Endothelial Bmx tyrosine kinase activity is essential for myocardial hypertrophy and remodeling.
Cardiac hypertrophy accompanies many forms of heart disease, including ischemic disease, hypertension, heart failure, and valvular disease, and it is a strong predictor of increased cardiovascular morbidity and mortality. Deletion of bone marrow kinase in chromosome X (Bmx), an arterial nonreceptor tyrosine kinase, has been shown to inhibit cardiac hypertrophy in mice. This finding raised the possibility of therapeutic use of Bmx tyrosine kinase inhibitors, which we have addressed here by analyzing cardiac hypertrophy in gene-targeted mice deficient in Bmx tyrosine kinase activity. We found that angiotensin II (Ang II)-induced cardiac hypertrophy is significantly reduced in mice deficient in Bmx and in mice with inactivated Bmx tyrosine kinase compared with WT mice. Genome-wide transcriptomic profiling showed that Bmx inactivation suppresses myocardial expression of genes related to Ang II-induced inflammatory and extracellular matrix responses whereas expression of RNAs encoding mitochondrial proteins after Ang II administration was maintained in Bmx-inactivated hearts. Very little or no Bmx mRNA was expressed in human cardiomyocytes whereas human cardiac endothelial cells expressed abundant amounts. Ang II stimulation of endothelial cells increased Bmx phosphorylation, and Bmx gene silencing inhibited downstream STAT3 signaling, which has been implicated in cardiac hypertrophy. Furthermore, activation of the mechanistic target of rapamycin complex 1 pathway by Ang II treatment was decreased in the Bmx-deficient hearts. Our results demonstrate that inhibition of the cross-talk between endothelial cells and cardiomyocytes by Bmx inactivation suppresses Ang II-induced signals for cardiac hypertrophy. These results suggest that the endothelial Bmx tyrosine kinase could provide a target to attenuate the development of cardiac hypertrophy.


Prevalence of ulcers of the squamous gastric mucosa in standardbred horses.
This study was performed to determine the prevalence of ulcers in the gastric squamous mucosa in Standardbred racehorses. Observations were performed at monthly intervals between the beginning of their training season and their 1st qualifying race. This study also identified risk factors at different levels of race training. Forty-eight Standardbred racehorses from 3 training stables in Quebec, Canada, were studied. Baseline historical information and gastroscopic findings were recorded at the beginning of the trial, and once a month thereafter, between December 2001 and June 2002, until the horse's 1st qualifying race or the end of the training. Intensity of training ranged from jogging to intensive training just before the 1st race and was assigned an ordinal score. Location of squamous ulcers and their appearance were observed on gastroscopy, and an ordinal score was assigned. Prevalence of squamous ulcers from the 2nd through the 4th month (72-88%) of training remained at a significantly higher level (P = .002 to .04) than at the onset of the study (38%) and was also higher in intensely trained horses than in joggers (93% versus 56%). Moderate or more intensive training increased the odds (odds ratio [OR], 3.39; confidence interval [CI], 1.34-8.56; and OR, 11.4; CI, 3.21-40.5, respectively) of detecting ulcers with higher scores. These odds were also higher in trotters (OR, 2.17; CI, 1.07-4.43) than in pacers and generally increased with the duration of training. Duration of training, training level, and gait type also influenced the number of sites with ulcers in the same way. Ulcers had higher scores along the lesser curvature (LC) and the margo plicatus (MP) areas of the stomach. It was concluded that squamous ulcers appeared early in the training of Standardbred racehorses, that the number of sites affected and the ulcer score are related to the intensity of training, and that trotters are more prone to squamous ulcers than pacers.


Scavenging of dpph* radicals by vitamin E is accelerated by its partial ionization: the role of sequential proton loss electron transfer.
[reaction: see text] Rate constants for reaction of alpha-tocopherol, 2,2,5,7,8-pentamethyl-6-hydroxychroman, and 2,6-di-tert-butyl-4-methylphenol with 2,2-diphenyl-1-picrylhydrazyl radical were measured in solvents of different polarity and H-bond basicity. In ionization supporting solvents besides hydrogen atom transfer (HAT), the kinetics of the process is partially governed by sequential proton loss electron transfer (SPLET). Addition of acetic acid reduces the rate by eliminating SPLET to leave only HAT, while addition of water increases the rate by enhancing phenol deprotonation.


Microbiological aspects of Fournier's gangrene.
Fournier's gangrene (FG) is a devastating disease that is characterized by necrotizing fasciitis of the perineal, genital, or perianal region. Broad-spectrum antibiotics are the key component of its treatment. However, there is paucity of data regarding the optimal empirical antibiotherapy for FG. Data from patients who underwent surgery for FG between January 2007 and December 2012 were retrieved from a prospectively collected departmental FG database. Demographics, clinical characteristics, causative pathogens and drug susceptibility/resistance were evaluated. Fifty patients with a median age of 58.5 (22-83) years were included. The perianal origin (58%) was most commonly affected. A positive growth was found in specimen cultures of 48 (96%) patients. The median number of bacterial strains that grew in the cultures was 3 (0-10). Amikacin was the antibiotic with the highest frequency of sensitivity (74%), while the highest resistance was observed against ampicillin-sulbactam (64%). Escherichia coli was the most common microorganism (72%). Acinetobacter baumannii and Klebsiella pneumonia were significantly more common in patients who required mechanical ventilation. The mortality rate was 26%. An Uludag Fournier's Gangrene Severity Index (UFGSI) score of >9.5 and ventilatory support requirement were factors associated with an increased rate of mortality. Acinetobacter baumannii was the only microorganism which was associated with an increased mortality rate. Causative pathogens in FG appeared to be shifting; thus, empirical antibiotic treatment for this disease should be modified. We recommend 3rd-generation cephalosporin, metronidazole and amikacin for empirical therapy.


[Diagnostic values of polymerase chain reaction test in females with genital tuberculosis].
The previously offered procedure for detecting. Mycobacterium tuberculosis, which is based on the polymerase chain reaction (PCR), has been tested for diagnosing genital tuberculosis in females. PCR was used to examine endometrial curettage specimens in 44 patients with different nosological entities, which showed a high sensitivity (80%) and a high specificity in the diagnosis of genital tuberculosis.


Limitations to carrier mobility and phase-coherent transport in bilayer graphene.
We present transport measurements on high-mobility bilayer graphene fully encapsulated in hexagonal boron nitride. We show two terminal quantum Hall effect measurements which exhibit full symmetry broken Landau levels at low magnetic fields. From weak localization measurements, we extract gate-tunable phase-coherence times τϕ as well as the inter- and intravalley scattering times τi and τ*, respectively. While τϕ is in qualitative agreement with an electron-electron interaction-mediated dephasing mechanism, electron spin-flip scattering processes are limiting τϕ at low temperatures. The analysis of τi and τ* points to local strain fluctuation as the most probable mechanism for limiting the mobility in high-quality bilayer graphene.


Emotional distress and substance abuse as risk factors for suicide attempts.
Both depression and hopelessness have been found to be closely related to suicide risk among adolescents and adults. Substance abuse has also been found to play a role in the suicide process with adults, but it is still unclear how much substance abuse influences suicide in adolescents. The present study examined the relationship between substance abuse, emotional distress, and suicidal intent among 115 adolescent psychiatric inpatients who had attempted suicide. Measures of emotional distress, as well as the measures of substance abuse, were significantly intercorrelated. Correlations across domains (emotional distress versus substance abuse), however, varied by gender. Among adolescent females, both depression and hopelessness were significantly related to suicidal intent, whereas among adolescent males, only depression was related to suicidal intent. Also, alcohol abuse was significantly related to depression and hopelessness in adolescent males. Hopelessness may not be as useful an indicator of suicide risk among adolescent males as it is with adolescent females. Intervention and prevention programs designed for adolescent females should identify and address feelings of depression and hopelessness. New intervention and prevention programs may need to be developed for adolescent males.


Apparent dose-dependent oral absorption of cyclosporin A in rats.
The oral absorption of cyclosporin A (CyA) was studied in rats after 6, 12, 18, and 23 mg kg-1 doses were given in an olive oil solution to determine if CyA absorption from the gastrointestinal tract was dose-dependent. Using serial blood samples obtained at various times after the respective doses, analysis of the resultant blood CyA concentration-time curves suggested that the rate of CyA absorption for all four doses was an apparent zero-order process. Moreover, the rate of CyA absorption appeared to be dose-dependent, increasing as the dose of CyA increased. Similarly, the extent of CyA absorption (F) also exhibited dose-dependent characteristics in this study. F increased from 0.13 after the 6 mg kg-1 dose to 0.22 with the 18 and 23 mg kg-1 doses (p less than 0.05). In the present investigation, the observed values for the duration of drug absorption (T), terminal first-order rate constant (beta) and corresponding elimination half-life (T 1/2 beta) of approximately 4-5 h, 0.030 h-1 and 21-28 h, respectively, were similar for all CyA doses. Moreover, no difference in beta was observed after oral or intravenous drug administration. Absorption lag times of 1-2 h were found. The results suggested that the dose-dependent absorption of CyA observed in the present study was possibly related to the effects of olive oil on gastric emptying and that CyA might be unstable in the gastric fluids and/or metabolized by the gastric mucosa.


Effects of Defects on the Mechanical Properties of Kinked Silicon Nanowires.
Kinked silicon nanowires (KSiNWs) have many special properties that make them attractive for a number of applications. The mechanical properties of KSiNWs play important roles in the performance of sensors. In this work, the effects of defects on the mechanical properties of KSiNWs are studied using molecular dynamics simulations and indirectly validated by experiments. It is found that kinks are weak points in the nanowire (NW) because of inharmonious deformation, resulting in a smaller elastic modulus than that of straight NWs. In addition, surface defects have more significant effects on the mechanical properties of KSiNWs than internal defects. The effects of the width or the diameter of the defects are larger than those of the length of the defects. Overall, the elastic modulus of KSiNWs is not sensitive to defects; therefore, KSiNWs have a great potential as strain or stress sensors in special applications.


Turn-off, drop-out: functional state switching of cadherins.
The classic cadherins are a group of calcium dependent, homophilic cell-cell adhesion molecules that drive morphogenetic rearrangements and maintain the integrity of cell groups through the formation of adherens junctions. The formation and maintenance of cadherin-mediated adhesions is a multistep process and mechanisms have evolved to regulate each step. This suggests that functional state switching plays an important role in development. Among the many challenges ahead is to determine the developmental role that functional state switching plays in tissue morphogenesis and to define the roles of each of the several regulatory interactions that participate in switching. One correlate of the loss of cadherin-mediated adhesion, the "turn-off" of cadherin function, is the exit, or "drop-out" of cells from neural and epithelial layers and their conversion to a motile phenotype. We suggest that epithelial mesenchymal conversions may be initiated by signaling pathways that result in the loss of cadherin function. Tyrosine phosphorylation of beta-catenin is one such mechanism. Enhanced phosphorylation of tyrosine residues on beta-catenin is almost invariably associated with loss of the cadherin-actin connection concomitant with loss of adhesive function. There are several tyrosine kinases and phosphatases that have been shown to have the potential to alter the phosphorylation state of beta-catenin and thus the function of cadherins. Our laboratory has focused on the role of the nonreceptor tyrosine phosphatase PTP1B in regulating the phosphorylation of beta-catenin on tyrosine residues. Our data suggest that PTP1B is crucial for maintenance of N-cadherin-mediated adhesions in embryonic neural retina cells. By using an L-cell model system constitutively expressing N-cadherin, we have worked out many of the molecular interactions essential for this regulatory interaction. Extracellular cues that bias this critical regulatory interaction toward increased phosphorylation of beta-catenin may be a critical component of many developmental events.


Evaluation of the viability of Lactobacillus spp. after the production of different solid dosage forms.
The work aims to provide evidence on the viability of Lactobacillus spp. and a spore form of Bacillus subtilis from nonprocessed bacteria to coated dosage forms (i.e., mini-tablets, pellets, and their coated forms). Lactobacillus spp. were cultivated overnight in MRS broth (10(9) cfu/mL) and B. subtilis spores were produced on plate count agar (10(7) cfu/mL) for 2 weeks. Bacteria and spores were freeze-dried in skim milk enriched with glycerol. The cakes were further processed into tablets (2.5 mm diameter) by direct compression with or without microcrystalline cellulose and inulin. Pellets (1-1.4 mm diameter) were produced by extrusion-spheronization of bacterial and spore suspensions with microcrystalline cellulose, lactose, inulin, and skim milk. Both tablets and pellets were film coated. The properties of the dosage forms, particularly the bacterial viability, were evaluated immediately after production and throughout storage for 6 months at 4 degrees C. The study has shown that for an adequate stabilization of the bacteria a protective matrix (e.g., skim milk) and cryoprotectors (e.g., glycerol) must be present at early stages of bacterial de-hydration. Tabletting had a less deleterious effect (<2 log units) on bacteria when compared to pelletization (in some cases 3 log units). Enteric coating (15%, w/w) of either tablets or pellets did not affect the viability of the bacteria.


Solution-prepared hybrid-nanoparticle dielectrics for high-performance low-voltage organic thin-film transistors.
Oleic acid capped barium strontium titanate (OA-BST) nanoparticles were synthesized for solution-prepared dielectrics in organic thin-film transistors (OTFTs). The as-synthesized nanoparticles were well-dispersed in organic solvents to deposit very homogeneous dielectric films by direct spin coating. Bottom-gate pentacene TFTs fabricated using these nanoparticle dielectric films showed high mobilities of 1-2 cm(2) V(-1) s(-1) with on/off ratios of 10(3) under a low driven voltage of -2.5 V. Top-gate poly(3,3'''-didodecylquaterthiophene) (PQT-12) TFTs with nanoparticle dielectrics also exhibited a low-voltage operation (-5 V) performance with mobilities of 0.01-0.1 cm(2) V(-1) s(-1) and on/off ratios of 10(3)-10(4). Detailed studies on the gate voltage-dependent mobility of the devices showed that only a low gate electric field needed to achieve the saturated mobility for the OA-BST-based pentacene OTFTs could be attributed to the low trapped-state densities (<3.9 x 10(11) cm(-2)) at the dielectric/semiconductor interfaces for these devices.


Autophagic tumor stroma: mechanisms and roles in tumor growth and progression.
Macroautophagy (hereafter autophagy) is a cellular homeostatic mechanism that involves protein and organelle degradation, and has a number of connections to human physiology and diseases. Autophagy in tumor parenchyma acts as either a tumor-promoting role or a tumor-inhibiting role depending on the types and stages of tumors. In recent years, attention to autophagy in tumor stroma that is referred as "autophagic tumor stroma" has created a new paradigm to understand the role of autophagy in cancer. Here we propose that the autophagic tumor stroma is a phenomenon of adaptation at a certain stage of tumor development, and has a prominent role in tumor growth, progression and spread of tumors. This idea is supported by recent studies: (i) Autophagic tumor stroma is activated by hypoxia and cancer cells induced oxidative stress, when tumors grow to a certain stage; (ii) Autophagic tumor stroma aids in providing essential nutrients to malignant cells, remodeling the tumor microenvironment, increasing DNA damage, genetic instability and stemness in cancer cells, and decreasing the apoptotic sensitivity of cancer cells. The autophagic tumor stroma is therefore a significant determinant in tumor growth and progression and implicates an important target for cancer therapies.


Role of the lateral habenula in memory through online processing of information.
Our memory abilities, whether they involve short-term working memory or long-term episodic or procedural memories, are essential for our well-being, our capacity to adapt to constraints of our environment and survival. Therefore, several key brain regions and neurotransmitter systems are engaged in the processing of sensory information to either maintain such information in working memory so that it will quickly be used, and/or participate in the elaboration and storage of enduring traces useful for longer periods of time. Animal research has recently attracted attention on the lateral habenula which, as shown in rodents and non-human primates, seems to process information stemming in the main regions involved in memory processing, e.g., the medial prefrontal cortex, the hippocampus, the amygdala, the septal region, the basal ganglia, and participates in the control of key memory-related neurotransmitters systems, i.e., dopamine, serotonin, acetylcholine. Recently, the lateral habenula has been involved in working and spatial reference memories, in rodents, likely by participating in online processing of contextual information. In addition, several behavioral studies strongly suggest that it is also involved in the processing of the emotional valance of incoming information in order to adapt to particularly stressful situations. Therefore, the lateral habenula appears like a key region at the interface between cognition and emotion to participate in the selection of appropriate behaviors.


Comorbidity of conduct disorder and bipolar disorder in clinically referred children and adolescents.
The co-occurrence of conduct disorder (CD) and bipolar disorder (BD) has been frequently reported in referred children and adolescents. We address the implications of this comorbidity in a naturalistic sample of youths with BD, CD, and CD+BD. The sample consisted of 307 patients (216 males and 91 females, age range 8-18 years, mean age 13.5 +/- 2.6 years) referred during a 5-year period and followed-up for at least 6 months, 106 with CD without BD, 109 with BD without CD, and 92 with CD+BD, diagnosed with a structured clinical interview (K-SADS-PL). Patients with CD alone were more predominantly males and with the lowest socio-economic status. Patients with CD without BD were the least severe at the baseline, while patients with BD alone presented the greatest improvement during the follow-up, and those with CD+BD had the poorest response. Patients with CD+BD presented higher rates of global aggression at the baseline, namely impulsive aggression, compared with CD alone, and the highest risk of substance abuse. Patients with BD alone presented higher rates of comorbid panic disorder and obsessive compulsive disorder, while patients with CD, with or without BD, had higher rates of ADHD. Bipolar-conduct disorder comorbidity may have meaningful implications in children and adolescents, in terms of presentation, course, and treatments.


Exploring Advancements in the Treatment of Amyotrophic Lateral Sclerosis: A Comprehensive Review of Current Modalities and Future Prospects.
Amyotrophic lateral sclerosis (ALS) is a fatal and incurable disease requiring a multidisciplinary treatment approach and a collaborative therapeutic effort. A combination of both upper and lower motor neuron degeneration ultimately leads to respiratory failure, similar to other dementia-type neurodegenerative diseases. The aim of this paper is to pioneer current ALS research by carrying out a narrative literature review of the current treatment modalities of the disease. Through these efforts, we hope to condense the most pertinent information regarding current treatments and enhance the management of ALS patients as a whole, giving these patients a better quality of life as the search for a cure continues. We used a Pubmed search strategy and specific MeSH terms for the selection of the literature articles using the keywords "ALS," "new treatment," "treatment," and "symptomatic treatment." A combination of pharmaceutical interventions, psychological support, and physical rehabilitation has been most effective in enhancing the quality of life of patients with ALS (PALS). Among potential pharmacological therapies, only a few have been approved by the US Food and Drug Administration(FDA) to be used to treat ALS and its symptoms. Other treatment modalities being considered include gene therapy, cellular therapy, psychological therapy, physical therapy, and speech therapy, alongside robotics, alternative feeding methods, and communication devices.


Clinical guidelines for posterior restorations based on Coverage, Adhesion, Resistance, Esthetics, and Subgingival management. The CARES concept: Part I – partial adhesive restorations
Important changes have occurred over the last decades in the clinical application of the strategies for posterior restorations - from amalgam to composites in direct restorations and from traditional resistance form crowns to adhesive partial restorations such as onlays. Despite much evidence available for these advances, there are still very few established guidelines for common clinical questions: When does an indirect restoration present a clinical advantage over a direct one? When should one perform adhesive cusp coverage such as an onlay? When to implement resistance form designs in adhesive restorations? Which conditions create limitations for adhesion so that a resistance form preparation with a stiffer material such as a traditional crown might be more appropriate? In order to provide clinical guidelines, the present authors consider five parameters to support and clarify decisions - Coverage of cusps, Adhesion advantages and limitations, Resistance forms to be implemented, Esthetic concerns, and Subgingival management - the CARES concept. In Part I of this three-part review article, the focus is on clinical decisions for partial adhesive restorations regarding indications for direct versus indirect materials as well as the need for cusp coverage and/or resistance form preparations based on remaining tooth structure and esthetics.


[Determination of beta-adrenergic agonists in pig urine and pig fodder using miniaturized capillary electrophoresis with electrochemical detection].
A method of miniaturized capillary electrophoresis with electrochemical detection has been developed for the determination of beta-adrenergic agonists in pig urine and pig fodder. Several important factors, including running buffer acidity, separation voltage, working electrode potential, etc., were evaluated to acquire optimum analysis conditions. Under the selected optimum conditions, these analytes can be well separated in 7 min. Good linear relationship was established between the peak current and the concentration of each analyte over 3 orders of magnitude. The detection limits ranged from 1.20 x 10(-7) to 2.06 x 10(-7) g/mL (S/N = 3). The proposed method has been successfully applied for the determination of beta-adrenergic agonist in pig urine and pig fodder with satisfactory results, providing a useful monitoring method for food safety.


Discrete bimodal probes for thrombus imaging.
Here we report a generalizable solid/solution-phase strategy for the synthesis of discrete bimodal fibrin-targeted imaging probes. A fibrin-specific peptide was conjugated with two distinct imaging reporters at the C- and N-termini. In vitro studies demonstrated retention of fibrin affinity and specificity. Imaging studies showed that these probes could detect fibrin over a wide range of probe concentrations by optical, magnetic resonance, and positron emission tomography imaging.


State-space modeling approach for fringe pattern demodulation.
A spatial carrier fringe demodulation technique is proposed based on a state-space modeling approach for phase estimation. The fringe background intensity, carrier frequency, and phase quadrature components are considered to be the elements of the state vector, which are estimated simultaneously. The state estimation is performed using the extended Kalman filter. The simulation and experimental results are provided to demonstrate the performance comparison of the proposed method with popular and state-of-the-art methods in terms of noise robustness and phase estimation accuracy.


The roles of several sensory neurons and the feedback from egg laying in regulating the germline response to a sex pheromone in C. elegans hermaphrodites.
Animals broadcast small molecule pheromones that can alter behavior and physiology in conspecifics. Neuronal circuits that regulate these processes remain largely unknown. In C. elegans, male-enriched ascaroside sex pheromone ascr#10, in addition to behavioral effects, expands the population of germline precursor cells in hermaphrodites. Previously, we identified several sensory neurons required for this effect. We also found that feedback from egg laying acts via serotonergic signaling to license the pheromone response in reproducing adults. Here, using newly available reagents, we confirm and extend several of our previous conclusions: a) the ADL neurons are essential for the ascr#10 response, b) phasmid neurons (PHA and PHB) are unlikely to be involved in the ascr#10 response, c) the mod-1 receptor is the main conduit of the serotonergic feedback from egg laying, and d) serotonin remains the only currently known signal of this feedback. Our findings better define the neuronal circuits that mediate the germline response to the major male pheromone.


Dietary beta-cryptoxanthin inhibits N-butyl-N-(4-hydroxybutyl)nitrosamine-induced urinary bladder carcinogenesis in male ICR mice.
Recent epidemiological studies have indicated that high dietary consumption of fruit and vegetables results in lower risk of bladder cancer. To confirm these findings, we investigated in the current study the effects of dietary administration with beta-cryptoxanthin extracted from Citras unshiu oranges on N-butyl-N-(4-hydroxybutyl)nitrosamine (OH-BBN)-induced urinary bladder carcinogenesis in mice. Male ICR mice were divided into 6 experimental and control groups. Groups 1 through 4 were given OH-BBN (500 ppm) in drinking water for 6 weeks to induced urinary bladder neoplasms. Mice in groups 2, 3 and 4 were fed the diets mixed with 1, 5 and 25 ppm of beta-cryptoxanthin, respectively, starting 1 week after the cessation of OH-BBN exposure, and kept on these diets for 24 weeks until the termination of the study. Group 5 was treated with the diet containing the test compound (25 ppm) alone, and group 6 served as an untreated control. All animals were sacrificed at week 32 for histopathology and immunohistochemistry (cyclin D1). Feeding with beta-cryptoxanthin decreased the incidence and multiplicity of preneoplastic and neoplastic lesions of urinary bladder. Notably, the highest dose (25 ppm) of the test chemical significantly lowered the occurrence of bladder carcinoma, in conjunction with reducing the cyclin D1-positive cell ratio. These findings suggest that beta-cryptoxanthin is able to prevent OH-BBN-induced bladder carcinogenesis in mice.


Should psychiatrists support the availability of nicotine e-cigarettes in Australia?
To examine the position statement of the Royal Australian and New Zealand College of Psychiatrists (RANZCP) regarding the availability of electronic cigarettes in Australia. There is limited evidence supporting the efficacy of nicotine e-cigarettes as an effective tobacco harm-reduction or cessation strategy for people with mental illness. The recommendations to increase their availability under regulation must be balanced with the physical and mental health risks of vapour inhalation and nicotine use, particularly for youth. Future recommendations by the RANZCP in relation to e-cigarettes must consider both the available evidence for harm reduction and the potential risks associated with youth e-cigarette use.


Can surgical repair for pectus excavatum contribute to lung growth?
This study investigates whether the surgical correction of chest deformity is associated with the growth of the lung parenchyma after surgery for pectus excavatum. Ten patients with pectus excavatum who were treated by the Nuss procedure were examined. The preoperative and postoperative computed tomography (2.5 ± 1.2 years after surgery) scans were performed, and the Haller index, lung volume and lung density were analyzed using a three-dimensional image analysis system (SYNAPSE VINCENT, Fujifilm, Japan). The radiological lung weight was calculated as follows: lung volume (ml) × lung density (g/ml). The average age of the 10 patients (men 8; women 2) was 13.8 years (range: 6-26 years). The Haller index was significantly improved from the preoperative value of 5.18 ± 2.20 to the postoperative value of 3.68 ± 1.38 (P = 0.0025). Both the lung volume and weight had significantly increased by 107.1 ± 19.6% and 121.6 ± 11.3%, respectively, after surgery. A significant increase in the weight of the lung after surgical correction suggests that the growth of the lung parenchyma is associated with the correction of chest deformity in younger patients with pectus excavatum.


Osmolarity hypersensitivity of hog1 deleted mutants is suppressed by mutation in KSS1 in budding yeast Saccharomyces cerevisiae.
An osmosensing mechanism of Saccharomyces cerevisiae involves a mitogen-activated protein kinase (MAPK) cascade (HOG pathway). This study aimed to investigate the response of the yeast to osmotic stress. A mutant strain, in which the HOG1 gene was disrupted by TRP1, was constructed. A spontaneous mutant, named YJY45, which suppresses the osmosensitive growth phenotype of the hog1 deletion mutant, was selected and showed a secondary phenotype of temperature sensitivity on YPD containing 0.5 M NaCl at 37 degrees C. Our data indicate that the spontaneous mutation in YJY45 mutant was mapped in KSS1, which is one of the MAPK family. The mutation in KSS1 suppresses the osmolarity-hypersensitive phenotype of the hog1 deletion mutation and restores GPD1 induction.


Initiation codon selection is accomplished by a scanning mechanism without crucial initiation factors in Sindbis virus subgenomic mRNA.
Translation initiation of alphavirus subgenomic mRNA (sgmRNA) can occur in the absence of several initiation factors (eIFs) in infected cells; however, the precise translation mechanism is still poorly understood. In this study, we have examined the mechanism of initiation and AUG selection in Sindbis virus (SINV) sgmRNA. Our present findings suggest that sgmRNA is translated via a scanning mechanism, since the presence of a hairpin structure before the initiation codon hampers protein synthesis directed by this mRNA. In addition, translation is partially recovered when an in-frame AUG codon is placed upstream of this hairpin. This scanning process takes place without the participation of eIF4A and active eIF2. These results, combined with our findings through modifying the SINV sgmRNA leader sequence, do not support the possibility of a direct initiation from the start codon without previous scanning, or a shunting mechanism. Moreover, studies carried out with sgmRNAs containing two alternative AUG codons within a good context for translation reveal differences in AUG selection which are dependent on the cellular context and the phosphorylation state of eIF2α. Thus, initiation at the additional AUG is strictly dependent on active eIF2, whereas the genuine AUG codon can start translation following eIF2α inactivation. Collectively, our results suggest that SINV sgmRNA is translated by a scanning mechanism without the potential participation of crucial eIFs. A model is presented that explains the mechanism of initiation of mRNAs bearing two alternative initiation codons.


Nursing's contribution to the literature on preterm labor and birth.
Although preterm labor and birth continues to plague us as an unsolved mystery in maternal/child health, much has actually been learned over the past few decades. Most reviews of the preterm labor literature examine the research in an interdisciplinary manner; this article instead looks at the active role that nurses have taken in the research concerning preterm labor and birth. This article will categorize research conducted by nurses over the past 30 years on preterm labor and birth, emphasizing some of the changes in nursing practice engendered by nursing's important research effort.


Cross-population selection signatures in Canchim composite beef cattle.
Analyses of livestock genomes have been used to detect selection signatures, which are genomic regions associated with traits under selection leading to a change in allele frequency. The objective of the present study was to characterize selection signatures in Canchim composite beef cattle using cross-population analyses with the founder Nelore and Charolais breeds. High-density single nucleotide polymorphism genotypes were available on 395 Canchim representing the target population, along with genotypes from 809 Nelore and 897 Charolais animals representing the reference populations. Most of the selection signatures were co-located with genes whose functions agree with the expectations of the breeding programs; these genes have previously been reported to associate with meat quality, as well as reproductive traits. Identified genes were related to immunity, adaptation, morphology, as well as behavior, could give new perspectives for understanding the genetic architecture of Canchim. Some selection signatures identified genes that were recently introduced in Canchim, such as the loci related to the polled trait.


Zinc-fortified oral rehydration solution improved intestinal permeability and small intestinal mucosal recovery.
A randomized double-blind placebo-controlled study was conducted in children admitted to hospital with gastroenteritis (≥3 loose stools per day). All were treated for 5 days following admission with either zinc (Zn, 3 mg) or without Zn-fortified rice-based oral rehydration solution (ORS). (13)C-sucrose breath test (SBT) and intestinal permeability (lactulose/rhamnose or L/R ratio) were performed concurrently prior to commencement of ORS with or without Zn and at day 5 post-admission. There was a significant improvement in the SBT results in both the Zn-fortified group, median (5th-95th percentile) 2.1% (0.4% to 8.3%) versus 4.4% (0.4% to 10.4%), P < .05, and control group, 1.4% (0.1% to 5.4%) versus 4.3% (0.4% to 11.4%), P < .05, between the day of admission and day 5 post-admission. In the Zn-fortified group, there was also a significant improvement in L/R ratio between the day of admission and day 5 post-admission, 53.0 (19.5-90.6) versus 17.7 (13.4-83.2), P < .05. Low levels of Zn improved intestinal permeability but did not enhance short-term recovery following diarrheal illness.


Vulvar lesions at risk. Prevention, clinical methodology and therapy.
In confronting the problem of prevention and early diagnosis of vulvar lesions at risk, the diagnostic methodology for their recognition and the therapeutic measures best taken are discussed. Through the use of routine, ambulatory screening tests, it is possible to detect and recognize those pathological situations which may evolve towards neoplasia. Among these, the vulvar dystrophies, some viral infections and sexually-transmitted diseases are particularly at risk. Patients with oncologic precedents are also at risk as well as patients receiving immunosuppressive therapy.


[Pregnancy in diabetic patients. A calculated risk].
In general, a diabetic woman may count upon delivering a healthy child--provided optimal antenatal care. Success or failure of pregnancy will in the individual case decisively depend on the experience and efforts of the attending physician. The directives for the care of pregnant diabetic women as practiced at the II. Univ.-Frauenklinik München are demonstrated.


Outcomes of Prediabetes Compared with Normoglycaemia and Diabetes Mellitus in Patients Undergoing Percutaneous Coronary Intervention: A Systematic Review and Meta-analysis.
Background: Patients with prediabetes are at increased risk of coronary artery disease (CAD). However, the association between prediabetes and adverse clinical outcomes following percutaneous coronary intervention (PCI) is inconsistent, in contrast to outcomes in patients with diabetes mellitus (DM). Thus, this meta-analysis evaluated the impact of dysglycaemia on PCI outcomes. Methods: The PubMed, Embase, Cochrane, and ClinicalTrials.gov databases were systematically reviewed from inception of databases until June 2022. In 17 studies, outcomes of PCI in patients with prediabetes were compared with patients who were normoglycaemic, and patients with DM. The primary outcome was all-cause mortality at the longest follow-up. Results: Included were 12 prospective and five retrospective studies, with 11,868, 14,894 and 13,536 patients undergoing PCI in the prediabetes, normoglycaemic and DM groups, respectively. Normoglycaemic patients had a statistically lower risk of all-cause mortality, (risk ratio [RR] 0.66, 95% confidence interval [CI] 0.52-0.84), myocardial infarction (MI; RR 0.76, 95% CI 0.61-0.95) and cardiac mortality (RR 0.58, 95% CI 0.39-0.87) compared with prediabetic patients undergoing PCI at the longest follow-up. Patients with prediabetes had a lower risk of all-cause mortality (RR=0.72 [95% CI 0.53-0.97]) and cardiac mortality (RR =0.47 [95% CI 0.23-0.93]) compared with patients with DM who underwent PCI. Conclusion: Among patients who underwent PCI for CAD, the risk of all-cause and cardiac mortality, major adverse cardiovascular events and MI in prediabetic patients was higher compared with normoglycaemic patients but lower compared with patients with DM.


Cryo-electron microscopy modeling by the molecular dynamics flexible fitting method.
The increasing power and popularity of cryo-electron microscopy (cryo-EM) in structural biology brought about the development of so-called hybrid methods, which permit the interpretation of cryo-EM density maps beyond their nominal resolution in terms of atomic models. The Cryo-EM Modeling Challenge 2010 is the first community effort to bring together developers of hybrid methods as well as cryo-EM experimentalists. Participating in the challenge, the molecular dynamics flexible fitting (MDFF) method was applied to a number of cryo-EM density maps. The results are described here with special emphasis on the use of symmetry-based restraints to improve the quality of atomic models derived from density maps of symmetric complexes; on a comparison of the stereochemical quality of atomic models resulting from different hybrid methods; and on application of MDFF to electron crystallography data.


Characterising recovery following abdominal aortic aneurysm repair using cardiopulmonary exercise testing and patient reported outcome measures.
Surgery is associated with a post-operative stress response, changes in cardiopulmonary reserve, and metabolic demand. Here recovery after abdominal aortic aneurysm repair is investigated using cardiopulmonary exercise testing and patient-reported questionnaires. Patients undergoing open (n = 21) or endovascular (n = 21) repair undertook cardiopulmonary exercise tests, activity, and health score questionnaires pre-operatively and, 8 and 16 weeks, post-operatively. Oxygen uptake and ventilatory parameters were measured, and routine blood tests were undertaken. Recovery was characterised by falls in anaerobic threshold, peak oxygen uptake, and oxygen pulse at 8 weeks which appeared to be associated with operative severity; the fall in peak oxygen uptake was greater following open vs. endovascular repair (3.5 vs. 1.6 ml.kg-1.min-1) and anaerobic threshold showed a similar tendency (3.1 vs. 1.7 ml.kg-1.min-1). In the smaller number of patients re-tested these changes resolved by 16 weeks. Reported health and activity did not change. Aortic repair is associated with falls in the anaerobic threshold, peak oxygen uptake, and oxygen pulse of a magnitude that reflects operative severity and appears to resolve by 16 weeks. Thus, post-operatively patients may be at higher risk of further metabolic insult e.g. infection. This further characterises physiological recovery from aortic surgery and may assist in defining post-operative shielding time.IMPLICATIONS FOR REHABILITATIONAbdominal aortic aneurysm repair is a life-saving operation, the outcome from which is influenced by pre-operative cardiopulmonary reserve; individuals with poor reserve being at greater risk of peri-operative complications and death. However, for this operation, the physiological impact of surgery has not been studied.In a relatively small sample, this study suggests that AAA repair is associated with a significant decline in cardiopulmonary reserve when measured 8 weeks post-operatively and appears to recover by 16 weeks. Moreover, the impact may be greater in endovascular vs. open repair.


Divergent Construction of Fully Substituted Pyrroles and Cyclopentadiene Derivatives by Ynamide Annulations: 1,2-Cyclopropyl Migration versus Proton Transfer.
A switchable cyclopropyl ynamide cyclization to construct fully substituted pyrroles and cyclopentadiene derivatives in the presence of a gold catalyst was developed. In this version of pyrrole generation, a novel method to furnish gold vinylidenes through [1,2]-cyclopropyl migration was described. On the contrary, the production of cyclopentadienes proceeded through a proton-transfer step. These intriguing mechanisms were proposed based on the structure identification of the alkynyl enamine intermediate and a crossover experiment. The feasibility of cyclobutyl ynamides to specifically construct cyclopentadienes through ring expansion was also investigated.


Can soil microbial diversity influence plant metabolites and life history traits of a rhizophagous insect? A demonstration in oilseed rape.
Interactions between plants and phytophagous insects play an important part in shaping the biochemical composition of plants. Reciprocally plant metabolites can influence major life history traits in these insects and largely contribute to their fitness. Plant rhizospheric microorganisms are an important biotic factor modulating plant metabolites and adaptation to stress. While plant-insects or plant-microorganisms interactions and their consequences on the plant metabolite signature are well-documented, the impact of soil microbial communities on plant defenses against phytophagous insects remains poorly known. In this study, we used oilseed rape (Brassica napus) and the cabbage root fly (Delia radicum) as biological models to tackle this question. Even though D. radicum is a belowground herbivore as a larva, its adult life history traits depend on aboveground signals. We therefore tested whether soil microbial diversity influenced emergence rate and fitness but also fly oviposition behavior, and tried to link possible effects to modifications in leaf and root metabolites. Through a removal-recolonization experiment, 3 soil microbial modalities ("high," "medium," "low") were established and assessed through amplicon sequencing of 16S and 18S ribosomal RNA genes. The "medium" modality in the rhizosphere significantly improved insect development traits. Plant-microorganism interactions were marginally associated to modulations of root metabolites profiles, which could partly explain these results. We highlighted the potential role of plant-microbial interaction in plant defenses against Delia radicum. Rhizospheric microbial communities must be taken into account when analyzing plant defenses against herbivores, being either below or aboveground.


Toxicity of trichlorotoluene isomers: a 28-day feeding study in the rat.
Groups of 10 male and 10 female rats were fed alpha,alpha,alpha-, alpha,2,6- or 2,3,6- trichlorotoluene (TCT) in their diet at 0, 0.5, 5.0, 50 or 500 ppm for 28 days. Growth rate and food consumption were not affected by treatment. No deaths occurred. Significant increases in liver weights were observed in male rats fed 5.0 and 500 ppm 2,3,6-TCT. Mild serum biochemical changes occurred in male rats. These included increased SDH activities in the groups fed 5.0 and 50 ppm alpha, alpha, alpha-TCT, and 5.0 ppm 2,3,6-TCT. Alpha, alpha, alpha-TCT at 500 ppm caused elevated LDH activities in male rats. Hepatic microsomal aminopyrine N-demethylase activities were increased in male rats fed 500 ppm alpha,2,6-TCT. Hematological parameters were not affected by treatment. Mild histological changes were seen in the liver, kidney and thyroid of treated rats. Data presented here suggest that alpha, alpha, alpha-, alpha,2,6- and 2,3,6-TCT possess a low order of oral toxicity in the rat.


[The antibiotic sensitivity of Corynebacterium diphtheriaе gravis tox+ in composition of mixed biofilms.]
The purpose of study is to determine sensibility of strains of C. diphtheriae gravis tox+ in the composition of mixed biofilms to antibacterial medications. The object of study was strains of Corynebacterium diphtheriae gravis tox+ № 665, Corynebacterium pseudodiphtheriticum (poly-resistant), Corynebacterium pseudodiphtheriticum (antibiotic-resistant). Two mixed biofilms (120- and 720-hours) of strain of Corynebacterium diphtheriae gravis tox+ № 665 with strains of Corynebacterium pseudodiphtheriticum (poly-resistant), Corynebacterium pseudodiphtheriticum (antibiotic-resistant) were formed. The sensibility of typical and biofilm cultures of Corynebacteria to antibiotic medications was established using technique of serial dilution in fluid growth medium on the basis of MPC (mg/l). The typical culture of museum strain C. diphtheriae gravis tox+ № 665, modeling mixed biofilms had a sensitivity to all used antibacterial medications. The analysis of antibiotic resistance of strain of C. diphtheriae gravis tox+ № 665 in content of biofilm with strain С. pseudodiphtheriticum, poly-resistant to four antibacterial medications (cefazolin, kanamycin, azithromycin, ciprofloxacin, IPC from 1.25±0,00 to >5±0,00 mkg/ml) set reduction (p≤0,05) sensitivity 120-hour biofilm cultures of this strain to cefazolin, azithromycin, ciprofloxacin (MIC of 0, 234 and up to ±0,11>5±0,00 ug / ml) established decreasing (p≤0,05) of sensitivity of 120-hours biofilm culture of this strain to cefazolin, azithromycin, ciprofloxacin (MIC from 0, 234±0,11 to >5±0,00 mkg/ml) and 720-hours culture - to all mentioned medications (MIC from 0,312±0,00 to >5±0,00 mkg/ml). The comparison of antibiotics resistance of biofilm cultures of strain C. diphtheriae gravis tox+ № 665 established that indices of MIC of most of antibacterial medications and especially to those that poly-resistant and forming biofilm strain С. рseudodiphtheriticum was resistant, were higher as related to biofilm cultures of diphtheritic bacteria separated from biofilm with antibiotic resistant strain С. рseudodiphtheriticum. The trend was established related to decreasing of antibiotic sensitivity of Corynebacteria at cultivation in content of mixed biofilms with representatives of opportunistic Corynebacteria having polyresistance to antibacterial medications.


Zerumbone induces gastric cancer cells apoptosis: Involving cyclophilin A.
Gastric cancer is one of the leading causes for cancer death. There is an urgent need to develop new therapeutic approaches targeting metastatic gastric cancer. It has been reported that zerumbone has the anti-cancer effects in various malignant cells. However, the effect and the mechanism of zerumbone on melanoma cells is still largely unknown. In the study, we determined the actions of zerumbone on the human gastric cancer cell line SGC-7901.We also observed the mechanism by which zerumbone induced gastric cancer cell apoptosis. Our data indicated that zerumbone significantly inhibited the growth of human gastric cancer cells in a dose-dependent manner and apoptosis was the main cause of decreased cell viability in zerumbone -treated cells. The treatment with zerumbone downregulated Cyp A and Bcl-2 levels, upregulated Bax levels, and caused Cytochrome c (Cyt-C) to release, activating Caspase-3. In summary, our study suggests that zerumbone mightinduced human gastric cancer cells apoptosis through down-regulating Cyp A and mitochondria-mediated pathways.


Stem Cell Properties of Gastric Cancer Stem-Like Cells under Stress Conditions Are Regulated via the c-Fos/UCH-L3/β-Catenin Axis.
Gastric cancer stem-like cells (GCSCs) possess stem cell properties, such as self-renewal and tumorigenicity, which are known to induce high chemoresistance and metastasis. These characteristics of GCSCs are further enhanced by autophagy, worsening the prognosis of patients. Currently, the mechanisms involved in the induction of stemness in GCSCs during autophagy remain unclear. In this study, we compared the cellular responses of GCSCs with those of gastric cancer intestinal cells (GCICs) whose stemness is not induced by autophagy. In response to glucose starvation, the levels of β-catenin and stemness-related genes were upregulated in GCSCs, while the levels of β-catenin declined in GCICs. The pattern of deubiquitinase ubiquitin C-terminal hydrolase-L3 (UCH-L3) expression in GCSCs and GCICs was similar to that of β-catenin expression depending on glucose deprivation. We also observed that inhibition of UCH-L3 activity reduced β-catenin protein levels. The interaction between UCH-L3 and β-catenin proteins was confirmed, and it reduced the ubiquitination of β-catenin. Our results suggest that UCH-L3 induces the stabilization of β-catenin, which is required to promote stemness during autophagy activation. Also, UCH-L3 expression was regulated by c-Fos, and the levels of c-Fos increased in response to autophagy activation. In summary, our findings suggest that the inhibition of UCH-L3 during nutrient deprivation could suppress stress resistance of GCSCs and increase the survival rates of gastric cancer patients.


Serial long-term phlebography after documented lower leg thrombosis.
Representative phlebograms from a series of 38 patients (86 phlebograms) followed up from 2 weeks to 6 years after the initial thrombotic episode are presented. The veins cleared earliest and most completely in patients with thrombosis, limited to the calf. Totally occluded veins cleared more slowly and less completely than non- or partially occluded veins. Post-thrombotic restoration of normal venous and valvular structures was commonly seen. The authors describe a phlebographic pattern which corresponds to previously documented pathological material, illustrating intimal thickening as a sequel to organization of thrombi onto the walls of the veins.


The Effects of Acute Neonatal Pain on Expression of Corticotropin-Releasing Hormone and Juvenile Anxiety in a Rodent Model.
Premature infants in the neonatal intensive care unit (NICU) may be subjected to numerous painful procedures without analgesics. One necessary, though acutely painful, procedure is the use of heel lances to monitor blood composition. The current study examined the acute effects of neonatal pain on maternal behavior as well as amygdalar and hypothalamic activation, and the long-term effects of neonatal pain on later-life anxiety-like behavior, using a rodent model. Neonatal manipulations consisted of either painful needle pricks or non-painful tactile stimulation in subjects' left plantar paw surface which occurred four times daily during the first week of life [postnatal day (PND)1-PND7]. Additionally, maternal behaviors in manipulated litters were compared against undisturbed litters via scoring of videotaped interactions to examine the long-term effects of pain on dam-pup interactions. Select subjects underwent neonatal brain collection (PND6) and fluorescent in situ hybridization (FISH) for corticotropin-releasing hormone (CRH) and the immediate early gene c-fos. Other subjects were raised to juvenile age (PND24 and PND25) and underwent innate anxiety testing utilizing an elevated plus maze (EPM) protocol. FISH indicated that neonatal pain influenced amygdalar CRH and c-fos expression, predominately in males. No significant increase in c-fos or CRH expression was observed in the hypothalamus. Additionally, neonatal pain altered anxiety behaviors independent of sex, with neonatal pain subjects showing the highest frequency of exploratory behavior. Neonatal manipulations did not alter maternal behaviors. Overall, neonatal pain drives CRH expression and produces behavioral changes in anxiety that persist until the juvenile stage.


Evaluation of PET Brain Radioligands for Imaging Pancreatic β-Cell Mass: Potential Utility of 11C-(+)-PHNO.
Type 1 diabetes mellitus (T1DM) is characterized by a loss of β-cells in the islets of Langerhans of the pancreas and subsequent deficient insulin secretion in response to hyperglycemia. Development of an in vivo test to measure β-cell mass (BCM) would greatly enhance the ability to track diabetes therapies. β-cells and neurologic tissues have common cellular receptors and transporters, therefore, we screened brain radioligands for their ability to identify β-cells. Methods: We examined a β-cell gene atlas for endocrine pancreas receptor targets and cross-referenced these targets with brain radioligands that were available at our institution. Twelve healthy control subjects and 2 T1DM subjects underwent dynamic PET/CT scans with 6 tracers. Results: The D2/D3 receptor agonist radioligand 11C-(+)-4-propyl-9-hydroxynaphthoxazine (PHNO) was the only radioligand to demonstrate sustained uptake in the pancreas with high contrast versus abdominal organs such as the kidneys, liver, and spleen, based on the first 30 min of data. Mean SUV from 20 to 30 min demonstrated high uptake of 11C-(+)-PHNO in healthy controls (SUV, 13.8) with a 71% reduction in a T1DM subject with undetectable levels of C-peptide (SUV, 4.0) and a 20% reduction in a T1DM subject with fasting C-peptide level of 0.38 ng/mL (SUV, 11.0). SUV in abdominal organs outside the pancreas did not show measurable differences between the control and T1DM subjects, suggesting that the changes in SUV of 11C-(+)-PHNO may be specific to changes in the pancreas between healthy controls and T1DM subjects. When D3 and D2 antagonists were used in nonhuman primates, specific pancreatic binding (SUVR-1) of 11C-PHNO was reduced by 57% and 38%, respectively. Conclusion:11C-(+)-PHNO is a potential marker of BCM, with 2:1 binding of D3 receptors over D2 receptors. Further in vitro and in vivo studies to establish D2/D3 receptor specificity to β-cells is warranted to characterize 11C-(+)-PHNO as a candidate for clinical measurement of BCM in healthy control and diabetic subjects.


Structure-activity relationships of the antimicrobial peptide arasin 1 - and mode of action studies of the N-terminal, proline-rich region.
Arasin 1 is a 37 amino acid long proline-rich antimicrobial peptide isolated from the spider crab, Hyas araneus. In this work the active region of arasin 1 was identified through structure-activity studies using different peptide fragments derived from the arasin 1 sequence. The pharmacophore was found to be located in the proline/arginine-rich NH(2) terminus of the peptide and the fragment arasin 1(1-23) was almost equally active to the full length peptide. Arasin 1 and its active fragment arasin 1(1-23) were shown to be non-toxic to human red blood cells and arasin 1(1-23) was able to bind chitin, a component of fungal cell walls and the crustacean shell. The mode of action of the fully active N-terminal arasin 1(1-23) was explored through killing kinetic and membrane permeabilization studies. At the minimal inhibitory concentration (MIC), arasin 1(1-23) was not bactericidal and had no membrane disruptive effect. In contrast, at concentrations of 5×MIC and above it was bactericidal and interfered with membrane integrity. We conclude that arasin 1(1-23) has a different mode of action than lytic peptides, like cecropin P1. Thus, we suggest a dual mode of action for arasin 1(1-23) involving membrane disruption at peptide concentrations above MIC, and an alternative mechanism of action, possibly involving intracellular targets, at MIC.


Three-dimensional echocardiography in adult congenital heart disease.
Congenital heart disease (CHD) is now more common in adults than in children due to improvements in fetal echo, neonatal and pediatric care, and surgical techniques leading to dramatically increased survivability into adulthood. Adult patients with CHD, regardless of prior cardiac surgery, experience further cardiac problems or therapeutic challenges; therefore, a non-invasive, easily accessible echocardiographic examination is an essential follow-up tool. Among echocardiographic modalities, three-dimensional (3D) echocardiography provides better delineation of spatial relationships in complex cardiac geometries and more accurate volumetric information without geometric assumptions. For atrial septal defects, an en face view of the tissue defect allows better decisions on device closure. For tricuspid valve malformations, an en face view provides diagnostic information that is difficult to obtain from routine 2D tomography. In repaired tetralogy of fallot with pulmonary regurgitation, preoperative 3D echocardiography- based right ventricular volume may be used to determine the timing of a pulmonary valve replacement in conjunction with cardiovascular magnetic imaging. For optimal adult CHD care, 3D echocardiography is an important complement to routine 2D echocardiography.


From paper to informatics: the Post Soft Care-App, an easy-to-use and fast tool to help therapists identify unmet needs in stroke patients.
Even after rehabilitation, post stroke patients remain disabled. The Post Stroke Checklist (PSC) was developed to highlight unmet needs of community-dwelling stroke patients. The present study set out to validate Post Soft Care-App, designed to administer the PSC using smartphones and tablets, in order to monitor unmet needs in chronic patients. Fifty-three patients and fifteen physiotherapists were enrolled. The therapists administered the PSC to patients using the app, and then completed a structured questionnaire on its usability and utility. The Post Soft Care-App highlighted the following unmet needs: increased spasticity (56.6%), reduced independence in activities of daily living (47.2%), reduced mobility (45.3%), absence of secondary prevention (45.3%). Therapists positively evaluated Post Soft Care-App as useful, practical, quick to complete (96.2%), and effective in helping improve communication with patients (75.5%). The Post Soft Care-App can be considered a valid assessment tool for helping therapists to monitor functional outcomes in chronic patients.


Epitope mapping of Ebola virus dominant and subdominant glycoprotein epitopes facilitates construction of an epitope-based DNA vaccine able to focus the antibody response in mice.
We performed epitope mapping studies on the major surface glycoprotein (GP) of Ebola virus (EBOV) using Chemically Linked Peptides on Scaffolds (CLIPS), which form linear and potential conformational epitopes. This method identified monoclonal antibody epitopes and predicted additional epitopes recognized by antibodies in polyclonal sera from animals experimentally vaccinated against or infected with EBOV. Using the information obtained along with structural modeling to predict epitope accessibility, we then constructed 2 DNA vaccines encoding immunodominant and subdominant epitopes predicted to be accessible on EBOV GP. Although a construct designed to produce a membrane-bound oligopeptide was poorly immunogenic, a construct generating a secreted oligopeptide elicited strong antibody responses in mice. When this construct was administered as a boost to a DNA vaccine expressing the complete EBOV GP gene, the resultant antibody response was focused largely toward the less immunodominant epitopes in the oligopeptide. Taken together, the results of this work suggest a utility for this method for immune focusing of antibody responses elicited by vaccination.


CD95-induced apoptosis contributes to loss of primed/memory but not resting/naive T cells in children infected with human immunodeficiency virus type 1.
Increased apoptosis of uninfected CD4+ T cells is involved in CD4+ T cell depletion in HIV-1+ individuals. Recently, a progressive loss of resting naive T cells has been shown during the asymptomatic stage of HIV infection in children and adults. The CD95 receptor/ligand system is a key regulator of T cell apoptosis. To elucidate the role of this system in the depletion of resting naive T cells, we studied expression of CD95 and sensitivity toward CD95-triggered apoptosis in T cell subsets defined by CD45 (leukocyte common antigen) isoforms and CD62L (lymphocyte homing receptor L-selectin) in a cohort of HIV-1+ children. In patients and healthy control subjects the level of CD95 expression increased from resting/naive (L-selectin(bright) CD45RA+) T cells to primed/memory (CD45RO+ CD45RA-) T cells. In HIV-1+ children the susceptibility of peripheral blood T cells for CD95-mediated apoptosis also increased with progressive differentiation toward primed/memory T cells. Resting/ naive T cells were resistant to spontaneous and anti-CD95-induced apoptosis. Loss of naive (CD45RA+ CD45RO-) T cells in HIV-1+ patients in vivo was found to be paralleled by an increase in the percentage of CD95high T cells as well as an increase in anti-CD95-induced apoptosis of CD4+ and CD8+ T cells. We conclude that loss of naive unprimed T cells during the asymptomatic phase of HIV-1 infection is caused by continuous generation of primed cells that exhibit increased sensitivity toward CD95-mediated apoptotic cell death in vitro.


A highly specific mechanism of histone H3-K4 recognition by histone demethylase LSD1.
Human lysine-specific demethylase (LSD1) is a chromatin-modifying enzyme that specifically removes methyl groups from mono- and dimethylated Lys4 of histone H3 (H3-K4). We used a combination of in vivo and in vitro experiments to characterize the substrate specificity and recognition by LSD1. Biochemical assays on histone peptides show that essentially all epigenetic modifications on the 21 N-terminal amino acids of histone H3 cause a significant reduction in enzymatic activity. Replacement of Lys4 with Arg greatly enhances binding affinity, and a histone peptide incorporating this mutation has a strong inhibitory power. Conversely, a peptide bearing a trimethylated Lys4 is only a weak inhibitor of the enzyme. Rapid kinetics measurements evidence that the enzyme is efficiently reoxidized by molecular oxygen with a second-order rate constant of 9.6x10(3) M-1 s-1, and that the presence of the reaction product does not greatly influence the rate of flavin reoxidation. In vivo experiments provide a correlation between the in vitro inhibitory properties of the tested peptides and their ability of affecting endogenous LSD1 activity. Our results show that epigenetic modifications on histone H3 need to be removed before Lys4 demethylation can efficiently occur. The complex formed by LSD1 with histone deacetylases 1/2 may function as a "double-blade razor" that first eliminates the acetyl groups from acetylated Lys residues and then removes the methyl group from Lys4. We suggest that after H3-K4 demethylation, LSD1 recruits the forthcoming chromatin remodelers leading to the introduction of gene repression marks.


23-gauge vitrectomy for retained lens material.
A technique for removal of retained lens material is described with a three-port 23-gauge vitrectomy system. Removal of the core vitreous is first performed, followed by removal of the cortical vitreous. All vitreous adhesions to the lens are cleared. The cut rate is then decreased to 1,500 cuts per minute, and vacuum increased to 600 mm Hg. The cortical lens material is cleared first, and then the nuclear material is taken with the same vitrectomy probe using the light pipe to assist in crushing the nuclear fragments. With this technique, even large dense nuclear and cortical retained lens material can be removed from the vitreous chamber without the need for a fragmatome.


Evidence for functional interactions between 5-HT1A and 5-HT2A receptors in rat thermoregulatory mechanisms.
The present study was designed to examine 1) functional interactions between 5-HT1A and 5-HT2A/C receptors in thermoregulation in rats and 2) the specific involvement of 5-HT2A and 5-HT2C receptors in such interactions. The 5-HT2A/C receptor agonist DOI (0.025 1.6 mg kg-1, subcutaneously) produced a dose-dependent hyperthermia in rats, which was enhanced by addition of either of two 5-HT1A receptor antagonists, (-)-pindolol (0.5-1.0 mg kg-1, subcutaneously) or WAY-100,635 (0.1-0.4 mg kg-1, subcutaneously). Furthermore, the DOI-induced hyperthermia was counteracted by pretreatment with the 5-HT1A receptor agonist 8-OH-DPAT (0.05 mg kg-1, subcutaneously). The hyperthermia produced by DOI, alone or in combination with WAY-100,635, was fully antagonized by pretreatment with the 5-HT2A/C receptor antagonist ritanserin (1.0 mg kg-1, subcutaneously), as well as with the selective 5-HT2A receptor antagonist amperozide (2.0 mg kg-1, subcutaneously). The present results provide evidence for functional interactions between 5-HT1A and 5-HT2A receptors in temperature regulation in rats, and also suggest an important role for postsynaptic 5-HT2A receptors in the mediation of DOI-induced hyperthermia.


Induction of differentiation in human promyelocytic HL-60 leukemia cells activates p21, WAF1/CIP1, expression in the absence of p53.
The melanoma differentiation associated gene, mda-6, which is identical to the P53-inducible gene WAF1/CIP1, encodes an M(r) 21,000 protein (p21) that can directly inhibit cell growth by repressing cyclin dependent kinases. mda-6 was identified using subtraction hybridization by virtue of its enhanced expression in human melanoma cells induced to terminally differentiate by treatment with human fibroblast interferon and the anti-leukemic compound mezerein (Jiang and Fisher, 1993). In the present study, we demonstrate that mda-6 (WAF1/CIP1) is an immediate early response gene induced during differentiation of the promyelocytic HL-60 leukemia cell line along the granulocytic or macrophage/monocyte pathway. mda-6 gene expression in HL-60 cells is induced within 1 to 3 h during differentiation along the macrophage/monocyte pathway evoked by 12-0-tetradecanoyl phorbol-13-acetate (TPA) or 1,25-dihydroxyvitamin D3 (Vit D3) or the granulocytic pathway produced by retinoic acid (RA) or dimethylsulfoxide (DMSO). Immunoprecipitation analyses using an anti-p21 antibody indicate a temporal induction of p21 protein following treatment with TPA, DMSO or RA. A relationship between rapid induction of mda-6 gene expression and differentiation is indicated by a delay in this expression in an HL-60 cell variant resistant to TPA-induced growth arrest and differentiation. A similar delay in mda-6 gene expression is not observed in Vit D3 treated TPA-resistant variant cells that are also sensitive to induction of monocytic differentiation. Since HL-60 cells have a null-p53 phenotype, these results demonstrate that p21 induction occurs during initiation of terminal differentiation in a p53-independent manner. In this context, p21 may play a more global role in growth control and differentiation than originally envisioned.


Is sexual ornamentation an honest signal of male quality in the Chinese grouse (Tetrastes sewerzowi)?
We examined the variation in sexual ornamentation of male Chinese grouse (Tetrastes sewerzowi) in the Gansu Province, China, seeking to identify factors involved in whether ornament size and brightness are honest signals of male quality. Compared to unmated males, mated males had significantly larger and redder combs and, although they did not have significantly larger territories, they defended them more vigorously. Mated males had significantly higher blood carotenoid and testosterone levels, significantly better body condition, and significantly lower parasite loads than unmated males. Our findings are thus consistent with the hypothesis that comb size and color are honest signals of better male quality in the grouse, mediated through lower parasite loads and/or higher testosterone levels.


Spouse abuse and alcohol problems among white, African American, and Hispanic U.S. Army soldiers.
Prior studies suggest racial/ethnic differences in the associations between alcohol misuse and spouse abuse. Some studies indicate that drinking patterns are a stronger predictor of spouse abuse for African Americans but not whites or Hispanics, while others report that drinking patterns are a stronger predictor for whites than African Americans or Hispanics. This study extends prior work by exploring associations between heavy drinking, alcohol-related problems, and risk for spouse abuse within racial/ethnic groups as well as variations associated with whether the perpetrator is drinking during the spouse abuse incident. Cases (N=7,996) were all active-duty male, enlisted Army spouse abusers identified in the Army's Central Registry (ACR) who had also completed an Army Health Risk Appraisal (HRA) Survey between 1991 and 1998. Controls (N=17,821) were matched on gender, rank, and marital and HRA status. We found 3 different patterns of association between alcohol use and domestic violence depending upon both the race/ethnicity of the perpetrator and whether or not alcohol was involved in the spouse abuse event. First, after adjusting for demographic and psychosocial factors, weekly heavy drinking (>14 drinks per week) and alcohol-related problems (yes to 2 or more of 6 alcohol-related problem questions, including the CAGE) were significant predictors of domestic violence among whites and Hispanics only. Also for the white soldiers, the presence of family problems mediated the effect of alcohol-related problems on spouse abuse. Second, alcohol-related problems predicted drinking during a spouse abuse incident for all 3 race groups, but this relation was moderated by typical alcohol consumption patterns in Hispanics and whites only. Finally, alcohol-related problems predicted drinking during a spouse abuse incident, but this was a complex association moderated by different psychosocial or behavioral variables within each race/ethnic group. These findings suggest important cultural/social influences that interact with drinking patterns.


Effects of hindlimb unloading and ionizing radiation on skeletal muscle resistance artery vasodilation and its relation to cancellous bone in mice.
Spaceflight has profound effects on vascular function as a result of weightlessness that may be further compounded by radiation exposure. The purpose of the present study was to assess the individual and combined effects of hindlimb unloading (HU) and radiation (Rad) on vasodilator responses in the skeletal muscle vasculature. Adult male C57BL/6J mice were randomized to one of four groups: control (Con), HU (tail suspension for 15 days), Rad (200 cGy of (137)Cs), and HU-Rad (15-day tail suspension and 200 cGy of (137)Cs). Endothelium-dependent vasodilation of gastrocnemius feed arteries was assessed in vitro using acetylcholine (ACh, 10(-9)-10(-4) M) and inhibitors of nitric oxide synthase (NOS) and cyclooxygenase (COX). Endothelium-independent vasodilation was assessed using Dea-NONOate (10(-9)-10(-4) M). Endothelium-dependent and -independent vasodilator responses were impaired relative to Con responses in all treatment groups; however, there was no further impairment from the combination of treatments (HU-Rad) relative to that in the HU and Rad groups. The NOS-mediated contribution to endothelium-dependent vasodilation was depressed with HU and Rad. This impairment in NOS signaling may have been partially compensated for by an enhancement of PGI2-mediated dilation. Changes in endothelium-dependent vasodilation were also associated with decrements in trabecular bone volume in the proximal tibia metaphysis. These data demonstrate that the simulated space environment (i.e., radiation exposure and unloading of muscle and bone) significantly impairs skeletal muscle artery vasodilation, mediated through endothelium-dependent reductions in NOS signaling and decrements in vascular smooth muscle cell responsiveness to NO.


A descriptive model for the kinetics of a homogeneous fluorometric immunoassay.
A descriptive mathematical model was chosen to fit the antigen-antibody association kinetics of a new homogeneous immunometric assay for prolactin, involving time-resolved fluorescence detection (TRACE technology, Time Resolved Amplified Cryptate Emission). We paid special attention to the methodology and criteria applied, to yield a convenient and statistically valid model, designed to allow potential exploitation of kinetic information in the data processing of the assay. We compared specific parameterizations of an hyperbolic model, the Gompertz, and the monomolecular models on the basis of morphological considerations, a statistical analysis of fit, and an assessment of the parameters estimation quality, over a wide range of antigen concentrations. The monomolecular model gave the best fit, and the most precise and stable estimation of its parameters. The study of parameter properties confirmed this choice.


Quantitative estimate of synaptic inputs to striatal neurons during up and down states in vitro.
Up states are prolonged membrane potential depolarizations critical for synaptic integration and action potential generation in cortical and striatal neurons. They commonly result from numerous concurrent synaptic inputs, whereas neurons reside in a down state when synaptic inputs are few. By quantifying the composition, frequency, and amplitude of synaptic inputs for both states, we provide important constraints for state transitions in striatal network dynamics. Up and down states occur naturally in cortex-striatum-substantia nigra cocultures, which were used as an in vitro model in the present study. Spontaneous synaptic inputs during down states were extracted automatically in spiny projection neurons and fast spiking interneurons of the striatum using a newly developed computer algorithm. Consistent with a heterogeneous population of synaptic inputs, PSPs and PSCs showed no correlation in amplitude and rise time and occurred at relatively low frequencies of 10-40 Hz during the down state. The number of synaptic inputs during up states, estimated from the up-state charge and the unitary charge of down-state PSCs, was 217 +/- 44. Given the average up-state duration of 284 +/- 34 msec, synaptic input frequency was approximately 800 Hz during up-states for both neuronal types. Many down-state events reversed at the chloride reversal potential and were blocked by GABA(A) antagonists. The high correlation between up- and down-state reversal potential suggests that despite these drastic changes in synaptic input frequency, the ratio of inhibitory to excitatory currents is similar during both states.


Association of MTNR1A and GDF9 gene allelles with the reproductive performance, response to oestrus induction treatments and prolificacy, in improved and non-improved local indigenous sheep breeds.
Sheep farming plays a crucial role for Mediterranean countries, wherefrom a plethora of dairy products is produced. Yet, numerous indigenous sheep breeds in temperate latitudes such as the Mediterranean present a serious drawback that milk production is impaired by the seasonality of reproduction. Towards the efforts for reduction of this phenomenon, the purpose of this study was to evaluate and compare different oestrus synchronization treatments, as well as to associate two genes alleles', namely the MTNR1A and the GDF9, with the response to those treatments. Three indigenous breeds were investigated (Florina, Chios and Karagouniko sheep) and inside each breed three different oestrus synchronization treatments were applied (A: intravaginal sponges, B: GNRH use and C: male effect). In group A, Florina ewes expressed oestrus at 90% in July and fecundity was 85%. Karagouniko and Chios ewes exhibited an oestrus expression of 100% with fecundity rates at 95% and 99%, respectively. In group B, Florina ewes expressed oestrus at 60% with fecundity at 57%, Karagouniko ewes expressed oestrus at 65% with fecundity at 54%, whereas Chios breed animals expressed oestrus at 87% with fecundity rate at 85%. In group C, 68% of the Florina breed expressed oestrus 20-25 days post ram induction, whereas this proportion was 84% and 94%, for Karagouniko and Chios breed, respectively. For the molecular analysis, partial segments of the two genes were sequenced and analysed, whereas alleles were scored based on the detected SNPs. All frequencies of the four detected SNPs in MTNR1A gene were statistically and significantly different in ewes that expressed oestrus in comparison with ewes that did not express oestrus in Florina and Karagouniko breeds concerning all treatments. Two SNP's were detected in GDF9 gene, G1 and FecG , from which, only the FecG mutation exhibited statistically significant difference in twins and triplets than in singles in Florina and Karagouniko breeds.


A computer-assisted population frequency study of 14 polymorphic blood grouping systems in North Carolina.
Results of a population frequency study conducted on 14 polymorphic blood grouping systems in the North Carolina white and black populations are reported. A microcomputer program has been developed to facilitate the handling and storage of the large volume of data generated during the two years it took to complete this study. This computer program was also designed to calculate the combined phenotypic frequency for a given set of blood types.


Activation of histamine type 2 receptors enhances intrinsic excitability of medium spiny neurons in the nucleus accumbens.
Histaminergic neurons are exclusively located in the hypothalamic tuberomammillary nucleus, from where they project to many brain areas including the nucleus accumbens (NAc), a brain area that integrates diverse monoaminergic inputs to coordinate motivated behaviours. While the NAc expresses various histamine receptor subtypes, the mechanisms by which histamine modulates NAc activity are still poorly understood. Using whole-cell patch-clamp recordings, we found that pharmacological activation of histamine 2 (H2) receptors elevates the excitability of NAc medium spiny neurons (MSNs), while activation of H1 receptors failed to significantly affect MSN excitability. The evoked firing of MSNs increased after seconds of local H2 agonist administration and remained elevated for minutes. H2 receptor (H2R) activation accelerated subthreshold depolarization in response to current injection, reduced the latency to fire, diminished action potential afterhyperpolarization and increased the action potential half-width. The increased excitability was protein kinase A-dependent and associated with decreased A-type K+ currents. In addition, selective pharmacological inhibition of the Kv4.2 channel, the main molecular determinant of A-type K+ currents in MSNs, mimicked and occluded the increased excitability induced by H2R activation. Our results indicate that histaminergic transmission in the NAc increases MSN intrinsic excitability through H2R-dependent modulation of Kv4.2 channels. Activation of H2R will significantly alter spike firing in MSNs in vivo, and this effect could be an important mechanism by which these receptors mediate certain aspects of goal-induced behaviours. KEY POINTS: Histamine is synthesized and released by hypothalamic neurons of the tuberomammillary nucleus and serves as a general modulator for whole-brain activity including the nucleus accumbens. Histamine receptors type 2 (HR2), which are expressed in the nucleus accumbens, couple to Gαs/off proteins which elevate cyclic adenosine monophosphate levels and activate protein kinase A. Whole-cell patch-clamp recordings revealed that H2R activation increased the evoked firing in medium spiny neurons of the nucleus accumbens via protein kinase A-dependent mechanisms. HR2 activation accelerated subthreshold depolarization in response to current injection, reduced the latency to fire, diminished action potential medium after-hyperpolarization and increased the action potential half-width. HR2 activation also reduced A-type potassium current. Selective pharmacological inhibition of the Kv4.2 channel mimicked and occluded the increased excitability induced by H2R activation.


Metastatic adenoid cystic carcinoma of lung: a case report.
A 48 year old male patient, operated five years back for sub mandibular swelling proved on histopathologic examination to be adenoid cystic carcinoma presented in the ENT department, I. G. medical hospital with pain on both sides of the chest. CT scan of the chest showed multiple lesions of variable sizes. CT guided FNAC as well as biopsy of the lung lesion was performed. Cytodiagnosis and histopathological examinations revealed features of cribiform type of adenoid cystic carcinoma. This case is reported here for its metastasis to the lungs and prolonged survival even with multiple metastasis.


Structure and receptor complexes of the hemagglutinin from a highly pathogenic H7N7 influenza virus.
Recurrence of highly pathogenic avian influenza (HPAI) virus subtype H7 in poultry continues to be a public health concern. In 2003, an HPAI H7N7 outbreak in The Netherlands infected 89 people in close contact with affected poultry and resulted in one fatal case. In previous studies, the virus isolated from this fatal case, A/Netherlands/219/2003 (NL219) caused a lethal infection in mouse models and had increased replication efficiency and a broader tissue distribution than nonlethal isolates from the same outbreak. A mutation which introduces a potential glycosylation site at Asn123 in the NL219 hemagglutinin was postulated to contribute to the pathogenic properties of this virus. To study this further, we have expressed the NL219 hemagglutinin in a baculovirus expression system and performed a structural analysis of the hemagglutinin in complex with avian and human receptor analogs. Glycan microarray and kinetic analysis were performed to compare the receptor binding profile of the wild-type recombinant NL219 HA to a variant with a threonine-to-alanine mutation at position 125, resulting in loss of the glycosylation site at Asn123. The results suggest that the additional glycosylation sequon increases binding affinity to avian-type α2-3-linked sialosides rather than switching to a human-like receptor specificity and highlight the mechanistic diversity of these pathogens, which calls attention to the need for further studies to fully understand the unique properties of these viruses.


[Cloning and expression analysis of lung carcinoma related gene HLCDG1].
High frequent loss of hetero- zygosity (LOH) of 3p, 5q, 6q, 9p, 10q, 11p, 13q, 17p, and 19p in lung carcinoma was detected by comparative genomic hybridization (CGH) and genomic-wide scan for analysis of genetic alteration with microsatellite allelotying. It was indicated that there might be some other unknown tumor susceptible genes or suppressor genes likely to be involved in lung carcinoma development and progression. The aim of this study was to clone the full-length cDNA of LXDD1,an expressed sequence tag(EST) isolated by mRNA differential display, which is significantly down-regulated in lung carcinoma and represents a novel gene. Differential expression of LXDD1 in lung carcinoma was confirmed by Northern blot analysis, the expression of the LXDD1 in human normal tissues and the size of the transcription of the LXDD1-representative gene were also determined using MTN (Multiple Tissues Northern Blots). The putative full-length cDNA of the EST-representative gene was cloned and analyzed by bioinformatics. In addition, differential reverse transcription polymerase chain reaction (RT-PCR) was used to detect the expression of the novel gene in various cancer cell lines, primary lung carcinomas, and matched normal lung tissues. The full length cDNA with no homology to any reported genes in the database of GenBank was successfully cloned and named HLCDG1 (Human lung carcinoma deleted gene 1, GenBank accession number AF447582). A transmembrane protein with 166 amino acids was deduced to come from the open reading frame of the 3113 bp full-length cDNA, HLCDG1 gene was confirmed to be located at chromosome band 5q33 by alignment of electric polymerase chain reaction (e-PCR). HLCDG1 is a novel gene down-regulated in lung carcinoma, which may be involved in the development of lung carcinoma.


Postinhibitory rebound delay and weak synchronization in Hodgkin-Huxley neuronal networks.
Noise-induced weak synchronized oscillatory activities in a globally inhibitory coupled Hodgkin-Huxley neuronal network are studied numerically. A kind of intrinsic delay induced by the postinhibitory rebound is observed and is found to be important in determining the overall frequency of the network. Synchronization occurs in an optimal range of noise intensity with a bell-shaped curve when the inhibitory coupling strength is sufficiently strong. Comparisons with the results for the excitatory coupling are also addressed.


A novel flow cytometry procoagulant assay for diagnosis of vaccine-induced immune thrombotic thrombocytopenia.
Vaccine-induced immune thrombotic thrombocytopenia (VITT) is a severe prothrombotic complication of adenoviral vaccines, including the ChAdOx1 nCoV-19 (Vaxzevria) vaccine. The putative mechanism involves formation of pathological anti-platelet factor 4 (PF4) antibodies that activate platelets via the low-affinity immunoglobulin G receptor FcγRIIa to drive thrombosis and thrombocytopenia. Functional assays are important for VITT diagnosis, as not all detectable anti-PF4 antibodies are pathogenic, and immunoassays have varying sensitivity. Combination of ligand binding of G protein-coupled receptors (protease-activated receptor-1) and immunoreceptor tyrosine-based activation motif-linked receptors (FcγRIIa) synergistically induce procoagulant platelet formation, which supports thrombin generation. Here, we describe a flow cytometry-based procoagulant platelet assay using cell death marker GSAO and P-selectin to diagnose VITT by exposing donor whole blood to patient plasma in the presence of a protease-activated receptor-1 agonist. Consecutive patients triaged for confirmatory functional VITT testing after screening using PF4/heparin ELISA were evaluated. In a development cohort of 47 patients with suspected VITT, plasma from ELISA-positive patients (n = 23), but not healthy donors (n = 32) or individuals exposed to the ChAdOx1 nCov-19 vaccine without VITT (n = 24), significantly increased the procoagulant platelet response. In a validation cohort of 99 VITT patients identified according to clinicopathologic adjudication, procoagulant flow cytometry identified 93% of VITT cases, including ELISA-negative and serotonin release assay-negative patients. The in vitro effect of intravenous immunoglobulin (IVIg) and fondaparinux trended with the clinical response seen in patients. Induction of FcγRIIa-dependent procoagulant response by patient plasma, suppressible by heparin and IVIg, is highly indicative of VITT, resulting in a sensitive and specific assay that has been adopted as part of a national diagnostic algorithm to identify vaccinated patients with platelet-activating antibodies.


Use of automobile restraining devices for infants.
Use of crash-tested and approved restraining devices for infants was studied in relationship to parents' locus of control, knowledge scores, and demographic data. Of 66 mothers who provided complete data, 19 (29 percent) owned and made proper use of the devices. Thirty-four mothers (52 percent) owned devices but did not use them properly.


A regular subunit pattern seen on non-infectious Newcastle disease virus particles.
A pseudo-crystalline array of subunits has been observed on particles of the La Sota, in contrast to the Ulster , strain of Newcastle disease virus (NDV) grown in MDBK tissue culture without trypsin. This regular arrangement of subunits was associated with the semi-permissive nature of the tissue culture system, as it disappeared when trypsin, which allows infectious virus to be made, was added. The phenomenon described was considered to be related to the crystalline array of matrix protein which has been described inside the envelope of Sendai virus and NDV by others.


Exogenous β-mannanase improves feed conversion efficiency and reduces somatic cell count in dairy cattle.
Exogenous fibrolytic enzymes have been shown to be a promising way to improve feed conversion efficiency (FCE). β-Mannanase is an important enzyme digesting the polysaccharide β-mannan in hemicellulose. Supplementation of diets with β-mannanase to improve FCE has been more extensively studied in nonruminants than in ruminants. The objective of this study was to investigate the effects of β-mannanase supplementation on nutrient digestibility, FCE, and nitrogen utilization in lactating Holstein dairy cows. Twelve post-peak-lactation multiparous Holstein cows producing 45.5±6.6kg/d of milk at 116±19.0d in milk were randomly allotted to 1 of 3 treatments in a 3×3 Latin square design with 3 periods of 18d (15d for adaptation plus 3d for sample collection). All cows were fed the same basal diet and the 3 treatments differed only by the β-mannanase dose: 0% dry matter (DM; control), 0.1% of DM (low supplement, LS), and 0.2% of DM (high supplement, HS) supplemented to the basal diet. Supplementation of β-mannanase enzyme at the LS dose reduced dry matter intake (DMI) but did not affect milk yield or milk composition. Cows receiving LS produced 90g more milk per kg of DMI compared with control cows. Somatic cell count (SCC) in milk was lower for cows fed the LS diet compared with cows fed control diets. Cows fed LS diet had lower DM, organic matter and crude protein digestibility compared with cows fed control diets. Starch, neutral detergent fiber, and acid detergent fiber digestibility were not affected by LS. Milk yield, DMI, SCC, and nutrient digestibility did not change for HS. Despite the reduced crude protein digestibility, reduced N intake led to similar fecal N excretions in LS cows and control cows (234 vs. 235g/cow per day). Urinary N excretions remained similar between enzyme-fed and control cows (~190g/cow per day), although the percentage of N intake partitioned to urinary N tended to be greater in LS than in control cows (31 vs. 27%). Cows fed LS significantly improved the percentage of apparently absorbed N partitioned to milk protein N (42 vs. 38%). When supplemented at 0.1% of dietary DM, β-mannanase can improve FCE and lower the SCC of dairy cows without affecting milk yield, milk composition, or total manure N excretions of dairy cows.


Modification of protocol with one extra drop of endovascular cyanoacrylate improved closure rates in incompetent great saphenous veins.
Great saphenous vein diameter (GSV) of >8 mm was predictor of recanalization following Venaseal cyanoacrylate treatment. The aim of this study was to report our modified protocol with a single extra-drop for treatment for GSV>8 mm, and comparative duplex results in closure rates. Patients in our single-centre registry treated with Venaseal were followed up by serial duplex examinations at week 1 and month(s)- 1, 6, 12, 18, 24, and then annually. The primary endpoint was successful obliteration of the GSV, secondary endpoints were closure distance from Saphenofemoral junction (SFJ), presence of endovenous glue-induced thrombosis (EGIT) or deep vein thrombosis. A total of 243 legs in 123 consecutive patients with duplex-proven SFJ/GSV incompetence were included in this study between September 2014 and October 2020. The median duplex follow-up period of this cohort of patients was 24 (range 0.2-58) months. Comparing closure rates in GSV diameter ≥8 mm treated with normal protocol, the 'extra-drop protocol' significantly improved closure rates (p = .034). However, the closure rates of ≥8 mm GSV treated with 'extra-drop protocol' was still not as good as GSV <8 mm (p < .001). There were no statistically significant differences in the stump distance between the three groups and no difference in the occurrence of EGIT. There were no deep vein thrombosis. Our experience showed that VenaSeal cyanoacrylate worked best in GSV<8 mm diameter. Even in GSV diameter of ≥8 mm which has a higher recanalization rate on follow-up duplex, our modified extra-drop protocol significantly improved the closure rates, and did not predispose to development of EGIT.


Formation of bioinorganic complexes by the corrosive adsorption of (S)-proline on Ni/Au(111).
Nickel nanoparticles modified by the adsorption of chiral amino acids are known to be effective enantioselective heterogeneous catalysts. The leaching of nickel by amino acids has a number of potential effects including the induction of chirality in the nickel atoms left behind in the nanoparticle and the creation of catalytically active nickel complexes. The adsorption of (S)-proline onto Au(111) precovered by two-dimensional nickel nanoclusters was investigated by scanning tunneling microscopy, X-ray photoelectron spectroscopy, and high-resolution electron energy loss spectroscopy. Adsorption of (S)-proline at 300 K resulted in the corrosion of the nickel clusters, the oxidation of the leached nickel, and the on-surface formation of bioinorganic complexes, which are concluded to contain three prolinate species in an octahedral arrangement around the central Ni ion. Two distinguishable forms of nickel prolinate complexes were identified. One form self-assembles into 1-D chains, and the other form gives rise to porous 2-D islands. Octahedral complexes of the type M(AB)3 are intrinsically chiral, resulting in two pairs of enantiomers. The mirror symmetry of each pair of enantiomers is broken when, as in this study, the bidentate ligand itself possesses a chiral center. DFT calculations are used to examine the relative energies of each Ni(prolinate)3 complex as isolated gas phase species and isolated adsorbed species.


Experimental and clinical effects of isradipine relevant to atherosclerosis.
A number of studies in experimental animal models have demonstrated the potential direct antiatherosclerotic effects of calcium antagonists. This class of compounds can influence several processes that are involved in the development of atherosclerotic lesions. This action is independent of either blood pressure reduction or hypercholesterolemia. A major problem encountered from the experimental data are the high doses used, which are several times higher than those used in the treatment of humans. One notable exception to this problem is the second-generation calcium antagonist isradipine, which exerts a direct antiatherosclerotic effect in rabbits at doses similar to those used in the clinic. Thus, this review is a summary of the effects and mechanisms of the antiatherosclerotic activity of isradipine.


Nonconvulsive Status Epilepticus: A Review for Emergency Clinicians.
Status epilepticus is associated with significant morbidity and mortality and is divided into convulsive status epilepticus and nonconvulsive status epilepticus (NCSE). This review provides a focused evaluation of NCSE for emergency clinicians. NCSE is a form of status epilepticus presenting with prolonged seizure activity. This disease is underdiagnosed, as it presents with nonspecific signs and symptoms, most commonly change in mental status without overt convulsive motor activity. Causes include epilepsy, cerebral pathology or injury, any systemic insult such as infection, and drugs or toxins. Mortality is primarily related to the underlying condition. Patients most commonly present with altered mental status, but other signs and symptoms include abnormal ocular movements and automatisms such as lip smacking or subtle motor twitches in the face or extremities. The diagnosis is divided into electrographic and electroclinical, and although electroencephalogram (EEG) is recommended for definitive diagnosis, emergency clinicians should consider this disease in patients with prolonged postictal state after a seizure with no improvement in mental status, altered mental status with acute cerebral pathology (e.g., stroke, hypoxic brain injury), and unexplained altered mental status. Assessment includes laboratory evaluation and neuroimaging with EEG. Management includes treating life-threatening conditions, including compromise of the airway, hypoglycemia, hyponatremia, and hypo- or hyperthermia, followed by rapid cessation of the seizure activity with benzodiazepines and other antiseizure medications. An understanding of the presentation and management of NCSE can assist emergency clinicians in the care of these patients.