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Κυριακή 4 Νοεμβρίου 2018

Effect of chronic corticosterone-induced depression on circadian rhythms and age-related phenotypes in mice

Abstract
Disrupted circadian rhythms are a recognized effect of depression, and our previous article demonstrated an association between depression and premature aging, but the underlying mechanisms are not well understood. In the present study, we used a mouse model of chronic corticosterone (CORT)-treated depression to elucidate a mechanism by which depression may be associated with the circadian clock and mediate age-related phenotypes. Mice received a daily injection of 20 mg/kg CORT for 21 consecutive days, and the depression-like behaviors of mice were identified by the sucrose intake test, tail suspension test and open field test. Our findings indicated that CORT injection may be correlated with the circadian clock by impairing circadian rhythms or shifting the phase values of clock genes. We also showed that CORT-treated mice exhibited a significant gradual reduction in body weight gain with increased oxidative stress, including reduced activity of antioxidant-related enzymes, reduced glutathione:glutathione disulfide ratio and cytochrome (Cyt)-C level, and elevated reactive oxygen species content. Moreover, chronic CORT injection affected inflammatory responses, the production of mitochondrial ATP and telomere shortening, which may be associated with the Sirtuin 3 (SIRT3) signaling pathway. Additionally, chronic CORT injection disrupted the circadian rhythms of some indexes of aging phenotypes and altered the phase values of these indexes. Our findings suggest that psychologically stressful conditions such as depression are linked to changes in circadian rhythms and age-related phenotypes.

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Sarcoidosis and Its Splenic Wonder: A Rare Case of Isolated Splenic Sarcoidosis

Sarcoidosis is a systemic granulomatous disease of unknown etiology characterized by presence of noncaseating granulomas in the involved organs. The pulmonary interstitium is most commonly affected but extrapulmonary involvement can occur in almost any other organ system. Such an involvement can occur with or without the presence of pulmonary involvement, but isolated extrapulmonary involvement has been noted only in around 10% of cases. Isolated splenomegaly is very rare and an uncommon presentation of sarcoidosis. It is clinically challenging because of the extensive differential diagnosis. Among the many considerations are hematologic malignancies, primary splenic or metastatic tumors, infiltrative disorders, inflammatory disorders, and infections. We hereby discuss an interesting case of a 40-year-old female with isolated splenic sarcoidosis.

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Foundation Recognized as One of 10 Best Medical Research Organizations

Charity NavigatorThe Focused Ultrasound Foundation was included in Charity Navigator's recent list of America's 10 Best Medical Research Organizations. The list highlights charities that are committed to funding cutting-edge research, finding breakthroughs for a spectrum of conditions and diseases, and using donors' funds wisely in their journey to find a cure. Charity Navigator is the nation's largest independent charity evaluator and leading donor advocate, and the Foundation has earned four stars, the highest rating awarded by the site.

SEE THE LIST >


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Mutations of RAS/RAF Proto-oncogenes Impair Survival After Cytoreductive Surgery and HIPEC for Peritoneal Metastasis of Colorectal Origin

imageBackground: Adequate selection of patients with peritoneal metastasis (PM) for cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC) remains critical for successful long-term outcomes. Factors reflecting tumor biology are currently poorly represented in the selection process. The prognostic relevance of RAS/RAF mutations in patients with PM remains unclear. Methods: Survival data of patients with colorectal PM operated in 6 European tertiary centers were retrospectively collected and predictive factors for survival identified by Cox regression analyses. A simple point-based risk score was developed to allow patient selection and outcome prediction. Results: Data of 524 patients with a median age of 59 years and a median peritoneal cancer index of 7 (interquartile range: 3–12) were collected. A complete resection was possible in 505 patients; overall morbidity and 90-day mortality were 50.9% and 2.1%, respectively. PCI [hazard ratio (HR): 1.08], N1 stage (HR: 2.15), N2 stage (HR: 2.57), G3 stage (HR: 1.80) as well as KRAS (HR: 1.46) and BRAF (HR: 3.97) mutations were found to significantly impair survival after CRS/HIPEC on multivariate analyses. Mutations of RAS/RAF impaired survival independently of targeted treatment against EGFR. Consequently, a simple point-based risk score termed BIOSCOPE (BIOlogical Score of COlorectal PEritoneal metastasis) based on PCI, N-, G-, and RAS/RAF status was developed, which showed good discrimination [development area under the curve (AUC) = 0.72, validation AUC = 0.70], calibration (P = 0.401) and allowed categorization of patients into 4 groups with strongly divergent survival outcomes. Conclusion: RAS/RAF mutations impair survival after CRS/HIPEC. The novel BIOSCOPE score reflects tumor biology, adequately stratifies long-term outcomes, and improves patient assessment and selection.

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The RESTORE Randomized Controlled Trial: Impact of a Multidisciplinary Rehabilitative Program on Cardiorespiratory Fitness in Esophagogastric cancer Survivorship

imageObjective: The Rehabilitation Strategies in Esophagogastric cancer (RESTORE) randomized controlled trial evaluated the efficacy of a 12-week multidisciplinary program to increase the cardiorespiratory fitness and health-related quality of life (HRQOL) of esophagogastric cancer survivors. Background: Patients following treatment for esophagogastric cancer are at risk of physical deconditioning, nutritional compromise, and sarcopenia. Accordingly, compelling rationale exists to target these impairments in recovery. Methods: Disease-free patients treated for esophagogastric cancer were randomized to either usual care or the 12-week RESTORE program (exercise training, dietary counseling, and multidisciplinary education). The primary outcome was cardiopulmonary exercise testing (VO2peak). Secondary outcomes included body composition (bioimpedance analysis), and HRQOL (EORTC-QLQ-C30). Outcomes were assessed at baseline (T0), postintervention (T1), and at 3-month follow-up (T2). Results: Twenty-two participants were randomized to the control group [mean (standard deviation) age 64.14 (10.46) yr, body mass index 25.67 (4.83) kg/m2, time postsurgery 33.68 (19.56) mo], and 21 to the intervention group [age 67.19(7.49) yr, body mass index 25.69(4.02) kg/m2, time postsurgery 23.52(15.23) mo]. Mean adherence to prescribed exercise sessions were 94(12)% (supervised) and 78(27)% (unsupervised). Correcting for baseline VO2peak, the intervention arm had significantly higher VO2peak at both T1, 22.20 (4.35) versus 21.41 (4.49) mL · min−1 · kg−1, P

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Losing doctors with integrity will harm patients and profession [Letters]



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The conscience rights of Canadian physicians require protection [Letters]



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Alcohol use, opioid overdose and socioeconomic status in Canada: A threat to life expectancy? [Commentary]



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Global Burden of Disease Study trends for Canada from 1990 to 2016 [Research]

BACKGROUND:

The Global Burden of Disease Study represents a large and systematic effort to describe the burden of diseases and injuries over the past 3 decades. We aimed to summarize the Canadian data on burden of diseases and injuries.

METHODS:

We summarized data from the 2016 iteration of the Global Burden of Disease Study to provide current (2016) and historical estimates for all-cause and cause-specific diseases and injuries using mortality, years of life lost, years lived with disability and disability-adjusted life years in Canada. We also compared changes in life expectancy and health-adjusted life expectancy between Canada and 21 countries with a high sociodemographic index.

RESULTS:

In 2016, leading causes of all-age disability-adjusted life years were neoplasms, cardiovascular diseases, musculoskeletal diseases, and mental and substance use disorders, which together accounted for about 56% of disability-adjusted life years. Between 2006 and 2016, the rate of all-cause age-standardized years of life lost declined by 12%, while the rate of all-cause age-standardized years lived with disability remained relatively stable (+1%), and the rate of all-cause age-standardized disability-adjusted life year declined by 5%. In 2016, Canada aligned with countries that have a similar high sociodemographic index in terms of life expectancy (82 yr) and health-adjusted life expectancy (71 yr).

INTERPRETATION:

The patterns of mortality and morbidity in Canada reflect an aging population and improving patterns of population health. If current trends continue, Canada will continue to face challenges of increasing population morbidity and disability alongside decreasing premature mortality.



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Medical school reserves seats for low-income students to increase diversity [News]



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Organ donation after medical assistance in dying at home [Practice]



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The "dimple swallow" sign for branchial cleft anomalies [Practice]



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Medical leaders urge system change to reduce physician burnout [News]



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Between a hermitage and a hospital [Humanities]



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Doctors conflicted about patients recording clinical visits [News]



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Worsening right hip pain



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Lambda interferons come to light: dual function cytokines mediating antiviral immunity and damage control

Evangelos Andreakos | Ivan Zanoni | Ioanna E Galani

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Harnessing the immune system in glioblastoma

Harnessing the immune system in glioblastoma

Harnessing the immune system in glioblastoma, Published online: 05 November 2018; doi:10.1038/s41416-018-0258-8

Harnessing the immune system in glioblastoma

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Pain Management during Rehabilitation after Distal Radius Fracture Stabilized with Volar Locking Plate: A Prospective Cohort Study

Introduction. Internal fixation with volar locking plate (VLP) was widely adopted as a first-line choice in treatment of distal radius fracture (DRF). Methods. Total 315 patients with distal radius fracture receiving VLP fixation were included for analysis in this study. The rehabilitation protocol was started immediately after surgery for all patients. During the initial two weeks after surgery, 149 patients received 200 mg celecoxib twice per day, 89 received buprenorphine transdermal patch at 5 μg/h, and 77 received 13 mg codeine plus 200 mg ibuprofen twice per day for pain management. Visual analog scale (VAS) scores of pain at rest, daily activity, and rehabilitative exercise were measured, respectively, every week according to the experiences of the past week in the initial six weeks after surgery. Functional outcomes including range of motion (ROM) for extension, flexion, pronation, supination, ulnar and radial abduction, the disabilities of arm, shoulder, and hand (DASH) score and the validated patient rated wrist evaluation (PRWE), and grip strength were collected at one, three, and six months after surgery. Results. We showed that patients receiving transdermal buprenorphine and codeine/ibuprofen had decreased VAS scores during rehabilitative exercise, better compliance to the rehabilitation program, and thus faster functional recovery. Conclusions. We recommend transdermal buprenorphine or codeine/ibuprofen for pain management during rehabilitation after distal radius fracture stabilized with VLP.

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The use of “QUAD Shot” in Anal Canal Squamous Cell Carcinoma: A Case Study with Review of the Literature

Patients with locoregional anal carcinoma who don't qualify for standard definitive chemoradiation are candidates for a short course of palliative hypofractionated radiotherapy such as QUAD Shot.

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Ethnic, Racial, and Sex Differences in Etiology, Symptoms, Treatment, and Symptom Outcomes of Patients with Gastroparesis

Gastroparesis is a chronic disorder of the stomach characterized by nausea, vomiting, early satiety, postprandial fullness, and abdominal pain. There is limited information on gastroparesis in minority populations. We assessed ethnic, racial, and sex variations in the etiology, symptoms, quality of life, gastric emptying, treatments, and symptom outcomes of patients with gastroparesis.

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Cardiogenic Dysphagia by Dysphagia Megalatriensis & Aortica



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Submission title: An unusual cause of hematochezia



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Tofacitinib for the Treatment of Pyoderma Gangrenosum



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Obliterative Portal Venopathy without Cirrhosis is Prevalent in Pediatric Cystic Fibrosis Liver Disease with Portal Hypertension



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Harnessing the immune system in glioblastoma



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FDA Alerts Patients and Health Care Professionals that Some EpiPen Auto-Injectors May Not Readily Slide Out of Carrier Tube

Audience: Consumer, Health Professional, Pharmacy [11/2/2018] FDA is alerting patients, caregivers and health care professionals that the labels attached to some EpiPen 0.3mg and EpiPen Jr 0.15mg auto-injectors, and the authorized generic versions,...

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FDA Alerts Patients and Health Care Professionals that Some EpiPen Auto-Injectors May Not Readily Slide Out of Carrier Tube

Audience: Consumer, Health Professional, Pharmacy [11/2/2018] FDA is alerting patients, caregivers and health care professionals that the labels attached to some EpiPen 0.3mg and EpiPen Jr 0.15mg auto-injectors, and the authorized generic versions,...

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Efficacy of 3 fine-needle biopsy techniques for suspected pancreatic malignancies in the absence of an on-site cytopathologist

EUS-guided fine-needle aspiration/biopsy (EUS-FNA/B) has a high diagnostic accuracy for pancreatic tumors. Most reports have focused on the diagnostic yield of cytology or histology; the ability of various FNA/B techniques to obtain an adequate mass of cells or tissue has rarely been investigated.

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Application of deep learning to predict advanced neoplasia using big clinical data in colorectal cancer screening of asymptomatic adults

We aimed to develop deep learning models for the prediction of the risk of advanced colorectal neoplasia (ACRN) in asymptomatic adults based on which colorectal cancer screening could be customized.

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Temporal Analysis of the Nuclear-to-cytoplasmic Translocation of a Herpes Simplex Virus 1 Protein by Immunofluorescent Confocal Microscopy

ICP0 undergoes nuclear-to-cytoplasmic translocation during HSV-1 infection. The molecular mechanism of this event is not known. Here we describe the use of confocal microscope as a tool to quantify ICP0 movement in HSV-1 infection, which lays the groundwork for quantitatively analyzing ICP0 translocation in future mechanistic studies.

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Lentiviral Vector-mediated Gene Therapy of Hepatocytes Ex Vivo for Autologous Transplantation in Swine

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This protocol is intended to describe porcine hepatocyte isolation and ex vivo gene delivery to cure models of metabolic diseases via autologous cell transplantation. Although this particular model enjoys unique advantages that favor successful therapy, the application is a relevant foundation to address additional diseases and indications.

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Reset Osmostat: A Challenging Case of Hyponatremia

Hyponatremia is the most common electrolyte abnormality seen in hospitalised patients with up to 15–20% of patients having a sodium level of less than 135 mmol/L (Reddy and Mooradian, 2009). Cases of hyponatremia were first described in the 1950s (George et al., 1955). As the differential diagnosis for hyponatremia is broad, a systematic and logical approach is needed to identify the cause. We describe a case of a 30-year-old gentleman who was found to have chronic hyponatremia. After a thorough workup, he was diagnosed to have reset osmostat. Reset osmostat is an uncommon and under recognised cause of hyponatremia which does not require any treatment. This diagnosis needs to be considered when the hyponatremia workup suggests SIADH, but the hyponatremia is not amenable to fluid restriction, salt or urea supplementation, and diuretic treatment.

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Controlled immobilization-traction based on intervertebral stability is conducive to the regeneration or repair of the degenerative disc: An in Vivo Study on the Rat coccygeal model

Publication date: Available online 3 November 2018

Source: The Spine Journal

Author(s): Yan-Jun Che, Jiang-Bo Guo, Ting Liang, Xi Chen, Wen Zhang, Hui-Lin Yang, Zong-Ping Luo

ABSTRACT
BACKGROUND CONTEXT

Previous studies have shown the potential for intervertebral disc tissue regeneration is very limited. While in vivo and in vitro studies have shown that traction can restore disc height and internal pressure, in many clinical studies it was shown that axial mechanical traction for the treatment of low back pain is ineffective.

PURPOSE

The aim of this study was to identify how the disc could be distracted, how to define the state of traction, and to further examine the feasibility of regenerating or restoring the degenerative disc by means of traction.

STUDY DESIGN

A macro- and micro-level structural analysis of degenerative discs of rat tail before and after controlled immobilization-traction.

METHODS

In this study, 49 6-month-old male Sprague-Dawley rats were randomly assigned to one of seven groups. Group A was the sham control group in which caudal vertebrae were instrumented with K-wires only. In Group B (model group), caudal vertebrae were immobilized using a custom-made external device to fix four caudal vertebrae (Co7-Co10) and Co8-Co9 underwent 4 weeks of compression to induce moderate disc degeneration. In Group C, vertebrae Co8-Co9 underwent 4 weeks of compression to induce moderate disc degeneration, followed by removal of the external apparatus. Rats in the other four groups (groups D-G), Co8-Co9 underwent 4 weeks of compression to induce moderate disc degeneration followed by 2 weeks, 4 weeks, 6 weeks, and 8 weeks of distraction, respectively. Caudal vertebrae were harvested and disc height, T2 signal intensity of the discs, disc morphology, total glycosaminoglycan content of the nucleus pulposus and the structure of the Co8-Co9 endplate were evaluated.

RESULTS

After 4 weeks of compression, the intervertebral height and T2 signal intensity of Co8-Co9 vertebrae of rats in groups B-G were significantly reduced compared with group A (sham group, all P < 0.0001). Histological scores of rats in group B averaged 10.14 and the total GAG of nucleus pulposus averaged 238.21μg GAG/ng DNA. The bony endplate structure showed significant changes in comparison with the control group. After 2 weeks to 8 weeks of traction, the disc space and T2 signal intensity of Co8-9 vertebrae in group E were significantly recovered compared to that of rats in group B (P < 0.0001), and the intervertebral height of the Co8-9 in group D, group F, and group G when compared with group B (P < 0.0001). Meanwhile, the T2 signal intensity of Co8-9 in group D, F and G when compared with group B (P < 0.001). Histological scores dropped from an average of 10.14 in group B to 5.57 in group E, and 5.86 in group F (all P < 0.0001). Furthermore, the total GAG content of the nucleus pulposus increased from an average of 238.21 μg GAG/ng DNA in group B to 601.02 μg GAG/ng DNA in group E (P < 0.0001). The number of pores of endplates in rats in groups D and E both were significantly increased when compared to that of rats in group B (groups D vs groups B, P < 0.05; groups E vs groups B, P < 0.0001).

CONCLUSIONS

A mechanical degenerative model was successfully established by using a custom-made device. We demonstrated that disc degeneration is a cascade of biochemical, mechanical, and structural changes mediated by cells in an abnormal mechanical environment. Not all levels of disc degeneration can be regenerated or repaired. Regeneration or recovery of disc degeneration requires specific conditions. Based on the immobilization-traction mode, the cascade cycle of disc degeneration is interrupted. Traction of 2-6 weeks is a sensitive period for regeneration of the degenerative disc. Moreover, the duration and extent of the traction loading must be moderately controllable, and beyond the limits that can lead to significant degeneration. These data may help improve our understanding of the pathogenesis of clinical disc degeneration and how to optimize the use of traction devices for possible regeneration.



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Conn. teachers awarded for saving student with CPR

Kevin DeAngelo and Marcia Sher-Kalter said their CPR first aid certification and lifeguard training helped them respond quickly

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Local Tensile Stress in the Development of Posttraumatic Osteoarthritis

The pathogenesis of posttraumatic osteoarthritis (PTOA) remains unrevealed. We speculate that cartilage crack caused by joint trauma will induce local abnormal tensile stress, leading to change in extracellular matrix (ECM) expression of chondrocytes, cartilage degeneration, and initiation of osteoarthritis. Finite element model was used to examine whether the local tensile stress could be produced around the crack. Cell experiments were conducted to test the effect of tensile strain on chondrocyte ECM expression. Animal tests in rabbits were carried out to examine the change around the cartilage crack. The results indicated that the local tensile stress was generated around the crack and varied with the crack angles. The maximum principal tensile stress was 0.59 MPa around the 45° crack, and no tensile stress was found at 90°. 10% tensile strain could significantly promote type I collagen mRNA expression and inhibit type II collagen and aggrecan (the proteoglycan core protein) mRNA expression. Type I collagen was detected around the 45° crack region in the cartilage with no change in type II collagen and proteoglycan. We conclude that the local tensile stress produced around the cartilage crack can cause the change in cartilage matrix expression which might lead to cartilage degeneration and initiation of osteoarthritis. This study provides biomechanical-based insight into the pathogenesis of PTOA and potentially new intervention in prevention and treatment of PTOA.

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Is Vibration Training Good for Your Bones? An Overview of Systematic Reviews

Whole-body vibration (WBV) intervention studies and reviews have been increasing lately. However, the results regarding its effects on bone tissue in different populations are still inconclusive. The goal of this overview was to summarize systematic reviews assessing the effects of WBV training on bone parameters. Three electronic databases were scanned for systematic reviews and meta-analyses evaluating the effects of WBV on bone tissue. The search had no time restrictions and was limited to articles written in English. Vibration protocols and the main bone parameters included in each review were extracted. Methodological quality was assessed and analyses were conducted stratifying by age. 17 reviews and meta-analyses fulfilled the inclusion criteria. No increase or small improvements in bone mineral density (BMD) after WBV interventions were observed in reviews regarding postmenopausal women. One intervention study regarding young adults was included and reported no bone-related benefits from WBV. Most reviews including children and adolescents with compromised bone mass showed an improvement of BMD at lower limbs, lumbar spine, and whole body. In conclusion, WBV interventions seem to help children and adolescents with compromised bone mass to increase their BMD, but these improvements are limited in postmenopausal women and there is insufficient evidence for young adults. Further research is also needed to identify the ideal parameters of WBV training focused on bone health.

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Simvastatin Impairs the Inflammatory and Repair Phases of the Postinjury Skeletal Muscle Regeneration

Background. Recent clinical data have suggested that the chronic use of high-lipophilic statins impairs the regenerative capacity of skeletal muscle. Because this activity of statins is poorly understood, we aimed to investigate the effect of simvastatin (SIM) on postinjury myofibre regeneration. Methods. The porcine model was used in this study. The animals were divided into two groups: nontreated (control; n=24) and SIM-treated (40 mg/day; n=24). On the 15th day (day 0) of the experiment, a bupivacaine hydrochloride- (BPVC-) induced muscle injury was established, and the animals were sacrificed in the following days after muscle injury. The degree of regeneration was assessed based on histopathological and immunohistochemical examinations. The presence and degree of extravasation, necrosis, and inflammation in the inflammatory phase were assessed, whereas the repair phase was evaluated based on the numbers of muscle precursor cells (MPCs), myotube and young myofibres. Results. In the inflammatory phase, SIM increased the distribution and prolonged the period of extravasation, prolonged the duration of necrosis, and prolonged and enhanced the infiltration of inflammatory cells. In the repair phase, SIM delayed and prolonged the activity of MPCs, delayed myotube formation, and delayed and decreased the formation of young myofibres. Our results indicated that SIM did not improve blood vessel stabilization at the site of the injury, did not exert an anti-inflammatory effect, prolonged and enhanced the inflammatory response, and impaired MPC activity, differentiation, and fusion. Moreover, SIM appeared to reduce M1 macrophage activity, resulting in slower removal of necrotic debris and sustained necrosis. Conclusion. This study shows that SIM negatively affects the inflammatory and repair phases of the postinjury muscle regeneration. These findings are unique, strengthen the available knowledge on the side effects of SIM, and provide evidence showing that statin therapy is associated with an increased risk of impairment of the regenerative capacity of muscle.

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A Comparative Study of Smartphone Game with Spirometry for Pulmonary Function Assessment in Stroke Patients

Background. The monitoring and rehabilitation of pulmonary function can be immensely important for long-term performance of daily life activities in stroke patients. In recent times, smartphone game-based assessment (SGA) has been gaining in popularity as an alternative to laboratory assessments. Hence, the aims of this study were (1) to quantify the reliability and validity of SGA for pulmonary function and (2) to assess the validity of SGA in comparison to spirometry. Materials/Methods. Thirty-four stroke subjects (age = 49.24 ± 8.25 years) performed spirometry and the smartphone game on different days. Spirometric values were obtained using a spirometer (SP-1, Schiller, USA). A breathing game application (Breathing+ package, Breathing Labs, Slovenia) was used to obtain the values for the SGA of pulmonary function. The concurrent validity was determined by comparing data collected from the 2 systems, and the reliability was determined by comparing data collected from 3 sessions of using the breathing game on a smartphone. Results. All parameters demonstrated excellent agreement with intraclass correlation coefficients (ICC (2.1)) values for reliability and concurrent validity. Conclusion. We compared the relationship between the SGA and the spirometry as certified pulmonary function test. The SGA data were statistically significant and reliable for pulmonary function assessment in stroke patients. It will therefore be useful during rehabilitation to improve pulmonary function and clinical monitoring in stroke patients.

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Clinical Course of Dual-Chamber Implantable Cardioverter-Defibrillator Recipients followed by Cardiac Remote Monitoring: Insights from the LION Registry

Patients receiving dual-chamber implantable cardioverter-defibrillator (DR-ICD) therapy are at risk of developing atrial arrhythmia because of the increased rate of ventricular pacing and the progression of heart failure. Remote monitoring (RM) may identify the patients at highest risk of adverse events such as atrial arrhythmias. A total of 283 patients with 91,632 remote transmissions during a 15-month follow-up (FU) period enrolled in the LION registry were analysed. The parameters retrieved included the pacing mode, lower rate limit, percentage of atrial (%AP) and ventricular pacing (%VP), and percentage of atrial arrhythmia burden (%AB). In 92.7% of patients, the devices were initially programmed in DDD(R) or DDI(R), with changes of the pacing mode in 19.3% only. The lower rate limit remained stable in 80.4% of patients. At the first transmission, 8.7% of patients suffered from RM-detected atrial arrhythmia, which reached 36% during FU. The %AP was not associated with increased AB (p = 0.67), but the %VP was different in patients developing RM-detected atrial arrhythmia (26.9% vs. 13.7%, p

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Clinical chemistry laboratory errors at St. Paul’s Hospital Millennium Medical College (SPHMMC), Addis Ababa, Ethiopia

This study was aimed to determine the magnitude of errors in clinical chemistry laboratory tests at different phases of the assay of clinical chemistry laboratory unit.

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Complete blood count data and leukocyte expression of cytokine genes and cytokine receptor genes associated with bovine respiratory disease in calves

The purpose of this study was to evaluate potential relationships between cytokine gene expression, complete blood counts (CBC) and animals that were sick or would become sick. The CBC and the transcript abund...

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Adaptation and validation of the Cyprus version of the Practice Environment Scale of the Nursing Work Index: a methodological study

The purpose of this study was to adapt and validate the Revised Practice Environment Scale of the Nursing Work Index, to be utilized among the Cyprus nurses' population. Validated research scales are valuable ...

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Magnitude of wasting and underweight among children 6–59 months of age in Sodo Zuria District, South Ethiopia: a community based cross-sectional study

The study aimed to determine the prevalence of wasting and underweight, and identify associated factors in Sodo Zuria district in South Ethiopia.

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The effect of breakfast with different macronutrient composition on PYY, ghrelin, and ad libitum intake 4 h after breakfast in Indonesian obese women

Gut hormones, such as PYY and ghrelin, are associated with appetite control and obesity. Protein is thought to be the most satiating nutrient and could affect the production of several gut hormones. The purpos...

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Erratum to “Extended lateral column tibial plateau fractures. How do we do it?” [Injury 49 (10) (2018) 1878–1885]

Publication date: Available online 3 November 2018

Source: Injury

Author(s): Harm Hoekstra, Jasper Vanhees, Juriaan van den Berg, Stefaan Nijs



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Comparison of Individual and Composite Radiographic Markers of Frailty in Trauma

Publication date: Available online 3 November 2018

Source: Injury

Author(s): Margaret H. Lauerman, Maxwell Raithel, Joseph Kufera, Kathirkamanathan Shanmuganathan, Brandon R. Bruns, Thomas M. Scalea, Deborah M. Stein

Abstract
Background

Clinical frailty scores usually involve questionnaires or physical testing. Many trauma patients are not able to participate in these. Radiographic measurement of frailty may be a viable alternative. Individual radiographic markers of frailty have been investigated, such as sarcopenia or osteopenia. The ideal radiographic variable (or variables) to measure frailty in trauma is unknown.

Study design

A retrospective review was performed of restrained drivers ages 40 and greater at a single institution from 2010-2015. Multiple markers of radiographic frailty were measured including: sarcopenia, osteopenia, vascular calcifications, sarcopenic obesity, emphysema, renal volume, cervical spine degeneration, and cerebral atrophy. Frailty was defined as the worst quartile for each radiographic variable, and these values were summed to create a composite marker of frailty. The primary outcome was discharge disposition. We hypothesized that a composite frailty score would be associated with discharge disposition while individual markers would not be associated with discharge disposition.

Results

Overall 489 patients were included in this study. Cerebral atrophy (p = 0.05), renal volume (p = 0.004), sarcopenia (p = 0.05), vascular calcifications (p = 0.02) and sarcopenic obesity (p = 0.01) were associated with discharge disposition. Pearson's correlation coefficients between radiographic frailty markers were all less than 0.4. Youden's Index was 0.26 (p < 0.001) at a composite score of 3. In multivariable analysis, the composite score of 3 or greater was associated with poor discharge disposition (OR 2.39, 95% CI 1.10-5.18, p = 0.03).

Conclusions

Individual radiographic frailty markers are inadequate markers of frailty, as they may miss patients who are frail. This study also suggests that a composite radiographic frailty score may better predict patient outcome than individual radiographic markers of frailty.



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Impact of rib fixation on Quality of life after major trauma with multiple rib fractures

Publication date: Available online 3 November 2018

Source: Injury

Author(s): Silvana F. Marasco, Kate Martin, Louise Niggemeyer, Robyn Summerhayes, Mark Fitzgerald, Michael Bailey

Abstract
Introduction

Multiple rib fractures have been shown to reduce quality of life both in the short and long term. Treatment of rib fractures with operative fixation reduces ventilator requirements, intensive care unit stay, and pulmonary complications in flail chest patients but has not been shown to improve quality of life in comparative studies to date. We therefore wanted to analyse a large cohort of multiple fractured rib trauma patients to see if rib fixation improved their quality of life.

Methods

Retrospective review (January 2012 - April 2015) of prospectively collected data on 1482 consecutive major trauma patients admitted to The Alfred Hospital with rib fractures.

The main outcome measures were Quality of Life over 24 months post injury assessed using the Glasgow Outcome Scale Extended (GOSErate) and Short Form (SF12) health assessment forms and a pain questionnaire.

Results

67 (4.5%) patients underwent rib fixation and were older, with a higher incidence of flail chest injury, and higher AIS and ISS scores than the remainder of the cohort. Rib fixation provided no benefit in pain, SF-12 or GOSErate scores over 24 months post injury.

Conclusions

This study has not been able to demonstrate any quality of life benefit of rib fixation over 24 months post injury in patients with major trauma.



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Influence of luminal stenosis in aneurysmal and non-aneurysmal blunt cerebrovascular injury

Publication date: Available online 3 November 2018

Source: Injury

Author(s): Margaret H. Lauerman, Karen Irizarry, Clint Sliker, Brandon R. Bruns, Ronald Tesoriero, Thomas M. Scalea, Deborah M. Stein

Abstract
Background

Current blunt cerebrovascular injury (BCVI) grading grossly differentiates injury characteristics such as luminal stenosis (LS) and aneurysmal disease. The effect of increasing degree of LS beyond the current BCVI grading scale on stroke formation is unknown.

Study Design

BCVI over a 3-year period were retrospectively reviewed. To investigate influence of LS beyond the BCVI grading scale within aneurysmal and non-aneurysmal BCVI, grade 2 BCVI were subdivided into BCVI with ≥ 25% and ≤ 50% LS and BCVI with > 50% and ≤ 99% LS. Grade 3 BCVI were subdivided into BCVI with pseudoaneurysm (PSA) without LS and BCVI with PSA and LS. We hypothesized increased LS beyond the current BCVI grade distinctions would be associated with higher rates of stroke formation.

Results

312 BCVI were included, of which 140 were carotid BCVI and 172 vertebral BCVI. Sixteen carotid BCVI underwent endovascular intervention (EI) and 19 suffered a stroke. In carotid BCVI stroke rates increased sequentially with BCVI grade except in grade 3. There was a stroke rate of 12% in grade 1 carotid BCVI, 18% in grade 2, 6% in grade 3, and 31% in grade 4. In subgroup analysis for grade 2 carotid BCVI, BCVI with > 50% and ≤ 99% LS had higher rates of stroke (22% vs. 15%, p = 0.44) than BCVI with ≥ 25% and ≤ 50% LS. In subgroup analysis of grade 3 carotid BCVI, BCVI with PSA and LS had higher rates of stroke (9% vs. 4%, p = 0.48) than BCVI with PSA without LS. Higher rates of EI in grade 2 carotid BCVI with > 50% and ≤ 99% LS (22% vs. 5%, p = 0.14) and grade 3 carotid BCVI with PSA and LS (35% vs. 4%, p = 0.01) were noted in subgroup analysis.

Conclusion

Higher percentage LS beyond the currently used BCVI grading scale has a non-significantly increased rate of stroke in both aneurysmal and non-aneurysmal BCVI. Grade 3 BCVI with PSA and LS seems to be a high-risk subgroup. Use of EI confounds modern measurement of stroke risk in higher LS BCVI.



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Purification and Characterization of Glutathione Binding Protein GsiB from Escherichia coli

Objectives. To purify and characterize the glutathione binding protein GsiB of glutathione importer (GSI) in Escherichia coli (E. coli). Results. The coding sequence of GsiB was cloned from E. coli MG1655 and expressed in BL21(DE3). GsiB protein was expressed and purified to homogeneity using Ni-affinity and gel filtration chromatography. SDS-PAGE of purified GsiB showed a single protein band of molecular mass 56 kDa, while native gel showed two bands around 56 kDa and 110 kDa. Gene knockout showed that GsiB was essential for GSI mediated glutathione import. Interactions of GsiA, B, C, and D were determined using bacterial two-hybrid method. Without glutathione, GsiB showed no direct interaction with the other three proteins. However, GsiB could interact with GsiC and GsiD when using glutathione as sole sulfur source. Conclusions. GsiB functions in E. coli was characterized which could help elucidate the glutathione import mechanism in gram-negative bacteria.

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Antagonism of Bacteria from Dog Dental Plaque against Human Cariogenic Bacteria

Dental caries are a process of demineralization and destruction of human teeth. They originate through many factors and are associated with biofilm formation, which consists of bacteria adhered to the teeth that form a structurally and functionally organized mass called dental plaque. Both the presence of Streptococcus mutans and the frequent consumption of sucrose correlate with a higher prevalence of caries in humans. In dogs, however, the incidence of this disease is low, due to factors such as differences in dental microbiota and/or their low consumption of sucrose. This work evaluated the antagonism of bacteria from dog's dental plaque against S. mutans, for the identification of producing strains of biotechnological products for use in preventing caries. This study used 95 bacterial isolates of canine dental plaque from the Veterinary Department at the Federal University of Viçosa, Minas Gerais, Brazil. A spot-on-the-lawn method was performed using Brain Heart Infusion agar with catalase for an initial identification of the antagonistic activity. Additional tests were conducted on the isolates classified as antagonists for confirmation of the activity, using modified Mann-Rogosa-Sharpe medium containing low dextrose concentration. These isolates were incubated at 37°C for 24 hours in anaerobiosis. The peptide nature of inhibition was evaluated using the following proteinases: proteinase K from Tritirachium album, bovine pancreatic trypsin, and type XII-A α-amylase from Bacillus licheniformis. In the initial identification of those strains exhibiting antimicrobial activity, 14 were classified as antagonists. One of the isolates (Bacillus sp.) indicated bacteriocinogenic activity, with a deformed inhibition halo on S. mutans by the addition of trypsin. These results suggest that this bacterial isolate may be applicable to biotechnological use to combat the main etiological agent of caries in humans. Further studies are needed to evaluate the bacteriocinogenic nature of the antimicrobial activities of the other 13 antagonistic bacterial isolates.

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Phosphoprotein Contributes to the Thermostability of Newcastle Disease Virus

Newcastle disease (ND), caused by Newcastle disease virus (NDV), is highly contagious and represents a major threat to the poultry industry. The thermostable vaccines are not insensitive to heat and ease of storage and transportation, but the mechanism of NDV thermostability remains unknown. The phosphoprotein (P), fusion protein (F), hemagglutinin-neuraminidase protein (HN), and large polymerase protein (L) are associated with NDV virulence. The association between F, HN, or L and viral thermostability has been, respectively, studied in different reports. However, the effects of P on NDV thermostability have not been demonstrated. Here, we utilized an existing reverse genetics system in our laboratory, to generate chimeric viruses by exchanging the P protein between the thermostable NDV4-C strain and the thermolabile LaSota strain. Chimeric viruses were found to possess similar growth properties, passage stability, and virulence, as compared to those of these parental strains. Interestingly, the thermostability of the chimera with P derived from the thermolabile LaSota strain was reduced compared to that of the parental virus, and P of the thermostable NDV4-C strain enhanced chimeric virus thermostability. Our data demonstrate that P is an important factor for the thermostability of NDV and provides information regarding the molecular mechanism of NDV thermostability; moreover, these results suggest a theoretical basis for using the NDV4-C strain as a thermostable vaccine.

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Efficacy of Alveolar Ridge Preservation after Maxillary Molar Extraction in Reducing Crestal Bone Resorption and Sinus Pneumatization: A Multicenter Prospective Case-Control Study

Aim. To evaluate, with three-dimensional analysis, the effectiveness of alveolar ridge preservation (ARP) after maxillary molar extraction in reducing alveolar bone resorption and maxillary sinus pneumatization when compared to unassisted socket healing. Methods. Patients were included in the study following inclusion criteria and underwent minimally traumatic maxillary molar extraction followed by ARP using synthetic nanohydroxyapatite (Fisiograft Bone, Ghimas, Italy) (test group) or unassisted socket healing (control group). Cone-beam computerized tomographies (CBCT) were performed immediately after tooth extraction (T0) and 6 months postoperatively (T1). CBCTs were superimposed by using a specific software (Amira, Thermo Fisher Scientific, USA) and the following items were analyzed in both groups: (i) postextractive maxillary sinus floor expansion in coronal direction and (ii) postextractive alveolar bone dimensional changes (both vertical and horizontal). All data were tested for normality and equality of variance and subsequently analyzed by independent samples T-test and Mann–Whitney test. Results. Thirty patients were treated by three centers and twenty-six (test n=13; control n=13) were included in the final analysis. Mean sinus pneumatization at T1 was 0.69±0.48 mm in the test group and 1.04±0.67 mm in the control group (p=0.15). Mean vertical reduction of the alveolar bone at T1 was 1.62±0.49 mm in the test group and 2.01±0.84 mm in the control group (p=0.08). Mean horizontal resorption of crestal bone at T1 was 2.73±1.68 mm in test group and 3.63±2.24 mm in control group (p=0.24). Conclusions. It could be suggested that ARP performed after maxillary molar extraction may reduce the entity of sinus pneumatization and alveolar bone resorption, compared to unassisted socket healing. This technique could decrease the necessity of advanced regenerative procedures prior to dental implant placement in posterior maxilla.

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Curative Anti-Inflammatory Properties of Chinese Optimized Yinxieling Formula in Models of Parkinson’s Disease

Parkinson's disease (PD) is marked by the progressive degeneration of dopaminergic neurons (DAN) accompanied by glial activation. Thus, inhibiting glial activation that occurs during this disease could be an effective method for treating PD. Optimized Yinxieling Formula (OYF), a Chinese medicinal formula, which is used to efficiently treat autoimmune disease psoriasis, has been proved to display potential immunomodulatory effects in inflammation-associated diseases. This study assessed the therapeutic benefits of OYF on glial-mediated neuroinflammation and neuroprotection in PD models in vitro and in vivo. First, the results showed that OYF significantly suppresses LPS-induced proinflammatory cytokine secretion and attenuates the overall inflammatory responses in BV-2 cells. Second, in vivo studies confirm that while the validity of our MPTP-induced PD mouse models possesses activated glia and significant neurobehavioral dysfunction, pretreatment with OYF prevents glial activation and ameliorates movement dysfunction in the MPTP-induced PD mouse models as evaluated by the pole and rotarod tests. Third, transcriptomic analyses were carried out to reveal the underlying molecular mechanism of the OYF treatment. Sixteen pathways were significantly upregulated in the OYF-treated PD model mice, including the cytokine-cytokine receptor interaction, cell adhesion molecules, coagulation, and complement cascades. Fifteen pathways were significantly downregulated in the OYF-treated PD model mice, such as the natural killer cell mediated cytotoxicity, hematopoietic cell lineage, phagosome, and others. These pathways share direct or indirect features of immunomodulation, suggesting that the physiological effects of OYF involve key roles of immune and inflammation regulations. Therefore, we prove that OYF is a useful immunomodulatory formula in developing prevention and treatment methods for neurodegenerative disease PD.

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Effect of Comorbidity on Lung Cancer Diagnosis Timing and Mortality: A Nationwide Population-Based Cohort Study in Taiwan

The effect of comorbidity on lung cancer patients' survival has been widely reported. The aim of this study was to investigate the effects of comorbidity on the establishment of the diagnosis of lung cancer and survival in lung cancer patients in Taiwan by using a nationwide population-based study design. This study collected various comorbidity patients and analyzed data regarding the lung cancer diagnosis and survival during a 16-year follow-up period (1995–2010). In total, 101,776 lung cancer patients were included, comprising 44,770 with and 57,006 without comorbidity. The Kaplan–Meier analyses were used to compare overall survival between lung cancer patients with and without comorbidity. In our cohort, chronic bronchitis patients who developed lung cancer had the lowest overall survival in one (45%), five (28.6%), and ten years (26.2%) since lung cancer diagnosis. Among lung cancer patients with nonpulmonary comorbidities, patients with hypertension had the lowest overall survival in one (47.9%), five (30.5%), and ten (28.2%) years since lung cancer diagnosis. In 2010, patients with and without comorbidity had 14.86 and 9.31 clinical visits, respectively. Lung cancer patients with preexisting comorbidity had higher frequency of physician visits. The presence of comorbid conditions was associated with early diagnosis of lung cancer.

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A Simple Guideline to Assess the Characteristics of RNA-Seq Data

Next-generation sequencing (NGS) techniques have been used to generate various molecular maps including genomes, epigenomes, and transcriptomes. Transcriptomes from a given cell population can be profiled via RNA-seq. However, there is no simple way to assess the characteristics of RNA-seq data systematically. In this study, we provide a simple method that can intuitively evaluate RNA-seq data using two different principal component analysis (PCA) plots. The gene expression PCA plot provides insights into the association between samples, while the transcript integrity number (TIN) score plot provides a quality map of given RNA-seq data. With this approach, we found that RNA-seq datasets deposited in public repositories often contain a few low-quality RNA-seq data that can lead to misinterpretations. The effect of sampling errors for differentially expressed gene (DEG) analysis was evaluated with ten RNA-seq data from invasive ductal carcinoma tissues and three RNA-seq data from adjacent normal tissues taken from a Korean breast cancer patient. The evaluation demonstrated that sampling errors, which select samples that do not represent a given population, can lead to different interpretations when conducting the DEG analysis. Therefore, the proposed approach can be used to avoid sampling errors prior to RNA-seq data analysis.

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Corrigendum to “Effective Treatment of Chronic Proliferative Cholangitis by Local Gentamicin Infusion in Rabbits”



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Mitochondrial dysfunction in affected skin and increased mitochondrial DNA in serum from patients with psoriasis

Experimental Dermatology, Volume 0, Issue ja, -Not available-.


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Effects of disparity on visual discomfort caused by short-term stereoscopic viewing based on electroencephalograph analysis

Discomfort evoked by stereoscopic depth has been widely concerned. Previous studies have proposed a comfortable disparity range and considered that disparities exceed this range would cause visual discomfort. ...

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Activography reveals aberrant proteolysis in desquamating diseases of differing backgrounds

Experimental Dermatology, Volume 0, Issue ja, -Not available-.


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Detection of fluid secretion of three‐dimensional reconstructed eccrine sweat glands by magnetic resonance imaging

Experimental Dermatology, Volume 0, Issue ja, -Not available-.


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Mutational activation of the EGFR down‐regulates MHC class I expression via the ERK in non–small cell lung cancer

Cancer Science, Volume 0, Issue ja, -Not available-.


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Vasoactive intestinal peptide increases apoptosis of hepatocellular carcinoma by inhibiting the cAMP/Bcl‐xL pathway

Cancer Science, Volume 0, Issue ja, -Not available-.


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Prevalence and Antimicrobial Susceptibility Profile of Salmonella Serovars Isolated from Slaughtered Cattle in Addis Ababa, Ethiopia

Salmonella is one of the top causes of foodborne bacterial illnesses in humans. The primary sources of human Salmonella infection are food producing animals such as cattle, poultry, and swine. A cross-sectional study was undertaken to estimate the prevalence and to determine the serovar distribution and antimicrobial susceptibility profiles of Salmonella spp. isolated from fecal (n=567) and carcass swab (n=159) samples of slaughtered cattle at Addis Ababa Abattoir Enterprise and Kara'alo PLC, Abattoirs, in Addis Ababa, Ethiopia between January 2014 and April 2015. Salmonella isolation was conducted according to Global Foodborne Infections Network Laboratory Protocol and isolates were confirmed by genus specific PCR and serotyped by slide agglutination test. Susceptibility of the isolates to 17 antimicrobials was testedusing the Kirby-Bauer disk diffusion method according to the guidelines of the Clinical and Laboratory Standards Institute. Out of the total 726 samples examined, 27 (3.7%) were positive for Salmonella. Salmonella was detected in 4.1% (23/567) fecal and 2.5% (4/159) carcass swab samples. Twelve different serovars were identified and the most predominant serovars were S. Dublin (n=10, 35.7%) and S. Virchow (n=5, 17.9%), followed by S. Braendrerup, S. Haifa, and S. Saintpaul which were isolated from 2 samples each (7.1%). All of the Salmonella isolates investigated were resistant or intermediately resistant to four or more of the 17 drugs tested. High resistance rate was recorded to streptomycin 25 (89.3%), cephalothin 20 (71.4%), ampicillin 19 (67.9%), and amoxicillin+clavulanic acid 19 (67.9%). Resistance to five or more antimicrobials was detected in 20 (71.5%) of the isolates. Multidrug resistance to more than 7 antimicrobials was detected in 5 (17.9%) of the isolates. Isolation of such multidrug resistant strains of Salmonella from slaughtered cattle poses a major public health concern. These findings imply the need for a strict biosecurity and regulation of antimicrobial use across the country.

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Evaluating the Longitudinal Item and Category Stability of the SF-36 Full and Summary Scales Using Rasch Analysis

Introduction. The Medical Outcome Study Short Form 36 (SF-36) is widely used for measuring Health-Related Quality of Life (HRQoL) and has undergone rigorous psychometric evaluation using Classic Test Theory (CTT). However, Item Response Theory-based evaluation of the SF-36 has been limited with an overwhelming focus on individual scales and cross-sectional data. Purpose. This study aimed to examine the longitudinal item and category stability of the SF-36 using Rasch analysis. Method. Using data from the 1921-1926 cohort of the Australian Longitudinal Study on Women's Health, responses of the SF-36 from six waves of data collection were analysed. Rasch analysis using Winsteps version 3.92.0 was performed on all 36 items of the SF-36 and items that constitute the physical health and mental health scales. Results. Rasch analysis revealed issues with the SF-36 not detected using classical methods. Redundancy was seen for items on the total measure and both scales across all waves of data. Person separation indexes indicate that the measure lacks sensitivity to discriminate between high and low performances in this sample. The presence of Differential Item Functioning suggests that responses to items were influenced by locality and marital status. Conclusion. Previous evaluations of the SF-36 have relied on cross-sectional data; however, the findings of the current study demonstrate the longitudinal efficacy of the measure. Application of the Rasch Measurement Model indicated issues with internal consistency, generalisability, and sensitivity when the measure was evaluated as a whole and as both physical and mental health summary scales. Implications for future research are discussed.

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