Progress against inequalities in mortality: register-based study of 15 European countries between 1990 and 2015.
Socioeconomic inequalities in mortality are a challenge for public health around the world, but appear to be resistant to policy-making. We aimed to identify European countries which have been more successful than others in narrowing inequalities in mortality, and the factors associated with narrowing inequalities. We collected and harmonised mortality data by educational level in 15 European countries over the last 25 years, and quantified changes in inequalities in mortality using a range of measures capturing different perspectives on inequality (e.g., 'relative' and 'absolute' inequalities, inequalities in 'attainment' and 'shortfall'). We determined which causes of death contributed to narrowing of inequalities, and conducted country- and period-fixed effects analyses to assess which country-level factors were associated with narrowing of inequalities in mortality. Mortality among the low educated has declined rapidly in all European countries, and a narrowing of absolute, but not relative inequalities was seen in many countries. Best performers were Austria, Italy (Turin) and Switzerland among men, and Spain (Barcelona), England and Wales, and Austria among women. Ischemic heart disease, smoking-related causes (men) and amenable causes often contributed to narrowing inequalities. Trends in income inequality, level of democracy and smoking were associated with widening inequalities, but rising health care expenditure was associated with narrowing inequalities. Trends in inequalities in mortality have not been as unfavourable as often claimed. Our results suggest that health care expansion has counteracted the inequalities widening effect of other influences.


Long-term comparison of video-assisted thoracic sympathectomy and clinical observation for the treatment of palmar hyperhidrosis in children younger than 14.
The results of video-assisted thoracic sympathectomy (VATS)in children are unknown. To investigate the improvement in quality of life (QOL) of a group of 45 children who did and did not undergo VATS for the treatment of palmar hyperhidrosis (PH) 4 years after the initial evaluation. Forty-five children with PH were initially evaluated. Children were divided into two groups: 30 in the VATS group and 15 in the control group. We studied the evolution of PH, negative effect of hyperhidrosis on the QOL before the treatment, and improvement in QOL after treatment. Twenty-five patients (83.4%) in the VATS group experienced great improvement in PH, and five (16.6%) experienced partial improvement; 12 (80.0%) children from the control group had some type of improvement, and three (20.0%) had partial improvement. Two (13.3%) children in the control group and 23 (76.7%) in the VATS group had great improvement in QOL. For children with PH and poor QOL, VATS is better than no treatment. It produces better results with regard to sweating and greater improvement in QOL.


ICSI does not improve reproductive outcomes in autologous ovarian response cycles with non-male factor subfertility.
Does the method of fertilisation improve reproductive outcomes in poor ovarian response (POR) cycles when compared to all other ovarian response categories in the absence of male factor subfertility? ICSI does not confer any benefit in improving the clinical pregnancy or live birth (LB) outcome in autologous ovarian response cycles in the absence of male factor subfertility when compared to IVF. ICSI is associated with an improved outcome when compared to IVF in patients with severe male factor subfertility. A retrospective study involving 1 376 454 ART cycles, of which 569 605 (41.4%) cycles fulfilled the inclusion and exclusion criteria for all autologous ovarian response categories: 272 433 (47.8%) IVF cycles and 297 172 (52.2%) ICSI cycles. Of these, the POR cohort represented 62 641 stimulated fresh cycles (11.0%): 33 436 (53.4%) IVF cycles and 29 205 (46.6%) ICSI cycles. All cycles recorded on the anonymised Human Fertilisation and Embryology Authority (HFEA) registry database between 1991 and 2016 were analysed. All fresh cycles with normal sperm parameters, performed after 1998 were included: frozen cycles, donor oocyte and sperm usage, intrauterine insemination cycles, preimplantation genetic testing (PGT) for aneuploidies (PGT-A), PGT for monogenic/single gene defects (PGT-M), PGT for chromosomal structural arrangements (PGT-SR) cycles, where the reason for stimulation was for storage and unstimulated cycles were excluded. ICSI did not confer any benefit in improving the LB outcome when compared to conventional IVF per treatment cycle (PTC), when adjusted for female age, number of previous ART treatment cycles, number of previous live births through ART, oocyte yield, stage of transfer, method of fertilisation and number of embryos transferred in the POR cohort (adjusted odds ratio [a OR] 1.03, 99.5% confidence interval [CI] 0.96-1.11, P = 0.261) and all autologous ovarian response categories (aOR 1.00, 99.5% CI 0.98-1.02, P = 0.900). The mean fertilisation rate was statistically lower for IVF treatment cycles (64.7%) when compared to ICSI treatment cycles (67.2%) in the POR cohort (mean difference -2.5%, 99.5% CI -3.3 to -1.6, P < 0.001). The failed fertilisation rate was marginally higher in IVF treatment cycles (17.3%, 95% binomial exact 16.9 to 17.7%) when compared to ICSI treatment cycles (17.0%, 95% binomial exact 16.6 to 17.4%); however, this did not reach statistical significance (P = 0.199). The results followed a similar trend when analysed for all autologous ovarian response categories with a higher rate of failed fertilisation in IVF treatment cycles (4.8%, 95% binomial exact 4.7 to 4.9%) when compared to ICSI treatment cycles (3.2%, 95% binomial exact 3.1 to 3.3%) (P < 0.001). The quality of data is reliant on the reporting system. Furthermore, success rates through ART have improved since 1991, with an increased number of blastocyst-stage embryo transfers. The inability to link the treatment cycle to the individual patient meant that we were unable to calculate the cumulative LB outcome per patient. This is the largest study to date which evaluates the impact of method of fertilisation in the POR patient and compares this to all autologous ovarian response categories. The results demonstrate that ICSI does not confer any benefit in improving reproductive outcomes in the absence of male factor subfertility, with no improvement seen in the clinical pregnancy or LB outcomes following a fresh treatment cycle. The study received no funding. C.M.B. is a member of the independent data monitoring group for a clinical endometriosis trial by ObsEva. He is on the scientific advisory board for Myovant and medical advisory board for Flo Health. He has received research grants from Bayer AG, MDNA Life Sciences, Volition Rx and Roche Diagnostics as well as from Wellbeing of Women, Medical Research Council UK, the NIH, the UK National Institute for Health Research and the European Union. He is the current Chair of the Endometriosis Guideline Development Group for ESHRE and was a co-opted member of the Endometriosis Guideline Group by the UK National Institute for Health and Care Excellence (NICE). I.G. has received research grants from Bayer AG, Wellbeing of Women, the European Union and Finox. Not applicable.


The impact of endurance training on arterial plasma K+ levels and swimming performance of rainbow trout
Arterial plasma K+ and lactate concentrations ([K+]a and [lactate]a), as well as blood oxygenation status, were measured in relation to increasing swimming speeds in rainbow trout Oncorhynchus mykiss. Neither [K+]a nor [lactate]a changed at swimming speeds below 1.5 BL s-1, where BL is total body length. Between 1.5 and 2.0 BL s-1, [K+]a started to increase, and above 2.0 BL s-1 both [K+]a and [lactate]a increased with swimming speed. Training shifted the onset of these increases to higher swimming speeds and increased the critical swimming speed (Ucrit) from 2.4 to 3.0 BL s-1. Blood oxygen content showed no changes in control fish, whereas in trained fish it increased by 22 % at the final swimming speed. From the [K+]a data, we suggest that no loss of K+ occurred from the working muscle at low swimming speeds, allowing an unlimited endurance, whereas moderate and higher speeds were probably associated with a loss of K+ from the working muscles, indicating a limited endurance. <P>


Fluoride concentration in foods from Iran.
Knowledge of fluoride intake is important in optimizing the caries-preventive role of fluoride, and the measurement of fluoride intake usually requires information on the fluoride concentration in foods and drinks. Most information comes from developed countries and there are no data on fluoride concentration in foods in Middle Eastern countries including Iran. The aim of the study was to: (a) describe a modification to the silicon-facilitated diffusion method for determining fluoride concentration, (b) provide information on fluoride content of foods in Iran to supplement food tables for the Middle East, and (c) determine the effect of variation in the fluoride concentration of drinking water on the fluoride concentration of prepared foods. Five hundred and ten samples of 84 popular foods and drinks were collected from three areas of Iran where water fluoride concentrations were 0.32, 0.58 and 4.05 mg/L. The mean recovery of fluoride added to food samples before diffusion was 98 +/- 5%. Values for duplicate analysis of 20 food samples were within 0.03 microgram F/g. Most of the samples of foods and drinks came from the area with 0.32 mg F/L in water supplies. For 30 of the 84 items, fluoride concentration was below 0.1 microgram/g. Fluoride concentrations in the cereals group (which constituted much of the diet) were mainly between 0.2 and 0.3 microgram/g, when prepared for consumption. It was concluded that: (a) modification of a published method for determining fluoride concentration of foods appeared to be an advance, (b) values for fluoride concentration of foods commonly consumed in Iran showed variation between groups but were in broad agreement with published data, and (c) concentration of fluoride in water influences positively fluoride concentration in foods cooked in water, but the increase in foods was less than the increase in fluoride concentration in water.


Managing acromio-clavicular joint pain: a scoping review.
Shoulder pain secondary to acromioclavicular joint pain is a common presentation in primary and secondary care but is often poorly managed as a result of uncertainty about optimal treatment strategies. Osteoarthritis is the commonest cause. Although acromioclavicular pain can be treated non-operatively and operatively, there appears to be no consensus on the best practice pathway of care for these patients, with variations in treatment being common place. The present study comprises a scoping review of the current published evidence for the management of isolated acromioclavicular pain (excluding acromioclavicular joint dislocation). A comprehensive search strategy was utilized in multiple medical databases to identify level 1 and 2 randomised controlled trials, nonrandomised controlled trials and systematic reviews for appraisal. Four systematic reviews and two randomised controlled trials were identified. No direct studies have compared the benefits or risks of conservative versus surgical management in a controlled environment. High-level studies on treatment modalities for acromioclavicular joint pain are limited. As such, there remains little evidence to support one intervention or treatment over another, making it difficult to develop any evidenced-based patient pathways of care for this condition.Level of evidence: 2A.


Optimization of the diagnostic management of clinically suspected pulmonary embolism in hospitalized patients.
Identical diagnostic algorithms for suspected pulmonary embolism (PE) are used for hospitalized patients and outpatients, while D-dimer levels, risk factors and pre-test probability for PE differ, and the percentage of patients managed without computerized tomography pulmonary angiography (CTPA) is lower in hospitalized patients. We aimed to improve the efficiency of the diagnostic algorithm by increasing the threshold of the D-dimer, the threshold of the Wells rule and by adjustments of the Wells rule. Six-hundred and twenty-four hospitalized patients from two previously performed management studies with a PE prevalence of 26% were studied. Adjustments were considered to be safe when the failure rate remained <2%. By applying standard management, 8% (49/624) were managed without CTPA with a failure rate of 0·0% (0/49; 95% confidence interval [CI] 0·0-7·3), and it was 1·7% (8/465; 95%CI 0·8-3·4) for all patients in whom PE was excluded at baseline. All evaluated adjustments resulted in an increase of the failure rate with very small improvements of the efficiency. Given these potentially small improvements and the increasing complexity of clinical practice if adjusted diagnostic algorithms for specific patient categories were introduced, we do not recommend further evaluation of any of the adjustments; we recommend that the standard diagnostic algorithm should continue to be applied.


Improvement in borderline personality disorder in relationship to age.
It is commonly believed that some features of borderline personality disorder (BPD) improve as individuals reach their late 30s and 40s. This study examined age-related change in borderline criteria and functional impairment, testing the hypothesis that older age would be associated with relatively more improvement than younger age. A total of 216 male and female participants with BPD were followed prospectively with yearly assessments over 6 years. Participants showed similar rates of improvement in borderline features regardless of age. A significant age by study year interaction showed functioning in older subjects to reverse direction and begin to decline in the latter part of the follow-up, in contrast to younger subjects who maintained or continued improvement over the 6 years. Despite the decline, functioning for the older subjects was comparable with or slightly better at year 6 than at year 1. Improvement in borderline features is not specific to the late 30s and 40s. There may be a reversal of improvement in functioning in some borderline patients in this older-age range.


Returning to life activities after hematopoietic cell transplantation in older adults.
The prevalence of hematopoietic cell transplant (HCT) among older adults with hematological malignancies has more than doubled over the last decade and continues to grow. HCT is an intense process that can impact functional status and health-related quality of life. The objective of this paper is to describe the experience of returning to life activities after HCT in patients 60 years of age and older and the resources required to adapt and cope to limitations in physical, psychological, and cognitive function. Twenty English speaking adults 60 years and older with hematological malignancy 3 to 12 months post-HCT completed semi-structured interviews. Open-ended questions and probes were guided by the Transactional Model of Stress and Coping to explore adaptive functioning, coping resources, and coping strategies. An integrated grounded theory approach was used to code the textual data to identify themes. The study took place at a tertiary comprehensive cancer center in the Midwest United States. Eight allogeneic and twelve autologous HCT recipients participated in the interviews. Nineteen participants were within 6-12 months and 1 participant was at 3 months post-HCT. Our findings identify the significant role of engaging in life activities and social support in the recovery of physical, psychological and cognitive function. Older HCT recipients are an understudied population. They are at high risk for functional decline. Our findings may provide community oncologists and primary care physicians with a context for providing care to older HCT survivors during their recovery.


Discharge care quality in hospitalised elderly patients: Extended validation of the Discharge Care Experiences Survey.
The Discharge Care Experiences Survey (DICARES) was previously developed to measure quality of discharge care in elderly patients (≥ 65 years). The objective of this study was to test the factorial validity of responses of the DICARES, and to investigate its association with existing quality indicators. We conducted a cross-sectional study at two hospitals in Bergen, Western Norway. A survey, including DICARES, was sent by postal mail to 1,418 patients 30 days after discharge from hospital. To test the previously identified three-factor structure of the DICARES we applied a first order confirmatory factor analysis with corresponding fit indices and reliability measures. Spearman's correlation coefficients, and linear regression, was used to investigate the association of DICARES scores with the quality indicators Nordic Patient Experiences Questionnaire and emergency readmission within 30 days. A total of 493 (35%) patients completed the survey. The mean age of the respondents was 79 years (SD = 8) and 52% were women. The confirmatory factor analysis showed acceptable fit. Cronbach's α between items within factors was 0.82 (Coping after discharge), 0.71 (Adherence to treatment), and 0.66 (Participation in discharge planning). DICARES was moderately correlated with the Nordic Patient Experiences Questionnaire (rho = 0.49, P < 0.001). DICARES overall score was higher in patients with no readmissions compared to those who were emergency readmitted within 30 days (P < 0.001), indicating that more positive experiences were associated with fewer readmissions. DICARES appears to be a feasible instrument for measuring quality of discharge care in elderly patients (≥ 65 years). This brief questionnaire seems to be sensitive with regard to readmission, and independent of comorbidity. Further studies of patients' experiences are warranted to identify elements that impact on discharge care in other patient groups.


Liquid metal-filled magnetorheological elastomer with positive piezoconductivity.
Conductive elastic composites have been used widely in soft electronics and soft robotics. These composites are typically a mixture of conductive fillers within elastomeric substrates. They can sense strain via changes in resistance resulting from separation of the fillers during elongation. Thus, most elastic composites exhibit a negative piezoconductive effect, i.e. the conductivity decreases under tensile strain. This property is undesirable for stretchable conductors since such composites may become less conductive during deformation. Here, we report a liquid metal-filled magnetorheological elastomer comprising a hybrid of fillers of liquid metal microdroplets and metallic magnetic microparticles. The composite's resistivity reaches a maximum value in the relaxed state and drops drastically under any deformation, indicating that the composite exhibits an unconventional positive piezoconductive effect. We further investigate the magnetic field-responsive thermal properties of the composite and demonstrate several proof-of-concept applications. This composite has prospective applications in sensors, stretchable conductors, and responsive thermal interfaces.


Quantitative proteomic characterization and comparison of T helper 17 and induced regulatory T cells.
The transcriptional network and protein regulators that govern T helper 17 (Th17) cell differentiation have been studied extensively using advanced genomic approaches. For a better understanding of these biological processes, we have moved a step forward, from gene- to protein-level characterization of Th17 cells. Mass spectrometry-based label-free quantitative (LFQ) proteomics analysis were made of in vitro differentiated murine Th17 and induced regulatory T (iTreg) cells. More than 4,000 proteins, covering almost all subcellular compartments, were detected. Quantitative comparison of the protein expression profiles resulted in the identification of proteins specifically expressed in the Th17 and iTreg cells. Importantly, our combined analysis of proteome and gene expression data revealed protein expression changes that were not associated with changes at the transcriptional level. Our dataset provides a valuable resource, with new insights into the proteomic characteristics of Th17 and iTreg cells, which may prove useful in developing treatment of autoimmune diseases and developing tumor immunotherapy.


Activation of SIRT3 by the NAD⁺ precursor nicotinamide riboside protects from noise-induced hearing loss.
Intense noise exposure causes hearing loss by inducing degeneration of spiral ganglia neurites that innervate cochlear hair cells. Nicotinamide adenine dinucleotide (NAD(+)) exhibits axon-protective effects in cultured neurons; however, its ability to block degeneration in vivo has been difficult to establish due to its poor cell permeability and serum instability. Here, we describe a strategy to increase cochlear NAD(+) levels in mice by administering nicotinamide riboside (NR), a recently described NAD(+) precursor. We find that administration of NR, even after noise exposure, prevents noise-induced hearing loss (NIHL) and spiral ganglia neurite degeneration. These effects are mediated by the NAD(+)-dependent mitochondrial sirtuin, SIRT3, since SIRT3-overexpressing mice are resistant to NIHL and SIRT3 deletion abrogates the protective effects of NR and expression of NAD(+) biosynthetic enzymes. These findings reveal that administration of NR activates a NAD(+)-SIRT3 pathway that reduces neurite degeneration caused by noise exposure.


Antitumor activity of sulfated hyaluronic acid fragments in pre-clinical models of bladder cancer.
Tumor cell-derived hyaluronidase HYAL-1 degrades hyaluronic acid (HA) into angiogenic fragments (AGF: 10-12 disaccharides). AGF support tumor growth and progression. Urine and tissue HAase/HYAL-1 levels are sensitive markers for high-grade bladder cancer (BCa) and its metastasis. In preclinical models of BCa, we evaluated whether o-sulfated AGF (sHA-F) inhibits HAase activity and has antitumor activity. At IC50 for HAase activity inhibition (5-20 μg/ml [0.4-1.7 μM]), sHA-F significantly inhibited proliferation, motility and invasion of HYAL-1 expressing BCa cells (253J-Lung, HT1376, UMUC-3), P<0.001. sHA-F did not affect the growth of HYAL-1 non-expressing BCa (5637, RT4, T24, TCCSUP) and normal urothelial (Urotsa, SV-HUC1) cells. sHA-F treatment induced apoptosis by death receptor pathway. sHA-F downregulated transcript and/or protein levels of HA receptors (CD44, RHAMM), p-AKT, β-catenin, pβ-Catenin(S552), Snail and Twist but increased levels of pβ-Catenin(T41/S45), pGSK-3α/β(S21/S9) and E-cadherin. sHA-F also inhibited CD44/Phosphoinositide 3-kinase (PI-3K) complex formation and PI-3K activity. AGF addition or myristoylated-AKT overexpression attenuated sHA-F effects. Contrarily, HYAL-1 expression sensitized RT4 cells to sHA-F treatment. In the 253J-L and HT1376 xenograft models, sHA-F treatment significantly inhibited tumor growth (P<0.001), plausibly by inhibiting angiogenesis and HA receptor-PI-3K/AKT signaling. This study delineates that sHA-F targets tumor-associated HA-HAase system and could be potentially useful in BCa treatment.


Albendazole treatment of HIV-1 and helminth co-infection: a randomized, double-blind, placebo-controlled trial.
Several co-infections have been shown to impact the progression of HIV-1 infection. We sought to determine if treatment of helminth co-infection in HIV-1-infected adults impacted markers of HIV-1 disease progression. To date, there have been no randomized trials to examine the effects of soil-transmitted helminth eradication on markers of HIV-1 progression. A randomized, double-blind, placebo-controlled trial of albendazole (400 mg daily for 3 days) in antiretroviral-naive HIV-1-infected adults (CD4 cell count >200 cells/microl) with soil-transmitted helminth infection was conducted at 10 sites in Kenya (ClinicalTrials.gov NCT00130910). CD4 and plasma HIV-1 RNA levels at 12 weeks following randomization were compared in the trial arms using linear regression, adjusting for baseline values. Of 1551 HIV-1-infected individuals screened for helminth infection, 299 were helminth infected. Two hundred and thirty-four adults were enrolled and underwent randomization and 208 individuals were included in intent-to-treat analyses. Mean CD4 cell count was 557 cells/microl and mean plasma viral load was 4.75 log10 copies/ml at enrollment. Albendazole therapy resulted in significantly higher CD4 cell counts among individuals with Ascaris lumbricoides infection after 12 weeks of follow-up (+109 cells/microl; 95% confidence interval +38.9 to +179.0, P = 0.003) and a trend for 0.54 log10 lower HIV-1 RNA levels (P = 0.09). These effects were not seen with treatment of other species of soil-transmitted helminths. Treatment of A. lumbricoides with albendazole in HIV-1-coinfected adults resulted in significantly increased CD4 cell counts during 3-month follow-up. Given the high prevalence of A. lumbricoides infection worldwide, deworming may be an important potential strategy to delay HIV-1 progression.


Novel medicinal mushroom blend suppresses growth and invasiveness of human breast cancer cells.
Mushrooms are an integral part of Traditional Chinese Medicine (TCM), and have been used for millennia to prevent or treat a variety of diseases. Currently mushrooms or their extracts are used globally in the form of dietary supplements. In the present study we have evaluated the anticancer effects of the dietary supplement, MycoPhyto® Complex (MC), a novel medicinal mushroom blend which consists of a blend of mushroom mycelia from the species Agaricus blazei, Cordyceps sinensis, Coriolus versicolor, Ganoderma lucidum, Grifola frondosa and Polyporus umbellatus, and β-1,3-glucan isolated from the yeast, Saccharomyces cerevisiae. Here, we show that MC demonstrates cytostatic effects through the inhibition of cell proliferation and cell cycle arrest at the G2/M phase of highly invasive human breast cancer cells MDA-MB-231. DNA-microarray analysis revealed that MC inhibits expression of cell cycle regulatory genes (ANAPC2, ANAPC2, BIRC5, Cyclin B1, Cyclin H, CDC20, CDK2, CKS1B, Cullin 1, E2F1, KPNA2, PKMYT1 and TFDP1). Moreover, MC also suppresses the metastatic behavior of MDA-MB-231 by the inhibition of cell adhesion, cell migration and cell invasion. The potency of MC to inhibit invasiveness of breast cancer cells is linked to the suppression of secretion of the urokinase plasminogen activator (uPA) from MDA-MB-231 cells. In conclusion, the MC dietary supplement could have potential therapeutic value in the treatment of invasive human breast cancer.


A transition-metal-free fast track to flavones and 3-arylcoumarins.
A highly regioselective and transition-metal free one-pot arylation of chromenones with arylboronic acids has been achieved employing K2S2O8. The procedure consists of a sequence of some reactions including an arylation/decarboxylation cascade and proceeds well in aqueous media to afford biologically interesting flavones and 3-arylcoumarins. This method exhibited excellent selectivity and functional group tolerance under mild conditions. The reaction also showed perfect efficacy for the preparation of styryl coumarins.


A phase I study of panobinostat in children with relapsed and refractory hematologic malignancies.
Background: Panobinostat demonstrates activity against pediatric cancers in vitro. A phase I trial in children with refractory hematologic malignancies was conducted. Study design: The trial evaluated two schedules of oral panobinostat using 3 + 3 dose escalations in 28-day cycles. For children with leukemia, panobinostat was given once daily three days a week each week at 24, 30 and 34 mg/m2/day. For children with lymphoma, panobinostat was given once daily three days a week every other week at 16, 20 and 24 mg/m2/day. Cerebrospinal fluid (CSF) from Day 29 of the first cycle, when available, was evaluated for PK. The study was registered on clinicaltrials.gov (NCT01321346) Results: Twenty-two subjects enrolled with leukemia. Five enrolled at dose level 1, 6 at dose level 2, and 11 at dose level 3. There was one dose limiting toxicity (DLT) in the leukemia arm at dose level 3 (Grade 4 hypertriglyceridemia), but no maximum tolerated dose (MTD) was identified. No subjects required removal from protocol therapy for QTc prolongation. PK studies were available in 11 subjects with similar exposure in children as in adults. Four Day 29 CSF specimens were found to have panobinostat levels below the lower limit of quantification. Five subjects with lymphoma were enrolled and received study drug, and 4 were evaluable for DLT. A DLT was reported (Grade 3 enteritis) on the lymphoma arm. Conclusions: Panobinostat was tolerated in heavily pretreated pediatric subjects. Gastrointestinal effects were observed on this study. There were no cardiac findings. There were no responses.


Femtosecond multidimensional imaging of a molecular dissociation.
The coupled electronic and vibrational motions governing chemical processes are best viewed from the molecule's point of view-the molecular frame. Measurements made in the laboratory frame often conceal information because of the random orientations the molecule can take. We used a combination of time-resolved photoelectron spectroscopy, multidimensional coincidence imaging spectroscopy, and ab initio computation to trace a complete reactant-to-product pathway-the photodissociation of the nitric oxide dimer-from the molecule's point of view, on the femtosecond time scale. This method revealed an elusive photochemical process involving intermediate electronic configurations.


[Displays of individually-typological features of animals and the person at a choice of strategy of goal-direction behavior].
In work the hypothesis according to which different forms of goal-directed behavior develop depending on the basis of the undervaluation/supervaluation of reinforcement by brain abilities at the conditions of its achievement uncertainty. From these positions such opposite biological characteristics of the subject, as impulsiveness/self-control, care/propensity to risk on which basis there are individually typological features in behavior of the person and animals are considered. In the article, our experimental data on animals and the persons by behavioral techniques and results of last years on research of neural networks of animal cortical and subcortical brain structures depending on the strategy in choice behavior are also analyzed.


Bilateral hypoplasia of the soft palate in a foal.
Bilateral hypoplasia of the soft palate and aspiration pneumonia occurred in a Standardbred foal. The filly was presented with a history of illthrift, dyspnoea, coughing and bilateral nasal discharge. Abnormal sounds (crackels and wheezes) were auscultated over all lung fields and the cervical trachea. Endoscopy revealed a shortened soft palate with a uvula-like mass protruding from the free border into the nasopharynx. Mucopurulent material was present in the trachea. Samples obtained by tracheal wash were submitted for cytology, culture and sensitivity testing. Results indicated a septic inflammatory process. On lateral radiographs of the thorax there were patchy areas of consolidation and air bronchograms. The foal was euthanased. Necropsy confirmed the presence of a palatal defect and aspiration pneumonia of moderate severity. No other congenital abnormalities were present.


Stereo using monocular cues within the tensor voting framework.
We address the fundamental problem of matching in two static images. The remaining challenges are related to occlusion and lack of texture. Our approach addresses these difficulties within a perceptual organization framework, considering both binocular and monocular cues. Initially, matching candidates for all pixels are generated by a combination of matching techniques. The matching candidates are then embedded in disparity space, where perceptual organization takes place in 3D neighborhoods and, thus, does not suffer from problems associated with scanline or image neighborhoods. The assumption is that correct matches produce salient, coherent surfaces, while wrong ones do not. Matching candidates that are consistent with the surfaces are kept and grouped into smooth layers. Thus, we achieve surface segmentation based on geometric and not photometric properties. Surface overextensions, which are due to occlusion, can be corrected by removing matches whose projections are not consistent in color with their neighbors of the same surface in both images. Finally, the projections of the refined surfaces on both images are used to obtain disparity hypotheses for unmatched pixels. The final disparities are selected after a second tensor voting stage, during which information is propagated from more reliable pixels to less reliable ones. We present results on widely used benchmark stereo pairs.


Active quinine-based films able to release antimicrobial compounds via melt quaternization at low temperature.
The fabrication of antibacterial films based on renewable materials (e.g., chitosan) has attracted significant interest in fields such as food packaging, health care and medicine. However, exploiting the antibacterial properties of cinchona alkaloids to design active nanostructured films able to release quinine-based antimicrobial compounds has not been considered previously. Herein, we develop two different routes to produce active quinine-based nanostructured cross-linked films by exploiting the multiple reactive sites of quinine and, specifically, both the nitrogen atom and the vinyl group of the quinuclidine portion of the molecule, as well as their corresponding orthogonal quaternization and thiol-ene coupling reactions. The first synthetic strategy produces stiff and brittle nanostructured quinine-based films of limited utility for practical applications. Conversely, the second approach produces active, flexible and nanostructured quinine-based films (Tg = -14 °C, Young's modulus = 1.3 GPa), which are able to release antimicrobial compounds against E. coli that, remarkably, are noncytotoxic against mouse macrophage and human dermal fibroblast cells. These kinds of active cinchona alkaloid-based coatings are easy to prepare by means of simple, solvent-free, melt quaternization/spreading procedures at a relatively low temperature (120 °C), making this second approach one of the most facile reported procedures to date to produce active nanostructured bio-based films.


Specific binding of tryptophan transfer RNA to avian myeloblastosis virus RNA-dependent DNA polymerase (reverse transcriptase).
The ability of tryptophan tRNA (tRNATrp) to initiate reverse transcription of the 70S RNA of avian RNA tumor viruses suggested that the reverse transcriptase (RNA-dependent DNA polymerase; deoxynucleosidetriphosphate: DNA deoxynucleotidyltransferase; EC 220.127.116.11) might have a specific binding site for the tRNA. A complex of tRNATrp and the avian myeloblastosis virus reverse transcriptase has been demonstrated using chromatography on Sephadex G-100 columns. Of all the chicken tRNAs, only tRNATrp and a tRNA4Met bind to the enzyme with high enough affinity to be selected from a mixture of the chicken cell tRNAs. The ability of tRNATrp to change the sedimentation rate of the enzyme indicates that tRNATrp is not binding to a contaminant in the enzyme preparation. Treatment of the enzyme with monospecific antibody to reverse transcriptase prevented binding of tRNA as well as inhibited the DNA polymerase activity of the enzyme. The ability of reverse transcriptase to utilize tRNATrp aa a primer for DNA synthesis, therefore, appears to involve a highly specific site on the enzyme.


Utility of 18F-FDG PET/CT uptake patterns in Waldeyer's ring for differentiating benign from malignant lesions in lateral pharyngeal recess of nasopharynx.
Focally increased (18)F-FDG uptake in the lateral pharyngeal recess (LPR) of the nasopharynx due to a benign or malignant lesion is not an uncommon finding on PET images. The aim of this study was to evaluate whether, on PET/CT images, (18)F-FDG uptake occurs with characteristic patterns and intensities in various regions of Waldeyer's ring that can improve our ability to differentiate benign from malignant lesions. Data generated from the (18)F-FDG PET/CT images of 1,628 subjects in our cancer-screening program were analyzed. Increased uptake in the LPR was observed in 80 subjects (4.9%) presenting with benign lesions, including 53 subjects without and 27 subjects with symptoms of upper airway discomfort. In addition, 30 healthy controls and 21 patients with newly diagnosed nasopharyngeal carcinoma were recruited for this study. Visual uptake, measurements of the lesions' standardized uptake value (SUV), and any abnormalities on PET/CT were evaluated. The receiver-operating-characteristic curve and area under the curve were applied to evaluate the discriminating power. Increased (18)F-FDG uptake (SUV, mean +/- SD) was found in the LPR, with a statistically significant (P < 0.001) difference between benign lesions (3.0 +/- 1.16) and malignant lesions (7.03 +/- 3.83). However, associated increased uptake exclusively in the palatine tonsil, lingual tonsil, and submandibular gland was found in both asymptomatic and symptomatic subjects. The ratio of LPR uptake to palatine tonsil uptake (N/P ratio) in benign lesions (0.81 +/- 0.37) was significantly (P < 0.001) lower than that in malignant lesions (2.30 +/- 1.62). Higher incidences of asymmetric (18)F-FDG LPR uptake, cervical lymph node uptake, and asymmetric wall thickening of the LPR on CT were observed in patients with nasopharyngeal carcinoma. When an SUV of less than 3.9 and an N/P ratio of less than 1.5 were used as cutoff points in subjects showing the combination of symmetric uptake in the LPR and normal or symmetric wall thickening, and detectable lymph node uptake, the area under the curve for benign lesions on PET/CT was 0.932 +/- 0.042 (95% confidence interval, 0.86-0.98), with a sensitivity of 90.4% and a specificity of 93.8%. The intensity and patterns of (18)F-FDG uptake in various regions of Waldeyer's ring along with CT scan findings provide a feasible modality to differentiate benign from malignant nasopharyngeal lesions.


Intraspecific Variability within Globodera tabacum solanacearum Using Random Amplified Polymorphic DNA.
Random amplified polymorphic DNA (RAPDs) were used to investigate the intraspecific variability among 19 geographic isolates of Globodera tabacum solanacearum from eight counties in Virginia and one county in North Carolina. Globodera tabacum tabacum, G. t. virginiae, and the Mexican cyst nematode (MCN) were included as outgroups. Six primers were used and 119 amplification products were observed. Each primer yielded reproducible differences in fragment patterns that differentiated the isolates and species. Hierarchical cluster analysis was performed to illustrate the relatedness among isolates and species. The average Jaccard's similarity index among isolates of G. t. solanacearum was 74%, possibly representing greater variation than that reported in the literature across different pathotypes of the potato cyst nematode, Globodera pallida, in studies where RAPD were also employed. The RAPD markers described here may be useful for the development of specific primers or probes that could improve the identification of TCN populations. Such improvements in the characterization of TCN genotypes would facilitate the effective deployment of existing and future resistant cultivars to control these economically important pests.


New strategies in acute myelogenous leukemia: leukemogenesis and personalized medicine.
Recent advances in molecular technology have unraveled the complexity of leukemogenesis and provided the opportunity to design more personalized and pathophysiology-targeted therapeutic strategies. Despite the use of intensive chemotherapy, relapse remains the most common cause for therapeutic failure in acute myelogenous leukemia (AML). The interactions between leukemia stem cells (LSC) and marrow microenvironment appear to be critical in promoting therapeutic resistance through progressive acquisition of genetic and epigenetic changes within leukemia cells and immune evasion, resulting in leukemia cell survival. With advances in genomic-sequencing efforts, epigenetic and phenotypic characterization, personalized therapeutic strategies aimed at critical leukemia survival mechanisms may be feasible in the near future. Here, we review select novel approaches to therapy of AML such as targeting LSC, altering leukemia/marrow microenvironment interactions, inhibiting DNA repair or cell-cycle checkpoints, and augmenting immune-based antileukemia activity.


Anesthetic Management of an Asian Pediatric Patient With Rubinstein-Taybi Syndrome for Dental Surgery.
Rubinstein-Taybi syndrome (RTS) is a rare genetic disorder that is associated with dysmorphism, moderate to severe intellectual disability and abnormalities involving multiple organ systems. For anesthetists, these patients pose unique challenges in the administration of anesthesia and airway management. We describe the anesthetic conduct of a pediatric patient with RTS coming for dental surgery as a day surgery case and will discuss the anesthetic considerations for such patients.


Development of asthmatic inflammation in mice following early-life exposure to ambient environmental particulates and chronic allergen challenge.
Childhood exposure to environmental particulates increases the risk of development of asthma. The underlying mechanisms might include oxidant injury to airway epithelial cells (AEC). We investigated the ability of ambient environmental particulates to contribute to sensitization via the airways, and thus to the pathogenesis of childhood asthma. To do so, we devised a novel model in which weanling BALB/c mice were exposed to both ambient particulate pollutants and ovalbumin for sensitization via the respiratory tract, followed by chronic inhalational challenge with a low mass concentration of the antigen. We also examined whether these particulates caused oxidant injury and activation of AEC in vitro. Furthermore, we assessed the potential benefit of minimizing oxidative stress to AEC through the period of sensitization and challenge by dietary intervention. We found that characteristic features of asthmatic inflammation developed only in animals that received particulates at the same time as respiratory sensitization, and were then chronically challenged with allergen. However, these animals did not develop airway hyper-responsiveness. Ambient particulates induced epithelial injury in vitro, with evidence of oxidative stress and production of both pro-inflammatory cytokines and Th2-promoting cytokines such as IL-33. Treatment of AEC with an antioxidant in vitro inhibited the pro-inflammatory cytokine response to these particulates. Ambient particulates also induced pro-inflammatory cytokine expression following administration to weanling mice. However, early-life dietary supplementation with antioxidants did not prevent the development of an asthmatic inflammatory response in animals that were exposed to particulates, sensitized and challenged. We conclude that injury to airway epithelium by ambient environmental particulates in early life is capable of promoting the development of an asthmatic inflammatory response in sensitized and antigen-challenged mice. These findings are likely to be relevant to the induction of childhood asthma.


Tumor-selective, futile redox cycle-induced bystander effects elicited by NQO1 bioactivatable radiosensitizing drugs in triple-negative breast cancers.
β-Lapachone (β-lap), a novel radiosensitizer with potent antitumor efficacy alone, selectively kills solid cancers that over-express quinone oxidoreductase 1 (NQO1). Since breast or other solid cancers have heterogeneous NQO1 expression, therapies that reduce the resistance (e.g., NQO1(low)) of tumor cells will have significant clinical advantages. We tested whether NQO1-proficient (NQO1(+)) cells generated sufficient hydrogen peroxide (H2O2) after β-lap treatment to elicit bystander effects, DNA damage, and cell death in neighboring NQO1(low) cells. β-Lap showed NQO1-dependent efficacy against two triple-negative breast cancer (TNBC) xenografts. NQO1 expression variations in human breast cancer patient samples were noted, where ~60% cancers over-expressed NQO1, with little or no expression in associated normal tissue. Differential DNA damage and lethality were noted in NQO1(+) versus NQO1-deficient (NQO1(-)) TNBC cells and xenografts after β-lap treatment. β-Lap-treated NQO1(+) cells died by programmed necrosis, whereas co-cultured NQO1(-) TNBC cells exhibited DNA damage and caspase-dependent apoptosis. NQO1 inhibition (dicoumarol) or H2O2 scavenging (catalase [CAT]) blocked all responses. Only NQO1(-) cells neighboring NQO1(+) TNBC cells responded to β-lap in vitro, and bystander effects correlated well with H2O2 diffusion. Bystander effects in NQO1(-) cells in vivo within mixed 50:50 co-cultured xenografts were dramatic and depended on NQO1(+) cells. However, normal human cells in vitro or in vivo did not show bystander effects, due to elevated endogenous CAT levels. Innovation and Conclusions: NQO1-dependent bystander effects elicited by NQO1 bioactivatable drugs (β-lap or deoxynyboquinone [DNQ]) likely contribute to their efficacies, killing NQO1(+) solid cancer cells and eliminating surrounding heterogeneous NQO1(low) cancer cells. Normal cells/tissue are protected by low NQO1:CAT ratios.


Quantifying the multi-scale response of avifauna to prescribed fire experiments in the southwest United States.
Landscape-scale disturbance events, including ecological restoration and fuel reduction activities, can modify habitat and affect relationships between species and their environment. To reduce the risk of uncharacteristic stand-replacing fires in the southwestern United States, land managers are implementing restoration and fuels treatments (e.g., mechanical thinning, prescribed fire) in progressively larger stands of dry, lower elevation ponderosa pine (Pinus ponderosa) forest. We used a Before-After/Control-Impact experimental design to quantify the multi-scale response of avifauna to large (approximately 250-400 ha) prescribed fire treatments on four sites in Arizona and New Mexico dominated by ponderosa pine. Using distance sampling and an information-theoretic approach, we estimated changes in density for 14 bird species detected before (May-June 2002-2003) and after (May-June 2004-2005) prescribed fire treatments. We observed few site-level differences in pre- and posttreatment density, and no species responded strongly to treatment on all four sites. Point-level spatial models of individual species response to treatment, habitat variables, and fire severity revealed ecological relationships that were more easily interpreted. At this scale, pretreatment forest structure and patch characteristics were important predictors of posttreatment differences in bird species density. Five species (Pygmy Nuthatch [Sitta pygmaea], Western Bluebird [Sialia mexicana], Steller's Jay [Cyanocitta stelleri], American Robin [Turdus migratorius], and Hairy Woodpecker [Picoides villosus]) exhibited a strong treatment response, and two of these species (American Robin and Hairy Woodpecker) could be associated with meaningful fire severity response functions. The avifaunal response patterns that we observed were not always consistent with those reported by more common studies of wildland fire events. Our results suggest that, in the short-term, the distribution and abundance of common members of the breeding bird community in Southwestern ponderosa pine forests appear to be tolerant of low- to moderate-intensity prescribed fire treatments at multiple spatial scales and across multiple geographic locations.


A Systematic Review of Ebola Treatment Trials to Assess the Extent to Which They Adhere to Ethical Guidelines.
Objective: To determine to what extent each trial met criteria specified in three research frameworks for ethical trial conduct. Design: Systematic review and narrative analysis. Data sources: MEDBASE and EMBASE databases were searched using a specific search strategy. The Cochrane database for systematic reviews, the PROSPERO database and trial registries were examined. A grey literature search and citation search were also carried out. Eligibility criteria for selecting studies: Studies were included where the intervention was being used to treat Ebola in human subjects regardless of study design, comparator or outcome measured. Studies were eligible if they had taken place after the 21st March 2014. Unpublished as well as published studies were included. Included studies: Sixteen studies were included in the data synthesis. Data was extracted on study characteristics as well as any information relating to ten ethical areas of interest specified in the three research frameworks for ethical trial conduct and an additional criterion of whether the study received ethics approval from a research ethics committee. Synthesis of results: Eight studies were judged to fully comply with all eleven criteria. The other eight studies all had at least one criteria where there was not enough information available to draw any conclusions. In two studies there were ethical concerns regarding the information provided in relation to at least one ethical criteria. Description of the effect: One study did not receive ethical approval as the authors argued that treating approximately one hundred patients consecutively for compassionate reasons did not constitute a clinical trial. Furthermore, after the patients were treated, physicians in Sierra Leone did not release reports of treatment results and so study conclusions had to be made based on unpublished observations. In another study the risk-benefit ratio of the trial drug does not appear to be favourable and the pre-trial evidence base for its effectiveness against Ebola is speculative. Some limited and appropriate deviation from standard research expectations in disaster situations is increasingly accepted. However, this is not an excuse for poor ethics oversight and international regulations are in place which should not be ignored. New guidelines are needed that better define the boundaries between using medicines for compassionate use and conducting a clinical trial. Greater support should be offered for local research ethics committees in affected areas so that they can provide robust ethical review. Further systematic reviews should be carried out in epidemics of any novel infectious diseases to assess if comparable findings arise.


Managing the increasing shortage of acute care hospital beds in Israel.
Israel's healthcare system has been facing increasing hospital bed shortage over the last few decades. Community-based services and shortening length of stay have helped to ease this problem, but hospitals continue to suffer from serious overload and saturation. The objective of this study is to present hospitalization trends in Israel's internal medicine departments. The data is based on the National Hospital Discharges database (NHDR) in the Israeli Health Ministry, pertaining to hospitalizations in all internal medicine departments nationwide between 2000 and 2012. Total yearly hospitalization days, representing healthcare burden, had increased by 4.2% during the study period, driven mainly by the most advanced age groups. The rate of total hospitalization days per 100,000 people for all the age groups has decreased by 17.6%, but the oldest patient group had a modest reduction in comparison (7.5%). The parameter of age correlated with length of stay and readmission rates, and neither decreased during the surveyed years. These results demonstrated that the healthcare burden on acute internal medicine services has been reduced mostly for middle-aged populations but only modestly for elderly populations. The length of hospital stay and the readmission rates have reached and maintained a plateau in recent years, regardless of age. The findings of this study call for planning specific to elderly populations in light of changing demographics. Possible directions may include renewed emphasis on internal medicine and geriatric medicine, and efforts to shorten hospitalization time by extended utilization of multidisciplinary primary care.


Astemizole arrests the proliferation of cancer cells by disrupting the EZH2-EED interaction of polycomb repressive complex 2.
Polycomb Repressive Complex 2 (PRC2) modulates the chromatin structure and transcriptional repression by trimethylation lysine 27 of histone H3 (H3K27me3), a process that necessitates the protein-protein interaction (PPI) between the catalytic subunit EZH2 and EED. Deregulated PRC2 is intimately involved in tumorigenesis and progression, making it an invaluable target for epigenetic cancer therapy. However, until now, there have been no reported small molecule compounds targeting the EZH2-EED interactions. In the present study, we identified astemizole, an FDA-approved drug, as a small molecule inhibitor of the EZH2-EED interaction of PRC2. The disruption of the EZH2-EED interaction by astemizole destabilizes the PRC2 complex and inhibits its methyltransferase activity in cancer cells. Multiple lines of evidence have demonstrated that astemizole arrests the proliferation of PRC2-driven lymphomas primarily by disabling the PRC2 complex. Our findings demonstrate the chemical tractability of the difficult PPI target by a small molecule compound, highlighting the therapeutic promise for PRC2-driven human cancers via targeted destruction of the EZH2-EED complex.


Challenges towards Economic Fuel Generation from Renewable Electricity: The Need for Efficient Electro-Catalysis.
Utilizing renewable sources of energy is very attractive to provide the growing population on earth in the future but demands the development of efficient storage to mitigate their intermittent nature. Chemical storage, with energy stored in the bonds of chemical compounds such as hydrogen or carbon-containing molecules, is promising as these energy vectors can be reserved and transported easily. In this review, we aim to present the advantages and drawbacks of the main water electrolysis technologies available today: alkaline and PEM electrolysis. The choice of electrode materials for utilization in very basic and very acid conditions is discussed, with specific focus on anodes for the oxygen evolution reaction, considered as the most demanding and energy consuming reaction in an electrolyzer. State-of-the-art performance of materials academically developed for two alternative technologies: electrolysis in neutral or seawater, and the direct electrochemical conversion from solar to hydrogen are also introduced.


Cytokine changes after surgical treatment of obstructive sleep apnoea syndrome.
Obstructive sleep apnoea syndrome (OSAS) is associated with inflammatory processes and elevated plasma cytokines. This study assesses the effect of surgery in cytokine levels of OSAS patients. A total of 24 male patients with mild to moderate OSAS, confirmed with polysomnography underwent septoplasty and uvulo-palato-pharyngoplasty in a period of a year. Control group consisted of 12 overweighted subjects and 15 obese subjects. Peripheral venous blood was collected from each patient 1 week before surgical treatment and 6 months postoperatively. Spontaneous production of tumour necrosis factor (TNF-a) by monocytes and serum levels of IL-1beta and IL-6 were investigated. Control subjects were also examined for the same pro-inflammatory cytokines. Production of TNF-a and IL-6 were significantly elevated in OSAS patients and obese controls compared with overweighted control subjects (p < 0.05). Serum levels of IL-1beta did not differ among the study groups. Preoperative cytokine values were significantly correlated with the preoperative body mass index (BMI) and the apnoea/hypopnoea index (AHI) in OSAS patients. Surgery resulted a significant reduction in the TNF-a and IL-6 values of the study group. Decrease in cytokine level was strongly correlated with the AHI decrease. The postoperative relative percentage change of IL-6 values was significantly higher than this of TNF-a (p < 0.001). Surgical management of mild to moderate OSAS leads to a significant reduction in TNF-a and IL-6 values. Our data indicate that AHI is an independent risk factor of systemic inflammation; however it affects cytokines to a lesser degree compared with the BMI.


Suicidal thoughts and attempts in First Nations communities: links to parental Indian residential school attendance across development.
The Indian residential school (IRS) system in Canada ran for over a century until the last school closed in 1996. Conditions in the IRSs resulted in generations of Indigenous children being exposed to chronic childhood adversity. The current investigation used data from the 2008-2010 First Nations Regional Health Survey to explore whether parental IRS attendance was associated with suicidal thoughts and attempts in childhood, adolescence and in adulthood among a representative sample of First Nations peoples living on-reserve across Canada. Analyses of the adult sample in Study 1 (unweighted n=7716; weighted n=186,830) revealed that having a parent who attended IRS was linked with increased risk for suicidal thoughts and attempts in adolescence and adulthood. Although females were negatively affected by having a parent who attended IRS, the link with suicidal ideation in adulthood was greater for males. Analyses of the youth sample in Study 2 (unweighted n=2883; weighted n=30,190) confirmed that parental IRS attendance was associated with an increased risk for suicidal ideation and attempts. In contrast to the adult sample, parental IRS attendance had a significantly greater relation with suicidal ideation among female youth. A significant interaction also emerged between parental IRS attendance and age in the youth sample, with the influence of parental attendance being particularly strong among youth ages 12-14, compared with those 15-17 years. These results underscore the need for culturally relevant early interventions for the large proportions of Indigenous children and youth intergenerationally affected by IRSs and other collective traumas.


Telemedicine: current status in developed and developing countries.
Many developed countries, including the United States, have made it a priority to incorporate telemedicine into their healthcare systems. Worldwide, this concept has been adopted by countries in effort to provide better healthcare for those in rural areas where hospitals may be at a distance and specialists may be even farther. Previous studies and reports have shown that the use of telemedicine, especially tele-dermatology, has proven to be an inexpensive method for providing care to those whose countries face financial, social, and environmental barriers to adequate healthcare. To assess the current status of, and address the potential for, improving healthcare by using telemedicine with emphasis on tele-dermatology in developed and developing countries. Current literature on telemedicine/tele-dermatology was reviewed and its efficiency critiqued in an attempt to improve dermatological care in developing areas. The U.S., while significantly incorporating telemedicine on a national basis, faces various issues from state to state regarding reimbursement and other legality concerns. Although current efforts using telemedicine have demonstrated positive effects in countries in need, they have not substantially reduced or compensated for a fundamental lack of healthcare. Countries with inadequate healthcare must incorporate telemedicine into their healthcare system through volunteer efforts of doctors in countries worldwide.


Modeling the role of fomites in a norovirus outbreak.
Norovirus accounts for a large portion of the gastroenteritis disease burden, and outbreaks have occurred in a wide variety of environments. Understanding the role of fomites in norovirus transmission will inform behavioral interventions, such as hand washing and surface disinfection. The purpose of this study was to estimate the contribution of fomite-mediated exposures to infection and illness risks in outbreaks. A simulation model in discrete time that accounted for hand-to-porous surfaces, hand-to-nonporous surfaces, hand-to-mouth, -eyes, -nose, and hand washing events was used to predict 17 hr of simulated human behavior. Norovirus concentrations originated from monitoring contamination levels on surfaces during an outbreak on houseboats. To predict infection risk, two dose-response models (fractional Poisson and 2F1 hypergeometric) were used to capture a range of infection risks. A triangular distribution describing the conditional probability of illness given an infection was multiplied by modeled infection risks to estimate illness risks. Infection risks ranged from 70.22% to 72.20% and illness risks ranged from 21.29% to 70.36%. A sensitivity analysis revealed that the number of hand-to-mouth contacts and the number of hand washing events had strong relationships with model-predicted doses. Predicted illness risks overlapped with leisure setting and environmental attack rates reported in the literature. In the outbreak associated with the viral concentrations used in this study, attack rates ranged from 50% to 86%. This model suggests that fomites may have accounted for 25% to 82% of illnesses in this outbreak. Fomite-mediated exposures may contribute to a large portion of total attack rates in outbreaks involving multiple transmission modes. The findings of this study reinforce the importance of frequent fomite cleaning and hand washing, especially when ill persons are present.


Concentration dependence of halide fluxes and selectivity of the anion pathway in toad skin.
The isolated toad (Bufo bufo) skin was mounted under voltage-clamp conditions in a chamber shown to cause no significant edge damage. The serosal side of the skin was bathed with NaCl-Ringer's, and the passive voltage-sensitive anion conductance studied in its fully voltage activated state, V = -80 mV (apical bath negative). The active sodium currents were eliminated by replacing external Na+ with K+. With [Cl-]o varying between 1.45 mM and 110 mM (gluconate substitution) and [I-]o = 3 mM, the total clamping current (y) and the sum of halide currents (x), estimated from flux measurements, were related by y = 1.0x-3.7 microA cm-2 (r2 = 0.98, n = 50 preparations). The increase in [Cl-]o produced a sigmoidal increase in Cl- influx and clamping current, with the rate coefficient for the influx increasing with [Cl-]o for 1.45 less than [Cl-]o less than 60 mM, but decreasing slightly again as [Cl-]o was further raised to 110 mM. A similar relationship was obtained between the rate coefficient for the Br- influx and [Br-]o, and the I- influx and [Cl-]o, indicating that these three ions are transported by a pathway that is activated by Cl-o and Br-o. The rate coefficients for the influxes ranked as follows, I-:Cl-:Br- = 0.7:1:1.3. The I-/Cl- selectivity was shown to be independent of the degree of Cl-o activation of the anion pathway, and identical with the I-/Cl- selectivity of a furosemide-sensitive, conductive pathway. With [Cl-]o, [Br-]o, or [I-]o = 110 mM, the currents ranked as follows, Cl-:Br-:I- = 1:0.68:0.06, indicating that Cl-, to a lesser extent Br-, and I-, poorly activate the conductive anion pathway. External I- was a potent inhibitor of the Cl-o activation of the Cl- conductance. The unidirectional I- fluxes ([I-]o = [I-]i = 3 mM, [Cl-]o = [Cl-]i = 110 mM) revealed passive transport for V less than -50 mV, active transport for V = o mV, and exchange diffusion for V = 50 mV, confirming our previous finding that depending on the transepithelial potential, the toad skin exhibits three modes of anion transport. A model that shares some properties with that of the anion transport system of the red cell membrane accounts for our findings, and for an inwardly directed active Cl- flux in terms of Cl-/HCO3- exchange.


ARNetMiT R Package: association rules based gene co-expression networks of miRNA targets.
miRNAs are key regulators that bind to target genes to suppress their gene expression level. The relations between miRNA-target genes enable users to derive co-expressed genes that may be involved in similar biological processes and functions in cells. We hypothesize that target genes of miRNAs are co-expressed, when they are regulated by multiple miRNAs. With the usage of these co-expressed genes, we can theoretically construct co-expression networks (GCNs) related to 152 diseases. In this study, we introduce ARNetMiT that utilize a hash based association rule algorithm in a novel way to infer the GCNs on miRNA-target genes data. We also present R package of ARNetMiT, which infers and visualizes GCNs of diseases that are selected by users. Our approach assumes miRNAs as transactions and target genes as their items. Support and confidence values are used to prune association rules on miRNA-target genes data to construct support based GCNs (sGCNs) along with support and confidence based GCNs (scGCNs). We use overlap analysis and the topological features for the performance analysis of GCNs. We also infer GCNs with popular GNI algorithms for comparison with the GCNs of ARNetMiT. Overlap analysis results show that ARNetMiT outperforms the compared GNI algorithms. We see that using high confidence values in scGCNs increase the ratio of the overlapped gene-gene interactions between the compared methods. According to the evaluation of the topological features of ARNetMiT based GCNs, the degrees of nodes have power-law distribution. The hub genes discovered by ARNetMiT based GCNs are consistent with the literature.


Synaptic NMDA receptor channels have a low open probability.
Realistic estimates of channel-gating parameters of synaptic receptors are essential to an understanding of synaptic transmission and modulation. However, the gating of N-methyl-D-aspartate (NMDA) channels appears to differ, depending on recording conditions; thus, it remains unclear what measurements are most relevant to synaptic receptors. To further explore this discrepancy, we examined the open probability (Po) of NMDA channels in whole-cell and outside-out patch recording from cultured hippocampal neurons. Currents were evoked by rapid application of saturating concentrations of NMDA in the presence or absence of the "irreversible" open channel blocker, MK-801 ((+)-5-methyl-10,11-dihydro-5H-dibenzo[a,d]cyclohepten-5,10-imine) . The reduction of the peak amplitude and the acceleration of the decay of the current in MK-801 were used to derive Po by fitting the current traces to a multistate kinetic model. The Po in whole cell was low (0.04), similar to that previously measured for synaptically activated NMDA channels. In contrast, ensemble average currents from outside-out patches were much more rapidly blocked in the presence of MK-801, indicative of a significantly higher Po. The Po also gradually increased with the duration of recording in both whole-cell and outside-out configurations, suggesting that channel gating is sensitive to mechanical alterations of the patch or that washout of cytoplasmic factors leads to an increase in channel open probability.(ABSTRACT TRUNCATED AT 250 WORDS)


Which potent opioid? Important criteria for selection.
Opioids remain the drugs of choice for the treatment of severe pain. In recent years several new potent opioids have become available for clinical use. These newer drugs are generally safer than the older morphine-like compounds and their differing pharmacological and pharmacokinetic properties allow the physician to choose an appropriate drug according to the clinical situation and need of an individual patient. These drugs are classified according to their activity at the opioid receptors. The opioid agonists produce their pharmacological effect by an almost exclusive action at mu-receptors. The agonist-antagonist group are kappa-receptor agonists and either competitive antagonists at the mu-receptor or weak mu-agonists. The use of the potent opioid agonists, because of their potential for causing respiratory depression, is restricted to hospitals. Fentanyl, the oldest drug of this class, is extensively used as a supplement to general anaesthesia, or in high doses as a 'complete' anaesthetic for patients undergoing cardiac surgery. Alfentanil and sufentanil are newer fentanyl derivatives. Alfentanil is unique in having a very short elimination half-life. This is a particular advantage during short operations and for day-case surgery. For longer operations alfentanil can be given as a continuous infusion to supplement nitrous oxide anaesthesia. Sufentanil is about 10 times more potent than fentanyl and is more rapidly eliminated. Initial reports suggest that it may be more effective than fentanyl as an anaesthetic supplement and that recovery may be more rapid. Both sufentanil and alfentanil are also used in cardiac anaesthesia. The newer agonist-antagonist opioids, butorphanol, nalbuphine and buprenorphine, have largely replaced pentazocine in clinical practice. Unlike pentazocine, they cause a low incidence of dysphoric side effects. Like the pure agonists, they cause respiratory depression; however, in contrast to the pure agonists this is not dose related, reaching a 'ceiling' as dose increases. The risk of dependence is also less, so that these drugs are safer for the treatment of chronic pain. Additionally, it is particularly worth noting that buprenorphine and nalbuphine cause minimal cardiovascular changes, and are safe and effective drugs for treatment of pain associated with myocardial infarction. Buprenorphine, which is effective parenterally, orally and sublingually, has a prolonged duration of action (up to 12 hours after a single dose).


Observer variation and quality control of cytodiagnosis.
The aim of quality control of a laboratory investigation is to ensure that similar results are obtained on the same material at different centres. To investigate its practicability in cytodiagnosis, the same cytological material was examined independently at six centres. Each centre supplied material from 20 cases, providing a total of 120 cases, ie, 100 cases excluding the donor centre's own material. The degree of agreement between the centres was studied using (a) the standard National Health Service cytology report terminology, (b) the centre's own terminology, and (c) the recommended recall time. The results revealed close agreement between five out of six centres in the reports obtained in relation to dysplasia and malignancy, namely, less than 3% false negative results and not more than 1.7% false positive results. The recommended recall time provided a similar order of agreement after discrepancies due to the management of inflammatory conditions had been eliminated. There was marked disagreement in the diagnosis of both presence and type of infection. The results indicate that improvement in the quality of cytological material would increase the consistency of cytodiagnosis. Cytodiagnosis itself, being an expression of opinion, does not appear to be an appropriate field for quality control.


How allosteric control of Staphylococcus aureus penicillin binding protein 2a enables methicillin resistance and physiological function.
The expression of penicillin binding protein 2a (PBP2a) is the basis for the broad clinical resistance to the β-lactam antibiotics by methicillin-resistant Staphylococcus aureus (MRSA). The high-molecular mass penicillin binding proteins of bacteria catalyze in separate domains the transglycosylase and transpeptidase activities required for the biosynthesis of the peptidoglycan polymer that comprises the bacterial cell wall. In bacteria susceptible to β-lactam antibiotics, the transpeptidase activity of their penicillin binding proteins (PBPs) is lost as a result of irreversible acylation of an active site serine by the β-lactam antibiotics. In contrast, the PBP2a of MRSA is resistant to β-lactam acylation and successfully catalyzes the DD-transpeptidation reaction necessary to complete the cell wall. The inability to contain MRSA infection with β-lactam antibiotics is a continuing public health concern. We report herein the identification of an allosteric binding domain--a remarkable 60 Å distant from the DD-transpeptidase active site--discovered by crystallographic analysis of a soluble construct of PBP2a. When this allosteric site is occupied, a multiresidue conformational change culminates in the opening of the active site to permit substrate entry. This same crystallographic analysis also reveals the identity of three allosteric ligands: muramic acid (a saccharide component of the peptidoglycan), the cell wall peptidoglycan, and ceftaroline, a recently approved anti-MRSA β-lactam antibiotic. The ability of an anti-MRSA β-lactam antibiotic to stimulate allosteric opening of the active site, thus predisposing PBP2a to inactivation by a second β-lactam molecule, opens an unprecedented realm for β-lactam antibiotic structure-based design.


Inflammation and Oxidative Stress: The Molecular Connectivity between Insulin Resistance, Obesity, and Alzheimer's Disease.
Type 2 diabetes (T2DM), Alzheimer's disease (AD), and insulin resistance are age-related conditions and increased prevalence is of public concern. Recent research has provided evidence that insulin resistance and impaired insulin signalling may be a contributory factor to the progression of diabetes, dementia, and other neurological disorders. Alzheimer's disease (AD) is the most common subtype of dementia. Reduced release (for T2DM) and decreased action of insulin are central to the development and progression of both T2DM and AD. A literature search was conducted to identify molecular commonalities between obesity, diabetes, and AD. Insulin resistance affects many tissues and organs, either through impaired insulin signalling or through aberrant changes in both glucose and lipid (cholesterol and triacylglycerol) metabolism and concentrations in the blood. Although epidemiological and biological evidence has highlighted an increased incidence of cognitive decline and AD in patients with T2DM, the common molecular basis of cell and tissue dysfunction is rapidly gaining recognition. As a cause or consequence, the chronic inflammatory response and oxidative stress associated with T2DM, amyloid-β (Aβ) protein accumulation, and mitochondrial dysfunction link T2DM and AD.


Structure and reaction mechanism of basil eugenol synthase.
Phenylpropenes, a large group of plant volatile compounds that serve in multiple roles in defense and pollinator attraction, contain a propenyl side chain. Eugenol synthase (EGS) catalyzes the reductive displacement of acetate from the propenyl side chain of the substrate coniferyl acetate to produce the allyl-phenylpropene eugenol. We report here the structure determination of EGS from basil (Ocimum basilicum) by protein x-ray crystallography. EGS is structurally related to the short-chain dehydrogenase/reductases (SDRs), and in particular, enzymes in the isoflavone-reductase-like subfamily. The structure of a ternary complex of EGS bound to the cofactor NADP(H) and a mixed competitive inhibitor EMDF ((7S,8S)-ethyl (7,8-methylene)-dihydroferulate) provides a detailed view of the binding interactions within the EGS active site and a starting point for mutagenic examination of the unusual reductive mechanism of EGS. The key interactions between EMDF and the EGS-holoenzyme include stacking of the phenyl ring of EMDF against the cofactor's nicotinamide ring and a water-mediated hydrogen-bonding interaction between the EMDF 4-hydroxy group and the side-chain amino moiety of a conserved lysine residue, Lys132. The C4 carbon of nicotinamide resides immediately adjacent to the site of hydride addition, the C7 carbon of cinnamyl acetate substrates. The inhibitor-bound EGS structure suggests a two-step reaction mechanism involving the formation of a quinone-methide prior to reduction. The formation of this intermediate is promoted by a hydrogen-bonding network that favors deprotonation of the substrate's 4-hydroxyl group and disfavors binding of the acetate moiety, akin to a push-pull catalytic mechanism. Notably, the catalytic involvement in EGS of the conserved Lys132 in preparing the phenolic substrate for quinone methide formation through the proton-relay network appears to be an adaptation of the analogous role in hydrogen bonding played by the equivalent lysine residue in other enzymes of the SDR family.


Association between the Geriatric Giants of urinary incontinence and falls in older people using data from the Leicestershire MRC Incontinence Study.
To determine whether urinary incontinence per se and different types of urinary incontinence individually are associated with an increased risk of falls in those aged 70 years and over. To investigate whether the presence of urinary symptoms, poor quality of life and physical limitations in this population with urinary incontinence is associated with falls. Study using data from the cross-sectional postal questionnaire undertaken in the Leicestershire Medical Research Council Incontinence Study. Leicestershire. A total of 5,474 people aged 70 years or more living in the community randomly selected from general practitioners' lists. Urinary incontinence and both urge and stress incontinence were positively related to falls (P < 0.0001, P < 0.001 and P = 0.007, respectively). The larger the volume of urine lost, the greater the risk of falls (P < 0.0001). Falls were associated with the presence of urinary symptoms (P = 0.01 or less), physical limitations (P = 0.001 or less) and having a poorer quality of life (P = 0.004 or less) in respondents with urinary incontinence. An association has been shown between falling and urinary leakage including the previously unreported association with stress leakage. Falling and urinary incontinence were found to be associated with physical limitations and had an impact on quality of life.


Loss of Binocular Vision in Monocularly Blind Patients Causes Selective Degeneration of the Superior Lateral Occipital Cortices.
Chronic ocular pathology, such as glaucoma and macular degeneration, is associated with neuroanatomic changes in the visual pathways. It is a challenge to determine the mechanism responsible for these changes. This could be functional deprivation or transsynaptic degeneration. Acquired monocular blindness provides a unique opportunity to establish which mechanism underlies neuroanatomic changes in ocular pathology in general, since the loss of input is well defined, and it causes selective functional deprivation due to the loss of stereopsis. Here, we assessed whether acquired monocular blindness is associated with neuroanatomic changes, and if so, where these changes are located. High-resolution T1-weighted magnetic resonance images were obtained in 15 monocularly blind patients and 18 healthy controls. We used voxel- and surface-based morphometry to compare gray and white matter volume, cortical thickness, mean curvature, and surface area between these groups. The gray matter volume in the bilateral superior lateral occipital cortices was decreased in the monocular blind patients, in the absence of volumetric differences in their early visual cortex. The volumetric decrease in the superior lateral occipital cortices is consistent with specific functional deprivation, as the superior lateral occipital cortices play an important role in depth perception. Moreover, in the absence of differences in the early visual cortex, the decrease is inconsistent with transsynaptic degeneration propagating from the degenerated retinal axons.


Assessment of total phenolic compounds and in vitro free radical scavenging potentials of water extracts of ten selected species of Zingiberaceae rhizomes use in folkloric medicine.
The use of herbal medicine and traditional healing practices for diagnosis, treatment and prevention of illness and ailment continue to have more awareness among the scientific community due to their safety and also as a source of alternatives to synthetic products. This research assessed the total phenolic compounds and in vitro total antioxidant potentials of water extracts in selected species of Zingiberaceae rhizomes use as spice, drinks and medicine. DPPH and FRAP were used to determine the antioxidant capacity, total flavonoid, phenolic acids and polyphenol contents assays to evaluate the quality of the antioxidant activity and the control was ascorbic acid. The results showed that all extracts contain significant antioxidant activity with Zingiber officinale having the highest activity in all assays. DPPH (222.30mg/TE/g DW), FRAP (98.04mg/TE/g DW), Flavonoid (38.58mg/NGN/g DW) phenolic acid (10.78mg/GAE/g DW) and polyphenols (22.84mg/GAE/g DW). Significant and positive linear correlation were found in DPPH, FRAP and total flavonoid, phenolic acids and polyphenol contents. This study reveals some phytochemicals present in Zingiberaceae species, which might be responsible for their biological activities and reason for it use in folkloric medicine in Southeast Asia.


Ischaemic heart disease: a secondary prevention trial using clofibrate. Report by a research committee of the Scottish Society of Physicians.
A trial is reported of the effects of giving clofibrate to prevent progression of pre-existing ischaemic heart disease. There were two groups randomly distributed between clofibrate (350 patients) and placebo (367 patients) regimens. The trial lasted about six years and was conducted in 19 hospitals in Scotland. The criteria of acceptance into the trial were precise and were monitored by one observer. The standards of diagnosis of events were defined and all protocols and electrocardiograms were read blind by one observer.THREE CATEGORIES OF PATIENTS WERE ADMISSIBLE TO THE TRIAL: (1) patients with one myocardial infarction (W.H.O. E.C.G. criteria) between 8 and 16 weeks before the start of the trial; (2) patients with angina of a duration of 3 to 24 months, provided their E.C.G. showed signs of myocardial ischaemia at rest or after exercise; and (3) patients with one recent myocardial infarction and pre-existing angina as defined above.There were fewer deaths in patients with angina (categories 2 and 3 above) treated with clofibrate than in those on placebo. The mortality in the former group was reduced by 62%, and this is a statistically significant difference. Clofibrate did not have any statistically significant effect in reducing the rate of non-fatal infarction in patients with angina or in those with myocardial infarction and pre-existing angina, though a beneficial trend was evident when both subgroups were combined (a 44% reduction compared with the placebo group). There was a significant reduction in all events (fatal and non-fatal) in patients with angina ("all anginas") in the clofibrate-treated group; the rate was reduced by 53%.Clofibrate did not alter the overall mortality or morbidity rates in patients admitted to the trial with recent myocardial infarction without preceding angina of more than three months' duration. In one subgroup there was a statistically significant adverse effect in the clofibrate-treated group. The lack of any overall effect in patients with myocardial infarction might be related to the unexpectedly low mortality rate (2.97%) in the placebo group; it is usually in the region of 4-9% per annum after first myocardial infarction.In patients categorized as "all anginas" there was significant reduction in events whether the initial serum cholesterol level was high (greater than 260 mg/100 ml) or normal. Clofibrate seemed to have a small but not significant beneficial effect in patients with myocardial infarction with initially high serum cholesterol levels, but was of no value in those with initially normal serum cholesterol levels. There was no significant relationship between the response or lack of response of serum cholesterol to clofibrate and the incidence of events either in patients with angina or in those with infarction.The main conclusion of this trial is that clofibrate had a beneficial effect in reducing mortality and, to a lesser extent, morbidity in patients who presented with angina ("all anginas"). This effect was independent of initial serum cholesterol levels or the extent to which serum cholesterol was lowered. The drug had no significant overall effect on prognosis in patients with myocardial infarction alone.


Effect of time to resumption of chemotherapy after definitive surgery on prognosis for non-metastatic osteosarcoma.
The dose intensity of chemotherapy has been described as affecting the outcome of the treatment of a number of different types of tumors. A delay in the resumption of chemotherapy after definitive surgery for the treatment of osteosarcoma can decrease the overall dose intensity. The goal of this study was to assess the prognostic significance of the time to resumption of chemotherapy after definitive surgery in patients with localized osteosarcoma in an extremity. The relationships of the time between definitive surgery and resumption of chemotherapy with death and adverse events in 703 patients with a localized resectable osteosarcoma in an extremity (556 treated in the Children's Oncology Group [COG] Study [INT 0133] and 147 treated at five tertiary care cancer centers) were assessed with use of Cox proportional hazards models. The twenty-fifth, fiftieth, and seventy-fifth percentiles of time from definitive surgery to resumption of chemotherapy were twelve, sixteen, and twenty-one days, respectively. Overall survival was poorer for patients who had had a delay of greater than twenty-one days before the resumption of chemotherapy compared with those who had had a shorter delay (hazard ratio = 1.57 [95% confidence interval = 1.04 to 2.36]; p = 0.03). Of seventy-one COG-study patients with postoperative complications, 32% (twenty-three) had a delay of more than twenty-one days before resumption of chemotherapy, but 20% (eighty-nine) of 444 patients with no complications had a similar delay. In this retrospective analysis, increased time from the definitive surgery to the resumption of chemotherapy was found to be associated with an increased risk of death of patients with localized osteosarcoma in an extremity. Within the limitations of a retrospective study, the data indicate that it is best to resume chemotherapy within twenty-one days after definitive surgery. Surgeons, oncologists, patients, and those responsible for scheduling need to work together to ensure timely resumption of chemotherapy after surgery.


Marketing Vegetables in Elementary School Cafeterias to Increase Uptake.
Children do not eat enough servings of vegetables, underscoring the need for effective interventions encouraging this behavior. The purpose of this research was to measure the impact that daily exposure to branded vegetable characters has on vegetable selection among boys and girls in elementary schools. In a large urban school district, 10 elementary schools agreed to participate in the study. They were randomly assigned to a control condition or 1 of 3 treatment conditions: (1) a vinyl banner displaying vegetable characters that was fastened around the base of the salad bar; (2) short television segments with health education delivered by vegetable characters; or (3) a combination of the vinyl banner and television segments. We collected 22 206 student-day observations over a 6-week period by tallying the number of boys and girls taking vegetables from the school's salad bar. Results show that 90.5% (from 12.6% to 24.0%; P = .04) more students took vegetables from the salad bar when exposed to the vinyl banner only, and 239.2% (from 10.2% to 34.6%; P < .001) more students visited the salad bar when exposed to both the television segments and vinyl banners. Both boys and girls responded positively to the vinyl banners (P < .05 in both cases). Evidence from this study highlights the positive impact of branded media on children's vegetable selection in the school cafeteria. Results from this study suggest potential opportunities for using branded media to encourage healthier choices for children.


Functional characterization of the extraclassical receptive field in macaque V1: contrast, orientation, and temporal dynamics.
Neurons in primary visual cortex, V1, very often have extraclassical receptive fields (eCRFs). The eCRF is defined as the region of visual space where stimuli cannot elicit a spiking response but can modulate the response of a stimulus in the classical receptive field (CRF). We investigated the dependence of the eCRF on stimulus contrast and orientation in macaque V1 cells for which the laminar location was determined. The eCRF was more sensitive to contrast than the CRF across the whole population of V1 cells with the greatest contrast differential in layer 2/3. We confirmed that many V1 cells experience stronger suppression for collinear than orthogonal stimuli in the eCRF. Laminar analysis revealed that the predominant bias for collinear suppression was found in layers 2/3 and 4b. The laminar pattern of contrast and orientation dependence suggests that eCRF suppression may derive from different neural circuits in different layers, and may be comprised of two distinct components: orientation-tuned and untuned suppression. On average tuned suppression was delayed by ∼25 ms compared with the onset of untuned suppression. Therefore, response modulation by the eCRF develops dynamically and rapidly in time.


Prevalence of obesity in children aged 6-12 years in Greece: nutritional behaviour and physical activity.
During the last two decades, obesity has proved to be one of the most important problems of public health, and it is considerably more frequent in developed countries, not only in adults, but in children, too. The aim of the current study is to evaluate the prevalence of overweight and obesity in children. Two thousand three hundred and seventy-four pupils in primary education were considered for the study (1206 boys and 1168 girls). In the population-based study, the proportion of overweight children was 23.9%, of obese children 7.3%, and of those with central obesity 35.5%. The boys were obese in a higher percentage than the girls (9.2% vs. 5.3%, p < 0.05). The obesity rates were gradually reduced as the children were growing older. The nutritional habits which were identified to have a positive association with obesity were the following: skipping breakfast, not consuming fruits and vegetables, and consuming bread and soft drinks. Children's healthy nutrition in school was related to lower rates of generalised and central obesity, while the hours spent watching TV were positively associated with all types of obesity. Results from the study suggest that a high proportion of children are overweight or obese. Therefore, it is important to adhere to a healthy lifestyle which emphasizes healthy food choices and habits, regular physical activity, and limiting screen time.


Hagfish and lamprey Hox genes reveal conservation of temporal colinearity in vertebrates.
Hox genes exert fundamental roles for proper regional specification along the main rostro-caudal axis of animal embryos. They are generally expressed in restricted spatial domains according to their position in the cluster (spatial colinearity)-a feature that is conserved across bilaterians. In jawed vertebrates (gnathostomes), the position in the cluster also determines the onset of expression of Hox genes (a feature known as whole-cluster temporal colinearity (WTC)), while in invertebrates this phenomenon is displayed as a subcluster-level temporal colinearity. However, little is known about the expression profile of Hox genes in jawless vertebrates (cyclostomes); therefore, the evolutionary origin of WTC, as seen in gnathostomes, remains a mystery. Here, we show that Hox genes in cyclostomes are expressed according to WTC during development. We investigated the Hox repertoire and Hox gene expression profiles in three different species-a hagfish, a lamprey and a shark-encompassing the two major groups of vertebrates, and found that these are expressed following a whole-cluster, temporally staggered pattern, indicating that WTC has been conserved during the past 500 million years despite drastically different genome evolution and morphological outputs between jawless and jawed vertebrates.


Advanced applications of robotics in digestive surgery.
Laparoscopy is widely recognized as feasible and safe approach to many oncologic and benign digestive conditions and is associated with an improved early outcome. Robotic surgery promises to overcome intrinsic limitations of laparoscopic surgery by a three-dimensional view and wristed instruments widening indications for a minimally invasive approach. To date, the more interesting applications of robotic surgery are those operations restricted to one abdominal quadrant and requiring a fine dissection and digestive reconstruction. While robot-assisted rectal and gastric surgery are becoming well-accepted options among the surgical community, applications of robotics in hepato-biliary and pancreatic surgery are still debated.


Television Viewing Time and Breast Cancer Incidence for Japanese Premenopausal and Postmenopausal Women: The JACC Study.
The evidence on effects of TV viewing time among premenopausal and postmenopausal women for breast cancer risk remains controversial and limited. A prospective study encompassing 33,276 (17,568 premenopausal, and 15,708 postmenopausal) women aged 40-79 years in whom TV viewing time, menstrual, and reproductive histories were determined by a self-administered questionnaire. The follow-up was from 1988 to 2009 and hazard ratios (HRs) with 95% confidence intervals (CIs) of breast cancer incidence were calculated for longer TV viewing time in reference to shorter TV viewing time by Cox proportional hazard models. During 16.8-year median follow-up, we found positive associations between TV viewing time and breast cancer incidence with a borderline significant trend among total women and a significant trend among postmenopausal women. Among total women, the multivariable HRs (95% CIs) for risk of breast cancer in reference to < 1.5 hr/day of TV viewing time were 0.89 (0.59-1.34) for 1.5 to < 3.0 hr/day, 1.19 (0.82-1.74) for 3.0 to < 4.5 hr/day, and 1.45 (0.91-2.32) for ≥ 4.5 hr/day (p for trend=0.053) and among postmenopausal women, the corresponding risk estimates were 1.10 (0.42-2.88), 2.54 (1.11-5.80), and 2.37 (0.92-6.10) (p for trend=0.009), respectively. Prolonged TV viewing time was associated with increased risk of breast cancer, especially among postmenopausal women.


Fiber-optic and articulating arm implementations of laminar optical tomography for clinical applications.
Laminar optical tomography (LOT) is a recently developed technique for depth-resolved in vivo imaging of absorption and fluorescence contrast. Until now, LOT has been implemented in a benchtop configuration, limiting accessibility to tissues and restricting imaging applications. Here we report on LOT implemented through an articulating arm and a fiber optic image bundle allowing flexible imaging for a range of clinical applications. We quantify the performance of these two implementations by imaging a tissue mimicking phantom.


The viral protein NSP1 acts as a ribosome gatekeeper for shutting down host translation and fostering SARS-CoV-2 translation.
SARS-CoV-2 coronavirus is responsible for Covid-19 pandemic. In the early phase of infection, the single-strand positive RNA genome is translated into non-structural proteins (NSP). One of the first proteins produced during viral infection, NSP1, binds to the host ribosome and blocks the mRNA entry channel. This triggers translation inhibition of cellular translation. In spite of the presence of NSP1 on the ribosome, viral translation proceeds however. The molecular mechanism of the so-called viral evasion to NSP1 inhibition remains elusive. Here, we confirm that viral translation is maintained in the presence of NSP1. The evasion to NSP1-inhibition is mediated by the cis-acting RNA hairpin SL1 in the 5'UTR of SARS-CoV-2. NSP1-evasion can be transferred on a reporter transcript by SL1 transplantation. The apical part of SL1 is only required for viral translation. We show that NSP1 remains bound on the ribosome during viral translation. We suggest that the interaction between NSP1 and SL1 frees the mRNA accommodation channel while maintaining NSP1 bound to the ribosome. Thus, NSP1 acts as a ribosome gatekeeper, shutting down host translation or fostering SARS-CoV-2 translation depending on the presence of the SL1 5'UTR hairpin. SL1 is also present and necessary for translation of sub-genomic RNAs in the late phase of the infectious program. Consequently, therapeutic strategies targeting SL1 should affect viral translation at early and late stages of infection. Therefore, SL1 might be seen as a genuine 'Achille heel' of the virus.


Isolation, Enumeration, and Identification of Gram-Positive Cocci from Frozen Crabmeat.
Bacterial levels in frozen crabmeat samples were determined by plate counts using four staphylococcal isolation media incubated for 24, 48, and 72 h at 26 and 35°C. Staphylococcal counts determined by the spread-plate Food and Drug Administration Baird-Parker protocol incubated at 35°C for 48 h (FDABP48-35) served as the standard for comparison. When FDABP48-35 counts were compared to counts from 29 combinations of media, time of incubation, and incubation temperature, only FDABP and Borrego, Florido, Mrocek, and Romero (BFMR) counts, representing 11 combinations, were statistically comparable to FDABP48-35 counts. Cocci (91.5%) were the dominant bacterial type; gram-positive rods (8.3%) and gram-negative isolates (0.2%) were also detected. Isolates tested by the coagulase reaction were predominantly coagulase negative (CN) (97.7%). Of 100 isolates analyzed by the BIOLOG identification procedure, 62% were classified as Staphylococcus lentus , S. hominis , and S. epidermidis . Three isolates were identified as Staphylococcus aureus . These data indicate that species identification of staphylococci from crabmeat can assist in determining the source of contamination, and that staphylococcal isolates from crabmeat are more likely to be coagulase negative.