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1.
J Clin Immunol ; 2021 Apr 07.
Artigo em Inglês | MEDLINE | ID: mdl-33825088

RESUMO

Inborn errors of the IL-17-mediated signaling have been associated with chronic mucocutaneous candidiasis (CMC). We describe a patient with CMC, atopic dermatitis, enamel dysplasia, and recurrent parotitis harboring a novel compound heterozygous mutation of TRAF3IP2, leading to autosomal recessive ACT1 deficiency and deficient IL-17 signaling.

2.
Artigo em Inglês | MEDLINE | ID: mdl-33832222

RESUMO

Quantum dots (QDs) light-emitting diodes (QLEDs) are considered the most promising candidate for application in displays. While the efficiency of QLEDs has been greatly developed in recent years and is comparable to that of organic light-emitting diodes (OLEDs), it still remains challenging to realize both high efficiency and long lifetimes. In this work, we report efficient and stable red QLEDs with the maximum current efficiency of 13.48 cd A-1, external quantum efficiency of 18.65%, and low efficiency roll-off at high luminance with a long lifetime exceeding ∼2.9 × 105 h, representing a 3-fold increase in stability. Tailoring the composition of QDs suppresses nonradiative Förster resonant energy transfer and Auger recombination and provides favorable valence band alignment to boost the hole injection. Our work suggests that tailoring the nanostructures of QDs offers an effective means to simultaneously achieve high efficiency and high stability, accelerating QLED technology for practical applications in displays and lighting.

3.
Molecules ; 26(7)2021 Mar 31.
Artigo em Inglês | MEDLINE | ID: mdl-33807252

RESUMO

Microwave heating technology is known as an alternative to traditional gas and electric heating sources. In this work, mesoporous methylsilsesquioxane (MSQ) aerogels were prepared via a sol-gel process accompanied by microwave heating technology, and microwave heating was used in the gelation of sol and the drying of wet gels, respectively. The effects of hexadecyltrimethylammonium chloride (CTAC) as a surfactant and template, hydrochloric acid (HCl) as a catalyst, ethanol as a solvent, sodium hydroxide (NaOH) as a gelation agent, and microwave power on the pore structure of as-prepared MSQ aerogels were investigated in detail. Microwave heating at low power results in the acceleration of sol-gel transition and achieves the gelation within a few minutes. Appropriate amounts of chemical reagents and microwave heating at high power allow the preparation of mesoporous MSQ aerogels with a BET-specific surface area of 681.6 m2·g-1 and a mesopore size of 19 nm, and the resultant MSQ aerogel still has a BET specific surface area as high as 134 m2·g-1 after heat treatment at 600 °C for 2 h, showing high thermal stability. The MSQ aerogels/fibre composite possesses a low thermal conductivity of 0.039 W/(m·k)-1, displaying good thermal insulation. Microwave heating technology is a promising heating method for the preparation of other aerogels.

4.
Theranostics ; 11(8): 3796-3812, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33664862

RESUMO

Rationale: Mechanisms underlying the compromised bone formation in type 1 diabetes mellitus (T1DM), which causes bone fragility and frequent fractures, remain poorly understood. Recent advances in organ-specific vascular endothelial cells (ECs) identify type H blood vessel injury in the bone, which actively direct osteogenesis, as a possible player. Methods: T1DM was induced in mice by streptozotocin (STZ) injection in two severity degrees. Bony endothelium, the coupling of angiogenesis and osteogenesis, and bone mass quality were evaluated. Insulin, antioxidants, and NADPH oxidase (NOX) inhibitors were administered to diabetic animals to investigate possible mechanisms and design therapeutic strategies. Results: T1DM in mice led to the holistic abnormality of the vascular system in the bone, especially type H vessels, resulting in the uncoupling of angiogenesis and osteogenesis and inhibition of bone formation. The severity of osteopathy was positively related to glycemic levels. These pathological changes were attenuated by early-started, but not late-started, insulin therapy. ECs in diabetic bones showed significantly higher levels of reactive oxygen species (ROS) and NOX 1 and 2. Impairments of bone vessels and bone mass were effectively ameliorated by treatment with anti-oxidants or NOX2 inhibitors, but not by a NOX1/4 inhibitor. GSK2795039 (GSK), a NOX2 inhibitor, significantly supplemented the insulin effect on the diabetic bone. Conclusions: Diabetic osteopathy could be a chronic microvascular complication of T1DM. The impairment of type H vessels by NOX2-mediated endothelial oxidative stress might be an important contributor that can serve as a therapeutic target for T1DM-induced osteopathy.

5.
Br J Neurosurg ; : 1-4, 2021 Mar 26.
Artigo em Inglês | MEDLINE | ID: mdl-33769177

RESUMO

Spinal instrumented rod migrating from the surgical site to another remote site in the body is rare. Some cases result in organ or blood vessel injury. Most reported cases were asymptomatic until the finally injuries were generated. We report a unique case of spinal implant failure in which the rod moved from lumbar spine into chest 13 years post lumbar instrumentation. The migrated rod caused no damage to the organs in the pleural cavity but did cause an atypical pleural irritation syndrome which seemed to correlate with the mechanical irritation caused by the rod. These atypical symptoms of rod migration have not been reported previously.

6.
World Neurosurg ; 2021 Mar 17.
Artigo em Inglês | MEDLINE | ID: mdl-33744424

RESUMO

OBJECTIVE: To evaluate the mechanical properties of a new connector rod aiming to preserve implants in revision surgery (RS) for adjacent segment disease, a problematic complication of instrumented spinal fusion, and to assess its clinical applicability. METHODS: The mechanical properties of the connector-rod construct (implant preservation) and traditional rod construct (implant replacement) were evaluated and compared. Forty-three patients underwent RS for adjacent segment disease in the thoracolumbar spine with implant preservation or replacement, and radiological and clinical outcomes were assessed. RESULTS: Mechanical properties in group A were comparable to those in group B. Total mean time from prior surgery to RS was 6.86 ± 1.08 years. Surgical time and blood loss values of group A were 40.14% and 29.29% statistically significantly smaller than values of group B. In group B, 12% (3/25) of patients developed surgical site infections. In both groups, the visual analog scale leg score decreased significantly after RS. Early postoperative (at 1-month and 3-month follow-up) Oswestry Disability Index and visual analog scale back scores of group A were significantly lower than those of group B; the difference in the visual analog scale back score between groups was significant until the 6-month follow-up. No implant failures occurred, and spinal fusion was achieved in all cases. CONCLUSIONS: The connector rod is considered safe and can reduce the surgical time, blood loss, risk of complications, and medical costs. Better early postoperative clinical outcomes can be achieved with the rod owing to less surgical trauma.

7.
Artigo em Inglês | MEDLINE | ID: mdl-33780079

RESUMO

Both elevated intolerance of uncertainty (IU) and maladaptive metacognitive beliefs (MBs) were associated with depression. However, the relationship between MBs and IU in clinical depression is unclear. The current study aimed to investigate the putative impairment of MBs and IU in major depressive disorder (MDD) and explore the relationship between these two factors with depressive symptoms. Metacognition Questionnaire-30 Items (MCQ-30), Intolerance of Uncertainty Scale-Short Form (IUS-12) and clinical rating scales were administered to 53 patients with MDD and 56 healthy controls (HCs). Stepwise regressions were performed to explore independent contributions of MBs and IU on depression. Mediation analysis was used to examine associations among variables. Patients with MDD reported higher IUS-12 and MCQ-30 scores than HCs. Stepwise regressions revealed a unique contribution of negative MBs concerning the consequences of not controlling thoughts (MCQ-NC) on depression symptoms while controlling the effects of age, gender, anxiety symptoms and IU. MCQ-NC and negative MBs concerning the uncontrollability and danger of negative thinking (MCQ-NEG) completely mediated the effects of IU on depression and anxiety symptoms. Our results provided clear evidence that maladaptive negative MBs are directly associated with depression symptoms, and mediated the effect of IU on depression and anxiety symptoms, suggesting that IU and MBs influence clinical symptoms in a hierarchical manner.

8.
Mater Sci Eng C Mater Biol Appl ; 122: 111908, 2021 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-33641904

RESUMO

The low power photothermal therapy can reduce the tissue damage caused by laser irradiation, thus the near-infrared (NIR) absorbing vehicles with high photothermal conversion efficiency are demanded in the low power treatment. Herein, the NIR-absorbing agent polydopamine (PDA) and carbon dots (CDs) were gated on the openings of hollow mesoporous carbon (HMC) to construct a photothermal enhanced multi-functional system (HMC-SS-PDA@CDs). Interestingly, the fluorescence emission wavelength of HMC-SS-PDA@CDs was red-shifted by FRET effect between PDA and CDs, which solved the dilemma of fluorescence quenching of carbon-based materials and was more conducive to cell imaging. The modification of PDA@CDs not only acts as the gatekeepers to realize multi-responsive release of pH, GSH and NIR, but also endows the HMC vehicle with excellent photothermal generation capacity, the possibility for bio-imaging as well as the enhanced stability. Naturally, both the cytological level and the multicellular tumor sphere level demonstrate that the delivery system has good low-power synergistic therapeutic with combination index (CI) of 0.348 and imaging effects. Meanwhile, the combined treatment group showed the highest tumor inhibition rate of 92.6% at 0.75 W/cm2. Therefore, DOX/HMC-SS-PDA@CDs nano-platform had broad application prospects in low power therapy and convenient imaging of carbon-based materials.

9.
Neurogastroenterol Motil ; : e14135, 2021 Mar 27.
Artigo em Inglês | MEDLINE | ID: mdl-33772944

RESUMO

BACKGROUND: Contractile segment impedance (CSI) obtained from high-resolution impedance manometry (HRIM) is a measure of mucosal integrity that predicts gastroesophageal reflux disease (GERD). While straight leg raise (SLR) maneuver augments esophageal peristaltic vigor, it remains unclear whether SLR affects CSI values. This study was aimed to evaluate whether CSI with SLR is feasible and useful to complement the diagnosis of GERD. METHODS: We prospectively recruited 48 patients with typical GERD symptoms who underwent esophagogastroduodenoscopy, HRIM with SLR maneuver, and multichannel intraluminal impedance-pH (MII-pH) testing. The capability of mean nocturnal baseline impedance (MNBI), resting baseline impedance (RBI), CSI with or without SLR maneuver in predicting GERD was assessed using receiver operating characteristics (ROC) analysis. KEY RESULTS: Among 20 GERD patients and 28 non-GERD patients, all values of impedance-based metrics were lower in GERD patients compared to non-GERD patients (p < 0.001). For GERD identification, area under receiver operating characteristic curve (AUROC) values of CSI with SLR maneuver, CSI, MNBI, and RBI were 0.901, 0.858, 0.865, and 0.797. Particularly in ineffective esophageal motility (IEM) patients, SLR maneuver increased mean distal contractile integral from 436 to 828.7 mmHg.s.cm (p = 0.018) and enhanced AUROC values of CSI for GERD identification from 0.917 to 0.958. CONCLUSIONS & INFERENCES: CSI measurement during HRIM appears to be a reliable, time-saving, and less invasive tool for complementing GERD diagnosis. Our results also suggest a simple SLR maneuver during HRIM could enhance diagnostic accuracy of CSI for GERD identification especially in IEM patients.

10.
Artigo em Inglês | MEDLINE | ID: mdl-33655767

RESUMO

The underlying causes of heartburn, characteristic symptom of gastro-esophageal reflux disease(GERD), remain incompletely understood. Superficial afferent innervation of the esophageal mucosa in nonerosive reflux disease(NERD) may drive nociceptive reflux perception, but its acid-sensing role has not yet been established. Transient receptor potential vanilloid subfamily member-1(TRPV1), transient receptor potential Melastatin 8(TRPM8), and acid sensing ion channel 3(ASIC3) are regulators of sensory nerve activity and could be important reflux-sensing receptors within the esophageal mucosa. We characterised TRPV1, TRPM8, and ASIC3 expression in esophageal mucosa of GERD patients. We studied 10 NERD, 10 erosive reflux disease(ERD), 7 functional heartburn(FH), and 8 Barrett's esophagus(BE) patients. Biopsies obtained from the distal esophageal mucosa were co-stained with TRPV1, TRPM8, or ASIC3, and CGRP, CD45, or E-cadherin. RNA expression of TRPV1, TRPM8, and ASIC3 was assessed using qPCR. NERD patients had significantly increased expression of TRPV1 on superficial sensory nerves compared to ERD (p=0.028) or BE (p=0.017). Deep intrapapillary nerve endings did not express TRPV1 in all phenotypes studied. ASIC3 was exclusively expressed on epithelial cells most significantly in NERD and ERD patients (p=<0.0001). TRPM8 was expressed on submucosal CD45+ leukocytes. Superficial localisation of TRPV1-immunoreactive nerves in NERD, and increased ASIC3 co-expression on epithelial cells in NERD and ERD suggests a mechanism for heartburn sensation. Esophageal epithelial cells may play a sensory role in acid reflux perception and act interdependently with TRPV1-expressing mucosal nerves to augment hypersensitivity in NERD patients, raising the enticing possibility of topical antagonists for these ion channels as a therapeutic option.

11.
Acta Pharmacol Sin ; 2021 Mar 08.
Artigo em Inglês | MEDLINE | ID: mdl-33686244

RESUMO

Cardiovascular safety assessment is vital for drug development, yet human cardiovascular cell models are lacking. In vitro mass-generated human pluripotent stem cell (hPSC)-derived cardiovascular cells are a suitable cell model for preclinical cardiovascular safety evaluations. In this study, we established a preclinical toxicology model using same-origin hPSC-differentiated cardiomyocytes (hPSC-CMs) and endothelial cells (hPSC-ECs). For validation of this cell model, alirocumab, a human antibody against proprotein convertase subtilisin kexin type 9 (PCSK9), was selected as an emerging safe lipid-lowering drug; atorvastatin, a common statin (the most effective type of lipid-lowering drug), was used as a drug with reported side effects at high concentrations, while doxorubicin was chosen as a positive cardiotoxic drug. The cytotoxicity of these drugs was assessed using CCK8, ATP, and lactate dehydrogenase release assays at 24, 48, and 72 h. The influences of these drugs on cardiomyocyte electrophysiology were detected using the patch-clamp technique, while their effects on endothelial function were determined by tube formation and Dil-acetylated low-density lipoprotein (Dil-Ac-LDL) uptake assays. We showed that alirocumab did not affect the cell viability or cardiomyocyte electrophysiology in agreement with the clinical results. Atorvastatin (5-50 µM) dose-dependently decreased cardiovascular cell viability over time, and at a high concentration (50 µM, ~100 times the normal peak serum concentration in clinic), it affected the action potentials of hPSC-CMs and damaged tube formation and Dil-Ac-LDL uptake of hPSC-ECs. The results demonstrate that the established same-origin hPSC-derived cardiovascular cell model can be used to evaluate lipid-lowering drug safety in cardiovascular cells and allow highly accurate preclinical assessment of potential drugs.

12.
Int J Mol Med ; 47(3): 1, 2021 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-33537801

RESUMO

Resveratrol (RES) is a natural phenol which possesses multiple pharmacological actions. The present study aimed to determine whether RES protects against myocardial ischemic injury in association with the inhibition of NF­κB­dependent inflammation and the enhancement of antioxidant defenses in mice following acute myocardial infarction (AMI). Male C57/BL mice were randomly assigned to 3 groups as follows: The sham­operated (sham) group, AMI + vehicle group and AMI + RES group. Rat H9C2 cells were also used to examine the effects of RES on hypoxia­induced oxidative injury in vitro. Redox homeostasis in the mouse myocardium and rat H9C2 cells was determined post­treatment. The mRNA and protein levels of phosphorylated (p­)IκB kinase (p­IKK), p­nuclear factor (NF)­κB p65, interleukin (IL)­1ß, IL­6, nerve growth factor (NGF) and insulin­like growth factor­1 (IGF­1) were measured by RT­qPCR and western blot analysis. It was found that RES slightly protected the myocardium against ischemic injury in mice, while it prevented the hypoxia­induced apoptosis of H9C2 cells. RES decreased the production of reactive oxygen species (ROS) and enhanced the activities of superoxide dismutase (SOD), glutathione (GSH) and glutathione peroxidase (GPx). RES also downregulated the protein and/or mRNA levels of p­IKK, p­NF­κB p65, IL­1ß, IL­6, NGF and IGF­1 at 7 and 28 days after infarction. On the whole, these data indicate that RES protects the myocardium against ischemic injury in association with the inhibition of oxidative stress and inflammatory responses. Thus, RES has the potential to be used as an adjunctive therapeutic drug for heart diseases.

13.
Stem Cell Res ; 52: 102241, 2021 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-33611045

RESUMO

Ephrin B2 (EFNB2) is the first identified and most widely used marker for arterial endothelial cells (AECs). We generated a heterozygous EFNB2-2A-mCherry reporter H1 cell line, H1-EFNB2-2A-mCherry+/- (WAe001-A-57), by CRISPR/Cas9-mediated insertion of 2A-mCherry cassette into the EFNB2 gene locus, immediately before the translation stop codon. The H1-EFNB2-2A-mCherry reporter cells were pluripotent and could differentiate into all three germ layer lineages. Simultaneous expression of mCherry was observed when expression of EFNB2 was increased during endothelial cell differentiation. Thus, the generated reporter cells enable live identification of EFNB2-positive AECs, and screening of small molecule compound and target genes that promote AEC differentiation.

14.
Artigo em Inglês | MEDLINE | ID: mdl-33608991

RESUMO

AIM: To elucidates the mechanism that disulfiram/copper complex (DSF/Cu) treatment activates chloride channels and induces apoptosis in prostate cancer cells. METHODS: Cellular membrane currents were measured by membrane clamp technique; western blot to detect protein expression; flow cytometry to detect apoptosis; immunofluorescence to detect target protein co-localization, and further validated by a combination of protein-protein interaction and mock protein molecular docking techniques. RESULTS: DSF/Cu activated chloride channels and induced apoptosis in LNCaP (a type of androgen-dependent prostate cancer cells) cells. The chloride currents activated by DSF/Cu were significantly reduced after knockdown of CLC3 with siRNA. In addition, DSF/Cu-activated chloride currents were reduced to background current levels after perfusion with genistein, a highly specific tyrosine kinase inhibitor. Conversely, DSF/Cu failed to activate chloride currents in LNCaP cells after 30 minutes of pre-incubation with genistein. When genistein was removed, and DSF/Cu was added, the activated currents were small and unstable, and gradually decreased. Immunofluorescence in LNCaP cells also showed co-localization of the CLC3 protein with tyrosine kinase 2ß (PTK2B). CONCLUSION: DSF/Cu can activate chloride channels and induce apoptosis in LNCaP cells with the involvement of tyrosine kinase. These results provide new insights into the target therapy of prostate cancer.

15.
Pflugers Arch ; 2021 Feb 17.
Artigo em Inglês | MEDLINE | ID: mdl-33595719

RESUMO

Cardiovascular diseases have consistently been one of the leading causes of mortality, despite investigations by many scientists and clinicians. Animal models are versatile platforms to illustrate various mechanisms of different diseases, but are lacking in accurately portraying cardiovascular disease phenotypes. The advent of human pluripotent stem cells (PSCs) has led to much development in the construction of cardiovascular disease models. In this review, we provide a brief overview of the history and utilization of PSCs for cardiovascular precision medicine, including disease modeling, drug screening, and gene editing, and elaborate on the current updated research status of patient-specific induced pluripotent stem cell (iPSC)-based disease models for cardiac channelopathies, cardiomyopathies, and other cardiovascular diseases. Furthermore, we highlight the development of novel human iPSC-derived engineered heart tissues for cardiovascular disease modeling. Finally, we put forward our own views on the existing advantages and difficulties for moving forward in this field.

16.
Sci Rep ; 11(1): 2856, 2021 Feb 03.
Artigo em Inglês | MEDLINE | ID: mdl-33536562

RESUMO

Early childhood is a critical stage for the foundation and development of the gut microbiome, large amounts of essential nutrients are required such as vitamin D. Vitamin D plays an important role in regulating calcium homeostasis, and deficiency can impair bone mineralization. In addition, most people know that breastfeeding is advocated to be the best thing for a newborn; however, exclusively breastfeeding infants are not easily able to absorb an adequate amount of vitamin D from breast milk. Understanding the effects of vitamin D supplementation on gut microbiome can improve the knowledge of infant health and development. A total of 62 fecal sample from healthy infants were collected in Taiwan. Of the 62 infants, 31 were exclusively breastfed infants and 31 were mixed- or formula-fed infants. For each feeding type, one subgroup of infants received 400 IU of vitamin D per day, and the remaining infants received a placebo. In total, there are 15 breastfed and 20 formula-fed infants with additional vitamin D supplementation, and 16 breastfed and 11 formula-fed infants belong to control group, respectively. We performed a comparative metagenomic analysis to investigate the distribution and diversity of infant gut microbiota among different types of feeding regimes with and without vitamin D supplementation. Our results reveal that the characteristics of infant gut microbiota not only depend on the feeding types but also on nutrients intake, and demonstrated that the vitamin D plays an important role in modulating the infant gut microbiota, especially increase the proportion of probiotics in breast-fed infants.

17.
Mol Genet Genomics ; 296(2): 369-378, 2021 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-33449159

RESUMO

The tradeoff between cost and efficiency is omnipresent in organisms. Specifically, how the evolutionary force shapes the tradeoff between biosynthetic cost and translation efficiency remains unclear. In the cancer community, whether the adjustment of cost-efficiency tradeoff acts as a strategy to facilitate tumor proliferation and contributes to oncogenesis is uninvestigated. To address this issue, we retrieved the gene expression profile in various cancer types and the matched normal samples from The Cancer Genome Atlas (TCGA). We found that the highly expressed genes in cancers generally have higher tAI/nitro ratios than those in normal samples. This is possibly caused by the higher tAI/nitro ratios observed in oncogenes than tumor suppressor genes (TSG). Furthermore, in the cancer samples, derived mutations in oncogenes usually lead to higher tAI/nitro ratios, while those mutations in TSG lead to lower tAI/nitro. For a special case of kidney cancer, we investigated several crucial genes in tumor samples versus normal samples, and discovered that the changes in tAI/nitro ratios are correlated with the changes in translation level. Our study for the first time revealed the optimization of cost-efficiency tradeoff in cancers. The cost-efficiency dilemma is optimized by the tumor cells, and is possibly beneficial for the translation and production of oncogenes, and eventually contributes to proliferation and oncogenesis. Our findings could provide novel perspectives in depicting the cancer genomes and might help unravel the cancer evolution.


Assuntos
Estudo de Associação Genômica Ampla/métodos , Neoplasias/genética , Nitrogênio/análise , RNA de Transferência/análise , Regulação para Cima , Biologia Computacional/métodos , Bases de Dados Genéticas , Perfilação da Expressão Gênica , Regulação Neoplásica da Expressão Gênica , Genes Supressores de Tumor , Humanos , Mutação , Oncogenes
18.
Environ Sci Process Impacts ; 23(2): 357-366, 2021 Mar 04.
Artigo em Inglês | MEDLINE | ID: mdl-33511973

RESUMO

Indoor dust ingestion is one of the main pathways for human exposure to organophosphate flame retardants (PFRs). The urinary concentrations of diesters (DAPs) are usually used as biomarkers to assess human exposure to PFRs. In this study, the PFR and DAP levels were measured in morning and evening urine samples of 30 workers from an e-waste dismantling site in southern China. The indoor dust samples were also collected from workshops and houses for analyzing associations between PFR and DAP levels in urine and dust. Tris(1-chloro-2-propyl) phosphate (TCIPP) and triphenyl phosphate (TPHP) were the dominant PFRs in dust, while bis(2-chloroethyl) phosphate (BCEP) and diphenyl phosphate (DPHP) were the major DAPs in dust. A significant positive correlation was observed between TPHP and DPHP concentrations in dust (p < 0.001), suggesting their potentially same source and the degradation of TPHP to form DPHP. TCIPP and tris(1,3-dichloro-2-propyl) phosphate (TDCIPP) were the predominant PFRs, and BCEP, bis(1,3-dichloro-2-propyl) phosphate (BDCIPP), and DPHP were the main DAPs in both the morning and evening urine samples. The DPHP levels in evening urine samples were significantly correlated with TPHP and DPHP levels (p < 0.01) in dust. A similar correlation was found for the BCEP levels in the evening urine samples and the TCEP and BCEP levels (p < 0.01) in dust. These results indicated that in addition to being biotransformed from their respective parent PFRs, direct ingestion from indoor dust could also be the potential source for urinary DPHP and BCEP. Since relatively low detection frequencies were observed for bis(1-chloro-2-propyl) phosphate (BCIPP) and bis(butoxyethyl) phosphate (BBOEP) in urine, they may not be the major metabolites of TCIPP and tris(2-butoxyethyl) phosphate (TBOEP), respectively, in the human body. However, BDCIPP can be considered a useful biomarker because it is a unique metabolite of TDCIPP and has high detection frequencies in urine samples. The results of this study indicated the limitations of solely using urinary DAPs as biomarkers for the evaluation of human exposure to PFRs, and certain PFRs as well as hydroxylated PFRs (OH-PFRs) should also be considered for urinary biomonitoring in future studies.


Assuntos
Resíduo Eletrônico , Retardadores de Chama , Monitoramento Biológico , China , Poeira/análise , Retardadores de Chama/análise , Humanos , Organofosfatos/análise
19.
J Psychiatry Neurosci ; 46(1): E196-E207, 2021 01 21.
Artigo em Inglês | MEDLINE | ID: mdl-33497170

RESUMO

Background: Depression is a common morbidity after traumatic brain injury. This network meta-analysis investigated the efficacy and tolerability of pharmacologic and nonpharmacologic interventions for depression after traumatic brain injury. Methods: We extracted randomized controlled trials examining pharmacologic or nonpharmacologic interventions with placebo- or active-controlled designs from PubMed, the Cochrane Library and ScienceDirect, from inception to October 30, 2018. We based study selection and extraction of a predefined list of variables on the Preferred Reporting Items for Systematic Review and Meta-Analyses (PRISMA) guidelines, and conducted meta-analysis procedures using random effects modelling. Primary outcomes were changes in depressive symptom severity after pharmacologic or nonpharmacologic treatment; the secondary outcome was tolerability, reflected in overall patient dropout rates. Results: Our analysis of 27 randomized controlled trials (10 pharmacologic, total n = 483, mean age = 37.9 yr; 17 nonpharmacologic, total n = 1083, mean age = 38.0 yr) showed that methylphenidate had significantly superior efficacy compared to placebo or control (standardized mean difference -0.91, 95% confidence interval [CI] -1.49 to -0.33). Sertraline was associated with significantly lower tolerability (i.e., a higher dropout rate) compared to placebo or control (odds ratio 2.65, 95% CI 1.27 to 5.54). No nonpharmacologic treatment was more effective than the others, and we found no significant differences in tolerability (i.e., dropout rates) among the nonpharmacologic treatments. Limitations: Heterogeneity in participant characteristics (e.g., comorbidities), study designs (e.g., trial duration) and psychopathology assessment tools, as well as small trial numbers for some treatment arms, could have been confounders. Conclusion: The present network meta-analysis suggests that methylphenidate might be the best pharmacologic intervention for depressive symptoms related to traumatic brain injury. None of the nonpharmacologic interventions was associated with better improvement in depressive symptoms than the others or than control conditions. None of the pharmacologic or nonpharmacologic treatments had inferior tolerability compared to placebo or controls except for sertraline, which had significantly lower tolerability than placebo.

20.
Hum Genomics ; 14(1): 44, 2020 Dec 07.
Artigo em Inglês | MEDLINE | ID: mdl-33287870

RESUMO

BACKGROUND: Epilepsy is a group of neurological disorders characterized by recurrent epileptic seizures. Epilepsy is affected by many factors, approximately 20-30% of cases are caused by acquired conditions, but in the remaining cases, genetic factors play an important role. Early establishment of a specific diagnosis is important to treat and manage this disease. METHODS: In this study, we have recruited 43 epileptic encephalopathy patients and the molecular genetic analysis of those children was performed by whole-exome sequencing (WES). RESULTS: Fourteen patients (32.6%, 14/43) had positive genetic diagnoses, including fifteen mutations in fourteen genes. The overall diagnostic yield was 32.6%. A total of 9 patients were diagnosed as pathogenic mutations, including 4 variants had been reported as pathogenic previously and 6 novel variants that had not been reported previously. Therefore, WES heralds promise as a tool for clinical diagnosis of patients with genetic disease. CONCLUSION: Early establishment of a specific diagnosis, on the one hand, is necessary for providing an accurate prognosis and recurrence risk as well as optimizing management and treatment options. On the other hand, to unveil the genetic architecture of epilepsy, it is of vital importance to investigate the phenotypic and genetic complexity of epilepsy.

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