Identification and expression profiles of sRNAs and their biogenesis and action-related genes in male and female cones of Pinus tabuliformis.
Small RNA (sRNA) play pivotal roles in reproductive development, and their biogenesis and action mechanisms are well characterised in angiosperm plants; however, corresponding studies in conifers are very limited. To improve our understanding of the roles of sRNA pathways in the reproductive development of conifers, the genes associated with sRNA biogenesis and action pathways were identified and analysed, and sRNA sequencing and parallel analysis of RNA ends (PARE) were performed in male and female cones of the Chinese pine (Pinus tabuliformis). Based on high-quality reference transcriptomic sequences, 21 high-confidence homologues involved in sRNA biogenesis and action in P. tabuliformis were identified, including two different DCL3 genes and one AGO4 gene. More than 75 % of genes involved in sRNA biogenesis and action have higher expression levels in female than in male cones. Twenty-six microRNA (miRNA) families and 74 targets, including 46 24-nt sRNAs with a 5' A, which are specifically expressed in male cones or female cones and probably bind to AGO4, were identified. The sRNA pathways have higher activity in female than in male cones, and the miRNA pathways are the main sRNA pathways in P. tabuliformis. The low level of 24-nt short-interfering RNAs in conifers is not caused by the absence of biogenesis-related genes or AGO-binding proteins, but most likely caused by the low accumulation of these key components. The identification of sRNAs and their targets, as well as genes associated with sRNA biogenesis and action, will provide a good starting point for investigations into the roles of sRNA pathways in cone development in conifers.


Evidence of random copolymer adsorption at fluctuating selective interfaces from Monte-Carlo simulation studies.
We perform Monte-Carlo simulations of a binary, strongly separated mixture of A- and B-type homopolymers with some amount of random AB copolymers added. The interface is analyzed and the interface tension is calculated using the model of capillary waves. We can clearly demonstrate that random copolymers are localized at real, fluctuating interfaces between incompatible polymer species and micellization is not favored over adsorption. Our study proves that random copolymers are potential candidates for compatibilization of polymer-polymer mixtures. By simulating random copolymers in a one-component bulk and comparing their free energy to the copolymers adsorbed at the two-phase interface we show that the adsorption is thermodynamically stable. We use scaling arguments developed for ideal and non-fluctuating interfaces to rationalize the simulation results and we calculate the reduction of interface tension with increasing amount of the adsorbed copolymers.


Composite nanofibers for highly efficient photocatalytic degradation of organic dyes from contaminated water.
In this study highly efficient photocatalyst based on composite nanofibers containing polyacrylonitrile (PAN), carbon nanotubes (CNT), and surface functionalized TiO2 nanoparticles was developed. The composite nanofibers were fabricated using electrospinning technique followed by chemical crosslinking. The surface modification and morphology changes of the fabricated composite nanofibers were examined through SEM, TEM, and FTIR analysis. The photocatalytic performance of the composite nanofibers for the degradation of model molecules, methylene blue and indigo carmine, under UV irradiation in aqueous solutions was investigated. The results demonstrated that high photodegradation efficiency was obtained in a short time and at low power intensity compared to other reported studies. The effective factors on the degradation of the dyes, such as the amount of catalyst, solution pH and irradiation time were investigated. The experimental kinetic data were fitted using pseudo-first order model. The effect of the composite nanofibers as individual components on the degradation efficiency of MB and IC was evaluated in order to understand the overall photodegradation mechanism. The results obtained showed that all the components possess significant effect on the photodegradation activity of the composite nanofibers. The stability studies demonstrated that the photodegradation efficiency can remain constant at the level of 99% after five consecutive cycles.


Multifactorial influence on duration of exclusive breastfeeding; a Danish cohort study.
The multifactorial aspects of breastfeeding require measures at many levels to identify mothers in need of breastfeeding support from healthcare professionals. Our objective was to examine the relative importance of sociodemographic, pre/perinatal-, infant-, psychosocial-, and interaction-related factors affecting duration of exclusive breastfeeding. We used self-reported data from a community-based trial including 1265 women (response rate 49%) giving birth from January 2017 to February 2018. Data on outcome, duration of exclusive breastfeeding, were collected three and nine months postpartum; data on the study variables concerning known risk factors for breastfeeding cessation were collected two weeks postpartum. Crude and multiple Cox proportional hazards models were used for statistical analyses with additional analyses for time varying effects. Factors with an independent prognostic influence on duration of exclusive breastfeeding in fully adjusted models included early skin-to-skin contact (HR = 1.18 CI:1.04-1.33), intention to breastfeed (HR = 0.77 CI: 0.73-0.80), positive outcome evaluation, meaning the value mothers attributed to breastfeeding (HR = 1.33 CI: 1.08-1.63), higher level of self-efficacy (HR = 1.46 CI: 1.24-1.72), and maternal sense of security in relation to breastfeeding (HR = 1.31 CI: 1.14-1.50). Higher maternal BMI, lower self-efficacy, shorter breastfeeding duration of previous child, and hospitalization during birth were time dependent by affecting the exclusive breastfeeding duration primarily in the first months following birth. The results suggest that target groups in special need of early breastfeeding support are defined by being hospitalized, obese, having low self-efficacy or short previous breastfeeding experience. The extensive influence of psychosocial factors emphasizes the importance of including both practical facilitating guidance and positive verbal encouragement to ensure effective breastfeeding support.


Innovative Alternative Technologies to Extract Carotenoids from Microalgae and Seaweeds.
Marine microalgae and seaweeds (microalgae) represent a sustainable source of various bioactive natural carotenoids, including β-carotene, lutein, astaxanthin, zeaxanthin, violaxanthin and fucoxanthin. Recently, the large-scale production of carotenoids from algal sources has gained significant interest with respect to commercial and industrial applications for health, nutrition, and cosmetic applications. Although conventional processing technologies, based on solvent extraction, offer a simple approach to isolating carotenoids, they suffer several, inherent limitations, including low efficiency (extraction yield), selectivity (purity), high solvent consumption, and long treatment times, which have led to advancements in the search for innovative extraction technologies. This comprehensive review summarizes the recent trends in the extraction of carotenoids from microalgae and seaweeds through the assistance of different innovative techniques, such as pulsed electric fields, liquid pressurization, supercritical fluids, subcritical fluids, microwaves, ultrasounds, and high-pressure homogenization. In particular, the review critically analyzes technologies, characteristics, advantages, and shortcomings of the different innovative processes, highlighting the differences in terms of yield, selectivity, and economic and environmental sustainability.


Coronary artery occlusions diagnosed by transthoracic Doppler.
Our aim was to assess whether anterograde flow velocities in septal perforating branches could identify an occluded contralateral coronary artery, and to assess the feasibility and accuracy of diagnosing occlusions in the three main coronary arteries by the combined use of several noninvasive parameters indicating collateral flow. A total of 108 patients scheduled for coronary angiography because of chest pain or acute coronary syndromes were studied using transthoracic Doppler echocardiography. Anterograde peak diastolic flow velocities (pDV) in septal perforating branches were higher in patients with angiographic occluded contralateral artery compared with corresponding velocities in patients without significant disease in the contralateral artery (0.80 ± 0.31 m/sec versus 0.37 ± 0.13 m/sec, p < 0.001). Receiver operating characteristic curve showed pDV ≥ 0.57 m/sec to be the optimal cutoff value to identify occluded contralateral artery, with a sensitivity of 79% and a specificity of 69%. Demonstration of at least one positive parameter (retrograde flow in main coronary arteries, reversed flow in septal perforating and left circumflex marginal branches, pDV ≥ 0.57 m/sec, or demonstration of other epicardial or intramyocardial collaterals) indicating collateral flow to an occluded main coronary artery had sensitivity, specificity, positive and negative predictive value of 89%, 94%, 63%, and 99%, respectively, for detection of a coronary occlusion. With this combined use of several parameters, 25 of 28 coronary occlusions were identified. By investigating several parameters indicating collateral flow, we were able to identify most of the main coronary occlusions in the patient cohort. Furthermore, our study demonstrated that coronary artery occlusions may result in complex and diverging coronary pathophysiology depending on which coronary artery segment is occluded and the extent of accompanying coronary artery disease. ClinicalTrials.gov number NTC00281346.


Digital evolution in time-dependent fitness landscapes.
We study the response of populations of digital organisms that adapt to a time-varying (periodic) fitness landscape of two oscillating peaks. We corroborate in general predictions from quasi-species theory in dynamic landscapes, such as adaptation to the average fitness landscape at small periods (high frequency) and quasistatic adaptation at large periods (low frequency). We also observe adaptive phase shifts (time lags between a change in the fitness landscape and an adaptive change in the population) that indicate a low-pass filter effect, in agreement with existing theory. Finally, we witness long-term adaptation to fluctuating environments not anticipated in previous theoretical work.


Mapping the structural and dynamical features of multiple p53 DNA binding domains: insights into loop 1 intrinsic dynamics.
The transcription factor p53 regulates cellular integrity in response to stress. p53 is mutated in more than half of cancerous cells, with a majority of the mutations localized to the DNA binding domain (DBD). In order to map the structural and dynamical features of the DBD, we carried out multiple copy molecular dynamics simulations (totaling 0.8 μs). Simulations show the loop 1 to be the most dynamic element among the DNA-contacting loops (loops 1-3). Loop 1 occupies two major conformational states: extended and recessed; the former but not the latter displays correlations in atomic fluctuations with those of loop 2 (~24 Å apart). Since loop 1 binds to the major groove whereas loop 2 binds to the minor groove of DNA, our results begin to provide some insight into the possible mechanism underpinning the cooperative nature of DBD binding to DNA. We propose (1) a novel mechanism underlying the dynamics of loop 1 and the possible tread-milling of p53 on DNA and (2) possible mutations on loop 1 residues to restore the transcriptional activity of an oncogenic mutation at a distant site.


Development and Evaluation of Real Time RT-PCR Assays for Detection and Typing of Bluetongue Virus.
Bluetongue virus is the type species of the genus Orbivirus, family Reoviridae. Bluetongue viruses (BTV) are transmitted between their vertebrate hosts primarily by biting midges (Culicoides spp.) in which they also replicate. Consequently BTV distribution is dependent on the activity, geographic distribution, and seasonal abundance of Culicoides spp. The virus can also be transmitted vertically in vertebrate hosts, and some strains/serotypes can be transmitted horizontally in the absence of insect vectors. The BTV genome is composed of ten linear segments of double-stranded (ds) RNA, numbered in order of decreasing size (Seg-1 to Seg-10). Genome segment 2 (Seg-2) encodes outer-capsid protein VP2, the most variable BTV protein and the primary target for neutralising antibodies. Consequently VP2 (and Seg-2) determine the identity of the twenty seven serotypes and two additional putative BTV serotypes that have been recognised so far. Current BTV vaccines are serotype specific and typing of outbreak strains is required in order to deploy appropriate vaccines. We report development and evaluation of multiple 'TaqMan' fluorescence-probe based quantitative real-time type-specific RT-PCR assays targeting Seg-2 of the 27+1 BTV types. The assays were evaluated using orbivirus isolates from the 'Orbivirus Reference Collection' (ORC) held at The Pirbright Institute. The assays are BTV-type specific and can be used for rapid, sensitive and reliable detection / identification (typing) of BTV RNA from samples of infected blood, tissues, homogenised Culicoides, or tissue culture supernatants. None of the assays amplified cDNAs from closely related but heterologous orbiviruses, or from uninfected host animals or cell cultures.


Genome-wide analysis of light-regulated alternative splicing mediated by photoreceptors in Physcomitrella patens.
Light is one of the most important factors regulating plant growth and development. Light-sensing photoreceptors tightly regulate gene expression to control photomorphogenic responses. Although many levels of gene expression are modulated by photoreceptors, regulation at the mRNA splicing step remains unclear. We performed high-throughput mRNA sequencing to analyze light-responsive changes in alternative splicing in the moss Physcomitrella patens, and found that a large number of alternative splicing events were induced by light in the moss protonema. Light-responsive intron retention preferentially occurred in transcripts involved in photosynthesis and translation. Many of the alternatively spliced transcripts were expressed from genes with a function relating to splicing or light signaling, suggesting a potential impact on pre-mRNA splicing and photomorphogenic gene regulation in response to light. Moreover, most light-regulated intron retention was induced immediately upon light exposure, while motif analysis identified a repetitive GAA motif that may function as an exonic regulatory cis element in light-mediated alternative splicing. Further analysis in gene-disrupted mutants was consistent with a function for multiple red-light photoreceptors in the upstream regulation of light-responsive alternative splicing. Our results indicate that intensive alternative splicing occurs in non-vascular plants and that, during photomorphogenesis, light regulates alternative splicing with transcript selectivity. We further suggest that alternative splicing is rapidly fine-tuned by light to modulate gene expression and reorganize metabolic processes, and that pre-mRNA cis elements are involved in photoreceptor-mediated splicing regulation.


Partial gastrectomy using natural orifice translumenal endoscopic surgery (NOTES) for gastric submucosal tumors: early experience in humans.
Transvaginal endoscopic gastric surgery is one of the cutting edge procedures in the field of natural orifice translumenal endoscopic surgery (NOTES). Its feasibility has been shown sporadically in bariatric cases but not in oncologic conditions. The authors report their early experience with hybrid transvaginal NOTES gastrectomy for gastric submucosal tumors (SMTs). Two female patients with SMTs in the distal stomach participated in this institutional review board (IRB)-approved study. Surgical indication was determined according to the National Comprehensive Cancer Network (NCCN) sarcoma guidelines, and the study adhered to the following oncologic principles: no direct handling of the lesion, full-thickness resection, and reasonable surgical margins. The study protocol required a minimum of two laparoscopic ports to ensure procedural safety and aforementioned oncologic appropriateness. Under laparoscopic guidance, a transvaginal route was created and secured with a 50-cm flexible overtube. A gastrointestinal endoscope was introduced, and the perigastric dissection was performed using an insulation-tipped diathermy knife (IT knife) and needle knife. This process was assisted with two laparoscopic graspers. After perigastric mobilization, the transvaginal endoscope was replaced with a digital stapling device, and partial gastrectomy was accomplished. The resected specimen was isolated and delivered through the vagina, and the vaginal wound was closed under direct vision. Outcomes measurements included surgical results, pain scoring, and clinical outcomes. Both operations were completed successfully in compliance with the aforementioned oncologic principles. The operating time was 365 and 170 min, respectively. The estimated blood loss was negligible. A minilaparotomy for specimen delivery was successfully avoided in both cases. A minimal vaginal incision was added for one patient at retrieval. Postoperatively, both patients reported no pain and recovered rapidly. The final diagnosis was hemorrhagic lipoma and gastrointestinal stromal tumor (GIST), respectively. Our initial experience with human transvaginal NOTES gastrectomy showed it to be feasible and safe for gastric SMTs. It is a complex but promising surgical alternative for female oncologic patients undergoing partial gastric resection.


Nightmares in Children with Foetal Alcohol Spectrum Disorders, Autism Spectrum Disorders, and Their Typically Developing Peers.
Children with Foetal Alcohol Spectrum Disorders (FASD) and Autism Spectrum Disorders (ASD) experience significantly higher rates of sleep disturbances than their typically developing (TD) peers. Pre-sleep anxiety and waking emotional content is known to affect the content and frequency of nightmares, which can be distressing to children and caregivers. This is the first study to analyse nightmare frequency and content in FASD, and to assess its association with psychometric outcomes. Using online caregiver questionnaires, we assessed reports from 277 caregivers of children with ASD (n = 61), FASD (n = 112), and TD children (n = 104) using the Children's Sleep Habits Questionnaire (CSHQ), the Child Behaviour Checklist (CBCL), the Spence Children's Anxiety Scale (SCAS), and the Behaviour Rating Inventory for Executive Functioning (BRIEF). Within the ASD group, 40.3% of caregivers reported their children had nightmares. Within the FASD group, 73.62% of caregivers reported their children had nightmares, and within the TD group, 21.36% of caregivers reported their children had nightmares. Correlation analysis revealed significant associations between anxiety and nightmares, maladaptive behaviour and nightmares, and executive functioning and nightmares in the TD and FASD groups, but not ASD group. This paper adds to the emerging body of work supporting the need for sleep interventions as part of clinical practice with regard to children with ASD and FASD. As a relatively niche but important area of study, this warrants much needed further research.


Oxidation-responsive micelles based on a selenium-containing polymeric superamphiphile.
We have fabricated a polymeric superamphiphile based on the electrostatic interaction between the double hydrophilic block copolymer of poly(ethylene glycol)-b-acrylic acid (PEG-b-PAA) and a selenium-containing surfactant (SeQTA). The polymeric superamphiphiles are able to self-assemble to form micelles in solution. The micelles can be disassembled with the addition of 0.1% H(2)O(2) because SeQTA is very sensitive to oxidation. The selenide group in SeQTA is oxidized into selenoxide (SeQTA-Ox) by H(2)O(2), which makes the surfactant more hydrophilic, thus leading to the disassembly of the micelles. In addition, small guest molecules such as fluorescein sodium can be loaded into the micelles made from the polymeric superamphiphiles and released in a controlled way under mild oxidation conditions. This study represents a new way to fabricate stimuli-responsive superamphiphiles for controlled self-assembly and disassembly.


GAD67 deficiency in parvalbumin interneurons produces deficits in inhibitory transmission and network disinhibition in mouse prefrontal cortex.
In mammalian neocortex, the delicate balance of neural circuits is regulated by a rich repertoire of inhibitory control mechanisms mediated by diverse classes of GABAergic interneurons. A key step common to all GABAergic neurons is the synthesis of GABA, catalyzed by 2 isoforms of glutamic acid decarboxylases (GAD). Among these, GAD67 is the rate-limiting enzyme. GAD67 level is regulated by neural activity and is altered in multiple neuropsychiatric disorders. The significance of altered GAD67 levels on inhibitory transmission, however, remains unclear. The presence of GAD65, postsynaptic GABA receptor regulation, and the diversity of cortical interneurons make the link from GAD67 levels to GABA transmission less than straightforward. Here, we selectively removed one allele of the GAD67 gene, Gad1, in PV interneurons in juvenile mice. We found substantial deficits in transmission from PV to pyramidal neurons in prefrontal cortex, along with increases of pyramidal cell excitability and excitation/inhibition balance in PV cells. Synaptic deficits recovered in adult mice, suggesting engagement of homeostatic and compensatory mechanisms. These results demonstrate that GAD67 levels directly influence synaptic inhibition. Thus, GAD67 deficiency in PV cells likely contributes to cortical dysfunction in disease states; the reversibility of synaptic deficits suggests nonpermanent damage to inhibitory circuitry.


Subjective ratings of age-of-acquisition: exploring issues of validity and rater reliability.
This study aimed to investigate concerns of validity and reliability in subjective ratings of age-of-acquisition (AoA), through exploring characteristics of the individual rater. An additional aim was to validate the obtained AoA ratings against two corpora - one of child speech and one of adult speech - specifically exploring whether words over-represented in the child-speech corpus are rated with lower AoA than words characteristic of the adult-speech corpus. The results show that less than one-third of participating informants' ratings are valid and reliable. However, individuals with high familiarity with preschool-aged children provide more valid and reliable ratings, compared to individuals who do not work with or have children of their own. The results further show a significant, age-adjacent difference in rated AoA for words from the two different corpora, thus strengthening their validity. The study provides AoA data, of high specificity, for 100 child-specific and 100 adult-specific Swedish words.


An initial evaluation of the clinical and fitness for work outcomes of a military group behavioural activation programme.
Behavioural Activation (BA) is an evidence-based psychological treatment for depression based on behavioural theory. However, in common with other talking therapies, there is limited evidence about occupational factors related to treatment. This is an important gap in the research given the emphasis placed on employment considerations in recent service initiatives. A service evaluation to investigate the clinical and fitness to work outcomes of a group BA programme for serving military personnel. 46 patients experiencing moderate to severe depression attended a 12-session Military Behavioural Activation and Rehabilitation Course (MBARC). The primary outcomes were the Patient Health Questionnaire-9 (PHQ-9), a self-report measure of depression and the patient's medical employability category. Clinical and statistically significant changes were found on the PHQ-9 between pre-course and 3-month follow-up. Pretreatment 3 patients (6.5%) were psychologically fit to deploy on full operational duties in their primary role; this increased to 25 (56.8%) and 29 (65.9%) at 3 and 6-months respectively. Preliminary findings suggest that MBARC is a clinically and occupationally effective treatment for depression in military personnel. Further research is required to identify if BA delivered in a group setting would be effective in non-military settings and whether treatment benefits are maintained in the longer term.


Associations between purine metabolites and clinical symptoms in schizophrenia.
The antioxidant defense system, which is known to be dysregulated in schizophrenia, is closely linked to the dynamics of purine pathway. Thus, alterations in the homeostatic balance in the purine pathway may be involved in the pathophysiology of schizophrenia. Breakdown products in purine pathway were measured using high-pressure liquid chromatography coupled with a coulometric multi-electrode array system for 25 first-episode neuroleptic-naïve patients with schizophrenia at baseline and at 4-weeks following initiation of treatment with antipsychotic medication. Associations between these metabolites and clinical and neurological symptoms were examined at both time points. The ratio of uric acid and guanine measured at baseline predicted clinical improvement following four weeks of treatment with antipsychotic medication. Baseline levels of purine metabolites also predicted clinical and neurological symtpoms recorded at baseline; level of guanosine was associated with degree of clinical thought disturbance, and the ratio of xanthosine to guanosine at baseline predicted degree of impairment in the repetition and sequencing of actions. Findings suggest an association between optimal levels of purine byproducts and dynamics in clinical symptoms and adjustment, as well as in the integrity of sensory and motor processing. Taken together, alterations in purine catabolism may have clinical relevance in schizophrenia pathology.


Pulmonary arterial hypertension complicating connective tissue diseases.
Pulmonary arterial hypertension (PAH) may complicate diverse connective tissue diseases (CTDs) such as systemic sclerosis (SSc), systemic lupus erythematosus (SLE), rheumatoid arthritis (RA), and mixed CTD (MCTD) and is an important cause of morbidity and mortality in this context. From a histological standpoint, the pulmonary vascular lesions in PAH complicating CTD are similar to those observed in idiopathic PAH (IPAH). However, prognosis and responsiveness to therapy are distinctly worse in PAH associated with CTD. PAH is most common in SSc (affecting up to 20% of patients with SSc), and most of the data regarding incidence, clinical features, and therapy of CTD-associated PAH are derived from patients with SSc (scleroderma). Although PAH may involve other CTDs, data are more limited (primarily small, uncontrolled series and case reports). Treatment strategies for PAH associated with CTD are similar to but are distinctly less effective than those for IPAH. Lung transplantation may be offered for a subset of patients with CTD-associated PAH, but results are less favorable than for IPAH due to comorbidities and specific complications associated with CTD (e.g., esophageal involvement, aspiration with SSc).


Timing of (supplemental) parenteral nutrition in critically ill patients: a systematic review.
Supplemental parenteral nutrition (SPN) is used in a step-up approach when full enteral support is contraindicated or fails to reach caloric targets. Recent nutrition guidelines present divergent advices regarding timing of SPN in critically ill patients ranging from early SPN (<48 h after admission; EPN) to postponing initiation of SPN until day 8 after Intensive Care Unit (ICU) admission (LPN). This systematic review summarizes results of prospective studies among adult ICU patients addressing the best timing of (supplemental) parenteral nutrition (S)PN. A structured PubMed search was conducted to identify eligible articles. Articles were screened and selected using predetermined criteria and appraised for relevance and validity. After critical appraisal, four randomized controlled trials (RCTs) and two prospective observational studies remained. One RCT found a higher percentage of alive discharge from the ICU at day 8 in the LPN group compared to EPN group (p = 0.007) but no differences in ICU and in-hospital mortality. None of the other RCTs found differences in ICU or in-hospital mortality rates. Contradicting or divergent results on other secondary outcomes were found for ICU length of stay, hospital length of stay, infection rates, nutrition targets, duration of mechanical ventilation, glucose control, duration of renal replacement therapy, muscle wasting and fat loss. Although the heterogeneity in quality and design of relevant studies precludes firm conclusions, it is reasonable to assume that in adult critically ill patients, there are no clinically relevant benefits of EPN compared with LPN with respect to morbidity or mortality end points, when full enteral support is contraindicated or fails to reach caloric targets. However, considering that infectious morbidity and resolution of organ failure may be negatively affected through mechanisms not yet clearly understood and acquisition costs of parenteral nutrition are higher, the early administration of parenteral nutrition cannot be recommended.


European multicenter experience with valve-sparing reoperations after the Ross procedure.
Autograft valve preservation at reoperation may conserve some of the advantages of the Ross procedure. However, results of long-term follow-up are lacking. In this retrospective multicenter study, we present our experience with valve-sparing reoperations after the Ross procedure, with a focus on long-term outcome. A total of 86 patients from 6 European centers, who underwent valve-sparing reoperation after the Ross procedure between 1997 and 2013, were included in the study. Reoperation was performed a median of 9.1 years after the Ross procedure in patients with a median age of 38.4 years (interquartile range: 27.1-51.6 years). Preoperative severe autograft regurgitation (grade ≥3) was present in 46% of patients. In-hospital mortality was 1%. During a median follow-up of 4.3 years, 3 more patients died of noncardiac causes, resulting in a cumulative survival at 8 years of 89% (95% confidence interval: 65%-97%). Fifteen patients required a reintervention after valve-sparing reoperation, mostly owing to prolapse or retraction of autograft cusps. Freedom from reintervention was 76% (95% confidence interval: 57%-87%) at 8 years. The reintervention hazard was increased in patients who had isolated and/or severe aortic regurgitation at valve-sparing reoperation. In patients without reintervention after valve-sparing autograft reoperation (n = 63), severe aortic regurgitation was present in 3% at last follow-up. Valve-sparing autograft reoperations after the Ross procedure carry a low operative risk, with acceptable reintervention rates in the first postoperative decade. Patients with isolated and/or severe autograft regurgitation have an increased hazard of reintervention after valve-sparing reoperation; for these patients, careful preoperative weighing of surgical options is required.


Spatial solitons of Maxwell's equations.
Spatial solitons of Maxwell's equations propagating in an isotropic Kerr material differ significantly from the classical soliton of the nonlinear Schrödinger equation unless the electric field is linearly polarized along a geometric axis of the soliton intensity pattern. In general the polarization state changes continuously as the beam propagates, with a period of millimeters for highly nonlinear materials. This effect is due to the form birefringence of the soliton-induced waveguide. Equivalently, a soliton of Maxwell's equations is composed of both the TE and TM modes of the axially uniform waveguide it induces. Modal beating leads to the polarization dynamics.


Can early introduction of egg prevent egg allergy in infants? A population-based study.
Infant feeding guidelines have long recommended delaying introduction of solids and allergenic foods to prevent allergy in high-risk infants, despite a paucity of evidence. We aimed to determine whether confirmed egg allergy in 12-month-old infants is associated with (1) duration of breast-feeding and (2) ages of introducing egg and solids. In a population-based cross-sectional study (HealthNuts) parents reported on infant feeding and potential confounding factors before skin prick testing for egg white. Egg-sensitized infants were then offered an egg oral food challenge. Multiple logistic regression was used to investigate associations between diet and egg allergy adjusted for possible confounding factors. A total of 2589 infants (73% response) participated. Compared with introduction at 4 to 6 months, introducing egg into the diet later was associated with higher risks of egg allergy (adjusted odds ratios [ORs], 1.6 [95% CI, 1.0-2.6] and 3.4 [95% CI, 1.8-6.5] for introduction at 10-12 and after 12 months, respectively). These findings persisted even in children without risk factors (OR, 3.3 [95% CI, 1.1-9.9]; 10-12 months). At age 4 to 6 months, first exposure as cooked egg reduced the risk of egg allergy compared with first exposure as egg in baked goods (OR, 0.2 [95% CI, 0.06-0.71]). Duration of breast-feeding and age at introduction of solids were not associated with egg allergy. Introduction of cooked egg at 4 to 6 months of age might protect against egg allergy. Changes in infant feeding guidelines could have a significant effect on childhood egg allergy and possibly food allergy more generally.


Autocrine VEGF Isoforms Differentially Regulate Endothelial Cell Behavior.
Vascular endothelial growth factor A (VEGF) is involved in all the essential biology of endothelial cells, from proliferation to vessel function, by mediating intercellular interactions and monolayer integrity. It is expressed as three major alternative spliced variants. In mice, these are VEGF120, VEGF164, and VEGF188, each with different affinities for extracellular matrices and cell surfaces, depending on the inclusion of heparin-binding sites, encoded by exons 6 and 7. To determine the role of each VEGF isoform in endothelial homeostasis, we compared phenotypes of primary endothelial cells isolated from lungs of mice expressing single VEGF isoforms in normoxic and hypoxic conditions. The differential expression and distribution of VEGF isoforms affect endothelial cell functions, such as proliferation, adhesion, migration, and integrity, which are dependent on the stability of and affinity to VEGF receptor 2 (VEGFR2). We found a correlation between autocrine VEGF164 and VEGFR2 stability, which is also associated with increased expression of proteins involved in cell adhesion. Endothelial cells expressing only VEGF188, which localizes to extracellular matrices or cell surfaces, presented a mesenchymal morphology and weakened monolayer integrity. Cells expressing only VEGF120 lacked stable VEGFR2 and dysfunctional downstream processes, rendering the cells unviable. Endothelial cells expressing these different isoforms in isolation also had differing rates of apoptosis, proliferation, and signaling via nitric oxide (NO) synthesis. These data indicate that autocrine signaling of each VEGF isoform has unique functions on endothelial homeostasis and response to hypoxia, due to both distinct VEGF distribution and VEGFR2 stability, which appears to be, at least partly, affected by differential NO production. This study demonstrates that each autocrine VEGF isoform has a distinct effect on downstream functions, namely VEGFR2-regulated endothelial cell homeostasis in normoxia and hypoxia.


Database-independent Protein Sequencing (DiPS) Enables Full-length de Novo Protein and Antibody Sequence Determination.
Traditional "bottom-up" proteomic approaches use proteolytic digestion, LC-MS/MS, and database searching to elucidate peptide identities and their parent proteins. Protein sequences absent from the database cannot be identified, and even if present in the database, complete sequence coverage is rarely achieved even for the most abundant proteins in the sample. Thus, sequencing of unknown proteins such as antibodies or constituents of metaproteomes remains a challenging problem. To date, there is no available method for full-length protein sequencing, independent of a reference database, in high throughput. Here, we present Database-independent Protein Sequencing, a method for unambiguous, rapid, database-independent, full-length protein sequencing. The method is a novel combination of non-enzymatic, semi-random cleavage of the protein, LC-MS/MS analysis, peptide de novo sequencing, extraction of peptide tags, and their assembly into a consensus sequence using an algorithm named "Peptide Tag Assembler." As proof-of-concept, the method was applied to samples of three known proteins representing three size classes and to a previously un-sequenced, clinically relevant monoclonal antibody. Excluding leucine/isoleucine and glutamic acid/deamidated glutamine ambiguities, end-to-end full-length de novo sequencing was achieved with 99-100% accuracy for all benchmarking proteins and the antibody light chain. Accuracy of the sequenced antibody heavy chain, including the entire variable region, was also 100%, but there was a 23-residue gap in the constant region sequence.


Auxin gradients across wood-instructive or incidental?
Various aspects of wood formation have been linked to the action of auxin, e.g. cambial activity, dormancy, secondary cell wall deposition and tension wood formation. The presence of a radial auxin concentration gradient across wood-forming tissue has been suggested to regulate cambial activity and differentiation of cambial derivatives by providing positional information to cells within the tissue. Similar patterning mechanisms that depend on the interpretation of auxin thresholds have subsequently been proposed for shoot and root apical meristems. However, direct evidence for the existence of auxin gradients has only been obtained for the cambium of various tree species. While the auxin gradient theory is based on a plethora of descriptive and pharmacological experiments, in recent years, auxin function on wood formation has been underpinned by molecular and functional data. Here, we review the latest progress in understanding the role of auxin in wood formation and discuss how auxin concentration gradients could be established and interpreted in wood-forming tissues.


Thickness dependence of the strain, band gap and transport properties of epitaxial In2O3 thin films grown on Y-stabilised ZrO2(111).
Epitaxial films of In(2)O(3) have been grown on Y-stabilised ZrO(2)(111) substrates by molecular beam epitaxy over a range of thicknesses between 35 and 420 nm. The thinnest films are strained, but display a 'cross-hatch' morphology associated with a network of misfit dislocations which allow partial accommodation of the lattice mismatch. With increasing thickness a 'dewetting' process occurs and the films break up into micron sized mesas, which coalesce into continuous films at the highest coverages. The changes in morphology are accompanied by a progressive release of strain and an increase in carrier mobility to a maximum value of 73 cm(2) V(-1) s(-1). The optical band gap in strained ultrathin films is found to be smaller than for thicker films. Modelling of the system, using a combination of classical pair-wise potentials and ab initio density functional theory, provides a microscopic description of the elastic contributions to the strained epitaxial growth, as well as the electronic effects that give rise to the observed band gap changes. The band gap increase induced by the uniaxial compression is offset by the band gap reduction associated with the epitaxial tensile strain.


Synthesis and evaluation of dummy molecularly imprinted microspheres for the specific solid-phase extraction of six anthraquinones from slimming tea.
Dummy molecularly imprinted microspheres with danthron as template were synthesized and their performance was evaluated. Accelerated solvent extraction can rapidly and effectively remove template molecules from the microspheres. The microspheres were applied as a specific sorbent for solid-phase extraction of six anthraquinones from slimming tea, showing excellent affinity and high selectivity to danthron and the target analytes. The molecular recognition mechanisms were discussed by the experimental validation with IR spectroscopy. The sample was treated using accelerated solvent extraction followed by dummy molecularly imprinted microspheres solid-phase extraction. Under the optimized ultra high performance liquid chromatographic conditions, the six target analytes can be baseline separated in 8 min, and good linearity was obtained in a range of 0.1-40 μg/mL with the correlation coefficient (r(2)) of ≥0.9998. The method limit of quantification was in a range of 1-2 mg/kg, it can ensure analysis of anthraquinones at mg/kg level. The intra- and interday precision (RSD, n = 6) for the analysis of the six analytes in a slimming tea was less than 4.5 and 5.4%, respectively. The developed method can be applied for the selective extraction, effective separation, and rapid determination of six anthraquinones in slimming tea.


Are molecular tools solving the challenges posed by detection of plant pathogenic bacteria and viruses?
Plant pathogenic bacteria, phytoplasmas, viruses and viroids are difficult to control, and preventive measures are essential to minimize the losses they cause each year in different crops. In this context, rapid and accurate methods for detection and diagnosis of these plant pathogens are required to apply treatments, undertake agronomic measures or proceed with eradication practices, particularly for quarantine pathogens. In recent years, there has been an exponential increase in the number of protocols based on nucleic-acid tools being those based on PCR or RT-PCR now routinely applied worldwide. Nucleic acid extraction is still necessary in many cases and in practice inhibition problems are decreasing the theoretical sensitivity of molecular detection. For these reasons, integrated protocols that include the use of molecular techniques as screening methods, followed by confirmation by other techniques supported by different biological principles are advisable. Overall, molecular techniques based on different types of PCR amplification and very especially on real-time PCR are leading to high throughput, faster and more accurate detection methods for the most severe plant pathogens, with important benefits for agriculture. Other technologies, such as isothermal amplification, microarrays, etc. have great potential, but their practical development in plant pathology is still underway. Despite these advances, there are some unsolved problems concerning the detection of many plant pathogens due to their low titre in the plants, their uneven distribution, the existence of latent infections and the lack of validated sampling protocols. Research based on genomic advances and innovative detection methods as well as better knowledge of the pathogens' lifecycle, will facilitate their early and accurate detection, thus improving the sanitary status of cultivated plants in the near future.


Biomechanical Stability of Primary and Revision Sacroiliac Joint Fusion Devices: A Cadaveric Study.
An in vitro biomechanics study. To evaluate the efficacy of triangular titanium implants in providing mechanical stabilization to a sacroiliac joint with primary and revision sized implants. Ten lumbopelvic cadaveric specimens were tested in 4 stages: intact, pubic symphysis sectioned, primary, and simulated revision. Primary treatment was performed using 3 laterally placed triangular titanium implants. To simulate revision conditions before and after bone ingrowth and ongrowth on the implants, 7.5-mm and 10.75-mm implants were randomly assigned to one side of each specimen during the simulated revision stage. A 6 degrees of freedom spinal loading frame was used to load specimens in 4 directions: flexion extension, lateral bending, axial torsion, and axial compression. Biomechanical evaluation was based on measures of sacroiliac joint rotational and translational motion. Both primary and revision implants showed the ability to reduce translational motion to a level significantly lower than the intact condition when loaded in axial compression. Simulated revision conditions showed no statistically significant differences compared with the primary implant condition, with the exception of flexion-extension range of motion where motions associated with the revised condition were significantly lower. Comparison of rotational and translation motions associated with the 7.5- and 10.75-mm implants showed no significant differences between the treatment conditions. These results indicate that implantation of laterally placed triangular titanium implants significantly reduces the motion of a sacroiliac joint using either the primary and revision sized implants. No statistically significant differences were detected when comparing the efficacy of primary, 7.5-mm revision, or 10.75-mm revision implants.


Cardiopulmonary Resuscitation Training Disparities in the United States.
Bystander cardiopulmonary resuscitation (CPR) is associated with increased survival from cardiac arrest, yet bystander CPR rates are low in many communities. The overall prevalence of CPR training in the United States and associated individual-level disparities are unknown. We sought to measure the national prevalence of CPR training and hypothesized that older age and lower socioeconomic status would be independently associated with a lower likelihood of CPR training. We administered a cross-sectional telephone survey to a nationally representative adult sample. We assessed the demographics of individuals trained in CPR within 2 years (currently trained) and those who had been trained in CPR at some point in time (ever trained). The association of CPR training and demographic variables were tested using survey weighted logistic regression. Between September 2015 and November 2015, 9022 individuals completed the survey; 18% reported being currently trained in CPR, and 65% reported training at some point previously. For each year of increased age, the likelihood of being currently CPR trained or ever trained decreased (currently trained: odds ratio, 0.98; 95% CI, 0.97-0.99; P<0.01; ever trained: OR, 0.99; 95% CI, 0.98-0.99; P=0.04). Furthermore, there was a greater then 4-fold difference in odds of being currently CPR trained from the 30-39 to 70-79 year old age groups (95% CI, 0.10-0.23). Factors associated with a lower likelihood of CPR training were lesser educational attainment and lower household income (P<0.01 for each of these variables). A minority of respondents reported current training in CPR. Older age, lesser education, and lower income were associated with reduced likelihood of CPR training. These findings illustrate important gaps in US CPR education and suggest the need to develop tailored CPR training efforts to address this variability.


Effect of aspirin desensitization on T-cell cytokines and plasma lipoxins in aspirin-exacerbated respiratory disease.
The pathogenesis of aspirin-exacerbated respiratory disease (AERD) is thought to be based on, mainly, overproduction of eicosanoid lipid mediators and on defective anti-inflammatory regulators. Aspirin desensitization treatment, the mainstay of controlling asthma and rhinitis in AERD patients, however, is the least understood aspect of the disease. The study was designed to determine the effect of aspirin desensitization on T-lymphocyte cytokine expression and on plasma lipoxin levels in AERD. Spirometry, skin-prick test and asthma control test were documented and intracellular cytokine expression in T lymphocytes and plasma lipoxin levels were measured in 23 AERD patients, 17 aspirin-tolerant asthmatic (ATA) patients, and 16 healthy controls. In the AERD group nasal symptom and smell scores were assessed. Of the 23 AERD patients 15 accepted to undergo aspirin desensitization protocol and 14 of them were desensitized successfully. In the desensitized AERD group, cytokine and lipoxin measurements were repeated after 1-month aspirin treatment. CD4(+) IL-10 levels were higher in AERD patients than in healthy controls and CD4(+) interferon (IFN) gamma levels were higher in AERD and ATA patients than in controls. Plasma lipoxin-A4 and 15-epi-lipoxin-A4 levels were similar among the three study groups. In the AERD group, subjects underwent aspirin desensitization followed by a 1-month aspirin treatment. Clinical parameters improved and CD4(+) IFN-gamma levels decreased significantly. No significant change in lipoxin levels was recorded. CD4(+) IFN-gamma and CD4(+) IL-10 levels in AERD patients after 1-month aspirin desensitization treatment were similar to the healthy controls. The study confirms aspirin desensitization is effective clinically in AERD patients and suggests that IFN gamma and IL-10 expression in CD4(+) T lymphocytes may be related to the mechanism of action.


Age, tumour stage, and preoperative serum albumin level are independent predictors of mortality after radical cystectomy for treatment of bladder cancer in Hong Kong Chinese.
To evaluate the association between patient age, other clinical factors and mortality following radical cystectomy for treatment of bladder cancer. Historical cohort study. A urology unit in Hong Kong. The outcomes of 117 patients who had radical cystectomies performed in one urological unit from 2003 to 2011 were reviewed. Demographic and perioperative data, including tumour stage, Charlson Comorbidity Index, and preoperative serum albumin levels were retrieved from computerised medical records. Risk factors for 30-day mortality, and cancer-specific, other-cause, and overall death rates at 5 years were calculated. The data were subsequently stratified and analysed according to age. Of the 117 patients, 83 (71%) were aged 75 years or below. The mean follow-up duration was 31 (standard deviation, 29) months. Age, tumour stage, and preoperative serum albumin level, but not the Charlson Comorbidity Index, were found to be predictors of survival following radical cystectomy. The overall 30-day mortality rate was 3% in the full sample, 1% in patients aged 75 years or below, and 10% in patients aged over 75 years. There was no significant difference in 5-year cancer-caused mortalities between patients aged 75 years or below and those aged over 75 years (33% vs 33%, P=0.956). In patients older than 75 years, the 5-year other-cause and overall mortality rates were 47% and 80%, respectively; such rates were higher than those for younger patients (13% and 46%, respectively). Age, tumour stage, and preoperative serum albumin level were predictors of survival after radical cystectomy. Non-cancer-related death played a crucial role in the overall mortality rate in elderly patients having radical cystectomy for bladder cancer.


Resistance of T-cells to apoptosis in autoimmune diabetic (NOD) mice is increased early in life and is associated with dysregulated expression of Bcl-x.
Activated lymphocytes of autoimmune non-obese diabetic (NOD) mice exhibit an increased resistance to programmed cell death (PCD) following withdrawal of interleukin-2 (IL-2). In the present study, we found that resistance of NOD T lymphocytes to PCD was increased as early as 1 week of age, hence several weeks before the invasion of the pancreas by inflammatory cells, which is compatible with a role of the NOD apoptotic phenotype in the autoimmune susceptibility of this strain. In the thymus, mature single positive but not double positive or double negative thymocytes were more resistant to PCD in NOD compared to B6 mice. Moreover, in both NOD and B6 mice, CD4+ T cells were more resistant to PCD induced by IL-2 deprivation than CD8+ cells. As a result, NOD CD4+ T cells were remarkably resistant to cell death induced in this manner. In relation with this increased resistance to apoptosis, expression of the anti-apoptotic Bcl-x protein was upregulated in activated T cells of NOD mice, most notably after 24 h of IL-2 deprivation. These results should help us to understand the relationship of the NOD apoptotic phenotype to the emergence of the NOD mouse autoimmune disease.


Fast growers sprint slower: effects of food deprivation and re-feeding on sprint swimming performance in individual juvenile European sea bass.
While many ectothermic species can withstand prolonged fasting without mortality, food deprivation may have sublethal effects of ecological importance, including reductions in locomotor ability. Little is known about how such changes in performance in individual animals are related to either mass loss during food deprivation or growth rate during re-feeding. This study followed changes in the maximum sprint swimming performance of individual European sea bass, Dicentrarchus labrax, throughout 45 days of food deprivation and 30 days of re-feeding. Maximum sprint speed did not show a significant decline until 45 days of food deprivation. Among individuals, the reduction in sprinting speed at this time was not related to mass loss. After 30 days of re-feeding, mean sprinting speed had recovered to match that of control fish. Among individuals, however, maximum sprinting speed was negatively correlated with growth rate after the resumption of feeding. This suggests that the rapid compensatory growth that occurs during re-feeding after a prolonged fast carries a physiological cost in terms of reduced sprinting capacity, the extent of which shows continuous variation among individuals in relation to growth rate. The long-term repeatability of maximum sprint speed was low when fish were fasted or fed a maintenance ration, but was high among control fish fed to satiation. Fish that had been previously food deprived continued to show low repeatability in sprinting ability even after the initiation of ad libitum feeding, probably stemming from variation in compensatory growth among individuals and its associated negative effects on sprinting ability. Together, these results suggest that food limitation can disrupt hierarchies of maximum sprint performance within populations. In the wild, the cumulative effects on locomotor capacity of fasting and re-feeding could lead to variable survival among individuals with different growth trajectories following a period of food deprivation.


Mechanism involved in insulin resistance via accumulation of β-amyloid and neurofibrillary tangles: link between type 2 diabetes and Alzheimer's disease.
The pathophysiological link between type 2 diabetes mellitus (T2DM) and Alzheimer's disease (AD) has been suggested in several reports. Few findings suggest that T2DM has strong link in the development process of AD, and the complete mechanism is yet to be revealed. Formation of amyloid plaques (APs) and neurofibrillary tangles (NFTs) are two central hallmarks in the AD. APs are the dense composites of β-amyloid protein (Aβ) which accumulates around the nerve cells. Moreover, NFTs are the twisted fibers containing hyperphosphorylated tau proteins present in certain residues of Aβ that build up inside the brain cells. Certain factors contribute to the aetiogenesis of AD by regulating insulin signaling pathway in the brain and accelerating the formation of neurotoxic Aβ and NFTs via various mechanisms, including GSK3β, JNK, CamKII, CDK5, CK1, MARK4, PLK2, Syk, DYRK1A, PPP, and P70S6K. Progression to AD could be influenced by insulin signaling pathway that is affected due to T2DM. Interestingly, NFTs and APs lead to the impairment of several crucial cascades, such as synaptogenesis, neurotrophy, and apoptosis, which are regulated by insulin, cholesterol, and glucose metabolism. The investigation of the molecular cascades through insulin functions in brain contributes to probe and perceive progressions of diabetes to AD. This review elaborates the molecular insights that would help to further understand the potential mechanisms linking T2DM and AD.


Identification and characterisation of capidermicin, a novel bacteriocin produced by Staphylococcus capitis.
One hundred human-derived coagulase negative staphylococci (CoNS) were screened for antimicrobial activity using agar-based deferred antagonism assays with a range of indicator bacteria. Based on the findings of the screen and subsequent well assays with cell free supernatants and whole cell extracts, one strain, designated CIT060, was selected for further investigation. It was identified as Staphylococcus capitis and herein we describe the purification and characterisation of the novel bacteriocin that the strain produces. This bacteriocin which we have named capidermicin was extracted from the cell-free supernatant of S. capitis CIT060 and purified to homogeneity using reversed-phase high performance liquid chromatography (RP-HPLC). Matrix-assisted laser desorption/ionization time-of-flight (MALDI-TOF) mass spectrometric (MS) analysis revealed that the capidermicin peptide has a mass of 5,464 Da. Minimal inhibitory concentration (MIC) experiments showed that capidermicin was active in the micro-molar range against all the Gram-positive bacteria that were tested. Antimicrobial activity was retained over a range of pHs (2-11) and temperatures (10-121°C x 15 mins). The draft genome sequence of S. capitis CIT060 was determined and the genes predicted to be involved in the biosynthesis of capidermicin were identified. These genes included the predicted capidermicin precursor gene, and genes that are predicted to encode a membrane transporter, an immunity protein and a transcriptional regulator. Homology searches suggest that capidermicin is a novel member of the family of class II leaderless bacteriocins.


Spironolactone decreases DOCA-salt-induced organ damage by blocking the activation of T helper 17 and the downregulation of regulatory T lymphocytes.
Adaptive immune response has been implicated in inflammation and fibrosis as a result of exposure to mineralocorticoids and a high-salt diet. We hypothesized that in mineralocorticoid-salt-induced hypertension, activation of the mineralocorticoid receptor alters the T-helper 17 lymphocyte (Th17)/regulatory T-lymphocyte/interleukin-17 (IL-17) pathway, contributing to cardiac and renal damage. We studied the inflammatory response and tissue damage in rats treated with deoxycorticosterone acetate and high-salt diet (DOCA-salt), with or without mineralocorticoid receptor inhibition by spironolactone. To determine whether Th17 differentiation in DOCA-salt rats is caused by hypertension per se, DOCA-salt rats received antihypertensive therapy. In addition, to evaluate the pathogenic role of IL-17 in hypertension and tissue damage, we studied the effect of IL-17 blockade with a specific antibody (anti-IL-17). We found activation of Th17 cells and downregulation of forkhead box P3 mRNA in peripheral tissues, heart, and kidneys of DOCA-salt-treated rats. Spironolactone treatment prevented Th17 cell activation and increased numbers of forkhead box P3-positive cells relative to DOCA-salt rats. Antihypertensive therapy did not ameliorate Th17 activation in rats. Treatment of DOCA-salt rats with anti-IL-17 significantly reduced arterial hypertension as well as expression of profibrotic and proinflammatory mediators and collagen deposits in the heart and kidney. We conclude that mineralocorticoid receptor activation alters the Th17/regulatory T-lymphocyte/IL-17 pathway in mineralocorticoid-dependent hypertension as part of an inflammatory mechanism contributing to fibrosis.


Concurrent Mild Traumatic Brain Injury and Posttraumatic Stress Disorder Is Associated With Elevated Tau Concentrations in Peripheral Blood Plasma.
Concurrent mild traumatic brain injury (mTBI) and posttraumatic stress disorder (PTSD) are common in U.S. military service members and veterans. Tau and amyloid-beta-42 (Aβ42) are proteins that have been linked to cognitive impairment, neurological hallmarks of Alzheimer's disease, and may also relate to recovery from mTBI. However, the role of these proteins in the maintenance or resolution of chronic symptoms has not yet been determined. Participants in the current study were 102 service members and veterans who had sustained an mTBI (n = 84) or injured controls (IC) without TBI (n = 18). They were categorized into three groups based on the presence or absence of mTBI and PTSD: IC/PTSD-Absent (n = 18), mTBI/PTSD-Absent (n = 63), and mTBI/PTSD-Present (n = 21). Concentrations of tau and Aβ42 in peripheral blood plasma were measured using SimoaTM , an ultrasensitive technology, and compared across groups. Tau concentrations were highest in the mTBI/PTSD-Present group, F(2, 99) = 4.33, p = .016, compared to the other two groups. Linear multiple regression was conducted to determine the independent effects of PTSD and mTBI on tau concentrations, controlling for gender and sleep medication. PTSD was a significant and independent predictor of tau concentrations, β = .25, p = .009, ηp 2 = .26. Aβ42 concentrations did not differ between the groups. The results indicated that PTSD was associated with an elevation of tau in peripheral blood and suggest that there may be increased biological effects of PTSD in this young cohort of service members and veterans following mTBI.


Sac behavior after aneurysm treatment with the Gore Excluder low-permeability aortic endoprosthesis: 12-month comparison to the original Excluder device.
The original Gore Excluder endoprosthesis (OGE) used both during and briefly after clinical trials was associated with less sac regression and more sac growth than some other devices, even without apparent endoleaks, presumably because of transmural movement of serous fluid across the expanded polytetrafluoroethylene material. In July 2004, the device was modified to decrease graft permeability. This study evaluated the efficacy of the new Excluder Low-Permeability Device (ELPD) at 1 year and compared it with the OGE and the Cook Zenith device (ZEN). From Food and Drug Administration approval of the Excluder in November 2002 until June 2005, 283 patients underwent endovascular repair of abdominal aortic aneurysms with the Gore Excluder or the ZEN. Postoperative surveillance included computed tomographic scans at 1 and 12 months; 181 (64%) patients completed both scans. The 1-month computed tomographic scan served as a baseline, and the minor axis diameter, measured at the largest axial cut of the abdominal aortic aneurysm, was compared with the same measurement at 1 year. A sac size change of 5 mm or more was considered significant. Sixty patients treated with the OGE were compared with 72 patients treated with the ELPD. Forty-nine patients treated during the same time period with the ZEN, known for early sac shrinkage, were used as a reference. All measurements were performed by one observer from a digital workstation. Wilcoxon signed rank tests (pairwise) or Kruskal-Wallis tests (three groups) were used for intergroup comparison of continuous variables, whereas chi2 statistics or Fisher exact tests were used to compare categorical variables. Patient age and sex and mean maximum aneurysm diameter at baseline were similar among groups (P = .59, .27, and .46, respectively). Graft migration, stent fractures, acute surgical conversion, late abdominal aortic aneurysm rupture, or aneurysm-related deaths were not observed. Type II endoleak rates were similar between ELPD and ZEN (23.6% and 20.4%; P = .68). Although a higher rate of endoleaks was seen with OGE (36.7%), this was not significant when compared with the other two devices (P = .11). At 1 year, patients treated with ELPD had a sac regression rate that was significantly higher than that for patients treated with OGE (63.9% vs 25%; P < 0.001) and was similar to that for patients treated with ZEN (65.3%). Significant sac expansion was not observed with ELPD. At 1 year, similar to ZEN, significant aneurysm sac regression and minimal sac expansion were noted after endovascular repair of abdominal aortic aneurysms with ELPD. Low-porosity fabric used in the construction of endoprostheses seems to be an important factor in early aneurysm sac shrinkage. Long-term efficacy regarding the prevention of sac enlargement remains unclear, and further follow-up is suggested.


Long-term outcomes in patients with high-risk myeloid malignancies following matched related donor hematopoietic cell transplantation with myeloablative conditioning of BU, etoposide and CY.
Patients with high-risk or advanced myeloid malignancies have limited effective treatment options. These include high-dose therapy followed by allogeneic hematopoietic cell transplantation (HCT). We report a single-institution, long-term follow-up of 96 patients, median age 50 (range, 20-60) years, who received HLA-matched related HCT between 1992 and 2007. All patients were treated with a uniform preparatory regimen intended to enhance the widely used regimen of BU and CY that included: BU 16.0 mg/kg (days -8 to -5), etoposide 60 mg/kg (day -4), CY 60 mg/kg (day -2) with GVHD prophylaxis of CsA or FK506 and prednisone. Disease status at transplantation was high-risk AML (n=41), CML in second chronic phase or blast crisis (n=8), myelofibrosis and myeloproliferative disorders (n=8), and myelodysplasia (n=39). Thirty-six percent (n=35) of patients received BM whereas 64% (n=61) received G-CSF-mobilized PBPC. With a median follow-up of 5.6 years (range, 1.6-14.6 years) actuarial 5-year OS was 32% (95% CI 22-42) and 5-year EFS was 31% (95% CI 21-41). Relapse rate was 24% (95% CI 15-33) at 2 and 5 years. Nonrelapse mortality was 29% (95% CI 20-38) at day 100 and 38% (95% CI 29-47) at 1 year. Cumulative incidence of acute (grade II-IV) and extensive chronic GVHD was 27% (95% CI 18-36) and 29% (95% CI 18-40), respectively. There was no statistically significant difference in OS (31 vs 32%, P=0.89) or relapse rates (17 vs 28%, P=0.22) for recipients of BM vs PBPC, respectively. These results confirm that patients with high-risk or advanced myeloid malignancies can achieve long-term survival following myeloablative allogeneic HCT with aggressive conditioning.


Interposition flaps in vesicovaginal fistula repairs can optimize cure rate.
To report the result of vesicovaginal fistula (VVF) repair using the transabdominal approach with flap interposition. Between January 2004 and the end of 2011, operative reports data and medical records systems were reviewed for all VVF cases operated and followed in Urology Department. All patients had detailed history taking and physical exam followed by intravenous pyelograms or contrast CT abdomen and pelvis to rule out the presence of ureterovaginal fistulae. We utilized the infra-umbilical transabdominal approach and transpose an omental flap or peritoneal flap between the vaginal and bladder incisions in all cases. Twenty-six patients with an average age of 46 years were managed for VVF through transabdominal route with interposition of omental flap or peritoneal flap by a single surgeon. Twelve cases of VVF were secondary to lower segment cesarean section (LSCS) and twelve cases of VVF were secondary to lower segment cesarean section (LSCS) and 14 cases following hysterectomies. We had 16 complex VVF with 4 cases that failed the previous abdominal repair outside the hospital. More than 95% (25) of our patients were cured at the first attempt, with no recurrence at a mean follow-up of 28.6 (range 8-73) months. Successful repair of VVF depends on the experience of the surgeon and adhering to basic surgical principles. Very high success rate was seen when flap interposition had been used.


Operability, Acceptability, and Usefulness of a Mobile App to Track Routine Immunization Performance in Rural Pakistan: Interview Study Among Vaccinators and Key Informants.
There has been a recent spate of mobile health (mHealth) app use for immunizations and other public health concerns in low- and middle-income countries. However, recent evidence has largely focused on app development or before-and-after effects on awareness or service coverage. There is little evidence on the factors that facilitate adoption of mHealth programs, which is critical to effectively embed digital technology into mainstream health systems. This study aimed to provide the qualitative experiences of frontline health staff and district managers while engaging with real-time digital technology to improve the coverage of routine childhood immunization in an underserved rural district in Pakistan. An Android-based app was iteratively developed and used for a 2-year period in 11 union councils of the Tando Muhammad Khan district, an underserved rural district with poor immunization coverage in Pakistan. We used iterative methods to examine the (1) acceptability and operability of the app, (2) validity of the collected data, and (3) use of the collected data. In addition, we collected the barriers and enablers for uptake of the mHealth app. Each of these topics was further explored related to changes in work as well as the enabling factors for and barriers to app use. In-depth interviews were conducted with the 26 vaccinators posted in the 11 union councils and 7 purposively selected key informants (government district managers) involved with the Expanded Program for Immunization. Findings were triangulated in line with the three broad research areas. Digital immunization tracking was considered acceptable by vaccinators and district managers. Real-time immunization data were used to monitor vaccination volume, track children with incomplete vaccinations, develop outreach visit plans, correct existing microplans, and disburse a fuel allowance for outreach sessions. The validity of the app data was perceived to be superior to that of data from manual records. Ease of operability, satisfaction with data, personal recognition, links to field support, and a sense of empowerment served as powerful enablers. Taking twice the time to complete both manual and digital entries and outdated phones over time were considered constraints. An unintended knock-on effect was improved coordination and strengthening of Expanded Program for Immunization review platforms across district stakeholders through digitalized data. Embedding digital technology into mainstream health systems relies on use by both end users and district stakeholders. Ease of operability, satisfaction with data reliability, personal recognition, links to field support, and empowerment are powerful enablers, whereas improved coordination as a result of easy, transparent data access can be an important by-product of digitalization. Findings are relevant not only for wide-scale implementation of immunization tracking apps in Pakistan but also for informing the use of digital technology for results-based delivery by frontline health workers.


Learning an atlas of a cognitive process in its functional geometry.
In this paper we construct an atlas that captures functional characteristics of a cognitive process from a population of individuals. The functional connectivity is encoded in a low-dimensional embedding space derived from a diffusion process on a graph that represents correlations of fMRI time courses. The atlas is represented by a common prior distribution for the embedded fMRI signals of all subjects. The atlas is not directly coupled to the anatomical space, and can represent functional networks that are variable in their spatial distribution. We derive an algorithm for fitting this generative model to the observed data in a population. Our results in a language fMRI study demonstrate that the method identifies coherent and functionally equivalent regions across subjects.


A multicentre randomised assessment of the DAWN AC computer-assisted oral anticoagulant dosage program.
Computer-assisted oral anticoagulant dosage is being increasingly used to meet growing demands for oral anticoagulation. The DAWN AC is one of the most widely used computer-dosage programs. Evidence of its value and that of other computer programs has been based previously only on laboratory evidence of "time in target INR range" (TIR) not on clinical safety in practice. A five-year international randomised clinical study of computer assistance with the DAWN AC program compared with manual dosage in 2,631 patients has been performed at 13 centres with established expertise in oral anticoagulation mainly in the EU. Safety assessment have been based on the comparison of bleeding or thrombotic events with DAWN AC compared with manual dosage in a randomised study. Safety of the DAWN AC program has been demonstrated. Clinical events of bleeding and thrombosis were almost identical with the experienced manual dosage group. Therapeutic control improved with DAWN AC to 66.8% from 63.4% TIR. The program failed to provide a dosage recommendation on only 5.7% of occasions. At a group of experienced centres with a special interest in oral anticoagulation, the DAWN AC computer-dosage program proved as safe clinically as manual dosage by experienced medical staff. With DAWN AC, laboratory control was improved, the difference being highly significant. The results should reassure hospitals and community clinics that the DAWN AC program is safe and facilitate greater and longer provision of warfarin treatment where required.


Effect of N-(n-butyl) thiophosphoric triamide and 3,4 dimethylpyrazole phosphate on gaseous emissions from grasslands under different soil water contents.
The intensification of grassland systems is leading to serious environmental risks due to the large input of nitrogen (N) in fertilizers and the subsequent gaseous losses. Addition of nitrification inhibitors (NI) or urease activity inhibitors to fertilizers could reduce these losses to the atmosphere. In the present study, the effects of the nitrification inhibitor 3,4-dimethylpyrazole phosphate (DMPP) and the urease activity inhibitor N-(n-butyl) thiophosphoric triamide (NBPT) were evaluated on NH3, N2O, NO, and CO2 emissions. Ammonium sulphate nitrate (ASN), urea and cattle slurry were applied at a rate of 70 kg N ha(-1) to a mixed clover-ryegrass sward in the Basque Country (northern Spain) under different soil water contents. NH3 and NO emissions were determined by photoacoustic and chemiluminescence respectively using an open chamber technique while N2O and CO2 emissions were measured by photoacoustic using a closed chamber technique. When the water filled pore space (WFPS) was under 60%, the application of NBPT reduced NO emissions a 34% on urea and an 18% on slurry, and the application of DMPP reduced them a 2% on ASN and a 4% on slurry. No significant effect was observed on NH3 losses. When WFPS was over 60%, no effect could be observed on NO and N2O emissions after the application of both inhibitors, but NH3 losses were reduced a 31% by NBPT when applied with the slurry. Carbon dioxide emissions were unaffected by the use of DMPP or NBPT at any soil water content. Neither grassland yield nor herbage N concentration were influenced by the application of both inhibitors.


Amelioration of some immunological disorders caused by the faeces of the dominant true house dust mites in El-Minia Governorate, Egypt.
House dust mites (HDMs) faeces are the main factor involved in respiratory disorder. The true HDMs, Dermatophagoides pteronyssinus and D. farinae, detected in the samples collected from the house dust are the most important causes of allergic disorders such as asthma. The aim of this investigation was to study the curcuma and karkade amelioration of the allergenic immunological disorder, especially some cytokines, IgE and ROS, caused by the faeces of the dominant true HDM, D. pteronyssinus and D. farinae in valley and desert houses in EL-Minia Governorate, respectively. HDM cultures, faeces isolation, plant extraction and ELISA techniques were used. Male albino rats were classified into control, inhaled, and treated groups. The present immunological study on the dominant allergenic true HDMs, D. pteronyssinus and D. farinae, revealed that significantly higher serum levels of TNF-α, IL-1β, IL-4, IL-13 and IgE were found in rats treated with both D. pteronyssinus and D. farinae faeces than the other groups. In addition, statistical analysis of ROS data showed significant difference between the curcuma- and karkade-treated groups and either the control or the faeces-treated groups (P<0.05). Some immunological disturbances caused by repeated exposure to the faeces of two dominant allergenic true HDM species (D. pteronyssinus and D. farinae) in the valley and desert houses could be ameliorated by curcuma and karkade.


A review of the effects of Capsicum annuum L. and its constituent, capsaicin, in metabolic syndrome.
Metabolic syndrome, a coexisting of high blood glucose, obesity, dyslipidemia and hypertension, is an important risk factor for cardiovascular disease occurrence and mortality. Recently, there is a rising demand for herbal drugs which have less adverse effects and have shown more beneficial effects in comparison with synthetic options. Red pepper, with the scientific name of Capsicum annuum, belongs to the Solanaceae family. The lipid-lowering, antihypertensive, antidiabetic and anti-obesity effects of C. annuum have been demonstrated in several studies. In this review, we summarized different animal and human studies on the effect of red pepper and capsaicin on different components of metabolic syndrome which are risk factors for cardiovascular diseases (CVDs). According to these studies, red pepper as well as capsaicin has ability to control of metabolic syndrome and its related disorders such as obesity, disrupted lipid profile, diabetes and its complications. Red pepper has beneficial effects on metabolic syndrome and can decrease the risk of mortality due to cardiovascular diseases, but still more research projects need to be done and confirm its advantageous especially in humans.


T-cell clonality assays: how do they compare?
The distinction between certain benign cutaneous lymphocytic infiltrates and cutaneous T-cell lymphoma (CTCL) can be a challenging problem in clinical practice. An imperfect but useful tool in this circumstance is the analysis of T-cell clonality or monoclonality by assessing T-cell receptor (TCR) gene rearrangements. "Monoclonality" describes the origin of a specific human malignant tumor from one single cell from which the entire tumor is derived. The term is used to describe the early steps in tumorigenesis; in later stages of tumor growth and progression, monoclonal tumor cells may acquire a mutator phenotype, rendering the genome unstable. The resulting genetic heterogeneity may ultimately lead to subclones in the formerly monoclonal population of tumor cells.


A fluid-filled soft robot that exhibits spontaneous switching among versatile spatiotemporal oscillatory patterns inspired by the true slime mold.
Behavioral diversity is an essential feature of living systems, enabling them to exhibit adaptive behavior in hostile and dynamically changing environments. However, traditional engineering approaches strive to avoid, or suppress, the behavioral diversity in artificial systems to achieve high performance in specific environments for given tasks. The goals of this research include understanding how living systems exhibit behavioral diversity and using these findings to build lifelike robots that exhibit truly adaptive behaviors. To this end, we have focused on one of the most primitive forms of intelligence concerning behavioral diversity, namely, a plasmodium of true slime mold. The plasmodium is a large amoeba-like unicellular organism that does not possess any nervous system or specialized organs. However, it exhibits versatile spatiotemporal oscillatory patterns and switches spontaneously between these. Inspired by the plasmodium, we built a mathematical model that exhibits versatile oscillatory patterns and spontaneously transitions between these patterns. This model demonstrates that, in contrast to coupled nonlinear oscillators with a well-designed complex diffusion network, physically interacting mechanosensory oscillators are capable of generating versatile oscillatory patterns without changing any parameters. Thus, the results are expected to shed new light on the design scheme for lifelike robots that exhibit amazingly versatile and adaptive behaviors.


Aquaporin-8 is involved in water transport in isolated superficial colonocytes from rat proximal colon.
Water is an essential nutrient because it must be introduced from exogenous sources to satisfy metabolic demand. Under physiologic conditions, the colon can absorb and secrete considerable amounts of water even against osmotic gradients, thus helping to maintain the body fluid balance. Here we describe studies on both aquaporin (AQP) expression and function using cells isolated from the superficial and lower crypt regions of the rat proximal colon. The expression of AQP-3, -4, and -8 in isolated colonocytes was determined by semiquantitative RT-PCR and by immunoblotting. The localization of AQP-8 in the colon was evaluated by immunohistochemistry. A stopped-flow light scattering method was used to examine osmotic water movement in isolated colonocytes. Moreover, the contribution of AQP-8 to overall water movement through isolated colonocytes was studied using RNA interference technology. Colonocytes from the proximal colon express AQP-3, -4, and -8 with increasing concentrations from the lower crypt cells toward those on the surface. Osmotic water permeability was higher in surface than in crypt colonocytes (P < 0.05); it was significantly inhibited by the water channel blocker dimethyl sulfoxide, and reversed by beta-mercaptoethanol (P < 0.05). Immunohistochemistry revealed a strong AQP-8 labeling in the apical membrane of the superficial colonocytes. Inhibition of aquaporin-8 expression by small interfering RNA significantly decreased osmotic water permeability (approximately 38%; P < 0.05). Current results indicate that aquaporin-8 may play a major role in water movement through the colon by acting on the apical side of the superficial cells.


Genetic testing: costs and access to intensive care unit care.
Critically ill patients require significant medical care and use limited healthcare resources. Furthermore, the mortality rate from most forms of critical illness is much higher than for noncritically ill hospitalized patients. Although genetic diseases increase mortality, most are easily identified at birth and have only limited treatments and prognoses. Recently, more subtle single nucleotide polymorphisms at key loci have been demonstrated to result in a profoundly different prevalences of acute illness and subsequent survival rates for subjects with apparently similar insults and otherwise similar phenotypes. With the maturation of the human genome project, this new discovery will allow for the characterization of individual subject's responsiveness and potential for recovery from a number of insults. This realization makes our definition of genetic diseases blurred and begs the questions, "Will these new insights allow for more effective healthcare resource utilization, as defined from patient, healthcare system, and societal perspectives?" and, perhaps more worrisome, "Should intensive care resources be limited to those with the greatest chance of benefit?" Similarly, as with other genetic predispositions such as cystic fibrosis and congenital hypercholesterolemia, to what extent should these data be available outside the patient-doctor relationship?


High blood pressure during pregnancy is associated with future cardiovascular disease: an observational cohort study.
The study aimed to determine if having a hypertensive disorder of pregnancy (HDP) is a risk factor for future cardiovascular disease (CVD), independent of age and body mass index (BMI). Data were sourced from the baseline questionnaire of the 45 and Up Study, Australia, an observational cohort study. Participants were randomly selected from the Australian Medicare Database within New South Wales. A total of 84 619 women were eligible for this study, of which 71 819 were included. These women had given birth between the ages of 18 and 45 years, had an intact uterus and ovaries, and had not been diagnosed with high blood pressure prior to their first pregnancy. HDP was associated with higher odds of having high blood pressure (<58 years: adjusted OR 3.79, 99% CI 3.38 to 4.24; p<0.001 and ≥58 years: 2.83, 2.58 to 3.12; p<0.001) and stroke (<58 years: 1.69, 1.02 to 2.82; p=0.008 and ≥58 years: 1.46, 1.13 to 1.88; p<0.001) in later life. Women with HDP had a younger age of onset of high blood pressure (45.6 vs 54.8 years, p<0.001) and stroke (58 vs 62.5 years, p<0.001). Women who had HDP and whose present day BMI was <25 had significantly higher odds of having high blood pressure, compared with women who were normotensive during pregnancy (<58 years: 4.55, 3.63 to 5.71; p<0.001 and ≥58 years, 2.94, 2.49 to 3.47; p<0.001). Women who had HDP and a present day BMI≥25 had significantly increased odds of high blood pressure (<58 years: 12.48, 10.63 to 14.66; p<0.001 and ≥58 years, 5.16, 4.54 to 5.86; p<0.001), compared with healthy weight women with a normotensive pregnancy. HDP is an independent risk factor for future CVD, and this risk is further exacerbated by the presence of overweight or obesity in later life.


Multiparametric analysis of immature cell populations in umbilical cord blood and bone marrow.
Adult stem cells are finding increased therapeutic potential not least in tissue regeneration protocols. The cell sources being proposed for such protocols include embryonic, umbilical cord blood (CB) and adult bone marrow (BM). Although embryonic sources are controversial, CB and marrow are available immediately. The appropriate cells of use in these sources are considered to be extremely rare and a characterisation of the starting cell source is important for the development of adult stem cell protocols and ex vivo expansion. Umbilical CB and BM mononuclear cells were labelled for the antigens CD34, CD133, CD117, CD164, Thy-1 or CD38, and additional intracellular CD34 antigen. Three dimensional flow-cytometric analyses were carried out together with dual laser confocal microscope analysis for antigen profile expression. Variable levels of immaturity were detected on CB and BM populations using internal and external CD34 antigen. For CB and BM cells, internal CD34 (intCD34+) could be detected on co-expressing CD133+ cells before expression of external CD34 antigen (extCD34+). CD38 co-expression analysis also showed that a small but distinct group of cells expressing low CD38 and no external CD34 antigen could be detected. Additional phenotyping of these cells using CD117, Thy-1, CD164 and CD133 demonstrated variable primitive status detectable within the external CD34- population. Newly harvested primary CB and BM populations were shown to contain not only cellular populations of known standard sequential maturity but also populations of more extreme rarity. The presence of cells which lacked extracellular CD34 antigen, in both CB and BM, but which possessed CD133, has important implications for purification of human stem cells in clinical applications.


Risk Factors for Posttracheostomy Tracheal Stenosis.
Objective To determine the incidence of posttracheostomy tracheal stenosis and to investigate variables related to the patient, hospitalization, or operation that may affect stenosis rates. Study Design A combined retrospective cohort and case-control study. Setting Tertiary care academic medical center. Subjects and Methods A total of 1656 patients who underwent tracheostomy at a tertiary care medical center from January 2011 to November 2016 were reviewed for evidence of subsequent tracheal stenosis on airway endoscopy or computed tomography. Forty-three confirmed cases of posttracheostomy tracheal stenosis (PTTS) were compared with a subgroup of 319 controls. Factors including medical comorbidity, type and setting of tracheostomy, and hospitalization details were analyzed. Results Five-year incidence of PTTS was 2.6%. Obesity was the sole demographic factor associated with stenosis. Hospitalization-related variables associated with stenosis included tracheostomy after 10 days of orotracheal intubation and endotracheal tube cuff pressure ≥30 mm H2O. The surgical variables associated with higher rates of stenosis included percutaneous technique and insertion of an initial tracheostomy tube size >6. Bjork flap creation was negatively associated with stenosis. In multivariable analysis, obesity and insertion of tracheostomy tube size >6 were identified as risk factors. Conclusion Greater than 10 days of orotracheal intubation prior to tracheostomy and endotracheal tube cuff pressure ≥30 mm H2O were associated with greater rates of subsequent tracheal stenosis. The only patient-related factor associated with tracheal stenosis was obesity. Surgical variables associated with increased rates of subsequent stenosis included placement of a tracheostomy tube size >6, use of percutaneous technique, and failure to create a Bjork flap.


Factors which influence the consumption of street foods and fast foods in South Africa--a national survey.
Very little is known about street food and fast food consumption patterns in South Africa despite this being a large sector of the national economy in terms of employment provided and sales of food. The objective of this study was to determine the use of street foods and fast foods purchased by South Africans living in different provinces and geographic areas. A cross-sectional survey was conducted. Structured interview-administered questionnaires in 11 official languages were conducted at the participants' homes. A nationally representative sample (n = 3287) was drawn from all ethnic groups, and provinces including participants 16 years and older. Logistic regression was done to evaluate factors impacting on fast food consumption. Frequent (2 ≥ times/week) street food consumption ranged from 1.8% in Northern Cape to 20.6% in Limpopo; frequent (2 ≥ times/week) fast food consumption ranged between 1.5% in North West Province to 14.7% in Gauteng. The highest intake of street food was in the medium socio-economic category (14.7%) while the highest intake of fast foods was in the high socio-economic category (13.2%). Overall, fruit was the most commonly purchased street food by all ethnic groups over the previous week although this practice was highest in black participants (35.8%). Purchases of soft drinks ranged from 4.8% in whites to 16.4% in blacks and savoury snacks from 2.3% to 14.5% in whites and blacks, respectively. Consumption of fast foods and street foods were influenced by a number of socio-demographic factors including ownership of major home appliances. Frequent fast food consumers had a significantly higher dietary diversity score (4.69; p < 0.0001) while frequent street food consumers had a significantly lower score (3.81; p < 0.0001). A large percentage of the population purchase street foods and fast foods. This is of some concern when one notes the high prevalence of soft drink consumption in terms of its association with obesity and non-communicable diseases. These findings need to be taken into consideration when evaluating dietary patterns and nutritional adequacy of population diets.


Association of catechol-O-methyltransferase variants with loudness dependence of auditory evoked potentials.
The loudness dependence of auditory evoked potentials (LDAEP) provides a measure of the central serotonergic activity. As dopamine transporter availabilities also correlate with LDAEP, a dopaminergic influence is probable. The enzyme catechol-O-methyltransferase (COMT) is involved in the inactivation of synaptic dopamine. The aim of this study was to investigate the relationship between genetic variants of the COMT gene influencing synaptic dopamine levels and the LDAEP. Rs737865 in intron 1, rs4680 coding for a Val158Met substitution and rs165599 in the 3' region were investigated in 95 carefully selected healthy subjects of German descent (41 males, 54 females). The LDAEP was calculated as a linear regression slope with stimulus intensity as independent and N1/P2-amplitude as dependent variables. Single marker analysis showed weak associations for two single nucleotide polymorphisms (SNPs) (rs737865: CC vs. T allele carrier; rs4680: G-allele carrier vs. AA homozygotes). A-G (rs4680-rs165599) was associated with lower LDAEP scores. Accordingly, haplotype analysis with all SNPs (rs737865-rs4680-rs165599) showed that the T-A-G haplotype was associated with lower scores. These findings support the hypothesis that the LDAEP is also influenced by dopaminergic transmission. However, replications of these very preliminary but potentially important findings in independent samples are needed.


Inclusion of Platinum Agents in Neoadjuvant Chemotherapy Regimens for Triple-Negative Breast Cancer Patients: Development of GRADE (Grades of Recommendation, Assessment, Development and Evaluation) Recommendation by the Italian Association of Medical Oncology (AIOM).
In the absence of identified therapeutic targets, chemotherapy is the main systemic treatment option for triple-negative breast cancer (TNBC). The achievement of a pathological complete response (pCR) after neoadjuvant chemotherapy leads to good outcome, whereas patients not achieving a pCR are at high risk of relapse. Various trials have evaluated the inclusion of platinum in neoadjuvant chemotherapy regimens for TNBC, leading to non-univocal results. The panel of the Italian Association of Medical Oncology (AIOM) Guidelines on Breast Cancer developed a clinical recommendation on the addition of platinum to anthracycline/taxane-based neoadjuvant chemotherapy for TNBC by using the Grades of Recommendation, Assessment, Development, and Evaluation (GRADE) methodology and the Evidence to Decision framework (EtD). Five studies were eligible. The panel identified the following outcomes of benefit: pCR (critical), disease/event-free survival (DFS/EFS, critical), and overall survival (OS, critical). The panel identified febrile neutropenia (critical), serious adverse events (critical), anemia grade 3-4 (important), thrombocytopenia grade 3-4 (important) as outcomes of harms. The probability of pCR was higher in the platinum-based chemotherapy group versus control group (RR = 1.45, 95%CI 1.28-1.64); however, no impact on long-term outcome was observed. Neoadjuvant treatment regimens containing platinum resulted in a non-significant increase in the risk of febrile neutropenia and in a significant increase in the risk serious adverse events, G3-G4 anemia and G3-G4 thrombocytopenia: 11.3% versus 0.8%, RR = 15.66 (95%CI 6.38-38.44). The panel judged uncertain/favorable the benefit/harms balance. The panel's final recommendation was conditional in favor of the inclusion of platinum in anthracycline/taxane-based neoadjuvant regimens for TNBC.


Ideal free distribution of fixed dispersal phenotypes in a wing dimorphic beetle in heterogeneous landscapes.
According to the ideal free distribution (IFD) theory, individuals that are able to perceive the quality of different patches in a landscape and disperse freely are expected to redistribute themselves proportionally to the carrying capacities of heterogeneous patches. Here, we argue that, when dispersal is unconditional and genetically fixed, a coalition of sedentary and dispersing phenotypes can attain an IFD under spatiotemporally uncorrelated variation in fitness. This not only leads to a stable polymorphism of both dispersal phenotypes, but also implies that the number of dispersing individuals should on average be equal among patches and determined by the carrying capacity of the smallest local populations in the landscape. Differences in carrying capacity among patches are thus only reflected by changes in the number of sedentary individuals. Individual-based simulations show that this mechanism can be generalized over a wide range of spatiotemporal conditions and dispersal strategies. Moreover, these expectations are in strong agreement with empirical data on the density of both dispersal phenotypes of the wing dimorphic ground beetle Pterostichus vernalis within and among 10 different landscapes. Hence, for the first time, these results demonstrate that this mechanism serves as a plausible alternative to the competition-colonization model to explain the spatial distribution of fixed dispersal phenotypes in heterogeneous landscapes. Understanding of the frequency distributions of individuals expressing discrete dispersal morphs moreover improves our predictive and management capabilities for a broad range of species, for which we currently typically rely on using mean dispersal rates.


The Impact of Verapamil Gel on Efficiency of Tissue Expander Device in Plastic and Reconstructive Surgery.
One of the weaknesses of recovering the skin defects by tissue expander device is that it needs relatively long time and it has complications. Since verapamil gel reduces the production of these capsules around silicone prosthesis and reduces the formation of collagen in the capsule areas. The aim of this study was to examine the effect of verapamil gel on efficiency of tissue expander device. Twenty patients were allocated equally into control and case groups based on age, sex, and location of the device. In both groups, the devices were placed in the areas needed and the conditions were identical. During the first operation, the length and width of the flaps and the initial size of prosthesis were determined. In the case group, verapamil gel was used daily, while a hydrogel was used as placebo locally in the control group. Then, other indicators were assessed. Verapamil gel had no impact on the length, width, area, and size of placed flaps. The opening degree and necrosis of tissue were not improved in patients of case group after using the gel. The effect of verapamil gel in different age groups and gender of people had no significant difference. Verapamil gel was shown not to have any significant impact on efficiency of tissue expander device.