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1.
Gene ; 722: 144101, 2020 Jan 05.
Artigo em Inglês | MEDLINE | ID: mdl-31479714

RESUMO

The catadromous species, eels, invariably exposed to variable Ca2+ concentrations circumstance i.e., lagoon or ocean. They need to maintain Ca2+ homeostasis by exchanging Ca2+ under different culture conditions. To understand the effects of environmental Ca2+ to fish, three types of genes coding for voltage-dependent L-type calcium channels (cacnb1, 2, 3) were cloned by screening an A. marmorata cDNA library. Tissue distribution analysis of Western blot showed that Cacnb1, 2, 3 had a significantly high expression in gill; while mRNA results showed the expressions of cacnb1 and cacnb3 were predominated in skin tissue but only cacnb2 was expressed in intestine. Serum osmolality and Ca2+ concentrations of A.marmorata were increased in a high calcium environment while reduced in a low calcium environment within 7 days; however, they were not significantly different among Ca2+ treatments after the eels were acclimated for 7 days. We also examined the influence of ambient Ca2+ levels on cacnbs expression of eels. With the increasing of exposure time, mRNA and protein expressions of cacnb1 were up-regulated in high level of Ca2+ (10 mM) and down-regulated in deficient Ca2+ (0 mM) compared to the control Ca2+ (2 mM). However, the opposite results were observed in cacnb2 and cacnb3. Notably, the cacnb2 expression was not significant different among Ca2+ treatments on day 7. Our study provided the insightful evidence that cacnbs play important roles in maintaining Ca2+ homeostasis of fish.


Assuntos
Anguilla/metabolismo , Canais de Cálcio Tipo L/metabolismo , Cálcio/fisiologia , Aclimatação , Anguilla/sangue , Anguilla/genética , Animais , Cálcio/sangue , Canais de Cálcio Tipo L/química , Canais de Cálcio Tipo L/genética , Clonagem Molecular , Brânquias/metabolismo , Concentração Osmolar , RNA Mensageiro/metabolismo , Distribuição Tecidual
2.
J Hazard Mater ; 382: 121023, 2020 Jan 15.
Artigo em Inglês | MEDLINE | ID: mdl-31476717

RESUMO

Pesticide residues pose a great threat to human health, and it is an urgent matter to realize fast and accurate detection of pesticide. SERS (Surface Enhanced Raman Scattering), as a nondestructive detection technology, performs a prominent role in fast detection field due to the strong surface plasmon resonance from short range effect between analyte and nanoparticle. Therefore, in order to solve the incompatibility between organochlorine pesticides molecules and noble metal nanoparticles, this paper proposed a concept of "bridge" substances acting as an interconnect function role to achieve a binding model (object-binder-metal (OBM)) and developed a droplet concentration method to enhance Raman signals. Both combination mode of pesticide molecules to bridge molecules and energy transfer of SERS experiment may relate to the compound ring according to the changes of peaks based on surface plasmon resonance. The selectivity and stability of different bridge substances interacting with pesticides molecules were illumined via binding energy of these two substances obtained by DFT calculations. A droplet can capture nanoparticles and analytes, which is conducive to SERS performance. Chloride ions in the solution contribute to rearrangement of nanoparticles and can validly promote surface activation of Ag nanoparticles to improve energy transfer efficiency of plasma resonance, resulting in superior SERS effect.

3.
J Nanosci Nanotechnol ; 20(3): 1660-1669, 2020 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-31492328

RESUMO

Cu-BTC was synthesised by hydrothermal method in this study to adsorb and remove the toxic heavy metal hexavalent chromium Cr(VI) in water. The EDTA-chitosan/Cu-BTC was prepared by the surface modification of Cu-BTC with EDTA-modified chitosan. The initial concentration effects of adsorbed chromium solution, adsorbent dosage, adsorption time, adsorption temperature and pH of chromium solution on adsorption capacity were estimated using the single-factor optimisation experiment. Results show that the adsorption capacity of the modified composite was higher than that of Cu-BTC. Cu-BTC and EDTA-chitosan/Cu-BTC exhibited significant adsorption of Cr(VI) under acidic conditions in water and basically independent of temperature. Their adsorption processes conformed with the pseudo-second-order model. The Langmuir adsorption isotherm model obtained the adsorption isotherm, which indicated that the adsorption process was single molecule adsorption. Isotherm fitting obtained the maximum adsorption amounts of Cr(VI) for Cu-BTC and EDTA-chitosan/Cu-BTC at 27.32 and 46.51 mg·g-1, respectively. Factor and principal component analyses show that the main factors affecting the adsorption of Cr(VI) in the EDTA-chitosan/Cu-BTC composites are pH, initial concentration and adsorption time. Therefore, EDTA-chitosan-modified Cu-BTC was a more feasible metal-organic framework material than Cu-BTC because of better adsorption performance, which can be used for adsorption removal of Cr(VI) in water.

5.
Environ Microbiol ; 2019 Oct 30.
Artigo em Inglês | MEDLINE | ID: mdl-31667948

RESUMO

Verticillium dahliae is a soil-borne fungus that causes vascular wilt on numerous plants worldwide. The fungus survives in the soil for up to 14 years by producing melanized microsclerotia. The protective function of melanin in abiotic stresses are well documented. Here, we found that the V. dahliae tetraspan transmembrane protein VdSho1, a homolog of the Saccharomyces cerevisiae Sho1, acts as an osmosensor, and is required for plant penetration and melanin biosynthesis. The deletion mutant ΔSho1 was incubated on a cellophane membrane substrate that mimics the plant epidermis, revealing that the penetration of ΔSho1 strain was reduced compared to the wild-type strain. Further, VdSho1 regulates melanin biosynthesis by a signaling mechanism requiring a kinase-kinase signaling module of Vst50-Vst11-Vst7. Strains, ΔVst50, ΔVst7 and ΔVst11 also displayed defective penetration and melanin production like the ΔSho1 strain. Defects in penetration and melanin production in ΔSho1 were restored by overexpression of Vst50, suggesting that Vst50 lies downstream of VdSho1 in the regulatory pathway governing penetration and melanin biosynthesis. Data analyses revealed that the transmembrane portion of VdSho1 was essential for both membrane penetration and melanin production. This study demonstrates that Vst50-Vst11-Vst7 module regulates VdSho1-mediated plant penetration and melanin production in V. dahliae, contributing to virulence. This article is protected by copyright. All rights reserved.

6.
J Ethnopharmacol ; : 112332, 2019 Oct 26.
Artigo em Inglês | MEDLINE | ID: mdl-31669443

RESUMO

ETHNOPHARMACOLOGICAL RELEVANCE: Dahuang Zhechong pill (DHZCP) is a commonly used traditional Chinese medicine for the treatment of hepatocarcinoma. AIM OF THE STUDY: Previous studies have found that DHZCP can exert anti-hepatocarcinoma effects and reverse drug resistance by inhibiting energy metabolism. The goal of this study was to further explore the pharmacodynamic substances that inhibit energy metabolism. METHODS: The components of DHZCP absorbed into plasma were identified by UHPLC-Q-TOF-MS/MS. The Swiss and STITCH databases were used for target collection. The DAVID database was used for pathway enrichment analysis. Cytoscape software was used for network construction. The CCK-8 method detected cell viability. Chemiluminescence was used to detect ATP levels. RESULTS: A total of 89 components absorbed into plasma were identified by UHPLC-Q-TOF-MS/MS. Based on this, 24 potential pharmacodynamic substances were selected by network pharmacology. Among them, 11 components such as rhein can significantly inhibit ATP levels. CONCLUSIONS: Rhein, emodin, chrysophanol, hypoxanthine, baicalein, baicalin, wogonoside, acteoside, formononetin, isoliquiritigenin, and glycyrrhizic acid were the pharmacodynamic substances responsible for inhibition of energy metabolism of DHZCP.

7.
Ecotoxicol Environ Saf ; 188: 109877, 2019 Nov 05.
Artigo em Inglês | MEDLINE | ID: mdl-31704320

RESUMO

Salinity represents a serious environmental threat to crop production and by extension, to world food supply, social and economic prosperity of the developing world. Salicylic acid (SA) is an endogenous plant signal molecule involved in regulating various plant responses to stress. In the present study, we characterized the regulatory role of exogenous SA for their ability to ameliorate deleterious effects of salt stress (0, 100, 150, 200 mM NaCl) in choysum plants through coordinated induction of antioxidants, ascorbate glutathione (AsA-GSH) cycle, and the glyoxalase enzymes. An increase in salt stress dramatically declined root and shoot growth, leaf chlorophyll and relative water content (RWC), subsequently increased electrolyte leakage (EL) and osmolytes accumulation in choysum plants. Salt stress disrupted the antioxidant and glyoxalase defense systems which persuaded oxidative damages and carbonyl toxicity, indicated by increased H2O2 generation, lipid peroxidation, and methylglyoxal (MG) content. However, application of SA had an additive effect on the growth of salt-affected choysum plants, which enhanced root length, plant biomass, chlorophyll contents, leaf area, and RWC. Moreover, SA application effectively eliminated the oxidative and carbonyl stress by improving AsA and GSH pool, upregulating the activities of antioxidant enzymes and the enzymes associated with AsA-GSH cycle and glyoxalase system. Overall, SA application completely counteracted the salinity-induced deleterious effects of 100 and 150 mM NaCl and partially mediated that of 200 mM NaCl stress. Therefore, we concluded that SA application induced tolerance to salinity stress in choysum plants due to the synchronized increase in activities of enzymatic and non-enzymatic antioxidants, enhanced efficiency of AsA-GSH cycle and the MG detoxification systems.

8.
BMJ Open ; 9(10): e027278, 2019 Oct 31.
Artigo em Inglês | MEDLINE | ID: mdl-31676643

RESUMO

OBJECTIVES: The aim of this study was to identify the prevalence of peripherally inserted central catheter (PICC) malposition and the influence of guide wire removal on tip location in PICCs and determine whether related factors, including age, sex, side of insertion and brand of catheter, influence the PICC tip location. SETTING: Single-centre research institute in China recruiting patients from the hospital. PARTICIPANTS: A total of 837 adult patients with inserted PICCs were recruited from October 2016 to May 2017. INTERVENTIONS: This was a cross-sectional study aiming to identify the prevalence of PICC malposition and the influence of guide wire removal on tip location in PICCs. A linear regression model and a variance of factorial design analysis were performed. The PICC tip location was documented on a postinsertion chest X-ray. Multivariable analyses were performed based on the following related factors: age, sex, side of insertion and brand of catheter. RESULTS: The tip location moved a mean of 17.4 mm among the 837 included patients. The prevalence of PICC malposition was 83.6% (700/837), while 16.4% (137/837) of PICCs remained in correct location. The mean movement caused by guide wire removal without an adjusted tail end was (-1.95±26.90) mm. The difference between tail end adjustment movement and actual tip position movement in each PICC was (33.0±17.1) mm in type C, which was significantly higher than the findings for type A (12.8±13.3) mm and type B (12.9±12.7) mm. CONCLUSIONS: PICC malposition is a frequent event. Different catheter brands were associated with different ranges of movement in tip location after guide wire removal. The age and sex of the patients and the insertion side did not influence the extent of movement.

9.
Chemosphere ; 242: 125112, 2019 Oct 22.
Artigo em Inglês | MEDLINE | ID: mdl-31669993

RESUMO

This investigation was made to examine the role of indole-3-acetic acid (IAA), gibberellin A3 (GA3), 6-Benzylaminopurine (6-BA), and 24-epibrassinolide (EBL) in improving stress tolerance and phytoremediation of the cadmium (Cd) and uranium (U) by mustard (Brassica juncea L.). The optimum concentrations of IAA, GA3, 6-BA, and EBL were determined based on plant biomass production, metal uptake, translocation, and removal efficiency. The biomass and total chlorophyll content decreased under Cd and U stress. Nevertheless, the application of IAA, GA3, and 6-BA significantly (p < 0.05) increased the growth and total chlorophyll content of mustard. The malondialdehyde (MDA) and H2O2 content of mustard were enhanced under Cd and U stress, but they were significantly (p < 0.05) decreased in plant growth regulators (PGRs) treatments (except for EBL). PGRs treatments increased activities of antioxidant enzymes such as superoxide dismutase, peroxidase, catalase, and ascorbate peroxidase, thus reducing the oxidative stress. Furthermore, the shoot uptake of Cd and U of IAA and EBL treatments was significantly (p < 0.05) higher than that of other treatments. IAA and EBL also have more significant effects on the translocation and remediation of Cd and U compared to GA3 and 6-BA. The removal efficiency of Cd and U reached the maximum in the 500 mg L-1 IAA treatment, which was 330.77% and 118.61% greater than that in the control (CK), respectively. These results suggested that PGRs could improve the stress tolerance and efficiency of phytoremediation using B. juncea in Cd- and U- contaminated soils.

10.
BMC Microbiol ; 19(1): 240, 2019 Nov 01.
Artigo em Inglês | MEDLINE | ID: mdl-31675928

RESUMO

BACKGROUND: Detection of ceftazidime/avibactam (CAZ/AVI) antibacterial activity is absolutely vital with the rapid growth of carbapenem resistant Enterobacteriaceae (CRE). But now, there is no available automated antimicrobial susceptibility testing card for CAZ/AVI, so Kirby-Bauer has become an economical and practical method for detecting CAZ/AVI antibacterial activity against Enterobacteriaceae. RESULT: In this study, antimicrobial susceptibility testing of CAZ/AVI against 386 Enterobacteriaceae (188 Klebsiella pneumoniae, 122 Escherichia coli, 76 Enterobacter cloacae) isolated from clinical patients was performed by broth microdilution. Of the 386 strains, 54 extended spectrum ß lactamases negative (ESBL(-)), 104 extended spectrum ß lactamases positive (ESBL(+)), 228 CRE. 287 isolates were susceptible to CAZ/AVI and 99 isolates were resistant to CAZ/AVI. At the same time, to obtain optimal content avibactam (AVI) disk containing ceftazidime (30 µg), inhibition zone diameter of four kinds of ceftazidime (30 µg) disk containing different AVI content (0 µg, 10 µg, 25 µg, 50 µg) were tested by Kirby-Bauer method. The microdilution broth method interpretation was used as the standard to estimate susceptible or resistance and then coherence analysis was carried out between Kirby-Bauer and broth microdilution. The result shows the inhibition zone diameter of 30 µg/50 µg disk, susceptible isolates: 20.5 mm-31.5 mm, resistance isolates: 8.25 mm-21.5 mm. The inhibition zone diameter of 30 µg/25 µg disk, susceptible isolates: 19.7 mm-31.3 mm, resistance isolates: 6.5 mm-19.2 mm. The inhibition zone diameter of 30 µg/10 µg disk, susceptible isolates: 19.5 mm-31 mm, resistance isolates: 6.5 mm-11 mm. The inhibition zone diameter of ceftazidime (30 µg), susceptible isolates: 6.5 mm-27.5 mm, resistance isolates 6.5 mm. CONCLUSION: Our results show that 30 µg/50 µg, 30 µg/25 µg, 30 µg/10 µg CAZ/AVI disk have significant statistical differences to determinate CAZ/AVI antibacterial activity, but for 30 µg/50 µg disk, there has a cross section between susceptible isolates (minimum 20.5 mm) and resistance isolates (maximum 21.5 mm). For 30 µg/25 µg disk, it is hard to distinguish the difference between susceptible isolates (minimum 19.7 mm) and resistance isolates (maximum 19.2 mm), so 30 µg/10 µg CAZ/AVI disk is more conducive to determinate antibacterial activity.

11.
Aging (Albany NY) ; 112019 Nov 07.
Artigo em Inglês | MEDLINE | ID: mdl-31697646

RESUMO

Impaired autophagy has been implicated in the pathogenesis of nonalcoholic fatty liver disease. Catalpol (CAT), a bioactive compound from Rehmannia (Di Huang) glutinosa, is known to ameliorate insulin resistance and the histological NAFLD spectrum in obese mice. Here, we investigated the effects of CAT on hepatic steatosis and autophagy in ob/ob and high-fat diet-induced obese mice, as well as in hepatocytes. In ob/ob mice, CAT reduced liver weight, liver triglyceride and cholesterol content, and hepatic lipogenic enzyme levels and increased fatty acid oxidase levels. In addition, CAT administration increased LC3-II levels and decreased SQSTM1/P62 levels in ob/ob mice. Similar effects on hepatic steatosis and autophagy were observed in high-fat diet-induced mice after administration of CAT. Additionally, we found that CAT stimulated AMPK and increased nuclear translocation of transcription factor EB (TFEB) in obese mice and hepatocytes. Inhibition of AMPK completely blocked the effects of CAT on TFEB nuclear localization, hepatic autophagy, and liver steatosis. These findings revealed that diminished AMPK/TFEB-dependent autophagy is involved in the pathogenesis of liver steatosis in obesity, and that CAT might be a novel therapeutic candidate for treatment of this condition.

12.
Viruses ; 11(11)2019 Oct 29.
Artigo em Inglês | MEDLINE | ID: mdl-31671825

RESUMO

Influenza D viruses (IDV) are known to co-circulate with viral and bacterial pathogens in cattle and other ruminants. Currently, there is limited knowledge regarding host responses to IDV infection and whether IDV infection affects host susceptibility to secondary bacterial infections. To begin to address this gap in knowledge, the current study utilized a combination of in vivo and in vitro approaches to evaluate host cellular responses against primary IDV infection and secondary bacterial infection with Staphylococcus aureus (S. aureus). Primary IDV infection in mice did not result in clinical signs of disease and it did not enhance the susceptibility to secondary S. aureus infection. Rather, IDV infection appeared to protect mice from the usual clinical features of secondary bacterial infection, as demonstrated by improved weight loss, survival, and recovery when compared to S. aureus infection alone. We found a notable increase in IFN-ß expression following IDV infection while utilizing human alveolar epithelial A549 cells to analyze early anti-viral responses to IDV infection. These results demonstrate for the first time that IDV infection does not increase the susceptibility to secondary bacterial infection with S. aureus, with evidence that anti-viral immune responses during IDV infection might protect the host against these potentially deadly outcomes.

13.
Reprod Fertil Dev ; 2019 Oct 03.
Artigo em Inglês | MEDLINE | ID: mdl-31578166

RESUMO

Mitochondrial DNA (mtDNA) has been widely associated with complex traits in farm animals. The present study evaluated the effects of mtDNA on litter size in pigs. Mitogenome sequencing of 1017 sows distinguished 232 variations, including 229 single nucleotide polymorphisms and three indels, which constituted 11 haplotypes and further clustered into two haplogroups that differed significantly (P<0.05) in litter size. In order to explain the associations between the effect of haplogroup on litter size and different maternal origins, extant mitogenome sequences were used for phylogenetic or principal component analyses. The results of these analyses led to the identification of two groups, representing Chinese and European origins. The haplotypes corresponding to high litter size were all in the Chinese cluster, whereas haplotypes corresponding to low litter size were all in the European cluster. The results of this study suggest that the effect of haplogroup on litter size in the pig could be caused by diverse maternal origins, and that mtDNA haplogroup may be a marker for genetic selection for pig litter size.

14.
Artigo em Inglês | MEDLINE | ID: mdl-31589566

RESUMO

Toxoplasma gondii is one of protozoan parasites resulting in zoonosis, which can infect nearly all of warm-blooded hosts, including humans and raccoon dogs (Nyctereutes procyonoides). However, related reports on prevalence and genetic characterization of T. gondii strains in raccoon dogs were few in China. The aim of this study was to survey the prevalence and genetic characterization of T. gondii strains in domestic raccoon dogs from Jilin, Liaoning, and Hebei provinces, northern China. During April 2016 to November 2017, a total of 337 tissue samples collected from domestic raccoon dogs were detected with B1 gene using a nested PCR. And the positive samples were genotyped at 11 genetic markers (SAG1, 5'-and 3'-SAG2, alternative SAG2, SAG3, BTUB, GRA6, L358, PK1, c22-8, c29-2, and Apico) using multilocus PCR-restriction fragment length polymorphism technology. Sixteen out of 337 sika deer (4.75%) were positive with B1 gene by nest PCR. Furthermore, four positive DNA samples were completely typed through further being genotyped, in which three samples were identified as ToxoDB Genotype #9, and one sample was confirmed as ToxoDB Genotype #10. The results of molecular detection not only revealed the existence of T. gondii in domestic raccoon dogs in Jilin, Liaoning, and Hebei for the first time, but also provided the information of genetic diversity. This study also indicated that ToxoDB Genotype #9 as a kind of potential reservoir for T. gondii transmission, may be main genotype in domestic raccoon dogs in China, posing a risk of infection in human health.

15.
Artigo em Inglês | MEDLINE | ID: mdl-31588504

RESUMO

CONTEXT: Weight loss is strongly recommended for overweight and obese adults with type 2 diabetes. Unintentional weight loss is associated with increased risk of all-cause mortality, but few studies have examined its association with cardiovascular outcomes in patients with diabetes. OBJECTIVE: To evaluate 2-year weight change and subsequent risk of cardiovascular events and mortality in established type 2 diabetes. DESIGN & SETTING: ADVANCE was an international, multisite 2x2 factorial trial of intensive glucose control and blood pressure control. We examined 5 categories of 2-year weight change: >10% loss, 4-10% loss, stable (± <4%), 4-10% gain, >10% gain. We used Cox regression with follow-up time starting at 2 years, adjusting for intervention arm, demographics, cardiovascular risk factors, and diabetes medication use from the 2-year visit. RESULTS: Among 10,081 participants with valid weight measurements, average age was 66 years. By the 2-year exam, 4.3% had >10% weight loss, 18.4% had 4-10% weight loss, and 5.3% had >10% weight gain. Over the following 3 years of the trial >10% weight loss was strongly associated with major macrovascular events (HR 1.75, 95% CI: 1.26, 2.44), cardiovascular mortality (HR 2.76, 1.87, 4.09), all-cause mortality (HR 2.79, 2.10, 3.79), but not major microvascular events (HR 0.91, 0.61, 1.36), compared to stable weight. There was no evidence of effect modification by baseline BMI, age, or type of diabetes medication. CONCLUSIONS: In the absence of substantial lifestyle changes, weight loss may be a warning sign of poor health meriting further work-up in patients with type 2 diabetes.

16.
Artigo em Inglês | MEDLINE | ID: mdl-31588853

RESUMO

Tissue-engineered graft substitutes have shown great potential to treat large bone defects. While we usually assume that therapeutic approaches developed for appendicular bone healing could be similarly translated for application in craniofacial reconstruction and vice versa, this is not necessarily accurate. In addition to those more well known healing associated factors, such as age, lifestyle (e.g., nutrition and smoking), preexisting disease (e.g., diabetes), medication, and poor blood supply, the developmental origins and surrounding tissue of the wound sites can largely affect the fracture healing outcome as well as designed treatments. Therefore, the strategies developed for long bone fracture repair might not be suitable or directly applicable to skull bone repair. In this review, we discuss aspects of development, healing process, structure, and tissue engineering considerations between calvarial and long bones to assist in designing the tailored bone repair strategies.

17.
J Integr Neurosci ; 18(3): 285-291, 2019 Sep 30.
Artigo em Inglês | MEDLINE | ID: mdl-31601077

RESUMO

The role of miR-361-3p in the pathology of Alzheimer's disease is unknown. The target scan was used to screen potential target genes of miR-361-3p, and ß-site amyloid precursor protein (APP) cleaving enzyme 1 (BACE1) was emphasized. Results from western blotting and reverse transcription-quantitative polymerase chain reaction (RT-PCR) showed that down-regulated miR-361-3p was correlated with up-regulated BACE1 in Alzheimer's disease patients' brains. Luciferase assay confirmed that miR-361-3p directly targets BACE1. MiR-361-3p overexpression and knockdown experiments were performed and found that miR-361-3p could regulate the expression of BACE1, and the accumulation of APP-ß in APPswe transfected SH-SY5Y cell. A Morris water maze test was performed and showed that overexpression of miR-361-3p improved cognitive deficits in APP/PS1 mice. We found miR-361-3p inhibited ß-amyloid accumulation by targeting BACE1, which thus weakened cognitive deficits in Alzheimer's disease.

18.
J Am Geriatr Soc ; 2019 Oct 24.
Artigo em Inglês | MEDLINE | ID: mdl-31647119

RESUMO

OBJECTIVES: Data on the virologic response and tolerability of direct-acting antivirals (DAAs) are lacking in older people because these individuals are underrepresented in clinical trials. This study aimed to assess the effectiveness and tolerability of DAA regimens in older individuals in a large cohort of real-life clinical practice. METHODS: In this retrospective study, patients with chronic hepatitis C infection between 2017 and 2018 were divided into patients aged 65 years and older and those younger than 65 years. We evaluated the sustained virologic response rates (SVRs) in both groups. Further subgroup analyses on the SVRs for patients aged 65 to 74, 75 to 84, and 85 years and older were performed. We also analyzed the predictors of treatment response in older individuals. RESULTS: Among 1151 eligible patients, 516 were in the older group and 635 were in the younger group. The overall treatment response in the entire cohort was 97.7%. A significantly higher percentage of patients presented with advanced stages of fibrosis in the older group (53.1% vs 39.5%; P = <.001). The SVR rates were similar between the two groups (98.3% vs 97.7%; P = .18). In multivariate models, age was not predictive of SVR after adjusting for confounders. Subgroup analyses in the age groups of 65 to 74, 75 to 84, and older than 85 years showed similar treatment response rates (97.4%, 97.2%, and 86.7, respectively; P = .06) and advanced fibrosis (50.8%, 61.5%, and 53.3%, respectively; P = .14). CONCLUSION: Although older people exhibit a significantly higher frequency of fibrosis, DAAs produce high rates of SVR in all age groups, and the age of the patient does not seem to have a significant impact on the efficacy of DAAs including patients in the oldest age category (≥75 y). Treatment should not be withheld in older individuals.

19.
J Appl Lab Med ; 3(4): 580-586, 2019 01.
Artigo em Inglês | MEDLINE | ID: mdl-31639727

RESUMO

BACKGROUND: Procalcitonin (PCT) is a well-established marker for bacterial infection. Recently the US Food and Drug Administration approved the expanded use of this biomarker to guide clinical decisions for antibiotic treatment in patients with lower respiratory tract infections. Both the Architect BRAHMS PCT (PCT-A) and Vidas BRAHMS PCT (PCT-V) are approved for this indication. The aim of this study is to evaluate analytical performance of PCT-A in comparison to PCT-V. METHODS: PCT-A and PCT-V were evaluated for intra- and interassay precision and functional sensitivity. To assess the accuracy of PCT-A, 108 residual plasma specimens were randomly selected from routine hospital orders, and PCT was measured concurrently with PCT-A and PCT-V. RESULTS: Both assays demonstrated excellent precision, with intraassay precision ranging from 2.2% to 4.0% CV and interassay precision ranging from 2.5% to 3.6% CV. The functional sensitivity was verified at 0.01 ng/mL for PCT-A and at 0.05 ng/mL for PCT-V. The Passing-Bablok regression revealed approximately 20% negative bias of PCT-A compared to PCT-V (PCT-A = 0.042 + 0.79 × PCT-V, r = 0.995). The concordance of the 2 methods at diagnostically important cutoffs (0.10, 0.25, 0.50, and 2.0 ng/mL) was excellent, with overall agreement >93% at each threshold. CONCLUSION: The results of our study show improved sensitivity and equivalent clinical performance of PCT-A compared to PCT-V. The availability of this test on common clinical immunoassay analyzers may help accelerate its adoption into antimicrobial stewardship programs and thereby improve antibiotic use and patient outcomes.

20.
Cephalalgia ; : 333102419883374, 2019 Oct 22.
Artigo em Inglês | MEDLINE | ID: mdl-31640402

RESUMO

BACKGROUND: Neurogenic inflammation, mediated by the activation of primary neurons, is thought to be an important factor in migraine pathophysiology. Programmed cell death ligand-1 (PD-L1) can suppress the immune response through the Programmed cell death-1 receptor. However, the role of PD-L1/PD-1 in migraine remains unclear. In this study we evaluated the expression and role of PD-L1/PD-1 in the trigeminal ganglia in an animal model of acute migraine. METHODS: Acute nitroglycerin induces acute mechanical hyperalgesia that can be used as a readout of migraine-like pain. We investigated the expression of PD-L1 and PD-1 in the trigeminal ganglia in a mouse model by means of immunofluorescence labeling, quantitative reverse transcription-polymerase chain reaction and western blotting. We explored the effects of PD-1 in a migraine model by the von Frey test and by analyzing the expression of calcitonin gene-related peptide, interleukin-1ß (IL-1ß), interleukin-18 (IL-18), Tumor Necrosis Factor-α (TNF-α), interleukin-6 (IL-6) and transient receptor potential vanilloid (TRPV4) after the intravenous injection of a PD-1 inhibitor. RESULTS: PD-L1 and PD-1 immunoreactivity were present in healthy trigeminal ganglia neurons. The mRNA levels of PD-L1 and PD-1 were significantly elevated 2 h, 4 h and 6 h after acute nitroglycerin treatment (p < 0.05). The protein levels of PD-L1 were significantly increased 2 h, 4 h and 6 h after treatment, and PD-1 was significantly increased at 2 h and 6 h. The blockade of PD-1 increased acute nitroglycerin-induced hyperalgesia, and this effect was accompanied by a more significant increase in calcitonin gene-related peptide, IL-1ß, TNF-α, IL-6 and IL-18 in the trigeminal ganglia. CONCLUSION: These findings suggest that PD-L1 and PD-1 might inhibit migraine-like pain by downregulating CGRP and inflammatory factors in the trigeminal ganglia. The use of PD-L1 and PD-1 as analgesics should be further studied.

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