PTSD, psychological morbidity and marital dissatisfaction in colonial war veterans.
Background: Forty years after Colonial War, veterans still show psychological disturbances affecting their marital and sexual satisfaction.Aims: This study analyzed the relationships between Post-Traumatic Stress Disorder (PTSD), number of PTSD symptoms and symptom clusters, psychological morbidity, marital dissatisfaction and sexual dissatisfaction; the variables that contributed to marital dissatisfaction and the mediator role of marital dissatisfaction and sexual dissatisfaction, in a sample of colonial War Veterans.Method: The sample included 138 Portuguese war veterans who answered Index of Marital Satisfaction; Index of Sexual Satisfaction; Beck Depression Inventory; State Trait Anxiety Inventory; Post-Traumatic Stress Disorder Scale.Results: PTSD, number of PTSD symptoms and symptom clusters were associated with psychological morbidity, marital and sexual dissatisfaction. Age, depression symptoms and sexual dissatisfaction contributed to marital dissatisfaction and the model explained 55% of the variance. Marital dissatisfaction mediated the relationship between depression symptoms and sexual dissatisfaction, as well as between number of PTSD symptoms and sexual dissatisfaction.Conclusions: Health professionals need to take into consideration the veteran's marital and sexual relationship in clinical routine consultations. As such, treating the veteran in the couple' context seems warranted.


Wide electrical tunability of a GaInAsP/InP microdisk resonator.
We report on the characterization of an InP/InGaAsP-material-based microdisk resonator optical filter. The originality here is constituted by the use of a localized control electrode that is used for the tuning of the resonance wavelength of the filter via the injection of a driving current. Tuning of the resonance wavelength close to 8 nm has been experimentally achieved for a drive current of 80 mA.


Monovalent salt enhances colloidal stability during the formation of chitosan/tripolyphosphate microgels.
Chitosan micro- and nanoparticles are routinely prepared through ionotropic gelation, where sodium tripolyphosphate (TPP) is added as a cross-linker to dilute chitosan solutions. Despite the wide use of these gel-like particles, their preparation currently relies on trial and error. To address this, we used isothermal titration calorimetry (ITC), dynamic light scattering (DLS), transmission electron microscopy (TEM), and ζ-potential measurements to investigate how the formation, structure, and colloidal stability of chitosan microgels are linked to the molecular interactions that underlie their self-assembly. The strength of the chitosan/TPP interactions was systematically varied through the addition of monovalent salt (NaCl). Remarkably, and contrary to other colloidal systems, this revealed that moderate amounts of NaCl (e.g., 150 mM) enhance the colloidal stability of chitosan/TPP microgels during their formation. This stems from the weakened chitosan/TPP binding, which apparently inhibits the bridging of the newly formed microgels by TPP. The enhanced colloidal stability during the ionic cross-linking process yields microgels with dramatically narrower size distributions, which hitherto have typically required the deacetylation and fractionation of the parent chitosan. Conversely, at high ionic strengths (ca. 500 mM) the chitosan/TPP binding is weakened to the point that the microgels cease to form, thus suggesting the existence of an optimal ionic strength for ionotropic microgel preparation.


Effects of Highly Bioavailable Curcumin Supplementation on Common Cold Symptoms and Immune and Inflammatory Functions in Healthy Japanese Subjects: A Randomized Controlled Study.
This study aimed to investigate the effects of 12-week consumption of highly bioavailable curcumin (150 mg/day of Theracurmin Super [TS-P1] or Theracurmin [CR-033P]) on common cold symptoms, immune function, and inflammatory markers. A randomized, double-blind, placebo-controlled study was conducted from November 2021 to May 2022 on 99 healthy Japanese adults. Using a computerized random number generator, each subject was randomly assigned to one of the following three groups: TS-P1, CR-033P, or placebo (n = 33 per group). For 12 weeks, each group consumed the four capsules that were given to them daily. The cumulative number of days for which common cold symptoms persisted was set as the primary outcome. Immunity parameters, inflammatory parameters, liver function parameters, and physical examination results were additional outcomes. A safety assessment was also performed. Ninety-four subjects completed the study, and the per protocol set included 30 subjects in the placebo group, 32 subjects in the TS-P1 group, and 33 subjects in the CR-033P group. The cumulative number of days for which common cold symptoms persisted was significantly lower in the TS-P1 and CR-033P groups than that in the placebo group. No adverse effects were observed. Consumption of highly bioavailable curcumin, TS-P1 or CR-033P (150 mg/day), for 12 weeks reduced the number of days for which common cold symptoms persisted in healthy Japanese adults.


Estimation of cholinesterase activity (EC 18.104.22.168; 184.108.40.206) in undiluted plasma and erythrocytes as a tool for measuring in vivo effects of reversible inhibitors.
In vivo effects of reversible inhibitors of cholinesterase activity were determined radiometrically in undiluted samples of erythrocytes and plasma. [14C]acetylcholine at substrate saturation, 25 degrees C and pH 7.4 permitted rapid and precise determination of butyrylcholinesterase (EC 220.127.116.11) and acetylcholinesterase (EC 22.214.171.124) activities. Reference values for acetylcholinesterase and butyrylcholinesterase were estimated in the plasma and erythrocyte haemolysate of 102 healthy volunteers. The time course of in vitro inhibition was monitored, starting immediately after addition of 9-amino-1,2,3,4-tetrahydroacridine (tacrine), eserine or pyridostigmine to undiluted human plasma. Maximal inhibition (in vitro) was seen within 60 min with tacrine and eserine, in contrast to 180 min with pyridostigmine. The inhibition remained constant for more than 10 h except with eserine, from which enzyme activity showed an early recovery. Concentration response experiments were performed in undiluted human plasma and undiluted human erythrocyte haemolysate. Ki-values of tacrine, eserine and pyridostigmine were estimated. In contrast to pyridostigmine and eserine, tacrine was found to have a higher affinity for butyrylcholinesterase than for acetylcholinesterase. Tacrine at 2.5 mumol/l resulted in complete inhibition of butyrylcholinesterase and 70% inhibition of acetylcholinesterase activity. Dilution of these samples up to 100-fold was accompanied by almost complete recovery of acetylcholinesterase and by 50% recovery of butyrylcholinesterase.


Influence of dairy matrices on nutrient release in a simulated gastrointestinal environment.
The objective of this study was to compare the kinetics of the release of nutrients (peptides and fatty acids) from different dairy matrices (milks, yogurts, and cheeses) in a simulated gastrointestinal environment. Prior to processing, different heat and homogenization treatments were applied to milks, and different drainage pH levels were used to control calcium concentration in cheeses. The dairy matrices were then subjected to simulated digestion. Matrix degradation, protein hydrolysis, and fat hydrolysis were analyzed during the gastric and intestinal digestion phases. Intense heat treatment of milk induced faster digestion of proteins in the gastric environment. Cheeses were more resistant to protein and lipid digestion than liquid or semi-solid matrices were. No direct relationship could be established between disintegration kinetics and cheese rheological properties. Fatty acid release in the intestinal phase was much faster when matrices were produced from homogenized milk. For cheeses, greater fatty acid release could not be related to faster matrix disintegration, suggesting that the lipid droplet size dispersion was more important than matrix breakdown was for the modulation of lipid digestion kinetics. Calcium soaps were produced in the intestinal environment, and their concentration was higher during the digestion of cheeses in comparison with milks and yogurts. These results suggest that processing-induced modifications to the composition, microstructure, and rheological properties of dairy matrices could be used to control nutrient delivery.


Effectiveness of a Faith-placed Cardiovascular Health Promotion Intervention for Rural Adults.
Cardiovascular disease (CVD) is the leading cause of mortality in the US. Further, rural US adults experience disproportionately high CVD prevalence and mortality compared to non-rural. Cardiovascular risk-reduction interventions for rural adults have shown short-term effectiveness, but long-term maintenance of outcomes remains a challenge. Faith organizations offer promise as collaborative partners for translating evidence-based interventions to reduce CVD. We adapted and implemented a collaborative, faith-placed, CVD risk-reduction intervention in rural Illinois. We used a quasi-experimental, pre-post design to compare changes in dietary and physical activity among participants. Intervention components included Heart Smart for Women (HSFW), an evidence-based program implemented weekly for 12 weeks followed by Heart Smart Maintenance (HSM), implemented monthly for two years. Participants engaged in HSFW only, HSM only, or both. We used regression and generalized estimating equations models to examine changes in outcomes after one year. Among participants who completed both baseline and one-year surveys (n = 131), HSFW+HSM participants had significantly higher vegetable consumption (p = .007) and combined fruit/vegetable consumption (p = .01) compared to the HSM-only group at one year. We found no differences in physical activity. Improving and maintaining CVD-risk behaviors is a persistent challenge in rural populations. Advancing research to improve our understanding of effective translation of CVD risk-reduction interventions in rural populations is critical.


Effect of different photoinitiator systems on conversion profiles of a model unfilled light-cured resin.
The aim of this study was to compare the efficiency of different camphorquinone (CQ)/amine photo-initiating systems for the photopolymerization of a model dental resin based in Bis-GMA/TEGDMA. The monomer conversion versus exposure time was measured in resins containing different types and concentrations of photoinitiators and subjected to different irradiation procedures. The conversion profiles during photopolymerization were investigated using near-infrared spectroscopy (NIR). CQ was used in combination with dimethylaminoethylmethacrylate (DMAEMA), ethyl-4-dimethylaminobenzoate (EDMAB), 4-(N,N-dimethylamino)phenethyl alcohol (DMPOH), and N,N-3,5-tetramethylaniline (TMA) at different concentrations. From the conversion profiles, the approximate order of the accelerating ability of the respective amines were EDMAB approximately DMPOH>TMA>DMAEMA. The conversion profiles of all resins were sensitive to the illumination period. For a given exposure time, samples cured by sequential illumination resulted in lower conversion than samples cured by continuous irradiation. These results were attributed to a combination of both photo and thermal effects. NIR demonstrated to be a convenient method to follow the evolution of the monomer conversion during the photopolymerization of dental resins and, consequently, it is of great utility as a method for determining the relative efficacy of different photoinitiator. The DMPOH/benzoyl peroxide redox system, has been recently proposed as a more biocompatible accelerator for the polymerization of acrylic resins. The results obtained in the present study reveal the potential usefulness of the DMPOH amine in light-cured dental composites.


[Treatment by nucleolysis using chymopapain of disk hernias of purely lumbalgic form].
16 patients suffering from a herniated disc with purely lumbalgic manifestations were treated with chymopapain nucleolysis. The results were very good in 5 cases, good in 6 cases and poor in 5 cases. These data, along with those scattered in the literature, led us to consider nucleolysis as a treatment, probably valid, of a herniated disc in its purely lumbalgic form.


Emotional support, education and self-rated health in 22 European countries.
The analyses focus on three aims: (1) to explore the associations between education and emotional support in 22 European countries, (2) to explore the associations between emotional support and self-rated health in the European countries, and (3) to analyse whether the association between education and self-rated health can be partly explained by emotional support. The study uses data from the European Social Survey 2003. Probability sampling from all private residents aged 15 years and older was applied in all countries. The European Social Survey includes 42,359 cases. Persons under age 25 were excluded to minimise the number of respondents whose education was not complete. Education was coded according to the International Standard Classification of Education. Perceived emotional support was assessed by the availability of a confidant with whom one can discuss intimate and personal matters with. Self-rated health was used as health indicator. Results of multiple logistic regression analyses show that emotional support is positively associated with education among women and men in most European countries. However, the magnitude of the association varies according to country and gender. Emotional support is positively associated with self-rated health. Again, gender and country differences in the association were observed. Emotional support explains little of the educational differences in self-rated health among women and men in most European countries. Results indicate that it is important to consider socio-economic factors like education and country-specific contexts in studies on health effects of emotional support.


Taking the alternative route: Women's experience of intranasal fentanyl, subcutaneous fentanyl or intramuscular pethidine for labour analgesia.
To compare women's experience of receiving either intranasal fentanyl, subcutaneous fentanyl or intramuscular pethidine for labour analgesia. A content analysis was undertaken as part of the third phase of a larger randomised controlled trial, using the per-protocol dataset to examine women's experiences of treatment received. Healthy women birthing at term, who received intranasal fentanyl (n=41), subcutaneous fentanyl (n=37) and/or intramuscular pethidine (n=38) for labour analgesia, were contacted at 6 weeks postpartum to complete a phone questionnaire. A tertiary and regional maternity unit in South Australia. Over 80% of women who received intranasal or subcutaneous fentanyl reported that they would use the treatment again compared to 44.8% of women who had received pethidine (self-administered intranasal fentanyl provided more expressive responses emphasising the route provided a strong sense of control and enablement. Route of administration influenced the women's experience, more women who self-administered intranasal fentanyl reported positive emotional responses, with women reporting increased autonomy and satisfaction. Whereas, women who relied on the midwife to administer subcutaneous fentanyl or intramuscular pethidine, were more often focused on the physical effect of the drug. Pethidine was the least preferred option due to adverse effects. For women requesting parenteral analgesia, fentanyl administered by less invasive routes offers women additional options that may better meet their emotional, cognitive and physical needs than the current practice of administering intramuscular pethidine.


Rational fabrication of a gold-coated AFM TERS tip by pulsed electrodeposition.
Reproducible fabrication of sharp gold- or silver-coated tips has become the bottleneck issue in tip-enhanced Raman spectroscopy, especially for atomic force microscopy (AFM)-based TERS. Herein, we developed a novel method based on pulsed electrodeposition to coat a thin gold layer over atomic force microscopy (AFM) tips to produce plasmonic TERS tips with high reproducibility. We systematically investigated the influence of the deposition potential and step time on the surface roughness and sharpness. This method allows the rational control of the radii of gold-coated TERS tips from a few to hundreds of nanometers, which allows us to systematically study the dependence of the TERS enhancement on the radius of the gold-coated AFM tip. The maximum TERS enhancement was achieved for the tip radius in the range of 60-75 nm in the gap mode. The coated gold layer has a strong adhesion with the silicon tip surface, which is highly stable in water, showing the great potential for application in the aqueous environment.


Reducing complications in trauma patients: use of a standardized quality improvement approach.
Injured patients are especially prone to developing complications. Using a multidisciplinary standardized approach to complication review is an effective method of evaluating quality improvement in patients on the trauma service. Collaboration between trauma surgeons and nurse clinicians is instrumental in improving the care of patients in each of the areas we identified. Using this consistently, quality improvement strategies can be put in place and tracked for outcomes. This has allowed for better quantification of the problem as well as any change that may result from applying this formal review process and subsequent intervention.


Laparoscopy as a diagnostic and therapeutic option in evaluating chronic unexplained right iliac fossa pain.
Management of chronic right iliac fossa (CRIF) pain is poorly documented in literature. No guidelines are available on the best therapeutic approach. Patients presenting from October 2007 to August 2009 with pain persisting or recurring in right lower abdomen over a period of 6 weeks or more were assessed. Severity of CRIF pain was documented using a ten-point visual analogue scale. Initial history and examination were followed by urine analysis, blood counts, X-ray and ultrasound scan of the abdomen. Full colonoscopy was performed in all negative cases. Diagnostic or therapeutic laparoscopy was offered to patients with normal initial investigations. The normal-looking appendix was removed in the absence of other positive laparoscopic findings. Patient's immediate complications, pain score at 8 weeks and histology of appendix were assessed. Nineteen patients with median age of 43 years (range 32-52 years) underwent laparoscopy. All were female. Median pain score was 5 (range 4-6). During surgery, 12 (64%) had positive findings. Of these, 6 (30%) had adhesions, which were separated. Three patients with congested appendices were removed. One caecal perforation, tubal mass and ovarian cyst were treated laparoscopically. Seven (36%) patients who had macroscopically normal appendices underwent appendicectomy. There were no immediate postoperative complications. Significant improvement was seen in overall pain score after surgery (median 5, range 4-6 versus median 0, range 0-6; p = 0.001). However, only 57% of patients with normal appendix had improved pain scores (median 5, range 4-6 versus median 1, range 0-6; p = 0.12). All patients with positive laparoscopic findings improved after surgery. Laparoscopy seems effective in evaluation and treatment of CRIF pain. The role of appendicectomy with normal-looking appendix needs further evaluation.


Hydrocortisone and Ascorbic Acid Synergistically Prevent and Repair Lipopolysaccharide-Induced Pulmonary Endothelial Barrier Dysfunction.
Sepsis refers to the dysregulated host immune response elicited by microbial infections resulting in life-threatening organ dysfunction. Sepsis represents a medical challenge, since it is associated with a rate of death as high as 60%. Septic shock is strongly associated with vascular dysfunction and elevated pulmonary capillary permeability. We recently reported that the combination of hydrocortisone (HC), ascorbic acid (vitC), and thiamine dramatically improves outcomes and reduces mortality in patients with sepsis. In the present study, we provide experimental evidence in support of the hypothesis that the combination of HC and vitC enhances endothelial barrier function. Human lung microvascular endothelial cells were exposed to lipopolysaccharide (LPS) in the absence or presence of HC and vitC. LPS alone induced profound hyperpermeability, as reflected in decreased values of transendothelial electrical resistance. vitC alone did not exhibit barrier enhancement properties nor did it affect the LPS-induced hyperpermeability. Similarly, HC alone exhibited only a minor barrier-enhancing and protective effect. Conversely, the combination of HC and vitC, either as before or after treatment, dramatically reversed the LPS-induced barrier dysfunction. The barrier-protective effects of HC and vitC were associated with reversal of LPS-induced p53 and phosphorylated cofilin downregulation and LPS-induced RhoA activation and myosin light chain phosphorylation. These data provide a novel mechanism of endothelial barrier protection and suggest one possible pathway that may contribute to the therapeutic effects of HC and vitC in patients with sepsis.


Restrictive cardiomyopathy: definition and diagnosis.
Restrictive cardiomyopathy (RCM) is a heterogeneous group of diseases characterized by restrictive left ventricular pathophysiology, i.e. a rapid rise in ventricular pressure with only small increases in filling volume due to increased myocardial stiffness. More precisely, the defining feature of RCM is the coexistence of persistent restrictive pathophysiology, diastolic dysfunction, non-dilated ventricles, and atrial dilatation, regardless of ventricular wall thickness and systolic function. Beyond this shared haemodynamic hallmark, the phenotypic spectrum of RCM is wide. The disorders manifesting as RCM may be classified according to four main disease mechanisms: (i) interstitial fibrosis and intrinsic myocardial dysfunction, (ii) infiltration of extracellular spaces, (iii) accumulation of storage material within cardiomyocytes, or (iv) endomyocardial fibrosis. Many disorders do not show restrictive pathophysiology throughout their natural history, but only at an initial stage (with an evolution towards a hypokinetic and dilated phenotype) or at a terminal stage (often progressing from a hypertrophic phenotype). Furthermore, elements of both hypertrophic and restrictive phenotypes may coexist in some patients, making the classification challenge. Restrictive pathophysiology can be demonstrated by cardiac catheterization or Doppler echocardiography. The specific conditions may usually be diagnosed based on clinical data, 12-lead electrocardiogram, echocardiography, nuclear medicine, or cardiovascular magnetic resonance, but further investigations may be needed, up to endomyocardial biopsy and genetic evaluation. The spectrum of therapies is also wide and heterogeneous, but disease-modifying treatments are available only for cardiac amyloidosis and, partially, for iron overload cardiomyopathy.


The relationship between quality of life and disability across the lifespan for people with spinal cord injury.
Prospective cross-sectional survey. To compare quality of life (QOL) for people with spinal cord injury (SCI) and their able-bodied peers and to investigate the relationship between QOL and disability (impairments, activity limitations and participation restrictions) across the lifespan, for people with SCI. A community outreach service for people with SCI in Queensland, Australia. A random sample of 270 individuals who sustained SCI during the past 60 years was surveyed using a guided telephone interview format. The sample was drawn from the archival records of a statewide rehabilitation service. QOL was measured using the World Health Organization Quality of Life Assessment Instrument-Bref, impairment was measured according to the American Spinal Injury Association classification and the Secondary Condition Surveillance Instrument, activity limitations using the motor subscale of the Functional Independence Measure and participation restrictions using the Community Integration Measure. Lifespan was considered in terms of age and time since injury. Correlation and regression analyses were employed to determine the relationship between QOL and components of disability across the lifespan. QOL was significantly poorer for people with SCI compared to the Australian norm. It was found to be associated with secondary impairments, activity limitations and participation restrictions but not with neurological level, age or time since injury. The single most important predictor of QOL was secondary impairments whereas the second most important predictor was participation. To optimize QOL across the lifespan, rehabilitation services must maintain their focus on functional attainment and minimizing secondary conditions, although at the same time enabling participation.


Target cell-induced calcium signals in human natural killer leukemia cells as revealed by confocal fluorescence microscopy.
The target cell-induced calcium response in natural killer (NK) cells was examined using indo-1 (a ratiometric fluorochrome), a newly developed video-rate ultraviolet laser-scanning confocal microscope system, and a human NK leukemia cell line, YTN. Susceptible target cells (JY cells), but not unsusceptible target cells (K562 cells), increased the intracellular calcium concentration ([Ca]i) in almost all indo-1-loaded YTN cells with a lag time, although the kinetics of increase in [Ca]i differed in individual YTN cells. The increase in [Ca]i was completely blocked by 2 mM EGTA and partially (around 50%) blocked by 10 microM nicardipine, the extents of inhibition of calcium response correlating well with those of inhibition of cytotoxic activity. Thus, the calcium response in YTN cells observed in this study may constitute a critical step in the manifestation of cytotoxic activity.


The nature and significance of peribronchial cuffing in pulmonary edema.
So-called "peribronchial cuffing" in acute pulmonary edema appears to be caused by edema involving the bronchila wall as well as the peribronchial interstitial space, and this was confirmed at autopsy in a patient with acute left heart failure. Edema of the bronchial wall indicates transdation from capillaries derived from the bronchial rather than the pulmonary atery, which may well explain all of the radiological manifestations of acute interstitial edema. The possible role of this circulation in the production of acute alveolar edema is also discussed. The significance of the bronchial artery circulation in the production of acute pulmonary edema warrants reevaluation.


Depression in Later-life: An Overview of Assessment and Management.
The elderly are the fastest growing segment of the global population with the number of people age 60 or older having doubled since 1980 and the number of people age 80 or older expected to increase more than 4-fold (to 395 million) by the year 2050. While depression is overall less common in older people compared to younger people, there are sub-groups of elderly, such as those with significant medical comorbidity, who are at greatly elevated risk for depression. Negative consequences of late-life depression include functional decline and disability, increased use of non-mental health services, increased mortality rates due to cardiovascular causes, increased cancer rates, and substantially greater risk for suicide. Geriatric suicide is a global epidemic, which is worsened in many countries and cultures by socioeconomic disparities and cultural/social upheaval. Geriatric depression should be carefully assessed and treated. Treatments for geriatric depression include biological modalities such as antidepressant medications and Electroconvulsive therapy (ECT) as well as psychotherapy and psychosocial interventions. When they are prescribed pharmacotherapies for depression, older adults are especially likely to experience adverse drug effects as a result of their multiple chronic diseases, use of multiple concomitant medications, and the pharmacokinetic and pharmacodynamic changes that accompany aging. Antidepressants that minimize side effects are generally preferred in elderly individuals although the expected therapeutic response to drug treatment is generally modest. Psychosocial and psychotherapeutic measures can also be effective in late-life depression. Complexities of assessment and treatment include the risk of missing a bipolar depressive diagnosis, which would contra-indicate the use of antidepressant monotherapy. Given the projected increased proportions and overall numbers of older people with mental disorders there is a need for all clinicians to be familiar with mental health issues in elderly patients.


Music Improves Subjective Feelings Leading to Cardiac Autonomic Nervous Modulation: A Pilot Study.
It is widely accepted that listening to music improves subjective feelings and reduces fatigue sensations, and different kinds of music lead to different activations of these feelings. Recently, cardiac autonomic nervous modulation has been proposed as a useful objective indicator of fatigue. However, scientific considerations of the relation between feelings of fatigue and cardiac autonomic nervous modulation while listening to music are still lacking. In this study, we examined which subjective feelings of fatigue are related to participants' cardiac autonomic nervous function while they listen to music. We used an album of comfortable and relaxing environmental music, with blended sounds from a piano and violin as well as natural sound sources. We performed a crossover trial of environmental music and silent sessions for 20 healthy subjects, 12 females, and 8 males, after their daily work shift. We measured changes in eight types of subjective feelings, including healing, fatigue, sleepiness, relaxation, and refreshment, using the KOKORO scale, a subjective mood measurement system for self-reported feelings. Further, we obtained measures of cardiac autonomic nervous function on the basis of heart rate variability before and after the sessions. During the music session, subjective feelings significantly shifted toward healing and a secure/relaxed feeling and these changes were greater than those in the silent session. Heart rates (ΔHR) in the music session significantly decreased compared with those in the silent session. Other cardiac autonomic parameters such as high-frequency (HF) component and the ratio of low-frequency (LF) and HF components (LF/HF) were similar in the two sessions. In the linear regression analysis of the feelings with ΔHR and changes in LF/HF (ΔLF/HF), increases and decreases in ΔHR were correlated to the feeling axes of Fatigue-Healing and Anxiety/Tension-Security/Relaxation, whereas those in ΔLF/HF were related to the feeling axes of Sleepiness-Wakefulness and Gloomy-Refreshed. This indicated that listening to music improved the participants' feelings of fatigue and decreased their heart rates. However, it did not reduce the cardiac LF/HF, suggesting that cardiac LF/HF might show a delayed response to fatigue. Thus, we demonstrated changes in cardiac autonomic nervous functions based on feelings of fatigue.


Helicobacter pylori modulates host cell responses by CagT4SS-dependent translocation of an intermediate metabolite of LPS inner core heptose biosynthesis.
Highly virulent Helicobacter pylori cause proinflammatory signaling inducing the transcriptional activation and secretion of cytokines such as IL-8 in epithelial cells. Responsible in part for this signaling is the cag pathogenicity island (cagPAI) that codetermines the risk for pathological sequelae of an H. pylori infection such as gastric cancer. The Cag type IV secretion system (CagT4SS), encoded on the cagPAI, can translocate various molecules into cells, the effector protein CagA, peptidoglycan metabolites and DNA. Although these transported molecules are known to contribute to cellular responses to some extent, a major part of the cagPAI-induced signaling leading to IL-8 secretion remains unexplained. We report here that biosynthesis of heptose-1,7-bisphosphate (HBP), an important intermediate metabolite of LPS inner heptose core, contributes in a major way to the H. pylori cagPAI-dependent induction of proinflammatory signaling and IL-8 secretion in human epithelial cells. Mutants defective in the genes required for synthesis of HBP exhibited a more than 95% reduction of IL-8 induction and impaired CagT4SS-dependent cellular signaling. The loss of HBP biosynthesis did not abolish the ability to translocate CagA. The human cellular adaptor TIFA, which was described before to mediate HBP-dependent activity in other Gram-negative bacteria, was crucial in the cagPAI- and HBP pathway-induced responses by H. pylori in different cell types. The active metabolite was present in H. pylori lysates but not enriched in bacterial supernatants. These novel results advance our mechanistic understanding of H. pylori cagPAI-dependent signaling mediated by intracellular pattern recognition receptors. They will also allow to better dissect immunomodulatory activities by H. pylori and to improve the possibilities of intervention in cagPAI- and inflammation-driven cancerogenesis.


Ultrafast dynamic switching of optical response based on nonlinear hyperbolic metamaterial platform: erratum.
We present an erratum to our previously published work ["Ultrafast dynamic switching of optical response based on nonlinear hyperbolic metamaterial platform," Opt. Express30(12), 21634 (2022).10.1364/OE.457875]. The corrections do not affect the results and conclusion of the original paper.


[Aspartate and alanine aminotransferase activity in the adrenal cortex of human embryos and fetuses].
Aspartate aminotransferase was detected in the adrenals of 6-7-week human embryos, the activity being the highest at the 7-9th and 12-14th weeks. Alanine aminotransferase was found in 15-week foetuses. During all the period investigated (6-28 weeks), the activity of aspartate aminotransferase was found to be higher than that of the second enzyme. The activity of both enzymes is higher in female foetuses than in male ones. However, age changes in the activity of both enzymes in male embryos and foetuses were of the same sign as in female ones.


Effect of historical land-use and climate change on tree-climate relationships in the upper Midwestern United States.
Contemporary forest inventory data are widely used to understand environmental controls on tree species distributions and to construct models to project forest responses to climate change, but the stability and representativeness of contemporary tree-climate relationships are poorly understood. We show that tree-climate relationships for 15 tree genera in the upper Midwestern US have significantly altered over the last two centuries due to historical land-use and climate change. Realised niches have shifted towards higher minimum temperatures and higher rainfall. A new attribution method implicates both historical climate change and land-use in these shifts, with the relative importance varying among genera and climate variables. Most climate/land-use interactions are compounding, in which historical land-use reinforces shifts in species-climate relationships toward wetter distributions, or confounding, in which land-use complicates shifts towards warmer distributions. Compounding interactions imply that contemporary-based models of species distributions may underestimate species resilience to climate change.


Nutrition and Physical Activity Counseling by General Practitioners in China.
To reduce unhealthy lifestyles in China, it is critical to implement effective strategies. Counseling provided by physicians is important for assisting patients in improving their lifestyles, and general practitioners (GPs) are the main providers of lifestyle counseling to patients. However, few studies have focused on the lifestyle counseling practices by GPs in China, particularly in regard to nutrition and physical activity. The aims of this study are: (i) to examine the current practice of Chinese GPs in counseling patients regarding nutrition and physical activity; (ii) to understand the common barriers to such counseling by Chinese GPs; and (iii) to study the association between GPs' personal lifestyle choices and their practices in lifestyle counseling. A cross-sectional, self-reported online questionnaire was conducted among GPs in Hunan province, China. A total of 198 GPs completed the questionnaire. The majority of GPs provide nutrition and physical activity counseling to less than 40% of their patients, spending less than three minutes per counseling session. The main reported barriers to counseling on nutrition and physical activity are inadequate time and a lack of knowledge or experience. GPs primarily acquire knowledge through medical books and journals, followed by science popularization. Furthermore, GPs who maintain healthier lifestyle habits, possess a better understanding of lifestyle guidelines, conduct longer office visits, and exhibit higher self-efficacy are more likely to provide counseling to patients. This study highlights the need for improvement in nutrition and physical activity counseling among Chinese GPs. GPs' personal nutrition and physical activity habits may measurably influence their counseling practice. We recommend that GPs themselves adopt healthier lifestyle habits to potentially improve their counseling practice. Moreover, proactive measures should be taken to assist GPs in overcoming barriers encountered with lifestyle counseling.


Non-invasive estimation of systolic blood pressure and diastolic blood pressure using photoplethysmograph components.
Photoplethysmography (PPG) is a noninvasive optical technology that detects changes in blood volume in the vascular system. This study aimed to investigate the possibilities of monitoring the cardiovascular system status by using PPG. Forced hemodynamic changes were induced using cardiac stimulants; dopamine and epinephrine, and PPG components were recorded by a noninvasive method at the peripheral blood vessels. The results were compared among 6 dogs. Endotracheal intubation was performed after an intramuscular injection of 25 mg/kg ketamine sulfate, and anesthesia was maintained with 2% enflurane. After stabilizing the animals for 15 min, 16 mg/mL diluted dopamine was injected into a vein for 2 min at 20 microg/kg min(-1) by using an infusion pump. Thereafter, the infusion pump was stopped, and 1 mg epinephrine was injected intravenously. Fluid administration was controlled to minimize preload change in blood pressure. After stimulant administration, systolic blood pressure (SBP) and diastolic blood pressures (DBP) increased. The direct current (DC) component, which reflects changes in blood volume, decreased while the alternating current (AC) component, which reflects changes in vascular compliance and resistance, increased. The correlation coefficient between SBP and the foot of the DC component was 0.939 (p < 0.01), while it was 0.942 (p < 0.01) for DBP and the peak of the DC component. The AC component could predict the increase in vascular resistance from a stable pulse blood volume, even with increased pulse pressure. These results support the possibility that PPG components may be used for easy and noninvasive measurement of hemodynamic changes in the cardiovascular system.


Recipient preparation for bone marrow transplantation. I. Efficacy of total-body irradiation and busulfan.
The efficacy of total body irradiation and busulfan were studied in recipient preparation for bone marrow transplantation. Male C57BL/6 (B6) mice were prepared for BMT with fractionated TBI or busulfan given in 4 equal doses over 3 days. Both TBI and busulfan are potent stem-cell killers. Both agents resulted in an exponential decrease in CFUs survival with increasing dose down to a 1 x 10(-4) CFUs survival. There appeared to be no break in the curve for either agent. Extrapolated fractional CFUs survival, as related to equivalent donor marrow engraftment or to equivalent 30-day survival without marrow transplantation, appeared lower for TBI as compared to busulfan. This may be due to the effect of busulfan and TBI on different stem-cell populations. Erythroid engraftment was tested after transplanting H-2 compatible LP marrow cells into treated B6 recipients. Greater than 80% of animals demonstrated complete engraftment with 3.4 mg busulfan or 1640 cGy TBI. At these 2 doses, the rate of recovery of donor marrow cellularity and CFUs content in treated recipients were identical for both preparative agents such that a selective effect on the host hematopoietic microenvironment harmful to engraftment was not seen. Complete engraftment in 100% of busulfan-prepared animals could not be achieved as such doses resulted in severe and fatal pulmonary vascular injury at 7-12 weeks posttransplant.


On three species of the spider genus Pimoa (Araneae, Pimoidae) from China.
Two new species of the spider genus Pimoa Chamberlin & Ivie, 1943 are described from Hunan and Yunnan Provinces, China: P.binchuanensis sp. nov. (♂♀) and P.xinjianensis sp. nov. (♂♀). In addition, the male of P.lata Xu & Li, 2009 is described for the first time. The DNA barcodes of the two new species are documented.


Quantitative proteomic analysis and verification identify global protein profiling dynamics in pig during the estrous cycle.
The current estrus detection method is generally time-consuming and has low accuracy. As such, a deeper understanding of the physiological processes during the estrous cycle accelerates the development of estrus detection efficiency and accuracy. In this study, the label-free acquisition mass spectrometry was used to explore salivary proteome profiles during the estrous cycle (day -3, day 0, day 3, and day 8) in pigs, and the parallel reaction monitoring (PRM) was applied to verify the relative profiles of protein expression. A total of 1,155 proteins were identified in the label-free analysis, of which 115 were identified as differentially expressed proteins (DEPs) among different groups (p ≤ 0.05). Functional annotation revealed that the DEPs were clustered in calcium ion binding, actin cytoskeleton, and lyase activity. PRM verified the relative profiles of protein expression, in which PHB domain-containing protein, growth factor receptor-bound protein 2, elongation factor Tu, carboxypeptidase D, carbonic anhydrase, and trefoil factor 3 were confirmed to be consistent in both label-free and PRM approaches. Comparative proteomic assays on saliva would increase our knowledge of the estrous cycle in sows and provide potential methods for estrus detection.


Evaluation of miR-122-regulated suicide gene therapy for hepatocellular carcinoma in an orthotopic mouse model.
Intratumoral administration of adenoviral vector encoding herpes simplex virus (HSV) thymidine kinase (TK) gene (Ad-TK) followed by systemic ganciclovir (GCV) is an effective approach in treating experimental hepatocellular carcinoma (HCC). However, hepatotoxicity due to unwanted vector spread and suicide gene expression limited the application of this therapy. miR-122 is an abundant, liver-specific microRNA whose expression is decreased in human primary HCC and HCC-derived cell lines. These different expression profiles provide an opportunity to induce tumor-specific gene expression by miR-122 regulation. By inserting miR-122 target sequences (miR-122T) in the 3' untranslated region (UTR) of TK gene, we constructed adenovirus (Ad) vectors expressing miR-122-regulated TK (Ad-TK-122T) and report genes. After intratumoral administration of Ad vectors into an orthotopic miR-122-deficient HCC mouse model, we observed the miR-122-regulated transgene expression and assessed the antitumor activity and safety of Ad-TK-122T. Insertion of miR-122T specifically down-regulated transgene expression in vitro and selectively protected the miR-122-positive cells from killing by TK/GCV treatment. Insertion of miR-122T led to significant reduction of tansgene expression in the liver without inhibition of its expression in tumors in vivo, resulting in an 11-fold improvement of tumor-specific transgene expression. Intratumoral injection of Ad vectors mediated TK/GCV system led to a vector dosage-dependent regression of tumor. The insertion of miR-122T does not influence the antitumor effects of suicide gene therapy. Whereas mice administrated with Ad-TK showed severe lethal hepatotoxicity at the effective therapeutic dose, no liver damage was found in Ad-TK-122T group. miR-122-regulated TK expression achieved effective anti-tumor effects and increased the safety of intratumoral delivery of adenovirus-mediated TK/GCV gene therapy for miR-122-deficient HCC.


Colloidal dual-band gap cell for photocatalytic hydrogen generation.
We report that the internal quantum efficiency for hydrogen generation in spherical, Pt-decorated CdS nanocrystals can be tuned by quantum confinement, resulting in higher efficiencies for smaller than for larger nanocrystals (17.3% for 2.8 nm and 11.4% for 4.6 nm diameter nanocrystals). We attribute this to a larger driving force for electron and hole transfer in the smaller nanocrystals. The larger internal quantum efficiency in smaller nanocrystals enables a novel colloidal dual-band gap cell utilising differently sized nanocrystals and showing larger external quantum efficiencies than cells with only one size of nanocrystals (9.4% for 2.8 nm particles only and 14.7% for 2.8 nm and 4.6 nm nanocrystals). This represents a proof-of-principle for future colloidal tandem cell.


Novel therapeutic approaches for haemophilia.
The major therapy for haemophilia is plasma derived or recombinant clotting factors which are evolving steadily to increase potency, stability and half-life. Research in the area of haemophilia therapeutics, however, is not restricted only to modifications in the recombinant products, but alternate therapeutic strategies are being developed which are in different phases of experimental and clinical trials. This chapter reviews the diverse molecular innovations which are being developed for alternate therapeutic approaches in haemophilia. The data is mainly extracted from the literature and the Conference abstracts. Some of the novel therapeutic approaches include inhibition of anticoagulant pathway factors (activated protein C, antithrombin, tissue factor pathway inhibitor) by monoclonal antibodies, peptide inhibitors, DNA or RNA aptamers, use of variant coagulation factors (factor Xa, factor Va) which are more resistant to inactivation or enzymatically more active and antibody-mediated therapy including a humanized anti-factor IXa/X bispecific antibody mimicking factor VIII. Other approaches include nonsense mutation suppression, induction of prothrombotic microparticles by P-selectin-immunoglobulin chimeras, suppression of fibrinolytic potential either by antifibrinolytics or by the use of mutant molecules of fibrinolytic inhibitors. Few products are proposed as 'stand alone' treatment for haemophilia, while a few can be used as adjuvant therapies to recombinant factors with an aim to reduce the amount of factor intake. All efforts are underway to produce an alternate, novel drug for haemophilia which will have an increased half-life, subcutaneously injectable, non-immunogenic and effective both in the presence and absence of inhibitors.


Emerging roles and underlying molecular mechanisms of DNAJB6 in cancer.
DNAJB6 also known as mammalian relative of DnaJ (MRJ) encodes a highly conserved member of the DnaJ/Hsp40 family of co-chaperone proteins that function with Hsp70 chaperones. DNAJB6 is widely expressed in all tissues, with higher expression levels detected in the brain. DNAJB6 is involved in diverse cellular functions ranging from murine placental development, reducing the formation and toxicity of mis-folded protein aggregates, to self-renewal of neural stem cells. Involvement of DNAJB6 is implicated in multiple pathologies such as Huntington's disease, Parkinson's diseases, limb-girdle muscular dystrophy, cardiomyocyte hypertrophy and cancer. This review summarizes the important involvement of the spliced isoforms of DNAJB6 in various pathologies with a specific focus on the emerging roles of human DNAJB6 in cancer and the underlying molecular mechanisms.


Dry powder inhalers: physicochemical and aerosolization properties of several size-fractions of a promising alterative carrier, freeze-dried mannitol.
The purpose of this work was to evaluate the physicochemical and inhalation characteristics of different size fractions of a promising carrier, i.e., freeze-dried mannitol (FDM). FDM was prepared and sieved into four size fractions. FDMs were then characterized in terms of micromeritic, solid-state and bulk properties. Dry powder inhaler (DPI) formulations were prepared using salbutamol sulphate (SS) and then evaluated in terms of drug content homogeneity and in vitro aerosolization performance. The results showed that the crystalline state of mannitol was maintained following freeze-drying for all size fractions of FDM. All FDM particles showed elongated morphology and contained mixtures of α-, β- and δ-mannitol. In comparison to small FDM particles, FDMs with larger particle sizes demonstrated narrower size distributions, higher bulk and tap densities, lower porosities and better flowability. Regardless of particle size, all FDMs generated a significantly higher (2.2-2.9-fold increase) fine particle fraction (FPF, 37.5 ± 0.9%-48.6 ± 2.8%) of SS in comparison to commercial mannitol. The FPFs of SS were related to the shape descriptors of FDM particles; however, FPFs did not prove quantitative apparent relationships with either particle size or powder bulk descriptors. Large FDM particles were more favourable than smaller particles because they produced DPI formulations with better flowability, better drug content homogeneity, lower amounts of the drug depositing on the throat and contained lower fine-particle-mannitol. Optimized stable DPI formulations with superior physicochemical and pharmaceutical properties can be achieved using larger particles of freeze-dried mannitol (FDM).


Two-stage flexor tendon reconstruction in zone II using Hunter's technique.
Tendon injuries in the digital flexor sheath area (zone II) are the most difficult to treat and remain a focus of both clinical attention and basic investigations. Although some new techniques have been developed, the clinical results are still not satisfying, especially in old injuries. This retrospective study was designed to investigate the results of delayed zone II flexor tendon repair using Hunter rods. Between July 1974 and June 1998, 81 patients at our institution underwent 2-stage reconstruction using Hunter's technique. Sixty-one patients with 106 fingers were included in this study. Digital flexor tendon resection and Hunter rod implantation were performed in the first-stage operation. Combined digital nerve injuries and damaged pulleys were repaired or reconstructed at the same time. Plaster was used to immobilize the hand for 3 weeks. During the second-stage operation, performed 2 to 6 months later, palmaris longus or plantaris were grafted into the pseudosheath formed surrounding the Hunter rods. The proximal end of the transplanted tendon was fixated with flexor digitorum profundus tendon using the Pulvertaft method, and the distal end was fixated to the distal phalanx using Bunnell's pullout wire method. Early controlled motion was performed in all cases. Evaluation based on total active motion was good to excellent in 84%, fair in 12%, and poor in 4% of patients. Flexor tendon reconstruction using Hunter technique is an effective way to restore digital function in delayed zone II flexor tendon injuries.


Sensitization of Candida albicans biofilms to fluconazole by terpenoids of plant origin.
Infections associated with the biofilms of Candida albicans are a challenge to antifungal treatment. Combinatorial therapy involving plant molecules with antifungal drugs would be an effective complementary approach against drug-resistant Candida biofilms. The aim of this study was to evaluate the efficacy of three bioactive terpenoids (carvacrol, eugenol and thymol) in combination with fluconazole against planktonic cells, biofilm development and mature biofilms of C. albicans. Activities of the selected molecules were tested using a microplate-based methodology, while their combinations with fluconazole were performed in a checkerboard format. Biofilms were quantitated by XTT-metabolic assay and confirmed by microscopic observations. Combinations of carvacrol and eugenol with fluconazole were found synergistic against planktonic growth of C. albicans, while that of thymol with fluconazole did not have any interaction. Biofilm development and mature biofilms were highly resistant to fluconazole, but susceptible to three terpenoids. Sensitization of cells by sub-inhibitory concentrations of carvacrol and eugenol resulted in prevention of biofilm formation at low fluconazole concentrations, i.e. 0.032 and 0.002 mg ml(-1), respectively. Addition of thymol could not potentiate activity of fluconazole against biofilm formation by C. albicans. Fractional inhibitory concentration indices (FICI) for carvacrol-fluconazole and eugenol-fluconazole combinations for biofilm formation were 0.311 and 0.25, respectively. The FICI value of 1.003 indicated a status of indifference for the combination of thymol and fluconazole against biofilm formation. Eugenol and thymol combinations with fluconazole did not have useful interaction against mature biofilms of C. albicans, but the presence of 0.5 mg ml(-1) of carvacrol caused inhibition of mature biofilms at a significantly low concentration (i.e. 0.032 mg ml(-1)) of fluconazole. The study indicated that carvacrol and eugenol combinations with fluconazole would be a potential alternative strategy for prevention and control of biofilm-associated C. albicans infections.


Molecular Basis of Encapsidation of Hepatitis C Virus Genome.
Hepatitis C virus (HCV), a major etiologic agent of human liver diseases, is a positive-sense single-stranded RNA virus and is classified in the Flaviviridae family. Although research findings for the assembly of HCV particles are accumulating due to development of HCV cell culture system, the mechanism(s) by which the HCV genome becomes encapsidated remains largely unclear. In general, viral RNA represents only a small fraction of the RNA molecules in the cells infected with RNA viruses, but the viral genomic RNA is considered to selectively packaged into virions. It was recently demonstrated that HCV RNAs containing 3' end of the genome are selectively incorporated into virus particles during the assembly process and the 3' untranslated region functions as a cis-acting element for RNA packaging. Here, we discuss the molecular basis of RNA encapsidation of HCV and classical flaviviruses, contrast with the packaging mechanism of HIV-1.


Generation of Whole-Genome Sequencing Data for Comparing Primary and Castration-Resistant Prostate Cancer.
Because castration-resistant prostate cancer (CRPC) does not respond to androgen deprivation therapy and has a very poor prognosis, it is critical to identify a prognostic indicator for predicting high-risk patients who will develop CRPC. Here, we report a dataset of whole genomes from four pairs of primary prostate cancer (PC) and CRPC samples. The analysis of the paired PC and CRPC samples in the whole-genome data showed that the average number of somatic mutations per patients was 7,927 in CRPC tissues compared with primary PC tissues (range, 1,691 to 21,705). Our whole-genome sequencing data of primary PC and CRPC may be useful for understanding the genomic changes and molecular mechanisms that occur during the progression from PC to CRPC.


Effect of endotoxin on lung fluid balance in unanesthetized sheep.
We used a gravimetric technique to test for increased pulmonary capillary permeability after Escherichia coli endotoxin infusion in unanesthetized sheep. The sheep were chronically prepared with cannulas placed into the left atrium and pulmonary artery 1-2 wk before the experiments. We estimated pulmonary capillary pressure (Pc) as the average of pulmonary arterial and left atrial pressures, and used the modified method of Pierce to estimate the ratio of extravascular fluid weight (EVF) to blood-free dry weight. In 15 sheep we inflated a left atrial balloon to raise Pc to -10.7, 5, 10, or 15 mmHg above plasma oncotic pressure (IIc) for 3 h, then measured EVF. EVF averaged 4.0 +/- 0.2 (base line), 4.3 +/- 0.1, 4.5 +/- 0.1, and 5.1 +/- 0.5 (SD), respectively, for the four levels of Pc - IIc. We gave seven additional sheep 1 microgram/kg of E. coli endotoxin (0127:B8) and measured EVF after 3 h of stable Pc. Endotoxin increased Pc in each sheep. EVF was higher than control for the endotoxin sheep with Pc - IIc greater than -1. This finding is consistent with an increase in pulmonary capillary permeability caused by endotoxin. However, EVF was not elevated in the endotoxin sheep with Pc - IIc less than 1 mmHg. This shows that the increased permeability was insufficient to cause edema unless Pc was elevated. Thus endotoxin may cause edema by two mechanisms, 1) an increase in capillary permeability, and 2) an increase in Pc.


Hepatitis C virus genome complexity correlates with response to interferon therapy: a study in French patients with chronic hepatitis C.
Recent studies performed in Japan have suggested that hepatitis C virus (HCV) genome heterogeneity might be taken as a predictive virological parameter of response to interferon alfa (IFN-alpha) treatment. However, there is presently no information on the impact of this virological parameter in patients from Western countries infected by different HCV genotypes. We have investigated this issue by using amplification of HCV E2 hypervariable region 1, followed by single-strand conformation polymorphism assay (PCR-SSCP). We have studied 95 French patients infected with various genotypes and treated with IFN-alpha-2b. We analyzed the impact of the following parameters by univariate and multivariate analyses: HCV heterogeneity, HCV genotype, viral load, and liver histology in response to therapy. Age >40 years (P < .01), viral load >35 x 10(5) Eq/mL (P < .01), genotype 1 (P < .01), and a number of SSCP bands >3 (P < .001) were significantly associated with nonresponse or relapse; cirrhosis was associated with nonresponse. In multivariate analysis, three variables were independently associated with the absence of long-term response: SSCP bands >3, genotype 1, and viral load >35 x 10(5) with odds ratios of 19, 7.5, and 11.8, respectively. Our data establish the major importance of HCV genome heterogeneity in patients infected with both HCV types associated with low (genotype 1b) or high (genotype 3a) response to IFN-alpha.


Expression of Cathepsins B, D, and G in Extracranial Arterio-Venous Malformation.
Objectives: We have previously identified a population of cells that expressed stemness-associated markers in extracranial arterio-venous malformation (AVM) and demonstrated expression of cathepsins B, D, and G on embryonic stem cell (ESC)-like populations in other vascular anomalies. This study investigated the expression of cathepsins B, D, and G, and their localization in relation to this primitive population in extracranial AVM. Methods: Immunohistochemical staining was performed on AVM tissue samples from 13 patients to demonstrate expression of cathepsins B, D, and G. Western blotting was performed on four AVM tissue samples and three AVM-derived primary cell lines to confirm protein expression of cathepsins B and D proteins. RT-qPCR was performed on three AVM-derived primary cell lines to demonstrate transcript expression of cathepsins B, D, and G. Enzymatic activity assays were performed on three AVM-derived primary cell lines to investigate if cathepsins B and D were active. Localization of the cathepsins was investigated using immunofluorescence dual-staining of the cathepsins with the ESC markers OCT4 and SOX2, and mast cells marker chymase on two of the 13 AVM tissue samples. Results: Immunohistochemical staining demonstrated expression of cathepsins B, D, and G in all 13 AVM tissue samples. Western blotting showed expression of cathepsins B and D proteins in all four AVM tissue samples and all three AVM-derived primary cell lines. RT-qPCR demonstrated transcripts of cathepsins B, D, and G in all three AVM-derived primary cell lines. Enzymatic activity assays showed that cathepsins B and D were active. Immunofluorescence staining showed expression of cathepsins B and D on the OCT4+/SOX2+ endothelium and media of the lesional vessels and cells within the stroma in AVM nidus. Cathepsin G was expressed on the chymase+ phenotypic mast cells. Conclusions: This study demonstrated the novel finding of the expression of cathepsins B, D, and G in AVM. Cathepsins B and D were expressed by the primitive population, and cathepsin G was localized to mast cells, within the AVM nidus.


Analysis of virulence and growth of a purine auxotrophic mutant of Xanthomonas oryzae pathovar oryzae.
Xanthomonas oryzae pv. oryzae (Xoo) causes bacterial blight of rice. A random insertional mutant library of Xoo KACC10331 was constructed using a Tn5-derived transposon, and the virulence of the mutants against the susceptible rice cultivar IR24 was assayed. After the virulence assay, the M793 (purD::Tn5) mutant that had reduced virulence against the rice plants was isolated. Thermal asymmetric interlaced-PCR and sequence analysis revealed that the transposon was inserted into the purD gene (encodes a phosphoribosylamine-glycine ligase) of the M793 mutant. The reverse transcriptase-PCR assay revealed that the mutation of the purD gene did not affect the expression of other purine biosynthesis genes. However, the M793 mutant required exogenous purines and thiamine for growth in minimal media. These results indicate that the purD gene plays a crucial role in the growth and virulence of Xoo.


Correlation of natural killer cell function with Leu 7 reactivity in patients with humoral immunodeficiency.
We studied the surface markers Leu 7, Leu 1, Leu 2a and Leu 3a on lymphocytes of 54 healthy blood donors and 19 patients with humoral immunodeficiencies and compared the relative numbers of positive cells with the natural killer cell (NK) activity. In controls, and in 12 out of 19 patients (group A) the percentage of the Leu 7+ cells was positively correlated with NK activity. Seven of 19 patients had increased relative numbers of Leu 7+ cells and low NK activity (group B). In controls and group A patients about 40% of the Leu 7+ cells simultaneously expressed the cell markers Leu 1 and Leu 2a. In group B patients approximately 70% of the Leu 7+ cells carried T cell antigens. Furthermore, a distinct suppressor T cell predominance was noticed and the large granular lymphocytes of these patients showed morphological abnormalities.


Environmental control of kisspeptin: implications for seasonal reproduction.
The KiSS-1 gene encodes the peptide hormone kisspeptin, which acts as a principal positive regulator of the reproductive axis by directly stimulating GnRH neuron activity. To gain insight into a potential role for kisspeptin in integrating and relaying reproductively relevant stimuli to the GnRH system, we investigated changes in kisspeptin peptide expression associated with photoperiodic changes in reproductive state as well as pituitary and gonadal responses to peripheral kisspeptin injections. Seasonally breeding rodents undergo pronounced fluctuations in reproductive state in response to changing day lengths. In common with other rodent species, a majority of male Siberian hamsters (Phodopus sungorus) exhibit reproductive decline after exposure to short-day lengths. A subset of individuals fails to respond to day length information, however, and maintains their reproductive function. We exploited these individual differences to examine whether kisspeptin may act at the interface between external stimuli and the reproductive system. After extended exposure to short days, animals with a quiescent reproductive axis displayed a marked reduction in kisspeptin cell labeling in the anteroventral periventricular nucleus but robust kisspeptin-immunoreactive staining in the arcuate nucleus. In contrast, animals with functional reproductive systems displayed high numbers of kisspeptin-immunoreactive neurons in the anteroventral periventricular nucleus but a paucity of expression in the arcuate nucleus. Kisspeptin injections significantly elevated LH over preinjection levels regardless of photoperiod or reproductive state. Collectively, these findings suggest an important role for kisspeptin in coordinating and relaying environmentally relevant information to the reproductive axis as well as a role for this peptide in regulating seasonal changes in reproductive function.


Effect of diltiazem on extent of ultimate myocardial injury resulting from temporary coronary artery occlusion in dogs.
The calcium antagonist, diltiazem, was evaluated for its ability to reduce the extent of myocardial injury resulting from 90 min of left circumflex (LCX) coronary artery occlusion in anesthetized dogs. Administration of diltiazem (0.75 mg/kg over 10 min, followed by 600 microgram/kg/h for 4 h) was initiated 30 min prior to LCX occlusion. Regional myocardial blood flow (RMBF) was measured with radioactive microspheres 30 min after LCX occlusion, and at 45 min and 24 h after reperfusion. At 24 h, after obtaining hemodynamic and RMBF measurements, excised hearts were processed by perfusion staining to determine the percent of left ventricle (LV) perfused by LCX (area at risk) and infarct size, with triphenyltetrazolium chloride. Infarct size, expressed as a percentage of the area at risk, was significantly lower in the diltiazem-treated group compared to the control group (27 +/- 4 vs. 42 +/- 5%, respectively). The area at risk, expressed as a percentage of left ventricular mass, was similar in both groups [41 +/- 2 and 44 +/- 3% (area at risk-LV)]. In addition, the marked elevation of tissue Ca2+ content in noninfarcted and infarcted myocardium within the area at risk (18 +/- 2 and 42 +/- 8 mumol Ca2+/g) in control animals was attenuated by diltiazem (6 +/- 3 and 18 +/- 8 mumol Ca2+/g). Diltiazem did not increase blood flow to ischemic myocardium during LCX occlusion. However, reflow to the inner layers of formerly ischemic myocardium during reperfusion was significantly greater in diltiazem-treated dogs. Both arterial blood pressure and heart rate were significantly lower in the diltiazem -treated group. In addition, mortality (1 vs. 4) and occurrence of ventricular arrhythmias during reperfusion were lower in diltiazem-treated dogs. The data suggest that diltiazem reduces myocardial ischemic injury by lowering myocardial oxygen demands indirectly via favorable hemodynamic alterations, and directly by limiting transmembrane Ca2+ fluxes during ischemia and reperfusion.


The genomes uncoupled-dependent signalling pathway coordinates plastid biogenesis with the synthesis of anthocyanins.
In recent years, it has become evident that plants perceive, integrate and communicate abiotic stress signals through chloroplasts. During the process of acclimation plastid-derived, retrograde signals control nuclear gene expression in response to developmental and environmental cues leading to complex genetic and metabolic reprogramming to preserve cellular homeostasis under challenging environmental conditions. Upon stress-induced dysfunction of chloroplasts, GENOMES UNCOUPLED (GUN) proteins participate in the repression of PHOTOSYNTHESIS-ASSOCIATED NUCLEAR GENES (PHANGs). Here, we show that the retrograde signal emitted by, or communicated through, GUN-proteins is also essential to induce the accumulation of photoprotective anthocyanin pigments when chloroplast development is attenuated. Comparative whole transcriptome sequencing and genetic analysis reveal GUN1 and GUN5-dependent signals as a source for the regulation of genes involved in anthocyanin biosynthesis. The signal transduction cascade includes well-known transcription factors for the control of anthocyanin biosynthesis, which are deregulated in gun mutants. We propose that regulation of PHANGs and genes contributing to anthocyanin biosynthesis are two, albeit oppositely, co-regulated processes during plastid biogenesis. This article is part of the theme issue 'Retrograde signalling from endosymbiotic organelles'.


[Hemodynamic changes and left ventricular function in patients with hypertension during an acute trial of urapidil].
The left ventricular hemodynamic changes were studied in 9 hypertensive patients (6 patients with hypertensive attack and 3 patients with a severe form of the disease) by simultaneous recordings of the M-type echocardiogram, apexcardiogram and phonocardiogram in an acute trial with Urapidil administered intravenously in a dose of 0,7 mg/kg body mass. The arterial pressure and the peripheral vascular resistance decrease. The stroke and the minute volume do not change. The heart rate increases. The telediastolic and telesystolic dimensions of the left ventricle decrease. The percentage amplitude of the aI-wave of the apexcardiogram also decreases. The fraction of the shortening of the left ventricular dimension increases with 23,0%, the ejection fraction increases with 13,5% and the average speed of the circumferential fibres shortening increases with 21,4%. Urapidil applied i.v. exerts a rapid hypotensive action and improves the left ventricular function.


T-wave alternans in patients with right ventricular tachycardia.
Microvolt T-wave alternans has been proposed as a new risk marker for ventricular arrhythmias. However, the clinical significance of T-wave alternans in patients with ventricular tachycardia (VT) originating from the right ventricle has been unknown. The study population consisted of 20 patients with arrhythmogenic right ventricular cardiomyopathy (ARVC) or idiopathic VT. T-wave alternans was measured during bicycle exercise testing using the CH 2000 system. Of the 7 patients with ARVC, 6 (86%) were positive for T-wave alternans. On the other hand, only 1 (8%) of 13 patients with idiopathic VT originating from the right-ventricular outflow tract was positive for T-wave alternans.


When expressions of faith in the Philippines becomes a potential COVID-19 'superspreader'.
The Filipino people are known for their strong religious faith. Even in the midst of the most trying moments of their collective history their faith remains steadfast. The isolation brought by the COVID-19 pandemic did not stop the Filipino Catholic faithful from expressing their faith but made it stronger. Allowed by the government to attend Church celebrations, the Filipino Catholic devotee flocked in the Quiapo Church just to attend the feast of the Black Nazarene and had a chance to hold its image with a firm conviction that the grace of God could protect them from the pandemic. However, the local medical experts called their devotion, in this time of crisis, as a 'superspreader', a sign not of hope but of despair.


First Report of Brown Rot of fruit on Vitis amurensis Caused by Monilinia polystroma in China.
Vitis amurensis Rupr. (Amur grape) is a wild grape genetic resource widely distributed in Heilongjiang, Jilin, Liaoning, and Inner Mongolia, among other places in China (Song et al. 2009) and the Russian Far East and Korean Peninsula. In September 2018, brown rot symptoms were observed at ripening stage on the fruits of a 5-year-old Amur grapevine germplasm resources nursery of the cultivar 'Beibinghong' and a few Russian resources in Zuojia Town, Jilin City, Jilin Province, China. The diseased fruit surface became brown with soft rot and produced buff to brownish-grey sporodochia with conidia. Around 180 plants of 'Beibinghong' were examined which had 8 % incidence. Forty five samples were collected from symptomatic fruits of 15 randomly sampled 'Beibinghong' grape clusters, cut into 5-mm2 pieces of diseased tissue, surface sterilized with 1% NaOCl for 2 min, rinsed three times with sterile water, dried on sterilized filter paper, and plated on potato dextrose agar (PDA). Thirteen monosporic isolates were obtained using the single-spore isolation method with incubation at 25°C and a 12-h light/12-h dark cycle. The average colony diameter was 46-49 mm after 4 days of culture on PDA. Colonies were white to grayish with even margins. Irregular black stromatal crusts were observed on the reverse side of dishes 10 days after inoculation. Conidial spores were produced when cultured on cherry agar at 25°C under near-ultravolet light. Spores were single-celled and hyaline, limoniform or ellipsoid, and were produced in branched monilioid chains, 12-22 × 8-13 µm (mean: 15.4 ± 1.03 × 9.01 ± 0.72 µm, n = 50). When conidia were cultured on water agar at 25°C for 18 h, the germ tubes were straight, 700-1,000 µm long, and often with two germ tubes per conidium. Morphological characteristics were consistent with those of Monilinia polystroma (van Leeuwen et al. 2002). To confirm the species identification, two DNA regions of the selected isolate 'VAMPWYZSH8' were amplified by polymerase chain reaction (PCR) and sequenced: the internal transcribed spacer region (ITS) was generated using primers ITS1/ ITS4 (Munda 2015) and β-tubulin (TUB2) was amplified using primers Bt2a/Bt2b (Zhu et al. 2016). A BLAST analysis of the nucleotide sequence of the PCR products revealed 100% identity with two M. polystroma sequences in the NCBI GenBank (KJ814976 for ITS, KR778970 for TUB2). Our sequences were deposited in GenBank with accession nos. MT038413 for ITS and MT038414 for TUB2. On the basis of these results, the isolate was identified as M. polystroma. To confirm pathogenicity, 78 fresh and healthy bunches of 'Beibinghong' grapes at ripening were collected, surface disinfected by immersion in 1% NaOCl for 1 min, rinsed three times with sterile water, then allowed to air dry. Under dry aseptic conditions, the fruits were inoculated using the pin prick method. Each wound was inoculated with 10 μl conidial suspension (106 spore ml-1) and incubated at 25°C with about 90% relative humidity and natural light. Inoculation with water was used as control and the experiment was repeated three times. After a 10-day incubation, typical symptoms of brown rot developed on inoculated fruits, while control fruits were symptomless. The fungus was consistently re-isolated only from diseased fruits and showed the same morphological characteristics as the original isolates, thus fulfilling Koch's postulates. This is the first report of M. polystroma on V. amurensis in China. The resulting disease decreases fruit quality and yield, necessitating the development of effective control measures.


Methylation Levels of LINE-1 As a Useful Marker for Venous Invasion in Both FFPE and Frozen Tumor Tissues of Gastric Cancer.
Long interspersed nuclear element-1 (LINE-1) is a retrotransposon that contains a CpG island in its 5'-untranslated region. The CpG island of LINE-1 is often heavily methylated in normal somatic cells, which is associated with poor prognosis in various cancers. DNA methylation can differ between formalin-fixed paraffin-embedded (FFPE) and frozen tissues. Therefore, this study aimed to compare the LINE-1 methylation status between the two tissue-storage conditions in gastric cancer (GC) clinical samples and to evaluate whether LINE-1 can be used as an independent prognostic marker for each tissue-storage type. We analyzed four CpG sites of LINE-1 and examined the methylation levels at these sites in 25 FFPE and 41 frozen GC tissues by quantitative bisulfite pyrosequencing. The LINE-1 methylation status was significantly different between the FFPE and frozen GC tissues (p < 0.001). We further analyzed the clinicopathological features in the two groups separately. In the frozen GC tissues, LINE-1 was significantly hypomethylated in GC tissues compared to their corresponding normal gastric mucosa tissues (p < 0.001), and its methylation status was associated with gender, differentiation state, and lymphatic and venous invasion of GC. In the FFPE GC tissues, the methylation levels of LINE-1 differed according to tumor location and venous invasion of GC. In conclusion, LINE-1 can be used as a useful methylation marker for venous invasion in both FFPE and frozen tumor tissues of GC.


A glance of the layered transition metal oxide cathodes in sodium and lithium-ion batteries: difference and similarities.
The fast-growing demand for energy storage devices has prompted diverse battery techniques, while the state-of-the-art Li-ion batteries (LIBs) continue to flourish, Na-ion batteries (SIBs) have been identified to be a promising alternative to share the burden with LIBs, particularly for large-scale grid storage applications. Both LIBs and SIBs techniques work based on similar fundamental mechanisms, with a heavy focus on the intercalation chemistry of layered transition metal oxides. However, the differences between Li-ion and Na-ion in terms of their size and Lewis acidity induce many different behaviors when crystallizing or diffusing in layered cathode materials. This minireview summarizes some typical cases where Li and Na-ion differ in layered cathode materials and discusses potential approaches to leverage their similarities and dissimilarities for future developments of high-performance SIBs.


Functional dissection of the paired segmentation gene in Drosophila embryos.
An ectopic expression assay in Drosophila embryos was used to investigate the roles of pair-rule segmentation genes in the spatial regulation of the segment-polarity gene, engrailed (en). It is hypothesized that the regions of overlap in expression of two genes, paired (prd) and even-skipped (eve), define the odd-numbered en expression stripes. Consistent with this combinatorial model, ectopic expression of prd caused these en stripes to be expanded posteriorly. Surprisingly, however, ectopic expression of a prd gene with a deletion of the conserved paired box resulted in loss of these odd-numbered en stripes. This dominant negative effect is a phenocopy of en expression in prd embryos and suggests that the paired box is necessary for normal prd- function. A similar deletion of odd-numbered en stripes was also observed after ectopic expression of a chimeric fushi tarazu (ftz) gene containing a substituted prd gene homeo box; in addition, in these embryos, the even-numbered en stripes were expanded anteriorly, as observed when the unaltered ftz gene is ectopically expressed. These effects suggest that the chimeric protein may have DNA or protein targets of both the normal Ftz and Prd proteins.


Salience is only briefly represented: evidence from probe-detection performance.
Salient objects in the visual field tend to capture attention. The present study aimed to examine the time-course of salience effects using a probe-detection task. Eight experiments investigated how the salience of different orientation singletons affected probe reaction time as a function of stimulus onset asynchrony (SOA) between the presentation of a singleton display and a probe display. The results demonstrate that salience consistently affected probe reaction time at the shortest SOA. The effect of salience disappeared as SOA increased. These results suggest that contrary to the assumption of major theories on visual selection, salience is transiently represented in our visual system allowing the effects of salience on attentional selection to be only short-lived.


Effects of Silexan on the serotonin-1A receptor and microstructure of the human brain: a randomized, placebo-controlled, double-blind, cross-over study with molecular and structural neuroimaging.
Recently, Silexan, a patented active substance comprised of an essential oil produced from Lavandula angustifolia flowers, has been authorized in Germany as a medicinal product for the treatment of states of restlessness related to anxious mood. Its efficacy has been shown in several forms of anxiety disorders. Findings from preclinical and clinical studies attribute a major role to the serotonin-1A receptor in the pathogenesis and treatment of anxiety. To elucidate the effect of Silexan on serotonin-1A receptor binding, 17 healthy men underwent 2 positron emission tomography measurements using the radioligand [carbonyl-(11)C]WAY-100635 following the daily intake of 160 mg Silexan or placebo for a minimum of 8 weeks (randomized, double-blind, cross-over design). Additionally, structural magnetic resonance imaging and voxel-based morphometry analysis was performed to determine potential effects on gray matter microstructure. Serotonin-1A receptor binding potential was shown to be significantly reduced following the intake of Silexan compared with placebo in 2 large clusters encompassing the temporal gyrus, the fusiform gyrus and the hippocampus on one hand as well as the insula and anterior cingulate cortex on the other hand. No effects of Silexan on gray matter volume could be detected in this investigation. This positron emission tomography study proposes an involvement of the serotonin-1A receptor in the anxiolytic effects of Silexan. The study was registered in the International Standard Randomized Controlled Trial Number Register as ISRCTN30885829 (http://www.controlled-trials.com/isrctn/).


Synthesis of oxaspiranic compounds through [3 + 2] annulation of cyclopropenones and donor–acceptor cyclopropanes.
The Sc(OTf)3-catalyzed [3 + 2]-annulation reaction between cyclopropenones and donor–acceptor cyclopropanes is described. The process leads directly to the formation of 4-oxaspiro[2.4]hept-1-ene derivatives in good to excellent reaction yields. Density functional theory calculations suggest that the [3 + 2]-annulation pathway is strongly preferred over the possible [3 + 3]-process.


Effect of macrophage colony-stimulating factor (M-CSF) on mouse immune responses in vivo.
We examined the effects of recombinant human M-CSF (rhM-CSF) on mouse macrophages and immune responses in vivo. Intraperitoneal administration of rhM-CSF (20-500 microgram/ml) increased Mac-1+ cell numbers in the peritoneal cavity. The tumoricidal activities of the macrophages from vehicle-administered (V-M phi) and from rhM-CSF-administered (M-M phi) mice were the same as those observed in vitro. However, when activated by lipopolysaccharide (LPS), the tumoricidal activity of M-M phi was stronger than that of V-M phi. Intravenous administration of rhM-CSF (500 micrograms/gk) increased the number of spleen cells. Flow cytometric analysis showed that administration of rhM-CSF increased Mac-1+, B220+ and NK 1.1+ cell counts in the spleen. However, CD4+ and CD8+ cell numbers did not change. Concomitant increases were observed in levels of IL-4 and IL-10 in mouse serum following rhM-CSF administration, but no significant changes were observed in the serum level of IFN-gamma. In experiments involving mouse immune responses, the administration of rhM-CSF reduced the contact sensitivity (CS) reaction against picryl chloride (PC) and augmented IgE production in response to 2,4-dinitrophenyl (DNP), but did not affect the production of either IgM or IgC1. These results suggest that administration of rhM-CSF not only activates murine macrophages, but modulates antigen-specific immune responses in vivo.


SGK1 signaling promotes glucose metabolism and survival in extracellular matrix detached cells.
Loss of integrin-mediated attachment to extracellular matrix (ECM) proteins can trigger a variety of cellular changes that affect cell viability. Foremost among these is the activation of anoikis, caspase-mediated cell death induced by ECM detachment. In addition, loss of ECM attachment causes profound alterations in cellular metabolism, which can lead to anoikis-independent cell death. Here, we describe a surprising role for serum and glucocorticoid kinase-1 (SGK1) in the promotion of energy production when cells are detached. Our data demonstrate that SGK1 activation is necessary and sufficient for ATP generation during ECM detachment and anchorage-independent growth. More specifically, SGK1 promotes a substantial elevation in glucose uptake because of elevated GLUT1 transcription. In addition, carbon flux into the pentose phosphate pathway (PPP) is necessary to accommodate elevated glucose uptake and PPP-mediated glyceraldehyde-3-phosphate (G3P) is necessary for ATP production. Thus, our data show SGK1 as master regulator of glucose metabolism and cell survival during ECM-detached conditions.


Effects of ascorbic acid on anxiety state and affect in a non-clinical sample.
Objective Given that the literature data indicates that ascorbic acid may have an anxiolytic effect, we hypothesized that a single oral administration of ascorbic acid could acutely affect emotional states. Methods The effects of acid ascorbic supplementation on anxiety and other emotional states were evaluated by the State‑Trait Anxiety Inventory (STAI), and Visual Analogue Mood Scale (VAMS). Immediately before, and 2 hours after receiving a single ascorbic acid dose (1000 mg) or placebo, 142 graduate students were evaluated by the STAI and VAMS in a randomized, double‑blind, placebo‑controlled trial. Results No changes from basal levels were observed in the STAI state‑anxiety or VAMS scores. However, the ingestion of ascorbic acid by the 25% more anxious healthy subjects (women; 14 control and 23 ascorbic acid), as defined by the STAI trait‑anxiety scale, produced a significant reduction from baseline anxiety scores in the STAI state‑anxiety scale and VAMS anxiety subscale. The study evaluated a small sample with narrow sociodemographic characteristics, composed mainly of healthy young females (> 94%) enrolled in post‑graduation courses, without controlling diet, physical activity, and formal psychiatric diagnosis. Despite the sample size limitation, this study provides the first evidence of an acute anxiolytic effect of ascorbic acid. Broader population studies are required to evaluate the clinical relevance of presented data.


Oysters: Composition of the Larval Shell.
The shell of the freeswimming veliger larval stage of the common North American oyster Crassostrea virginica (Gmelin, 1791) is composed of aragonite. This composition contrasts with that of the adult shell, which is composed mainly of calcite, the rhombohedral allomorph of calcium carbonate, and minor amounts of aragonite.


Profile of problem children from a rural county in Indiana.
In order to better identify and understand problems experienced by delinquent children and adolescents in a rural county in Indiana, in-the-trenches professionals working with these children were interviewed. Comparisons are drawn between observations of these professionals and existing research findings regarding Disruptive Behavior Disorders (i.e., ADHD, ODD, CD).


A new automated technique for platelet aggregation measurement.
A Multistat III Centrifugal Analyser (MCA) was used to measure platelet aggregation in vitro. It has a capacity of about 40 samples per h. In the analyser platelet-rich plasma and collagen-reagent were mixed, and the turbidity was measured as a function of time. The results were presented in arbitrary units ( arb . units), i.e. change in turbidity per min X 1000. The estimated 0.95 reference range was 50-95 arb . units, (n = 46) and the coefficient of correlation between MCA results and results obtained by conventional aggregometry ( Fibromat ) was 0.85 (P less than 0.001). The MCA method registered 50-75% reduction of platelet aggregation after intake of low dose acetylsalicylic acid (ASA) (1.2-4.0 mg/kg) during 3 days in 19 subjects. The MCA method is suitable to monitor ASA treatment routinely in order to establish an individual appropriate ASA dose during prophylactic treatment of arterial thromboembolic disease.


Isolation and characterization of polymorphic microsatellite markers from the Chinese medicinal herb Atractylodes macrocephala (Asteraceae).
Atractylodes macrocephala Koidz. (Asteraceae) is an economically important Chinese medicinal herb. In this study, 15 polymorphic microsatellite markers were developed from A. macrocephala using the compound microsatellite marker technique. Levels of polymorphism within the 15 markers were assessed using 83 individuals from two wild and two cultivated populations in China. The number of alleles per locus ranged from 2 to 20, with an average of 9.9 alleles. Observed and expected heterozygosities ranged from 0.083 to 1.000 and from 0.097 to 0.938, respectively. These markers will be valuable for germplasm classification and identification, as well as for assessing the genetic diversity and spatial genetic structure among wild and cultivated populations of A. macrocephala.


Bacteriophage endolysins and their applications.
Endolysins (lysins) are bacteriophage-encoded enzymes that have evolved to degrade specific bonds within the bacterial cell wall. These enzymes represent a novel class of antibacterial agents against infectious pathogens, especially in light of multidrug-resistant bacteria, which have made antibiotic therapy increasingly redundant. Lysins have been used successfully to eliminate/control bacterial pathogens in various anatomical locations in mouse and other animal models. Engineering tactics have also been successfully applied to improve lysin function. This review discusses the structure and function of lysins. It highlights protein-engineering tactics utilised to improve lysin activity. It also reviews the applications of lysins towards food biopreservation, therapeutics, biofilm elimination and diagnostics.


Effect of gossypol upon motility and ultrastructure of Trypanosoma cruzi.
Gossypol, a polyphenolic compound from the cotton plant, immobilizes and structurally alters cultured Trypanosoma cruzi epimastigotes. Ultrastructural changes observed in gossypol-treated parasites were first detected in the kinetoplast and mitochondrion. At 50 microM concentration, much disorganization was evident after 5 min of incubation. With 25 microM gossypol, the same effect occurred after 30 min. Most epimastigotes were rounded, containing various membranous structures that could not be related to known cell components.


Effect of Conducting Salts in Ionic Liquid Electrolytes for Enhanced Cyclability of Sodium-Ion Batteries.
The electrochemical performance of ionic liquid electrolytes containing different sodium salts dissolved in 1-butyl-1-methylpyrrolidinium bis(trifluoromethylsulfonyl)imide (BMPTFSI) evaluated in a half-cell configuration using spherical P2-Na0.6Co0.1Mn0.9O2+z (NCO) cathodes are reported. Among the various electrolytes investigated, sodium bis(fluorosulfonyl)imide (NaFSI) (0.5 M) in BMPTFSI shows the best electrochemical performance with a significant improvement in cycling stability (90% capacity retention after 500 cycles at 50 mA g-1 in a half cell versus Na metal anode) compared with conventional NaClO4 (1 M) in ethylene carbonate/propylene carbonate electrolytes (39% retention after 500 cycles). Cyclic voltammetry (CV) studies reveal that ionic liquid electrolytes are stable up to 4.8 V versus Na/Na+. When NaFSI and NaTFSI are used as conducting salts, X-ray photoelectron spectroscopy results prove that the cathode electrolyte interface (CEI) is composed of components resulting from the decomposition of the TFSI anion and the deposition of the BMP cation. On the other hand, the CEI layer of the electrode cycled in an electrolyte containing NaClO4 in BMPTFSI follows a different pathway of TFSI decomposition and consists mainly of sodium fluoride. Similarly, plating studies were used to understand the stability of different ionic liquids in contact with metallic sodium. It was found that the excellent capacity retention for the electrolyte consisting of NaFSI salt is related to the formation of a stable CEI and solid electrolyte interphase layers.


Balancing confidence and humility in the diagnostic process.
Humility in medicine can be difficult to achieve, yet arguably is one of the most important competencies to master. Overconfidence, on the contrary, is a natural tendency, having established its roots in evolution where quicker and more confident decisions likely conferred a selective advantage. Moreover, humility may evoke an image of weakness and vulnerability, antithetical to contemporary medicine, whose culture is dominated by overconfidence. Nevertheless, humility can be learned, and is important because overconfident behavior can be detrimental to our patients medically, psychosocially and legally, when it results in delayed or missed diagnoses. To achieve humility requires a great deal of metacognition, normalizing doubt and not being afraid to utilize tools that may feel beneath us. To practice humility requires strength and emotional resilience. In this paper we explore the definitions, roles and implications of humility in medicine, and we pose suggestions of how to accomplish this in the diagnostic process.


Transcriptome Profile of Rat Adrenal Evoked by Gonadectomy and Testosterone or Estradiol Replacement.
Sex differences in adrenal cortex structure and function are well known in different species. In the rat, they are manifested as larger adrenal cortex and higher corticosterone secretion by females compared with males. These sex differences depend, among others, on functioning of the hypothalamic-pituitary-adrenal axis (HPA). In this aspect, it is widely accepted that testosterone exerts an inhibitory and estradiol stimulatory effect on the said axis. The molecular bases of these sex-related differences are poorly understood. Therefore, we performed studies aimed to demonstrate the effect of testosterone and estradiol on the expression of differentially regulated genes in rat adrenal gland. The classical method applied in the study-gonadectomy and gonadal hormone replacement-allows obtaining results suggesting a physiological role of the tested hormone (testosterone or estradiol) in the regulation of the specific genes. Adult male and female rats were either gonadectomized or sham operated. Half of orchiectomized rats were replaced with testosterone while ovariectomized ones with estradiol. Transcriptome was identified by means of Affymetrix® Rat Gene 2.1 ST Array. Differentially expressed genes were analyzed by means of DAVID web-based bioinformatic tools and confirmed by means of Gene Set Enrichment Analysis. For selected genes, validation of the results was performed using QPCR. Performed experiments have provided unexpected results. Contrary to expectations, in orchiectomized rats, testosterone replacement stimulates expression of numerous genes, mainly those associated with lipids and cholesterol metabolism. However, in ovariectomized animals, estradiol replacement inhibits the expression of genes, mainly those involved in intracellular signaling pathways. The physiological relevance of these findings awaits further research.


SiBIC: a web server for generating gene set networks based on biclusters obtained by maximal frequent itemset mining.
Detecting biclusters from expression data is useful, since biclusters are coexpressed genes under only part of all given experimental conditions. We present a software called SiBIC, which from a given expression dataset, first exhaustively enumerates biclusters, which are then merged into rather independent biclusters, which finally are used to generate gene set networks, in which a gene set assigned to one node has coexpressed genes. We evaluated each step of this procedure: 1) significance of the generated biclusters biologically and statistically, 2) biological quality of merged biclusters, and 3) biological significance of gene set networks. We emphasize that gene set networks, in which nodes are not genes but gene sets, can be more compact than usual gene networks, meaning that gene set networks are more comprehensible. SiBIC is available at http://utrecht.kuicr.kyoto-u.ac.jp:8080/miami/faces/index.jsp.


Associations among bullying, cyberbullying, and suicide in high school students.
This study examined associations among depression, suicidal behaviors, and bullying and victimization experiences in 1491 high school students using data from the 2009 Youth Risk Behavior Survey. Results demonstrated that depression mediated the association between bullying/victimization and suicide attempts, but differently for males and females. Specifically, depression mediated the link between traditional victimization and suicide attempts similarly across gender, whereas depression mediated the link between cyber victimization and suicide attempts only for females. Similarly, depression mediated the link between traditional bullying and suicide attempts for females only. Depression did not mediate the link between cyberbullying and suicide attempts for either gender. Implications of the findings are discussed, including the importance of greater detection of depression among students involved in bullying, and the need for a suicide prevention and intervention component in anti-bullying programs. Findings suggest that bullying prevention efforts be extended from middle school students to include high school students.