Molecular mechanisms of resistance to 5-fluorocytosine in laboratory mutants of Candida glabrata.
Resistance to 5-fluorocytosine (5-FC) has been poorly investigated in the yeast Candida glabrata. This study was conducted on laboratory mutants obtained by exposure of a wild-type isolate to 5-FC. Based on their susceptibility to 5-fluorouracil (5-FU), two of these mutants were selected for further analysis of the molecular mechanisms of 5-FC resistance. One mutant, resistant to both compounds, exhibited a missense mutation in the gene coding the cytosine deaminase and a decrease in the expression level of the gene coding the uridine monophosphate pyrophosphorylase. The other mutant that showed a reduced susceptibility to 5-FC and 5-FU exhibited an overexpression of the genes coding the thymidylate synthase and a cytosine permease, associated with a missense mutation in the last gene. Thus, beside mutations in the FUR1 gene which represent the most common cause of resistance to 5-FC, other mechanisms may also occur in C. glabrata.


Computational modeling of the bHLH domain of the transcription factor TWIST1 and R118C, S144R and K145E mutants.
Human TWIST1 is a highly conserved member of the regulatory basic helix-loop-helix (bHLH) transcription factors. TWIST1 forms homo- or heterodimers with E-box proteins, such as E2A (isoforms E12 and E47), MYOD and HAND2. Haploinsufficiency germ-line mutations of the twist1 gene in humans are the main cause of Saethre-Chotzen syndrome (SCS), which is characterized by limb abnormalities and premature fusion of cranial sutures. Because of the importance of TWIST1 in the regulation of embryonic development and its relationship with SCS, along with the lack of an experimentally solved 3D structure, we performed comparative modeling for the TWIST1 bHLH region arranged into wild-type homodimers and heterodimers with E47. In addition, three mutations that promote DNA binding failure (R118C, S144R and K145E) were studied on the TWIST1 monomer. We also explored the behavior of the mutant forms in aqueous solution using molecular dynamics (MD) simulations, focusing on the structural changes of the wild-type versus mutant dimers. The solvent-accessible surface area of the homodimers was smaller on wild-type dimers, which indicates that the cleft between the monomers remained more open on the mutant homodimers. RMSD and RMSF analyses indicated that mutated dimers presented values that were higher than those for the wild-type dimers. For a more careful investigation, the monomer was subdivided into four regions: basic, helix I, loop and helix II. The basic domain presented a higher flexibility in all of the parameters that were analyzed, and the mutant dimer basic domains presented values that were higher than the wild-type dimers. The essential dynamic analysis also indicated a higher collective motion for the basic domain. Our results suggest the mutations studied turned the dimers into more unstable structures with a wider cleft, which may be a reason for the loss of DNA binding capacity observed for in vitro circumstances.


In Vitro Cartilage Regeneration with a Three-Dimensional Polyglycolic Acid (PGA) Implant in a Bovine Cartilage Punch Model.
Resorbable polyglycolic acid (PGA) chondrocyte grafts are clinically established for human articular cartilage defects. Long-term implant performance was addressed in a standardized in vitro model. PGA implants (+/- bovine chondrocytes) were placed inside cartilage rings punched out of bovine femoral trochleas (outer Ø 6 mm; inner defect Ø 2 mm) and cultured for 84 days (12 weeks). Cartilage/PGA hybrids were subsequently analyzed by histology (hematoxylin/eosin; safranin O), immunohistochemistry (aggrecan, collagens 1 and 2), protein assays, quantitative real-time polymerase chain reactions, and implant push-out force measurements. Cartilage/PGA hybrids remained vital with intact matrix until 12 weeks, limited loss of proteoglycans from "host" cartilage or cartilage-PGA interface, and progressively diminishing release of proteoglycans into the supernatant. By contrast, the collagen 2 content in cartilage and cartilage-PGA interface remained approximately constant during culture (with only little collagen 1). Both implants (+/- cells) displayed implant colonization and progressively increased aggrecan and collagen 2 mRNA, but significantly decreased push-out forces over time. Cell-loaded PGA showed significantly accelerated cell colonization and significantly extended deposition of aggrecan. Augmented chondrogenic differentiation in PGA and cartilage/PGA-interface for up to 84 days suggests initial cartilage regeneration. Due to the PGA resorbability, however, the model exhibits limitations in assessing the "lateral implant bonding".


Coalescence-Induced Droplet Jumping on Superhydrophobic Surfaces with Annular Wedge-Shaped Micropillar Arrays.
The coalescence-induced droplet jumping on superhydrophobic surfaces has extensive application potential in water harvesting, thermal management of electronic devices, and microfluidics. The rational design of the surface structure can influence the interaction between the droplet and the surface, thereby controlling the velocity and direction of the droplet's jumping. In this study, we fabricate the superhydrophobic surface with annular wedge-shaped micropillar arrays, examine the dynamic behavior of condensate droplets on the surface, and measure the temporal and spatial variations of droplet density, average radius, and surface coverage with wedge-shaped micropillars of varying sizes. In addition, the energy analysis of the coalescence-induced droplet jumping reveals that the two primary factors influencing the jumping are the relative size and position of the droplets and micropillars. Further numerical simulations find that the wedge-shaped micropillars cause an asymmetric distribution of pressure within the droplet and at the solid-liquid contact surface, which generates an unbalanced force driving the droplet in the gradient direction of the wedge-shaped micropillar, causing the droplet to jump off the surface with both vertical and gradient-direction velocities. The capacity of the wedge-shaped micropillar surface to transport droplets in the gradient direction increases and then decreases as the relative size of the droplets and micropillars increases. The relative position of the droplet center-of-mass line perpendicular to the bottom edge of the wedge micropillars' trapezoidal shape is more favorable for droplet transport. This work reveals the influence mechanism of surface structure on the velocity and direction of droplet jumping, and the results can guide the microstructure design of superhydrophobic surfaces, which has significant implications for the application of droplet jumping.


Pd(0)-catalyzed oxy- and aminoalkynylation of olefins for the synthesis of tetrahydrofurans and pyrrolidines.
The first Pd(0)-catalyzed intramolecular oxy- and aminoalkynylation of nonactivated olefins is reported. The reaction gives access to important tetrahydrofuran and pyrrolidine heterocycles with high diastereoselectivity. The unique synthetic potential of acetylenes is further exploited to access key building blocks for the synthesis of bioactive natural products.


Racial Differences in Electrocardiographic Characteristics and Prognostic Significance in Whites Versus Asians.
Racial differences in electrocardiographic (ECG) characteristics and prognostic significance among Whites and Asians are not well described. We studied 2677 White Framingham Heart Study participants (57% women) and 2972 Asian (64% women) Singapore Longitudinal Aging Study participants (mean age 66 years in both) free of myocardial infarction or heart failure. Racial differences in ECG characteristics and effect on mortality were assessed. In linear regression models, PR interval was longer in Asians compared with Whites (multivariable-adjusted β±SE 5.0±1.4 ms in men and 6.6±0.9 ms in women, both P<0.0006). QT interval was shorter in Asian men (β±SE -6.2±1.2 ms, P<0.0001) and longer in Asian women (β±SE 3.6±0.9 ms, P=0.02) compared to White men and women, respectively. Asians had greater odds of having ECG left ventricular hypertrophy (LVH) compared with Whites (odds ratio [OR] 3.56, 95% confidence interval [CI] 1.36-9.35 for men, OR 1.93, 95% CI 1.35-2.76 for women, both P<0.02). Over a mean follow-up of 11±3 years in Framingham and 8±3 years in Singapore, mortality rates were 24.5 and 13.4 per 1000 person-years among Whites and Asians, respectively. In Cox models, the presence of LVH had a greater effect on all-cause mortality in Asians compared with Whites (hazard ratio [HR] 2.66, 95% CI 1.83-3.88 vs HR 1.30, 95% CI 0.90-1.89, P for interaction=0.02). Our findings from two large community-based cohorts show prominent race differences in ECG characteristics between Whites and Asians, and also suggest a differential association with mortality. These differences may carry implications for race-specific ECG reference ranges and cardiovascular risk.


Exploration of population and practice characteristics explaining differences between practices in the proportion of hospital admissions that are emergencies.
Emergency (unscheduled) and elective (scheduled) use of secondary care varies between practices. Past studies have described factors associated with the number of emergency admissions; however, high quality care of chronic conditions, which might include increased specialist referrals, could be followed by reduced unscheduled care. We sought to characterise practices according to the proportion of total hospital admissions that were emergency admissions, and identify predictors of this proportion. The study included 229 general practices in Leicestershire, Northamptonshire and Rutland, England. Publicly available data were obtained on scheduled and unscheduled secondary care usage, and on practice and patient characteristics: age; gender; list size; observed prevalence, expected prevalence and the prevalence gap of coronary heart disease, hypertension and stroke; deprivation; headcount number of GPs per 1000 patients; total and clinical quality and outcomes framework (QOF) scores; ethnicity; proportion of patients seen within two days by a GP; proportion able to see their preferred GP. Using the proportion of admissions that were emergency admissions, seven categories of practices were created, and a regression analysis was undertaken to identify predictors of the proportion. In univariate analysis, practices with higher proportions of admissions that were emergencies tended to have fewer older patients, higher proportions of male patients, fewer white patients, greater levels of deprivation, smaller list sizes, lower recorded prevalence of coronary heart disease and stroke, a bigger gap between the expected and recorded levels of stroke, and lower proportions of total and clinical QOF points achieved. In the multivariate regression, higher deprivation, fewer white patients, more male patients, lower recorded prevalence of hypertension, more outpatient appointments, and smaller practice list size were associated with higher proportions of total admissions being emergencies. In monitoring use of secondary care services, the role of population characteristics in determining levels of use is important, but so too is the ability of practices to meet the demands for care that face them. The level of resources, and the way in which available resources are used, are likely to be key in determining whether a practice is able to meet the health care needs of its patients.


Sleep bruxism associated with obstructive sleep apnea syndrome in children.
Sleep bruxism (SB) and obstructive sleep apnea syndrome (OSAS) are often observed in children and may have several health implications. The aim of this paper is to evaluate their prevalence and to test for possible associations between these two conditions. The sample consisted of 496 children randomly selected among the preschoolers of Taubaté, Brazil; 249 (50·2%) were boys and 247 (49·8%) were girls. Diagnoses of SB and OSAS were made by clinical examinations and questionnaires filled out by the children's parents in a cross-sectional design. Analysis of variance and Chi-square tests were applied to verify possible association among the variables in question. The average age was 4·49 years (SD: ±1·04 years). A total of 25·6% were diagnosed with SB, while 4·83% were diagnosed with OSAS, and only 2·82% presented both conditions. A statistical association was found between SB and OSAS (P<0·001; Chi-square test): 11·03% of subjects with SB also presented with OSAS, and 97·18% of subjects without SB did not present with OSAS. No association was found among children's gender and age and the presence of SB or OSAS. Within the limits of this study, SB was associated with OSAS.


Standardization of Prothrombin Time/International Normalized Ratio (PT/INR).
The prothrombin time (PT) represents the most commonly used coagulation test in clinical laboratories. The PT is mathematically converted to the international normalized ratio (INR) for use in monitoring anticoagulant therapy with vitamin K antagonists such as warfarin in order to provide test results that are adjusted for thromboplastin and instrument used. The INR is created using two major PT 'correction factors', namely the mean normal PT (MNPT) and the international sensitivity index (ISI). Manufacturers of reagents and coagulometers have made some efforts to harmonizing INRs, for example, by tailoring reagents to specific coagulometers and provide associated ISI values. Thus, two types of ISIs may be generated, with one being a 'general' or 'generic' ISI and others being reagent/coagulometer-specific ISI values. Although these play a crucial role in improving INR results between laboratories, these laboratories reported INR values are known to still differ, even when laboratories use the same thromboplastin reagent and coagulometer. Moreover, ISI values for a specific thromboplastin can vary among different models of coagulometers from a manufacturer using the same method for clot identification. All these factors can be sources of error for INR reporting, which in turn can significantly affect patient management. In this narrative review, we provide some guidance to appropriate ISI verification/validation, which may help decrease the variability in cross laboratory reporting of INRs.


Medication errors: the impact of prescribing and transcribing errors on preventable harm in hospitalised patients.
Medication errors (MEs) affect patient safety to a significant extent. Because these errors can lead to preventable adverse drug events (pADEs), it is important to know what type of ME is the most prevalent cause of these pADEs. This study determined the impact of the various types of prescribing (administrative, dosing and therapeutic) and transcribing errors on pADEs in hospitalised patients. During a 5-month period, data for patients admitted to a total of five internal medicine wards of one university and one teaching hospital in The Netherlands were prospectively collected by chart review. In each hospital, MEs were detected and classified by the same pharmacist, using the classification scheme for MEs developed by The Netherlands Association of Hospital Pharmacists. The primary outcome measure was the prevalence of pADEs during hospital stay. In consensus meetings, five pharmacists assessed the causal relationship between MEs and pADEs. The association between type of ME and pADEs was determined by a multivariate regression analysis taking into account potential confounders. The study included 592 hospital admissions with 7286 medication orders (MOs), of which 60% contained at least one prescribing or transcribing error. 1.4% of all MOs led to pADEs, concerning 14.8% of all admitted patients. The total number of pADEs was 103, and in 92 of these cases patients experienced temporary harm, in eight cases hospital admission was prolongued, two cases were life-threatening, and one was fatal. Therapeutic errors were most strongly associated with pADEs (OR 1.98; 95% CI 1.53 to 2.56). Although many prescribing and transcribing errors occur in the process of medication use of hospitalised patients, a minority lead to pADEs. In particular, therapeutic errors are the cause of these pADEs and are therefore clinically relevant. Intervention and prevention programmes should primarily focus on this type of medication error.


Tricyclic antidepressants and non-Hodgkin lymphoma.
An increased risk of non-Hodgkin lymphoma (NHL) has been reported among long-term users of tricyclic antidepressants. The incidence of NHL among 43,932 users of any antidepressant medication (2 or more prescriptions) in the county of North Jutland, Denmark, during 1989-2003 was compared with NHL incidence in all those not using antidepressants (0 or 1 prescription). We used Poisson regression analysis adjusted for age, sex, period, use of immunosuppressive drugs, corticosteroids, or nonsteroidal anti-inflammatory drugs. Use of tricyclic antidepressants was associated with an overall increased incidence of NHL (adjusted incidence rate ratio [IRR] = 1.53; 95% confidence interval [CI] = 1.06-2.21) compared with nonuse. The IRR in users with > or =10 prescriptions and 5 or more years of follow-up was 2.50 (CI = 1.43-4.34). Users of other types of antidepressants were not at increased risk of NHL. Our results indicate an increased risk of non-Hodgkin lymphoma specifically among long-term users of tricyclic antidepressant medications.


Effects of vaccination with Haemophilus influenzae on adrenoceptor function of tracheal and parenchymal strips.
Haemophilus influenzae is a bacterium that can be isolated from the deeper airways of asthmatic patients. We investigated the effect of vaccination with H. influenzae on alpha and beta adrenoceptor function in guinea-pig tracheal spirals and lung parenchymal strips. The tracheal spirals from H. influenzae-vaccinated animals showed significantly less relaxation to isoproterenol as compared to controls, independent of whether the trachea was maximally contracted with carbachol or only exhibited an intrinsic tone. Furthermore, an increased contractile response to carbachol was observed in these spirals. To isoproterenol in the presence of a beta-2 adrenergic antagonist (H35/25), or to salbutamol alone, the tracheal preparations from H. influenzae-vaccinated animals also showed a decreased relaxation. These results suggest involvement of both beta-1 and beta-2 subtype adrenoceptors. On the other hand, lung parenchymal strips from vaccinated guinea-pigs relaxed significntly more to these drugs. This effect was not influenced by H35/25 but could be inhibited by phenoxybenzamine. Histamine-induced contraction did not differ between the groups. These results indicated that H. influenzae causes a partial blockade of the beta adrenoceptors in tracheal spirals and, therefore, may have important implications in asthmatic bronchitis. In contrast, parenchymal lung strips of the H. influenzae-pretreated group showed an increased relaxation.


Impact of persistent left superior vena cava on radiofrequency catheter ablation in patients with atrial fibrillation.
The impact of persistent left superior vena cava (PLSVC) in atrial fibrillation (AF) patients undergoing radiofrequency catheter ablation (RFCA) is not well known. We performed this analysis to evaluate the electrophysiological characteristics of PLSVC and its role in triggering and maintaining AF. Patients with AF referred to two tertiary hospitals were screened and patients with PLSVC in pre-RFCA imaging studies were enrolled. Among 3967 patients, PLSVC was present in 36 patients (0.9%). There were four morphological types of PLSVC: type 1, atresia of the right superior vena cava (SVC) (n = 2); type 2A, dual SVCs with an anastomosis between right and left SVCs (n = 15); type 2B, dual SVCs without an anastomosis (n = 16); type 3, PLSVC draining into the left atrium (LA; n = 2); and unclassified in one patient. Thirty-two patients underwent RFCA and electrophysiology study focusing on PLSVC: PLSVC was the trigger of AF in 48.4% of patients and the driver of AF in 46.9% of patients. Cumulatively, PLSVC was a trigger or driver of AF in 22 patients (68.8%). Whether to ablate PLSVC was determined by the results of electrophysiology study, and no significant difference in the late recurrence rate was observed between patients who did and did not have either trigger or driver from PLSVC. Pre-RFCA cardiac imaging revealed PLSVC in 0.9% of AF patients. This study demonstrated that PLSVC has an important role in initiating and maintaining AF in substantial proportion of patients. Electrophysiology study focusing on PLSVC can help to decide whether to ablate PLSVC.


[Aminopeptidase activity in the neurons of the nodose ganglion of the vagus nerve in acute experimental emotional stress].
Histological investigation was carried out to study the activity of aminopeptidase (AMP) in neurons of the nodose ganglion of immobilized rabbits with acute experimental emotional stress induced by electrical stimulation of ventromedial hypothalamic nuclei and skin. On the basis of the pattern of cardiovascular reactions, two groups of animals were distinguished: resistant and susceptible to the stress effects. In control animals, AMP activity was found to vary in neurons of different size. The highest activity was recorded in large cells, whereas small cells showed the minimum activity. In resistant animals AMP activity was found to be on control level in all groups of nerve cells. In susceptible rabbits AMP activity rose significantly, with maximum increase of AMP activity being observed in the large and medium-sized neurons.


Structural and mutational analysis of archaeal ATP-dependent RNA ligase identifies amino acids required for RNA binding and catalysis.
An ATP-dependent RNA ligase from Methanobacterium thermoautotrophicum (MthRnl) catalyzes intramolecular ligation of single-stranded RNA to form a closed circular RNA via covalent ligase-AMP and RNA-adenylylate intermediate. Here, we report the X-ray crystal structures of an MthRnl•ATP complex as well as the covalent MthRnl-AMP intermediate. We also performed structure-guided mutational analysis to survey the functions of 36 residues in three component steps of the ligation pathway including ligase-adenylylation (step 1), RNA adenylylation (step 2) and phosphodiester bond synthesis (step 3). Kinetic analysis underscored the importance of motif 1a loop structure in promoting phosphodiester bond synthesis. Alanine substitutions of Thr117 or Arg118 favor the reverse step 2 reaction to deadenylate the 5'-AMP from the RNA-adenylate, thereby inhibiting step 3 reaction. Tyr159, Phe281 and Glu285, which are conserved among archaeal ATP-dependent RNA ligases and are situated on the surface of the enzyme, are required for RNA binding. We propose an RNA binding interface of the MthRnl based on the mutational studies and two sulfate ions that co-crystallized at the active site cleft in the MthRnl-AMP complex.


Urinary-derived extracellular vesicle microRNAs as non-invasive diagnostic biomarkers for early-stage renal cell carcinoma.
The potential of urinary-derived extracellular vesicle (uEV) microRNAs (miRNAs) as noninvasive molecular biomarkers for identifying early-stage renal cell carcinoma (RCC) patients is rarely explored. The present study aims to explore the possibility of uEV miRNAs as novel molecular biomarkers for distinguishing early-stage RCC. uEVs were extracted by ExoQuick-TC™ kit and miRNA concentrations were measured by RT-qPCR. ROC curves and bioinformatics analysis were employed to predict the diagnostic efficacy and regulatory mechanisms of dysregulated miRNAs. Through a multiphase case-control study on uEV miRNAs screening, training, and validation in RCC cells (ACHN, Caki-1) and control cells (HK-2) and in uEVs of 125 RCC patients and 128 age- and sex-matched controls, we successfully identified four uEVs miRNAs (miR-135b-5p, miR-196b-5p, miR-200c-3p, and miR-203a-3p) were significantly and stably upregulated in RCC in vitro and in vivo. When adjusted with estimated glomerular filtration rate (eGFR), the AUC of the three-uEV miRNA panel (miR-135b-5p, miR-200c-3p, and miR-203a-3p) was 0.785 (95 % CI = 0.729-0.842, P < 0.0001) for discriminating RCC patients from controls. Notably, this panel exhibited similar performance in distinguishing early-stage (stage Ⅰ) RCC patients, with an AUC of 0.786 (95 %CI = 0.727-0.844, P < 0.0001). Bioinformatics analysis predicted that candidate miRNAs were involved in cancer progressing. Our study identified a four uEV miRNAs panel (miR-135b-5p, miR-196b-5p, miR-200c-3p, and miR-203a-3p) may serve as an auxiliary noninvasive indication of early-stage RCC.


Adjuvant lapatinib for women with early-stage HER2-positive breast cancer: a randomised, controlled, phase 3 trial.
Worldwide, many patients with HER2-positive early stage breast cancer do not receive trastuzumab-the standard adjuvant treatment. We investigated the efficacy and safety of adjuvant lapatinib for patients with trastuzumab-naive HER2-positive early-stage breast cancer, started at any time after diagnosis. This study was a placebo-controlled, multicentre, randomised phase 3 trial. Women outpatients from 405 [corrected] centres in 33 countries [corrected] with HER2-positive early-breast cancer who had previously received adjuvant chemotherapy but not trastuzumab were randomly assigned (1:1) to receive daily lapatinib (1500 mg) or daily placebo for 12 months. Randomisation was done with a computer-generated sequence, stratified by time since diagnosis, lymph node involvement at diagnosis, and tumour hormone-receptor status. Investigators, site staff, and patients were masked to treatment assignment. The primary endpoint was disease-free survival in the intention-to-treat population. This study is registered with ClinicalTrials.gov, number NCT00374322. Between August, 2006, and May, 2008, 3161 women were enrolled and 3147 were assigned to lapatinib (n=1571) or placebo (n=1576). After a median follow-up of 47·4 months (range 0·4-60·0) in the lapatinib group and 48·3 (0·7-61·3) in the placebo group, 210 (13%) disease-free survival events had occurred in the lapatinib group versus 264 (17%) in the placebo group (hazard ratio [HR] 0·83, 95% CI 0·70-1·00; p=0·053). Central review of HER2 status showed that only 2490 (79%) of the randomised women were HER2-positive. 157 (13%) of 1230 confirmed HER2-positive patients in the lapatinib group and in 208 (17%) of 1260 in the placebo group had a disease-free survival event (HR 0·82, 95% 0·67-1·00; p=0·04). Serious adverse events occurred in 99 (6%) of 1573 patients taking lapatinib and 77 (5%) of 1574 patients taking placebo, with higher incidences of grade 3-4 diarrhoea (97 [6%] vs nine [<1%]), rash (72 [5%] vs three [<1%]), and hepatobiliary disorders (36 [2%] vs one [<1%]). Our data show that there was no significant difference in disease-free survival between groups when analysed in the intention-to-treat population. However, exploratory analyses restricted to patients who had HER2-positive disease confirmed by central fluorescence in-situ hybridisation review suggested marginal benefit with lapatinib in terms of disease-free survival. Thus lapatinib might be an option for women with HER2-positive breast cancer who do not or cannot receive adjuvant trastuzumab. GlaxoSmithKline.


[A Case of Refractory Hemorrhagic Cystitis in which Bleeding Control was Finally Achieved by Cystectomy].
A 60-year-old man presented at our hospital with gross hematuria. He had been treated for nephrotic syndrome with cyclophosphamide and steroids since he was in his 20s. We detected diffuse hemorrhagic cystitis on cystoscopy and diagnosed him with cyclophosphamide-induced hemorrhagic cystitis. He was hospitalized due to clot retention. We treated him with blood transfusion for severe anemia and conducted continuous bladder irrigation. We performed hyperbaric oxygen therapy and transurethral electric coagulation, and increased the steroid dose. However, we could not control the hematuria. Finally, we performed cystectomy, and he is now well without hematuria. Although cystectomy is the final option, it is important to decide it in a timely manner because a delay decreases the quality of life.


The VersaLive platform enables microfluidic mammalian cell culture for versatile applications.
Microfluidic-based cell culture allows for precise spatio-temporal regulation of microenvironment, live cell imaging and better recapitulation of physiological conditions, while minimizing reagents' consumption. Despite their usefulness, most microfluidic systems are designed with one specific application in mind and usually require specialized equipment and expertise for their operation. All these requirements prevent microfluidic-based cell culture to be widely adopted. Here, we designed and implemented a versatile and easy-to-use perfusion cell culture microfluidic platform for multiple applications (VersaLive) requiring only standard pipettes. Here, we showcase the multiple uses of VersaLive (e.g., time-lapse live cell imaging, immunostaining, cell recovery, cell lysis, plasmid transfection) in mammalian cell lines and primary cells. VersaLive could replace standard cell culture formats in several applications, thus decreasing costs and increasing reproducibility across laboratories. The layout, documentation and protocols are open-source and available online at https://versalive.tigem.it/ .


Long-distance dispersal and speciation of Australasian and American species of Cortinarius sect. Cortinarius.
We present a multigene phylogeny (partial nuc rDNA and RPB2) of Cortinarius sect. Cortinarius (i.e. the C. violaceus group), which reveals eight species distributed in Europe, Australasia, South America, Central America and North America. Relaxed molecular clock analyses suggested that diversification began during the Miocene, thus rejecting more ancient Gondwanan origin scenarios among the taxa currently occurring in the northern and southern hemispheres. There was strong support for an Australasian origin of the C. violaceus group with initial dispersal to the Neotropics, followed by migration into North America and Europe. A dispersal-extinction cladogenesis model that includes a parameter for founder effects was the most highly supported biogeographic model in the program BioGeoBEARS. A maximum likelihood analysis showed the most recent common ancestor of sect. Cortinarius was an angiosperm ectomycorrhizal associate. Ancestral associations at the plant family level, however, were ambiguous. Of eight recovered species-level lineages, C. violaceus is the only one that associates with Pinaceae and the only species to associate with both Pinaceae and angiosperms. This analysis showed that long-distance dispersal and founder event speciation have been important factors during evolution of the C. violaceus group.


DNA protective properties of vanillin against gamma-radiation under different conditions: possible mechanisms.
Ionizing radiation is an important genotoxic agent. Protecting against this form of toxicant, especially by a dietary component, has several potential applications. In the present study, we have examined the ability of vanillin (4-hydroxy-3-methoxybenzaldehyde), a naturally occurring food flavouring agent, to inhibit radiation-induced DNA damage measured as strand breaks under in vitro, ex vivo and in vivo conditions besides the possible mechanisms behind the observed protection. Our study showed that there was a concentration-dependent inhibition of the disappearance of super-coiled (ccc) form of plasmid pBR322 (in vitro) upon exposure to 50 Gy of gamma-radiation. Presence of 0.5 mM vanillin has a dose-modifying factor (DMF) of 6.75 for 50% inactivation of ccc form. Exposure of human peripheral blood leucocytes (ex vivo) to gamma-radiation causes strand breaks in the cellular DNA, as assessed by comet assay. When leucocytes were exposed to 2 Gy of gamma-radiation there was an increase in parameters of comet assay such as %DNA in tail, tail length, 'tail moment' and 'Olive tail moment'. The presence of 0.5 mM vanillin during irradiation significantly reduced these parameters. Damage to DNA in mouse peripheral blood leucocytes after whole-body exposure of mice (in vivo) to gamma-radiation was studied at 1 and 2 h post-irradiation. There was recovery of DNA damage in terms of the above-mentioned parameters at 2 h post-irradiation. This was more than that observed at 1 h. The recovery was more in vanillin treated mice. Hence our studies showed that vanillin offers protection to DNA against radiation-induced damage possibly imparting a role other than modulation of DNA repair. To examine the possible mechanisms of radioprotection, in terms of radiation-derived radicals, we carried out the reaction of vanillin with ABTS*(+) radical spectrophotometrically besides with DNA peroxyl and carbonyl radicals by using pulse radiolysis. Our present investigations show that vanillin has ability to protect against DNA damage in plasmid pBR322, human and mouse peripheral blood leucocytes and splenic lymphocytes besides enhancing survival in splenic lymphocytes against gamma-radiation, and that the possible mechanism may involve scavenging of radicals generated during radiation, apart from modulation of DNA repair observed earlier.


Ginkgo biloba extract (EGb 761) in Alzheimer's disease: is there any evidence?
For centuries, extracts from the leaves of the Ginkgo biloba tree have been used as Chinese herbal medicine to treat a variety of health disorders. The standardized Ginkgo biloba extract EGb 761 was marketed in France and Germany 30 years ago for various vascular and cerebral deficits and is now classified as a food supplement in the United States. EGb 761 is currently the focus of phase-III clinical trials, GEM and GuidAge studies, to evaluate its efficacy on the prevention of Alzheimer's disease (AD) in subjects over 70 years old. This review summarizes recent advancements in our understanding of the potential role of EGb 761 in the prevention of AD. Besides its well-known free radical scavenging properties, the ability of EGb 761 to protect neurons probably also involves other intracellular pathways. We will point out potential targets of EGb 761 in the amyloid cascade such as its antiamyloidogenic properties or the regulation of gene expression. Moreover we will discuss the complexity of the cellular and molecular mechanisms of EGb 761 and the significance of the synergic effect of different constituents of EGb 761.


Self-audit: its effect on quality of care.
Using a crossover design, it is shown that an individual criteria setting followed by immediate feedback of previous performance produced a sustained and continuing improvement in recording for two common conditions (cystitis and vaginitis). The intervention, which is simple and could easily be applied in other settings, produced improvements significant at the P = .001 level. The study controlled for overall improvement in record keeping. Further testing of this method of influencing physician performance is warranted.


Plasma B-6 vitamer and plasma and urinary 4-pyridoxic acid concentrations in young women as determined using high performance liquid chromatography.
Plasma B-6 vitamer and plasma and urinary 4-pyridoxic acid concentrations of 21 young white women, 21-27 years, having radiomonitored pyridoxal 5'-phosphate and coenzyme stimulation of erythrocyte alanine aminotransferase activities indicative of adequate vitamin B-6 status were determined in an effort to establish normal ranges for plasma B-6 vitamers. B-6 vitamers and 4-pyridoxic acid were quantitated using reversed phase high performance liquid chromatography with fluorometric and ultraviolet detection. Pyridoxal phosphate values obtained by radioenzymatic and chromatographic, fluorometric and ultraviolet, assays were highly correlated as were pyridoxine phosphate values determined using both detectors. The B-6 vitamer and 4-pyridoxic acid values of these subjects should be of use in the establishment of normal ranges of these congeners in women.


Dehydration of Fructose to 5-HMF over Acidic TiO2 Catalysts.
Different solid sulfonic titania-based catalysts were investigated for the hydrothermal dehydration of fructose to 5-hydroxymethylfurfural (5-HMF). The catalytic behavior of the materials was evaluated in terms of fructose conversion and selectivity to 5-HMF. The surface and structural properties of the catalysts were investigated by means of X-ray diffraction (XRD), N2 adsorption isotherms, thermo-gravimetric analysis (TGA), X-ray photoelectron spectroscopy (XPS) and acid capacity measurements. Special attention was focused on the reaction conditions, both in terms of 5-HMF selectivity and the sustainability of the process, choosing water as the solvent. Among the various process condition studied, TiO2-SO3H catalyzed a complete conversion (99%) of 1.1M fructose and 5-HMF selectivity (50%) and yield (50%) at 165 °C. An important improvement of the HMF selectivity (71%) was achieved when the reaction was carried out by using a lower fructose concentration (0.1M) and lower temperature (140 °C). The catalytic activities of the materials were related to their acid capacities as much as their textural properties. In particular, a counterbalance between the acidity and the structure of the pores in which the catalytic sites are located, results in the key issue for switch the selectivity towards the achievement of 5-HMF.


"It's not a priority when we're in combat": public health professionals and military tobacco control policy.
Tobacco use is prevalent among service members, but civilian public health groups have not effectively addressed military tobacco control policy issues. We conducted focus groups in 2010 and 2012 with participants from public health and tobacco control organizations regarding their understanding of the military and of tobacco use in that context. Misperceptions were common. Military personnel were believed to be young, from marginalized populations, and motivated to join by lack of other options. Tobacco use was considered integral to military life; participants were sometimes reluctant to endorse stronger tobacco control policies than those applied to civilians, although some believed the military could be a social policy leader. Engaging public health professionals as effective partners in tobacco-free military efforts may require education about and reframing of military service and tobacco control policy.


Engineering of a self-adjuvanted iTEP-delivered CTL vaccine.
Cytotoxic T lymphocyte (CTL) epitope peptide-based vaccines are widely used in cancer and infectious disease therapy. We previously generated an immune-tolerant elastin-like polypeptides (iTEPs)-based carrier to deliver a peptide CTL vaccine and enhance the efficiency of the vaccine. To further optimize the vaccine carrier, we intended to potentiate its function by designing an iTEP-based carrier that was able to deliver adjuvant and a vaccine epitope as one molecule. Thus, we fused a 9-mer H100, a peptide derived from the high-mobility group box 1 protein (HMGB1) that could induce activation of dendritic cells (DCs), with an iTEP polymer to generate a new iTEP polymer named H100-iTEP. The H100-iTEP still kept the feature of reversible phase transition of iTEPs and should be able to be used as a polymer carrier to deliver peptide vaccines. The expression levels of CD80/CD86 on DCs were assessed using flow cytometry. The iTEP fusion-stimulated IL-6 secretion by DCs was measured with ELISA. Activation of antigen-specific CD8+ T cells induced by iTEP fusions was examined through a B3Z hybridoma cell activation assay. In vivo CTL activation promoted by iTEP fusions was detected by an IFN-γ-based ELISPOT assay. The iTEP fused with H100 could induce maturation of DCs in vitro as evidenced by increased CD80 and CD86 expression. The iTEP fusion also promoted activation of DCs by increasing secretion of a proinflammatory cytokine IL-6. The N-terminus or C-terminus fusion of H100 to iTEP had a similar effect and a reduced form of cysteine in iTEP fusions was required for DC stimulation. iTEP fusions potentiated a co-administrated CTL vaccine by increasing an antigen-specific CTL response in vitro and in vivo. When the H100-iTEP was fused to a CTL epitope to generate a one-molecule vaccine, this self-adjuvanted vaccine elicited a stronger antigen-specific CTL response than a vaccine adjuvanted by Incomplete Freund's Adjuvant. Thus, we have successfully generated a functional, one-molecule iTEP-based self-adjuvanted vaccine.


Concentration of 123I-metaiodobenzylguanidine in left and right liver lobes. Findings indicate regional differences in function in the normal liver.
Normal radioactivity in the liver is often shown to be higher in the left lobe than in the right lobe at clinical examination by single photon emission computed tomography (SPECT) with 123I-metaiodobenzylguanidine (123I-MIBG). Our objective was to determine whether this represents a pathological condition. The distribution of 123I-MIBG in the liver was retrospectively studied in clinical patients who had normal CT examinations of the liver and spleen. In the SPECT sections of 27 123I-MIBG examinations, we determined the activity ratios between the left and right lobes. The control group comprised 33 examinations with (111)In-pentetreotide (OctreoScan) and 23 examinations with 99mTc-antigranulocyte antibody. The mean activity ratio between left and right lobes for 123I-MIBG was 1.24, and for (111)In-pentetreotide 0.87. These figures differed significantly both from each other and from 1.00. The mean ratio for 99mTc-antibody at the early examinations was 0.99, and at the late examinations 0.95. These figures differed significantly from the values for 123I-MIBG and (111)In-pentetreotide. The increased concentration of 123I-MIBG in the left lobe of the liver compared to the right lobe is a normal finding. The reason for this cannot be explained. The difference in the way in which the left and right lobes deal with the three radiopharmaceuticals is a new finding and indicates a regional difference in liver function that has not been reported previously.


Artificial Intelligence Assisted Multi-modal Photoacoustic-Ultrasound Imaging for Studying Renal Tissue Function and Hemodynamics.
Combined functional-anatomic imaging modalities, which integrate the benefits of visualizing gross anatomy along with the functional or metabolic information of tissue has revolutionized the world of medical imaging. However, such existing imaging modalities are very costly. An alternative option could be a hybrid modality combining contrast-enhanced ultrasound, doppler and photoacoustic imaging. In the current study, we propose an artificial intelligence assisted multi-modal imaging platform where we have used U-net model for segmenting the anatomical features from the ultrasound images obtained from an animal model study. The neural network has performed accurately for three different cases, each with a high dice score. The model was co-validated with doppler images. Further, blood perfusion and tissue oxygenation information from the predicted anatomical structures were also studied. The present findings confirm the feasibility of using this multimodal imaging modality facilitated by artificial intelligence for better understanding of the hemodynamics of the kidney.Clinical Relevance-A multi-modal imaging technique has been proposed which would provide anatomical and functional information to the clinicians for early detection and tracking of the disease prognosis. Unlike existing imaging modalities like PET-CT (Positron Emission Tomography- Computed Tomography), the proposed modality is much more costeffective and radiation free (non-ionizing nature).


Clinical spectrum of food allergies: a comprehensive review.
Food allergy is defined as an adverse immune response towards food proteins or as a form of a food intolerance associated with a hypersensitive immune response. It should also be reproducible by a double-blind placebo-controlled food challenge. Many reported that food reactions are not allergic but are intolerances. Food allergy often presents to clinicians as a symptom complex. This review focuses on the clinical spectrum and manifestations of various forms of food allergies. According to clinical presentations and allergy testing, there are three types of food allergy: IgE mediated, mixed (IgE/Non-IgE), and non-IgE mediated (cellular, delayed type hypersensitivity). Recent advances in food allergy in early childhood have highlighted increasing recognition of a spectrum of delayed-onset non-IgE-mediated manifestation of food allergy. Common presentations of food allergy in infancy including atopic eczema, infantile colic, and gastroesophageal reflux. These clinical observations are frequently associated with food hypersensitivity and respond to dietary elimination. Non-IgE-mediated food allergy includes a wide range of diseases, from atopic dermatitis to food protein-induced enterocolitis and from eosinophilic esophagitis to celiac disease. The most common food allergies in children include milk, egg, soy, wheat, peanut, treenut, fish, and shellfish. Milk and egg allergies are usually outgrown, but peanut and treenut allergy tends to persist. The prevalence of food allergy in infancy is increasing and may affect up to 15-20 % of infants. The alarming rate of increase calls for a public health approach in the prevention and treatment of food allergy in children.


Robust audio-visual speech recognition under noisy audio-video conditions.
This paper presents the maximum weighted stream posterior (MWSP) model as a robust and efficient stream integration method for audio-visual speech recognition in environments, where the audio or video streams may be subjected to unknown and time-varying corruption. A significant advantage of MWSP is that it does not require any specific measurements of the signal in either stream to calculate appropriate stream weights during recognition, and as such it is modality-independent. This also means that MWSP complements and can be used alongside many of the other approaches that have been proposed in the literature for this problem. For evaluation we used the large XM2VTS database for speaker-independent audio-visual speech recognition. The extensive tests include both clean and corrupted utterances with corruption added in either/both the video and audio streams using a variety of types (e.g., MPEG-4 video compression) and levels of noise. The experiments show that this approach gives excellent performance in comparison to another well-known dynamic stream weighting approach and also compared to any fixed-weighted integration approach in both clean conditions or when noise is added to either stream. Furthermore, our experiments show that the MWSP approach dynamically selects suitable integration weights on a frame-by-frame basis according to the level of noise in the streams and also according to the naturally fluctuating relative reliability of the modalities even in clean conditions. The MWSP approach is shown to maintain robust recognition performance in all tested conditions, while requiring no prior knowledge about the type or level of noise.


Self-assembly of three-dimensional prestressed tensegrity structures from DNA.
Tensegrity, or tensional integrity, is a property of a structure indicating a reliance on a balance between components that are either in pure compression or pure tension for stability. Tensegrity structures exhibit extremely high strength-to-weight ratios and great resilience, and are therefore widely used in engineering, robotics and architecture. Here, we report nanoscale, prestressed, three-dimensional tensegrity structures in which rigid bundles of DNA double helices resist compressive forces exerted by segments of single-stranded DNA that act as tension-bearing cables. Our DNA tensegrity structures can self-assemble against forces up to 14 pN, which is twice the stall force of powerful molecular motors such as kinesin or myosin. The forces generated by this molecular prestressing mechanism can be used to bend the DNA bundles or to actuate the entire structure through enzymatic cleavage at specific sites. In addition to being building blocks for nanostructures, tensile structural elements made of single-stranded DNA could be used to study molecular forces, cellular mechanotransduction and other fundamental biological processes.


[Use of low-frequency currents in the treatment of severe intestinal paralysis].
Low-frequency impulse currents (Bernar current) are suggested for treatment of paralytic intestinal obstruction. The method was used in 108 patients, in whom the cause of paresis was as follows: acute purulent peritonitis, pancreatitis, operations on the abdominal aorta and its branches. In 102 patients the stimulation proved to be effective, in 6 cases of progressive purulent peritonitis no effect was gained. In a number of patients the procedure had to be repeated during 2--3 days. Generally, diadynamic currents were employed in a complex with other measures: syphon enema, paranephral blockade, cholinergics, etc. A grave cardiac pathology and oncological diseases are considered as contraindications.


ECG left ventricular hypertrophy in aortic stenosis: Relationship with cardiac structure, invasive hemodynamics, and long-term mortality.
In aortic stenosis (AS), left ventricular hypertrophy (LVH) is the response to pressure overload and represents the substrate for a maladaptive cascade, the so-called AS-related cardiac damage. We hypothesized that in AS patients electrocardiogram (ECG) LVH not only predicts echocardiography LVH but also other noninvasive and invasive markers of cardiac damage and prognosis after aortic valve replacement (AVR). In 279 patients with severe AS undergoing ECG, echocardiography, and cardiac catheterization before AVR, the Sokolow-Lyon index, the Cornell product, the Romhilt-Estes score, and the Peguero-Lo Presti score were assessed. The mean left ventricular mass index was 109 ± 34 g/m2 , and 131 (47%) patients had echocardiography LVH. The areas under the receiver operator characteristics curve (AUC) for the Sokolow-Lyon index, the Cornell product, the Romhilt-Estes score, and the Peguero-Lo Presti score for the prediction of echocardiography LVH were 0.59, 0.70, 0.63, and 0.65. The Peguero-Lo Presti score had the numerically greatest AUC for the prediction of left ventricular end-diastolic pressure >15 mmHg, mean pulmonary artery wedge pressure >15 mmHg, pulmonary vascular resistance >3 Wood units, mean right atrial pressure >14 mmHg, and stroke volume index <31 mL/m2 . After a median follow-up of 1365 (interquartile range: 931-1851) days after AVR only the Peguero-Lo Presti score was significantly associated with all-cause mortality [hazard ratio: 1.24 (95% confidence interval: 1.01-1.54); per 1 mV increase; p = .045]. Among severe AS patients, the Peguero-Lo Presti score is associated with abnormalities in cardiac structure including LVH, invasive measures of cardiac damage, and long-term mortality after AVR.


Inhaled oxytocin increases positive social behaviors in newborn macaques.
Early caregiver-infant interactions are critical for infants' socioemotional and cognitive development. Several hormones and neuromodulators, including oxytocin, affect these interactions. Exogenous oxytocin promotes social behaviors in several species, including human and nonhuman primates. Although exogenous oxytocin increases social function in adults--including expression recognition and affiliation--it is unknown whether oxytocin can increase social interactions in infants. We hypothesized that nebulized oxytocin would increase affiliative social behaviors and such effects would be modulated by infants' social skills, measured earlier in development. We also hypothesized that oxytocin's effects on social behaviors may be due to its anxiolytic effects. We tested these hypotheses in a blind study by nebulizing 7- to 14-d-old macaques (n = 28) with oxytocin or saline. Following oxytocin administration, infants' facial gesturing at a human caregiver increased, and infants' salivary oxytocin was positively correlated with the time spent in close proximity to a caregiver. Infants' imitative skill (measured earlier in development: 1-7 d of age) predicted oxytocin-associated increases in affiliative behaviors--lip smacking, visual attention to a caregiver, and time in close proximity to a caregiver--suggesting that infants with higher propensities for positive social interactions are more sensitive to exogenous oxytocin. Oxytocin also decreased salivary cortisol, but not stress-related behaviors (e.g., scratching), suggesting the possibility of some anxiolytic effects. To our knowledge, this study provides the first evidence that oxytocin increases positive social behaviors in newborns. This information is of critical importance for potential interventions aimed at ameliorating inadequate social behaviors in infants with higher likelihood of developing neurodevelopmental disorder.


Lack of any impact of histopathology type on prognosis in patients with early-stage adenocarcinoma and squamous cell carcinoma of the uterine cervix.
The aim of this study was to evaluate the prognosis of patients with stage IA-IIB cervical carcinoma and to investigate a possible correlation of histology with prognosis. Two hundred fifty one patients with adenocarcinoma and squamous cell carcinoma (SCC) histology for FIGO (International Federation of Gynecology and Obstetrics) stage IA-IIB uterine cervical carcinomas at the Radiation Oncology Clinic of GH Okmeydani Training and Research Hospital between January 1996 and December 2006 were selected, analyzed retrospectively and evaluated in terms of general characteristics and survival. Disease-free survival (DFS) and overall survival (OS) was calculated using the Kaplan-Meier method and differences were compared with the log-rank test. Multivariate analysis using a Cox-proportional hazards model was used to adjust for prognostic factors and to estimate hazard ratio (HR) with 95% confidence interval (CI). There was no differences between the two tumour types in age, stage, pelvic nodal metastasis, parametrial invasion, surgical margin status, DSI, LVSI, maximal tumor diameter, grade, and treatment modalities. 5-year OS and DFS were 73% and 77%, versus 64% and 69%, for SCC and adenocarcinoma, respectively (p> 0.05). Multivariate analysis revealed independent prognostic factors including pelvic nodal metastasis and resection margin status for OS (p=0.008, p=0.002, respectively). Prognosis of FIGO stage IA-IIB cervical cancer patients was found to be the same for those with adenocarcinoma and SCC.


An economic analysis of community-level fast food prices and individual-level fast food intake: a longitudinal study.
While dietary intake is shaped by cost, there is minimal research on the association between community-level food prices and dietary intake. We used nationally representative, longitudinal data to examine how community-level food price variation was associated with individual-level fast food intake by race/ethnicity and income across waves II (1996) and III (2001-2002) of the National Longitudinal Study of Adolescent Health (n=11,088) from 158 baseline and 363 follow-up US counties. Negative binomial regression models predicting the number of fast food meals per week show strong relationships between fast food consumption and prices of fast food and soda that varied by gender and race/ethnicity. We found relatively stronger association between food prices and fast food intake for males and relatively greater price sensitivity for soda versus burgers. In the group with strongest associations (black males), a 20% increase in the price of soda was associated with a decrease of 0.25 visits to a fast food restaurant per week. Economic incentives may be an effective mechanism to address fast food intake in an age group at high risk for obesity.


Evaluation of five mediums for the stabilization of Brucella abortus strain 19 dessicated by lyophilization.
Lyophilized Brucella abortus Strain 19 vaccines were prepared using five recommended mediums. These five vaccines were compared with each other and with liquid vaccine relative to their suitability for (1) maintaning distinguishing cultural characteristics; (2) maintaining viability during lyophilization; (3) quality of restoration; (4) maintaining viability under various storage temperatures and (5) maintaining stable, antigenic and virulence qualities.


Efficacy of convenience meal-type foods designed for diabetes in the management of metabolic syndrome based on a 3-week trial.
This study aimed to assess the effect of meal-type food for diabetes on improving metabolic syndrome risk factors in adults. The participants were adult men and women aged 40-55 y with 1 or more risk factors for metabolic syndrome. They were provided with a diabetic diet (a meal-type food) and general diet in the form of home meal replacement for 3 wk. The current research used a crossover design. All participants had iso-caloric meal replacement per day, and there was a 2-wk washout period between each diet. The nutritional standards of a diabetic diet were based on the guidelines of the Ministry of Food and Drug Safety, which are: <50% carbohydrates, <10% sugars, <7% saturated fat, and >10 g dietary fiber. The average caloric content was 489.1 ± 45.0 kcal. The composition of the general diet was similar to that of the diabetic diet; however, there were differences in sugar content. In total, 15 participants were included in the research, and there was no significant difference between the 2 groups in terms of nutrient intake during the intervention period. Body weight (P = 0.001), body mass index (P = 0.004), waist circumference (P = 0.030), triacylglycerol (P = 0.002), total cholesterol (P = 0.001), and low-density lipoprotein cholesterol (P = 0.008) levels were significantly lower in the diabetic diet intervention period than before and after 3 wk of the intervention. In addition, reduction in body weight (P = 0.001), body mass index (P = 0.006), waist circumference (P = 0.032), and triacylglycerol (P = 0.036) and total cholesterol (P = 0.007) levels in the diabetic diet intervention period significantly differed compared with those in the general diet intervention period. Replacing 1 meal per day with meal-type food for diabetes improved body composition and blood lipid levels in adults with metabolic syndrome risk factors.


Gender Comparison of Young People Charged With Murder in England and Wales.
This study investigated gender differences regarding young people charged with murder in England and Wales. A sample of 318 cases was collected from the Home Office's Homicide Index and analysed. Of these cases, 93% of the offenders were male and 7% female. The analyses explored gender differences in terms of the offender's race, offender's age, victim's age, victim's gender, weapon used, offender-victim relationship, and circumstances of the offence. The study found that a female offender was significantly more likely to murder a family member than a male offender, and a male offender was significantly more likely to murder a stranger than a female offender. In addition, a female offender was significantly more likely to murder a victim below the age of 5 than a male offender. Implications for interventions with young people who are charged with murder are discussed.


How to evaluate the child presenting with an apparent life-threatening event?
Infants who have experienced an apparent life-threatening event typically undergo an extensive evaluation to rule out serious underlying conditions. To evaluate the yield of different tests performed after an apparent life-threatening event and to identify high risk groups in which more extensive diagnostic tests are required. A retrospective study was conducted in a children's hospital for a 4 year period and the charts of infants who were admitted with an apparent life-threatening event were reviewed. The yield for each diagnostic test was established according to the ratio of positive results contributing to the diagnosis of the apparent life-threatening event. The study included 69 infants between the ages of 1 week and 1 year. There were abnormal findings in 36% of the cases. Gastroesophageal reflux was the most common diagnosis (60%). In the remaining patients the diagnosis was either seizures (12%) or respiratory tract infections (28%). Tests used for the diagnosis of cardiac, metabolic and nonrespiratory infections had no yield. A positive correlation was found between abnormal test results and abnormal physical examination (P = 0.001), an abnormal perinatal history (P = 0.017), and age older than 2 months (P = 0.002). The yield of most of the tests performed after an apparent life-threatening event is low, especially in infants with a normal perinatal history and physical examination.


Curcumin-PVP improves the in vitro efficacy of ivermectin against resistant and susceptible Haemonchus contortus.
Ivermectin (IVM) resistance in parasitic nematodes such as Haemonchus contortus has spurred a search for substances that help to recover its efficacy. One potential agent is the natural product curcumin (CUR). In this study, CUR was combined with polyvinylpyrrolidone (PVP) (CUR/PVP) to improve its solubility and biological applicability. This study determined the effect of CUR preincubation on the EC50 of IVM in three H. contortus isolates with different susceptibilities to IVM. The IVM effective concentration 50% (EC50) was determined for three H. contortus isolates with different IVM susceptibilities using the larval migration inhibition (LMI) test. The three isolates were (i) PARAISO (IVM resistant), (ii) FMVZ-UADY (IVM susceptible), and (iii) CENID-SAI INIFAP (reference IVM susceptible). The L3 of each isolate were preincubated for 3 h with one of three concentrations of CUR (μg curcumin/mL): CONC-1 (3.67), CONC-2 (5.67), or CONC-3 (8.48). Corresponding controls were performed without CUR. The EC50 of IVM was determined for each isolate after they were exposed to the different CUR concentrations. The EC50 of IVM differed between the isolates PARAISO > FMVZ-UADY > CENID-SAI INIFAP (P < 0.05). The CUR preincubation at CONC-1 did not decrease the EC50 of IVM for any of the three isolates, suggesting a hormetic effect. By contrast, CUR preincubation at CONC-2 or CONC-3 decreased the IVM EC50 for the PARAISO isolate (P < 0.05) compared with the reference isolate and reduced the EC50 of IVM for the FMVZ-UADY and CENID-SAI INIFAP isolates below the EC50 for the CENID-SAI INIFAP isolate without CUR preincubation. In conclusion, Preincubation of H. contortus L3 with CUR reduced the EC50 of IVM for field isolates classified as resistant and susceptible to IVM. The CUR preincubation reduced the IVM RF in the different isolates tested.


Association of immune responses of Zebu and Holstein-Friesian cattle and resistance to mycobacteria in a BCG challenge model.
Mycobacterium bovis is the main cause of bovine tuberculosis (BTB) in cattle and can also infect humans. Zebu cattle are considered more resistant to some infectious diseases compared with Holstein-Friesian (HF) cattle, including BTB. However, epidemiological studies may not take into account usage differences of the two types of cattle. HF cattle may suffer greater metabolic stress due to their more or less exclusive dairy use, whereas Zebu cattle are mainly used for beef production. In experiments conducted so far, the number of animals has been too small to draw statistically robust conclusions on the resistance differences between these cattle breeds. Here, we used a BCG challenge model to compare the ability of naïve and vaccinated Zebu and HF cattle to control/kill mycobacteria. Young cattle of both breeds with similar ages were housed in the same accommodation for the duration of the experiment. After correcting for multiple comparisons, we found no difference between naïve HF and Zebu (ρ = 0.862) cattle. However, there was a trend for vaccinated HF cattle to have lower cfu numbers than non-vaccinated HF cattle (ρ = 0.057); no such trend was observed between vaccinated and non-vaccinated Zebu cattle (ρ = 0.560). Evaluation of antigen-specific IFNγ secretion by PBMC indicated that Zebu and HF cattle differed in their response to mycobacteria. Thus, whilst there may be difference in immune responses, our data indicate that with the number of animals included in the study and under the conditions used in this work, we were unable to measure any differences between Zebu and HF cattle in the overall control of mycobacteria. Whilst determination of different susceptibilities between Zebu and HF cattle using the BCG challenge model will require larger numbers of animals than the number of animals used in this experiment, these data should inform future experiments.


IGF-IR internalizes with Caveolin-1 and PTRF/Cavin in HaCat cells.
Insulin-like growth factor-I receptor (IGF-IR) is a tyrosine kinase receptor (RTK) associated with caveolae, invaginations of the plasma membrane that regulate vesicular transport, endocytosis and intracellular signaling. IGF-IR internalization represents a key mechanism of down-modulation of receptors number on plasma membrane. IGF-IR interacts directly with Caveolin-1 (Cav-1), the most relevant protein of caveolae. Recently it has been demonstrated that the Polymerase I and Transcript Release Factor I (PTRF/Cavin) is required for caveolae biogenesis and function. The role of Cav-1 and PTRF/Cavin in IGF-IR internalization is still to be clarified. We have investigated the interaction of IGF-IR with Cav-1 and PTRF/Cavin in the presence of IGF1in human Hacat cells. We show that IGF-IR internalization triggers Cav-1 and PTRF/Cavin translocation from plasma membrane to cytosol and increases IGF-IR interaction with these proteins. In fact, Cav-1 and PTRF/Cavin co-immunoprecipitate with IGF-IR during receptor internalization. We found a different time course of co-immunoprecipitation between IGF-IR and Cav-1 compared to IGF-IR and PTRF/Cavin. Cav-1 and PTRF/Cavin silencing by siRNA differently affect surface IGF-IR levels following IGF1 treatment: Cav-1 and PTRF/Cavin silencing significantly affect IGF-IR rate of internalization, while PTRF/Cavin silencing also decreases IGF-IR plasma membrane recovery. Since Cav-1 phosphorylation could have a role in IGF-IR internalization, the mutant Cav-1Y14F lacking Tyr14 was transfected. Cav-1Y14F transfected cells showed a reduced internalization of IGF-IR compared with cells expressing wild type Cav-1. Receptor internalization was not impaired by Clathrin silencing. These findings support a critical role of caveolae in IGF-IR intracellular traveling. These data indicate that Caveolae play a role in IGF-IR internalization. Based on these findings, Cav-1 and PTRF/Cavin could represent two relevant and distinct targets to modulate IGF-IR function.


Modelling in vitro growth of dense root networks.
Hairy roots are plants genetically transformed by Agrobacterium rhizogenes, which do not produce shoots and are composed mainly by roots. Hairy roots of Ophiorrhiza mungos Linn. are currently gaining interest of pharmacologists, since a secondary product of their metabolism, camptothecin, is used in chemotherapy. To optimize the production of valuable secondary metabolites it is necessary to understand the metabolism and growth of these roots systems. In this work, a mathematical model for description of apical growth of a dense root network (e.g. hairy roots) is derived. A continuous approach is used to define densities of root tips and root volume. Equations are posed to describe the evolution of these and are coupled to the distribution of nutrient concentration in the medium and inside the network. Following the principles of irreversible thermodynamics, growth velocity is defined as the sum over three different driving forces: nutrient concentration gradients, space gradients and root tip diffusion. A finite volume scheme was used for the simulation and parameters were chosen to fit experimental data from O. mungos Linn. hairy roots. Internal nutrient concentration determines short-term growth. Long-term behavior is limited by the total nutrient amount in the medium. Therefore, mass yield could be increased by guaranteeing a constant supply of nutrients. Increasing the initial mass of inoculation did not result in higher mass yields, since nutrient consumption due to metabolism also rose. Four different growth strategies are compared and their properties discussed. This allowed to understand which strategy might be the best to increase mass production optimally. The model is able to describe very well the temporal evolution of mass increase and nutrient uptake. Our results provide further understanding of growth and density distribution of hairy root network and therefore it is a sound base for future applications to describe, e.g., secondary metabolite production.


The structure of confined oxygen in silica xerogels.
The microscopic structure of oxygen confined in silica xerogels has been studied as a function of temperature. In large pores, a crystalline solid forms with a structure consistent with that of the bulk. The size of the crystallites is much larger than the pore size, indicating that cooperative effects among pores are important in freezing. As the pore size is decreased, a crossover occurs where solidification results in an amorphous phase in the pores. The resulting amorphous phase is solid but is less ordered than the liquid phase.


A new questionnaire to detect sleep disorders.
Sleep disorders remain largely undiagnosed in the general population. The current study assessed whether the Global Sleep Assessment Questionnaire (GSAQ) could: (1), distinguish between sleep disorders (including no sleep disorder); (2), be a reliable and valid sleep disorder screener; and (3), serve as a practical, user-friendly screening tool for primary care and sleep centers. Two hundred and twelve adults from five sleep centers and two primary care clinics completed the GSAQ and received confirmed diagnoses from a sleep specialist. Of the 212 patients, 139 (65.6%) had at least one sleep disorder, 60 (28.3%) had two or more sleep disorders, and 13 (6.1%) had no confirmed sleep disorder. Ninety-one (43%) individuals completed the GSAQ a second time for reliability testing. Scores for each sleep disorder including, but not limited to, primary insomnia (I), insomnia associated with a mental disorder (IME), obstructive sleep apnea (OSA), periodic limb movement (PLM), and parasomnia (P) were computed. The sensitivity and specificity were estimated using comprehensive clinical diagnosis as the gold standard and mean domain scores as a cutpoint. The mean participant age was 45 years, 52% were female. Observed frequencies were: 36 (I), 14 (IME), 31 (OSA), 7 (PLM) and 4% (P). Test-retest reliability ranged from 0.51 to 0.92. Pearson correlation coefficients suggested that the GSAQ discriminated between diagnoses. The sensitivities and specificities were 79/57, 83/51, 93/58, 93/52, and 100/49 for I, IME, OSA, PLM, and P, respectively. Our findings suggest that the GSAQ can aid in recognizing sleep disorders. Future studies should focus on characterizing its predictive values in primary care settings.


Ventricular arrhythmia and sudden cardiac death in Fabry disease: a systematic review of risk factors in clinical practice.
Fabry disease (FD) is an X-linked lysosomal storage disorder caused by deficiency of α-galactosidase A enzyme. Cardiovascular (CV) disease is a common cause of mortality in FD, in particular as a result of heart failure and arrhythmia, with a significant proportion of events categorized as sudden. There are no clear models for risk prediction in FD. This systematic review aims to identify the risk factors for ventricular arrhythmia (VA) and sudden cardiac deaths (SCD) in FD. A systematic search was performed following PRISMA guidelines of EMBASE, Medline, PubMed, Web of Science, and Cochrane from inception to August 2016, focusing on identification of risk factors for the development of VA or SCD. Thirteen studies were included in the review (n = 4185 patients) from 1189 articles, with follow-up of 1.2-10 years. Weighted average age was 37.6 years, and 50% were male. Death from any cause was reported in 8.3%. Of these, 75% was due to CV problems, with the majority being SCD events (62% of reported deaths). Ventricular tachycardia was reported in 7 studies, with an average prevalence of 15.3%. Risk factors associated with SCD events were age, male gender, left ventricular hypertrophy, late gadolinium enhancement on CV magnetic resonance imaging, and non-sustained ventricular tachycardia. Although a multi-system disease, FD is a predominantly cardiac disease from a mortality perspective, with death mainly from SCD events. Limited evidence highlights the importance of clinical and imaging risk factors that could contribute to improved decision-making in the management of FD.


Early rebleeding in patients with subarachnoid haemorrhage under intensive blood pressure management.
The objective of this study was to report the frequency and clinical characteristics of early rebleeding in subarachnoid haemorrhage (SAH) patients who underwent intensive blood pressure (BP) management. Patients with aneurysmal SAH frequently present to the emergency department (ED) with elevated BP. Intensive BP management has been recommended to lower the risk of early rebleeding. However, few studies have reported the frequency of early rebleeding in SAH patients undergoing BP management. In our institution, SAH patients with systolic BP (SBP)>140 mmHg received continuous intravenous nicardipine to maintain their SBP within 120±20 mmHg after diagnosis. An attempt to implement intensive BP management was made on 309 consecutive SAH patients who presented to our ED within 48 hours of SAH onset. Overall, 24 (7.8%) of the 309 patients sustained early rebleeding. Fifteen patients sustained early rebleeding before the implementation of BP management, and the other nine sustained early rebleeding after the implementation of BP management. Therefore, the frequency of early rebleeding under BP management was 3.1% (9/294). When the 309 patients were dichotomised using ED SBP of 140 mmHg as a cut off (SBP>140 mmHg; n=239 versus SBP⩽140 mmHg; n=70), the latter counter-intuitively exhibited a significantly higher frequency of early rebleeding (5.9% versus 14.2%; p=0.04). This relatively low frequency of early rebleeding under BP management may be acceptable. However, early rebleeding is not eradicated even with strict BP control as factors other than elevated BP are involved. ED SBP within the target range (SBP⩽140 mmHg) does not negate the risk of early rebleeding. Other treatment options that reduce the risk should also be explored.


Neutrophils Encompass a Regulatory Subset Suppressing T Cells in Apparently Healthy Cattle and Mice.
Neutrophils that reside in the bone marrow are swiftly recruited from circulating blood to fight infections. For a long time, these first line defenders were considered as microbe killers. However their role is far more complex as cross talk with T cells or dendritic cells have been described for human or mouse neutrophils. In cattle, these new roles are not documented yet. We identified a new subset of regulatory neutrophils that is present in the mouse bone marrow or circulate in cattle blood under steady state conditions. These regulatory neutrophils that display MHC-II on the surface are morphologically indistinguishable from classical MHC-IIneg neutrophils. However MHC-IIpos and MHC-IIneg neutrophils display distinct transcriptomic profiles. While MHC-IIneg and MHC-IIpos neutrophils display similar bacterial phagocytosis or killing activity, MHC-IIpos only are able to suppress T cell proliferation under contact-dependent mechanisms. Regulatory neutrophils are highly enriched in lymphoid organs as compared to their MHC-IIneg counterparts and in the mouse they express PDL-1, an immune checkpoint involved in T-cell blockade. Our results emphasize neutrophils as true partners of the adaptive immune response, including in domestic species. They open the way for discovery of new biomarkers and therapeutic interventions to better control cattle diseases.


Pharmacotherapy of alcohol dependence: past, present and future research.
Alcohol dependence represents a chronic, relapsing condition with a multifactorial aetiology that includes genetic, neurobiological,psychological, and environmental components. Evidence for the effectiveness of medications in alcohol dependence treatment along with the increased number of compounds available is increasing the use of adjunctive pharmacotherapies. In particular, pharmacotherapies could conceivably address some of the biological aspects of alcohol dependence. Treating a complex behavioral disorder such as alcohol dependence with both pharmacotherapy and psychosocial therapy may give people the best options for recovery. To address the exciting developments in the use of pharmacotherapies for alcohol dependence, we planned this special issue for Current Pharmaceutical Design, entitled "Old and new pharmacotherapies in the management of patients with alcohol dependence". The overall purpose of this special issue is to provide a resource, that researchers and clinicians interested in the pharmacotherapy of alcohol dependence may use, as well as to stimulate how current findings and ongoing research may improve the treatment of our alcohol-dependent patients


Using cognitive fit theory to evaluate the effectiveness of information visualizations: an example using quality assurance data.
Cognitive fit theory, along with the proximity compatibility principle, is investigated as a basis to evaluate the effectiveness of information visualizations to support a decision-making task. The task used in this study manipulates varying levels of task complexity for quality control decisions in a high-volume discrete manufacturing environment. The volume of process monitoring and quality control data produced in this type of environment can be daunting. Today's managers need effective decision support tools to sort through the morass of data in a timely fashion to make critical decisions on product and process quality.


Calculation of vibrational spectra of linear tetrapyrroles. 3. Hydrogen-bonded hexamethylpyrromethene dimers.
The structure and vibrational spectra of hexamethylpyrromethene (HMPM) have been investigated by X-ray crystallography, IR and Raman spectroscopies, and density functional theory calculations. HMPM crystallizes in the form of dimers, which are held together by bifurcated N-H(...N)(2) hydrogen bonds, involving one intramolecular and one intermolecular N-H...N interaction. The monomers are essentially planar, and the mean planes of the monomers lie approximately perpendicular to one another, so that the four N atoms in the dimer form a distorted tetrahedron. The structure of the HMPM dimer is well-reproduced by B3LYP/6-31G calculations. A comparison of the calculated geometry of the dimer with that of the monomer reveals only small changes in the N-H...N entity and the methine bridge angles upon dimerization. These are a result of weakening of the intramolecular N-H...N hydrogen bond and the formation of a more linear N-H...N intermolecular hydrogen bond. Using an empirical relation between the shift of the N-H stretching frequency of pyrrole and the enthalpy of adduct formation with bases [Nozari, M. S.; Drago, R. S. J. Am. Chem. Soc. 1970, 92, 7086-7090], estimates of the strength of the intra- and intermolecular hydrogen bonds are obtained. IR and Raman spectroscopies of HMPM and its isotopomers deuterated at the pyrrolic nitrogen atom and at the methine bridge reveal that the molecule is monomeric in nonpolar organic solvents but dimeric in a solid Ar matrix and in KBr pellets. The matrix IR spectra show a splitting of vibrational modes for the dimer, particularly those involving the N-H coordinates. Due to intrinsic deficiencies of the B3LYP/6-31G approximation, a satisfactory reproduction of these modes of the monomeric and dimeric HMPM requires specific adjustments of the NH scaling factors for the calculated force constants and, in the case of the NH out-of-plane modes of HMPM dimers, also of intra- and intermolecular coupling constants. This parametrization does not significantly affect the other calculated modes, which in general reveal a very good agreement with the experimental data.


Effects of anti-inflammatory drugs on lipopolysaccharide-challenged and -unchallenged equine synovial explants.
To evaluate the effects of anti-inflammatory drugs on lipopolysaccharide (LPS)-challenged and -unchallenged equine synovial membrane in terms of production of prostaglandin E2 (PGE2) and hyaluronan, viability, and histomorphologic characteristics. Synovial membranes were collected from the carpal, tarsocrural, and femoropatellar joints of 6 adult horses. Synovial membranes from each horse were minced and pooled and explants were treated with one of the following: no drug (control), drug, LPS alone, or LPS and drug. Treatment drugs were phenylbutazone (PBZ), flunixin meglumine (FNX), ketoprofen (KET), carprofen (CRP), meloxicam (MEL), low-concentration methylprednisolone (METH), high-concentration METH, dimethyl sulfoxide (DMSO), or an experimental COX-2 inhibitor (dissolved in DMSO). Following 48 hours of culture, medium was assayed for PGE2 and hyaluronan concentration. Synovial explants were assessed for viability and histomorphologic characteristics. For the LPS-challenged explants, PBZ, FNX, KTP CRF MEL, and low-concentration METH suppressed PGE2 production, compared with LPS challenge alone. Only MEL suppressed PGE2 production from LPS-challenged explants, compared with unchallenged explants. Synovial explants maintained > 90% viability and there was no significant difference in viability or hyaluronan production among explants. Histomorphologic scores were significantly decreased for explants treated with low-concentration METH or DMSO. PBZ, FNX, KTP, CRFP MEL, and low-concentration METH suppressed PGE2 production in LPS-challenged explants. Meloxicam appeared to have more selective suppression of COX-2 activity. Histomorphologic scores suggest detrimental effects of METH, DMSO, and the experimental COX-2 inhibitor. Commonly used nonsteroidal anti-inflammatory drugs suppress induced synovial membrane PGE2 production without detrimental effects on synovial membrane viability and function.


[Clinical efficacy of image processing of grid detection and suppression (GDS) in computed radiography].
In projection radiography, stationary grids are indispensable accessories to the improvement of diagnostic imaging. On the other hand, they are becoming one of the issues facing digital image processing. The lead foil that composes the grid can produce moiré on printed films and monitors according to the sampling interval at which the image is read by computed radiography (CR), creating a major obstacle to diagnosing images. The subject of this study on Grid Detection and Suppression (GDS) was the development of comprehensive image-processing software to detect and suppress grid lines automatically. Our results showed that applying GDS parameters 3 approximately 5 could provide a sufficient effect on suppression with little impact on images through the use of a multi-purpose grid (grid ratio 8:1, density 34 lp/cm) for general purposes. In projection radiography, it is expected that soft copy diagnosis will increase because the digital transition is proceeding, and the establishment of high-speed networks is becoming easier. Therefore, the digital environment is expected to improve and the choice of grids and monitors to expand, by using software such as GDS that does not require special skills.


[A burrow of a little ground squirrel as a consortium].
Structure of consortia as an animal community inhabiting a mammalian burrow with an example of the little souslik Spermophilus pygmaeus Pallas from Western Kazakhstan was studied. Species composition, numbers and distribution of invertebrates in different types of burrows and nests of the little souslik were examined on the background to their food dependencies on the host. The consortia is considered as a system of concenters around the host of burrow (center of community, CC). Recognized concenters are given with ranks based on food relations between invertebrate inhabitants and CC: concenter of I rank includes direct parasites and predators of CC, II rank is represented by consumers of dead bodies of the souslik and its life activity products; III rank includes predators and parasites of souslik's cohabitants, and concenter of IV rank encompasses animals, which use the burrow as a refuge only. Within limits of each concenter, a number of "rondos", groups of animals attributed to certain systematic category, for example ticks, gamasid mites, certain insect orders etc., may be recognized.


Lifestyle and Dietary Patterns during the COVID-19 Lockdown in Bahrain: A Web-Based Cross-Sectional Study.
Lifestyle factors such as dietary habits, perceived weight, sleep, and physical activity worsened during the COVID-19 pandemic. Through this study, we aimed to understand the impact of COVID-19 on these lifestyle factors in Bahrain. A cross-sectional study was conducted among 1005 adult Bahrainis. Data were collected online using a structured and validated questionnaire for the assessment of eating habits, physical activity, and lifestyle during the COVID-19 pandemic. Participants were snowballed through those who agreed to answer the online questionnaire. There was a higher consumption of fast food, and a higher dependence on takeaways during the COVID-19 pandemic. About 63.5% of the participants consumed >4 meals per day, compared to 36.5% before the COVID-19. About 30% reported consumption of sugar sweetened beverages from two to three times a day. Weight loss was predominantly observed in persons exercising 1-3 times a week. The consumption of sugar-sweetened beverages was also high, with about 19% reporting drinking sweet beverages once every day, 10.6% from two to three times a day, and 40.4% from one to four times a week. A higher proportion of the participants reported poor sleep quality during the pandemic (31.2%) compared to before (12.2%), and 39.7% of the participants reported feeling lazy. Screen time use also doubled during the pandemic, with participants spending more than five hours per day on screens for entertainment, which went from 22.4% before to 51.9% during the pandemic. The lifestyle and dietary habits changed drastically for our study participants during the pandemic. The increased reliance on processed fast food instead of healthier options is a challenge to be tackled in any future pandemic situation. Future research needs to focus on strategies to promote healthier lifestyle modifications during situations such as the COVID-19 pandemic.


Submicron hierarchy of cellulose nanofibril films with etherified hemicelluloses.
The lack of simple differentiation of all-polysaccharide-film components in nanoscale hinders unveiling their structure-property dependency. Submicron hierarchy of films of cellulose nanofibrils (CNFs) and carbohydrate-based additives was revealed via visualization of the components by their differentiating adhesion to an Atomic Force Microscope (AFM) tip. The differentiation of the film components revealed that distribution of hydroxypropylated hemicellulose in the CNF matrix could be tuned by addition of a plasticizer. The hemicellulose hydroxypropylation degree of substitution (DS) was detected to be another parameter affecting the film structure due to the water-solubility depending on the DS. This was further verified via Quartz Crystal Microbalance with Dissipation Monitoring (QCM-D). The translucent, self-standing films comprising CNFs, sorbitol and hydroxypropylated hemicellulose were tested for mechanical, optical and oxygen diffusion performance. The performance was linked to their structural evenness, which confirmed that the oxygen diffusion through the film is tremendously affected by the film nano hierarchy.


[Characteristics of poliomyelitis viruses isolated from sewage].
Studies of the genetic markers of 39 (57.4%) strains of poliomyelitis virus type I isolated from sewage showed 7 of them to have genetic markers ret+40, Gu+, A+, Ag+ (Mahoney, Koñkov), 3 to be ret+40, Gu+, A+, Ag+ (Koñkov, Sabin), and 10 to be ret+40, Gu-, A-, Ag- (LSc 2ab). Among 20 (29.4%) strains of poliovirus type II two were ret+40, Gu+, A+, N+, Ag+ (MEF-1), and 2 were ret-40, Gu-, A-, N-, Ag- (P712 Ch2ab), and among 9 (15.2%) strains of type III only one (Saukett) had the genetic markers ret+40, Gu+, A+, Ag+. In the other 43 poliovirus strains under study the genetic markers did not correlate with each other. The possibility of using counter immunoelectrophoresis alongside with gel precipitation test for the study of antigenic intratype differences of polioviruses was demonstrated.


Alteration in Bacillus thuringiensis toxicity by curing gut flora: novel approach for mosquito resistance management.
Mosquitoes are known for acquiring resistance against insecticides in many ways, namely target side mutation, enzyme modification, sequestration, quick elimination, etc. But, the role of microflora present in abundance in the larval midgut is less explored with respect to their role in insecticide resistance. During the course of their development, mosquitoes are continuously exposed to microbes and have naturally acquired midgut microbial flora. This midgut flora can modulate the mosquito's susceptibility to Bacillus thuringiensis (Bt) infection by degrading toxic Bt protein forms through an unknown mechanism. In this study, we show that microbe-free aseptic mosquito larvae displayed an increased susceptibility to Bt toxicity compared to larvae harboring natural microbial flora. Fourth instar larvae of Anopheles stephensi were treated separately with penicillin, streptomycin, erythromycin (100 μg/ml), and mixtures of all three antibiotics and then analyzed for Bt toxicity. We have also examined the influence of the mosquito's midgut microbial flora under microaerophilic condition on the Bt protein degradation through plate, broth, TLC, and UV-vis spectrophotometric assay. A better understanding of the roles of microbiota in preventing Bt toxicity to mosquitoes could potentially lead to the development of new sustainable mosquito control strategies.


The Prevalence of Depression among Patients with the Top Ten Most Common Cancers in South Korea.
Among the various psychiatric disorders, depression is a common comorbid condition in cancer patients. Due to the distinct and diverse nature of cancer, the prevalence of depression may be assumed to be affected by differences in primary cancer sites. In this study, we explored the prevalence rates of depression among the ten most prevalent cancers in South Korea using a national patient sample. This was a 1-year cross-sectional study using a national patient sample provided by the South Korean National Health Insurance in 2011. We selected all patients who had received ICD-10 codes of the 10 most prevalent cancers and major depressive disorder. Afterwards, the cancer and depression groups were merged and analyzed. The MDD prevalence rate was highest in lung cancer (11.0%), followed by non-Hodgkin's lymphoma (9.2%), prostate (9.1%), bladder (8.8%), breast (7.8%), cervix (7.8%), colorectal (7.7%), stomach (6.9%), liver (6.5%), and thyroid cancer (5.6%). Within all cancer groups, patients with a MDD diagnosis were significantly older (p<0.05) than non-MDD patients. Colorectal, stomach, and thyroid cancer displayed a higher female proportion in the MDD group than the non-MDD group. In the subgroup analysis, the prevalence rate differed by age and sex. The prevalence of depression varied according to cancer types. Patients with lung cancer were the most prone to experience depression. Because clinical and psychological factors may influence MDD prevalence, these factors will need to be studied more closely in the future.


hERG1 channels in human esophagus: evidence for their aberrant expression in the malignant progression of Barrett's esophagus.
Ion channels regulate a broad range of cellular activities. Alteration in ion channel function has been reported in different human pathologies, such as cardiac, neuromuscular, autoimmune diseases, and cancer. We investigated the expression of hERG1 K+ channels in the human upper gastrointestinal tract, focusing our attention on the lower esophagus. In particular, we analyzed by both Reverse transcription and polymerase chain reaction (RT-PCR) and immunohistochemistry (IHC) endoscopic samples obtained from normal subjects, from patients suffering from gastroesophageal reflux, associated or not with esophagitis, and from patients affected by Barrett's esophagus (BE), that is, intestinal metaplasia. None of the normal samples, nor those from patients with gastro-esophageal reflux symptoms and reflux esophagitis expressed the hERG1 protein. On the other hand, 69% of patients with BE expressed hERG1. Since BE is a preneoplastic lesion, dysplasias (Ds) and adenocarcinomas (ADKs) arising on a previously diagnosed BE were also analyzed, and all the samples showed a high expression of the hERG1 protein. The surveillance of patients with BE showed that 89% of those who later developed ADKs displayed hERG1 expression. Data here reported, support the hypothesis that hERG1 expression marks an early step of the progression of normality to cancer in the human esophagus through a metaplastic and dysplastic stage.


Inspiratory Muscle Training with Isokinetic Device to Help Ventilatory Weaning in a Patient with Guillain-Barré Syndrome by Zika Virus.
Zika is an arbovirus infection mainly transmitted by the mosquito Aedes aegypti. In 2016, the burden of Zika epidemic in Brazil was significant. Patients affected by Zika virus can develop Guillain-Barré syndrome, evolving to muscle respiratory failure requiring mechanical ventilation. In this setting, delayed recovery of the muscle weakness can result in prolonged weaning, a condition that by itself is related to a high mortality rate. The study is reporting a case of a patient with Zika and Guillain-Barré syndrome who underwent an inspiratory muscle training program starting after twenty-five days of mechanical ventilation and guided by serial measurements of the timed inspiratory effort (TIE) index. The patient was successfully weaned in two weeks and discharged from the hospital 30 days after extubation.


Antimicrobial resistance of Staphylococcus aureus isolated from skin infections and its implications in various clinical conditions in Korea.
Periodic investigations into patterns of antimicrobial resistance can help to optimize the efficacy of treatment and limit the development of resistance. The aim of this study was to update information on patterns of antimicrobial resistance in Staphylococcus aureus isolated from skin infections in South Korea. We retrospectively analyzed clinical information and in vitro antimicrobial resistance data for 965 clinical S. aureus isolates obtained from skin infections during 2010-2013 in a university hospital in South Korea. The rate of resistance to oxacillin (methicillin-resistant S. aureus [MRSA]) was 47.4%. Similar rates of resistance to erythromycin (45.6%), fusidic acid (44.0%), and clindamycin (42.3%) were noted. The rate of resistance to mupirocin was 8.4%. Overall, 4.9% of isolates were resistant to both fusidic acid and mupirocin. None of the isolates showed resistance to habekacin, synercid, teicoplanin, or vancomycin. Generally, antimicrobial resistance rates did not increase from 2010 to 2013 except with reference to a few agents such as mupirocin and rifampin. Isolates from surgical patients, inpatients, non-dermatology outpatients, and adult patients showed relatively high rates of resistance to multiple antimicrobials. Resistance to mupirocin was not only lower than that to fusidic acid but was consistent across clinical contexts. The prevalence of MRSA in skin infections in South Korea did not increase during 2010-2013. Isolates from dermatology outpatients showed relatively lower rates of resistance to multiple antimicrobials than isolates from non-dermatology outpatients. Among topical antimicrobials, resistance to mupirocin was relatively low regardless of clinical condition.


Transcriptome alterations and genotoxic influences in zebrafish larvae after exposure to dissolved aluminum and aluminum oxide nanoparticles.
Manufactured nanoparticles (NPs) can potentially cause negative effects on molecular (proteins and nucleic acids), subcellular, cellular, tissue, organ, and organism due to their unusual physicochemical characteristics. Ionizable NPs in water (e.g., Al2O3-NPs) may create toxic effects on aquatic animals. The present research determined the influences of Al2O3-NPs and appropriate concentrations of ionizing Al(III) using water-soluble AlCl3 in zebrafish larvae (72 h post-fertilization, Danio rerio) by analyzing transcriptional alterations of stress-associated genes (rad51, p53, mt2) with quantitative real-time PCR (qRT-PCR). In addition, genotoxic effects of Al(III) and Al2O3-NPs were evaluated. The lethal concentrations that cause death of 50% (LC50) of zebrafish larvae when exposed to 0-50 mg/l Al(III) and 0-500 mg/l Al2O3-NPs were 3.26 ± 0.38 and 130.19 ± 5.59 mg/l, respectively, for 96 h. A concentration-dependent increase was observed in the genotoxicity in cells of larvae exposed to Al(III) and Al2O3-NPs for 96 h. DNA damage was more severe in larvae exposed to Al(III) (41.0% tail) than that of Al2O3-NPs (21.8% tail). A complex induction of stress-associated genes was observed in fish and this induction was not directly related to the concentrations of Al(III) and Al2O3-NPs, although a significant induction was detected in mt2 gene of larvae exposed to Al(III) and Al2O3-NPs relative to control group. The induction levels of mt2 were 4.13 ± 0.1 and 2.13 ± 0.1-fold change (mean ± S.E.M.) in larvae at 15 mg/l of Al(III) and 100 mg/l of Al2O3-NP concentrations, respectively.