Molecular , Fosfotransferasas/química , Acetatos/metabolismo , Sitios de Unión , Escherichia coli/genética , Proteínas de Escherichia coli/genética , Proteínas de Escherichia coli/metabolismo , Interacciones Hidrofóbicas e Hidrofílicas , Proteínas de la Membrana/genética , Proteínas de la Membrana/metabolismo , Fosfotransferasas/genética , Fosfotransferasas/metabolismo , FilogeniaRESUMEN
INTRODUCTION: Young-onset dementia prevalence is understudied internationally. Previous studies have been limited by low case numbers, reliance on single sources of routinely collected health data for case identification and inclusion of a limited age range. Our objective was to determine the 1-year period prevalence of diagnosed dementia in people aged 0-64 in the entire New Zealand population using routinely collected health data. METHODS: A population-based descriptive study was carried out in New Zealand (population 4.8 million) using routinely collected deidentified health data from 2016 to 2020. Dementia cases in seven linked health datasets in the New Zealand Integrated Data Infrastructure were identified using diagnostic codes and/or use of antidementia medication. Prevalence for each of the four study years was calculated by age, sex and ethnicity. RESULTS: From a total population of 4 027 332-4 169 754 individuals aged 0-64, we identified 3396-3474 cases of 'all-cause' dementia in each of the study years (prevalence crude range: 83-84/100 000 people aged 0-64; 139-141/100 000 people aged 30-64 years; 204-207/100 000 people aged 45-64 years). Age-standardised prevalence was higher in males than females. Age-standardised and sex-standardised prevalence was higher in Maori and Pacific People than European and Asian. DISCUSSION: By using a large study population and multiple national health datasets, we have minimised selection bias and estimated the national prevalence of diagnosed young-onset dementia with precision. Young-onset dementia prevalence for the total New Zealand population was similar to reported global prevalence, validating previous estimates. Prevalence differed by ethnicity, which has important implications for service planning.
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Since self-healing of cementitious materials can theoretically improve the service-life of concrete structures, it has gathered significant attention from both researchers and industry during the last two decades. Many researchers have proposed different methods to assess and quantify the self-healing capacity (i.e. the ability of cementitious materials to heal cracks) that is generated in concrete autogenously as well as autonomously. Even though many methodologies can be found in the literature, a way to accurately quantify the healing products produced by any self-healing mechanism has not been yet achieved. In this study, a methodology is proposed to observe and to quantify in-time formation of healing products based on active thin sections. Thin sections of Portland cement paste have been prepared with no epoxy impregnation to facilitate reactions between the cement matrix and the surrounding environment. Artificial cracks (260 µm wide) were induced at 28 days of age and the crystal growth was continuously monitored up to 28 days of self-healing. Through image analysis of the micrographs, it was calculated that the autogenous self-healing capacity of paste (triggered by portlandite carbonation in uncontrolled indoor conditions) was around 55% after 28 days of self-healing. Healing products were further characterised through Environmental Scanning Electron Microscope analysis. Based on the results obtained in this study, the proposed methodology seems to be promising to compare the self-healing mechanisms triggered by different healing agents.
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The neonatal mortality rate in Rwanda remains above the United Nations Sustainable Development Goal 3 target of 12 deaths per 1000 live births. As part of a larger effort to reduce preventable neonatal deaths in the country, we conducted a study to examine risk factors for low birthweight. The data were collected via a cost-efficient cluster-based outcome-dependent sampling (ODS) scheme wherein clusters of individuals (health centers) were selected on the basis of, in part, the outcome rate of the individuals. For a given data set collected via a cluster-based ODS scheme, estimation for a marginal model may proceed via inverse-probability-weighted generalized estimating equations, where the cluster-specific weights are the inverse probability of the health center's inclusion in the sample. In this paper, we provide a detailed treatment of the asymptotic properties of this estimator, together with an explicit expression for the asymptotic variance and a corresponding estimator. Furthermore, motivated by the study we conducted in Rwanda, we propose a number of small-sample bias corrections to both the point estimates and the standard error estimates. Through simulation, we show that applying these corrections when the number of clusters is small generally reduces the bias in the point estimates, and results in closer to nominal coverage. The proposed methods are applied to data from 18 health centers and 1 district hospital in Rwanda.
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Peso al Nacer , Sesgo , Simulación por Computador , Humanos , Recién Nacido , Factores de Riesgo , Rwanda/epidemiologíaRESUMEN
Churches can be important settings for promoting physical activity (PA) among Latinx populations. Little is known about what factors across the church context-social, organizational, and physical (outdoor spaces)-are associated with Latinx PA to inform faith-based PA interventions. This study investigated associations of church contextual factors with Latinx PA. We used cross-sectional data from a Latinx adult sample recruited from 6 churches that each had a nearby park in Los Angeles, California (n = 373). Linear or logistic regression models examined associations of church PA social support, PA social norms, perceived quality and concerns about the park near one's church, and church PA programming with 4 outcomes: accelerometer-based moderate-to-vigorous PA (MVPA) and self-reported adherence to PA recommendations, use of the park near one's church, and park-based PA. Park quality and concerns were positively associated with using the park near one's church. Church PA programming was positively associated with park-based PA. None of the factors were related to accelerometer-based MVPA or meeting PA recommendations. Findings suggest targeting church PA programming and nearby parks may be key to improving Latinx park use. Church and local parks department partnerships may help enhance park conditions to support churchgoing Latinx PA and health.