Entrustable Professional Activities: The Future of Competency-based Education in Surgery May Already Be Here

No abstract available

http://bit.ly/2RK2yRH

NID1 variant associated with occipital cephaloceles in a family expressing a spectrum of phenotypes

Autosomal dominant Dandy‐Walker malformation and occipital cephalocele (ADDWOC) is a rare, congenital, and incompletely penetrant malformation that is considered to be part of the Dandy‐Walker spectrum of disorders. Affected individuals often present with an occipital cephalocele with a bony skull defect, but typically have normal neurological development. Here, we report on a three‐generation family in which individuals have variable phenotypes that are consistent with the ADDWOC spectrum: arachnoid cysts in the proband and his maternal grandfather, an occipital cephalocele in the proband and his brother, and a small bony defect in the proband's mother. Whole exome sequencing identified a rare heterozygous variant in NID1 (NM_002508.2:c.1162C>T, (p.Gln388Ter)) in the proband, his brother, and his mother. Sanger sequencing confirmed the presence of this variant in the maternal grandfather. The identical c.1162C>T variant was previously identified in variably affected members of a three‐generation family with ADDWOC. This case report provides further evidence that variants in NID1 may be clinically relevant for the development of a phenotype that is consistent with ADDWOC, and extends the phenotype of NID1‐associated ADDWOC to include arachnoid cysts. Given that the Dandy‐Walker malformation itself is not a pre‐requisite to this spectrum of phenotypes, we also suggest a novel term for the NID1‐associated disorder in order to give emphasis to this phenotypic variability: "Autosomal Dominant Posterior Fossa Anomalies with Occipital Cephaloceles."

http://bit.ly/2Gz1uPw

Diastolic dysfunction on echocardiography does not predict survival after transjugular intrahepatic portosystemic stent‐shunt in patients with cirrhosis

Summary

Background

Cardiac dysfunction is frequently observed in patients with cirrhosis. There remains a paucity of data from routine clinical practice regarding the role of echocardiography in the pre‐assessment of transjugular intrahepatic portosystemic stent‐shunt.

Aim

Our study aimed to investigate if echocardiography parameters predict outcomes after transjugular intrahepatic portosystemic stent‐shunt insertion in cirrhosis.

Methods

Patients who underwent echocardiography and transjugular intrahepatic portosystemic stent‐shunt insertion at the liver unit (Birmingham, UK) between 1999 and 2016 were included. All echocardiography measures (including left ventricle ejection fraction; early maximal ventricular filling/late filling velocity ratio, diastolic dysfunction as per British Society of Echocardiography guidelines) were independently reviewed by a cardiologist. Predictors of 30‐day and overall transplant free‐survival were assessed.

Results

One Hundred and Seventeen patients with cirrhosis (median age 56 years; 54% alcohol; Child‐Pugh B/C 71/14.5%; Model For End‐Stage Liver Disease 12) underwent transjugular intrahepatic portosystemic stent‐shunt for ascites (n = 78) and variceal haemorrhage (n = 39). Thirty‐day and overall transplant‐free survival was 90% (n = 105) and 31% (n = 36), respectively, over a median 663 (IQR 385‐2368) days follow‐up. Model for End‐Stage Liver Disease (P < 0.001) and Child‐Pugh Score (P = 0.002) significantly predicted 30‐day and overall transplant‐free survival. Model for End‐Stage Liver Disease ≥15 implied three‐fold risk of death. Six per cent (n = 7) of patients pre‐transjugular intrahepatic portosystemic stent‐shunt had a history of ischaemic heart disease and 34% (n = 40) had 1 or more cardiovascular disease risk factors. Fifty per cent (n = 59) had an abnormal echocardiogram and 33% (n = 39) had grade 1‐3 diastolic dysfunction. On univariate analysis none of the echocardiography measures pre‐intervention were related to 30‐day or overall transplant‐free survival post‐transjugular intrahepatic portosystemic stent‐shunt.

Conclusions

Ventricular, in particular diastolic dysfunction in patients with cirrhosis does not predict survival after transjugular intrahepatic portosystemic stent‐shunt insertion. Model for End‐Stage Liver Disease and Child‐Pugh scores remain the best predictors of survival. Further prospective study is required to clarify the role of routine echocardiography prior to transjugular intrahepatic portosystemic stent‐shunt insertion.

http://bit.ly/2SGPrWP

Balloon Eustachian Tuboplasty for Chronic Eustachian Tube Dysfunction

Two weeks after having balloon eustachian tuboplasty, Robin Goebel was on a flight to South America, where she hiked at...

http://bit.ly/2SGN3iF

McGovern Society Leaders Give Students a Roadmap Through Medical School

Pediatric otolaryngologist Zi Yang Jiang, MD, is one of 30 McGovern Society leaders who mentor new medical students, helping them...

http://bit.ly/2DMClgu

Without Borders: Dr. Amber Luong Joins a Mission to Vietnam

Born in Vietnam, Amber Luong, MD, PhD, was 3 in April 1975 when her family left the country the day...

http://bit.ly/2SI6wj1

Status Epilepticus in the Neonate: Updates in Treatment Strategies

Abstract

Purpose of review

The purpose of this review is to report recent advances in treatment of neonatal seizures, with a specific focus on new literature since a 2013 systematic review performed by this author (Slaughter) and others. There is a paucity of data with regard to well-defined status epilepticus (SE) in neonates, so treatment of recurrent seizures was also included in this inquiry. We aimed to summarize the efficacy and safety profiles of current therapeutic options as well as describe trends in medication selection in the neonatal intensive care unit (NICU) setting.

Recent findings

Phenobarbital remains first-line therapy in practice, though there is increasing evidence of its neurotoxicity and long-term sequelae. Bumetanide failed an open-label trial for efficacy, demonstrated an increased risk for hearing loss, and has since fallen out of favor for use in this population. New agents, such as levetiracetam and topiramate, still have very limited data but appear to be as efficacious as older medications, with more favorable side effect profiles.

Summary

There are limited high-level evidence-based data to guide treatment of neonatal seizures. Emerging research focusing on drug mechanisms and safety profiles may provide additional information to guide decisions; however, further research is needed.

http://bit.ly/2BI1aKm

Expression and regulation of miR-449a and AREG in cerebral ischemic injury

Abstract

Rodent focal ischemia models are widely used to mimic and examine human strokes. To the best of our knowledge, no investigation has systematically examined the expression changes of microRNA (miR)-449a and Amphiregulin (AREG) as well as their biological relationship during middle cerebral artery occlusion (MCAO) and oxygen and glucose deprivation/reperfusion (OGD/R). The present study examined the histological and behavioral outcomes of MCAO and the function of miR-449a and AREG in cerebral ischemic injury. Rats were subjected to 2 h MCAO, which was followed by reperfusion. miR-449a and AREG were examined in the injury tissues of MCAO rats and the OGD/R cell line by reverse transcription-quantitative polymerase chain reaction. Protein expressions of AREG in the injury tissues of MCAO rats was measured using an immunohistochemistry and the protein expression levels of AREG, epidermal growth factor receptor (EGFR), phosphatidylinositol 3-kinase (PI3K)/ protein kinase B (Akt) and the phosphorylation level of Akt (p-Akt) were analyzed by western blotting. Cell apoptosis was examined following the knock down and subsequent overexpression of AREG in a human OGD/R neuronal cell line by small interfering RNAs (siRNAs) and plasmid transfection. Luciferase reporter assays were used to validate the target of miR-449a. The expression changes and regulatory mechanisms of miR-449a and AREG in an ischemia/reperfusion (I/R) injury model were examined in vivo and in vitro. The neurological deficit score, brain edema volume, cerebral infarct area, and the number of apoptosis cells in ischemic rats were all markedly elevated, than that in the control rats. The expression of miR-449a was decreased and AREG was increased in the MCAO rats and human OGD/R neuronal cell line. miR-449a inhibition or AREG overexpression in OGD/R cells resulted in a significant decrease in apoptotic cells, and AREG was revealed to be one of the direct targets of miR-449a. Molecular recovery was observed following transfection with miR-449a mimics and AREG knockdown in an OGD/R model in vitro. The present study demonstrated that miR-449a was downregulated while AREG was upregulated in cerebral ischemic injury, and the recovery of neurological function can be obtained following the overexpression of miR-449a and the knockdown of AREG in an I/R injury model. miR-449a functions in ischemic stroke via directly targeting AREG. These findings suggest a novel mechanism involving in cerebral I/R injury model and may aid investigators in gaining a deeper understanding of strokes in a clinical setting.

http://bit.ly/2TTG9mR

Leigh syndrome caused by mutations in MTFMT is associated with a better prognosis

Abstract

Objectives

Mitochondrial methionyl‐tRNA formyltransferase (MTFMT) is required for the initiation of translation and elongation of mitochondrial protein synthesis. Pathogenic variants in MTFMT have been associated with Leigh syndrome (LS) and mitochondrial multiple respiratory chain deficiencies. We sought to elucidate the spectrum of clinical, neuroradiological and molecular genetic findings of patients with bi‐allelic pathogenic variants in MTFMT.

Methods

Retrospective cohort study combining new cases and previously published cases.

Results

Thirty‐eight patients with pathogenic variants in MTFMT were identified, including eight new cases. The median age of presentation was 14 months (range: birth to 17 years, interquartile range [IQR] 4.5 years), with developmental delay and motor symptoms being the most frequent initial manifestation. Twenty‐nine percent of the patients survived into adulthood. MRI headings in MTFMT pathogenic variants included symmetrical basal ganglia changes (62%), periventricular and subcortical white matter abnormalities (55%), and brainstem lesions (48%). Isolated complex I and combined respiratory chain deficiencies were identified in 31% and 59% of the cases, respectively. Reduction of the mitochondrial complex I and complex IV subunits was identified in the fibroblasts (13/13). Sixteen pathogenic variants were identified, of which c.626C>T was the most common. Seventy‐four percent of the patients were alive at their last clinical review (median 6.8 years, range: 14 months to 31 years, IQR 14.5 years).

Interpretation

Patients that harbour pathogenic variants in MTFMT have a milder clinical phenotype and disease progression compared to LS caused by other nuclear defects. Fibroblasts may preclude the need for muscle biopsy, to prove causality of any novel variant.

http://bit.ly/2SWBCCT

Motor‐imagery ability and function of hemiplegic upper limb in stroke patients

Abstract

Objectives

We quantitatively examined the motor‐imagery ability in stroke patients using a bimanual circle‐line coordination task (BCT) and clarified the relationship between motor‐imagery ability and motor function of hemiplegic upper limbs and the level of use of paralyzed limbs.

Methods

We enrolled 31 stroke patients. Tasks included unimanual‐line (U‐L)—drawing straight lines on the nonparalyzed side; bimanual circle‐line (B‐CL)—drawing straight lines with the nonparalyzed limb while drawing circles with the paralyzed limb; and imagery circle‐line (I‐CL)—drawing straight lines on the nonparalyzed side during imagery drawing on the paralyzed side, using a tablet personal computer. We calculated the ovalization index (OI) and motor‐imagery ability (image OI). We used the Fugl–Meyer motor assessment (FMA), amount of use (AOU), and quality of motion (QOM) of the motor activity log (MAL) as the three variables for cluster analysis and performed mediation analysis.

Results

Clusters 1 (FMA <26 points) and 2 (FMA ≥26 points) were formed. In cluster 2, we found significant associations between image OI and FMA, AOU, and QOM. When AOU and QOM were mediated between image OI and FMA, we observed no significant direct association between image OI and FMA, and a significant indirect effect of AOU and QOM.

Interpretation

In stroke patients with moderate‐to‐mild movement disorder, image OI directly affects AOU of hemiplegic upper limbs and their QOM in daily life and indirectly influences the motor functions via those parameters.

http://bit.ly/2Na90kg

Genetic and Environmental Determinants of Immune Response to Cutaneous Melanoma

The immune response to melanoma improves the survival in untreated patients and predicts the response to immune checkpoint blockade. Here, we report genetic and environmental predictors of the immune response in a large primary cutaneous melanoma cohort. Bioinformatic analysis of 703 tumor transcriptomes was used to infer immune cell infiltration and to categorize tumors into immune subgroups, which were then investigated for association with biological pathways, clinicopathologic factors, and copy number alterations. Three subgroups, with "low", "intermediate", and "high" immune signals, were identified in primary tumors and replicated in metastatic tumors. Genes in the low subgroup were enriched for cell-cycle and metabolic pathways, whereas genes in the high subgroup were enriched for IFN and NF-κB signaling. We identified high MYC expression partially driven by amplification, HLA-B downregulation, and deletion of IFNγ and NF-κB pathway genes as the regulators of immune suppression. Furthermore, we showed that cigarette smoking, a globally detrimental environmental factor, modulates immunity, reducing the survival primarily in patients with a strong immune response. Together, these analyses identify a set of factors that can be easily assessed that may serve as predictors of response to immunotherapy in patients with melanoma.Significance: These findings identify novel genetic and environmental modulators of the immune response against primary cutaneous melanoma and predict their impact on patient survival.

http://bit.ly/2tsMfyW

Effect of glycine betaine on chilling injury in relation to energy metabolism in papaya fruit during cold storage

Glycine betaine (GB) treatment enhanced chilling tolerance in papaya fruit during cold storage, which might be ascribed to improved energy status in association with increased activities of energy metabolism‐related enzymes. GB treatment could be an effective strategy to ameliorate chilling injury (CI) in harvested papaya fruit during cold storage.

Abstract

"Zhongbai" papaya fruit were treated with 15 mmol/L glycine betaine (GB) and then refrigerated at 6°C for 40 days to study the influence of GB on chilling injury (CI) and possible mechanism associated with energy metabolism. The results exhibited that GB treatment remarkably reduced the CI severity as indicated by lower CI index during storage. GB treatment lowered electrolyte leakage and malondialdehyde content, which accounted for maintenance of membrane integrity and reduced lipid peroxidation. Moreover, GB treatment improved the energy status as revealed by increased adenosine triphosphate (ATP) level, energy charge, and activities of energy metabolism‐related enzymes including mitochondrial membrane H⁺‐adenosine triphosphatase (H⁺‐ATPase) and Ca²⁺‐adenosine triphosphatase (Ca²⁺‐ATPase), succinate dehydrogenase (SDH), and cytochrome C oxidase (CCO). The results indicate that enhanced chilling tolerance in papaya fruit by GB treatment during cold storage might be ascribed to improved energy status in association with increased activities of energy metabolism‐related enzymes.

http://bit.ly/2EgMtzG

Impacts of Free-falling Spheres on a Deep Liquid Pool with Altered Fluid and Impactor Surface Conditions

This protocol demonstrates the basic experimental configuration for water entry experiments with free-falling spheres. Methods for the alteration of liquid surface with penetrable fabrics, the preparation of chemically non-wetting spheres, and steps for splash visualization and data extraction are discussed.

http://bit.ly/2T42Fwp

Microinjection-based System for In Vivo Implantation of Embryonic Cardiomyocytes in the Avian Embryo

In this method, embryonic cardiac tissues are surgically microdissected, dissociated, fluorescently labeled, and implanted into host embryonic tissues. This provides a platform for studying the individual or tissue level developmental organization under ectopic hemodynamic conditions, and/or altered paracrine/juxtacrine environments.

http://bit.ly/2IjUkQY

Targeted and Selective Treatment of Pluripotent Stem Cell-derived Teratomas Using External Beam Radiation in a Small-animal Model

Research on treatment strategies for pluripotent stem cell-derived teratomas is important for the clinical translation of stem cell therapy. Here, we describe a protocol to, first, generate stem cell-derived teratomas in mice and, then, to selectively target and treat these tumors in vivo using a small-animal irradiator.

http://bit.ly/2TXSK8Q

Imaging Diagnosis of Transient Ischemic Attack in Clinic and Traditional Chinese Medicine

Neuroimaging plays a pivotal role in Transient Ischemic Attack (TIA). Generally, clinicians focus on the specific changes in morphology and function, but the diagnosis of TIA often depends on imaging evidence. Whereas Traditional Chinese Medicine (TCM) is concerned with the performance of clinical symptoms, they began to use imaging methods to diagnose TIA. CT and MRI are the recommended modality to diagnose TIA and image ischemic lesions. In addition, Transcranial Doppler sonography (TCD) and Digital Subtraction Angiography (DSA) are two acceptable alternatives for diagnosing TIA patients. This article elaborates the update of imaging modalities in clinic and the development of imaging modalities in TCM. Besides, multiple joint imaging technologies also will be evaluated whether enhanced diagnostic yields availably.

http://bit.ly/2SSgPAB

Network Pharmacology Analysis of Damnacanthus indicus C.F.Gaertn in Gene-Phenotype

Damnacanthus indicus C.F.Gaertn is known as Huci in traditional Chinese medicine. It contains a component having anthraquinone-like structure which is a part of the many used anticancer drugs. This study was to collect the evidence of disease-modulatory activities of Huci by analyzing the published literature on the chemicals and drugs. A list of its compounds and direct protein targets is predicted by using Bioinformatics Analysis Tool for Molecular Mechanism of TCM. A protein-protein interaction network using links between its directed targets and the other known targets was constructed. The DPT-associated genes in net were scrutinized by WebGestalt. Exploring the cancer genomics data related to Huci through cBio Portal. Survival analysis for the overlap genes is done by using UALCAN. We got 16 compounds and it predicts 62 direct protein targets and 100 DPTs and they were identified for these compounds. DPT-associated genes were analyzed by WebGestalt. Through the enrichment analysis, we got top 10 identified KEGG pathways. Refined analysis of KEGG pathways showed that one of these ten pathways is linked to Rap1 signaling pathway and another one is related to breast cancer. The survival analysis for the overlap genes shows the significant negative effect of these genes on the breast cancer patients. Through the research results of Damnacanthus indicus C.F.Gaertn, it is shown that medicine network pharmacology may be regarded as a new paradigm for guiding the future studies of the traditional Chinese medicine in different fields.

http://bit.ly/2GvLQUS

Preparedness for chemical crisis situations: experiences from European medical response exercises

OBJECTIVE: This study investigated how European first responders and hospital personnel, along with CBRN experts, approach an overwhelming surge situation after a chemical incident. Surge capacity and capability bottlenecks were discussed.

MATERIALS AND METHODS: Two chemical warfare agent (CWA) scenarios were developed: in the first, a nerve agent was released indoors; in the second, there was an outdoor explosion containing a blister agent. CBRNE experts, first responders and hospital specialists from across Europe participated in a two-day table-top exercise to discuss pre-hospital and hospital CBRNE preparedness, triage, surge capacity and communication issues. This was followed by a medical response exercise at a level 2 Emergency Department in Italy.

RESULTS: Several surge capacity challenges and lessons were identified. Critical resources were rapidly exhausted and sourcing from national/international medical stockpiles was not feasible in the time critical scenarios. Secondary contamination in the blister agent scenario was considered plausible and hospitals are currently unprepared for this situation. The medical response exercise highlighted further training needs.

CONCLUSIONS: The majority of the lessons are not new and have been reported in North American studies. However, this study is the first to describe these CWA challenges from a European perspective. Medical facilities across the region should consider these lessons to evaluate and improve their surge capacity, capability and response.

L'articolo Preparedness for chemical crisis situations: experiences from European medical response exercises sembra essere il primo su European Review.

http://bit.ly/2SVzmM7

A Model to Predict In-Hospital Mortality in HIV/AIDS Patients with Pneumocystis Pneumonia in China: The Clinical Practice in Real World

We aimed to develop and validate a predictive model to evaluate in-hospital mortality risk in HIV/AIDS patients with PCP in China. 1001 HIV/AIDS patients with PCP admitted in the Beijing Ditan hospital from August 2009 to January 2018 were included in this study. Multivariate Cox proportional hazard model was used to identify independent risk factors of death, and a predictive model was devised based on risk factors. The overall in-hospital mortality was 17.3%. The patients were randomly assigned into derivation cohort (801cases) and validation cohort (200 cases) in 8:2 ratio, respectively, in which in derivation cohort we found that 7 predictors, including LDH >350U/L, HR>130 times/min, room air PaO2

http://bit.ly/2SGp8Ad

The Association between Absence of Abdominal Pain and Mortality in Lower Intestinal Perforation in Patients with Autoimmune Rheumatic Diseases

Objective. To determine mortality and predictive factors for lower intestinal perforation (LIP) among patients with autoimmune rheumatic diseases. Methods. This retrospective, single-center, observational study analyzed mortality rates in 31 autoimmune rheumatic disease patients with LIP who were admitted to our hospital from January 2002 to June 2017. The primary outcome was the mortality rate during hospitalization. Results. The median age at the time of LIP was 61 years, and the survival rate at discharge was 64.5%. Eleven patients died of sepsis during hospitalization. Cox univariable analysis for mortality during hospitalization showed that absence of abdominal pain (hazard ratio (HR) 5.61, 95% confidence interval (CI) 1.38–22.9), higher age (HR 1.06, 95% CI 1.01–1.11), chronic kidney disease (HR 6.89, 95% CI 1.85–25.7), systemic vasculitis (HR 3.95, 95% CI 1.14–13.6), higher blood urea nitrogen (HR 1.02, 95% CI 1.01–1.04), higher serum creatinine (HR 1.41, 95% CI 1.06–1.87), and LIP due to malignancy (HR 14.3, 95% CI 1.95–105.1) significantly increased mortality. Conclusion. Abdominal pain was absent in 16% of LIP patients with autoimmune rheumatic diseases, and this absence was a poor prognostic factor in this cohort. Moreover, higher age, chronic kidney disease, systemic vasculitis, and LIP due to malignancy were associated with significantly increased mortality. Physicians should be aware of LIP in autoimmune disease patients with higher age, chronic kidney diseases, or systemic vasculitis even if patients reveal mild abdominal symptoms.

http://bit.ly/2DMIucs

Avelumab plus Axitinib versus Sunitinib for Advanced Renal-Cell Carcinoma

New England Journal of Medicine, Ahead of Print.


http://bit.ly/2SUQ66s

Combination Therapy as First-Line Treatment in Metastatic Renal-Cell Carcinoma

New England Journal of Medicine, Ahead of Print.


http://bit.ly/2Nb1qpv

Pembrolizumab plus Axitinib versus Sunitinib for Advanced Renal-Cell Carcinoma

New England Journal of Medicine, Ahead of Print.


http://bit.ly/2SZXRaY

Acutherapy for Knee Osteoarthritis Relief in the Elderly: A Systematic Review and Meta-Analysis

Purpose. This systematic review and meta-analysis was conducted to investigate the effects of various acutherapies on knee osteoarthritis (KOA) relief in the elderly. Methods. Five databases were accessed from inception to July 2017 for searching randomized controlled trials (RCTs) on acutherapy for KOA relief in the elderly. Data were pooled after trial quality assessment for meta-analysis. Outcomes were the scores of knee pain, knee stiffness, and physical function accessed by Western Ontario and McMaster Universities Osteoarthritis (WOMAC) Index. Results. 17 RCTs including 4774 subjects were included. The results indicated that acutherapy significantly affected knee pain (standardized mean difference, i.e., SMD = - 0.73, [95% CI, -0.98 to -0.47], P

http://bit.ly/2SHQDcC

Improved Quality of Corn Silage When Combining Cellulose-Decomposing Bacteria and Lactobacillus buchneri during Silage Fermentation

This study aimed to investigate the effects of the combined use of cellulose-decomposing bacteria (CDB) and heterolactic lactic acid bacteria (LAB) on corn silage fermentation. Fresh maize was treated with heterolactic LAB or CDB combined with heterolactic LAB inoculants or without any treatment. Chemical and microbiological analyses were conducted at specific times after ensiling. A comprehensive value evaluation was conducted using the principal component analysis model. Although all treatments significantly affected the microorganism numbers during fermentation, the numbers of aerobic bacteria, LAB, yeast, and molds in the groups with combined CDB and LAB were significantly higher than those in the group with LAB only (P

http://bit.ly/2X2DgCl

Association Study of the Caspase Gene Family and Psoriasis Vulgaris Susceptibility in Northeastern China

Background. Abnormal apoptosis of keratinocytes is one of the pathological changes of psoriasis. Caspases (CASPs) are the central engines of apoptosis. Studies to date have shown that some SNPs alter the expression of related genes and lead to changes in disease risk. However, no studies have investigated the associations between gene polymorphisms and the risk of psoriasis in Han population in northeast China. Therefore, we conducted a case-control study to explore this question in Han population of northeastern China. Methods. 540 patients with PsV and 612 healthy age- and sex-matched controls were enrolled in this study. We determined the genotypes of 17 single nucleotide polymorphisms (SNPs) from 11 genes of caspase family by the improved multiplex ligation detection reaction (iMLDR) method. A model-based single SNP frequentist test and haplotype association studies were performed to evaluate the association between SNPs and PsV. Results. In the single SNP tests, rs6704688 in CASP8 was significantly associated with psoriasis vulgaris (PsV) in Han population of northeastern China (P = 0.0169, P' = 0.0179 under the additive model; P = 0.0126, P' = 0.0149 under the heterozygous model). In haplotype analyses, the CASP7 haplotype GC was found to be associated with PsV risk (case group versus control group, 47.2% versus 54.4%, respectively, p = 0.0149). Conclusions. Our study presented that the gene polymorphisms of CASP7 and CASP8 were significantly associated with PsV in Han population of northeastern China, which implied the functional relationship between PsV and caspase genes. CASP8 and CASP7 SNPs could be new potential biomarkers for risk stratification and prevention of PsV.

http://bit.ly/2S7x5sX

Posterolateral Endoscopic Lumbar Decompression Rotate-to-Retract Technique for Foraminal Disc Herniation: A Technical Report

Background and Study Aim. Foraminal disc herniations present the unique surgical challenge for exiting nerve root retraction and decompression. The aim of current study is to describe an innovative maneuver and evaluate its usefulness for endoscopic decompression of foraminal disc herniations. Material and Methods. A retrospective review was performed including cases of foraminal disc herniations who underwent endoscopic discectomy utilizing the rotate-to-retract technique. Data on patient demographics and improvement in VAS/ODI scores were collected and analyzed statistically. Results. There were ten patients (three male; seven female) in the final analysis. Seven procedures were done at the L4-L5 level, two were done at the L5-S1 level, and one was done at the L3-L4 level. The average VAS scores improved from preoperatively 7.5 to postoperatively 4.4 (p= 0.001). The mean preoperative ODI was 67.8 and improved to 26.6 postoperatively (p

http://bit.ly/2X7NSjj

Muscle Atrophy Marker Expression Differs between Rotary Cell Culture System and Animal Studies

Muscular atrophy, defined as the loss of muscle tissue, is a serious issue for immobilized patients on Earth and for humans during spaceflight, where microgravity prevents normal muscle loading. In vitro modeling is an important step in understanding atrophy mechanisms and testing countermeasures before animal trials. The most ideal environment for modeling must be empirically determined to best mimic known responses in vivo. To simulate microgravity conditions, murine C2C12 myoblasts were cultured in a rotary cell culture system (RCCS). Alginate encapsulation was compared against polystyrene microcarrier beads as a substrate for culturing these adherent muscle cells. Changes after culture under simulated microgravity were characterized by assessing mRNA expression of MuRF1, MAFbx, Caspase 3, Akt2, mTOR, Ankrd1, and Foxo3. Protein concentration of myosin heavy chain 4 (Myh4) was used as a differentiation marker. Cell morphology and substrate structure were evaluated with brightfield and fluorescent imaging. Differentiated C2C12 cells encapsulated in alginate had a significant increase in MuRF1 only following simulated microgravity culture and were morphologically dissimilar to normal cultured muscle tissue. On the other hand, C2C12 cells cultured on polystyrene microcarriers had significantly increased expression of MuRF1, Caspase 3, and Foxo3 and easily identifiable multinucleated myotubes. The extent of differentiation was higher in simulated microgravity and protein synthesis more active with increased Myh4, Akt2, and mTOR. The in vitro microcarrier model described herein significantly increases expression of several of the same atrophy markers as in vivo models. However, unlike animal models, MAFbx and Ankrd1 were not significantly increased and the fold change in MuRF1 and Foxo3 was lower than expected. Using a standard commercially available RCCS, the substrates and culture methods described only partially model changes in mRNAs associated with atrophy in vivo.

http://bit.ly/2S8nwdf

Avelumab plus Axitinib versus Sunitinib for Advanced Renal-Cell Carcinoma

New England Journal of Medicine, Ahead of Print.


http://bit.ly/2SUQ66s

Combination Therapy as First-Line Treatment in Metastatic Renal-Cell Carcinoma

New England Journal of Medicine, Ahead of Print.


http://bit.ly/2Nb1qpv

Pembrolizumab plus Axitinib versus Sunitinib for Advanced Renal-Cell Carcinoma

New England Journal of Medicine, Ahead of Print.


http://bit.ly/2SZXRaY

Therapeutic Efficiency of an External Chinese Herbal Formula of Mammary Precancerous Lesions by BATMAN-TCM Online Bioinformatics Analysis Tool and Experimental Validation

Ruyan Neixiao Cream (RYNXC), a patented Chinese herbal formula, was reported to have the effect of treating mammary precancerous disease. In this study, we predicted the potential targets, pathways, and diseases of the ingredients contained in each herbal of RYNXC and constructed an ingredients-targets-diseases network. Then, we analyzed molecular mechanisms of this Chinese herbal formula by MCF-10AT cells and model rats of breast precancerous lesions. BATMAN-TCM prediction showed that ESR1, PGR, PTGS2, EGFR, and Src were mRNA targets of RYNXC. Our results suggested that RYNXC transdermal fluid downregulated ESR1, PGR, PTGS2, EGFR, and Src expression at gene and protein level in MCF-10AT cells. In the rat breast precancerous lesions model, high and low dose RYNXC could also significantly reduce genes and proteins expression of ESR1, PGR, PTGS2, EGFR, and Src. Taken together these data indicate that RYNXC targets multiple molecules responsible for breast precancerous lesion and is an effective Chinese herbal formula. So RYNXC may be a promising external drug for breast precancerous lesions.

http://bit.ly/2DKEnOa

Heuchera Creme Brulee and Mahogany Medicinal Value under Water Stress and Oligosaccharide (COS) Treatment

Food borne pathogens cause serious human illnesses and diseases and their control using natural bioactive compounds becomes essential for the progress of agricultural and food industries. Developing novel tools to enhance the medicinal values of traditional horticultural medicinal crops is one of the promising methods for achieving food borne pathogens control. In this study, oligosaccharide water solutions were applied to Heuchera Creme Brulee and Mahogany subjected to a normal irrigation interval (2 days) or to prolonged irrigation intervals (6 days) for 6 weeks. Plant morphological, physiological, and metabolic markers associated with the bioactivity of leaf extracts against selected microbes. Oligosaccharide-treated plants showed significant increases in all morphological parameters during normal and prolonged irrigation intervals as compared to those of the controls. Morphological improvement associated with a significant increase in chlorophyll, carbohydrates, proline, K, Ca, phenols, and free and total ascorbate and antioxidants. Superoxide dismutase, catalase, and ascorbate peroxidase activities were higher, while H2O2 accumulated to a lower extent in oligosaccharide-treated plants. These morphological and metabolic changes associated with increased antibacterial and antifungal activities of leaf extracts and their activities were comparable to antibiotics and antifungal agents (minimum inhibitory concentrations values were 0.5 -0.20 mg−1mL for bacteria and 0.08 -0.20 mg−1mL for fungi in Mahogany). The application of oligosaccharide and/or water stress might be of great value for producing natural bioactive compounds for food borne pathogens control.

http://bit.ly/2TZflSt

Gastroprotective Effects of Paeonia Extract Mixture HT074 against Experimental Gastric Ulcers in Rats

Background. Paeonia extract mixture HT074 is a standardized multiherbal mixture comprising extracts from Inula britannica flowers and Paeonia lactiflora roots, which are used to treat digestive disorders in traditional Korean medicine. This study was focused on elucidating the underlying mechanisms of the gastroprotective effects of HT074 in different gastric ulcer models. Methods. Gastric lesions were induced in rats by an HCl/EtOH solution, water immersion-restraint stress (WIRS), and indomethacin. Gastric secretions were studied in pylorus-ligated rats, while mucus secretions were assessed by measuring alcian blue-binding capacity of mucus in the rat model of HCl/EtOH-induced gastric ulcer. Additionally, the involvement of nitric oxide (NO) and sulfhydryl compounds in HT074-mediated mucosal protection was elucidated using their inhibitors, i.e., NG-nitro--arginine methyl ester hydrochloride (L-NAME) and N-ethylmaleimide (NEM), respectively. Furthermore, the effects on indomethacin-induced cell death and prostaglandin E2 (PGE2) levels were assessed in AGS cells. Results. Oral administration of HT074 significantly decreased gastric lesions induced by HCl/EtOH, WIRS, and indomethacin. Furthermore, it significantly decreased the volume, acidity, and total acidity of gastric juice in pylorus-ligated rats and increased the alcian blue-stained gastric mucus in HCl/EtOH-induced gastric ulcer in rats. Pretreatment with NEM abolished the gastroprotective effects of HT074, while L-NAME did not. In AGS cells, HT074 significantly reduced indomethacin-induced cell death and increased the PGE2 levels. Conclusions. These findings suggest that HT074 has gastroprotective effects against various ulcerogens, including HCl/EtOH, immersion stress, and NSAIDs. These effects are attributed to the inhibition of gastric secretions and preservation of the gastric mucosal barrier by increased mucus production, which is partially mediated through endogenous sulfhydryl compounds and PGE2. Based on these findings, we propose that HT074 may be a promising therapeutic agent for gastritis and gastric ulcer.

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Combination of Ligusticum Chuanxiong and Radix Paeonia Promotes Angiogenesis in Ischemic Myocardium through Notch Signalling and Mobilization of Stem Cells

Objective. To study the cardioprotective mechanism by which the combination of Chuanxiong (CX) and Chishao (CS) promotes angiogenesis. Methods. Myocardial infarction (MI) mouse models were induced by ligation of the left anterior descending coronary artery. The effects on cardiac function were evaluated in the perindopril tert-butylamine group (PB group) (3 mg/kg/d), CX group (55 mg/kg/d), CS group (55 mg/kg/d), and CX and CS combination (CX-CS) group (27.5 mg/kg/d CX plus 27.5 mg/kg/d CS). RO4929097, an inhibitor of Notch γ secretase, was used (10 mg/kg/d) to explore the role of Notch signalling in the CX-CS-induced promotion of angiogenesis in the myocardial infarcted border zone (IBZ). The left ventricular ejection fraction (LVEF) and percentage of MI area were evaluated with animal ultrasound and Masson staining. The average optical densities (AODs) of CD31 and vWF in the myocardial IBZ were detected by immunofluorescence. Angiogenesis-related proteins including hypoxia-inducible factor 1-alpha (HIF-1α), fibroblast growth factor receptor 1 (FGFR-1), Notch1 and Notch intracellular domain (NICD), and stem cell mobilization-related proteins including stromal cell-derived factor 1 (SDF-1), C-X-C chemokine receptor type 4 (CXCR-4), and cardiotrophin1 were detected by western blot analysis. Results. Compared with the model group, the CX-CS and PB groups both showed markedly improved LVEF and decreased percentage of MI area after 21 days of treatment. Although the CX group and CS group showed increased LVEF and decreased MI areas compared with the model group, the difference was not significant. The AOD of CD31 in the IBZ in both the model and the CX-CS-I group was markedly reduced compared with that in the sham group. CX-CS significantly increased the CD31 AOD in the IBZ and decreased the AODs of CD31 and vWF in the infarct zone compared with those in the model group. The expression of HIF-1α in both the model group and the CX-CS group was higher than that in the sham group. Compared with the model group, the expression of FGFR-1, SDF-1, cardiotrophin1, Notch1, and NICD was increased in the CX-CS group. Notch1 and NICD expression in the CX-CS-I group was reduced compared with that in the CX-CS group. Conclusions. The combination of CX and CS protected cardiomyocytes in the IBZ better than CX or CS alone. The mechanism by which CX-CS protects ischemic myocardium may be related to the proangiogenesis effect of CX-CS exerted through Notch signalling and the mobilization of stem cells to the IBZ.

http://bit.ly/2TSSJ5Y

Pulmonary Artery Sling Presenting as Pneumonia and Inhalation of a Foreign Body

Pulmonary artery sling is a rare cause of respiratory distress created by compression of the lower trachea and right mainstem bronchus due to an aberrant origin of the left pulmonary artery. The condition is frequently associated with recurrent respiratory infections and other congenital malformations including tracheal rings. We present the case of an infant presenting with pulmonary distress and a history of recurrent respiratory infection. The infant underwent surgery to remove a foreign object; however, the symptoms did not resolve. Bronchoscopy revealed bronchus stenosis, and subsequent echocardiogram and CT scans revealed the presence of a pulmonary artery sling. We prescribed infection prophylaxis with the immunomodulator OM-85 to mitigate the risk of further infections prior to surgery. PAS and bronchus stenosis were corrected successfully by surgical intervention leading to resolution of symptoms of respiratory distress and a reduction in the incidence of respiratory infection.

http://bit.ly/2SZdG1N

A New Approach for the Diagnosis of Systemic and Oral Diseases Based on Salivary Biomolecules

Early diagnosis represents the target of contemporary medicine and has an important role in the prognosis and further treatment. Saliva is a biofluid that generated a high interest among researchers due to its multiple advantages over other body fluids. The multitude of components that can act as biomarkers influenced the existing technologies to develop protocols that could allow saliva to become the new noninvasive diagnostic method. Saliva as a diagnostic tool can bring substantial addition to the diagnostic armamentarium, providing important information about oral and general health. The diagnostic applications of saliva extended and had a rapid evolution due to the advancement in salivaomics. The present review summarizes the latest researches in saliva-related studies and explores the information and correlations that saliva can offer regarding the systemic and oral diseases, highlighting its great potential of diagnosis. It is expected that in the future specific guidelines and results regarding the salivary diagnostics are to be available, together with high-sensitivity and specificity tests for multiple systemic and oral diseases.

http://bit.ly/2TUd5vx