Comprehensive analysis of pan-cancer reveals the potential of SLC16A1 as a prognostic and immunological biomarker.
SLC16A1 plays an important role in the development of multiple cancer types. Pan-cancer analysis may have significant impacts on the exploration of the relationship between SLC16A1 gene expression, prognosis and the molecular mechanisms of tumorigenesis. In this study, through the analysis of TCGA and GEO datasets, we explored the expression level and survival prognosis of SLC16A1 in pan-cancer, and further explored the differences in SLC16A1 gene mutation, methylation, and phosphorylation between tumor and normal tissues. In addition, we focused on the biological function of this gene and the relationship between the prognosis and immune infiltration by immune infiltration analysis and enrichment analysis, in order to evaluate the diagnostic and prognostic significance of SLC16A1 in carcinomas. The study found that SLC16A1 was highly expressed in 14 kinds of tumors, and there were statistically significant differences in the prognosis of 9 tumors. The phosphorylation level of S467 increased in OV, RCC, and UCEC. There was a statistically negative correlation between the CD8+ T-cell infiltration level and the SLC16A1 expression in HNSC, LUSC, SARC, TGCT, and KIRC. The cancer-related fibroblasts were positively correlated with SLC16A1 expression in BLCA, BRCA, KIRC, KIRP, PAAD, PCPG, and THCA. The enrichment analysis indicated that the tumorigenesis mechanism of this gene was mainly related to "glycolysis and glucose metabolism synthesis." SLC16A1 was a promising prognostic and immunological biomarker in pan-cancer.


[Evaluation of the degree of implementation of tobacco control interventions in the Catalan Network of Smoke-Free Hospitals].
To evaluate the degree of implementation of tobacco prevention and control interventions and to determine the prevalence of smoking in the Catalan Network of Smoke-Free Hospitals according to the stage of adhesion to the project. We performed an observational, descriptive, cross sectional study in 16 hospitals actively involved in the Catalan Network of Smoke-Free Hospitals (April 2005). Data were collected using the results of the self-audit, 9-item questionnaire of the European Network for Smoke Free Hospitals. To study tobacco consumption, we interviewed 3,896 employees. Data on sociodemographic characteristics, tobacco consumption, job category, tobacco control indicators, the project's stage of implementation, and adherence to the project were gathered. The prevalence of smoking was 35%. The implementation stage among all the hospitals studied was 53.3%. The items with high implementation scores (above 70%) were commitment, communication, consumption control, environmental control, and follow-up. Higher scores in implemented activities were observed in hospitals that had passed from the registration phase (x- = 26.6; standard deviation [SD] = 16.7) to subsequent phases (x- = 59.7; SD = 14.1), with a statistically significant difference in the overall score (p = 0.05). The prevalence of smoking in the Catalan Network of Smoke-Free Hospitals remains high. However, the prevalence was lower among professionals serving as role models (physicians and nurses) than among the general population. The project's implementation increased according to the time since enrollment in the network, especially in the first year.


Up-regulation and pre-activation of TRAF3 and TRAF5 in inflammatory bowel disease.
TRAF3 and TRAF5 share a common ancestral gene, and interact as essential components of signaling pathways in immunity. TRAF3 and TRAF5 are overexpressed in the colon of rat/mouse models with colitis. However, the expressions of TRAF3 and TRAF5 in patients with inflammatory bowel disease have not been elucidated. The aim of the present study is to explore the potential roles of TRAF3 and TRAF5 in patients with inflammatory bowel disease. Plasma levels of TRAF3 and TRAF5 proteins were detected by Enzyme-linked Immunosorbent Assay (ELISA). Colonic expression of TRAF3 and TRAF5 proteins was detected by western blot analysis. Quantitative Real-time PCR (qRT-PCR) was applied for gene expression. Inflamed intestinal mucosa and non-inflamed intestinal mucosa in patients with inflammatory bowel disease and normal mucosa was analyzed from healthy controls. The plasma levels of TRAF3 and TRAF5 were significantly higher both in patients with Crohn's disease and ulcerative colitis than in healthy controls. Only soluble TRAF5 showed a weak correlation with endoscopic disease activity index (Baron score) in patients with ulcerative colitis (spearman's r=0.358, P=0.022). Gene expressions of TRAF3 and TRAF5 in peripheral blood mononuclear cells were significantly higher both in patients with Crohn's disease and ulcerative colitis than in healthy controls (all P<0.0001). Gene and protein expressions of TRAF3 and TRAF5 were significantly higher in inflamed colonic mucosa of patients with Crohn's disease and ulcerative colitis than in non-inflamed colonic mucosa and normal mucosa of healthy controls (all P<0.0001). Furthermore, gene and protein expressions of TRAF3 and TRAF5 were also significantly higher in non-inflamed colonic mucosa of patients with Crohn's disease and ulcerative colitis than in normal mucosa of healthy controls. TRAF3 and TRAF5 are overexpressed in inflammatory bowel disease. Although the endoscopic appearance can be normal, TRAF3 and TRAF5 pre-activation can be detected in non-inflamed colonic segments.


[Nursing process in heart failure].
The nursing process is a method that guides nursing actions, which are necessary to foster a fast recovery in patients. This process may be developed in a holistic way based on several nursing models, according to the needs of the patient coursing with some kind of cardiac failure. The objective of this investigation was to collect epidemiological and clinical data, as well as on diagnostic and therapeutic actions for cardiac failure. We also describe the physiopathology of the diseases to inform the nursing staff on the relevance of the nursing process within hospitals and how it will result in better care, decreasing time and costs of hospitalization and increasing benefits, which are the goals proposed.


Wall shear stress in portal vein of cirrhotic patients with portal hypertension.
To investigate wall shear stress (WSS) magnitude and distribution in cirrhotic patients with portal hypertension using computational fluid dynamics. Idealized portal vein (PV) system models were reconstructed with different angles of the PV-splenic vein (SV) and superior mesenteric vein (SMV)-SV. Patient-specific models were created according to enhanced computed tomography images. WSS was simulated by using a finite-element analyzer, regarding the blood as a Newtonian fluid and the vessel as a rigid wall. Analysis was carried out to compare the WSS in the portal hypertension group with that in healthy controls. For the idealized models, WSS in the portal hypertension group (0-10 dyn/cm2) was significantly lower than that in the healthy controls (10-20 dyn/cm2), and low WSS area (0-1 dyn/cm2) only occurred in the left wall of the PV in the portal hypertension group. Different angles of PV-SV and SMV-SV had different effects on the magnitude and distribution of WSS, and low WSS area often occurred in smaller PV-SV angle and larger SMV-SV angle. In the patient-specific models, WSS in the cirrhotic patients with portal hypertension (10.13 ± 1.34 dyn/cm2) was also significantly lower than that in the healthy controls (P < 0.05). Low WSS area often occurred in the junction area of SV and SMV into the PV, in the area of the division of PV into left and right PV, and in the outer wall of the curving SV in the control group. In the cirrhotic patients with portal hypertension, the low WSS area extended to wider levels and the magnitude of WSS reached lower levels, thereby being more prone to disturbed flow occurrence. Cirrhotic patients with portal hypertension show dramatic hemodynamic changes with lower WSS and greater potential for disturbed flow, representing a possible causative factor of PV thrombosis.


Outcomes of video-assisted thoracoscopic surgery lobectomy in septuagenarians.
Spread of technology and increased surveillance have led to more patients with lung cancers being identified than ever before. Increasingly, patients from the elderly population are referred for surgery; however, many studies do not focus on this patient group. We reviewed the outcomes of septuagenarians who underwent lobectomy via an open thoracotomy (OT) or video-assisted thoracoscopic surgery (VATS) approach to determine whether the VATS approach would result in superior post-operative outcomes. Between January 2010 and June 2016, a total of 96 patients aged 70 years or older underwent a lobectomy for non-small cell lung carcinoma. Patients who underwent resection for metastatic disease, small cell lung cancer or neuroendocrine tumour were excluded. Demographic details, early and late post-operative outcomes including post-operative arrhythmia, myocardial infarction, respiratory failure, cerebrovascular events, infection, prolonged air leak, delirium, readmission and 30-day mortality were studied. Mean follow-up duration was 23 ± 19.1 months. Seventy-five patients underwent lobectomy via a VATS approach and 21 patients underwent lobectomy via an OT approach. There was no 30-day mortality and no difference in overall survival between the two techniques (P = 0.25). There was no significant difference between the two techniques with regard to post-operative stroke, myocardial infarction, atrial fibrillation, pneumonia, delirium or bronchopleural fistula. VATS patients had a significantly shorter mean hospital length of stay (VATS 4.7 days, OT 9.3 days, P = 0.005). Septuagenarians with non-small cell lung carcinoma can successfully undergo curative lung resection with a low incidence of post-operative complications.


[November 1944. Reanimation and surgery in the First French Army].
The American 6th Army Group with General Devers in command to which the French 1st Army commanded by General de Lattre de Tassigny belonged, had been brought to a standstill in the Vosges during hard fights against strongly entrenched German troops. The French anaesthesists of the Army used the technique first worked out by British and American colleagues. In spite of numerous obstacles, surgery for multiples "poly-injuries" and especially reanimation led to unexpected progress in medical knowledge.


Silicon-bridge effects on photophysical properties of silafluorenes.
The preparation of 4,5-dimethylsilylene- or 4,5-tetramethyldisilylene-bridged 9-silafluorenes was achieved by lithiation of 2,2',6,6'-tetrabromobiphenyls followed by silylation with dichlorodimethylsilane or 1,2-dichloro-1,1,2,2-tetramethyldisilane, respectively. X-ray analysis of the silylene-bridged silafluorene revealed that the molecular framework was perfectly planar and four Si-C(methyl) sigma bonds were completely orthogonal to the plane. Both the silicon atoms and the benzene rings were significantly deformed from the normal tetrahedral and hexagon shapes, respectively. The silicon bridge at the 4,5-positions was found to induce a red shift of the absorption and fluorescence spectra measured in cyclohexane, compared with 9-silafluorenes. It is remarkable that the disilylene-bridged silafluorene emitted blue light (lambda(em)=450 nm) with a large Stokes shift. The emission maxima of the silicon-bridged silafluorenes in thin films were similar to those measured in cyclohexane solution. DFT calculations suggested that introduction of the silicon bridge led to increases in both the HOMO and LUMO levels compared with 9-silafluorene.


Well-Adhering, Easily Producible Photonic Reflective Coatings for Plastic Substrates.
The development of well-adhering, easily producible photonic reflective coatings is still a challenge. Here, an easy-to-produce, industrial viable process is reported that uses a primer layer of the so-called type II photoinitiator to obtain an excellent adhesion between a plastic substrate and one-dimensional (1D) photonic liquid crystalline coatings. Furthermore, a good alignment of the reactive cholesteric liquid crystal mixture is obtained using a bar-coating process, without alignment layers or surfactants. After photopolymerization, cross-hatch tape tests show a good adhesion of the photonic coating having a reflection band of 50% transmission with almost no scattering. Additionally, we demonstrate the ability to create well-adhering ∼100% reflective coatings by coating double layers and the ability to create single-layered cholesteric broadband reflectors using solely a reactivity gradient created by the primer layer. Our new interfacial method gives new opportunities to use reflecting 1D photonic coatings in industrial processes and applications and allows the bonding of almost any polymer to a plastic substrate.


Machine learning powered tools for automated analysis of muscle sympathetic nerve activity recordings.
Automated analysis and quantification of physiological signals in clinical practice and medical research can reduce manual labor, increase efficiency, and provide more objective, reproducible results. To build a novel platform for the analysis of muscle sympathetic nerve activity (MSNA), we employed state-of-the-art data processing and machine learning applications. Data processing methods for integrated MSNA recordings were developed to evaluate signals regarding the overall quality of the signal, the validity of individual signal peaks regarding the potential to be MSNA bursts and the timing of their occurrence. An overall probability score was derived from this flexible platform to evaluate each individual signal peak automatically. Overall, three deep neural networks were designed and trained to validate individual signal peaks randomly sampled from recordings representing only electrical noise and valid microneurography recordings. A novel data processing method for the whole signal was developed to differentiate between periods of valid MSNA signal recordings and periods in which the signal was not available or lost due to involuntary movement of the recording electrode. A probabilistic model for timing of the signal bursts was implemented as part of the system. Machine Learning algorithms and data processing tools were implemented to replicate the complex decision-making process of manual MSNA analysis. Validation of manual MSNA analysis including intra- and inter-rater validity and a comparison with automated MSNA tools is required. The developed toolbox for automated MSNA analysis can be extended in a flexible way to include algorithms based on other datasets.


Extremely high Q-factor terahertz metasurface using reconstructive coherent mode resonance.
High Q-factor resonance has a pivotal role in wide applications for manipulating electromagnetic waves. However, high Q-factor resonance, especially in the terahertz (THz) regime, has been a challenge faced by plasmonic metamaterials due to the inherent ohmic and radiation losses. Here, we theoretically present a unique metasurface scheme to produce extremely high Q-factor Fano resonance of the reconstructive coherent mode in the THz regime. The THz metasurface is composed of periodically arranged vertical symmetric split ring resonators (SRRs), which can produce perfect reconstructive coherent coupling effect in the sense that dipole radiation is destructively suppressed. Under the polarized electric field perpendicular to SRR gap, the surface currents are out of phase for an individual SRR, leading to the cancellation of net dipole moment. The reconstructive coherent mode resonance can occur between each SRR and its neighboring SRRs, accompanied by destructive interference of the scattered fields of each SRR. This is due to the coupling between the localized resonance of individual particles and the Rayleigh anomaly of the array. The proposed metasurface can significantly suppress far-field radiation and perform an extremely high Q-factor beyond 104 level with large modulation depth in the THz region, which pushes the advancement of THz high Q-factor resonance. The extremely high Q-factor of reconstructive coherent mode is tunable by adjusting the geometry parameters. The design strategy is useful to develop ultra-sensitive sensors, narrow-band filters and strong interaction of field-matter in the THz regime.


[Editing of articles accepted for publication by the Nederlands Tijdschrift voor Geneeskunde].
The Nederlands Tijdschrift voor Geneeskunde has been publishing medical science in Dutch for 140 years. To bridge the gap between the specialist science and the general medical reader several sections in the accepted papers have to be clarified, simplified and shortened by post acceptance editing. The style and language of the authors is treated with respect. Changes are made if the article does not comply with internationally accepted rules on scientific reporting, if the article can not be understood using currently authoritative general and medical books of reference, and if its language does not comply with generally accepted Dutch rules for grammar and spelling.


Tracheostomy in Infants in the Neonatal Intensive Care Unit.
Approximately half of all pediatric tracheostomies are performed in infants younger than 1 year. Most tracheostomies in patients in the NICU are performed in cases of chronic respiratory failure requiring prolonged mechanical ventilation or upper airway obstruction. With improvements in ventilation and management of long-term intubation, indications for tracheostomy and perioperative management in this population continue to evolve. Evidence-based protocols to guide routine postoperative care, prevent and manage tracheostomy emergencies including accidental decannulation and tube obstruction, and attempt elective decannulation are sparse. Clinician awareness of safe tracheostomy practices and larger, prospective studies in infants are needed to improve clinical care of this vulnerable population.


Purpose in life in ALS patient-caregiver dyads: A multilevel longitudinal analysis.
Eudaemonic positive psychological health (PPH), such as purpose in life (PIL), may be maintained more than hedonic PPH, such as quality of life (QOL), for patients with amyotrophic lateral sclerosis (ALS) and their caregivers across the disease course. Furthermore, patients' and caregivers' PPH may impact one another. The present study examined (a) PIL and QOL variance structures; (b) PIL and QOL trajectories from diagnosis, approaching death, with disease severity; and (c) between-dyad and within-dyad relationships for PIL and QOL in patients with ALS and their caregivers. PIL and QOL were assessed in patient-caregiver dyads (N = 110) up to 7 times over 18 months. Multilevel models revealed the proportion of variance attributed to stable between-person differences was higher for PIL (patients = 74%; caregivers = 76%) than QOL (patients = 60%; caregivers = 55%). PIL and QOL declined in relation to disease severity and time. For PIL, proximity to diagnosis and death moderated within-person change; decline was generally faster following diagnosis and approaching death. Longitudinal within-dyad relationships revealed that patients' fluctuations in PIL were mirrored in their caregiver and vice versa. PIL was more stable than QOL and was therefore a potential psychological resource for patients and caregivers. Critical periods-after diagnosis and approaching death-accompanied more rapid PIL decline. QOL was also impacted by proximity to critical periods. PIL within-dyad relationships may reflect a shared disease experience. Psychological intervention focused on enhancing purpose, particularly during critical periods, is a promising direction for future study. (PsycINFO Database Record


Use of sugar in coffee and tea and long-term risk of mortality in older adult Danish men: 32 years of follow-up from a prospective cohort study.
Tea and coffee are the most consumed beverages worldwide and very often sweetened with sugar. However, the association between the use of sugar in tea or coffee and adverse events is currently unclear. To investigate the association between the addition of sugar to coffee or tea, and the risk of all-cause mortality, cardiovascular mortality, cancer mortality and incident diabetes mellitus. Participants from the prospective Copenhagen Male Study, included from 1985 to 1986, without cardiovascular disease, cancer or diabetes mellitus at inclusion, who reported regular coffee or tea consumption were included. Self-reported number of cups of coffee and tea and use of sugar were derived from the study questionnaires. Quantity of sugar use was not reported. Primary outcome was all-cause mortality and secondary endpoints were cardiovascular mortality, cancer mortality and incident diabetes mellitus, all assessed through the Danish national registries. The association between adding sugar and all-cause mortality was analyzed by Cox regression analysis. Age, smoking status, daily alcohol intake, systolic blood pressure, body mass index, number of cups of coffee and/or tea consumed per day and socioeconomic status were included as covariates. Vital status of patients up and until 22.03.2017 was assessed. Sugar could be added to either coffee, tea or both. In total, 2923 men (mean age at inclusion: 63±5 years) were included, of which 1007 (34.5%) added sugar. In 32 years of follow-up, 2581 participants (88.3%) died, 1677 in the non-sugar group (87.5%) versus 904 in the sugar group (89.9%). Hazard ratio of the sugar group compared to the non-sugar group was 1.06 (95% CI 0.98;1.16) for all-cause mortality. An interaction term between number of cups of coffee and/or tea per day and adding sugar was 0.99 (0.96;1.01). A subgroup analysis of coffee-only drinkers showed a hazard ratio of 1.11 (0.99;1.26). The interaction term was 0.98 (0.94;1.02). Hazard ratios for the sugar group compared to the non-sugar group were 1.11 (95% CI 0.97;1.26) for cardiovascular disease mortality, 1.01 (95% CI 0.87;1.17) for cancer mortality and 1.04 (95% CI 0.79;1.36) for incident diabetes mellitus. In the present population of Danish men, use of sugar in tea and/or coffee was not significantly associated with increased risk of mortality or incident diabetes.


Physically Active Lessons Improve Lesson Activity and On-Task Behavior: A Cluster-Randomized Controlled Trial of the "Virtual Traveller" Intervention.
Physically active lessons have not often been assessed with randomized controlled trials. Evaluate the effects of the "Virtual Traveller" (VT) intervention delivered using classroom interactive whiteboards on physical activity, on-task behavior, and student engagement. Participants were 219 children aged 8 to 9 years from 10 schools in Greater London, assessed in a cluster-randomized controlled trial between March 2015 and May 2016. For 6 weeks, intervention children received 10-minute VT sessions three times a week during math and English lessons (VT group: n = 113). Children in control schools received regular teaching (COM group: n = 106). Outcomes were school-day, weekend-day, and lesson-time sedentary behavior (SB), light physical activity (LPA) and moderate-to-vigorous physical activity (MVPA), and on-task behavior and student engagement, assessed at baseline (T0), 2 weeks (T1), and 4 weeks (T2) during the VT intervention and 1 week (T3) and 3 months (T4) postintervention using multilevel modeling. VT pupils engaged in significantly more school-day MVPA at T1 only, with no other significant differences between groups in overall school-day or weekend-day activity. VT pupils engaged in significantly less SB and more MVPA during lesson time than COM pupils. More on-task behavior was shown in VT pupils than COM pupils but there was no difference in student engagement. VT reduced sedentary behavior and increased physical activity during lesson time but not across overall school or weekend days. VT improved on-task behavior but had no effect on student engagement. Physical activity can be integrated into teaching using interactive whiteboards with no detriment to educational outcomes.


Chemical requirements for inhibition of gap junction communication by the biologically active lipid oleamide.
Oleamide is an endogenous fatty acid primary amide that possesses sleep-inducing properties in animals and has been shown to effect serotonergic systems and block gap junction communication in a structurally specific manner. Herein, the structural features of oleamide required for inhibition of the gap junction-mediated chemical and electrical transmission in rat glial cells are defined. The effective inhibitors fall into two classes of fatty acid primary amides of which oleamide and arachidonamide are the prototypical members. Of these two, oleamide constitutes the most effective, and its structural requirements for inhibition of the gap junction are well defined. It requires a chain length of 16-24 carbons of which 16-18 carbons appears optimal, a polarized terminal carbonyl group capable of accepting but not necessarily donating a hydrogen bond, a Delta9 cis double bond, and a hydrophobic methyl terminus. Within these constraints, a range of modifications are possible, many of which may be expected to improve in vivo properties. A select set of agents has been identified that serves both as oleamide agonists and as inhibitors of fatty acid amide hydrolase, which is responsible for the rapid inactivation of oleamide.


Radiation-induced synthesis of tween 80 stabilized silver nanoparticles for antibacterial applications.
Recently, Silver nanoparticles (AgNPs) have become widely applied nanomaterial in human contacting areas such as cosmetics, food and medicine due to their antibacterial property. On the other hand, surfactants are essential ingredient of several industrial and consumer formulations. Based on these important applications, the current research was aimed to carry out the synthesis and characterization of Tween 80 capped silver nanoparticles (T80-AgNPs) using gamma radiation reduction method. Characterization of T80-AgNPs was occurred by using UV-Vis, XRD, FTIR and TEM techniques. UV-Visible spectra showed surface plasmon resonance (SPR) peak in the range of 420 nm signifying the synthesis of colloidal AgNPs. TEM confirmed the formation of spherical and uniformly distributed AgNPs with average size of 18 nm. XRD analysis illustrated the formation of pure crystalline AgNPs. The FTIR analysis provides evidence for the stabilization of AgNPs by Tween 80. The synthesized T80-AgNPs were evaluated for antibacterial activity against both Escherichia coli (E. coli) as gram negative (G -ve) bacteria and Staphylococcus aureus (S. aureus) as gram positive (G + ve) bacteria and anti-biofilm activity to P. aeruginosa. The results show that T80-AgNPs exhibits excellent antibacterial and antibiofilm activities.


Recent advances on Toll-like receptor 4 modulation: new therapeutic perspectives.
Activation or inhibition of TLR4 by small molecules will provide in the next few years a new generation of therapeutics. TLR4 stimulation (agonism) by high-affinity ligands mimicking lipid A gave vaccine adjuvants with improved specificity and efficacy that have been licensed and entered into the market. TLR4 inhibition (antagonism) prevents cytokine production at a very early stage; this is in principle a more efficient method to block inflammatory diseases compared to cytokines neutralization by antibodies. Advances in TLR4 modulation by drug-like small molecules achieved in the last years are reviewed. Recently discovered TLR4 agonists and antagonists of natural and synthetic origin are presented, and their mechanism of action and structure-activity relationship are discussed.


Increasing the solubility of strong reducing agents containing Mo(2)(4+) units and alkyl-substituted guanidinate ligands.
Six very soluble paddlewheel compounds containing Mo2n+ units, n = 4, 5, 6, and two alkyl-substituted bicyclic guanidinate ligands have been synthesized. The quadruply bonded complexes with n = 4, Mo2(TMhpp)4 and Mo2(TEhpp)4, (TMhpp = the anion of 3,3,9,9-tetramethyl-1,5,7-triazabicyclo[4.4.0]dec-4-ene and TEhpp = the anion of 3,3,9,9-tetraethyl-1,5,7-triazabicyclo[4.4.0]dec-4-ene) are easily oxidized. The electrode potentials in THF are -1.08 and -1.17 V vs. Ag/AgCl, respectively, for the Mo(2)(5+/4+) couple. These potentials are in accord with the low ionization potentials for the quadruply bonded compounds. Because of the high solubility of the Mo(2)(4+) compounds in most common organic solvents they are attractive candidates for use as strong reducing agents in homogeneous systems.


Self-assembled films of hemoglobin/laponite/chitosan: application for the direct electrochemistry and catalysis to hydrogen peroxide.
A highly stable biological film was formed on the functional glassy carbon electrode (GCE) via step-by-step self-assembly of chitosan (CHT), laponite, and hemoglobin (Hb). Cyclic voltammetry (CV) of the Hb/laponite/CHT/GCE showed a pair of stable and quasi-reversible peaks for the Hb-Fe(III)/Fe(II) redox couple at about -0.035 V versus a saturated calomel electrode in pH 6.0 phosphate buffer at a scan rate of 0.1 V s(-1). The electrochemical reaction of Hb entrapped on the laponite/CHT self-assembled film exhibited a surface-controlled electrode process. The formal potential of the Hb-heme-Fe(III)/Fe(II) couple varied linearly with the increase of pH over the range of 3.0-8.0 with a slope of -63 mV pH(-1), which implied that an electron transfer was accompanied by single-proton transfer in the electrochemical reaction. The position of the Soret absorption band of this self-assembled Hb/laponite/CHT film suggested that the entrapped Hb kept its secondary structure similar to its native state. The self-assembled film showed excellent long-term stability, the CV peak potentials kept in the same positions, and the cathodic peak currents retained 90% of their values after 60 days. The film was used as a biological catalyst to catalyze the reduction of hydrogen peroxide. The electrocatalytic response showed a linear dependence on the H2O2 concentration ranging widely from 6.2 x 10(-6) to 2.55 x 10(-3) M with a detection limit of 6.2 x 10(-6) M at 3 sigma.


Effect of Physical Properties on Mechanical Behaviors of Sandstone under Uniaxial and Triaxial Compressions.
Mechanical properties of sandstone, such as compressive strength and young's modulus, are commonly used in the design of geotechnical structures and numerical simulation of underground reservoirs using models such as the digital groundwater, equivalent porous medium, and Discrete Fracture Network (DFN) models. A better understanding of the mechanical behaviors of sandstone under different loading conditions is imperative when assessing the stability of geotechnical structures. This paper highlights the effect of the physical properties (i.e., porosity, mean grain size) and environmental conditions (i.e., water content and confining stress) on uniaxial compressive strength, triaxial compressive strength, and young's modulus of sandstone. A series of uniaxial and triaxial compression experiments are conducted on sandstone formations from Wyoming. In addition, experimental data on sandstones from the literature are compiled and integrated into this study. Prediction equations for the compressive strengths and young's modulus of sandstone are established based on commonly available physical properties and known environmental conditions. The results show that the mean Uniaxial Compressive Strength (UCS) decreases as the porosity, water content, and mean grain size increase. Furthermore, a predictive empirical relationship for the triaxial compressive strength is established under different confinements and porosity. The relationship suggests that the mean peak compressive strength increases at a higher confinement and decreases at a higher porosity. The results and recommendations provide a useful framework for evaluating the strength and deformation of most sandstone.


Cytotoxic styryl-lactones from the leaves and twigs of Polyalthia crassa.
Four new styryl-lactones, crassalactones A-D (1-4), were isolated from a cytotoxic ethyl acetate-soluble extract of the leaves and twigs of Polyalthia crassa, together with seven known compounds, (+)-3-acetylaltholactone, (+)-altholactone, aristolactam AII, cinnamic acid, (+)-goniofufurone, (+)-goniopypyrone, and (+)-howiinol A. Their structures were determined on the basis of spectroscopic methods. The absolute configuration of 1-3 was established by chemical conversions. Single-crystal X-ray analysis and the Mosher ester method were used to confirm the absolute stereochemistry of 4. Cytotoxic evaluation against several mammalian cancer cell lines was performed on all new isolates, aristolactam AII, and the modified (+)-tricinnamate derivative 11 obtained from 1.


Crosstalk between endoplasmic reticulum stress and oxidative stress in apoptosis induced by α-tocopheryl succinate in human gastric carcinoma cells.
α-Tocopheryl succinate (α-TOS) has been shown to be a potent apoptosis inducer and growth inhibitor in a variety of cancer cells. Our previous studies showed the important role of endoplasmic reticulum (ER) stress and reactive oxygen species (ROS) generation in the apoptosis induced by α-TOS. However, the relationship of oxidative stress with ER stress is still controversial. The objective of the present study was to investigate the interplay between the two stress responses induced by α-TOS in SGC-7901 human gastric cancer cells. In response to α-TOS, cytological changes typical of apoptosis, induction of glucose-regulated protein 78 (GRP78) and CCAAT/enhancer-binding protein (C/EBP) homologous protein transcription factor (CHOP), and activation of caspase-4 were observed. And the antioxidant N-acetyl-l-cysteine inhibited induction of both GRP78 and CHOP by α-TOS transcriptionally and translationally. Furthermore, knocking down CHOP by RNA interference decreased ROS generation, increased glutathione level and induced glutathione peroxidase mRNA expression in α-TOS-treated cells, whereas catalase and superoxide dismutases mRNA expression were not altered. The results imply that α-TOS induces ER stress response through ROS production, while CHOP perturbs the redox state of SGC-7901 cells treated with α-TOS.


Effects of freezing/thawing on motile sperm subpopulations of boar and donkey ejaculates.
The main aim of this study is to assess the influence of freeze/thawing on motile sperm subpopulations in ejaculates from two phylogenetically different mammalian species, boar and donkey. Our results indicate that, whereas boar and donkey sperm respond very differently in their mean motion characteristics to freezing/thawing, this process did not change the existence of a 4-subpopulations structure in the ejaculates in either species when these subpopulations were defined by taking values of curvilinear velocity (VCL) as reference. Moreover, the freezing/thawing-linked changes in mean sperm-motion characteristics in both boar and donkey semen were especially due to changes in the proportion among each concrete subpopulation. In this way, the freezing/thawing-induced mean increase in motion characteristics observed in boar sperm was a result of the decrease in the percentage of sperm in Subpopulation 1 (from 53.9%+/-4.7% to 31.2%+/-3.9% after thawing) and a concomitant increase of sperm from Subpopulations 3 (from 13.3%+/-2.5% to 32.6%+/-3.9% after thawing) and 4 (from 3.4%+/-0.9% to 8.0%+/-1.1% after thawing). On the contrary, changes in mean motility of frozen/thawed donkey sperm were linked to an increase in the percentage of sperm in Subpopulation 1 (from 31.5%+/-4.3% to 58.8%+/-4.9% after thawing) and a concomitant decrease of sperm from Subpopulations 3 (from 32.4%+/-3.2% to 6.6%+/-1.8% after thawing) and 4 (from 12.2%+/-2.5% to 7.3%+/-1.9% after thawing). In conclusion, our results seem to indicate that motility changes induced by the freezing/thawing protocol are linked to concomitant changes in both the specific parameters and, more importantly, to the specific percentage of each of the motile sperm subpopulations. These changes did not affect the overall proportion of motile sperm present in both boar and donkey, which is conserved despite the detrimental effect caused by freezing/thawing in both species. Finally, the presence of some kind of motile sperm subpopulations structure has been described in mammalian species with a very great phylogenetic distance, thus suggesting that this structure could play some role in the maintenance of the overall function of mammalian ejaculates.


MicroRNA profile of immune response in gills of zebrafish (Danio rerio) upon Staphylococcus aureus infection.
The gills of fish are large mucosal surfaces that are very important portals for pathogen entry. Investigations have shown that microRNAs (miRNAs) are key regulators of immune response to bacterial infections in the gills of fish; however, how miRNA expression changes in response to infection by Gram-positive bacteria remains largely unknown. To further investigate the immunological role of miRNAs in fish gills under pathogen stress induced by Gram-positive bacterial infection, this study investigated Staphylococcus aureus (SA)-induced changes in the miRNAs levels in gills of adult zebrafish (Danio rerio). miRNA microarrays were used to analyze expression profiles of known miRNA in the gills of zebrafish in response to SA infection and compared these to uninfected control fish. A total of 30 differentially expressed miRNAs (DEMs) were identified. Target genes likely regulated by DEMs were predicted, and functional enrichment analyses were performed. The results indicated that DEM targets were primarily involved in innate immune processes, apoptosis, defense responses, and antibacterial responses. Pathways involving bacterial infection, innate immunity, metabolic process, disease, and apoptosis were mediated by DEMs. Furthermore, real-time quantitative PCR experiments for nine key SA-responsive DEMs that regulated the "SA infection" pathway validated the accuracy of microarray results. Dynamic variations in gene expression were surveyed in detail for these key SA-responsive DEMs for PBS control and at 6, 12, 24, and 48 h after SA challenge in detail. This study provides novel insight into the mechanisms underlying the miRNA regulation during the SA-induced immune response in zebrafish gills, and provides basic knowledge on the innate immune response against Gram-positive bacterial infection in bony fish.


Compensation for red-green contrast loss in anomalous trichromats.
For anomalous trichromats, threshold contrasts for color differences captured by the L and M cones and their anomalous analogs are much higher than for normal trichromats. The greater spectral overlap of the cone sensitivities reduces chromatic contrast both at and above threshold. But above threshold, adaptively nonlinear processing might compensate for the chromatically impoverished photoreceptor inputs. Ratios of sensitivity for threshold variations and for color appearance along the two cardinal axes of MacLeod-Boynton chromaticity space were calculated for three groups: normals (N = 15), deuteranomals (N = 9), and protanomals (N = 5). Using a four-alternative forced choice (4AFC) task, threshold sensitivity was measured in four color-directions along the two cardinal axes. For the same participants, we reconstructed perceptual color spaces for the positions of 25 hues using multidimensional scaling (MDS). From the reconstructed color spaces we extracted "color difference ratios," defined as ratios for the size of perceived color differences along the L/(L + M) axis relative to those along the S/(L + M) axis, analogous to "sensitivity ratios" extracted from the 4AFC task. In the 4AFC task, sensitivity ratios were 38% of normal for deuteranomals and 19% of normal for protanomals. Yet, in the MDS results, color difference ratios were 86% of normal for deuteranomals and 67% of normal for protanomals. Thus, the contraction along the L/(L + M) axis shown in the perceptual color spaces of anomalous trichromats is far smaller than predicted by their reduced sensitivity, suggesting that an adaptive adjustment of postreceptoral gain may magnify the cone signals of anomalous trichromats to exploit the range of available postreceptoral neural signals.


Interdisciplinary: Cultural competency and culturally congruent education for millennials in health professions.
The increasingly diverse multicultural and multigenerational student population in the United States requires that educators at all levels develop cultural knowledge, awareness, and sensitivity to help diverse learners fulfill their potential and to avoid cultural misunderstandings that can become obstacles or barriers to learning. The purpose of this study was to design and implement eclectic, creative, evidence-based interdisciplinary educational activities, along with culturally congruent teaching strategies, within a semester-long university course that promoted positive and culturally competent learning outcomes for culturally diverse, largely millennial students. The interdisciplinary course would prepare health professional students with the requisite knowledge and skills, through transformative learning that produces change agents, to provide culturally congruent and quality team-based care to diverse populations. This was a qualitative and quantitative study, which measured students' level of cultural awareness, competence, and proficiency pre and post the educational intervention. Instruments used for data collection included the Inventory for Assessing The Process of Cultural Competence-Student Version (IAPCC-SV) by Campinha-Bacote, course evaluations, students' feedback, and portfolio reflections. The study was conducted at a private academic institution located in the Mid-Atlantic region and the sample population included inter-professional students (N=106) from various health professions including nursing, pharmacy, and allied health sciences. Results from the pre- and post-test IAPCC-SV survey revealed that mean scores increased significantly from pre-test (60.8) to post-test (70.6). Thus, students' levels of cultural competency (awareness, knowledge, skills, desire, encounter) improved post-educational intervention, indicating that the teaching methods used in the course might be applied on a larger scale across the university system to cater to the nation's increasingly multi-cultural population.


Sexual and Gender Minority Differences in Likelihood of Being a Caregiver and Levels of Caregiver Strain in a Sample of Older Adults.
Over the next two decades, the number of caregivers is expected to climb dramatically alongside a rise in older adults, particularly sexual and gender minority (SGM) older adults, yet little research has assessed differences between SGM and non-SGM care partners. Data for these analyses come from the Columbus Healthy Aging Project (N = 79). This study was designed to assess several domains of health among adults aged ≥50 years in Columbus, Ohio, US. Multivariable regression models were used to examine the likelihood of being a care partner, the SGM identity of the primary care recipient, and caregiver strain. In our sample, 227 (28.6%) participants self-identified as care partners for at least one individual. Compared to heterosexuals, gay/lesbian (aOR = 8.38; 95% CI: 5.29, 13.29) participants were more likely to be care partners but did not experience elevated caregiver strain. Bisexual individuals (aIRR = 1.70, 95% CI: 1.11, 2.61) reported greater caregiver strain, while those identifying as a different sexual identity reported lower caregiver strain (aIRR = 0.46, 95% CI: 0.23, 0.96). In turn, caregiver strain was reduced significantly when the care recipient identified as a member of the SGM community (aIRR = 0.67: 95% CI: 0.55, 0.80). These results suggest that SGM care partners may be at risk of unique stressors which may contribute to extant health disparities.


Opposite effects of substance P on conductance and resistance coronary vessels in conscious dogs.
The effects of substance P (SP) on epicardial coronary diameter (CD) and coronary blood flow (CBF) were examined in conscious dogs. SP (5.0 ng/kg) induced transient increases (P less than 0.01) in CBF by 139 +/- 19% from 26.5 +/- 1.5 ml/min followed by sustained decreases (P less than 0.01) averaging 22 +/- 2% when mean arterial pressure had returned to preinjection base line. CD increased (P less than 0.01) by 6.7 +/- 1.4% from 3.47 +/- 0.35 mm. After ganglionic blockade with hexamethonium (35 mg/kg), the transient increases (P less than 0.01) in CBF (95 +/- 10% from 28.6 +/- 1.9 ml/min) were smaller (P less than 0.05), but the late decreases (P less than 0.01) in CBF averaged 23 +/- 3%, similar to responses before ganglionic blockade. Increases (P less than 0.01) in CD (4.1 +/- 0.7% from 3.49 +/- 0.35 mm) were smaller (P less than 0.05) than before ganglionic blockade. During steady-state effects of SP (5.0 ng.kg-1.min-1) under ganglionic blockade, CBF fell (P less than 0.01) by 39 +/- 3% from 26.4 +/- 2.3 ml/min, but CD increased (P less than 0.01) by 6.6 +/- 1.6% from 3.45 +/- 0.40 mm. Additional experiments indicated that coronary sinus blood oxygen content fell and myocardial arteriovenous O2 difference increased during steady-state effects of SP under ganglionic blockade. Cyclooxygenase inhibition did not alter coronary responses to SP. Endothelial denudation abolished increases in CD after SP. Therefore, under steady-state conditions and in the absence of autonomic reflexes, SP is a potent endothelium-dependent dilator of conductance coronary vessels but paradoxically a constrictor of resistance coronary vessels.


Upregulation of drug transporter expression by osteopontin in prostate cancer cells.
Multidrug resistance is a major cause of chemotherapy failure. Recent studies indicate that drug resistance can be rapidly induced by some soluble factors, such as cytokines, chemokines, growth factors, and cell adhesion factors in the tumor microenvironment. Osteopontin (OPN), an extracellular matrix protein, has a functional arginine-glycine-aspartic acid (RGD) domain for binding to integrin. Here we found OPN expression to be upregulated by hypoxic condition in PC-3 prostate tumor cells. OPN increased the mRNA and protein expression of p-glycoprotein (P-gp), a subfamily of ATP-binding cassette transporter in a concentration- and time-dependent manner. The increase in P-gp transporter by OPN was mediated by binding to αvβ3 integrin. Daunomycin (DUN), a chemotherapeutic agent with autofluorescence, was used to evaluate the pump activity, and OPN increased the drug pumping-out activity. OPN inhibited DUN-induced cell death, which was antagonized by αvβ3 monoclonal antibody. Long-term treatment with DUN further enhanced the expression of OPN. Knockdown of endogenous OPN potentiated the DUN-induced apoptosis of PC-3 cells. Furthermore, knockdown of OPN enhanced cell death caused by other drugs, including paclitaxel, doxorubicin, actinomycin-D, and rapamycin, which are also P-gp substrates. The animal studies also showed that OPN knockdown enhanced the cytotoxic action of DUN. These results indicate that OPN is a potential therapeutic target for cancer therapy to reduce drug resistance in sensitive tumors.


Comment on' Superconducting transition in Nb nanowires fabricated using a focused-ion beam'.
In a recent paper Tettamanzi et al (2009 Nanotechnology 20 465302) describe the fabrication of superconducting Nb nanowires using a focused-ion beam. They interpret their conductivity data in the framework of thermal and quantum phase slips below T(c). In the following we will argue that their analysis is inappropriate and incomplete, leading to contradictory results. Instead, we propose an interpretation of the data within an SN proximity model.


A case of acute kidney injury with marked hyperuricemia during mizoribine administration.
A 52-year-old woman was diagnosed with Blau syndrome and rheumatoid arthritis and was treated with prednisolone and methotrexate. Joint pain and skin ulcers were poorly controlled; therefore, mizoribine (MZ; 150 mg/day) was administered once daily from March 2011. In early July 2011, the patient was hospitalized because of acute kidney injury (AKI) and acute pancreatitis. We reasoned that AKI resulted from hyperuricemia during MZ administration because serum concentrations of uric acid (31.6 mg/dL) and MZ (trough level, 5.14 µg/mL) were markedly elevated on admission. MZ should be administered with caution because of the risk of marked hyperuricemia leading to AKI.


A new ellagic acid derivative from the fruits of Eucalyptus globulus Labill.
Four ellagic acid derivatives have been isolated from the fruits of Eucalyptus globulus Labill., one of which is new compound, identified as 3-O-methylellagic acid 4'-O-alpha-L-2"-O-acetyl-rhamnopyranoside (1), the known compounds were identified as 3-O-methylellagic acid 4'-O-alpha-L-rhamnopyranoside (2), ellagic acid (3) and 3-O-methylellagic acid (4), on the basis of the analysis of 1H NMR, 13C NMR, HSQC, HMBC, IR and MS spectral data. It is alsoassignment the 13C NMR signals of 3-O-methylellagic acid 4'-O-alpha-L-rhamnopyranoside for the first.


Long-term prognosis of successfully operated oesophageal atresia-with aspects on physical and psychological development.
From 1966 to 1973, 43 oesophageal atresia patients with no other significant anomalies underwent successful anastomosis. The late mortalities of the 5 patients were due to the complications of gastro-oesophageal reflux and tracheal problems. These deaths and all the serious complications occurred before the age of 3 years. The survivors were followed up for a mean of 12.7 years and 34 of the 38 long-term survivors were re-examined by the author. The subjective results of the remaining 4 patients were obtained by means of a questionnaire. The results, according to Desjardins et al, were: "excellent" 31, "good" 6 and, "fair" 1. The growth of the patients was normal and the majority of them also possessed normal intelligence and body image. Oesophagograms revealed pathological peristalsis in every patient but only 1 of them demonstrated a somewhat narrowed anastomosis. Very few patients, however, complained of symptoms arising from the abnormal motility of the oesophagus. The long-term prognosis and the quality of life of oesophageal atresia patients seems good after the frequent problems which might occur in the early years have been overcome.


Factors contributing to the hospitalization of patients with congestive heart failure.
This study identifies acute precipitants of hospitalization and evaluates utilization of angiotension-converting enzyme inhibitors in patients admitted with congestive heart failure. Cross-sectional chart-review study was done of 435 patients admitted nonelectively from February 1993 to February 1994 to an urban university hospital with a complaint of shortness of breath or fatigue and evidence of congestive heart failure. The most common identifiable abnormalities associated with clinical deterioration prior to admission were acute anginal chest pain (33%), respiratory infection (16%), uncontrolled hypertension with initial systolic blood pressure > or = 180 mm Hg (15%), atrial arrhythmia with heart rate > or = 120 (8%), and noncompliance with medications (15%) or diet (6%); in 34% of patients, no clear cause could be identified. After exclusion of those who were already on a different vasodilator or who had relative contraindications, 18 (32%) of the patients with ejection fractions < or = 0.35 measured prior to admission were not taking an angiotensin-converting enzyme inhibitor on presentation to the hospital. Interventions to improve compliance, the control of hypertension, and the appropriate use of angiotensin-converting enzyme inhibitors may prevent many hospitalizations of heart-failure patients.


[Cloning and bioinformatic analysis of a novel gene HCR2 up-regulated in aorta of hypercoagulable rat].
The aim of this study was to clone the full-length cDNA of HCR2 up-regulated in aorta of hypercoagulable rat and make the relevant bioinformatic analysis. Rapid amplification of cDNA end (RACE) and nested PCR technique was used to amplify the full-length cDNA of HCR2 from an EST (GenBank accession number BQ901227) which was significantly up-regulated in hypercoagulable rat. The full-length cDNA of HCR2 has been obtained (GenBank accession number AY234417). Semi-quantitative RT-PCR demonstrated that HCR2 is up-regulated in aorta of hypercoagulable rat. Bioinformatic analysis showed that HCR2 gene is located in rat chromosome 4q11. The full-length cDNA of HCR2 is 1275 bp, coding for a 78 amino acids polypeptide with a theoretical molecular weight of 8841.7 and isoelectric point of 8. 59. This protein has no signal peptide and transmembrane sequence. It may be a nuclear protein. It shares no significant homology with any known protein. The successful cloning of HCR2 has laid a solid foundation for further study of its function and its possible role in the occurrence and development of hypercoagulability.


Cognitive and emotional factors associated with elective breast augmentation among young women.
The purpose of this research was to propose and evaluate a psychosocial model of young women's intentions to obtain breast implants and the preparatory steps taken towards having breast implant surgery. The model integrated anticipated regret, descriptive norms and image norms from the media into the theory of planned behaviour (TPB). Focus groups (n = 58) informed development of measures of outcome expectancies, preparatory steps and normative influence. The model was tested and replicated among two samples of young women who had ever considered getting breast implants (n = 200, n = 152). Intentions and preparatory steps served as outcomes. Model constructs and outcomes were initially assessed; outcomes were re-assessed 11 weeks later. Evaluative attitudes and anticipated regret predicted intentions; in turn, intentions, along with descriptive norms, predicted subsequent preparatory steps. Perceived risk (susceptibility, severity) of negative medical consequences of breast implants predicted anticipated regret, which predicted evaluative attitudes. Intentions and preparatory steps exhibited interplay over time. This research provides the first comprehensive model predicting intentions and preparatory steps towards breast augmentation surgery. It supports the addition of anticipated regret to the TPB and suggests mutual influence between intentions and preparatory steps towards a final behavioural outcome.


Differences in Neural Correlates of Speech Perception in 3 Month Olds at High and Low Risk for Autism Spectrum Disorder.
In this study, we investigated neural precursors of language acquisition as potential endophenotypes of autism spectrum disorder (ASD) in 3-month-old infants at high and low familial ASD risk. Infants were imaged using functional near-infrared spectroscopy while they listened to auditory stimuli containing syllable repetitions; their neural responses were analyzed over left and right temporal regions. While female low risk infants showed initial neural activation that decreased over exposure to repetition-based stimuli, potentially indicating a habituation response to repetition in speech, female high risk infants showed no changes in neural activity over exposure. This finding may indicate a potential neural endophenotype of language development or ASD specific to females at risk for the disorder.


Characterization of early gene transcripts of molluscum contagiosum virus.
Molluscum contagiosum virus (MCV), a member of the family Poxviridae, replicates well in vivo but cannot be propagated in cell culture. The coding capacity of the MCV genome was previously determined by DNA nucleotide sequence analysis. The objective of the present study was to establish experimental systems for the identification and characterization of early MCV gene transcripts. MCV mRNA was obtained in three ways: (1) MCV early mRNA was synthesized in vitro using permeabilized virions, (2) MCV mRNA was extracted from MCV-infected skin tissue, and (3) MCV mRNA was extracted from MCV-infected human embryonic fibroblasts. RNA/DNA hybridization experiments showed significant early transcriptional activity in two parts of the MCV genome. Transcripts of 11 early MCV genes located in these parts of the genome, including two subunits of the MCV DNA-dependent RNA polymerase (mc077R and mc079R), the MCV poly(A)+ polymerase gene (mc076R), and the MCV MHC class I homolog (mc080R), were detected in reverse transcription-polymerase chain reaction experiments. Total RNA obtained from MCV-infected skin tissue was used to confirm these results. Three MCV early transcripts, mc002L, mc004.1L, and mc005L, produced distinct bands on rapid amplification of their 3' ends (3' RACE). The 5' mapping of transcription start sites of MCV open reading frames (ORFs) mc002L, mc004.1L, mc005L, and mc148R revealed that the MCV RNA polymerase transcription start sites are consistently located between 11 and 13 nucleotides downstream of the early MCV consensus promoter signal. When cDNA from both 5' and 3' mapping experiments was analyzed, MCV ORFs mc004. 1L and mc005L were found to be transcribed as a single bicistronic mRNA. The transcript from MCV ORF mc066L, encoding a glutathione peroxidase, was detected in in vitro synthesized MCV mRNA as well as in total RNA from MCV-infected human embryonic fibroblasts and MCV-infected skin. This indicates that despite the lack of an early MCV consensus promoter signal immediately proximal to the start codon, this particular gene is transcribed early during MCV infection.


Development and application of a heterologous radioimmunoassay for ovine follicle-stimulating hormone.
A highly specific and sensitive heterologous double antibody radioimmunoassay for ovine follicle-stimulating hormone (oFSH) is described in detail. The assay using a rabbit antiserum to human FSH and either 125I-labelled rat FSH or 125I-labelled oFSH as tracer is specific for FSH. A maximum cross-reaction (B/Bo = 50%) of 0-1% was observed with other ovine, rat or human pituitary hormones or human chorionic gonadotrophin. Serum levels of oFSH in samples collected daily throughout the oestrous cycle showed large individual variations. In five out of nine animals a peak of FSH was observed on the day of oestrus.


Effects of chlorpyrifos on life cycle parameters, cytochrome P450S expression, and antioxidant systems in the monogonont rotifer Brachionus koreanus.
Chlorpyrifos is a widely used organophosphorus insecticide for controlling diverse insect pests of crops. In the monogonont rotifer Brachionus koreanus, population growth retardation with the inhibition of lifespan, fecundity, and individual body size of ovigerous females was shown over 10 d in response to chlorpyrifos exposure. At the molecular and biochemical levels, the rotifer B. koreanus defensome, composed of cytochrome P450 complements, heat shock protein 70, and antioxidant enzymatic systems (i.e., glutathione, glutathione peroxidase, glutathione reductase, and glutathione S-transferase), was significantly induced in response to different concentrations of chlorpyrifos. Thus, chlorpyrifos strongly induced a defensome system to mitigate the deleterious effects of chlorpyrifos at in vivo and in vitro levels as a trade-off in fitness costs. Environ Toxicol Chem 2016;35:1449-1457. © 2015 SETAC.


BLOC-1 is required for cargo-specific sorting from vacuolar early endosomes toward lysosome-related organelles.
Hermansky-Pudlak syndrome (HPS) is a genetic disorder characterized by defects in the formation and function of lysosome-related organelles such as melanosomes. HPS in humans or mice is caused by mutations in any of 15 genes, five of which encode subunits of biogenesis of lysosome-related organelles complex (BLOC)-1, a protein complex with no known function. Here, we show that BLOC-1 functions in selective cargo exit from early endosomes toward melanosomes. BLOC-1-deficient melanocytes accumulate the melanosomal protein tyrosinase-related protein-1 (Tyrp1), but not other melanosomal proteins, in endosomal vacuoles and the cell surface due to failed biosynthetic transit from early endosomes to melanosomes and consequent increased endocytic flux. The defects are corrected by restoration of the missing BLOC-1 subunit. Melanocytes from HPS model mice lacking a different protein complex, BLOC-2, accumulate Tyrp1 in distinct downstream endosomal intermediates, suggesting that BLOC-1 and BLOC-2 act sequentially in the same pathway. By contrast, intracellular Tyrp1 is correctly targeted to melanosomes in melanocytes lacking another HPS-associated protein complex, adaptor protein (AP)-3. The results indicate that melanosome maturation requires at least two cargo transport pathways directly from early endosomes to melanosomes, one pathway mediated by AP-3 and one pathway mediated by BLOC-1 and BLOC-2, that are deficient in several forms of HPS.


Association between Change in the peripheral biomarkers of inflammation, astrocyte activation, and neuroprotection at one week of critical illness and hospital mortality in patients with delirium: A prospective cohort study.
In critically ill adults with delirium, biomarkers of systemic inflammation, astrocyte activation, neuroprotection, and systemic inflammation measured at one week of critical illness may be associated with mortality. Prospective observational study. Intensive care unit (ICU). 178 ICU patients with delirium, alive and remaining in ICU at one week. None. Blood samples collected for a pair of previously published, negative, clinical trials were utilized. Samples were collected at study enrollment/ICU admission (Day 1 sample) and one week later (Day 8 sample), and analyzed for interleukins (IL)-6, 8, 10, Insulin-like Growth Factor (IGF), S100 Binding Protein (S100B), Tumor Necrosis Factor Alpha (TNF-A) and C-Reactive Protein (CRP). Delirium, delirium severity, and coma were assessed twice daily using Confusion Assessment Method for the Intensive Care Unit (CAM-ICU), CAM-ICU-7, and Richmond Agitation-Sedation Scale (RASS), respectively. Mortality was assessed until discharge using the electronic medical record. Logistic regression models adjusting for age, sex, severity of illness, comorbidities, sepsis, and randomization status, were used to assess the relationship among biomarkers and mortality. Higher IL-10 quartiles at day 8 were associated with increased odds of hospital mortality (IL-10: OR 2.00 95%CI: 1.1-3.65, p = 0.023). There was a significant interaction between day 1 and day 8 biomarker quartiles only for IL-6. Patients with IL-6 values in the first three quartiles on admission to the ICU that transitioned to higher IL-6 quartiles at day 8 had increased probability of hospital mortality. In this hypothesis-generating study, higher IL-6 and IL-10 quartiles at one week, and increase in IL-6 from day 1 to day 8 were associated with increased hospital mortality. Studies with larger sample sizes are needed to confirm the mechanisms for these observations.


Thyroid hormone supplementation for the prevention of morbidity and mortality in infants undergoing cardiac surgery.
Paediatric studies have demonstrated that cardiopulmonary bypass is associated with a decline in thyroid hormone levels. Adult patients who undergo open heart surgery and receive triiodothyronine supplementation have demonstrated a dose-dependent increase in cardiac output which has been associated with an improved clinical outcome. Thyroid hormone supplementation in infants may also reduce post-operative morbidity and mortality. To determine if peri-operative thyroid hormone supplementation or replacement in infants undergoing cardiac surgery on cardiopulmonary bypass improves post-operative and longer term morbidity and mortality. The standard search strategy of the Cochrane Neonatal Review Group was used. This included searches of The Oxford Database of Perinatal Trials, MEDLINE (1966 - December 2003), EMBASE (1980 - December 2003), CINAHL (1982 - December 2003), The Cochrane Central Register of Controlled Trials (The Cochrane Library, Issue 2, 2003), previous reviews including cross references, abstracts, conferences, symposia proceedings, expert informants and journal handsearching in the English language. All trials using random allocation to peri-operative thyroid hormone therapy (supplementation or replacement) compared to control (placebo or no therapy) in infants (birth to one year of age) undergoing cardiac surgery requiring cardiopulmonary bypass. Thyroid hormone therapy must be tri-iodothyronine. Primary clinical outcomes included measures of post-operative morbidity and mortality. The standard methods of the Cochrane Neonatal Review Group were used in the assessment of trial quality. Treatment effects were expressed using relative risk (RR) and mean difference (MD). Two very small studies were identified that tested peri-operative thyroid hormone supplementation or replacement in infants aged less than one year undergoing cardiac surgery (Chowdhury 2001; Portman 2000). In the Chowdhury 2001 study, a subgroup of nine neonates was eligible for this review. No deaths occurred during either study. Chowdhury 2001 found no significant effect of peri-operative thyroid hormone supplementation in neonates on either length of hospital stay or duration of mechanical ventilation. Portman 2000 found no significant difference in dopamine requirements for the treatment versus control groups for the first 24 hours post operatively, while in the Chowdhury neonatal subgroup, inotrope requirements were significantly lower in the treatment group. Portman 2000 reported significant differences between the two groups at 1 and 24 hours post operatively for free T3 and at 1 hour post operatively for total T3 levels. Total T4 levels showed no significant difference between groups, either pre-cardiopulmonary bypass or up to 72 hours post operatively. At present, there is a lack of evidence concerning the effects of tri-iodothyronine supplementation in infants undergoing cardiac surgery. Further randomised controlled trials which include sufficiently large subject numbers in a variety of different age strata (neonates, infants and older children) need to be undertaken.


Comparative Genomics of Wild Bee and Flower Isolated Lactobacillus Reveals Potential Adaptation to the Bee Host.
Symbiosis with bacteria is common across insects, resulting in adaptive host phenotypes. The recently described bacterial symbionts Lactobacillus micheneri, Lactobacillus timberlakei, and Lactobacillus quenuiae are found in wild bee pollen provisions, bee guts, and flowers but have small genomes in comparison to other lactobacilli. We sequenced, assembled, and analyzed 27 new L. micheneri clade genomes to identify their possible ecological functions in flower and bee hosts. We determined possible key functions for the L. micheneri clade by identifying genes under positive selection, balancing selection, genes gained or lost, and population structure. A host adherence factor shows signatures of positive selection, whereas other orthologous copies are variable within the L. micheneri clade. The host adherence factors serve as strong evidence that these lactobacilli are adapted to animal hosts as their targets are found in the digestive tract of insects. Next, the L. micheneri clade is adapted toward a nutrient-rich environment, corroborating observations of where L. micheneri is most abundant. Additionally, genes involved in osmotolerance, pH tolerance, temperature resistance, detoxification, and oxidative stress response show signatures of selection that allow these bacteria to thrive in pollen and nectar masses in bee nests and in the bee gut. Altogether, these findings not only suggest that the L. micheneri clade is primarily adapted to the wild bee gut but also exhibit genomic features that would be beneficial to survival in flowers.


A computer system for the numerical analysis of nonstress tests.
The development and clinical validation of a computer system for the numerical analysis of nonstress tests is reviewed, and recent improvements are reported. The analysis was developed by using a database of 73,802 nonstress test readings to provide a numerical definition of reactivity that is tailored to the gestational age of the fetus and independent of the presence of accelerations. When used at the bedside, the analysis minimizes monitoring time by alerting the operator when monitoring can be safely stopped because the fetal heart rate is normal. It also detects potentially sinister sinusoidal patterns and improves the quality of nonstress test readings by quantifying signal loss and, if significant, alerting the operator.


The legal aspects of medical defence.
Defence organisations provide many varied "services" to members. Litigation involving doctors includes giving reports, giving evidence in court for or against the plaintiff or defendant, appearing as a witness at inquiries, e.g. coronial inquiries, and actions against doctors, generally alleging negligence. Patients do not seek treatment with the intent of eventually commencing proceedings. What are the catalysts for a patient commencing legal action or seeking legal advice? What should the doctor do to assist his/her defence? These questions are addressed in the article.


Growth of Triple Negative and Progesterone Positive Breast Cancer Causes Oxidative Stress and Down-Regulates Neuroprotective Transcription Factor NPAS4 and NPAS4-Regulated Genes in Hippocampal Tissues of TumorGraft Mice-an Aging Connection.
While the refinement of existing and the development of new chemotherapeutic regimens has significantly improved cancer treatment outcomes and patient survival, chemotherapy still causes many persistent side effects. Central nervous system (CNS) toxicity is of particular concern, as cancer patients experience significant deficits in memory, learning, cognition, and decision-making. These chemotherapy-induced cognitive changes are termed chemo brain, and manifest in more than half of cancer survivors. Moreover, recent studies have emerged suggesting that neurocognitive deficits manifest prior to cancer diagnosis and treatment, and thus may be associated with tumor presence, a phenomenon recently termed "tumor brain." To dissect the molecular mechanisms of tumor brain, we used TumorGraftTM models, wherein part of a patient's tumor is grafted into immune-deficient mice. Here, we analyzed molecular changes in the hippocampal tissues of mice carrying triple negative (TNBC) or progesterone receptor positive (PR+BC) xenografts. TNBC growth led to increased oxidative damage, as detected by elevated levels of 4-hydroxy-2-nonenal, a product of lipid peroxidation. Furthermore, the growth of TNBC and PR+BC tumors altered global gene expression in the murine hippocampus and affected multiple pathways implicated in PI3K-Akt and MAPK signaling, as well as other pathways crucial for the proper functioning of hippocampal neurons. TNBC and PR+BC tumor growth also led to a significant decrease in the levels of neuronal transcription factor NPAS4, a regulator that governs the expression of brain-derived neurotrophic factor (BDNF), and several other key brain neurotrophic factors and pro-survival molecules. The decreased expression of ERK1/2, NPAS4, and BDNF are also seen in neurodegenerative conditions and aging, and may constitute an important tumor brain mechanism.


Rapid and sensitive detection of auxins and flavonoids in plant samples by high-performance liquid chromatography coupled with tandem mass spectrometry.
Simultaneous determination of indole-3-acetic acid and methyl indole-3-acetic acid ester in small amounts of plant tissue is essential for elucidating their mutual transformation mechanism and the in vivo function of methyl indole-3-acetic acid ester. Rapid quantification of flavonoids in the same sample is important for clarifying their roles in the transport of auxins and other phytohormones. Herein, we describe a simple method for the simultaneous determination of indole-3-acetic acid and its methyl ester in the roots of the Arabidopsis thaliana seedlings and a protocol for the rapid extraction and quantification of quercetin and kaempferol in these seedlings. High-performance liquid chromatography coupled with electrospray ionization time-of-flight tandem mass spectrometry was used for the detection of all the compounds. Negative data for indole-3-acetic acid and positive data for methyl indole-3-acetic acid ester were collected in two successive files with a single injection of the extracted sample. Under optimized conditions, the limit of detection for the four compounds was 2 ng/mL for indole-3-acetic acid, 0.5 ng/mL for methyl indole-3-acetic acid ester, 5 ng/mL for quercetin, and 1 ng/mL for kaempferol, respectively. Because of the high sensitivity of the assay, only 2-10 mg of the plant material was required to obtain quantitative results.


Description of a new species of Nososticta Hagen (Odonata: Platycnemididae: Disparoneurinae) from Central Nicobar Islands, India.
A new damselfly species, Nososticta nancowra Rajeshkumar sp. nov. is described based on eight males and three females from Central Nicobar Islands, India. The diagnostic characteristics of the new species separating it from congeners are discussed. Morphological variations observed in the anal appendages of males and the pronotum of females are documented. A description of the new species using photographs and drawings is given. An identification key to species of the genus Nososticta occurring in Nicobar Islands is given for both sexes.


Higher baseline global leukocyte DNA methylation is associated with MTX non-response in early RA patients.
Low-dose methotrexate (MTX) is the first-line therapy in early rheumatoid arthritis (eRA). Up to 40% of eRA patients do not benefit from MTX therapy. MTX has been shown to inhibit one-carbon metabolism, which is involved in the donation of methyl groups. In this study, we investigate baseline global DNA methylation and changes in DNA methylation during treatment in relation to clinical non-response after 3 months of MTX treatment. Two hundred ninety-four blood samples were collected from the Treatment in the Rotterdam Early Arthritis Cohort (tREACH, ISRCTN26791028), a multicenter, stratified single-blind clinical trial of eRA patients. Global DNA (hydroxy)methylation was quantified using liquid chromatography-electrospray ionization-tandem mass spectrometry (LC-ESI-MS/MS) and validated with a global DNA LINE-1 methylation technique. MTX response was determined as ΔDAS28. Additionally, patients were stratified into two response groups according to the European League Against Rheumatism (EULAR) response criteria. Associations between global DNA methylation and response were examined using univariate regression models adjusted for baseline DAS28, baseline erythrocyte folate levels, and body mass index (BMI). Higher baseline global DNA methylation was associated with less decrease of DAS28 (β = 0.15, p = 0.013) and with MTX non-response (OR = 0.010, 95% CI = 0.001-0.188). This result was validated in LINE-1 elements (β = 0.22, p = 0.026). Changes in global DNA (hydroxy)methylation were not associated with MTX response over 3 months. These results show that higher baseline global DNA methylation in treatment naïve eRA patients is associated with decreased clinical response after 3 months of treatment of eRA patients and can be further evaluated as a predictor for MTX therapy non-response. ISRCTN, ISRCTN26791028 , registered 23 August 2007-retrospectively registered.


2D beam steerer based on metalens on silicon photonics.
Beam steering with solid-state devices represents the cutting-edge technology for next-generation LiDARs and free-space communication transceivers. Here we demonstrate a platform based on a metalens on a 2D array of switchable silicon microring emitters. This platform enables scalable, efficient, and compact devices that steer in two dimensions using a single wavelength. We show a field of view of 12.4° × 26.8° using an electrical power of less than 83 mW, offering a solution for practical miniature beam steerers.


A Simple Zinc-Mediated Method for Selenium Addition to Michael Acceptors.
In this work, we focused our attention on seleno-Michael type reactions. These were performed using zinc-selenolates generated in situ from diphenyl diselenide 1, 1,2-bis(3-phenylpropyl)diselenide 30, and protected selenocystine 31 via an efficient biphasic Zn/HCl-based reducing system. Alkenes with a variety of electron-withdrawing groups were investigated in order to gauge the scope and limitations of the process. Results demonstrated that the addition to acyclic α,β-unsaturated ketones, aldehydes, esters amides, and acids was effectively achieved and that alkyl substituents at the reactive β-centre can be accommodated. Similarly, cyclic enones undergo efficient Se-addition and the corresponding adducts were isolated in moderate to good yield. Vinyl sulfones, α,β-unsaturated nitriles, and chalcones are not compatible with these reaction conditions. A recycling experiment demonstrated that the unreacted Zn/HCl reducing system can be effectively reused for seven reaction cycles (91% conversion yield at the 7° recycling rounds).


Harnessing function of EMT in hepatocellular carcinoma: From biological view to nanotechnological standpoint.
Management of cancer metastasis has been associated with remarkable reduction in progression of cancer cells and improving survival rate of patients. Since 90% of mortality are due to cancer metastasis, its suppression can improve ability in cancer fighting. The EMT has been an underlying cause in increasing cancer migration and it is followed by mesenchymal transformation of epithelial cells. HCC is the predominant kind of liver tumor threatening life of many people around the world with poor prognosis. Increasing patient prognosis can be obtained via inhibiting tumor metastasis. HCC metastasis modulation by EMT and HCC therapy by nanoparticles are discussed here. First of all, EMT happens during progression and advanced stages of HCC and therefore, its inhibition can reduce tumor malignancy. Moreover, anti-cancer compounds including all-trans retinoic acid and plumbaging, among others, have been considered as inhibitors of EMT. The EMT association with chemoresistance has been evaluated. Moreover, ZEB1/2, TGF-β, Snail and Twist are EMT modulators in HCC and enhancing cancer invasion. Therefore, EMT mechanism and related molecular mechanisms in HCC are evaluated. The treatment of HCC has not been only emphasized on targeting molecular pathways with pharmacological compounds and since drugs have low bioavailability, their targeted delivery by nanoparticles promotes HCC elimination. Moreover, nanoparticle-mediated phototherapy impairs tumorigenesis in HCC by triggering cell death. Metastasis of HCC and even EMT mechanism can be suppressed by cargo-loaded nanoparticles.


Chemokine Receptor Crystal Structures: What Can Be Learned from Them?
Chemokine receptors belong to the class A of G protein-coupled receptors (GPCRs) and are implicated in a wide variety of physiologic functions, mostly related to the homeostasis of the immune system. Chemokine receptors are also involved in multiple pathologic processes, including immune and autoimmune diseases, as well as cancer. Hence, several members of this GPCR subfamily are considered to be very relevant therapeutic targets. Since drug discovery efforts can be significantly reinforced by the availability of crystal structures, substantial efforts in the area of chemokine receptor structural biology could dramatically increase the outcome of drug discovery campaigns. This short review summarizes the available data on chemokine receptor crystal structures, discusses the numerous applications from chemokine receptor structures that can enhance the daily work of molecular pharmacologists, and describes the challenges and pitfalls to consider when relying on crystal structures for further research applications. SIGNIFICANCE STATEMENT: This short review summarizes the available data on chemokine receptor crystal structures, discusses the numerous applications from chemokine receptor structures that can enhance the daily work of molecular pharmacologists, and describes the challenges and pitfalls to consider when relying on crystal structures for further research applications.


Endometriosis in a woman with mosaic Turner's syndrome: case report.
The coexistence of endometriosis and Turner's syndrome is extremely rare, and therefore poses certain questions on the mechanisms of endometriosis. We present a case of a 27-year-old woman with Turner's syndrome [(46, X(x) (q10); 45X], primary amenorrhea and menopausal hormonal profile in which peritoneal endometriosis was revealed laparoscopically.


Atrial pacemaker complex preserved radiofrequency maze procedure reducing the incidence of sick sinus syndrome in patients with atrial fibrillation.
The Cox maze III procedure can effectively restore sinus rhythm in most patients with permanent atrial fibrillation (AF). However, previous studies have shown that the maze procedure results in significant sinus node dysfunction, and, consequently, a considerable number of patients required postoperative pacemaker implantation. This study investigates the hypothesis that the modification of the Cox III maze procedure, to avoid injuring the sinus node and the atrial physiologic pacemaker complex, will reduce the incidence of sick sinus syndrome following surgery. This study investigated 71 patients with permanent AF and mitral valve disease who were undergoing concomitant open-heart surgery. Most atrial incisions in the Cox maze III procedure were replaced with radiofrequency ablation, and the intercaval counterablation was moved posterolaterally to avoid injury to the sinus node and atrial pacemaker complex. At a mean (+/- SD) follow-up time of 46.5 +/- 24 months, 59 patients (83.1%) regained sinus rhythm without receiving antiarrhythmic drug therapy or undergoing electrical cardioversion. The transmitral atrial wave was observed in 44 patients (62%), and the transtricuspid atrial wave was also observed in 53 patients (74.6%). Late sinus node dysfunction developed in only two patients (2.8%), who received permanent pacemaker implantation. This modified radiofrequency maze procedure produces few patients with sick sinus syndrome and effectively restores sinus rhythm and atrial transport function in most patients with permanent AF undergoing concomitant open-heart surgery.


Multidisciplinary Collaboration in Professional Networks for PD A Mixed-Method Analysis.
ParkinsonNet, a nationwide organization with regionally oriented professional health networks in TheNetherlands, aims to improve the quality of Parkinson care. Facilitation of multidisciplinary collaboration is a key objective of ParkinsonNet. This study examined whether the concept enhances multidisciplinary collaboration between healthcare professionals involved in Parkinson care. A regional network involving 101 healthcare professionals was newly established. Participants received two questionnaires. One aimed at documenting direct working relationships ('connections') between professionals and the other aimed at evaluating multidisciplinary team performance. Additionally, thirteen healthcare professionals were interviewed to identify barriers and facilitators for multidisciplinary collaboration. 'Social network analysis' focused on sub-networks around three community hospitals at baseline and one year after the implementation. The number of 'knowing each other' connections increased from 1431 to 2175 (52% , p < 0.001) and 'professional contact' connections increased from 664 to 891 (34% , p < 0.001). Large differences between sub-networks were found, positive changes being associated with a central role of neurologists and nurse specialists committed to multidisciplinary care. The perceived team performance did not change. Participants experienced problems with information exchange and interdisciplinary communication. Generally, participants were unaware of other healthcare professionals involved in individual patients and what treatments they provide simultaneously. ParkinsonNet partially enhanced multidisciplinary collaboration between healthcare professionals involved in Parkinson care. Crucial facilitators of this were a central role of nurse specialists and the commitment to collaborate with and refer to expert therapists among neurologists. Additional measures are needed to further improve multidisciplinary care across different institutions and around individual patients.


[Research progress on seaweed bed ecosystem and its engineering].
Seaweed bed ecosystem is one of the typical nearshore ecosystems. Because of its unique structure and function, the ecology and engineering of this ecosystem have received much attention around the world in recent years. In this paper, the concept, structure, and function of seaweed bed ecosystem, as well as the definition and implementing steps of seaweed bed ecosystem engineering were introduced, and the most recent development in the research of seaweed bed ecosystem in developed countries was reviewed, with the research projects in the United States and Japan as examples. More basic research in seaweed bed ecosystems in China was urgent to be conducted to promote the marine economy and the development of relevant sciences and technologies.


Colorism attitudes and use of skin lightening agents in the United States.
Skin lightening (SL) is a practice involving the use of chemicals to lighten the skin that is more common among skin of color (SOC) individuals, particularly women, and can lead to adverse health consequences. In this study, we examine SL habits, including both general lightening and lightening for the treatment of a skin condition, among SOC individuals in the United States and the role of colorism in motivating these behaviors. A cross-sectional survey was administered to SOC individuals through ResearchMatch, an online national health registry. Demographics, rates of SL, SL habits, and perceived colorism among SL users and nonusers were collected and analyzed with χ2, Fisher's exact, Analysis of variance (ANOVA), Spearman correlation, and t tests. A total of 455 participants completed the survey. Ninety-seven participants (21.3%) reported using SL agents: 73.2% (71/97) used SL agents for the treatment of a skin condition and 26.8% (26/97) used the products for general SL. Only 22.6% (22/97) of SL users consulted a medical provider before using the products. Forty-four participants (45.4%) were unaware of their SL product ingredients, and 35.1% (34/97) reported using hydroquinone-based products. Composite colorism scores were significantly higher in SL users than nonusers (20.03 vs 18.20; P < .001). This study used self-reported racial/ethnic groups to characterize those with SOC rather than assessing actual skin tones of participants, which could have led to variability. SL among SOC individuals is prevalent in the U.S. and poses a health risk, as many SL users are unaware of product ingredients, do not consult a medical provider before use, and have access to potentially unsafe formulations. Dermatologists should address skin tone and pigmentary concerns with their SOC patients.


Effect observation of anti epileptic drugs on serum folic acid and vitamin B12 of epileptic patients.
Comparative analysis of the effect of antiepileptic drugs on the epileptic (tonic clonic seizure type) patient's serum folate and vitamin B12 concentrations. Consecutively, 84 cases from September 2010 to September 2014 from the Department of Internal Medicine of our hospital were considered to diagnose as epilepsy nerve. Among which, 49 cases received anti epileptic drug treatment (treatment group), 35 cases received treatment without anti epileptic drugs (non-treatment group); At the same period, 42 nonepileptic patients (control group) underwent the analysis of the difference of serum folate and vitamin B12 concentrations of among the three groups of patients before the test, and at the end of test with the contrast analysis of difference of clinical efficiency and thrombosis rate. Serum folic acid level of patients in the treatment group decreased significantly after test, vitamin B12 level was significantly higher, the differences were statistically significant (P<0.05), but folic acid and vitamin B12 concentration of non-treatment group and the control group did not change, and the differences were not statistically significant (P>0.05). Clinical efficiency of treatment group patients was significantly higher than that of the non-treatment group; the incidence of thrombosis was significantly lower than that of the non-treatment group, and the difference was statistically significant (P<0.05). Antiepileptic drugs can significantly improve clinical efficacy of the epilepsy tonic clonic seizure type patients, which may be related to the decrease of serum levels of folate and vitamin B12-increased concentration.


Population Pharmacokinetic Model-Based Evaluation of Standard Dosing Regimens for Cefuroxime Used in Coronary Artery Bypass Graft Surgery with Cardiopulmonary Bypass.
The purpose of this study was to investigate the population pharmacokinetics (PK) of cefuroxime in patients undergoing coronary artery bypass graft (CABG) surgery. In this observational pharmacokinetic study, multiple blood samples were collected over a 48-h interval of intravenous cefuroxime administration. The samples were analyzed by using a validated high-performance liquid chromatography (HPLC) method. Population pharmacokinetic models were developed using Monolix (version 4.4) software. Pharmacokinetic-pharmacodynamic (PD) simulations were performed to explore the ability of different dosage regimens to achieve the pharmacodynamic targets. A total of 468 blood samples from 78 patients were analyzed. The PK for cefuroxime were best described by a two-compartment model with between-subject variability on clearance, the volume of distribution of the central compartment, and the volume of distribution of the peripheral compartment. The clearance of cefuroxime was related to creatinine clearance (CLCR). Dosing simulations showed that standard dosing regimens of 1.5 g could achieve the PK-PD target of the percentage of the time that the free concentration is maintained above the MIC during a dosing interval (fTMIC) of 65% for an MIC of 8 mg/liter in patients with a CLCR of 30, 60, or 90 ml/min, whereas this dosing regimen failed to achieve the PK-PD target in patients with a CLCR of ≥125 ml/min. In conclusion, administration of standard doses of 1.5 g three times daily provided adequate antibiotic prophylaxis in patients undergoing CABG surgery. Lower doses failed to achieve the PK-PD target. Patients with high CLCR values required either higher doses or shorter intervals of cefuroxime dosing. On the other hand, lower doses (1 g three times daily) produced adequate target attainment for patients with low CLCR values (≤30 ml/min).


Efficacy and safety of ritlecitinib in adolescents with alopecia areata: Results from the ALLEGRO phase 2b/3 randomized, double-blind, placebo-controlled trial.
This subgroup analysis of the ALLEGRO phase 2b/3 trial (NCT03732807) evaluated the efficacy and safety of ritlecitinib, an oral, selective dual JAK3/TEC family kinase inhibitor, for the treatment of alopecia areata (AA) in patients aged 12-17 years. In ALLEGRO-2b/3, patients aged ≥12 years with AA and ≥50% scalp hair loss received once-daily ritlecitinib 50 or 30 mg (±4-week 200-mg loading dose) or 10 mg or placebo for 24 weeks. In a subsequent 24-week extension period, ritlecitinib groups continued their doses, and patients initially assigned to placebo switched to 200/50 or 50 mg daily. Clinician- and patient-reported hair regrowth outcomes and safety were assessed. In total, 105 adolescents were randomized. At Week 24, 17%-28% of adolescents achieved a Severity of Alopecia Tool (SALT) score ≤20 (≤20% scalp without hair) in the ritlecitinib 30 mg and higher treatment groups versus 0% for placebo. At Week 48, 25%-50% of patients had a SALT score ≤20 across ritlecitinib treatment groups (30 mg and higher). Adolescents reporting that their AA "moderately" or "greatly" improved were 45%-61% in the ritlecitinib groups (30 mg and higher) (vs. 10%-22% for placebo) at Week 24 and 44%-80% at Week 48. The most common adverse events in adolescents were headache, acne, and nasopharyngitis. No deaths, major adverse cardiovascular events, malignancies, pulmonary embolisms, opportunistic infections, or herpes zoster infections were reported. Ritlecitinib treatment demonstrated clinician-reported efficacy, patient-reported improvement, and an acceptable safety profile through Week 48 in adolescents with AA with ≥50% scalp hair loss.


Changes to the Intestinal Microbiome With Parenteral Nutrition: Review of a Murine Model and Potential Clinical Implications.
Parenteral nutrition (PN) dependence, while life sustaining, carries a significant risk of septic complications associated with epithelial barrier dysfunction and translocation of gut-derived microbiota. Increasing evidence suggests that PN-associated changes in the intestinal microbiota play a central role in the breakdown of the intestinal epithelial barrier. This review outlines the clinical and experimental evidence of epithelial barrier dysfunction with PN, the role of gut inflammatory dysregulation in driving this process, and the role of the intestinal microbiome in modulating inflammation in the gut and systemically. The article summarizes the most current work of our laboratory and others and describes many of the laboratory findings behind our current understanding of the PN enteral environment. Understanding the interaction between nutrient delivery, the intestinal microbiome, and PN-associated complications may lead to the development of novel therapies to enhance safety and quality of life for patients requiring PN.


No evidence that HLA genotype influences the driver mutations that occur in cancer patients.
The major histocompatibility (MHC) molecules are capable of presenting neoantigens resulting from somatic mutations on cell surfaces, potentially directing immune responses against cancer. This led to the hypothesis that cancer driver mutations may occur in gaps in the capacity to present neoantigens that are dependent on MHC genotype. If this is correct, it has important implications for understanding oncogenesis and may help to predict driver mutations based on genotype data. In support of this hypothesis, it has been reported that driver mutations that occur frequently tend to be poorly presented by common MHC alleles and that the capacity of a patient's MHC alleles to present the resulting neoantigens is predictive of the driver mutations that are observed in their tumor. Here we show that these reports of a strong relationship between driver mutation occurrence and patient MHC alleles are a consequence of unjustified statistical assumptions. Our reanalysis of the data provides no evidence of an effect of MHC genotype on the oncogenic mutation landscape.


Study of Serum Uric Acid Levels in Myocardial Infarction and Its Association With Killip Class.
The present study aimed to compare the serum level of uric acid in patients with and without heart failure and also to determine the association between uric acid level and clinical status by Killip class in patients with STEMI. This case-control study was conducted on 50 consecutives as control group and 50 patients with acute heart failure, (20 patients had acute STEMI), who documented by both clinical conditions and echocardiography assessment. The mean plasma level of uric acid in the case group was 7.6±1.6 milligrams/deciliter (mg/dL) and in the control group was 4.5±1.5 respectively (P<0.001). These values in patients with STEMI was about 9.2±0.86, but in patients with acute heart failure in absence of STEMI was 6.5±1.04 (P<0.001). Moreover, there was significant difference among the level of uric acid and Killip classes (P<0.001). Also there was significant difference for uric acid level between HFrEF (HF with reduced EF) and severe LV systolic dysfunction (0.049). In STEMI patients with culprit LAD, mean uric acid was significantly higher than cases with culprit LCX [(9.7±0.98 versus 8.6±0.52 respectively) P=0.012]. Regarding treatment plan in patients with STEMI, mean level of uric acid in those considered for CABG was significantly higher than who were considered for PCI, 9.9±0.82 versus 8.9±0.76 respectively, P=0.029. In STEMI patients with higher killip class, higher level of uric acid was seen. Also, the severity of LV systolic dysfunction was associated with higher level of uric acid.


Yoshida ascites sarcoma grown in mice.
Xenogeneic Yoshida ascites sarcoma grows well in the abdominal cavity of thymectomized, irradiated mice reconstituted with syngeneic bone marrow. These animals displayed a 100-percent mortality. In control sham-thymectomized, irradiated mice reconstituted with syngeneic bone marrow mortality was significantly lower. The tumor growth could be neutralized by means of single intravenous injection of nonimmune spleen cells inoculated at the same time as the tumor. Tumor cells grown in mice killed normal rats and were rejected by normal mice.


Prevalence of skin diseases in old age.
The prevalence of skin disorders was studied in an elderly population comprising 584 individuals. The mean age was 80 years (range 55-106). The prevalence of pityriasis of the scalp and asteatosis was high, 44.3% and 28.9%, respectively. Psoriasis vulgaris was found in 2.9%, vitiligo in 1.2%, and contact dermatitis in 3.8% of the group.