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Clinical Research
[Intratympatic budesonide injection for treatment of refractorysudden sensorineural hearing loss].
May 21, 2018   Lin Chuang Er Bi Yan Hou Tou Jing Wai Ke Za Zhi = Journal Of Clinical Otorhinolaryngology, Head, And Neck Surgery
Sun RX, Zhao Y, Liu J
[Intratympatic budesonide injection for treatment of refractorysudden sensorineural hearing loss].
May 21, 2018
Lin Chuang Er Bi Yan Hou Tou Jing Wai Ke Za Zhi = Journal Of Clinical Otorhinolaryngology, Head, And Neck Surgery
Objective:To investigate intratympanic steroid injection for treatment of sudden sensorineural hearing loss after failure of initial systemic therapy,and discuss the role of steroid in refractory sudden sensorineural hearing loss.Method:We included 90 patients who did not response to initial systemic therapy of sudden hearing loss.This research adopted the randomized,controlled trial of clinical research.Ninety qualified patients were divided into 3 groups,30 for each group,intratympanic budesonide for experimental group,dexamethasone for control group-1 while control group-2 did not take intratympanic steroid injection but continue another round of systemic therapy.Intratympanic injection was performed 3 times a week and last for 2 weeks.Alprostadil,mecobalamin,ginkgo biloba extract injection,PNS injection and intravenous hyperbaric oxygen fluid were used for consecutive 10 days in the control group-2.Pure tone audiometry and speech Discrimination Score was retaken at the end of each therapy.Result:The results show that the average PTA of damaged frequencies improved more than 10 dB was considered significant,we had 26.7%(8/30) patients meet this criteria in experiment group,30.0%(9/30) in the control group-1 and 6.7%(2/30) in the control group-2.And the recovery rate between these 3 groups is statistically significant(P<0.05),the average PTA improvement in the experimental group,control group-1 and control-2 was(5.0±11.1)dB,(4.2±12.5)dB and (0±3.33)dB respectively,P<0.05,control group-2 was significantly different from control group-1 and experimental group.The Speech Discrimination Score improvement rates in the experimental group,control group-1 and control-2 was 16.7%,12.0% and 4.2% respectively,but the difference in those 3 groups was not significant.Conclusion:Budesonide intratympanic injection is a save method in treating refractory sudden hearing loss ,and it is as effective as dexamethasone.Intratympanic steroids could be an option for refractory sudden sensorineural hearing loss patients.
Genome-wide haplotype association analysis of primary biliary cholangitis risk in Japanese.
May 22, 2018   Scientific Reports
Im C, Sapkota Y, Moon W, Kawashima M, Nakamura M, Tokunaga K, Yasui Y
Genome-wide haplotype association analysis of primary biliary cholangitis risk in Japanese.
May 22, 2018
Scientific Reports
Primary biliary cholangitis (PBC) susceptibility loci have largely been discovered through single SNP association testing. In this study, we report genic haplotype patterns associated with PBC risk genome-wide in two Japanese cohorts. Among the 74 genic PBC risk haplotype candidates we detected with a novel methodological approach in a discovery cohort of 1,937 Japanese, nearly two-thirds were replicated (49 haplotypes, Bonferroni-corrected P 
Association of childhood adiposity measures with adulthood knee cartilage defects and bone marrow lesions: a 25-year cohort study.
May 28, 2018   Osteoarthritis And Cartilage
Meng T, Thayer S, Venn A, Wu F, Cicuttini F, March L, Dwyer T, Halliday A, Cross M, Laslett LL, Jones G, Ding C, Antony B
Association of childhood adiposity measures with adulthood knee cartilage defects and bone marrow lesions: a 25-year cohort study.
May 28, 2018
Osteoarthritis And Cartilage
OBJECTIVE: To describe the associations between childhood adiposity measures and adulthood knee cartilage defects and bone marrow lesions (BMLs) measured 25 years later. METHODS: 327 participants from the Australian Schools Health and Fitness Survey (ASHFS) of 1985 (aged 7-15 years) were followed up 25 years later (aged 31-41 years). Childhood measures (weight, height and skinfolds) were collected in 1985. Body mass index (BMI), overweight status and fat mass were calculated. Participants underwent 1.5 T knee magnetic resonance imaging (MRI) during 2008-2010, and cartilage defects and BMLs were scored from knee MRI scans. Log binomial regressions were used to examine the associations. RESULTS: Among 327 participants (47.1% females), 21 (6.4%) were overweight in childhood. Childhood adiposity measures were associated with the increased risk of adulthood patellar cartilage defects (Weight relative risk (RR) 1.05/kg, 95% confidence interval (CI) 1.01-1.09; BMI 1.10/kg/m2, 1.01-1.19; Overweight 2.22/yes, 1.21-4.08; fat mass 1.11/kg, 1.01-1.22), but not tibiofemoral cartilage defects. Childhood adiposity measures were not significantly associated with adulthood knee BMLs except for the association between childhood overweight status and adulthood patellar BMLs (RR 2.87/yes, 95% CI 1.10-7.53). These significant associations persisted after adjustment for corresponding adulthood adiposity measure. CONCLUSION: Childhood adiposity measures were associated with the increased risk of adulthood patellar cartilage defects and, to a lesser extent, BMLs, independent of adulthood adiposity measures. These results suggest that adiposity in childhood has long-term effects on patellar structural abnormalities in young adults.
Humanin Analogue (HNG) Enhances the Protective Effect of Dexrazoxane against Doxorubicin-induced Cardiotoxicity.
May 18, 2018   American Journal Of Physiology. Heart And Circulatory Physiology
Lue Y, Gao C, Swerdloff RS, Hoang J, Avetisyan R,   . . . . . .   , Zhang Y, Chen M, Song Y, Wang Y, Wang C
Humanin Analogue (HNG) Enhances the Protective Effect of Dexrazoxane against Doxorubicin-induced Cardiotoxicity.
May 18, 2018
American Journal Of Physiology. Heart And Circulatory Physiology
The chemotherapeutic effect of Doxorubicin (Dox) is limited by cumulative dose-dependent cardiotoxicity in cancer survivors. Dexrazoxane (DRZ) is approved to prevent Dox-induced cardiotoxicity. Humanin and its synthetic analog HNG have cytoprotective effect on the heart. To investigate the cardioprotective efficacy of HNG alone or in combination with DRZ against Dox-induced cardiotoxicity, eighty adult male mice were randomly divided into 8 groups to receive the following treatments via intraperitoneal injection: saline daily; HNG (5mg/kg) daily; DRZ (60mg/kg) weekly; Dox (3mg/kg) weekly; DRZ+HNG, Dox+HNG; Dox+DRZ and Dox+HNG+DRZ. Echocardiogram was performed before and at 4, 8 and 9.5 weeks after beginning of treatment. All mice were euthanized at 10 weeks. In the absence of Dox, HNG, DRZ or DRZ+HNG had no adverse effect on the heart. Dox treatment caused decreases in ejection fraction and cardiac mass, and increases in cardiomyocyte apoptosis and intracardiac fibrosis. HNG or DRZ alone blunted the Dox-induced decrease in left ventricle posterior wall thickness and modestly ameliorated Dox-induced decrease in ejection fraction. HNG+DRZ significantly ameliorated Dox-induced decreases in ejection function, cardiac fibrosis, and cardiac mass. Using a targeted analysis for the mitochondrial gene array and protein expression in heart tissues, we demonstrated that HNG+DRZ reversed DOX-induced altered transcripts that were biomarkers of cardiac damage and uncoupling protein 2. We conclude that HNG enhances the cardiac protective effect of DRZ against Dox-induced cardiotoxicity. HNG+DRZ protects mitochondria from Dox-induced cardiac damage and blunts the onset of cardiac dysfunction. Thus, HNG may be an adjuvant to DRZ in preventing Dox-induced cardiotoxicity.
Blood-based biomarkers in breast cancer: From proteins to circulating tumor cells to circulating tumor DNA.
May 22, 2018   Tumour Biology : The Journal Of The International Society For Oncodevelopmental Biology And Medicine
Duffy MJ, McDermott EW, Crown J
Blood-based biomarkers in breast cancer: From proteins to circulating tumor cells to circulating tumor DNA.
May 22, 2018
Tumour Biology : The Journal Of The International Society For Oncodevelopmental Biology And Medicine
Biomarkers are the key to personalized treatment in patients with breast cancer. While tissue biomarkers are most useful in determining prognosis and upfront predicting response to therapy, circulating protein biomarkers such as CA 15-3 and carcinoembryonic antigen are mainly used in monitoring response to endocrine or chemotherapy in patients with advanced disease. Although several centers measure biomarkers in asymptomatic patients following curative surgery for primary breast cancer, the clinical utility of this practice is unclear. Promising new biomarkers for breast cancer include circulating tumor DNA and circulating tumor cells. In contrast to circulating protein biomarkers, measurement of circulating tumor DNA-based biomarkers is potentially useful in identifying mechanisms of resistance to ongoing therapies as well as identifying new targets for further treatment. To increase clinical utility, both the established and emerging circulating biomarkers should where possible be incorporated into randomized trials evaluating new therapies in patients with breast cancer.
Blood-flow restricted resistance training in patients with sporadic inclusion body myositis: a randomized controlled trial.
May 18, 2018   Scandinavian Journal Of Rheumatology
Jørgensen AN, Aagaard P, Frandsen U, Boyle E, Diederichsen LP
Blood-flow restricted resistance training in patients with sporadic inclusion body myositis: a randomized controlled trial.
May 18, 2018
Scandinavian Journal Of Rheumatology
OBJECTIVES: To investigate the effect of 12 weeks of low-load blood-flow restricted resistance (BFR) training on self-reported and objective physical function, and maximal muscle strength in patients with sporadic inclusion body myositis (sIBM). METHOD: Twenty-two patients with sIBM were randomized into a training group (BFR group) or a non-exercising control group, according to CONsolidated Standards Of Reporting Trials (CONSORT) guidelines. The BFR group performed 12 weeks of BFR training twice per week. The primary outcome was the physical function domain of the 36-item Short Form Health Survey (pf-SF-36), which was used to measure self-reported physical function. All patients performed physical function tests (2-Minute Walk Test, Timed Up and Go, and 30-Second Chair Stand), completed the Inclusion Body Myositis Functional Rating Scale (IBMFRS), and were tested for isolated knee extensor muscle strength. RESULTS: No effects of the training intervention were observed for pf-SF-36 or the objective physical function tests. Leg muscle strength decreased in controls (-9.2%, p = 0.02), but was unaltered in the BFR group (+0.9%, p = 0.87), resulting in a between-group difference in the per-protocol analysis (p = 0.026). Between-group differences in baseline to follow-up changes emerged for IBMFRS, in favour of the BFR group (p = 0.018). CONCLUSION: Twelve weeks of BFR training did not improve self-reported or objective physical function in these sIBM patients. However, the training protocol had a preventive (retaining) effect on the disease-related decline in leg muscle strength, which may aid the long-term preservation of physical function and postpone the need for healthcare assistance.
[Advertent problems about gastric stump cancer surgery].
May 18, 2018   Zhonghua Wei Chang Wai Ke Za Zhi = Chinese Journal Of Gastrointestinal Surgery
Liang H
[Advertent problems about gastric stump cancer surgery].
May 18, 2018
Zhonghua Wei Chang Wai Ke Za Zhi = Chinese Journal Of Gastrointestinal Surgery
Due to different disease background of gastric stump cancer(GSC) patients (benign or malignant lesion, reconstruction of digestive tract, etc.), the GSC surgical procedure and the difficulty of lymphadenectomy are also different. The extent of radical lymphadenectomy for gastric stump cancer should extend beyond D2 lymphadenectomy, according to the different backgrounds of initial disease, reconstructions, and tumor location. A lymphadenectomy should include the lymph nodes in anterior (No.17) and posterior (No.13) surface of the pancreatic head, along the superior mesenteric vein (No.14v), jejunal mesenteric lymph nodes, the splenic hilum (No.10), infra-diaphragm (No.19), esophageal hiatus of the diaphragm(No.20), para-esophageal nodes in the lower thorax (No.110) and supra-diaphragm (No.111). To achieve R0 resection, combined adjacent organ (transverse colon and spleen) resection is necessary in some cases. The indication for endoscopic submucosal dissection of early remnant gastric cancer is similar to primary early gastric cancer in selected patients. The advantages of laparoscopic and robot-assisted surgery for early remnant gastric cancer need to be confirmed through multicenter studies. Compared with primary proximal gastric cancer, remnant gastric cancer showed an equivalent survival rate. Roux-en-Y is the first choice for digestive tract reconstruction.
Long-term Schneiderian membrane thickness changes following zygomatic implant placement: A retrospective radiographic analysis using cone beam computed tomography.
May 18, 2018   Clinical Oral Implants Research
Zhao K, Lian M, Fan S, Huang W, Wang F, Wu Y
Long-term Schneiderian membrane thickness changes following zygomatic implant placement: A retrospective radiographic analysis using cone beam computed tomography.
May 18, 2018
Clinical Oral Implants Research
OBJECTIVES: The purpose of this retrospective study was to evaluate the long-term changes in the thickness of Schneiderian membranes after zygomatic implant placement using cone beam computed tomography (CBCT). MATERIAL AND METHODS: Twenty-five consecutive patients were included in this study. All the patients underwent bilateral zygomatic implant placement. Schneiderian membrane thickness (SMT) in 49 maxillary sinuses (one sinus was not included because of early loss of the zygomatic implants) was measured using CBCT before and at least 1 year after zygomatic implant placement. Ostium patency of each sinus was also evaluated and recorded. RESULTS: In total, 84 zygomatic implants and 30 regular implants were placed in included patients. Two unilateral maxillary zygomatic implants in one patient were removed 2 months after implant placement. The SMT increased from 1.03 mm (inter-quartile range: 1.57 mm) to 1.33 mm (inter-quartile range: 1.98 mm) after a median follow-up time of 23.00 months (inter-quartile range: 14 months), and the difference was statistically significant. Before zygomatic implant insertion, 24.5% (12/49) of sinuses had SMT greater than 2 mm, whereas this value was 28.6% (14/49) after zygomatic implant placement. The percentage of sinuses observed with ostium patency also increased from 2.0% (1/49) to 12.2% (6/49). CONCLUSIONS: Chronic Schneiderian membrane thickening could result from zygomatic implant insertion. Intensive postoperative care and clinical and radiographic monitoring are recommended after zygomatic implant placement.
Analysis of type 2 diabetes and obesity genetic variants in Mexican Pima Indians: Marked allelic differentiation among Amerindians at HLA.
May 22, 2018   Annals Of Human Genetics
Hsueh WC, Bennett PH, Esparza-Romero J, Urquidez-Romero R, Valencia ME, Ravussin E, Williams RC, Knowler WC, Baier LJ, Schulz LO, Hanson RL
Analysis of type 2 diabetes and obesity genetic variants in Mexican Pima Indians: Marked allelic differentiation among Amerindians at HLA.
May 22, 2018
Annals Of Human Genetics
Prevalence of diabetes and obesity in Mexican Pima Indians is low, while prevalence in US Pima Indians is high. Although lifestyle likely accounts for much of the difference, the role of genetic factors is not well explored. To examine this, we genotyped 359 single nucleotide polymorphisms, including established type 2 diabetes and obesity variants from genome-wide association studies (GWAS) and 96 random markers, in 342 Mexican Pimas. A multimarker risk score of obesity variants was associated with body mass index (BMI; β = 0.81 kg/m2 per SD, P = 0.0066). The mean value of the score was lower in Mexican Pimas than in US Pimas (P = 4.3 × 10-11 ), and differences in allele frequencies at established loci could account for approximately 7% of the population difference in BMI; however, the difference in risk scores was consistent with evolutionary neutrality given genetic distance. To identify loci potentially under recent natural selection, allele frequencies at 283 variants were compared between US and Mexican Pimas, accounting for genetic distance. The largest differences were seen at HLA markers (e.g., rs9271720, difference = 0.75, P = 8.7 × 10-9 ); genetic distances at HLA were greater than at random markers (P = 1.6 × 10-46 ). Analyses of GWAS data in 937 US Pimas also showed sharing of alleles identical by descent at HLA that exceeds its genomic expectation (P = 7.0 × 10-10 ). These results suggest that, in addition to the widely recognized balancing selection at HLA, recent directional selection may also occur, resulting in marked allelic differentiation between closely related populations.
Efficacy of vedolizumab for induction of clinical response and remission in patients with moderate to severe inflammatory bowel disease who failed at least two TNF antagonists.
May 20, 2018   United European Gastroenterology Journal
De Vos M, Dhooghe B, Vermeire S, Louis E, Mana F,   . . . . . .   , Hindryckx P, Dewit O, Holvoet T, Franchimont D, Belgian Inflammatory Bowel Disease Research and Development (BIRD)
Efficacy of vedolizumab for induction of clinical response and remission in patients with moderate to severe inflammatory bowel disease who failed at least two TNF antagonists.
May 20, 2018
United European Gastroenterology Journal
Background: Vedolizumab is a recently available monoclonal antibody targeting α4β7 integrin for the treatment of ulcerative colitis (UC) and Crohn's disease (CD). Objective: The objective of this article is to evaluate the efficacy of vedolizumab induction therapy in anti-TNF-refractory/intolerant UC and CD patients in real life. Methods: A cohort of 149 moderately to severely active UC and CD patients who failed or showed intolerance to at least two TNF antagonists participated in a medical need program and received vedolizumab in 37 Belgian centers (April-September 2015). Rates of clinical response and remission were retrospectively evaluated at Week 10 for UC and Week 14 for CD using the physician's global assessment (PGA), Mayo score and Harvey Bradshaw index (HBI) or Crohn's disease activity score (CDAI) scores. Results: Eighty-four patients (29 UC, 55 CD) had sufficient data for analysis. For UC patients, clinical response was observed in 76% based on PGA and 59% based on the Mayo score. The corresponding percentages for CD patients were 80% for PGA and 65% for HBI/CDAI. Clinical remission rates were 10% and 40% for UC and CD, respectively. Steroid-free remission was observed in respectively 10% and 35%. Globally, corticosteroids were stopped in 14 out of 48 patients (29%). No new safety signals were reported. Conclusion: Up to 70% TNF-refractory/intolerant UC and CD patients achieved a clinical response after 10 to 14 weeks of vedolizumab treatment in this real-life cohort.
Orexin A Differentially Influences the Extinction Retention of Recent and Remote Fear Memory.
May 20, 2018   Frontiers In Neuroscience
Shi L, Chen W, Deng J, Chen S, Han Y, Khan MZ, Liu J, Que J, Bao Y, Lu L, Shi J
Orexin A Differentially Influences the Extinction Retention of Recent and Remote Fear Memory.
May 20, 2018
Frontiers In Neuroscience
Recently the role of the orexin system in the learning and memory, especially orexin A, which could enhance fear memory through regulating the activity of amygdala, has drawn considerable attention. However, the relationship between orexin A and extinction memory remains unclear. To investigate the effect of orexin A on extinction memory in humans, we recruited 43 male subjects and divided them into a recent group and remote group. After acquiring Pavlovian fear conditioning, individuals in recent group experienced fear extinction 24 h after acquisition, and remote group underwent extinction 2 weeks later. Meanwhile, plasma orexin A levels before extinction were measured by enzyme-linked immunosorbent assay. Both groups received memory test 24 h after fear extinction. The results showed that both recent and remote groups successfully acquired fear conditioning and had spontaneous recovery at test. In particular, the correlational analysis indicated that orexin A levels before extinction were negatively associated with fear responses during test only in recent group, but not in remote group. Moreover, individuals with high orexin A levels still kept low fear responses after extinction in recent group by subgroup analyses. The results suggest that orexin A could influence the retention of recent fear memory extinction, without affecting remote fear extinction. These findings remind us the orexin system can be a potential treatment target for fear-related disorders, and the mechanisms of recent and remote fear extinction may be different.
Effect of dual antiplatelet on recurrent stroke in minor stroke or TIA depends on bodyweight.
May 20, 2018   Therapeutics And Clinical Risk Management
Ma Y, Liu Y, Xu J, Wang Y, Wang Y, Du F
Effect of dual antiplatelet on recurrent stroke in minor stroke or TIA depends on bodyweight.
May 20, 2018
Therapeutics And Clinical Risk Management
Objective: To assess whether bodyweight influences the efficacy and safety of dual antiplatelet therapy (DAT) in male patients with minor stroke or transient ischemic attack patients. Materials and methods: All 3,420 male participants coming from the Clopidogrel in High-Risk Patients with Acute Non-disabling Cerebrovascular Events trial were divided into 3 groups based on bodyweight (
Impact of timing of trastuzumab initiation on long-term outcome of patients with early-stage HER2-positive breast cancer: the "one thousand HER2 patients" project.
May 18, 2018   British Journal Of Cancer
Gullo G, Walsh N, Fennelly D, Bose R, Walshe J,   . . . . . .   , Evoy D, Prichard R, Geraghty J, Amstrong J, Crown J
Impact of timing of trastuzumab initiation on long-term outcome of patients with early-stage HER2-positive breast cancer: the "one thousand HER2 patients" project.
May 18, 2018
British Journal Of Cancer
BACKGROUND: The optimal timing of (neo)adjuvant trastuzumab initiation with respect to chemotherapy and surgery remains undefined. METHODS: Retrospective analysis of a large institutional database of HER2-positive patients who received anti-HER2 therapy. We included all Stage I to III patients treated with trastuzumab with a minimum follow up of 3 years. The date of first breast biopsy was recorded as initial diagnosis. RESULTS: A total of 506 patients [adjuvant: 386 (76%)-neo-adjuvant: 120 (24%)] were included. The median time-to-first-trastuzumab (TFT) from diagnosis was 12 weeks (range 1.9-122.3). Median follow-up is 73.3 months (range 1.4-176.3). TFT was significantly shorter in the neo-adjuvant than in the adjuvant cohort (median: 4.4 vs. 14 weeks, p 
Editorial: provision of services to people with mental illness.
May 30, 2018   Current Opinion In Psychiatry
Becker T, de Girolamo G
Cardiac pacemaker channel (HCN4) inhibition and atrial arrhythmogenesis after releasing cardiac sympathetic activation.
May 25, 2018   Scientific Reports
Chobanyan-Jürgens K, Heusser K, Duncker D, Veltmann C, May M, Mehling H, Luft FC, Schröder C, Jordan J, Tank J
Cardiac pacemaker channel (HCN4) inhibition and atrial arrhythmogenesis after releasing cardiac sympathetic activation.
May 25, 2018
Scientific Reports
Clinical trials and studies with ivabradine implicate cardiac pacemaker channels (HCN4) in the pathogenesis of atrial arrhythmias. Because acute changes in cardiac autonomic tone predispose to atrial arrhythmias, we studied humans in whom profound cardiac sympathetic activation was rapidly relieved to test influences of HCN4 inhibition with ivabradine on atrial arrhythmias. We tested 19 healthy participants with ivabradine, metoprolol, or placebo in a double blind, randomized, cross-over fashion on top of selective norepinephrine reuptake inhibition with reboxetine. Subjects underwent combined head up tilt plus lower body negative pressure testing followed by rapid return to the supine position. In the current secondary analysis with predefined endpoints before data unblinding, continuous finger blood pressure and ECG recordings were analyzed by two experienced cardiac electrophysiologists and a physician, blinded for treatment assignment. The total atrial premature activity (referred to as atrial events) at baseline did not differ between treatments. After backwards tilting, atrial events were significantly higher with ivabradine compared with metoprolol or with placebo. Unlike beta-adrenoreceptor blockade, HCN4 inhibition while lowering heart rate does not protect from atrial arrhythmias under conditions of experimental cardiac sympathetic activation. The model in addition to providing insight in the role of HCN4 in human atrial arrhythmogenesis may have utility in gauging potential atrial pro-arrhythmic drug properties.
New insights into mechanisms of material ejection in MALDI mass spectrometry for a wide range of spot sizes.
May 25, 2018   Scientific Reports
Niehaus M, Soltwisch J
New insights into mechanisms of material ejection in MALDI mass spectrometry for a wide range of spot sizes.
May 25, 2018
Scientific Reports
Matrix-assisted laser desorption/ionization mass spectrometry (MALDI-MS) is widely used for the analysis of large biomolecules in numerous applications. The technique utilizes nanosecond-long laser pulses at various spot sizes to eject and ionize large molecules embedded in a highly absorptive chemical matrix. Despite the methods name, 'molecular desorption' from the matrix crystal surface is not the sole mechanism discussed for material ejection in MALDI, but additional ablation of larger clusters has been reported. Here we present results on the influence of laser fluence and spot size on the mechanisms of the initial material ejection in MALDI and subsequent plume development. We used a laser-based postionization (MALDI-2) as well as a complementary photoacoustic method to monitor the material ejection step. The photoacoustic data reveal a quasi-thermal sublimation process up to a transition fluence. Above this threshold fluence additional ablation processes are observed. Complementary investigations on plume dynamics by MALDI-2 showed an ejection of predominantly fast particles for desorption conditions while ablation produces considerably slower ejecta. Additionally the presented results revealed a peculiar influence of the spot size on analyte fragmentation as well as plume development and allows for new insights into the unexplained spot size effect reported for MALDI.
A novel small molecule chaperone of rod opsin and its potential therapy for retinal degeneration.
May 23, 2018   Nature Communications
Chen Y, Chen Y, Jastrzebska B, Golczak M, Gulati S,   . . . . . .   , Heidari-Torkabadi H, Stewart PL, Harte WE, Tochtrop GP, Palczewski K
A novel small molecule chaperone of rod opsin and its potential therapy for retinal degeneration.
May 23, 2018
Nature Communications
Rhodopsin homeostasis is tightly coupled to rod photoreceptor cell survival and vision. Mutations resulting in the misfolding of rhodopsin can lead to autosomal dominant retinitis pigmentosa (adRP), a progressive retinal degeneration that currently is untreatable. Using a cell-based high-throughput screen (HTS) to identify small molecules that can stabilize the P23H-opsin mutant, which causes most cases of adRP, we identified a novel pharmacological chaperone of rod photoreceptor opsin, YC-001. As a non-retinoid molecule, YC-001 demonstrates micromolar potency and efficacy greater than 9-cis-retinal with lower cytotoxicity. YC-001 binds to bovine rod opsin with an EC50 similar to 9-cis-retinal. The chaperone activity of YC-001 is evidenced by its ability to rescue the transport of multiple rod opsin mutants in mammalian cells. YC-001 is also an inverse agonist that non-competitively antagonizes rod opsin signaling. Significantly, a single dose of YC-001 protects Abca4 -/- Rdh8 -/- mice from bright light-induced retinal degeneration, suggesting its broad therapeutic potential.
Diagnosis, Incidence, Predictors and Management of Postreperfusion Syndrome in Pediatric Deceased Donor Liver Transplantation: A Single-Center Study.
May 18, 2018   Annals Of Transplantation
Zhang L, Tian M, Xue F, Zhu Z
Diagnosis, Incidence, Predictors and Management of Postreperfusion Syndrome in Pediatric Deceased Donor Liver Transplantation: A Single-Center Study.
May 18, 2018
Annals Of Transplantation
BACKGROUND Postreperfusion syndrome (PRS) is a dreadful and well-documented complication in adult liver transplantation (LT). However, information regarding PRS in pediatric LT is still scarce. We aimed to identify the incidence, risk factors and associated outcomes of pediatric LT in a single-center study. MATERIAL AND METHODS The medical records of 75 consecutive pediatric patients who underwent deceased donor liver transplantation (DDLT) from July 2015 to October 2017 were retrospectively reviewed. PRS was determined according to the Peking criteria when significant arrhythmia or refractory hypotension occurred following revascularization of the liver graft. Patients were divided into PRS and non-PRS groups. Preoperative, intraoperative, and postoperative data were collected and compared between the 2 groups. Independent risk factors for PRS were analyzed using binary logistic regression analysis. RESULTS PRS occurred in 26 patients (34.7%). Univariate analysis showed that the graft-to-recipient weight ratio (P=0.023), donor warm ischemia time (P
Genomic insights into the emergence and spread of antimicrobial-resistant bacterial pathogens.
May 21, 2018   Science (New York, N.Y.)
Baker S, Thomson N, Weill FX, Holt KE
Genomic insights into the emergence and spread of antimicrobial-resistant bacterial pathogens.
May 21, 2018
Science (New York, N.Y.)
Whole-genome sequencing (WGS) has been vital for revealing the rapid temporal and spatial evolution of antimicrobial resistance (AMR) in bacterial pathogens. Some antimicrobial-resistant pathogens have outpaced us, with untreatable infections appearing in hospitals and the community. However, WGS has additionally provided us with enough knowledge to initiate countermeasures. Although we cannot stop bacterial adaptation, the predictability of many evolutionary processes in AMR bacteria offers us an opportunity to channel them using new control strategies. Furthermore, by using WGS for coordinating surveillance and to create a more fundamental understanding of the outcome of antimicrobial treatment and AMR mechanisms, we can use current and future antimicrobials more effectively and aim to extend their longevity.
Transcriptional activities of DUX4 fusions in B-cell acute lymphoblastic leukemia.
May 18, 2018   Haematologica
Tanaka Y, Kawazu M, Yasuda T, Tamura M, Hayakawa F, Kojima S, Ueno T, Kiyoi H, Naoe T, Mano H
Safety of Iohexol Administration to Measure Glomerular Filtration Rate in Different Patient Populations: A 25-Year Experience.
May 17, 2018   Nephron
Gaspari F, Thakar S, Carrara F, Perna A, Trillini M, Aparicio MC, Diadei O, Ferrari S, Cannata A, Stucchi N, Ruggenenti P, Remuzzi G, Perico N
Safety of Iohexol Administration to Measure Glomerular Filtration Rate in Different Patient Populations: A 25-Year Experience.
May 17, 2018
Nephron
BACKGROUND/AIM: In clinical research setting, accurate and precise measurement of glomerular filtration rate (GFR) is essential to overcome the limitations of GFR estimation with equations, which are often unreliable. In recent decades, a method for measuring GFR by plasma clearance of iohexol, a non-ionic radiocontrast agent, was developed. To evaluate the safety of the procedure, we aimed to review all immediate adverse reactions that could be related to iohexol administration in our group's 25 years worth of experience. METHODS: We retrospectively reviewed all GFR investigations in 2,891 patients, between 1992 and 2016, as part of 37 clinical trials coordinated by our group. Subjects with disparate renal diseases, kidney transplant recipients, and living donors - all with different renal function categories - were included in the surveyed clinical trials. RESULTS: During 15,147 GFR measurements, only one treatment-related event of moderate intensity was identified. Flushing, urticaria, and itching were observed in a diabetic patient a few minutes after iohexol administration during the first GFR measurement. The event recovered without sequelae after intravenous injection of methylprednisolone sodium succinate. The patient was not hospitalized and the event was categorized as non-serious. Eight additional non-serious events observed closely following iohexol injection were considered as not related to treatment. Thus, independent of disease conditions and GFR categories, the overall rate of treatment-related events was 0.0066%. CONCLUSION: Iohexol administration for GFR measurement is a safe procedure, even in repeated investigations in the same subject, that should be adopted in clinical research and, when needed, also in clinical practice.
Neurocognitive dysfunction in subjects at clinical high risk for psychosis: A meta-analysis.
Jun 19, 2018   Journal Of Psychiatric Research
Zheng W, Zhang QE, Cai DB, Ng CH, Ungvari GS, Ning YP, Xiang YT
Neurocognitive dysfunction in subjects at clinical high risk for psychosis: A meta-analysis.
Jun 19, 2018
Journal Of Psychiatric Research
Findings of neurocognitive dysfunction in subjects at Clinical High Risk for Psychosis (CHR-P) have been controversial. This meta-analysis systematically examined studies of neurocognitive functions using the MATRICS Consensus Cognitive Battery (MCCB) in CHR-P. An independent literature search of both English and Chinese databases was conducted by two reviewers. Standardized mean difference (SMD) was calculated using a random effects model to evaluate the effect size of the meta-analytic results. Six case-control studies (n = 396) comparing neurocognitive functions between CHR-P subjects (n = 197) and healthy controls (n = 199) using the MCCB were identified; 4 (66.7%) studies were rated as "high quality". Compared to healthy controls, CHR-P subjects showed impairment with large effect size in overall cognition (n = 128, SMD = -1.00, 95%CI: -1.38, -0.63, P 
Comparison of Intraoral Bone Regeneration with Iliac and Alveolar BMSCs.
May 17, 2018   Journal Of Dental Research
Wang F, Zhou Y, Zhou J, Xu M, Zheng W, Huang W, Zhou W, Shen Y, Zhao K, Wu Y, Zou D
Comparison of Intraoral Bone Regeneration with Iliac and Alveolar BMSCs.
May 17, 2018
Journal Of Dental Research
This study compared the osteogenic potential of bone marrow mesenchymal stem cells (BMSCs) of iliac and alveolar origins (I-BMSCs and Al-BMSCs, respectively), which were transplanted in combination with β tricalcium phosphate (β-TCP) in peri-implant bone defects to investigate the osseointegration between dental implants and tissue-engineered bone in dogs. Specifically, I-BMSCs and Al-BMSCs were cultured, characterized, and seeded on β-TCP and subjected to immunoblotting analyses and alkaline phosphatase activity assays. Subsequently, these cell-seeded scaffolds were implanted into defects that were freshly generated in the mandibular premolar areas of 4 dogs. The defects were covered with β-TCP + Al-BMSCs ( n = 6), β-TCP + I-BMSCs ( n = 6), or β-TCP ( n = 6) or served as the blank control ( n = 6). After healing for 12 wk, the formation and mineralization of new bones were assessed through micro-computed tomographic, histologic, and histomorphometric analyses, and bone-to-implant contacts were measured in the specimens. It was evident that in this large animal model, I-BMSCs and Al-BMSCs manifested similarly strong osteogenic potential, as significantly more new bone was formed in the Al-BMSC and I-BMSC groups than otherwise ( P < 0.01). Therefore, Al-BMSCs are emerging as an efficient alternative for autologous mesenchymal stem cells in regenerative dental and maxillofacial therapies. I-BMSCs, if not restricted in their bioavailability, can also be of great utility in bone tissue-engineering applications.
Analysis of risk factors for mild cognitive impairment based on word list memory test results and questionnaire responses in healthy Japanese individuals registered in an online database.
Jun 01, 2018   PloS One
Ogawa M, Sone D, Maruo K, Shimada H, Suzuki K, Watanabe H, Matsuda H, Mizusawa H
Analysis of risk factors for mild cognitive impairment based on word list memory test results and questionnaire responses in healthy Japanese individuals registered in an online database.
Jun 01, 2018
PloS One
Although the development of effective therapeutic drugs and radical treatment options for dementia and Alzheimer's disease (AD) remains urgent, progress in recent clinical trials of AD drugs has been less than adequate. In order to advance the progress of clinical trials, it is necessary to establish more efficient methods of recruitment. In Japan, there are registration systems stratified by mild cognitive impairment and preclinical and clinical stages of early and advanced stage dementia, but there is no registration system for healthy individuals yet. Therefore, in the present study, we developed a large-scale, internet-based health registry to investigate factors associated with cognitive function among registered participants. A total of 1038 participants completed the initial questionnaire and word list memory test. Among these participants, 353 individuals completed a second questionnaire and memory test. Stepwise multiple regression analysis was performed using IBM SPSS version 23.0 for Windows at a statistical significance level of p
A cone-beam computed tomography study of the mesial cervical concavity of maxillary first premolars.
Jun 10, 2018   Archives Of Oral Biology
Fan L, Yuan K, Niu C, Ma R, Huang Z
A cone-beam computed tomography study of the mesial cervical concavity of maxillary first premolars.
Jun 10, 2018
Archives Of Oral Biology
OBJECTIVE: To investigate the mesial cervical concavity of maxillary first premolars and its relationship with root and canal configuration using cone-beam computed tomography (CBCT). DESIGN: Images of maxillary first premolars (n = 1056) were collected from patients (n = 601) who had undergonein vivo CBCT scanning. The root and canal number and morphology were evaluated. The following measurements of the mesial cervical concavity of the maxillary first premolars were evaluated in section images: dentine thickness (in concavity at the cemento-enamel junction), concavity angle, depression depth (distance from mesial dentinal surface at concavity to mesial proximity), concavity position (distance from mesial dentinal wall at invagination to the top of the mesial marginal ridge). The reliability of the data was analyzed with an unpaired Student's t test and Fisher's exact test. RESULTS: The percentages of maxillary first premolars with one root, two, and three roots were 55.5%, 43.7%, and 0.8% respectively. Mesial cervical concavity was recorded in 64.5% of single-root maxillary premolars. The prevalence of two-root maxillary first premolars with mesial cervical concavity was 73.8%. The means of the aforementioned four measurements were 1.705, 147.9, 1.640, and 5.247 mm. The values of dentine thickness (mm), depression depth (mm), and concavity position (mm) of the mesial cervical concavity were largest in two-root maxillary first premolars. The smallest concavity angle of the mesial cervical concavity was found in three-root maxillary first premolars. CONCLUSIONS: There is a high prevalence of mesial cervical concavity among maxillary first premolars. The mesial root concavity is more prevalent in single-rooted maxillary first premolars when there are two canals present, and its prevalence and degree of concavity increase with the number of roots.

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