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1.
BMC Med ; 18(1): 27, 2020 Feb 14.
Artigo em Inglês | MEDLINE | ID: mdl-32054535

RESUMO

BACKGROUND: Cesarean section (CS) rate has risen dramatically and stayed at a very high level in China over the past two to three decades. Given the short- and long-term adverse effects of CS, effective strategies are needed to reduce unnecessary CS. We aimed to evaluate whether a multifaceted intervention would decrease the CS rate in China. METHODS: We carried out a cluster-randomized field trial with a multifaceted intervention in Shanghai, China, from 2015 to 2017. A total of 20 hospitals were randomly allocated into an intervention or a control group. The intervention consisted of more targeted health education to pregnant women, improved hospital CS policy, and training of midwives/doulas for 8 months. The study included a baseline survey, the intervention, and an evaluation survey. The primary outcome was the changes of overall CS rate from the pre-intervention to the post-intervention period. A subgroup analysis stratified by the Robson classification was also conducted to examine the CS change among women with various obstetric characteristics. RESULTS: A total of 10,752 deliveries were randomly selected from the pre-intervention period and 10,521 from the post-intervention period. The baseline CS rates were 42.5% and 41.5% in the intervention and control groups, respectively, while the post-intervention CS rates were 43.4% and 42.4%, respectively. Compared with the control group, the intervention did not significantly reduce the CS rate (adjusted OR = 0.92; 95% CI 0.73, 1.15). Similar results were obtained in subgroup analyses stratified by the risk level of pregnancy, maternal age, number of previous CS, or parity. Scarred uterus and maternal request remained the primary reasons for CS after the interventions in both groups. The intervention did not alter the perinatal outcomes (adjusted change of risk score = - 0.06; 95%CI - 0.43, 0.31). CONCLUSIONS: A multifaceted intervention including more targeted prenatal health education, improved hospital CS policy, and training of midwives/doulas, did not significantly reduce the CS rate in Shanghai, China. However, our experience in implementing a multifaceted intervention may provide useful information to other similar areas with high CS use. TRIAL REGISTRATION: This trial was registered at the Chinese Clinical Trial Registry (www.chictr.org.cn) (ChiCTR-IOR-16009041) on 17 August 2016.

2.
Eur J Med Chem ; 190: 112080, 2020 Jan 22.
Artigo em Inglês | MEDLINE | ID: mdl-32018094

RESUMO

Disulfide re-bridging strategy has demonstrated significant advantages in the construction of homogeneous antibody drug conjugates (ADCs). However, a major issue that disulfide scrambling at the hinge region of antibody leads to the formation of "half-antibody" has appeared for many re-bridging linkers. We present bis(vinylsulfonyl)piperazines (BVP) as efficient linkers to selectively re-bridge disulfides at the antigen-binding fragment (Fab) regions and produce highly homogeneous conjugates with a loading of two drugs without disulfide scrambling. We also found that optically active (S)-configuration linkers led to more sufficient conjugation compared with (R)-configuration. The BVP-linked ADCs demonstrated superior efficacy and antigen-selectivity in vitro cytotoxicity.

3.
Perit Dial Int ; 40(1): 26-33, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-32063144

RESUMO

BACKGROUND: This study was to analyze the incidence, risk factors, and clinical outcomes of peritonitis in elderly continuous ambulatory peritoneal dialysis (CAPD) patients. METHODS: Incident patients undergone CAPD from 1 January 2006 to 30 June 2015 in our center were enrolled and divided into aged < 65 years and ≥ 65 years groups. Risk factors were evaluated using a logistic regression model, and outcome comparison was evaluated using a Cox proportional model. RESULTS: Among 1953 patients, 111(33.2%) in elderly (n = 334) and 470 (29.0%) in younger (n = 1619) developed at least one episode of peritonitis. Comparing with younger patients, elderly ones had a higher peritonitis rate (0.203 vs. 0.145 episodes/patient-year, p < 0.05). The multivariate Cox regression showed that advanced age (hazard ratio (HR) = 1.06, 95% confidence interval (CI) = 1.01-1.11, p = 0.015), assistant-assisted peritoneal dialysis (PD; HR = 2.64, 95% CI = 1.23-5.64, p = 0.012), higher body mass index (BMI; HR = 1.11, 95% CI = 1.02-1.20, p = 0.010), and low serum albumin level (HR = 0.94, 95% CI = 0.90-0.98, p = 0.004) were associated with increased peritonitis risk in elderly patients. Compared with younger ones with peritonitis, elderly patients had an approximately fourfold increased risk of peritonitis-related mortality (odd ratio (OR) = 3.57, 95% CI = 1.38-9.28, p = 0.009). During the cohort, peritonitis was the risk factor associated with technique failure (HR = 3.19, 95% CI = 2.33-4.39, p < 0.001) in younger patient but not in the elderly population (HR = 1.82, 95% CI = 0.84-3.94, p = 0.132). CONCLUSIONS: Elderly PD patients had higher prevalence for peritonitis and peritonitis-related mortality. Advanced age, assistant-assisted PD, a higher BMI, and lower serum albumin level were independently associated with the first episode of peritonitis in elderly patients. However, peritonitis was not the predictor of death-censored technique failure in elderly ones.

4.
Brain Res Bull ; 2020 Feb 11.
Artigo em Inglês | MEDLINE | ID: mdl-32057952

RESUMO

Interneurons not only contribute to the global balance of activity in cortical networks but also mediate the precise gating of information through specific proteins. Accumulating evidence demonstrates that peroxisome-proliferator-activated receptor-gamma co-activator 1 alpha (PGC-1α) is concentrated in inhibitory interneurons and that it plays an important role in neuropsychiatric diseases. However, the functions of the transcriptional coactivator PGC-1α in sensorimotor gating, short-term habituation and spatial reference memory are still not entirely clear. To investigate the precise involvement of PGC-1α in the progression of psychiatric disorders, we first generated PGC-1α conditional knockout mice through transgenic expression of Cre recombinase under the control of dlx5/6 promoter, Cre-mediated excision events occurred specifically in γ-amino-butyric-acid-(GABA)ergic neurons. Short-term habituation and spatial reference memory in Dlx5/6-Cre-PGC-1αf/f mice were evaluated using the novel object recognition test and the Morris water maze test, and sensorimotor gating was measured by prepulse inhibition of the acoustic startle reflex. Protein expression of parvalbumin (PV) in specific brain regions was studied by western blotting, immunofluorescence and immunohistochemistry. Here, we show that mice lacking the PGC-1α gene in GABAergic neurons exhibit deficits in short-term habituation, hyperactivity, reduced prepulse inhibition and exaggerated startle reactivity but normal associative spatial reference memory. In particular, these mice display aberrant salience, whereby more attention is paid to a further copy of the original object (now familiar) (relative to the first presentation of the original object, and relative to the presentation of the novel object). These behavioral dysfunctions were associated with decreased PV expression in the cortex (including somatosensory and motor cortex) as well as in the hippocampus, especially in its CA1 and CA3 regions. Together, these findings draw attention to a hyper-response phenotype of PGC-1α conditional knockout mice and indicate that PGC-1α is a novel regulator of gene expression and function in PV-positive interneurons and a potential therapeutic target for psychiatric disorders associated with PGC-1α dysregulation.

5.
Nat Struct Mol Biol ; 27(2): 192-201, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-32042150

RESUMO

Point mutations in cysteine string protein-α (CSPα) cause dominantly inherited adult-onset neuronal ceroid lipofuscinosis (ANCL), a rapidly progressing and lethal neurodegenerative disease with no treatment. ANCL mutations are proposed to trigger CSPα aggregation/oligomerization, but the mechanism of oligomer formation remains unclear. Here we use purified proteins, mouse primary neurons and patient-derived induced neurons to show that the normally palmitoylated cysteine string region of CSPα loses palmitoylation in ANCL mutants. This allows oligomerization of mutant CSPα via ectopic binding of iron-sulfur (Fe-S) clusters. The resulting oligomerization of mutant CSPα causes its mislocalization and consequent loss of its synaptic SNARE-chaperoning function. We then find that pharmacological iron chelation mitigates the oligomerization of mutant CSPα, accompanied by partial rescue of the downstream SNARE defects and the pathological hallmark of lipofuscin accumulation. Thus, the iron chelators deferiprone (L1) and deferoxamine (Dfx), which are already used to treat iron overload in humans, offer a new approach for treating ANCL.

6.
Int Immunopharmacol ; 81: 106278, 2020 Feb 09.
Artigo em Inglês | MEDLINE | ID: mdl-32050156

RESUMO

Osteoarthritis (OA) is a chronic inflammatory joint disease characterized by degradation of articular cartilage. Ubiquitin-fold modifier 1 (UFM1)-specific ligase 1 (UFL1) is an UFM1 E3 ligase that has been identified as a regulator of inflammatory response. However, the role of UFL1 in OA remains unknown. The aim of the present study was to explore the function of UFL1 in an in vitro OA system in chondrocytes. Our results showed that UFL1 was lowly expressed in both OA articular tissues and chondrocytes with IL-1ß induction. Ectopic expression of UFL1 improved cell viability of IL-1ß-induced chondrocytes. UFL1 suppressed the production of NO and PGE2, as well the expression levels of iNOS and COX-2 in IL-1ß-induced chondrocytes. The IL-1ß-induced increases in TNF-α and IL-6 levels were attenuated by UFL1. Ectopic expression of UFL1 inhibited the production of extracellular matrix (ECM) degrading enzymes including matrix metalloproteinase 3 (MMP-3), MMP-13, ADAMTS-4 and ADAMTS-5 in chondrocytes with IL-1ß induction. Additionally, UFL1 suppressed IL-1ß-induced activation of NF-κB signaling pathway in chondrocytes. In conclusion, these findings indicated that UFL1 exerted protective effect on IL-1ß-induced chondrocytes. Thus, UFL1 might be a potential target for the treatment of OA.

7.
Ecotoxicol Environ Saf ; 192: 110291, 2020 Feb 12.
Artigo em Inglês | MEDLINE | ID: mdl-32061984

RESUMO

Partially substituting chemical fertilizer with organic manure can aid in the disposal of agricultural wastes via recycling into agricultural land, reduce chemical fertilizer application, and influence nitrogen (N) transformation. However, relatively few studies have investigated the association between soil physicochemical properties, denitrifier communities and N2O emission after short-term substitution of organic manure in vegetable fields. We conducted a short-term vegetable field experiment which included one control treatment (CT, no fertilizer) and three fertilization treatments containing equal amount of total N, phosphorus and potassium (CF, chemical fertilizer only; CMR, chemical fertilizer plus mushroom residue; COM, chemical fertilizer plus cattle manure). The results showed that partial substitution of chemical fertilizer with organic manure greatly increased cumulative N2O emissions, N2O emission factors and yield-scaled N2O emissions by 122-203%, 238-600% and 128-181%, respectively. Compared with the CF treatment, short-term substitution with organic manure reduced the abundance of nirS- and nosZ-type denitrifiers, and increased that of nirK-type denitrifiers. Modeling indicated that nirS abundance, together with soil available N, NIR activity, nirK abundance, SOC, NH4+, and NO3- were the primary factors associated with cumulative N2O emissions. The denitrifier community composition of the CF- treated soil was separated from that of soils treated with CMR and COM, and was primarily influenced by soil NH4+ concentration. NIR activity showed a significant correlation with denitrifier community composition. Overall, short-term substitution of chemical fertilizer with cattle manure (lower C/N ratio) reduced the abundance of nirS- and nosZ-type denitrifiers, but stimulated N2O emission.

8.
J Cell Physiol ; 2020 Feb 04.
Artigo em Inglês | MEDLINE | ID: mdl-32017059

RESUMO

Histone deacetylase 6 (HDAC6) participates in mouse oocyte maturation by deacetylating α-tubulin. However, how HDAC6 expression is regulated in oocytes remains unknown. In the present study, we discovered that mouse oocytes had a high level of HDAC6 expression and a low level of DNA methylation status in their promoter region. Then, a selective HDAC6 inhibitor, tubastatin A (Tub-A) was chosen to investigate the role of HDAC6 in oocyte maturation. Our results revealed that inhibition of HDAC6 caused meiotic progression arrest, disturbed spindle/chromosome organization, and kinetochore-microtubule attachments without impairing spindle assembly checkpoint function. Moreover, inhibition of HDAC6 not only increased the acetylation of α-tubulin but also elevated the acetylation status of H4K16 and decreased the phosphorylation level of H3T3 and H3S10. Conversely, depressed H3T3 phosphorylation by its kinase inhibitor increased the acetylation level of H4K16. Finally, single cell RNA-seq analysis revealed that the cell cycle-related genes CCNB1, CDK2, SMAD3, YWHAZ and the methylation-related genes DNMT1 and DNMT3B were strongly repressed in Tub-A treated oocytes. Taken together, our results indicate that HDAC6 plays important roles in chromosome condensation and kinetochore function via regulating several key histone modifications and messenger RNA transcription during oocyte meiosis.

9.
Sleep Breath ; 2020 Jan 09.
Artigo em Inglês | MEDLINE | ID: mdl-31919715

RESUMO

OBJECTIVE: A new index, approximate entropy (ApEn) of oxygen saturation, was used to assess the severity of hypoxemia in patients with obstructive sleep apnea-hypopnea syndrome (OSAHS), determine the correlation with other parameters, and explore its clinical value. METHODS: A retrospective analysis was performed on 1200 patients with OSAHS and snorers (normal control). All subjects underwent sleep apnea monitoring for 6 h. Subjects were divided into four subgroups by apnea-hypopnea index (AHI): normal control (AHI < 5), mild OSAHS (5 ≤ AHI < 15), moderate OSAHS (15 ≤ AHI < 30), and severe OSAHS 104 (AHI ≥ 30). ApEn was initially compared among the subgroups. Then a correlation analysis of AHI with ApEn and a correlation analysis of ApEn with oxygen desaturation index (ODI), lowest oxygen saturation (LO2), and T < 90% were performed. (2) The AHI was used as the gold standard, and an attempt was performed to determine the value of ApEn to assess the severity of hypoxemia in OSAHS. RESULTS: Among the 1200 subjects, 822 subjects were men (72%) and mean age was 53.2 ± 15.2 years (range 24-95 years). The ApEn in each group was significantly different (P <0.001), and the ApEn synchronously increased with AHI. Furthermore, a significant difference in ApEn was found among the groups (P <0.001). In addition, ApEn had a good correlation with ODI, LO2, and T <90%. According to the ROC analysis results, the boundary value of ApEn to judge OSAHS patients with mild, moderate, and severe hypoxia was 16.72, 17.84, and 20.06, respectively. CONCLUSION: ApEn synchronously increased with the AHI and had a good correlation with AHI, ODI, LO2, and T <90%. These findings suggest that ApEn may have clinical value for assessing hypoxia severity in OSAHS patients.

10.
Brain Res Bull ; 156: 76-85, 2020 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-31931119

RESUMO

OBJECTIVE: Diabetes mellitus (DM) can increase the risk of cognitive dysfunction, but its exact mechanisms remain unclear. The involvement of aberrant O-GlcNAcylation has been identified in hyperglycemia and DM, as well as the pathogenesis of Alzheimer's disease via competition with tau phosphorylation. This study was designed to investigate the role of O-GlcNAcylation in diabetes-associated cognitive dysfunction (DACD). METHODS: Fifteen-week old male KK-Ay mice were used as DACD models, and advanced glycation end product (AGE)-treated HT22 cells were used as a model of high glucose toxicity. Morris water maze tests, histological staining, real-time quantitative PCR, and Western blot were also applied. RESULTS: Mice with DACD exhibited evident obesity, hyperinsulinemia, hyperglycemia, and impaired learning and memory function. O-GlcNAcylation levels decreased and tau phosphorylation levels at Ser396, Ser404, Thr212, and Thr231 increased in the hippocampus of mice with DACD, as well as in AGE-treated HT22 cells. Hypoglycemic therapy improved these anomalies and elevated O-GlcNAc transferase (OGT) levels in mice with DACD. OGT plasmid transfection in HT22 cells partially reversed AGE-induced decreases in O-GlcNAcylation levels and increased tau phosphorylation levels. CONCLUSIONS: Chronic hyperglycemia can induce tau hyperphosphorylation by downregulating OGT-involved O-GlcNAcylation in vivo and in vitro, which mediates DACD.

11.
ACS Appl Mater Interfaces ; 12(3): 3465-3473, 2020 Jan 22.
Artigo em Inglês | MEDLINE | ID: mdl-31913004

RESUMO

The high-resolution technique transmission electron microscopy (TEM), with OsO4 as the traditional fixative, is an essential tool for cell biology and medicine. Although OsO4 has been extensively used, it is far from perfect because of its high volatility and toxicity. Os(II) polypyridyl complexes like [Os(phen)2(dppz)]2+ (phen = 1,10-phenanthroline; dppz = dipyridophenazine) are not only the well-known molecular DNA "light-switches" but also the potential ideal candidates for TEM studies. Here, we report that the cell-impermeable cationic [Os(phen)2(dppz)]2+ can be preferentially delivered into the live-cell nucleus through ion-pairing with chlorophenolate counter-anions, where it functions as an unparalleled enantioselective nuclear DNA imaging reagent especially suitable for correlative light and electron microscopy (CLEM) studies in both living and fixed cells, which can clearly visualize chromosome aggregation and decondensation during mitosis simultaneously. We propose that the chiral Os(II) polypyridyl complexes can be used as a distinctive group of enantioselective high-resolution CLEM imaging probes for live-cell nuclear DNA studies.

12.
Fitoterapia ; 141: 104476, 2020 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-31927012

RESUMO

Gentimilegenins A, B (1, 2), (6R, 8R)-6-hydroxy swerimuslactone A (3), (6R, 8S)-6-hydroxy swerimuslactone A (4), 4-hydroxy roburic acid methyl ester (5), (±) 3'-hydroxy gentioxepine (6), N-heptacosanoyl anthranilic acid (7a), N-nonacosanoyl anthranilic acid (7b), together with 40 known compounds were isolated from the roots of Gentiana macrophylla Pall. Their structures were elucidated on the basis of comprehensive analysis of HRESIMS, IR, 1D-, 2D-NMR and X-ray diffraction. The anti-inflammatory effects of selected compounds were also evaluated through the detection of their inhibitory effects on NO production in LPS-induced RAW264.7 macrophage cells.

13.
Carbohydr Polym ; 230: 115650, 2020 Feb 15.
Artigo em Inglês | MEDLINE | ID: mdl-31887904

RESUMO

Chondroitin sulfate (CS) is a naturally derived bioactive macromolecule and the major component of extracellular matrix (ECM), which widely distributed in various organisms and has attracted much attention due to their significant bioactivities. It is regarded as a favorable biomaterial that has been applied extensively in field of drug delivery and tissue engineering due to its property of non-poisonous, biodegradation, biocompatible and as a major component of ECM. The present article reviews the structure and bioactivities of CS, from the preparation to structure analysis, and emphatically focuses on the biomaterial exertion in delivery system and tissue engineering. At the same time, the present application status and prospect of CS are analyzed and the biomaterial exertion of CS in delivery system and various tissue engineering are also comparatively discussed in view of biomaterial development.

14.
Magn Reson Med ; 2020 Jan 23.
Artigo em Inglês | MEDLINE | ID: mdl-31975432

RESUMO

PURPOSE: To develop and test the feasibility of a sub-3-minute imaging strategy for non-contrast evaluation of the extracranial carotid arteries using ungated quiescent interval slice-selective (QISS) MRA, combining single-shot radial sampling with deep neural network-based image processing to optimize image quality. METHODS: The extracranial carotid arteries of 12 human subjects were imaged at 3 T using ungated QISS MRA. In 7 healthy volunteers, the effects of radial and Cartesian k-space sampling, single-shot and multishot image acquisition (1.1-3.3 seconds/slice, 141-423 seconds/volume), and deep learning-based image processing were evaluated using segmental image quality scoring, arterial temporal SNR, arterial-to-background contrast and apparent contrast-to-noise ratio, and structural similarity index. Comparison of deep learning-based image processing was made with block matching and 3D filtering denoising. RESULTS: Compared with Cartesian sampling, radial k-space sampling increased arterial temporal SNR 107% (P < .001) and improved image quality during 1-shot imaging (P < .05). The carotid arteries were depicted with similar image quality on the rapid 1-shot and much lengthier 3-shot radial QISS protocols (P = not significant), which was corroborated in patient studies. Deep learning-based image processing outperformed block matching and 3D filtering denoising in terms of structural similarity index (P < .001). Compared with original QISS source images, deep learning image processing provided 24% and 195% increases in arterial-to-background contrast (P < .001) and apparent contrast-to-noise ratio (P < .001), and provided source images that were preferred by radiologists (P < .001). CONCLUSION: Rapid, sub-3-minute evaluation of the extracranial carotid arteries is feasible with ungated single-shot radial QISS, and benefits from the use of deep learning-based image processing to enhance source image quality.

15.
Bioorg Chem ; 95: 102927, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31931286

RESUMO

Three new methylated Δ8-pregnene steroids, stemphylisteroids A-C (1-3) were isolated from the medicinal plant Polyalthia laui-derived fungus Stemphylium sp. AZGP4-2. Their structures were elucidated by the detailed analysis of comprehensive spectroscopic data. The absolute configuration of 1 was determined by X-ray crystallographic analysis. Compound 1 show antibacterial activity against Escherichia coli with the MIC value of 6.25 µg/mL, and 2 exhibited a broad spectrum of antibacterial activities against six pathogenic bacteria with the MIC values ranging from 12.5 to 50 µg/mL. The discovery of three methylated Δ8-pregnene steroids 1-3 are a further addition to diverse and complex array of methylated steroids.

16.
Cell Cycle ; 19(3): 354-362, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-31910069

RESUMO

The smallest histone deacetylase (HDAC) and the solely member of class IV, HDAC11, is reported to regulate mitosis process and tumorigenesis, yet its roles in meiosis process remain unknown. In the present study, we first analyzed the expression of HDAC11 in mouse oocytes. HDAC11 showed gradual lower expression from GV (Germinal Vesicle) to MII (Metaphase II) stage oocytes. Then, the specific inhibitor of HDAC11, JB3-22 was used to explore the role of HDAC11 during mouse oocytes maturation. We found that inhibition of HDAC11 significantly interrupted mouse oocytes meiosis progress, caused abnormal spindle organization and misaligned chromosomes, impaired kinetochore-microtubule attachment and spindle assembly checkpoint (SAC) function. Moreover, HDAC11 inhibition significantly increased the acetylation level of α-tubulin that is associated with microtubule stability, and increased acetylation level of H4K16 that is important for kinetochore function. In conclusion, our study indicates that HDAC11 is an essential factor for oocytes maturation and it promotes meiotic process most likely though decreasing acetylation status of α-tubulin and H4K16.

17.
J Pediatr Gastroenterol Nutr ; 70(1): 121-126, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31651801

RESUMO

BACKGROUND: Post-endoscopic retrograde cholangiopancreatography (post-ERCP) pancreatitis (PEP) is reported to occur in up to 11% of pediatric patients. To date, no study has prospectively evaluated an intervention to prevent PEP in children. It is unclear if such a study is even feasible. OBJECTIVE: The aim of the study was to evaluate the feasibility of studying IV ibuprofen for PEP prevention in the pediatric population. METHODS: This was a prospective randomized double-blind placebo-controlled feasibility study. Patients younger than 19 years of age undergoing ERCP were randomized to receive 10 mg/kg IV ibuprofen (max of 800 mg) or placebo (saline) at the time of ERCP. The primary outcome was PEP. Secondary outcomes included post-ERCP-related bleeding, rates of other procedural and medication-related adverse events. RESULTS: Fifty-eight patients were randomized and received either IV ibuprofen or placebo. Preprocedure- and procedure-related factors were not significantly different between the groups except that patients in the placebo group tended to weigh less (48.7 vs 63.7 kg, P = 0.03). There were 7 episodes of PEP (12%). PEP was less frequently identified in the Ibuprofen group than in the control group (7% vs 17%), but this was not statistically significant (P = 0.42). Mean postprocedural abdominal pain scores were significantly lower in the IV Ibuprofen group than in the control group (1.1 vs 3.1, P = 0.01) and the number of patients who had increased abdominal pain after the procedure was significantly lower in ibuprofen group than in the control group (3% vs 38%, P = 0.002). There were no significant differences in procedure-related or drug-related adverse events. CONCLUSIONS: Postprocedural pain scores and the number of patients who had increased abdominal pain after the procedure were significantly lower in the IV ibuprofen group. The current study provides encouraging, but only very weak evidence that IV ibuprofen decreases PEP in children. Power analysis suggests that a small handful of high-volume pediatric centers would be able to perform an adequate clinical trial in a reasonable time frame. Focusing on all cause postprocedural pain (PEP and non-PEP) may allow for a more efficiency study design and be just as clinically relevant.

18.
Pediatr Crit Care Med ; 21(1): 59-66, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31568262

RESUMO

OBJECTIVES: To elucidate etiologies, treatment, functional and neurocognitive outcomes of children with new-onset refractory status epilepticus. DESIGN: A single-center retrospective study. SETTING: A tertiary care children's hospital. PATIENTS: All patients between 1 month and 21 years old admitted with new-onset refractory status epilepticus between January 2004 and July 2017. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Clinical presentation, laboratory data, imaging studies, and treatments were collected during hospitalization. Outcomes were assessed at hospital discharge and follow-up in the outpatient neurology clinic based on functional and neurocognitive outcomes as well as development of epilepsy. A total of 674 unique patients presented with status epilepticus of which 40 had new-onset refractory status epilepticus. Patients were classified into either refractory status epilepticus or super-refractory status epilepticus. The etiology of most children with new-onset refractory status epilepticus remained cryptogenic. The most common identified etiology was viral (20%). None of the patients had a contributory positive neuronal antibody test. Several treatments were tried including immunotherapy which was used in half of the patients. Five patients died (12.5%) during the acute phase of their disease, with four lost to follow-up. Twenty out of the remaining 31 patients (65%) developed epilepsy and 18 (58%) had persistent neurocognitive impairment. There was no statistical significant difference in various outcome measures and various etiologies, patients' characteristics, and treatments. CONCLUSIONS: In this single-center cohort, more than half of the children with new-onset refractory status epilepticus did not have an identifiable etiology. Unlike adult patients, the presence of positive neuronal antibody syndrome was rare. There was no difference in outcome between those with or without an identifiable etiology. As expected, patients with super-refractory status epilepticus had worse functional and neurocognitive outcomes. More standardized diagnostic and treatment algorithms are needed along with prospective multicenter studies.

19.
Dev Comp Immunol ; 104: 103567, 2020 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-31830501

RESUMO

Galectins are members of evolutionary conserved lectin family and play important roles in the innate and adaptive immunity of both vertebrates and invertebrates. Galectin-3 is the only chimera galectin with one C-terminal carbohydrate recognition domain (CRD) connected to the N-terminal end. Here, a galectin-3 (named CiGal3) from grass carp was identified and characterized, which encodes polypeptides 362 amino acids with a predicted molecular mass of 36.45 kDa and theoretical isoelectric point of 4.91. The sugar binding motifs involved in carbohydrate binding activity (H-N-R, V-N and W--E-R) were detected in CRD. In comparison to other species, CiGal3 showed the highest similarity and identity to Cyprinus carpio (95.3% sequence similarity and 92.5% sequence identity). The subcellular localization of CiGal3 was distributed in the cytoplasm and nucleus of transfected cells. The CiGal3 transcripts were ubiquitously expressed in all checked tissues and highly expressed in immune tissues. In addition, the expression of CiGal3 in liver and spleen was induced post grass carp reovirus (GCRV), lipopolysaccharide (LPS), and polyinosinic:polycytidylic acid (poly I:C) challenge. These results suggest that CiGal3 plays a vital role in the immune system.

20.
Arch Virol ; 165(3): 709-714, 2020 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-31873767

RESUMO

Duck Tembusu virus (DTMUV) has caused significant economic losses in China since 2010. However, there is still a lack of effective methods to diagnose the disease caused by this virus, and especially to differentiate infection from vaccination. In this study, we established a novel indirect enzyme-linked immunosorbent assay (iELISA) and performed a retrospective serological survey for DTMUV in Anhui province, China. Our results show that the iELISA displayed high specificity sensitivity, and with no serological cross-reaction with other duck pathogens. These findings indicate that the newly developed iELISA could be a useful screening tool for large-scale monitoring of the epidemiology of DTMUV infection in ducks.

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