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1.
Aging (Albany NY) ; 112019 Oct 31.
Artigo em Inglês | MEDLINE | ID: mdl-31672930

RESUMO

BACKGROUND: Numerous patients with clear cell renal cell carcinoma (ccRCC) experience drug resistance after immunotherapy. Regulatory T (Treg) cells may work as a suppressor for anti-tumor immune response. PURPOSE: We performed bioinformatics analysis to better understand the role of Treg cells in ccRCC. RESULTS: Module 10 revealed the most relevance with Treg cells. Functional annotation showed that biological processes and pathways were mainly related to activation of the immune system and the processes of immunoreaction. Four hub genes were selected: LCK, MAP4K1, SLAMF6, and RHOH. Further validation showed that the four hub genes well-distinguished tumor and normal tissues and were good prognostic biomarkers for ccRCC. CONCLUSION: The identified hub genes facilitate our knowledge of the underlying molecular mechanism of how Treg cells affect ccRCC in anti-tumor immune therapy. METHODS: The CIBERSORT algorithm was performed to evaluate tumor-infiltrating immune cells based on the Cancer Genome Atlas cohort. Weighted gene co-expression network analysis was conducted to explore the modules related to Treg cells. Gene Ontology analysis and pathway enrichment analysis were performed for functional annotation and a protein-protein interaction network was built. Samples from the International Cancer Genomics Consortium database was used as a validation set.

2.
Medicine (Baltimore) ; 98(44): e17548, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31689756

RESUMO

BACKGROUND: The incidence of atrial fibrillation (AF) varies from 5.4% to 47.1% in patients with mitral annulus calcification (MAC). We conducted a systematic review and meta-analysis on the association between MAC and AF, as well as the relation between MAC and major cardiac adverse events (MACEs) in AF patients. METHODS: We conducted comprehensive search for literature on associations between MAC and AF using the following databases: MEDLINE, PubMed, Embase, and the Web of Science. The pooled odds ratio (OR) or relative risk and the corresponding 95% confidence intervals (CIs) were calculated to assess the relationship between MAC and AF, as well as the rates of MACEs in AF patients with or without MAC. RESULTS: Thirteen studies met our eligibility criteria on associations between MAC and AF, including 6232 patients with MAC and 15,199 patients without MAC. Moreover, 5 studies met our eligibility criteria on the rates of MACEs in AF patients with or without MAC. The pooled analysis demonstrated a statistically significant increased risk of development of incident AF in patients with MAC than those without MAC (random effects OR: 2.34; 95% CI: 1.91, 2.85; P = .000). And the pooled analysis demonstrated a statistically significant increased risk of development of MACEs in AF patients with MAC (random effects OR: 2.34; 95% CI: 1.24, 4.41; P = .009). CONCLUSION: MAC was independently associated with AF and AF patients with MAC were at greater risk for cardiovascular and cerebrovascular events.

3.
Anal Chem ; 2019 Nov 06.
Artigo em Inglês | MEDLINE | ID: mdl-31691558

RESUMO

It has been reported that the piRNAs play critical roles in activating invasion and metastasis, evading growth suppressors and sustaining proliferative signaling of cancer and can be regarded as a novel biomarker candidate. Thus, it is necessary to develop an effective method for imaging and regulating cancer-related piRNAs to diagnose and treat cancers. Herein, we designed aptamer-functionalized activatable DNA tetrahedron nanoprobes (apt-ADTNs) to image and regulate endogenous piRNAs in cancer cells. As proof of concept, overexpressed piRNA-36026 in MCF-7 cells was used for this study. In brief, aptamer AS1411 and piRNA-36026 anti-sequence with Cy5 fluorescent dye are appended from DNA tetrahedron, then a short oligonucleotide with black hole quencher 2 (Q-oligo) is complementary with piRNA-36026 anti-sequence to quench the fluorescence of Cy5. The apt-ADTNs can recognize the MCF-7 cells through aptamer AS1411 and then enter the cells. Q-oligo is detached from the apt-ADTNs because of the binding between apt-ADTNs and piRNA-36026, leading to the recovery of Cy5 fluorescence signal. Meanwhile, the hybridization of apt-ADTNs and piRNAs-36026 results in down-regulating of dissociative piRNAs-36026 in cytoplasm and the subsequent apoptosis of MCF-7 cells. As the achievement of synchronously imaging and regulating piRNA-36026 in MCF-7 cells, we believe that this design holds great promise in application of diagnosis and therapy for cancer.

4.
BMC Infect Dis ; 19(1): 925, 2019 Oct 30.
Artigo em Inglês | MEDLINE | ID: mdl-31666015

RESUMO

BACKGROUND: Ruili is a border city in southwest China along the heroin trafficking route. In recent decades, the city has witnessed increased in HIV transmission. The current study aims to explore the spatiotemporal trends in HIV prevalence identify and map the spatial variation and clustering of factors associated with HIV transmission through drug use and heterosexual contact transmissions at the village level from 1989 through 2016. METHODS: Geographic information system-based spatiotemporal analyses, including global and local spatial autocorrelation analyses and space-time scanning statistics, were applied to detect the location and extent of HIV/AIDS high-risk areas. RESULTS: Drug use and heterosexual contact were identified as the major transmission routes causing infection in Ruili. Results of global spatial analysis showed significant clustering throughout the city caused by transmission via drug use in the early phase of the epidemic and transmission via heterosexual contact in the late phase of the epidemic during the study period. Hotspots of transmission from drug use were randomly distributed throughout the city. However, the hotspots of transmission by heterosexual contact were located in the central area only around the Jiegao China-Myanmar land port. Space-time scanning showed that transmission from drug use clustered in the southwest area between 1989 and 1990, while transmission by heterosexual contact clustered in the central area between 2004 and 2014. CONCLUSIONS: Heterosexual contact has become the dominant mode of transmission. Interventions should focus on highly clustered area where is around the Jiegao land port.

5.
Artigo em Inglês | MEDLINE | ID: mdl-31654302

RESUMO

Fermentation slurry from food waste (FSFW) produced at different temperatures (20, 37, and 55 °C) was utilized as external carbon source for promoting nitrogen removal in this study. It was found that high temperatures improved the hydrolysis rate by promoting the hydrolytic enzyme activity. Mesophilic temperature (37 °C) was favorable for organic acid (especially lactic acid) production by selectively enriching the Lactobacillus (with a relative abundance of 90.6%), while thermophilic temperature (55 °C) would restrict the acidogenesis rate (18.9%) and result in the accumulation of carbohydrate in the fermented slurry. Organic acids in the FSFW act as easily biodegradable carbon sources, but the macromolecular and particulate organic components can be utilized as slowly biodegradable carbon sources in the denitrification processes. Using the FSFW as carbon sources to enhance nitrogen removal from wastewater in sequencing batch reactors (SBRs) for more than 150 days, the FSFW produced at thermophilic temperature could significantly promote the microbial metabolic capacity of the activated sludge and improve the nitrogen and phosphate removal efficiencies.

6.
Diabetes Metab Res Rev ; : e3226, 2019 Oct 26.
Artigo em Inglês | MEDLINE | ID: mdl-31655001

RESUMO

BACKGROUND: The impact of hypoglycaemic episode (HE) on the risk of ventricular arrhythmia (VA) and sudden cardiac arrest (SCA) remains unclear. We hypothesized that HE increases the risk of both VA and SCA and that glucose-lowering agents causing HE also increase the risk of VA/SCA in patients with type 2 diabetes (T2D). METHODS: Patients aged 20 years or older with newly diagnosed T2D were identified using the Taiwan National Health Insurance Database. HE was defined as the presentation of hypoglycaemic coma or specified/unspecified hypoglycaemia. The control group consisted of T2D patients without HE. The primary outcome was the occurrence of VA (including ventricular tachycardia and fibrillation) and SCA during the defined follow-up periods. A multivariate Cox hazards regression model was used to evaluate the hazard ratio (HR) for VA or SCA. RESULTS: A total of 54 303 patients were screened, with 1037 patients with HE assigned to the HE group and 4148 frequency-matched patients without HE constituting the control group. During a mean follow-up period of 3.3 ± 2.5 years, 29 VA/SCA events occurred. Compared with the control group, HE group had a higher incidence of VA/SCA (adjusted HR: 2.42, P = .04). Patients who had used insulin for glycaemic control showed an increased risk of VA/SCA compared with patients who did not receive insulin (adjusted HR: 3.05, P = .01). CONCLUSIONS: The HEs in patients with T2D increased the risk of VA/SCA, compared with those who did not experience HEs. Use of insulin also independently increased the risk of VA/SCA.

8.
Artigo em Inglês | MEDLINE | ID: mdl-31662475

RESUMO

Glycolytic enzyme phosphoglycerate mutase 1 (PGAM1) plays a critical role in cancer metabolism by coordinating glycolysis and biosynthesis. A well-validated PGAM1 inhibitor, however, has not been reported for treating pancreatic ductal adenocarcinoma (PDAC), which is one of the deadliest malignancies worldwide. By uncovering the elevated PGAM1 expressions were statistically related to worse prognosis of PDAC in a cohort of 50 patients, we developed a series of allosteric PGAM1 inhibitors by structure-guided optimization. The compound KH3 significantly suppressed proliferation of various PDAC cells by down-regulating the levels of glycolysis and mitochondrial respiration in correlation with PGAM1 expression. Similar to PGAM1 depletion, KH3 dramatically hampered the canonic pathways highly involved in cancer metabolism and development. Additionally, we observed the shared expression profiles of several signature pathways at 12 h after treatment in multiple PDAC primary cells of which the matched patient-derived xenograft (PDX) models responded similarly to KH3 in the 2 wk treatment. The better responses to KH3 in PDXs were associated with higher expression of PGAM1 and longer/stronger suppressions of cancer metabolic pathways. Taken together, our findings demonstrate a strategy of targeting cancer metabolism by PGAM1 inhibition in PDAC. Also, this work provided "proof of concept" for the potential application of metabolic treatment in clinical practice.

9.
Curr Pharm Des ; 2019 Oct 28.
Artigo em Inglês | MEDLINE | ID: mdl-31663471

RESUMO

Traumatic brain injury (TBI) can cause disorders of consciousness (DOC) by impairing the neuronal circuits of the ascending reticular activating system (ARAS) structures, including the hypothalamus, which are responsible for the maintenance of the wakefulness and awareness. Current awakening therapies for TBI-induced DOC comprise, among others, the regulation of excitatory and inhibitory neurotransmitters and the stimulation of the peripheral or central nervous system (CNS). However, the effects of these awakening therapies are still not satisfactory. Hypothalamus has been identified as a sleep/wake center, and its anterior and posterior regions have diverse roles in the regulation of the sleep/wake function. In particular, posterior hypothalamus (PH) possesses several types of neurons, including the orexin neurons in the lateral hypothalamus (LH) with widespread projections to other wakefulness-related regions of the brain. Orexins have been known to affect feeding and appetite, and recently their profound effect on sleep disorders and DOC has been identified. Orexin antagonists are used for the treatment of insomnia, and orexin agonists can be used for narcolepsy. Additionally, several studies demonstrated that the agonists of orexin might be effective in the treatment of DOC, providing novel therapeutic opportunities in this field.

10.
Aging Clin Exp Res ; 2019 Oct 19.
Artigo em Inglês | MEDLINE | ID: mdl-31630377

RESUMO

BACKGROUND AND AIM: Providing care to an older adult with a disability has been associated with increased risk to the caregiver's health, but most previous studies of caregiving and health compare persons who are already caregivers with poorly matched non-caregiving controls and are often based on convenience samples. In this report, we describe the enrollment of persons who transitioned into a family caregiving role while participating in a national epidemiological study. METHODS: Participants in the REasons for Geographic And Racial Differences in Stroke (REGARDS) study were asked on two occasions 9-14 years apart if they were providing care on an ongoing basis to a family member with a chronic illness or disability. Those who answered "no" and "yes", respectively, to this caregiving question and reported sufficient caregiving responsibilities after their transitions were enrolled in the present study as incident caregivers (N = 251). Participants matched on multiple demographic and health history variables and who reported no history of caregiving were enrolled as non-caregiving controls (N = 251). RESULTS: Among eligible participants, 84% agreed to participate, and 47% of caregivers reported caring for a person with dementia. Descriptive analyses confirmed the success of the matching procedures for balancing the groups on multiple demographic and pre-caregiving health variables. Depressive symptoms and perceived stress increased significantly after the transition to caregiving. CONCLUSION: Comparable, population-based samples of incident caregivers and matched non-caregivers have been enrolled. Future analyses will examine within-person changes in health and circulating biomarkers as a function of the transition to caregiving.

11.
PLoS Med ; 16(10): e1002953, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31652273

RESUMO

BACKGROUND: Polycystic ovary syndrome (PCOS) is associated with increased metabolic risk, though data on long-term follow-up of cardiometabolic traits are limited. We postulated that Chinese women with PCOS would have higher risk of incident diabetes and cardiometabolic abnormalities than those without PCOS during long-term follow-up. METHODS AND FINDINGS: One hundred ninety-nine Chinese women with PCOS diagnosed by the Rotterdam criteria and with a mean age of 41.2 years (SD = 6.4) completed a follow-up evaluation after an average of 10.6 ± 1.3 years. Two hundred twenty-five women without PCOS (mean age: 54.1 ± 6.7 years) who underwent baseline and follow-up evaluation over the same period were used for comparison. Progression of glycaemic status of women both with and without PCOS was assessed by using 75-g oral glucose tolerance test (OGTT) screening with the adoption of 2009 American Diabetes Association diagnostic criteria. The frequency of impaired glucose regulation, hypertension, and hyperlipidaemia of women with PCOS at follow-up has increased from 31.7% (95% CI 25.2%-38.1%) to 47.2% (95% CI 40.3%-54.2%), 16.1% (95% CI 11.0%-21.2%) to 34.7% (95% CI 28.1%-41.3%), and 52.3% (95% CI 45.3%-59.2%) to 64.3% (95% CI 57.7%-71.0%), respectively. The cumulative incidence of diabetes mellitus (DM) in follow-up women with PCOS is 26.1% (95% CI 20.0%-32.2%), almost double that in the cohort of women without PCOS (p < 0.001). Age-standardised incidence of diabetes among women with PCOS was 22.12 per 1,000 person-years (95% CI 10.86-33.37) compared with the local female population incidence rate of 8.76 per 1,000 person-years (95% CI 8.72-8.80) and 10.09 per 1,000 person-years (95% CI 4.92-15.26, p < 0.001) for women without PCOS in our study. Incidence rate for women with PCOS aged 30-39 years was 20.56 per 1,000 person-years (95% CI 12.57-31.87), which is approximately 10-fold higher than that of the age-matched general female population in Hong Kong (1.88 per 1,000 person-years, [95% CI 1.85-1.92]). The incidence rate of type 2 DM (T2DM) of both normal-weight and overweight women with PCOS was around double that of corresponding control groups (normal weight: 8.96 [95% CI 3.92-17.72] versus 4.86 per 1,000 person-years [95% CI 2.13-9.62], p > 0.05; overweight/obese: 28.64 [95% CI 19.55-40.60] versus 14.1 per 1,000 person-years [95% CI 8.20-22.76], p < 0.05). Logistic regression analysis identified that baseline waist-to-hip ratio (odds ratio [OR] = 1.71 [95% CI 1.08-2.69], p < 0.05) and elevated triglyceride (OR = 6.63 [95% CI 1.23-35.69], p < 0.05) are associated with the progression to T2DM in PCOS. Limitations of this study include moderate sample size with limited number of incident diabetes during follow-up period and potential selection bias. CONCLUSIONS: High risk of diabetes and increased cardiovascular disease risk factors among Chinese women with PCOS are highlighted in this long-term follow-up study. Diabetes onset was, on average, 10 years earlier among women with PCOS than in women without PCOS.

12.
Aging (Albany NY) ; 11(19): 8542-8555, 2019 Oct 07.
Artigo em Inglês | MEDLINE | ID: mdl-31590160

RESUMO

Oxidative stress plays a vital role in the initiation and progression of age-related neurodegenerative diseases. Ameliorating oxidative damage is therefore considered as a beneficial strategy for the treatment of age-related neurodegenerative disorders. Probucol (Prob), a lipid-lowering prototype agent, was reported to treat cardiovascular diseases, chronic kidney disease and diabetes mellitus. However, whether Prob has an effect on age-related neurodegenerative diseases remains unknown. In the study, it was found that Prob ameliorated D-galactose (D-gal) induced cognitive deficits and neuronal loss in the hippocampal CA1 region. Moreover, Prob alleviated ROS and MDA levels by elevating SOD, GSH-PX and HO-1 mRNA and protein expressions, and improving plasmic and cerebral SOD and GSH-PX activities in D-gal treated mice. Furthermore, Prob promoted the dissociation of Keap1/Nrf2 complex leading to the accumulation of Nrf2 in nucleus, implying that the improved anti-oxidant property of Prob is mediated by Keap1/Nrf2 pathway. The study firstly demonstrates the favorable effects of Prob against cognitive impairments in a senescent mouse model, rendering this compound a promising agent for the treatment or prevention of age-related neurodegenerative disease.

13.
Cells ; 8(10)2019 Oct 11.
Artigo em Inglês | MEDLINE | ID: mdl-31614673

RESUMO

: Non-alcoholic fatty liver disease (NAFLD) is one of the most common liver diseases worldwide. Reactive oxygen species (ROS), as potent oxidants in cells, have been shown to promote the development of NAFLD. Previous studies reported that for ROS-induced cellular oxidative stress, promoting lipid droplet (LD) accumulation is associated with the cellular antioxidation process. However, the regulatory role of LDs in relieving cellular oxidative stress is poorly understood. Here, we showed that Perilipin 5 (PLIN5), a key LD protein related to mitochondria-LD contact, reduced ROS levels and improved mitochondrial function in HepG2 cells. Both mRNA and protein levels of PLIN5 were significantly increased in cells with hydrogen peroxide or lipopolysaccharide (LPS) treatment (p < 0.05). Additionally, the overexpression of PLIN5 promoted LD formation and mitochondria-LD contact, reduced cellular ROS levels and up-regulated mitochondrial function-related genes such as COX and CS. Knockdown PLIN5, meanwhile, showed opposite effects. Furthermore, we identified that cellular oxidative stress up-regulated PLIN5 expression via the JNK-p38-ATF pathway. This study shows that the up-regulation of PLIN5 is a kind of survival strategy for cells in response to stress. PLIN5 can be a potential therapeutic target in NAFLD.

14.
PLoS One ; 14(10): e0222772, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31574102

RESUMO

BACKGROUND: In this research, an meta-analysis was performed for assessment of the associations between O6-methyguanine-DNA methyltransferase (MGMT) promoter hypermethylation possessing low-grade intraepithelial lesion (LSIL), high-grade intraepithelial lesion (HSIL), cervical cancer (CC), and clinicopathological characters of CC. METHODS: Literature selection were conducted through searching PubMed, Web of science, EMBASE, China National Knowledge Infrastructure and Wanfang databases (up to November 2018). An assessment of associations between MGMT methylation and LSIL, HSIL, CC risk and clinicopathological characteristics was performed through pooled odds ratios (ORs) with relevant 95% confidence intervals (CIs). Subgroup analyses, meta-regressions and Galbraith plots were conducted to conduct an exploration on the possible sources of heterogeneity. The genome-wide DNA methylation array studies were extracted from Gene Expression Omnibus (GEO) databases for validation of these outcomes. RESULTS: In this meta-analysis of 25 published articles, MGMT hypermethylation gradually elevated the rates among control group (12.16%), LSIL (20.92%), HSIL (36.33%) and CC (41.50%) specimens. MGMT promoter methylation was significant associated with the increased risk of LSIL by 1.74-fold (P<0.001), HSIL by 3.71-fold (P<0.001) and CC by 7.08-fold (P<0.001) compared with control. A significant association between MGMT promoter methylation with FIGO stage was also found (OR = 2.81, 95% CI: 1.79-4.41, p<0.001). The results of GEO datasets showed that 5 CpG sites in MGMT with a great diagnostic value for the screening of cervical cancer. CONCLUSION: The meta-analysis indicated the association between MGMT promoter hypermethylation and squamous intraepithelial lesion and cervical cancer. MGMT methylation detection might have a potential value to be an epigenetic marker for the clinical diagnosis of cervical cancer.

15.
Molecules ; 24(19)2019 Oct 07.
Artigo em Inglês | MEDLINE | ID: mdl-31591309

RESUMO

Ralstonia solanacearum (R. solanacearum)-induced bacterial wilt of the nightshade family causes a great loss in agricultural production annually. Although there has been some efficient pesticides against R. solanacearum, inaccurate pesticide releasing according to the onset time of bacterial wilt during the use of pesticides still hinders the disease management efficiency. Herein, on the basis of the soil pH change during R. solanacearum growth, and pH sensitivity of the Schiff base structure, a pH-sensitive oxidized alginate-based double-crosslinked gel was fabricated as a pesticide carrier. The gel was prepared by crosslinking oxidized sodium alginate (OSA) via adipic dihydrazide (ADH) and Ca2+. After loading tetramycin into the gel, it showed a pH-dependent pesticide releasing behavior and anti-bacterial activity against R. solanacearum. Further study also showed that the inhibition rate of the tetramycin-loaded gel was higher than that of industrial pesticide difenoconazole. This work aimed to reduce the difficulty of pesticide administration in the high incidence period of bacterial wilt and we believe it has a great application potential in nightshade production.

16.
Int J Biol Sci ; 15(10): 2182-2197, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31592234

RESUMO

Previous studies indicated that let-7 enhances osteogenesis and bone formation of human adipose-derived mesenchymal stem cells (MSCs). We also have confirmed that let-7f-5p expression was upregulated during osteoblast differentiation in rat bone marrow-derived MSCs (BMSCs) and was downregulated in the vertebrae of patients with glucocorticoid (GC)-induced osteoporosis (GIOP). The study was performed to determine the role of let-7f-5p in GC-inhibited osteogenic differentiation of murine BMSCs in vitro and in GIOP in vivo. Here, we report that dexamethasone (Dex) inhibited osteogenic differentiation of BMSCs and let-7f-5p expression, while increasing the expression of transforming growth factor beta receptor 1 (TGFBR1), a direct target of let-7f-5p during osteoblast differentiation under Dex conditions. In addition, let-7f-5p promoted osteogenic differentiation of BMSCs, as indicated by the promotion of alkaline phosphatase (ALP) staining and activity, Von Kossa staining, and osteogenic marker expression (Runx2,Osx, Alp, and Ocn), but decreased TGFBR1 expression in the presence of Dex. However, overexpression of TGFBR1 reversed the upregulation of let-7f-5p during Dex-treated osteoblast differentiation. Knockdown of TGFBR1 reversed the effect of let-7f-5p downregulation during Dex-treated osteogenic differentiation of BMSCs. We also found that glucocorticoid receptor (GR) mediated transcriptional silencing of let-7f-5p and its knockdown enhanced Dex-inhibited osteogenic differentiation. Further, when injected in vivo, agomiR-let-7f-5p significantly reversed bone loss induced by Dex, as well as increased osteogenic marker expression (Runx2, Osx, Alp, and Ocn) and decreased TGFBR1 expression in bone extracts. These findings indicated that the regulatory axis of GR/let-7f-5p/TGFBR1 may be important for Dex-inhibited osteoblast differentiation and that let-7f-5p may be a useful therapeutic target for GIOP.

17.
Bioresour Technol ; 294: 122218, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31606600

RESUMO

Fermentation slurry from food waste (FSFW) generated by acidogenic fermentation at mesophilic temperature was utilized to improve the nutrients removal from wastewater. Organic acids (such as lactate and volatile fatty acids) in the FSFW behaved as readily biodegradable carbon sources, while the particulate and macromolecular organics acted as slowly biodegradable carbon sources during denitrification processes. The FSFW dosage significantly influenced the nitrogen removal performance, and a C/N ratio (in terms of chemical oxygen demand to nitrogen ratio) of 8 could achieve complete denitrification in the batch tests. In a sequencing batch reactor (SBR) using FSFW for long-term wastewater treatment, extracellular polymeric substances (EPS) gradually accumulated, sludge particle size significantly increased, and microbial communities were selectively enriched, which contributed to promoting the nitrogen (>80%) and phosphate (90.1%) removal efficiencies. Overall, the FSFW produced by acidogenic fermentation under mesophilic temperature served as an excellent intermediary between FW valorization and wastewater treatment.


Assuntos
Eliminação de Resíduos , Águas Residuárias , Reatores Biológicos , Carbono , Desnitrificação , Fermentação , Alimentos , Nitrogênio , Nutrientes , Esgotos , Eliminação de Resíduos Líquidos
18.
Lung Cancer ; 138: 88-94, 2019 Oct 16.
Artigo em Inglês | MEDLINE | ID: mdl-31655368

RESUMO

OBJECTIVE: The purpose of this study was to estimate the cost-effectiveness analysis of pembrolizumab versus chemotherapy as first-line treatment in locally advance or metastatic non-small cell lung cancer (NSCLC) with programmed death ligand 1 (PD-L1) tumor proportion score (TPS) 1% or greater from the United States (US) payer perspective. MATERIALS AND METHODS: This Markov structure was developed to estimate cost and effectiveness of pembrolizumab vs chemotherapy in the first-line treatment of locally advance or metastatic NSCLC based on the data from KEYNOTE-042. Cost and health outcomes were estimated at a willingness-to-pay (WTP) threshold of $150,000 per quality adjusted life year (QALY) in three PD-L1 TPS populations (≥50%, ≥20% and ≥1%). One-way, two-way and probabilistic sensitivity analysis were to test the model stability. Subgroup analysis were performed in three PD-L1 TPS populations (≥50%, ≥20% and ≥1%). RESULTS: The incremental costs and QALYs that pembrolizumab yielded, compared with chemotherapy, were $86164.87 and 0.63, $74562.25 and 0.46 and $70886.65 and 0.39 for the populations with a PD-L1 TPS ≥ 50%, TPS ≥ 20% and TPS ≥ 1%, leading an incremental cost-effective ratio (ICER) of $136,228.82, $160,625.98 and $179,530.17 per QALY, respectively. CONCLUSION: First-line treatment with pembrolizumab is a cost-effective strategy compared with platinum-based chemotherapy when the value of WTP was $150,000 per QALY in locally advanced or metastatic NSCLC patients with PD-L1 TPS ≥ 50% and without epidermal growth factor receptor (EGFR) and anaplastic lymphoma kinase (ALK) mutations, but not in the TPS ≥ 20% and 1% populations.

19.
Opt Express ; 27(16): 23307-23320, 2019 Aug 05.
Artigo em Inglês | MEDLINE | ID: mdl-31510611

RESUMO

Reactive ion etching (RIE) is crucial for fabricating high-quality fused silica optics since this technique can be used as a first step before dynamic chemical etching (DCE) for tracelessly removing the fractured defects in subsurface layer. The final quality of the optics is dramatically influenced by the plasma etching condition but still lacks sufficient information for practical application. In this work, combination of RIE and DCE was investigated deeply on polished fused silica surface by changing the gas type and flow rate. We show that the proper choice of fluorine-containing plasma condition during the RIE process allows the simultaneous occurrence of high surface quality and a low concentration of etching-introduced defects on fused silica. This leads to an ultrahigh laser-induced damage threshold at 355 nm while substantially keeping the surface roughness unchanged. This study paves the way for designing and developing a next-generation surface modification ability of high-quality fused silica with the great potential for high-power laser application.

20.
Top Stroke Rehabil ; : 1-7, 2019 Sep 04.
Artigo em Inglês | MEDLINE | ID: mdl-31483738

RESUMO

Background: Caregivers (CGs) are critical in helping stroke survivors (SSs) retain function and receive adequate healthcare. Objectives: We aimed to identify the activities that CGs are engaged in over the course of stroke care from open-ended SS interviews and explore the association between CG engagement and SS healthcare utilization post-stroke. Methods: We qualitatively analyzed 9-month post-stroke interviews with 118 SSs about their experiences before, during and following acute care from the Caring for Adults Recovering from the Effects of Stroke (CARES) study. We classified each SS as having either an engaged or non-engaged CG based on whether the SS indicated CG involvement in any part of their stroke care. We compared differences between groups in self-reported use of outpatient therapy, home health care, ambulatory care, mental health services, and acute care. Results: SSs who were interviewed most often described CG involvement as driving the SS to the hospital or calling 911 (n = 48; 23.4%), coordinating medical appointments (n = 43; 21.0%) and monitoring recovery (n = 23; 11.2%). SSs with engaged CGs were more likely to see a speech-language pathologist and had more emergency room visits compared to those with non-engaged CGs. No differences were observed after adjusting for stroke severity. Conclusions: Higher rates of healthcare utilization by SSs with engaged CGs may be driven by greater stroke severity and greater need for services. Interestingly, the presence of an engaged CG did not facilitate more care for the SS after adjusting for stroke severity.

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