Efficacy of stapler versus hand-sewn closure after distal pancreatectomy (DISPACT): a randomised, controlled multicentre trial.
The ideal closure technique of the pancreas after distal pancreatectomy is unknown. We postulated that standardised closure with a stapler device would prevent pancreatic fistula more effectively than would a hand-sewn closure of the remnant. This multicentre, randomised, controlled, parallel group-sequential superiority trial was done in 21 European hospitals. Patients with diseases of the pancreatic body and tail undergoing distal pancreatectomy were eligible and were randomly assigned by central randomisation before operation to either stapler or hand-sewn closure of the pancreatic remnant. Surgical performance was assessed with intraoperative photo documentation. The primary endpoint was the combination of pancreatic fistula and death until postoperative day 7. Patients and outcome assessors were masked to group assignment. Interim and final analysis were by intention to treat in all patients in whom a left resection was done. This trial is registered, ISRCTN18452029. Between Nov 16, 2006, and July 3, 2009, 450 patients were randomly assigned to treatment groups (221 stapler; 229 hand-sewn closure), of whom 352 patients (177 stapler, 175 hand-sewn closure) were analysed. Pancreatic fistula rate or mortality did not differ between stapler (56 [32%] of 177) and hand-sewn closure (49 [28%] of 175; OR 0·84, 95% CI 0·53–1·33; p=0·56). One patient died within the fi rst 7 days after surgery in the hand-sewn group; no deaths occurred in the stapler group. Serious adverse events did not differ between groups. Stapler closure did not reduce the rate of pancreatic fistula compared with hand-sewn closure for distal pancreatectomy. New strategies, including innovative surgical techniques, need to be identified to reduce this adverse outcome. German Federal Ministry of Education and Research.


Fully Closed Genome Sequences of Five Type Strains of the Genus Cronobacter and One Cronobacter sakazakii Strain.
Cronobacteris associated with infant infections and the consumption of reconstituted infant formula. Here we sequenced and closed six genomes ofC. condimenti(T),C. muytjensii(T),C. universalis(T),C. malonaticus(T),C. dublinensis(T), andC. sakazakiithat can be used as reference genomes in single nucleotide polymorphism (SNP)-based next-generation sequencing (NGS) analysis for source tracking investigations.


Questionnaire study of application about sentinel lymph node biopsy surgery in locally advanced breast cancer patients who received neoadjuvant chemotherapy.
Nodal staging from sentinel lymph node (SLN) biopsy has become the standard procedure for early-stage breast cancer patients. SLN biopsy implementation after chemotherapy has previously been evaluated. This questionnaire study aimed to investigate the current trend of SLN biopsy after neoadjuvant chemotherapy (NAC) for locally advanced breast cancer. We conducted a web-based survey among breast surgeons who are members of the Korean Breast Cancer Society. The survey comprised 14 questions about axillary surgery after NAC. Of 135 respondents, 48.1% used a combined method of dye and radioactive isotope (RI). In the absence of SLN metastasis, 67.7% would perform only SLN biopsy, while 3% would perform ALN dissection. In case of SLN metastasis, the proportions of surgeons who would proceed with ALN dissection were 60.2% and 67.2% for less than two and more than three positive SLNs, respectively. The present study confirmed the increasing tendency to adopt SLN biopsy for axillary staging in patients who achieved complete response with initial nodal metastasis. It could be expected that the mapping methods for patients receiving NAC have become diverse, including RI, vital dye, and indocyanine green fluorescence. The implementation of SLN biopsy after NAC will grow in the coming years due to an increasing demand of minimally invasive surgery.


Large-scale profiling of noncoding RNA function in yeast.
Noncoding RNAs (ncRNAs) are emerging as key regulators of cellular function. We have exploited the recently developed barcoded ncRNA gene deletion strain collections in the yeast Saccharomyces cerevisiae to investigate the numerous ncRNAs in yeast with no known function. The ncRNA deletion collection contains deletions of tRNAs, snoRNAs, snRNAs, stable unannotated transcripts (SUTs), cryptic unstable transcripts (CUTs) and other annotated ncRNAs encompassing 532 different individual ncRNA deletions. We have profiled the fitness of the diploid heterozygous ncRNA deletion strain collection in six conditions using batch and continuous liquid culture, as well as the haploid ncRNA deletion strain collections arrayed individually onto solid rich media. These analyses revealed many novel environmental-specific haplo-insufficient and haplo-proficient phenotypes providing key information on the importance of each specific ncRNA in every condition. Co-fitness analysis using fitness data from the heterozygous ncRNA deletion strain collection identified two ncRNA groups required for growth during heat stress and nutrient deprivation. The extensive fitness data for each ncRNA deletion strain has been compiled into an easy to navigate database called Yeast ncRNA Analysis (YNCA). By expanding the original ncRNA deletion strain collection we identified four novel essential ncRNAs; SUT527, SUT075, SUT367 and SUT259/691. We defined the effects of each new essential ncRNA on adjacent gene expression in the heterozygote background identifying both repression and induction of nearby genes. Additionally, we discovered a function for SUT527 in the expression, 3' end formation and localization of SEC4, an essential protein coding mRNA. Finally, using plasmid complementation we rescued the SUT075 lethal phenotype revealing that this ncRNA acts in trans. Overall, our findings provide important new insights into the function of ncRNAs.


[The medical use of the disabled among overusers of Medical Aid in Korea].
In Korea, the top 10% of Medical Aid recipients represent nearly 60% of total payment, with the costs for those disabled for over 365 days representing approximately 30% of total payment. The purpose of this study was to compare Medical Aid use of the disabled with non-disabled recipients, and to identify contributing factors to the total payment in the top 2% of recipients identified as Medical Aid overusers. Subjects (n=2,211) selected were > or =18-years-of-age and received >1000 days of co-payment-free type I Medical Aid. Case managers (n=200) conducted interviews in December 2006, and collected data from Health Insurance Review & Assessment Service. Amounts over the 9 months from January September 2006 were analyzed descriptively and using Chi-square, ANCOVA, and robust multiple linear regression. Disabled individuals (mean age 61.3 years) composed 36.6% of subjects; 44.8% of the disabled were male. On a monthly basis per capita, the disabled group averaged 10.5 outpatient days, total payment of 523,000 Korean Won(), inpatient payment of 359,000, and outpatient payment of 183,000. All values exceeded the monthly average for non-disabled individuals. Contributing factors were identified as male gender (82,000), elementary school or lower educational level (64,000), residence in a small city (82,000), lack of family support (61,000), kidney disability (673,000), intellectual disability (151,000), and multiple disabilities (119,000). The identification of contributing factors to Medical Aid use by those defined as disabled supports the adoption of comprehensive alternative policies such as strengthening of education and consultation services, provision of alternative facilities, and promotion of self-care.


Bipolar plasma enucleation of the prostate vs open prostatectomy in large benign prostatic hyperplasia cases - a medium term, prospective, randomized comparison.
WHAT'S KNOWN ON THE SUBJECT? AND WHAT DOES THE STUDY ADD?: According to the EAU Guidelines 2012, large size benign prostatic hyperplasia (BPH) cases (>80 mL) continue to have open prostatectomy as the first line treatment alternative, despite the substantial peri-operative morbidity and extended catheterization and convalescence periods related to this undoubtedly invasive approach. During the past two decades, holmium laser enucleation of the prostate was constantly described as a successful choice for this category of patients. According to rather numerous studies, the technique displayed superior results in terms of surgical safety and postoperative recovery compared with the open procedure. On the other hand, the concept of electrosurgical enucleation of the prostate, using either a monopolar or bipolar cutting current, materialized into several technical applications that eventually failed to gain general acknowledgement as reliable alternatives to the BPH transurethral approach. While keeping in mind the already proved advantage of enucleating substantial quantities of BPH tissue, bipolar plasma enucleation of the prostate was introduced as a novel endoscopic approach in cases of large prostates. The present trial represents the first prospective, medium-term, randomized comparison to be published of this innovative technique with standard open prostatectomy. Basically, the premises for a viable alternative relied on the practical advantages provided by the 'button' electrode, mainly the large surface creating the conditions for a fast enucleation process, continuous vaporization and concomitant haemostasis. Eventually, it was concluded that the plasma enucleation procedure distinguished itself as a successful treatment option in large BPH patients, characterized by good surgical efficiency, significantly reduced complications, faster postoperative recovery, similar prostatic tissue ablation capabilities and satisfactory follow-up results compared with the open technique. Most importantly, plasma-button enucleation patients benefited from a similar 12 months' outcome from the perspectives of symptom scores and voiding parameters when drawing a parallel with open surgery results, thus underlining the reliable viability of this type of endoscopic approach. To evaluate the viability of bipolar plasma enucleation of the prostate (BPEP) by comparison with open transvesical prostatectomy (OP) in cases of large prostates with regard to surgical efficacy and peri-operative morbidity. To compare the medium-term follow-up parameters specific for the two methods. A total of 140 benign prostatic hyperplasia (BPH) patients with prostate volume >80 mL, maximum flow rate (Qmax ) <10 mL/s and International Prostate Symptom Score (IPSS) >19 were randomized in the two study arms. All cases were assessed preoperatively and at 1, 3, 6 and 12 months after surgery by IPSS, Qmax , quality of life score (QoL) and post-voiding residual urinary volume (PVR). The prostate volume and prostate specific antigen (PSA) level were measured at 6 and 12 months. The BPEP and OP techniques emphasized similar mean operating durations (91.4 vs 87.5 min) and resected tissue weights (108.3 vs 115.4 g). The postoperative haematuria rate (2.9% vs 12.9%) as well as the mean haemoglobin drop (1.7 vs 3.1 g/dL), catheterization period (1.5 vs 5.8 days) and hospital stay (2.1 vs 6.9 days) were significantly improved for BPEP. Recatheterization for acute urinary retention was more frequent in the OP group (8.6% vs 1.4%), while the rates of early irritative symptoms were similar for BPEP and OP (11.4% vs 7.1%). During the follow-up period, no statistically significant difference was determined in terms of IPSS, Qmax , QoL, PVR, PSA level and postoperative prostate volume between the two series. BPEP represents a promising endoscopic approach in large BPH cases, characterized by good surgical efficiency and similar BPH tissue removal capabilities compared with standard transvesical prostatectomy. BPEP patients benefited from significantly reduced complications, shorter convalescence and satisfactory follow-up symptom scores and voiding parameters.


Silicone nipple discharge: A case report of an unusual presentation of breast implant rupture.
Breast implant rupture is a well-documented complication of breast implant surgery. Diagnosis of ruptured silicone implants can be difficult due to the lack of overt symptoms. This is the first reported case of a patient with silicone breast implant rupture presenting with clear nipple discharge and is presented in line with SCARCE 2018 Guidelines [1]. A 45-year-old-female was referred to a breast surgeon with viscous clear nipple discharge, on a background of bilateral mastopexy-augmentation surgery 10 years prior. Imaging revealed extensive intraductal and free silicone causing significant stromal deformity secondary to breast implant rupture. Cytology of the nipple discharge was consistent with silicone gel. The patient was also found to have fibroadenoma without atypia in the right breast. She underwent an oncoplastic excision of free silicone and change of bilateral breast implants by a team of breast and plastic surgeons. With breast implants being an increasingly common procedure worldwide, we can expect an increase in these unusual presentations. Clinicians and patients need to be aware of these in order to avoid an unnecessary delay in diagnosis. Silicone implant rupture is a well-known complication and the rate of rupture increases over the life of the implant. Diagnosis of ruptured silicone implants is rare on clinical examination however remains an essential component of a doctor's examination of the patient and nipple discharge must be considered a symptom of rupture.


[Radiology of the infantile hand as a mirror of clinical syndromes (author's transl)].
Significant radiographic findings of the pediatric hand are described as far as they are useful for the diagnosis of a suspected clinical syndrome. Normal variants that can simulate pathological findings are demonstrated. Deviations of skeletal age from chronological age and their clinical significance are discussed. Diagnostically useful malformations (hexadactyly, syndactyly, brachyphalangy, cone shaped epiphyses and anomalies of the thumb) are presented in the context of typical cases of selected syndromes. The importance of establishing a correct diagnosis in these cases is stressed with regard to individual prognosis of the patient and genetic counselling of the family.


Acquired equivalence and distinctiveness of cues using a sensory-preconditioning procedure.
In Experiment 1 rats were presented with two flavours, A and B, that were accompanied either by a third common flavour, X, or by two different flavours, X and Y, respectively. An aversion was then established to A, and the extent to which this aversion generalized to B was measured. Stimulus generalization was found to be more marked when A and B had both been presented with the same flavour, X, during pre-exposure than when A and B had been presented with X and Y. In Experiment 2 three target flavours, A, B, and C, were initially presented. In one pre-exposure condition presentations of A and B were accompanied by X, and C was presented alone; in a second condition A and B were presented in isolation, and C was accompanied by X. After an aversion had been established to A, half of the animals in each of the pre-exposure conditions were tested with B, and the remainder were tested with C. In both of the pre-exposure conditions the generalized aversion was more substantial to B than to C. An analysis of these results in terms of the mechanisms that have been supposed to underlie sensory preconditioning is presented.


Psychiatric syndromes from a clinical and a biostatistical point of view.
Syndromes are typical combinations of symptoms. They may be conceived at different levels of complexity, intuitively from a clinical point of view and objectively by means of factor- or cluster-analyses. Primary factors of symptom scores obtained with the aid of psychiatric rating scales represent syndromes of low complexity, secondary factors represent syndromes of higher complexity. The highest level is achieved by rotating only the first factors extracted from the matrix of intercorrelations among primary factors of psychopathology. Principal component analysis of 12 Inpatient Multidimensional Psychiatric Scale factors that reflect the psychopathological states at admission of 1,080 psychotic inpatients yielded the highly complex endogenomorphic syndromes of schizophrenic and manic-depressive symptomatology, respectively, in a two-factor solution. These syndromes were cut down to lower order syndromes in the four-factor solution resulting from rotation according to the conventional Kaiser criterion. They represent a syndrome of psychotic excitement, a paranoid-hallucinatory syndrome, a syndrome of endogenomorphic (retarded) depression and a syndrome of organic symptomatology. The different factor solutions may be useful for describing psychopathological phenoma objectively at different levels of complexity.


Synergistic PET and SENSE MR Image Reconstruction Using Joint Sparsity Regularization.
In this paper, we propose a generalized joint sparsity regularization prior and reconstruction framework for the synergistic reconstruction of positron emission tomography (PET) and under sampled sensitivity encoded magnetic resonance imaging data with the aim of improving image quality beyond that obtained through conventional independent reconstructions. The proposed prior improves upon the joint total variation (TV) using a non-convex potential function that assigns a relatively lower penalty for the PET and MR gradients, whose magnitudes are jointly large, thus permitting the preservation and formation of common boundaries irrespective of their relative orientation. The alternating direction method of multipliers (ADMM) optimization framework was exploited for the joint PET-MR image reconstruction. In this framework, the joint maximum a posteriori objective function was effectively optimized by alternating between well-established regularized PET and MR image reconstructions. Moreover, the dependency of the joint prior on the PET and MR signal intensities was addressed by a novel alternating scaling of the distribution of the gradient vectors. The proposed prior was compared with the separate TV and joint TV regularization methods using extensive simulation and real clinical data. In addition, the proposed joint prior was compared with the recently proposed linear parallel level sets (PLSs) method using a benchmark simulation data set. Our simulation and clinical data results demonstrated the improved quality of the synergistically reconstructed PET-MR images compared with the unregularized and conventional separately regularized methods. It was also found that the proposed prior can outperform both the joint TV and linear PLS regularization methods in assisting edge preservation and recovery of details, which are otherwise impaired by noise and aliasing artifacts. In conclusion, the proposed joint sparsity regularization within the presented a ADMM reconstruction framework is a promising technique, nonetheless our clinical results showed that the clinical applicability of joint reconstruction might be limited in current PET-MR scanners, mainly due to the lower resolution of PET images.


Conscious perception of natural images is constrained by category-related visual features.
Conscious perception is crucial for adaptive behaviour yet access to consciousness varies for different types of objects. The visual system comprises regions with widely distributed category information and exemplar-level representations that cluster according to category. Does this categorical organisation in the brain provide insight into object-specific access to consciousness? We address this question using the Attentional Blink approach with visual objects as targets. We find large differences across categories in the attentional blink. We then employ activation patterns extracted from a deep convolutional neural network to reveal that these differences depend on mid- to high-level, rather than low-level, visual features. We further show that these visual features can be used to explain variance in performance across trials. Taken together, our results suggest that the specific organisation of the higher-tier visual system underlies important functions relevant for conscious perception of differing natural images.


Evaluation of potential salivary acetaldehyde production from ethanol in oral cancer patients and healthy subjects.
Acetaldehyde has been implicated as a major factor in oral carcinogenesis associated with alcohol consumption. In this study, saliva samples from oral cancer patients and healthy individuals were incubated in vitro with ethanol in order to investigate factors which can influence salivary acetaldehyde production. A total of 66 individuals (40 males and 26 females, mean age 52 years) participated in the study. Participants were classified into three groups: Group 1 (oral cancer patients [n = 20]); Group 2 (poor dental health status [n = 25]) and Group 3 (good dental health status [n=21]). Every patient chewed a 1g piece of paraffin chewing gum for 1 minute then saliva samples were collected from all individuals. After in vitro incubation of the samples with ethanol, the levels of salivary acetaldehyde production was measured by head space gas chromatography. Kruskal-Wallis and Mann-Whitney tests and Spearman's Correlations analysis were performed for statistical analyses. The salivary acetaldehyde production was significantly higher (p <0.0001) in both group 1 and group 2 when compared to group 3. However, there was no significant difference between group 1 and group 2. Poor dental health status, infrequent oral hygiene habits and dental visits, smoking and presence of a dental prosthesis were significant parameters for increased levels of salivary acetaldehyde production from alcohol. The evaluation of salivary acetaldehyde production after in vitro incubation with ethanol may be useful for early detection of oral cancer. According to the results of this study, the significantly higher levels of salivary acetaldehyde production in oral cancer patients and individuals with poor dental health status may suggest a possible link between increased salivary acetaldehyde production and oral cancer. Improved oral hygiene can effectively decrease the level of salivary acetaldehyde production in oral cavity. Hippokratia 2014; 18 (3): 269-274.


Effect of Diffusion on Discoloration of Congo Red by Alginate Entrapped Turnip (Brassica rapa) Peroxidase.
Enzymatic discoloration of the diazo dye, Congo red (CR), by immobilized plant peroxidase from turnip "Brassica rapa" is investigated. Partially purified turnip peroxidase (TP) was immobilized by entrapment in spherical particles of calcium alginate and was assayed for the discoloration of aqueous CR solution. Experimental data revealed that pH, reaction time, temperature, colorant, and H2O2 concentration play a significant role in dye degradation. Maximum CR removal was found at pH 2.0, constant temperature of 40°C in the presence of 10 mM H2O2, and 180 mg/L of CR. More than 94% of CR was removed by alginate immobilized TP after 1 h of incubation in a batch process under optimal conditions. About 74% removal efficiency was retained after four recycles. Diffusional limitations in alginate beads such as effectiveness factor η, Thiele modulus Φ, and effective diffusion coefficients (D e ) of Congo red were predicted assuming a first-order biodegradation kinetic. Results showed that intraparticle diffusion resistance has a significant effect on the CR biodegradation rate.


Eye-tracking retrospective think-aloud as a novel approach for a usability evaluation.
To report on the use of an eye-tracking retrospective think-aloud for usability evaluation and to describe its application in assessing the usability of a mobile health app. We used an eye-tracking retrospective think-aloud to evaluate the usability of an HIV prevention mobile app among 20 young men (15-18 years) in New York City, NY; Birmingham, AL; and Chicago, IL. Task performance metrics, critical errors, a task completion rate per participant, and a task completion rate per task, were measured. Eye-tracking metrics including fixation, saccades, time to first fixation, time spent, and revisits were measured and compared among participants with/without a critical error. Using task performance analysis, we identified 19 critical errors on four activities, and of those, two activities had a task completion rate of less than 78%. To better understand these usability issues, we thoroughly analyzed participants' corresponding eye movements and verbal comments using an in-depth problem analysis. In areas of interest created for the activity with critical usability problems, there were significant differences in time spent (p = 0.008), revisits (p = 0.004), and total numbers of fixations (p = 0.007) by participants with/without a critical error. The overall mean score of perceived usability rated by the Health IT Usability Evaluation Scale was 4.64 (SD = 0.33), reflecting strong usability of the app. An eye-tracking retrospective think-aloud enabled us to identify critical usability problems as well as gain an in-depth understanding of the usability issues related to interactions between end-users and the app. Findings from this study highlight the utility of an eye-tracking retrospective think-aloud in consumer health usability evaluation research.


Determination of the electronic portal imaging device pixel-sensitivity-map for quality assurance applications. Part 1: Comparison of methods.
Calibration of a radiotherapy electronic portal imaging device (EPID) using the pixel-sensitivity-map (PSM) in place of the flood field correction improves the utility of the EPID for quality assurance applications. Multiple methods are available for determining the PSM and this study provides an evaluation to inform on which is superior. Three different empirical methods ("Calvary Mater Newcastle" [CMN], "Varian," and "WashU") and a Monte Carlo-based method of PSM determination were investigated on a single Varian TrueBeam STx linear accelerator (linac) with an aS1200 EPID panel. PSM measurements were performed for each empirical method three successive times using the 6 MV beam. The resulting PSM from each method was compared to the Monte Carlo method as a reference using 2D percentage deviation maps and histograms plus crossplane profiles. The repeatability of generated PSMs was also assessed via 2D standard deviation (SD) maps and histograms. Additionally, the Beam-Response generated by removal of the PSM from a raw EPID image for each method was visually contrasted. Finally, the practicality of each method was assessed qualitatively and via the measured time required to acquire and export the required images. The median pixel-by-pixel percentage deviation between each of the empirical PSM methods and the Monte Carlo PSM was -0.36%, 0.24%, and 0.74% for the CMN, Varian, and WashU methods, respectively. Ninety-five percent of pixels were found to be repeatable to within -0.21%, 0.08%, 0.19%, and 0.35% (1 SD) for the CMN, Monte Carlo, Varian, and WashU methods, respectively. The WashU method was found to be quickest for data acquisition and export and the CMN the slowest. For the first time four methods of generating the EPID PSM have been compared in detail and strengths and weaknesses of each method have been identified. All methods are considered likely to be clinically acceptable and with similar practical requirements.


Fascin-1 Is a Novel Prognostic Biomarker Associated With Tumor Invasiveness in Adrenocortical Carcinoma.
Novel tumor markers are urgently needed to better stratify adrenocortical cancer (ACC) patients and improve therapies for this aggressive neoplasm. To assess the diagnostic and prognostic value of the actin-bundling protein fascin-1 (FSCN1) in adrenocortical tumors. A local series of 37 malignant/37 benign adrenocortical tumors at Careggi University Hospital and two independent validation ACC cohorts (Cochin, TCGA) from the European Network for the Study of Adrenal Tumors were studied. FSCN1 expression was quantified by immunohistochemistry, Western blot and quantitative RT-PCR in ACC specimens; overall and disease-free survival associated with FSCN1 expression were assessed by Kaplan-Meier analysis and compared with that of Ki67 labeling index and tumor stage. Despite the low diagnostic power, in the Florence ACC series, FSCN1 immunohistochemical detection appeared as an independent prognostic factor, also refining results obtained with staging and Ki67 labeling index. The robust prognostic power of FSCN1 levels was further confirmed in two independent ACC cohorts. A positive correlation was found between FSCN1 and steroidogenic factor-1 (SF-1), with a substantially higher expression of both factors in ACCs at advanced stages and with at least one of the three Weiss score parameters associated with invasiveness. Moreover, we demonstrated FSCN1 role in promoting cell invasion in a human ACC cell line only in the case of increased SF-1 dosage. These findings show that FSCN1 is a novel independent prognostic marker in ACC and may serve as a potential therapeutic target to block tumor spread.


Dehydration triggers differential microRNA expression in Xenopus laevis brain.
African clawed frogs, Xenopus laevis, although primarily aquatic, have a high tolerance for dehydration, being capable of withstanding the loss of up to 32-35% of total water body water. Recent studies have shown that microRNAs play a role in the response to dehydration by the liver, kidney and ventral skin of X. laevis. MicroRNAs act by modulating the expression of mRNA transcripts, thereby affecting diverse biochemical pathways. In this study, 43 microRNAs were assessed in frog brains comparing control and dehydrated (31.2±0.83% of total body water lost) conditions. MicroRNAs of interest were measured using a modified protocol which employs polyadenylation of microRNAs prior to reverse transcription and qPCR. Twelve microRNAs that showed a significant decrease in expression (to 41-77% of control levels) in brains from dehydrated frogs (xla-miR-15a, -150, -181a, -191, -211, -218, -219b, -30c, -30e, -31, -34a, and -34b) were identified. Genomic analysis showed that the sequences of these dehydration-responsive microRNAs were highly conserved as compared with the comparable microRNAs of mice (91-100%). Suppression of these microRNAs implies that translation of the mRNA transcripts under their control could be enhanced in response to dehydration. Bioinformatic analysis using the DIANA miRPath program (v.2.0) predicted the top two KEGG pathways that these microRNAs collectively regulate: 1. Axon guidance, and 2. Long-term potentiation. Previous studies indicated that suppression of these microRNAs promotes neuroprotective pathways by increasing the expression of brain-derived neurotrophic factor and activating anti-apoptotic pathways. This suggests that similar actions may be triggered in X. laevis brains as a protective response to dehydration.


Relationship between in vitro human immunodeficiency virus type 1 replication rate and virus load in plasma.
Although plasma human immunodeficiency virus type 1 (HIV-1) RNA concentration is a major determinant of the rate of HIV-1 disease progression, the reasons for variability in plasma virus loads among infected individuals are not fully understood. We conducted investigations with 15 HIV-1-infected individuals who were not receiving antiretroviral therapy to evaluate the hypothesis that HIV-1 replication rate in vitro is a significant determinant of plasma virus load. Virus could not be isolated from one subject. Two subjects were excluded because they had features previously associated with distinct plasma virus loads and altered rates of disease progression; one harbored a syncytium-inducing virus and the second was heterozygous for a 32-bp deletion from the CCR5 gene. HIV-1 replication rates were determined by culturing autologous virus isolates in phytohemagglutinin-treated peripheral blood mononuclear cells (PBMC) and determining the rate of p24 antigen production during the logarithmic phase of viral replication. The contribution of HIV-1 reverse transcriptase (RT) and protease (PR) alleles to replication capacity was assessed using recombinant viruses in a single-cycle infection assay. HIV-1 replication rates ranged from 0.15 to 0.76 log(10) pg/ml/day and were reproducible within the same donor PBMC (coefficient of variation +/- 4%). RT-PR replication capacity ranged from 14 to 95% of that of control virus and was linearly related to replication rate (r(2) = 0.53; P = 0.007). Plasma HIV-1 RNA concentration was linearly related to replication rate (r(2) = 0.71; P < 0.001) and RT-PR replication capacity (r(2) = 0.44; P = 0.019). These data suggest that different RT-PR alleles are important determinants of HIV-1 replication rates and that HIV-1 replication rate explains much of the variability in plasma virus load in chronic HIV-1 infection.


A new label-free amperometric immunosenor for rubella vaccine.
A novel label-free amperometric immunosensor for the detection of rubella vaccine was developed by immobilizing anti-rubella serum on bilayer nano-Au/polymerized o-phenylenediamine film with electrodeposited Prussian Blue (PB) as an electrode transfer mediator on the platinum electrode. The redox reactions of PB as a probe on the platinum surface were blocked due to the binding of the antibody to the antigen, which was investigated by cyclic voltammetry. Therefore, the interaction of the antibody with various concentrations of antigen could be detected by measurements of amperometric response in PBS, and the amperometric response on the surface of the modified electrode was inversely proportional to the concentration of rubella vaccine in the sample. The immunosensor showed a specific response to rubella vaccine in the range 8.1x10(-8)-8.0x10(-6) lgCCID50/ml (cell culture infectious dose) and a detection limit of 4.010(-8) lgCCID50/ml at a signal-to-noise ratio of 3. To summarize, the present work provides a low-cost, fast response time, highly sensitive and easy-to-prepare method for the determination of antigen in biological products.


Senescence marker protein-30 (SMP30) induces formation of microvilli and bile canaliculi in Hep G2 cells.
Senescence marker protein-30 (SMP30) is an androgen-independent factor that decreases with aging. To elucidate the physiological functions of SMP30, we transfected human SMP30 cDNA into the human hepatoma cell line, Hep G2. These Hep G2/SMP30 transfectants, which stably expressed large amounts of SMP30, proliferated at a slower rate and synthesized less DNA than mock transfectants (Hep G2/pcDNA3 controls). Thus, enhanced expression of SMP30 retarded the growth of Hep G2/SMP30 cells. Ultrastructural studies by scanning electron microscopy revealed numerous microvilli covering the surfaces of Hep G2/SMP30 cells, whereas few microvilli appeared on control cells. Subsequently, transmission electron microscopy revealed that groups of Hep G2/SMP30 cells exhibited bile canaliculi and possessed specialized adhesion contacts, such as tight junctions and desmosomes, at interplasmic membranes. However, in controls, units of only two cells were seen, and these lacked specialized adhesion junctions. Moesin and ZO-1 are known to be concentrated in microvilli and at tight junctions, respectively. Double-immunostaining was performed to examine whether moesin and ZO-1 were expressed in bile canaliculi with microvilli at the apical regions of Hep G2/SMP30 cells. The intensity of moesin and ZO-1 staining in the contact regions of each cell was markedly higher in Hep G2/SMP30 than in control cells. Moreover, moesin stained more interior areas, which corresponded to the microvilli of bile canaliculi. Clearly, bile canaliculi with microvilli formed at the apical ends of Hep G2/SMP30 cells. These results indicate that SMP30 has an important physiological function as a participant in cell-to-cell interactions and imply that the down-regulation of SMP30 during the aging process contributes to the deterioration of cellular interactivity.


Driving factors in amiloride recognition of HIV RNA targets.
Noncoding RNAs are increasingly promising drug targets yet ligand design is hindered by a paucity of methods that reveal driving factors in selective small molecule : RNA interactions, particularly given the difficulties of high-resolution structural characterization. HIV RNAs are excellent model systems for method development given their targeting history, known structure-function relationships, and the unmet need for more effective treatments. Herein we report a strategy combining synthetic diversification, profiling against multiple RNA targets, and predictive cheminformatic analysis to identify driving factors for selectivity and affinity of small molecules for distinct HIV RNA targets. Using this strategy, we discovered improved ligands for multiple targets and the first ligands for ESSV, an exonic splicing silencer critical to replication. Computational analysis revealed guiding principles for future designs and a predictive cheminformatics model of small molecule : RNA binding. These methods are expected to facilitate progress toward selective targeting of disease-causing RNAs.


Microbial interactions in the anaerobic oxidation of methane: model simulations constrained by process rates and activity patterns.
Proposed syntrophic interactions between the archaeal and bacterial cells mediating anaerobic oxidation of methane coupled with sulfate reduction include electron transfer through (1) the exchange of H2 or small organic molecules between methane-oxidizing archaea and sulfate-reducing bacteria, (2) the delivery of disulfide from methane-oxidizing archaea to bacteria for disproportionation and (3) direct interspecies electron transfer. Each of these mechanisms was implemented in a reactive transport model. The simulated activities across different arrangements of archaeal and bacterial cells and aggregate sizes were compared to empirical data for AOM rates and intra-aggregate spatial patterns of cell-specific anabolic activity determined by FISH-nanoSIMS. Simulation results showed that rates for chemical diffusion by mechanism (1) were limited by the build-up of metabolites, while mechanisms (2) and (3) yielded cell specific rates and archaeal activity distributions that were consistent with observations from single cell resolved FISH-nanoSIMS analyses. The novel integration of both intra-aggregate and environmental data provided powerful constraints on the model results, but the similarities in model outcomes for mechanisms (2) and (3) highlight the need for additional observational data (e.g. genomic or physiological) on electron transfer and metabolic functioning of these globally important methanotrophic consortia.


Pediatric posterior reversible encephalopathy syndrome presenting with isolated cerebellar edema and obstructive hydrocephalus.
In this report, the authors describe the case of a teenage boy who presented with hypertensive emergency, posterior reversible encephalopathy syndrome, and hydrocephalus due to fourth ventricle outlet obstruction. Posterior reversible encephalopathy syndrome is a well-characterized but uncommon syndrome in children that is generally triggered by severe hypertension. The unusual clinical picture of this patient, who had isolated cerebellar edema leading to obstructive hydrocephalus, has been rarely described in children.


Experimental adaptation of Salmonella typhimurium to mice.
Experimental evolution is a powerful approach to study the dynamics and mechanisms of bacterial niche specialization. By serial passage in mice, we evolved 18 independent lineages of Salmonella typhimurium LT2 and examined the rate and extent of adaptation to a mainly reticuloendothelial host environment. Bacterial mutation rates and population sizes were varied by using wild-type and DNA repair-defective mutator (mutS) strains with normal and high mutation rates, respectively, and by varying the number of bacteria intraperitoneally injected into mice. After <200 generations of adaptation all lineages showed an increased fitness as measured by a faster growth rate in mice (selection coefficients 0.11-0.58). Using a generally applicable mathematical model we calculated the adaptive mutation rate for the wild-type bacterium to be >10(-6)/cell/generation, suggesting that the majority of adaptive mutations are not simple point mutations. For the mutator lineages, adaptation to mice was associated with a loss of fitness in secondary environments as seen by a reduced metabolic capability. During adaptation there was no indication that a high mutation rate was counterselected. These data show that S. typhimurium can rapidly and extensively increase its fitness in mice but this niche specialization is, at least in mutators, associated with a cost.


Epidemiology of Diabetes Mellitus in the United Arab Emirates.
Diabetes mellitus is a non-communicable disease which has become a major global public health issue. This systematic review summarized epidemiological studies related to the prevalence, risk factors, complications, incidence, knowledge, attitude and practices of Diabetes Mellitus (DM) among Arab population in the United Arab Emirates (UAE). PubMed, Scopus databases, Science direct, Wiley online library, and other local journals were searched to identify relevant literature using appropriate keywords to retrieve studies conducted in the UAE. Search limits were restricted to studies in English language, between 2007 and 2016, and on UAE population (both citizens and expatriates). Electronic database search yielded 24 studies about the prevalence, incidence, complications, risk factors, knowledge, attitudes and practices of diabetes, including cross sectional studies (n =18), population-based survey (n = 1), retrospective cohort studies (n = 3), qualitative (n=1), and randomized controlled trial (n = 1). Countrywide prevalence estimates of Diabetes Mellitus were reported to be high. The major determinants of Diabetes Mellitus involved hypertension, physical inactivity, sedentary lifestyle, and unhealthy diet. Even though past evidences have promulgated the role of numerous causative factors, the epidemiological implications of some of the risk factors including family history, educational level, and the use of alcohol remain elusive. This systematic review signifies epidemiology of Diabetes Mellitus in the United Arab Emirates and suggests that extra efforts are needed for preventive and curative strategies in order to decrease the burden of this non-communicable disease.


Hyperglucagonemia in hepatic cirrhosis: its relation to hepatocellular dysfunction and normalization on recovery.
Plasma glucagon, insulin and glucose concentrations, and liver function tests were determined after an overnight fast in 24 normal subjects and 50 male cirrhotic patients. In cirrhotic patients with normal liver profiles, plasma glucagon remained within normal limits, irrespective of the presence of portasystemic anastomoses either pathological or surgical. Hyperglucagonemia was documented in presence of advanced liver dysfunction alone. Significant correlations were established between plasma glucagon and several liver function tests, i.e., serum bilirubin, albumin/globulin ratio, and prothrombin time. Moreover, hyperglucagonemia normalized on recovery from clinical manifestations and improvement in liver profile. Plasma insulin was raised primarily in the presence of a significant portasystemic shunting and maximum levels were observed in patients manifesting advanced liver dysfunction as well. However, no correlation was evident between plasma insulin and any of the liver function tests. Fasting plasma glucose was not altered in cirrhotic patients. Therefore, it is concluded that in hepatic cirrhosis, glucagon secretion by pancreatic alpha-cell may be dependent on the severity of the hepatocellular damage whereas portasystemic shunting may be responsible for hyperinsulinemia which may be further exaggerated in presence of advanced liver dysfunction.


Epitope mapping of recombinant HeLa SmB and B' peptides obtained by the polymerase chain reaction.
SmB and SmB' are the major antigenic proteins contained within small nuclear RNP particles that are recognized by both human SLE and MRL mouse anti-Sm sera. We amplified cDNA obtained from HeLa cells by using the polymerase chain reaction and identified two clones, U2 and L13, that encode SmB and SmB', respectively. The nucleotide sequences of these two clones were identical except for the insertion of a 145-bp sequence in U2 that contained an early in frame termination codon and a potential 3' consensus splice site. The predicted amino acid sequences of HeLa SmB and B' proteins were therefore identical except for the COOH terminal 2 (U2) and 11 (L13) amino acids. U2, L13, and four subclones of U2 (F-B, B-R, F-X, and X-B) were ligated to pATH vectors and expressed as trpE fusion proteins. Epitope mapping with 12 human SLE and 12 MRL/lpr mouse anti-SmB/B' sera revealed that antibodies directed against the X-B peptide accounted for most (65.5 +/- 15.4 and 63.2 +/- 25.3%), B-R intermediate levels (51.5 +/- 30.8 and 18 +/- 19.6%), and F-X none of the anti-SmB activity in human and mouse sera, respectively. Ten human and two mouse sera contained antibodies that cross-reacted with epitopes located within the proline-rich, COOH-terminal, 27-residue peptide encoded by B-R and the NH2-proximal F-B peptide. These observations suggest that a) the polymerase chain reaction is a powerful ancillary method to synthesize autoantigens, b) SmB and B' in HeLa cells are derived from alternative splicing of a common RNA transcript, and c) both SLE and MRL anti-SmB/B' sera recognize multiple epitopes (some shared and some unique) on these proteins.


EPO receptor gain-of-function causes hereditary polycythemia, alters CD34 cell differentiation and increases circulating endothelial precursors.
Gain-of-function of erythropoietin receptor (EPOR) mutations represent the major cause of primary hereditary polycythemia. EPOR is also found in non-erythroid tissues, although its physiological role is still undefined. We describe a family with polycythemia due to a heterozygous mutation of the EPOR gene that causes a G-->T change at nucleotide 1251 of exon 8. The novel EPOR G1251T mutation results in the replacement of a glutamate residue by a stop codon at amino acid 393. Differently from polycythemia vera, EPOR G1251T CD34(+) cells proliferate and differentiate towards the erythroid phenotype in the presence of minimal amounts of EPO. Moreover, the affected individuals show a 20-fold increase of circulating endothelial precursors. The analysis of erythroid precursor membranes demonstrates a heretofore undescribed accumulation of the truncated EPOR, probably due to the absence of residues involved in the EPO-dependent receptor internalization and degradation. Mutated receptor expression in EPOR-negative cells results in EPOR and Stat5 phosphorylation. Moreover, patient erythroid precursors present an increased activation of EPOR and its effectors, including Stat5 and Erk1/2 pathway. Our data provide an unanticipated mechanism for autosomal dominant inherited polycythemia due to a heterozygous EPOR mutation and suggest a regulatory role of EPO/EPOR pathway in human circulating endothelial precursors homeostasis.


DNA-binding proteins specified by herpesvirus saimiri.
Herpesvirus saimiri-specific proteins from the nuclear fractions of productively infected owl monkey kidney cells were dissociated from virus and host DNA by treatment with 2 M-NaCl or separation on Urografin density gradients. Empty virus capsids remained intact and could be separated from major non-structural proteins (110K, 51K and 48K) and from a subset of structural proteins (130K, 29K and 12K), either by Urografin gradient sedimentation or differential centrifugation. The DNA in such soluble extracts of nuclear proteins was efficiently removed by spermine precipitation, together with the host cell histones and large fractions of the 130K and 12K structural proteins. Proteins in the spermine-soluble fraction were analysed by affinity chromatography on columns of single-stranded calf thymus DNA coupled to cellulose. Two major structural proteins (130K and 12K), whose synthesis was sensitive to phosphonoacetic acid (PAA), and one minor PAA-resistant structural protein (29K) bound to DNA-cellulose. The major PAA-resistant 110K non-structural protein and the PAA-resistant non-structural 51K and 48K phosphoproteins were efficiently released into the spermine-soluble fraction and also bound to DNA-cellulose as did the 76K protein and minor species of 42K, 39K, 34K, 25K and 21K. Virus-specific proteins were eluted from such columns by buffers containing 0.4 M-NaCl or by heparin in low-salt buffers. Polypeptides from virus particles, infected cell extracts, or samples of eluates from DNA-cellulose chromatography, were separated by SDS-polyacrylamide gel electrophoresis, transferred onto nitrocellulose filters and probed for their ability to bind labelled polynucleotides. The non-structural 51K phosphoprotein, the 12K and 29K structural proteins and a 100K virion polypeptide all bound labelled DNA. However, the binding activities of the 130K protein from virions or purified by affinity chromatography and of the 110K polypeptide could not be demonstrated reproducibly after transfer from SDS gels to nitrocellulose. Comparisons of the present results on the properties of the herpesvirus saimiri-specified DNA-binding proteins with published accounts of the DNA-binding proteins of other herpesviruses, suggest some striking similarities with the DNA-binding proteins of the Epstein-Barr virus.


Substance Use and Associated Factors among University Students in Ethiopia: A Cross-Sectional Study.
Studies indicate that substance use among Ethiopian adolescents is considerably rising; in particular college and university students are the most at risk of substance use. The aim of the study was to assess substance use and associated factors among university students. A cross-sectional survey was carried out among 1040 Haramaya University students using self-administered structured questionnaire. Multistage sampling technique was used to select students. Descriptive statistics, bivariate, and multivariate analysis were done. About two-thirds (62.4%) of the participants used at least one substance. The most commonly used substance was alcohol (50.2%). Being male had strong association with substance use (AOR (95% CI), 3.11 (2.20, 4.40)). The odds of substance use behaviour is higher among third year students (AOR (95% CI), 1.48 (1.01, 2.16)). Being a follower of Muslim (AOR (95% CI), 0.62 (0.44, 0.87)) and Protestant (AOR (95% CI), 0.25 (0.17, 0.36)) religions was shown to be protective of substance use. Married (AOR (95% CI), 1.92 (1.12, 3.30)) and depressed (AOR (95% CI), 3.30 (2.31, 4.72)) students were more likely to use substances than others. The magnitude of substance use was high. This demands special attention, emergency preventive measures, and targeted information, education and communication activity.


Revealing the Dynamic Nature of Amplitude Modulated Neural Entrainment With Holo-Hilbert Spectral Analysis.
Patterns in external sensory stimuli can rapidly entrain neuronally generated oscillations observed in electrophysiological data. Here, we manipulated the temporal dynamics of visual stimuli with cross-frequency coupling (CFC) characteristics to generate steady-state visual evoked potentials (SSVEPs). Although CFC plays a pivotal role in neural communication, some cases reporting CFC may be false positives due to non-sinusoidal oscillations that can generate artificially inflated coupling values. Additionally, temporal characteristics of dynamic and non-linear neural oscillations cannot be fully derived with conventional Fourier-based analyses mainly due to trade off of temporal resolution for frequency precision. In an attempt to resolve these limitations of linear analytical methods, Holo-Hilbert Spectral Analysis (HHSA) was investigated as a potential approach for examination of non-linear and non-stationary CFC dynamics in this study. Results from both simulation and SSVEPs demonstrated that temporal dynamic and non-linear CFC features can be revealed with HHSA. Specifically, the results of simulation showed that the HHSA is less affected by the non-sinusoidal oscillation and showed possible cross frequency interactions embedded in the simulation without any a priori assumptions. In the SSVEPs, we found that the time-varying cross-frequency interaction and the bidirectional coupling between delta and alpha/beta bands can be observed using HHSA, confirming dynamic physiological signatures of neural entrainment related to cross-frequency coupling. These findings not only validate the efficacy of the HHSA in revealing the natural characteristics of signals, but also shed new light on further applications in analysis of brain electrophysiological data with the aim of understanding the functional roles of neuronal oscillation in various cognitive functions.


Radiation-induced DNA breaks in different human satellite DNA sequence areas, analyzed by DNA breakage detection-fluorescence in situ hybridization.
Human blood leukocytes were exposed to X rays to analyze the initial level of DNA breakage induced within different satellite DNA sequence areas and telomeres, using the DNA breakage detection-FISH procedure. The satellite DNA families analyzed comprised alphoid sequences, satellite 1, and 5-bp classical satellite DNA sequences from chromosome 1 (D1Z1 locus), from chromosome 9 (D9Z3 locus), and from the Y chromosome (DYZ1 locus). Since the control hybridization signal was quite different in each of the DNA targets, the relative increase in whole fluorescence intensity with respect to unirradiated controls was the parameter used for comparison. Irradiation of nucleoids obtained after protein removal demonstrated that the alkaline unwinding solution generates around half the amount of signal when breaks are present in the 5-bp classical DNA satellites as when the same numbers of breaks are present the genome overall, whereas the signal is slightly stronger when the breaks are within the alphoids or satellite 1 sequences. After correction for differences in sensitivity to the alkaline unwinding-renaturation, DNA housed in chromatin corresponding to 5-bp classical satellites proved to be more sensitive to breakage than the overall genome, whereas DNA in the chromatin corresponding to alphoids or satellite 1 showed a sensitivity similar to that of the whole genome. The minimum detectable dose was 0.1 Gy for the whole genome, 0.2 Gy for alphoids and satellite 1, and 0.4 Gy for the 5-bp classical satellites. Telomeric DNA sequences appeared to be maximally labeled in unirradiated cells. Thus telomeric ends behave like DNA breaks, constituting a source of background in alkaline unwinding assays.


Influence of NG-nitro-L-arginine methyl ester on clinical and biochemical effects of methylene blue in pentylenetetrazole-evoked convulsions.
Despite years of research in a number of experimental models the question whether nitric oxide (NO) and methylene blue (MB) have pro- or anticonvulsant effects remains to be fully resolved. Methods. In adult Wistar rats the influence of a nonselective inhibitor of nitric oxide synthase NG-nitro-L-arginine methyl ester (L-NAME, 10 microg) on clinical and biochemical effects of MB (10 microg) given before the intraperitoneally administered chemical convulsant pentylenetetrazole (PTZ, 80 mg/kg) was examined. MB and L-NAME were applied intracerebroventricularly. PTZ application was followed by a 4-minute observation time, after which rats were sacrificed and elements of oxido-reductive balance were measured in a crude mitochondrial fraction of forebrain cortex, hippocampus and striatum. Convulsive responses (forelimb dystonia--FLD, generalised clonic- and clonic-tonic convulsions--GCC and GCTC respectively) were observed in all rats received PTZ, together with significantly decreased lipid peroxidation in the forebrain cortex and striatum and increased superoxide dismutase activity in the hippocampus, in comparison to controls (saline treated). It was registered anticonvulsant effects of L-NAME pretreatment. However, these effects were insignificant. In the hippocampus of these animals there was decreased lipid peroxidation (p < 0.01, p < 0.05 vs saline-treated and PTZ-treated rats, respectively) and reverted PTZ-induced increase of superoxide dismutase activity. But MB individually pretreatment significantly decreased the incidence of CTCs and GCCs (FLD: p = 0.0513), prolonged the convulsive latent time for FLD, GCTCs and GCCs, in all the examined brain regions increased lipid peroxidation and decreased the level of superoxide anion. Administration of L-NAME 10 minutes before MB reverted all MB-evoked clinical and biochemical effects. Methylene blue applied individually before PTZ has strong anticonvulsant effects that were eliminated by L-NAME pretreatment. These effects and changed biochemical parameters in the brains of animals treated by L-NAME before MB in comparison to MB-treated group suggest involvement of NO in MB's effects in the animal model of PTZ-evoked convulsions.


Alternative splicing of the angiogenesis associated extra-domain B of fibronectin regulates the accessibility of the B-C loop of the type III repeat 8.
Fibronectin (FN) is a multi-domain molecule involved in many cellular processes, including tissue repair, embryogenesis, blood clotting, and cell migration/adhesion. The biological activities of FN are mediated by exposed loops located mainly at the interdomain interfaces that interact with various molecules such as, but not only, integrins. Different FN isoforms arise from the alternative splicing of the pre-mRNA. In malignancies, the splicing pattern of FN pre-mRNA is altered; in particular, the FN isoform containing the extra-domain B (ED-B), a complete FN type III repeat constituted by 91 residues, is undetectable in normal adult tissues, but exhibits a much greater expression in fetal and tumor tissues, and is accumulated around neovasculature during angiogenic processes, thus making ED-B one of the best markers and targets of angiogenesis. The functions of ED-B are still unclear; however, it has been postulated that the insertion of an extra-domain such as ED-B modifies the domain-domain interface and may unmask loops that are otherwise cryptic, thus giving FN new potential activities. We used the mAb C6, which reacts with ED-B containing FN, but not with ED-B-free FN and various recombinant FN fragments containing mutations, to precisely localize the epitopes recognized by the mAb C6. We formally demonstrated that the inclusion of the alternatively spliced angiogenesis-associated ED-B leads to the unmasking of the FNIII 8 B-C loop that is cryptic in FN molecules lacking ED-B. Thus, the mAb C6, in addition to providing a new reagent for angiogenesis targeting, represents a new tool for the study of the potential biological functions of the B-C loop of the repeat FNIII 8 that is unmasked during angiogenic processes.


Suppression of transformed phenotype and tumorigenicity after transfer of chromosome 4 into U251 human glioma cells.
The development of primary human brain tumors, particularly glioblastoma multiforme (GBM), has been associated with a number of molecular and chromosomal abnormalities. In this study, a novel tumor suppressor locus was identified and localized after the transfer of a human chromosome 4 into U251 human GBM cells. Hybrid clones containing a transferred neomycin-resistance tagged chromosome 4 revealed an inability to form tumors in nude mice and a greatly decreased efficiency of soft agarose colony formation. As a control, clones containing a transferred chromosome 2 were generated, and these retained the tumorigenic phenotype of the parental U251 cells. The presence of the transferred chromosomes was demonstrated by gain of polymorphic loci and FISH analyses. Several suppressed hybrid clones were shown to contain spontaneously reduced versions of the transferred chromosome 4. A common region of the fragmented chromosome 4 was retained among these clones that included the epidermal growth factor locus at 4q24-26 and several adjacent markers. The identification of a common fragment in the suppressed clones suggests the presence of a tumor suppressor gene or genes in this region, involved in glioma oncogenesis.


Role of Health Literacy in Health-Related Information-Seeking Behavior Online: Cross-sectional Study.
The internet has emerged as a main venue of health information delivery and health-related activities. However, few studies have examined how health literacy determines online health-related behavior. The aim of this study was to investigate the current level of health-related information-seeking using the internet and how health literacy, access to technology, and sociodemographic characteristics impact health-related information-seeking behavior. We conducted a cross-sectional study through a survey with Minnesotan adults (N=614) to examine their health literacy, access to technology, and health-related information-seeking internet use. We used multivariate regression analysis to assess the relationship between health-related information-seeking on the internet and health literacy and access to technology, controlling for sociodemographic characteristics. Better health literacy (β=.35, SE 0.12) and greater access to technological devices (eg, mobile phone and computer or tablet PC; β=.06, SE 0.19) were both associated with more health-related information-seeking behavior on the internet after adjusting for all other sociodemographic characteristics. Possession of a graduate degree (β=.28, SE 0.07), female gender (β=.15, SE 0.05), poor health (β=.22, SE 0.06), participation in social groups (β=.13, SE 0.05), and having an annual health exam (β=.35, SE 0.12) were all associated with online health-related information-seeking. Our findings indicate that access to online health-related information is not uniformly distributed throughout the population, which may exacerbate disparities in health and health care. Research, policy, and practice attention are needed to address the disparities in access to health information as well as to ensure the quality of the information and improve health literacy.


[Scientific ethics of therapeutic abortion].
Therapeutic abortion is proposed when a pregnancy threatens a woman's life and the fetus is not viable ex utero. As the intention is not to kill the fetus, this action should be named "therapeutic interruption of pregnancy". However, in some cases the fetus directly hampers the mother's health. Thus, the removal of the cause of the disease coincides with killing the fetus. Therapeutic abortion has been proposed for several situations. A) When pregnancy and not the fetus, impairs maternal life (e.g. ovular infection, ectopic pregnancy, decompensation of a preexisting disease or diseases of pregnancy as pre-eclampsia/eclampsia, HELLP and Ballantyne syndromes, choriocarcinoma). B) A risk for maternal survival caused by the embryo or fetal genetic constitution: autoimmune diseases of the mother generated by fetal antigens, some types of eclampsia with or without HELLP syndrome due to an immune or exaggerated inflammatory response of the mother, Ballantyne syndrome associated to eclampsia due to fetal-maternal genetic incompatibility, the classic fetus-maternal genetic incompatibility, embryo or fetus diseases caused by their genomic constitution, mainly hydatidiform mole and the triploid, or fetal cancer. Scientific knowledge and a prudential Medical Ethics are capable to solve most cases.


Effect of physiotherapy on the strength of tibial internal rotator muscles in males after anterior cruciate ligament reconstruction (ACLR).
The goal of this study was to evaluate the effect of physiotherapy on the strength of muscles responsible for tibial internal rotation (IR) in male patients after anterior cruciate ligament reconstruction (ACLR) using autografts of the semitendinosus and gracilis muscles (STGR). Fifty-nine males were examined. The first group consisted of 19 patients subjected to 4-stage physiotherapy following ACLR. The second group consisted of 20 males without knee injuries. The third group consisted of 20 males who had not undergone systematic physiotherapy within the last 12 months following lower limb injuries. Moments of maximal strength (MMS), isometric torque (IT), and peak torque (PT) were measured under static and isokinetic conditions using the Humac Norm System. In the first group, IT measurements were performed during the 13th and 21st week of physiotherapy, while PT measurements were performed during the 16th and 21st weeks of physiotherapy following ACLR. In the control groups (II and III) the measurements were performed once. In the first group, the IT (13 weeks) and PT (16 weeks) values of internal tibial rotator muscles, obtained from the operated extremities were significantly lower than the values obtained from the uninvolved knees and the control group results. During the 21st week of physiotherapy, the results obtained for IT and PT in patients after ACLR were similar to the values obtained from the uninvolved knees and the results of the second group subjects. The 21-week physiotherapy in ACLR patients favorably affected the PT values of tibial rotator muscles of the operated knees. In the third group, the IT values did not indicate a complete improvement after 12 months without systematic physiotherapy.


Physiological control of an in-series connected pulsatile VAD: numerical simulation study.
This paper investigates ventricular assist device (VAD)-assisted cardiovascular dynamics under proportion-integration-differentiation (PID) feedback control. Previously, we have studied the cardiovascular responses under the support of an in-series connected reciprocating-valve VAD through numerical simulation, and no feedback control was applied in the VAD. In this research, we explore the contribution of the VAD control on the circulatory dynamics assisted by the reciprocating-valve VAD, in response to the changing physiological conditions. The classical PID control algorithm is implemented to regulate the VAD stroke beat-to-beat, based on the error signal between the expected and the realistic mean aortic pressures. Simulation results show that under the PID VAD control, physiological variables such as left atrial, ventricular and systemic arterial pressures, cardiac output and ventricular volumes are satisfactorily maintained in the physiological ranges. With the online PID feedback control, operation of the reciprocating-valve VAD can be satisfactorily regulated to accommodate metabolic requirements under various physiological conditions including normal resting and exercise situations.


Status incongruity in Samoan youth: a biocultural analysis of culture change, stress, and immune function.
In Samoa, the presence of a matai title in the family has historically been a valued source of social status. However, as the process of Westernization continues, new sources of social status are emerging. This study explores the degree to which new and old markers of social status agree--or disagree--and the consequences they have for the experience of stress in 329 Samoan adolescents. The study integrates cultural and biological methods and data, and measures an aspect of immune function (antibodies against the Epstein-Barr virus) as a biomarker of psychosocial stress. Results indicate that status "incongruent" adolescents experience significantly more stress (indicated by reduced immune function), and that emerging markers of social status are becoming inextricably linked to "traditional" markers in such a way that discordance between them is a significant source of stress. This study proposes new conceptual models for future studies of culture change and suggests that biomarkers may represent ethnographic tools that can provide insight into hidden cultural dynamics and the experience of stress.


Fast perspective volume ray casting method using GPU-based acceleration techniques for translucency rendering in 3D endoluminal CT colonography.
Recent advances in graphics processing unit (GPU) have enabled direct volume rendering at interactive rates. However, although perspective volume rendering for opaque isosurface is rapidly performed using conventional GPU-based method, perspective volume rendering for non-opaque volume such as translucency rendering is still slow. In this paper, we propose an efficient GPU-based acceleration technique of fast perspective volume ray casting for translucency rendering in computed tomography (CT) colonography. The empty space searching step is separated from the shading and compositing steps, and they are divided into separate processing passes in the GPU. Using this multi-pass acceleration, empty space leaping is performed exactly at the voxel level rather than at the block level, so that the efficiency of empty space leaping is maximized for colon data set, which has many curved or narrow regions. In addition, the numbers of shading and compositing steps are fixed, and additional empty space leapings between colon walls are performed to increase computational efficiency further near the haustral folds. Experiments were performed to illustrate the efficiency of the proposed scheme compared with the conventional GPU-based method, which has been known to be the fastest algorithm. The experimental results showed that the rendering speed of our method was 7.72fps for translucency rendering of 1024x1024 colonoscopy image, which was about 3.54 times faster than that of the conventional method. Since our method performed the fully optimized empty space leaping for any kind of colon inner shapes, the frame-rate variations of our method were about two times smaller than that of the conventional method to guarantee smooth navigation. The proposed method could be successfully applied to help diagnose colon cancer using translucency rendering in virtual colonoscopy.


Body proportions for the facilitation of walking, running and flying: the case of partridges.
Predation is one of the most important natural selection forces. Prey species can optimize feeding behavior and escape from predators based on mobility conditioned by body proportions. With age, mobility capacity increases and individuals are more efficient in finding resources and safety (e.g., food and refuge). Birds' mobility is driven by the dimensions, of the head and torso, as well as the extremities and flight feathers. To assess the relationship between body traits and to understand how body proportions are organized in wild Red-legged partridges (Alectoris rufa), we used biometric data from nearly 14,000 individuals, obtained during a long-term study (1988-2011) on a wild population. We used GLMs and regressions to model the relationship between body mass and the size of body parts. We found that wing length was the morphological part best explained by other body trait measures. Wing length models were better predictors in juveniles than in adults and in females than in males. Wing length and feather length, mass and total length are the most strongly related parts; mass and wing length, total length and feather length are moderately related. The association between mass and wing length is intermediated by feather length and total length. Social inclusion, feeding and predator evasion may be affected by body structure intermediated by mobility and health. Our results suggest that proportions of the body, extremities and flight feathers drive mobility which is intimately associated with ecology, biological efficiency, health and physical optimization. Our findings showed that wing size was strongly allied to other body part measurements, enhancing the importance of body structure conformation for flight. Our study highlights the scaled relationship of body structure among age-sex classes and its relevance to social cohesion, flock movement and the balance between predation and starvation.


Differential sensitivity of chromium-mediated DNA interstrand crosslinks and DNA-protein crosslinks to disruption by alkali and EDTA.
Some compounds of hexavalent chromium are well-established carcinogens. Chromium enters mammalian cells in the hexavalent form and is reduced to chromium (III). Treatment of purified DNA with chromium (III) produces DNA-DNA interstrand crosslinks (DDC) which obstruct the progression of DNA polymerases in vitro. DDC were also detected in chromate-treated cultured normal human lung cells using the renaturing agarose gel electrophoresis (RAGE) assay and correlated with base-specific inhibition of DNA replication. Curiously, DDC have gone undetected in studies of cultured cells using the alkaline elution (AE) technique, whereas chromium-mediated DNA-protein crosslinks (DPC) were readily detected by AE. We tested the hypothesis that AE conditions [60 mM tetraethyl ammonium hydroxide (TEA), 20 mM EDTA, pH 12.6, for 16 h at room temperature] dissociate DDC but not DPC using chromium(III)-treated plasmid DNA and the RAGE assay. Dose-dependent chromium-induced DDC were unaffected by TEA (pH 11.8) alone or by more rigorous alkaline denaturation conditions (200 mM NaOH, pH 13.5, for 16 h). DDC were, however, completely disrupted by EDTA (pH 12.6) alone or the combination of TEA and EDTA (pH 12.6). In contrast, DPC remained largely intact under these conditions. Therefore, past AE-based studies which have failed to detect chromium-induced DDC do not prove the absence of this lesion. AE may not be suitable for detecting DDC induced by EDTA-chelatable agents such as metals.


Epidemiology of oral clefts in a large South American sample.
A total of 849,381 newborn children were examined during the years 1967 to 1981, in 56 hospitals of eight countries, in the Latin American Collaborative Study of Congenital Malformations (ECLAMC). Of these, 741 had a cleft lip with or without a cleft palate (CL +/- P), yielding a global prevalence of 0.87 per thousand, and 115 had cleft palate (CP) only (frequency: 0.13 per thousand). CP frequencies by country and by year were essentially homogeneous, but those for CL +/- P showed heterogeneity by country (but no temporal trends). Patients thus ascertained, with matched, appropriate controls, have been subjected to a detailed epidemiologic study. For CP, only the sex ratio deviated from the control values; but for CL +/- P the marked divergence in sex ratio was accompanied by differences in the two series on the frequency of twin births, birth weight, neonatal survival, birth order, medicine use, and occurrence of acute or chronic illnesses during the first trimester of pregnancy. Lack of agreement of these results with previous data may be due to different types of patient ascertainment, sample sizes, and methods of analysis.


A deficiency in CCR2+ monocytes: the hidden side of Alzheimer's disease.
Alzheimer's disease (AD) is a neurodegenerative disorder characterized by intracellular neurofibrillary tangle formation and extracellular amyloid-β (Aβ) deposition. To date, microglia seem to act as double-edged swords, being either beneficial (e.g. clearance of Aβ) or detrimental (e.g. secretion of neurotoxic factors) in AD. Following a rather intense debate on the question, a consensus has emerged that microglia can renew themselves via proliferation of already differentiated microglia as well as via the de novo recruitment of monocytes of mouse models of AD. However, recent advances suggest distinct function for resident and bone marrow-derived microglia (BMDM), and have emphasized the neuroprotective functions of BMDM. BMDM is the only subset of cells that restrict cerebral amyloidosis in the AD brain, which has been recently attributed to CCR2(+) monocytes. Moreover, an impaired recruitment of CCR2(+) monocytes has been reported in AD patients, as seen from the CCR2(+) monocytopenia found in the bloodstream and BM. The present review summarizes the current knowledge on the roles and dysfunctions of CCR2(+) monocytes in AD and their potential as key therapeutic targets.


Extracting rules from trained neural networks.
This paper presents an algorithm for extracting rules from trained neural networks. The algorithm is a decompositional approach which can be applied to any neural network whose output function is monotone such as sigmoid function. Therefore, the algorithm can be applied to multilayer neural networks, recurrent neural networks and so on. It does not depend on training algorithms, and its computational complexity is polynomial. The basic idea is that the units of neural networks are approximated by Boolean functions. But the computational complexity of the approximation is exponential, and so a polynomial algorithm is presented. The author has applied the algorithm to several problems to extract understandable and accurate rules. This paper shows the results for the votes data, mushroom data, and others. The algorithm is extended to the continuous domain, where extracted rules are continuous Boolean functions. Roughly speaking, the representation by continuous Boolean functions means the representation using conjunction, disjunction, direct proportion, and reverse proportion. This paper shows the results for iris data.


Navigating through perplex morphologic changes after exogenous hormone usage.
Clinical application of exogenous hormone as a method of contraception and/or treatment of various gynecologic disorders is exceedingly common. Unfortunately, the concurrent use of these agents also complicates the interpretation of pathology specimens. Various studies have shown that morphologic changes induced by hormonal therapies are present in both non-neoplastic and neoplastic tissues within the women's reproductive tract. It is important to understand the exogenous hormone induced morphologic changes, as it helps the pathologists make the accurate diagnosis, and in turn, guide clinicians to make optimal clinical decisions. In this review, we summarize the morphologic changes in both neoplastic and non-neoplastic endometrial, cervical, and myometrial surgical specimens after hormonal therapies, particularly after progestin treatment. In the endometrium, particularly in the scenario of progestin-treated atypical endometrial hyperplasia/endometrioid intraepithelial neoplasia (AEH/EIN), there is notoriously poor interobserver agreement and difficulty in assessing for the residual disease. We summarize current literature and propose our recommended approach in assessing these challenging endometrial biopsies, including a diagnostic algorism, the use of PAX-2, PTEN, beta-catenin immunohistochemistry panel, as well as consistency in diagnostic wording of the report. In the cervix, progestin makes dysplastic lesions appear metaplastic, thus high-grade squamous dysplastic lesions may be easily missed. Within the myometrium, lesions such as adenomyosis may show various degree of decidualization, while smooth muscle neoplasms may show apoplectic changes, and stromal lesions including endometrial stromal sarcoma may show more eosinophilic cytoplasm. All such changes may pose more or less diagnostic challenges in our daily practice. However, most are readily recognizable when we understand particular hormone related scenarios.


Participatory Design and Evaluation of the "Stem Cells Australia" Website for Delivering Complex Health Knowledge: Mixed Methods Study.
The internet has become a commonly used information source for people seeking to understand their health care options. However, inconsistent representation about what stem cell treatments are available and from whom, coupled with the lack of transparency about what has been shown to work or is even safe, can distract and mislead users. Given these challenges, there is a need to develop effective evidence-based tools for delivering information about health care options involving stem cells. A need to redesign an existing website in Australia was identified to provide trustworthy information about stem cell research and to counter misinformation. Using a participatory design approach to generate an understanding of what information users need for stem cell treatments, the Stem Cells Australia website serves as a case study for the development and evaluation of websites delivering complex messages about science and health. This study comprised 3 steps. First, a focus group and several one-on-one interviews with a purposive sample of users (n=12) were conducted to identify their needs and requirements. Second, we designed a new version of the website based on findings from the focus group and interviews. Finally, for evaluating the participatory design process, we collected 180 days of Google Analytics data for both the original and redesigned versions (90 days for each) and compared their differences using 2-sample z tests. The feedback from participants was grouped into 3 themes-needed and unwanted information, how and where to obtain information, and their information preferences. These were translated into requirements for rebuilding the website. The redesigned version reached users in other continents, despite the daily numbers of users (-61.2%; P<.001) and sessions (-61.7%; P<.001) decreasing. The redesigned version also showed substantial decrease in daily bounce rate (-97.2%; P<.001), significant increase in the daily average of page reads per session (+110.8%; P<.001), and long daily average for session duration (+22.9%; P=.045). Navigation flow analysis showed more traffic toward web pages related to health conditions in the redesigned version. Websites about stem cell research need to provide content for vulnerable global audiences. Participatory design that addresses knowledge gaps and information needs can produce better performance and engagement, which can be evaluated using Google Analytics, a common web analytics tool used by many websites. Learnings for improving the metrics regarding website identity, research updates, and clinical trials are concluded, which can inform the future design of websites seeking to engage users and provide reliable and accessible science and health information including but not limited to stem cell research and therapies.


Can oral vitamin D prevent the cardiovascular diseases among migrants in Australia? Provider perspective using Markov modelling.
The study was designed to model the effectiveness and cost effectiveness of oral Vitamin D supplementation as a primary prevention strategy for cardiovascular disease among a migrant population in Australia. It was carried out in the Community Health Service, Kensington, Melbourne. Best-case scenario analysis using a Markov model was employed to look at the health care providers' perspective. Adult migrants who were vitamin D deficient and free from cardiovascular disease visiting the medical centre at least once during the period from 1 January 2010 to 31 December 2012 were included in the study. The blood pressure-lowering effect of vitamin D was taken from a published meta-analysis and applied in the Framingham 10 year cardiovascular risk algorithm (with and without oral vitamin D supplements) to generate the probabilities of cardiovascular events. A Markov decision model was used to estimate the provider costs associated with the events and treatments. Uncertainties were derived by Monte Carlo simulation. Vitamin D oral supplementation (1000 IU/day) for 10 years could potentially prevent 31 (interquartile range (IQR) 26 to 37) non-fatal and 11 (IQR 10 to 15) fatal cardiovascular events in a migrant population of 10,000 assuming 100% compliance. The provider perspective incremental cost effectiveness per year of life saved was AU$3,992 (IQR 583 to 8558). This study suggests subsidised supplementation of oral vitamin D may be a cost effective intervention to reduce non-fatal and fatal cardiovascular outcomes in high-risk migrant populations.


[ESBL-producing enterobacteria in Passo Fundo, state of Rio Grande do Sul, Brazil].
The main emerging resistance mechanism relating to Enterobacteriaceae is represented by production of extended spectrum beta-lactamases (ESBLs). These enzymes have the capacity to hydrolyze broad-spectrum cephalosporins and are greatly used for antimicrobial chemotherapy on enterobacterial infections. Although resistance to these agents presents remarkable geographical variability, the resistance rates are high in many countries A retrospective observational cross-sectional descriptive study was developed to evaluate the frequency of ESBLs among Enterobacteriaceae strains obtained from Hospital São Vicente de Paulo, Brazil ESBL production was noted in 24.8% (n = 208/838) of the isolates evaluated. Isolates of Escherichia coli represented 46.2% (n = 96/208) of the ESBL producers, followed by Enterobacter species (30.3%; n = 63/208). The sensitivity of these isolates to meropenem was 91.4% and to piperacillin/tazobactam, 67.4% The ESBL levels founded confirm the worldwide concern regarding this resistance mechanism.


The effects of city streets on an urban disease vector.
With increasing urbanization vector-borne diseases are quickly developing in cities, and urban control strategies are needed. If streets are shown to be barriers to disease vectors, city blocks could be used as a convenient and relevant spatial unit of study and control. Unfortunately, existing spatial analysis tools do not allow for assessment of the impact of an urban grid on the presence of disease agents. Here, we first propose a method to test for the significance of the impact of streets on vector infestation based on a decomposition of Moran's spatial autocorrelation index; and second, develop a Gaussian Field Latent Class model to finely describe the effect of streets while controlling for cofactors and imperfect detection of vectors. We apply these methods to cross-sectional data of infestation by the Chagas disease vector Triatoma infestans in the city of Arequipa, Peru. Our Moran's decomposition test reveals that the distribution of T. infestans in this urban environment is significantly constrained by streets (p<0.05). With the Gaussian Field Latent Class model we confirm that streets provide a barrier against infestation and further show that greater than 90% of the spatial component of the probability of vector presence is explained by the correlation among houses within city blocks. The city block is thus likely to be an appropriate spatial unit to describe and control T. infestans in an urban context. Characteristics of the urban grid can influence the spatial dynamics of vector borne disease and should be considered when designing public health policies.


Synthesis and physicochemical properties of oligonucleotides built with either alpha-L or beta-L nucleotides units and covalently linked to an acridine derivative.
Modified deoxynucleosides 2'-deoxy-beta-L-uridine, beta-L-thymidine, alpha-L-thymidine, 2'-deoxy-beta-L-adenosine and 2'-deoxy-alpha-L-adenosine were synthesized and assembled as homooligomers, respectively: octa-beta-L-deoxyuridylates, octa beta-L and alpha-L-thymidylates and tetra beta-L and alpha-L-deoxyadenylates. These unnatural oligomers were then substituted with an acridine derivative. The binding studies of these modified oligonucleotides with D-ribo- and D-deoxyribopolynucleotides were carried out by absorption spectroscopy. While beta-L-d(Up)8m5Acr, beta-L-(Tp)8m5Acr, alpha-L-(Tp)8m5Acr did not interact with poly(rA) and poly(dA), beta-L-d(Ap)4m5Acr and alpha-L-d(Ap)4m5Acr did form double and triple helices with poly(rU) and poly(dT), respectively. Their stability towards nuclease digestion was studied through comparison with that of octa-beta-D-thymidylate and tetra beta-D-deoxyadenylate covalently linked to an acridine derivative. One endonuclease (nuclease P1 from Penicillium citrinum) and two exonucleases (a 3'-exonuclease from Crotalus durissus venom and a 5'-exonuclease extracted from calf thymus) were employed. beta-L- and alpha-L-oligomers demonstrate a high resistance toward nuclease digestion.


Design and synthesis of thiazolo[5,4-f]quinazolines as DYRK1A inhibitors, part I.
The convenient synthesis of a library of novel 6,6,5-tricyclic thiazolo[5,4-f] quinazolines (forty molecules) was achieved mainly under microwave irradiation. Dimroth rearrangement and 4,5-dichloro-1,2,3,-dithiazolium chloride (Appel salt) chemistry were associated for the synthesis of a novel 6-aminobenzo[d]thiazole-2,7-dicarbonitrile (16) a versatile molecular platform for the synthesis of various bioactive derivatives. Kinase inhibition of the final compounds was evaluated on a panel of four Ser/Thr kinases (DYRK1A, CDK5, CK1 and GSK3) chosen for their strong implications in various regulation processes, especially Alzheimer's disease (AD). In view of the results of this preliminary screening, thiazolo[5,4-f]quinazoline scaffolds constitutes a promising source of inspiration for the synthesis of novel bioactive molecules. Among the compounds of this novel chemolibrary, 7i, 8i and 9i inhibited DYRK1A with IC50 values ranging in the double-digit nanomolar range (40, 47 and 50 nM, respectively).


Electrically poled vapor-deposited organic glasses for integrated electro-optics.
We introduce electrically poled small molecule assemblies that can serve as the active electro-optic material in nano-scale guided-wave circuits such as those of the silicon photonics platform. These monolithic organic materials can be vacuum-deposited to homogeneously fill nanometer-size integrated-optics structures, and electrically poled at higher temperatures to impart an orientational non-centrosymmetric order that remains stable at room temperature. An initial demonstration using the DDMEBT molecule and corona poling delivered a material with the required high optical quality, an effective glass transition temperature of the order of ∼80°C, and an electro-optic coefficient of 20 pm/V.


Comparative effectiveness of cryotherapy vs brachytherapy for localised prostate cancer.
Despite the increased popularity of emerging therapies for localised prostate cancer, such as cryotherapy and brachytherapy, outcomes data remains sparse beyond single-centre comparative studies. The present study identified that although less costly, cryotherapy was associated with more urinary and ED complications and a greater need for salvage ADT. Conversely, cryotherapy was associated with fewer bowel complications. Patients and providers alike should consider these population-based outcomes when discussing therapeutic options for localised prostate cancer. To compare prostate cryotherapy vs brachytherapy outcomes and costs, as despite the greater popularity of these emerging therapies for localised prostate cancer, outcomes data remains sparse beyond single-centre comparative studies. Observational study of 10 928 men who underwent primary cryotherapy (943 patients) or brachytherapy (9985) with ≥2 years of follow-up using USA Surveillance, Epidemiology, and End Results (SEER-) Medicare linked data. Weighted propensity score methods were used. Use of cryotherapy increased four-fold whereas brachytherapy utilization remained the same from 2001 to 2005 (P < 0.001). Men who underwent cryotherapy vs brachytherapy were older (P < 0.001), more likely to be Black (P < 0.001), less likely to live in areas of higher education (P < 0.001), less likely to live in areas with greater income (P < 0.001), and were more likely to live in urban vs rural areas (P = 0.007). In propensity score-weighted analyses, cryotherapy was associated with more urinary (41.4% vs 22.2%, P < 0.001) and erectile dysfunction (ED) complications (34.7% vs 21.0%, P < 0.001) while brachytherapy was associated with more bowel complications (19.0% vs 12.1%, P < 0.001). Cryotherapy was associated with greater use of salvage androgen deprivation therapy (ADT; 1.4 vs 0.5 per 100 person-years, P < 0.001), suggesting worse cancer control. Finally costs were significantly greater for brachytherapy vs cryotherapy ($16 887 vs $12 629 USA dollars, P < 0.001). Although less costly, cryotherapy was associated with more urinary and ED complications and greater need for salvage ADT. Conversely, cryotherapy was associated with fewer bowel complications. Patients and providers alike should consider these population-based outcomes when discussing therapeutic options for localised prostate cancer.


Antibacterial efficacy of NanoCare, Fullerene (C60) activated by UV light, and Morinda Oleifera against S.Mutans and bond integrity of composite resin to Caries affected dentin.
Assessment of the impact of contemporary disinfection techniques Moringa Oleifera (M. Oleifera), NanoCare Plus Silver Gold® (Nanocare), and Fullerene (C60) on survival rates of S.Mutans and shear bond strength (SBS) of composite to the carious affected dentin (CAD) MATERIAL AND METHODS: Sixty mandibular molars having caries progression till the middle 1/3rd of the dentin were disinfected. The CAD surface of twenty samples was inoculated with S.mutans. Based on different disinfection regimens samples were arbitrarily assigned to four groups (n:15) Group 1: 2% CHX, Group 2:NanoCare, Group 3:Fullerene (C60), and Group 4 (M. Oleifera. This was followed by calculating the survival rate of S.mutans. Ten samples from each group were then restored with composite restoration and thermocycled. Assessment of SBS and failure mode was performed using a universal testing machine and stereomicroscope at 40X magnification. Statistical significance among groups was assessed using analysis of variance (ANOVA) and Tukey's test at a significance level of p=0.05 RESULTS: Group 2 samples treated with NanoCare exhibited the lowest survival rate (0.39 ±0.02 CFU/ml) of S.Mutans. However, Group 1 (CHX) samples exhibited the highest survival count (0.51±0.10 CFU/ml). Furthermore, the highest composite to CAD bond was observed in Group 3 Fullerene(C60) (18.44±0.25 MPa) samples and the lowest SBS was observed in Group 1 (CHX) (12.48±1.69 MPa) CONCLUSION: Fullerene(C60) and Moringa Oleifera extract hold promise as potential substitutes for chlorhexidine (CHX) in clinical applications, offering the potential for improved S.Mutans elimination and enhanced bond strength to CAD surface.


Response of asthmatics to isoprenaline and salbutamol aerosols administered by intermittent positive-pressure ventilation.
The bronchodilator and cardiac effects produced by aerosols of 0.5% isoprenaline and of 0.25, 0.5, and 1% salbutamol administered in 40% oxygen by intermittent positive-pressure ventilation were compared in 24 asthmatic patients. Isoprenaline and salbutamol in concentrations of 0.5% were equipotent in peak bronchodilator effect; salbutamol was superior in total bronchodilator effect and duration of average effect, but the peak bronchodilator effect occurred earlier after isoprenaline. Significantly greater tachycardia was produced by 0.5% isoprenaline than by the same concentration of salbutamol. The 0.25, 0.5, and 1% concentrations of salbutamol had about the same peak bronchodilator effect, but there was a stepwise increase in total effect and duration of average effect in relation to the concentration used. A similar stepwise increase in heart rate was also noted, but with all concentrations this was significantly less than with 0.5% isoprenaline. It was concluded that a 0.5% solution of salbutamol, which provided maximal bronchodilatation without important tachycardia, was therapeutically superior to the other three treatments.


Biting midges of the genus Culicoides in South Carolina zoos.
Biting midges of the genus Culicoides (Diptera: Ceratopogonidae) were collected during the summer of 2007 at the Greenville and Riverbanks Zoos in South Carolina with Centers for Disease Control and Prevention (CDC) traps equipped with ultraviolet or incandescent lights and baited with carbon dioxide. Sixteen species of Culicoides were collected, four of which represented more than 80%. They were Culicoides guttipennis (Coquillett), Culicoides mulrenanni Beck, Culicoides obsoletus (Meigen), and Culicoides sanguisuga (Coquillett). C. guttipennis was found on a dead colobus monkey and a dead golden-headed lion tamarin; Culicoides husseyi Wirth & Blanton was collected from an unidentified, abandoned bird's nest. Ultraviolet light-equipped traps captured significantly more Culicoides specimens than traps with incandescent light. Half of the collected species previously have been associated with vertebrate pathogens, indicating a potential risk to captive animals.


Outcomes of Early and Intensive Use of a Palm and Digit Extension Orthosis in Young Children After Burn Injury.
Burns to the palmar aspect of the hand are prevalent in young children. The development of scar tissue across the flexor surface of the hand combined with the years of growth ahead may result in considerable complications. This study was undertaken to describe outcomes of early and intensive use of a palm and digit extension orthosis with the elbow immobilized at 90° flexion following a palmar hand burn. A retrospective review of 107 children (mean age 18 months [SD 10]) treated at a statewide Pediatric Burns Unit from 2012 to 2016 was performed. Three children (3%) developed contracture during the 24-month study follow-up period. The other 104 children (97%) had full ROM at 24 months or at either the point of discharge or loss to follow-up. Early signs of contracture, defined as loss of full movement or significant banding, developed in 26 children (24%) in the first 9 months after burn. With intensive physiotherapy, 23 children regained full movement by 12 months after burn. Children who did not achieve complete wound healing at 1 month after burn and children with hypertrophic scarring at 2 months after burn were significantly more represented among cases of early signs of contracture (P = .013). When undertaken with regular clinical review, early and intensive use of a palm and digit extension orthosis can maintain full extension of the palm and digits in children after palmar burn.