Fibrinogen adsorption, platelet adhesion and activation on mixed hydroxyl-/methyl-terminated self-assembled monolayers.
The effect of surface wettability on fibrinogen adsorption, platelet adhesion and platelet activation was investigated using self-assembled monolayers (SAMs) containing different ratios of longer chain methyl- and shorter chain hydroxyl-terminated alkanethiols (C15CH3 vs. C11OH) on gold. Protein adsorption studies were performed using radiolabeled human fibrinogen (HFG). Platelet adhesion and activation studies with and without pre-adsorbed fibrinogen, albumin and plasma were assessed using scanning electron microscopy (SEM) and a glutaraldehyde-induced fluorescence technique (GIFT). Results demonstrated a linear decrease of HFG adsorption with the increase of OH groups on the monolayer (increase of the hydrophilicity). Platelet adhesion and activation also decrease with increase of hydrophilicity of surface. Concerning SAMs pre-immersed in proteins, fibrinogen adsorption was related with high platelet adhesion and activation. The passivant effect of albumin on platelet adhesion and activation was only demonstrated on SAMs contained C11OH. When all the blood proteins are present (plasma) platelet adhesion was almost absent on SAMs with 65% and 100% C11OH. This could be explained by the higher albumin affinity of the SAMs with 65% C11OH and the lower total protein adsorption associated with SAMs with 100% C11OH.


ATF4-mediated autophagy-dependent glycolysis plays an important role in attenuating apoptosis induced by Cr (VI) in A549 cells.
Chromium (Cr) (VI) compounds are known to be serious toxic and carcinogenic, but the mechanism is not clear. In our previous study, we found that Cr (VI)-induced ER stress plays an important role in the crosstalk between apoptosis and autophagy, while autophagy was apoptosis-dependent and subsequently prevents apoptosis cell death to keep A549 cells resistant to Cr (VI)-induced toxicity. In this study, we found that Cr (VI) could induce aerobic glycolysis in A549 cells. Both ER stress inhibitor, phenylbutyric acid (4-PBA) and the inhibitor of autophagy, 3-MA, repressed Cr (VI)-induced glycolysis, indicating that both ER stress and autophagy were involved in Cr (VI)-induced glycolysis in A549 cells. Co-treatment of the inhibitor of aerobic glycolysis, 2-DG and Cr (VI) for 24 h increased Cr (VI)-induced cleaved caspase-3, caspase-9 and the number of apoptotic cells, demonstrating that aerobic glycolysis played an important role in attenuating Cr (VI)-induced apoptosis. Furthermore, knockdown of ATF4 by siATF4 significantly decreased Cr (VI)-induced aerobic glycolysis and apoptosis, suggesting that ATF4 was involved in Cr (VI)-induced aerobic glycolysis and its effect of attenuating apoptosis in A549 cells. Taken together, our results demonstrated that autophagy-dependent glycolysis played a role in attenuating Cr (VI)-induced apoptosis. ER stress was involved in facilitating glycolysis, whose induction was mediated by ATF4. These findings open a window for the development of therapeutic interventions to prevent Cr (VI)-induced toxicity.


Fabrication of alginate-based stimuli-responsive, non-cytotoxic, terpolymric semi-IPN hydrogel as a carrier for controlled release of bovine albumin serum and 5-amino salicylic acid.
Herein, we report a functionalized alginate(Alg)-based terpolymeric semi-interpenetrating (semi-IPN) hydrogel, synthesized via free radical polymerization for the delivery of bovine albumin serum (BSA) and 5-amino salicylic acid (5-ASA). To improve mechanical properties, and to modulate surface morphology of Alg, 2-hydroxyethyl acrylate (HEA) was grafted on alginate and then crosslinked using poly(ethylene glycol) diacrylate (PEGDA). The probable structure and compositions of the synthesized semi-IPN terpolymer were identified by FTIR, 1H-HR-MAS NMR, and TGA analyses. Achievement of equilibrium swelling state (ESS) and higher elastic modulus values confirmed terpolymer gel formation in aqueous media. Differences in the ESS of the prepared gel at pH 2.5 and 7.4 signify its stimuli-responsive behaviour. The influence of PEGDA on swelling, mechanical properties, surface morphology, cell viability and proliferation, and BSA and 5-ASA delivery were characterized. SEM images show that higher % PEGDA resulted in smaller sized pores in the gel network. Texture analyses demonstrate that hardness, adhesiveness and chewiness of the gel were enhanced at higher PEGDA concentrations. Increases in PEGDA concentration also induced increases in osteoblastic cell viability and higher rates of cell proliferation compared with gels containing lower concentrations of PEGDA. The release results indicate that the gels containing higher concentrations of PEGDA more sustainably release BSA and 5-ASA at 5 days and 30 h, respectively. The experimental data revealed that the synthesized terpolymeric semi-IPN hydrogel may have useful biomedical applications, especially as a carrier of protein (BSA), or 5-ASA (a therapeutic option for conditions of the colon such as Crohn's Disease and Ulcerative Colitis).


Quantifying the likelihood and costs of hip replacement surgery after sports injury: A population-level analysis.
To quantify the likelihood of hip replacement (HR) surgery at a population level up to 15 years after sports injury. Cohort study. Public and private hospitals in the state of Victoria, Australia. The cohort was established by linking administrative datasets capturing all hospital admissions and emergency department (ED) presentations. All sports injury presentations from 2000 to 2005 and HR admissions from 2000 to 2015 were identified using ICD-10-AM codes. Time to HR (number of days from sports injury admission to HR admission). Over the study period there were 64,750 sports injuries (including 815 hip or thigh musculoskeletal injuries) that resulted in ED presentation or hospitalisation, and 368 HR procedures. Compared to all other sports injuries, having a hip or thigh injury tripled the hazard of subsequent HR in multivariate analysis (hazard ratio 3.07, 95%CI 2.00-4.72). Of the main hip or thigh injury types, femoral fractures (hazard ratio 3.08, 95%CI 1.77-5.36) and hip dislocations (hazard ratio 5.64, 95%CI 2.34-13.58) were significantly associated with HR. Sports-related hip or thigh musculoskeletal injury is associated with a significantly higher likelihood of HR within 15 years. Effective injury prevention and appropriate post-injury management are needed to curtail this population burden.


Association of epicardial adipose tissue with different stages of coronary artery disease: A cross-sectional UK Biobank cardiovascular magnetic resonance imaging substudy.
Increased epicardial adipose tissue (EAT) has been identified as a risk factor for the development of coronary artery disease (CAD). However, the exact role of EAT in the development of CAD is unclear. This study aims to compare EAT volumes between healthy controls and individuals with stable CAD and a history of myocardial infarction (MI). Furthermore, associations between clinical and biochemical parameters with EAT volumes are examined. This retrospective cross-sectional study included 171 participants from the United Kingdom Biobank (56 healthy controls; 60 stable CAD; 55 post MI), whom were balanced for age, sex and body mass index (BMI). EAT volumes were quantified on end-diastolic cardiac magnetic resonance (CMR) imaging short-axis slices along the left and right ventricle and indexed for body surface area (iEAT) and iEAT volumes were compared between groups. iEAT volumes were comparable between control, CAD and MI cases (median [IQR]: 66.1[54.4-77.0] vs. 70.9[55.8-85.5] vs. 67.6[58.6-82.3] mL/m2, respectively (p > 0.005 for all). Increased HDL-cholesterol was associated with decreased iEAT volume (β = -14.8, CI = -24.6 to -4.97, p = 0.003) and suggestive associations (P-value < 0.05 and ≥ 0.005) were observed between iEAT and triglycerides (β = 3.26, CI = 0.42 to 6.09, p = 0.02), Apo-lipoprotein A (β = -16.3, CI = -30.3 to -2.24, p = 0.02) and LDL-cholesterol (β = 3.99, CI = -7.15 to -0.84, p = 0.01). No significant differences in iEAT volumes were observed between patients with CAD, MI and healthy controls. Our results indicate the importance of correcting for confounding by CVD risk factors, including circulating lipid levels, when studying the relationship between EAT volume and CAD. Further mechanistic studies on causal pathways and the role of EAT composition are warranted.


Evaluation of Raman spectroscopy to detect fullerenes in geological materials.
Fullerene C(60) was determined repeatedly from a few types of carbonaceous matter from geological environments. Detailed investigation of structural aspects of pure carbonaceous matrices as well as of their experimental mixtures with fullerene C(60) permits better understanding of the occurrence mode of fullerenes inside the network of natural samples. However, it appears that Raman microspectrometry is not competitive in the case of investigated current geological carbonaceous matrices with added fullerenes, when the concentration of fullerene C(60) is 100 ppm or lower. In such a situation, C(60) is highly dispersed and careful interpretation of the results of Raman microspectrometry does not permit us to obtain valuable quantitative structural data. Obtained sensitivity for detecting C(60) in investigated matrices was only 1%. Analytical reasons for these results are discussed.


1,7,7-Trimethyl-3-(naphthalen-2-ylcarbon-yl)bi-cyclo-[2.2.1]heptan-2-one.
The title compound, C21H22O2, crystallizes in its keto form. The mol-ecules are connected via weak C-H⋯O inter-actions, forming infinite chains perpendic-ular to the [001] axis.


A machine learning analysis to evaluate the outcome measures in inflammatory myopathies.
To assess the long-term outcome in patients with Idiopathic Inflammatory Myopathies (IIM), focusing on damage and activity disease indexes using artificial intelligence (AI). IIM are a group of rare diseases characterized by involvement of different organs in addition to the musculoskeletal. Machine Learning analyses large amounts of information, using different algorithms, decision-making processes and self-learning neural networks. We evaluate the long-term outcome of 103 patients with IIM, diagnosed on 2017 EULAR/ACR criteria. We considered different parameters, including clinical manifestations and organ involvement, number and type of treatments, serum creatine kinase levels, muscle strength (MMT8 score), disease activity (MITAX score), disability (HAQ-DI score), disease damage (MDI score), and physician and patient global assessment (PGA). The data collected were analysed, applying, with R, supervised ML algorithms such as lasso, ridge, elastic net, classification, and regression trees (CART), random forest and support vector machines (SVM) to find the factors that best predict disease outcome. Using artificial intelligence algorithms we identified the parameters that best correlate with the disease outcome in IIM. The best result was on MMT8 at follow-up, predicted by a CART regression tree algorithm. MITAX was predicted based on clinical features such as the presence of RP-ILD and skin involvement. A good predictive capacity was also demonstrated on damage scores: MDI and HAQ-DI. In the future Machine Learning will allow us to identify the strengths or weaknesses of the composite disease activity and damage scores, to validate new criteria or to implement classification criteria.


Robotically assisted total gastrectomy for lymphadenopathy after long-term follow-up for multiple type 1 gastric neuroendocrine tumor (NET): a case report.
Type 1 gastric neuroendrine tumor (NET) is usually associated with chronic atrophic gastritis and forms multiple lesions. While most cases of type 1 gastric NET are generally slowly growing, some develop regional lymph node metastases even after long-term dormancy. A 73-year-old male patient with a 32-year history of multiple gastric NET was being followed-up at the study center after endoscopic submucosal dissection (ESD) of a large gastric NET. A blood examination revealed high serum gastrin (> 3000 pg/ml). An endoscopic examination found atrophic mucosa and multiple, elevated lesions in the upper to lower stomach body. Computed tomography (CT) revealed regional lymphadenopathy in the greater omentum along the gastroepiploic artery. Robotically assisted total gastrectomy was performed with D2 lymphadenectomy and Roux-en-Y reconstruction. Pathological analysis revealed a large number of gastric NET (grade 1) with a maximum size of 4.5 mm invading the submucosal layer. A single lymph node metastasis was also detected pathologically at station #4d. The postoperative course was uneventful, and serum gastrin normalized postoperatively. At postoperative year 3, the patient has been doing well without any recurrences. The present case of multiple gastric NET with a single regional lymph node metastasis at year 32 of follow-up was successfully treated with a robotically assisted total gastrectomy.


Selection of intestinal segments for bladder substitution: physical and physiological characteristics.
Detubularized bowel segments provide greater capacity at lower pressure and require a shorter length of intestine than do intact segments. Four factors account for their superiority: 1) their configuration takes advantage of the geometric fact that volume increases by the square of the radius so that a patch or pouch has a larger diameter than a tube, 2) they accommodate to filling more readily because, as LaPlace's law states, the container with the greater radius and, thus, the greater mural tension will hold larger volumes at lower pressure, 3) compliance is superior to that of the tubular bowel and 4) contractile ability is blunted by the failure of contractions to encompass the entire circumference. For these reasons detubularized segments store more urine at lower pressures.


Erythromycin vs azithromycin for treatment of preterm prelabor rupture of membranes: a systematic review and meta-analysis.
This study aimed to estimate the effect of erythromycin vs azithromycin on the duration of latency and the rate of clinical chorioamnionitis in women with preterm prelabor rupture of membranes by performing a systematic review and meta-analysis of the existing literature. From inception to October 2021, we explored MEDLINE, Scopus, Embase, CINAHL, ClinicalTrials.gov, and Cochrane Central Register of Controlled Trials. Studies comparing the duration of latency and the rate of clinical chorioamnionitis between women with preterm prelabor rupture of membranes who were treated with erythromycin and those who were treated with azithromycin at the time of diagnosis were included. Here, 2 reviewers separately ascertained studies, obtained data, and gauged study quality. The mean length of latency and the rate of clinical chorioamnionitis were compared and mean differences and odds ratios with 95% confidence intervals were estimated. A total of 5 studies with 1289 women were identified. The mean length of latency in women with preterm prelabor rupture of membranes was similar between individuals treated with erythromycin and those treated with azithromycin: 6.6 days vs 6.7 days (mean difference, 0.07 days; 95% confidence interval, -0.45 to 0.60; I2, 0%). The median point prevalence rates of clinical chorioamnionitis were 25% (95% confidence interval, 12-32) in women treated with erythromycin and 14% (95% confidence interval, 9-24) in women treated with azithromycin. The overall clinical chorioamnionitis rate in women treated with azithromycin was lower than women treated with erythromycin (pooled odds ratio, 0.53; 95% confidence interval, 0.39-0.71; I2, 0%). The administration of azithromycin in women with preterm prelabor rupture of membranes was associated with a similar latency period but a lower rate of clinical chorioamnionitis than the administration of erythromycin.


The effects of drugs with immunosuppressive or immunomodulatory activities on xenobiotics-metabolizing enzymes expression in primary human hepatocytes.
In this paper we investigated the effects of several drugs used in transplant medicine, i.e. cyclosporine A, tacrolimus, rapamycin, everolimus, mycophenolate mofetil, fluvastatin and rosuvastatin, on the expression of major drug-metabolizing enzymes in human hepatocytes. Moreover, we tested the ability of these drugs to affect transcriptional activity of glucocorticoid (GR) and aryl hydrocarbon receptor (AhR). We found that most of tested compounds did not induce expression of CYP1A1/1A2/3A4/2A6/2B6/2C9 mRNAs in human hepatocytes. Slight induction was observed for CYP2A6/2C9 mRNAs and CYP2A6 protein in the rapamycin-treated hepatocytes. Decrease of CYP2A6 and CYP2B6 proteins was observed in rosuvastatin-treated cells. Mycophenolate mofetil antagonized the effects of dexamethasone on GR but it potentiated the action of dioxin on AhR. Induction of CYP1A1 mRNA in HepG2 cells by dioxin was modestly antagonized by mycophenolate mofetil, while the induction by benzo[a]pyren or S-omeprazole was significantly potentiated by this drug. In general, tested compounds can be considered safe in the terms of possible drug-drug interaction caused by induction of drug-metabolizing cytochromes P450. Nevertheless, mycophenolate mofetil is of possible concern and its combination with drugs, environmental pollutants or food constituents, which activate AhR, may represent a significant toxicological risk.


Visceral adiposity indicators as predictors of metabolic syndrome in postmenopausal women.
The aim of the present study was to evaluate the importance of visceral adiposity indicators on metabolic parameters in postmenopausal women. This cross-sectional study included 200 postmenopausal subjects. Postmenopausal women were divided into two groups based on the presence of metabolic syndrome (MetS) as MetS+ and MetS-. Comparisons of clinical and metabolic characteristics were performed between the groups. The current study included 200 postmenopausal women and 63 subjects were diagnosed as having MetS. Postmenopausal women with MetS demonstrated significantly higher values with respect to systolic and diastolic blood pressures, body mass index (BMI), waist-hip ratio (WHR), triglyceride (TG), lipid ratios, Homeostasis Model Assessment Insulin Resistance (HOMA) index, TG glucose (TyG), Visceral Adiposity Index (VAI), and lipid accumulation product (LAP) when compared with women without MetS. Correlation analyses showed that LAP and VAI were positively correlated with waist circumference, WHR, BMI, TG, lipid ratios, TyG and HOMA index, and with each other. LAP was also positively correlated with blood pressures. Visceral adiposity indicators may be useful as predictors of MetS in postmenopausal women.


Renal cell carcinoma associated with Xp11.2 translocation/TFE gene fusion: imaging findings in 21 patients.
To characterize imaging features of renal cell carcinoma (RCC) associated with Xp11.2 translocation/TFE gene fusion. Twenty-one patients with Xp11.2/TFE RCC were retrospectively evaluated. Tumour location, size, density, cystic or solid appearance, calcification, capsule sign, enhancement pattern and metastases were assessed. Fourteen women and seven men were identified with 12 being 25 years old or younger. Tumours were solitary and cystic-solid (76.2 %) masses with a capsule (76.2 %); 90.5 % were located in the medulla. Calcifications and lymph node metastases were each observed in 24 %. On unenhanced CT, tumour attenuation was greater than in normal renal parenchyma (85.7 %). Tumour enhancement was less than in normal renal cortex on all enhanced phases, greater than in normal renal medulla on cortical and medullary phases, but less than in normal renal medulla on delayed phase. On MR, the tumours were isointense on T1WI, heterogeneously hypointense on T2WI and slightly hyperintense on diffusion-weighted imaging. Xp11.2/TFE RCC usually occurs in young women. It is a cystic-solid, hyperdense mass with a capsule. It arises from the renal medulla with enhancement less than in the cortex but greater than in the medulla in all phases except the delayed phase, when it is lower than in the medulla. • Xp11.2/TFE RCC was more prevalent in young women. • On unenhanced CT, Xp11.2/TFE RCC attenuation was greater than in renal parenchyma. • Xp111/2TFE RCC arises primarily from the renal medulla. • Xp11.2/TFE RCC enhancement was less than in the cortex on all phases. • Enhancement was greater than in the medulla in arterial and corticomedullary phase.


The Current Landscape of Targeted Clinical Trials in Non-WNT/Non-SHH Medulloblastoma.
Medulloblastoma is an embryonal pediatric brain tumor and can be divided into at least four molecularly defined groups. The category non-WNT/non-SHH medulloblastoma summarizes medulloblastoma groups 3 and 4 and is characterized by considerable genetic and clinical heterogeneity. New therapeutic strategies are needed to increase survival rates and to reduce treatment-related toxicity. We performed a noncomprehensive targeted review of the current clinical trial landscape and literature to summarize innovative treatment options for non-WNT/non-SHH medulloblastoma. A multitude of new drugs is currently evaluated in trials for which non-WNT/non-SHH patients are eligible, for instance immunotherapy, kinase inhibitors, and drugs targeting the epigenome. However, the majority of these trials is not restricted to medulloblastoma and lacks molecular classification. Whereas many new molecular targets have been identified in the last decade, which are currently tested in clinical trials, several challenges remain on the way to reach a new therapeutic strategy for non-WNT/non-SHH medulloblastoma. These include the severe lack of faithful preclinical models and predictive biomarkers, the question on how to stratify patients for clinical trials, and the relative lack of studies that recruit large, homogeneous patient collectives. Innovative trial designs and international collaboration will be a key to eventually overcome these obstacles.


Pelvic neurilemmoma.
A rare case of benign pelvic neurilemmoma with bladder infiltration and ureteral obstruction is presented. This neurally originated tumor may occur anywhere in the body, but involvement of the urinary tract is rare. Management depends upon location and other clinical findings, and in this case, since complete removal was impossible, urinary derivation was employed as a palliative treatment.


Fuchs' endothelial corneal dystrophy: a controlled prospective study on visual recovery after endothelial keratoplasty.
To investigate the determining factors of vision and subjective outcome after Descemet's stripping automated endothelial keratoplasty (DSAEK) for Fuchs' endothelial dystrophy (FECD). In a prospective study, 41 FECD patients who received DSAEK were compared to 40 cataract patients with normal corneas who received cataract surgery (control group). Subjects were recruited between March 2013 and July 2014. Observational procedures included the following: best-corrected visual acuity (BCVA), contrast sensitivity (CS), Catquest-9SF questionnaire, Scheimpflug tomography and anterior OCT. Examinations were carried out before surgery and at 3-, 6- and 12-month follow-up. Main outcome measures were associations between corneal optics and visual parameters, as well as subjective improvement (Catquest-9SF effect size) RESULTS: Best-corrected visual acuity (BCVA) negatively correlated with anterior higher-order aberrations (HOA's) (p < 0.001) and central corneal thickness (p = 0.001). Contrast sensitivity (CS) was negatively correlated with anterior HOA's (p = 0.002) and positively correlated with posterior densitometry (p = 0.008). Catquest-9SF effect size was 1.32 (CI: 1.0-1.6) in the control group, 1.84 (CI: 1.4-2.3) in FECD patients who received phacoemulsification and intra-ocular lens implantation in combination with DSAEK (n = 26) and 1.37 (CI: 0.6-2.1) in pseudophakic FECD patients who received DSAEK (n = 15). DSAEK surgery leads to considerable improvement in patient-reported outcome in FECD patients. There was a strong correlation between anterior HOA's and vision after DSAEK, suggesting that anterior corneal pathology constitutes the major limitation for visual recovery after DSAEK.


The effect of dissolved oxygen tension and the utility of oxygen uptake rate in insect cell culture.
Dissolved oxygen tension and oxygen uptake rate are critical parameters in animal cell culture. However, only scarce information of such variables is available for insect cell culture. In this work, the effect of dissolved oxygen tension (DOT) and the utility of on-line oxygen uptake rate (OUR) measurements in monitoring Spodoptera frugiperda (Sf9) cultures were determined. Sf9 cells were grown at constant dissolved oxygen tensions in the range of 0 to 30%. Sf9 metabolism was affected only at DOT below 10%, as no significant differences on specific growth rate, cell concentration, amino acid consumption/production nor carbohydrates consumption rates were found at DOT between 10 and 30%. The specific growth rate and specific oxygen uptake rate followed typical Monod kinetics with respect to DOT. The calculated μ(max) and [Formula: see text] max were 0.033 h(-1) and 3.82×10(-10) mole cell(-1)h(-1), respectively, and the corresponding saturation constants were 1.91 and 1.57%, respectively. In all aerated cultures, lactate was consumed only after glucose and fructose had been exhausted. The yield of lactate increased with decreasing DOT. It is proposed, that an 'apparent' DOT in non-instrumented cultures can be inferred from the lactate yield of bioreactors as a function of DOT. Such a concept, can be a useful and important tool for determining the average dissolved oxygen tension in non-instrumented cultures. It was shown that the dynamic behavior of OUR can be correlated with monosaccharide (fructose and glucose) depletion and viable cell concentration. Accordingly, OUR can have two important applications in insect cell culture: for on-line estimation of viable cells, and as a possible feed-back control variable in automatic strategies of nutrient addition.


Role of activation of cholinergic influences in recovery of electrical activity of the stomach and small intestine during the early postoperative period in rats.
The effects of neostigmine and calcium pantothenate on electrical activity of the stomach and small intestine were studied in chronic experiments on rats after laparotomy with implantation of a probe into the jejunum and electrodes into different portions of the gastrointestinal tract. At the early terms after surgery, stimulation of endogenous acetylcholine release intensified electrical activity of the stomach, duodenum, and jejunum. Treatment with neostigmine and calcium pantothenate did not accelerate the recovery of the migrating myoelectrical complex, but promoted the recovery of the general intensity of action potential generation in the stomach and small intestine.


Medicating patients during extracorporeal membrane oxygenation: the evidence is building.
This article is one of ten reviews selected from the Annual Update in Intensive Care and Emergency Medicine 2017. Other selected articles can be found online at http://ccforum.com/series/annualupdate2017 . Further information about the Annual Update in Intensive Care and Emergency Medicine is available from http://www.springer.com/series/8901 .


Palliative radiation for vertebral metastases: the effect of variation in prescription parameters on the dose received at depth.
To assess the effect of prescription parameters on the dose received by the spine during palliative radiotherapy. In a survey, members of the Canadian Association of Radiation Oncologists were asked to define their prescription parameters for vertebral metastases. The depth of the spinal canal and vertebral body at 8 spinal levels was measured in 20 magnetic resonance imaging studies (MRIs). Survey results were applied to the measurements to assess the dose received at depth. The depth of spinal structures assessed at simulation and by diagnostic imaging was compared. Prescriptions were most commonly to D(max) 3 cm or 5 cm using 60Co-6MV photons delivering 8-30 Gy in 1-10 fractions. Mean depths from MRI were: posterior spinal canal, 5.5 cm; anterior spinal canal, 6.9 cm; and anterior vertebral body, 9.6 cm. Application of the prescription parameters from the survey to these measurements showed a wide range in the dose at depth with variation in technique. Depths measured at simulation correlated well with diagnostic imaging. The spinal canal and vertebral body lie >5 cm beneath the skin, and the dose received varies by up to 50% with changes in prescription depth. We suggest a suitable prescription point for vertebral metastases and a method for determining this at simulation.


Discoveries in Down syndrome: moving basic science to clinical care.
This review describes recent discoveries in neurobiology of Down syndrome (DS) achieved with use of mouse genetic models and provides an overview of experimental approaches aimed at development of pharmacological restoration of cognitive function in people with this developmental disorder. Changes in structure and function of synaptic connections within the hippocampal formation of DS model mice, as well as alterations in innervations of the hippocampus by noradrenergic and cholinergic neuromodulatory systems, provided important clues for potential pharmacological treatments of cognitive disabilities in DS. Possible molecular and cellular mechanisms underlying this genetic disorder have been addressed. We discuss novel mechanisms engaging misprocessing of amyloid precursor protein (App) and other proteins, through their affect on axonal transport and endosomal dysfunction, to "Alzheimer-type" neurodegenerative processes that affect cognition later in life. In conclusion, a number of therapeutic strategies have been defined that may restore cognitive function in mouse models of DS. In the juvenile and young animals, these strategists focus on restoration of synaptic plasticity, rate of adult neurogenesis, and functions of the neuromodulatory subcortical systems. Later in life, the major focus is on recuperation of misprocessed App and related proteins. It is hoped that the identification of an increasing number of potential targets for pharmacotherapy of cognitive deficits in DS will add to the momentum for creating and completing clinical trials.


Exon shuffling: mapping polymorphic determinants on hybrid mouse transplantation antigens.
The mouse major transplantation antigens H-2K, H-2D and H-2L are highly polymorphic cell-surface glycoproteins which may serve as recognition elements in cell-cell interactions. Each antigen possesses a number of alloantigenic determinants defined by antisera of various specificities. Recently, monoclonal antibodies have been produced which redefine and extend our knowledge of these determinants2,3, but structural information has not yet been correlated with the serological definition of the antigens. We have previously reported the molecular cloning of genes for H-2Ld and H-2Dd transplantation antigens from the BALB/c mouse and the expression of these genes in mouse L cells4,5. To localize the serological determinants to discrete regions of the H-2 protein, we have now constructed new H-2 antigen genes by joining together fragments of the H-2Ld and H-2Dd genes. In L cells, these genes direct the synthesis of hybrid H-2 proteins and by using monoclonal antibodies of defined specificities, we have mapped classically defined serological specificities to structurally defined domains of the transplantation antigen protein. We conclude that polymorphic determinants recognized by monoclonal antibodies are located in functionally distinct portions of the protein.


A survey to assess use patterns and perceptions of efficacy of eczema action plans among pediatric dermatologists.
Eczema action plans (EAPs) are written, customizable documents that guide patients through the self-management of atopic dermatitis. Here, we distributed a survey regarding the use patterns and perceptions of eczema action plans to 1068 members of the Society for Pediatric Dermatology and received 87 responses. Although a strong majority of respondents endorsed the ability of EAPs to improve adherence (79%) and improve prevention and/or management of flares (70%), reported rates of EAP editing or provision sharply decline from initial to follow-up visits (61%-33%). The development of a standardized, low-literacy web-based tool could improve the efficacy of EAPs for patients and physicians by improving comprehensibility and retention.


Determination of Trichinella spiralis in pig muscles using Mid-Fourier Transform Infrared Spectroscopy (MID-FTIR) with Attenuated Total Reflectance (ATR) and Soft Independent Modeling of Class Analogy (SIMCA).
The aim of this work was to study the feasibility of detection of Trichinella spiralis in swine meat using Middle Infrared Spectroscopy Fourier Transform with Attenuated Total Reflectance (ATR) and Soft Independent Modeling of Class Analogy (MID-FTIR-ATR-SIMCA). Five male Pigs were orally infected at different larvae concentrations (13,000, 6500, 3500, 1625, 812 larvae/pig) and after 24 weeks the animals were euthanized. Five types of muscles were studied (leg, loin, rib, masseter, and diaphragm). Results showed that MID-FTIR-ATR-SIMCA was useful to determine the presence of T. spiralis in the samples, as the interclass distance between infected and non infected muscles varied from 13.5 to 36.8. This technique was also useful to discriminate among pig muscles, where masseter showed the largest interclass distance, while rib presented the smallest one. In all cases the recognition and rejection rates were 100%, which means that the methodology is capable of accurately separating T. spiralis infected from non infected swine meat.


Neural changes underlying early stages of L2 vocabulary acquisition.
Research has shown neural changes following second language (L2) acquisition after weeks or months of instruction. But are such changes detectable even earlier than previously shown? The present study examines the electrophysiological changes underlying the earliest stages of second language vocabulary acquisition by recording event-related potentials (ERPs) within the first week of learning. Adult native English speakers with no previous Spanish experience completed less than four hours of Spanish vocabulary training, with pre- and post-training ERPs recorded to a backward translation task. Results indicate that beginning L2 learners show rapid neural changes following learning, manifested in changes to the N400 - an ERP component sensitive to lexicosemantic processing and degree of L2 proficiency. Specifically, learners in early stages of L2 acquisition show growth in N400 amplitude to L2 words following learning as well as a backward translation N400 priming effect that was absent pre-training. These results were shown within days of minimal L2 training, suggesting that the neural changes captured during adult second language acquisition are more rapid than previously shown. Such findings are consistent with models of early stages of bilingualism in adult learners of L2 (e.g. Kroll and Stewart's RHM) and reinforce the use of ERP measures to assess L2 learning.


Aldosterone does not alter apical cell-surface expression of epithelial Na+ channels in the amphibian cell line A6.
The steroid hormone aldosterone regulates reabsorptive Na+ transport across specific high resistance epithelia. The increase in Na+ transport induced by aldosterone is dependent on protein synthesis and is due, in part, to an increase in Na+ conductance of the apical membrane mediated by amiloride-sensitive Na+ channels. To examine whether an increment in the biochemical pool of Na+ channels expressed at the apical cell surface is a mechanism by which aldosterone increases apical membrane Na+ conductance, apical cell-surface proteins from the epithelial cell line A6 were specifically labeled by an enzyme-catalyzed radioiodination procedure following exposure of cells to aldosterone. Labeled Na+ channels were immunoprecipitated to quantify the biochemical pool of Na+ channels at the apical cell surface. The activation of Na+ transport across A6 cells by aldosterone was not accompanied by alterations in the biochemical pool of Na+ channels at the apical plasma membrane, despite a 3.7-4.2-fold increase in transepithelial Na+ transport. Similarly, no change in the distribution of immunoreactive protein was resolved by immunofluorescence microscopy. The oligomeric subunit composition of the channel remained unaltered, with one exception. A 75,000-Da polypeptide and a broad 70,000-Da polypeptide were observed in controls. Following addition of aldosterone, the 75,000-Da polypeptide was not resolved, and the 70,000-Da polypeptide was the major polypeptide found in this molecular mass region. Aldosterone did not alter rates of Na+ channel biosynthesis. These data suggest that neither changes in rates of Na+ channel biosynthesis nor changes in its apical cell-surface expression are required for activation of transepithelial Na+ transport by aldosterone. Post-translational modification of the Na+ channel, possibly the 75,000 or 70,000-Da polypeptide, may be one of the cellular events required for Na+ channel activation by aldosterone.


A helical processing pipeline for EM structure determination of membrane proteins.
Electron crystallography plays a key role in the structural biology of integral membrane proteins (IMPs) by offering one of the most direct means of providing insight into the functional state of these molecular machines in their lipid-associated forms, and also has the potential to facilitate examination of physiologically relevant transitional states and complexes. Helical or tubular crystals, which are the natural product of proteins crystallizing on the surface of a cylindrical vesicle, offer some unique advantages, such as three-dimensional (3D) information from a single view, compared to other crystalline forms. While a number of software packages are available for processing images of helical crystals to produce 3D electron density maps, widespread exploitation of helical image reconstruction is limited by a lack of standardized approaches and the initial effort and specialized expertise required. Our goal is to develop an integrated pipeline to enable structure determination by transmission electron microscopy (TEM) of IMPs in the form of tubular crystals. We describe here the integration of standard Fourier-Bessel helical analysis techniques into Appion, an integrated, database-driven pipeline.


Magnesium Modifies the Structural Features of Enzymatically Mineralized Collagen Gels Affecting the Retraction Capabilities of Human Dermal Fibroblasts Embedded within This 3D System.
Mineralized collagen gels have been developed as in vitro models to better understand the mechanisms regulating the calcification process and the behavior of a variety of cell types. The vast majority of data are related to stem cells and to osteoblast-like cells, whereas little information is available for dermal fibroblasts, although these cells have been associated with ectopic calcification and consequently to a number of pathological conditions. Therefore, we developed and characterized an enzymatically mineralized collagen gel in which fibroblasts were encapsulated within the 3D structure. MgCl₂ was also added during gel polymerization, given its role as (i) modulator of ectopic calcification; (ii) component of biomaterials used for bone replacement; and (iii) constituent of pathological mineral deposits. Results demonstrate that, in a short time, an enzymatically mineralized collagen gel can be prepared in which mineral deposits and viable cells are homogeneously distributed. MgCl₂ is present in mineral deposits and significantly affects collagen fibril assembly and organization. Consequently, cell shape and the ability of fibroblasts to retract collagen gels were modified. The development of three-dimensional (3D) mineralized collagen matrices with both different structural features and mineral composition together with the use of fibroblasts, as a prototype of soft connective tissue mesenchymal cells, may pave new ways for the study of ectopic calcification.


Sleep Deficiency in Adolescents: The School Start Time Debate.
Adolescence is commonly accepted as a challenging time for sleep, with multiple factors contributing to sleep deficiency in adolescents. These include physiologic changes with shifts in their circadian rhythm; medical sleep disorders; and social, cultural, and environmental factors. Early school start times negatively affect sleep in adolescents as well, with poorer outcomes in their overall health, wellbeing, and performance. This article highlights the different contributing factors for sleep deficiency in adolescents and the consequences of sleep deficiency. In addition, the authors discuss the impact of delayed school start times in improving adolescents' sleep and overall function.


Results of surgery on adults with functional single ventricle without prior cardiac surgery in childhood.
Patients with unoperated functional single ventricle (FSV) rarely survive into adulthood with good functional status and there are few reports about surgical results of adult patients with FSV. This study retrospectively reviews our experience with surgery in adult patients with FSV. From January 2008 to September 2017, 65 adult patients with FSV underwent surgery in our hospital. Twenty underwent Blalock-Taussig shunt or bidirectional Glenn procedures in other hospitals prior, and four were lost to follow-up. Finally, 41 patients were included in this study. The early postoperative mortality was 7.3% (3/41). Postoperative systemic arterial oxygen saturation (SpO2 , 83.7% ± 4.8%) was significantly higher than preoperative SpO2 (77.9% ± 10.1%, P < .01). The mean follow-up time was 3.9 ± 3.1 years (range 1-11 years). There was only one case of late mortality and massive hemoptysis was the cause of death. Right ventricular morphology and severe atrioventricular valve regurgitation (AVVR) were the risk factors of postoperative death for patients with pulmonary stenosis(PS). There was no death case in patients who received Fontan procedure. In a follow-up, we found the grade of AVVR was reduced and the grade of heart function (New York Heart Association) was improved. Adult patients with FSV can also undergo surgery. The mortality was acceptable and late results were satisfactory. After surgery, oxygen saturations increased, grades of AVVR decreased and the heart functions improved. Right ventricular morphology and severe AVVR were risk factors for patients with PS.


Intrauterine adhesion after hysteroscopic myomectomy of submucous myomas.
To evaluate the frequency of intrauterine adhesion (IUA) after hysteroscopic myomectomy, and to analyze the association of IUA and the location of submucous myomas and the use of postoperative barrier (POB). Hysteroscopic myomectomy was performed in 217 patients with submucous myomas. The retrospective investigation was performed, and the cases were divided into three groups: cases with solitary submucous myoma (SSM; group 1), cases with apposing submucous myomas (ASMs; group 2) and cases with submucous myomas that were far from each other or not in apposition to one another (not apposing submucous myomas: NASMs; group 3). As POB, intrauterine device with oxidized regenerated cellulose and silicon sheet was inserted immediately after surgery. IUA formation after hysteroscopic myomectomy was more frequent in group 2 than groups 1 and 3 (p = 0.03 and 0.01, respectively), despite the higher rates of POB use (p = 0.02). There was no significant difference in IUA formation in cases with POB between each group (p = 0.06 and 0.21, respectively). But in cases without POB, group 2 showed higher rates of IUA formation than group 1 (p = 0.04) and group 3 (p = 0.03). Multivariable analysis for IUA formation demonstrated that ASMs were a risk factor of IUA (hazard ratio [HR] = 27.9, p < 0.01), and the use of POB was a prognostic factor for reduction of IUA formation (HR = 0.08, p < 0.01). ASMs appear to be a risk factor for IUA formation. The use of POB may be associated with preventing IUA formation after hysteroscopic myomectomy.


Associations of lifestyle with physical, hearing, visual, and mental functional impairments among older adults: Findings from two prospective cohort studies.
To examine the associations between lifestyle habits and functional impairments among older adults. The study includes 20,545 women and 14,374 men aged 70 years or older at the time of the function assessment. Participants were from two prospective cohort studies: the Shanghai Women's Health Study (SWHS, enrollment from 1996 to 2000) and the Shanghai Men's Health Study (SMHS, enrollment from 2002 to 2006). Lifestyle information was collected at study enrollment and a healthy lifestyle score (HLS) was derived. Functional impairment information was collected at the follow-up survey conducted in 2012-2017. Logistic regression analyses were applied to estimate the associations of HLS with functional impairments. The average age at lifestyle and functional impairment assessment was 62.3 (range: 49.9-70.9) and 77.7 (range: 70.0-89.4) for women and 67.5 (range: 55.1-74.9) and 77.4 (range: 70.0-88.6) for men. After a median follow-up of 14.4 years, we found that the HLS was inversely associated with overall severe functional impairment: odds ratio (95% confidence interval), 0.78(0.71-0.86) and individual severe functional impairment: 0.67(0.62-0.73) for independent walking, 0.85(0.77-0.94) for hearing/vision, 0.79(0.70-0.88) for memory, and 0.74(0.67-0.82) for decision-making impairment, comparing the highest with the lowest HLS categories. Such associations were similar among individuals with/without cardiometabolic diseases at baseline. The associations between each lifestyle factor and functional impairments differed. A healthy lifestyle was associated with reduced odds of physical and mental impairment among older Chinese adults, emphasizing the importance of promoting and maintaining a healthy lifestyle to prevent or postpone age-related functional impairments.


Concentration of human thymidine kinase 1 discover invisible malignant human tumours.
Early discover of risk progression of invisible carcinomas is important for a prerequisite successful treatment. Here, we investigated whether concentration of human thymidine kinase 1 (HTK1) discover invisible malignant human tumours. The HTK1 concentration of tumour cellular based on HTK1 IgY-polyclonal-antibody (HTK1-IgY-pAb) was determined by using a novel automatic chemiluminescence analyser with sandwich biotin-streptavidin (SBSA) platform. Minimum number of cells able to be detected by this technology used cells with low and high concentration of HTK1. The limit visibility by tumour imaging is approximately 1 mm in diameter, corresponding to approximately 109 cells with a cell diameter of 1 µm. Based on a HTK1 standard curve and a molecular weight of HTK1 of 96 kD, the HTK1protein (HTK1p) concentration per cell was calculated to be 0.021 pg. Assuming 200 pg in total protein/cell, approximately 50 × 106 growing malignant cells in the body were calculated to releases HTK1 into 5-liter blood. A HTK1 values of 3.914, 0.435 and 0.009 pmol/L corresponds to 10 × 105, 2 × 105 and 1 × 105 growing malignant cells, respectively. The lowest detectable sensitivity of HTK1 is 0.009 pmol/L in 1 × 105 growing malignant cells and 0.01 pmol/L in blood serum, detectable in health screening. Comparing the novel automatic chemiluminescence analyser with the original ECL dot-blot assay using serum HTK1p (health screening, n = 265) showed high correlation (r = 0.8743, P < .000). In conclusion, the novel automatic chemiluminescence analyser with SBSA platform is a reliable method with high accuracy to determine carcinoma invisible.


Airway management in the lateral position: a randomized controlled trial.
It may be required to ensure patency of the airway in the lateral position in certain circumstances. We performed a prospective randomized clinical trial investigating the effects of left lateral patient positioning on airway anatomy and subsequent airway management. Laryngoscopic airway examination was performed in anesthetized patients, in the supine and left lateral positions, and in the presence and absence of cricoid pressure. Patients were randomized to airway management via an endotracheal tube or laryngeal mask airway (LMA). The left lateral position resulted in a deterioration of laryngoscopic view in 35% of patients and improvement in none. In the lateral position, failure of airway management occurred in more patients with the endotracheal tube versus LMA (8 of 39 versus 1 of 30; P = 0.03), and the mean time to successful completion of airway management was longer with tracheal intubation compared with the LMA (39 +/- 19 s versus 26 +/- 12 s; P = 0.002). LMA use results in more reliable airway control compared to tracheal intubation in the lateral position. The LMA should be considered as the primary airway device when instituting airway management in this position. Inadequate airway management may be fatal. There are recommendations for airway difficulties, but the evidence favoring any specific strategy is limited. This study suggests that, in the lateral position, a laryngeal mask airway more rapidly and reliably establishes airway control than attempts at endotracheal intubation. It further suggests that placing a patient with an inadequate airway into the lateral position will hinder, not help, airway management.


Comparison of fronto-frontal and temporo-parietal unilateral non-dominant ECT. A retrograde memory study.
An intraindividual, double blind cross-over comparison of the retrograde effect on memory of unilateral non-dominant fronto-frontal (FF) and temporo-parietal (TP) ECT was performed in connection with the second and third treatments of ECT-series. Treatment technique was standardized and seizure duration was measured by means of EEG. Memory functions were examined 1 hour before and 2 hours after ECT with four tests. The influence on forgetting over this time was taken as a measure of the memory disturbance. There were no differences between FF and TP ECT as regards the amount of methohexital and suxamethonium chloride, mean time of stimulation and seizure duration. The influence of forgetting was similar in all memory tests. The result is in agreement with a previous anterograde study. It is concluded that no essential gain in terms of reduced memory disturbance can be obtained by substituting the routine non-dominant temporo-parietal with fronto-frontal electrode positions.


Retinal Screening Acceptance, Laser Treatment Uptake and Follow-up Response in Diabetics Requiring Laser Therapy in an Urban Diabetes Care Centre.
To determine the acceptance of retinal screening, Laser uptake and subsequent follow-up in diabetic patients attending the Diabetes Centre of Diabetic Association of Pakistan (DAP), Karachi. Observational case series. Diabetic Centre of Diabetic Association of Pakistan (DAP), Karachi, from January 2011 to December 2012. All the diabetic patients were screened for Diabetic Retinopathy (DR) with non-Mydriatic Fundus Camera (NMFC). Patients with DR were examined by the ophthalmologist using fundus lens and slit lamp. DR was graded for severity on the basis of modified Airlie House Classification. Patients with Sight Threatening Diabetic Retinopathy (STDR) were advised Laser treatment. Each patient was followed-up for at least 6 months. The records of patients recommended Laser were retrieved, and called for re-examination. Retinal screening was accepted by all of the 8368 registered diabetics attending DAP Centre. On fundus photography, 21.2% (1777) individuals were found to have DR. Seven hundred and five (39.5%) patients were found to have STDR. Laser was advised to 96.4% (680) of STDR patients; amongst whom 70.5% (480) accepted Laser treatment. Out of 480 patients who had Laser treatment, 21.2% (107) turned out for follow-up after 6 months. Acceptance of retinal screening and Laser application was good; but follow-up was suboptional.


Awareness, attitudes and perceptions on epilepsy in Southern Brazil.
To verify awareness and attitudes toward epilepsy in Southern Brazil. A questionnaire about familiarity with the disease, awareness and attitudes toward epileptics was applied to 832 inhabitants of Caxias do Sul. The answers were analyzed in three different groups: G1, non-university students; G2, university students up to the second year; and G3, university students with more than two years education and university graduates. University students and graduates are better informed regarding causes and treatment of epilepsy. Moreover, those interviewees present less negative attitudes toward epileptics. However, a large part of that group lacks some basic information on the disease. There is lack of information on epilepsy among Brazilians. Education campaigns should be carried out in order to clarify some aspects concerning epilepsy.


[The application of fluorescence in situ hybridization performed on the decolorized G-banding chromosomes in detecting the marker chromosomes of gastric cancer].
Using a rapid, accurate method that detects the marker chromosomes of gastric cancer and enhancing the ability of discriminating complicated chromosome rearrangements of gastric cancer. The improved method of fluorescence in situ hybridization(FISH) performed on the decolorized G-banding chromosome was used. The changes of two marker chromosomes (M1, M2) of the cell line(SGC-7901) of gastric cancer and one marker chromosomes(M3) of one primary gastric cancer were respectively analyzed by this method. The M1, M2 and M3 had complicated structural chromosome aberrations: del(7)(p15)/del(7)(q22), t(1;3)(p11;q11) and del(7)(q32). This method showed strong signals, low backgrounds and well-repetitions. It may play an important part in exploring the chromosome rearrangements in the process of pathogenesis and development of gastric cancer.


Hairy Leaf 6, an AP2/ERF Transcription Factor, Interacts with OsWOX3B and Regulates Trichome Formation in Rice.
Trichome formation has been extensively studied as a mechanistic model for epidermal cell differentiation and cell morphogenesis in plants. However, the genetic and molecular mechanisms underlying trichome formation (i.e., initiation and elongation) in rice remain largely unclear. Here, we report an AP2/ERF transcription factor, Hairy Leaf 6 (HL6), which controls trichome formation in rice. Functional analyses revealed that HL6 transcriptionally regulates trichome elongation in rice, which is dependent on functional OsWOX3B, a homeodomain-containing protein that acts as a key regulator in trichome initiation. Biochemical and molecular genetic analyses demonstrated that HL6 physically interacts with OsWOX3B, and both of them regulate the expression of some auxin-related genes during trichome formation, in which OsWOX3B likely enhances the binding ability of HL6 with one of its direct target gene, OsYUCCA5. Population genetic analysis indicated that HL6 was under negative selection during rice domestication. Taken together, our findings provide new insights into the molecular regulatory network of trichome formation in rice.


Coupling physical selection with biological selection for the startup of a pilot-scale, continuous flow, aerobic granular sludge reactor without treatment interruption.
This study removes two technical constraints for transitioning full-scale activated sludge infrastructure to continuous flow, aerobic granular sludge (AGS) facilities. The first of these is the loss of treatment capacity as a result of the rapid washout of flocculent sludge inventory and in turn the potential loss of nitrification during initial AGS reactor startup. The second is the physical selector design which currently is limited to either the complex sequencing batch reactor selection or sidestream hydrocyclones. Briefly, real wastewater data collected from this study suggested that by increasing the surface overflow rate (SOR) of an upflow clarifier to 10 m h - 1, the clarifier can be taken advantage of as a physical selector to separate flocculant sludge from AGS. Redirecting the physical selector underflow and overflow sludge to the feast and famine zones of a treatment train, respectively, can create a biological selection that not only promotes AGS formation but also safeguards the effluent quality throughout the AGS reactor startup period. This study provides a novel concept for economically implementing continuous flow AGS within existing full-scale, continuous flow treatment trains.


The vestibulo-ocular reflex: an outdated concept?
Traditionally, the vestibulo-ocular reflex (VOR) is described as a distinct, phylogenetically old oculomotor subsystem, which serves to stabilize gaze direction. It is supposed to act as a stereotyped reflex with definite input-output relations, which can be measured by rotating a subject passively in darkness, and which are kept at an ideal level by adaptive, parametric adjustments. This paper argues that such a view is not realistic: (1) the VOR in darkness does not have an ideal, or even well defined, gain; (2) a fixed, automatic VOR is not appropriate in most behavioural situations, and would need continuous conditioning by other subsystems. As there is no compelling phylogenetic, physiological or anatomical evidence for an independent VOR subsystem, a more fruitful hypothesis may be that vestibular signals are just one of many inputs to a spatial localization process, which computes the relative position (and motion) between the subject and a target of his choice. The VOR in darkness may represent no more than a default operation, based on incomplete information, of this larger, multiple input gaze control system. Likewise, adaptation phenomena of the VOR in darkness may be merely an epiphenomenon of adaptation of gaze control with vision active.


Spectrophotometric determination of oxidized and reduced pyridine nucleotides in erythrocytes using a single extraction procedure.
Several methods are available for the extraction and quantitation of oxidized and reduced pyridine nucleotides in erythrocytes. Enzymatic methods, however, are complicated by the presence of hemoglobin, which causes oxidation of NADH and NADPH during extraction. Although hemoglobin-mediated oxidation can be prevented by the addition of reducing agents, these interfere with spectrophotometric cycling assays for these nucleotides. Therefore, we have developed a method for determining oxidized and reduced NAD and NADP in human erythrocytes using a single extract. Our extraction method eliminates the need for reducing agents and thus allows the use of a spectrophotometric cycling assay. Using this method, we obtained full recovery of all added nucleotides with both normal and reticulocyte-enriched red blood cells. Our method is suitable for the determination of NAD+, NADH, NADP+, and NADPH in normal human erythrocytes and in red cells from patients with hemolytic anemia with a higher proportion of reticulocytes.


Comparison between dexmedetomidine and remifentanil for controlled hypotension and recovery in endoscopic sinus surgery.
We compared the efficacy of dexmedetomidine and remifentanil hydrochloride in intraoperative field conditions and recovery during endoscopic sinus surgery. Sixty-six patients (American Society of Anesthesiologists physical status I and II) scheduled for elective endoscopic sinus surgery were enrolled in this prospective, double-blinded, randomized study. The patients were randomly assigned to two groups. Propofol, 2 to 2.5 mg/kg, was administered to both groups to induce anesthesia, which was maintained with desflurane. One group received dexmedetomidine 1 microg/kg over 10 minutes at anesthesia induction, followed by 0.4 to 0.8 microg/kg per hour infusion during maintenance, whereas the other group received remifentanil 1 microg/kg over 1 minute at anesthesia induction, followed by 0.2 to 0.4 microg/kg per minute infusion during maintenance. Surgical conditions, hemodynamic parameters, intraoperative blood loss, time to extubation, sedation, and pain in the postanesthesia care unit (PACU) were recorded. There were no significant differences between the two groups with respect to surgical field conditions, blood loss, or extubation time. The sedation score (Modified Observer's Assessment of Alertness/Sedation) in the PACU was significantly lower in the dexmedetomidine group than in the remifentanil group (p < 0.001). No differences were found in total blood loss, surgical field conditions, hemodynamic parameters, time to extubation, or pain in the PACU when the two groups were compared (p > 0.05). Although remifentanil and dexmedetomidine both enabled hypotensive anesthesia and good intraoperative fields for endoscopic sinus surgery, recovery was faster with remifentanil than with dexmedetomidine in the immediate postoperative period.


Trends in Non-Melanoma Skin Cancer (Basal Cell Carcinoma and Squamous Cell Carcinoma) in Canada: A Descriptive Analysis of Available Data.
Despite its increased incidence and status as the most prevalent cancer in Canada, there is a paucity of epidemiological data on non-melanoma skin cancer (NMSC). To assess trends of keratinocyte carcinomas (KC) in Canada over 5 decades. Articles published from 1960 to 2015 on NMSC in Canada were identified through MEDLINE. Six articles met our search criteria. Overall, KC has increased. However, the rate of increase in the past decade has slowed down and decreased in younger age cohorts. Men had higher incidences of KC. In both sexes, the basal cell carcinoma and squamous cell carcinoma ratio was ≥2.5:1. Keratinocyte carcinomas were most commonly located on the head and neck, and increasing rates are occurring on the trunk. The methods of registering skin cancer cases vary among different provinces. Keratinocyte carcinomas incidence is overall increasing; however, there may be evidence that the incidence is leveling off and decreasing in younger age cohorts.


Rapidity distribution at soft-virtual and beyond for n-colorless particles to N 4 LO in QCD.
We present a systematic framework to study the threshold contributions of the differential rapidity distribution for the production of any number of colorless particles in the hadronic colliders. This has been achieved based on the universality structure of the soft enhancements associated with the real emissions, along with the factorization property of the differential cross section and the renormalization group invariance. In this formalism, we present a universal soft-collinear operator to compute the soft virtual differential cross section for a generic 2 → n scattering process up to next-to-next-to-next-to-next-to-leading order ( N 4 LO) in perturbative QCD. We also provide a universal operator to perform the threshold resummation to next-to-next-to-next-to-leading logarithmic ( N 3 LL) accuracy. We explicitly present the approximate analytical results of the rapidity distributions at N 4 LO and N 3 LL for the Higgs boson production through gluon fusion and bottom quark annihilation, and also for the Drell-Yan production at the hadronic collider. We extend our framework to include the next to threshold contributions for the diagonal partonic channels.


MicroRNA‑186‑5p is expressed highly in ethanol‑induced cardiomyocytes and regulates apoptosis via the target gene XIAP.
Ethanol has a toxic effect on the heart, resulting in cardiomyocyte damage. Long‑term high intake of ethanol leads to a non‑ischemic dilated cardiomyopathy termed alcoholic cardiomyopathy (ACM). However, the pathogenesis of alcoholic cardiomyopathy remains unclear. The apoptosis of cardiomyocytes serves an important role in the pathogenesis of ACM. X‑linked inhibitor of apoptosis protein (XIAP) is an important anti‑apoptotic protein in human tissue cells. To the best of our knowledge, no studies have reported on its function in ethanol‑induced cardiomyopathy. Previous works have screened the ACM‑associated differentially expressed microRNAs (miRs), including miR‑186‑5p and miR‑488‑3p. TargetScan bioinformatics software was used to predict 949 target genes associated with miR‑186‑5p, and XIAP was demonstrated to be a target of miR‑186‑5p. The present study firstly analyzed the levels of apoptosis in ethanol‑treated cardiomyocytes using flow cytometry. Alterations in the expression levels of miR‑186‑5p and XIAP were subsequently evaluated in ethanol‑treated AC16 cardiomyocytes to assess the specific molecular mechanisms of ethanol‑induced cardiomyocyte apoptosis. The levels of apoptosis in AC16 cardiomyocytes increased following ethanol treatment, and further increased with the rise in concentration and action time of ethanol. The expression levels of miR‑186‑5p were upregulated, and the expression levels of XIAP were downregulated in ethanol‑treated cardiomyocytes. miR‑186‑5p may regulate ethanol‑induced apoptosis in cardiomyocytes using XIAP as the direct target gene. This study provides a novel therapeutic target for the prevention and treatment of ACM.


Ellagic acid enhances the antinociceptive action of venlafaxine in mouse acetic acid-induced pain: An isobolographic analysis.
Several antidepressants have been used to treat severe pain in clinics. Recently, it has been shown that ellagic acid (EA), a major constituent of pomegranate juice, produced antinociceptive and anti-inflammatory effect through the central and peripheral sites of action. In this study, we examined the interaction between EA and venlafaxine (VLF) on pain induced by intraperitoneal acetic acid in mice using isobolographic analysis. EA (0.3-10mg/kg, ip) and VLF (3-60 mg/kg, ip) produced a dose-dependent inhibition of the writhing response evoked by acetic acid. Fifty percent effective dose (ED50) values against writhing behaviors were 1.02 (0.86-1.19)mg/kg and 12.37 (9.74-15.37)mg/kg for EA and VLF, respectively, and also with higher potency than that of VLF. Co-administration of increasing fractional increments of ED50 doses of EA and VLF produced synergistic interaction against writhing behaviors, as revealed by isobolographic analysis. The synergistic action of EA and VLF provides valuable tool referring to the management of visceral pain.


Ezrin...a metastatic detERMinant?
The insidious process of tumor metastasis is the most devastating and least well-understood aspect of cancer. Metastasis is very complex and employs many cellular processes, suggesting that individual metastatic determinants may not be easily identified. Mounting evidence, culminating in the work described in two recent articles, strongly suggests that the membrane:cytoskeleton organizer Ezrin can promote tumor metastasis. Ultimately, a better understanding of exactly how Ezrin confers metastatic advantage will provide important insight into this key problem in cancer biology.


Levorphanol but not dextrorphan suppresses the foot-lifting response to an aversive thermal stimulus in the terrestrial snail, Cepaea nemoralis.
The terrestrial snail, Cepaea nemoralis, when placed on a surface heated at 40 degrees C lifts the anterior portion of its foot from the source of heat. This stereotyped response, which suggests aversion, can be inhibited by injections of small doses of morphine and levorphanol, but is not affected by similar or larger doses of dextrorphan. It is suggested that the "analgesic" effect of the opiates in these animals involves interaction with stereochemically specific opiate receptors that may be fundamentally similar to those occurring in mammals.


Effects of reflexology on premenstrual syndrome: a systematic review and meta-analysis.
Premenstrual syndrome (PMS) refers to a set of somatic and psychological symptoms that occur cyclically in the luteal phase of a menstrual cycle. There is no report of final result of reflexology on PMS. Therefore, the present study aimed to determine the effect of reflexology on PMS through a systematic review and meta-analysis study. The present study was a systematic review and meta-analysis that was conducted by searching in 8 electronic databases including PubMed, EMBASE, Cochrane Library, Web of Science, ProQuest, Scopus, Google Scholar, and SID until December 28, 2018. In this regard, interventional studies, which examined the impact of reflexology on women with premenstrual syndrome, were included. These studies were published during 1993 to 2018. The Cochrane Collaboration's Risk of Bias Tool was used to assess the quality of studies. Meta-analysis was performed by the help of CMA 2 software. Nine out of 407 studies finally remained after screening, and quantitative and quantitative analyses were performed on them. The total number of research samples was 475. The mean treatment time with reflexology was 40.55 min per session that was performed in 6 to 10 sessions of treatment in 66.67% of studies. According to the meta-analysis and based on the random effects model, the reflexology could decrease the severity of PMS in the intervention group compared to the control group (SMD = - 2.717, 95% CI: - 3.722 to - 1.712). Meta-regression results indicated that the duration of intervention sessions (β = - 0.1124, 95% CI - 0.142 to - 0.084, p < 0.001) had a significant impact on the severity of PMS. Reflexology could also significantly affect somatic (SMD = - 1.142, 95% CI: - 1.481 to - 0.803) and psychological (SMD = - 1.380, 95% CI: - 2.082 to - 0.677) symptoms arising from PMS. In general, results of the present study indicated that the reflexology could relieve PMS symptoms, so that overall scores, somatic and psychological symptoms of PMS decreased by applying the reflexology intervention. Furthermore, an increase in the length of reflexology time in each session increased its efficiency. Reflexology can be used as an effective intervention in a patient care program by nurses and its efficiency can be enhanced by increasing intervention time in each reflexology treatment session.


Epidural analgesia during birth and adverse neonatal outcomes: A population-based cohort study.
In general, epidural analgesia is considered a safe and efficient way to relieve pain during active labour and is increasingly used in childbirth. It is well documented that epidural analgesia during birth has benefits but also adverse effects. However, evidence is limited on how epidural analgesia influences neonatal outcome in a low-risk population of birthing women. To examine low Apgar score, foetal hypoxia and admission to the neonatal intensive care unit in neonates of low-risk women receiving epidural analgesia during birth. A cohort study using registry data to investigate a population of 23,272 low-risk women giving birth at a university hospital. Epidural analgesia was used in 21.6% of low-risk women during birth. Low Apgar score, foetal hypoxia, and admission to the neonatal intensive care unit were found in 0.6%, 0.6%, and 10.0%, respectively in neonates of mothers receiving epidural analgesia during birth compared to 0.3%, 0.6%, and 5.6%, respectively in the non-exposed group. Epidural analgesia was associated with low Apgar score, adjusted odds ratio 1.76 (95% CI 1.07-2.90) and admission to the neonatal intensive care unit, adjusted odds ratio 1.43 (95% CI 1.26-1.62). A mediation analysis indicates the impact of epidural analgesia on adverse neonatal outcomes was mediated by obstetric complications like maternal fever, labour augmentation, and foetal malpresentation. This study found use of epidural analgesia during birth in low-risk pregnant women was associated with infant low Apgar score and admission to the neonatal intensive care unit.


Ginkgo biloba extract (EGb-761) confers neuroprotection against ischemic stroke by augmenting autophagic/lysosomal signaling pathway.
Ginkgo biloba extract (EGb-761) is well-recognized to have neuroprotective properties. Meanwhile, autophagy machinery is extensively involved in the pathophysiological processes of ischemic stroke. The EGb-761 is widely used in the clinical treatment of stroke patients. However, its neuroprotective mechanisms against ischemic stroke are still not fully understood. The present study was conducted to uncover whether the pharmacological effects of EGb-761 can be executed by modulation of the autophagic/lysosomal signaling axis. A Sprague-Dawley rat model of ischemic stroke was established by middle cerebral artery occlusion (MCAO) for 90 min, followed by reperfusion. The EGb-761 was then administered to the MCAO rats once daily for a total of 7 days. Thereafter, the penumbral tissues were acquired to detect proteins involved in the autophagic/lysosomal pathway including Beclin1, LC-3, SQSTM1/p62, ubiquitin, cathepsin B, and cathepsin D by western blot and immunofluorescence, respectively. Subsequently, the therapeutic outcomes were evaluated by measuring the infarct volume, neurological deficits, and neuron survival. The results showed that the autophagic activities of Beclin1 and LC3-II in neurons were markedly promoted by 7 days of EGb-761 therapy. Meanwhile, the autophagic cargoes of insoluble p62 and ubiquitinated proteins were effectively degraded by EGb-761-augmented lysosomal activity of cathepsin B and cathepsin D. Moreover, the infarction size, neurological deficiencies, and neuron death were also substantially attenuated by EGb-761 therapy. Taken together, our study suggests that EGb-761 exerts a neuroprotective effect against ischemic stroke by promoting autophagic/lysosomal signaling in neurons at the penumbra. Thus, it might be a new therapeutic target for treating ischemic stroke.


Tobacco Smoking, Eating Behaviors, and Body Weight: A Review.
This narrative review provides an overview of the relationships among tobacco smoking, eating behaviors, and body weight. The aims are to (1) examine the concurrent and longitudinal associations between tobacco smoking and body weight, (2) describe potential mechanisms underlying the relationships between smoking and body weight, with a focus on mechanisms related to eating behaviors and appetite, and (3) discuss management of concomitant tobacco smoking and obesity. Adolescents who smoke tobacco tend to have body mass indexes (BMI) the same as or higher than nonsmokers. However, adult tobacco smokers tend to have lower BMIs and unhealthier diets relative to nonsmokers. Smoking cessation is associated with a mean body weight gain of 4.67 kg after 12 months of abstinence, though there is substantial variability. An emerging literature suggests that metabolic factors known to regulate food intake (e.g., ghrelin, leptin) may also play an important role in smoking-related behaviors. While the neural mechanisms underlying tobacco smoking-induced weight gain remain unclear, brain imaging studies indicate that smoking and eating cues overlap in several brain regions associated with learning, memory, motivation and reward. Behavioral and pharmacological treatments have shown short-term effects in limiting post-cessation weight gain; however, their longer-term efficacy is limited. Further studies are needed to identify the exact mechanisms underlying smoking, eating behaviors, and body weight. Moreover, effective treatment options are needed to prevent long-term weight gain during smoking abstinence.


An indirect haemagglutination reaction for the demonstration of Schistosoma mansoni circulating anodic antigen.
Using the IgG fraction of a monospecific sheep antiserum against the circulating anodic antigen (CAA) of Schistosoma mansoni, an indirect haemagglutination reaction for the determination of this antigen was developed. This is the first time that an IHA has been applied to the detection of circulating antigens in parasite infections. The IHA proved to be highly sensitive; CAA levels up to 20 ng/ml could be measured. At the moment it appears to be the most sensitive technique for the determination of CAA levels. CAA could readily be detected in the sera of S. mansoni infected hamsters and in the immune complexes isolated from these sera, but never in sera from human schistosome infections.


Ethyl Acetate and Aqueous Fractions of Ziziphus jujuba Prevent Acute Hypertension Induced by Angiotensin II in Rats.
The effect of hydroalcoholic extract of Ziziphus jujuba (ZJ) on hypertension has been reported previously. This experiment investigates the effect of two ethyl acetate (EA, a polar and semi-polar compound) and aqueous fractions (AQ, a polar compound) of ZJ extract on cardiovascular parameters in acute hypertension induced by angiotensin II (AngII). Rats were randomly divided into following groups (n=7 in each group): 1) Control; 2) AngII (50 ng/kg); 3) Losartan (LOS, 30 mg/kg) + AngII; 4, 5) ethyl acetate fraction (EA150 and EA300 mg/kg) + AngII and 6, 7) aqueous fraction (AQ150 and AQ300 mg/kg) + AngII. Rats were treated with both fractions and LOS orally for four weeks and in the experiment day (28th) AngII intravenously injected and cardiovascular parameters (Systolic Blood Pressure (SBP), Mean Arterial Pressure (MAP) and Heart Rate (HR)) directly were recorded by a power lab system. AngII could significantly increase SBP and MAP (P<0.001) and decrease HR with respect to the control and these responses were attenuated by LOS. The SBP and MAP in both doses of EA+ AngII and the higher dose of AQ fractions + AngII were significantly lower than the AngII group (P<0.05 to P<0.001). Bradycardia induced by AngII was also reduced by LOS and both fractions. The comparison of two fractions also showed that the effect of EA fraction is greater than the AQ. This study indicates that both fractions of the ZJ extract have a beneficial effect on hypertension. Because effect of EA was greater than AQ, we suggested that antihypertensive effects of ZJ mediated polar and nonpolar compounds.


Home based rehabilitation after a knee replacement is as effective as physiotherapy.
The studyBarker KL, Room J, Knight R, et al. Outpatient physiotherapy versus home-based rehabilitation for patients at risk of poor outcomes after knee arthroplasty: CORKA RCT. Health Technol Assess 2020;24:1-116.To read the full NIHR Alert, go to: https://evidence.nihr.ac.uk/alert/knee-replacements-home-based-rehabilitation-as-effective-physiotherapy/.


Exploring Synthesis and Chemotherapeutic Potential of Thiosemicarbazide Analogs.
Cancer is a leading cause of death worldwide, accounting for nearly 10 million deaths in 2020. Researchers are continually finding new and more effective medications to battle the diseases. The objective of this study is to identify the emerging role of Thiosemicarbazide analogs for different types of cancer targets with a glance at different novel synthetic routes reported for their synthesis. A systematic literature review was conducted from various sources over the last 15 years with the inclusion of published research and review articles that involves the synthesis and use of thiosemicarbazide analogs for different targets of cancer. Data from the literature review for synthesis and anticancer potential for specific targets for cancer studies of thiosemicarbazide analogs are summarized in the paper. There are several emerging studies for new synthetic routes of thiosemicarbazide derivatives with their role in various types of cancers. The main limitation is the lack of clinical trial of the key findings for the emergence of new anticancer medication with thiosemicarbazide moiety. Emerging therapies exist for use of a limited number of medications for the treatment of cancer; results of the ongoing studies will provide more robust evidence in the future.


U-Shaped Association between Waist-to-Hip Ratio and All-Cause Mortality in Stage 3-5 Chronic Kidney Disease Patients with Body Mass Index Paradox.
The obesity paradox, referring to the association of high body mass index (BMI) with low all-cause mortality risk, is found in patients with chronic kidney disease (CKD). Central obesity is associated with metabolic syndrome and may have better prognostic value than BMI for all-cause mortality. Whether central obesity is associated with all-cause mortality in cases of obesity paradox in CKD patients remains unknown. We included 3262 patients with stage 3-5 CKD, grouped into five quintiles (Q1-5) by waist-to-hip ratio (WHR). Low WHR and BMI were associated with malnutrition and inflammation. In Cox regression, high BMI was not associated with all-cause mortality, but BMI < 22.5 kg/m2 increased the mortality risk. A U-shaped association between central obesity and all-cause mortality was found: WHR Q1, Q4, and Q5 had higher risk for all-cause mortality. The hazard ratio (95% confidence interval) of WHR Q5 and Q1 for all-cause mortality was 1.39 (1.03-1.87) and 1.53 (1.13-2.05) in male and 1.42 (1.02-1.99) and 1.28 (0.88-1.85) in female, respectively. Waist-to-height ratio and conicity index showed similar results. Low WHR or low BMI and high WHR, but not high BMI, are associated with all-cause mortality in advanced CKD.


3-Hy-droxy-1-[(morpholin-4-yl)meth-yl]pyridazin-6(1H)-one.
In the title compound, C9H13N3O3, the morpholine ring adopts a chair conformation and its mean plane makes a dihedral angle of 68.00 (11)° with the pyridazine ring. The carbonyl O atom deviates from the plane of the pyridazine ring by 0.0482 (12) Å. An intra-molecular C-H⋯O hydrogen bond occurs. In the crystal, mol-ecules are linked by O-H⋯O and C-H⋯O hydrogen bonds, forming chains along [1-10].


Telomere length analysis in Down syndrome birth.
Human reproductive fitness depends upon telomere chemistry. Maternal age, meiotic nondisjunction error and telomere length of mother of trisomic child are someway associated. Reports exhibiting maternal inheritance of telomere length in Down syndrome child are very scanty. To investigate this, we collected peripheral blood from 170 mothers of Down syndrome child and 186 age matched mothers of euploid child with their newly born babies. Telomere length was measured by restriction digestion - southern blotting technique. Meiotic nondisjunction error was detected by STR genotyping. Subjects are classified by age (old >35 years and young ˂35 years) and by meiotic error (MI and MII). Linear regression was run to explore the age - telomere length relationship in each maternal groups. The study reveals that with age, telomere erodes in length. Old MII mothers carry the shortest (p˂0.001), control mothers have the longest telomere and MI lies in between. Babies from older mother have longer telomere (p˂0.001) moreover; telomeres are longer in Down syndrome babies than control babies (p˂0.001). To conclude, this study represents not only the relation between maternal aging and telomere length but also explore the maternal heritability of telomere length in families with Down syndrome child.


Is there involvement of the central nervous system in hereditary sensory radicular neuropathy?
There is pathological evidence that hereditary sensory radicular neuropathy (HSN type I) is a disorder related to multi-system atrophy with marked cell loss in the cerebral cortex, thalamus, brain stem and cerebellum. We report here a clinical study of a case of HSN-I including audiometric testing, autonomic functions, electromyography, transcranial magnetic stimulation and magnetic resonance imaging of the brain. There were no signs of central nervous system involvement. It is stated that HSN-I remains a disorder of dorsal root ganglia and sensory nerves, leading to painless perforating ulceration and mutilation, within the course of the disease peripheral motor nerve involvement, but without involvement of central motor pathways.


Proposals for massive expansion of psychological therapies would be counterproductive across society.
In 2007 the UK Government announced a substantial expansion of funding for psychological therapies in England to provide better support for people with conditions such as anxiety and depression. Will these services result in the medicalisation of normal distress? Or are they simply an evidenced-based solution for a previously unmet need? In this debate Derek Summerfield and David Veale discuss the issues raised by these controversial proposals.


Toxic effects of sub-chronic exposure of male albino rats to emamectin benzoate and possible ameliorative role of Foeniculum vulgare essential oil.
Emamectin benzoate (EB) is an avermectin insecticide used extensively in pest control on vegetable and field crops. Few studies have been done for evaluating adverse effects of EB. In the current study, we evaluated the toxic effects of EB on male rats and the possible ameliorative role of fennel essential oil (FEO). Thirty two male rats were randomly divided into 4 equal groups. All groups were treated orally with distilled water (control group), 0.5mlFEOkg(-1) BW (FEO group), 2.5mgEBkg(-1) BW (EB group), and 0.5mlFEOkg(-1) BW+2.5mgEBkg(-1) BW (FEO+EB group) for 28 days. The obtained results showed that EB treatment resulted in a significant decrease in body weight, body weight gain, RBC count, Hb concentration, % PCV, MCV and MCHC. Moreover, EB significantly decreased total leukocyte, lymphocyte, monocyte and platelet count but significantly increased granulocyte count. EB markedly decreased total protein, albumin, globulin, IgG and IgM concentrations with a significant increase in TNF-α secretion. EB had a negative impact on the liver as it significantly increased ALT, ALP, and MDA, while decreasing SOD activity. Regarding to the histopathological examination, EB treatment induced coagulative necrosis and blood vessels congestion of the liver in treated rats. Furthermore, it resulted in depletion and necrosis of the white pulp of the spleen in treated rats. The co-administration of FEO with EB, however, improved the majority of parameters studied, suggesting that FEO is an important substance in decreasing toxic effects of EB.


Evaluating the preceptor-preceptee relationship among Pharm D students at the King Saud University School of Pharmacy.
To evaluate preceptee satisfaction concerning preceptorship and the preceptor-preceptee relationship among pharmacy students. A cross-sectional study was conducted from May 2017 to August 2017 on senior Pharm D students at King Saud University (KSU) College of Pharmacy. A survey instrument was used to get feedback from students regarding their clinical rotations and internships and to evaluate their satisfaction toward preceptorship to meet the goals of the curriculum. Data were entered into SPSS, version 24. Of the 52 students surveyed, 36 (69.2%) were female. More than half of respondents were somewhat satisfied with their preceptors and 11.5% were satisfied. Additionally, only 17% of students rated their preceptors as having excellent clinical teaching skills; about 19% of students rated them as "needs improvement." About 40% of students rated their preceptors as very good, concerned, competent, and safe in their care for persons living with serious co-morbidities and diseases. About half of students (48.1%) rated their non-faculty KSU preceptors' teaching behavior as not satisfactory compared with only four respondents with respect to KSU faculty preceptors' teaching behavior. Pharm D students were somewhat satisfied with their preceptors' teaching behaviors in communication skills, practice, and teaching skills as well as feedback and evaluation to students. To enhance the quality of experiential education, preceptors should be trained to develop programs that direct and energize advancement.


Quality of life of patients with Hirschsprung disease after Duhamel and Soave pull-through procedures: A mixed-methods sequential explanatory cohort study.
Quality of life (QoL) is one of the important outcomes for patients with Hirschsprung disease (HSCR) after pull-through that provides qualitative data concerning the long-term outcomes, however, it has not been well-studied. The HSCR/anorectal malformation quality of life questionnaire (HAQL) is considered valid and reliable to evaluate the QoL of HSCR patients. A mixed-method sequential explanatory cohort study was conducted to compare the QoL of HSCR patients after Duhamel and Soave pull-through at Dr. Sardjito Hospital between 2013 and 2018 using an Indonesian adaptation of the HAQL, followed by a qualitative study. We ascertained eleven HSCR patients (Duhamel: five HAQL parents and one HAQL adolescent vs. Soave: four HAQL parents and one HAQL adult). For the quantitative study, the mean HAQL score was 2.50 and 2.79 for the Duhamel and Soave groups, respectively. For the qualitative study, interviewed patients' parents expressed how their child's life had improved after surgery. However, frequent bloating was a major complaint following Soave surgery, whereas hardened stools were a major problem after Duhamel procedure. Here, for the first time using a mixed-method sequential explanatory cohort design, we show that patients with HSCR after Soave tended to have a higher overall QoL score compared to the Duhamel group. Further multicenter study with a larger sample size is mandatory to give better understanding about QoL of HSCR patients following pull-through.


Assessment of intracellular mucin content in vivo.
Airway mucus presents a first line of defense against inhaled materials. It also, however, is a significant pathological contributor to chronic lung diseases, such as asthma, cystic fibrosis, and chronic obstructive pulmonary disease. Thus, gaining a better understanding of the mechanisms of mucus production and secretion is an important goal for improving respiratory health. Mucins, the chief glycoprotein components of airway mucus, are very large polymeric glycoproteins, and measuring their production and secretion in experimental animals presents significant technical challenges. Over the past several years, we have developed assays for accurately quantifying mucin production and secretion using histological and biochemical assays. These methods are described here.


Nonsteroidal anti-inflammatory drug-exacerbated respiratory disease: diagnosis and current management.
Nonsteroidal anti‑inflammatory drug-exacerbated respiratory disease (N‑ERD) is a unique and often clinically severe disease affecting a subgroup of adults with asthma, chronic rhinosinusitis with nasal polyposis, and respiratory reactions with exposure to all cyclooxygenase 1-inhibiting nonsteroidal anti‑inflammatory drugs. N‑ERD has a high disease burden and is estimated to affect 7% of adults with asthma and 30% of patients who have both asthma and nasal polyps. The disease is underdiagnosed and underrecognized by physicians on a routine basis, which leads to a delay in appropriate management. The goal of this review is to focus on the disease recognition, diagnosis, and different modes of up‑to‑date therapies, including medical management, surgical intervention, aspirin desensitization, and biologic therapy.


Sex-dependent impact of microbiota status on cerebral μ-opioid receptor density in fischer rats.
μ-opioid receptors (MOPr) play a critical role in social play, reward and pain, in a sex- and age-dependent manner. There is evidence to suggest that sex and age differences in brain MOPr density may be responsible for this variability; however, little is known about the factors driving these differences in cerebral MOPr density. Emerging evidence highlights gut microbiota's critical influence and its bidirectional interaction with the brain on neurodevelopment. Therefore, we aimed to determine the impact of gut microbiota on MOPr density in male and female brains at different developmental stages. Quantitative [3 H]DAMGO autoradiographic binding was carried out in the forebrain of male and female conventional (CON) and germ-free (GF) rats at postnatal days (PND) 8, 22 and 116-150. Significant 'microbiota status X sex', 'age X brain region' interactions and microbiota status- and age-dependent effects on MOPr binding were uncovered. Microbiota status influenced MOPr levels in males but not females, with higher MOPr levels observed in GF versus CON rats overall regions and age groups. In contrast, no overall sex differences were observed in GF or CON rats. Interestingly, within-age planned comparison analysis conducted in frontal cortical and brain regions associated with reward revealed that this microbiota effect was restricted only to PND22 rats. Thus, this pilot study uncovers the critical sex-dependent role of gut microbiota in regulating cerebral MOPr density, which is restricted to the sensitive developmental period of weaning. This may have implications in understanding the importance of microbiota during early development on opioid signalling and associated behaviours.


Optical Microphone-Based Speech Reconstruction System With Deep Learning for Individuals With Hearing Loss.
Although many speech enhancement (SE) algorithms have been proposed to promote speech perception in hearing-impaired patients, the conventional SE approaches that perform well under quiet and/or stationary noises fail under nonstationary noises and/or when the speaker is at a considerable distance. Therefore, the objective of this study is to overcome the limitations of the conventional speech enhancement approaches. This study proposes a speaker-closed deep learning-based SE method together with an optical microphone to acquire and enhance the speech of a target speaker. The objective evaluation scores achieved by the proposed method outperformed the baseline methods by a margin of 0.21-0.27 and 0.34-0.64 in speech quality (HASQI) and speech comprehension/intelligibility (HASPI), respectively, for seven typical hearing loss types. The results suggest that the proposed method can enhance speech perception by cutting off noise from speech signals and mitigating interference caused by distance. The results of this study show a potential way that can help improve the listening experience in enhancing speech quality and speech comprehension/intelligibility for hearing-impaired people.


Electrophysiological abnormalities of the atrial muscle in patients with paroxysmal atrial fibrillation associated with hyperthyroidism.
Atrial fibrillation (AF) is common in patients with hyperthyroidism. Although the choice of an antiarrhythmic agent should be based on its electrophysiological effects and the electrophysiological properties of the arrhythmia in question, the atrial electrophysiological features of AF associated with hyperthyroidism are unknown. The purposes of this study are to clarify the atrial electrophysiological abnormalities of AF with hyperthyroidism, and to propose effective therapies for AF in patients with hyperthyroidism. This study included 117 patients who underwent electrophysiological study and were evaluated for thyroid function: 29 patients without AF or hyperthyroidism (Group I), 78 patients with lone paroxysmal AF (Group II), and 10 patients with paroxysmal AF and hyperthyroidism (Group III). The following electrophysiological parameters were assessed and measured quantitatively: (1) the incidence of abnormal right atrial electrograms during sinus rhythm, indicating areas of altered anatomy and conduction where AF is likely to develop; (2) the atrial effective refractory period (ERP); and (3) the atrial conduction delay (CD), which is induced by early atrial premature beats close to the atrial ERP and is thought to facilitate the occurrence of AF. The incidence of abnormal right atrial electrograms during sinus rhythm was significantly higher in Group II (67.1%) than in Group I (20.0%, P < 0.001) and Group III (22.2%, P = 0.009). The atrial ERP was significantly shorter in Group III (187 +/- 7 ms) than in Group I (215 +/- 36 ms, P = 0.019) and Group II (208 +/- 28 ms, P = 0.022). The atrial CD was observed in Group III as well as in Group II. Our data indicate that the electrophysiological features of paroxysmal AF associated with hyperthyroidism are essentially different from those of lone paroxysmal AF. In patients with paroxysmal AF and hyperthyroidism, a shortening of the refractory period in association with a facilitation of the atrial CD could be expected to increase the propensity for AF, and a pre-existent arrhythmogenic substrate might not be essential to the genesis of AF. These findings suggest that the agents that prolong the atrial ERP are effective against AF in patients with hyperthyroidism.


Regulation of cell adhesion, a central mechanism in the anticancer action of essential fatty acids (review).
Certain members of essential fatty acids (EFAs) are known to have anticancer functions. It has been established in recent years that some of these anticancer actions are via the effects of these fatty acids on the adhesive properties of cancer cells, including cell-cell and cell-matrix adhesions. These discoveries have implicated EFAs as a group of novel agents, able to regulate adhesive function of cancer cells and thus bearing clinical importance.


Characterizing the function of EPB41L4A in the predisposition to papillary thyroid carcinoma.
Papillary thyroid carcinoma (PTC) is the most common histotype of thyroid carcinoma. The heritability of PTC is high compared to other cancers, but its underlying causes are unknown. A recent genome-wide association study revealed the association of a variant at the 5q22 locus, rs73227498, with PTC predisposition. We report that rs17134155, a variant in high linkage disequilibrium with rs73227498, is located in an enhancer region downstream of coding transcripts of EPB41L4A. Rs17134155 showed significant enhancer activity in luciferase assays, and haplotypes containing the protective allele of this variant conferred a significantly lower risk of PTC. While the index SNP, rs73227498, acted as a significant cis-eQTL for expression of EPB41L4A, rs17134155 was a significant cis-sQTL for the alternative splicing of a non-coding transcript of EPB41L4A, called EPB41L4A-203. We also performed knockdown of EPB41L4A followed by microarray analysis. Some of the top differentially-expressed genes were represented among regulators of the WNT/β-catenin signaling pathway. Our results indicate that an enhancer region at 5q22 regulates the expression and splicing of EPB41L4A transcripts. We also provide evidence that EPB41L4A expression is involved in regulating growth and differentiation pathways, suggesting that decreased expression of EPB41L4A is a mechanism in the predisposition to PTC.