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1.
Biol Pharm Bull ; 42(9): 1554-1561, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31474715

RESUMO

Obesity, which is characterized by an excessive accumulation of body fat, is one of the critical factors causing metabolic syndrome. Many studies have been performed to identify appropriate agents to control obesity, but toxicity remains a problem. Herein, we identified that phenylbutyrate (PBA), which has been used to treat urea cycle disorder with very low toxicity for a long time, efficiently inhibited high fat-induced body weight gain in a diet-induced obesity mouse model (DIO model). PBA treatment decreased body fat mass and increased lean composition. Moreover, PBA increased brown adipose tissue (BAT) activity by increasing glucose uptake, thereby improving glucose tolerance and insulin tolerance. Interestingly, PBA could induce the expression of liver type phosphofructokinase (PFKL), a key enzyme in the glycolytic pathway, and knocking down PFKL dramatically repressed the expression level of Ucp1 as well as those of Prdm16, Cidea, Pgc1α, and Pparγ, which are marker genes for BAT activation. These results strongly suggested that PBA could increase energy expenditure by increasing BAT activity via the induction of PFKL. Taken together, PBA could be used as a therapeutic agent for people with obesity to prevent the development of metabolic syndrome.

2.
Am J Infect Control ; 2019 Sep 05.
Artigo em Inglês | MEDLINE | ID: mdl-31493935

RESUMO

BACKGROUND: Central line-associated bloodstream infections (CLABSIs) are preventable health care-associated infections that can lead to increased mortality. Therefore, we investigated trends in CLABSI rates, and the factors associated with changing trends over a 10-year period using the Korean National Healthcare-associated Infections Surveillance System (KONIS). METHODS: We investigated annual CLABSI rates from 2006 to 2015 in 190 KONIS-participating intensive care units (ICUs) from 107 participating hospitals. We collected data associated with hospital and ICU characteristics and analyzed trends using generalized autoregressive moving average models. RESULTS: The CLABSI pooled mean rate decreased from 3.40 in 2006 to 2.20 in 2015 (per 1,000 catheter-days). The trend analysis also showed a significant decreasing trend in CLABSI rates in unadjusted models (annual increase, -0.137; P < .001). After adjusting for hospital and ICU characteristics, significant decreasing trends were identified (annual increase, -0.109; P < .001). However, there were no significant changes in subgroups with non-university-affiliated hospitals, hospitals in metropolitan areas near Seoul, small hospitals (300-699 beds), or surgical ICUs. CONCLUSIONS: In South Korea, CLABSI rates have shown significant reductions in the past 10 years with participation in the KONIS. However, CLABSI rates may be reduced by encouraging more hospitals to participate in the KONIS and by improved policy support for hospitals lacking infection control resources.

3.
J Magn Reson Imaging ; 2019 Aug 27.
Artigo em Inglês | MEDLINE | ID: mdl-31456328

RESUMO

BACKGROUND: Magnetic resonance elastography (MRE) using a gradient-recalled echo (GRE) or a recently available spin-echo echo-planar imaging (SE-EPI) sequence is a promising noninvasive method for measuring liver stiffness. However, it sometimes fails to measure stiffness values, thereby resulting in technical failures. PURPOSE: To assess and compare technical failures of MRE for measuring liver stiffness between GRE and SE-EPI sequences. STUDY TYPE: Systematic review and meta-analysis. POPULATION: Eight studies with both GRE and SE-EPI, 22 studies with only GRE, one study with only SE-EPI. FIELD STRENGTH/SEQUENCE: Either 1.5 or 3T MRE using GRE and/or SE-EPI. ASSESSMENT: Through an Ovid-MEDLINE and EMBASE database search, original articles investigating the proportion of MRE technical failures in the measurement of liver stiffness published up until October 2018 were screened and selected. STATISTICAL ANALYSIS: The pooled proportions of technical failures under GRE and SE-EPI were calculated using random-effects meta-analysis of single proportions and inverse variance for calculating weights. Subgroup analyses were performed to explore the covariates affecting heterogeneity. Head-to-head comparisons of technical failure between the sequences were conducted with eight MRE studies using both GRE and SE-EPI. RESULTS: The pooled proportion of technical failure under GRE MRE was 5.8% (95% confidence interval [CI], 4.6-7.4%), and a subgroup analysis showed higher technical failure rates at 3T than at 1.5T. The pooled proportion of technical failure under SE-EPI MRE was 2.0% (95% CI, 1.3-3.4%), without significant differences (P = 0.38-0.89) being observed in the subgroup analyses. In the eight studies comparing the two sequences, failure was more frequently observed with GRE than with SE-EPI (9.4% vs. 1.9%; P < 0.01). DATA CONCLUSION: MRE conducted with SE-EPI sequences showed a lower technical failure rate than GRE sequences. With GRE sequences, a magnetic field of 3T was associated with higher technical failure rates than was 1.5T. LEVEL OF EVIDENCE: 1 Technical Efficacy Stage: 3 J. Magn. Reson. Imaging 2019.

4.
PLoS One ; 14(8): e0220895, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31430319

RESUMO

PURPOSE: To assess changes in clinical practice patterns after implementing diagnosis-related group (DRG) payment system in July 2013 and its effect on the quality of care for pelvic organ prolapse (POP). MATERIALS AND METHODS: Using the 2011-2016 administrative database from National Health Insurance claim data, we reviewed medical information of 7362 patients who underwent hysterectomies for POP in Korean tertiary hospitals. We compared changes in several variables including length of stay, concomitant procedures, outpatient visits and readmission within 30 days after discharge, and retreatment for POP or stress urinary incontinence within postoperative 1 year before and after DRG system. RESULTS: After the introduction of DRG system, the average length of stay decreased (7.74 ± 2.88 to 6.63 ± 2.18 days, p<0.001) without increasing readmission rates. However, the number of outpatient visits increased (2.78±2.33 to 2.98±2.47, p<0.001). Regarding concomitant procedures, the rates of colpopexy and midurethral slings significantly decreased (7.87% and 9.84% to 4.93% and 2.93%, respectively, all p<0.001). Even though there was no difference in the reoperation rates, pessary insertion for recurrent POP significantly increased after the introduction of DRG system (0.10% to 0.38%, p = 0.015). CONCLUSION: The implementation of DRG in Korean tertiary hospitals has led to increase of outpatient visits and reduced surgical management for POP, which indicates that the uniform application of DRG influences the quality of care for POP patients.

5.
Int J Nanomedicine ; 14: 5381-5396, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31409994

RESUMO

Background: Tacrolimus (TCR), also known as FK-506, is a biopharmaceutics classification system (BCS) class II drug that is insoluble in water because of its high log P values. After dermal application, TCR remains in the stratum corneum and passes through the skin layers with difficulty. Purpose: The objectives of this study were to develop and evaluate solid lipid nanoparticles (SLNs) with thermosensitive properties to improve penetration and retention. Methods: We prepared TCR-loaded thermosensitive solid lipid nanoparticles (TCR-SLNs) with different types of surfactants on the shell of the particle, which conferred the advantages of enhancing skin permeation and distribution. We also characterized them from a physic point of view and performed in vitro and in vivo evaluations. Results: The TCR contained in the prepared TCR-SLN was in an amorphous state and entrapped in the particles with a high loading efficiency. The assessment of ex vivo skin penetration using excised rat dorsal skin showed that the TCR-SLNs penetrated to a deeper layer than the reference product (0.1% Protopic®). In addition, the in vivo skin penetration test demonstrated that TCR-SLNs delivered more drug into deeper skin layers than the reference product. FT-IR images also confirmed drug distribution of TCR-SLNs into deeper layers of the skin. Conclusion: These results revealed the potential application of thermosensitive SLNs for the delivery of difficult-to-permeate, poorly water-soluble drugs into deep skin layers.

6.
Drug Des Devel Ther ; 13: 2459-2474, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31413543

RESUMO

Introduction: In this study, a dual release bi-layer tablet containing Fesoterodine fumarate (Fst) 5 mg and Mirabegron (Mrb) 50 mg was prepared to investigate the different release behavior of each drug in bilayer tablet. The bilayer tablet was prepared based on monolayer-tablet formulation of each drug. Methods: The optimized bi-layer tablet showed an in vitro dissolution profile similar to commercial reference tablets Toviaz and Betmiga, based on a satisfactory similarity factor. Drug-release kinetics of each drug in the bilayer tablet were evaluated based on dissolution profiles. Drug-release behavior was evaluated by observing the surface of each layer by scanning electron microscopy and measuring the changes in weight and volume of the tablet during dissolution. Drug transfer between each layer was also investigated by Fourier -transform infrared spectroscopic imaging by observing the cross-section of the bilayer tablet cut vertically during dissolution. Results: The release of Fst was well suited for the Higuchi model, and the release of Mrb was well suited for the Hixson-crowell model. Compared with dissolution rate of each monolayer tablet, that of Fst in the bilayer tablet was slightly reduced (5%), but the dissolution rate of Mrb in bilayer tablet was dramatically decreased (20%). Also, a drug-release study confirmed that polymer swelling was dominant in Fst layer compared with polymer erosion, and degradation was dominant in MRB layer. Fourier-transform infrared imaging and 3-D image reconstruction showed that drug transfer in the bilayer tablet correlates with the results of drug-release behavior. Conclusion: These findings are expected to provide scientific insights in the development of a dual-release bilayer drug-delivery system for Fst and Mrb.

7.
Chem Asian J ; 2019 Jul 24.
Artigo em Inglês | MEDLINE | ID: mdl-31340087

RESUMO

The so-called colloidal template synthesis has been applied to the preparation of surface-engineered nanoadsorbents. Colloidal microporous organic network nanotemplates (C-MONs), which showed a high surface area (611 m2 g-1 ) and enhanced microporosity, were prepared through the networking of organic building blocks in the presence of poly(vinylpyrrolidone) (PVP). Owing to entrapment of the PVP in networks, the C-MONs showed good colloidal dispersion in EtOH. MoS2 precursors were incorporated into the C-MONs and heat treatment afforded core-shell-type C@MoS2 nanoparticles with a diameter of 80 nm, a negative zeta potential (-39.5 mV), a high surface area (508 m2 g-1 ), and excellent adsorption performance towards cationic dyes (qmax =343.6 and 421.9 mg g-1 for methylene blue and rhodamine B, respectively).

8.
Surg Obes Relat Dis ; 15(8): 1348-1354, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31302000

RESUMO

BACKGROUND: The AspireAssist is the first Food and Drug Administration-approved endoluminal device indicated for treatment of class II and III obesity. OBJECTIVES: We earlier reported 1-year results of the PATHWAY study. Here, we report 4-year outcomes. SETTING: United States-based, 10-center, randomized controlled trial involving 171 participants with the treatment arm receiving Aspiration Therapy (AT) plus Lifestyle Therapy and the control arm receiving Lifestyle Therapy (2:1 randomization). METHODS: AT participants were permitted to continue in the study for an additional year up to a maximum of 5 years providing they maintained at least 10% total weight loss (TWL) from baseline at each year end. For AT participants who continued the study, 5 medical monitoring visits were provided at weeks 60, 68, 76, 90, and 104 and thereafter once every 13 weeks up to week 260. Exclusion criteria were a history of eating disorder or evidence of eating disorder on a validated questionnaire. Follow-up weight, quality of life, and co-morbidities were compared with the baseline levels. In addition, rates of serious adverse event, persistent fistula, withdrawal, and A-tube replacement were reported. All analyses were performed using a per-protocol analysis. RESULTS: Of the 82 AT participants who completed 1 year, 58 continued to this phase of the trial. Mean baseline body mass index of these 58 patients was 41.6 ± 4.5 kg/m2. At the end of first year (at the beginning of the follow-up study), these 58 patients had a body mass index of 34.1 ± 5.4 kg/m2 and had achieved an 18.3 ± 8.0% TWL. On a per protocol basis, patients experienced 14.2%, 15.3%, 16.6%, and 18.7% TWL at 1, 2, 3, and 4 years, respectively (P < .01 for all). Forty of 58 patients (69%) achieved at least 10% TWL at 4 years or at time of study withdrawal. Improvements in quality of life scores and select cardiometabolic parameters were also maintained through 4 years. There were 2 serious adverse events reported in the second through fourth years, both of which resolved with removal or replacement of the A tube. Two persistent fistulas required surgical repair, representing approximately 2% of all tube removals. There were no clinically significant metabolic or electrolytes disorders observed, nor any evidence for development of any eating disorders. CONCLUSIONS: The results of this midterm study have shown that AT is a safe, effective, and durable weight loss alternative for people with class II and III obesity and who are willing to commit to using the therapy and adhere to adjustments in eating behavior.

9.
Stem Cell Res ; 39: 101499, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31352199

RESUMO

Pituitary homeobox 3 (Pitx3) is a key transcription factor that plays an important role in the development and maintenance of midbrain dopaminergic (mDA) neurons. Here, we established a PITX3-mCherry knock-in reporter human embryonic stem cell (hESC) line using the CRISPR/Cas9 system. PITX3-mCherry hESCs maintained pluripotency marker expression and exhibited the capacity to generate all 3 germ layers and a normal karyotype. After differentiation into mDA neurons, most PITX3 immunoreactivity overlapped with the red fluorescence of mCherry. This reporter cell line may be used to study the development of mDA neurons or to enrich mDA populations for transplantation.

10.
PLoS One ; 14(7): e0219308, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31269074

RESUMO

In this study, we compared ultrasound (US) features between normal parotid parenchyma (NPP) and incidental diffuse parotid disease (DPD). From January 2008 to December 2017, 180 patients underwent neck US before parotid surgery at our hospital. From these, 82 were excluded because of the lack of histopathological data concerning the parotid parenchyma or inadequate US images. A single radiologist blinded to the clinicoserological data and histopathological results, retrospectively investigated all US features and categorizations for the parotid glands using a picture archiving and communication system. Retrospective histopathological analysis of the parotid parenchyma was performed by a single pathologist. On the basis of the histopathological analyses, the 98 patients were divided into NPP (n = 70) and DPD (n = 28) groups. Among US features, parenchymal echogenicity and echotexture showed statistically significant differences between the two groups (p < 0.0001), whereas the gland size, margin, and vascularity showed no significant differences (p > 0.05). The US-based categorization significantly differentiated between NPP and DPD (p < 0.0001), and receiver operating characteristic curve analysis revealed that US categorization based on ≥2 abnormal US features showed the best diagnostic performance for detecting DPD. Thus, US can aid in differentiating DPD from NPP.

11.
Int J Hematol ; 2019 Jul 15.
Artigo em Inglês | MEDLINE | ID: mdl-31309419

RESUMO

Graft-versus-host disease (GVHD) is a serious complication of allogeneic stem cell transplantation (SCT). Here, we report a rare case of GVHD involving the central nervous system (CNS). A 35-year-old woman was diagnosed with myelodysplastic syndrome unclassifiable and underwent allogeneic peripheral blood SCT for disease progression to myelodysplastic syndrome with excess blasts-2. One year following SCT, she experienced chronic oral and hepatic GVHD symptoms, which were managed with oral steroids and tacrolimus. Sixteen months after SCT, she developed sudden-onset, generalized, tonic-clonic-type seizures. Magnetic resonance imaging and cerebrospinal fluid evaluation showed multiple discrete white lesions and elevated IgG levels. Brain biopsy revealed periventricular plaques with the destruction of axons, representing a demyelinating disease of the CNS. We diagnosed the case as CNS GVHD. Neurologic symptoms gradually improved with methylprednisolone pulse therapy and total plasma exchange combined with a calcineurin inhibitor; the brain lesions nearly disappeared after decreasing steroid maintenance dosage, and were completely resolved 1 year after the onset of CNS GVHD. The patient is CNS GVHD-symptom-free, 3-year post-transplantation. Thus, CNS GVHD should be considered in cases of newly developed neurologic symptoms in SCT recipients showing evidence of preceding chronic GVHD.

12.
J Ethnopharmacol ; : 112082, 2019 Jul 13.
Artigo em Inglês | MEDLINE | ID: mdl-31310829

RESUMO

ETHNOPHARMACOLOGICAL RELEVANCE: Eriobotrya japonica leaves has a very long history of medicinal use as an anti-inflammatory and antitussive agent for bronchial inflammation. AIM OF THE STUDY: The aim of this study was to evaluate the anti-inflammatory activities of Eriobotrya japonica (EJ) leaf water extract in an ovalbumin (OVA)-induced murine asthma model and human tracheal smooth muscle cell (HTSMC). MATERIALS AND METHODS: Mice were sensitized by intra peritoneal OVA and challenged with nebulized OVA. EJ extract was administered orally at various dose. Bronchoalveolar lavage fluid (BALF) was quantified for nitric oxide (NO), eosinophil peroxidase (EPO), interleukin (IL)-4, IL-13 level and immunoglobulin (Ig) E was quantified in serum. Lung tissue sections were stained with hematoxylin and eosin for assessment of inflammatory cell infiltration whereas mucus production and goblet cell hyperplasia were studied by periodic acid schiff staining. Western blot was done for analysis of pERK1/2 expression and NFκB translocation in HTSMC whereas iNOS and COX-2 expression in RAW264.7 cell. RESULTS: EJ significantly reduced the levels of BALF's NO, EPO, MMPs, IL-4, IL-13, and serum IgE. It also decreases inflammatory cell infiltration and mucus production. EJ also attenuated the proliferation of HTSMC, inhibits overexpression of ERK 1/2 and translocation of NFκB in HTSMC as well as iNOS and COX-2 expression in RAW 264.7 cell. CONCLUSION: Present study suggest that, EJ effectively protects against allergic airway inflammation thus possessing potential therapeutic option for allergic asthma management.

13.
Leukemia ; 33(8): 1835-1850, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31209280

RESUMO

Outcomes for patients with chronic myeloid leukemia (CML) have substantially improved due to advances in drug development and rational treatment intervention strategies. Despite these significant advances there are still unanswered questions on patient management regarding how to more reliably predict treatment failure at the time of diagnosis and how to select frontline tyrosine kinase inhibitor (TKI) therapy for optimal outcome. The BCR-ABL1 transcript level at diagnosis has no established prognostic impact and cannot guide frontline TKI selection. BCR-ABL1 mutations are detected in ~50% of TKI resistant patients but are rarely responsible for primary resistance. Other resistance mechanisms are largely uncharacterized and there are no other routine molecular testing strategies to facilitate the evaluation and further stratification of TKI resistance. Advances in next-generation sequencing technology has aided the management of a growing number of other malignancies, enabling the incorporation of somatic mutation profiles in diagnosis, classification, and prognostication. A largely unexplored area in CML research is whether expanded genomic analysis at diagnosis, resistance, and disease transformation can enhance patient management decisions, as has occurred for other cancers. The aim of this article is to review publications that reported mutated cancer-associated genes in CML patients at various disease phases. We discuss the frequency and type of such variants at initial diagnosis and at the time of treatment failure and transformation. Current limitations in the evaluation of mutants and recommendations for future reporting are outlined. The collective evaluation of mutational studies over more than a decade suggests a limited set of cancer-associated genes are indeed recurrently mutated in CML and some at a relatively high frequency. Genomic studies have the potential to lay the foundation for improved diagnostic risk classification according to clinical and genomic risk, and to enable more precise early identification of TKI resistance.

14.
Epilepsy Behav ; 97: 67-74, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31195326

RESUMO

OBJECTIVE: The objective of this trial was to compare the effectiveness of levetiracetam (LEV) and topiramate (TPM) as adjunctive treatment for patients with focal seizures in Korea. METHODS: In this Phase IV, open-label, multicenter trial (NCT01229735), adults were randomized to treatment with LEV (1000-3000 mg/day) or TPM (200-400 mg/day). Only patients achieving LEV ≥1000 mg/day or TPM ≥100 mg/day after a 4-week up-titration entered the 20-week dose-finding and subsequent 28-week maintenance periods. The primary outcome was the 52-week retention rate; others included safety and exploratory efficacy outcomes. RESULTS: Of 343 randomized patients (LEV 177; TPM 166), 211 (61.5%) completed the trial. In the full analysis set (FAS), retention rate was 59.1% with LEV vs 56.6% with TPM (p = 0.7007), while in the prespecified sensitivity analysis, based on data from patients who received drug doses in the recommended range (LEV 176; TPM 113), it was 59.1% with LEV vs 42.5% with TPM (p = 0.0086). In the FAS, median percent reduction in seizure frequency from baseline was 74.47% with LEV and 67.86% with TPM (p = 0.0665); ≥50% responder rate was 69.0% vs 64.8% (p = 0.4205), and the 6-month seizure-freedom rate was 35.8% vs 22.3% (p = 0.0061). In the sensitivity analysis, differences between groups were greater, favoring LEV. Incidences of treatment-emergent adverse events (TEAEs) were 70.6% with LEV vs 77.1% with TPM; most frequently somnolence (20.3%), dizziness (18.1%), and nasopharyngitis (13.6%) with LEV; and decreased appetite (15.7%), dizziness (14.5%), and headache (14.5%) with TPM. Discontinuations due to TEAEs were 7.9% with LEV and 12.7% with TPM. CONCLUSIONS: In this open-label trial, the 52-week retention rate was not significantly different between LEV and TPM. However, LEV was associated with a substantially higher seizure freedom rate and a more favorable safety profile than TPM in this population of Korean patients with focal seizures.

15.
ACS Nano ; 13(6): 7175-7184, 2019 Jun 25.
Artigo em Inglês | MEDLINE | ID: mdl-31149801

RESUMO

With the advent of foldable electronics, it is necessary to develop a technology ensuring foldability when the circuit lines are placed on the topmost substrate rather than in the neutral plane used in the present industry. Considering the potential technological impacts, conversion of the conventional printed circuit boards to foldable ones is most desirable to achieve the topmost circuitry. This study realizes this unconventional conversion concept by coating an ultrathin anisotropic conductive film (UACF) on a printed metal circuit board. This study presents rapid large-area synthesis of hydrogenated amorphous carbon (a-C:H) thin films and their use as the UACF. Since the synthesized a-C:H thin film has electrical transparency, the metal/a-C:H hybrid board reflects the complexity of the underlying metal circuit board. The a-C:H thin film electrically connects the cracked area of the metal line; thus, the hybrid circuit board is foldable without resistance change during repeated folding cycles. The metal/UACF hybrid circuit board can be applied to the fabrication of various foldable electronic devices.

16.
Artigo em Inglês | MEDLINE | ID: mdl-31173897

RESUMO

The absence of relevant guidelines for Wilms tumor 1 (WT1) gene quantification as a measurable residual disease (MRD) assessment for patients with acute myeloid leukemia (AML) undergoing allogeneic hematopoietic stem cell transplantation (allo-HSCT) has limited the widespread use in practice. We investigated optimal time points, thresholds, and candidates for the bone marrow WT1 MRD assay in 425 consecutive patients with AML who underwent allo-HSCT. WT1 expression kinetics before allo-HSCT and at 1 or 3 months after allo-HSCT were determined by real-time PCR using the European LeukemiaNet (ELN) normalized method. Relapsed patients had significantly higher WT1 levels before allo-HSCT and at 3 months after allo-HSCT. The best time point for the WT1 MRD assay was before allo-HSCT by the receiver operating characteristic curve. Among various thresholds, 250 copies recommended from ELN researchers were mostly predictive of post-transplant relapse. In multivariate analysis, WT1 MRD positivity independently predicted relapse, resulting in inferior survival. In subgroup analyses, pretransplant WT1 MRD positivity was predictive of post-transplant relapse in the intermediate group, whereas WT1 MRD positivity occurred at 3 months after allo-HSCT in favorable and adverse risk groups. Among MRD-positive patients before allo-HSCT, all patients who were MRD positive at 3 months relapsed within 6 months. The WT1 MRD assay before allo-HSCT or 3 months after allo-HSCT is useful for predicting post-transplant relapse with a different significance in each risk group by time points, showing the benefit of multiple tests over time. Such monitoring is particularly available in patients with AML without specific molecular targets.

17.
Artigo em Inglês | MEDLINE | ID: mdl-31195137

RESUMO

Patients undergoing hematopoietic stem cell transplantation (HSCT) frequently receive empiric antibiotics during the neutropenic period before engraftment. Several recent studies have shown that anaerobes in the intestine are important mediators of intestinal homeostasis, and that commensal bacteria can be potent modulators of the severity of acute graft-versus-host disease (aGVHD). However, the relationships among the type of antibiotic used during the neutropenic period, changes in the intestinal microbiota, and subsequent occurrence of aGVHD are not clear. In this study, a total of 211 patients undergoing HSCT were stratified into 3 groups: patients not treated with any antibiotics during the neutropenic period (group 1; n = 43), patients treated with cefepime only (group 2; n = 87), and patients treated with carbapenem antibiotics, defined as meropenem or prepenem with or without previous cefepime therapy (group 3; n = 81). Intestinal microbiota analyses were performed on pre- and post-HSCT stool samples, and immunophenotypic analyses were performed on pre- and post-HSCT peripheral blood samples. Among the 211 patients, 95 (45%) developed aGVHD (grade ≥II), including 54 with intestinal GVHD. The incidence of intestinal GVHD was higher in group 3 compared with group 1 and group 2 (32.1%, 11.6%, and 26.4%, respectively; P = .044). After adjusting for potentially significant variables identified by univariate analysis, multivariate analyses identified broad-spectrum antibiotic use during the neutropenic period as associated with the occurrence of intestinal GVHD (hazard ratio, 3.25; 95% confidence interval, 1.13 to 9.34; P = .029). Accordingly, loss of bacterial diversity in terms of alterations in intestinal microbiota after HSCT was observed in patients who received broad-spectrum antibiotics. Moreover, alterations in the frequencies of several intestinal bacteria phyla were associated with the occurrence of intestinal GVHD. Evaluation of circulating immune cell subsets according to type of antibiotic used during the neutropenic period revealed delayed recovery of myeloid-derived suppressor cells in the broad-spectrum antibiotic use group. Our data indicate that the use of broad-spectrum antibiotics during the neutropenic period is associated with a higher incidence of intestinal GVHD via loss of microbiome diversity. Further studies are needed to determine whether maintaining bacterial diversity can help prevent the development of aGVHD.

18.
Endocr Pract ; 2019 Jun 26.
Artigo em Inglês | MEDLINE | ID: mdl-31241363

RESUMO

Objective: This study aimed to evaluate factors influencing the successful maintenance of postoperative euthyroidism in patients who did not undergo immediate thyroid hormone replacement after lobectomy for papillary thyroid microcarcinoma (PTMC). Methods: From September 2015 to June 2017, 186 patients underwent lobectomy for PTMC in our hospital. Patients taking medications for hypothyroidism and hyperthyroidism before and after lobectomy were excluded. Multiple parameters, including sex; age; preoperative free T4, thyroid-stimulating hormone (TSH), thyroglobulin (TG), and thyroid autoantibody levels; body mass index (BMI); postoperative histopathology of the thyroid gland; remnant thyroid gland volume; and session number of levothyroxine discontinuation, were retrospectively evaluated. These factors were compared between groups based on the maintenance of postoperative euthyroidism. Results: In 88 of the 175 patients (50.3%), postoperative euthyroidism was successfully maintained without thyroid hormone replacement during the first year after lobectomy. There were significant differences in sex (p = 0.003), preoperative TSH levels (p = 0.002), and histopathology of the thyroid gland (p = 0.035) between the groups showing maintenance success and failure. The group showing successful maintenance had a higher percentage of male patients, lower levels of preoperative TSH, and normal parenchymal histology of the thyroid gland. However, there were no significant between-group differences in age, preoperative free T4, TG, and thyroid autoantibody levels, BMI, remnant thyroid gland volume, and session number of levothyroxine discontinuation. Conclusion: Patient sex, preoperative TSH levels, and histopathology of the thyroid gland may influence the maintenance of postoperative euthyroidism after lobectomy.

19.
Plant Cell Environ ; 2019 Jun 28.
Artigo em Inglês | MEDLINE | ID: mdl-31250458

RESUMO

Shigella, which infects primates, can be transmitted via fresh vegetables; however, its molecular interactions with plants have not been elucidated. Here, we show that four Shigella strains, Shigella boydii, Shigella sonnei, Shigella flexneri 2a, and S. flexneri 5a, proliferate at different levels in Arabidopsis thaliana. Microscopic studies revealed that these bacteria were present inside leaves and damaged plant cells. Green fluorescent protein (GFP)-tagged S. boydii and S. flexneri 5a colonized leaves only, whereas S. flexneri 2a colonized both leaves and roots. Using Shigella mutants lacking type III secretion systems (T3SSs), we found that T3SSs that regulate the pathogenesis of shigellosis in humans also play a central role in bacterial proliferation in Arabidopsis. Strikingly, the immunosuppressive activity of two T3S effectors, OspF and OspG, was required for proliferation of Shigella in Arabidopsis. Of note, delivery of OspF or OspG effectors inside plant cells upon Shigella inoculation was confirmed using a split GFP system. These findings demonstrate that the human pathogen Shigella can proliferate in plants by adapting immunosuppressive machinery used in the original host human.

20.
Sci Rep ; 9(1): 6994, 2019 May 06.
Artigo em Inglês | MEDLINE | ID: mdl-31061433

RESUMO

The Cox proportional hazards model commonly used to evaluate prognostic variables in survival of cancer patients may be too simplistic to properly predict a cancer patient's outcome since it assumes that the outcome is a linear combination of covariates. In this retrospective study including 255 patients suitable for analysis who underwent surgical treatment in our department from 2000 to 2017, we applied a deep learning-based survival prediction method in oral squamous cell carcinoma (SCC) patients and validated its performance. Survival prediction using DeepSurv, a deep learning based-survival prediction algorithm, was compared with random survival forest (RSF) and the Cox proportional hazard model (CPH). DeepSurv showed the best performance among the three models, the c-index of the training and testing sets reaching 0.810 and 0.781, respectively, followed by RSF (0.770/0.764), and CPH (0.756/0.694). The performance of DeepSurv steadily improved with added features. Thus, deep learning-based survival prediction may improve prediction accuracy and guide clinicians both in choosing treatment options for better survival and in avoiding unnecessary treatments.

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