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1.
Genes (Basel) ; 12(12)2021 Nov 30.
Artigo em Inglês | MEDLINE | ID: mdl-34946879

RESUMO

Due to newborn screening for X-linked adrenoleukodystrophy (ALD), and the use of exome sequencing in clinical practice, the detection of variants of unknown significance (VUS) in the ABCD1 gene is increasing. In these cases, functional tests in fibroblasts may help to classify a variant as (likely) benign or pathogenic. We sought to establish reference ranges for these tests in ALD patients and control subjects with the aim of helping to determine the pathogenicity of VUS in ABCD1. Fibroblasts from 36 male patients with confirmed ALD, 26 healthy control subjects and 17 individuals without a family history of ALD, all with an uncertain clinical diagnosis and a VUS identified in ABCD1, were included. We performed a combination of tests: (i) a test for very-long-chain fatty acids (VLCFA) levels, (ii) a D3-C22:0 loading test to study the VLCFA metabolism and (iii) immunoblotting for ALD protein. All ALD patient fibroblasts had elevated VLCFA levels and a reduced peroxisomal ß-oxidation capacity (as measured by the D3-C16:0/D3-C22:0 ratio in the D3-C22:0 loading test) compared to the control subjects. Of the VUS cases, the VLCFA metabolism was not significantly impaired (most test results were within the reference range) in 6/17, the VLCFA metabolism was significantly impaired (most test results were within/near the ALD range) in 9/17 and a definite conclusion could not be drawn in 2/17 of the cases. Biochemical studies in fibroblasts provided clearly defined reference and disease ranges for the VLCFA metabolism. In 15/17 (88%) VUS we were able to classify the variant as being likely benign or pathogenic. This is of great clinical importance as new variants will be detected.

2.
Front Cell Dev Biol ; 9: 777890, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34917617

RESUMO

Previous studies have shown that LBX1 is associated with adolescent idiopathic scoliosis (AIS) in multiple populations. For the first time, rs1322330 located in the putative promoter region of LBX1 was found significantly associated with AIS in the Chinese population [p = 6.08 × 10-14, odds ratio (OR) = 1.42, 95% confidence interval of 1.03-1.55]. Moreover, the luciferase assay and electrophoretic mobility shift assay supported that the allele A of rs1322330 could down-regulate the expression of LBX1 in the paraspinal muscles of AIS. In addition, silencing LBX1 in the myosatellite cells resulted in significantly inhibited cell viability and myotube formation, which supported an essential role of LBX1 in muscle development of AIS. To summarize, rs1322330 may be a novel functional SNP regulating the expression of LBX1, which was involved in the etiology of AIS possibly via regulation of myogenesis in the paraspinal muscles.

3.
Front Endocrinol (Lausanne) ; 12: 708248, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34557159

RESUMO

Purpose: The inhibition of estrogen receptor alpha (ERα) or the activation of ERß can inhibit papillary thyroid cancer (PTC), but the precise mechanism is not known. We aimed to explore the role of ERα and ERß on the production of endogenous peroxisome proliferator-activated receptor gamma (PPARγ) ligands in PTC. Methods: 2 PTC cell lines, 32 pairs of PTC tissues and matched normal thyroid tissues were used in this study. The levels of endogenous PPARγ ligands 15(S)-hydroxyeicosatetraenoic acid (15(S)-HETE), 13-S-hydroxyoctadecadienoic acid (13(S)-HODE), and15-deoxy-Δ12,14-prostaglandin J2 (PGJ2) were measured by ELISA. Results: The levels of PGJ2 and 15(S)-HETE were significantly reduced in PTC, but 13(S)-HODE was not changed. Activation of ERα or inhibition of ERß significantly downregulated the production of PGJ2, 15(S)-HETE and 13(S)-HODE, whereas inhibition of ERα or activation of ERß markedly upregulated the production of these three ligands. Application of endogenous PPARγ ligands inhibited growth, induced apoptosis of cancer cells, and promoted the efficacy of chemotherapy. Conclusion: The levels of endogenous PPARγ ligands PGJ2 and 15(S)-HETE are significantly decreased in PTC. The inhibition of ERα or activation of ERß can inhibit PTC by stimulating the production of endogenous PPARγ ligands to induce apoptosis in cancer cells.

4.
Genes (Basel) ; 12(7)2021 07 01.
Artigo em Inglês | MEDLINE | ID: mdl-34356049

RESUMO

Adolescent Idiopathic Scoliosis (AIS) is a prevalent and important spine disorder in the pediatric age group. An increased family tendency was observed for a long time, but the underlying genetic mechanism was uncertain. In 1999, Dr. Yves Cotrel founded the Cotrel Foundation in the Institut de France, which supported collaboration of international researchers to work together to better understand the etiology of AIS. This new concept of AIS as a complex trait evolved in this setting among researchers who joined the annual Cotrel meetings. It is now over a decade since the first proposal of the complex trait genetic model for AIS. Here, we review in detail the vast information about the genetic and environmental factors in AIS pathogenesis gathered to date. More importantly, new insights into AIS etiology were brought to us through new research data under the perspective of a complex trait. Hopefully, future research directions may lead to better management of AIS, which has a tremendous impact on affected adolescents in terms of both physical growth and psychological development.

5.
Nutrients ; 13(7)2021 Jul 05.
Artigo em Inglês | MEDLINE | ID: mdl-34371826

RESUMO

BACKGROUND: Sarcopenia is a major health problem in older adults. Exercise and nutrient supplementation have been shown to be effective interventions but there are limited studies to investigate their effects on the management of sarcopenia and its possible underlying mechanisms. Here, we studied T cell gene expression responses to interventions in sarcopenia. METHODS: The results of this study were part of a completed trial examining the effectiveness of a 12-week intervention with exercise and nutrition supplementation in community-dwelling Chinese older adults with sarcopenia, based on the available blood samples at baseline and 12 weeks from 46 randomized participants from three study groups, namely: exercise program alone (n = 11), combined-exercise program and nutrition supplement (n = 23), and waitlist control group (n = 12). T cell gene expression was evaluated, with emphasis on inflammation-related genes. Real-time PCR (RT-PCR) was performed on CD3 T cells in 38 selected genes. Correlation analysis was performed to relate the results of gene expression analysis with lower limb muscle strength performance, measured using leg extension tests. RESULTS: Our results showed a significant improvement in leg extension for both the exercise program alone and the combined groups (p < 0.001). Nine genes showed significant pre- and post-difference in gene expression over 12 weeks of intervention in the combined group. Seven genes (RASGRP1, BIN1, LEF1, ANXA6, IL-7R, LRRN3, and PRKCQ) showed an interaction effect between intervention and gene expression levels on leg extension in the confirmatory analysis, with confounder variables controlled and FDR correction. CONCLUSIONS: Our findings showed that T cell-specific inflammatory gene expression was changed significantly after 12 weeks of intervention with combined exercise and HMB supplementation in sarcopenia, and that this was associated with lower limb muscle strength performance.


Assuntos
Suplementos Nutricionais , Exercício Físico/fisiologia , Expressão Gênica/genética , Sarcopenia/terapia , Linfócitos T/metabolismo , Valeratos/administração & dosagem , Idoso , Idoso de 80 Anos ou mais , Terapia Combinada , Análise Fatorial , Feminino , Humanos , Vida Independente , Extremidade Inferior/fisiopatologia , Masculino , Força Muscular/genética , Músculo Esquelético/fisiopatologia , Treinamento de Força/métodos , Sarcopenia/genética , Resultado do Tratamento
6.
Genes (Basel) ; 12(7)2021 06 25.
Artigo em Inglês | MEDLINE | ID: mdl-34202032

RESUMO

Peripheral blood transcriptome is a highly promising area for biomarker development. However, transcript abundances (TA) in these cell mixture samples are confounded by proportions of the component leukocyte subpopulations. This poses a challenge to clinical applications, as the cell of origin of any change in TA is not known without prior cell separation procedure. We developed a framework to develop a cell-type informative TA biomarkers which enable determination of TA of a single cell-type (B lymphocytes) directly in cell mixture samples of peripheral blood (e.g., peripheral blood mononuclear cells, PBMC) without the need for subpopulation separation. It is applicable to a panel of genes called B cell informative genes. Then a ratio of two B cell informative genes (a target gene and a stably expressed reference gene) obtained in PBMC was used as a new biomarker to represent the target gene expression in purified B lymphocytes. This approach, which eliminates the tedious procedure of cell separation and directly determines TA of a leukocyte subpopulation in peripheral blood samples, is called the Direct LS-TA method. This method is applied to gene expression datasets collected in influenza vaccination trials as early predictive biomarkers of seroconversion. By using TNFRSF17 or TXNDC5 as the target genes and TNFRSF13C or FCRLA as the reference genes, the Direct LS-TA B cell biomarkers were determined directly in the PBMC transcriptome data and were highly correlated with TA of the corresponding target genes in purified B lymphocytes. Vaccination responders had almost a 2-fold higher Direct LS-TA biomarker level of TNFRSF17 (log 2 SMD = 0.84, 95% CI = 0.47-1.21) on day 7 after vaccination. The sensitivity of these Direct LS-TA biomarkers in the prediction of seroconversion was greater than 0.7 and area-under curves (AUC) were over 0.8 in many datasets. In this paper, we report a straightforward approach to directly estimate B lymphocyte gene expression in PBMC, which could be used in a routine clinical setting. Moreover, the method enables the practice of precision medicine in the prediction of vaccination response. More importantly, seroconversion could now be predicted as early as day 7. As the acquired immunology pathway is common to vaccination against influenza and COVID-19, these biomarkers could also be useful to predict seroconversion for the new COVID-19 vaccines.


Assuntos
Linfócitos B/fisiologia , Expressão Gênica , Vacinas contra Influenza/imunologia , Soroconversão/genética , Receptor do Fator Ativador de Células B/genética , Biomarcadores/análise , Vacinas contra COVID-19/imunologia , Biologia Computacional/métodos , Bases de Dados Genéticas , Humanos , Leucócitos Mononucleares/fisiologia , Modelos Teóricos , Metanálise em Rede , Isomerases de Dissulfetos de Proteínas/genética , Curva ROC , Receptores Fc/genética , Soroconversão/fisiologia
9.
Genome Med ; 13(1): 29, 2021 02 19.
Artigo em Inglês | MEDLINE | ID: mdl-33608049

RESUMO

BACKGROUND: The clinical utility of personal genomic information in identifying individuals at increased risks for dyslipidemia and cardiovascular diseases remains unclear. METHODS: We used data from Biobank Japan (n = 70,657-128,305) and developed novel East Asian-specific genome-wide polygenic risk scores (PRSs) for four lipid traits. We validated (n = 4271) and subsequently tested associations of these scores with 3-year lipid changes in adolescents (n = 620), carotid intima-media thickness (cIMT) in adult women (n = 781), dyslipidemia (n = 7723), and coronary heart disease (CHD) (n = 2374 cases and 6246 controls) in type 2 diabetes (T2D) patients. RESULTS: Our PRSs aggregating 84-549 genetic variants (0.251 < correlation coefficients (r) < 0.272) had comparably stronger association with lipid variations than the typical PRSs derived based on the genome-wide significant variants (0.089 < r < 0.240). Our PRSs were robustly associated with their corresponding lipid levels (7.5 × 10- 103 < P < 1.3 × 10- 75) and 3-year lipid changes (1.4 × 10- 6 < P < 0.0130) which started to emerge in childhood and adolescence. With the adjustments for principal components (PCs), sex, age, and body mass index, there was an elevation of 5.3% in TC (ß ± SE = 0.052 ± 0.002), 11.7% in TG (ß ± SE = 0.111 ± 0.006), 5.8% in HDL-C (ß ± SE = 0.057 ± 0.003), and 8.4% in LDL-C (ß ± SE = 0.081 ± 0.004) per one standard deviation increase in the corresponding PRS. However, their predictive power was attenuated in T2D patients (0.183 < r < 0.231). When we included each PRS (for TC, TG, and LDL-C) in addition to the clinical factors and PCs, the AUC for dyslipidemia was significantly increased by 0.032-0.057 in the general population (7.5 × 10- 3 < P < 0.0400) and 0.029-0.069 in T2D patients (2.1 × 10- 10 < P < 0.0428). Moreover, the quintile of TC-related PRS was moderately associated with cIMT in adult women (ß ± SE = 0.011 ± 0.005, Ptrend = 0.0182). Independent of conventional risk factors, the quintile of PRSs for TC [OR (95% CI) = 1.07 (1.03-1.11)], TG [OR (95% CI) = 1.05 (1.01-1.09)], and LDL-C [OR (95% CI) = 1.05 (1.01-1.09)] were significantly associated with increased risk of CHD in T2D patients (4.8 × 10- 4 < P < 0.0197). Further adjustment for baseline lipid drug use notably attenuated the CHD association. CONCLUSIONS: The PRSs derived and validated here highlight the potential for early genomic screening and personalized risk assessment for cardiovascular disease.

10.
J Emerg Med ; 60(1): 98-102, 2021 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-33303278

RESUMO

BACKGROUND: Life-threatening hemorrhage from extremity injuries can be effectively controlled in the prehospital environment through direct pressure, wound packing, and the use of tourniquets. Early tourniquet application has been prioritized for rapid control of severe extremity hemorrhage and is a cornerstone of prehospital trauma resuscitation guidelines. Emergency physicians must be knowledgeable regarding the initial assessment and appropriate management of patients who present with a prehospital tourniquet in place. DISCUSSION: An interdisciplinary group of experts including emergency physicians, trauma surgeons, and tactical and Emergency Medical Services physicians collaborated to develop a stepwise approach to the assessment and removal (discontinuation) of an extremity tourniquet in the emergency department after being placed in the prehospital setting. We have developed a best-practices guideline to serve as a resource to aid the emergency physician in how to safely remove a tourniquet. The guideline contains five steps that include: 1) Determine how long the tourniquet has been in place; 2) Evaluate for contraindications to tourniquet removal; 3) Prepare for tourniquet removal; 4) Release the tourniquet; and 5) Monitor and reassess the patient. CONCLUSION: These steps outlined will help emergency medicine clinicians appropriately evaluate and manage patients presenting with tourniquets in place. Tourniquet removal should be performed in a systematic manner with plans in place to immediately address complications.


Assuntos
Serviços Médicos de Emergência , Torniquetes , Serviço Hospitalar de Emergência , Extremidades , Hemorragia/etiologia , Hemorragia/terapia , Humanos
11.
Cureus ; 12(11): e11312, 2020 Nov 03.
Artigo em Inglês | MEDLINE | ID: mdl-33282588

RESUMO

INTRODUCTION: The opioid crisis continues to claim lives at historically unprecedented levels and shows few signs of abating. One means of mitigating the harm from opioid abuse and unintentional overdose is training and equipping police officers to administer intranasal (IN) naloxone as part of a broader public health response. While an increasing number of state and local agencies have implemented law enforcement officer (LEO) naloxone training programs, due to the novelty of these programs, the evidence of program efficacy is limited. This study describes the implementation and evaluation of a LEO training program in opioid overdose recognition, management, and administration of IN naloxone. METHODS: This evaluation consisted of a secondary analysis of de-identified administrative quality assurance data. Police officers in Howard County, Maryland (n=281) underwent an IN naloxone training program between June and July 2015. The training program entailed a 30-minute online component, a 45-minute in-service session, and a 15-question post-test (n=228). The success of the training program was evaluated via an opioid overdose knowledge survey administered at 30 days (n=207) and 6 months (n=182) after training. RESULTS: The 30-day and 6-month scores for all knowledge outcomes indicated that officers retained the contents of the training program well over time. After six months, 100% of respondents correctly identified the physiological effects of naloxone administration, and 95.6% correctly identified the opioid-containing drugs that may result in overdose. At the six-month mark, 74.59% correctly identified the initial signs of opioid overdose, and 60.99% correctly identified the time required for IN to begin working. CONCLUSION: LEOs exhibit the ability to retain the contents of IN training over 30-day and 6-month periods and express confidence in their ability to assist suspected opioid overdose victims. Further research is necessary to determine the degree to which further knowledge decay might occur, the sustained ability to implement this knowledge under real-world conditions, and the subsequent effects on overdose victim survival.

12.
Front Genet ; 11: 1003, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33133133

RESUMO

In this study, we looked for potential gene-gene interaction in susceptibility to schizophrenia by an exhaustive searching for SNP-SNP interactions in 3 GWAS datasets (phs000021:phg000013, phs000021:phg000014, phs000167) using our recently published algorithm. The search space for SNP-SNP interaction was confined to 8 biologically plausible ways of interaction under dominant-dominant or recessive-recessive modes. First, we performed our search of all pair-wise combination of 729,454 SNPs after filtering by SNP genotype quality. All possible pairwise interactions of any 2 SNPs (5 × 1011) were exhausted to search for significant interaction which was defined by p-value of chi-square tests. Nine out the top 10 interactions, protein coding genes were partnered with non-coding RNA (ncRNA) which suggested a new alternative insight into interaction biology other than the frequently sought-after protein-protein interaction. Therefore, we extended to look for replication among the top 10,000 interaction SNP pairs and high proportion of concurrent genes forming the interaction pairs were found. The results indicated that an enrichment of signals over noise was present in the top 10,000 interactions. Then, replications of SNP-SNP interaction were confirmed for 14 SNPs-pairs in both replication datasets. Biological insight was highlighted by a potential binding between FHIT (protein coding gene) and LINC00969 (lncRNA) which showed a replicable interaction between their SNPs. Both of them were reported to have expression in brain. Our study represented an early attempt of exhaustive interaction analysis of GWAS data which also yield replicated interaction and new insight into understanding of genetic interaction in schizophrenia.

14.
Genomics Proteomics Bioinformatics ; 18(5): 489-500, 2020 10.
Artigo em Inglês | MEDLINE | ID: mdl-32822870

RESUMO

Solar energy, which is essential for the origin and evolution of all life forms on Earth, can be objectively recorded through attributes such as climatic ambient temperature (CAT), ultraviolet radiation (UVR), and sunlight duration (SD). These attributes have specific geographical variations and may cause different adaptation traits. However, the adaptation profile of each attribute and the selective role of solar energy as a whole during human evolution remain elusive. Here, we performed a genome-wide adaptation study with respect to CAT, UVR, and SD using the Human Genome Diversity Project-Centre Etude Polymorphism Humain (HGDP-CEPH) panel data. We singled out CAT as the most important driving force with the highest number of adaptive loci (6 SNPs at the genome-wide 1 × 10-7 level; 401 at the suggestive 1 × 10-5 level). Five of the six genome-wide significant adaptation SNPs were successfully replicated in an independent Chinese population (N = 1395). The corresponding 316 CAT adaptation genes were mostly involved in development and immunity. In addition, 265 (84%) genes were related to at least one genome-wide association study (GWAS)-mapped human trait, being significantly enriched in anthropometric loci such as those associated with body mass index (χ2; P < 0.005), immunity, metabolic syndrome, and cancer (χ2; P < 0.05). For these adaptive SNPs, balancing selection was evident in Euro-Asians, whereas obvious positive and/or purifying selection was observed in Africans. Taken together, our study indicates that CAT is the most important attribute of solar energy that has driven genetic adaptation in development and immunity among global human populations. It also supports the non-neutral hypothesis for the origin of disease-predisposition alleles in common diseases.


Assuntos
Estudo de Associação Genômica Ampla , Desenvolvimento Humano , Imunidade , Temperatura , Alelos , Humanos , Polimorfismo de Nucleotídeo Único , Luz Solar , Raios Ultravioleta
15.
Pathology ; 52(4): 439-446, 2020 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-32276787

RESUMO

The objectives were to determine the reference intervals of spot urine copper excretion indexes in pre-school children and to evaluate their utility in screening for Wilson disease (WD). With spot urine collected from a control sample of preschool children (aged 3-7 years, n=153), the reference intervals of spot urine copper excretion indexes and their biological variation were defined. In order to investigate their utility performance in screening for WD in this age group, multiple spot urine samples from six WD patients who were diagnosed at presymptomatic stage were also analysed and compared. Cut-off values useful for detection of WD were defined by receiver operator curve (ROC) analysis. Biological (inter-individual) variation of spot urine copper indexes expressed as coefficient of variation (CVg) were around 60% at this age group, which was moderate and similar to other clinically useful urine tests, such as urine albumin excretion ratio. Spot urine copper excretion strongly correlated with both urine creatinine and osmolality. Linear regression against both creatinine and osmolality showed that ∼94% of data points in healthy preschool children fell within the prediction interval, suggesting that both were useful normalisation factors. ROC showed that copper to osmolality ratio was the best index with an area under curve (AUC) greater than 0.98. Cut-off values of 0.5 µmol/L, 0.1 µmol/mmol and 0.00085 µmol/mOsmol (32 µg/L, 56 µg/g creatinine and 0.054 µg/mOsmol, respectively, in conventional units) for spot urine copper concentration, copper to creatinine ratio and copper to osmolality ratio, respectively, have potential application in the differentiation of WD patients. Based on the data, a new WD screening strategy targeting preschool children is proposed. Application of a bivariate screening strategy using spot urine copper concentration and urine osmolality may be useful in a population-wide screening program for WD among preschool children.


Assuntos
Cobre/urina , Degeneração Hepatolenticular/diagnóstico , Degeneração Hepatolenticular/urina , Urinálise/normas , Variação Biológica Individual , Criança , Pré-Escolar , Creatinina/urina , Feminino , Humanos , Masculino , Programas de Rastreamento/normas , Valores de Referência
16.
Breast ; 50: 30-38, 2020 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-31978815

RESUMO

OBJECTIVES: Chemotherapy-induced nausea and vomiting (CINV) are distressing symptoms. This randomized study evaluated the antiemetic efficacies of standard antiemetic regimen with/without olanzapine. PATIENTS AND METHODS: Eligible patients were chemotherapy-naive Chinese breast cancer patients who were planned for (neo)adjuvant doxorubicin/cyclophosphamide. Antiemetic regimen for all studied population included aprepitant, ondansetron and dexamethasone; patients were randomized to Olanzapine (with olanzapine) or Standard arms (without olanzapine). Patients filled in self-reported diaries and completed visual analogue scales for nausea, as well as Functional Living Index-Emesis questionnaires. Blood profiles including fasting glucose and lipids were monitored. RESULTS: 120 patients were randomized. In Cycle 1 doxorubicin/cyclophosphamide, the Olanzapine arm had significantly higher rates of "Complete Response" than the Standard arm: 65.0% vs 38.3% in the overall period (p = 0.0035), 70.0% vs 51.7% in the acute period (p = 0.0397) and 92.9% vs 74.2% in the delayed period (p = 0.0254). Olanzapine arm also had significantly higher rates of "No significant nausea" and "No nausea" during all 3 time-frames and better QOL. Similar findings were also revealed throughout multiple cycles. Pre-study abnormalities in glucose and lipids occurred in 39.7% and 34.2% of the studied population respectively; there were no differences in these parameters between the two arms at end-of-study assessment. CONCLUSION: The addition of olanzapine to standard aprepitant-based antiemetic regimen provides clinically meaningful improvement in controlling CINV. This was associated with a positive impact on QOL and tolerable toxicity profiles among Chinese breast cancer patients receiving doxorubicin/cyclophosphamide chemotherapy. Further studies on metabolic profiles of breast cancer patients are warranted.


Assuntos
Antieméticos/uso terapêutico , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Neoplasias da Mama/tratamento farmacológico , Náusea/prevenção & controle , Olanzapina/uso terapêutico , Vômito/prevenção & controle , Adulto , Idoso , Aprepitanto/uso terapêutico , China/epidemiologia , Ciclofosfamida/efeitos adversos , Dexametasona/uso terapêutico , Doxorrubicina/efeitos adversos , Feminino , Humanos , Pessoa de Meia-Idade , Náusea/induzido quimicamente , Ondansetron/uso terapêutico , Vômito/induzido quimicamente
17.
Eur J Nutr ; 59(7): 3303-3311, 2020 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31897598

RESUMO

PURPOSE: Environmental and lifestyle factors that affect oxidative stress and inflammation may influence telomere length (TL). There are limited data to relate dietary patterns with TL. This study examined the association of various dietary patterns with TL in Chinese older adults. METHODS: We conducted a cross-sectional analysis and performed multivariate linear regression analyses using available data from 1981 (965 men, 1016 women) community-dwelling Chinese adults aged 65 years and over in Hong Kong. The interviewer administered questionnaires that covered dietary intake estimation and dietary pattern generation from the food frequency questionnaire, demographic and lifestyle factors, and self-reported medical history. TL was measured by quantitative real-time polymerase chain reaction. RESULTS: None of the dietary pattern scores including the Diet Quality Index-International (DQI-I) score, the Dietary Approaches to Stop Hypertension (DASH) score, the Mediterranean-DASH Intervention for Neurodegenerative Delay Diet (MIND) score, the Mediterranean Diet Score (MDS), the Okinawan diet score, as well as the "vegetables-fruits" pattern score, the "snacks-drinks-milk" pattern score, and the "meat-fish" pattern score were associated with TL in the age- and sex-adjusted model and the multivariate adjusted model. CONCLUSION: Our findings suggest a minimal role of dietary patterns in telomere length in community-dwelling Chinese older adults.


Assuntos
/estatística & dados numéricos , Dieta/estatística & dados numéricos , Comportamento Alimentar , Vida Independente/estatística & dados numéricos , Telômero , Idoso , Estudos Transversais , Feminino , Hong Kong/epidemiologia , Humanos , Masculino
18.
Artigo em Inglês | MEDLINE | ID: mdl-31996363

RESUMO

OBJECTIVES: This is a prospective study evaluating NEPA in patients with breast cancer (the NEPA group), who received (neo)adjuvant AC chemotherapy (consisting of doxorubicin 60 mg/m2 and cyclophosphamide 600 mg/m2). The primary objectives were to assess the efficacy and safety of NEPA in controlling chemotherapy-induced nausea and vomiting (CINV). The secondary objectives were to compare CINV between the NEPA group and historical controls (the APR group) who received aprepitant in an earlier prospective randomised study. PATIENTS AND METHODS: 60 patients participated in the NEPA group; 62 were in the APR group. Eligibility criteria of both groups were similar, that is, Chinese patients with breast cancer who were treated with (neo)adjuvant AC. NEPA group received NEPA and dexamethasone; APR group received aprepitant, ondansetron and dexamethasone. Individuals filled in self-reported diary, visual analogue scale for nausea and Functional Living Index-Emesis questionnaire. RESULTS: Within the NEPA group, 70.0%, 85.7% and 60.0%, respectively reported complete response in the acute, delayed and overall phases in cycle 1 AC. When compared with the historical APR group during cycle 1 AC, NEPA group achieved significantly higher rates of complete response, complete protection, total control, 'no significant nausea' and 'no nausea' in the delayed phase; similar findings were noted in the overall phase with significantly better quality of life. Superior efficacy of NEPA was maintained over multiple cycles. Both antiemetic regimens were well tolerated. CONCLUSION: In this study on Chinese patients with breast cancer who were uniformly receiving AC, NEPA was effective in controlling CINV. TRIAL REGISTRATION NUMBER: NCT03386617.

19.
Curr Alzheimer Res ; 17(13): 1232-1237, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33557736

RESUMO

BACKGROUND: Pin1 is a propyl cis-trans isomerase and it has been associated with age-atonset of Alzheimer's disease (AD) and other pathological characteristics of AD. DNA methylation is one of the gene regulation mechanisms and it might affect the gene expression. OBJECTIVE: This study was aimed to examine the correlation between DNA methylation and gene expression of Pin1 and its effect on the risk of AD in a Chinese population. METHODS: 80 AD patients and 180 normal controls were recruited in this study and their cognitive functions were assessed. Pin1 gene expression and methylation were quantified by real-time RT-PCR and Melting Curve Analysis-Methylation assay (MCA-Meth), respectively. RESULTS: Our finding revealed a positive correlation between methylation and gene expression of Pin1 (p=0.001) and increased Pin1 methylation was predisposed to the risk of AD (p<0.001). CG genotype of Pin1 SNP rs2287839 was associated with higher gene expression of Pin1 (p=0.036) and the effect was only prominent in normal controls as AD patients were already methylated at Pin1 promoter. Furthermore, methylation of Pin1 was associated with better performance in cognition (p=0.018). CONCLUSION: Our result further supported the involvement of Pin1 in AD and the increased level of Pin1 might be a protective factor for AD.


Assuntos
Doença de Alzheimer/genética , Metilação de DNA , Expressão Gênica , Peptidilprolil Isomerase de Interação com NIMA/genética , Idoso de 80 Anos ou mais , /estatística & dados numéricos , China , Cognição , Feminino , Humanos , Masculino , Regiões Promotoras Genéticas
20.
Nat Commun ; 10(1): 2358, 2019 May 24.
Artigo em Inglês | MEDLINE | ID: mdl-31127096

RESUMO

The original HTML version of this Article was updated shortly after publication to add links to the Peer Review file.In addition, affiliations 16 and 17 incorrectly read 'School of Medicine Sydney, University of Notre Dame Australia, Sydney, WA, 6160, Australia' and 'St Vincent's Clinical School, University of New South Wales Medicine, University of New South Wales, Sydney, NSW, 2052, Australia.' This has now been corrected in both the PDF and HTML versions of the Article.

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