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Mutations in the LRRK2 gene are the most common genetic cause of familial Parkinson's Disease (LRRK2-PD) and an important risk factor for sporadic PD (sPD). Multiple clinical trials are ongoing to evaluate the benefits associated with the therapeutical reduction of LRRK2 kinase activity. In this study, we described the changes of transcriptomic profiles (whole blood mRNA levels) of LRRK2 protein interactors in sPD and LRRK2-PD cases as compared to healthy controls with the aim of comparing the two PD conditions. We went on to model the protein-protein interaction (PPI) network centred on LRRK2, which was weighted to reflect the transcriptomic changes on expression and co-expression levels of LRRK2 protein interactors. Our results showed that LRRK2 interactors present both similar and distinct alterations in expression levels and co-expression behaviours in the sPD and LRRK2-PD cases; suggesting that, albeit being classified as the same disease based on clinical features, LRRK2-PD and sPD display significant differences from a molecular perspective. Interestingly, the similar changes across the two PD conditions result in decreased connectivity within a topological cluster of the LRRK2 PPI network associated with protein metabolism/biosynthesis and ribosomal metabolism suggesting protein homoeostasis and ribosomal dynamics might be affected in both sporadic and familial PD in comparison with controls.
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BACKGROUND: Physical activity (PA) is essential in mitigating frailty syndrome, and it is necessary to measure PA in older adults with frailty. Assessment of Physical Activity in Frail Older People (APAFOP) is a suitable patient-reported outcome measure (PROM) for assessing PA among older adults with frailty. This study aimed to determine the reliability, validity and minimal detectable change of the Chinese version of the APAFOP (APAFOP-C). METHODS: This cross-sectional validation study was designed to measure the reliability and criterion validity of the APAFOP-C with 124 frail community-residing older adults. APAFOP-C was completed twice within an interval of 7-17 days to determine test-retest reliability. The investigator triangulation method was used to investigate inter-rater reliability, and a pedometer was used as the reference measurement to assess the criterion validity. Reliability and criterion validity were assessed using the intraclass correlation coefficient (ICC2,1), Pearson correlation coefficient for normally distributed variables, Spearman correlation coefficient, Wilcoxon signed-rank test for skewed variables, and the minimal detectable change at 95% level of confidence (MDC95). Agreement assessment was conducted using Bland-Altman plots for inter-rater reliability and criterion validity. Kendall's W test assessed absolute agreement among three raters in inter-rater reliability. The Mann-Whitney U test was used to evaluate whether any particular day was more representative of certain daily activities. RESULTS: Total PA on any arbitrarily chosen day illustrates daily activity (Z= -0.84, p = 0.40). The APAFOP-C exhibited strong-to-very strong test-retest reliability (ICC2,1=0.73-0.97; Spearman ρ = 0.67-0.89), and the total PA score demonstrated MDC95 < 10%. Inter-rater reliability was also strong-to-very strong (ICC2,1=0.96-0.98; Spearman ρ = 0.88-1.00), and moderate criterion validity when compared with total PA score on pedometer readings (Spearman ρ = 0.61). Limits of agreement among different raters regarding the APAFOP-C and the pedometer were narrow. CONCLUSION: The APAFOP-C was found to have limited but acceptable psychometric properties for measuring PA among community-dwelling older adults with frailty in China. It was a feasible comparative PROM for assessing PA worldwide. Practitioners can develop individualized exercise programs for frail older adults and efficiently track changes in PA utilizing the APAFOP-C.
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Ejercicio Físico , Anciano Frágil , Fragilidad , Fragilidad/prevención & control , Reproducibilidad de los Resultados , Femenino , Anciano de 80 o más Años , Actividades Cotidianas , Estudios Transversales , Anciano , PsicometríaRESUMEN
AIMS: Lansoprazole is one of the many proton pump inhibitors (PPIs) that acts more strongly with ABCB1 and ABCG2. The present study is to investigate the potential of lansoprazole on reversal of ABCB1/G2-mediated MDR in cancer, in vitro and in vivo. METHODS: Reversal studies and combination evaluation were conducted to determine the synergistic anti-MDR effects on lansoprazole. Lysosomal staining was used to determination of lansoprazole on ABCB1-mediated lysosomal sequestration. Substrate accumulation and efflux assays, ATPase activity, and molecular docking were conducted to evaluate lansoprazole on ABCB1/G2 functions. Western blot and immunofluorescence were used to detect lansoprazole on ABCB1/G2 expression and subcellular localization. MDR nude mice models were established to evaluate the effects of lansoprazole on MDR in vivo. RESULTS: Lansoprazole attenuated ABCB1/G2-mediated MDR and exhibited synergistic effects with substrate drugs in MDR cells. In vivo experiments demonstrated that lansoprazole attenuated ABCB1/G2-mediated MDR and exhibited synergistic effects that augmented the sensitivity of substrate anticancer drugs in ABCB1/G2-mediated settings without obvious toxicity. Lansoprazole impeded lysosomal sequestration mediated by ABCB1, leading to a substantial increase in intracellular accumulation of substrate drugs. The effects of lansoprazole were not attributable to downregulation or alterations in subcellular localization of ABCB1/G2. Lansoprazole promoted the ATPase activity of ABCB1/G2 and competitively bound to the substrate-binding region of ABCB1/G2. CONCLUSIONS: These findings present novel therapeutic avenues whereby the combination of lansoprazole and chemotherapeutic agents mitigates MDR mediated by ABCB1/G2 overexpression.
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Subfamilia B de Transportador de Casetes de Unión a ATP , Resistencia a Múltiples Medicamentos , Resistencia a Antineoplásicos , Lansoprazol , Lisosomas , Inhibidores de la Bomba de Protones , Animales , Humanos , Ratones , Antineoplásicos/farmacología , Subfamilia B de Transportador de Casetes de Unión a ATP/metabolismo , Subfamilia B de Transportador de Casetes de Unión a ATP/genética , Transportador de Casetes de Unión a ATP, Subfamilia G, Miembro 2/metabolismo , Transportador de Casetes de Unión a ATP, Subfamilia G, Miembro 2/genética , Línea Celular Tumoral , Resistencia a Múltiples Medicamentos/efectos de los fármacos , Resistencia a Antineoplásicos/efectos de los fármacos , Lansoprazol/farmacología , Lisosomas/metabolismo , Lisosomas/efectos de los fármacos , Ratones Desnudos , Simulación del Acoplamiento Molecular , Proteínas de Neoplasias , Neoplasias/tratamiento farmacológico , Neoplasias/metabolismo , Neoplasias/patología , Inhibidores de la Bomba de Protones/farmacología , Ensayos Antitumor por Modelo de XenoinjertoRESUMEN
Researchers are increasingly concerned about antimony (Sb) in ecosystems and the environment. Sb primarily enters the environment through anthropogenic (urbanization, industries, coal mining, cars, and biosolid wastes) and geological (natural and chemical weathering of parent material, leaching, and wet deposition) processes. Sb is a hazardous metal that can potentially harm human health. However, no comprehensive information is available on its sources, how it behaves in soil, and its bioaccumulation. Thus, this study reviews more than 160 peer-reviewed studies examining Sb's origins, geochemical distribution and speciation in soil, biogeochemical mechanisms regulating Sb mobilization, bioavailability, and plant phytotoxicity. In addition, Sb exposure effects plant physio-morphological and biochemical attributes were investigated. The toxicity of Sb has a pronounced impact on various aspects of plant life, including a reduction in seed germination and impeding plant growth and development, resulting from restricted essential nutrient uptake, oxidative damages, disruption of photosynthetic system, and amino acid and protein synthesis. Various widely employed methods for Sb remediation, such as organic manure and compost, coal fly ash, biochar, phytoremediation, microbial-based bioremediation, micronutrients, clay minerals, and nanoremediation, are reviewed with a critical assessment of their effectiveness, cost-efficiency, and suitability for use in agricultural soils. This review shows how plants deal with Sb stress, providing insights into lowering Sb levels in the environment and lessening risks to ecosystems and human health along the food chain. Examining different methods like bioaccumulation, bio-sorption, electrostatic attraction, and complexation actively works to reduce toxicity in contaminated agricultural soil caused by Sb. In the end, the exploration of recent advancements in genetics and molecular biology techniques are highlighted, which offers valuable insights into combating Sb toxicity. In conclusion, the findings of this comprehensive review should help develop innovative and useful strategies for minimizing Sb absorption and contamination and thus successfully managing Sb-polluted soil and plants to reduce environmental and public health risks.
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Antimonio , Biodegradación Ambiental , Plantas , Contaminantes del Suelo , Suelo , Antimonio/metabolismo , Contaminantes del Suelo/metabolismo , Contaminantes del Suelo/toxicidad , Contaminantes del Suelo/análisis , Plantas/metabolismo , Plantas/efectos de los fármacos , Suelo/química , Restauración y Remediación Ambiental/métodos , Contaminación Ambiental , EcosistemaRESUMEN
PURPOSE: Recently, there has been rapid development in model-informed drug development, which has the potential to reduce animal experiments and accelerate drug discovery. Physiologically based pharmacokinetic (PBPK) and machine learning (ML) models are commonly used in early drug discovery to predict drug properties. However, basic PBPK models require a large number of molecule-specific inputs from in vitro experiments, which hinders the efficiency and accuracy of these models. To address this issue, this paper introduces a new computational platform that combines ML and PBPK models. The platform predicts molecule PK profiles with high accuracy and without the need for experimental data. METHODS: This study developed a whole-body PBPK model and ML models of plasma protein fraction unbound ( f up ), Caco-2 cell permeability, and total plasma clearance to predict the PK of small molecules after intravenous administration. Pharmacokinetic profiles were simulated using a "bottom-up" PBPK modeling approach with ML inputs. Additionally, 40 compounds were used to evaluate the platform's accuracy. RESULTS: Results showed that the ML-PBPK model predicted the area under the concentration-time curve (AUC) with 65.0 % accuracy within a 2-fold range, which was higher than using in vitro inputs with 47.5 % accuracy. CONCLUSION: The ML-PBPK model platform provides high accuracy in prediction and reduces the number of experiments and time required compared to traditional PBPK approaches. The platform successfully predicts human PK parameters without in vitro and in vivo experiments and can potentially guide early drug discovery and development.
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Aprendizaje Automático , Modelos Biológicos , Humanos , Células CACO-2 , Simulación por Computador , Farmacocinética , Descubrimiento de Drogas/métodos , Área Bajo la Curva , Administración Intravenosa , Masculino , Preparaciones Farmacéuticas/metabolismo , Proteínas Sanguíneas/metabolismoRESUMEN
Iron-nanoparticles (Fe-NPs) are increasingly been utilized in environmental applications due to their efficacy and strong catalytic activities. The novelty of nanoparticle science had attracted many researchers and especially for their green synthesis, which can effectively reuse biological resources during the polymerization reactions. Thus, the synthesis of Fe-NPs utilizing plant extracts could be considered as the eco-friendly, simple, rapid, energy-efficient, sustainable, and cost-effective. The green synthesis route can be recognized as a practical, valuable, and economically effective alternative for large-scale production. During the production process, some biomolecules present in the extracts undergo metal salts reduction, which can serve as both a capping and reducing mechanism, enhancing the reactivity and stability of green-synthesized Fe-NPs. The diversity of species provided a wide range of potential sources for green synthesis of Fe-NPs. With improved understanding of the specific biomolecules involved in the bioreduction and stabilization processes, it will become easier to identify and utilize new, potential plant materials for Fe-NPs synthesis. Newly synthesized Fe-NPs require different characterization techniques such as transmission electron microscope, ultraviolet-visible spectrophotometry, and X-ray absorption fine structure, etc, for the determination of size, composition, and structure. This review described and assessed the recent advancements in understanding green-synthesized Fe-NPs derived from plant-based material. Detailed information on various plant materials suitable of yielding valuable biomolecules with potential diverse applications in environmental safety. Additionally, this review examined the characterization techniques employed to analyze Fe-NPs, their stability, accumulation, mobility, and fate in the environment. Holistically, the review assessed the applications of Fe-NPs in remediating wastewaters, organic residues, and inorganic contaminants. The toxicity of Fe-NPs was also addressed; emphasizing the need to refine the synthesis of green Fe-NPs to ensure safety and environmental friendliness. Moving forward, the future challenges and opportunities associated with the green synthesis of Fe-NPs would motivate novel research about nanoparticles in new directions.
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Contaminantes Ambientales , Tecnología Química Verde , Hierro , Nanopartículas del Metal , Extractos Vegetales , Tecnología Química Verde/métodos , Nanopartículas del Metal/química , Hierro/química , Contaminantes Ambientales/química , Extractos Vegetales/química , Restauración y Remediación Ambiental/métodosRESUMEN
PURPOSE: Evidence suggests that oncology patients are satisfied with and sometimes prefer telemedicine compared with in-person visits; however, data are scarce on when telemedicine is appropriate for specific cancer populations. In this study, we aim to identify factors that influence patient experience and appropriateness of telemedicine use among a head and neck cancer (HNC) population. METHODS: We performed a mixed-methods study at a multisite cancer center. First, we surveyed patients with HNC and analyzed factors that may influence their telemedicine experience using multivariate regression. We then conducted focus groups among HNC oncologists (n = 15) to evaluate their perception on appropriate use of telemedicine. RESULTS: From January to December 2020, we collected 1,071 completed surveys (response rate 24%), of which 551 first unique surveys were analyzed. About half of all patients (56%) reported telemedicine as "same or better" compared with in-person visits, whereas the other half (44%) reported "not as good or unsure." In multivariate analyses, patients with thyroid cancer were more likely to find telemedicine "same or better" (adjusted odds ratio, 2.08 [95% CI, 1.35 to 3.25]) compared with other HNC populations (mucosal/salivary HNC). Consistently, physician focus group noted that patients with thyroid cancer were particularly suited for telemedicine because of less emphasis on in-person examinations. Physicians also underscored factors that influence telemedicine use, including clinical suitability (treatment status, visit purpose, examination necessity), patient benefits (travel time, access), and barriers (technology, rapport-building). CONCLUSION: Patient experience with telemedicine is diverse among the HNC population. Notably, patients with thyroid cancer had overall better experience and were identified to be more appropriate for telemedicine compared with other patients with HNC. Future research that optimizes patient experience and selection is needed to ensure successful integration of telemedicine into routine oncology practice.
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Neoplasias de Cabeza y Cuello , Telemedicina , Humanos , Neoplasias de Cabeza y Cuello/terapia , Femenino , Masculino , Persona de Mediana Edad , Adulto , Anciano , Médicos/psicología , Encuestas y Cuestionarios , Satisfacción del PacienteRESUMEN
OBJECTIVE: To broaden the currently limited reach of genomic innovations, research is needed to understand how psychosocial and cultural factors influence reactions to genetic testing in diverse subgroups. Cancer fatalism is important in cancer prevention and deserves theoretical and empirical attention in the context of genomics and behavior change. METHODS: The current study employed data from a randomized controlled trial (N = 593) offering skin cancer genetic testing (using the melanocortin-1 receptor [MC1R] gene) in primary care in Albuquerque, New Mexico, USA. We examined interrelations of cancer fatalism with demographics, general health beliefs, perceived risk, perceived control, sun protection and skin screening behaviors and cancer worry in the skin cancer context stratified across Hispanic versus non-Hispanic ethnicity, and examined cancer fatalism as a moderator of intervention effects on study primary outcomes, including 3-month sun protection, cancer worry and perceived risk. RESULTS: Cancer fatalism was significantly related to the perception of control over skin cancer risk behaviors (ps ≤ 0.01) and demographics (ethnicity, education, health literacy; ps < 0.05), but not consistently related to general health beliefs or risk perception. Cancer fatalism did not moderate intervention effects on primary outcomes, except those with higher cancer fatalism randomized to intervention had higher levels of 3-month cancer worry (p = 0.019). CONCLUSIONS: These findings will guide future work considering the role of cancer fatalism in use of genomic technologies in the general population. This work anticipates strategies required to address cancer fatalism as translational genomics becomes more commonly available to diverse general population subgroups.
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Conocimientos, Actitudes y Práctica en Salud , Neoplasias Cutáneas , Humanos , Neoplasias Cutáneas/genética , Neoplasias Cutáneas/prevención & control , Neoplasias Cutáneas/psicología , Hispánicos o Latinos/psicología , Pruebas Genéticas , Atención Primaria de SaludRESUMEN
The quality of the recipient cytoplasm was reported as a crucial factor in maintaining the vitality of SCNT embryos and SCNT efficiency for dairy cows. Compared with oocytes matured in vivo, oocytes matured in vitro showed abnormal accumulation and metabolism of cytoplasmic lipids. L-carnitine treatment was found to control fatty acid transport into the mitochondrial ß-oxidation pathway, which improved the process of lipid metabolism. The results of this study show that 0.5 mg/ml L-carnitine significantly reduced the cytoplasmic lipid content relative to control. No significant difference was observed in the rate of oocyte nuclear maturation, but the in vitro developmental competence of SCNT embryos was improved in terms of increased blastocyst production and lower apoptotic index in the L-carnitine treatment group. In addition, the pregnancy rate with SCNT embryos in the treatment group was significantly higher than in the control group. In conclusion, the present study demonstrated that adding L-carnitine to the maturation culture medium could improve the developmental competence of SCNT embryos both in vitro and in vivo by reducing the lipid content of the recipient cytoplasm.
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Carnitina , Desarrollo Embrionario , Técnicas de Maduración In Vitro de los Oocitos , Oocitos , Carnitina/farmacología , Animales , Técnicas de Maduración In Vitro de los Oocitos/veterinaria , Técnicas de Maduración In Vitro de los Oocitos/métodos , Femenino , Desarrollo Embrionario/efectos de los fármacos , Bovinos , Oocitos/efectos de los fármacos , Clonación de Organismos/veterinaria , Clonación de Organismos/métodos , Técnicas de Transferencia Nuclear/veterinaria , Embarazo , Técnicas de Cultivo de Embriones , Metabolismo de los Lípidos/efectos de los fármacos , Blastocisto/efectos de los fármacosRESUMEN
Previous studies have provided valuable insights into the impact of green space (GS) on land surface temperature (LST). However, there is a need for in-depth comparative research on changing landscape patterns in cities and their effects on the urban thermal environment. This study investigates the spatial arrangement of GS and the influence of impervious surfaces on LST in urban areas, examining their cooling and warming effects in the urban landscapes of Beijing and Islamabad. The study aims to assess the impact of the spatial arrangement of GS on LST using a moving window of 1 km2 to analyze the overall effect of landscape patterns on the urban environment. Using Gaofen (GF-2) and Landsat-8 satellite data, we examined the biophysical surface properties of core urban areas. The results indicate a significant difference in the mean LST of 5.44 °C and 3.31 °C between impervious surfaces and GS in Beijing and Islamabad, respectively. The barren land and GS in Islamabad experience a higher LST of 3.39 °C compared to Beijing, which accounts for 1.39 °C. In Beijing, configuration metrics show no significant effect on urban LST, while edge density (ED) exhibits a slightly negative trend. In contrast, in the city of Islamabad, the landscape shape index (LSI), patch density (PD), and number of patches (NP) metrics have a significant influence on LST. The cooling effect of GS patches (0.1-0.5 ha) is more pronounced, while that of GS patches of 15-20 ha shows no significant effect on LST. The temperature difference (TD) of 5.01 °C was observed from the edge of GS in Beijing and 3.3 °C in Islamabad. Considering Islamabad's lush green scape compared to Beijing, this study suggests that Islamabad may experience an increase in LST in the future due to urbanization. This study's findings may assist urban policy-makers in designing sustainable green city layouts that effectively address future planning considerations.
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PURPOSE: While clinical research has shown that Tai Chi exercise may improve the sleep quality of older adults, there is a lack of robust evidence-based verification. Therefore, this study conducted a systematic review of published research on the effect of Tai Chi exercise on the sleep quality of community-dwelling older adults, aiming to provide solid evidence-based medicine to enhance their sleep quality. METHODS: A systematic search was conducted on PubMed, Embase, Cochrane Library, Web of Science, CNKI, WanFang, VIP, and SinoMed databases from their inception to December 9, 2022. The Cochrane risk of bias assessment tool 2.0 was used to assess the risk of bias in the included studies. RESULTS: This systematic review included 12 original articles, involving a total of 1,058 community-dwelling older adults, with 553 in the Tai Chi group and 505 in the control group. The meta-analysis results revealed a significant improvement in the sleep quality of community-dwelling older adults who practiced Tai Chi compared to the control group [WMD = - 1.96 (95% CI: - 3.02 to - 0.90, z = 3.62, P < 0.001)]. Subgroup analysis showed that Tai Chi had significantly beneficial effects regardless of age, country/region, intervention time, and Tai Chi type. CONCLUSIONS: Tai Chi exercise can serve as an effective non-medication approach for addressing sleep problems in this demographic. Among the various types of Tai Chi exercises, the 24-form Tai Chi exercise emerges as a preferred option. Moreover, Tai Chi exercise proves to be an excellent choice for older people in their later years, promoting their overall well-being and health.
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Vida Independiente , Calidad del Sueño , Taichi Chuan , Taichi Chuan/métodos , Humanos , Anciano , Anciano de 80 o más Años , Femenino , MasculinoRESUMEN
PURPOSE: Understanding people's response to the pandemic needs to consider individual differences in priorities and concerns. The present study sought to understand how individual differences in cognitive-appraisal processes might moderate the impact of three COVID-specific factors-hardship, worry, and social support-on reported depression. METHODS: This longitudinal study of the psychosocial impact of the COVID-19 pandemic included 771 people with data at three timepoints over 15.5 months. Participants were recruited from panels of chronically ill or general population samples. Depression was measured by an item response theory validated depression index created using items from existing measures that reflected similar content to the Patient Health Questionnaire-8. COVID-specific factors of hardship, worry, and social support were assessed with items compiled by the National Institutes of Health. The Quality of Life Appraisal Profilev2 Short-Form assessed cognitive appraisal processes. A series of random effects models examined whether appraisal moderated the effects of hardship, worry, and social support on depression over time. RESULTS: Over time the association between low social support and depression was greater (p = 0.0181). Emphasizing the negative was associated with exacerbated depression, in particular for those with low social support (p = 0.0007). Focusing on demands and habituation was associated with exacerbated depression unless one experienced greater hardship (p = 0.0074). There was a stronger positive connection between recent changes and depression for those people with higher worry scores early in the pandemic as compared to later, but a stronger positive correlation for those with lower worry scores later in the pandemic (p = 0.0015). Increased endorsement of standards of comparison, emphasizing the negative, problem goals, and health goals was associated with worse depression scores (all p < 0.0001). People who were younger, disabled, or had greater difficulty paying bills also reported worse depression (p < 0.0001, 0.0001, and 0.002, respectively). CONCLUSION: At the aggregate level, COVID-specific stressors changed over the course of the pandemic, whereas depression and social-support resources seemed stable. However, deeper analysis revealed substantial individual differences. Cognitive-appraisal processes showed considerable variability across individuals and moderated the impact of COVID-specific stressors and resources over time. Future work is needed to investigate whether coaching individuals away from maladaptive cognitive-appraisal processes can reduce depression and lead to better overall well-being.
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COVID-19 , Humanos , COVID-19/epidemiología , Pandemias , Calidad de Vida/psicología , Individualidad , Estudios Longitudinales , Apoyo SocialRESUMEN
Objectives: To describe the clinical feature of a very recently identified phenotype associated with ATAD3A variation. Methods: A neonate with Harel-Yoon syndrome was identified. We describe the proband's clinical and radiological features. The affected newborn and her parents underwent whole-exome sequencing and PCR-Sanger sequencing. Results: Previously reported clinical manifestations were rare in the neonatal period, including unmanageable seizures necessitating the use of multiple drugs, congenital laryngeal stridor, hypotonia, challenges with feeding, corneal opacity, and subsequent demise due to respiratory failure. Molecular investigations have unveiled the presence of a newly identified heterozygous single-base substitution (c.1517A > C; p.Q506P) within the ATAD3A gene. Discussion: This study unveils a novel single-base substitution, thereby expanding the mutation spectrum associated with ATAD3A. Furthermore, the clinical characteristics exhibited during the neonatal phase are comprehensively described, potentially facilitating improved clinical recognition of ATAD3A-associated HAYOS.
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Tropical and subtropical forests play a crucial role in global carbon (C) pools, and their responses to warming can significantly impact C-climate feedback and predictions of future global warming. Despite earth system models projecting reductions in land C storage with warming, the magnitude of this response varies greatly between models, particularly in tropical and subtropical regions. Here, we conducted a field ecosystem-level warming experiment in a subtropical forest in southern China, by translocating mesocosms (ecosystem composed of soils and plants) across 600 m elevation gradients with temperature gradients of 2.1°C (moderate warming), to explore the response of ecosystem C dynamics of the subtropical forest to continuous 6-year warming. Compared with the control, the ecosystem C stock decreased by 3.8% under the first year of 2.1°C warming; but increased by 13.4% by the sixth year of 2.1°C warming. The increased ecosystem C stock by the sixth year of warming was mainly attributed to a combination of sustained increased plant C stock due to the maintenance of a high plant growth rate and unchanged soil C stock. The unchanged soil C stock was driven by compensating and offsetting thermal adaptation of soil microorganisms (unresponsive soil respiration and enzyme activity, and more stable microbial community), increased plant C input, and inhibitory C loss (decreased C leaching and inhibited temperature sensitivity of soil respiration) from soil drying. These results suggest that the humid subtropical forest C pool would not necessarily diminish consistently under future long-term warming. We highlight that differential and asynchronous responses of plant and soil C processes over relatively long-term periods should be considered when predicting the effects of climate warming on ecosystem C dynamics of subtropical forests.
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Secuestro de Carbono , Ecosistema , Cambio Climático , Bosques , Carbono , SueloRESUMEN
Wildfires and post-fire management exert profound effects on soil properties and microbial communities in forest ecosystems. Understanding microbial community recovery from fire and what the best post-fire management should be is very important but needs to be sufficiently studied. In light of these gaps in our understanding, this study aimed to assess the short-term effects of wildfire and post-fire management on both bacteria and fungi community composition, diversity, structure, and co-occurrence networks, and to identify the principal determinants of soil processes influencing the restoration of these communities. Specifically, we investigated soil bacterial and fungal community composition, diversity, structure, and co-occurrence networks in lower subtropical forests during a short-term (<3 years) post-fire recovery period at four main sites in Guangdong Province, southern China. Our results revealed significant effects of wildfires on fungal community composition, diversity, and co-occurrence patterns. Network analysis indicated reduced bacterial network complexity and connectivity post-fire, while the same features were enhanced in fungal networks. However, post-fire management effects on microbial communities were negligible. Bacterial diversity correlated positively with soil microbial biomass nitrogen, soil organic carbon, and soil total nitrogen. Conversely, based on the best random forest model, fungal community dynamics were negatively linked to nitrate-nitrogen and soil water content. Spearman's correlation analysis suggested positive associations between bacterial networks and soil factors, whereas fungal networks exhibited predominantly negative associations. This study elucidates the pivotal role of post-fire management in shaping ecological outcomes. Additionally, it accentuates the discernible distinctions between bacterial and fungal responses to fire throughout a short-term recovery period. These findings contribute novel insights that bear significance in evaluating the efficacy of environmental management strategies.
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Incendios , Microbiota , Ecosistema , Suelo/química , Carbono , Bacterias , Nitrógeno/análisis , Microbiología del SueloRESUMEN
PURPOSE: Hepatocellular carcinoma (HCC), the fourth most common cancer in Africa, has a dismal overall survival of only 3 months like in sub-Saharan Africa. This is affected by the low gross domestic product and human development index, absence of coherent guidelines, and other factors. METHODS: An open forum for HCC-experienced health care workers from Africa and the rest of the world was held in October 2021. Participants completed a survey to help assess the real-life access to screening, diagnoses, and treatment in the North and Southern Africa (NS), East and West Africa (EW), Central Africa (C), and the rest of the world. RESULTS: Of 461 participants from all relevant subspecialties, 372 were from Africa. Most African participants provided hepatitis B vaccination and treatment for hepatitis B and C. More than half of the participants use serum alpha-fetoprotein and ultrasound for surveillance. Only 20% reported using image-guided diagnostic liver biopsy. The Barcelona Clinic Liver Cancer is the most used staging system (52%). Liver transplant is available for only 28% of NS and 3% EW. C reported a significantly lower availability of resection. Availability of local therapy ranged from 94% in NS to 62% in C. Sorafenib is the most commonly used systemic therapy (66%). Only 12.9% reported access to other medications including immune checkpoint inhibitors. Besides 42% access to regorafenib in NS, second-line treatments were not provided. CONCLUSION: Similarities and differences in the care for patients with HCC in Africa are reported. This reconfirms the major gaps in access and availability especially in C and marginally less so in EW. This is a call for concerted multidisciplinary efforts to achieve and sustain a reduction in incidence and mortality from HCC in Africa.
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Carcinoma Hepatocelular , Hepatitis B , Neoplasias Hepáticas , Humanos , Carcinoma Hepatocelular/terapia , Carcinoma Hepatocelular/tratamiento farmacológico , Neoplasias Hepáticas/terapia , Neoplasias Hepáticas/tratamiento farmacológico , Sorafenib/uso terapéutico , África/epidemiologíaRESUMEN
Reperfusion after ischemia would cause massive myocardial injury, which leads to oxidative stress (OS). Calcium homeostasis imbalance plays an essential role in myocardial OS injury. CaV1.2 calcium channel mediates calcium influx into cardiomyocytes, and its activity is modulated by a region of calpastatin (CAST) domain L, CSL54-64. In this study, the effect of Ahf-caltide, derived from CSL54-64, on myocardial OS injury was investigated. Ahf-caltide decreased the levels of LDH, MDA and ROS and increased heart rate, coronary flow, cell survival and SOD activity during OS. In addition, Ahf-caltide permeated into H9c2 cells and increased CaV1.2, CaVß2 and CAST levels by inhibiting protein degradation. At different Ca2+ concentrations (25 nM, 10 µM, 1 mM), the binding of CSL to the IQ motif in the C terminus of the CaV1.2 channel was increased in a H2O2 concentration-dependent manner. CSL54-64 was predicted to be responsible for the binding of CSL to CaV1.2. In conclusion, Ahf-caltide exerted a cardioprotective effect on myocardial OS injury by stabilizing CaV1.2 protein expression. Our study, for the first time, proposed that restoring calcium homeostasis by targeting the CaV1.2 calcium channel and its regulating factor CAST could be a novel treatment for myocardial OS injury.
Asunto(s)
Calcio , Peróxido de Hidrógeno , Calcio/metabolismo , Peróxido de Hidrógeno/farmacología , Peróxido de Hidrógeno/metabolismo , Canales de Calcio Tipo L/metabolismo , Miocitos Cardíacos/metabolismo , Péptidos/farmacología , Estrés OxidativoRESUMEN
Psychologically-based chronic pain variables measure multiple domains of the pain experience such as anxiety, depression, catastrophizing, acceptance and stages of change. These variables measure specific areas such as emotional and cognitive states towards chronic pain and its management, acceptance towards the chronic pain condition, and an individual's readiness to move towards self-management methods. Conceptually, these variables appear to be interrelated to each other, and also form groupings of similar underlying themes. Groupings that have been previously discussed for these variables include positive and negative affect, and improved and poor adjustment. Psychological experience of chronic pain as a whole is mostly understood through conceptually consolidating individual scores across different measures covering multiple domains. A map of these variables in relation to each other can offer an overview for further understanding and exploration. We hereby visualize highlights of relationships among 11 psychosocial chronic pain variables including measures examining physical and somatic aspects, using three-dimensional biplots. Variables roughly form two groupings, with one grouping consisting of items of negative affect, cognition, and physical state ratings, and the other grouping consisting of items of acceptance and the later three stages of change (contemplation, action, maintenance). Also, we follow up with canonical correlation as a complement to further identify key relationships between bimodal groupings. Key variables linking bimodal relationships consist of catastrophizing, depression and anxiety in one grouping and activity engagement in the other. Results are discussed in the context of existing literature.