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1.
J Craniofac Surg ; 2024 Sep 13.
Artículo en Inglés | MEDLINE | ID: mdl-39265187

RESUMEN

Positional plagiocephaly is a craniofacial condition resulting from infant positioning that applies pressure consistently to a part of the skull. This study analyzed the prevalence of, and costs associated with orthotic helmet treatment for positional plagiocephaly and assessed inequities in treatment between medically underserved areas (MUAs) and non-MUAs using health insurance claims data from the Center for Health Information and Analysis (CHIA) in Massachusetts for the years 2016-2021. The mean percentage of patients receiving orthotic helmet therapy was 4.3% (SD=0.49, 95% CI=3.88-4.91, P=0.44). MUAs contained 37.2% of patients with positional plagiocephaly and 2.9% of MUA patients were treated with helmets compared with 5.2% of non-MUA patients (P<0.01). There was a significant decline in the percentage of patients prescribed helmeting therapy over the course of the study (P<0.01). The average copay amount for public insurance was $0.00, and for private insurance, it was $559.8 (SD=160.7, 95% CI=529.1-590.5, P<0.01). Of 3295 claims for orthotic helmet treatment, 92 were fully denied (2.8%). Private insurers issued more fully denied claims (3.8%) than public insurance (1.1%) (P<0.01). We found that public insurance is favorable for patients seeking treatment due to a lower likelihood of full denial and lower copayments. In addition, we found that there is a significant disparity in the prevalence of helmet treatment in MUAs, and the percentage of patients treated with helmeting therapy has declined over time.

2.
Animals (Basel) ; 14(17)2024 Sep 06.
Artículo en Inglés | MEDLINE | ID: mdl-39272387

RESUMEN

African swine fever virus (ASFV) has been responsible for the globally devastating epidemics in wild and domesticated pigs. Of the 24 identified ASFV genotypes, genotype II is the primary cause for the pandemic occurring in Europe and Asia since its emergence in Georgia in 2007. The current study aimed to characterize the full-length genomic pattern of the ASFV strain from Thailand, TH1_22/CR (Accession No. PP915735), which was then compared with genomic diversity across other Asian isolates using Georgia 2007/1 (Accession No. FR682468) as the reference. Viral DNA was isolated from the pig spleen sample following library preparation and paired-end sequencing using the MiSeq Illumina platform. The sequenced TH1_22/CR isolate spanned 189,395 nucleotides encoding 193 open reading frames (ORFs), exhibiting maximum nucleotide similarity (99.99%) with Georgian (Georgia 2007/1) and Chinese (Wuhan 2019-1 and China HLJ) isolates. Based on phylogenetic analysis, the TH1_22/CR isolate (Accession No. PP915735) was characterized as genotype II, serogroup 8, and IGR-II due to the presence of three tandem repeat sequences (TRSs). Genetic variations including SNPs and single and polynucleotide indels were identified in TH1_22/CR in agreement with other Asian isolates. For comprehensive analysis, the genome was divided into four regions (I-IV) based on gene location. Overall, the TH1_22/CR isolate demonstrated eight SNPs and indels in its genome. Two unique SNPs were reported in the coding regions of the TH1_22/CR isolate, out of which, a C-591-T substitution was seen in MGF 360-4L and a C-297-T was found in A238L, and four unique SNPs were reported in non-coding regions (NCRs). Furthermore, a 29 bp deletion was observed in the IGR between MGF 110-13La and MGF 110-13Lb, as well as 52 bp deletion in the ASFV G ACD 00350 gene. This comparative analysis establishes the foundational information for future studies on the diversity and phylogeography of this regionally significant genetic sub-group of ASFV.

3.
Support Care Cancer ; 32(9): 581, 2024 Aug 09.
Artículo en Inglés | MEDLINE | ID: mdl-39120733

RESUMEN

PURPOSE: Cancer imposes a substantial financial burden on patients because of the high out-of-pocket expenses and the significant hardships. Financial toxicity describes the impact of cancer care costs at the patient level. Although the financial impact of cancer has been recognized, understanding the extent and determinants of financial toxicity in specific contexts is crucial. This study investigated the level of financial toxicity and its associated factors among patients with cancer at an oncology hospital in central Vietnam. METHODS: This cross-sectional study included 334 patients with cancer. Direct interviews and medical record reviews were used for data collection. Financial toxicity was assessed using the 11-item Comprehensive Score for financial Toxicity (COST). A logistic regression model was used to determine factors associated with financial toxicity. RESULTS: A notable 87.7% of patients experienced financial toxicity due to cancer cost, with 37.7% experiencing mild financial toxicity and 49.7% suffering from moderate financial toxicity, 0.3% reporting severe financial toxicity. Individuals with low household income exhibited a higher proportion of financial toxicity compared to that of those with higher income (odds ratio (OR) = 5.78, 95% confidence interval (CI): 1.29-25.68). Compared with that of participants in the early stages, a higher burden was found in patients with advanced-stage cancer (OR = 3.88, 95% CI: 1.36-11.11). CONCLUSION: Our study indicates that patients with cancer in Vietnam facefinancial toxicity. It is thus necessary for interventions to mitigate the financial burden on patients with cancer, focusing on vulnerable individuals and patients in the advanced stages.


Asunto(s)
Costo de Enfermedad , Neoplasias , Humanos , Estudios Transversales , Vietnam , Masculino , Femenino , Persona de Mediana Edad , Neoplasias/economía , Adulto , Anciano , Modelos Logísticos , Gastos en Salud/estadística & datos numéricos , Instituciones Oncológicas/economía , Adulto Joven
4.
Animals (Basel) ; 14(15)2024 Jul 26.
Artículo en Inglés | MEDLINE | ID: mdl-39123713

RESUMEN

African Swine Fever (ASF) is a lethal contagious hemorrhagic viral disease affecting the swine population. The causative agent is African Swine Fever Virus (ASFV). There is no treatment or commercial vaccine available at present. This virus poses a significant threat to the global swine industry and economy, with 100% mortality rate in acute cases. ASFV transmission occurs through both direct and indirect contact, with control measures limited to early detection, isolation, and culling of infected pigs. ASFV exhibits a complex genomic structure and encodes for more than 50 structural and 100 non-structural proteins and has 150 to 167 open reading frames (ORFs). While many of the proteins are non-essential for viral replication, they play crucial roles in mediating with the host to ensure longevity and transmission of virus in the host. The dynamic nature of ASFV research necessitates constant updates, with ongoing exploration of various genes and their functions, vaccine development, and other ASF-related domains. This comprehensive review aims to elucidate the structural and functional roles of both newly discovered and previously recorded genes involved in distinct stages of ASFV infection and immunomodulation. Additionally, the review discusses the virulence genes and genes with unknown functions, and proposes future interventions.

5.
Patient ; 2024 Jul 13.
Artículo en Inglés | MEDLINE | ID: mdl-39002094

RESUMEN

BACKGROUND: The prevalence of anxiety and depressive symptoms in young people have increased in many countries around the world. Web-based mental health interventions (or W-MHIs) have the potential to reduce anxiety and depression symptoms for young people. Although W-MHIs have become more widely used by young people since the coronavirus disease 2019 (COVID-19) pandemic, real-world engagement in these W-MHIs has remained low compared with engagement reported in research studies. Moreover, there are limited studies examining factors influencing engagement with W-MHIs in the post-COVID-19 pandemic years. OBJECTIVE: This study aims to explore barriers and facilitators of engagement with W-MHIs for anxiety and depression among young people. METHOD: Seventeen semi-structured interviews and one focus group with three participants were conducted online via Zoom between February and March 2023. Participants were young people aged 18-25 years who had self-reported experience of anxiety and/or depression in the past 6 months, lived in Australia, and considered using W-MHIs to manage their anxiety and/or depression symptoms. Inductive thematic analysis was performed to understand the key barriers and facilitators of young people's engagement with W-MHIs. RESULTS: Both individual- and intervention-related factors influenced young people's engagement with W-MHIs. Facilitators of engagement included personal trust and beliefs in W-MHIs, ability to contact a health professional, programme suitability (e.g., affordability, content aligning with user needs), programme usability (e.g., user interface), and accessibility of the online platform. Barriers included concerns about online security, lack of human interaction and immediate responses from health professionals (if any), and negative experience with mental health programmes. Participants expressed greater willingness to pay if they could contact health professionals during the programme. CONCLUSION: Better promotion strategies for mental health and W-MHI awareness are needed to increase the perceived importance and priority of mental health interventions among young people. Young people should be involved in the W-MHI co-design to enhance the programme suitability and usability for young people, fostering their engagement with W-MHIs.

6.
Value Health ; 2024 Jul 06.
Artículo en Inglés | MEDLINE | ID: mdl-38977195

RESUMEN

OBJECTIVES: To accurately capture informal care in healthcare evaluations, rigorous approaches are required to measure and value this important care component. In this systematic review and meta-analysis, we intended to summarize the current methods of measuring and valuing informal care costs in healthcare evaluations (full and partial healthcare evaluations, including cost of illness and cost analysis) in stroke. METHODS: A systematic search was conducted in MEDLINE, Embase, EconLit, and CINAHL. We used EndNote 20, Research Screener, and Covidence platforms for screening and data extraction. A meta-analysis was performed on informal care hours, and a subgroup meta-analysis was conducted based on stroke severity. RESULTS: A total of 31 articles were included in the qualitative synthesis. There was variation among the studies in the informal care measurement and valuation approaches. The meta-analysis of studies where data on informal care hours were available showed an estimate of informal care hours of 25.76 per week (95% CI 13.36-38.16) with a high heterogeneity (I2 = 99.97%). The overall risk of bias in the studies was assessed as low. CONCLUSIONS: Standardizing the measurement and valuation of informal care costs is essential for improving the consistency and comparability of economic evaluations. Pilot studies that incorporate standardized informal care cost valuation methods can help identify any practical challenges and capture the impact of informal care more accurately.

7.
Nanoscale ; 16(27): 13148-13160, 2024 Jul 11.
Artículo en Inglés | MEDLINE | ID: mdl-38912906

RESUMEN

In this comprehensive investigation, we explore the effectiveness of 55 dual-atom catalysts (DACs) supported on graphitic carbon nitride (gCN) for both alkaline and acidic hydrogen evolution reactions (HER). Employing density functional theory (DFT), we scrutinize the thermodynamic and kinetic profiles of these DACs, revealing their considerable potential across a diverse pH spectrum. For acidic HER, our results identify catalysts such as FePd-gCN, CrCr-gCN, and NiPd-gCN, displaying promising ΔGH* values of 0.0, 0.0, and -0.15 eV, respectively. This highlights their potential effectiveness in acidic environments, thereby expanding the scope of their applicability. Within the domain of alkaline HER, this study delves into the thermodynamic and kinetic profiles of DACs supported on gCN, utilizing DFT to illuminate their efficacy in alkaline HER. Through systematic evaluation, we identify that DACs such as CrCo-gCN, FeRu-gCN, and FeIr-gCN not only demonstrate favorable Gibbs free energy change (ΔGmax) for the overall water splitting reaction of 0.02, 0.27, and 0.38 eV, respectively, but also feature low activation energies (Ea) for water dissociation, with CrCo-gCN, FeRu-gCN, and FeIr-gCN notably exhibiting the Ea of just 0.42, 0.33, and 0.42 eV, respectively. The introduction of an electronic descriptor (φ), derived from d electron count (Nd) and electronegativity (ETM), provides a quantifiable relationship with catalytic activity, where a lower φ corresponds to enhanced reaction kinetics. Specifically, φ values between 4.0-4.6 correlate with the lowest kinetic barriers, signifying a streamlined HER process. Our findings suggest that DACs with optimized φ values present a robust approach for the development of high-performance alkaline HER electrocatalysts, offering a pathway towards the rational design of energy-efficient catalytic systems.

8.
Tob Use Insights ; 17: 1179173X241257683, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38826851

RESUMEN

Background: Secondhand smoke (SHS) has detrimental effects on community health, including coronary heart diseases, stroke, lung cancer etc. This manuscript exploited data from the Vietnam Population-based Provincial Global Adult Tobacco Survey (PGATS) in 2022 to update the prevalence of adult exposure to SHS and associated socio-demographic factors. Methods: With the sample size of 71,981 adults aged 15+ throughout 30 provinces and cities in Vietnam, data was collected using the Global Adult Tobacco Survey (GATS) questionnaire. Bivariate analysis and multivariate logistic regression modelling were performed. Results: In the past 30 days, 44.4% (95% CI: 44.0%-44.9%) adults aged 15+ exposed to SHS at home while 23.1% (95% CI: 22.6%-23.6%) exposed to SHS at work. Female exposure to SHS in the past 30 days was higher at homes but lower at indoor workplaces. Participants aged 15-24 were likely to have higher odds of SHS exposure in the past 30 days to other age groups. Those living in the urban areas had 1.15 times higher odds (95% CI: 1.08-1.22) of exposure to SHS than those in the rural areas. Current smokers tended to have 2.2 times higher odds of exposure to SHS at the indoor workplaces compared to non-smokers (95% CI: 2.05-2.37). Conclusions: The prevalence of exposure to SHS at home was still relatively high amongst the adult population. While there was a significant reduction of SHS exposure at indoor workplaces, there was a higher prevalence of women being exposed to SHS at home. The Government of Vietnam should continue to strictly implement the smoke-free environment resolution at indoor workplaces and appropriate communication campaigns to protect people, especially women from SHS exposure at homes.

9.
Nat Med ; 30(5): 1292-1299, 2024 May.
Artículo en Inglés | MEDLINE | ID: mdl-38632391

RESUMEN

Targeted tissue ablation involving the anterior hippocampus is the standard of care for patients with drug-resistant mesial temporal lobe epilepsy. However, a substantial proportion continues to suffer from seizures even after surgery. We identified the fasciola cinereum (FC) neurons of the posterior hippocampal tail as an important seizure node in both mice and humans with epilepsy. Genetically defined FC neurons were highly active during spontaneous seizures in epileptic mice, and closed-loop optogenetic inhibition of these neurons potently reduced seizure duration. Furthermore, we specifically targeted and found the prominent involvement of FC during seizures in a cohort of six patients with epilepsy. In particular, targeted lesioning of the FC in a patient reduced the seizure burden present after ablation of anterior mesial temporal structures. Thus, the FC may be a promising interventional target in epilepsy.


Asunto(s)
Hipocampo , Neuronas , Animales , Hipocampo/patología , Humanos , Ratones , Neuronas/patología , Epilepsia/patología , Masculino , Optogenética , Femenino , Convulsiones , Epilepsia del Lóbulo Temporal/fisiopatología , Epilepsia del Lóbulo Temporal/patología , Adulto
10.
Genesis ; 62(2): e23597, 2024 04.
Artículo en Inglés | MEDLINE | ID: mdl-38590121

RESUMEN

Sensory signals detected by olfactory sensory organs are critical regulators of animal behavior. An accessory olfactory organ, the vomeronasal organ, detects cues from other animals and plays a pivotal role in intra- and inter-species interactions in mice. However, how ethologically relevant cues control mouse behavior through approximately 350 vomeronasal sensory receptor proteins largely remains elusive. The type 2 vomeronasal receptor-A4 (V2R-A4) subfamily members have been repeatedly detected from vomeronasal sensory neurons responsive to predator cues, suggesting a potential role of this receptor subfamily as a sensor for predators. This review focuses on this intriguing subfamily, delving into its receptor functions and genetic characteristics.


Asunto(s)
Bulbo Olfatorio , Órgano Vomeronasal , Ratones , Animales , Bulbo Olfatorio/fisiología , Células Receptoras Sensoriales/metabolismo , Órgano Vomeronasal/metabolismo
11.
Immunity ; 57(5): 1141-1159.e11, 2024 May 14.
Artículo en Inglés | MEDLINE | ID: mdl-38670113

RESUMEN

Broadly neutralizing antibodies (bnAbs) targeting the hemagglutinin (HA) stem of influenza A viruses (IAVs) tend to be effective against either group 1 or group 2 viral diversity. In rarer cases, intergroup protective bnAbs can be generated by human antibody paratopes that accommodate the conserved glycan differences between the group 1 and group 2 stems. We applied germline-engaging nanoparticle immunogens to elicit a class of cross-group bnAbs from physiological precursor frequency within a humanized mouse model. Cross-group protection depended on the presence of the human bnAb precursors within the B cell repertoire, and the vaccine-expanded antibodies enriched for an N55T substitution in the CDRH2 loop, a hallmark of the bnAb class. Structurally, this single mutation introduced a flexible fulcrum to accommodate glycosylation differences and could alone enable cross-group protection. Thus, broad IAV immunity can be expanded from the germline repertoire via minimal antigenic input and an exceptionally simple antibody development pathway.


Asunto(s)
Anticuerpos Neutralizantes , Anticuerpos Antivirales , Virus de la Influenza A , Vacunas contra la Influenza , Infecciones por Orthomyxoviridae , Vacunación , Animales , Ratones , Humanos , Anticuerpos Antivirales/inmunología , Vacunas contra la Influenza/inmunología , Virus de la Influenza A/inmunología , Anticuerpos Neutralizantes/inmunología , Infecciones por Orthomyxoviridae/inmunología , Infecciones por Orthomyxoviridae/prevención & control , Glicoproteínas Hemaglutininas del Virus de la Influenza/inmunología , Sustitución de Aminoácidos , Linfocitos B/inmunología , Gripe Humana/inmunología , Gripe Humana/prevención & control , Anticuerpos ampliamente neutralizantes/inmunología
12.
Respir Res ; 25(1): 161, 2024 Apr 13.
Artículo en Inglés | MEDLINE | ID: mdl-38614991

RESUMEN

BACKGROUND: Longitudinal studies have identified childhood asthma as a risk factor for obstructive pulmonary disease (COPD) and asthma-COPD overlap (ACO) where persistent airflow limitation can develop more aggressively. However, a causal link between childhood asthma and COPD/ACO remains to be established. Our study aimed to model the natural history of childhood asthma and COPD and to investigate the cellular/molecular mechanisms that drive disease progression. METHODS: Allergic airways disease was established in three-week-old young C57BL/6 mice using house dust mite (HDM) extract. Mice were subsequently exposed to cigarette smoke (CS) and HDM for 8 weeks. Airspace enlargement (emphysema) was measured by the mean linear intercept method. Flow cytometry was utilised to phenotype lung immune cells. Bulk RNA-sequencing was performed on lung tissue. Volatile organic compounds (VOCs) in bronchoalveolar lavage-fluid were analysed to screen for disease-specific biomarkers. RESULTS: Chronic CS exposure induced emphysema that was significantly augmented by HDM challenge. Increased emphysematous changes were associated with more abundant immune cell lung infiltration consisting of neutrophils, interstitial macrophages, eosinophils and lymphocytes. Transcriptomic analyses identified a gene signature where disease-specific changes induced by HDM or CS alone were conserved in the HDM-CS group, and further revealed an enrichment of Mmp12, Il33 and Il13, and gene expression consistent with greater expansion of alternatively activated macrophages. VOC analysis also identified four compounds increased by CS exposure that were paradoxically reduced in the HDM-CS group. CONCLUSIONS: Early-life allergic airways disease worsened emphysematous lung pathology in CS-exposed mice and markedly alters the lung transcriptome.


Asunto(s)
Asma , Fumar Cigarrillos , Enfisema , Hipersensibilidad , Enfisema Pulmonar , Humanos , Animales , Ratones , Ratones Endogámicos C57BL , Pyroglyphidae , Fumar Cigarrillos/efectos adversos , Enfisema Pulmonar/etiología , Inflamación
13.
Carbohydr Polym ; 334: 122043, 2024 Jun 15.
Artículo en Inglés | MEDLINE | ID: mdl-38553239

RESUMEN

Here, we prepared ionically crosslinked films using pectin extracted from agro-wastes, specifically ambarella peels (AFP) and jackfruit seed slimy sheath (JFS). Physiochemical properties of pectins, including moisture content, molecular weight (Mw), degree of esterification (DE), and galacturonic acid (GA), were analyzed. Optimal extraction was determined, i.e., citric acid concentration 0.3 M, time 60 min, solid/liquid ratio 1:25, and temperature 90 °C for AFP or 85 °C for JFS. Pectin yields under these conditions were 29.67 % ± 0.35 % and 29.93 ± 0.49 %, respectively. AFP pectin revealed Mw, DE, and GA values of 533.20 kDa, 67.08 % ± 0.68 %, and 75.39 ± 0.82 %, while JFS pectin exhibited values of 859.94 kDa, 63.04 % ± 0.47 %, and 78.63 % ± 0.71 %, respectively. The pectin films crosslinked with Ca2+, Cu2+, Fe3+, or Zn2+ exhibited enhanced tensile strength and Young's modulus, along with reduced elongation at break, moisture content, water solubility, water vapor permeability, and oxygen permeability. Structural analyses indicated metal ions were effectively crosslinked with carboxyl groups of pectin. Notably, the Cu2+-crosslinked film demonstrated superior water resistance, mechanical properties, and exhibited the highest antioxidant and antibacterial activities among all tested films. Therefore, the pectin films represent a promising avenue to produce eco-friendly food packaging materials with excellent properties.


Asunto(s)
Artocarpus , Pectinas , Artocarpus/química , Embalaje de Alimentos , Frutas/química , Iones/análisis , Pectinas/química , Semillas
15.
Artículo en Inglés | MEDLINE | ID: mdl-38356043

RESUMEN

Many young people (YP) are diagnosed with mental illnesses and require support. Web-based mental health interventions (W-MHIs) have been increasingly utilized by YP, healthcare providers, and parents due to reasons including convenience and anonymity. W-MHIs are effective in improving mental health in YP. However, real-world engagement with W-MHIs remains low. Therefore, understanding barriers/facilitators of user engagement with W-MHIs is necessary to promote W-MHIs and help users gain optimal benefits through higher engagement. This review aims to identify barriers/facilitators of user engagement with W-MHIs in YP aged 10-24 years. A systematic search of five databases for English language, peer-reviewed publications was conducted between January 2010 and February 2023. Studies examining factors influencing user engagement with W-MHIs, described as barriers or facilitators, were included. Study quality was assessed using the Mixed Methods Appraisal Tool. A narrative synthesis was performed. Of 4088 articles identified, 69 studies were included. Barriers/facilitators were reported by young people (63 studies), providers (17 studies), and parents/caregivers (8 studies). YP perceived that usefulness and connectedness were the most common facilitators, whereas low-perceived need was the most reported barrier. Both providers and parents reported that perceived usefulness for YP was the most common facilitator, whereas concerns about program effectiveness and privacy were noted as barriers. This review found that program- and individual-related factors were important determinants of engagement with W-MHIs. This review provides guidance on the future design and development of new interventions, narrowing the gap between existing W-MHIs and unmet needs of users.

16.
Data Brief ; 52: 110046, 2024 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-38299106

RESUMEN

Rice holds a significant position in the global food supply chain, particularly in Asian, African, and Latin American countries. However, rice pests and diseases cause significant damage to the supply and growth of the rice cultivation industry. Therefore, this article provides a high-quality dataset that has been reviewed by agricultural experts. The dataset is well-suited to support the development of automation systems and smart farming practices. It plays a vital role in facilitating the automatic construction, detection, and classification of rice diseases. However, challenges arise due to the diversity of the dataset collected from various sources, varying in terms of disease types and sizes. This necessitates support for upgrading and enhancing the dataset through various operations in data processing, preprocessing, and statistical analysis. The dataset is provided completely free of charge and has been rigorously evaluated by agricultural experts, making it a reliable resource for system development, research, and communication needs.

17.
J Biomol Struct Dyn ; : 1-9, 2024 Feb 28.
Artículo en Inglés | MEDLINE | ID: mdl-38419271

RESUMEN

VP39, an essential 2'-O-RNA methyltransferase enzyme discovered in Monkeypox virus (MPXV), plays a vital role in viral RNA replication and transcription. Inhibition of the enzyme may prevent viral replication. In this context, using a combination of molecular docking and molecular dynamics (MDs) simulations, the inhibitory ability of NCI Diversity Set VII natural compounds to VP39 protein was investigated. It should be noted that the computed binding free energy of ligand via molecular docking and linear interaction energy (LIE) approaches are in good agreement with the corresponding experiments with coefficients of R=0.72 and 0.75, respectively. NSC 319990, NSC 196515 and NSC 376254 compounds were demonstrated that can inhibit MPVX methyltransferase VP39 protein with the similar affinity compared to available inhibitor sinefungin. Moreover, nine residues involving Gln39, Gly68, Gly72, Asp95, Arg97, Val116, Asp138, Arg140 and Asn156 may be argued that they play an important role in binding process of inhibitors to VP39.Communicated by Ramaswamy H. Sarma.

18.
Science ; 383(6679): 205-211, 2024 01 12.
Artículo en Inglés | MEDLINE | ID: mdl-38207021

RESUMEN

Antibodies are produced at high rates to provide immunoprotection, which puts pressure on the B cell translational machinery. Here, we identified a pattern of codon usage conserved across antibody genes. One feature thereof is the hyperutilization of codons that lack genome-encoded Watson-Crick transfer RNAs (tRNAs), instead relying on the posttranscriptional tRNA modification inosine (I34), which expands the decoding capacity of specific tRNAs through wobbling. Antibody-secreting cells had increased I34 levels and were more reliant on I34 for protein production than naïve B cells. Furthermore, antibody I34-dependent codon usage may influence B cell passage through regulatory checkpoints. Our work elucidates the interface between the tRNA pool and protein production in the immune system and has implications for the design and selection of antibodies for vaccines and therapeutics.


Asunto(s)
Anticuerpos , Formación de Anticuerpos , Linfocitos B , Uso de Codones , Cadenas Pesadas de Inmunoglobulina , Inosina , ARN de Transferencia , Formación de Anticuerpos/genética , Codón/genética , Inosina/genética , Inosina/metabolismo , ARN de Transferencia/genética , Anticuerpos/genética , Humanos , Linfocitos B/inmunología , Cadenas Pesadas de Inmunoglobulina/genética
19.
BMC Public Health ; 24(1): 34, 2024 01 02.
Artículo en Inglés | MEDLINE | ID: mdl-38166740

RESUMEN

BACKGROUND: Vietnam is undergoing a rapid epidemiological transition with a considerable burden of non-communicable diseases (NCDs), especially hypertension and diabetes (T2DM). Continuity of care (COC) is widely acknowledged as a benchmark for an efficient health system. This study aimed to determine the COC level for hypertension and T2DM within and across care levels and to investigate its associations with health outcomes and disease control. METHODS: A cross-sectional study was conducted on 602 people with T2DM and/or hypertension managed in primary care settings. We utilized both the Nijmegen continuity of care questionnaire (NCQ) and the Bice - Boxerman continuity of care index (COCI) to comprehensively measure three domains of COC: interpersonal, informational, and management continuity. ANOVA, paired-sample t-test, and bivariate and multivariable logistic regression analysis were performed to examine the predictors of COC. RESULTS: Mean values of COC indices were: NCQ: 3.59 and COCI: 0.77. The proportion of people with low NCQ levels was 68.8%, and that with low COCI levels was 47.3%. Primary care offered higher informational continuity than specialists (p < 0.01); management continuity was higher within the primary care team than between primary and specialist care (p < 0.001). Gender, living areas, hospital admission and emergency department encounters, frequency of health visits, disease duration, blood pressure and blood glucose levels, and disease control were demonstrated to be statistically associated with higher levels of COC. CONCLUSIONS: Continuity of primary care is not sufficiently achieved for hypertension and diabetes mellitus in Vietnam. Strengthening robust primary care services, improving the collaboration between healthcare providers through multidisciplinary team-based care and integrated care approach, and promoting patient education programs and shared decision-making interventions are priorities to improve COC for chronic care.


Asunto(s)
Diabetes Mellitus Tipo 2 , Hipertensión , Humanos , Diabetes Mellitus Tipo 2/epidemiología , Diabetes Mellitus Tipo 2/terapia , Estudios Transversales , Vietnam/epidemiología , Continuidad de la Atención al Paciente , Hipertensión/epidemiología , Hipertensión/terapia , Evaluación de Resultado en la Atención de Salud
20.
Nat Commun ; 15(1): 601, 2024 Jan 18.
Artículo en Inglés | MEDLINE | ID: mdl-38238329

RESUMEN

Epilepsy is a prevalent disorder involving neuronal network hyperexcitability, yet existing therapeutic strategies often fail to provide optimal patient outcomes. Chemogenetic approaches, where exogenous receptors are expressed in defined brain areas and specifically activated by selective agonists, are appealing methods to constrain overactive neuronal activity. We developed BARNI (Bradanicline- and Acetylcholine-activated Receptor for Neuronal Inhibition), an engineered channel comprised of the α7 nicotinic acetylcholine receptor ligand-binding domain coupled to an α1 glycine receptor anion pore domain. Here we demonstrate that BARNI activation by the clinical stage α7 nicotinic acetylcholine receptor-selective agonist bradanicline effectively suppressed targeted neuronal activity, and controlled both acute and chronic seizures in male mice. Our results provide evidence for the use of an inhibitory acetylcholine-based engineered channel activatable by both exogenous and endogenous agonists as a potential therapeutic approach to treating epilepsy.


Asunto(s)
Epilepsia , Receptores Nicotínicos , Ratones , Masculino , Humanos , Animales , Receptores Colinérgicos , Receptor Nicotínico de Acetilcolina alfa 7/genética , Receptores Nicotínicos/genética , Agonistas Nicotínicos/farmacología , Acetilcolina/farmacología , Convulsiones/genética
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