Παρασκευή, 28 Οκτωβρίου 2016

Creation of an injectable in situ gelling native extracellular matrix for nucleus pulposus tissue engineering

Disc degeneration is the leading cause of low back pain and is often characterized by a loss of disc height, resulting from cleavage of chondroitin sulfate proteoglycans (CSPGs) present in the nucleus pulposus. Intact CSPGs are critical to water retention and maintenance of the nucleus osmotic pressure. Decellularization of healthy nucleus pulposus tissue has the potential to serve as an ideal matrix for tissue engineering of the disc because of the presence of native disc proteins and CSPGs. Injectable in situ gelling matrices are the most viable therapeutic option to prevent damage to the anulus fibrosus and future disc degeneration.

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Why EMS needs more protection on roadway incidents

Roadways are the most dangerous scene types for EMS providers and require increased safety measures from hazardous exposure to minimize death and serious injury of public safety personnel.

We regularly share news stories of fire apparatus struck while attending a motor vehicle collision, EMS providers struck while tending to a patient and police officers killed after stopping a speeding driver or checking on a disabled vehicle.

In late October, a medical helicopter was struck and tipped over in New Mexico by an intoxicated driver who drove around barricades meant to block traffic. The reckless driver also hit a fire truck. No injuries were reported, but we don't know the impact of the transport delay on the patient's outcome. We also don't know the potential impact of traumatic stress on the EMS and fire personnel who were in the midst of caring for a patient when a out-of-control vehicle plowed into their scene.

Six months ago, nearly to the day, another medical helicopter was struck by a drunk driver who swerved through emergency vehicles before striking the helicopter's tail rotor. The impact of this central Florida incident on the patient's outcome, as well as the emergency responders, is unknown.

Because of the frequency with which emergency personnel, vehicles and now helicopters are struck, we need to accept that erecting barricades, parking a couple of blocking vehicles, waving orange flags or setting-up temporary signs is inadequate scene protection. High-visibility apparel looks great, but if the fire truck and flashing lights don't get a drunk or distracted driver's attention, then a neon-reflective vest is the equivalent of an invisible cloak.

Roadway is a hazardous materials hot zone
Any time you are working on or near a roadway, you are in the hot zone of a hazardous materials incident. Vehicles, blunt trauma-inflicting machines, hurtle around you under the loose control of undertrained, often impaired and often distracted operators. Protect your life, livelihood and family's future by protecting yourself with time, distance and shielding.

Time: As little as possible
A lethal dose exposure on a roadway can happen in a fraction of a second. Minimize EMS personnel exposure by clearing the patient to an area of relative or improved safety as quickly as possible. Pick helicopter landing zones with limited and securable access.

A firefighter injured in a structure fire is not treated in the midst of the flames and smoke — a highly hazardous and unstable environment. Instead, the firefighter is evacuated quickly and aggressively out of the structure. The awaiting ambulance or helicopter is parked well outside of the building's collapse zone. Start visualizing any roadway incident as a fully-involved, multiple story structure fire.

Distance: Get out of the striking zone
Visual warnings — signs, flares, spotters — to drivers are nice, but not enough. Increase the frequency, visual loudness and upstream distance of warning signs from the incident.

It's even better to get out of the striking zone. Move the ambulance off the road as quickly as possible. Load and go to a parking lot, access road or location that is well outside of the striking range of impaired and reckless drivers. Find and use landing zones that are not within the accessible distance of a driver.

Shielding: Bigger and stronger wall
If personnel are stuck on the road because the patient requires prolonged extrication, build a bigger and stronger wall that is impenetrable by motor vehicles. If the opportunity exists to go around, through or over the wall of blocking vehicles, we can be sure that a determined, distracted or impaired driver will make an attempt to break through the shielding.

Finally, our brains are wired to see what we are expecting to see and poorly wired to see what we are not expecting. If you have ever driven west across South Dakota, you know that there are Wall Drug signs every few miles. Because your brain is expecting Wall Drug signs, you see nearly every one regardless of its size, distance from the road or message.

Very few drivers are ever overtaken by an emergency vehicle and thus often default to blissful unawareness or fight-or-flight driven erratic movement. Even fewer drivers are expecting a helicopter to be parked on the center line. Don't expect or rely on their impaired or distracted cognitive function to identify and react appropriately to this unexpected and never before encountered environmental change.



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Distinguishing spinocerebellar ataxia with pure cerebellar manifestation from multiple system atrophy (MSA-C) through saccade profiles

Motor coordination is achieved by the cerebellum, which sets the amplitude of the initial pulse that causes a movement, predicting the correct moment through an internal model to excite agonists and antagonists to start and stop the limb at the desired location and avoid overshoot, thereby enabling elements of coordinated and smooth actions and even integrating these into a complex action (Itoh, 2010). In order to induce coordinated motor actions, the cerebellar output acts as accelerator and brake to give the movement the appropriate speed and to stop it at the appropriate time.

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Pathological and Physiological Muscle Co-activation during Active Elbow Extension in Children with Unilateral Cerebral Palsy

Cerebral palsy (CP) is a neurological pathology caused by a defect or lesion of the immature brain, which leads to disorders of movement and posture. CP is characterized by a combination of motor impairments, including spasticity, hyper-reflexia, muscle weakness, loss of selective motor control and excessive muscle co-activation (CA). These motor impairments can severely limit activities of daily living (O'Shea 2008).

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Frequency-independent characteristics of high-frequency oscillations in epileptic and non-epileptic regions

Over the past few years, there has been growing interest in the analysis of interictal high frequency oscillations (HFO), primarily with the goal of understanding their value for identifying the epileptogenic zone and their correlation with epileptogenicity. HFO promise to be more specific than interictal spikes for epileptogenic brain tissue and even more specific than the seizure-onset area (Jacobs et al. 2008).

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Evidence-based guidelines on the therapeutic use of transcranial direct current stimulation (tDCS)

Principles and mechanisms of action of transcranial direct current stimulation Alterations of neuroplasticity and cortical excitability are important pathophysiological factors in many neuropsychiatric diseases. Thus, to modify cortical activities by using non-invasive brain stimulation (NIBS) might be a valuable therapeutic approach. One of these NIBS approaches is transcranial direct current stimulation (tDCS). Fifty years ago, it has been demonstrated in anesthetized rats that neural activity and cortical excitability could be modified by the application of direct current on the sensorimotor cortex, these effects depending on stimulation polarity and persisting for hours after the end of stimulation (Bindman et al., 1964).

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Bereitschaftspotential preceding spontaneous and voluntary eyelid blinks in normal individuals

The eyelid blink is affected in numerous neurological diseases, occurring with increasing frequency, as observed in dementia, hyperkinetic movement disorders, and schizophrenia, or its reduction, as in Parkinson's patients (Stevens, 1978; Chen et al., 2003; Bologna et al., 2009; Chan et al., 2010). In addition to the protective and moisturizing function of the cornea, the eyelid blink actively participates in saccadic eye movements, fixations, visual cognitive processing and emotional expressions (Delgado-García et al., 2002, 2003).

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Mycophenolate mofetil is a valid option in patients with inflammatory bowel disease resistant to TNF-α inhibitors and conventional immunosuppressants

Few studies investigated the role of mycophenolate mofetil in inflammatory bowel disease, and none of them had specifically focused on patients with previous multiple intolerances and/or nonresponses to conventional immunosuppressants and biologics.

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Isolated hypoganglionosis in young man with autism

A 30-year-old autistic man, presented recurrent sub-occlusive episodes since five years. The CT-scan suggested a bowel obstruction due to volvulus of sigmoid colon with a marked gaseous distention of the right colon inducing liver dislocation on the left and vena cava compression (Fig. 1). A colonoscopy was performed to derotate the volvulus. However, for the appearance of megacolon up to a diameter of 16cm, a total colectomy was performed. Histological examination showed a framework of intestinal hypoganglionosis (Fig.

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Bereitschaftspotential preceding spontaneous and voluntary eyelid blinks in normal individuals

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Publication date: Available online 28 October 2016
Source:Clinical Neurophysiology
Author(s): Isabella Araujo Mota, Otávio Gomes Lins
ObjectiveTo investigate the Bereitschaftspotential (BP) preceding spontaneous and voluntary eyelid blinks in normal subjects.MethodsEighteen healthy individuals (10 female) between 17 and 60 years (mean 35) were studied. The EEG was recorded from 11 scalp positions of the 10-20 international electrode placement system referenced to linked mastoids. The vertical electrooculogram (VEOG) was recorded from two electrodes positioned above and below the right eye. The ground electrode was placed in the right clavicle. The recordings were obtained during spontaneous and voluntary eyelid blinks. Two-second EEG segments before the onset of the blink potential (visually identified at the VEOG channel) were averaged and analyzed off-line. The statistical significance of differences was evaluated by repeated-measures analysis of variance with Geisser-Greenhouse correction for violation of sphericity and the Newman-Keuls test was used for post-hoc comparisons.ResultsA BP starting around -1700 ms prior to the onset of voluntary blink was observed; it had average amplitude in the negative peak of 3.3 μV. There was no BP preceding spontaneous blinking. Conclusion: A BP precedes voluntary blinks but not spontaneous blinks.SignificanceThis is the first study evaluating the BP preceding spontaneous and voluntary eye blinks.



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Mycophenolate mofetil is a valid option in patients with inflammatory bowel disease resistant to TNF-α inhibitors and conventional immunosuppressants

Few studies investigated the role of mycophenolate mofetil in inflammatory bowel disease, and none of them had specifically focused on patients with previous multiple intolerances and/or nonresponses to conventional immunosuppressants and biologics.

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Isolated hypoganglionosis in young man with autism

A 30-year-old autistic man, presented recurrent sub-occlusive episodes since five years. The CT-scan suggested a bowel obstruction due to volvulus of sigmoid colon with a marked gaseous distention of the right colon inducing liver dislocation on the left and vena cava compression (Fig. 1). A colonoscopy was performed to derotate the volvulus. However, for the appearance of megacolon up to a diameter of 16cm, a total colectomy was performed. Histological examination showed a framework of intestinal hypoganglionosis (Fig.

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Impact of ejection fraction on infectious, renal, and respiratory morbidity for patients undergoing noncardiac surgery

We sought to determine if decreased left ventricular systolic function was associated with an increased risk of postoperative infectious, respiratory, or renal complications in patients undergoing noncardiac surgery.

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Pan Drug-Resistant Environmental Isolate of Acinetobacter baumannii from Croatia

Microbial Drug Resistance , Vol. 0, No. 0.


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Global cognitive function and processing speed are associated with gait and balance dysfunction in Parkinson’s disease

Our primary objective was to determine the relationship between global cognitive function and specific domains of gait and balance in a cohort of Parkinson's disease (PD) subjects. In a secondary analysis, we ...

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Sequence analysis and expression profiles of TaABI5 , a pre-harvest sprouting resistance gene in wheat

Abstract

Pre-harvest sprouting (PHS) is the germination of grains in the spike under wet conditions before harvest, which causes a severe reduction in crop yield and flour quality. The phytohormone abscisic acid plays a key role in regulating seed dormancy, which inhibits pre-harvest spouting or vivipary for many important crops. TaABI5, belonging to a family of basic leucine zipper transcription factors could regulate a subset of late embryogenesis abundant genes during seed development, was isolated and characterized. Phylogenetic analysis revealed that TaABI5 homologous gene belonged to the ABI5 subgroup of the ABF/AREB/ABI5 subfamily. TaABI5 consist of four conserved domains and one bZip domain. The expression pattern of TaABI5 indicated that it was seed-specific and accumulated at late stages of seed development. Accumulation of TaABI5 in synthetic hexaploid wheat SHW-L1 (PHS resistance) was 8.93-fold higher than that in wheat cultivar Chuanmai 32 (PHS susceptible) at 25 days post anthesis. Four expression quantitative trait loci (eQTL) of TaABI5 on chromosome 2DS, 4DS, 6DS, and 7DL were characterized from SHW-L1/Chuanmai 32 derived recombinant inbred line population.



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Maternal genetic polymorphisms and unexplained recurrent miscarriage: a systematic review and meta-analysis

Abstract

Background

The roles of genetic polymorphisms in the pathogenesis of recurrent miscarriage (RM) have been intensively studied. However, the results of these studies were inconsistent, especially when conducted in different populations. Therefore, we performed the current study to systematically review the broad spectrum of genetic polymorphisms that were suspected to be involved in RM, and discussed potential genetic biomarkers of RM.

Methods

Eligible articles were identified in PubMed, Medline, Embase and CNKI. Odd ratios (ORs) and 95% confidence intervals (CIs) were used to describe the strength of association, and a probability value (P value) of 0.05 or less was considered as statistically significant.

Results

A total of 425 eligible articles were included in this systematic review and 369 articles evaluating 124 polymorphisms of 73 genes were meta-analyzed. A sSignificant associations was were found between RM and 53 genetic polymorphisms of 37 genes. Our findings suggest that genetic variants of HLA-G, IFNG, TNF, IL-6, IL-10, FII, FV, FXIII, ITGB3, MTR, MTHFR, PAI-1, NOS3, KDR, TP53, VEGFA, CYP17, CYP1A1, CYP2D6, ANXA5, and XCI may serve as potential biological markers of RM.

Conclusions

The present study indicates that over-active immunological responeses, thrombophilia, abnormal placental function, and disturbance of metabolic regulation may be implicated in the pathogenesis of RM.

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Graphical Abstract



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Population screening for spinal muscular atrophy: A mixed methods study of the views of affected families

Autosomal recessive conditions are a significant health burden with few treatments. Population carrier screening has been suggested as a means to tackle them. Little is known about the views of affected families despite the potential for direct impacts on them. Data are presented on attitudes among families affected by Spinal Muscular Atrophy (SMA) toward two population screening programs, pre-conception, and prenatal. Data were gathered through qualitative interviews (n = 36) and a survey (n = 337). Eighty-two survey participants had SMA and 255 were family members. The majority were in favor of screening (75%). Reasons for supporting pre-conception screening support were a belief that it would reduce SMA-related terminations and raise awareness of SMA in the population. For prenatal screening, reasons for support included a belief in the importance of informed decision-making and the need to reduce suffering. Key reasons for non-support of pre-conception screening included concerns about carrier stigmatization and social engineering. For prenatal screening, concerns focused on the collateral loss of high quality of life lives affected by SMA. This study highlights that those affected by SMA are predominantly in favor of screening, although pre-conception screening is most favored. While family members and adults with SMA had largely consistent views, perceptions varied according to the severity (type) of SMA, with those affected by SMA type II the least likely to support screening. These findings suggest that screening for SMA is a complex issue for affected families, underscoring the need to consider and include their views when planning and implementing screening programs. © 2016 Wiley Periodicals, Inc.



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Much ado about something 2: Reflections on the state of the American Journal of Medical Genetics 2016



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Review of familial cerebral cavernous malformations and report of seven additional families

Cerebral cavernous malformations are vascular anomalies of the central nervous system characterized by clusters of enlarged, leaky capillaries. They are caused by loss-of-function mutations in KRIT1, CCM2, or PDCD10. The proteins encoded by these genes are involved in four partially interconnected signaling pathways that control angiogenesis and endothelial permeability. Cerebral cavernous malformations can occur sporadically, or as a familial autosomal dominant disorder (FCCM) with incomplete clinical and neuroradiological penetrance and great inter-individual variability. Although the clinical course is unpredictable, symptoms typically present during adult life and include headaches, focal neurological deficits, seizures, and potentially fatal stroke. In addition to neural lesions, extraneural cavernous malformations have been described in familial disease in several tissues, in particular the skin. We here present seven novel FCCM families with neurologic and cutaneous lesions. We review histopathological and clinical features and provide an update on the pathophysiology of cerebral cavernous malformations and associated cutaneous vascular lesions. © 2016 Wiley Periodicals, Inc.



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Camptodactyly and the 22q11.2 deletion syndrome

We describe a 5-day-old male with minor facial anomalies, a congenital laryngeal web, severe laryngomalacia, and prominent fixed flexion of the proximal interphalangeal joints of digits 2 through 5 bilaterally. A whole genome SNP microarray analysis identified a 2.55 Mb interstitial deletion of 22q11.21, typical of that seen in the DiGeorge and Velocardiofacial syndromes. A review of the literature identifies 10 other cases with camptodactyly. Camptodactyly appears to be an associated but rarely reported anomaly in patients with the 22q11.2 microdeletion syndrome. © 2016 Wiley Periodicals, Inc.



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Sudden infant death “syndrome”—Insights and future directions from a Utah population database analysis

"Sudden Infant Death syndrome" (SIDS) represents the commonest category of infant death after the first month of life. As genome scale sequencing greatly facilitates the identification of new candidate disease variants, the challenges of ascribing causation to these variants persists. In order to determine the extent to which SIDS occurs in related individuals and their pedigree structure we undertook an analysis of SIDS using the Utah Population Database, recording, for example, evidence of enrichment for genetic causation following the back-to-sleep recommendations of 1992 and 1994. Our evaluation of the pre- and post back-to-sleep incidence of SIDS in Utah showed a decrease in SIDS incidence on the order of eightfold following back-to-sleep. An odds ratio of 4.2 for SIDS recurrence among sibs was identified from 1968 to 2013 which was similar to the odds ratio of 4.84 for death due to other or unknown cause among sibs of SIDS cases for the same time period. Combining first through thid degree relatives yielded an odds ratio of SIDS recurrence of 9.29 in the post-back-to-sleep (1995–2013) subset of SIDS cases where similar calculations of first-third degree relatives for the entire time period of 1968–2013 showed an odds ratio of 2.95. Expanded multigenertional pedigrees showing enrichment for SIDS were also identified. Based on these findings we hypothesize that post back-to-sleep SIDS, especially recurrences within a family, are potentially enriched for genetic causes due to the impact of safe sleeping guidelines in mitigating environmental risk factors. © 2016 Wiley Periodicals, Inc.



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Trisomy 18 and eye anomalies



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ARL2BP mutations account for 0.1% of autosomal recessive rod-cone dystrophies with the report of a novel splice variant.

Thumbnail image of graphical abstract

Graphical Abstract



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Acupuncture does not restore metabolic disturbances in the P450 aromatase inhibitor induced-polycystic ovary syndrome rat model

Low-frequency electroacupuncture restores sex steroid synthesis and sympathetic activity in women with polycystic ovary syndrome, which may improve its metabolic disturbances likely by modulating sympathetic nerve activity or sex steroid synthesis. We investigated whether low-frequency electroacupuncture regulates the metabolic function to the same extent as treatment with estradiol or β-adrenergic blocking in a rat model of polycystic ovary syndrome induced by a P450 aromatase inhibitor (letrozole). Letrozole (200 μg per day) or placebo pellets were implanted in pre-pubertal Wistar rats. Six weeks thereafter, rats were treated for 5–6 weeks with: low-frequency electroacupuncture (5 days per week), a β-adrenergic blocker (propranolol hydrochloride, 0.1 mg kg−1) (5 days per week), or 17β-estradiol (2.0 μg) every fourth day. Body weight development, body composition, locomotor activity, insulin sensitivity, tissue specific glucose uptake, lipid profile, adipocyte size, adiponectin and insulin serum concentrations, and gene expression in inguinal fat were measured. All treatments increased circulating levels of LDL-cholesterol. Estradiol treatment restored locomotor activity and increased insulin sensitivity but did not modify the glucose uptake in muscle and fat. An upregulation of genes related to insulin sensitivity and downregulation of genes related to adipogenesis were observed in subcutaneous adipose tissue from rats exposed to letrozole. Only estradiol treatment normalized the expression of these genes. In conclusions, low-frequency electroacupuncture increased LDL-cholesterol without affecting the insulin sensitivity or adipose tissue function, which could suggest effects on hepatic lipid regulation probably mediated by estradiol action or β-adrenergic pathway.

This article is protected by copyright. All rights reserved



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Feasibility of laparoscopic total mesorectal excision with extended lateral pelvic lymph node dissection for advanced lower rectal cancer after preoperative chemoradiotherapy

World Journal of Surgery

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Evaluation of a potential interaction between new regimens to treat hepatitis C and warfarin

Annals of Pharmacotherapy

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Results of laparoscopic sleeve gastrectomy--5-year follow-up study in an eastern European emerging bariatric center

Obesity Surgery

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Long-term outcomes of heart transplant recipients with hepatitis C positivity: The data from the U.S. Transplant Registry

Clinical Transplantation

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Closed-loop gastric electrical stimulation versus laparoscopic adjustable gastric band for the treatment of obesity: A randomized 12-month multicenter study

International Journal of Obesity

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Sufentanil sublingual tablet 30 mcg for the management of pain following abdominal surgery: A randomized, placebo-controlled, phase-3 study

Pain Practice

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Epigenetic regulation of early- and late-response genes in acute pancreatitis

The Journal of Immunology

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Efficacy and safety of sofosbuvir-based interferon-free therapies for hepatitis C in liver transplant recipients

Journal of Gastroenterology and Hepatology

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Successful donation after cardiac death liver transplants with prolonged warm ischemia time using normothermic regional perfusion

Liver Transplantation

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Survival outcomes in asymptomatic patients with normal conventional imaging but raised carcinoembryonic antigen levels in colorectal cancer following positron emission tomography-computed tomography imaging

The Oncologist

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Prevalence and phenotypic characterization of MC4R variants in a large pediatric cohort

International Journal of Obesity

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Therapeutic management of inflammatory bowel disease in real-life practice in the current era of anti-TNF agents: Analysis of the French administrative health databases 2009-2014

Alimentary Pharmacology and Therapeutics

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Role of vitamin D in inflammatory bowel disease

Nutrition in Clinical Practice

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Probiotics and prevention of antibiotic-associated diarrhea in kids

JAMA

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Surgical strategy and outcome in patients undergoing pancreaticoduodenectomy after gastric resection: A three-center experience with 39 patients

World Journal of Surgery

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Amelogenin specific IgA and IgG in children with untreated coeliac disease

European Journal of Oral Sciences

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Survival at 2 years among liver cirrhotic patients is influenced by left atrial volume and left ventricular mass

Liver International

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Results of Sofosbuvir based combination therapy for chronic hepatitis C cohort of Indian patients in real life clinical practice

Journal of Gastroenterology and Hepatology

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Externalized stents for pancreatoduodenectomy provide value only in high-risk scenarios

Journal of Gastrointestinal Surgery

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Novel methods for the treatment of non-alcoholic steatohepatitis - targeting the gut immune system to decrease the systemic inflammatory response without immune suppression

Alimentary Pharmacology and Therapeutics

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Comparison of miRNA profiling during airway epithelial repair in undifferentiated and differentiated cells in vitro

Abstract

Respiratory epithelium is a highly integrated structure that efficiently protects lungs from extrinsic irritants thanks to rapid repair of the wound. The repair is a complex process that requires coordinated expression of networks of genes. Plausible regulators of this process are microRNAs. We investigated whether global miRNA silencing influences the epithelial repair, and whether changes in miRNA expression profile during repair are similar between two bronchial epithelial cell cultures: differentiated and undifferentiated cells. Two bronchial cell types were used:16HBE14o- and NHBE. Transfection was performed with siRNAs against Drosha and Dicer. For miRNA profiling, non-transfected cells were cultured until confluent and harvested for RNA isolation at baseline (cells before wounding) and at different time post-wounding (8, 16, 24, and 48 h). MicroRNA expression profiling was performed using TaqMan Array Human MicroRNA Card A. Target prediction was done in miRNA body map, and pathway analysis using DAVID. Cells with downregulated Drosha and Dicer demonstrated a significantly delayed wound repair in comparison to control in both cell lines. MiRNA expression profiling revealed that ten miRNAs exhibited significant changes over time after cell injury. These genes showed a similar expression pattern in both cell lines. The predicted targets of these miRNAs were then clustered by pathway analysis into six biological groups related to wound repair. Silencing of global miRNA expression confirmed that miRNAs are crucial for airway epithelial repair. Moreover, epithelial cells of two different origins demonstrated some similarities in miRNA expression pattern during wound repair, independent of differentiation state.



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Modified DNA polymerases for PCR troubleshooting

Abstract

PCR has become an essential tool in biological science. However, researchers often encounter problems with difficult targets, inhibitors accompanying the samples, or PCR trouble related to DNA polymerase. Therefore, PCR optimization is necessary to obtain better results. One solution is using modified DNA polymerases with desirable properties for the experiments. In this article, PCR troubleshooting, depending on the DNA polymerase used, is shown. In addition, the reasons that might justify the need for modification of DNA polymerases, type of modifications, and links between modified DNA polymerases and PCR efficiency are described.



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Modelling of atorvastatin pharmacokinetics and the identification of the effect of a BCRP polymorphism in the Japanese population.

Aim: Ethnicity plays a modulating role in atorvastatin pharmacokinetics (PK), with Asian patients reported to have higher exposure compared with Caucasians. Therefore, it is difficult to safely extrapolate atorvastatin PK data and models across ethnic groups. This work aims to develop a population PK model for atorvastatin and its pharmacologically active metabolites specifically for the Japanese population. Subsequently, it aimed to identify genetic polymorphisms affecting atorvastatin PK in this population. Methods: Atorvastatin acid (ATA) and ortho-hydroxy-atorvastatin acid (o-OH-ATA) plasma concentrations, clinical/demographic characteristics and genotypes for 18 (3, 3, 1, 1, 7, 2 and 1 in the ABCB1, ABCG2, CYP3A4, CYP3A5, SLCO1B1, SLCO2B1 and PPARA genes, respectively) genetic polymorphisms were collected from 27 Japanese individuals (taking 10 mg atorvastatin once daily) and analysed using a population PK modelling approach. Results: The population PK model developed (one-compartment for ATA linked through metabolite formation to an additional compartment describing the disposition of o-OH-ATA) accurately described the observed data and the associated population variability. Our analysis suggested that patients carrying one variant allele for the rs2622604 polymorphism (ABCG2) show a 55% (95% confidence interval: 16-131%) increase in atorvastatin oral bioavailability relative to the value in individuals without the variant allele. Conclusion: The current work reports the identification in the Japanese population of a BCRP polymorphism, not previously associated with the PK of any statin, that markedly increases ATA and o-OH-ATA exposure. The model developed may be of clinical importance to guide dosing recommendations tailored specifically for the Japanese. Copyright (C) 2016 Wolters Kluwer Health, Inc. All rights reserved.

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Globe, DuPont, and NVFC announce more winners in 2016 Gear Giveaway

A total of 52 sets of gear will be awarded in 2016 Globe, DuPont Protection Solutions (DuPont), and the National Volunteer Fire Council (NVFC) have announced the latest round of winners in the 2016 Globe Gear Giveaway. This is the fifth year that Globe has partnered with DuPont and the NVFC to provide volunteer departments with critically needed sets of turnout gear. The Northwest Washington Volunteer ...

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Strain elastography for assessment of liver fibrosis and prognosis in patients with chronic liver diseases

Abstract

Background

Estimation of liver stiffness is essential in the treatment of liver diseases. Various procedures alternative to liver biopsy have been developed, and transient elastography using shear wave is an established method for evaluating liver stiffness and has been shown to be a prognostic indicator. In contrast, strain elastography (SE) has been applied to evaluate liver stiffness, however the significance remains uncertain.

Methods

We retrospectively analyzed 598 patients who underwent SE to evaluate the ability of estimating liver stiffness and the prognosis. Elasticity index (EI) was evaluated as an indicator of liver stiffness in this study.

Results

EI was increased as histological fibrosis advanced. EI was significantly different between mild fibrosis (F0–2) and advanced fibrosis (F3, 4). In contrast, EI was similar among those with different activity scores. EI showed better diagnostic performance in estimating advanced fibrosis than other serological markers and good reproducibility. Furthermore, EI was shown to be an independent prognostic factor in patients with chronic liver diseases and also with hepatocellular carcinoma (HCC) with advanced stage.

Conclusions

SE could estimate advanced liver fibrosis without influence of liver inflammation unlike other serological liver fibrosis markers. SE might be a prognostic factor in chronic liver diseases and HCC.



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