Wnt-1 protein as a prognostic biomarker for hepatitis B-related and hepatitis C-related hepatocellular carcinoma after surgery.
Up-regulation of Wnt-1 protein has been reported in hepatitis B virus (HBV)-related and hepatitis C virus (HCV)-related hepatocellular carcinoma (HCC) tissues and cell lines. It is known to play a fundamental role in signaling cancer progression, whereas its prognostic role in HCC remains unexplored. As a prognostic biomarker, this study analyzed Wnt-1 protein expression in 63 histology-verified HCC patients receiving curative resection. In each paired tumor and nontumor specimen, Wnt-1 levels were semiquantitatively measured by Western blotting and expressed by tumor/nontumor ratio. The data were further correlated with quantitative real-time PCR as well as with beta-catenin and E-cadherin expression by immunohistochemistry. Cumulative tumor recurrence-free survival curves were constructed using the Kaplan-Meier method and compared by the log-rank test. The results showed that 26 (group I) and 37 (group II) HCC patients had an expression ratio of Wnt-1 > or =1.5 and <1.5, respectively. The amount of Wnt-1 estimated by tumor/nontumor ratio correlated with the results by quantitative real-time PCR. High tumor Wnt-1 expression correlated with enhanced nuclear beta-catenin accumulation, diminished membranous E-cadherin expression, and increased tumor recurrence after curative tumor resection. These results suggest that Wnt-1 may be used as a predisposing risk factor for HCC recurrence. The use of tumor Wnt-1 as prognostic biomarker may identify patients with HBV- and/or HCV-related HCC patients with a high risk of tumor recurrence who may then benefit from further intensive therapy after surgery.


A 45 to 55 MHz needle-based ultrasound system for invasive imaging.
The design, construction and fabrication of a high frequency needle-based ultrasound imaging system is described. A miniature lead zirconate titanate transducer was mounted opposite a parabolic mirror in a stainless steel needle. By inserting the needle into a tissue, a cross section image of the tissue can be made. Two needle probes were built, a 45 MHz 2.8 mm diameter probe with 125 microns lateral, 55 microns axial resolution and a 55 MHz 1.6 mm diameter probe with 105 microns lateral, 40 microns axial resolution. Preliminary phantom and in vitro tissue images demonstrate the feasibility of high frequency needle-based imaging.


Effects of visual guidance on the reduction of impacts during landings.
While a common view is that vision is essential to motor performance, some recent studies have shown that continuous visual guidance may not always be required within certain time constraints. This study investigated a landing-related task (self-released falls) to assess the extent to which visual information enhances the ability to reduce the impacts at touchdown. Six individuals performed six blocked trials from four height categories in semi-counterbalanced order (5-10, 20-25, 60-65, and 90-95 cm) in vision and no-vision conditions randomly assigned. A series of two-way ANOVA with repeated measures were carried out separately on each dependent variable collapsed over six trials. The results indicated that vision during the flight did not produce softer landings. Indeed, in analysing the first peak (PFP) a main effect for visual condition was revealed in that the mean amplitude was slightly higher when vision was available (F(1,5) = 6.57; p less than 0.05), thus implicating higher forces at impact. The results obtained when the time to the first peak (TFP) was applied showed no significant differences between conditions (F(1,5) less than 1). As expected, in all cases, the analyses yielded significant main effects for the height categories factor. It appears that during self-initiated falls in which the environmental cues are known before the event, visual guidance is not necessary in order to adopt a softer landing strategy.


Reconstructing influenza incidence by deconvolution of daily mortality time series.
We propose a mathematically straightforward method to infer the incidence curve of an epidemic from a recorded daily death curve and time-to-death distribution; the method is based on the Richardson-Lucy deconvolution scheme from optics. We apply the method to reconstruct the incidence curves for the 1918 influenza epidemic in Philadelphia and New York State. The incidence curves are then used to estimate epidemiological quantities, such as daily reproductive numbers and infectivity ratios. We found that during a brief period before the official control measures were implemented in Philadelphia, the drop in the daily number of new infections due to an average infector was much larger than expected from the depletion of susceptibles during that period; this finding was subjected to extensive sensitivity analysis. Combining this with recorded evidence about public behavior, we conclude that public awareness and change in behavior is likely to have had a major role in the slowdown of the epidemic even in a city whose response to the 1918 influenza epidemic is considered to have been among the worst in the U.S.


Intimate Partner Violence in Urban, Rural, and Remote Areas: An Investigation of Offense Severity and Risk Factors.
This study compared the severity of intimate partner violence (IPV) and the relationship between risk factors for IPV and overall risk judgments of future IPV in urban, rural, and remote areas. IPV risk assessments conducted by the Swedish police between 2010 and 2014 in urban ( n = 564), rural ( n = 456), and remote ( n = 196) areas were examined. Rurality was associated with the severity of IPV reported, as well as the presence of risk factors and their relationship to overall risk judgments. Cases in remote areas included more severe IPV as well as more risk factors.


Impact of the 1990 contract for general practitioners on night visiting.
The 1990 contract for general practitioners extended the hours of eligibility for night visiting claims by 25% and introduced financial incentives to discourage the use of deputizing services. This study set out to examine the impact of these contract changes on the rate and pattern of night visiting. Family health services authority data were used to compare trends in night visiting before and after the introduction of the new contract. Rates were calculated separately for those authorities which might be expected to have a high rate of visiting because of their demographic structure and those that might be expected to have a high rate because of their socioeconomic composition, thus separating out these two sets of factors combined in the Jarman index. Rates of night visiting increased by 33% between 1989 and 1990 while the proportion of visits made by deputies fell by 19%. These changes could not simply be explained either by the extension of eligible hours or the success of financial incentives in changing behaviour in the appropriate direction. It was found that the effect of the new contract was to increase visiting most in family health services authorities with a high proportion of elderly people living alone, that is, where demand would be expected to be higher. In previous years there had been little variation in visiting rates between authorities with a high proportion of those aged 65 years and over living alone and those with a low proportion. The effect of the contract was also to increase rates of visiting most in affluent authorities, that is, where demand would be predicted to be lower. This again marked a sharp break with trends in previous years in that the gap between the high rates in the deprived family health services authorities and lower rates in the most affluent authorities narrowed. The 1990 contract achieved the government's policy aims of promoting night visiting by principals and discouraging the use of deputies in its first year. However, the finding that doctors responded more to demand from elderly people and affluent people than from deprived people presents a challenge both for analysis and for policy. It underlines the importance of disaggregating the Jarman index when examining the impact of policy change on local populations and suggests that general practitioners in the most deprived family health services authorities may lack the capacity or the incentive to respond to the changes introduced in the 1990 contract.


Importance of modelling hERG binding in predicting drug-induced action potential prolongations for drug safety assessment.
Reduction of the rapid delayed rectifier potassium current (I Kr) via drug binding to the human Ether-à-go-go-Related Gene (hERG) channel is a well recognised mechanism that can contribute to an increased risk of Torsades de Pointes. Mathematical models have been created to replicate the effects of channel blockers, such as reducing the ionic conductance of the channel. Here, we study the impact of including state-dependent drug binding in a mathematical model of hERG when translating hERG inhibition to action potential changes. We show that the difference in action potential predictions when modelling drug binding of hERG using a state-dependent model versus a conductance scaling model depends not only on the properties of the drug and whether the experiment achieves steady state, but also on the experimental protocols. Furthermore, through exploring the model parameter space, we demonstrate that the state-dependent model and the conductance scaling model generally predict different action potential prolongations and are not interchangeable, while at high binding and unbinding rates, the conductance scaling model tends to predict shorter action potential prolongations. Finally, we observe that the difference in simulated action potentials between the models is determined by the binding and unbinding rate, rather than the trapping mechanism. This study demonstrates the importance of modelling drug binding and highlights the need for improved understanding of drug trapping which can have implications for the uses in drug safety assessment.


Searching for storm water inflows in foul sewers using fibre-optic distributed temperature sensing.
A major drawback of separate sewer systems is the occurrence of illicit connections: unintended sewer cross-connections that connect foul water outlets from residential or industrial premises to the storm water system and/or storm water outlets to the foul sewer system. The amount of unwanted storm water in foul sewer systems can be significant, resulting in a number of detrimental effects on the performance of the wastewater system. Efficient removal of storm water inflows into foul sewers requires knowledge of the exact locations of the inflows. This paper presents the use of distributed temperature sensing (DTS) monitoring data to localize illicit storm water inflows into foul sewer systems. Data results from two monitoring campaigns in foul sewer systems in the Netherlands and Germany are presented. For both areas a number of storm water inflow locations can be derived from the data. Storm water inflow can only be detected as long as the temperature of this inflow differs from the in-sewer temperatures prior to the event. Also, the in-sewer propagation of storm and wastewater can be monitored, enabling a detailed view on advection.


Psychological support for chronic conditions.
Haematological conditions are varied, and every condition presents unique psychosocial challenges to patients and their families. There is a growing body of evidence about high levels of psychological distress, negative impact on outcomes and evidence-based treatments, yet service provision is patchy and demand far exceeds supply. This article focuses on the major subspecialty areas and associated neuropsychiatric comorbidities - haematological malignancies, issues related to stem cell transplants, haemoglobinopathies and haemophilia. The subsequent sections focus on common psychiatric comorbidities, considerations across the life span and models of care. Anxiety disorders and depression have higher prevalence in people with haematological conditions. The stressors faced by the individual can vary based on their condition and their stage of life. Early diagnosis and integrated management of comorbid psychiatric illness can improve quality of life and clinical outcomes. A stepped care model is recommended to ensure that psychological distress is identified and managed appropriately, and evidence for a collaborative care model is provided.


A survey of genomic traces reveals a common sequencing error, RNA editing, and DNA editing.
While it is widely held that an organism's genomic information should remain constant, several protein families are known to modify it. Members of the AID/APOBEC protein family can deaminate DNA. Similarly, members of the ADAR family can deaminate RNA. Characterizing the scope of these events is challenging. Here we use large genomic data sets, such as the two billion sequences in the NCBI Trace Archive, to look for clusters of mismatches of the same type, which are a hallmark of editing events caused by APOBEC3 and ADAR. We align 603,249,815 traces from the NCBI trace archive to their reference genomes. In clusters of mismatches of increasing size, at least one systematic sequencing error dominates the results (G-to-A). It is still present in mismatches with 99% accuracy and only vanishes in mismatches at 99.99% accuracy or higher. The error appears to have entered into about 1% of the HapMap, possibly affecting other users that rely on this resource. Further investigation, using stringent quality thresholds, uncovers thousands of mismatch clusters with no apparent defects in their chromatograms. These traces provide the first reported candidates of endogenous DNA editing in human, further elucidating RNA editing in human and mouse and also revealing, for the first time, extensive RNA editing in Xenopus tropicalis. We show that the NCBI Trace Archive provides a valuable resource for the investigation of the phenomena of DNA and RNA editing, as well as setting the stage for a comprehensive mapping of editing events in large-scale genomic datasets.


Duplications in Caenorhabditis elegans.
Thirteen chromosomal duplications, all unlinked to their linkage of origin, have been identified following X-irradiation. Ten are X-chromosome duplications, of which six are half-translocations on three autosomomal linkage groups and four are free fragments. Five of the half-translocations are homozygous fertile and two are recognizable cytologically as chromosome satellites, both of which show some mitotic instability. The free-X duplications show varying tendencies for loss. Three appear not to overlap in extent previously identified free-X duplications. The fourth carries genes from linkage group V, as well as X. Three duplications of a portion of linkage group II were identified and found to be free and quite stable in hyperploids. Some of the free duplications tend to disjoin from the X chromosome in males. New X-chromosome map data are presented.


A fiber-optic sorbitol biosensor based on NADH fluorescence detection toward rapid diagnosis of diabetic complications.
Accumulation of sorbitol in the tissue is known to cause microvascular diabetic complications. In this paper, a fiber-optic biosensor for sorbitol which is used as a biomarker of diabetic complications was developed and tested. The biosensor used a sorbitol dehydrogenase from microorganisms of the genus Flavimonas with high substrate specificity and detected the fluorescence of reduced nicotinamide adenine dinucleotide (NADH) by the enzymatic reaction. An ultraviolet light emitting diode (UV-LED) was used as the excitation light source of NADH. The fluorescence of NADH was detected using a spectrometer or a photomultiplier tube (PMT). The UV-LED and the photodetector were coupled using a Y-shaped optical fiber. In the experiment, an optical fiber probe with a sorbitol dehydrogenase immobilized membrane was placed in a cuvette filled with a phosphate buffer containing the oxidized form of nicotinamide adenine dinucleotide (NAD(+)). The changes in NADH fluorescence intensity were measured after adding a standard sorbitol solution. According to the experimental assessment, the calibration range of the sorbitol biosensor systems using a spectrometer and a PMT was 5.0-1000 μmol L(-1) and 1.0-1000 μmol L(-1), respectively. The sorbitol biosensor system using the sorbitol dehydrogenase from microorganisms of the genus Flavimonas has high selectivity and sensitivity compared with that from sheep liver. The sorbitol biosensor allows for point-of-care testing applications or daily health care tests for diabetes patients.


Lack of evidence of IgE allergic sensitisation from working with lactic acid bacteria in the dairy foods industry.
This research communication aimed to evaluate the level of immunoglobulin E from lactic acid bacteria (LAB) that are used in dairy industries. Previous studies have demonstrated that workers report symptoms of irritation and are frequently IgG-sensitised to LAB. Workers (n = 44) from a probiotic production unity and the control lab were seen by a medical practitioner and responded to an occupational questionnaire. Specific IgE by the DELFIA® technique against 6 strains of LAB were measured on 44 exposed workers and 31 controls sera. Levels of specific IgE were low and no difference was observed between the two groups. This lack of IgE response could be explained by a healthy worker effect, an efficient implementation of personal protective equipment or by an absence of allergic mechanisms to account for the self-reported irritative symptoms. Despite the high concentrations of LAB, preventive measures are effective enough to guarantee no allergic effect and to prevent other adverse health effects. The implementation of preventive measures to avoid or reduce exposure to dust of LAB, and more generally to milk powder, is recommended in all dairy industry.


Hypertension in pregnancy is a risk factor for microalbuminuria later in life.
The authors aimed to compare renal function by estimated glomerular filtration rate and albuminuria in 3 groups of women: nulliparous women, women with a history of normotensive pregnancies, and women with a history of at least one hypertensive pregnancy. Women who participated in the second Family Blood Pressure Program Study visit (2000-2004) and had serum creatinine and urine albumin measurements (n=3015) were categorized as having had no pregnancy lasting >6 months (n=341), having had only normotensive pregnancies (n=2199), or having had at least 1 pregnancy with hypertension (n=475) based on a standardized questionnaire. Women who reported having had at least one pregnancy with hypertension were significantly more likely to be hypertensive (75.6% vs 59.4%, P<.001), diabetic (34.2% vs 27.3%, P≤.001), and have higher body mass index (32.8 vs 30.5, P<.001) than those who reported normotensive pregnancies. There was a significantly greater risk of microalbuminuria (urine albumin-creatinine ratio >25 mg/g) in those who reported at least one pregnancy with hypertension (odds ratio, 1.37; confidence interval, 1.02-1.85; P=.04) than in those with normotensive pregnancies, after adjusting for risk factors for chronic kidney and cardiovascular disease. Hypertension in pregnancy is associated with an increased risk of future microalbuminuria.


Activity, not submergence, explains diving heart rates of captive loggerhead sea turtles.
Marine turtles spend their life at sea and can rest on the seafloor for hours. As air-breathers, the breath-hold capacity of marine turtles is a function of oxygen (O2) stores, O2 consumption during dives and hypoxia tolerance. However, some physiological adaptations to diving observed in mammals are absent in marine turtles. This study examined cardiovascular responses in loggerhead sea turtles, which have even fewer adaptations to diving than other marine turtles, but can dive for extended durations. Heart rates (fH) of eight undisturbed loggerhead turtles in shallow tanks were measured using self-contained ECG data loggers under five conditions: spontaneous dives, resting motionless on the tank bottom, resting in shallow water with their head out of water, feeding on squid, and swimming at the surface between dives. There was no significant difference between resting fH while resting on the bottom of the tank, diving or resting in shallow water with their head out of water. fH rose as soon as turtles began to move and was highest between dives when turtles were swimming at the surface. These results suggest cardiovascular responses in captive loggerhead turtles are driven by activity and apneic fH is not reduced by submergence under these conditions.


Multiple Holdouts With Stability: Improving the Generalizability of Machine Learning Analyses of Brain-Behavior Relationships.
In 2009, the National Institute of Mental Health launched the Research Domain Criteria, an attempt to move beyond diagnostic categories and ground psychiatry within neurobiological constructs that combine different levels of measures (e.g., brain imaging and behavior). Statistical methods that can integrate such multimodal data, however, are often vulnerable to overfitting, poor generalization, and difficulties in interpreting the results. We propose an innovative machine learning framework combining multiple holdouts and a stability criterion with regularized multivariate techniques, such as sparse partial least squares and kernel canonical correlation analysis, for identifying hidden dimensions of cross-modality relationships. To illustrate the approach, we investigated structural brain-behavior associations in an extensively phenotyped developmental sample of 345 participants (312 healthy and 33 with clinical depression). The brain data consisted of whole-brain voxel-based gray matter volumes, and the behavioral data included item-level self-report questionnaires and IQ and demographic measures. Both sparse partial least squares and kernel canonical correlation analysis captured two hidden dimensions of brain-behavior relationships: one related to age and drinking and the other one related to depression. The applied machine learning framework indicates that these results are stable and generalize well to new data. Indeed, the identified brain-behavior associations are in agreement with previous findings in the literature concerning age, alcohol use, and depression-related changes in brain volume. Multivariate techniques (such as sparse partial least squares and kernel canonical correlation analysis) embedded in our novel framework are promising tools to link behavior and/or symptoms to neurobiology and thus have great potential to contribute to a biologically grounded definition of psychiatric disorders.


Swallowing and urine flow responses of ovine fetuses to 24 h of hypoxia.
The aim of this study was to determine the effects of 24 h of hypoxia on fetal swallowing and urine flow rates. The study design included successive 24-h control, hypoxia, and recovery periods. To induce hypoxia, we infused nitrogen into the trachea of late-gestation pregnant sheep. During hypoxia, there were decreases in fetal arterial oxygen saturation [from 62.7 +/- 2.2 to 30.9 +/- 2.9% (SE)] and PO2 (from 21.1 +/- 1.0 to 14.1 +/- 0.9 mmHg) (n = 7). Fetal arterial pH decreased maximally by 0.04 +/- 0.01 at 6 h and returned to control thereafter. Fetal swallowing decreased from 13.4 +/- 2.1 to 0.6 +/- 0.2 ml.h-1.kg fetal wt-1 with the onset of hypoxia and gradually increased, but only to one-half control levels, during the last 12 h of hypoxia. Fetal urine flow gradually decreased from 9.6 +/- 1.6 ml.h-1.kg-1 to a minimum of 5.3 +/- 0.5 ml.h-1.kg-1 at 2-3 h of hypoxia and returned to control thereafter. During the first hour of the recovery period, fetal swallowing transiently increased to twice control levels before returning to control. This was followed by a delayed, transient increase in urine flow to 63% above control levels at 2-6 h after hypoxia. We conclude that the fetal swallowing and urine flow responses to prolonged hypoxia in the absence of acidemia are distinctly different from the initial inhibitory responses, in that swallowing partially and urine flow fully recovers from the initial suppression.


Pneumocystis carinii pneumonitis: a serological study.
Sera from 23 proven or clinically suspected cases of Pneumocystis carinii pneumonitis (PCP) in immunosuppressed patients predominantly with acute lymphoblastic leukaemia, and from 91 normal people, were examined for antibody to P. carinii by indirect immunofluorescence. Low levels of antibody were found in 51 of 91 normal people and elevated or rising titres of antibody in 18 out of 21 cases from whom paired or serial convalescent sera could be obtained.


Effects of Tobacco Versus Electronic Cigarette Usage on Nonsuicidal Self-Injury and Suicidality Among Chinese Youth: Cross-Sectional Self-Report Survey Study.
The increase in tobacco/conventional cigarette (CC) and electronic cigarette (EC) usage among Chinese youth has become a growing public health concern. This is the first large-scale study to compare the impact of CC and EC usage on risk for nonsuicidal self-injury (NSSI) and suicidality in cis-heterosexual and sexual and gender minority (SGM) youth populations in China. This study examines the CC and EC risks for NSSI and suicidality among Chinese youth and compares the extent to which SGM and cis-heterosexual youth's risks for NSSI and suicidality are influenced by their CC and EC usage and dependence. A total of 89,342 Chinese participants completed a cross-sectional self-report survey in 2021. Sociodemographic information, sexual orientations, gender identities, CC and EC usage, CC and EC dependence, and risks for suicidality and NSSI were assessed. The Mann-Whitney U test and chi-square test were performed for nonnormally distributed continuous variables and categorical variables, respectively. The multivariable linear regression model was used to examine both the influence of CC and EC usage and CC and EC dependence on NSSI and suicidality as well as the interaction effects of CC and EC usage and CC and EC dependence on NSSI and suicidality by group. The prevalence of CC usage (P<.001) and dependence (P<.001) among SGM participants was lower than that among their cis-heterosexual counterparts. However, the prevalence of EC usage (P=.03) and EC dependence (P<.001) among SGM participants was higher than that among their cis-heterosexual counterparts. The multivariable linear regression model showed that CC dependence and EC dependence had a unique effect on NSSI and suicidality (CCs: B=0.02, P<.001; B=0.09, P<.001; ECs: B=0.05, P<.001; B=0.14, P<.001, respectively). The interaction effects of (1) CC usage and group type on NSSI and suicidality (B=0.34, P<.001; B=0.24, P=.03, respectively) and dual usage and group type on NSSI and suicidality (B=0.54, P<.001; B=0.84, P<.001, respectively) were significant, (2) CC dependence and group type on NSSI were significant (B=0.07, P<.001), and (3) EC dependence and group type on NSSI and suicidality were significant (B=0.04, P<.001; B=0.09, P<.001, respectively). No significant interaction effect was observed between EC usage and group type on NSSI and suicidality (B=0.15, P=.12; B=0.33, P=.32, respectively) and between CC dependence and group type on suicidality (B=-0.01, P=.72). Our study shows evidence of intergroup differences in NSSI and suicidality risks between SGM and cis-heterosexual youth related to CC and EC usage. These findings contribute to the growing literature on CC and EC in cis-heterosexual and SGM populations. Concerted efforts are necessary at a societal level to curb the aggressive marketing strategies of the EC industry and media coverage and to maximize the impact of educational campaigns on EC prevention and intervention among the youth population.


Monoclonal Antibody against G Glycoprotein Increases Respiratory Syncytial Virus Clearance In Vivo and Prevents Vaccine-Enhanced Diseases.
Respiratory syncytial virus (RSV) is a common cause of lower respiratory tract illness in infants, young children, and the elderly. The G glycoprotein plays a role in host cell attachment and also modulates the host immune response, thereby inducing disease pathogenesis. We generated two monoclonal antibodies (mAbs; 5H6 and 3A5) against G protein core fragment (Gcf), which consisted of amino acid residues 131 to 230 from RSV A2 G protein. Epitope mapping study revealed that 5H6 specifically binds to the G/164-176 peptide that includes conserved sequences shared by both RSV A and B subtypes, and 3A5 binds to the G/190-204 peptide. Studies with mutant Gcf proteins in which cysteine residues were substituted with alanine revealed that 5H6 requires four cysteines for binding and 3A5 binds to Gcf variants with alanine substitutions better than wild-type. To determine if these mAbs reduce pulmonary viral infection, BALB/c mice were administered mAb and subsequently challenged with RSV. On day 4 post-infection, lung viral titers were reduced by up to 93% with the 5H6 injection and 90% with the 3A5 injection, indicating that prophylactic injection of these mAbs contributes to RSV clearance in vivo. Importantly, 5H6 injection reduced vaccine-enhanced diseases. Overall, our results suggest that this novel anti-G mAb could be used as a prophylactic regimen against RSV diseases.


Mycoplasma Ocular Infection in Subretinal Graft Transplantation of iPS Cells-Derived Retinal Pigment Epithelial Cells.
To report occurrence of acute severe inflammation after surgical implantation of mycoplasma-infected induced pluripotent stem cell-derived RPE (iPS-RPE) cells into the eyes of healthy primates, and determine the immunopathological mechanisms of the inflammation. Ophthalmic allogeneic transplantation of iPS-RPE cells was performed in the subretina of major histocompatibility complex (MHC)-matched (two eyes) and MHC-mismatched (one eye) healthy cynomolgus monkeys. The clinical course after transplantation was observed using color fundus photography, fluorescence angiography, and optical coherence tomography. After the animals were killed at 1 month after surgery, eyeballs were removed and pathologically examined. Microorganisms were analyzed by PCR methods and BLAST analysis using preserved graft iPS-RPE cells and the recipients' vitreous humor. Mixed lymphocyte-RPE assay was performed on the mycoplasma-infected and noninfected iPS-RPE cells in vitro. In tested eyes, abnormal findings were observed in the grafted retina 2 weeks after surgery. Here, we observed retinal vasculitis and hemorrhage, retinal detachment, and infiltration of inflammatory cells into the retina of the eyes. One month after surgery, animals were killed due to the severe immune responses observed. Using PCR methods, sequence analysis detected mycoplasma-DNA (Mycoplasma arginini species) in both the grafted RPE cells and the collected vitreous fluids of the monkeys. Mixed lymphocyte-RPE assay revealed that the infected iPS-RPE cells enhanced the proliferation of inflammatory cells in vitro. Transplantation of graft iPS-RPE cells contaminated with mycoplasma into the subretina caused severe ocular inflammation. Mycoplasma possesses the ability to cause immune responses in the host.


[Effect of exogenous phosphatidylserine on cognitive function and hippocampus phospholipid turnover in old rats].
The aim of the research was to examine possible role of exogenous phosphatidylserine in the modulation of the phospholipid turnover in the hippocampus and cognitive function of old rats. It has been determined that phosphatidylserine content in the hippocampus of the old rats intragastrically fed with lipids increased up to the level of phosphatidylserine in the brain of young animals. The exogenous phosphatidylserine had no effect on the phosphatidylethanolamine turnover and increase phosphatidylcholine synthesis in the hippocampus of old rats. Cognitive function of lipid-fed and control 24-month-old rats were studied with the aid of the active avoidance test in shuttle box. It has been determined that phosphatidylserine increased the number of active avoidances and decreased latency of active avoidance reaction in the learning session as compared with control rats.


The role of feelings of intimacy on perceptions of risk for a sexually transmitted disease and condom use in the sexual relationships of adolescent African-American females.
A core construct targeted by behavioural interventions is the perception that one is at risk for acquiring a sexually transmitted disease (STD). The objective of this analysis was to examine the role of intimacy on perceptions of risk for an STD (PRSTD) and condom use within late adolescent females' main relationships. A clinical sample of African-American women aged 14-19 years at enrolment were followed prospectively for 3 years. At each semiannual interview, participants reported their partner-specific PRSTD, feelings of intimacy, perceptions of partner's concurrency and condom use at last sex for each of their main sex partners. A total of 285 individuals reported 724 main relationships. Using generalised estimating equations, intimacy was negatively associated with risk perception, after adjusting for perceptions of partner concurrency (OR: 0.68; 95% CI 0.60 to 0.76). PRSTD was no longer associated with condom use after adjusting for intimacy (OR: 1.30; 95% CI 0.83 to 2.02. Intimacy was found to be associated with risk perception and condom use within adolescent main relationships. Adolescents may not view their intimate partners as sources of infection. The success of individual-level STD prevention efforts, such as condom promotion, might be limited as condoms may be in conflict with adolescents' expectations about intimate relationships.


Numb family proteins: novel players in cardiac morphogenesis and cardiac progenitor cell differentiation.
Vertebrate heart formation is a spatiotemporally regulated morphogenic process that initiates with bilaterally symmetric cardiac primordial cells migrating toward the midline to form a linear heart tube. The heart tube then elongates and undergoes a series of looping morphogenesis, followed by expansions of regions that are destined to become primitive heart chambers. During the cardiac morphogenesis, cells derived from the first heart field contribute to the primary heart tube, and cells from the secondary heart field, cardiac neural crest, and pro-epicardial organ are added to the heart tube in a precise spatiotemporal manner. The coordinated addition of these cells and the accompanying endocardial cushion morphogenesis yield the atrial, ventricular, and valvular septa, resulting in the formation of a four-chambered heart. Perturbation of progenitor cells' deployment and differentiation leads to a spectrum of congenital heart diseases. Two of the genes that were recently discovered to be involved in cardiac morphogenesis are Numb and Numblike. Numb, an intracellular adaptor protein, distinguishes sibling cell fates by its asymmetric distribution between the two daughter cells and its ability to inhibit Notch signaling. Numb regulates cardiac progenitor cell differentiation in Drosophila and controls heart tube laterality in Zebrafish. In mice, Numb and Numblike, the Numb family proteins (NFPs), function redundantly and have been shown to be essential for epicardial development, cardiac progenitor cell differentiation, outflow tract alignment, atrioventricular septum morphogenesis, myocardial trabeculation, and compaction. In this review, we will summarize the functions of NFPs in cardiac development and discuss potential mechanisms of NFPs in the regulation of cardiac development.


Using Lung Point-of-care Ultrasound in Suspected COVID-19: Case Series and Proposed Triage Algorithm.
First detected in December 2019, the severe acute respiratory syndrome coronavirus 2 pandemic upended the global community in a few short months. Diagnostic testing is currently limited in availability, accuracy, and efficiency. Imaging modalities such as chest radiograph (CXR), computed tomography, and lung ultrasound each demonstrate characteristic findings of coronavirus disease 2019 (COVID-19). Lung ultrasound offers benefits over other imaging modalities including portability, cost, reduced exposure of healthcare workers as well as decreased contamination of equipment such as computed tomography scanners. Here we present a case series describing consistent lung ultrasound findings in patients with confirmed COVID-19 despite variable clinical presentations and CXR findings. We discuss a triage algorithm for clinical applicability and utility of lung point-of-care ultrasound in the setting of COVID-19 and advocate for judicious and targeted use of this tool. Lung point-of-care ultrasound can provide valuable data supporting diagnostic and triage decisions surrounding suspected cases of COVID-19. Prospective studies validating our proposed triage algorithm are warranted.


[A gastroduodenal probe].
The methods to examine several gastrointestinal organs have been developed using a new probe. The probe is useful in analyzing the basal and stimulated gastric juice, duodenal contents of A and B groups according to the first method, secretion of the pancreas in order to detect pancreatic enzymes (trypsin, amylase, lipase), and gastric juice (basal and stimulated secretion) following the second method.


Effect of hoof characteristics on the propensity of cattle to slip.
Bovine hooves were assessed for their linear and volumetric characteristics and ranked in sets of four for hoof volume. An artificial cow was constructed with the hooves set into metal cylinders underneath a platform containing a known weight. The device was connected via a strain gauge to a pulling handle operated by two people, and the horizontal force required to move each set of hooves was determined three times. The coefficient of friction, calculated as the horizontal force divided by the fixed vertical force, was positively correlated with hoof volume. The same exercise was repeated with the hooves ranked for toe angle, and the hooves with steep toe angles had a lower coefficient of friction than the hooves with shallow toe angles. However, since both hoof volume and toe angle were related to toe length, the relationship between friction and toe angle was believed to derive from the larger size of claws with shallow toe angles. The results indicate that young cattle that have small claws with smooth surfaces and steep toe angles are more likely to slip.


Effects of cue validity on attentional selection.
Visual attention can be allocated to locations or objects, leading to enhanced processing of information at the specific location (space-based effects) or specific object (object-based effects). Previous studies have observed object-based effects to be smaller and less robust than space-based effects, with large individual differences in their temporal occurrence. Studies on space- and object-based effects are often based on a two-rectangle paradigm in which targets appear at cued locations more often than uncued locations. It is, however, unclear whether and how the target's spatial probability affects the temporal occurrence of these effects. In three experiments with different cue validities (80%, 50% and 33%), we systematically changed the interval between the cue and the target from 50 to 600 ms. On a group level and for individuals, we examined how cue validity affects the occurrence of object- and space-based effects. We observed that the magnitude and the prevalence of space-based effects heavily decreased with reduced cue validity. Object-based effects became even more sparse and turned increasingly negative with decreasing cue validity, representing a different-object rather than a same-object advantage. These findings indicate that changes in cue-validity affect both space- and object-based effects, but it does not account for the low prevalence and magnitude of object-based effects.


Compressed Animated Light Fields with Real-Time View-Dependent Reconstruction.
We propose an end-to-end solution for presenting movie quality animated graphics to the user while still allowing the sense of presence afforded by free viewpoint head motion. By transforming offline rendered movie content into a novel immersive representation, we display the content in real-time according to the tracked head pose. For each frame, we generate a set of cubemap images per frame (colors and depths) using a sparse set of of cameras placed in the vicinity of the potential viewer locations. The cameras are placed with an optimization process so that the rendered data maximise coverage with minimum redundancy, depending on the lighting environment complexity. We compress the colors and depths separately, introducing an integrated spatial and temporal scheme tailored to high performance on GPUs for Virtual Reality applications. A view-dependent decompression algorithm decodes only the parts of the compressed video streams that are visible to users. We detail a real-time rendering algorithm using multi-view ray casting, with a variant that can handle strong view dependent effects such as mirror surfaces and glass. Compression rates of 150:1 and greater are demonstrated with quantitative analysis of image reconstruction quality and performance.


Clinical Implications of FDG-PET in Pancreatic Ductal Adenocarcinoma Patients Treated with Neoadjuvant Therapy.
To evaluate the clinical significance of 18F-fluorodeoxyglucose positron emission tomography/computed tomography in patients with pancreatic ductal adenocarcinoma who underwent neoadjuvant therapy. Among 285 consecutive patients who underwent pancreatic resection for pancreatic ductal adenocarcinoma between 2015 and 2021, 86 who underwent preoperative 18F-fluorodeoxyglucose positron emission tomography/computed tomography after completion of neoadjuvant treatment were reviewed. Among preoperative factors, including post-treatment maximum standardized uptake value, predictors of early recurrence and poor prognosis were identified using multivariate analysis for decision making in surgery. Nineteen (22%) patients with pancreatic ductal adenocarcinoma demonstrated high maximum standardized uptake (≥ 4.5). High post-treatment maximum standardized uptake (≥ 4.5) predicted early recurrence within 6 months after surgery and correlated with shorter recurrence-free survival. Elevated post-treatment CA19-9 level (> 37 U/ml) and maximum standardized uptake ≥ 4.5 were independent prognostic factors. Post-treatment, a high maximum standardized uptake value indicated a poorer prognosis than a low maximum standardized uptake value in both patients with elevated CA19-9 and normal CA19-9 levels. The median overall survival in patients with elevated post-treatment CA19-9 and high maximum standardized uptake was only 17 months; 67% experienced early recurrence. Dynamic changes in maximum standardized uptake during neoadjuvant therapy were correlated with pathological response to neoadjuvant therapy, but not with radiological response or change in CA19-9 level. Post-treatment assessment using maximum standardized uptake value is useful for stratifying patients with pancreatic ductal adenocarcinoma who will benefit from surgery. Instead of subsequent curative resection, additional neoadjuvant therapy should be considered in patients with a persistently high maximum standardized uptake value.


It's Not a Race, It's a Marathon! Families Living with a Young Adult Suffering from Mental Illness.
The aim of this study is to explore families' perceptions of everyday life when living with a young adult suffering from mental illness. Findings include: 1) Families balance between letting go and enabling the young adult to become independent while remaining close to help him/her complete education, work and have a social life. 2) Young adults try to deal with symptoms of mental illness by themselves and not be a burden, although longing for family members to understand them and the situation. 3) Healthcare professionals still hold back information although young adults have consented to giving family members insight.


Factors affecting bone marrow toxicity following administration of carboplatin and paclitaxel in patients with non-small cell lung cancer.
Despite accounting for more than half of the patients diagnosed with non-small cell lung cancer (NSCLC), only 20% of elderly patients receive chemotherapy. One reason for withholding systemic therapy is the concern for an increased incidence of side-effects, especially cytopenia from bone marrow toxicity. Limited data exist regarding specific factors that affect blood count nadirs following chemotherapy. A retrospective chart review was conducted of chemotherapy-naïve patients who had received standard doses of carboplatin and paclitaxel for NSCLC. Hemoglobin levels, total white blood cell counts (WBC) and platelet counts before each chemotherapy cycle and nadir counts following each cycle were obtained. Wilcoxon test and Chi-square test were used for univariate comparisons of patient characteristics and unpaired t-test for hematological parameters. Multivariate analyses of change over time in the hematological parameters by age groups were performed using mixed models while adjusting for other clinical factors. Of the 91 consecutive patients identified from the medical records between 1992 and 2007, 37 (41%) were <60 years old at diagnosis. Pre-chemotherapy and nadir values for hemoglobin, WBC and platelet counts did not vary by age over time. The nadir values correlated with the corresponding pre-chemotherapy values. Both the pre-chemotherapy and nadir values showed a decreasing trend with increasing numbers of chemotherapy cycles administered. Age does not affect the nadir counts of hemoglobin, WBC and platelets following administration of carboplatin and paclitaxel for NSCLC. Pre-chemotherapy blood counts are more important determinants of hematologic toxicity following administration of carboplatin and paclitaxel for advanced NSCLC.


VEGF suppresses T-lymphocyte infiltration in the tumor microenvironment through inhibition of NF-κB-induced endothelial activation.
Antiangiogenic treatment targeting the vascular endothelial growth factor (VEGF) signaling pathway is in clinical use, but its effect on vascular function and the tumor microenvironment is poorly understood. Here, we investigate cross-talk between VEGF and proinflammatory TNF-α signaling in endothelial cells and its impact on leukocyte recruitment. We found that cotreatment with VEGF decreased TNF-α-induced Jurkat cell adhesion to human microvascular endothelial cells by 40%. This was associated with inhibition of TNF-α-mediated regulation of 86 genes, including 2 T-lymphocyte-attracting chemokines, CXCL10 and CXCL11 [TNF-α concentration 1 ng/ml; 50% inhibition/inhibitory concentration (IC50) VEGF, 3 ng/ml]. Notably, VEGF directly suppressed TNF-α-induced gene expression through negative cross-talk with the NF-κB-signaling pathway, leading to an early decrease in IFN regulatory factor 1 (IRF-1) expression and reduced phosphorylation of signal transducer and activator of transcription 1 (p-Stat1) at later times. Inhibition of VEGF signaling in B16 melanoma tumor-bearing mice by sunitinib treatment resulted in up-regulation of CXCL10 and CXCL11 in tumor vessels, accompanied by up to 18-fold increased infiltration of CD3(+) T-lymphocytes in B16 tumors. Our results demonstrate a novel role of VEGF in negative regulation of NF-κB signaling and endothelial activation in the tumor microenvironment and provide evidence that pharmacological inhibition of VEGF signaling enhances T-lymphocyte recruitment through up-regulation of chemokines CXCL10 and CXCL11.


[Microalgae as the source of natural products].
More than 90% of herbal products and herbal medicines have been derived from higher plants recently, but due to independent circumstances, several photosynthetic microalgal species are in focus in this point of view. In the last 50 years, many carbohydrate-, peptide-, terpenoid-, alkaloid- and phenol-type components were described from algae because of the developing structural determination and analytical methods, algae mass production and also artificial algae technologies. At the same time, based partly on traditional causes and partly on the clinical and preclinical data of today, some dried products of algae are directly used as food supplements. Hereinafter, the historical background, economic significance and metabolic background of the mostly used microalgal species will be reviewed. The diverse metabolite production of these organisms will be demonstrated by some molecules with special bioactivity. Several preclinical and clinical studies will be described relating to the microalgal species Spirulina sp., Chlorella sp., Haematococcus sp. and Dunaliella sp. Orv Hetil. 2018; 159(18): 703-708.


Methamphetamine-induced insulin release.
Administration of methamphetamine or amphetamine to rats and mice produces a rapid increase in the level of immunoassayable plasma insulin not attributable to hyperglycemia. While in the mouse this release of insulin is followed consistently by a profound hypoglycemia, in the rat this response is variable. Studies in vitro demonstrate that insulin is released by a direct effect of methamphetamine on the pancreas.


New guidelines for fluorophore application in peroxisome targeting analyses in transient plant expression systems.
Peroxisome research has been revolutionized by proteome studies combined with in vivo subcellular targeting analyses. Yellow and cyan fluorescent protein (YFP and CFP) are the classical fluorophores of plant peroxisome research. In the new transient expression system of Arabidopsis seedlings co-cultivated with Agrobacterium we detected the YFP fusion of one candidate protein in peroxisomes, but only upon co-transformation with the peroxisome marker, CFP-PTS1. The data suggested that the YFP fusion was directed to peroxisomes due to its weak heterodimerization ability with CFP-PTS1, allowing piggy-back import into peroxisomes. Indeed, if co-expressed with monomeric Cerulean-PTS1 (mCer-PTS1), the YFP fusion was no longer matrix localized. We systematically investigated the occurrence and extent of dimerization-based piggy-back import for different fluorophore combinations in five major transient plant expression systems. In Arabidopsis seedlings and tobacco leaves both untagged YFP and monomeric Venus were imported into peroxisomes if co-expressed with CFP-PTS1 but not with mCer-PTS1. By contrast, piggy-back import of cytosolic proteins was not observed in Arabidopsis and tobacco protoplasts or in onion epidermal cells for any fluorophore combination at any time point. Based on these important results we formulate new guidelines for fluorophore usage and experimental design to guarantee reliable identification of novel plant peroxisomal proteins.


Clinical holistic medicine: the Dean Ornish program ("opening the heart") in cardiovascular disease.
Dean Ornish of the Preventive Medicine Research Institute in Sausalito, California has created an intensive holistic treatment for coronary heart patients with improved diet (low fat, whole foods, plant based), exercise, stress management, and social support that has proven to be efficient. In this paper, we analyze the rationale behind his cure in relation to contemporary holistic medical theory. In spite of a complex treatment program, the principles seem to be simple and in accordance with holistic medical theories, like the Antonovsky concept of rehabilitating the sense of coherence and the life mission theory for holistic medicine. We believe there is a need for the allocation of resources for further research into the aspects of holistic health and its methods, where positive and significant results have been proven and reproduced at several sites.


Time reverse automata patterns generated by Spencer-Brown's modulator: invertibility based on autopoiesis.
In the present paper the self-consistency or operational closure of autopoiesis is described by introducing time explicitly. It is an extension of Spencer-Brown's idea of time, however. The definition of time is segregated into two parts, corresponding to the syntax and semantics of language, respectively. In this context, time reversibility is defined by the formalization of the relationship between time and self-consistency. This idea has also been discussed in the context of designation and/or naming. Here we will discuss it in the context of cellular automata and explain the structure of one-to-many type mappings. Our approach is the first attempt to extend autopoietic systems in terms of dynamics. It illustrates how to introduce an autopoietic time which looks irreversible, but without the concept of entropy.


[Effects of aspartic acid in the electroreceptors of the skate].
To identify the afferent transmitter in ampullary electroreceptors of the marine skates effects of L-aspartic acid (L-ASP) were examined using bath application of the drug. Perfusion of the basal membrane with L-ASP produced an increase in activity in most experiments (threshold concentrations 10(-7) M). L-GLU and L-ASP were identical in their ability to activate the afferents. In the presence of presynaptic blockade (high Mg2+) bath application of L-ASP restored the resting activity, suggesting a postsynaptic action of L-ASP. The results are consistent with the view that L-GLU, L-ASP or a related compound may play a role in afferent transmission in the ampullae of Lorenzini of skates.


Anxiety and mood disorder in young males with mitral valve prolapse.
This study explored the prevalence of panic disorder and other psychiatric disorders in young Han Chinese males with mitral valve prolapse (MVP). With the factors of age, sex, and ethnicity controlled, the specific role of MVP in panic disorder was analyzed. Subjects with chest pain aged between 18 and 25 years were assessed with the echocardiograph for MVP and the Chinese version of the Mini-International Neuropsychiatric Interview for panic disorder (n = 39). Of the 39 participants, 35.9% met the diagnosis of anxiety disorder, 46.2% met at least one criterion of anxiety disorder, and 23.1% met the diagnostic criteria of major depressive disorder. There was no statistically significant difference in the prevalence of panic disorder between one of the (8.3%) MVP patients, and two (7.4%) control participants. There is a high prevalence of psychiatric disorder, including anxiety disorder and major depressive disorder, in those who report pain symptoms, so that diagnosis and treatment of these patients is of great importance. In addition, individuals with MVP did not have an increased risk for panic disorder. Whether MVP may be a modifier or mediating factor for panic disorder needs to be further assessed in a larger scale study.


Roadblocks and resilience: A qualitative study of the impact of pediatric tuberculosis on Tanzanian households and solutions from caregivers.
Distinct from quantifying the economic sequelae of tuberculosis (TB) in adults, data are scarce regarding lived experiences of youth and their caregivers seeking and sustaining TB treatment in low income communities. Children ages 4-17 diagnosed with TB and their caregivers were recruited from rural and semi-urban northern Tanzania. Using a grounded theory approach, a qualitative interview guide was developed, informed by exploratory research. Twenty-four interviews were conducted in Kiswahili, audio-recorded and analyzed for emerging and consistent themes. Dominant themes found were socioemotional impacts of TB on households, including adverse effects on work productivity, and facilitators and obstacles to TB care, including general financial hardship and transportation challenges. The median percentage of household monthly income spent to attend a TB clinic visit was 34% (minimum: 1%, maximum: 220%). The most common solutions identified by caregivers to mitigate adverse impacts were transportation assistance and nutrition supplementation. To end TB, healthcare systems must acknowledge the total financial burden shouldered by low wealth families seeking pediatric TB care, provide consultations and medications locally, and increase access to TB-specific communal funds to mitigate burdens such as inadequate nutrition.Trial registration: planned sub-study of the registered prospective study, NCT05283967.Trial registration: ClinicalTrials.gov identifier: NCT05283967.


Homologous stress adaptation, antibiotic resistance, and biofilm forming ability of Salmonella enterica serovar Heidelberg ATCC8326 on different food-contact surfaces following exposure to sublethal chlorine concentrations1.
Salmonella enterica serovar Heidelberg (American Type Culture Collection; ATCC 8326) was examined for the ability to adapt to the homologous stress of chlorine through exposure to increasing chlorine concentrations (25 ppm daily increments) in tryptic soy broth (TSB). The tested strain exhibited an acquired tolerance to chlorine in TSB with the tolerant cells growing in concentrations up to 400 ppm. In addition, the chlorine stressed cells displayed rugose morphology on tryptic soy agar (TSA) plates at 37°C. The minimum inhibitory concentration (MIC) of chlorine for adapted (rugose and smooth) cells was determined to be 550 ppm and 500 ppm, respectively whereas the MIC for the control was 450 ppm. The biofilm forming ability of the adapted and control cells were examined on both plastic and stainless steel surface at room temperature and 37°C. The rugose variant, in contrast to the smooth (adapted and control) showed the ability to form strong biofilms (P ≤ 0.05) on a plastic surface at room temperature and 37°C. Rugose cells compared to smooth and control attached more (P ≤ 0.05) to steel surfaces as well. The possibility of cross-adaptation was examined by exposing the adapted and control cells to different antibiotics according to the Clinical & Laboratory Standards Institute guidelines. Adapted cells exhibited reduced susceptibility to some of the antibiotics tested as compared to control. The findings of this study suggest that exposure to sublethal chlorine concentration during the sanitization procedure can result in tolerant Salmonella cells. Chlorine may confer cross-protection that aids in the survival of the tolerant population to other environmental stresses.


Levels of the conversion endoproteases PC1 (PC3) and PC2 distinguish between insulin-producing pancreatic islet beta cells and non-beta cells.
PC1 (PC3) and PC2, members of the mammalian family of proprotein convertases homologous to the yeast Kex2 gene product, are both expressed in pancreatic islets of Langerhans. Recent studies have suggested that PC1 and PC2 are responsible for the conversion of proinsulin to insulin and connecting peptide (C-peptide) in the islet beta cells. However, the insulin-secreting beta cells are not the only cells present in these complex micro-organs, prompting us to evaluate the expression of PC1 and PC2 in islet beta and non-beta cells. Rat islet cells were sorted by autofluorescence-activated flow cytometry to separate beta cells from non-beta cells, and conversion endoprotease levels were analysed by Western blotting. The immunolabel ratio of PC1/PC2 in beta cells was 2.6. Non-beta cells displayed much lower levels of PC1 than beta cells, but twice as much PC2 (PC1/PC2 = 0.05). Post-translational modification of the convertases themselves was found to differ between the cell types. In particular, a 75 kDa precursor form of PC2 (pro-PC2) was found to accumulate in beta cells, whereas only the fully processed 67 kDa form was detected in the non-beta cells. Finally, the quantification of PC1 and PC2 and their precursor forms in transformed cells (insulin-producing beta-TC and glucagon-producing alpha-TC) showed that transformation appeared to be accompanied by unusually high levels of the precursors.


A facile method for highly uniform GaN-based nanorod light-emitting diodes with InGaN/GaN multi-quantum-wells.
We report on a simple and reproducible method for fabricating InGaN/GaN multi-quantum-well (MQW) nanorod light-emitting diodes (LEDs), prepared by combining a SiO2 nanosphere lithography and dry-etch process. Focused-ion-beam (FIB)-deposited Pt was contacted to both ends of the nanorod LEDs, producing bright electroluminescence from the LEDs under forward bias conditions. The turn-on voltage in these nanorod LEDs was higher (13 V) than in companion thin film devices (3 V) and this can be attributed to the high contact resistance between the FIB-deposited Pt and nanorod LEDs and the damage induced by inductively-coupled plasma and Ga + -ions. Our method to obtain uniform MQW nanorod LEDs shows promise for improving the reproducibility of nano-optoelectronics.


Foregut caustic injuries: results of the world society of emergency surgery consensus conference.
Lesions of the upper digestive tract due to ingestion of caustic agents still represent a major medical and surgical emergency worldwide. The work-up of these patients is poorly defined and no clear therapeutic guidelines are available. The aim of this study was to provide an evidence-based international consensus on primary and secondary prevention, diagnosis, staging, and treatment of this life-threatening and potentially disabling condition. An extensive literature search was performed by an international panel of experts under the auspices of the World Society of Emergency Surgery (WSES). The level of evidence of the screened publications was graded using the Oxford 2011 criteria. The level of evidence of the literature and the main topics regarding foregut caustic injuries were discussed during a dedicated meeting in Milan, Italy (April 2015), and during the 3rd Annual Congress of the World Society of Emergency Surgery in Jerusalem, Israel (July 2015). One-hundred-forty-seven full papers which addressed the relevant clinical questions of the research were admitted to the consensus conference. There was an unanimous consensus on the fact that the current literature on foregut caustic injuries lacks homogeneous classification systems and prospective methodology. Moreover, the non-standardized definition of technical and clinical success precludes any accurate comparison of therapeutic modalities. Key recommendations and algorithms based on expert opinions, retrospective studies and literature reviews were proposed and approved during the final consensus conference. The clinical practice guidelines resulting from the consensus conference were approved by the WSES council. The recommendations emerging from this consensus conference, although based on a low level of evidence, have important clinical implications. A world registry of foregut caustic injuries could be useful to collect a homogeneous data-base for prospective clinical studies that may help improving the current clinical practice guidelines.


Comparison of Criteria for Choosing the Number of Classes in Bayesian Finite Mixture Models.
Identifying the number of classes in Bayesian finite mixture models is a challenging problem. Several criteria have been proposed, such as adaptations of the deviance information criterion, marginal likelihoods, Bayes factors, and reversible jump MCMC techniques. It was recently shown that in overfitted mixture models, the overfitted latent classes will asymptotically become empty under specific conditions for the prior of the class proportions. This result may be used to construct a criterion for finding the true number of latent classes, based on the removal of latent classes that have negligible proportions. Unlike some alternative criteria, this criterion can easily be implemented in complex statistical models such as latent class mixed-effects models and multivariate mixture models using standard Bayesian software. We performed an extensive simulation study to develop practical guidelines to determine the appropriate number of latent classes based on the posterior distribution of the class proportions, and to compare this criterion with alternative criteria. The performance of the proposed criterion is illustrated using a data set of repeatedly measured hemoglobin values of blood donors.


The impact of decongestive physical therapy and elastic bandaging on the control of pain in patients with venous ulcers.
to evaluate pain in individuals with venous ulcers treated with elastic bandage and decongestant physical therapy. we studied 90 patients, divided into three groups with 30 patients each: a group treated with elastic bandage and decongestant physical therapy; a group treated with elastic bandage; and a group treated only with primary dressing according to tissue type and presence of exudate. We used the Pain Numerical Scale to quantify pain intensity and the McGill Pain Questionnaire for pain qualitative assessment. in the first evaluation, all patients who participated in the study reported intense pain. In the fifth evaluation, the majority of patients treated with elastic bandaging and decongestant physical therapy did not report pain; the majority of patients in the elastic bandage group reported mild pain; and most patients treated only with primary dressing reported mild to moderate pain. During all five assessments using the McGill questionnaire, most patients in the elastic bandaging and primary dressing groups used descriptors of the sensory, affective, evaluative and miscellaneous groups to describe their pain. However, in the fourth and fifth evaluations, most patients who received decongestant physical therapy combined with elastic bandaging treatment did not use any of the descriptors. patients treated with decongestant physical therapy and elastic bandage presented pain improvement from the third evaluation performed on.


Seasonal Variations of Heavy Metals in the Soil Around a Coal-Fired Thermal Power Plant, South-West Coast of India.
This study focuses on seasonal variations of heavy metals in the soil around a coal fired thermal power plant in Udupi district, which is a densely populated town in the tropical southwest coast of India. This study, pertaining to 48 soil samples, collected during the pre-monsoon, early-monsoon, monsoon and post-monsoon seasons for one year, reveals that the chemistry of collected soil samples is influenced by non-pedogenic (anthropogenic) sources such as fly-ash deposition from the thermal power plant and vehicular emissions. This was concluded based on grouping of similar behaved elements through correlation-regression analysis. The distance-wise distribution of heavy metals and backward wind-trajectory analysis suggests that pre-monsoon and post-monsoonal samples are more influenced by anthropogenic activities compared to rest of the seasons. This is supported by high concentration of Zn in pre-monsoon (25.21 mg/kg) and post-monsoon (21.32 mg/kg) seasons compared to early-monsoon (17.05 mg/kg) and monsoon (8.60 mg/kg) seasons.


Optical guiding-based cell focusing for Raman flow cell cytometer.
We report the use of an optical guiding arrangement generated in a microfluidic channel to produce a stream of single cells in a line for single-cell Raman spectroscopic analysis. The optical guiding arrangement consisted of dual-line optical tweezers, generated using a 1064 nm laser, aligned in the shape of a '' symbol. By controlling the laser power in the tweezers and the flow rate in the microfluidic channel, a single line flow of cells could be produced in the tail of the guiding arrangement, where the 514.5 nm Raman excitation beam was also located. Furthermore, by resonantly exciting the Raman spectrum, a good-quality Raman spectrum could be recorded from the flowing single cells as they passed through the Raman excitation focal spot without the need to trap the cells. As a proof of concept, it was shown that red blood cells (RBCs) could be guided to the tail of the optical guide and the Raman spectra of the resonantly excited cells could be recorded in a continuous manner without trapping the cells at a cell flow rate of ∼500 cells per h. From the recorded spectra, we were able to distinguish between RBCs containing hemoglobin in the normal form (normal-RBCs) and the met form (met-RBCs) from a mixture of RBCs comprising met-RBCs and normal-RBCs in a ratio of 1 : 9.


Allergic bronchopulmonary aspergillosis in two patients with cystic fibrosis.
Allergic bronchopulmonary aspergillosis (ABPA) is hypersensitivity to Aspergillus fumigatus which manifests as episodic wheezing, usually refractory to bronchodilator therapy, with fixed and transient pulmonary infiltrates, central bronchiectasis, blood eosinophilia, elevated serum IgE level, immediate skin reactivity to an A. fumigatus antigen and precipitating antibodies to A. fumigatus. It is an unusual complication of asthma and cystic fibrosis (CF). We present two cystic fibrosis patients with ABPA treated successfully with prednisone and, in Case 1 also with itraconazole. The physician should be alert to the possibility of ABPA whenever CF patients present with the new infiltrates, high serum total IgE and other positive parameters of A. fumigatus sensitization. Treatment with systemic steroids should be started in order to prevent irreversible lung damage.


Peripheral noxious stimulation reduces withdrawal threshold to mechanical stimuli after spinal cord injury: role of tumor necrosis factor alpha and apoptosis.
We previously showed that peripheral noxious input after spinal cord injury (SCI) inhibits beneficial spinal plasticity and impairs recovery of locomotor and bladder functions. These observations suggest that noxious input may similarly affect the development and maintenance of chronic neuropathic pain, an important consequence of SCI. In adult rats with a moderate contusion SCI, we investigated the effect of noxious tail stimulation, administered 1 day after SCI on mechanical withdrawal responses to von Frey stimuli from 1 to 28 days after treatment. In addition, because the proinflammatory cytokine tumor necrosis factor alpha (TNFα) is implicated in numerous injury-induced processes including pain hypersensitivity, we assessed the temporal and spatial expression of TNFα, TNF receptors, and several downstream signaling targets after stimulation. Our results showed that unlike sham surgery or SCI only, nociceptive stimulation after SCI induced mechanical sensitivity by 24h. These behavioral changes were accompanied by increased expression of TNFα. Cellular assessments of downstream targets of TNFα revealed that nociceptive stimulation increased the expression of caspase 8 and the active subunit (12 kDa) of caspase 3, indicative of active apoptosis at a time point consistent with the onset of mechanical allodynia. In addition, immunohistochemical analysis revealed distinct morphological signs of apoptosis in neurons and microglia at 24h after stimulation. Interestingly, expression of the inflammatory mediator NFκB was unaltered by nociceptive stimulation. These results suggest that noxious input caudal to the level of SCI can increase the onset and expression of behavioral responses indicative of pain, potentially involving TNFα signaling.


An integrative approach to phylogeny reveals patterns of environmental distribution and novel evolutionary relationships in a major group of ciliates.
Peritrichs are a major group of ciliates with worldwide distribution. Yet, its internal phylogeny remains unresolved owing to limited sampling. Additionally, ecological distributions of peritrichs are poorly known. We performed substantially expanded phylogenetic analyses of peritrichs that incorporated SSU rDNA sequences of samples collected from three continents, revealing a number of new relationships between and within major lineages that greatly challenged the classic view of the group. Interrogation of a dataset comprising new environmental sequences from an estuary and the open ocean generated with high throughput sequencing and clone libraries plus putative environmental peritrich sequences at Genbank, produced a comprehensive tree of peritrichs from a variety of habitats and revealed unique ecological distribution patterns of several lineages for the first time. Also, evidence of adaptation to extreme environments in the Astylozoidae clade greatly broadened the phylogenetic range of peritrichs capable of living in extreme environments. Reconstruction of ancestral states revealed that peritrichs may have transitioned repeatedly from freshwater to brackish/marine/hypersaline environments. This work establishes a phylogenetic framework for more mature investigations of peritrichs in the future, and the approach used here provides a model of how to elucidate evolution in the context of ecological niches in any lineage of microbial eukaryotes.


Sweetening Inhaled Antibiotic Treatment for Eradication of Chronic Respiratory Biofilm Infection.
The failure of chronic therapy with antibiotics to clear persistent respiratory infection is the key morbidity and mortality factor for patients with chronic lung diseases, primarily due to the presence of biofilm in the lungs. It is hypothesised that carbon sources, such as mannitol, could stimulate the metabolic activity of persister cells within biofilms and restore their susceptibility to antibiotics. The aims of the current study are to: (1) establish a representative in vitro model of Pseudomonas aeruginosa biofilm lung infection, and (2) investigate the effects of nebulised mannitol on antibiotic efficacy, focusing on ciprofloxacin, in the eradication of biofilm. Air interface biofilm was cultured onto Snapwell inserts incorporated into a modified pharmacopeia deposition apparatus, the Anderson Cascade Impactor (ACI). Three different formulations including mannitol only, ciprofloxacin only and combined ciprofloxacin and mannitol were nebulised onto the P. aeruginosa biofilm using the modified ACI. Antibacterial effectiveness was evaluated using colony-forming units counts, biofilm penetration and scanning electron microscopy. Nebulised mannitol promotes the dispersion of bacteria from the biofilm and demonstrated a synergistic enhancement of the antibacterial efficacy of ciprofloxacin compared to delivery of antibiotic alone. The combination of ciprofloxacin and mannitol may provide an important new strategy to improve antibiotic therapy for the treatment of chronic lung infections. Furthermore, the development of a representative lung model of bacterial biofilm could potentially be used as a platform for future new antimicrobial pre-clinical screening.


The aspiration test reveals an instability of the posterior horn of the lateral meniscus in almost one-third of ACL-injured patients.
Anterior cruciate ligament (ACL) injuries often lead to associated injuries of the posterior horn of the lateral meniscus (PHLM). Arthroscopic, assessment of PHLM instability may be difficult in the absence of a visible meniscus damage. The main objective of this prospective multi-center study was to compare the ability of the probing and aspiration tests to identify PHLM instability in a population of patients undergoing ACL reconstruction (ACLR) and a control group of patients with an intact ACL undergoing knee arthroscopy. A prospective case-control analysis was performed in three sports medicine centers. One-hundred and three consecutive patients operated for a primary isolated ACLR without structural lateral meniscus damage other than a root tear were included. They were compared to a control group of 29 consecutive patients who had a knee arthroscopy with an intact ACL and no structural lateral meniscus lesion. The probing and aspiration tests were consecutively executed according to previously published methods. In the control group, no lateral meniscus lesions were visualized during arthroscopy, and both probing and aspiration tests were negative in all patients. In the group of ACL-injured patients, a Forkel type I-III posterolateral meniscus root tear (PLMRT) was found in 12 patients (12%). In this subgroup, the probing test was positive in 4/12 patients (33%) and the aspiration test in 5 additional patients (75%). In 15 patients (15%), an elongation of the posterior root of the lateral meniscus (defined as type IV PLMRT as an addendum to the Forkel classification) could be observed during arthroscopy. In this subgroup, only 1 patient displayed a PHLM instability with the probing test (7%), whereas the aspiration test was positive in 13/15 patients (87%). In the remaining 76 patients (74%), no structural lesion of the PHLM could be identified. Nevertheless, an instability of the PHLM could be identified in 8 of them (11%) with the probing test, and the aspiration test was positive in 2 additional knees (13%) of this apparently normal subgroup. Altogether, in the entire ACL injury cohort, a positive probing test was observed in 13/103 patients (13%) and a positive aspiration test in 32/103 knees (31%) (p < 0.01). Careful observation and examination of the PHLM with the aspiration test revealed a substantial amount of previously undiagnosed lateral meniscus instabilities in ACL-injured knees. The prevalence of PHLM instability as evaluated by the aspiration test was high (31%). The aspiration test was superior to the probing test in detecting an instability of the PHLM in a population of ACL-injured patients. II.


Evolution of the speech-ready brain: The voice/jaw connection in the human motor cortex.
A prominent model of the origins of speech, known as the "frame/content" theory, posits that oscillatory lowering and raising of the jaw provided an evolutionary scaffold for the development of syllable structure in speech. Because such oscillations are nonvocal in most nonhuman primates, the evolution of speech required the addition of vocalization onto this scaffold in order to turn such jaw oscillations into vocalized syllables. In the present functional MRI study, we demonstrate overlapping somatotopic representations between the larynx and the jaw muscles in the human primary motor cortex. This proximity between the larynx and jaw in the brain might support the coupling between vocalization and jaw oscillations to generate syllable structure. This model suggests that humans inherited voluntary control of jaw oscillations from ancestral species, but added voluntary control of vocalization onto this via the evolution of a new brain area that came to be situated near the jaw region in the human motor cortex.


Investigation of the Effect of Lasmiditan on the Pharmacokinetics of P-Glycoprotein and Breast Cancer Resistance Protein Substrates.
Lasmiditan is an in vitro inhibitor of P-glycoprotein (P-gp) and breast cancer resistance protein (BCRP) efflux transporters. We aimed to confirm predictions from physiologically based pharmacokinetic models of lasmiditan, and assess the safety and tolerability of rosuvastatin and dabigatran co-administered with lasmiditan. In this open-label, post-marketing drug-drug interaction, phase 1 clinical trial, eligible participants were adults aged 21-70 years with a body mass index of 18.5-35.0 kg/m2 . Part 1 (P-gp, 150 mg dabigatran etexilate with 200 mg lasmiditan) and part 2 (BCRP, 10 mg rosuvastatin with 200 mg lasmiditan) employed similar designs: a single dose of probe substrate administered on day -2 with pharmacokinetic evaluation; 1-week washout; lasmiditan administered on days 8 and 9 alone; lasmiditan co-administered with a single dose of probe substrate on day 10, with pharmacokinetic evaluation of probe substrate and lasmiditan. Sixty-six participants were included in part 1 and 30 participants were included in part 2. Following dabigatran co-administration with lasmiditan, versus dabigatran alone, 90% confidence intervals for geometric least-squares (LS) mean ratios of area under the plasma concentration-time curve from time 0 extrapolated to infinity (AUC0-∞ ) and maximum observed drug concentration (Cmax ) were not contained within the non-effect boundaries (0.80 to 1.25). Dabigatran AUC0-∞ increased by 25% and Cmax increased by 22%. The median time of maximum observed drug concentration (tmax ) for dabigatran was 2.0 to 3.0 hours. Following rosuvastatin co-administration with lasmiditan, versus rosuvastatin alone, 90%CIs for geometric LS mean ratios of AUC0-∞ and Cmax were contained within non-effect boundaries (0.80-1.25). Rosuvastatin AUC0-∞ increased by 15% and Cmax increased by 7%. The median tmax for rosuvastatin was 4.0 hours. Results suggest that lasmiditan has a weak effect on P-gp substrates and no clinically relevant effect on BCRP substrates.


Assessment of utility of ductal lavage and ductoscopy in breast cancer-a retrospective analysis of mastectomy specimens.
Early detection of breast lesions continues to be an important goal in the management of breast cancer. At present, mammographic imaging in addition to physical examination is the main screening method for the detection of cancer. Fiberoptic ductoscopy and duct lavage are being recently used to evaluate patients at risk for breast cancer. Both techniques examine the nipple and central duct area to identify intraductal lesions. In this study, we examined the frequency of involvement of these structures in mastectomy specimens as a surrogate marker to estimate the utility of these methods in breast cancer patients. The presence and type of involvement of the nipple and central duct area was retrospectively evaluated in 801 mastectomy specimens from a 4-year period that had been performed for infiltrating or in situ carcinoma. Atypical proliferation or cells, when seen in the ducts of this region, was considered as evidence of nipple involvement, even if definite evidence of malignancy was lacking. The review of 801 mastectomies showed nipple and central duct involvement in 179 (22%) cases. Among the 665 cases of infiltrating carcinoma, 17% did not have an intraductal component. The relative rarity of nipple and central duct in mastectomy specimens and the lack of an in situ component in many cases raise questions about the utility of fiberoptic ductoscopy and duct lavage as methods for screening of breast cancer. Additionally, as these methods examine only 1-2 ducts of the 15-20 ducts that open at the nipple, they might fail to detect focal abnormalities.


Integrin αIIbβ3-Dependent ERK Signaling Is Regulated by Src and Rho Kinases in Both Leu33 and Pro33 Polymorphic Isoforms.
Platelet integrin αIIbβ3 possesses a Leu/Pro polymorphism at residue 33 (Leu33/HPA-1a or Pro33/HPA-1b). The Pro33 isoform has been suggested to exhibit prothrombotic features. αIIbβ3-expressing CHO (Chinese hamster ovary) cells on immobilized fibrinogen show activation of the MAP kinase family member ERK2, with an enhanced ERK2 activity in Pro33 cells compared to Leu33 cells. In our present work, we examined how the Leu/Pro polymorphism modulates the ERK2 activation stimulated by 2 differently triggered outside-in signalings. We either treated the CHO cells with Mn2+ or allowed them to adhere to fibrinogen. Moreover, we studied which signaling cascades are involved in ERK2 activation. In contrast to immobilized fibrinogen, Mn2+ did not significantly increase ERK2 activation. However, Mn2+ had a synergistic effect on ERK2 phosphorylation when combined with immobilized fibrinogen. Pro33 cells adherent to fibrinogen exhibited a significantly greater ERK2 activity than Leu33 cells in the presence of Mn2+, which peaked after 10 min of adhesion. Our data showed that Src family and rho kinases play a crucial role in the integrin αIIbβ3-dependent outside-in signaling to ERK2.


Occupational health and safety of anti-tumour necrosis factor alpha monoclonal antibodies with casual exposure.
As the incidence of chronic inflammatory diseases continues to rise, so has cumulative use of biological therapy particularly anti-tumour necrosis factor (TNF) alpha agents. As longer term data emerges about the safety of these drugs, there is increasing attention drawn to safety of those with casual exposure. At present, there is little in the published literature to give guidance for healthcare workers regarding their health and safety in handling of anti-TNF agents, nor the appropriate precautions required. The aim of this review is to summarize the currently known adverse effects, risk assessment tools for classifying and handling hazardous substances, and present evidence for systemic absorption through occupational exposure in handling anti-TNF antibodies at the level of reconstitution. There is no evidence for systemic absorption of these drugs in context of handling or accidental spillage and no reports of subsequent biological adverse effects. Given the need of this class of medication to be used for long-term maintenance therapy and their increasing indications, improved efficiency and cost-containing measures are recommended. As such, simple universal precautions of protective clothing of glove, gown, facemask and eye goggles are appropriate measures for reconstitution of anti-TNF antibodies.


[Biologically active food additives].
More than half out of 40 projects for the medical science development by the year of 2000 have been connected with the bio-active edible additives that are called "the food of XXI century", non-pharmacological means for many diseases. Most of these additives--nutricevtics and parapharmacevtics--are intended for the enrichment of food rations for the sick or healthy people. The ecologicaly safest and most effective are combined domestic adaptogens with immuno-modulating and antioxidating action that give anabolic and stimulating effect,--"leveton", "phytoton" and "adapton". The MKTs-229 tablets are residue discharge means. For atherosclerosis and general adiposis they recommend "tsar tablets" and "aiconol (ikhtien)"--on the base of cod-liver oil or "splat" made out of seaweed (algae). All these preparations have been clinically tested and received hygiene certificates from the Institute of Dietology of the Russian Academy of Medical Science.


Ocean acidification at a coastal CO2 vent induces expression of stress-related transcripts and transposable elements in the sea anemone Anemonia viridis.
Ocean acidification threatens to disrupt interactions between organisms throughout marine ecosystems. The diversity of reef-building organisms decreases as seawater CO2 increases along natural gradients, yet soft-bodied animals, such as sea anemones, are often resilient. We sequenced the polyA-enriched transcriptome of adult sea anemone Anemonia viridis and its dinoflagellate symbiont sampled along a natural CO2 gradient in Italy to assess stress levels in these organisms. We found that about 3.1% of the anemone transcripts, but <1% of the Symbiodinium sp. transcripts were differentially expressed. Processes enriched at high seawater CO2 were linked to cellular stress and inflammation, including significant up-regulation of protective cellular functions and down-regulation of metabolic pathways. Transposable elements were differentially expressed at high seawater CO2, with an extreme up-regulation (> 100-fold) of the BEL-family of long terminal repeat retrotransposons. Seawater acidified by CO2 generated a significant stress reaction in A. viridis, but no bleaching was observed and Symbiodinium sp. appeared to be less affected. These observed changes indicate the mechanisms by which A. viridis acclimate to survive chronic exposure to ocean acidification conditions. We conclude that many organisms that are common in acidified conditions may nevertheless incur costs due to hypercapnia and/or lowered carbonate saturation states.


Multi-omic data integration for the study of production, carcass, and meat quality traits in Nellore cattle.
Data integration using hierarchical analysis based on the central dogma or common pathway enrichment analysis may not reveal non-obvious relationships among omic data. Here, we applied factor analysis (FA) and Bayesian network (BN) modeling to integrate different omic data and complex traits by latent variables (production, carcass, and meat quality traits). A total of 14 latent variables were identified: five for phenotype, three for miRNA, four for protein, and two for mRNA data. Pearson correlation coefficients showed negative correlations between latent variables miRNA 1 (mirna1) and miRNA 2 (mirna2) (-0.47), ribeye area (REA) and protein 4 (prot4) (-0.33), REA and protein 2 (prot2) (-0.3), carcass and prot4 (-0.31), carcass and prot2 (-0.28), and backfat thickness (BFT) and miRNA 3 (mirna3) (-0.25). Positive correlations were observed among the four protein factors (0.45-0.83): between meat quality and fat content (0.71), fat content and carcass (0.74), fat content and REA (0.76), and REA and carcass (0.99). BN presented arcs from the carcass, meat quality, prot2, and prot4 latent variables to REA; from meat quality, REA, mirna2, and gene expression mRNA1 to fat content; from protein 1 (prot1) and mirna2 to protein 5 (prot5); and from prot5 and carcass to prot2. The relations of protein latent variables suggest new hypotheses about the impact of these proteins on REA. The network also showed relationships among miRNAs and nebulin proteins. REA seems to be the central node in the network, influencing carcass, prot2, prot4, mRNA1, and meat quality, suggesting that REA is a good indicator of meat quality. The connection among miRNA latent variables, BFT, and fat content relates to the influence of miRNAs on lipid metabolism. The relationship between mirna1 and prot5 composed of isoforms of nebulin needs further investigation. The FA identified latent variables, decreasing the dimensionality and complexity of the data. The BN was capable of generating interrelationships among latent variables from different types of data, allowing the integration of omics and complex traits and identifying conditional independencies. Our framework based on FA and BN is capable of generating new hypotheses for molecular research, by integrating different types of data and exploring non-obvious relationships.


Induction of cell cycle arrest in prostate cancer cells by the dietary compound isoliquiritigenin.
Isoliquiritigenin (ISL), a flavonoid chalcone that is present in licorice, shallot, and bean sprouts, is known to have antitumorigenic activities. The present study examined whether ISL alters prostate cancer cell cycle progression. DU145 human and MatLyLu (MLL) rat prostate cancer cells were cultured with various concentrations of ISL. In both DU145 and MLL cells treated with ISL, the percentage of cells in the G1 phase increased, and the incorporation of [(3)H]thymidine decreased. ISL decreased the protein levels of cyclin D1, cyclin E, and cyclin-dependent kinase (CDK) 4, whereas cyclin A and CDK2 expressions were unaltered in cells treated with ISL. The expression of the CDK inhibitor p27(KIP1) was increased in cells treated with 20 micromol/L ISL. In addition, treatment of cells with 20 micromol/L ISL for 24 hours led to G2/M cell cycle arrest. Cell division control (CDC) 2 protein levels remained unchanged. The protein levels of phospho-CDC2 (Tyr15) and cyclin B1 were increased, and the CDC25C level was decreased by ISL dose-dependently. We demonstrate that ISL promotes cell cycle arrest in DU145 and MLL cells, thereby providing insights into the mechanisms underlying its antitumorigenic activities.


Questionnaire survey of proliferative enteropathy on British pig farms.
Risk factors for proliferative enteropathy were investigated by means of a postal questionnaire survey of randomly selected British pig farms. Replies were received from 319 (56 per cent) of the 569 questionnaires posted, representing 1.5 per cent of the total number of pig farms in Britain. Thirty-one per cent of the farms had experienced at least one episode of proliferative enteropathy within the previous three years, usually confirmed by their veterinary surgeon. There was a strong association for the occurrence of proliferative enteropathy in herds of over 500 sows (P < 0.005) and in herds with enzootic pneumonia (P < 0.01). Outbreaks had occurred in five of the six nucleus herds surveyed, the other had only 80 sows. Outbreaks occurred in 32 of 69 herds that had obtained their replacement boars from nucleus herds (P < 0.05), suggesting that infected boars may carry the disease into distant herds. The use of either fully slatted (P < 0.05) or fully meshed floors (P < 0.01) above sunken pits in buildings used to house pigs immediately after weaning, and the use of partially (P < 0.05) or fully slatted floors (P < 0.05) in buildings used to house pigs two to six months old, were risk factors for outbreaks of proliferative enteropathy, compared with the use of straw bedding or solid floors. The destocking of entire buildings containing pigs two to four months old before the introduction of fresh pigs, was associated with a reduced risk (P < 0.05), but the destocking of selected pens rather than the whole building had no such association. The type of diet, or feeding or watering system and the types of buildings used were not identified as risk factors.


Towards systems biology of human pulmonary fibrosis.
The integrated effect of multiple pathways, molecules, genetic polymorphisms, environmental stimuli, and possible infection determines the lung phenotype in idiopathic pulmonary fibrosis (IPF), a chronic progressive and often lethal lung disease. Systems biology approaches aim to provide a systemwide view of biological process using computational tools and high-throughput technologies. Although much of the analysis of genome-level transcriptional high-resolution profiles of IPF was reductionist, usually focusing on a single factor in the disease process, there are some studies that implement systems approaches. We discuss these analyses and provide examples of the global analysis of IPF, hypersensitivity pneumonitis, and nonspecific interstitial pneumonia. Detailed quantitative phenotyping and correlation with microarray results as well as high-throughput genotyping should provide us with the datasets to implement systems biology approaches in fibrosis research. Interdisciplinary teams and training of junior investigators in the vocabulary of systems biology should allow us to use these datasets integratively and generate a global model of human pulmonary fibrosis.


A prospective study of fetal head growth, autistic traits and autism spectrum disorder.
Altered trajectories of brain growth are often reported in Autism Spectrum Disorder (ASD), particularly during the first year of life. However, less is known about prenatal head growth trajectories, and no study has examined the relation with postnatal autistic symptom severity. The current study prospectively examined the association between fetal head growth and the spectrum of autistic symptom severity in two large population-based cohorts, including a sample of individuals with clinically diagnosed ASD. This study included 3,820 children from two longitudinal prenatal cohorts in The Netherlands and Australia, comprising 60 individuals with a confirmed diagnosis of ASD. Latent growth curve models were used to examine the relationship between fetal head circumference measured at three different time points and autistic traits measured in postnatal life using either the Social Responsiveness Scale or the Autism-Spectrum Quotient. While lower initial prenatal HC was weakly associated with increasing autistic traits in the Dutch cohort, this relationship was not observed in the Australian cohort, nor when the two cohorts were analysed together. No differences in prenatal head growth were found between individuals with ASD and controls. This large population-based study identified no consistent association across two cohorts between prenatal head growth and postnatal autistic traits. Our mixed findings suggest that further research in this area is needed. Autism Res 2018, 11: 602-612. © 2018 The Authors Autism Research published by International Society for Autism Research and Wiley Periodicals, Inc. It is not known whether different patterns of postnatal brain growth in Autism Spectrum Disorder (ASD) also occurs prenatally. We examined fetal head growth and autistic symptoms in two large groups from The Netherlands and Australia. Lower initial prenatal head circumference was associated with autistic traits in the Dutch, but not the Australian, group. No differences in head growth were found in individuals with ASD and controls when the data was combined. Our mixed findings suggest that more research in this area is needed.


Dobutamine-stress echocardiography in asymptomatic patients with aortic regurgitation.
Decreased contractile reserve may already be present in asymptomatic patients with aortic regurgitation and normal ejection fraction (EF), thus indicating the need for frequent and accurate assessments of the left ventricular function for the early detection of systolic dysfunction. To analyze if increments in EF with low dose dobutamine could predict surgery and/or death in patients with aortic regurgitation. Dobutamine-stress echocardiography was performed in 24 patients with aortic regurgitation in order to analyze whether EF increments at low dobutamine doses could predict the need for surgery and/or death in this group of patients. Mean age was 37.8+/-16.8 years and 16 patients (66%) were male. EF increased from a mean baseline value of 62.3+/-7.9% to 71.5+/-10.5% at a dobutamine dose of 20 microg/kg/min (p<0.001). The patients were followed-up for 36.6+/-20.1 months; two patients died (one of cardiovascular death) and five underwent cardiac surgery. Baseline EF was correlated with surgery and death in the follow-up of patients. Baseline EF was correlated with surgery or death in the follow-up of young patients with aortic regurgitation. However, the percentage increase in EF at low dobutamine doses did not allow us to predict events in these patients.