A Comparison of the Learning Curves of Laparoscopic Liver Surgeons in Differing Stages of the IDEAL Paradigm of Surgical Innovation: Standing on the Shoulders of Pioneers

Objective: To compare the learning curves of the self-taught "pioneers" of laparoscopic liver surgery (LLS) with those of the trained "early adopters" in terms of short- and medium-term patient outcomes to establish if the learning curve can be reduced with specific training. Summary of Background Data: It is expected that a wider adoption of a laparoscopic approach to liver surgery will be seen in the next few years. Current guidelines stress the need for an incremental, stepwise progression through the learning curve in order to minimize harm to patients. Previous studies have examined the learning curve in Stage 2 of the IDEAL paradigm of surgical innovation; however, LLS is now in stage 3 with specific training being provided to surgeons. Methods: Using risk-adjusted cumulative sum analysis, the learning curves and short- and medium-term outcomes of 4 "pioneering" surgeons from stage 2 were compared with 4 "early adapting" surgeons from stage 3 who had received specific training for LLS. Results: After 46 procedures, the short- and medium-term outcomes of the "early adopters" were comparable to those achieved by the "pioneers" following 150 procedures in similar cases. Conclusions: With specific training, "early adapting" laparoscopic liver surgeons are able to overcome the learning curve for minor and major liver resections faster than the "pioneers" who were self-taught in LLS. The findings of this study are applicable to all surgical specialties and highlight the importance of specific training in the safe expansion of novel surgical practice.

http://bit.ly/2AMl2eX

Influences of Corydalis decumbens on the Activities of CYP450 Enzymes in Rats with a Cocktail Approach

Corydalis decumbens, a Traditional Chinese Medicine, has been widely used for the alternative and/or complementary therapy of hypertension, arrhythmias rheumatoid arthritis, sciatica, stroke, hemiplegia, paraplegia, and vascular embolism. The aim of this study was to determinate the potential effects of Corydalis decumbens on the five cytochrome P450 (CYP) enzyme activities (CYP1A2, CYP3A4, CYP2C9, CYP2C19, and CYP2D6) by cocktail approach. To evaluate whether concurrent use of Corydalis decumbens interferes with the effect of several prescription drugs, saline (control group) or Corydalis decumbens (XTW group) were administrated via gavage for 7 successive days. A probe cocktail solution (phenacetin, omeprazole, metoprolol, tolbutamide, and midazolam) was given 24 h after the last dose of saline or Corydalis decumbens. A specific and sensitive UHPLC–MS/MS method was validated for the determination of five substrates and their metabolites in control group and XTW group. Our results indicated that Corydalis decumbens could have inductive effects of CYP2C19 and inhibit the activities of CYP1A2 and CYP3A4. However, Corydalis decumbens had no significant influence on CYP2C9 and CYP2D6. The herb-drug interaction should require more attention by careful monitoring and appropriate drug dosing adjustments to the concurrent use of western medications which were metabolized by CYP1A2, CYP2C19, and CYP3A4 in human—Corydalis decumbens, Cytochrome P450, Cocktail, Pharmacokinetics, herb–drug interactions.

http://bit.ly/2MnWIEz

Role of Multidetector Computed Tomography (CT) Virtual Hysteroscopy in the Evaluation of Abnormal Uterine Bleeding in Reproductive Age

Background. Abnormal uterine bleeding (AUB) may be acute or chronic and is defined as bleeding from the uterine corpus that is abnormal in regularity, volume, frequency, or duration and occurs in the absence of pregnancy. It is a widespread complaint in the primary care units. The prevalence of abnormal bleeding is up to 30% among women of reproductive age. Objective. To assess the role of CT virtual hysteroscopy in the evaluation of the uterine cavity in cases with abnormal uterine bleeding in reproductive age. Methods. Cross sectional study was performed at Obstetrics and Gynecology Department and Radiology Department, Zagazig University hospitals, Egypt, on 124 women with abnormal uterine bleeding in reproductive age, and their uterine cavity was evaluated by both row multidetector computed tomography (MDCT) scanner and Office hysteroscopy. Results. Mean age of studied group was 28.54 ± 5.99 years, and virtual hysteroscopy showed sensitivity 91.1% and specificity 85.3% in detection of abnormalities within uterine cavity. It showed sensitivity 91.1% and specificity 85.3% in cases of endometrial polyps. It yielded 88.5 % sensitivity and 100 % specificity in cases with submucous fibroids, while it yielded only 57.9 % sensitivity and 82.9% specificity in cases of thick endometrium. Conclusion. Virtual CT hysteroscopy is a good negative test in cases of abnormal uterine bleeding but has some limitations that decrease its sensitivity.

http://bit.ly/2sDJ5rS

Burnout Syndrome among Emergency Department Staff: Prevalence and Associated Factors

Objectives. Emergency department (ED) professionals are exposed to burnout syndrome due to excessive workload and high demands for care. The objective of our study was to assess the prevalence burnout among all ED staff and to determine associated factors. Methods. A cross-sectional survey was conducted in 3 EDs. The data were collected using a standardized questionnaire. It included demographical and occupational data, general health questions, burnout level (Maslach Burnout Inventory), job strain (Karasek), and quality of life (Medical Outcome Study Short Form). Results. Of the 529 professionals working in EDs, 379 responses were collected (participation rate of 71.6%). Emotional exhaustion (EE) and depersonalization (DP), the major components of burnout, were reported, respectively, by 15.8% and 29.6% of the professionals. Burnout prevalence was 34.6%, defined as a severely abnormal level of either EE or DP. The medical category was significantly more affected by the burnout compared with their colleagues: nearly one ED physician out of two had a burnout (50.7%). In the multivariate analysis of covariance, job strain and a low mental component score were the two main factors independently associated with burnout (p

http://bit.ly/2MlZWZj

Peroxynitrite and 4-Hydroxynonenal Inactivate Breast Cancer Resistance Protein/ABCG2

Oxidative stress may arise from a variety of pathologies and results in the formation of toxic and reactive chemical species. Extensive research has been done to establish mechanisms of formation and cytotoxic effects of a number of different products of oxidation stress including peroxynitrite (PN) and 4-hydroxynonenal (4HNE). However, relatively few studies have investigated their effects on ATP-binding cassette (ABC) transporters. The objective of this investigation was to determine the effects of PN and 4HNE on BCRP/ABCG2. To eliminate the effect of metabolic enzymes, the experiments were carried out with inside-out Sf9 membrane vesicles overexpressing BCRP/ABCG2 using riboflavin as a substrate. The experiments revealed that PN produced IC50 of about 31.2 ± 2.7 μM, based upon initial concentrations. The IC50 for 4HNE was estimated to be 92 ± 1.4 μM. Preincubation of membrane vesicles with either PN or 4HNE caused the maximal rate of transport () to drop drastically, up to 19 times, with no or much smaller effect on . Thus, PN and 4NE can inhibit BCRP transport activity.

http://bit.ly/2sEoILg

Asymptomatic Right Ventricular Hypoplasia in Twin Siblings: A Normal Variant or Cause of Early Mortality?

Right ventricular (RV) hypoplasia may develop secondary to pulmonary or tricuspid valve atresia. These patients are usually symptomatic early in life and need prompt intervention. Isolated RV hypoplasia is a rare congenital heart disease. We report a case of 23-year-old twins who have been monitored for the last 14 years for isolated right ventricular hypoplasia. ECHO and MRI studies showed a small, heavily trabeculated, nonapex-forming RV and mild tricuspid valve insufficiency. The girl has a patent foramen ovale (PFO). Otherwise, the cardiac anatomy and function was normal. They have both been completely asymptomatic from the cardiac standpoint. The family history is remarkable for death of father at the age of 30 years with autopsy suggestive of a hypoplastic RV. The paternal uncle also died at the age of 46 years, and his son has an unidentified congenital heart disease. The family history appears to suggest an autosomal dominant pattern of inheritance with variable expressivity. However, the chromosome microarray analysis of the twins did not identify any variations of clinical significance.

http://bit.ly/2W6wg6X

Potential life-threatening complication of tonsillectomy: cervicofacial surgical emphysema

A 30-year-old woman presented to the accident and emergency department 3 days post-tonsillectomy with bleeding from the tonsillar fossa and left-sided facial swelling. The patient denied any dysphagia or breathing difficulties but experienced pain on neck movement. On examination, although the bleeding had stopped on reaching the emergency department, a small clot was noted in her left tonsillar fossa. A left facial/submandibular swelling was seen, which had been present since her operation and was slowly enlarging. Flexible nasendoscopy showed a mild left sided oropharyngeal swelling but was otherwise normal. She was treated initially with antibiotics and hydrogen peroxide gargles. After 24 hours of observation and a slight worsening of the swelling she underwent a CT of the neck. This showed widespread indurated subcutaneous surgical emphysema, originating from the left tonsillar bed. Following a period of observation and improvement in her symptoms, she was discharged home with safety netting.

http://bit.ly/2RVSE3M

An uncommon cause of leg oedema

http://bit.ly/2HopndW

Novel intronic DICER1 variation associated with pleuropulmonary blastoma in two siblings

Pleuropulmonary blastomas (PPB) are rare aggressive paediatric lung malignancies associated with DICER1 variants. We present two cases, a 2-year-old girl with upper respiratory tract symptoms as well as a 6-month-old girl sibling undergoing screening due to family history of malignancy. Imaging of the 2-year-old girl revealed a large mass filling the right hemithorax which was determined to be a type II PPB after pathological examination. Imaging of the 6-month-old sibling demonstrated a small cystic lesion in the posterior basal segment of the right lower lobe which was determined to be a type 1r PPB after pathological examination. The 2-year-old girl received adjuvant chemotherapy while the baby sister underwent resection alone and both are alive and well at 12 months and 7 months, respectively. Sequence analysis in both cases confirmed the same DICER1 variation, c.2437-2A>G (likely pathogenic), which has not been previously described in the literature.

http://bit.ly/2RXzlH1

Recurrent vulvar melanoma in a patient with neurofibromatosis and gastrointestinal stromal tumour

We report a case of a 51-year-old woman with neurofibromatosis who presented in 2012 with postmenopausal bleeding. Excision biopsy of a pigmented lesion of the labia minora was consistent with an ulcerated vulvar BRAF wild type malignant melanoma (MM). Initial excision was followed by radical vulvectomy and adjuvant interferon. Local recurrence in January 2017 was further resected. Positron emission tomography (PET)-CT in May 2017 identified an FDG avid omental deposit; consistent histologically with MM when resected. Postoperative PET-CT in August 2017 demonstrated local recurrence. In the setting of resected stage IV disease and a third local recurrence, the decision was made to instigate immunotherapy. Vulvar melanoma is rare accounting for 0.2% of all melanoma. Presentation is typically a decade later than cutaneous melanoma with a tendency to late metastases and poorer prognosis. Given their rarity the treatment paradigm is less clearly defined and largely extrapolated from that of cutaneous melanomas.

http://bit.ly/2HpsIcB

Clear cell, giant myoepithelioma of tongue base: a diagnostic and surgical challenge

Clear cell variant is a rare histological type of myoepithelioma seen in parotid and soft palate. This article describes clear cell variant of myoepithelioma in the tongue base, which has not been reported in the literature so far. A 34-year-old man presented with dysphagia and foreign body sensation of throat. Video laryngostroboscopy using a 70° rigid telescope showed a smooth globular mass in the oropharynx arising from the tongue base. Based on clinical and radiological findings, the lesion was considered as benign. Fine needle aspiration cytology was not attempted fearing risk of bleeding, aspiration and airway compromise. Hence, an excisional biopsy followed by definitive histopathological examination without frozen section was planned. The patient underwent coblator-assisted excision and subsequently sent for histopathological analysis. There were cuboidal cell nests with abundant clear cytoplasm which stained positive for p63 by immunohistochemistry. This helped in establishing the diagnosis of clear cell myoepithelioma.

http://bit.ly/2sBpuIC

Clinical features of scleromyxoedema in an Afro-Caribbean man

http://bit.ly/2Mkyif7

Successful treatment of stage III hidradenitis suppurativa with botulinum toxin A

A 41-year-old obese Native American woman presented with hidradenitis suppurativa (HS) after failing all available treatment options. Her HS was more pronounced in the axillary and groin regions (Hurley stage III) and was a major source of her pain and a barrier for home exercise and aquatic therapy. She received a botulinum toxin A injection every 3 months (four times thus far), which has significantly helped alleviate her pain and curb the progress of her HS by resolving abscesses and healing draining sinuses.

http://bit.ly/2sA7uOZ

Managing psychotic depression and diagnostic uncertainty in liaison psychiatry

A middle-aged woman presented with a history of symptoms of depression with psychotic features severely affecting her physical health. Neuroimaging of her brain suggested pathological changes out of keeping with her age, leading to further investigations including genetic testing for cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL). Anti-N-methyl-D-aspartate receptor (NMDAR) encephalitis was also considered as a differential diagnosis as an initial serum test for anti-NMDAR autoantibodies was positive. Her symptoms resolved following treatment with electroconvulsive therapy. Despite her initial neuroimaging, her genetic test for CADASIL was negative and her subsequent test for anti-NMDAR autoantibodies was negative, suggesting that the initial test may have been a false positive.

http://bit.ly/2MmzLSe

Bottleneck [Humanities]

http://bit.ly/2CCLWpl

Medicine slow to recognize social media as window into the patient experience [News]

http://bit.ly/2REsHGC

Routine collection of sexual orientation and gender identity data: a mixed-methods study [Research]

BACKGROUND:

Sexual orientation and gender identity are key social determinants of health, but data on these characteristics are rarely routinely collected. We examined patients' reactions to being asked routinely about their sexual orientation and gender identity, and compared answers to the gender identity question against other data in the medical chart on gender identity.

METHODS:

We analyzed data on any patient who answered at least 1 question on a routinely administered sociodemographic survey between Dec. 1, 2013, and Mar. 31, 2016. We also conducted semistructured interviews with 27 patients after survey completion.

RESULTS:

The survey was offered to 15 221 patients and 14 247 (93.6%) responded to at least 1 of the sociodemographic survey questions. Most respondents answered the sexual orientation (90.6%) and gender identity (96.1%) questions. Many patients who had been classified as transgender or gender diverse in their medical chart did not self-identify as transgender, but rather selected female (22.9%) or male (15.4%). In the semistructured interviews, many patients expressed appreciation at the variety of options available, although some did not see their identities reflected in the options and some felt uncomfortable answering the questions.

INTERPRETATION:

We found a high response rate to questions about sexual orientation and gender identity. Fitting with other research, we suggest using a 2-part question to explore gender identity. Future research should evaluate the acceptability and feasibility of administering these questions in a variety of care settings. These data can help organizations identify health inequities related to sexual orientation and gender identity.

http://bit.ly/2CCLY0r

Dont foredoom cannabis legalization to failure [Letters]

http://bit.ly/2RDiH08

Management of gender dysphoria in adolescents in primary care [Review]

http://bit.ly/2Czfa8G

Developing inclusive primary care for trans, gender-diverse and nonbinary people [Commentary]

http://bit.ly/2RGLXDk

Locally advanced cervical cancer in a transgender man [Practice]

http://bit.ly/2CxrjLs

Will use of cannabis increase more rapidly with legalization than during prohibition? [Letters]

http://bit.ly/2RISLjX

Transgender-inclusive care [Practice]

http://bit.ly/2Cy1pXS

Medical specialists break away from OMA at "worst possible time" warns Quebec specialist group [News]

http://bit.ly/2REmfzd

FLUX: responding to head and neck cancer [Humanities]

http://bit.ly/2Cxrh6i

Are medical editors responsible if articles they publish cause harm? [News]

http://bit.ly/2RFGWuN

Fifty years’ follow‐up of childhood epilepsy: Medical outcome, morbidity, and medication

Summary

Objective

To describe the long‐term prognosis of childhood epilepsy, with special emphasis on seizure remission, relapse, medication, associated neurologic impairment, mortality rate, and cause of death.

Methods

A prospective longitudinal study on a population‐based total cohort of 195 children with epileptic seizures in 1962‐1964. Data were collected from medical records and a questionnaire.

Results

Follow‐up data from 94% of the initial cohort showed the best long‐term prognosis for seizure freedom for children with no intellectual or neurologic impairment. These children had later seizure onset, shorter total duration of epilepsy, and were more often medication free. Only a few of them had isolated relapses. Generalized, rather than focal, epilepsy was associated with fewer relapses and less ongoing medication. The "true incidence" group, with onsets during the inclusion period of 1962‐1964, had the best long‐term prognosis for seizure freedom, with 90% seizure‐free after 50 years. Although only 10% of this group had ongoing seizures at follow‐up, 22% still used anticonvulsive medication, often with old drugs, that is, phenobarbital or phenytoin, as one of the anticonvulsive drugs. The standardized mortality ratio (SMR) was 2.61 for the whole group, with no difference between those with or without other neurodeficits. Those who died young either had neurologic impairment or died from epilepsy‐related conditions; later deaths often followed non–epilepsy‐related conditions. No one in the incidence group died of SUDEP (sudden unexpected death in epilepsy).

Significance

This 50‐year, long‐term follow‐up of a cohort of persons with childhood epilepsy in general demonstrates a better outcome for seizure freedom compared to our follow‐up after 12 years and to previous reports. We also report a low incidence of seizure relapses. Remission of seizures does not automatically lead to termination of medication. The mortality rate associated with SUDEP was lower than previously reported.

http://bit.ly/2AVezyh

Early demise of twins in a cohort of stillbirths and second trimester miscarriages

Twins, particularly monochorionic (MC) pairs, are at increased risk for fetal death. Whereas previous work has sought to understand the mechanisms for this increased mortality, most studies analyze viable twin pregnancies or liveborn twin cohorts. In the Wisconsin Stillbirth Service Program cohort of 3,137 stillbirths and second trimester miscarriages, we identified 175 twin pregnancies for a twinning rate of 56/1,000, which is approximately double the general population. The excess of twins among miscarriages and stillbirths was attributable to MC pairs as the incidence of dizygotic (DZ) twinning was not increased compared to livebirth data. The leading causes of fetal demise among twins were twin–twin transfusion, acardia, and twin–twin disruption. Maternal causes of death, primarily premature rupture of membranes, were moderately increased in both MC and DZ twins relative to singletons. Although deceased twins were smaller than expected for viable twins at comparable gestational ages, placenta weights of deceased MC pairs were large compared to combined fetal weight, which indicates placental inefficiency likely due to vascular shunting. Co‐twin survival was much lower for MC than for DZ pairs. Therefore, earlier diagnosis and treatment of MC twinning complications may decrease prenatal mortality.

http://bit.ly/2REpIOq

Randomised clinical trial: pregabalin vs placebo for irritable bowel syndrome

Summary

Background

Pregabalin is a calcium channel α2δ ligand that modifies visceral hypersensitivity in IBS patients. Clinical data for pregabalin in IBS are lacking.

Aim

To test the efficacy of pregabalin on gastrointestinal symptoms in IBS patients.

Methods

A double‐blind, placebo‐controlled trial was performed. Adults meeting IBS Rome III criteria with ≥3 pain attacks per month were randomised to pregabalin 225 mg vs placebo twice daily for 12 weeks. Questionnaires were completed weekly. The primary endpoint was average pain Bowel Symptom Scale (BSS) scores weeks 9‐12. An intention‐to‐treat analysis of covariance evaluated treatment effects on quantitative endpoints, adjusting for age and gender. Adequate relief and change in pain score were assessed using a chi‐squared test.

Results

Eighty‐five patients were recruited and randomised. Sample characteristics include: mean age 39.4 (SD = 14.6); 73 (86%) female; 37 (44%) IBS‐D, 29 (35%) IBS‐M, 18 (21%) IBS‐C. The pregabalin arm had lower average pain‐BSS scores weeks 9‐12 (25 vs 42, P = 0.008). Compared with placebo, the overall IBS BSS severity score was lower in the pregabalin arm (26 vs 42, P = 0.009). Differences were observed for the diarrhoea‐BSS and bloating‐BSS scores (P = 0.049 and 0.016, respectively). No differences between groups were seen for constipation‐BSS scores. Adequate relief was not different between the two arms (46% vs 36%, P = 0.35). 63% pregabalin vs 45% placebo had a change in pain score ≥30 at week 12 from baseline (P = 0.10). Post‐treatment IBS‐QoL scores did not differ between groups.

Conclusion

This trial suggests that pregabalin may be beneficial for IBS abdominal pain, bloating and diarrhoea.

http://bit.ly/2T0kg4V

Plasma tau/amyloid-β1–42 ratio predicts brain tau deposition and neurodegeneration in Alzheimer’s disease

Abstract

One of the hallmarks of Alzheimer's disease is abnormal deposition of tau proteins in the brain. Although plasma tau has been proposed as a potential biomarker for Alzheimer's disease, a direct link to brain deposition of tau is limited. Here, we estimated the amount of in vivo tau deposition in the brain by PET imaging and measured plasma levels of total tau (t-tau), phosphorylated tau (p-tau, T181) and amyloid-β_1–42. We found significant correlations of plasma p-tau, t-tau, p-tau/amyloid-β_1–42, and t-tau/amyloid-β_1–42 with brain tau deposition in cross-sectional and longitudinal manners. In particular, t-tau/amyloid-β_1–42 in plasma was highly predictive of brain tau deposition, exhibiting 80% sensitivity and 91% specificity. Interestingly, the brain regions where plasma t-tau/amyloid-β_1–42 correlated with brain tau were similar to the typical deposition sites of neurofibrillary tangles in Alzheimer's disease. Furthermore, the longitudinal changes in cerebral amyloid deposition, brain glucose metabolism, and hippocampal volume change were also highly associated with plasma t-tau/amyloid-β_1–42. These results indicate that combination of plasma tau and amyloid-β_1–42 levels might be potential biomarkers for predicting brain tau pathology and neurodegeneration.

http://bit.ly/2FRbhiy

Associations between physical activity and asthma, eczema and obesity in children aged 12-16: an observational cohort study

Objectives

To compare the physical activity of adolescents with three common long-term conditions (asthma, eczema and obesity) with adolescents without these conditions.

Design

Cross-sectional and longitudinal analyses of adolescents at ages 12, 14 and 16 in a large UK cohort study.

Setting

The Avon Longitudinal Study of Parents and Children.

Participants

6473 adolescents with complete accelerometer data at at least one time point.

Methods

Mean minutes of moderate to vigorous intensity physical activity (MVPA) and sedentary time per day were derived from accelerometer-based measurements at ages 12, 14 and 16. Obesity was defined at each time point from height and weight measurements. Parents reported doctor-assessed asthma or eczema. Cross-sectional and longitudinal regression models examined any differences in MVPA or sedentary time for adolescents with asthma, eczema or obesity compared with those without.

Results

In longitudinal models, boys engaged in an average of 69.7 (95% CI 67.6 to 71.7) min MVPA at age 12, declining by 3.1 (95% CI 2.6 to 3.6) min/year while girls' average MVPA was 47.5 (95% CI 46.1 to 48.9) min at age 12, declining by 1.8 (95% CI 1.5 to 2.1) min/year. There was no strong evidence of differences in physical activity patterns of those with and without asthma or eczema. Obese boys engaged in 11.1 (95% CI 8.7 to 13.6) fewer minutes of MVPA, and obese girls in 5.0 (95% CI 3.3 to 6.8) fewer minutes than their non-obese counterparts. Cross-sectional models showed comparable findings.

Conclusions

Mean minutes of MVPA per day did not differ between adolescents with asthma or eczema and those without, but obese adolescents engaged in fewer minutes of MVPA. Findings reinforce the need for strategies to help obese adolescents be more active but suggest no need to develop bespoke physical activity strategies for adolescents with mild asthma or eczema.

http://bit.ly/2HlbrBu

Dravet Syndrome in Lebanon: First Report on Cases with SCN1A Mutations

Dravet syndrome, also known as severe myoclonic epilepsy in infancy, is a rare disease characterized by the appearance of different types of seizures in a healthy baby, triggered by various factors and stressful events. We report 8 Lebanese cases referred for molecular analysis of the SCN1A gene. Results were positive in 7 cases and revealed de novo variants at the heterozygous state in different exons of the gene for all except one, where the variant was intronic. Four variants were novel. Confirmation of Dravet syndrome is important for a better follow-up and treatment, preventing the occurrence of status epilepticus and severe neurological deterioration.

http://bit.ly/2W7QBIQ

Correlations between Repeated Use of Dry Sauna for 4 x 10 Minutes, Physiological Parameters, Anthropometric Features, and Body Composition in Young Sedentary and Overweight Men: Health Implications

Background. The effect of thermal stress on the physiological parameters of young overweight and sedentary men who sporadically use the sauna remains insufficiently investigated. Aim. The aim of the study was to determine the effect of sauna bathing on the physiological parameters of young overweight, physically inactive men and to test the correlations between physiological parameters versus anthropometric features and body composition parameters. Materials and Methods. Forty-five overweight and sedentary men aged 20.76±2.4 y were exposed to four sauna sessions of 10 minutes each (temperature: 90-91°C; relative humidity: 14-16 %) with four 5-minute cool-down breaks. Body composition was determined before sauna, and body mass and blood pressure were measured before and after sauna. Physiological parameters were monitored during four 10-minute sauna sessions. Results. A significant (p

http://bit.ly/2QXgZl7

Translation and Initial Validation of the Chinese Version of the Action Research Arm Test in People with Stroke

Purpose. This study aimed to translate the English version of the Action Research Arm Test (ARAT) into Chinese and to evaluate the initial validation of the Chinese version (C-ARAT) in patients with a first stroke. Methods. An expert group translated the original ARAT from English into Chinese using a forward-backward procedure. Forty-four patients (36 men and 8 women) aged 22–80 years with a first stroke were enrolled in this study. The participants were evaluated using 3 stroke-specific outcome measures: C-ARAT, the upper extremity section of the Fugl–Meyer assessment (UE-FMA), and the Wolf Motor Function Test (WMFT). Internal consistency was analysed using Cronbach's α coefficients and item-scale correlations. Concurrent validity was determined using Spearman's rank correlation coefficients. Floor and ceiling effects were considered to be present when more than 20% of patients fell outside the preliminarily set lower or upper boundary, respectively. Results. The C-ARAT items yielded excellent internal consistency, with a Cronbach's α of 0.98 (p

http://bit.ly/2W3bu8a

Development and Implementation of a Multi-Disciplinary Technology Enhanced Care Pathway for Youth and Adults with Concussion

A multidisciplinary carepath to standardize disparate concussion care was developed and implemented at the Cleveland Clinic. The Cleveland Clinic Concussion (C3) mobile application was used to enable the carepath through biomechanical outcomes characterizing cognitive and motor function. Patient outcomes improved while cost of care was reduced following implementation.

http://bit.ly/2sDRwUa

Detection of Protease Activity by Fluorescent Peptide Zymography

Here, we present a detailed protocol for a modified zymographic technique in which fluorescent peptides are used as the degradable substrate in place of native proteins. Electrophoresis of biological samples in fluorescent peptide zymograms enables detection of a wider range of proteases than previous zymographic techniques.

http://bit.ly/2MrUWm5

In Vitro Differentiation Model of Human Normal Memory B Cells to Long-lived Plasma Cells

Using multi-step culture systems, we report an in vitro B cell to plasma cell differentiation model.

http://bit.ly/2sDRvzA

Simultaneous Measurements of Intracellular Calcium and Membrane Potential in Freshly Isolated and Intact Mouse Cerebral Endothelium

Demonstrated here are protocols for (1) freshly isolating intact cerebral endothelial "tubes" and (2) simultaneous measurements of endothelial calcium and membrane potential during endothelium-derived hyperpolarization. Further, these methods allow for pharmacological tuning of endothelial cell calcium and electrical signaling as individual or interactive experimental variables.

http://bit.ly/2CABL4T

A Vibrotactile Feedback Device for Seated Balance Assessment and Training

A sitting platform has been developed and assembled that passively destabilizes sitting posture in humans. During the user's stabilizing task, an inertial measurement unit records the device's motion, and vibrating elements deliver performance-based feedback to the seat. The portable, versatile device may be used in rehabilitation, assessment, and training paradigms.

http://bit.ly/2RAE0zk

Orthotopic Injection of Breast Cancer Cells into the Mice Mammary Fat Pad

Here, we present a protocol to implant breast cancer cells into the mammary fat pad in a simple, less invasive, and easy-to-handle way, and this mouse orthotopic breast cancer model with a proper mammary fat pad environment can be used to investigate various aspects of cancer.

http://bit.ly/2RDdEwB

Optimized Interferon-gamma ELISpot Assay to Measure T Cell Responses in the Guinea Pig Model after Vaccination

The development of the interferon-gamma ELISpot assay for guinea pig PBMCs allows the characterization of T-cell responses in this highly relevant model for studying infectious diseases. We have applied the assay to measure T cell responses associated with intradermal delivery of DNA vaccines.

http://bit.ly/2CAoNUR

Streptococcus agalactiae from Ethiopian pregnant women; prevalence, associated factors and antimicrobial resistance: alarming for prophylaxis

Maternal Streptococcus agalactiae (Group B Streptococcus, GBS) colonization rates and its antibiotic resistance patterns provide important information useful in guiding prevention strategies. There is a paucity o...

http://bit.ly/2CA753J

Giant cellulitis-like Sweet syndrome as an initial clinical presentation of acute myeloblastic leukemia with t(6;9)(p23;q34): DEK-CAN and internal duplications of FMS-like tyrosine kinase 3

http://bit.ly/2W61ifh

Blastic plasmacytoid dendritic cell neoplasm with response to pralatrexate

http://bit.ly/2R3OTEO

Prominent regression of corneal crystalline deposits in multiple myeloma after treatment with proteasome inhibitor

http://bit.ly/2W69Gv9

Management of an adult patient with sickle cell disease and acute chest syndrome by veno-venous extracorporeal membrane oxygenation

http://bit.ly/2R3ONgq

Cytotoxic T-lymphocyte-associated antigen 4-positive aggressive adult T cell leukemia/lymphoma

http://bit.ly/2W69uMr

Cytogenetically cryptic insertion of PML segment into RARA on chromosome 17q resulting PML-RARA fusion in acute promyelocytic leukemia

http://bit.ly/2QWIN9f

Autoimmune myelitis in a CLL patient undergoing treatment with ibrutinib

http://bit.ly/2W69nAv

Assessment of Dietary Patterns Represents a Potential, Yet Variable, Measure of Inflammatory Status: A Review and Update

Chronic low-grade, systemic inflammation is a well-characterized risk factor in the development of chronic metabolic diseases, such as cardiovascular disease, type 2 diabetes, and metabolic syndrome. Diet could be an effective strategy for reducing inflammation associated with chronic disease. While anti-inflammatory properties of isolated dietary bioactive and functional foods have been routinely studied, the evaluation of dietary patterns on inflammation warrants further review—especially given the recent inclusion of dietary pattern recommendations into dietary guidelines and policies. Therefore, the objective of this narrative review is to examine current evidence linking diet to low-grade, systemic inflammation within the context of chronic disease. Specifically, we provide an update on the findings from human trials that have characterized anti-inflammatory properties of dietary patterns, defined by various methods and indexes. Given the complexity of interpreting results from dietary pattern analysis, we further present recent evidence on the anti-inflammatory roles of isolated bioactive nutrients and functional foods that are common components of distinct dietary patterns, in addition to considerations for interpreting dietary pattern research, population-specific dietary recommendations, and future studies. Overall, we observe a vast range of variability in the evidence from observational studies that have evaluated the relationships between healthy dietary patterns and inflammatory markers. These studies highlight the need for additional intervention studies with study designs that account for metabolic status, diversity in populations, breadth of inflammatory measurements, fasting vs. postprandial effects of diet, and control of confounding factors (e.g., genotype, microbiome profiles, and dietary adherence) in order to better understand the effect that diet has, as a whole, on inflammation. These strategies will help to strengthen diet recommendations aimed at reducing inflammation and chronic disease risk.

http://bit.ly/2RWQDEd

Elevated serum HER‐2 predicts poor prognosis in breast cancer and is correlated to ADAM10 expression

Serum HER‐2 ECD shedding is correlated to ADAM10 overexpression. Serum HER‐2 ECD could be a biomarker to identify the subgroup of poorer outcome among HER‐2 overexpression breast cancer patients. Inhibition of ADAM10 activity may have potential therapeutic benefit for this most aggressive tumor subgroup.

Abstract

Human epidermal growth factor receptor‐2 (HER‐2) overexpression in breast tumor tissues is associated with a poor prognosis but may benefit from treatment with trastuzumab. The extracellular domain (ECD) of HER‐2 can be measured in serum and which has been a new inspection item in clinical laboratory of several hospitals. However, whether serum HER‐2 ECD can be a marker of HER‐2 status in tumor tissues still confused clinicians. This study is a retrospective observation to explore the correlation between serum HER‐2 ECD shedding and tissue HER‐2 status in breast cancer patients. Meanwhile, we will further uncover the potential clinical significance of serum HER‐2 ECD detection. A total of 545 unselected breast cancer patients from Fudan University Shanghai Cancer Center were enrolled in this study. At primary diagnosis without any treatment, serum HER‐2 ECD was measured on ADVIA Centaur assay; meanwhile, tissue HER‐2 from core needle biopsy was tested through immunohistochemistry (IHC) and fluorescent in situ hybridization (FISH). We showed that serum HER‐2 ECD concentration was related to tissue HER‐2 status. Nevertheless, 36.9% of patients with tissue HER‐2 overexpression had low levels of HER‐2 ECD shedding (<15 ng/mL) in serum. Here, we demonstrated that HER‐2 ECD shedding was also associated with protein expression and alpha‐secretase activity of a disintegrin and metalloproteinase 10 (ADAM10) using tumor tissues and cell lines. Progression‐free survival (PFS) data from breast cancer patients in TNM phase II and III with tissue HER‐2 IHC 3+ were analyzed using Kaplan‐Meier plotter. The patients with serum HER‐2 ECD above 15 ng/mL had lower progression‐free survival than those with serum HER‐2 ECD <15 ng/mL. Thus, serum HER‐2 ECD could be a biomarker to identify the subgroup of poorer outcome among HER‐2 overexpression breast cancer patients. Inhibition of ADAM10 activity may have potential therapeutic benefit for this most aggressive tumor subgroup.

http://bit.ly/2AVcmCV

Louqin Zhisou Decoction Inhibits Mucus Hypersecretion for Acute Exacerbation of Chronic Obstructive Pulmonary Disease Rats by Suppressing EGFR-PI3K-AKT Signaling Pathway and Restoring Th17/Treg Balance

Airway mucus hypersecretion is the main pathogenic factor in acute exacerbation of chronic obstructive pulmonary disease (AECOPD) and the control of mucus secretion is closely associated with survival. Louqin Zhisou decoction (LQZS) has been found to improve lung function and reduce sputum in AECOPD patients, but the mechanism remains unclear. This study aimed to explore the mechanism of LQZS against mucus hypersecretion in lung tissues of rat AECOPD model. Wistar rats were used to establish AECOPD model by intratracheal instillation of LPS in combination with the continuous cigarette smoking. Rats were administrated LQZS/clarithromycin (CAM)/distilled water via gavage every day and all rats were sacrificed after 30 days. BALF and lung tissues were obtained. Lung morphology, cytokines levels, MUC5AC mRNA transcription and protein expression, phosphorylation of the EGFR-PI3K-AKT signaling pathway, and molecules involved in Th17/Treg balance were evaluated. The results demonstrated that LQZS protected rats from decline in pulmonary function and ameliorated lung injury. LQZS treatment decreased the number of goblet cells in airway and suppressed MUC5AC mRNA and protein expression of lung tissues. Furthermore, LQZS attenuated the level of phospho-EGFR, phospho-PI3K and phospho-AKT in AECOPD rats. In addition, LQZS could inhibit the production of proinflammatory cytokines in BALF, including IL-6 and IL-17A and downregulate the secretion of NE and MCP-1, indicating that LQZS could limit inflammatory responses in AECOPD. Moreover, LQZS reversed RORγt and Foxp3 expression, the key transcription factors of Th17 and Treg, respectively. In conclusion, this research demonstrated the inhibitory effects of LQZS against mucus hypersecretion in AECOPD via suppressing EGFR-PI3K-AKT signaling pathway and restoring Th17/Treg balance.

http://bit.ly/2RAbWw9

The Role of Serum CEA and CA19-9 in Efficacy Evaluations and Progression-Free Survival Predictions for Patients Treated with Cetuximab Combined with FOLFOX4 or FOLFIRI as a First-Line Treatment for Advanced Colorectal Cancer

Background. Previously, it was demonstrated that serum levels of tumor markers, CEA and CA19-9, correlated with chemotherapy. Consequently, it has been hypothesized that dynamic monitoring of changes in these markers may predict the shrinkage or growth of colorectal cancers. To test this hypothesis, we analyzed CEA and CA19-9 serum levels in patients with advanced colorectal cancer who received cetuximab in combination with chemotherapy. These levels were evaluated at various time points to identify their potential to serve as early efficacy predictors during treatment and early predictors of disease progression. Patients and Methods. Measurements of tumor markers, CEA and CA 19-9, in patients with metastatic colorectal cancer () who received cetuximab plus folinic acid, fluorouracil, and oxaliplatin or irinotecan (FOLFOX4/FOLFIRI) as a first-line treatment at our center were retrospectively analyzed. These levels were also compared with objective responses according to the World Health Organization criteria. Initially, 65 patients had elevated CEA levels (>5 ng/ml), and 59 patients had elevated levels of CA19-9 (>37 U/ml). A total of 172 cycles and 165 cycles of computed tomography/magnetic resonance imaging observations were available for review from these two patient groups. Results. After completing three cycles of treatment, the best diagnosis of cetuximab resistance was achieved when CEA increased by 35% (efficacy, 83.33%; sensitivity, 75.41%) and when CA19-9 increased by 28% (efficacy, 80.00%; sensitivity, 84.31%). Next, the efficacy of cetuximab at the time of diagnosis (at the first imaging examination/after three cycles of treatment) was evaluated after the first cycle of chemotherapy. When CEA decreased by 60% from its baseline level, the best effective rate and sensitivity were observed (63.64% and 80.95%, respectively). Similarly, when CA19-9 was 45% lower than its baseline level, the best effective rate and sensitivity were observed (84.21% and 93.18%, respectively). To evaluate progression-free survival (PFS), levels of both CEA and CA19-9 were evaluated after the third cycle of chemotherapy. Increases of 35% and 28%, respectively, resulted in a shorter PFS period compared with the other patients (3.15 months vs. 9.10 months, respectively; ). Conversely, when the evaluation was performed after the first cycle of chemotherapy, patients exhibiting a 60% decrease in CEA and a 45% decrease in CA19-9 had a longer PFS period (11.13 months vs. 8.10 months, respectively; ).Conclusions. CEA and CA19-9 are useful indicators of therapeutic curative effect from cetuximab combined with first-line chemotherapy. These markers also helped assess cetuximab resistance and served as early predictors of initial treatment effectiveness. Furthermore, a simultaneous increase or decrease in the levels of both indicators was consistent with the observed differences in PFS.

http://bit.ly/2MiJvga

Are melanocortin peptides future therapeutics for cutaneous wound healing?

Abstract

Cutaneous wound healing is a complex process divided into different phases, i. e. an inflammatory, proliferative and remodelling phase. During these phases a variety of resident skin cell types but also cells of the immune system orchestrate the healing process. In the last year it has been shown that the majority of cutaneous cell types express the melanocortin 1 receptor (MC1R) that binds α‐melanocyte‐stimulating hormone (α‐MSH) with high affinity and elicits pleiotropic biological effects, e. g. modulation of inflammation and immune responses, cytoprotection, antioxidative defence, and collagen turnover. Truncated α‐MSH peptides such as Lys‐Pro‐Val (KPV) as well as derivatives like Lys‐d‐Pro‐Thr (KdPT), the latter containing the amino acid sequence 193‐195 of interleukin‐1β, have been found to possess anti‐inflammatory effects but to lack the pigment‐inducing activity of α‐MSH. We propose here that such peptides are promising future candidates for the treatment of cutaneous wounds and skin ulcers. Experimental approaches in silico, in vitro, ex vivo and in animal models are outlined. This is followed by an unbiased discussion of the pro and contra arguments of such peptides as future candidates for the therapeutic management of cutaneous wounds and a review of the so‐far available data on melanocortin peptides and derivatives in wound healing.

This article is protected by copyright. All rights reserved.

http://bit.ly/2CwZRxl

Identifying predictors of under‐triage in injured older adults after implementation of statewide geriatric trauma triage criteria

Abstract

Objectives

Identify factors associated with transport of injured older adults meeting statewide geriatric trauma triage criteria to a trauma center.

Methods

An observational retrospective cohort study using the 2009‐2011 Ohio Trauma Registry. Subjects were adults ≥70 years old who met Ohio's geriatric triage criteria for trauma center transport by emergency medical services. We created multivariable logistic regression models to identify predictors of initial and ultimate (e.g. inter‐facility transfer) transport to a Level I or II trauma center and to a Level I, II, or III center.

Results

Of 10,411 subjects, 47% were initially and 59% were ultimately transported to a Level I or II trauma center with rates of 66% and 74% respectively for transport to a Level I, II, or III center. For initial transport to a Level I or II center, age 80‐89 (odds ratio [OR 0.89]), age ≥90 (OR 0.76) and either only a Level 3 (OR 0.3) or no trauma center (OR 0.11) in county of residence had decreased odds of transport, while male sex (OR 1.38), black race (OR 2.07), injury severity score (ISS) 10‐15 (OR 1.99), ISS>15 (OR 2.85), and Glasgow coma scale (GCS)<9 (OR 2.11) had increased odds. Results were similar for ultimate transport to a Level I or II center. Analyzing transport to a Level I, II, or III center demonstrated similar results except a Level 3 trauma center in county of residence was associated with increased odds (OR 2.00 for initial and 2.21 for ultimate) of transport to a Level I, II, or III center.

Conclusions

We identified factors independently associated with failure to transport injured older adults to trauma centers in statewide data collected after adoption of geriatric triage criteria. Lack of a trauma center in the county of residence remained a factor even in analyses which included ultimate transport.

This article is protected by copyright. All rights reserved.

http://bit.ly/2Cyvarr

Accuracy of detecting vertical root fractures in non‐root filled teeth using cone beam computed tomography: effect of voxel size and fracture width

Abstract

Aim

To investigate simultaneously the effect of voxel size and fracture width on the accuracy of detecting vertical root fractures (VRF) in non‐root filled teeth when using cone beam computed tomography.

Methodology

Fifty‐one of 161 extracted human permanent teeth (16 anterior teeth, 132 premolars, 13 mandibular molars) were selected randomly for VRF induction with two fracture widths. All teeth were scanned with four CBCT units at different voxel sizes provided by the units. Three observers classified the presence or absence of VRF using a 5‐point scale. Sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV) and area under the ROC curve (AUC) were calculated. AUCs among voxel sizes and between the fracture widths were compared using the Z test. Intra‐ and inter‐observer agreement were assessed using weighted Cohen kappa.

Results

For the NewTom VGi and ProMax 3D Mid CBCT unit, no significant differences were found among voxel sizes for the AUCs, irrespective of the fracture width (P > 0.05). There were significant differences between images scanned with voxel size 250 μm and 160 μm (P = 0.02), and images scanned with voxel size 250 μm and 80 μm for AUCs in the narrow VRF group for the 3D Accuitomo 170 unit (P = 0.03). For i‐CAT FLX, significant differences were found between the voxel protocols of 300 μm and of the other three voxel sizes for AUC, sensitivity and NPV (P < 0.05). Significant differences between the wide and the narrow VRF groups for AUCs were found for 3D Accuitomo 170 (P = 0.01) and ProMax 3D Mid (P < 0.01).

Conclusions

CBCT was accurate for detecting VRF in non‐root filled teeth. Fracture width had an effect on the detection of VRF. The effect of the voxel size on the detection of VRF depended on the CBCT unit used.

This article is protected by copyright. All rights reserved.

http://bit.ly/2Hzodwn

Cancers, Vol. 11, Pages 121: The Oncogene Addiction Switch from NOTCH to PI3K Requires Simultaneous Targeting of NOTCH and PI3K Pathway Inhibition in Glioblastoma

Cancers, Vol. 11, Pages 121: The Oncogene Addiction Switch from NOTCH to PI3K Requires Simultaneous Targeting of NOTCH and PI3K Pathway Inhibition in Glioblastoma

Cancers doi: 10.3390/cancers11010121

Authors: Norihiko Saito Nozomi Hirai Kazuya Aoki Ryo Suzuki Satoshi Fujita Haruo Nakayama Morito Hayashi Keisuke Ito Takatoshi Sakurai Satoshi Iwabuchi

The NOTCH pathway regulates neural stem cells and glioma initiating cells (GICs). However, blocking NOTCH activity with &gamma;-secretase inhibitors (GSIs) fails to alter the growth of GICs, as GSIs seem to be active in only a fraction of GICs lines with constitutive NOTCH activity. Here we report loss of PTEN function as a critical event leading to resistance to NOTCH inhibition, which causes the transfer of oncogene addiction from the NOTCH pathway to the PI3K pathway. Drug cytotoxicity testing of eight GICs showed a differential growth response to GSI, and the GICs were thus stratified into two groups: sensitive and resistant. In the sensitive group, GICs with loss of PTEN function appeared less sensitive to GSI treatment. Here we show that NOTCH regulates PTEN expression and the activity of the PI3K pathway in GICs, as treatment with GSI attenuated the NOTCH pathway and increased PTEN expression. NOTCH regulates PTEN expression via Hes-1, as knockdown of Notch or Hes1 increased expression of PTEN. This novel observation suggests that both pathways must be simultaneously inhibited in order to improve therapeutic efficacy in human glioblastomas (GBMs).

http://bit.ly/2W5kfP9

Factors predicting cessation of status epilepticus in clinical practice – data from a prospective observational registry (SENSE)

Abstract

Objective

To investigate the initial termination rate of status epilepticus (SE) in a large observational study, and to explore associated variables.

Methods

Data of adults treated for SE were collected prospectively in centers in Germany, Austria, and Switzerland, during 4.5 years. Incident episodes of 1,049 patients were analyzed using uni‐ and multivariate statistics to determine factors predicting cessation of SE within 1 hour (for generalized convulsive SE, GCSE) and 12 hours (for non‐GCSE) of initiating treatment.

Results

Median age at SE onset was 70 years; most frequent etiologies were remote (32%) and acute (31%). GCSE was documented in 43%. Median latency between SE onset and first treatment was 30 minutes in GCSE and 150 minutes in non‐GCSE. The first intravenous compound was a benzodiazepine in 86% in GCSE, and 73% in non‐GCSE. Bolus doses of the first treatment step were lower than recommended by current guidelines in 76% of the GCSE patients and 78% of the non‐GCSE patients. In 319 GCSE patients (70%), SE was ongoing 1 hour after initiating treatment, and in 342 non‐GCSE patients (58%) 12 hours after initiating treatment. Multivariate Cox regression demonstrated that the use of benzodiazepines as first treatment step, and a higher cumulative dose of anticonvulsants within the first period of treatment were associated with shorter time to cessation of SE for both groups.

Interpretation

In clinical practice, treatment guidelines were not followed in a substantial proportion of patients. This under‐dosing correlated with lack of cessation of SE. Our data suggest that sufficiently dosed benzodiazepines should be used as first treatment step.

This article is protected by copyright. All rights reserved.

http://bit.ly/2RCumfv

Ly6C+ Monocytes and Kupffer Cells Orchestrate Liver Immune Responses Against Hepatitis B Virus in Mice

Abstract

To understand the mechanism(s) of age‐dependent outcomes of HBV infection in humans, we previously established an age‐related HBV mouse model in which six‐week‐old (N6W) C3H/HeN exhibited virus tolerance, while 12‐week‐old (N12W) counterparts represented virus clearance. By investigating the hepatic myeloid cell dynamics in mice of these two ages, we aim to identify factors associated with HBV clearance. C3H/HeN mice were transfected with an HBV plasmid by hydrodynamic injection (HDI). Serum HBV markers were monitored weekly. Hepatic leucocyte populations and their cytokine/chemokine productions were examined at baseline, day 3 (D3), D7, and D14 post injection. CCR2 antagonist and clodronate were respectively, administrated to N12W and N6W mice, to study the roles of Ly6C⁺ monocytes and kupffer cells (KCs) in viral clearance. Twelve‐week‐old mice had a significantly higher number of TNF‐α‐secreting Ly6C⁺ monocytes and fewer IL‐10‐secreting KCs at D3 in the liver than their younger N6W counterparts after HBV transfection. In addition, the elevated number of IFNγ⁺TNFα⁺CD8⁺ T cells at D7 was only seen in the older cohort. The enhanced Ly6C⁺ monocyte induction in N12W resulted from elevated CCL2 secretion by hepatocytes. CCR2 antagonist administration hampered Ly6C⁺ monocyte recruitment and degree of KC reduction, and delayed HBV clearance in 12‐week‐old animals. Depletion of KCs by clodronate liposomes enhanced Ly6C⁺ monocyte recruitment and accelerated HBV clearance in six‐week‐old mice. Conclusions.Ly6C⁺ monocytes and KCs may, respectively, represent the resistance and tolerance arms of host defenses. These two cell types play an essential role in determining HBV clearance/tolerance. Manipulation of these cells is a promising avenue for immunotherapy of HBV‐related liver diseases.

This article is protected by copyright. All rights reserved.

http://bit.ly/2T5tJYz

The nonsteroidal FXR agonist cilofexor (GS‐9674) improves markers of cholestasis and liver injury in patients with PSC

Abstract

Primary sclerosing cholangitis (PSC) represents a major unmet medical need. In a Phase 2 double‐blind, placebo‐controlled study, we tested the safety and efficacy of cilofexor (formerly GS‐9674), a nonsteroidal farnesoid X receptor (FXR) agonist in non‐cirrhotic patients with large duct PSC. Patients were randomized to receive cilofexor 100 mg (n=22), 30 mg (n=20), or placebo (n=10) orally once daily for 12 weeks. All patients had serum alkaline phosphatase (ALP) >1.67xULN and total bilirubin ≤2 mg/dL at baseline. Safety, tolerability, pharmacodynamic effects of cilofexor (serum C4 and bile acids), and changes in liver biochemistry and serum fibrosis markers were evaluated. Overall, 52 patients were randomized (median age 43 years, 58% male, 60% with IBD, 46% on UDCA). Baseline median serum ALP and bilirubin were 348 U/L (IQR 288‐439) and 0.7 mg/dL (0.5‐1.0), respectively. Dose‐dependent reductions in liver biochemistry were observed. At week 12, cilofexor 100 mg led to significant reductions in serum ALP (median reduction ‐21%; p=0.029 vs placebo), GGT (‐30%;p<0.001), ALT (‐49%;p=0.009), and AST (‐42%;p=0.019). Cilofexor reduced serum C4 compared with placebo; reductions in bile acids were greatest with 100 mg. Relative reductions in ALP were similar between UDCA‐treated and untreated patients. At week 12, cilofexor‐treated patients with a ≥25% relative reduction in ALP had greater reductions in serum ALT, AST, GGT, TIMP‐1, CRP, and bile acids than non‐responders. Adverse events were similar between cilofexor and placebo‐treated patients. Rates of Grade 2 or 3 pruritus were 14% with 100 mg, 20% with 30 mg, and 40% with placebo. Conclusions In this 12‐week, randomized, placebo‐controlled study, cilofexor was well tolerated and led to significant improvements in liver biochemistries and markers of cholestasis in patients with PSC.

This article is protected by copyright. All rights reserved.

http://bit.ly/2ASieNe

Motor behavior unmasks residual cognition in disorders of consciousness

Abstract

Disorders of consciousness (DOC) are a common consequence of severe brain injuries, and clinical evaluation is critical to provide a correct diagnosis and prognosis. The revised Motor Behavior Tool (MBT‐r) is a clinical complementary tool aiming to identify subtle motor behaviors that might reflect residual cognition in DOC. In this prospective study including 30 DOC patients in the early stage after brain injury, we show that the revised MBT‐r has an excellent inter‐rater agreement and has the ability to identify a subgroup of patients, underestimated by the Coma Recovery Scale‐Revised, showing residual cognition and a subsequent recovery of consciousness.

This article is protected by copyright. All rights reserved.

http://bit.ly/2FKQywZ

The clinical learning environment of a maternity ward: A qualitative study

Publication date: Available online 18 January 2019

Source: Women and Birth

Author(s): Masoumeh Rahimi, Fariba Haghani, Shahnaz Kohan, Majid Shirani

Abstract

Background

Clinical learning environments influence the learning and performance of learners by creating learning opportunities and experiences. The maternity ward offers a major educational opportunity for midwifery students, obstetrics and gynecology residents and medical interns to acquire and improve crucial skills.

Objectives

This study seeks to determine the way in which the clinical learning environment of the maternity ward creates learning opportunities and enables the accumulation of experiences for the noted learners.

Methods

This qualitative study was conducted using inductive content analysis at the Maternity Ward of Shahid Beheshti Hospital, affiliated with University of Medical Sciences. Midwifery students, medical interns and obstetrics and gynecology residents spend a certain period of time in this ward as a mandatory part of their obstetrics and gynecology training. Data were collected through semi-structured individual interviews and observations and were then analyzed in MAXQDA concurrently with data collection.

Results

Three main categories emerged from the analysis of the data collected from the interviews and observations: disorganized learning opportunities, heavy emotional load and learners' abandonment in the care-provider and learner role.

Conclusion

The maternity ward lacked the necessary organization to generate an environment conducive to learning and independent practice for the three groups of learners. The learners' training and acquired skills were thus affected by the clinical learning environment.

http://bit.ly/2QZsGrp

Cancers, Vol. 11, Pages 120: Combination of Different Fecal Immunochemical Tests in Colorectal Cancer Screening: Any Gain in Diagnostic Performance?

Cancers, Vol. 11, Pages 120: Combination of Different Fecal Immunochemical Tests in Colorectal Cancer Screening: Any Gain in Diagnostic Performance?

Cancers doi: 10.3390/cancers11010120

Authors: Gies Cuk Schrotz-King Brenner

A variety of fecal immunochemical tests (FITs) are used for colorectal cancer screening. FIT performance could be improved further. It is unclear, whether the combination of different FITs with different analytical characteristics (such as, different antibodies for the detection of fecal hemoglobin) can yield a better diagnostic performance. Fecal samples were obtained from 2042 participants of screening colonoscopy. All participants with advanced neoplasm (AN, colorectal cancer (n = 16) or advanced adenoma (n = 200)) and 300 randomly selected participants without AN were included. Nine quantitative FITs were evaluated simultaneously. Sensitivity and specificity was calculated for single tests (n = 9) and for their pairwise test combinations (n = 36) (requiring either both FITs (P++) or at least one FIT (P+) to be positive for defining a positive test result). Mean age of the participants (n = 516) was 63 (range: 50&ndash;79) years and 56% were men. At cutoffs yielding a specificity of 96.7% for single FITs, the median gain in specificity by P++ combination was +1.0%, whereas the median loss in sensitivity for AN was &minus;4.2%. For P+ combination the median gain in sensitivity for AN was +2.8%, at a prize of median loss of &minus;1.0% of specificity. Combinations of different FITs do not yield any relevant gain in diagnostic performance.

http://bit.ly/2DopAtH

Effect of spinal decompression on back pain in lumbar spinal stenosis: A Canadian Spine Outcomes Research Network (CSORN) study

Publication date: Available online 19 January 2019

Source: The Spine Journal

Author(s): Shreya Srinivas, Jerome Paquet, Chris Bailey, Andrew Nataraj, Alexandra Stratton, Michael Johnson, Paul Salo, Sean Christie, Charles Fisher, Hamilton Hall, Neil Manson, Y Raja Rampersaud, Kenneth Thomas, Greg McIntosh, Nicloas Dea

ABSTRACT

Background context

Surgical decompression is usually offered for improvement of neurogenic claudication in patients with symptomatic lumbar canal stenosis. These patients often have associated low back pain (LBP) and little is known about the effect of decompression on this symptom.

Purpose

The goal of the present study is to specifically quantify the improvement in LBP following surgical decompression for lumbar canal stenosis and to identify factors associated with changes in LBP in this population.

Study Design

This is a multicenter, retrospective review of consecutive spine surgery patients enrolled by the Canadian Spine Outcomes and Research Network (CSORN).

Patient Sample

Consecutive patients who underwent surgical treatment for symptomatic lumbar spine stenosis without instability between 2014 and 2017

Outcome Measures

Change in low back pain on the Numeric Rating Scale

Methods

Patient-reported outcomes were collected at baseline and at 3,12 and 24 months after surgery. The primary outcome was change in LBP on the Numeric Rating Scale (NRS). Multivariable logistic regression was used to model the relationship between the outcome and potential factors associated with achieving minimal clinical important difference (MCID) in back pain using a backward selection procedure.

Results

In all, 1221 patients were included in the analysis. Mean age was 64 years and 58% were males. Baseline back pain scores were available in 1133 patients and follow-up evaluations were available in 968/1133 (85%) patients at 3 months, 649/903 (72%) patients at 12 months and 331/454 (73%) at 24 months. LBP significantly improved 3 months after surgery and the improvement was sustained at 24 months (P < 0.001). We found that 74% of patients reached the MCID in back pain. Predictive factors for sustained improvement (12 and 24 months) in LBP after surgical intervention were absence of narcotic usage or compensation claims and increased severity of LBP prior to surgery (high NRS).

Conclusions

Alleviation of clinically significant LBP was observed at 3 months after lumbar decompression surgery for neurogenic claudication and was maintained at 12 and 24 months after surgery in the majority of patients.

http://bit.ly/2Hk7wVd

Prevalence of Staphylococcus Species Colonization in Healthy and Sick Cats

Staphylococcus is one of the most frequently isolated genera of opportunistic bacteria in animals and human beings. Staphylococci in mammals mostly inhabit the skin and mucous membranes. The objectives of the study were to investigate the distribution of staphylococcal species in healthy and sick cats in order to find diagnostic markers. The risk factors associated with colonization were also explored. Isolates from healthy (n=520) and sick cats (n=67) were identified at the species level using matrix-assisted laser desorption ionization time of flight mass spectrometry (MALDI-TOF MS). Swabs from conjunctival sacs, nares, skin, anus, and wounds were investigated using this technique. The diversity of the Staphylococcus species was high: 26 and 17 species in healthy and sick cats, respectively, and predominantly coagulase-negative staphylococci (CoNS) were isolated. The most frequently observed were S. felis and S. epidermidis in healthy cats, whereas S. felis and S. haemolyticus were most often found in sick animals. S. aureus strains were only isolated from healthy cats, whereas the only coagulase-positive Staphylococcus (CoPS) which occurred in the sick cats group was S. pseudintermedius. The sick, more frequently than the healthy animals, were colonized with S. pseudintermedius and S. haemolyticus and the relationship was statistically significant. Mostly, regardless of the state of their health, similar Staphylococcus species were isolated from cats; therefore, particular attention should be paid during the interpretation of diagnostic results.

http://bit.ly/2B4R5a7

A Rare Case of Spontaneous Hemorrhage in a Giant Accessory Spleen in a Child

Accessory spleen (AS) is a condition found in about 20% of patients and is most commonly located in the hilar region of the spleen. It is more often asymptomatic, single, and smaller than 2 cm. In the present study, we report the rare case of a 13-year-old boy with giant accessory spleen underwent spontaneous intrasplenic hemorrhage who presented with recurrent abdominal pain. Contrast-enhanced MRI was mandatory for the diagnosis before surgical procedure.

http://bit.ly/2DoMzof

Decreased Expression of Cannabinoid Receptors in the Eutopic and Ectopic Endometrium of Patients with Adenomyosis

Objective. Adenomyosis is a common gynecologic benign disease that may have a life-long negative impact on women. Previous studies have indicated that the endocannabinoid system may participate in the progress of endometriosis. Our research aims to analyze the expression patterns of the typical cannabinoid receptors (CB1 and CB2), the main constituents of the endocannabinoid system, in endometrial samples derived from patients diagnosed as adenomyosis or not. Methods. Eutopic and corresponding ectopic endometrium from 45 premenopausal women diagnosed as adenomyosis and normal endometrium from 34 age-matched women lacking evidence of adenomyosis were examined by immunohistochemistry and quantitative real-time polymerase chain reaction (qRT-PCR) to determine the CB1 and CB2 expression levels. Results. In either the proliferative or the secretory phase, CB1 and CB2 protein and mRNA levels were both significantly lower in the eutopic and ectopic endometrium of adenomyosis when compared with normal endometrium. For women with adenomyosis, CB1 and CB2 protein and mRNA levels were much lower in the ectopic endometrium than the eutopic in both phases of the cycle. Both CB1 and CB2 protein and mRNA levels were increased during the secretory phase in normal endometrium, while CB1 lost its cyclic variation in the eutopic and ectopic endometrium from patients diagnosed as adenomyosis. Conclusion. The decreased expression of CB1 and CB2 in the eutopic and ectopic endometrium from patients diagnosed as adenomyosis suggests that cannabinoid receptors may participate in the pathogenesis of adenomyosis.

http://bit.ly/2T4NkrZ

Facilitators and barriers to the clinical application of teamwork skills taught in multidisciplinary simulated Trauma Team Training

Publication date: Available online 19 January 2019

Source: Injury

Author(s): Margaret Murphy, Kate Curtis, Andrea McCloughen

Abstract

Background

Efforts to improve teamwork in trauma include simulation-based team training with a non-technical skills (NTS) focus. However, there is a lack of evidence to inform the development of team training programs for maximum uptake of NTS in clinical practice. This descriptive paper aims to evaluate the extent NTS were practiced by the trauma team in a Level 1 trauma hospital after NTS training and to identify facilitators and barriers to use of NTS in clinical practice.

Method

A 38-item questionnaire targeting clinicians who attended a simulation based multidisciplinary trauma team training program was developed. The questionnaire was developed using the Theoretical Domains Framework, a validated tool to identify what practices need to change. It included questions on the current practice of NTS in real life trauma resuscitation.

Results

Eighty six of 235 eligible participants (rate 37%) responded to the questionnaire. All relevant professions and clinical services were represented. There were 15 facilitators and 12 barriers identified. Barriers and facilitators were allocated to categories of factors known to influence trauma team practices. These were: (1) organisational factors that influence the trauma team, (2) team factors that influence teamwork and (3) cognitive factors that influence team decision making.

Conclusion

NTS were being used by frontline clinicians in real world trauma resuscitations to varying degrees, depending on organisational, team and cognitive facilitators and barriers. Facilitators to the implementation of NTS skills during trauma emergencies included team composition, roles and responsibilities, procedural compliance and leadership. Barriers included decision making and communication. This study described team members experience of using NTS in 'real world trauma resuscitation' to inform future team training interventions.

http://bit.ly/2FBUsJj

Use of a Dual mobility cup to prevent hip early arthroplasty dislocation in patients at high falls risk

Publication date: Available online 18 January 2019

Source: Injury

Author(s): D. Nonne, F. Sanna, A. Bardelli, P. Milano, F. Rivera

Abstract

Introduction

Hip fracture is a common serious injury that occurs mainly in elderly. Dual-mobility hip arthroplasty or bipolar emiarthroplasty for its treatment remains a controversial decision. Co-morbidities and risk of fall represent additional aspects to be considered. The aim of our study was to determine the rate of mechanical complications for these two types of implants related to fall risk status of patients.

Patients and Methods

Our study is a retrospective clinical trial of patients operated with a biarticular hemiarthroplasty or a dual-mobility total hip arthroplasty. Primary outcome was dislocation rate and need for any revision procedure. Patients were treated in a single center from January 2013 to March 2017. In all cases Morse Fall Scale (MSF) was calculated at patient admission to evaluate the risk of postoperative fall. Inclusion criteria to the study were: subcapital or femoral neck fracture of non-pathologic nature, patients with neuromuscular disorders or cognitive dysfunction, age > 75 years with MFS ≥ 45. The patients were reviewed postoperatively at 8 weeks, 6 months, 12 months, and then annually. Patients had clinical (Harris hip score) and radiological assessment.

Results

The mean duration of the follow-up was 28,3 months. There were five dislocations in Group A (5,6%) and no dislocations in Group B (0%). All dislocations occurred within the first 6 months after surgery. The mean Harris Hip score was 81,7 in Group A patients and 79, 8 in Group B patients.

Discussion

Treatment of hip fractures on non-cooperative patients still represents a dilemma. Falls and runaway motions represent high risk factors of dislocation. Use of dual-mobility cup has been found to be associated with a not statistically proved decrease of dislocation compared to traditional cups.

Conclusion

Dual-mobility cups might be considered a valuable option to prevent postoperative dislocation but further study is needed before extending the indications for dual-mobility following a fracture of the femoral neck, to assess the potential cost and complications of a longer procedure. So far, despite a lower dislocation risk, the authors actually cannot recommend widely use of a dual-motility cup instead of emiarthroplasty in high falls risk patients.

http://bit.ly/2FJggC9

Unintentional injuries: a profile of hospitalization and risk factors for in-hospital mortality in Beijing, China

Publication date: Available online 18 January 2019

Source: Injury

Author(s): Meng Zhang, Moning Guo, Xiaopeng Guo, Lu Gao, Jingya Zhou, Xue Bai, Shengnan Cui, Cheng Pang, Lingling Gao, Bing Xing, Yi Wang

Abstract

Introduction

Unintentional injuries (UIs) impose a significant burden on low- and middle-income countries (LMICs). However, available UI epidemiological data are limited for LMICs, including China. This article aimed to provide an overview of the UI hospitalization profile, identify risk factors for in-hospital mortality and provide diagnosis-specific survival risk ratios (SRRs) for reference by LMICs using hospital discharge abstract data (DAD) from Beijing, China.

Patients and Methods

A cross-sectional study was conducted for patients sustaining UIs requiring admission. Information was retrieved from 138 hospitals in Beijing to describe the demographics, injury nature, mechanisms, severity and hospital outcomes. Multivariate logistic regression was performed to identify and evaluate risk factors for in-hospital mortality for UIs.

Results

Falls (57.1%), transport accidents (19.9%) and exposure to inanimate mechanical forces (16.4%) were the leading causes of UI hospitalization. Falls and transport accidents were responsible for 94.2% of the in-hospital deaths caused by UIs. Injury mechanisms differed among sex (χ² = 5322.1, P <  0.001) and age (χ² = 24143.3, P <  0.001) groups. Male sex (OR: 1.50, 95% confidence interval (CI): 1.23-1.79), age ≥ 85 years (OR: 16.39, 95% CI: 7.46-36.00), Barthel Index at admission ≤ 60 (OR: 25.78, 95% CI: 13.30-49.95), modified Charlson comorbidity index ≥ 6 (OR: 2.60, 95% CI: 1.91-3.55), International Classification of Diseases-based injury severity score (ICISS) < 0.85 (OR: 15.17, 95% CI: 12.57-18.30), sustaining injuries to the head/neck (OR: 23.20, 95% CI: 7.31-73.64), injuries caused by foreign body entering through natural orifice (OR: 34.00, 95%CI: 6.37-181.54) and injuries resulting from transport accidents (OR: 1.71, 95% CI: 1.41-2.07) were important risk factors for in-hospital mortality for UIs.

Conclusions

Hospital DAD are an objective and cost-effective data source that allows for a hospital-based perspective of UI epidemiology. Sex, age, functional status at admission, comorbidities, injury nature, severity and mechanism are significantly associated with the in-hospital mortality of UIs in China. This study generates a reference dataset of diagnosis-specific SRRs from a large trauma population in China, which may be more applicable in injury severity estimation using ICISS in LMICs.

http://bit.ly/2FBUpgB

CHOICE OF THREE DIFFERENT INTRAMEDULLARY NAILS IN THE TREATMENT OF TROCHANTERIC FRACTURES: OUTCOME, ANALYSIS AND CONSIDERATION IN MIDTERM

Publication date: Available online 18 January 2019

Source: Injury

Author(s): Persiani Pietro, Ranaldi Filippo Maria, Michele Gurzì, Formica Alessandro, Graci Iole, De Cristo Claudia, Grasso Raffaele, Villani Ciro Chief

Abstract

The purpose of this study is to compare the results obtained using three different systems of osteosynthesis, developed for the surgical treatment of fractures of the trochanteric region of the femur, based on the principle intramedullary nailing: the Gamma nail, the Affixus nail and the ZNN nail. This is a retrospective study: 72 trochanteric fractures treated with the Gamma nail, 68 treated with the Affixus nail and 69 treated with the ZNN nail, between the years 2012 and 2014, with the prerequisite of a minimum follow-up of 18 months. The fractures were classified according to the AO system; the most commonly reported subtype was the A2 fracture. Clinical and radiographic examinations were performed, both at hospital admission and post-operatively, at 1, 3, 6, 12 and 18 months. Of the 209 patients, 171 were women and 38 were men. The average age was 83.12 years old.

All three systems guaranteed an early mobilization and ambulation in most of the patients. There were no significant differences in the use of the three nails in terms of recovery of previous functional capacity, or in terms of the time required for the fracture to heal.

There were no advantages encountered with the use of one intramedullary nail over another and, in particular, when observing the complications and patient outcome, there were no statistically significant differences detected.

http://bit.ly/2FMtjT7

Imperatorin Suppresses Anaphylactic Reaction and IgE-Mediated Allergic Responses by Inhibiting Multiple Steps of FceRI Signaling in Mast Cells: IMP Alleviates Allergic Responses in PCA

This study is to investigate the effects of imperatorin (IMP) on allergic responses mediated by mast cells, both in vitro and in vivo. Passive cutaneous anaphylaxis (PCA) model was established. Histological detection was performed to assess the ear histology. ELISA and Western blot analysis were used to detect the levels of corresponding cytokines and signalling pathway proteins. IMP decreased the leakage of Evans blue and the ear thickness in the PCA models, in a dose-dependent manner, and alleviated the degranulation of mast cells. Moreover, IMP reduced the expression of TNF-α, IL-4, IL-1β, IL-8, and IL-13. Furthermore, IMP inhibited the phosphorylation levels of Syk, Lyn, PLC-γ1, and Gab2, as well as the downstream MAPK, PI3K/AKT, and NF-κB signaling pathways. In addition, IMP inhibited the mast cell-mediated allergic responses through the Nrf2/HO-1 pathway. IMP attenuates the allergic responses through inhibiting the degranulation and decreasing the expression levels of proinflammatory cytokines in the mast cells, involving the PI3K/Akt, MAPK, NF-κB, and Nrf2/HO-1 pathways.

http://bit.ly/2U5RSyx

Relationships of SLC2A4, RBP4, PCK1, and PI3K Gene Polymorphisms with Gestational Diabetes Mellitus in a Chinese Population

Background. Solute carrier family 2 member 4- (SLC2A4-) retinol binding protein-4- (RBP4-) phosphoenolpyruvate carboxykinase 1 (PCK1)/phosphoinositide 3-kinase (PI3K) is an adipocyte derived "signalling pathway" that may contribute to the pathogenesis of type 2 diabetes mellitus (T2DM). We explored whether single nucleotide polymorphisms (SNPs) of these "signalling pathway" genes are associated with gestational diabetes mellitus (GDM). Methods. Case-control studies were conducted to compare GDM and control groups. A total of 334 cases and 367 controls were recruited. Seventeen candidate SNPs of the pathway were selected. Chi-square tests, logistic regression, and linear regression were used to estimate the relationships of SNPs with GDM risk and oral glucose tolerance test (OGTT), fasting insulin, and homeostasis model assessment of insulin resistance (HOMA-IR) levels. Model-based multifactor dimensionality reduction was used to estimate the adjusted interactions between genes. Regression and interaction analyses were adjusted by maternal age, prepregnancy BMI, and weekly BMI growth. The Bonferroni correction was applied for multiple comparisons. Results. RBP4 rs7091052 was significantly associated with GDM risk. SLC2A4 rs5435, RBP4 rs7091052, PCK1 rs1042531 and rs2236745, and PIK3R1 (coding gene of the PI3K P85 subunit) rs34309 were associated with OGTT, fasting insulin, and HOMA-IR levels in the linear regression analysis. The gene-gene interaction analysis showed that, compared with pregnant women with other genotype combinations, women with SLC2A4 rs5435 (CC/CT), RBP4 rs7091052 (CC), PCK1 rs1042531 (TT/TG) and rs2236745 (TT), and PIK3R1 rs34309 (AA) had lower GDM risk. Conclusion. SLC2A4, RBP4, PCK1, and PIK3R1 genes may be involved in the pathogenesis of GDM.

http://bit.ly/2DnkWvR

Diagnostic and Prognostic Values of BMPER in Patients with Urosepsis following Ureteroscopic Lithotripsy

The present study aims to investigate the risk factors for urosepsis and the diagnostic and prognostic values of the bone morphogenetic protein endothelial cell precursor-derived regulator (BMPER) in patients with urosepsis following ureteroscopic lithotripsy. A total of 305 patients with unilateral ureteral obstruction caused by calculi were included in the study. Patients were divided into three groups, namely, high, medium, and low perfusion pressure groups. The serum C-reactive protein, procalcitonin, lactate (LAC), and BMPER were measured after operation. A logistic regression model was used to assess the risk factors for postoperative urosepsis. The relationships of BMPER with laboratory parameters were explored with a multiple linear regression model. Receiver operating characteristic (ROC) curves were used to diagnosis urosepsis. The cumulative incidence of the adverse events after operation was calculated and compared by log-rank test. Forty-five patients (14.8%) had an episode of urosepsis after operation. Irrigation pressure was an independent risk factor for urosepsis. LAC and sequential organ failure assessment (SOFA) were associated with BMPER after operation. The area under curve value of BMPER for urosepsis was 0.829 (95% confidence interval [CI], 0.773 to 0.884). Uroseptic patients with higher BMPER concentration exhibited more adverse outcome. BMPER possesses valuable discriminative capacity for urosepsis and is a strong predictor of adverse outcome in patients with urosepsis.

http://bit.ly/2U1sMk8

Effects of Four Compounds from Gentianella acuta (Michx.) Hulten on Hydrogen Peroxide-Induced Injury in H9c2 Cells

In previous studies, Gentianella acuta (Michx.) Hulten was reported to contain xanthones, iridoids, terpenoids, and sterols and is mainly used to cure hepatitis, jaundice, fever, headache, and angina pectoris. In this study, we used bioassay guided fractionation to identify compounds from G. acuta and investigated their activity against hydrogen peroxide (H2O2)-induced apoptosis of H9c2 cells using the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) method. The levels of nuclear factor erythroid 2-related factor 2 (Nrf2), heme oxygenase-1 (HO-1), and glutamate-cysteine ligase catalytic (GCLC) expression were assessed using quantitative real-time polymerase chain reaction (qRT-PCR). Protein expression was evaluated using western blot. The results showed that all four compounds had protective effects on H9c2 cells. The transcription levels of HO-1 and GCLC significantly increased in H9c2 cells pretreated with norswertianolin (1), swetrianolin (2), demethylbellidifolin (3), and bellidifolin (4). However, compared to the model group, the transcription levels of Nrf2 were not enhanced by pretreatment with compounds 1, 2, and 4. The protein expression levels of HO-1 and GCLC in H9c2 cells were greater than that in the H2O2-treated group, and the expression of Nrf2 was not significantly changed except by swetrianolin treatment; inhibitors can reverse the protective effect by ZnPP (15 μM), BSO (10 μM), and brusatol (10 μM). The results indicated that the four compounds isolated from G. acuta inhibited the oxidative injury induced by H2O2 by activating the Nrf2/ARE pathway in H9c2 cells and provide evidence that G. acuta may be a potential therapeutic agent for the treatment of cardiovascular diseases.

http://bit.ly/2Dn4ED6

A Rare Occurrence of Isolated Brain Metastases from Gastric Cancer

Background. Gastric cancer is the fourth most common cancer worldwide and the second most common cause of cancer-related death. The majority of newly diagnosed gastric cancer cases present either as locally advanced tumor growth or with distant metastases. Case Report. Here, we describe a case of isolated brain metastases in a male patient with gastric cancer. Initially, our patient presented with dysphagia and was diagnosed with gastric cancer after a thorough evaluation. One year after chemotherapy and surgical resection of his gastric cancer, he presented with headaches, nausea, dizziness, and photophobia. Further evaluation of these symptoms led to the discovery of three metastatic brain lesions without evidence of extracranial metastases. Conclusions. Our review of the literature has found that such cases are rare. Additionally, our review of the literature demonstrates the poor outcomes associated with metastatic brain lesions from gastric cancer and highlights the importance of surgical resection in increasing overall survival time.

http://bit.ly/2Dn4LP2

45,X/46,XY Mosaicism and Normozoospermia in a Patient with Male Phenotype

The phenotypic spectrum of 45,X/46,XY mosaic males varies greatly. Previous reports have only described cases with either oligozoospermia, growth retardation, or elevated gonadotropins. However, the present case presented with normozoospermia, and normal height, sperm DNA fragmentation index (DFI), and gonadotropins. The male and his spouse were referred to The Fertility Clinic, Skive Regional Hospital, due to 2 years of infertility. After failure of several attempts of assisted reproductive treatment (ART), the male underwent genetic analysis. Conventional karyotyping in peripheral lymphocytes yielded a low-grade 45,X/46,XY mosaicism, confirmed by fluorescence in situ hybridization (FISH) showing 6% 45,X cells. A FISH test performed on interphase nuclei from buccal mucosal cells yielded one cell with only one X-signal (0.6%), explaining the normal phenotype of the patient, but not the infertility. FISH test for sperm aneuploidy showed normal range parameters, except for a 10-fold elevated gonosomal nullisomy rate (2.1%). Hence, germinal mosaicism may be an explanation of the infertility of the case. Increased sex nullisomy levels may reflect an aberrant testicular environment compromising fertility even though sperm euploidy rates and other sperm parameters do not preclude a successful treatment with ART. Based on these results, the couple decided to use donor semen for their subsequent intrauterine insemination treatment and obtained a successful pregnancy.

http://bit.ly/2FGqBQb

ΒΟΗΘΗΜΑΤΑ ΑΚΟΗΣ,ΑΚΟΥΣΤΙΚΑ ΒΑΡΗΚΟΙΑΣ,ΕΝΙΣΧΥΤΕΣ ΑΚΟΗΣ

Οπισθωτιαία
Εφαρμόζονται πίσω από το αυτί και συνδέονται με το κατάλληλο εκμαγείο

Ενδοκαναλικά
Αθέατα,Είναι μικρότερα σε μέγεθος και εφαρμόζονται μέσα στον ακουστικό πόρο.

Καθαρή και διαυγή μετάδοση της φωνής των συνομιλούντων
Έξυπνη φραγή των θορύβων

Άριστη ποιοτική ενίσχυση και απόδοση του ήχου,εύκολα στη χρήση,άνετα στην εφαρμογή,όμορφα για καλύτερη αισθητική όσο αφορά το μέγεθος και την εξωτερική εμφάνιση,χωρίς καμμία ιδιαίτερη συντήρηση.

Ενδοωτιαίο Ακουστικό Βοήθημα με ελεγχόμενη ένταση,
Ενδοωτιαίο Ακουστικό Βοήθημα Υψηλής Πιστότητας,
Ενδοωτιαίο Ακουστικό Βοήθημα Δώρο Χαράς Σε Όσους Αγαπάτε και Φροντίζετε,
Ενδοωτιαίο Ακουστικό Βοήθημα με πιστοποίηση γνησιότητας και ποιότητας,
Ενδοωτιαίο Ακουστικό Βοήθημα υποαλλεργικά άριστης εφαρμογής,
Ενδοωτιαίο Ακουστικό Βοήθημα όμορφα μικρά αόρατα με άριστες αποδόσεις,
Ενδοωτιαίο Ακουστικό Βοήθημα όμορφα μικρά αόρατα με άριστες αποδόσεις για μεσαίες εως υψηλές βαρηκοΐες,
Ενδοωτιαίο Ακουστικό Βοήθημα Οδηγίες Χρήσης,

https://akoustika-ellas.blogspot.com/,
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Οπισθοωτιαίο Ακουστικό Βαρηκοίας υψηλής ποιότητας,
Οπισθοωτιαίο Ακουστικό Βαρηκοίας υψηλής ποιότητας επαναφορτιζόμενο,
Οπισθοωτιαίο Ακουστικό Βαρηκοίας υψηλής ποιότητας επαναφορτιζόμενο με έξυπνη φραγή όλων των θορύβων,
Οπισθοωτιαίο Ακουστικό Βαρηκοίας υψηλής ποιότητας επαναφορτιζόμενο με μπαταρία μακράς διάρκειας,

https://akoustika-ellas-2.blogspot.com/,
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Οπισθοωτιαίο Ακουστικό Βαρηκοίας υψηλής ποιότητας επαναφορτιζόμενο με έξυπνη φραγή όλων των θορύβων με μπαταρία μακράς διάρκειας,
Οπισθοωτιαίο Ακουστικό Βαρηκοίας υψηλής ποιότητας επαναφορτιζόμενο με έξυπνη φραγή όλων των θορύβων με επεξεργαστή IC Extra Low Noise,
Οπισθοωτιαίο Ακουστικό Βαρηκοίας υψηλής ποιότητας επαναφορτιζόμενο με έξυπνη φραγή όλων των θορύβων με επεξεργαστή IC sound processing technology,
Οπισθοωτιαίο Ακουστικό Βαρηκοίας υψηλής ποιότητας επαναφορτιζόμενο με έξυπνη φραγή όλων των θορύβων με επεξεργαστή IC Extra Low Noise με μπαταρία μακράς διάρκειας και γρήγορης φόρτισης,
Οπισθοωτιαίο Ακουστικό Βαρηκοίας υψηλής ποιότητας επαναφορτιζόμενο με μπαταρία μακράς διάρκειας 12 εως 18 ωρών φόρτιση σε θύρα USB,
Οπισθοωτιαίο Ακουστικό Βαρηκοίας υψηλής ποιότητας επαναφορτιζόμενο με έξυπνη φραγή όλων των θορύβων με επεξεργαστή IC Extra Low Noise με μπαταρία μακράς διάρκειας και γρήγορης φόρτισης 5γρ εύκολη χρήση,

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Cancers, Vol. 11, Pages 119: Platinum Resistance in Ovarian Cancer: Role of DNA Repair

Cancers, Vol. 11, Pages 119: Platinum Resistance in Ovarian Cancer: Role of DNA Repair

Cancers doi: 10.3390/cancers11010119

Authors: Giovanna Damia Massimo Broggini

Epithelial ovarian cancer (EOC) is the most lethal gynecological cancer. It is initially responsive to cisplatin and carboplatin, two DNA damaging agents used in first line therapy. However, almost invariably, patients relapse with a tumor resistant to subsequent treatment with platinum containing drugs. Several mechanisms associated with the development of acquired drug resistance have been reported. Here we focused our attention on DNA repair mechanisms, which are fundamental for recognition and removal of platinum adducts and hence for the ability of these drugs to exert their activity. We analyzed the major DNA repair pathways potentially involved in drug resistance, detailing gene mutation, duplication or deletion as well as polymorphisms as potential biomarkers for drug resistance development. We dissected potential ways to overcome DNA repair-associated drug resistance thanks to the development of new combinations and/or drugs directly targeting DNA repair proteins or taking advantage of the vulnerability arising from DNA repair defects in EOCs.

http://bit.ly/2FLzXJo

Salvia miltiorrhiza Bunge (Danshen) for Treatment and Prevention of Urolithiasis: A Drosophila Animal Study

Traditional Chinese medicine (TCM) has been prescribed for the treatment of stone disease for thousands of years. Salvia miltiorrhiza (Danshen) was previously shown to have potential for treatment of stone disease in animal and clinical studies. In this study, we further studied the antiurolithiasis effect of Danshen in a fly model. Wild-type male Drosophila melanogaster CS flies were used in this study, with 0.25% ethylene glycol (EG) as a lithogenic agent. 2% potassium citrate (K-citrate) was the positive control agent for prevention (all agents added at the start of experiment) and treatment (drugs added after 2-week addition of lithogenic agent) studies compared with 15, 30, and 60 μg/ml of Danshen extract. In the prevention study, both 2% K-citrate and Danshen (30 and 60 μg/ml) significantly inhibited EG-induced calcium oxalate (CaOx) crystal formation. In the treatment study, only 2% K-citrate and high-dose of Danshen (60 μg/ml) significantly inhibited EG-induced CaOx crystal formation. Survival analysis for EG with Danshen was compared with that for EG with K-citrate. The mean lifespan was significantly reduced by administration of EG, and the results in the Danshen group were similar to those in the control group. In conclusion, Danshen revealed both preventive and treatment effects on CaOx crystal formation in a fly model.

http://bit.ly/2FB797f