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1.
Clin Psychol Rev ; 112: 102463, 2024 Jun 27.
Artículo en Inglés | MEDLINE | ID: mdl-38968690

RESUMEN

Identifying factors that impact psychological treatment outcomes in older people with common mental health problems (CMHP) has important implications for supporting healthier and longer lives. The aim of the present study was to synthesise the evidence on predictors of psychological treatment outcomes in older people (aged 65+). PubMed, Scopus, Web of Science and PsycINFO were searched and 3929 articles were identified and screened, with 42 studies (N = 7978, M age = 68.9, SD age = 2.85) included: depression: k = 21, anxiety: k = 11, panic disorder: k = 3, mixed anxiety & depression: k = 3, PTSD: k = 2, various CMHP: k = 2, with CBT being the most common treatment (71%). The review identified 28 factors reported as significant predictors of treatment outcome in at least one study, across different domains: psychosocial (n = 9), clinical (n = 6), treatment-related (n = 6), socio-demographic (n = 4), neurobiological (n = 3). Homework completion was the most consistent predictor of positive treatment outcome. Baseline symptom severity was the most frequently studied significant predictor and across all conditions, with higher baseline symptom severity largely linked to worse treatment outcomes. No significant effects on treatment outcome were reported for gender, income and physical comorbidities. For a large majority of factors evidence was mixed or inconclusive. Further studies are required to identify factors affecting psychological treatment outcomes, which will be important for the development of personalised treatment approaches.

2.
Stat Med ; 2024 Jul 02.
Artículo en Inglés | MEDLINE | ID: mdl-38956865

RESUMEN

We propose a multivariate GARCH model for non-stationary health time series by modifying the observation-level variance of the standard state space model. The proposed model provides an intuitive and novel way of dealing with heteroskedastic data using the conditional nature of state-space models. We follow the Bayesian paradigm to perform the inference procedure. In particular, we use Markov chain Monte Carlo methods to obtain samples from the resultant posterior distribution. We use the forward filtering backward sampling algorithm to efficiently obtain samples from the posterior distribution of the latent state. The proposed model also handles missing data in a fully Bayesian fashion. We validate our model on synthetic data and analyze a data set obtained from an intensive care unit in a Montreal hospital and the MIMIC dataset. We further show that our proposed models offer better performance, in terms of WAIC than standard state space models. The proposed model provides a new way to model multivariate heteroskedastic non-stationary time series data. Model comparison can then be easily performed using the WAIC.

3.
Artículo en Inglés | MEDLINE | ID: mdl-38924496

RESUMEN

RATIONALE: Outdoor fine particulate air pollution (PM2.5) contributes to millions of deaths around the world each year, but much less is known about the long-term health impacts of other particulate air pollutants including ultrafine particles (a.k.a. nanoparticles) which are in the nanometer size range (<100 nm), widespread in urban environments, and not currently regulated. OBJECTIVES: Estimate the associations between long-term exposure to outdoor ultrafine particles and mortality. METHODS: Outdoor air pollution levels were linked to the residential addresses of a large, population-based cohort from 2001 - 2016. Associations between long-term exposure to outdoor ultrafine particles and nonaccidental and cause-specific mortality were estimated using Cox proportional hazards models. MEASUREMENTS: An increase in long-term exposure to outdoor ultrafine particles was associated with an increased risk of nonaccidental mortality (Hazard Ratio = 1. 073, 95% Confidence Interval = 1. 061, 1. 085) and cause-specific mortality, the strongest of which was respiratory mortality (Hazard Ratio = 1.174, 95% Confidence Interval = 1.130, 1.220). MAIN RESULTS: Long-term exposure to outdoor ultrafine particles was associated with increased risk of mortality. We estimated the mortality burden for outdoor ultrafine particles in Montreal and Toronto, Canada to be approximately 1100 additional nonaccidental deaths every year. Furthermore, we observed possible confounding by particle size which suggests that previous studies may have underestimated or missed important health risks associated with ultrafine particles. CONCLUSIONS: As outdoor ultrafine particles are not currently regulated, there is great potential for future regulatory interventions to improve population health by targeting these common outdoor air pollutants.

4.
Sci Rep ; 14(1): 10003, 2024 05 01.
Artículo en Inglés | MEDLINE | ID: mdl-38693192

RESUMEN

Zika, a viral disease transmitted to humans by Aedes mosquitoes, emerged in the Americas in 2015, causing large-scale epidemics. Colombia alone reported over 72,000 Zika cases between 2015 and 2016. Using national surveillance data from 1121 municipalities over 70 weeks, we identified sociodemographic and environmental factors associated with Zika's emergence, re-emergence, persistence, and transmission intensity in Colombia. We fitted a zero-state Markov-switching model under the Bayesian framework, assuming Zika switched between periods of presence and absence according to spatially and temporally varying probabilities of emergence/re-emergence (from absence to presence) and persistence (from presence to presence). These probabilities were assumed to follow a series of mixed multiple logistic regressions. When Zika was present, assuming that the cases follow a negative binomial distribution, we estimated the transmission intensity rate. Our results indicate that Zika emerged/re-emerged sooner and that transmission was intensified in municipalities that were more densely populated, at lower altitudes and/or with less vegetation cover. Warmer temperatures and less weekly-accumulated rain were also associated with Zika emergence. Zika cases persisted for longer in more densely populated areas with more cases reported in the previous week. Overall, population density, elevation, and temperature were identified as the main contributors to the first Zika epidemic in Colombia. We also estimated the probability of Zika presence by municipality and week, and the results suggest that the disease circulated undetected by the surveillance system on many occasions. Our results offer insights into priority areas for public health interventions against emerging and re-emerging Aedes-borne diseases.


Asunto(s)
Aedes , Cadenas de Markov , Infección por el Virus Zika , Virus Zika , Infección por el Virus Zika/transmisión , Infección por el Virus Zika/epidemiología , Colombia/epidemiología , Humanos , Animales , Aedes/virología , Teorema de Bayes , Mosquitos Vectores/virología , Brotes de Enfermedades
5.
PLoS One ; 19(4): e0302261, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38626124

RESUMEN

This in-vitro study aimed to analyse the effect of brushing and different brushing parameters (kind of toothpaste, kind of toothbrush, brushing force) on erosive tooth wear of primary bovine enamel and dentin. Specimens were prepared from primary bovine enamel or dentin (each group n = 12) and cyclically eroded (6 × 60 s/d, citric acid, pH 2.4) and brushed with children's toothbrushes (2 × 15 s/d) over 5 days. The brushing parameters under investigation were: toothpaste (fluoridated, fluoride-free), toothbrush (manual; rotating-oscillating and sonic, each at two different activation modes) and brushing force (1 N, 2 N). Specimens that were only eroded and not brushed served as controls. Enamel and dentin wear was quantified using widefield confocal microscopy. Statistical analysis was performed using three- and one-way ANOVAs followed by Scheffe's (enamel) or Tamhane's (dentin) post-hoc tests (p < 0.05). Brushing with the fluoridated toothpaste was able to significantly reduce erosive wear in enamel (by 15 to 37%, 6 of 10 groups) and in dentin (by 58 to 72%, all groups), while brushing with the fluoride-free toothpaste was not different from the controls. Considering the kind of toothpaste and brushing force, slight differences between the toothbrushes were observed in enamel, but not in dentin. Within the same toothbrush and activation mode, almost no differences between 1 and 2 N brushing force were detected. In conclusion, erosive tooth wear on primary bovine dental hard tissue mainly depends on the kind of toothpaste, rather than on the kind of toothbrush and the brushing force.


Asunto(s)
Abrasión de los Dientes , Erosión de los Dientes , Desgaste de los Dientes , Cepillado Dental , Abrasión de los Dientes/etiología , Pastas de Dientes/farmacología , Animales , Bovinos , Esmalte Dental , Dentina
6.
J Clin Invest ; 2024 Apr 30.
Artículo en Inglés | MEDLINE | ID: mdl-38687608

RESUMEN

Dicarboxylic fatty acids are generated in the liver and kidney in a minor pathway called fatty acid ω-oxidation. The effects of consuming dicarboxylic fatty acids as an alternative source of dietary fat have not been explored. Here, we fed dodecanedioic acid, a 12-carbon dicarboxylic (DC12), to mice at 20% of daily caloric intake for nine weeks. DC12 increased metabolic rate, reduced body fat, reduced liver fat, and improved glucose tolerance. We observed DC12-specific breakdown products in liver, kidney, muscle, heart, and brain, indicating that oral DC12 escaped first-pass liver metabolism and was utilized by many tissues. In tissues expressing the "a" isoform of acyl-CoA oxidase-1 (ACOX1), a key peroxisomal fatty acid oxidation enzyme, DC12 was chain shortened to the TCA cycle intermediate succinyl-CoA. In tissues with low peroxisomal fatty acid oxidation capacity, DC12 was oxidized by mitochondria. In vitro, DC12 was catabolized even by adipose tissue and was not stored intracellularly. We conclude that DC12 and other dicarboxylic acids may be useful for combatting obesity and for treating metabolic disorders.

7.
PLoS Genet ; 20(4): e1011139, 2024 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-38669217

RESUMEN

As essential components of gene expression networks, transcription factors regulate neural circuit assembly. The homeobox transcription factor encoding gene, gs homeobox 1 (gsx1), is expressed in the developing visual system; however, no studies have examined its role in visual system formation. In zebrafish, retinal ganglion cell (RGC) axons that transmit visual information to the brain terminate in ten arborization fields (AFs) in the optic tectum (TeO), pretectum (Pr), and thalamus. Pretectal AFs (AF1-AF9) mediate distinct visual behaviors, yet we understand less about their development compared to AF10 in the TeO. Using gsx1 zebrafish mutants, immunohistochemistry, and transgenic lines, we observed that gsx1 is required for vesicular glutamate transporter, Tg(slc17a6b:DsRed), expression in the Pr, but not overall neuron number. gsx1 mutants have normal eye morphology, yet they exhibit impaired visual ability during prey capture. RGC axon volume in the gsx1 mutant Pr and TeO is reduced, and AF7 that is active during feeding is missing which is consistent with reduced hunting performance. Timed laser ablation of Tg(slc17a6b:DsRed)-positive cells reveals that they are necessary for AF7 formation. This work is the first to implicate gsx1 in establishing cell identity and functional neural circuits in the visual system.


Asunto(s)
Animales Modificados Genéticamente , Regulación del Desarrollo de la Expresión Génica , Proteínas de Homeodominio , Células Ganglionares de la Retina , Proteínas de Pez Cebra , Pez Cebra , Animales , Axones/metabolismo , Axones/fisiología , Proteínas de Homeodominio/genética , Proteínas de Homeodominio/metabolismo , Mutación , Células Ganglionares de la Retina/metabolismo , Colículos Superiores/metabolismo , Colículos Superiores/crecimiento & desarrollo , Factores de Transcripción/genética , Factores de Transcripción/metabolismo , Vías Visuales/crecimiento & desarrollo , Vías Visuales/metabolismo , Pez Cebra/genética , Proteínas de Pez Cebra/genética , Proteínas de Pez Cebra/metabolismo
8.
J Pain Res ; 17: 873-885, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38476877

RESUMEN

Purpose: Substance use disorders (SUD) are a challenging comorbidity in patients with chronic non-cancer pain (CNCP) as they complicate diagnosis and therapy, especially when opioids are part of the therapeutic regimen. A definite diagnosis of opioid use disorder (OUD) in patients with CNCP on long-term opioid therapy (LTOT) is a prerequisite for effective and targeted therapy but may be complicated as some criteria of OUD might be attributed to the desire of the patient to relieve the pain. For instance, the desire to increase the dose can be based on both a SUD as well as inadequate pain therapy. Many scientific studies use standardized questions. Therefore, potential misunderstandings due to possible diagnostic overlaps often cannot be clarified. Methods: 14 qualitative guided interviews were conducted and analyzed (Kuckartz content analysis), with the intention to verify if patient's initial response to simple questions based on the wording of the DSM-5, as commonly used in research and practice, were consistent with the results of a more in-depth inquiry. Results: The results suggest that without in-depth investigation, there is a particular risk of false-positive assessment of the DSM-5 criteria for OUD when opioids are prescribed, especially when the questions are considered independently of chronic pain. The risk of a false-negative assessment has also been shown in isolated cases. Conclusion: Only after asking for and describing specific situations it was possible to determine whether the patient's positive or negative answers were based on a misunderstanding of the question. To avoid misdiagnosis, staff conducting DSM-5 interviews should be trained in pain-specific follow-up questions that may help to uncover diagnostic confounding.

9.
Elife ; 122024 Mar 15.
Artículo en Inglés | MEDLINE | ID: mdl-38488477

RESUMEN

Ancient environmental DNA (aeDNA) from lake sediments has yielded remarkable insights for the reconstruction of past ecosystems, including suggestions of late survival of extinct species. However, translocation and lateral inflow of DNA in sediments can potentially distort the stratigraphic signal of the DNA. Using three different approaches on two short lake sediment cores of the Yamal peninsula, West Siberia, with ages spanning only the past hundreds of years, we detect DNA and identified mitochondrial genomes of multiple mammoth and woolly rhinoceros individuals-both species that have been extinct for thousands of years on the mainland. The occurrence of clearly identifiable aeDNA of extinct Pleistocene megafauna (e.g. >400 K reads in one core) throughout these two short subsurface cores, along with specificities of sedimentology and dating, confirm that processes acting on regional scales, such as extensive permafrost thawing, can influence the aeDNA record and should be accounted for in aeDNA paleoecology.


Asunto(s)
Genoma Mitocondrial , Humanos , Lagos , Ecosistema , ADN , Análisis de Secuencia de ADN , ADN Antiguo
10.
Front Physiol ; 15: 1370539, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38487262

RESUMEN

Myosin binding protein C (MyBPC) is a multi-domain protein with each region having a distinct functional role in muscle contraction. The central domains of MyBPC have often been overlooked due to their unclear roles. However, recent research shows promise in understanding their potential structural and regulatory functions. Understanding the central region of MyBPC is important because it may have specialized function that can be used as drug targets or for disease-specific therapies. In this review, we provide a brief overview of the evolution of our understanding of the central domains of MyBPC in regard to its domain structures, arrangement and dynamics, interaction partners, hypothesized functions, disease-causing mutations, and post-translational modifications. We highlight key research studies that have helped advance our understanding of the central region. Lastly, we discuss gaps in our current understanding and potential avenues to further research and discovery.

11.
Eur Respir J ; 2024 Feb 08.
Artículo en Inglés | MEDLINE | ID: mdl-38331459

RESUMEN

BACKGROUND: Long COVID impacts ∼10% of people diagnosed with COVID-19, yet the pathophysiology driving ongoing symptoms is poorly understood. We hypothesised that 129Xe magnetic resonance imaging (MRI) could identify unique pulmonary phenotypic subgroups of long COVID, therefore we evaluated ventilation and gas exchange measurements with cluster analysis to generate imaging-based phenotypes. METHODS: COVID-negative controls and participants who previously tested positive for COVID-19 underwent 129XeMRI ∼14-months post-acute infection across three centres. Long COVID was defined as persistent dyspnea, chest tightness, cough, fatigue, nausea and/or loss of taste/smell at MRI; participants reporting no symptoms were considered fully-recovered. 129XeMRI ventilation defect percent (VDP) and membrane (Mem)/Gas, red blood cell (RBC)/Mem and RBC/Gas ratios were used in k-means clustering for long COVID, and measurements were compared using ANOVA with post-hoc Bonferroni correction. RESULTS: We evaluated 135 participants across three centres: 28 COVID-negative (40±16yrs), 34 fully-recovered (42±14yrs) and 73 long COVID (49±13yrs). RBC/Mem (p=0.03) and FEV1 (p=0.04) were different between long- and COVID-negative; FEV1 and all other pulmonary function tests (PFTs) were within normal ranges. Four unique long COVID clusters were identified compared with recovered and COVID-negative. Cluster1 was the youngest with normal MRI and mild gas-trapping; Cluster2 was the oldest, characterised by reduced RBC/Mem but normal PFTs; Cluster3 had mildly increased Mem/Gas with normal PFTs; and Cluster4 had markedly increased Mem/Gas with concomitant reduction in RBC/Mem and restrictive PFT pattern. CONCLUSION: We identified four 129XeMRI long COVID phenotypes with distinct characteristics. 129XeMRI can dissect pathophysiologic heterogeneity of long COVID to enable personalised patient care.

12.
J Am Soc Nephrol ; 35(2): 135-148, 2024 Feb 01.
Artículo en Inglés | MEDLINE | ID: mdl-38044490

RESUMEN

SIGNIFICANCE STATEMENT: In this study, we demonstrate that a common, low-cost compound known as octanedioic acid (DC 8 ) can protect mice from kidney damage typically caused by ischemia-reperfusion injury or the chemotherapy drug cisplatin. This compound seems to enhance peroxisomal activity, which is responsible for breaking down fats, without adversely affecting mitochondrial function. DC 8 is not only affordable and easy to administer but also effective. These encouraging findings suggest that DC 8 could potentially be used to assist patients who are at risk of experiencing this type of kidney damage. BACKGROUND: Proximal tubules are rich in peroxisomes, which are damaged during AKI. Previous studies demonstrated that increasing peroxisomal fatty acid oxidation (FAO) is renoprotective, but no therapy has emerged to leverage this mechanism. METHODS: Mice were fed with either a control diet or a diet enriched with dicarboxylic acids, which are peroxisome-specific FAO substrates, then subjected to either ischemia-reperfusion injury-AKI or cisplatin-AKI models. Biochemical, histologic, genetic, and proteomic analyses were performed. RESULTS: Both octanedioic acid (DC 8 ) and dodecanedioic acid (DC 12 ) prevented the rise of AKI markers in mice that were exposed to renal injury. Proteomics analysis demonstrated that DC 8 preserved the peroxisomal and mitochondrial proteomes while inducing extensive remodeling of the lysine succinylome. This latter finding indicates that DC 8 is chain shortened to the anaplerotic substrate succinate and that peroxisomal FAO was increased by DC 8 . CONCLUSIONS: DC 8 supplementation protects kidney mitochondria and peroxisomes and increases peroxisomal FAO, thereby protecting against AKI.


Asunto(s)
Lesión Renal Aguda , Ácidos Dicarboxílicos , Suplementos Dietéticos , Daño por Reperfusión , Animales , Humanos , Ratones , Lesión Renal Aguda/prevención & control , Lesión Renal Aguda/patología , Cisplatino , Ácidos Dicarboxílicos/administración & dosificación , Ácidos Grasos , Proteómica , Daño por Reperfusión/prevención & control , Daño por Reperfusión/patología
13.
Gesundheitswesen ; 86(5): 380-388, 2024 May.
Artículo en Alemán | MEDLINE | ID: mdl-38134915

RESUMEN

BACKGROUND: The aim of this study was to investigate the experiences, barriers, and solutions in communication during the provision of care for people with intellectual developmental disabilities in Germany. As there are approximately 350,000 people living with intellectual or developmental disabilities in Germany, who rely on assistance when communicating with healthcare providers, this study was conducted to examine the communication challenges and potential solutions in this population. The analysis especially focused on the potentials of digital applications facilitating information transfer. METHODS: Thirteen expert interviews were conducted using a structured interview guide with caregivers and medical providers to people with intellectual developmental disabilities. The interviews were analyzed using an inductive and deductive content analysis approach, according to Meuser and Nagel. RESULTS: The results revealed that the provision of care for people with intellectual developmental disabilities was characterized by time constraints and uncertainty when caregivers lack experience in caring for this population. Additionally, information transfer increased in complexity due to an overload of individual information provided by caregivers verbally or paper-based as well due to the passive role of patients who were usually not actively involved in the communication process. With regard to the potential for integrating digital applications for information transfer, a controversy between opportunity and risk emerged. CONCLUSION: The findings demonstrate that there is a need to implement training programs for professionals to enable them to offer improved health care for people with intellectual developmental disabilities. It is essential that caregivers are given sufficient time to communicate with patients, and that digital applications are utilized to support information transfer. Moreover, other research shows that digital applications offer new possibilities to communicate with people with intellectual developmental disabilities, such as the use of simplified or pictorial language. By addressing these communication challenges, healthcare professionals may be able to provide more effective and efficient care to this population. However, this requires further research, which addresses the controversial results regarding digital applications outlined in this paper.


Asunto(s)
Discapacidad Intelectual , Humanos , Discapacidad Intelectual/terapia , Discapacidad Intelectual/psicología , Alemania , Femenino , Adulto , Masculino , Cuidadores/psicología , Persona de Mediana Edad , Comunicación
14.
Commun Biol ; 6(1): 1241, 2023 12 08.
Artículo en Inglés | MEDLINE | ID: mdl-38066075

RESUMEN

Soil invertebrates are among the least understood metazoans on Earth. Thus far, the lack of taxonomically broad and dense genomic resources has made it hard to thoroughly investigate their evolution and ecology. With MetaInvert we provide draft genome assemblies for 232 soil invertebrate species, representing 14 common groups and 94 families. We show that this data substantially extends the taxonomic scope of DNA- or RNA-based taxonomic identification. Moreover, we confirm that theories of genome evolution cannot be generalised across evolutionarily distinct invertebrate groups. The soil invertebrate genomes presented here will support the management of soil biodiversity through molecular monitoring of community composition and function, and the discovery of evolutionary adaptations to the challenges of soil conditions.


Asunto(s)
Invertebrados , Suelo , Humanos , Animales , Invertebrados/genética , Biodiversidad , Ecología , Genómica
15.
Sci Rep ; 13(1): 21633, 2023 12 07.
Artículo en Inglés | MEDLINE | ID: mdl-38062116

RESUMEN

Deprescribing of inappropriate long-term proton pump inhibitors (PPI) is challenging and there is a lack of useful methods for general practitioners to tackle this. The objective of this randomized controlled trial was to evaluate the effectiveness of the electronic decision aid tool arriba-PPI on reduction of long-term PPI intake. Participants (64.5 ± 12.9 years; 54.4% women) with a PPI intake of at least 6 months were randomized to receive either consultation with arriba-PPI from their general practitioner (n = 1256) or treatment as usual (n = 1131). PPI prescriptions were monitored 6 months before, 6 and 12 months after study initiation. In 49.2% of the consultations with arriba-PPI, the general practitioners and their patients made the decision to reduce or discontinue PPI intake. At 6 months, there was a significant reduction by 22.3% (95% CI 18.55 to 25.98; p < 0.0001) of defined daily doses (DDD) of PPI. A reduction of 3.3% (95% CI - 7.18 to + 0.62) was observed in the control group. At 12 months, the reduction of DDD-PPI remained stable in intervention patients (+ 3.5%, 95% CI - 0.99 to + 8.03), whereas control patients showed a reduction of DDD-PPI (- 10.2%, 95% CI - 6.01 to - 14.33). Consultation with arriba-PPI led to reduced prescription rates of PPI in primary care practices. Arriba-PPI can be a helpful tool for general practitioners to start a conversation with their patients about risks of long-term PPI intake, reduction or deprescribing unnecessary PPI medication.


Asunto(s)
Médicos Generales , Inhibidores de la Bomba de Protones , Humanos , Femenino , Masculino , Inhibidores de la Bomba de Protones/uso terapéutico , Comunicación , Pautas de la Práctica en Medicina , Cognición
16.
Sci Rep ; 13(1): 20052, 2023 11 16.
Artículo en Inglés | MEDLINE | ID: mdl-37973963

RESUMEN

Glycemic variability remains frequent in patients with type 1 diabetes treated with insulin pumps. Heterogeneous spreads of insulin infused by pump in the subcutaneous (SC) tissue are suspected but were barely studied. We propose a new real-time ex-vivo method built by combining high-precision imaging with simultaneous pressure measurements, to obtain a real-time follow-up of insulin subcutaneous propagation. Human skin explants from post-bariatric surgery are imaged in a micro-computed tomography scanner, with optimised parameters to reach one 3D image every 5 min during 3 h of 1UI/h infusion. Pressure inside the tubing is recorded. A new index of dispersion (IoD) is introduced and computed upon the segmented 3D insulin depot per time-step. Infusions were hypodermal in 58.3% among 24 assays, others being intradermal or extradermal. Several minor bubbles and one occlusion were observed. IoD increases with time for all injections. Inter-assay variability is the smallest for hypodermal infusions. Pressure elevations were observed, synchronised with air bubbles arrivals in the tissue. Results encourage the use of this method to compare infusion parameters such as pump model, basal rate, catheter characteristics, infusion site characteristics or patient phenotype.


Asunto(s)
Diabetes Mellitus Tipo 1 , Insulina , Humanos , Hipoglucemiantes/uso terapéutico , Microtomografía por Rayos X , Diabetes Mellitus Tipo 1/tratamiento farmacológico , Tejido Subcutáneo , Sistemas de Infusión de Insulina
17.
World Dev ; 167: 106253, 2023 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-37767357

RESUMEN

Background: Identifying urban deprived areas, including slums, can facilitate more targeted planning and development policies in cities to reduce socio-economic and health inequities, but methods to identify them are often ad-hoc, resource intensive, and cannot keep pace with rapidly urbanizing communities. Objectives: We apply a spatial modelling approach to identify census enumeration areas (EAs) in the Greater Accra Metropolitan Area (GAMA) of Ghana with a high probability of being a deprived area using publicly available census and remote sensing data. Methods: We obtained United Nations (UN) supported field mapping data that identified deprived "slum" areas in Accra's urban core, data on housing and population conditions from the most recent census, and remotely sensed data on environmental conditions in the GAMA. We first fitted a Bayesian logistic regression model on the data in Accra's urban core (n=2,414 EAs) that estimated the relationship between housing, population, and environmental predictors and being a deprived area according to the UN's deprived area assessment. Using these relationships, we predicted the probability of being a deprived area for each of the 4,615 urban EAs in GAMA. Results: 899 (19%) of the 4,615 urban EAs in GAMA, with an estimated 745,714 residents (22% of its urban population), had a high predicted probability (≥80%) of being a deprived area. These deprived EAs were dispersed across GAMA and relatively heterogeneous in their housing and environmental conditions, but shared some common features including a higher population density, lower elevation and vegetation abundance, and less access to indoor piped water and sanitation. Conclusion: Our approach using ubiquitously available administrative and satellite data can be used to identify deprived neighbourhoods where interventions are warranted to improve living conditions, and track progress in achieving the Sustainable Development Goals aiming to reduce the population living in unsafe or vulnerable human settlements.

18.
Int J Mol Sci ; 24(16)2023 Aug 09.
Artículo en Inglés | MEDLINE | ID: mdl-37628798

RESUMEN

Hepatocellular carcinoma (HCC) is one of the leading causes of cancer deaths globally. Incidence rates are steadily increasing, creating an unmet need for new therapeutic options. Recently, the inhibition of sirtuin-2 (Sirt2) was proposed as a potential treatment for HCC, despite contradictory findings of its role as both a tumor promoter and suppressor in vitro. Sirt2 functions as a lysine deacetylase enzyme. However, little is known about its biological influence, despite its implication in several age-related diseases. This study evaluated Sirt2's role in HCC in vivo using an inducible c-MYC transgene in Sirt2+/+ and Sirt2-/- mice. Sirt2-/- HCC mice had smaller, less proliferative, and more differentiated liver tumors, suggesting that Sirt2 functions as a tumor promoter in this context. Furthermore, Sirt2-/- HCCs had significantly less c-MYC oncoprotein and reduction in c-MYC nuclear localization. The RNA-seq showed that only three genes were significantly dysregulated due to loss of Sirt2, suggesting the underlying mechanism is due to Sirt2-mediated changes in the acetylome, and that the therapeutic inhibition of Sirt2 would not perturb the oncogenic transcriptome. The findings of this study suggest that Sirt2 inhibition could be a promising molecular target for slowing HCC growth.


Asunto(s)
Carcinoma Hepatocelular , Neoplasias Hepáticas , Animales , Ratones , Ratones Transgénicos , Carcinoma Hepatocelular/genética , Sirtuina 2/genética , Neoplasias Hepáticas/genética , Carcinógenos , Modelos Animales de Enfermedad
19.
Infect Dis Model ; 8(4): 947-963, 2023 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-37608881

RESUMEN

For many infectious disease outbreaks, the at-risk population changes their behavior in response to the outbreak severity, causing the transmission dynamics to change in real-time. Behavioral change is often ignored in epidemic modeling efforts, making these models less useful than they could be. We address this by introducing a novel class of data-driven epidemic models which characterize and accurately estimate behavioral change. Our proposed model allows time-varying transmission to be captured by the level of "alarm" in the population, with alarm specified as a function of the past epidemic trajectory. We investigate the estimability of the population alarm across a wide range of scenarios, applying both parametric functions and non-parametric functions using splines and Gaussian processes. The model is set in the data-augmented Bayesian framework to allow estimation on partially observed epidemic data. The benefit and utility of the proposed approach is illustrated through applications to data from real epidemics.

20.
Sci Rep ; 13(1): 10884, 2023 07 05.
Artículo en Inglés | MEDLINE | ID: mdl-37407760

RESUMEN

This in vitro study aimed to analyse the effect of various children's toothpastes on erosive tooth wear of primary bovine enamel and dentin. Enamel and dentin specimens (n = 12) were cyclically eroded (6 × 60 s/d, citric acid, pH 2.4) and brushed (2 × 15 s/d, 2 N) over 5 days. Nine fluoride toothpastes (500 to 1450 ppm) and eight toothpastes containing no fluoride or other active ingredients (hydroxyapatite and/or xylitol) were tested. Unbrushed specimens served as control. Tissue loss was quantified using widefield confocal microscopy and statistically analysed using two-way and one-way ANOVAs followed by Scheffe's (enamel) or Tamhane's (dentin) post-hoc tests (p < 0.05). Only one fluoride toothpaste (1400 ppm) was able to reduce erosive wear of enamel significantly by 15% compared to the control (padj. = 0.002). All fluoridated toothpastes reduced dentin surface loss significantly by 32 to 69% compared to the control (padj. ≤ 0.001), while fluoride-free toothpastes were unable to reduce dentin loss significantly (padj. ≥ 0.971). Most fluoridated toothpastes caused less erosive wear compared to fluoride-free toothpastes. Children toothpastes containing fluoride were more effective in reducing erosive wear compared to toothpastes containing no fluoride or other active ingredients.


Asunto(s)
Erosión de los Dientes , Desgaste de los Dientes , Humanos , Bovinos , Animales , Niño , Fluoruro de Sodio/farmacología , Pastas de Dientes/farmacología , Erosión de los Dientes/prevención & control , Fluoruros/farmacología , Dentina , Esmalte Dental , Cepillado Dental
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