Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 223
Filtrar
1.
Front Endocrinol (Lausanne) ; 12: 778737, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34858347

RESUMO

The exponential global increase in the incidence of obesity may be partly attributable to environmental chemical (EC) exposure. Humans are constantly exposed to ECs, primarily through environmental components. This review compiled human epidemiological study findings of associations between blood and/or urinary exposure levels of ECs and anthropometric overweight and obesity indices. The findings reveal research gaps that should be addressed. We searched MEDLINE (PubMed) for full text English articles published in 2006-2020 using the keywords "environmental exposure" and "obesity". A total of 821 articles were retrieved; 102 reported relationships between environmental exposure and obesity indices. ECs were the predominantly studied environmental exposure compounds. The ECs were grouped into phenols, phthalates, and persistent organic pollutants (POPs) to evaluate obesogenic roles. In total, 106 articles meeting the inclusion criteria were summarized after an additional search by each group of EC combined with obesity in the PubMed and Scopus databases. Dose-dependent positive associations between bisphenol A (BPA) and various obesity indices were revealed. Both individual and summed di(2-ethylhexyl) phthalate (DEHP) and non-DEHP metabolites showed inconsistent associations with overweight and obesity indices, although mono-butyl phthalate (MBP), mono-ethyl phthalate (MEP), and mono-benzyl phthalate (MBzP) seem to have obesogenic roles in adolescents, adults, and the elderly. Maternal exposure levels of individual POP metabolites or congeners showed inconsistent associations, whereas dichlorodiphenyldichloroethylene (DDE) and perfluorooctanoic acid (PFOA) were positively associated with obesity indices. There was insufficient evidence of associations between early childhood EC exposure and the subsequent development of overweight and obesity in late childhood. Overall, human evidence explicitly reveals the consistent obesogenic roles of BPA, DDE, and PFOA, but inconsistent roles of phthalate metabolites and other POPs. Further prospective studies may yield deeper insights into the overall scenario.

2.
Nephron ; : 1-6, 2021 Nov 22.
Artigo em Inglês | MEDLINE | ID: mdl-34808632

RESUMO

Fabry disease (FD) is an inherited X-linked lysosomal storage disorder, with hemizygous males being more severely affected than heterozygous females. Herein, we report a rare case of FD in a heterozygous female with a severe phenotype. The patient had obesity and hyperlipidemia and had her first cerebral infarction at the age of 33 years. She underwent renal biopsy and was diagnosed with FD with morphological features of focal segmental glomerulosclerosis nephropathy at the age of 34 years. Her leukocyte alpha-galactosidase A activity was 2.3 Agal/U (normal: >20 Agal/U), and genetic analysis revealed the presence of the classical phenotype. Enzyme replacement therapy (ERT) was initiated at the age of 35 years; however, peritoneal dialysis owing to end-stage renal failure occurred at the age of 37 years. The patient died of a cerebral hemorrhage at the age of 44 years. Her Mainz Severity Score Index at the time of death was 48/76, suggestive of the severe phenotype. Autopsy findings revealed remarkable globotriaosylceramide accumulation on electron microscopy, particularly in the major organs and their vascular smooth muscle cells. Regarding the vertebral arteries which sourced the cerebral hemorrhage, the effects of FD-induced vascular thickening and long-term renal failure-induced atherosclerosis were confirmed. Furthermore, the patient's vascular sclerosis was modified with acquired factors such as lifestyle-related disease associated with obesity. We recommend intensified treatment for metabolic factors simultaneous with ERT to help in delaying the progression of FD.

3.
Cells ; 10(11)2021 Nov 01.
Artigo em Inglês | MEDLINE | ID: mdl-34831193

RESUMO

Although glioblastoma (GBM) stem-like cells (GSCs), which retain chemo-radio resistance and recurrence, are key prognostic factors in GBM patients, the molecular mechanisms of GSC development are largely unknown. Recently, several studies revealed that extrinsic ribosome incorporation into somatic cells resulted in stem cell properties and served as a key trigger and factor for the cell reprogramming process. In this study, we aimed to investigate the mechanisms underlying GSCs development by focusing on extrinsic ribosome incorporation into GBM cells. Ribosome-induced cancer cell spheroid (RICCS) formation was significantly upregulated by ribosome incorporation. RICCS showed the stem-like cell characters (number of cell spheroid, stem cell markers, and ability for trans differentiation towards adipocytes and osteocytes). In RICCS, the phosphorylation and protein expression of ribosomal protein S6 (RPS6), an intrinsic ribosomal protein, and STAT3 phosphorylation were upregulated, and involved in the regulation of cell spheroid formation. Consistent with those results, glioma-derived extrinsic ribosome also promoted GBM-RICCS formation through intrinsic RPS6 phosphorylation. Moreover, in glioma patients, RPS6 phosphorylation was dominantly observed in high-grade glioma tissues, and predominantly upregulated in GSCs niches, such as the perinecrosis niche and perivascular niche. Those results indicate the potential biological and clinical significance of extrinsic ribosomal proteins in GSC development.

4.
Cancers (Basel) ; 13(22)2021 Nov 12.
Artigo em Inglês | MEDLINE | ID: mdl-34830830

RESUMO

(1) Background: multiple myeloma patients have benefited from bortezomib therapy, though it has often been discontinued owing to diarrhea. The objective of this study was to verify serum bortezomib concentration in the emergence of diarrhea. (2) Methods: this prospective, observational case-control, and monocentric study was performed with an approval by the Ethics Committee of Kumamoto University Hospital in 2015 (No. 1121) from February 2015 to April 2017. (3) Results: twenty-four patients with bortezomib therapy were recruited; eight patients (33.3%) developed diarrhea at day 3 as median. Median measured trough bortezomib concentration at 24 h after first or second dose for patients with or without diarrhea was 0.87 or 0.48 ng/mL, respectively (p = 0.04, Wilcoxon signed rank test). Receiver operation characteristic (ROC) analysis produced the cut-off concentration of 0.857 ng/mL (area under the ROC curve of 0.797, sensitivity of 0.625, specificity of 0.875). The survival curves between patients with and without diarrhea were similar (p = 0.667); those between patients with higher and lower concentration than median value (0.61 ng/mL) were also similar (p = 0.940). (4) Conclusions: this study indicated the possible involvement of serum bortezomib concentration in the emergence of diarrhea in bortezomib therapy in patients with multiple myeloma.

5.
Acta Med Okayama ; 75(5): 641-645, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34703048

RESUMO

This case report highlights the importance of using a dental operating microscope (DOM) and ultrasonic endodontic tips (UETs) to locate all root canals in the lower first premolar. A 53-year-old woman presented to our clinic with pain in the lower right first premolar. After a detailed search using a DOM and UETs, three root canals were found, prepared with rotary HyFlex endodontic files, and obturated using the lateral condensation technique. At the five-year follow-up after treatment, the tooth was completely restored and fulfilling its function, with no signs or symptoms of any post-treatment flare-up.

6.
Tohoku J Exp Med ; 255(1): 9-17, 2021 09.
Artigo em Inglês | MEDLINE | ID: mdl-34497247

RESUMO

Promoting generic drugs can reduce the financial burden on patients and improve healthcare finances. The insurers have been conducting promotional efforts, such as direct-mail campaigns, but little is known about the public's perception of generic drugs and effective message strategies for promotion. In 2018, we conducted a web-based survey of middle-aged Japanese men and women that investigated: (i) their perceptions of generic drugs, (ii) the association between perceptions and willingness-to-pay for brand-name drugs relative to generic drugs, and (iii) potentially effective forms of information provision to alter individuals' perceptions. Of the 1,005 respondents, over half perceived generic drugs as having the same level of efficacy and safety as brand-name drugs. While willingness-to-pay was dispersed among respondents, two factors were associated with small willingness-to-pay: (a) perceiving generic drugs as having the same level of efficacy and safety as brand-name drugs and (b) perceiving that promoting the use of generic drugs is important for controlling medical expenditures. Moreover, presenting potential savings over five years by choosing generic drugs was a potentially effective tool for altering perceptions, relative to showing monthly savings. Our findings suggest that certain parts of the population still have high willingness-to-pay for brand-name drugs, and strategic communication to alter perception could be effective in promoting the use of generic drugs among those who are price-inelastic.


Assuntos
Medicamentos Genéricos/economia , Adulto , Estudos Transversais , Feminino , Gastos em Saúde , Humanos , Renda , Japão , Masculino , Pessoa de Meia-Idade , Conhecimento do Paciente sobre a Medicação/economia , Percepção , Honorários por Prescrição de Medicamentos , Inquéritos e Questionários
7.
Ann Rehabil Med ; 45(4): 304-313, 2021 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-34496473

RESUMO

OBJECTIVE: To examine the relationship between the time constant of oxygen uptake kinetics during the onset of exercise (τVO2) estimated from a single exercise bout and that obtained from three averaged exercise bouts in individuals with stroke. METHODS: Twenty participants with stroke performed three bouts of a constant-load pedaling exercise at approximately 80% of the workload corresponding to the ventilatory threshold to estimate τVO2. The VO2 data from the first trial of three bouts were used to estimate τVO2 for a single bout. Additionally, data collected from three bouts were ensemble-averaged to obtain τVO2 for three averaged bouts as the criterion. RESULTS: There was a very high correlation between τVO2 for a single bout (34.8±14.0 seconds) and τVO2 for three averaged bouts (38.5±13.4 seconds) (r=0.926, p<0.001). However, τVO2 for a single bout was smaller than that for three averaged bouts (p=0.006). CONCLUSION: τVO2 for a single bout could reflect the relative difference in τVO2 for three averaged bouts among individuals with stroke. However, it should be noted that τVO2 for a single bout may be underestimated compared to τVO2 for three averaged bouts.

8.
Ind Health ; 59(6): 383-392, 2021 Nov 29.
Artigo em Inglês | MEDLINE | ID: mdl-34588381

RESUMO

2-Ethyl-1-hexanol (2EH) is a volatile organic compound known to cause sick building syndrome. However, 2EH-induced hepatotoxicity has been mainly evaluated in experiments orally administering 2EH as a metabolite of di(2-ethylhexyl) phthalate. To evaluate the hepatotoxicity risk of 2EH as an indoor air pollutant, we exposed 10-wk-old male ICR mice to 2EH by inhalation for 8 h/d, 5 d/wk for 3 months (0, 20, 60, or 150 ppm) or 6 months (0, 0.5, 10, or 100 ppm). In both experiments, relative liver weights significantly increased in the highest exposure groups. The 3-month exposure increased histopathological lipid droplets in the liver in a dose-dependent manner, hepatic triglyceride at all exposure levels, hepatic phospholipid at 150 ppm, and microsomal triglyceride transfer protein at 60 and 150 ppm; however, these changes were not observed following the 6-month of exposure. Following the 3-month exposure, alanine transaminase and peroxisomal bifunctional proteins, known markers of liver injury and peroxisome proliferation, respectively, remained unaltered. Therefore, in the present study, the inhalation concentration range of 2EH induced a toxic hypertrophic change, revealing a limited role of peroxisome proliferator-activated receptor alpha (PPARα). The liver weights may have presumably increased via a mechanism independent of PPARα activation.


Assuntos
Exposição por Inalação , PPAR alfa , Animais , Hepatomegalia/induzido quimicamente , Hexanóis , Exposição por Inalação/efeitos adversos , Masculino , Camundongos , Camundongos Endogâmicos ICR
9.
PLoS One ; 16(9): e0254394, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34570785

RESUMO

Identification of medical conditions using claims data is generally conducted with algorithms based on subject-matter knowledge. However, these claims-based algorithms (CBAs) are highly dependent on the knowledge level and not necessarily optimized for target conditions. We investigated whether machine learning methods can supplement researchers' knowledge of target conditions in building CBAs. Retrospective cohort study using a claims database combined with annual health check-up results of employees' health insurance programs for fiscal year 2016-17 in Japan (study population for hypertension, N = 631,289; diabetes, N = 152,368; dyslipidemia, N = 614,434). We constructed CBAs with logistic regression, k-nearest neighbor, support vector machine, penalized logistic regression, tree-based model, and neural network for identifying patients with three common chronic conditions: hypertension, diabetes, and dyslipidemia. We then compared their association measures using a completely hold-out test set (25% of the study population). Among the test cohorts of 157,822, 38,092, and 153,608 enrollees for hypertension, diabetes, and dyslipidemia, 25.4%, 8.4%, and 38.7% of them had a diagnosis of the corresponding condition. The areas under the receiver operating characteristic curve (AUCs) of the logistic regression with/without subject-matter knowledge about the target condition were .923/.921 for hypertension, .957/.938 for diabetes, and .739/.747 for dyslipidemia. The logistic lasso, logistic elastic-net, and tree-based methods yielded AUCs comparable to those of the logistic regression with subject-matter knowledge: .923-.931 for hypertension; .958-.966 for diabetes; .747-.773 for dyslipidemia. We found that machine learning methods can attain AUCs comparable to the conventional knowledge-based method in building CBAs.


Assuntos
Algoritmos , Bases de Dados Factuais , Diabetes Mellitus/diagnóstico , Dislipidemias/diagnóstico , Hipertensão/diagnóstico , Revisão da Utilização de Seguros/estatística & dados numéricos , Aprendizado de Máquina , Doença Crônica , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Redes Neurais de Computação , Estudos Retrospectivos , Máquina de Vetores de Suporte
10.
Artigo em Inglês | MEDLINE | ID: mdl-34416000

RESUMO

CONTEXT: Maternal cholesterol is important for fetal development. Whether maternal serum total cholesterol (maternal TC) levels in mid-pregnancy are associated with small- (SGA) or large- (LGA) for-gestational-age independent of pre-pregnancy body mass index (BMI) and weight gain during pregnancy is inconclusive. OBJECTIVE: To prospectively investigate the association between maternal TC in mid-pregnancy and SGA or LGA. DESIGN AND SETTING: The Japan Environment and Children's Study is a nationwide prospective birth cohort study in Japan. PARTICIPANTS: A total of 37,449 non-diabetic, non-hypertensive mothers with singleton birth at term without congenital abnormalities. OUTCOME MEASURES: Birth weight for the gestational age <10 percentile and ≥90 percentile were respectively defined as SGA and LGA by the Japanese neonatal anthropometric charts. RESULTS: The mean gestational age at blood sampling was 22.7±4.0 weeks. After adjustment for maternal age, sex of child, parity, weight gain during pregnancy, pre-pregnancy BMI, smoking, alcohol drinking, blood glucose levels, household income, and Study Areas, one standard deviation decrement of maternal TC was linearly associated with SGA [odds ratio (OR): 95% confidence intervals (CI) = 1.20: 1.15-1.25]. In contrast, one standard deviation increment of maternal TC was linearly associated with LGA [OR: 95% CI = 1.13: 1.09-1.16]. Associations did not differ according to pre-pregnancy BMI and gestational weight gain (p for interaction>0.20). CONCLUSION: Maternal TC levels in mid-pregnancy were associated with SGA or LGA in Japanese. Maternal TC in mid-pregnancy may help to predict SGA and LGA. Favorable maternal lipid profiles for fetal development must be explored.

11.
Artigo em Inglês | MEDLINE | ID: mdl-34423359

RESUMO

OBJECTIVES: This study investigates whether the surgical correction of chest deformity is associated with the growth of the lung parenchyma after surgery for pectus excavatum. METHODS: Ten patients with pectus excavatum who were treated by the Nuss procedure were examined. The preoperative and postoperative computed tomography (2.5 ± 1.2 years after surgery) scans were performed, and the Haller index, lung volume and lung density were analyzed using a three-dimensional image analysis system (SYNAPSE VINCENT, Fujifilm, Japan). The radiological lung weight was calculated as follows: lung volume (ml) × lung density (g/ml). RESULTS: The average age of the 10 patients (men 8; women 2) was 13.8 years (range: 6-26 years). The Haller index was significantly improved from the preoperative value of 5.18 ± 2.20 to the postoperative value of 3.68 ± 1.38 (P = 0.0025). Both the lung volume and weight had significantly increased by 107.1 ± 19.6% and 121.6 ± 11.3%, respectively, after surgery. CONCLUSIONS: A significant increase in the weight of the lung after surgical correction suggests that the growth of the lung parenchyma is associated with the correction of chest deformity in younger patients with pectus excavatum.

12.
Graefes Arch Clin Exp Ophthalmol ; 259(12): 3537-3548, 2021 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-34244824

RESUMO

PURPOSE: Choroidal vascular structures are likely to be affected in diabetic patients. The aim of this study was to conduct a meta-analysis of choroidal vascular structures in diabetic eyes with no diabetic retinopathy (NDR) and healthy control eyes, which was systematically evaluated by various factors involving the measurements. METHODS: This study identified clinical data from publications in PubMed and web of science until May 2020. Independent retrospective or prospective clinical studies comparing NDR and healthy control eyes regarding choroidal vascular structures were extracted. Five related studies were enrolled, cumulating in a total of 282 diabetic eyes and 511 control eyes examined in this study. Heterogeneity was statistically quantified by I2 statistics, and meta-analysis was performed using a random effects model. This study included 2 different algorisms of binarization determining the ratio of luminal areas in total choroidal areas, both of which were consolidated and called "choroidal vascular ratio." RESULTS: Meta-analysis clearly showed that the choroidal vascular ratio was significantly lower in NDR eyes than in healthy control eyes (weighted mean difference = - 2.16; 95%CI: - 3.19 to - 1.13; P < 0.005). Similar results were obtained in sub-analysis based on adjustment of serum HbA1c levels and duration of diabetes. CONCLUSIONS: The choroidal vascular ratio of NDR eyes was significantly lower than that of healthy control eyes. The ratio might contribute to a better understanding of the pathophysiology involved in the development of diabetic retinopathy, although there was some heterogeneity in primary analysis studies.


Assuntos
Diabetes Mellitus , Retinopatia Diabética , Corioide , Retinopatia Diabética/diagnóstico , Humanos , Estudos Prospectivos , Estudos Retrospectivos , Tomografia de Coerência Óptica
13.
Vet Immunol Immunopathol ; 238: 110292, 2021 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-34246811

RESUMO

Activated lymphocyte therapy is one of the immunotherapies for cancer patients that is expected to prolong life without any adverse effects and maintain satisfactory quality of life (QOL). However, the objective assessment and maintenance of a standardized evaluation of QOL are not easy. We aimed to evaluate activated autologous lymphocyte therapy for cancer dogs using the characteristics of the cultured cells and QOL as perceived by owners. In in vitro experiments, peripheral blood mononuclear cells (PBMCs) collected from healthy dogs were stimulated using anti-CD3 antibody and recombinant interleukin-2 under a closed system. The number of CD4+ and CD8+ T lymphocytes in the cultured cells was higher than that of PBMCs (P < 0.05). Natural killer activity, proenkephalin (known as the precursor of endogenous opioids) and interferon-γ mRNA in activated lymphocytes were significantly higher than in PBMCs (P < 0.05). Met-enkephalin was detected in activated lymphocytes. QOL of 58 dogs afflicted with common types of cancers in humans increased after every administration of activated lymphocyte therapy (P < 0.05). Overall, these results indicated that activated lymphocyte therapy could have beneficial effects on QOL in dogs with cancers. This was objectively evaluated and this improvement was related to presence of opioid-producing lymphocytes.


Assuntos
Analgésicos Opioides/metabolismo , Doenças do Cão/terapia , Imunoterapia Adotiva/veterinária , Neoplasias/veterinária , Linfócitos T/classificação , Linfócitos T/metabolismo , Animais , Técnicas de Cultura de Células/métodos , Citotoxicidade Imunológica , Cães , Imunoterapia Adotiva/métodos , Neoplasias/patologia , Neoplasias/terapia
14.
Eur J Ophthalmol ; : 11206721211027103, 2021 Jun 23.
Artigo em Inglês | MEDLINE | ID: mdl-34159829

RESUMO

PURPOSE: To examine changes of the choroidal morphology in patients with diabetic macular edema (DME) before and after local treatments. METHODS: This study was on 20 eyes with DME, observed for more than 24 months. All patients underwent laser photocoagulation (Laser), sub-tenon triamcinolone acetonide injection (TA), or intravitreal aflibercept injection (IVA). Central macular and choroidal thicknesses (CMT/CCT), and choroidal vascular structures consisting of the total choroidal area (TCA), luminal area (LA), and stromal area (SA) were measured by a binarization method. The ratios of LA in TCA were eventually determined as the L/C ratio in each case. RESULTS: The L/C ratio significantly decreased for 24 months in patients with DME (p = 0.01), whereas no significant differences were noted in other parameters including TCA, LA, SA, or CCT. Among patients treated with Laser ± TA ± IVA, a significant correlation was found between a high L/C ratio at pretreatment and a lower cumulative number of injections (1-2 times/24 months) (p = 0.04). The L/C ratio in pretreatment showed a significantly inverse correlation with CMT (-0.60, p = 0.02) and subsequent BCVA (logMAR) (-0.59, p = 0.03). CONCLUSION: This study highlighted that the L/C ratio in pretreatment might predict a change of the visual acuity in DME.

15.
Sci Rep ; 11(1): 12780, 2021 06 17.
Artigo em Inglês | MEDLINE | ID: mdl-34140566

RESUMO

Physical deconditioning after stroke may induce post-stroke fatigue. However, research on this association is limited. Our primary objective was to investigate the associations of post-stroke fatigue severity with oxygen uptake ([Formula: see text]O2) at peak exercise and the time constant of [Formula: see text]O2 kinetics (τ[Formula: see text]O2) at exercise onset. The secondary objective was to examine the associations between fatigue and cardiorespiratory variables potentially affecting [Formula: see text]O2 during exercise. Twenty-three inpatients from a subacute rehabilitation ward were enrolled in this study. The median (interquartile range) Fatigue Severity Scale (FSS) score, as a measure of fatigue, was 32 (range 27-42) points. The FSS score was not associated with [Formula: see text]O2 at peak exercise during a symptom-limited graded exercise test (rho = - 0.264; p = 0.224), whereas it was significantly associated with τ[Formula: see text]O2 during a submaximal constant-load exercise test (rho = 0.530; p = 0.009). A higher FSS score also significantly correlated with a longer time constant of cardiac output (CO) kinetics (rho = 0.476; p = 0.022). Our findings suggest that severe post-stroke fatigue is associated with delayed increases in [Formula: see text]O2 and CO at the onset of exercise. Our findings can contribute to the development of an appropriate rehabilitation programme for individuals with post-stroke fatigue.


Assuntos
Exercício Físico/fisiologia , Fadiga/fisiopatologia , Coração/fisiopatologia , Respiração , Índice de Gravidade de Doença , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Consumo de Oxigênio/fisiologia
16.
Adv Exp Med Biol ; 1269: 95-99, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33966201

RESUMO

INTRODUCTION: The Borg scale rating of perceived exertion is a reliable indicator and widely used to monitor and guide exercise intensity. We aimed to evaluate the relationships between the Borg scale score and oxygenated hemoglobin (O2Hb) and deoxygenated hemoglobin (HHb) concentrations in the leg muscle as measured by near-infrared spectroscopy (NIRS) during cardiopulmonary exercise testing (CPET) in healthy adult men. We also investigated the relationships between the Borg scale score and the work rate (WR), heart rate (HR), oxygen uptake (VO2), and minute ventilation (VE). METHODS: Participants comprised 12 healthy men. Cardiopulmonary and NIRS parameters were assessed during each minute of CPET and at the end of the test. RESULTS: The Borg scale score was significantly correlated with cardiopulmonary parameters including WR, HR, VO2, and VE during CPET (Rs = 0.87-0.95; p < 0.05). Furthermore, the Borg scale score was significantly correlated with NIRS parameters including O2Hb and HHb levels during CPET (Rs = -0.48 and 0.45, respectively; p < 0.05). DISCUSSION: The Borg scale score is significantly correlated with cardiopulmonary parameters (WR, HR, VO2, and VE), as well as with leg-muscle oxygenation parameters as assessed by NIRS, during CPET in healthy adults. The correlation coefficients obtained from NIRS parameters were lower than those of cardiopulmonary parameters. CONCLUSIONS: The Borg scale score might better reflect cardiopulmonary responses than muscle deoxygenation during exercise. These results can aid in the planning of rehabilitation programs for healthy adults.


Assuntos
Perna (Membro) , Esforço Físico , Adulto , Exercício Físico , Teste de Esforço , Humanos , Masculino , Consumo de Oxigênio
17.
J Occup Health ; 63(1): e12218, 2021 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-33779022

RESUMO

OBJECTIVES: The comprehensive detection of environmental chemicals in biospecimens, an indispensable task in exposome research, is advancing. This study aimed to develop an exposomic approach to identify urinary metabolites of organophosphate (OP) pesticides, specifically cadusafos and prothiofos metabolites, as an example chemical group, using an original metabolome dataset generated from animal experiments. METHODS: Urine samples from 73 university students were analyzed using liquid chromatography-high-resolution mass spectrometry. The metabolome data, including the exact masses, retention time (tR ), and tandem mass spectra obtained from the human samples, were compared with the existing reference databases and with our original metabolome dataset for cadusafos and prothiofos, which was produced from mice to whom two doses of these OPs were orally administered. RESULTS: Using the existing databases, one chromatographic peak was annotated as 2,4-dichlorophenol, which could be a prothiofos metabolite. Using our original dataset, one peak was annotated as a putative cadusafos metabolite and three peaks as putative prothiofos metabolites. Of these, all three peaks suggestive of prothiofos metabolites, 2,4-dichlorophenol, 3,4,5-trihydroxy-6-(2,4-dichlorophenoxy) oxane-2-carboxylic acid, and (2,4-dichlorophenyl) hydrogen sulfate were confirmed as authentic compounds by comparing their peak data with both the original dataset and peak data of the standard reagents. The putative cadusafos metabolite was identified as a level C compound (metabolite candidate with limited plausibility). CONCLUSIONS: Our developed method successfully identified prothiofos metabolites that are usually not a target of biomonitoring studies. Our approach is extensively applicable to various environmental contaminants beyond OP pesticides.


Assuntos
Monitoramento Ambiental/métodos , Metabolômica/métodos , Organotiofosfatos/urina , Compostos Organotiofosforados/urina , Praguicidas/urina , Animais , Cromatografia Líquida , Bases de Dados Factuais , Humanos , Metaboloma , Camundongos , Exposição Ocupacional/análise , Valores de Referência , Espectrometria de Massas em Tandem
19.
Clin J Gastroenterol ; 14(3): 842-845, 2021 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-33675512

RESUMO

The outbreak of coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), was identified in 2019; thereafter, the COVID-19 outbreak became a health emergency of international concern. The impact of COVID-19 on liver-transplant recipients is unclear. Thus, it is currently unknown whether liver-transplant recipients are at a higher risk of developing complications related to COVID-19. Here, we report the case of liver-transplant recipients who were infected with SARS-CoV-2. A 20-year-old man who had undergone living-donor liver transplantation from his father at 5 years of age because of congenital biliary atresia was referred to our hospital for SARS-CoV-2 infection. Chest computed tomography did not show any abnormalities; however, laboratory results revealed liver dysfunction. He received tacrolimus as maintenance therapy that was continued at the same dose. He has not developed severe pulmonary disease and was discharged after 10 days of hospitalization. Limited data are available on post-transplant patients with COVID-19, and this case of a young patient without metabolic comorbidities did not show any association of severe COVID-19 under tacrolimus treatment. The progression of COVID-19 in liver-transplant recipients is complex, and COVID-19 risk should be evaluated in each patient until the establishment of optimal guidelines.


Assuntos
COVID-19/diagnóstico , Imunossupressores/uso terapêutico , Transplante de Fígado/efeitos adversos , Complicações Pós-Operatórias/tratamento farmacológico , SARS-CoV-2/isolamento & purificação , Tacrolimo/uso terapêutico , Adulto , Teste para COVID-19 , Humanos , Hospedeiro Imunocomprometido , Doadores Vivos , Masculino , Complicações Pós-Operatórias/diagnóstico , Complicações Pós-Operatórias/etiologia , SARS-CoV-2/imunologia , Transplantados , Resultado do Tratamento , Adulto Jovem
20.
Int J Cancer ; 148(12): 3008-3018, 2021 06 15.
Artigo em Inglês | MEDLINE | ID: mdl-33533494

RESUMO

Patients with idiopathic pulmonary fibrosis (IPF) are at higher risk of developing lung cancers including squamous cell lung carcinoma (SCC), which typically carries a poor prognosis. Although the molecular basis of cancer development subsequent to IPF has not been fully investigated, we recently reported two epigenetic phenotypes characterized by frequent and infrequent DNA hypermethylation in SCC, and an association of the infrequent hypermethylation phenotype with IPF-associated SCCs. Here, we conducted targeted exon sequencing in SCCs with and without IPF using the Human Lung Cancer Panel to investigate the genetic basis of IPF-associated SCC. SCCs with and without IPF displayed comparable numbers of total mutations (137 ± 22 vs 131 ± 27, P = .5), nonsynonymous mutations (72 ± 14 vs 69 ± 16, P = .5), indels (3.0 ± 3.5 vs 3.0 ± 3.9, P = 1) and synonymous mutations (62 ± 9.1 vs 60 ± 12, P = .5). Signature 1 was the predominant signature in SCCs with and without IPF. SETD2 and NFE2L2 mutations were significantly associated with IPF (44% vs 13%, P = .03 for SETD2; 38% vs 10%, P = .04 for NFE2L2). MYC amplification, assessed by copy number variant analysis, was also significantly associated with IPF (18.8% vs 0%, P = .04). Mutations in TP53 and CDKN2A were observed relatively frequently in SCCs with frequent hypermethylation (P = .02 for TP53 and P = .06 for CDKN2A). Survival analysis revealed that the SETD2 mutation was significantly associated with worse prognosis (P = .04). Collectively, we found frequent involvement of SETD2 and NFE2L2 mutations and MYC amplification in SCCs with IPF, and an association of a SETD2 mutation with poorer prognosis.


Assuntos
Carcinoma Pulmonar de Células não Pequenas/genética , Carcinoma de Células Escamosas/genética , Histona-Lisina N-Metiltransferase/genética , Fibrose Pulmonar Idiopática/genética , Fator 2 Relacionado a NF-E2/genética , Proteínas Proto-Oncogênicas c-myc/genética , Idoso , Carcinoma Pulmonar de Células não Pequenas/etiologia , Carcinoma de Células Escamosas/etiologia , Inibidor p16 de Quinase Dependente de Ciclina/genética , Metilação de DNA , Epigênese Genética , Exoma , Feminino , Amplificação de Genes , Estudos de Associação Genética , Testes Genéticos , Humanos , Fibrose Pulmonar Idiopática/complicações , Masculino , Pessoa de Meia-Idade , Mutação , Prognóstico , Análise de Sequência de DNA , Análise de Sobrevida , Proteína Supressora de Tumor p53/genética
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA
...