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2.
J Nutr ; 2024 Jul 23.
Artigo em Inglês | MEDLINE | ID: mdl-39053606

RESUMO

BACKGROUND: Limited evidence exists on determinants of maternal and child diet quality. OBJECTIVES: This study examined the role of Social and Behavior Change Communication (SBCC) and nutrition-sensitive social protection (NSSP) programs on maternal and child diet quality. METHODS: Data were from cross-sectional phone survey on 6,627 Indian mothers that took place in late 2021. The Diet Quality Questionnaire (DQQ) was used to measure maternal and child diet quality, including minimum dietary diversity (MDD), dietary diversity scores (DDS), non-communicable disease (NCD)-Protect and NCD-Risk, adherence to dietary guidelines (All-5 and India-All-6), and unhealthy child feeding. Multivariate regression models were used to explore the association between diet indicators and coverage of SBCC and NSSP programs. RESULTS: Maternal and child diet quality was suboptimal, with more mothers (57%) achieving MDD than children (23%). SBCC was positively associated with healthy food consumption in children (Odds Ratio, OR=2.14 for MDD, ß=0.60 for DDS and 0.54 for NCD-Protect), and mothers (ß=0.38 for DDS and 0.43 for NCD-Protect). Cash transfers were associated with healthier diets in mothers (OR=1.45 for MDD, 1.86 for All-5, and 2.14 for India-All-6, ß=0.43 for DDS and 0.26 for NCD-Protect), but less associations for children (ß=0.14 for NCD-Protect). Receiving food was associated with healthier diets in mothers (OR 1.47 for MDD, ß= 0.27 for DDS and 0.33 for NCD-Protect) and children (ß=0.19 for DDS and 0.15 for NCD-Protect), but also with unhealthy food in children (OR=1.34). Exposure to multiple programs showed stronger associations with diet quality. CONCLUSION: SBCC had greater positive impact on child feeding than food and cash transfers, while cash had a stronger association with improved maternal diets. Food and cash are also associated with unhealthy food consumption. Our study underscores the importance of interventions that combine education, resource provision, and targeted support to promote maternal and child diet quality.

3.
Disabil Rehabil Assist Technol ; : 1-9, 2024 Jul 16.
Artigo em Inglês | MEDLINE | ID: mdl-39011569

RESUMO

Robot-assisted physical rehabilitation offers promising benefits for patients, yet its adoption among therapists remains a complex challenge. This study investigates the acceptance of robot-assisted physical rehabilitation technology among therapists in Vietnam, a middle-income country with a growing demand for rehabilitation services. Drawing on the Technology Acceptance Model 2 (TAM2) and the Theory of Planned Behaviour (TPB), an online survey and semi-structured interviews were conducted to explore therapists' attitudes and intentions towards using this technology. The results show that Vietnamese therapists recognised its potential benefits and expressed a willingness to use it. Although having similar acceptance patterns compared to developed regions, they demonstrated significantly higher levels of agreement across acceptance constructs. This may be attributed to factors such as the novelty effect, cultural perceptions of robots, and the high workload of therapists in Vietnam. Gender and location were found to influence two acceptance constructs-subjective norms and image, respectively-highlighting the need for tailored strategies in technology implementation. The study underscores the importance of considering socio-cultural factors in the adoption of technology and provides insights for enhancing the acceptance and effectiveness of robot-assisted physical rehabilitation in Vietnam. This contributes to the global understanding of therapist acceptance of technology in this field.


While robot-assisted physical rehabilitation offers promising benefits, there is limited understanding of therapist acceptance on a global scale, highlighting the need for more research in this area.This study in a middle-income country, Vietnam, reveals a generally positive view among therapists, but specific issues such as the novelty effect, cultural perceptions of robots, and high therapist workload impact acceptance levels, indicating the need for tailored strategies.Strategies for implementing robot-assisted physical rehabilitation should include addressing training needs, providing technological support, and considering sociocultural factors to enhance acceptance and effectiveness.

4.
Int J Public Health ; 69: 1606536, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-39027014

RESUMO

Objectives: To assess the pre-training knowledge of Commune Health Stations (CHSs) physicians in Vietnam on pregnancy and child care. Methods: A cross-sectional study was conducted and a pre-training questionnaire was administered with physicians working at CHSs in three mountainous provinces of northern Vietnam. Calculated mean knowledge score and estimated adjusted odds ratios (AOR) to compare the relative odds of occurrence of the outcome "answering more than half of questions correct," given exposure to the physicians' characteristics. Results: A total of 302 CHS physicians participated. The mean number of correct answers across all participants was 5.4 out of 11. Female physicians are 2.20 (95% CI: 1.35-3.59, p = 0.002) times more likely to answer correctly than their male counterparts. Physicians aged 35 years or more were significantly less likely to answer correctly (AOR 0.35, 95% CI: 0.15-0.81, p = 0.014). Conclusion: The study found that participating physicians possessed relatively low knowledge of pregnancy and child care. The study also found significant disparities in this knowledge according to the physicians' characteristics. Thus, it is recommended the requirement for continuing targeted medical education to improve doctors' proficiency in these areas.


Assuntos
Conhecimentos, Atitudes e Prática em Saúde , Humanos , Estudos Transversais , Feminino , Adulto , Masculino , Vietnã , Gravidez , Pessoa de Meia-Idade , Inquéritos e Questionários , Atenção Primária à Saúde , Médicos , Competência Clínica
5.
BMJ Case Rep ; 17(7)2024 Jul 23.
Artigo em Inglês | MEDLINE | ID: mdl-39043462

RESUMO

Headache and neurological deficits with cerebrospinal fluid (CSF) lymphocytosis (HaNDL) is a rare condition characterised by recurrent episodes of headache and transient neurological deficits. This case report presents a young patient initially diagnosed with hemiplegic migraine, having a normal brain CT, with focal cerebral perfusion mismatch not restricted to a single vascular territory on CT angiography. Brain MRI revealed a cytotoxic lesion of the splenium in the corpus callosum (CLOCC), a feature also reported in migraine. However, recurrent headaches with neurological deficits prompted further investigations with CSF analysis and brain MRI, confirming HaNDL and demonstrating reversibility of CLOCC. Recognising HaNDL as a differential diagnosis is essential in patients with recurrent headaches with focal neurological deficits, given the differences in therapeutic approach. The relationship between migraine and HaNDL is not fully understood, but they may share a pathophysiological link. Awareness of this is crucial for accurate diagnosis.


Assuntos
Corpo Caloso , Cefaleia , Linfocitose , Imageamento por Ressonância Magnética , Humanos , Linfocitose/líquido cefalorraquidiano , Linfocitose/diagnóstico , Linfocitose/complicações , Corpo Caloso/diagnóstico por imagem , Corpo Caloso/patologia , Cefaleia/etiologia , Diagnóstico Diferencial , Adulto , Masculino , Feminino , Síndrome
6.
Arch Plast Surg ; 51(4): 367-371, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-39034983

RESUMO

Skin defects of the total nasal columella can significantly impact both nasal respiratory function and aesthetics. The reconstruction of total columella is a complex process and represents a significant challenge for plastic surgeons. Various factors can cause the loss of the columella. Numerous columella reconstruction procedures have been proposed, each with their own set of advantages and disadvantages. The main issues to address include the need for regional flaps from the forehead or nasofacial sulcus, a long pedicle to reach the columella, and the double angular folding that causes a risk of malnutrition or venous congestion. Additionally, using horizontal nasolabial flaps may lead to deformation of the upper lip. In this study, we present a new procedure to reconstruct the nasal columella using "Domino flaps" with two flaps (the horizontal upper lip island flap and nasocheek island flap). This new procedure ensures adequate skin for reconstruction of nasal columella and partial tip, minimizes rotation angle, reduces the angular folding of the pedicle, furthermore limits deformation of the upper lip. "Domino flaps" are a valuable option for surgeons when reconstructing the total nasal columella. However, it is important to consider whether the patient has a beard at the donor sites.

7.
Arthritis Rheumatol ; 2024 Jul 25.
Artigo em Inglês | MEDLINE | ID: mdl-39054665

RESUMO

OBJECTIVES: CD4+CD8+ T cells are increased in patients with rheumatoid arthritis (RA). They are not only associated with joint erosions in established disease, but are also present in the pre-clinical stages of RA. This study aims to further investigate their expansion in the context of T cell clonality in patients with RA, as well as their responsiveness to T cell targeted treatment. METHODS: Single-cell-(sc)RNA- and scTCR-sequencing data were used to determine co-receptor expression and T cell receptor sequences to assess clonality of CD4+CD8+ T cells in RA (n=3) patients and healthy controls (n=2). Peripheral CD4+CD8+ T cells and their subpopulations were measured in patients with RA (n=53), PsA (n=52) and healthy donors (n=50) using flow cytometry. In addition, changes in CD4+CD8+ T cell frequency were prospectively followed in RA patients receiving therapy with abatacept for 12 weeks. RESULTS: We observed an increase of CD4+ T cells expressing CD8α in RA patients, both in comparison to PsA patients and to healthy controls. Clonality analysis revealed, that these CD4+CD8αlow T cells are part of large T cell clones, which cluster separately from CD4+CD8- T cell clones in the scRNA-seq gene expression analysis. Treatment with abatacept significantly reduced the frequency of peripheral CD4+CD8αlow T cells, and this was linked to reduction in disease activity. CONCLUSION: In RA, clonal expansion of CD4+ T cell clones culminates in the emergence of peripheral CD4+CD8αlow T cells, which are associated with disease activity and diminished upon abatacept treatment, and which could contribute to disease pathogenesis.

8.
Chem Biodivers ; : e202400997, 2024 Jul 26.
Artigo em Inglês | MEDLINE | ID: mdl-39054897

RESUMO

Golden camellia is defined as a species of the Camellia genus with yellow flowers, which have long been used as a medicine, food, and cosmetic in many Asian countries. To date, more than 50 golden camellia species are considered endemic in Vietnam; however, more information is needed about its chemical constituents and biological activity. This work aims to unveil the potential of Camellia tienii Ninh, a golden camellia species, as an herbal beverage by examining the presence and abundance of chemical components in flowers and leaves. A comprehensive strategy has been developed using both liquid and gas chromatography coupled with mass spectrometry. Specifically, LC-MS-based widely targeted analyses were opted to characterize 158 polar metabolites belonging mainly to flavonoids, catechins, and amino acids classes, and an untargeted approach using GC-MS annotated 42 major volatile compounds such as terpenes and fatty acids. The extensive profile revealed by these techniques could help understand the significant discrimination between two organs. C. tienii flowers accumulated more flavonoids, amino acids, and fatty acids, while leaves contain more terpenes, suggesting different pharmacological properties of these materials. Overall, this pipeline can be applied for other Camellia species and valorization of these valuable resources for health benefits purposes.

9.
J Org Chem ; 89(13): 9681-9685, 2024 Jul 05.
Artigo em Inglês | MEDLINE | ID: mdl-38965938

RESUMO

The CF3 group is well noted for being noninteractive with other functional groups. In this Note, we present a highly rigid model system containing a significant hydrogen bonding interaction between a charged N-H donor and a CF3 acceptor that challenges this accepted wisdom. Spectroscopic and single crystal X-ray crystallography data characterize this interaction, consistent with a weak to moderate hydrogen bond that would be difficult to observe in an intermolecular system.

10.
Value Health ; 2024 Jul 06.
Artigo em Inglês | MEDLINE | ID: mdl-38977195

RESUMO

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 sub-group 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% Confidence interval [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.

11.
BMJ Glob Health ; 9(6)2024 Jun 05.
Artigo em Inglês | MEDLINE | ID: mdl-38843899

RESUMO

The International Health Regulations Monitoring and Evaluation Framework (IHRMEF) includes four components regularly conducted by States Parties to measure the current status of International Health Regulations (IHR) 2005 core capacities and provide recommendations for strengthening these capacities. However, the four components are conducted independently of one another and have no systematic referral to each other before, during or after each process, despite being largely conducted by the same team, country and support organisations. This analysis sets out to identify ways in which IHRMEF components could work more synergistically to effectively measure the status of IHR core capacities, taking into account the country's priority risks. We developed a methodology to allow these independent components to communicate with each other, including expert consultation, a qualitative crosswalk analysis and a country-level quantitative analysis. The demonstrated results act as a proof of concept and illustrate a methodology to provide benefits across all four components before, during and after implementation.


Assuntos
Saúde Global , Regulamento Sanitário Internacional , Humanos , Cooperação Internacional
12.
J Pediatr Endocrinol Metab ; 37(7): 644-651, 2024 Jul 26.
Artigo em Inglês | MEDLINE | ID: mdl-38829694

RESUMO

OBJECTIVES: This study is aimed to explore the correlation between bisphenol A (BPA) and phthalates, including diethylhexylphthalate (DEHP) and dibutylphthalate (DBP), and precocious puberty (PP). METHODS: A case-control study was conducted in Ho Chi Minh City, Vietnam, from November 2021 to April 2022, involving 250 children, with 124 of them diagnosed with PP and 126 serving as controls. We assessed the levels of urinary BPA, DEHP, and DBP in all participants and examined their association with the risk of PP. RESULTS: BPA was detected in 11.3 % of PP cases but was not found in any individuals in the control group (p<0.001). Diethylhexylphthalate metabolite (MEHP) was not detected in any of the samples. Positive urinary results for dibutylphthalate metabolite (MBP) were observed in 8.1 % of PP cases and 2.4 % in the control group, with an odds ratio of 3.6 (95 % confidence interval: 0.97-13.4, p=0.03). CONCLUSIONS: The PP group exhibited a higher prevalence of positive urinary BPA and DBP levels compared to the control group.


Assuntos
Compostos Benzidrílicos , Fenóis , Ácidos Ftálicos , Puberdade Precoce , Humanos , Fenóis/urina , Puberdade Precoce/urina , Puberdade Precoce/induzido quimicamente , Puberdade Precoce/epidemiologia , Compostos Benzidrílicos/urina , Feminino , Vietnã/epidemiologia , Estudos de Casos e Controles , Masculino , Ácidos Ftálicos/urina , Criança , Exposição Ambiental/efeitos adversos , Exposição Ambiental/análise , Dietilexilftalato/urina , Seguimentos , Dibutilftalato/urina , Dibutilftalato/análise , Prognóstico , Disruptores Endócrinos/urina , População do Sudeste Asiático
13.
ACS Omega ; 9(21): 22734-22743, 2024 May 28.
Artigo em Inglês | MEDLINE | ID: mdl-38826561

RESUMO

Cu-doping contents in the TiO2 lattice structure were studied to show the effects on the crystal structure, morphology, and photocatalytic activity of TiO2 nanoparticles and thus composite cellulosic nanofibrous membranes. Pristine and copper-doped TiO2 nanoparticles were synthesized using the sol-gel technique, a wet chemical method with the advantages of low synthesizing temperature, uniform nanosize distribution, and purity. The as-synthesized semiconductor nanoparticles were first tested with the dye removal process and then impregnated onto electrospun cellulose nanofibers (CL nanofibers) to acquire modified nanofibers with self-cleaning properties. The as-prepared composite CL nanofibers consisting of doped and undoped TiO2 nanoparticles were characterized by various techniques, such as field emission scanning electron microscopy, transmission electron microscopy, UV-vis, X-ray diffraction, Fourier transform infrared spectroscopy, and tensile tests. The copper-doped TiO2 molar ratio in the nanocomposite was found to possess a pronounced impact on the dye removal and self-cleaning effects under the visible light spectrum, whereas TiO2 is highly effective under specific UV-light irradiation. Optical measurements and dye decomposition showed that the Cu-doped TiO2 nanocomposite was optimized at a 1% molar ratio by the copper-doping concentration regarding dye removal and self-cleaning applications under the visible light range.

14.
Lancet Reg Health Southeast Asia ; 26: 100427, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-38827143

RESUMO

Background: Globally, alcohol consumption is a leading risk factor for deaths and disability and a causal factor in over 200 diseases, injuries, and health conditions. In April 2016, the manufacture, transport, sale, and consumption of alcohol was banned in Bihar, a populous Indian state. We sought to estimate the impacts of this ban on health outcomes and domestic violence. Methods: Data from the Indian National Family Health Surveys (2005-06, 2015-16, 2019-21), Annual Health Survey (2013), and District Level Household Survey (2012), were used to conduct difference-in-differences (DID) analysis, comparing Bihar (n = 10,733 men, n = 88,188 women) and neighbouring states (n = 38,674 men, n = 284,820 women) before and after the ban. Outcomes included frequent (daily or weekly) alcohol consumption, underweight, obesity, hypertension, diabetes, and intimate partner violence. A triple difference model adding male-female interaction to the DID model was also estimated. Attributable averted cases were calculated to estimate the impact of the ban. Findings: Across all models, the ban led to reduced frequent alcohol consumption (DID: -7.1 percentage points (pp) (95% CI -9.6pp, -4.6pp), lower overweight/obesity (-5.6pp (-8.9, -2.2) among males, and reduced experiences of emotional (-4.8pp (-8.2pp, -1.4pp) and sexual (-5.5pp (-8.7pp, -2.3pp) violence among females. The ban prevented approximately 2.4 million cases of daily/weekly alcohol consumption and 1.8 million cases of overweight/obesity among males, and 2.1 million cases of intimate partner violence among females. Interpretation: Strict alcohol regulation policies may yield significant population level health benefits for frequent drinkers and many victims of intimate partner violence. Funding: No funding was received for this work.

15.
Neuroradiol J ; : 19714009241260796, 2024 Jun 10.
Artigo em Inglês | MEDLINE | ID: mdl-38856642

RESUMO

In traumatic brain injury, white matter diffusion restriction can be an imaging manifestation of non-hemorrhagic axonal injury. In this article, a different pattern of widespread white matter diffusion restriction associated with ipsilateral cortical damage, all noted in pediatric and young adult TBI patients, is presented. Its atypical pattern of distribution and extensive scope on imaging suggest excitotoxicity and intramyelinic edema as possible underlying mechanisms.

16.
Leuk Res ; 143: 107531, 2024 Jun 04.
Artigo em Inglês | MEDLINE | ID: mdl-38851084

RESUMO

The treatment landscape of chronic lymphocytic leukemia (CLL) has advanced remarkably over the past decade. The advent and approval of the BTK inhibitor ibrutinib and BCL-2 inhibitor venetoclax, as well as monoclonal anti-CD20 antibodies rituximab and obinutuzumab, have resulted in deep remissions and substantially improved survival outcomes for patients. However, CLL remains a complex disease with many patients still experiencing relapse and unsatisfactory treatment responses. CLL cells are highly dependent on their pro-leukemic tumor microenvironment (TME), which comprises different cellular and soluble factors. A large body of evidence suggests that CLL-associated macrophages shaped by leukemic cells play a pivotal role in maintaining CLL cell survival. In this review, we summarize the pro-survival interactions between CLL cells and macrophages, as well as the impact of the current first-line treatment agents, including ibrutinib, venetoclax, and CD20 antibodies on leukemia-associated macrophages.

17.
Environ Res ; 258: 119396, 2024 Jun 12.
Artigo em Inglês | MEDLINE | ID: mdl-38871276

RESUMO

Adsorption of essential amino acid, Tryptophan (Tryp) on synthesized gibbsite nanoparticles and their applications in eliminating of antibiotic ciprofloxacin (CFX) and bacteria Escherichia coli (E. coli) in aqueous solution. Nano-gibbsite which was successfully fabricated, was characterized by XRD, TEM-SAED, FT-IR, SEM-EDX and zeta potential measurements. The selected parameters for Tryp adsorption on nano-gibbsite to form biomaterial, Tryp/gibbsite were pH 11, gibbsite dosage 20 mg/mL and 1400 mg/L Tryp. The optimum conditions for CFX removal using Tryp/gibbsite were adsorption time 60 min, pH 5, and 20 mg/mL Tryp/gibbsite dosage. The CFX removal significantly raised from 63 to 90% when using Tryp/gibbsite. The Freundlich and pseudo-second-order models achieved the best fits for CFX adsorption isotherm and kinetic on Tryp/gibbsite, respectively. The amount of CFX increased with increasing ionic strength, suggesting that both electrostatic and non-electrostatic interactions were important. After four reused time, CFX removal was greater than 66%, demonstrating that Tryp/gibbsite is reusable with high performance in removing CFX. The application in bacterial activity in term of E. coli reached greater than 98% that was the best material for bacteria inactivation. The present study reveals that Tryp/gibbsite is an excellent bio-material for removing CFX and E. coli.

18.
JMIR Bioinform Biotechnol ; 5: e56884, 2024 May 07.
Artigo em Inglês | MEDLINE | ID: mdl-38935968

RESUMO

BACKGROUND: The etiology of ischemic stroke is multifactorial. Several gene mutations have been identified as leading causes of cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL), a hereditary disease that causes stroke and other neurological symptoms. OBJECTIVE: We aimed to identify the variants of NOTCH3 and thrombophilia genes, and their complex interactions with other factors. METHODS: We conducted a hierarchical cluster analysis (HCA) on the data of 100 patients diagnosed with ischemic stroke. The variants of NOTCH3 and thrombophilia genes were identified by polymerase chain reaction with confronting 2-pair primers and real-time polymerase chain reaction. The overall preclinical characteristics, cumulative cutpoint values, and factors associated with these somatic mutations were analyzed in unidimensional and multidimensional scaling models. RESULTS: We identified the following optimal cutpoints: creatinine, 83.67 (SD 9.19) µmol/L; age, 54 (SD 5) years; prothrombin (PT) time, 13.25 (SD 0.17) seconds; and international normalized ratio (INR), 1.02 (SD 0.03). Using the Nagelkerke method, cutpoint 50% values of the Glasgow Coma Scale score; modified Rankin scale score; and National Institutes of Health Stroke Scale scores at admission, after 24 hours, and at discharge were 12.77, 2.86 (SD 1.21), 9.83 (SD 2.85), 7.29 (SD 2.04), and 6.85 (SD 2.90), respectively. CONCLUSIONS: The variants of MTHFR (C677T and A1298C) and NOTCH3 p.R544C may influence the stroke severity under specific conditions of PT, creatinine, INR, and BMI, with risk ratios of 4.8 (95% CI 1.53-15.04) and 3.13 (95% CI 1.60-6.11), respectively (Pfisher<.05). It is interesting that although there are many genes linked to increased atrial fibrillation risk, not all of them are associated with ischemic stroke risk. With the detection of stroke risk loci, more information can be gained on their impacts and interconnections, especially in young patients.

19.
J Nutr ; 2024 Jun 25.
Artigo em Inglês | MEDLINE | ID: mdl-38936548

RESUMO

BACKGROUND: Children born preterm and/or small for gestational age (SGA) are at increased risk of poor cognitive outcomes, particularly in low and middle-income countries (LMICs). OBJECTIVES: This study aimed to examine the cognitive and academic deficits during the school-age years in children born preterm or SGA compared with those in children born term adequate for gestational age (AGA) in rural Vietnam. METHODS: Children born to women in a preconception micronutrient supplementation trial in Vietnam were classified into 3 groups: preterm AGA (n =138), term SGA (n =169), and term AGA (n = 1134). Cognitive abilities were assessed using the Wechsler Intelligence Scale for Children, measuring 4 domains [verbal comprehension index (VCI), perceptual reasoning index (PRI), working memory index (WMI), and processing speed index (PSI) scores] and full-scale intelligence quotient (FSIQ) at 6-7 and 10-11 y. Academic achievement was assessed with mathematic and language tests. Analysis of variance and multiple regression models were used to analyze differences in cognitive function and academic achievement at 6-7 and 10-11 y by birth phenotypes. RESULTS: Compared with term AGA children, those born SGA had lower cognitive scores at both 6-7 y (VCI, -2.3; PRI, -3.7; PSI -2.1; and FSIQ, -2.9) and 10-11 y (VCI, -3.7; PRI, -3.5; WMI, -2.7; PSI, -1.9; and FSIQ, -3.9). Children born SGA also had poorer academic achievement with lower language (5.3) and mathematic (2.5) scores. Adjustments for maternal factors and home environment attenuated the associations, but the differences in VCI, PRI, FSIQ, and language at 10-11 y remained significant. There were no differences in cognitive function and academic achievement between children born preterm and AGA. CONCLUSIONS: Our findings highlight the enduring association of birth phenotype on cognitive functioning and academic achievement during the school years, despite adjustments for maternal education and family environment. Further research is needed to implement effective interventions to improve birth outcomes and optimize child health and development in LMICs. The trial was registered at clinicaltrials.gov as NCT01665378 (URL: https://clinicaltrials.gov/ct2/show/NCT01665378).

20.
Nat Commun ; 15(1): 5388, 2024 Jun 25.
Artigo em Inglês | MEDLINE | ID: mdl-38918376

RESUMO

Heparan sulfate (HS) is degraded in lysosome by a series of glycosidases. Before the glycosidases can act, the terminal glucosamine of HS must be acetylated by the integral lysosomal membrane enzyme heparan-α-glucosaminide N-acetyltransferase (HGSNAT). Mutations of HGSNAT cause HS accumulation and consequently mucopolysaccharidosis IIIC, a devastating lysosomal storage disease characterized by progressive neurological deterioration and early death where no treatment is available. HGSNAT catalyzes a unique transmembrane acetylation reaction where the acetyl group of cytosolic acetyl-CoA is transported across the lysosomal membrane and attached to HS in one reaction. However, the reaction mechanism remains elusive. Here we report six cryo-EM structures of HGSNAT along the reaction pathway. These structures reveal a dimer arrangement and a unique structural fold, which enables the elucidation of the reaction mechanism. We find that a central pore within each monomer traverses the membrane and controls access of cytosolic acetyl-CoA to the active site at its luminal mouth where glucosamine binds. A histidine-aspartic acid catalytic dyad catalyzes the transfer reaction via a ternary complex mechanism. Furthermore, the structures allow the mapping of disease-causing variants and reveal their potential impact on the function, thus creating a framework to guide structure-based drug discovery efforts.


Assuntos
Acetiltransferases , Microscopia Crioeletrônica , Lisossomos , Mucopolissacaridose III , Mucopolissacaridose III/genética , Mucopolissacaridose III/metabolismo , Mucopolissacaridose III/enzimologia , Humanos , Lisossomos/metabolismo , Lisossomos/enzimologia , Acetiltransferases/metabolismo , Acetiltransferases/química , Acetiltransferases/genética , Domínio Catalítico , Mutação , Heparitina Sulfato/metabolismo , Acetilcoenzima A/metabolismo , Acetilcoenzima A/química , Modelos Moleculares , Glucosamina/metabolismo , Glucosamina/química , Acetilação , Membranas Intracelulares/metabolismo
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