A 6-month comparison between formoterol and salmeterol in patients with reversible obstructive airways disease.
The aim of this randomized, open, parallel group study was to compare the clinical efficacy of formoterol dry powder capsule 12 micrograms b.i.d. and salmeterol dry powder 50 micrograms b.i.d. in the treatment of patients with reversible obstructive airways disease. The 6-month treatment was preceded by a 2 week run-in period. Morning pre-dose peak expiratory flow (PEF) during the last 7 days of treatment was the primary variable. Throughout the study, patients recorded morning and evening pre-dose PEF, use of rescue medication, respiratory symptoms and adverse events. Clinic visits were scheduled at monthly intervals. Of the 482 patients randomized (equal numbers in the two treatment groups), 428 completed the study. Four hundred and twenty-five patients were included in the efficacy analysis for the primary variable. For mean morning pre-dose PEF during the last 7 days of treatment, the 95% confidence interval (CI) for the treatment contrast formoterol minus salmeterol was included entirely in the pre-defined range of equivalence (CI limits = -8.69, +9.841 min-1). This was also the case for the morning PEF during the last week before each clinic visit. For mean evening pre-dose PEF, the estimated treatment contrasts showed a trend towards superiority of formoterol over salmeterol, which became statistically significant at 2, 3 and 4 months (P < 0.05; estimated contrasts 7.27, 10.45 and 10.511 min-1, respectively). No treatment group differences were found in use of rescue medication and respiratory symptom scores. The incidence of adverse events was similar in the two groups. These findings demonstrate that formoterol 12 micrograms b.i.d. and salmeterol 50 micrograms b.i.d., both formulated as dry powders, have similar long-term efficacy and safety profiles in patients with reversible obstructive airways disease.


Hepatitis C virus in pregnancy: case reports and literature review.
Hepatitis C virus (HCV) is now recognized as the cause of 90% of non-A, non-B (NANB) hepatitis. This virus is responsible for a large percentage of chronic persistent and chronic active hepatitis in the United States. Parenteral and sexual transmission are well described, so a significant population of pregnant patients is at risk. Vertical transmission of the virus to the fetus is dependent upon the level of maternal viremia. The cases described in the following report demonstrate that fulminant disease may present in pregnancy. They also demonstrate the cofactors promoting the severity of illness, methods of diagnosis, potential treatment, and outcome of the infection. HCV may be encountered in pregnancy. Although most acute-phase illness will be self limiting, some patients will manifest liver failure during gestation. Because vertical transmission to the fetus is possible, the pediatrician should be informed of the maternal disease. Chronic hepatitis is almost the rule rather than the exception, so patients require close postpartum follow-up. Interferon, which may alter the course of the chronic disease, has been used on rare occasions in pregnancy.


In vivo self-assembly of TMV-like particles in yeast and bacteria for nanotechnological applications.
Heterologous expression of tobacco mosaic virus coat protein and in vivo assembly of rod-shaped TMV-like particles encapsidating viral or host RNA were compared between Escherichia coli and Schizosaccharomyces pombe. TMV-like particles were produced in both hosts, irrespective of whether the TMV origin of assembly was present. The additional plasmid providing an OAS-containing RNA was able to alter the length distribution of the TMV-like particles. Plant and yeast-expressed CP behaved similarly upon isoelectric focusing, whereas CP expressed in bacteria migrated differently. After purification by buoyant density centrifugation, the encapsidated nucleic acids were determined to be of host origin as well as of viral origin. OAS-containing mRNA was packaged preferentially in yeast to some extent (8%). In consequence, the majority of TMV-like particles showed the same length distribution similar to those in the absence of OAS-containing mRNA, likely due to host RNA being primarily encapsidated. Notwithstanding this limitation for tailoring particle sizes, the heterologous expression system provides a new avenue to deliver versatile nucleoprotein scaffolds for a diversity of nanotechnological applications, without the need for an infectious virus. The results are discussed with reference to the competition of translation and packaging as well as to the selective decay of TMV RNA.


Effect of Toll-like receptor 4 deficiency on clinical severity and expression of Th1/Th2/Th17-associated cytokines in a murine model of experimental autoimmune neuritis.
The aim was to observe the effect of Toll-like receptor 4 (TLR4) deficiency on clinical severity and expression of Th1/Th2/Th17-associated cytokines in experimental autoimmune neuritis (EAN). We selected C57BL/10 wild type (WT) mice and TLR4 knockout (KO) mice with the C57BL/10 background for induction of the EAN model by immunizing mice twice (days 0 and 8) via subcutaneous injection of 180 μg P0 peptide 180-199 emulsion in 25 μl of PBS and 0.5 mg Mycobacterium tuberculosis (Difco, USA) in 25 μl of Freund's incomplete adjuvant into the back of mice. The concentrations of serum cytokines (IL-2, IL-4, IL-6, IL-10, IL-17A, IFN-γ and TNF) were determined using the Ms Th1/Th2/Th17 CBA kit. We found that TLR4 deficiency could attenuate the clinical severity and delay the onset of EAN. Moreover, our data showed that the sera levels of IFN-γ, TNF, IL-6 and IL-17A were elevated in the WT mice with EAN when compared with the naive WT mice, but only the production of IL-17A was significantly lower in the TLR4 KO mice with EAN than in their WT counterparts. Based on these findings, TLR4 may contribute to the pathogenesis of EAN by regulating Th17 cells and the production of Th17-associated factors. However, the exact mechanism remains unclear and more evidence is needed to elucidate its role in EAN.


The Appendix Orchestrates T-Cell Mediated Immunosurveillance in Colitis-Associated Cancer.
Although appendectomy may reduce colorectal inflammation in patients with ulcerative colitis (UC), this surgical procedure has been suggested to be associated with an increased risk of colitis-associated cancer (CAC). Our aim was to explore the mechanism underlying the appendectomy-associated increased risk of CAC. Five-week-old male BALB/c mice underwent appendectomy, appendicitis induction, or sham laparotomy. They were then exposed to azoxymethane/dextran sodium sulfate (AOM/DSS) to induce CAC. Mice were killed 12 weeks later, and colons were taken for pathological analysis and immunohistochemistry (CD3 and CD8 staining). Human colonic tumors from 21 patients with UC who underwent surgical resection for CAC were immunophenotyped and stratified according to appendectomy status. Whereas appendectomy significantly reduced colitis severity and increased CAC number, appendicitis induction without appendectomy led to opposite results. Intratumor CD3+ and CD8+ T-cell densities were lower after appendectomy and higher after appendicitis induction compared with the sham laparotomy group. Blocking lymphocyte trafficking to the colon with the anti-α4β7 integrin antibody or a sphingosine-1-phosphate receptor agonist suppressed the inducing effect of the appendectomy on tumors' number and on CD3+/CD8+ intratumoral density. CD8+ or CD3+ T cells isolated from inflammatory neo-appendix and intravenously injected into AOM/DSS-treated recipient mice increased CD3+/CD8+ T-cell tumor infiltration and decreased tumor number. In UC patients with a history of appendectomy, intratumor CD3+ and CD8+ T-cell densities were decreased compared with UC patients without history of appendectomy. In UC, appendectomy could suppress a major site of T-cell priming, resulting in a less efficient CAC immunosurveillance.


Facile Proton Transport in Ammonium Borosulfate-An Unhumidified Solid Acid Polyelectrolyte for Intermediate Temperatures.
High proton conductivity is reported for unhumidified ammonium borosulfate, NH4 [B(SO4 )2 ], a solid acid coordination polymer that contains 1D, hydrogen-bonded NH4 + ···1 ∞ [B(SO4 )4/2 ]- chains. NH4 [B(SO4 )2 ] is thermally stable to 320 °C and is amenable to sintering into monolithic, polycrystalline discs at 200 °C and about 300 MPa of uniaxial pressure. Impedance spectroscopy measurements reveal ionic conductivities for sintered ammonium borosulfate of 0.1 mS cm-1 at 25 °C and up to 10 mS cm-1 at 180 °C in ambient air. No superprotonic transition is observed in the temperature range of 25-180 °C. Ab initio molecular dynamics simulations show these high conductivities are aided by free rotation of the NH4 + units and significant gyrational mobility of the SO4 tetrahedra, which, in turn, provide facile pathways for proton locomotion. High conductivities, a wide operational temperature window, and tolerance to both ambient and anhydrous conditions make NH4 [B(SO4 )]2 an attractive candidate electrolyte for intermediate-temperature hydrogen fuel cells that may enable operation at temperatures as high as 300 °C without active humidification.


CD34(+)/interleukin-5Ralpha messenger RNA+ cells in the bronchial mucosa in asthma: potential airway eosinophil progenitors.
Eosinophil differentiation is thought to occur by the action of interleukin (IL)-5 on CD34(+) progenitor cells. The allergen-induced increase in eosinophil numbers in isolated airway preparations in vitro, and detection of increased numbers of circulating CD34(+) cells in atopic subjects, led us to the hypothesis that the eosinophil infiltration of the airway in asthma may result from local mucosal differentiation, in addition to recruitment from the bone marrow. We examined CD34(+) cell numbers by immunohistochemistry and IL-5 receptor alpha (IL-5Ralpha) messenger RNA (mRNA) expression by in situ hybridization in bronchial biopsies from atopic asthmatic patients, and from atopic and nonatopic control subjects. CD34(+) cell numbers were increased in the airway in atopic asthmatic and atopic nonasthmatic subjects. In contrast, CD34(+)/ IL-5Ralpha mRNA+ cells were increased in asthmatic subjects when compared with both atopic and nonatopic control subjects. Airway numbers of CD34(+)/IL-5Ralpha mRNA+ cells were correlated to airway caliber in asthmatic subjects and to eosinophil numbers. These findings support the concept that eosinophils may differentiate locally in the airway in asthma.


Prevalence of cardiovascular diseases in elderly Chinese people in Taiwan.
In order to study the health status and prevalence of diseases in elderly Chinese people in Taiwan, a hospital-based, physician-conducted epidemiological survey was undertaken. Study subjects were people aged > or = 65 years who were randomly selected from four regions of Taiwan. A total of 2600 subjects were studied. Most of the study subjects visited the hospitals for detailed history taking, physical examination and laboratory tests, including urinalysis, blood chemistry, electrocardiography, and chest and lumbar spine radiography. The cardiovascular data of 2518 subjects (males 1283) comprised this report. The prevalence of hypertension in the aged Chinese in Taiwan was high in both males and females (males 33.2%, females 40.9%, combined 37%). Coronary artery disease was also common (11.4%), but the prevalence was relatively low compared with Western people. Other cardiovascular diseases such as aortic aneurysm and valvular heart disease were rare. About 70% of the electrocardiograms were found abnormal. This well-organized, large-scale epidemiological survey not only presents useful information for local medical care for the elderly but also provides important data for comparison between different people in the world.


Leukocyte transcellular diapedesis: Rap1b is in control.
The neutrophil transmigration across the blood endothelial cell barrier represents the prerequisite step of innate inflammation. It is well known that neutrophils cross the endothelial barrier by transmigrating at the endothelial cell junction ('paracellular'). However, in vivo and in vitro evidence have clearly demonstrated occurrence of an alternate mode of migration directly through the endothelial cell body ('transcellular'). Despite our knowledge on mechanisms of transendothelial migration, it remains unclear which factors determine distinct modes of migration. We recently found that the Ras-like Rap1b GTPase limits neutrophil transcellular migration. Rap1b restrains transcellular migration by suppressing Akt-driven invasive protrusions while leaving the paracellular route unaffected. Furthermore, Rap1b limits neutrophil tissue infiltration in mice and prevents hyper susceptibility to endotoxin shock. These findings uncover a novel role for Rap1b in neutrophil migration and inflammation. Importantly, they offer emerging evidences that paracellular and transcellular migration of neutrophils are regulated by separate mechanisms. Here, we discuss the mechanisms of neutrophil transmigration and their clinical importance for vascular integrity and innate inflammation.


The development of a high-affinity conformation-sensitive antibody mimetic using a biocompatible copolymer carrier (iBody).
Peptide display methods are a powerful tool for discovering new ligands of pharmacologically relevant targets. However, the selected ligands often suffer from low affinity. Using phage display, we identified a new bicyclic peptide binder of prostate-specific membrane antigen (PSMA), a metalloprotease frequently overexpressed in prostate cancer. We show that linking multiple copies of a selected low-affinity peptide to a biocompatible water-soluble N-(2-hydroxypropyl)methacrylamide copolymer carrier (iBody) improved binding of the conjugate by several orders of magnitude. Furthermore, using ELISA, enzyme kinetics, confocal microscopy, and other approaches, we demonstrate that the resulting iBody can distinguish between different conformations of the target protein. The possibility to develop stable, fully synthetic, conformation-selective antibody mimetics has potential applications for molecular recognition, diagnosis and treatment of many pathologies. This strategy could significantly contribute to more effective drug discovery and design.


Identification by suppression subtractive hybridization of genes expressed in pear (Pyrus spp.) upon infestation with Cacopsylla pyri (Homoptera: Psyllidae).
The molecular interaction between pear tree (Pyrus spp.) and the phloem-feeding psylla Cacopsylla pyri (Linnaeus) was investigated through the construction and characterization of cDNA subtracted libraries. Genes expressed upon insect infestation were identified in the susceptible pear cultivar Bartlett and in the resistant selection NY10355. In both interactions, genes involved in the plant defense response were induced, confirming the observed similarity between the response to pathogens and to insects with piercing/sucking mouthparts. However, the two expression profiles were found to be different, with more genes involved in the response to biotic and abiotic stress being activated in the resistant plant than in the susceptible one. Further characterization of the identified genes could lead to the development of molecular markers associated with tolerance/resistance to pear psylla.


Kupffer Cells Mediate Systemic Antifungal Immunity.
Patients with liver dysfunction have increased susceptibility to fungal infections. A recently published article (Sun et al.) describes the potential mechanism underlying this association, which maps to the antifungal activity of liver-resident Kupffer cells. This research highlights the importance of understanding tissue-specific immune responses in disease pathogenesis.


Experimental study of Forsythoside A on prevention and treatment of avian infectious bronchitis.
Forsythoside A is the main active ingredient in the Chinese medicine Forsythia suspensa, which has antiviral, anti-inflammatory, antioxidation, and immunoregulatory effects. It is reported that Forsythoside A can significantly inhibit the replication of the avian infectious bronchitis virus(IBV) in cells, but there is no report in chickens. The present study aimed to investigate the effect of Forsythoside A on IBV-M41, experiments were designed using 120 chickens at 12 days of age. The chickens were randomly divided into eight groups: Forsythoside A high-, medium-, and low-dose prevention groups, Forsythoside A high-, medium-, and low-dose treatment groups, model control group and normal control group. All chickens, except the normal control group, were inoculated with 0.2 ml of IBV-M41 at 15 days of age.The antiviral effects were evaluated by clinical signs, weight, histopathology, T-,B-lymphocyte proliferation, T-lymphocyte subsets and cytokine levels.The results showed that the infection rate in each Forsythoside A prevention group was significantly lower than that in the treatment group and model control group (P < 0.05). The recovery rate in each Forsythoside A treatment group was significantly higher than that in the model control group (P < 0.05), and the recovery rate in high- and medium-dose treatment group was the highest, at up to 86.67%. Lymphocytic transformation ability significantly improved in the prevention and treatment groups. Forsythoside A significantly improved the CD3+, CD4+, and CD8+ T-lymphocyte of infected chickens. The cytokine level was able to maintain high concentrations of IL-2 and IFN-α for a long time and maintain a dynamic IL-4-concentration balance. A number of results showed that Forsythoside A had both preventive and therapeutic effects in IBV-M41-infected chickens, among which the high-dose (80 mg/kg/d) prevention group,the high- (80 mg/kg/d) and medium (40 mg/kg/d) -dose treatment group had significant effects.


Novel fractional order SIDARTHE mathematical model of COVID-19 pandemic.
Nowadays, COVID-19 has put a significant responsibility on all of us around the world from its detection to its remediation. The globe suffer from lockdown due to COVID-19 pandemic. The researchers are doing their best to discover the nature of this pandemic and try to produce the possible plans to control it. One of the most effective method to understand and control the evolution of this pandemic is to model it via an efficient mathematical model. In this paper, we propose to model COVID-19 pandemic by fractional order SIDARTHE model which did not appear in the literature before. The existence of a stable solution of the fractional order COVID-19 SIDARTHE model is proved and the fractional order necessary conditions of four proposed control strategies are produced. The sensitivity of the fractional order COVID-19 SIDARTHE model to the fractional order and the infection rate parameters are displayed. All studies are numerically simulated using MATLAB software via fractional order differential equation solver.


Influence of a long-term high-fat diet on ghrelin secretion and ghrelin-induced food intake in rats.
The aims of this study were: (1) to define the extent to which a high-fat (HF) diet given on a long-term basis reduces resting plasma ghrelin (total [acyl+des-acyl]) levels and the plasma ghrelin (total) response to fasting, (2) to determine whether a chronic HF diet modifies the orexigenic activity of acyl-ghrelin, (3) whether insulin pretreatment inhibits the plasma ghrelin (total) response to fasting, and (4) the extent to which pioglitazone (PIO) treatment will increase stomach and plasma ghrelin (total) levels in rats fed a HF diet. PIO is a drug given to diabetics which improves insulin resistance. Our findings show that a chronic HF diet given for either 10 or 60 weeks exerts a persistent inhibitory effect on resting plasma ghrelin (total) levels. Additionally, the plasma ghrelin (total) elevation to overnight fasting is not altered in rats fed a HF diet on a long-term basis. A HF diet does not impair the ingestive response to acyl-ghrelin. Together, these results suggest that acyl-ghrelin serves as an important orexigenic factor. Results show that insulin pretreatment does not inhibit the plasma ghrelin (total) response to fasting suggesting that meal-induced insulin secretion does not have a role in reducing ghrelin (total) secretion. In rats fed a HF diet, PIO administration increases stomach ghrelin (total) levels. Because PIO can reduce systemic glucose and lipid levels, our findings suggest that elevated glucose and lipid levels are part of the inhibitory mechanism behind reduced ghrelin (total) secretion in rats fed a HF diet.


A modified pectoralis muscle flap for closure of postpneumonectomy esophagopleural fistula: technique and results.
In surgical treatment of late postpneumonectomy esophagopleural fistula, closure of the empyema space is of prime importance. A wide thoracoplasty and ample decapitation of the empyema cavity allow sufficient room for a modified pectoralis muscle flap, which provides sufficient mass to obliterate the entire empyema cavity. We present the cases of 2 patients in whom an esophagopleural fistula occurring 3 and 16 years after pneumonectomy was successfully closed by this method.


Renal hemodynamic response to intrarenal infusion of calcitonin gene-related peptide in dogs.
The renal hemodynamic and excretory effects of intrarenal infusions of synthetic beta-human calcitonin gene-related peptide (beta-hCGRP) were examined in normal sodium replete dogs (Group 1, n = 6), in sodium replete dogs pretreated with indomethacin (Group 2, n = 6), and in sodium deplete dogs (Group 3, n = 5). In all groups of anesthetized dogs beta-hCGRP was infused at 5 and 10 ng.kg-1.min-1 for 50 min periods each. In the sodium replete group, beta-hCGRP infusions strikingly increased renal blood flow, but this response was markedly attenuated in the other 2 groups. During beta-hCGRP infusions, the clearance of creatinine also increased significantly in the sodium replete and deplete groups, but not in the indomethacin pretreated animals. No consistent changes in urinary sodium excretion or plasma renin activity were observed with beta-hCGRP infusions in any of the 3 groups of dogs. These results indicate that beta-hCGRP is a potent renal vasodilator and can increase renal blood flow and glomerular filtration. The data also suggest that the renal hemodynamic actions of beta-hCGRP are partially mediated by renal prostaglandins, and that the vasodilatory effects of beta-hCGRP may be antagonized by high circulating levels of endogenous angiotensin II in sodium-volume depletion. Finally, beta-hCGRP does not appear to have significant actions on urinary sodium excretion or plasma renin activity under the experimental conditions of the present study.


Effect of abnormal notochord delamination on hindgut development in the Adriamycin mouse model.
Adriamycin mouse model (AMM) is a model of VACTERL anomalies. Sonic hedgehog (Shh) pathway, sourced by the notochord, is implicated of anorectal malformations. We hypothesized hindgut anomalies observed in the AMM are the result of abnormal effect of the notochord. Time-mated CBA/Ca mice received two intraperitoneal injections of Adriamycin (6 mg/kg) or saline as control on embryonic day (E) 7 and 8. Fetuses were harvested from E9 to E11, stained following whole mount in situ hybridization with labeled RNA probes to detect Shh and Fork head box F1(Foxf1) transcripts. Immunolocalization with endoderm marker Hnf3β was used to visualize morphology. Embryos were scanned by OPT to obtain 3D representations of expressions. In AMM, the notochord was abnormally displaced ventrally with attachment to the hindgut endoderm in 71 % of the specimens. In 32 % of the treated embryos abnormal hindgut ended blindly in a cystic structure, and both of types were remarked in 29 % of treated embryos. Endodermal Shh and mesenchymal Foxf1 genes expression were preserved around the hindgut cystic malformation. The delamination of the developing notochord in the AMM is disrupted, which may influence signaling mechanisms from the notochord to the hindgut resulting in abnormal patterning of the hindgut.


Brachybacterium nesterenkovii isolated from a human blood culture-a first report.
Brachybacterium is a genus of Gram-positive bacteria that rarely causes infections in humans. Here we report the case of an 8-month-old infant who presented with an acute febrile illness. During the diagnostic process, a blood culture was positive with Gram-positive cocci that were identified as Brachybacterium nesterenkovii by MALDI-TOF. As a result of the unclear clinical significance of this isolate and the continuous febrile state, a second blood culture was taken and returned B. nesterenkovii once more. To our knowledge this is the first time that B. nesterenkovii has been isolated from human blood cultures during the course of a systemic infection.


30-day Readmission After Pancreatic Resection: A Systematic Review of the Literature and Meta-analysis.
The aim of this study was to identify and compare common reasons and risk factors for 30-day readmission after pancreatic resection. Hospital readmission after pancreatic resection is common and costly. Many studies have evaluated this problem and numerous discrepancies exist regarding the primary reasons and risk factors for readmission. Multiple electronic databases were searched from 2002 to 2016, and 15 relevant articles identified. Overall readmission rate was calculated from individual study estimates using a random-effects model. Study data were combined and overall estimates of odds ratios (ORs) and 95% confidence intervals (CIs) were calculated for each risk factor. Multivariable data were qualitatively synthesized. The overall 30-day readmission rate was 19.1% (95% CI 17.4-20.7) across all studies. Infectious complications and gastrointestinal disorders, such as failure to thrive and delayed gastric emptying, together accounted for 58.9% of all readmissions. Demographic factors did not predict readmission. Heart disease (OR 1.37, 95% CI 1.12-1.67), hypertension (OR 1.44, 95% CI 1.09-1.91), and intraoperative blood transfusion (OR 1.45, 95% CI 1.15-1.83) were weak predictors of readmission, while any postoperative complications (OR 2.22, 95% CI 1.55-3.18) or severe complications (OR 2.84, 95% CI 1.65-4.89) were stronger predictors. Readmission after pancreatic resection is common and can largely be attributed to infectious complications and inability to maintain adequate hydration and nutrition. Focus on outpatient resources and follow-up to address these issues will prove valuable in reducing readmissions.


Rep-PCR genotyping of infectious Acinetobacter spp. strains from patients treated in Intensive Care Unit of Emergency Department (ICU of ED)--preliminary report.
Strains of Acinetobacter spp. are responsible for a considerable percentage of hospital infections. These pathogens have colonized hospital environment and developed resistance to many currently available antibiotics. The aim of this study was one year-long analysis of the occurrence of multiresistant strains of Acinetobacter spp. in population of patients hospitalized in ICU of ED and determination of their genetic similarity. Subject of research was the population of patients admitted to ED of University Hospital in Bialystok in the period from 01.08.2010 to 01.08.2011. In the analysed group of patients, infections were identified on the basis of the guidelines of CDC. Identification and drug susceptibility of strains was specified using the automatic methods with the analyzer Vitek 2XL. Genotyping using Rep-PCR method in DiversiLab system was performed on strains of Acinetobacter spp. to determinate their genetic similarity. During analyzed period 405 patients were hospitalized, from 14 of them multiresistant strains of Acinetobacter spp. were isolated. Conducted genetic research allowed to detect 5 clones. Rep-PCR method in DiversiLab system enabled to learn that different clone of multiresistant strain of Acinetobacter spp. is responsible for variable forms of infection. Results of conducted research suggest that genotyping with rep-PCR method in DiversiLab system is useful tool in diagnostics of clones of multiresistant pathogens isolated from patients requiring intensive care, hospitalized in ED. Genotyping with rep-PCR method combined with epidemiological investigation enables to establish ways of spreading of multiresistant strains of Acinetobacter spp. in ED.


General Complications after Endoscopic Sinus Surgery in Smokers: A 2005-2016 NSQIP Analysis.
Exposure to cigarette smoke has been associated with a higher incidence of postoperative complications across a variety of surgical specialties. However, it is unclear if smoking increases this risk after endoscopic sinus surgery (ESS). Because complication rates after ESS are relatively low, a large national database allows for a statistically meaningful study of this topic. The American College of Surgeons National Surgical Quality Improvement Program (ACS-NSQIP) dataset from 2005 to 2016 was analyzed. Patients who underwent ESS were identified. Thirty-day postoperative complication rates between smokers and nonsmokers were compared. Complications included infection, thromboembolic events, reintubation, readmission, acute renal failure, and cardiovascular events. 921 patients who underwent ESS were identified. 182 (20%) were smokers and 739 (80%) were nonsmokers. 609 patients underwent outpatient ESS, while 312 patients underwent inpatient ESS. A total of 12 patients experienced postoperative surgical site infections involving the deeper tissues beyond the wound (organ/space SSI). On univariate analysis, smoking was associated with a higher incidence of organ/space SSI (P = .0067) and pulmonary embolism (P = .0321) after ESS. On multivariate logistic regression, smoking was associated with increased odds (4.495, 1.11- 8.17, P = .0347) of organ/space SSI after ESS. This study demonstrates an association between exposure to cigarette smoke and potentially serious surgical site infections in the 30-day postoperative period after ESS. Our findings may help when counseling smokers who are considering ESS. Further study is required to understand the nature of these infections and ways to prevent them.Level of Evidence: 2c ("health outcomes").


Inductive bias strength in knowledge-based neural networks: application to magnetic resonance spectroscopy of breast tissues.
The integration of symbolic knowledge with artificial neural networks is becoming an increasingly popular paradigm for solving real-world applications. The paradigm provides means for using prior knowledge to determine the network architecture, to program a subset of weights to induce a learning bias which guide network training, and to extract knowledge from trained networks. The role of neural networks then becomes that of knowledge refinement. It thus provides a methodology for dealing with uncertainty in the prior knowledge. We address the open question of how to determine the strength of the inductive bias of programmed weights; we present a quantitative solution which takes the network architecture, the prior knowledge, and the training data into consideration. We apply our solution to the difficult problem of analyzing breast tissue from magnetic resonance spectroscopy (MRS); the available database is extremely limited and cannot be adequately explained by expert knowledge alone.


An evaluation of the use of the auditory brain-stem electric response test in paediatric audiological assessment.
A retrospective study was made of hearing thresholds determined by the click-evoked Brain Stem Electric Response (BSER) and behavioural tests of hearing in 200 babies and children. BSER thresholds were found to agree within 20 dB with high frequency hearing levels in 89 out of 99 children who performed free-field tests of hearing and in 87% of ears in children tested with pure-tone audiometry. In 61 children who were too young or too handicapped to perform on behavioural tests of hearing, a hearing loss was indicated by BSER in 48 out of 121 ears. The majority of these losses occurred in the handicapped group. The advantages and limitations of behavioural tests and BSER are discussed.


Bone Progenitors Pull the Strings on the Early Metabolic Rewiring Occurring in Prostate Cancer Cells.
Metastatic prostate cancer (PCa) cells soiling in the bone require a metabolic adaptation. Here, we identified the metabolic genes fueling the seeding of PCa in the bone niche. Using a transwell co-culture system of PCa (PC3) and bone progenitor cells (MC3T3 or Raw264.7), we assessed the transcriptome of PC3 cells modulated by soluble factors released from bone precursors. In a Principal Component Analysis using transcriptomic data from human PCa samples (GSE74685), the altered metabolic genes found in vitro were able to stratify PCa patients in two defined groups: primary PCa and bone metastasis, confirmed by an unsupervised clustering analysis. Thus, the early transcriptional metabolic profile triggered in the in vitro model has a clinical correlate in human bone metastatic samples. Further, the expression levels of five metabolic genes (VDR, PPARA, SLC16A1, GPX1 and PAPSS2) were independent risk-predictors of death in the SU2C-PCF dataset and a risk score model built using this lipid-associated signature was able to discriminate a subgroup of bone metastatic PCa patients with a 23-fold higher risk of death. This signature was validated in a PDX pre-clinical model when comparing MDA-PCa-183 growing intrafemorally vs. subcutaneously, and appears to be under the regulatory control of the Protein Kinase A (PKA) signaling pathway. Secretome analyses of conditioned media showcased fibronectin and type-1 collagen as critical bone-secreted factors that could regulate tumoral PKA. Overall, we identified a novel lipid gene signature, driving PCa aggressive metastatic disease pointing to PKA as a potential hub to halt progression.


Effects of nucleotide pool imbalances on the excision repair of ultraviolet-induced damage in the DNA of human diploid fibroblasts.
Recent studies in our laboratory and others have demonstrated that DNA polymerase inhibitors such as the ara nucleosides, aphicolin and dideoxythymidine are potent inhibitors of the DNA excision repair process in confluent human fibroblasts as evidenced by the agent-dependent accumulation of single-strand interruptions in the DNA of UV-irradiated, but not in unirradiated, cellular DNA. In rapidly cycling cells, on the other hand, these agents are weak inhibitors at best but when used in combination with the ribonucleotide reductase inhibitor, hydroxyurea, a significant enhancement of inhibitory capacity is seen. In an attempt to better understand the mechanism of repair inhibition by DNA polymerase inhibitors, and the nature of this hydroxyurea enhancement, experiments were initiated in which the effects of a series of ribonucleotide reductase inhibitors on dNTP pools and on the DNA repair process were determined in both quiescent cultures and log-phase cultures of human fibroblasts. It was determined that hydroxyurea, deoxyadenosine, pyridine-2-carboxaldehyde thiosemicarbazone (TSC), pyrozoloimidazole (IMPY), 3,5-diamino-1,2,4-triazole (guanazole), 3,4,5-trihydroxy benzohydroxamic acid (THBA) and 3,4-dihydroxy benzohydroxamic acid (DHBA) are all effective inhibitors of the DNA repair process in confluent cells but not in log-phase cells. Moreover, the effects of these inhibitors can be reversed by the addition of certain combinations of deoxynucleosides. These reversal studies and the direct analysis of dNTP pool modulation by these compounds in log phase and confluent cultures support the notion that specific pool depletions rather than general imbalance of pools gives rise to the inhibition of the DNA excision repair process.


Neuromuscular system of the causative agent of dicrocoeliosis, Dicrocoelium lanceatum. II. Neuropeptide FMRFamide immunoreactivity in nervous system.
The parasitic flatworm, trematoda Dicrocoelium lanceatum or lancet fluke is the causative agent of a widespread parasite disease of grazing ruminants, dicrocoeliosis. The aim of this work is the study of the presence and localization of neuropeptide FMRFamide immunoreactive elements in the nervous system of D. lanceatum using immunocytochemical technique and confocal scanning laser microscopy. For the first time the data on the presence and distribution of the FMRFamide-immunopositive components in the central and peripheral departments of the nervous system of D. lanceatum has been obtained. FMRFamidergic neurons and neurites were identified in paired brain ganglia, in the brain commissure, longitudinal nerve cords and connective nerve commissures. The innervation of the oral and ventral suckers by peptidergic nerve structures was revealed. The distal part of the reproductive system is innervated by FMRFamide immunopositive neurites. The data obtained suggest that the neuropeptides of FMRFamide family can be involved in the regulation of functions of the attachment organs and the reproductive system in D. lanceatum. The study of neurotransmitters and their functions in flatworms expand our knowledge on the structure and function of the nervous system of trematodes of various taxonomic groups. The results obtained on the morphological organization of D. lanceatum nervous system support the exploitation of the FMRFamidergic components as an anthelmintic target.


Resource utilization associated with cervical hematoma after thyroid and parathyroid surgery.
Postoperative cervical hematoma (PCH) after thyroid and parathyroid surgery is a well-known complication. This study used data from the Nationwide Inpatient Sample to identify risk factors, estimate mortality, length of stay (LOS), and total costs attributable to PCH in patients undergoing procedures for thyroid and parathyroid diseases. Patients aged >18 y who underwent thyroid or parathyroid surgery between 2001 and 2011 were identified and stratified by the occurrence of PCH. Univariate analyses of patient demographics, clinical and hospital characteristics were performed. Multivariable logistic regression was used to determine risk factors for hematoma formation. LOS and costs were fit to linear regression models to determine the effect of PCH after adjusting for patient and hospital characteristics. Of patients who underwent thyroid or parathyroid surgery, 619 patients (0.8%) had a PCH. Predisposing factors included nonelective admission (emergent: OR = 2.01, P < 0.0001; urgent: OR = 1.47, P = 0.003), diagnosis of Graves' disease (OR = 1.90, P < 0.0001), or other benign pathology (OR = 1.43, P = 0.011) and having ≥2 comorbidities (2-3 comorbidities, OR = 1.24; P = 0.036 and ≥ 4 comorbidities, OR = 2.28; P < 0.0001). After adjusting for those characteristics, the total excess LOS and costs attributable to PCH were 2.1 d (P < 0.0001) and $7316 (P < 0.0001), respectively. In addition, after risk adjustment, odds of mortality more than tripled (P < 0.0001) in the setting of PCH. Because risk for PCH is largely driven by preoperative patient risk factors, five clinicians have an opportunity to stratify patients accordingly and thereby minimize the resource utilization and health care spending among those with lowest risk.


Comparison of different techniques for in microgravity-a simple mathematic estimation of cardiopulmonary resuscitation quality for space environment.
Since astronauts are selected carefully, are usually young, and are intensively observed before and during training, relevant medical problems are rare. Nevertheless, there is a certain risk for a cardiac arrest in space requiring cardiopulmonary resuscitation (CPR). Up to now, there are 5 known techniques to perform CPR in microgravity. The aim of the present study was to analyze different techniques for CPR during microgravity about quality of CPR. To identify relevant publications on CPR quality in microgravity, a systematic analysis with defined searching criteria was performed in the PubMed database (http://www.pubmed.com). For analysis, the keywords ("reanimation" or "CPR" or "resuscitation") and ("space" or "microgravity" or "weightlessness") and the specific names of the techniques ("Standard-technique" or "Straddling-manoeuvre" or "Reverse-bear-hug-technique" or "Evetts-Russomano-technique" or "Hand-stand-technique") were used. To compare quality and effectiveness of different techniques, we used the compression product (CP), a mathematical estimation for cardiac output. Using the predefined keywords for literature search, 4 different publications were identified (parabolic flight or under simulated conditions on earth) dealing with CPR efforts in microgravity and giving specific numbers. No study was performed under real-space conditions. Regarding compression depth, the handstand (HS) technique as well as the reverse bear hug (RBH) technique met parameters of the guidelines for CPR in 1G environments best (HS ratio, 0.91 ± 0.07; RBH ratio, 0.82 ± 0.13). Concerning compression rate, 4 of 5 techniques reached the required compression rate (ratio: HS, 1.08 ± 0.11; Evetts-Russomano [ER], 1.01 ± 0.06; standard side straddle, 1.00 ± 0.03; and straddling maneuver, 1.03 ± 0.12). The RBH method did not meet the required criteria (0.89 ± 0.09). The HS method showed the highest cardiac output (69.3% above the required CP), followed by the ER technique (33.0% above the required CP). Concerning CPR quality, the HS seems to be most effective to treat a cardiac arrest. In some environmental conditions where this technique cannot be used, the ER technique is a good alternative because CPR quality is only slightly lower.


Preparation and characterization of radioactive castanospermine.
A procedure for the preparation of tritiated castanospermine is described. The tritiated alkaloid was shown to be chromatographically identical to the native material and exhibited the same inhibitory properties. Radiolabeled castanospermine tightly bound to purified intestinal sucrase. Following gel chromatography, each mole of enzyme was shown to have bound 1 mol of the radioactive alkaloid. Cultured MDCK cells were also shown to take up the labeled castanospermine. This compound should be a useful tool in the investigation of enzymes that are responsible for the processing of glycoprotein oligosaccharides.


[Acrosome--its protein composition and function].
In situ studies on total proteins and some hydrolytic enzymes extracted by acid treatment of the bull sperm acrosomes were carried out. The acrosomal proteins studied by cathodic disc electrophoresis (pH 4.3) were found to be polymorphic, with three phenotypes. The isoenzyme pattern of the acrosomal enzymes under study (acrosin, acid phosphatase and non-specific esterases) was identified as well.


Pre and post axial polysyndactyly, microcephaly and ptosis.
A five-year-old boy of Iranian origin with multiple anomalies is described. His parents are first and second cousins. He presented with short stature, psychomotor retardation, microcephaly, ptosis, dacryostenosis, partial left nerve deafness, high arched palate, bifid uvula, total fusion between incisors, asymmetric preaxial and postaxial polysyndactyly, brachyphalangy, kyphosis and spina bifida occulta of S1. To our knowledge, a similar case has not been reported previously.


The change of vascular reactivity to angiotensin II and norepinephrine in the two-kidney, one-clip renovascular hypertensive rabbit.
The change of the response to angiotensin II (AII) and norepinephrine (NE) was evaluated in vivo and vitro in the chronic phase of two-kidney, one-clip renovascular hypertensive rabbits. In the constricted group, systemic blood pressure (BP) was significantly higher and plasma renin activity (PRA) was significantly lower than in the control group. Subpressor doses of AII and NE injections in the constricted group produced significant elevations of BP. In the aortic, renal and iliac arterial strips, the reactivity to AII (10(-10) to 10(-8) M) and NE (10(-10) to 10(-7) M) was significantly increased in the constricted group as compared to the control group. In the constricted group, sodium loading produced BP elevation with decreased PRA and shifted the dose-response curves by AII and NE to the left, whereas sodium restriction decreased BP and shifted the curves to the right. In the control group, altered sodium intake did not affect BP but affected only the dose-response curves by AII. These results suggested that in the chronic phase of renovascular hypertensive rabbits, the increased reactivity to AII and NE may contribute to the maintenance of hypertension.


5-Alkyl-2-[(methylthiomethyl)thio]-6-(benzyl)-pyrimidin-4-(1H)-ones as potent non-nucleoside reverse transcriptase inhibitors of S-DABO series.
Novel dihydroalkoxybenzyloxopyrimidine (S-DABO) derivatives targeting the non-nucleoside inhibitor (NNI) binding site of human immunodeficiency virus (HIV) reverse transcriptase (RT) have been synthesized using a novel computer model for the NNI binding pocket and tested for their RT inhibitory activity in cell-free assays using purified recombinant HIV RT as well as for their anti-HIV activity in HTL VIIIB-infected peripheral blood mononuclear cells. Our computational approach allowed the identification of several ligand derivatization sites for the generation of more potent S-DABO derivatives. Our lead S-DABO derivative, 5-isopropyl-2-[(methylthiomethyl)thio]-6-(benzyl)-pyrimidin-4-(1H)-one (compound 3), elicited potent anti-HIV activity with an IC50 value of less than 1nM for inhibition of HIV replication without any evidence of cytotoxicity and an unprecedented selectivity index of > 100,000.


Size effects of latex nanomaterials on lung inflammation in mice.
Effects of nano-sized materials (nanomaterials) on sensitive population have not been well elucidated. This study examined the effects of pulmonary exposure to (latex) nanomaterials on lung inflammation related to lipopolysaccharide (LPS) or allergen in mice, especially in terms of their size-dependency. In protocol 1, ICR male mice were divided into 8 experimental groups that intratracheally received a single exposure to vehicle, latex nanomaterials (250 microg/animal) with three sizes (25, 50, and 100 nm), LPS (75 microg/animal), or LPS plus latex nanomaterials. In protocol 2, ICR male mice were divided into 8 experimental groups that intratracheally received repeated exposure to vehicle, latex nanomaterials (100 microg/animal), allergen (ovalbumin: OVA; 1 microg/animal), or allergen plus latex nanomaterials. In protocol 1, latex nanomaterials with all sizes exacerbated lung inflammation elicited by LPS, showing an overall trend of amplified lung expressions of proinflammatory cytokines. Furthermore, LPS plus nanomaterials, especially with size less than 50 nm, significantly elevated circulatory levels of fibrinogen, macrophage chemoattractant protein-1, and keratinocyte-derived chemoattractant, and von Willebrand factor as compared with LPS alone. The enhancement tended overall to be greater with the smaller nanomaterials than with the larger ones. In protocol 2, latex nanomaterials with all sizes did not significantly enhance the pathophysiology of allergic asthma, characterized by eosinophilic lung inflammation and Igs production, although latex nanomaterials with less than 50 nm significantly induced/enhanced neutrophilic lung inflammation. These results suggest that latex nanomaterials differentially affect two types of (innate and adaptive immunity-dominant) lung inflammation.


[An epidemiological study on canine leishmaniasis (CanL) and sand flies in Northern Cyprus].
In this study, the investigation on the prevalence of canine leishmaniasis (CanL) and sand fly species incriminated as potential vectors of leishmaniasis in the northern part of the Cyprus were aimed. This research was conducted in two periods; 2004 and 2012. Serological (IFAT and rK39) and molecular (PCR) tests were performed on 83 dog blood samples during the 2004 survey. PCR was performed using primers 13A/13B targeting kinetoplastid minicircle constant region. Genomic Nested-PCR was applied using R221/R332 and R323/333 primers for 5 clinically suspected dog samples in 2012. Sand flies were collected from the Lapithos town and Kyreniae province using CDC light traps and midgut dissection was done for the presence of Leishmania parasites during the 2012 survey. Three (3.61%) out of 83 dogs were found to be positive for CanL in 2004, while 3 out of 5 clinically suspected dogs were positive in 2012. In total 296 female sand flies were dissected and 9 species belonging to Phlebotomus and Sergentomyia genera were determined. No promastigote was found in the dissected females. The results obtained in two different periods showed that the importance and risk of canine disease are increasing in the northern Cyprus and further studies should be performed in northern Cyprus for determining the incidence of canine and human leishmaniasis.


Polydatin alleviates alcohol-induced acute liver injury in mice: Relevance of matrix metalloproteinases (MMPs) and hepatic antioxidants.
Alcohol, a most commonly consumed beverage, is the foremost cause of liver injury throughout the world. Polydatin, a stilbenoid glucoside, was known to possess antioxidant and anti-inflammatory properties and is being investigated for use in various disorders. The present study was intended at investigating the hepatoprotective efficacy of polydatin against acute-alcohol induced liver injury model in mice. C57BL/6 mice were fed with five doses of 50% ethyl alcohol (10ml/kg body weight) to induce acute liver injury. Effect of polydatin against alcohol induced hepatic injury was investigated by giving 50 or 100mg/kg polydatin, orally, for 8 days. Serum markers of liver injury, morphology, histology and fibrosis of liver tissue, levels of enzymatic and non-enzymatic antioxidants and the mitochondrial respiratory enzyme activities in liver tissue were investigated. The activities and the protein expression of matrix metalloproteinases (MMP-2 and -9), the expression of NF-κB in the liver tissue were also studied. Polydatin pre-treatment significantly alleviated the alcohol induced hepatic injury by reducing the serum liver injury markers, alanine aminotransferase (ALT) and aspartate aminotransferase (AST), attenuating oxidative stress and restoring antioxidant balance in the hepatic tissue. Simultaneously, polydatin pre-treatment also prevented alcohol induced mitochondrial damage and refurbished the matrix metalloproteinases levels of the hepatic tissue. The findings of the present study suggest that polydatin may have a potential benefit in preventing alcohol-induced acute hepatic injury.


Slip versus Slop: A Head-to-Head Comparison of UV-Protective Clothing to Sunscreen.
Ultraviolet radiation (UVR) exposure is the most important modifiable risk factor for skin cancer development. Although sunscreen and sun-protective clothing are essential tools to minimize UVR exposure, few studies have compared the two modalities head-to-head. This study evaluates the UV-protective capacity of four modern, sun-protective textiles and two broad-spectrum, organic sunscreens (SPF 30 and 50). Sun Protection Factor (SPF), Ultraviolet Protection Factor (UPF), Critical Wavelength (CW), and % UVA- and % UVB-blocking were measured for each fabric. UPF, CW, % UVA- and % UVB-blocking were measured for each sunscreen at 2 mg/cm2 (recommended areal density) and 1 mg/cm2 (simulating real-world consumer application). The four textiles provided superior UVR protection when compared to the two sunscreens tested. All fabrics blocked erythemogenic UVR better than the sunscreens, as measured by SPF, UPF, and % UVB-blocking. Each fabric was superior to the sunscreens in blocking full-spectrum UVR, as measured by CW and % UVA-blocking. Our data demonstrate the limitations of sunscreen and UV-protective clothing labeling and suggest the combination of SPF or UPF with % UVA-blocking may provide more suitable measures for broad-spectrum protection. While sunscreen remains an important photoprotective modality (especially for sites where clothing is impractical), these data suggest that clothing should be considered the cornerstone of UV protection.


Spatiotemporal processing of somatosensory stimuli in schizotypy.
Unusual interaction behaviors and perceptual aberrations, like those occurring in schizotypy and schizophrenia, may in part originate from impaired remapping of environmental stimuli in the body space. Such remapping is contributed by the integration of tactile and proprioceptive information about current body posture with other exteroceptive spatial information. Surprisingly, no study has investigated whether alterations in such remapping occur in psychosis-prone individuals. Four hundred eleven students were screened with respect to schizotypal traits using the Schizotypal Personality Questionnaire. A subgroup of them, classified as low, moderate, and high schizotypes were to perform a temporal order judgment task of tactile stimuli delivered on their hands, with both uncrossed and crossed arms. Results revealed marked differences in touch remapping in the high schizotypes as compared to low and moderate schizotypes. For the first time here we reveal that the remapping of environmental stimuli in the body space, an essential function to demarcate the boundaries between self and external world, is altered in schizotypy. Results are discussed in relation to recent models of 'self-disorders' as due to perceptual incoherence.


An ultrasensitive microchip electrophoresis chemiluminescence assay platform for detection of trace biomolecules.
An ultrasensitive microchip electrophoresis chemiluminescence (MCE-CL) assay platform based on separation assisted cascade signal amplification was developed for detection of trace biomolecules. In this work, the aptamer was used as a target probe to bind target molecule and triggering cascade signal amplification reaction. The horseradish peroxide labeled DNA (HRP-DNA) was used as signal probe, utilizing nucleic acid hybridization and exonuclease cutting technology realized ultrasensitive detection of biomolecules on the MCE-CL assay platform. Taking gamma interferon (IFN-γ) as a model analyte, the linear range for IFN-γ detection is 8.0 × 10-15-1.0 × 10-8 M, the detection limit is 1.6 fM, which is six orders magnitude lower than that of without signal amplification. The proposed method was successfully applied for the quantification of IFN-γ in human plasma samples. It was demonstrated that the MCE-CL assay platform was quick, sensitive, and highly selective. It may serve as a tool for clinical analysis of IFN-γ to assist in the diagnosis of disease.


Ion-assisted deposition of oxide materials at room temperature by use of different ion sources.
Thin films of SiO(2), TiO(2), Ta(2)O(5), ZrO(2), and the mixed oxide H4 (Merck) have been deposited onto nonheated glass substrates by electron-beam evaporation in commercial coating plants. All depositions have been carried out with ion assistance provided by three different ion or plasma sources (end-hall, plasma, and cold-cathode sources). The optical film properties such as index of refraction, extinction coefficient, light scattering, and absorption have been examined by spectrophotometry, laser calorimetry, and total integrated light-scatter measurements. Surface morphology has been investigated by atomic force microscopy studies. Furthermore, films have undergone sand erosion tests for the determination of relative wear resistance. The film properties are compared for the three different ion sources.


Translation initiator EIF4G1 mutations in familial Parkinson disease.
Genome-wide analysis of a multi-incident family with autosomal-dominant parkinsonism has implicated a locus on chromosomal region 3q26-q28. Linkage and disease segregation is explained by a missense mutation c.3614G>A (p.Arg1205His) in eukaryotic translation initiation factor 4-gamma (EIF4G1). Subsequent sequence and genotype analysis identified EIF4G1 c.1505C>T (p.Ala502Val), c.2056G>T (p.Gly686Cys), c.3490A>C (p.Ser1164Arg), c.3589C>T (p.Arg1197Trp) and c.3614G>A (p.Arg1205His) substitutions in affected subjects with familial parkinsonism and idiopathic Lewy body disease but not in control subjects. Despite different countries of origin, persons with EIF4G1 c.1505C>T (p.Ala502Val) or c.3614G>A (p.Arg1205His) mutations appear to share haplotypes consistent with ancestral founders. eIF4G1 p.Ala502Val and p.Arg1205His disrupt eIF4E or eIF3e binding, although the wild-type protein does not, and render mutant cells more vulnerable to reactive oxidative species. EIF4G1 mutations implicate mRNA translation initiation in familial parkinsonism and highlight a convergent pathway for monogenic, toxin and perhaps virally-induced Parkinson disease.


LC-MS/MS separation and quantitation of ribavirin in chicken and comparison of different mass spectrometric platforms.
A liquid chromatography-tandem mass spectrometry (LC-MS/MS) method was developed for the analysis of ribavirin in chicken. Samples was extracted with 0.1% formic acid and purified by Hypercarb cartridge prior to LC-MS/MS analysis. The eluates were evaporated to dryness, reconstituted in 1 mL 5mM ammonium acetate containing 5% acetonitrile (v/v) and 0.1% (v/v) formic acid. Chromatographic separation was performed on a Hypercarb analytical column under a gradient elution program with acetonitrile and 0.1% (v/v) formic acid in 5 mM ammonium acetate at a flow rate of 0.6 ml/min. The intraday and interday accuracy ranged from - 7.83 - 1.39%, and - 6.38 - 2.25%, with precisions between 1.34 - 3.88%% and 1.10 - 4.67%. The limits of detection (LODs) and limits of quantitation (LOQs) of ribavirin was 0.1 ng/mL and 0.5 ng/mL, respectively. The method was validated for linearity, accuracy, precision, matrix effect and stability. Application of the method confirmed 3 ribavirin positive samples out of 50 commercial chicken samples, with concentrations of ribavirin ranging from 0.9 μg/kg to 5.8 μg/kg a, respectively. Additionally, both AB Sciex 5500 and Agilent 6945B were proven to be suitable in ribavirin separation and quantification. The described method is suitable for the determination of ribavirin in chicken in analytical practice to monitor illegal addition of this kind of anti-viral drug.


What makes a Grand Slam champion? Early engagement, late specialization and timely transition from having fun to dedication.
In order to provide adequate support for young tennis players, it is important to understand the development path and factors which can have a positive or negative impact on the development of a player. The aim of this research was to determine the factors that affected sports specialization in tennis by means of qualitative analysis (early, optimal, or late). As well as to deepen the knowledge around the phenomenon of specialization in tennis among players of differing success levels through their personal experiences, in order to contribute to a better understanding of their specialization. The authors interviewed 30 tennis players of differing levels, including 10 participants from the most elite level (Grand Slam champions), exploring their contrasting experiences of development. The data set was analyzed using reflexive thematic analysis. Three topics were generated, which included the following: engaging in sport, decisions, and time of specialization. The obtained results offer a stimulus to reflect on numerous aspects of athlete development.


Clinical prediction of violence as a conditional judgment.
Previous research on the prediction of violence in mentally ill individuals has focused primarily on determinations about the appropriateness of institutional confinement. The assessment and management of violent, mentally ill individuals in the community, however, requires clinicians to take a more detailed look at the factors that might precipitate or inhibit violence in the community. This paper examines a model of conditional prediction, in which clinicians provide assessments of the factors that they expect to be associated with violence in particular patients. These types of predictions were elicited from clinicians for a sample of 712 patients seen in an urban psychiatric emergency room. These patients were then followed in the community for 6 months, using both interviews and official records. Results showed that clinicians were generally accurate about the seriousness and location of the violence, but overestimated the role of medication compliance and drug use in the violent incidents.


3D live fluorescence imaging of cellular dynamics using Bessel beam plane illumination microscopy.
3D live imaging is important for a better understanding of biological processes, but it is challenging with current techniques such as spinning-disk confocal microscopy. Bessel beam plane illumination microscopy allows high-speed 3D live fluorescence imaging of living cellular and multicellular specimens with nearly isotropic spatial resolution, low photobleaching and low photodamage. Unlike conventional fluorescence imaging techniques that usually have a unique operation mode, Bessel plane illumination has several modes that offer different performance with different imaging metrics. To achieve optimal results from this technique, the appropriate operation mode needs to be selected and the experimental setting must be optimized for the specific application and associated sample properties. Here we explain the fundamental working principles of this technique, discuss the pros and cons of each operational mode and show through examples how to optimize experimental parameters. We also describe the procedures needed to construct, align and operate a Bessel beam plane illumination microscope by using our previously reported system as an example, and we list the necessary equipment to build such a microscope. Assuming all components are readily available, it would take a person skilled in optical instrumentation ∼1 month to assemble and operate a microscope according to this protocol.


Expression and Clinical Significance of Mucin Gene in Chronic Rhinosinusitis.
This review highlights the expression and regulation of mucin in CRS and discusses its clinical implications. Chronic rhinosinusitis (CRS) is common chronic nasal disease; one of its main manifestations and important features is mucus overproduction. Mucin is the major component of mucus and plays a critical role in the pathophysiological changes in CRS. The phenotype of CRS affects the expression of various mucins, especially in nasal polyps (NP). Corticosteroids(CS), human neutrophil elastase (HNE), and transforming growth factor-β1 (TGF-β1) are closely related to the tissue remodeling of CRS and regulate mucin expression, mainly MUC1, MUC4, MUC5AC, and MUC5B. "It is expected that CS, HNE and TGF - β could be used to regulate the expression of mucin in CRS." However, at present, the research on mucin is mainly focused on mucin 5AC and mucin 5B, which is bad for finding new therapeutic targets. Investigating the expression and location of mucin in nasal mucosa and understanding the role of various inflammatory factors in mucin expression are helpful to figure out regulatory mechanisms of airway mucin hypersecretion. It is of great significance for the treatment of CRS.


[Neurogenic spinal deformities. I. Conservative and surgical treatment of spinal deformities].
Neurogenic spinal deformities develop primarily due to insufficient dynamic stabilization against gravity. Unilateral muscle overactivity is another but rare cause. The aim of treatment is to provide stability as well as to prevent deformity. In mild cases, the treatment of choice is a spinal brace because stabilization can be combined with residual mobility and adequate correction of shape. Seating shells are more readily accepted but less appropriate for this purpose. In severe cases, surgery is a good option despite the considerable effort involved and high rate of complications.


Functional sulfur amino acid production and seawater remediation system by sterile Ulva sp. (Chlorophyta).
Sterile Ulva, which is a macroalga, has the potential to grow stably; therefore, this seaweed is expected to be an efficient resource of functional food containing various nutrients such as sulfur amino acids, proteins, carbohydrates, and minerals. Ulva latuca was selected from the "Marine Park" in Tokyo Bay, and its growth rate (g-dry/[m2.d]) was measured using model reactors located on the land or on the surface of the sea at Yokohama. The growth rate of U. lactuca was recorded to be approx 20 g-dry/(m2.d), which is estimated to be 10 times greater than that in a natural field in the Marine Park. In addition, this growth rate was higher than that of conventional crops such as corn and rice on a farm or paddy. These data led us to newly design and propose a floating type of labor-efficient U. lactuca production system. d-Cysteinolic acid, which is included in U. lactuca as a major sulfur amino acid, inhibited the Fenton reaction, resulting in suppression of hydroxyl radical production and singlet oxygen. Addition of the sulfur amino acid (1 microM) to HepG2 cells markedly decreased the intracellular triglyceride level. Hence, this proposed facility also has the potential for industrial production of a valuable resource for the primary prevention of lifestyle-related diseases using enriched or eutrophied seawater.


Characteristics and significance of DNA binding activity of plasmid stabilization protein ParD from the broad host-range plasmid RK2.
A region of the plasmid RK2 has been shown to stabilize plasmid replicons in a broad host-range manner. This region encodes two divergently transcribed operons: parCBA and parDE. The parCBA operon specifies a multimer resolution system, while the parDE operon alone is capable of stabilizing an RK2-derived minireplicon under defined growth conditions in several different Gram-negative bacteria. The observed autoregulation of the parDE operon is most likely the result of ParD protein binding within the PparDE region. The characteristics of ParD binding to this region and the role of such binding in plasmid stabilization were examined with purified ParD protein. The results indicate that the binding of a single dimer of ParD protein to the promoter region most likely blocks interaction of RNA polymerase holoenzyme with the promoter. DNase I protection experiments indicate that ParD binds to a discrete sequence of 48 base pairs in length. While the binding of ParD to PparDE is essential for proper regulation of expression of the ParD and ParE proteins in vivo, the analyses of binding properties of mutant ParD proteins suggest that binding to this region does not play a direct role in plasmid stabilization.


Synthesis and characterization of TiO2 pillared montmorillonites: application for methylene blue degradation.
TiO2 pillared clay composites were prepared by modifying of montmorillonite (Mt) with cetyl-trimethyammoniumbromide (CTAB) and then using an acidic solution of hydrolyzed Ti alkoxide to intercalate into the interlayer space of the organic modified Mt. The as-prepared materials were characterized by XRD, FTIR, TEM, SEM TG-DTA, specific surface area and porosity measurements. The composites had a porous delaminated structure with pillared fragments and well dispersed TiO2 nanoparticles. Introduction of CTAB into the synthetic system accelerated the hydrolysis and condensation of the Ti source, which promoted TiO2 formation. In addition, the CTAB also significantly increased the porosity and surface area of the composites. A number of anatase particles, with crystal sizes of 5-10 nm, were homogenously distributed on the surface of the Mt as the result of the templating role of CTAB. The resultant TiO2 pillared Mt exhibited good thermal stability as indicated by its surface area after calcination at 800°C. No phase transformations from anatase to rutile were observed even under calcination at 900°C. The grain size of the anatase in prepared sample increased from 2.67 nm to 13.42 nm as the calcination temperature increased from 300°C to 900°C. The photocatalytic performance of these new porous materials was evaluated by using methylene blue degradation. The composite exhibited better photocatalytic property than P 25. The maximum removal efficiency of this composite was up to 99% within 60 min.


Co-administration of morphine and gabapentin leads to dose dependent synergistic effects in a rat model of postoperative pain.
Despite much evidence that combination of morphine and gabapentin can be beneficial for managing postoperative pain, the nature of the pharmacological interaction of the two drugs remains unclear. The aim of this study was to assess the interaction of morphine and gabapentin in range of different dose combinations and investigate whether co-administration leads to synergistic effects in a preclinical model of postoperative pain. The pharmacodynamic effects of morphine (1, 3 and 7mg/kg), gabapentin (10, 30 and 100mg/kg) or their combination (9 combinations in total) were evaluated in the rat plantar incision model using an electronic von Frey device. The percentage of maximum possible effect (%MPE) and the area under the response curve (AUC) were used for evaluation of the antihyperalgesic effects of the drugs. Identification of synergistic interactions was based on Loewe additivity response surface analyses. The combination of morphine and gabapentin resulted in synergistic antihyperalgesic effects in a preclinical model of postoperative pain. The synergistic interactions were found to be dose dependent and the increase in observed response compared to the theoretical additive response ranged between 26 and 58% for the synergistic doses. The finding of dose-dependent synergistic effects highlights that choosing the right dose-dose combination is of importance in postoperative pain therapy. Our results indicate benefit of high doses of gabapentin as adjuvant to morphine. If these findings translate to humans, they might have important implications for the treatment of pain in postoperative patients.


Prolotherapy Versus Phonophoresis and Corticosteroid Injections for the Treatment of Plantar Fasciitis: A Randomized, Double-Blind Clinical Trial.
The aim of this study was to compare the effectiveness of prolotherapy with phonophoresis and steroid injection in patients with plantar fasciitis (PF). One hundred forty-six patients with PF were randomly divided into prolotherapy, phonophoresis, and injection groups. The treatment method to be applied to them was determined by drawing lots of equal numbers of papers with "Prolotherapy," "Corticosteroid," and "Phonophoress" written on it among those who accepted to be treated. Patients were evaluated using heel sensitivity index (HSI), visual analog scale (VAS), foot function index (FFI), and Short Form (SF)-36 at baseline, first and third months after the therapy. Plantar fascia thickness (PFT) was measured by ultrasonography (USG) at baseline, first and third months after the therapy. Statistically significant improvements were found in all parameters at 1 and 3 months after treatment in all groups (p < .05). There was no significant difference between VAS and FFI scores between the 3 groups (p > .05). Improvement in the HSI (p = .021) and SF-36 general health (GH) subscales at the third month after treatment in the prolotherapy group was significantly better at the first and third months compared to the other groups (p = .033 and p < .01). No complications were observed in any of the patients. Our study results suggest that prolotherapy, phonophoresis, and steroid injection are beneficial as safe treatment modalities in the early period of PF treatment. The improvement of HSI and SF-36 GH subscale lasts longer with prolotherapy, but ultrasonographic findings do not change in the third month of these treatment applications.


Adaptive alterations on gill Na⁺, K⁺-ATPase activity and mitochondrion-rich cells of juvenile Acipenser sinensis acclimated to brackish water.
Understanding the physiological changes and osmoregulatory strategy is critical for anadromous species to adapt to large changes between freshwater and marine environments. In this study, juvenile Chinese sturgeon (Acipenser sinensis) were acclimated for 2 months to freshwater (FW, c. 0‰) and brackish water (BW, 15‰). Blood was assessed for changes in osmolality and ions. Gill tissue was assayed for Na(+), K(+)-ATPase (NKA) activity and immunohistochemical analysis on mitochondria-rich cells (MRCs). Serum osmolality and ions concentrations (Na(+), Cl(-) and K(+)) examined, except K(+), increased significantly in those specimens adapted to BW. However, the variations were within the range of effective hyperosmotic adaptation. The specific activity of gill NKA of juveniles adapted to BW was significantly higher (c. 1.6 times) than that of fish adapted to FW. MRCs were mainly presented in the interlamellar region of the filament and at the base of the lamella in either FW- or BW-acclimated individuals. In BW, the number and size of MRCs on filaments greatly increased. However, there was no significant difference in the number and size of the MRCs at the lamella region. Results show that juvenile Chinese sturgeon keep osmotic homeostasis in hyperosmotic environments by increasing gill NKA activity and MRCs' size and number, which is similar to other sturgeons and euryhaline teleosts.


Pharyngeal spasticity due to dantrolene.
Dantrolene can be combined with baclofen to better treat spasticity, but may cause muscular weakness and dysphagia. We instead describe a pharyngeal spasm due to dantrolene. A 12-year-old male received dantrolene 3 mg/kg/day in adjunct to baclofen 2 mg/kg/day, to improve spasticity. After 5 days of full-dose dantrolene, his dysphagia worsened and he developed pharyngeal spasm. Dantrolene was suspected for an adverse reaction and removed. The patient subsequently improved. Causality analysis determined a probable relationship between dantrolene and pharyngeal spasm. This may be due to direct muscle contraction by dantrolene, an effect seen previously in vitro.


Sleep misestimation among older adults suffering from insomnia with short and normal objective sleep duration and the effects of cognitive behavior therapy.
Compare the degree of sleep misestimation in older adults with insomnia presenting with objectively short relative to normal sleep duration, and investigate the differential therapeutic response on sleep misestimation between the proposed sleep duration phenotypes to cognitive-behavior therapy for insomnia (CBTi). Ninety-one adults (male = 43, mean age = 63.34, SD = 6.41) with sleep maintenance insomnia were classified as short sleepers (SS; <6 h total sleep time [TST]) or normal sleepers (NS; ≥6 h TST) based on one night of home-based polysomnography. Participants were randomly allocated to CBTi (N = 30 SS, N = 33 NS) or to a wait-list control condition (N = 9 SS, N = 19 NS). Sleep misestimation was calculated as the difference scores of subjective (sleep diary reported) and objective (derived from actigraphy) sleep onset latency (SOL), wake after sleep onset (WASO), and TST at pre- and post-treatment, and 3-month follow-up. Prior to treatment, perception of SOL, WASO, and TST did not differ between patients with objectively short sleep duration relative to those with objectively normal sleep duration. Patients' perception of WASO and TST, improved immediately following treatment and at 3-month follow-up relative to the waitlist group. These improvements did not differ significantly between those with short or normal objective sleep duration prior to treatment. The degree of sleep misestimation is similar for older adults suffering from chronic insomnia with short or normal objective sleep duration. Irrespective of objective sleep duration prior to treatment, CBTi produces significant improvements in sleep perception. ACTRN12620000883910.


Differential expression of aromatase, estrogen receptor alpha and 17β-HSD associated with the processes of total testicular regression and recrudescence in the bat Myotis nigricans (Chiroptera: Vespertilionidae).
Despite the worldwide distribution and many unique reproductive adaptations that bats present, many aspects of their reproductive hormonal regulation have not been adequately studied, especially in species that presented patterns of total testicular regression. Thus, this study aimed to evaluate the testicular expression of 17β-HSD type 1, aromatase and ERα in the bat Myotis nigricans, during the four periods of its reproductive cycle. Immunoreactivity for ERα was detected only in the cytoplasm of elongated spermatids and in the nuclei of spermatogonia and Sertoli cells. Expression of aromatase was observed in round and elongated spermatids and in Sertoli and Leydig cells. Immunoreactivity for 17β-HSD was restricted to the cytoplasm of Leydig cells. The three expression patterns varied significantly during the four periods of the reproductive cycle. Expression of ERα and aromatase in spermatids was continuous, while expression of ERα in spermatogonia occurred only in initial types (Ap). Expression of ERα and aromatase in Sertoli cells varied, with expression only in periods of spermatogenetic activities; and the same variation was observed for the expression of aromatase and 17β-HSD in Leydig cells. We, therefore, propose that the processes of total testicular regression and posterior recrudescence suffered by M. nigricans from September to January in the northwest of the São Paulo State of Brazil, are directly regulated by testosterone and estrogen. This occurs via the production of testosterone by 17β-HSD, its conversion into estrogen by aromatase, and activation/deactivation of Sertoli cells' AR and spermatogonia's ERα.


Three-Year Glycaemic Control and Management in Patients with Type 2 Diabetes Initiating Second-Line Treatment in Japan: A Prospective Observational Study, J-DISCOVER.
J-DISCOVER is a prospective, observational cohort study that aimed to understand characteristics, glycaemic control, comorbidities and real-world management of patients with early-stage type 2 diabetes mellitus (T2DM) in Japan, by enrolling patients initiating second-line treatment from both diabetes specialist and non-specialist care settings. As part of the global DISCOVER programme, J-DISCOVER enrolled 1798 patients with T2DM aged at least 20 years old from 142 sites across Japan, from September 2014 to December 2015, and followed these patients for 3 years. Glycaemic control, body mass index (BMI), blood pressure, lipid profiles, treatment patterns, and prevalence of CKD and retinopathy were examined from baseline to 6, 12, 24 and 36 months, stratified by class of second-line treatment. At baseline, the median time after T2DM diagnosis was 3.1 years and mean glycated haemoglobin (HbA1c) was 7.7%. The mean individualized HbA1c target was 6.7 ± 0.5%, and 55.3% of patients were set the target of < 7.0%. HbA1c reductions were noted from 6 months and mean HbA1c was 7.1% at 36 months. The proportion of patients with HbA1c < 7.0% increased from 28.8% at baseline to 53.3% at 36 months, and the achievement rate of individualized HbA1c targets increased from 6.1% to 30.3%. Only two cases of severe hypoglycaemia occurred during the study. No major changes in BMI, blood pressure, lipid profile or prescription of antihypertensive or dyslipidaemia medications were observed. The frequencies of screening to detect retinopathy and chronic kidney disease (CKD) were 17.0-21.0% and 14.5-16.0%, respectively, during the follow-up period. The prevalence of CKD, but not retinopathy, increased over the follow-up period. This study provided an overview of the 3-year management of early-stage T2DM in patients initiating second-line treatment. Contemporary management improved glycaemic control with an acceptable risk-benefit balance, although hurdles remain to sufficient implementation of guideline-recommended treatments in current clinical practice. ClinicalTrials.gov identifier, NCT02226822.


A novel heterogeneous transfer learning method based on data stitching for the sequential coding brain computer interface.
For the brain computer interface (BCI), it is necessary to collect enough electroencephalography (EEG) signals to train the classification model. When the operation dimension of BCI is large, it will bring great burden to data acquisition. Fortunately, this problem can be solved by our proposed transfer learning method. For the sequential coding experimental paradigm, the multi-band data stitching with label alignment and tangent space mapping (MDSLATSM) algorithm is proposed as a novel heterogeneous transfer learning method. After filtering by multi-band filtering, the artificial signals can be obtained by data stitching from the source domain, which build a bridge between the source domain and target domain. To make the distribution of two domains closer, their covariance matrices are aligned by label alignment. After mapping to the tangent space, the features are extracted from the Riemannian manifold. Finally, the classification results are obtained with feature selection and classification. Our data set includes the EEG signals from 16 subjects. For the heterogeneous transfer learning of cross-label, the average classification accuracy is 78.28%. MDSLATSM is also tested for cross-subject, and the average classification accuracy is 64.01%, which is better than existing methods. Combining multi-band filtering, data stitching, label alignment and tangent space mapping, a novel heterogeneous transfer learning method can be achieved with superior performance, which promotes the practical application of the BCI systems.


Studies on the binding of wheat germ agglutinin (Triticum vulgaris) to O-glycans.
The binding profile of Triticum vulgaris (WGA, wheat germ) agglutinin to 23 O-glycans (GalNAc alpha1-->Ser/Thr containing glycoproteins, GPs) was quantitated by the precipitin assay and its specific interactions with O-glycans were confirmed by the precipitin inhibition assay. Of the 28 glycoforms tested, six complex O-glycans (hog gastric mucins, one human blood group A active and two precursor cyst GPs) reacted strongly with WGA and completely precipitated the lectin added. All of the other human blood group A active O-glycans and human blood group precursor GPs also reacted well with the lectin and precipitated over two-thirds of the agglutinin used. They reacted 4-50 times stronger than N-glycans (asialo-fetuin and asialo-human alpha1 acid GP). The binding of WGA to O-glycans was inhibited by either p-NO2-phenyl alpha,betaGlcNAc or GalNAc. From these results, it is highly possible that cluster (multivalent) effects through the high density of weak inhibitory determinants on glycans, such as GalNAc alpha1-->Ser/Thr (Tn), GalNAc at the nonreducing terminal, GlcNAc beta1--> at the non-reducing end and/or as an internal residue, play important roles in precipitation, while the GlcNAc beta1-->4GlcNAc disaccharide may play a minor role in the precipitation of mammalian glycan-WGA complexes.


Risk of lung cancer and renin-angiotensin blockade: a concise review.
The blockade of the renin-angiotensin-aldosterone system (RAAS) by angiotensin-converting enzyme inhibitors (ACEIs) or angiotensin receptor blockers (ARBs) is one of the most common treatments for hypertension, heart failure and renal diseases. However, concerns have been raised about a possible link between RAAS-blockers and an increased risk of cancer, particularly of lung cancer. This narrative review aims to give a critical appraisal of current evidence and to help physicians understand potential links between RAAS blockade and de novo lung cancer development. Numerous pharmaco-epidemiologic studies, mostly retrospective cohort analyses, evaluated the association of RAAS blockade with lung cancer incidence and reported inconsistent findings. Meta-analyses could not further clarify a possible link between RAAS blockade and the risk of lung cancer. International regulatory agencies (FDA, EMA) have concluded that the use of RAAS blockers is not associated with an increased risk of developing lung cancer. Co-administration of RAAS blockers to systemic therapy of advanced non-small cell lung cancer seems to have positive effects on the outcome. Until more comprehensive analyses have been completed, there is no need to change clinical practise. Additional prospective randomized trials with long-term follow-up are needed to investigate the effects of these drugs on the development and progression of lung cancer.


Effect of different sweeteners on the thermal, rheological, and water mobility properties of soft wheat flour and their application to cookies as an alternative to sugar.
The effects of different sweeteners on the physicochemical properties of soft wheat flour were investigated mainly in terms of thermal, rheological, and water mobility features, and their feasibilities as an alternative to sugar were evaluated in the cookie system. Kestose significantly reduced the solvent retention capacity of wheat flour, followed by sucrose, fructose, and allulose. Thermal analysis showed that the sucrose and kestose distinctly led to an increase in the gelatinization temperature of wheat flour, which was explained by lower T2 relaxation times. In addition, the pasting viscosities and thermo-mechanical properties of wheat flour containing kestose became lower compared to allulose, and these differences were morphologically confirmed by the real-time microscopic measurements during heating. Furthermore, when the sweeteners were incorporated into the cookie formulations, kestose played a positive role as a sugar replacer in the cookie system by presenting a comparable spread factor, texture, and color to cookies with sucrose.


Household economic hardship as a moderator of the associations between maternal spanking and child externalizing behavior problems.
Spanking is associated with detrimental outcomes for young children. Research shows that spanking is more commonly used in low-income households. To examine whether economic hardship, measured by household income-to-poverty ratio at the time of the child's birth, moderated the longitudinal associations between maternal spanking and child externalizing behavior problems during the first nine years of childhood. Mother-child pairs (N = 4,149) from a cohort study of urban families in 20 US cities. Cross-lagged path models examined associations between maternal spanking and externalizing behavior when children were between the ages of 1 and 9. Multigroup analyses examined whether income-to-poverty ratio moderated these associations. Bivariate analyses showed that income-to-poverty ratio was associated with child externalizing behavior problems at each time point; income-to-poverty ratio was associated with maternal spanking at age 3 only. Longitudinal path model results indicated that, for low- and middle-income groups, maternal spanking at each age had significant associations with child externalizing behavior at each subsequent age. For the high-income group, maternal spanking at age 1 and age 3 had significant associations with child externalizing behavior at each subsequent age; however, spanking at age 5 was not associated with child externalizing behavior at age 9. Spanking is disadvantageous for children at all income levels, with more persistent effects in low- and middle-income families. For higher-income families, the associations of maternal spanking with child externalizing behavior problems may be attenuated as child age increases. Regardless of income level, parents should be advised against spanking.


Identification of elements essential for transcription in Brugia malayi promoters.
Little is known concerning promoter structure in the filarial parasites. Recently, transient transfection methods have been developed for the human filarial parasite Brugia malayi. These methods have been employed to localize the promoter for the 70kDa heat shock protein (BmHSP70) to a region extending 394nt upstream from the initiating codon of the BmHSP70 open reading frame. Replacement mutagenesis was used to define the elements necessary for BmHSP70 promoter activity in detail. Four domains, ranging in size from six to 22 nucleotides, were found to be necessary for full promoter activity. The two most distal domains encoded a binding site for the heat shock transcription factor and a putative binding site for the GAGA transcription factor, motifs that are found in many other HSP70 promoters. However, none of the essential domains contained sequences typical of cis elements that are usually found in the core domain of a eukaryotic promoter. The largest essential domain was located at positions -53 to -32, and included the splice leader addition site. These data suggest that the regulatory domains of the BmHSP70 promoter were similar to those found in other eukaryotes, but that the core promoter domain exhibited features that appeared to be distinct from those found in most other well-characterized eukaryotic promoters. An analysis of two additional promoters of B.malayi highly transcribed genes suggests that they also lack features commonly found in most eukaryotic core promoters, suggesting that the unique features of the BmHSP70 core promoter are not confined to this gene.


Added cancer yield of MRI in screening the contralateral breast of women recently diagnosed with breast cancer: results from the International Breast Magnetic Resonance Consortium (IBMC) trial.
To estimate the added cancer yield of magnetic resonance imaging (MRI) over mammography in the contralateral breast of patients with a recent diagnosis of breast cancer. We conducted a prospective, international study of mammography and MRI in women with a recent diagnosis of unilateral breast cancer. Each subject received a mammogram, clinical breast exam (CBE), and MRI of the unaffected breast within a 90 day time period. Definitive diagnosis of suspicious findings was determined through biopsy and central pathology review. Of the 103 eligible women included in study analyses, MRI detected 4 cancers in the contralateral breast while mammography detected none. MRI resulted in 12% (95% CI, 6%-20%) of women recommended for biopsy and 10% of women undergoing additional biopsy. The added cancer yield of MRI was 4% (95% CI, 1%-10%) and the positive predictive value of an abnormal MRI was 33% (95% CI, 10%-65%). Forty percent (4/10) of the biopsies performed based on the MRI recommendation were positive for malignancy. In women with a recent breast cancer diagnosis, approximately 4% will have an otherwise occult invasive breast cancer detected in the opposite breast by MRI alone.


Preoperative diagnosis of Meckel's diverticulum with 99mTc-pertechnetate.
99mTc-pertechnetate scintigraphy of the digestive tract was performed on 4 children with intestinal bleeding. Two of them showed a focal uptake in the right lower abdominal quadrant and a diagnosis of bleeding Meckel's diverticulum was confirmed by surgery. This procedure being easy to perform, non-invasive and remunerative, should be systematically applied in paediatric intestinal bleeding.


High strain rate compressive properties of bovine muscle tissue determined using a split Hopkinson bar apparatus.
The polymeric split Hopkinson pressure bar (PSHPB) apparatus is introduced as a means for measuring the high strain rate (1,000-2,500 s(-1)) compressive properties of soft tissues. Issues related to specimen design are discussed, and protocols are presented for specimen preparation. Proposed specimen geometries were validated using high-speed photography. Stress-strain data were obtained for high strain rate compression of bovine muscle tissue to strains as high as 80%. The stress-strain curves were found to be strain rate-sensitive and concave upward, as is typical of soft tissues. Rigor had a significant impact on the material properties between 5 and 24 h post mortem, while at longer times, properties returned essentially to their pre-rigor values. This study presents some of the first published high rate properties of muscle tissue, data that are urgently for advanced modeling of the human body and for evaluation of safety systems for the human body.


Relation Between a Simple Lifestyle Risk Score and Established Biological Risk Factors for Cardiovascular Disease.
Although cardiovascular disease (CVD) and diabetes mellitus are largely lifestyle driven, lifestyle metrics are not used in clinical practice. This study examined the relevance of using a simple lifestyle risk score designed for primary care medicine by testing its ability to predict biological CVD risk factors in a cohort of 3,712 individuals involved in a workplace health evaluation or management program ("Grand Défi Entreprise" project). Using a lifestyle risk score based on waist circumference, fitness, nutritional quality, and physical activity level, employees were categorized into 3 distinct estimated lifestyle risk levels (low, intermediate, and high). A biological CVD risk score was also calculated, which included high-density lipoprotein cholesterol (HDL-C), triglycerides (TG), cholesterol-to-HDL-C ratio, blood pressure, hemoglobin glycated levels, and medication use. Diastolic blood pressure, TG levels, and the cholesterol-to-HDL-C ratio increased across categories of lifestyle risk score, whereas HDL-C decreased (p <0.05). Calculated Framingham and diabetes risk scores as well as the prevalence of hypertriglyceridemic waist phenotype also increased across categories of lifestyle risk score (p <0.05). Finally, 1-way analysis of variance revealed that the biological risk score significantly increased across the lifestyle risk score categories (p <0.0001). Our study provides evidence that lifestyle variables can be measured and targeted in clinical practice.


NEXUS: an extensible file format for systematic information.
NEXUS is a file format designed to contain systematic data for use by computer programs. The goals of the format are to allow future expansion, to include diverse kinds of information, to be independent of particular computer operating systems, and to be easily processed by a program. To this end, the format is modular, with a file consisting of separate blocks, each containing one particular kind of information, and consisting of standardized commands. Public blocks (those containing information utilized by several programs) house information about taxa, morphological and molecular characters, distances, genetic codes, assumptions, sets, trees, etc.; private blocks contain information of relevance to single programs. A detailed description of commands in public blocks is given. Guidelines are provided for reading and writing NEXUS files and for extending the format.


mHealth App for Cannabis Users: Satisfaction and Perceived Usefulness.
The aim of this study was to describe the characteristics of cannabis users and their levels of satisfaction with Stop-cannabis, an app intended for cannabis users who want to stop or reduce their cannabis use or prevent relapse. A cross-sectional online survey was administered to users of Stop-cannabis, a French-language app for iOS and Android devices. All app users were invited to participate in the survey via a message sent to the app. For hundred and eighty-two users answered the survey. The app was used daily by 348 of the participants (around 70%). More than 80% of participants (397) considered the app to have helped them "a little" or "a lot" to stop or reduce cannabis consumption. Most of the users' suggestions were related to the number or the quality of the messages sent by, or displayed in, the app. This pilot study supports the feasibility of such an app and its perceived usefulness. A self-selection bias, however, limits the conclusions of the study. The efficacy of the app should be evaluated in a randomized controlled trial.


Occurrence of alternariol, alternariol monomethyl ether and tenuazonic acid in Argentinean tomato puree.
The occurrence ofAlternaria mycotoxins was investigated in 80 samples of tomato puree processed and sold in Argentina. Alternariol (AOH), alternariol monomethyl ether (AME) and tenuazonic acid (TA) were searched for by liquid chromatography. Thirty-nine of the 80 samples showed mycotoxin contamination. TA was found in 23 samples (39-4021 μg/kg), AOH in 5 samples (187-8756 μg/kg), and AME in 21 samples (84-1734 μg/kg). Co-occurrence of two of these toxins was detected in 10 samples. This is the first report of natural occurrence of AOH, AME and TA in tomato products in Argentina.


Functional changes in the lungs of guinea pigs exposed to sodium sulfite aerosols.
Guinea pigs were exposed head only for 1 hr to submicrometer sodium sulfite aerosols (mass median aerodynamic diameter = 0.36 micron, sigma g = 2.96) at 474, 669, and 972 micrograms SO3(2-)/m3. Respiratory mechanics were measured in unanaesthetized animals before, during, and after exposure. Dose-related increases in resistance and decreases in compliance were observed. At 972 micrograms SO3(2-)/m3, the sodium sulfite aerosol caused a 50% increase in resistance and a 19% decrease in compliance. These changes were still present 1 hr after the end of exposure. The results were used to assess the irritant potency of sodium sulfite aerosol. Another group of guinea pigs was exposed whole body for 1 hr to the same aerosol at 0, 204, 395, and 1152 micrograms SO3(2-)/m3. Immediately after the exposures, lung volume, diffusion capacity for carbon monoxide (DLCO), and wet lung weight were evaluated in anesthetized, tracheotomized animals. As compared to controls, total lung capacity, vital capacity, functional residual capacity, residual volume, and DLCO were all decreased with increasing concentrations of sodium sulfite. Dose-related increases in wet lung weights were also observed. These results were compared with the irritant responses of animals exposed to zinc oxide and sulfur dioxide mixed under different conditions of temperature and humidity.