Wild plant species growing closely connected in a subalpine meadow host distinct root-associated bacterial communities.
Plant roots are known to harbor large and diverse communities of bacteria. It has been suggested that plant identity can structure these root-associated communities, but few studies have specifically assessed how the composition of root microbiota varies within and between plant species growing under natural conditions. We assessed the community composition of endophytic and epiphytic bacteria through high throughput sequencing using 16S rDNA derived from root tissues collected from a population of a wild, clonal plant (Orange hawkweed-Pilosella aurantiaca) as well as two neighboring plant species (Oxeye daisy-Leucanthemum vulgare and Alsike clover-Trifolium hybridum). Our first goal was to determine if plant species growing in close proximity, under similar environmental conditions, still hosted unique root microbiota. Our results showed that plants of different species host distinct bacterial communities in their roots. In terms of community composition, Betaproteobacteria (especially the family Oxalobacteraceae) were found to dominate in the root microbiota of L. vulgare and T. hybridum samples, whereas the root microbiota of P. aurantiaca had a more heterogeneous distribution of bacterial abundances where Gammaproteobacteria and Acidobacteria occupied a larger portion of the community. We also explored the extent of individual variance within each plant species investigated, and found that in the plant species thought to have the least genetic variance among individuals (P. aurantiaca) still hosted just as diverse microbial communities. Whether all plant species host their own distinct root microbiota and plants more closely related to each other share more similar bacterial communities still remains to be fully explored, but among the plants examined in this experiment there was no trend that the two species belonging to the same family shared more similarities in terms of bacterial community composition.


Interaction between methionine synthase isoforms and MMACHC: characterization in cblG-variant, cblG and cblC inherited causes of megaloblastic anaemia.
The cblG and cblC disorders of cobalamin (Cbl) metabolism are two inherited causes of megaloblastic anaemia. In cblG, mutations in methionine synthase (MTR) decrease conversion of hydroxocobalamin (HOCbl) to methylcobalamin, while in cblC, mutations in MMACHC disrupt formation of cob(II)alamin (detected as HOCbl). Cases with undetectable methionine synthase (MS) activity are extremely rare and classified as 'cblG-variant'. In four 'cblG-variant' cases, we observed a decreased conversion of cyanocobalamin to HOCbl that is also seen in cblC cases. To explore this observation, we studied the gene defects, splicing products and expression of MS, as well as MS/MMACHC protein interactions in cblG-variant, cblG, cblC and control fibroblasts. We observed a full-size MS encoded by MTR-001 and a 124 kDa truncated MS encoded by MTR-201 in cblG, cblC, control fibroblasts and HEK cells, but only the MTR-201 transcript and inactive truncated MS in cblG-variant cells. Co-immunoprecipitation and proximity ligation assay showed interaction between truncated MS and MMACHC in cblG-variant cells. This interaction decreased 2.2, 1.5 and 5.0-fold in the proximity ligation assay of cblC cells with p.R161Q and p.R206W mutations, and HEK cells with knock down expression of MS by siRNA, respectively, when compared with control cells. In 3D modelling and docking analysis, both truncated and full-size MS provide a loop anchored to MMACHC, which makes contacts with R-161 and R-206 residues. Our data suggest that the interaction of MS with MMACHC may play a role in the regulation of the cellular processing of Cbls that is required for Cbl cofactor synthesis.


Basal Serum Cortisol and Testosterone/Cortisol Ratio Are Related to Rate of Na+ Lost During Exercise in Elite Soccer Players.
During exercise, the human body maintains optimal body temperature through thermoregulatory sweating, which implies the loss of water, sodium (Na+), and other electrolytes. Sweat rate and sweat Na+ concentration show high interindividual variability, even in individuals exercising under similar conditions. Testosterone and cortisol may regulate sweat Na+ loss by modifying the expression/activity of the cystic fibrosis transmembrane conductance regulator. This has not been tested. As a first approximation, the authors aimed to determine whether basal serum concentrations of testosterone or cortisol, or the testosterone/cortisol ratio relate to sweat Na+ loss during exercise. A total of 22 male elite soccer players participated in the study. Testosterone and cortisol were measured in blood samples before exercise (basal). Sweat samples were collected during a training session, and sweat Na+ concentration was determined. The basal serum concentrations of testosterone and cortisol and their ratio were (mean [SD]) 13.6 (3.3) pg/ml, 228.9 (41.4) ng/ml, and 0.06 (0.02), respectively. During exercise, the rate of Na+ loss was related to cortisol (r = .43; p < .05) and to the testosterone/cortisol ratio (r = -.46; p < .01), independently of the sweating rate. The results suggest that cortisol and the testosterone/cortisol ratio may influence Na+ loss during exercise. It is unknown whether this regulation depends on the cystic fibrosis transmembrane conductance regulator.


From Virtual Reality to Immersive Analytics in Bioinformatics.
Bioinformatics-related research produces huge heterogeneous amounts of data. This wealth of information includes data describing metabolic mechanisms and pathways, proteomics, transcriptomics, and metabolomics. Often, the visualization and exploration of related structural - usually molecular - data plays an important role in the aforementioned contexts. For decades, virtual reality (VR)-related technologies were developed and applied to Bioinformatics problems. Often, these approaches provide "just" visual support of the analysis, e.g. in the case of exploring and interacting with a protein on a 3D monitor and compatible interaction hardware. Moreover, in the past these approaches were limited to cost-intensive professional visualization facilities. The advent of new affordable, and often mobile technologies, provides high potential for using similar approaches on a regular basis for daily research. Visual Analytics is successfully being used for several years to analyze complex and heterogeneous datasets. Immersive Analytics combines these approaches now with new immersive and interactive technologies. This publication provides a short overview of related technologies, their history and Bioinformatics-related approaches. Six new applications on the path from VR to Immersive Analytics are being introduced and discussed.


Population surveys in Greenland 1993-2009: temporal trend of PCBs and pesticides in the general Inuit population by age and urbanisation.
The purpose of the study was to analyse temporal trends (1993-2009) of the concentrations of organochlorine contaminants (14 congeners of polychlorinated biphenyls (PCB) and 11 pesticides) in the blood of Greenland Inuit according to age and urbanisation. Statistical determinants for the contaminant concentrations included (for PCB congener 153) age (Δr(2)=0.35), marine diet (Δr(2)=0.10), smoking (Δr(2)=0.02), and sex (Δr(2)=0.01) with comparable results for other organochlorine contaminants. After adjustment for age, diet, smoking, and sex a significant decreasing trend was present for all contaminants ranging from 41% for mirex to 56% for hexachlorobenzene. The temporal trend was most pronounced among participants below the age of 65 years. The decrease started later in villages than in towns. The decrease was present in all age groups and in the capital, other towns, and villages. The decrease is probably due to a combination of reduced concentrations of the contaminants in the wildlife and a slight temporal reduction in the consumption of marine mammals. The significant downwards trend of legacy POPs shows that the legislation works but it must be kept in mind that according to the cumulated scientific evidence there are a multitude of non-regulated persistent organic contaminants in the diet as well as high levels of methylmercury.


Pneumococcal LytR Protein Is Required for the Surface Attachment of Both Capsular Polysaccharide and Teichoic Acids: Essential for Pneumococcal Virulence.
The LytR-Cps-Psr family proteins are commonly present in Gram-positive bacteria, which have been shown to implicate in anchoring cell wall-related glycopolymers to the peptidoglycan. Here, we report the cellular function of SPD_1741 (LytR) in Streptococcus pneumoniae and its role in virulence of pneumococci. Pneumococcal ΔlytR mutants have been successfully constructed by replacing the lytR gene with erm cassette. The role of LytR in pneumococcal growth was determined by growth experiments, and surface accessibility of the LytR protein was analyzed using flow cytometry. Transmission electron microscopy (TEM) and immunoblotting were used to reveal the changes in capsular polysaccharide (CPS). Dot blot and ELISA were used to quantify the amount of teichoic acids (TAs). The contribution of LytR on bacterial virulence was assessed using in vitro phagocytosis assays and infection experiments. Compared to the wild-type strain, the ΔlytR mutant showed a defect in growth which merely grew to a maximal OD620 of 0.2 in the liquid medium. The growth of the ΔlytR mutant could be restored by addition of recombinant ΔTM-LytR protein in culture medium in a dose-dependent manner. TEM results showed that the D39ΔlytR mutant was impaired in the surface attachment of CPS. Deletion of lytR gene also impaired the retention of TAs on the surface of pneumococci. The reduction of CPS and TAs on the pneumocccal cells were confirmed using Dot blot and ELISA assays. Compared to wild-type D39, the ΔlytR mutant was more susceptible to the phagocytosis. Animal studies showed that the ability to colonize the nasophaynx and virulence of pneumococci were affected by impairment of the lytR gene. Collectively, these results suggest that pneumococcal LytR is involved in anchoring both the CPS and TAs to cell wall, which is important for virulence of pneumococci.


To Evaluate the Severity, Distribution of Occlusal Tooth Wear and its Correlation with Bite Force in Young North Indian Adults.
To determine the severity and distribution of occlusal tooth wear among young North Indian adults and to evaluate the correlation of occlusal tooth wear with bite force. A total of 164 subjects were enrolled in the present study. Inclusion criteria included subjects with age range of 25-40 years having a full complement of natural dentition (excluding third molars), with no history of orthodontic treatment, FPD and trauma. Maxillary and mandibular casts of each subject were taken. Tooth wear score of anterior and posterior teeth of both the arches was calculated using a five-point (0 to 4) ordinal scoring system. The calculated tooth wear scores were then compared with data concerning age, sex, number of daily meals, vegetarian/non-vegetarian diet, Group function/Canine guided occlusion and bite force. Nonparametric (Mann-Whitney) test was used to determine the relationship between various factors and occlusal tooth wear. Spearman's correlation coefficient was used to determine the correlation between tooth wear and bite force. After applying statistical analysis to the data collected, total tooth wear score of the whole sample was 30.07 ± 6.39. Anterior teeth had significantly higher wear score than posteriors (P < 0.01). Males showed significantly higher (P < 0.001) tooth wear in both arches factors such as bite force and age showed significant correlation with tooth wear (P=0.000), however, the number of meals taken per day did not show any significant correlation. Higher tooth wear loss was seen in non vegetarian dietary pattern but it was statistically insignificant. It was also found that Group function occlusion showed significantly higher mean tooth wear loss 45.76 ± 9.19 as compared to Canine guided occlusion 26.37 ± 10.68 (P=0.000).


A 2.4 GHz ULP OOK Single-Chip Transceiver for Healthcare Applications.
This paper describes an ultra-low power (ULP) single chip transceiver for wireless body area network (WBAN) applications. It supports on-off keying (OOK) modulation, and it operates in the 2.36-2.4 GHz medical BAN and 2.4-2.485 GHz ISM bands. It is implemented in 90 nm CMOS technology. The direct modulated transmitter transmits OOK signal with 0 dBm peak power, and it consumes 2.59 mW with 50% OOK. The transmitter front-end supports up to 10 Mbps. The transmitter digital baseband enables digital pulse-shaping to improve spectrum efficiency. The super-regenerative receiver front-end supports up to 5 Mbps with -75 dBm sensitivity. Including the digital part, the receiver consumes 715 μW at 1 Mbps data rate, oversampled at 3 MHz. At the system level the transceiver achieves PER=10 (-2) at 25 meters line of site with 62.5 kbps data rate and 288 bits packet size. The transceiver is integrated in an electrocardiogram (ECG) necklace to monitor the heart's electrical property.


INbreast: toward a full-field digital mammographic database.
Computer-aided detection and diagnosis (CAD) systems have been developed in the past two decades to assist radiologists in the detection and diagnosis of lesions seen on breast imaging exams, thus providing a second opinion. Mammographic databases play an important role in the development of algorithms aiming at the detection and diagnosis of mammary lesions. However, available databases often do not take into consideration all the requirements needed for research and study purposes. This article aims to present and detail a new mammographic database. Images were acquired at a breast center located in a university hospital (Centro Hospitalar de S. João [CHSJ], Breast Centre, Porto) with the permission of the Portuguese National Committee of Data Protection and Hospital's Ethics Committee. MammoNovation Siemens full-field digital mammography, with a solid-state detector of amorphous selenium was used. The new database-INbreast-has a total of 115 cases (410 images) from which 90 cases are from women with both breasts affected (four images per case) and 25 cases are from mastectomy patients (two images per case). Several types of lesions (masses, calcifications, asymmetries, and distortions) were included. Accurate contours made by specialists are also provided in XML format. The strengths of the actually presented database-INbreast-relies on the fact that it was built with full-field digital mammograms (in opposition to digitized mammograms), it presents a wide variability of cases, and is made publicly available together with precise annotations. We believe that this database can be a reference for future works centered or related to breast cancer imaging.


Nanostructure of the deep eutectic solvent/platinum electrode interface as a function of potential and water content.
The interfacial nanostructure of the three most widely-studied Deep Eutectic Solvents (DESs), choline chloride:urea (ChCl:Urea), choline chloride:ethylene glycol (ChCl:EG), and choline chloride:glycerol (ChCl:Gly) at a Pt(111) electrode has been studied as a function of applied potential and water content up to 50 wt%. Contact mode atomic force microscope (AFM) force-distance curves reveal that for all three DESs, addition of water increases the interfacial nanostructure up to ∼40 wt%, after which it decreases. This differs starkly from ionic liquids, where addition of small amounts of water rapidly decreases the interfacial nanostructure. For the pure DESs, only one interfacial layer is measured at OCP at 0.5 nm, which increases to 3 to 6 layers extending ∼5 nm from the surface at 40 or 50 wt% water. Application of a potential of ±0.25 V to the Pt electrode for the pure DESs increases the number of near surface layers to 3. However, when water is present the applied potential attenuates the steps in the force curve, which are replaced by a short-range exponential decay. This change was most pronounced for ChCl:EG with 30 wt% or 50 wt% water, so this system was probed using cyclic voltammetry, which confirms the interfacial nanostructure is akin to a salt solution.


Prevalence of Musculoskeletal Symptoms and Ergonomics Among Plastic Surgery Residents: Results of a National Survey and Analysis of Contributing Factors.
Musculoskeletal symptoms and injuries among surgeons are underestimated but are increasingly recognized to constitute a major problem. However, it has not been established when symptoms start and what factors contribute to the development of symptoms. A 19-question survey approved by our institution's review board, and American Council of Academic Plastic Surgery was sent to all plastic surgery residents enrolled in Accreditation Council for Graduate Medical Education-accredited plastic surgery training programs in the United States. The presence of various musculoskeletal symptoms was calculated, and predictors of these symptoms were evaluated. We received 104 total responses. Ninety-four percent of residents had experienced musculoskeletal pain in the operating room. The neck was the most commonly affected area (54%) followed by the back (32%) and extremities (12%). Interestingly, 52% of responders developed these symptoms during the first 2 years of their residency. Furthermore, increasing postgraduate year level (P = 0.3) and independent versus integrated status (P = 0.6) had no correlation with pain, suggesting that symptoms began early in training.Pain symptoms were frequent for 47%, whereas 5% reported experiencing symptoms during every case. The use of a headlight correlated with frequent pain (odds ratio, 2.5; P = 0.027). The use of microscope and loupes did not correlate with frequent pain. Eighty-nine percent of responders were aware of having bad surgical posture, but only 22% had received some form of ergonomics training at their institution. Sixty-four percent of responders believe that the operating room culture does not allow them to report the onset of symptoms and ask for adjustments. This was more common among residents reporting frequent pain (odds ratio, 3.12; P = 0.009). Plastic surgeons are at high risk for occupational symptoms and injuries. Surprisingly, symptoms start early during residency. Because residents are aware of the problem and looking for solutions, this suggests an opportunity for educational intervention to improve the health and career longevity of the next generation of surgeons.


Pressure control inverse ratio ventilation in the treatment of adult respiratory distress syndrome in patients with blunt chest trauma.
The objective of this study was to evaluate the efficacy of pressure control inverse ratio ventilation (PCIRV) in improving oxygenation in trauma patients with adult respiratory distress syndrome (ARDS) and to assess the potential risks associated with this form of treatment. This was a cohort study assessing the trends in hemodynamic and ventilatory parameters after the initiation of PCIRV, conducted at a community Level I trauma center intensive care unit. The study comprised 15 trauma patients developing severe, progressive ARDS [two or more of the following criteria: positive end-expiratory pressure (PEEP) >10 cm H2O; arterial partial pressure of oxygen divided by fraction of inspired oxygen (PaO2:FiO2) ratio <150; and peak inspiratory pressure (PIP) >45 cm H2O]: ten due to blunt chest injuries, three due to sepsis, and two due to fat emboli syndrome. PCIRV was initiated. Main outcome measures were PIP, PEEP (total, auto), oxygen saturation, cardiac index, oxygen delivery, PaO2:FiO2 ratio, compliance, evidence of complications of PCIRV, and mortality. Within 24 hours of conversion to PCIRV, the patients stabilized and the mean PaO2:FiO2 ratio rose from 96.3+/-57.8 to 146.8+/-91.1 (P<0.05) and PIP fell from 47.9+/-13.8 to 38.8+/-8.4 cm H2O; auto-PEEP increased from 0.5+/-1.9 to 7.5+/-5.6 cm H2O (P<0.05); oxygen delivery index remained stable (563+/-152 to 497+/-175 mL/min/m2); three patients developed evidence of barotrauma, one patient developed critical illness polyneuropathy, and two patients died (13%). PCIRV is an effective salvage mode of ventilation in patients with severe ARDS, but it is not without complications. Auto-PEEP levels and cardiac index should be monitored to ensure tissue oxygen delivery is maintained.


Effect of the interaction between mental stress and eating pattern on body mass index gain in healthy Japanese male workers.
The effect of the interaction between long-term mental stress and eating habits on weight gain has not been confirmed in humans. A population of 1080 healthy Japanese male local government employees without lifestyle-related diseases at baseline were studied [corrected]. Height and weight were measured and perception of mental stress and the frequency of eating to satiety, drinking, smoking, and exercise were surveyed by means of a questionnaire in both 1997 and 2002. Exposure patterns during this 5-year period were classified as low or high. Information on daily food and energy intake was collected in 2002. The effect of the interaction between stress and the frequency of eating to satiety on change in BMI (DeltaBMI) during this 5-year period was examined by 2-way analysis of variance (ANOVA) and covariance (ANCOVA) adjusted for age, BMI at baseline, and other lifestyle habits. The association between satiation eating and DeltaBMI was compared between participants with high and low levels of stress. Stress and satiation eating were not significantly mutually correlated. Two-way ANCOVA showed a significant interaction (F = 4.90, P = 0.03) between mental stress and satiation eating. Among participants with a high level of stress, BMI gain was significantly larger in those who ate to satiety than in those who ate moderately, when DeltaBMI was unadjusted or adjusted for covariates (adjusted mean [SE]: 0.34 +/- 0.06 kg/m(2) vs. 0.12 +/- 0.07 kg/m(2), P = 0.002). Among participants with a low level of stress no such difference was observed. These results were unchanged after further adjustment for energy intake in 2002. In this population, eating pattern interacted with long-term mental stress to produce a larger body mass gain in satiation eaters than in moderate eaters among participants with a high level of stress, independent of energy intake or other lifestyle habits.


Rationale and initial experience with the Tri-Ad Adams tricuspid annuloplasty ring.
Controversy exists regarding the indication and method of repair of functional tricuspid regurgitation (TR) in patients undergoing mitral valve surgery. Whereas the American College of Cardiology/American Heart Association guidelines recommend tricuspid repair in the setting of severe TR, tricuspid repair is advised for less than severe TR in the setting of annular dilation or pulmonary hypertension. Although multiple repair strategies exist, the use of a ring annuloplasty (semirigid remodeling rings vs flexible bands) is the preferred method of therapy to avoid short- and long-term recurrence of TR. The new Tri-Ad Adams annuloplasty ring combines elements of semirigid and flexible bands that will not only allow for annular remodeling in the region of the right ventricular free wall but also potentially reduce injury to the conduction system with its flexible and "open" ends. In this article, we discuss the rational for an aggressive approach to functional tricuspid regurgitation, and show our initial clinical experience with the Tri-Ad Adams annuloplasty ring.


The effect of interfacial tension on droplet formation in flow-focusing microfluidic device.
Interfacial tension plays an important role in microfluidic emulsification, which is the process of preparing emulsions. A promising method which controls droplet behavior according to the function of the interfacial tension in the process of microfluidic emulsification is reported. The droplet size and generation frequency changed regularly to obtain appropriate concentrations of surfactant. This method could be of great help for setting up the size-controllable droplet generation systems, and ameliorating the emulsification technology. The interfacial tension effect was first analyzed by computational simulation before the real experiment, which significantly improved the efficiency of the whole research process.


[Mild and moderate hypothermia as a new therapy concept in treatment of cerebral ischemia and craniocerebral trauma. Pathophysiologic principles].
Hypothermia protects the brain and other vital organs during periods of ischaemia. We differentiate between mild (36-34 degrees C), moderate (33-29 degrees C), deep (28-17 degrees C) and profund (16-4 degrees C) hypothermia. During hypothermia, cerebral metabolic rate and cerebral blood flow decrease dependent on temperature. The relation between temperature and cerebral metabolism is expressed by the temperature coeffizient Q10, which is the ratio between two metabolic rates separated by 10 degrees C. The following factors contribute to decreases in cerebral blood flow seen during hypothermia: cerebral metabolic depression, decreases in cardiac output, and decreases in arterial blood pressure with pH-stat management, increases in hematocrit and in blood viscosity. Mild or moderate hypothermia reduces histopathological damage and neurological deficits if started before and during cerebral ischaemia. Hypothermia may also improve neurologic outcome if initiated following focal cerebral ischaemia, but is less effective after global ischaemic insults. Mild hypothermia appears to be safer and more effective compared to moderate hypothermia. In most instances, deep hypothermia renders neurologic outcome worse, which is most likely related to the generation of toxic metabolites and inadequate myocardial function during rewarming. The neuroprotective effects of hypothermia are related to several mechanisms along the ischaemic cascade: prevention of postischaemic hypoperfusion, reduction of functional and basal metabolism, decreased accumulation of lactic acid and oedema formation, inhibition of excitatory neurotransmitter release, prevention of Ca(++)- and Na(+)-influx, inhibition of lipid peroxidase activity, and free radical formation, stimulation of regenerative immediate early genes. The side effects of hypothermia include myocardial ischaemia, cardiac arrhythmias, decreased left ventricular contractility, coagulation abnormalities, and suppression of metabolic and immunological processes.


Inflammatory bowel disease and colon cancer.
The inflammatory bowel diseases (IBD); Crohn's and Ulcerative colitis, result from an altered host response to intestinal flora. Recurrent inflammation with ulceration and tissue restitution confers an increased risk of cancer in both UC and Crohns, and genome wide searches have identified a number of disease susceptibility alleles. The carcinogenesis pathway in colitis-associated colorectal cancer (CACRC) is less clearly understood than it's sporadic counterpart. Clonal ordering experiments have indicated the order and timing of chromosomal instability and common genetic mutations. Epigenetic changes such as DNA methylation and histone modification are thought to play an increasingly important role in inflammation induced carcinogenesis. Clonal expansion of procarcinogenic mutations can lead to large fields of mutant tissue from which colitis associated cancers can arise (field cancerisation). Endoscopic screening is the mainstay of surveillance in high-risk patients although the development of appropriate, clinically applicable biomarkers remains a research priority. Despite the expanding field of biological therapy in inflammatory bowel disease the ASA compounds remain the best-studied and most efficacious chemopreventive agents. Colitis associated CRC appears to have a different aetiology, carcinogenesis pathway and clinical course to its sporadic counterpart. Further research including long-term follow up of patient cohorts taking biological therapies will improve the detection and treatment of these important, inflammation-induced malignancies.


Increase in hepatic NKT cells in leukocyte cell-derived chemotaxin 2-deficient mice contributes to severe concanavalin A-induced hepatitis.
Leukocyte cell-derived chemotaxin 2 (LECT2) was originally identified for its possible chemotactic activity against human neutrophils in vitro. It is a 16-kDa protein that is preferentially expressed in the liver. Its homologues have been widely identified in many vertebrates. Current evidence suggests that LECT2 may be a multifunctional protein like cytokines. However, the function of LECT2 in vivo remains unclear. To elucidate the role of this protein in vivo, we have generated LECT2-deficient (LECT2(-/-)) mice. We found that the proportion of NKT cells in the liver increased significantly in LECT2(-/-) mice, although those of conventional T cells, NK cells, and other cell types were comparable with those in wild-type mice. Consistent with increased hepatic NKT cell number, the production of IL-4 and IFN-gamma was augmented in LECT2(-/-) mice upon stimulation with alpha-galactosylceramide, which specifically activates Valpha14 NKT cells. In addition, NKT cell-mediated cytotoxic activity against syngeneic thymocytes increased in hepatic mononuclear cells obtained from LECT2(-/-) mice in vitro. Interestingly, the hepatic injury was exacerbated in LECT2(-/-) mice upon treatment with Con A, possibly because of the significantly higher expression of IL-4 and Fas ligand. These results suggest that LECT2 might regulate the homeostasis of NKT cells in the liver and might be involved in the pathogenesis of hepatitis.


MeCP2 modulates gene expression pathways in astrocytes.
Mutations in MECP2 encoding methyl-CpG-binding protein 2 (MeCP2) cause the X-linked neurodevelopmental disorder Rett syndrome. Rett syndrome patients exhibit neurological symptoms that include irregular breathing, impaired mobility, stereotypic hand movements, and loss of speech. MeCP2 protein epigenetically modulates gene expression through genome-wide binding to methylated CpG dinucleotides. While neurons have the highest level of MeCP2 expression, astrocytes and other cell types also express detectable levels of MeCP2. Recent studies suggest that astrocytes likely control the progression of Rett syndrome. Thus, the object of these studies was to identify gene targets that are affected by loss of MeCP2 binding in astrocytes. To identify gene targets of MeCP2 in astrocytes, combined approaches of expression microarray and chromatin immunoprecipitation of MeCP2 followed by sequencing (ChIP-seq) were compared between wild-type and MeCP2-deficient astrocytes. MeCP2 gene targets were compared with genes in the top 10% of MeCP2 binding levels in gene windows either within 2 kb upstream of the transcription start site, or the 'gene body' that extended from transcription start to end site, or 2 kb downstream of the transcription end site. A total of 118 gene transcripts surpassed the highly significant threshold (P < 0.005, fold change > 1.2) in expression microarray analysis from triplicate cultures. The top 10% of genes with the highest levels of MeCP2 binding were identified in two independent ChIP-seq experiments. Together this integrated, genome-wide screen for MeCP2 target genes provided an overlapping list of 19 high-confidence MeCP2-responsive gene transcripts in astrocytes. Validation of candidate target gene transcripts by RT-PCR revealed that expression of Apoc2, Cdon, Csrp and Nrep were consistently responsive to MeCP2 deficiency in astrocytes. The first MeCP2 ChIP-seq and gene expression microarray analysis in astrocytes reveals a set of potential MeCP2 target genes that may contribute to normal astrocyte signaling, cell division and neuronal support functions, the loss of which may contribute to the Rett syndrome phenotype.


Cognitive flexibility in adolescence: neural and behavioral mechanisms of reward prediction error processing in adaptive decision making during development.
Adolescence is associated with quickly changing environmental demands which require excellent adaptive skills and high cognitive flexibility. Feedback-guided adaptive learning and cognitive flexibility are driven by reward prediction error (RPE) signals, which indicate the accuracy of expectations and can be estimated using computational models. Despite the importance of cognitive flexibility during adolescence, only little is known about how RPE processing in cognitive flexibility deviates between adolescence and adulthood. In this study, we investigated the developmental aspects of cognitive flexibility by means of computational models and functional magnetic resonance imaging (fMRI). We compared the neural and behavioral correlates of cognitive flexibility in healthy adolescents (12-16years) to adults performing a probabilistic reversal learning task. Using a modified risk-sensitive reinforcement learning model, we found that adolescents learned faster from negative RPEs than adults. The fMRI analysis revealed that within the RPE network, the adolescents had a significantly altered RPE-response in the anterior insula. This effect seemed to be mainly driven by increased responses to negative prediction errors. In summary, our findings indicate that decision making in adolescence goes beyond merely increased reward-seeking behavior and provides a developmental perspective to the behavioral and neural mechanisms underlying cognitive flexibility in the context of reinforcement learning.


Evolution of Acid-Sensing Olfactory Circuits in Drosophilids.
Animals adapt their behaviors to specific ecological niches, but the genetic and cellular basis of nervous system evolution is poorly understood. We have compared the olfactory circuits of the specialist Drosophila sechellia-which feeds exclusively on Morinda citrifolia fruit-with its generalist cousins D. melanogaster and D. simulans. We show that D. sechellia exhibits derived odor-evoked attraction and physiological sensitivity to the abundant Morinda volatile hexanoic acid and characterize how the responsible sensory receptor (the variant ionotropic glutamate receptor IR75b) and attraction-mediating circuit have evolved. A single amino acid change in IR75b is sufficient to recode it as a hexanoic acid detector. Expanded representation of this sensory pathway in the brain relies on additional changes in the IR75b promoter and trans-acting loci. By contrast, higher-order circuit adaptations are not apparent, suggesting conserved central processing. Our work links olfactory ecology to structural and regulatory genetic changes influencing nervous system anatomy and function.


Under-5 Mortality in Central America: 1990-2016.
We aimed to calculate the change in under-5 mortality rates (U5MRs) (1990-2016), to assess countries' status regarding Sustainable Development Goal (SDG) 3.2.1 (reducing the U5MR to ≤25 deaths per 1000 live births by 2030), to list the most important causes of death (1990, 2016), and to examine the association between selected SDG indicators and U5MRs using a linear mixed-effects regression. Ecological study in which we used estimates from the Global Burden of Disease Study 2016 for Central American countries. Results were expressed as U5MRs (deaths per 1000 live births), cause-specific mortality rates (deaths per 100 000 population <5 years of age), and regression coefficients with 95% confidence intervals. U5MRs decreased 65% (1990-2016), and in 2016, all countries but Guatemala had met SDG 3.2.1. The main causes of death were diarrheal diseases (1990; 311.1 per 100 000) and lower respiratory infections (LRIs) (2016; 78.1 per 100 000). When disaggregated by country (2016), congenital birth defects were the most important cause of death in all countries except for in Honduras (neonatal preterm birth) and Guatemala (LRIs). Nutritional status; availability of water, sanitation, and hygiene services; coverage of vaccines; and coverage of contraception were associated with a reduction in U5MRs. Central America has achieved a large reduction in U5MRs. Countries must address both the high mortality caused by LRIs and the rising mortality caused by noncommunicable causes of death through an improvement of SDG indicators that guarantees equitable progress in child survival in the region.


Higher M30 and high mobility group box 1 protein levels in ex vivo lung perfusate are associated with primary graft dysfunction after human lung transplantation.
Ex vivo lung perfusion (EVLP) enables assessment of marginal donor lungs for transplantation, with similar clinical outcomes to conventional lung transplantation. We investigated whether cell death-related proteins in the EVLP perfusate could predict primary graft dysfunction (PGD) after transplantation. M30 (indicating epithelial apoptosis), M65 (indicating total epithelial cell death), and high mobility group box 1 (HMGB-1, related to cell death and inflammation) protein levels in EVLP perfusate were measured by enzyme-linked immunosorbent assay and correlated with clinical outcomes. From 100 sequential EVLP patients, 79 lungs were transplanted. Patients who were bridged with extracorporeal life support (ECLS, n = 6) or who received lobar/single lung (n = 25) were excluded. PGD grade 3 (partial pressure of arterial oxygen/fraction of inspired oxygen <200 or need for ECLS) developed in 11 at any time within 72 hours after transplantation (PGD Group). PGD grade 3 did not develop in 34 patients (Control Group). M30 was significantly higher in the PGD Group than in the Control Group at 1 hour (PGD: 73.3 ± 24.9, control: 53.9 ± 15.9 U/liter; p < 0.01) and at 4 hours (PGD: 137.0 ± 146.6, Control: 72.4 ± 40.0 U/liter; p = 0.046) of EVLP. The increase of HMGB-1 from 1 to 4 hours of EVLP was significantly greater in the PGD Group (PGD: 37.0 ± 25.4, Control: 7.2 ± 16.8 ng/ml; p < 0.001). Higher levels of or a greater increase in M30 and a greater increase in HMGB-1 were associated with higher mortality in Cox regression. Levels of M30 and HMGB-1 in the EVLP perfusate correlate with PGD after lung transplantation and might therefore be useful biomarkers to improve donor lung assessment during EVLP.


Heterogeneous Configuration of a Ag Nanowire/Polymer Composite Structure for Selectively Stretchable Transparent Electrodes.
One of the most important aspects that we need to consider in the design of intrinsically stretchable electrodes is that most electronic devices that can be formed on them are not stretchable themselves. This discrepancy can induce severe stress singularities at the interfaces between stiff devices and stretchable electrodes, leading to catastrophic device delamination when the substrate is stretched. Here, we suggest a novel solution to this challenge which involves introducing a photolithography-based rigid-island approach to fabricate the heterogeneous configuration of a silver nanowire (AgNW)/polymer composite structure. For this, we designed two new transparent polymers: a photopatternable polymer that is rigid yet flexible, and a stretchable polymer, both of which have identical acrylate functional groups. Patterning of the rigid polymer and subsequent overcoating of the soft polymer formed rigid island disks embedded in the soft polymer, resulting in a selectively stretchable transparent film. Strong covalent bonds instead of weak physical interactions between the polymers strengthened the cohesive force at the interface of the rigid/soft polymers. Inverted-layer processing with a percolated AgNW network was used to form a heterogeneous AgNW/polymer composite structure that can be used as a selectively stretchable transparent electrode. An optimized structural configuration prevented the resistance of the rigid electrode from varying up to a lateral strain of 70%. A repeated stretch/release test with 60% strain for 5000 cycles did not cause any severe damage to the structure, revealing that the fabricated structure was mechanically stable and reliable.


Pilot study of sentinel-node-based adoptive immunotherapy in advanced colorectal cancer.
Despite optimal surgical treatment and modern adjuvant therapies, 50% of patients diagnosed with colorectal cancer die within 5 years. Immunotherapy offers an appealing complement to traditional chemotherapy, with possible long-term protection against tumor recurrences through immunological memory. We have conducted a pilot study of a novel adoptive immunotherapy, using autologous, in vitro expanded lymphocytes isolated from the tumor-draining sentinel lymph node. Sentinel nodes were recovered from 16 patients with disseminated or locally advanced, high-risk colorectal cancer. Single-cell suspensions of sentinel-node-acquired lymphocytes were clonally expanded in vitro in the presence of autologous tumor extract and returned as a transfusion. Patients were followed with clinical and radiological evaluations. Long-term survival was compared with traditionally treated controls. Sentinel-node-acquired CD4(+) Th1-lymphocytes could be clonally expanded in vitro and safely administered to all 16 patients without side-effects. In four out of nine stage IV patients, complete tumor regression occurred. Median survival time in the stage IV patients (n = 9) was 2.6 years, as compared with 0.8 years in conventionally treated controls. A dose-dependent effect with regards to reduced tumor burden and long-term survival was observed. Sentinel-node-based adoptive immunotherapy is feasible; the method has shown no apparent side-effects and appears to convey therapeutic antitumor effects. Further studies are justified to determine its efficacy and precise role in the treatment of colorectal cancer.


Deletion of Plasmodium falciparum Protein RON3 Affects the Functional Translocation of Exported Proteins and Glucose Uptake.
The survival of Plasmodium spp. within the host red blood cell (RBC) depends on the function of a membrane protein complex, termed the Plasmodium translocon of exported proteins (PTEX), that exports certain parasite proteins, collectively referred to as the exportome, across the parasitophorous vacuolar membrane (PVM) that encases the parasite in the host RBC cytoplasm. The core of PTEX consists of three proteins: EXP2, PTEX150, and the HSP101 ATPase; of these three proteins, only EXP2 is a membrane protein. Studying the PTEX-dependent transport of members of the exportome, we discovered that exported proteins, such as ring-infected erythrocyte surface antigen (RESA), failed to be transported in parasites in which the parasite rhoptry protein RON3 was conditionally disrupted. RON3-deficient parasites also failed to develop beyond the ring stage, and glucose uptake was significantly decreased. These findings provide evidence that RON3 influences two translocation functions, namely, transport of the parasite exportome through PTEX and the transport of glucose from the RBC cytoplasm to the parasitophorous vacuolar (PV) space where it can enter the parasite via the hexose transporter (HT) in the parasite plasma membrane.IMPORTANCE The malarial parasite within the erythrocyte is surrounded by two membranes. Plasmodium translocon of exported proteins (PTEX) in the parasite vacuolar membrane critically transports proteins from the parasite to the erythrocytic cytosol and membrane to create protein infrastructure important for virulence. The components of PTEX are stored within the dense granule, which is secreted from the parasite during invasion. We now describe a protein, RON3, from another invasion organelle, the rhoptry, that is also secreted during invasion. We find that RON3 is required for the protein transport function of the PTEX and for glucose transport from the RBC cytoplasm to the parasite, a function thought to be mediated by PTEX component EXP2.


Targeting and tailoring an intervention for adolescents who are overweight: some ethical concerns.
There are important ethical issues to be examined before launching any public health intervention, particularly when targeting vulnerable groups. The aim of this article is to identify and discuss ethical concerns that may arise when intervening for health behavior change among adolescents identified as overweight. These concerns originate from an intervention designed to capacitate adolescents to increase self-determined physical activity. Utilizing an ethical framework for prevention of overweight and obesity, we identified three ethical aspects as particularly significant: the attribution of responsibility for health behavior, liberty to choose, and the effect on the participants' psychosocial well-being. It is discussed whether and how measures can be taken to deal with these aspects. It seems evident that the ethical aspects are mainly concerned with the vulnerability of adolescents identified as overweight. However, we claim that when individual feedback and counseling is provided, tailored interventions have a unique potential to empower adolescents to make ethically anchored decisions about their own health behavior.


Omega-3 Fatty Acid and Iron Supplementation Alone, but Not in Combination, Lower Inflammation and Anemia of Infection in Mycobacterium tuberculosis-Infected Mice.
Progressive inflammation and anemia are common in tuberculosis (TB) and linked to poor clinical outcomes. Eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) have inflammation-resolving properties, whereas iron supplementation in TB may have limited efficacy and enhance bacterial growth. We investigated effects of iron and EPA/DHA supplementation, alone and in combination, on inflammation, anemia, iron status markers and clinical outcomes in Mycobacterium tuberculosis-infected C3HeB/FeJ mice. One week post-infection, mice received the AIN-93 diet without (control) or with supplemental iron (Fe), EPA/DHA, or Fe+EPA/DHA for 3 weeks. Mice supplemented with Fe or EPA/DHA had lower soluble transferrin receptor, ferritin and hepcidin than controls, but these effects were attenuated in Fe+EPA/DHA mice. EPA/DHA increased inflammation-resolving lipid mediators and lowered lung IL-1α, IFN-γ, plasma IL-1β, and TNF-α. Fe lowered lung IL-1α, IL-1β, plasma IL-1β, TNF-α, and IL-6. However, the cytokine-lowering effects in the lungs were attenuated with Fe+EPA/DHA. Mice supplemented with EPA/DHA had lower lung bacterial loads than controls, but this effect was attenuated in Fe+EPA/DHA mice. Thus, individually, post-infection EPA/DHA and iron supplementation lowered systemic and lung inflammation and mitigated anemia of infection in TB, but not when combined. EPA/DHA also enhanced bactericidal effects and could support inflammation resolution and management of anemia.


Depression, Anxiety, and Emergency Department Use for Asthma.
Asthma is responsible for ∼1.7 million emergency department (ED) visits annually in the United States. Studies in adults have shown that anxiety and depression are associated with increased asthma-related ED use. Our objective was to assess this association in pediatric patients with asthma. We identified patients aged 6 to 21 years with asthma in the Massachusetts All-Payer Claims Database for 2014 to 2015 using International Classification of Diseases, Ninth and 10th Revision codes. We examined the association between the presence of anxiety, depression, or comorbid anxiety and depression and the rate of asthma-related ED visits per 100 child-years using bivariate and multivariable analyses with negative binomial regression. Of 65 342 patients with asthma, 24.7% had a diagnosis of anxiety, depression, or both (11.2% anxiety only, 5.8% depression only, and 7.7% both). The overall rate of asthma-related ED use was 17.1 ED visits per 100 child-years (95% confidence interval [CI]: 16.7-17.5). Controlling for age, sex, insurance type, and other chronic illness, patients with anxiety had a rate of 18.9 (95% CI: 17.0-20.8) ED visits per 100 child-years, patients with depression had a rate of 21.7 (95% CI: 18.3-25.0), and patients with both depression and anxiety had a rate of 27.6 (95% CI: 24.8-30.3). These rates were higher than those of patients who had no diagnosis of anxiety or depression (15.5 visits per 100 child-years; 95% CI: 14.5-16.4; P < .001). Children with asthma and anxiety or depression alone, or comorbid anxiety and depression, have higher rates of asthma-related ED use compared with those without either diagnosis.


Elimination of phase singularity to achieve superresolution in lossy metamaterials.
The presence of absorption losses softens the singular behavior of transmission resonances and leads to a good image in spite of limited effective spatial frequency range. Nonetheless, we found that the phase singularity does not disappear despite the considerably reduced retardation effects by softening the transmission resonances. Because the phase singularity severely deteriorates the ideal image reconstruction, broad transmission bandwidth in spatial frequency domain is not sufficient enough to achieve superresolution in TiO(2) thin film lens. The present work predicts successful elimination of the phase singularity and the achievement of approximately lambda /12.9 superresolution in TiO(2) thin film lens through the phase correction method.


Schizotypal perceptual aberrations of time: correlation between score, behavior and brain activity.
A fundamental trait of the human self is its continuum experience of space and time. Perceptual aberrations of this spatial and temporal continuity is a major characteristic of schizophrenia spectrum disturbances--including schizophrenia, schizotypal personality disorder and schizotypy. We have previously found the classical Perceptual Aberration Scale (PAS) scores, related to body and space, to be positively correlated with both behavior and temporo-parietal activation in healthy participants performing a task involving self-projection in space. However, not much is known about the relationship between temporal perceptual aberration, behavior and brain activity. To this aim, we composed a temporal Perceptual Aberration Scale (tPAS) similar to the traditional PAS. Testing on 170 participants suggested similar performance for PAS and tPAS. We then correlated tPAS and PAS scores to participants' performance and neural activity in a task of self-projection in time. tPAS scores correlated positively with reaction times across task conditions, as did PAS scores. Evoked potential mapping and electrical neuroimaging showed self-projection in time to recruit a network of brain regions at the left anterior temporal cortex, right temporo-parietal junction, and occipito-temporal cortex, and duration of activation in this network positively correlated with tPAS and PAS scores. These data demonstrate that schizotypal perceptual aberrations of both time and space, as reflected by tPAS and PAS scores, are positively correlated with performance and brain activation during self-projection in time in healthy individuals along the schizophrenia spectrum.


Aerodynamic Characteristics of Growl Voice and Reinforced Falsetto in Metal Singing.
The present study aimed to assess the aerodynamic characteristics of vocally healthy metal singers when producing growl voice or reinforced falsetto. Fifty-four participants (metal singers) were initially enrolled in this study, with 23 meeting the inclusion criteria. Sixteen participants performed growl voice and seven performed reinforced falsetto as a voice resource during metal singing. All participants were asked to undergo rigid laryngeal videostroboscopy to confirm the absence of laryngeal pathology. Then, subjects were aerodynamically assessed while performing growl voice or reinforced falsetto. Higher glottal airflow rate, sound pressure level, and subglottic pressure (Psub) for growl voice samples compared to vowel production without growl voice (keeping the same fundamental frequency [F0]) were found. Higher Psub, sound pressure level, and glottal resistance for high-pitched reinforced falsetto compared to naïve falsetto (keeping the same F0) were found. No differences for F0 were found for neither growl voice nor reinforced falsetto. It seems that growl voice is produced by decreasing vocal folds adduction and increasing Psub, which in turn, promotes an increased airflow rate. Reinforced falsetto is characterized by an increased vocal fold adduction and an increased Psub. A proper resonance strategy in reinforced falsetto and a decreased glottal adduction in growl voice might probably be the factors that contribute to prevent voice problems in singers who use these vocal resources, classically labeled as vocal abuse.


Preoperative predictors of resource utilization in liver transplantation.
Orthotopic liver transplantation (OLT) has been shown to be effective in prolonging life and improving its quality in patients with end-stage liver disease. However, it remains one of the most expensive surgical procedures performed today. In an era when economic efficiency and financial accountability are being emphasized, it is imperative to consider resource utilization in evaluating candidates for OLT. We prospectively followed 106 patients who underwent OLT at the Mayo Clinic for primary biliary cirrhosis and primary sclerosing cholangitis between 1990 and 1994. Hospital and professional charges for the initial hospitalization were obtained on all patients. Univariate and multivariate models were constructed using preoperative clinical variables that had been previously found to be important in predicting clinical outcomes. The preoperative variables considered were age, gender, diagnosis of liver disease, Mayo risk score, Child's score, nutritional status, Karnofsky score, INR, serum levels of albumin, bilirubin, and creatinine, and the presence/absence of ascites, edema, encephalopathy, renal failure (serum creatinine >2.0) and gastrointestinal bleeding. Of the 106 patients, 3 were excluded from the analysis because they received multiple transplants during the initial hospitalization. Of the hospital charges we analyzed, the surgical fee for transplantation and donor acquisition expense were fixed in advance and, therefore, excluded. The following preoperative variables were found to be significant in the univariate analysis: Mayo risk score, Child's score, nutritional status, Karnofsky score, INR, serum levels of bilirubin and creatinine, presence of renal failure, and gastrointestinal bleeding. In the multivariate analyses, Karnofsky score of 40 or less was associated with a 48% increase in total charges. Poor nutritional status and renal failure were associated with a 34% and 31% increase, respectively. We identified 3 preoperative variables as significant independent predictors of resource utilization in liver transplantation. In an effort to maximize the economic efficiency with which liver transplantation is performed, we believe these factors should be taken into consideration in determining both the timing of transplantation and the suitability of potential transplant recipients.


Assessment of liver tumor response to therapy: role of quantitative imaging.
Quantitative imaging is the analysis of retrieved numeric data from images with the goal of reducing subjective assessment. It is an increasingly important radiologic tool to assess treatment response in oncology patients. Quantification of response to therapy depends on the tumor type and method of treatment. Anatomic imaging biomarkers that quantify liver tumor response to cytotoxic therapy are based on temporal change in the size of the tumors. Anatomic biomarkers have been incorporated into the World Health Organization criteria and the Response Evaluation Criteria in Solid Tumors (RECIST) versions 1.0 and 1.1. However, the development of novel therapies with different mechanisms of action, such as antiangiogenesis or radioembolization, has required new methods for measuring response to therapy. This need has led to development of tumor- or therapy-specific guidelines such as the Modified CT Response Evaluation (Choi) Criteria for gastrointestinal stromal tumors, the European Association for Study of the Liver (EASL) criteria, and modified RECIST for hepatocellular carcinoma, among many others. The authors review the current quantification criteria used in the evaluation of treatment response in liver tumors, summarizing their indications, advantages, and disadvantages, and discuss future directions with newer methods that have the potential for assessment of treatment response. Knowledge of these quantitative methods is important to facilitate pivotal communication between oncologists and radiologists about cancer treatment, with benefit ultimately accruing to the patient.


A novel role for HNO in local and spreading vasodilatation in rat mesenteric resistance arteries.
Nitric oxide-mediated vasodilatation has previously been attributed to the uncharged form of the molecule (NO(•)), but increasing evidence suggests that nitroxyl (HNO) may play a significant role in endothelium-dependent relaxation. The aim of this study was to investigate the mechanisms underlying HNO-mediated vasodilatation in phenylephrine pre-constricted pressurized (70 mmHg) mesenteric arteries, and on membrane currents in isolated smooth muscle cells using whole cell and perforated patch clamp recordings. Angeli's salt (AS: nitroxyl donor), evoked concentration-dependent vasodilatation that was insensitive to the NO(•) scavengers carboxy-PTIO and hydroxocobalamin (HXC), but sensitive to either the HNO scavenger L-cysteine, K-channel blockers (4-AP and iberiotoxin), raised [K(+)](o), or inhibition of soluble guanylyl cyclase (ODQ). AS-evoked smooth muscle hyperpolarization significantly augmented K(V) current in an ODQ sensitive manner, and also increased the BK(Ca) current. Importantly, 30 μM AS initiated conducted or spreading vasodilatation, and following blockade of endothelial K-channels (TRAM-34 and apamin), ACh was able to evoke similar L-cysteine-sensitive conducted dilatation. These data show that vasodilatation induced by HNO is mediated by both K(V) and BK(Ca) channels, and suggest a physiological role in vasodilatation through the vasculature.


Alterations in sperm long RNA contribute to the epigenetic inheritance of the effects of postnatal trauma.
Psychiatric diseases have a strong heritable component known to not be restricted to DNA sequence-based genetic inheritance alone but to also involve epigenetic factors in germ cells. Initial evidence suggested that sperm RNA is causally linked to the transmission of symptoms induced by traumatic experiences. Here, we show that alterations in long RNA in sperm contribute to the inheritance of specific trauma symptoms. Injection of long RNA fraction from sperm of males exposed to postnatal trauma recapitulates the effects on food intake, glucose response to insulin and risk-taking in adulthood whereas the small RNA fraction alters body weight and behavioural despair. Alterations in long RNA are maintained after fertilization, suggesting a direct link between sperm and embryo RNA.


Detection and investigation of temporal clusters of congenital anomaly in Europe: seven years of experience of the EUROCAT surveillance system.
Detection and investigation of congenital anomaly clusters is one part of surveillance to detect new or changing teratogenic exposures in the population. The EUROCAT (European Surveillance of Congenital Anomalies) cluster monitoring system and results are described here. Monitoring was conducted annually from 2007 to 2013 for 18 registries covering an annual birth population up to 0.5 million births. For each registry and 72 anomaly subgroups, the scan "moving window" technique was used to detect clusters in time occurring within the last 2 years based on estimated date of conception. Registries conducted preliminary investigations using a standardised protocol to determine whether there was cause for concern, and expert review was used at key points. 165 clusters were detected, a rate of 3.4% of all 4823 cluster tests performed over 7 years, more than expected by chance. Preliminary investigations of 126 new clusters confirmed that 35% were an unusual aggregation of cases, while 56% were explained by data quality or diagnostic issues, and 9% were not investigated. For confirmed clusters, the registries' course of action was continuing monitoring. Three confirmed clusters continued to grow in size for a limited period in subsequent monitoring. This system is best suited to early detection of exposures which are sudden, widespread and/or highly teratogenic, and was reassuring in demonstrating an absence of a sustained exposure of this type. Such proactive monitoring can be run efficiently without overwhelming the surveillance system with false positives, and serves an additional purpose of data quality control.


Effect of UV irradiation on Sulfolobus acidocaldarius and involvement of the general transcription factor TFB3 in the early UV response.
Exposure to UV light can result in severe DNA damage. The alternative general transcription factor (GTF) TFB3 has been proposed to play a key role in the UV stress response in the thermoacidophilic crenarchaeon Sulfolobus acidocaldarius. Reporter gene assays confirmed that tfb3 is upregulated 90-180 min after UV treatment. In vivo tagging and immunodetection of TFB3 confirmed the induced expression at 90 min. Analysis of a tfb3 insertion mutant showed that genes encoding proteins of the Ups pili and the Ced DNA importer are no longer induced in a tfb3 insertion mutant after UV treatment, which was confirmed by aggregation assays. Thus, TFB3 plays a crucial role in the activation of these genes. Genome wide transcriptome analysis allowed a differentiation between a TFB3-dependent and a TFB3-independent early UV response. The TFB3-dependent UV response is characterized by the early induction of TFB3, followed by TFB3-dependent expression of genes involved in e.g. Ups pili formation and the Ced DNA importer. Many genes were downregulated in the tfb3 insertion mutant confirming the hypothesis that TFB3 acts as an activator of transcription. The TFB3-independent UV response includes the repression of nucleotide metabolism, replication and cell cycle progression in order to allow DNA repair.


Safety of strength training in premenopausal women: musculoskeletal injuries from a two-year randomized trial.
The health benefits of strength training must be weighed against risks, including injuries. A prior study observed 4.2 injuries that limited usual activities for a day per 1000 strength training sessions among men and women. The analysis herein explores the incidence rates of musculoskeletal injuries from strength training in women. Randomized controlled trial. SETTING; Free-living community. A total of 163 injury-free, overweight, sedentary, premenopausal women aged 25 to 44 years. Two years of strength training (n = 81) or standard care (n = 82). The intervention followed published guidelines (U.S. Department of Health and Human Services) with hypothesized injury prevention strategies. An injury survey was administered at years 1 and 2. Injury was defined as physical activity or strength training associated injuries that limited daily activities for 1 week or more. Denominators for rate calculation were accelerometer-measured physical activity and strength training attendance (strength training only). The between-group probability of injuries was assessed using generalized estimating equations. Injury incidence rates were higher in strength training compared with standard care. In strength training, the injury rates were 3.6 per 1000 strength training sessions (95% confidence interval: 2.5-4.8 per 1000) for physical activity-related injuries, and 2.6 per 1000 (95% confidence interval: 1.5-3.6 per 1000) for strength training-related injuries. Injury rates varied by definition and denominator. Strength training had lower injury rates than previously reported, providing preliminary support for the prevention strategies. The finding of strength training injuries underscores the need for balancing the benefits against the potential risks of this exercise modality.


Evaluating "old" definitions for the "new" bronchopulmonary dysplasia.
To examine the accuracy of different criteria for the diagnosis of bronchopulmonary dysplasia (BPD), based on the final age at which oxygen therapy was stopped, in predicting pulmonary and neurologic outcomes at 18-month corrected age. Data were collected prospectively on infants with birth weights between 500 and 999 g enrolled in the Trial of Indomethacin Prophylaxis in Preterms (TIPP) who survived to discharge home. Differing postnatal ages and postmenstrual ages at which supplemental oxygen therapy was no longer required formed the criteria for defining BPD. Diagnostic accuracy of each criterion for defining BPD was calculated for both poor pulmonary and poor neurosensory outcomes. The prevalence of poor pulmonary outcome was 54% and of poor neurosensory outcome was 34% in the 956 infants who were eligible for this analysis. Accuracy of different definitions of BPD was limited but greatest when using supplemental oxygen requirement at 36 weeks' postmenstrual age to predict long-term pulmonary outcome (63%) and 40 weeks to predict long-term neurosensory outcome (68%). Poor pulmonary outcome and poor neurosensory outcome are common late adverse outcomes in this population. BPD as defined by duration of oxygen therapy is a less accurate surrogate currently than in previous eras.


Developing a high-efficiency operating room for total joint arthroplasty in an academic setting.
Developing a high-efficiency operating room (OR) for total joint arthroplasty (TJA) in an academic setting is challenging given the preexisting work cultures, bureaucratic road blocks, and departmental silo mentalities. Also, academic institutions and aligned surgeons must have strategies to become more efficient and productive in the rapidly changing healthcare marketplace to ensure future financial viability. We identified specific resources and personnel dedicated to our OR for TJA, assessed the typical associated work process delays, and implemented changes and set goals to improve OR efficiencies, including more on-time starts and shorter turnover times, to perform more TJA cases per OR. We then compared these variables before and after project initiation to determine whether our goals were achieved. We gathered 1 year of retrospective TJA OR time data (starting, completion, turnover times) and combined these data with 1 month of prospective observations of the workflow (patient check-in, patient processing and preparation, OR setup, anesthesia, surgeon behaviors, patient pathway). The summarized information, including delays and inefficiencies, was presented to a multidisciplinary committee of stakeholders; recommendations were formulated, implemented, and revised quarterly. Key strategies included dedicated OR efficiency teams, parallel processing, dedicated hospital resources, and modified physician behavior. OR data were gathered and compared 3 years later. After project changes, on-time OR starts increased from less than 60% to greater than 90% and average turnover time decreased from greater than 60 minutes to 35 minutes. Our average number of TJA cases per OR increased by 29% during the course of this project. Our project achieved improved OR efficiency and productivity using strategies such as process and resource analysis, improved communication, elimination of silo mentalities, and team work.


A Computer Model of Drafting Effects on Collective Behavior in Elite 10,000-m Runners.
Drafting in cycling influences collective behavior of pelotons. Although evidence for collective behavior in competitive running events exists, it is not clear if this results from energetic savings conferred by drafting. This study modeled the effects of drafting on behavior in elite 10,000-m runners. Using performance data from a men's elite 10,000-m track running event, computer simulations were constructed using Netlogo 5.1 to test the effects of 3 different drafting quantities on collective behavior: no drafting, drafting to 3 m behind with up to ~8% energy savings (a realistic running draft), and drafting up to 3 m behind with up to 38% energy savings (a realistic cycling draft). Three measures of collective behavior were analyzed in each condition: mean speed, mean group stretch (distance between first- and last-placed runner), and runner-convergence ratio (RCR), which represents the degree of drafting benefit obtained by the follower in a pair of coupled runners. Mean speeds were 6.32 ± 0.28, 5.57 ± 0.18, and 5.51 ± 0.13 m/s in the cycling-draft, runner-draft, and no-draft conditions, respectively (all P < .001). RCR was lower in the cycling-draft condition but did not differ between the other 2. Mean stretch did not differ between conditions. Collective behaviors observed in running events cannot be fully explained through energetic savings conferred by realistic drafting benefits. They may therefore result from other, possibly psychological, processes. The benefits or otherwise of engaging in such behavior are as yet unclear.


The multiplicity and interdependency of factors influencing the health of street-based sex workers: a qualitative study.
To obtain a detailed understanding of the lives of street-based commercial sex workers (SSWs) and how factors in their lives interrelate to affect their health. In-depth interviews with 22 SSW working in Bristol, England. The SSWs described their working day as a continuous cycle of selling sex, buying and using drugs, then returning to work. They explained that they placed themselves at risk of sexually transmitted infections, rape, physical assault, verbal abuse and murder when selling sex and physical violence when buying drugs. Most of the women injected drugs and detailed how this behaviour had resulted in life-threatening illnesses, including deep vein thromboses, pulmonary emboli and abscesses. Some interviewees gave accounts of sleeping in crack houses, on friends' floors or car parks, and most participants mentioned that they did not eat, drink or sleep regularly. This self-neglect led to weight loss and physical and mental ill-health. Respondents described pressures that forced them back out to work, such as unstable accommodation, separation from children and other individuals taking their drugs or money. SSWs are trapped in a cycle of selling sex and buying and using drugs. Multiple pressures from within and outwith this cycle keep them in this situation. The multiplicity and interdependency of health problems and pressures suggest that this group are best supported with integrated multi-agency services that work flexibly across all areas of their lives. A rigid or punitive approach is likely to be counterproductive and may increase risks to the wellbeing of SSWs.


Differences in dietary habits between patients with inflammatory bowel disease in clinical remission and a healthy population.
Although patients with active inflammatory bowel disease (IBD) change their dietary habits according to suggestions from their healthcare team, no restriction is required in the remission phase. Accordingly, we compared eating patterns in IBD patients with drug-induced clinical remission with those in healthy subjects. A total of 150 IBD patients, 84 with Crohn's disease (CD) and 66 with ulcerative colitis (UC), in clinical remission, receiving immunomodulator/biologic therapy, and 100 healthy volunteers (controls) were enrolled. The IBD diagnosis had previously been established by a combined assessment of symptoms, endoscopy, histology and abdominal imaging. Clinical remission was defined as a Harvey Bradshaw index <5 for CD and a partial Mayo score <2 for UC. An experienced nutritionist guided the compilation of a food diary for 7 days according to current guidelines. Macronutrient and fiber intake was evaluated using dedicated software. Comparison between continuous variables was performed using Student's t-test or analysis of variance plus Bonferroni post-hoc analysis. Categorical variables were tested with the χ2 test. No difference in protein and carbohydrate intake was observed. IBD patients ate more calories (1970.7±348.4 vs. 1882.1±280.2 kcal/day, P=0.03), more lipids (68.9±15.2 vs. 59.4±19.0 g/day, P<0.001) and less fibers (11.9±4.7 vs. 15.5±8.3 g/day, P<0.001) than controls. No significant difference in total calories, proteins, lipids, carbohydrates or fibers was seen between CD and UC patients. IBD patients have a different macronutrient and fiber intake compared to healthy subjects, even when clinical remission and no symptoms do not dictate dietary restrictions. Therefore, psychological issues may be involved.


Parasitic plants of the genus Cuscuta and their interaction with susceptible and resistant host plants.
By comparison with plant-microbe interaction, little is known about the interaction of parasitic plants with their hosts. Plants of the genus Cuscuta belong to the family of Cuscutaceae and comprise about 200 species, all of which live as stem holoparasites on other plants. Cuscuta spp. possess no roots nor fully expanded leaves and the vegetative portion appears to be a stem only. The parasite winds around plants and penetrates the host stems via haustoria, forming direct connections to the vascular bundles of their hosts to withdraw water, carbohydrates, and other solutes. Besides susceptible hosts, a few plants exist that exhibit an active resistance against infestation by Cuscuta spp. For example, cultivated tomato (Solanum lycopersicum) fends off Cuscuta reflexa by means of a hypersensitive-type response occurring in the early penetration phase. This report on the plant-plant dialog between Cuscuta spp. and its host plants focuses on the incompatible interaction of C. reflexa with tomato.


Choroideremia: The Endpoint Endgame.
Choroideremia is an X-linked retinal degeneration resulting from the progressive, centripetal loss of photoreceptors and choriocapillaris, secondary to the degeneration of the retinal pigment epithelium. Affected individuals present in late childhood or early teenage years with nyctalopia and progressive peripheral visual loss. Typically, by the fourth decade, the macula and fovea also degenerate, resulting in advanced sight loss. Currently, there are no approved treatments for this condition. Gene therapy offers the most promising therapeutic modality for halting or regressing functional loss. The aims of the current review are to highlight the lessons learnt from clinical trials in choroideremia, review endpoints, and propose a future strategy for clinical trials.


Liver and thyroid monitoring in ambulatory patients prescribed amiodarone in 10 HMOs.
Amiodarone can cause liver and thyroid toxicity, but little is known about compliance with laboratory tests to evaluate liver and thyroid function among ambulatory patients who are dispensed amiodarone. The primary objective of this study was to identify the proportion of ambulatory patients who had liver aminotransferase and thyroid function tests during amiodarone therapy. Secondary objectives were to (1) describe factors associated with receipt of laboratory tests and (2) determine the accuracy of administrative data for assessing aminotransferase and thyroid function monitoring. This retrospective cohort study was conducted at 10 health maintenance organizations (HMOs) for the dates of service from January 1, 1999, through June 30, 2001. Participants included 1,055 patients dispensed amiodarone for at least 180 days within this date range; these patients were not necessarily new starts on amiodarone. Administrative claims data were analyzed to assess the percentage of patients with completed alanine/aspartate aminotransferase and thyroid function tests. Depending on the HMO site, electronic or paper medical records were reviewed to evaluate the validity of administrative claims data. Logistic regression models were used to explore factors associated with receipt of laboratory tests. Both aminotransferase and thyroid function tests were completed in 53.3% of patients within a 210-day follow-up period that included the 180-day period of amiodarone dispensings plus 30 days. Thyroid function, with or without liver function (aminotransferase tests), was assessed in 61.9% of patients, and aminotransferase tests, with or without thyroid function, were assessed in 68.2% of patients. After adjusting for patient characteristics and site, the factor most strongly associated with having both types of laboratory tests evaluated was concomitant therapy with a statin (adjusted odds ratio (OR) 1.55; 95% confidence interval (CI), 1.05-2.29). Other factors associated with having both types of laboratory tests evaluated included the number of outpatient visits in the 6 months before the period of amiodarone dispensings (adjusted OR 1.06; 95% CI, 1.00- 1.13 for each additional 5 visits) and living in a neighborhood where a higher median percentage of people had a high school or higher education (adjusted OR 1.09; 95% CI, 1.00-1.18 for every 10% increase in educational level at the block level). There was no association between monitoring and patient illness severity as measured by the number of comorbid conditions. On the basis of an evaluation of a randomly selected subset of 104 patient records, the sensitivity and specificity of automated data were 94.2% and 85.7% for aminotransferase tests and 83.3% and 81.1% for thyroid function tests, respectively. Approximately half of ambulatory patients dispensed amiodarone received both recommended laboratory tests for liver and thyroid function. Improved rates of testing for liver aminotransferase and thyroid function are needed for patients who receive amiodarone.


Spectroscopic observation of neutral carbon during photodissociation of explosive-related compounds in the vapor phase.
We perform time-resolved laser-induced fluorescence measurements of mononitrotoluenes (MNTs) and dinitrotoluenes (DNTs) in nitrogen and air. We observe the multipeak emission spectrum of NO and find that the emission peak intensity in the 247-248 nm range is stronger than expected compared to the other NO emission peak intensities. This increased emission intensity is believed to be due to neutral carbon [C(I)], which has a strong emission peak at 247.85 nm. By comparing the ratios of integrated emission peak intensities with those expected from the Franck-Condon factors for NO, we are able to identify samples that exhibit C(I) emission. We show that the DNTs exhibit C(I) emission for gate delays of 1500 ns and beyond, while the MNTs exhibit C(I) emission for gate delays of only up to about 500 ns. Carbon deposits in the analysis chamber confirm the presence of C. Ambient NO in air enhances the observed NO+C(I) signal from MNTs and DNTs.


Timing of physical activity across adulthood on later-life cognition: 30 years follow-up in the 1946 British birth cohort.
To assess how timing, frequency and maintenance of being physically active, spanning over 30 years in adulthood, is associated with later-life cognitive function. Participants (n=1417, 53% female) were from the prospective longitudinal cohort study, 1946 British birth cohort. Participation in leisure time physical activity was reported five times between ages 36 and 69, categorised into: not active (no participation in physical activity/month); moderately active (participated 1-4 times/month); most active (participated 5 or more times/month). Cognition at age 69 was assessed by tests of cognitive state (Addenbrooke's Cognitive Examination-III), verbal memory (word learning test) and processing speed (visual search speed). Being physically active, at all assessments in adulthood, was associated with higher cognition at age 69. For cognitive state and verbal memory, the effect sizes were similar across all adult ages, and between those who were moderately and most physically active. The strongest association was between sustained cumulative physical activity and later-life cognitive state, in a dose-response manner. Adjusting for childhood cognition, childhood socioeconomic position and education largely attenuated these associations but results mainly remained significant at the 5% level. Being physically active at any time in adulthood, and to any extent, is linked with higher later-life cognitive state, but lifelong maintenance of physical activity was most optimal. These relationships were partly explained by childhood cognition and education, but independent of cardiovascular and mental health and APOE-E4, suggestive of the importance of education on the lifelong impacts of physical activity.


Viral and host factors related to the clinical outcome of COVID-19.
In December 2019, coronavirus disease 2019 (COVID-19), which is caused by the new coronavirus severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), was identified in Wuhan (Hubei province, China)1; it soon spread across the world. In this ongoing pandemic, public health concerns and the urgent need for effective therapeutic measures require a deep understanding of the epidemiology, transmissibility and pathogenesis of COVID-19. Here we analysed clinical, molecular and immunological data from 326 patients with confirmed SARS-CoV-2 infection in Shanghai. The genomic sequences of SARS-CoV-2, assembled from 112 high-quality samples together with sequences in the Global Initiative on Sharing All Influenza Data (GISAID) dataset, showed a stable evolution and suggested that there were two major lineages with differential exposure history during the early phase of the outbreak in Wuhan. Nevertheless, they exhibited similar virulence and clinical outcomes. Lymphocytopenia, especially reduced CD4+ and CD8+ T cell counts upon hospital admission, was predictive of disease progression. High levels of interleukin (IL)-6 and IL-8 during treatment were observed in patients with severe or critical disease and correlated with decreased lymphocyte count. The determinants of disease severity seemed to stem mostly from host factors such as age and lymphocytopenia (and its associated cytokine storm), whereas viral genetic variation did not significantly affect outcomes.


Sensory organization of balance control in children with developmental coordination disorder.
This study aimed to (1) compare functional balance performance and sensory organization of postural control between children with and without developmental coordination disorder (DCD) and (2) determine the association between postural control and participation diversity among children with DCD. We recruited 81 children with DCD and 67 typically developing children. Balance was evaluated with the Sensory Organization Test (SOT) and the Movement Assessment Battery for Children-2 (Movement ABC-2). Participation patterns were evaluated using the Children Assessment of Participation and Enjoyment assessment. Analysis of variance was used to compare outcome variables between the two groups. A multiple regression analysis was performed to examine the relationship between participation diversity and balance performance in children with DCD. The DCD group had significantly lower Movement ABC-2 balance scores, SOT-derived equilibrium scores, and sensory ratios than the control group (p<0.05). However, only the Movement ABC-2 balance score was significantly associated with participation diversity in children with DCD. After accounting for the effects of age and gender, Movement ABC-2 balance score remained significantly associated with participation diversity, explaining 10.9% of the variance (F(change1,77) = 9.494, p = 0.003). Children with DCD demonstrate deficits in sensory organization of balance control. This suboptimal balance ability contributes to limited participation in activities.


Toward stronger evidence on quality improvement. Draft publication guidelines: the beginning of a consensus project.
In contrast with the primary goals of science, which are to discover and disseminate new knowledge, the primary goal of improvement is to change performance. Unfortunately, scholarly accounts of the methods, experiences, and results of most medical quality improvement work are not published, either in print or electronic form. In our view this failure to publish is a serious deficiency: it limits the available evidence on efficacy, prevents critical scrutiny, deprives staff of the opportunity and incentive to clarify thinking, slows dissemination of established improvements, inhibits discovery of innovations, and compromises the ethical obligation to return valuable information to the public.The reasons for this failure are many: competing service responsibilities of and lack of academic rewards for improvement staff; editors' and peer reviewers' unfamiliarity with improvement goals and methods; and lack of publication guidelines that are appropriate for rigorous, scholarly improvement work. We propose here a draft set of guidelines designed to help with writing, reviewing, editing, interpreting, and using such reports. We envisage this draft as the starting point for collaborative development of more definitive guidelines. We suggest that medical quality improvement will not reach its full potential unless accurate and transparent reports of improvement work are published frequently and widely.


Eyeglasses based wireless electrolyte and metabolite sensor platform.
The demand for wearable sensors has grown rapidly in recent years, with increasing attention being given to epidermal chemical sensing. Here, we present the first example of a fully integrated eyeglasses wireless multiplexed chemical sensing platform capable of real-time monitoring of sweat electrolytes and metabolites. The new concept has been realized by integrating an amperometric lactate biosensor and a potentiometric potassium ion-selective electrode into the two nose-bridge pads of the glasses and interfacing them with a wireless electronic backbone placed on the glasses' arms. Simultaneous real-time monitoring of sweat lactate and potassium levels with no apparent cross-talk is demonstrated along with wireless signal transduction. The electrochemical sensors were screen-printed on polyethylene terephthalate (PET) stickers and placed on each side of the glasses' nose pads in order to monitor sweat metabolites and electrolytes. The electronic backbone on the arms of the glasses' frame offers control of the amperometric and potentiometric transducers and enables Bluetooth wireless data transmission to the host device. The new eyeglasses system offers an interchangeable-sensor feature in connection with a variety of different nose-bridge amperometric and potentiometric sensor stickers. For example, the lactate bridge-pad sensor was replaced with a glucose one to offer convenient monitoring of sweat glucose. Such a fully integrated wireless "Lab-on-a-Glass" multiplexed biosensor platform can be readily expanded for the simultaneous monitoring of additional sweat electrolytes and metabolites.


The Role of Core Needle Biopsy for Thyroid Nodules with Initially Indeterminate Results on Previous Fine-Needle Aspiration: A Systematic Review and Meta-Analysis.
Sonography-guided fine-needle aspiration leads to relatively frequent cases of indeterminate cytology for the diagnosis of thyroid nodules. Our aim was to evaluate the efficacy and safety of core needle biopsy for the examination of thyroid nodules with initially indeterminate results on fine-needle aspiration. A computerized search of the MEDLINE and Embase databases was performed to identify relevant original articles. Studies investigating the use of core needle biopsy for thyroid nodules with initially indeterminate results on previous fine-needle aspiration were eligible for inclusion. The pooled proportions for nondiagnostic results, inconclusive results, malignancy on core needle biopsy, the ability of core needle biopsy to diagnose malignancy, and the related complications of the procedure were analyzed. The meta-analytic pooling was based on a random-effects model. Nine eligible studies, involving 2240 patients with 2245 thyroid nodules, were included. The pooled proportion for nondiagnostic results was 1.8% (95% CI, 0.4%-3.2%), and the pooled proportion for inconclusive results was 25.1% (95% CI, 15.4%-34.9%). The pooled proportion for malignancy was 18.9% (95% CI, 8.4%-29.5%). With regard to the diagnostic performance for malignancy, the sensitivity of core needle biopsy varied, ranging from 44.7% to 85.0%, but the specificity was 100% in all cases. No major complications of core needle biopsy were observed. The relatively small number of included studies and retrospective nature were limitations. Core needle biopsy has low nondiagnostic result rates and high specificity for the diagnosis of malignancy. It is a safe diagnostic technique with a higher diagnostic yield, especially when molecular testing is not available or fine-needle aspiration did not yield enough cells for molecular testing.


Isolation of multipotent neural precursors residing in the cortex of the adult human brain.
Multipotent precursors able to generate neurons, astrocytes, and oligodendrocytes have previously been isolated from human brain embryos and recently from neurogenic regions of the adult human brains. The isolation of multipotent neural precursors from adult human should open new perspectives to study adult neurogenesis and for brain repair. The present study describes the in vitro isolation from adult human brains of a progenitor responsive to both epidermal and basic fibroblast growth factors that forms spheres as it proliferates. Single spheres derived from various regions of the brain generate in vitro neurons, astrocytes, and oligodendrocytes. The clonal origin of the spheres was revealed by genomic viral insertion using lentiviral vector. Interestingly, this vector appears to be a potent tool for gene transfer into human neural progeny. Ninety-six percent of the spheres investigated were multipotent. Multipotent precursors were isolated from all brain regions studied, including the temporal and the frontal cortex, the amygdala, the hippocampus, and the ventricular zone. This study is the first evidence that primitive precursors such as multipotent precursors exist in the adult human cortex and can reside far from the ventricles. Neurogenesis derived from adult human progenitors differ to murine neurogenesis by the requirement of laminin for oligodendrocyte generation and by the action of basic-fibroblast growth factor and platelet derived growth factor that prevented the formation of oligodendrocytes and neurons. Moreover, the differentiation of human adult precursors seems to differ from fetal ones: adult precursors do not necessitate the removal of mitogen for differentiation. These results indicate that the study of adult multipotent precursors is a new platform to study adult human neurogenesis, potentially generate neural cells for transplantation, and design protocols for in vivo stimulation.


Molecular wires--impact of π-conjugation and implementation of molecular bottlenecks.
In this review we highlight recent progress in the field of photochemically and thermally induced electron transport through molecular bridges as integrative parts of electron donor-bridge-acceptor conjugates. The major emphasis is hereby on the design and the modular composition of the bridges. To this end, we will demonstrate that control over attenuation factors and reorganization energies, on one hand, as well as electronic and electron-vibration couplings, on the other hand, enables tuning electron transport over distances as short as 3.5 Å and as large as 50 Å by up to nine orders of magnitude. In terms of electron transport, the maximum extreme is given by carbon-bridged oligo-p-phenylenevinylenes of different lengths, while a zinc tetraphenylporphyrin free base tetraphenylporphyrin dyad constitutes the minimum extreme.


Patterns and Determinants of Physical Inactivity in Rural and Urban Areas in Peru: A Population-Based Study.
Physical inactivity and sedentary behaviors have been linked with impaired health outcomes. Establishing the physical inactivity profiles of a given population is needed to establish program targets and to contribute to international monitoring efforts. We report the prevalence of, and explore sociodemographical and built environment factors associated with physical inactivity in 4 resource-limited settings in Peru: rural Puno, urban Puno, Pampas de San Juan de Miraflores (urban), and Tumbes (semiurban). Cross-sectional analysis of the CRONICAS Cohort Study's baseline assessment. Outcomes of interest were physical inactivity of leisure time (<600 MET-min/week) and transport-related physical activity (not reporting walking or cycling trips) domains of the IPAQ, as well as watching TV, as a proxy of sedentarism (≥2 hours per day). Exposures included demographic factors and perceptions about neighborhood's safety. Associations were explored using Poisson regression models with robust standard errors. Prevalence ratios (PR) and 95% confidence intervals (95% CI) are presented. Data from 3593 individuals were included: 48.5% males, mean age 55.1 (SD: 12.7) years. Physical inactivity was present at rates of 93.7% (95% CI 93.0%-94.5%) and 9.3% (95% CI 8.3%-10.2%) within the leisure time and transport domains, respectively. In addition, 41.7% (95% CI 40.1%-43.3%) of participants reported watching TV for more than 2 hours per day. Rates varied according to study settings (P < .001). In multivariable analysis, being from rural settings was associated with 3% higher prevalence of leisure time physical inactivity relative to highly urban Lima. The pattern was different for transport-related physical inactivity: both Puno sites had around 75% to 50% lower prevalence of physical inactivity. Too much traffic was associated with higher levels of transport-related physical inactivity (PR = 1.24; 95% CI 1.01-1.54). Our study showed high levels of inactivity and marked contrasting patterns by rural/urban sites. These findings highlight the need to generate synergies to expand nationwide physical activity surveillance systems.


Chemotherapy with mitoxantrone plus prednisone or prednisone alone for symptomatic hormone-resistant prostate cancer: a Canadian randomized trial with palliative end points.
To investigate the benefit of chemotherapy in patients with symptomatic hormone-resistant prostate cancer using relevant end points of palliation in a randomized controlled trial. We randomized 161 hormone-refractory patients with pain to receive mitoxantrone plus prednisone or prednisone alone (10 mg daily). Nonresponding patients on prednisone could receive mitoxantrone subsequently. The primary end point was a palliative response defined as a 2-point decrease in pain as assessed by a 6-point pain scale completed by patients (or complete loss of pain if initially 1 +) without an increase in analgesic medication and maintained for two consecutive evaluations at least 3 weeks apart. Secondary end points were a decrease of > or = 50% in use of analgesic medication without an increase in pain, duration of response, and survival. Health-related quality of life was evaluated with a series of linear analog self-assessment scales (LASA and the Prostate Cancer-Specific Quality-of-Life Instrument [PROSQOLI]), the core questionnaire of the European Organization for Research and Treatment of Cancer (EORTC), and a disease-specific module. Palliative response was observed in 23 of 80 patients (29%; 95% confidence interval, 19% to 40%) who received mitoxantrone plus prednisone, and in 10 of 81 patients (12%; 95% confidence interval, 6% to 22%) who received prednisone alone (P = .01). An additional seven patients in each group reduced analgesic medication > or = 50% without an increase in pain. The duration of palliation was longer in patients who received chemotherapy (median, 43 and 18 weeks; P < .0001, log-rank). Eleven of 50 patients randomized to prednisone treatment responded after addition of mitoxantrone. There was no difference in overall survival. Treatment was well tolerated, except for five episodes of possible cardiac toxicity in 130 patients who received mitoxantrone. Most responding patients had an improvement in quality-of-life scales and a decrease in serum prostate-specific antigen (PSA) level. Chemotherapy with mitoxantrone and prednisone provides palliation for some patients with symptomatic hormone-resistant prostate cancer.


Rapid calculation algorithm of Fresnel computer-generated-hologram using look-up table and wavefront-recording plane methods for three-dimensional display.
A rapid calculation method of Fresnel computer-generated-hologram (CGH) using look-up table and wavefront-recording plane (WRP) methods toward three-dimensional (3D) display is presented. The method consists of two steps: the first step is the calculation of a WRP that is placed between a 3D object and a CGH. In the second step, we obtain an amplitude-type or phase-type CGH to execute diffraction calculation from the WRP to the CGH. The first step of the previous WRP method was difficult to calculate in real-time due to the calculation cost. In this paper, in order to obtain greater acceleration, we apply a look-up table method to the first step. In addition, we use a graphics processing unit in the second step. The total computational complexity is dramatically reduced in comparison with conventional CGH calculations. We show optical reconstructions from a 2,048×2,048 phase-type CGH generated by about 3×10(4) object points over 10 frames per second.