Type 1 cannabinoid receptor modulates water deprivation-induced homeostatic responses.
The present study investigated the type 1 cannabinoid receptor (CB1R) as a potential candidate to mediate the homeostatic responses triggered by 24 h of water deprivation, which constitutes primarily a hydroelectrolytic challenge and also significantly impacts energy homeostasis. The present results demonstrated for the first time that CB1R mRNA expression is increased in the hypothalamus of water-deprived (WD) rats. Furthermore, the administration of ACEA, a CB1R selective agonist, potentiated WD-induced dipsogenic effect, whereas AM251, a CB1R antagonist, attenuated not only water but also salt intake in response to WD. In parallel with the modulation of thirst and salt appetite, we confirmed that CB1Rs are essential for the development of appropriated neuroendocrine responses. Although the administration of ACEA or AM251 did not produce any effects on WD-induced arginine vasopressin (AVP) secretion, oxytocin (OXT) plasma concentrations were significantly decreased in WD rats treated with ACEA. At the genomic level, ACEA significantly decreased AVP and OXT mRNA expression in the hypothalamus of WD rats, whereas AM251 potentiated both basal and WD-induced stimulatory effects on the transcription of AVP and OXT genes. In addition, we showed that water deprivation alone upregulated proopiomelanocortin, Agouti-related peptide, melanin-concentrating hormone, and orexin A mRNA levels in the hypothalamus, and that CB1Rs regulate main central peptidergic pathways controlling food intake, being that most of these effects were also significantly influenced by the hydration status. In conclusion, the present study demonstrated that CB1Rs participate in the homeostatic responses regulating fluid balance and energy homeostasis during water deprivation.


Reversible granulocyte killing defect in anorexia nervosa.
Three patients are described with anorexia nervosa in whom malnutrition was present with neutropenia and a granulocyte bactericidal degect. Their peripheral blood granulocytes were found to have a reduced rate of killing of Staphylococcus aureus and E. coli in vitro. The opsonic activity of the patients' sera towards Staphylococcus aureus was normal. One of these patients had recurrent episodes of infection which stopped after she had gained 13 kg in weight. Clinical recovery was associated with a return of granulocyte function to normal. It is concluded that granulocyte bactericidal capacity towards a variety of bacteria may be reduced in patients with anorexia nervosa who have malnutrition. This type of acquired granulocyte bactericidal deficiency appears to be reversible.


Pancreas divisum: analysis and therapeutic alternatives with a case report.
Pancreas divisum is a relatively common pancreatic duct anatomic variant, firstly described in the 17th century. We reported a 2-year-old child admitted to the Pediatric Clinic with breathing difficulties and abdominal pains. Examination and X-ray image, showed a vast right hydrothorax containing rusty coloured solution with a high degree of amylase. Ultrasound and computed tomography examination revealed pancreatic polycyclic pseudocysts; following magnetic resonance cholangiopancreatography (MRCP), the diagnosis of pancreas divisum was confirmed. The general condition of the patient worsened, requiring an urgent operation. External drainage of the perforated pancreatic pseudocyst was performed. Following external fistula maturation, a change from external to internal drainage was performed using Roux-en-Y fistulojejunostomy. A 3-year postoperative period was uneventful. Pancreas divisum cases are unique requiring clinical experience, rational approach, and complex multimodal management. MRCP is a valuable diagnostic method. Amongst therapeutic options, outer and internal drainage can be seen as reliable methods. Further investigations are absolutely required to determine practical and appropriate conclusions.


[An autophagic mechanism study on effect of electroacupuncture at different times pretreating myocardial ischemia-reperfusion injury].
To investigate the difference of protective effect of electroacupuncture (EA) at different times pretreating myocardial ischemia-reperfusion injury (MIRI) and the protein expressions of ULK1 and Beclin-1 in myocardial tissue, so as to explore the relation of the difference and autophagic mechanism. Sixty-three male SD rats were randomized into 7 groups, a sham group, a model group, an EA pretreating for 1 d (EA-1d) group, an EA pretreating for 2 d (EA-2d) group, an EA pretreating for 3 d (EA-3d) group, an EA pretreating for 4 d (EA-4d) group, an EA pretreating for 5 d (EA-5d) group, 9 rats in each group. All the rats in the pretreating groups were treated with EA 1-5 days before MIRI surgery. EA (2 Hz/100 Hz, 2 mA) was used at bilateral "Neiguan (PC 6)" for 20 min. All the rats except for those in the sham group was underwent left thoracotomy and ligation of the left anterior descending (LAD) coronary artery for 30 minutes followed by 4 hours of reperfusion to establish the MIRI model. The same operation was performed in the sham group except for the ligation of the LAD. Throughout the experiment, electrocardiogram was continuously monitored. The myocardial infarct sizes were assessed by Evans blue and triphenyltetrazolium chloride (TTC) staining. The serum concentrations of cardiac troponinⅠ(cTnⅠ) was detected by ELISA. The expressions of ULK1 and Beclin-1 in the heart tissues were analyze by Western blot. Compared with the sham group, the concentrations of cTnⅠ and the protein expressions of ULK1 and Beclin-1 increased in the model group (all P<0.05). Compared with the model group, the infarct sizes decreased in the EA-1d, EA-2d, EA-3d, EA-4d and EA-5d groups (all P<0.05), with less risk sizes in the EA-3d, EA-4d and EA-5d groups (all P<0.05). The levels of cTnⅠin the EA-4d and EA-5d groups decreased ( both P<0.05); the expressions of ULK1 protein decreased in the EA-1d, EA-2d, EA-3d, EA-4d and EA-5d groups (all P<0.05); the expressions of Beclin-1 protein decreased in the EA-2d, EA-3d, EA-4d and EA-5d groups (all P<0.05). The infarct sizes in the EA-4d and EA-5d groups were lower than that in the EA-1d group (both P<0.05). The cTnⅠconcentration in the EA-4d group was less than that in the EA-1d group (P<0.05). Pretreatment with EA for 1-5 days can improve the infarct size in MIRI, with better effect of the pretreatment for 4-5 days. The cardioprotective effect may be related to the inhibition of autophagy. But the difference of the protective effects is not related to the protein expressions of ULK1 and Beclin-1.


The growing impact of air quality on lung-related illness: a narrative review.
Poor air quality can be harmful to human well-being. There are a variety of respiratory disorders associated with toxins present within the atmosphere, such as bronchitis and asthma, which eventually lead to heart or lung complications over time. Fine particles like particulate matter 2.5 (PM2.5) accumulate in the small airways of the lung. These irritants can cause epigenetic modifications in gene regulation, leading to changes responsible for both benign and malignant lung diseases. In this review we will discuss known associations between environmental factors and pulmonary complications, consider preventative measures and offer further areas for future investigation. This review presents a summary of the literature outlining the current work done on air quality and its effects on lung-related illnesses. We discuss regional differences in air quality and consider the causes, such as manufacturing, traffic density, increase in fuel usage and natural events. We further explore disparities based on geography, race, and other social determinants. A comprehensive literature review was performed using keywords related to air quality, pollution and lung disease within the PubMed database as well as MEDLINE and Google Scholar. The Clean Air Act of 1970 marked an essential transition for air quality improvement. The legislation led to decreased emissions and control measures to address atmosphere contamination. Despite these actions, poor atmospheric conditions still persist today and have become an ongoing issue. These poor conditions affect individuals living in metropolitan areas more significantly than suburban or rural areas. Pollution from industrial operations and transportation vehicles have led to increased emission outputs recently. Climate change further aggravates air quality problems by raising pollutant and allergen concentrations. The detrimental consequences of poor air quality include increased incidence of disease processes like asthma, chronic obstructive pulmonary disease (COPD) and lung cancer. To keep up with the well-being of people globally, it is important that actions be taken to battle contamination in the climate so its impact on public health can be limited. Poor air quality and recent worsening of industrial emissions have had a negative impact on lung-related illnesses. Future mitigation strategies should be taken to reduce pollution and treat diseases earlier in their course. Some of these strategies include more reliance on alternative energy sources, creation of mass transit systems and increased rates of recycling.


Oral administration of Kaempferia parviflora did not disturb male reproduction in rats.
To investigate the androgenic effect of Kaempferia parviflora (KP), a Thai herbal plant, adult male rats were randomized into control and KP-treatment groups. Rats were treated orally with water in the control group and with 1,000 mg/kg/day of KP in the treatment group for 45 days. Blood samples were collected on days 10, 20, 30 and 45 for measurement of the serum follicle stimulating hormone (FSH), luteinizing hormone (LH), testosterone, progesterone and corticosterone levels. The reproductive and non-reproductive organs were dissected on day 45 and weighed. Mating behavior was also observed on days 20 and 30. Body weight was measured throughout the study period. The results showed that KP induced an increase in body weight compared with the controls. There were no significant differences in the weights of either reproductive (testis, seminal vesicle plus coagulating gland, levator ani muscle plus bulbocarvernosus muscle and glans penis, except the prostate gland) or non-reproductive organs (kidney, adrenal gland and gastracnemius muscle). There were no significant differences in serum levels of either FSH or LH between the two groups. The serum testosterone and progesterone levels were insignificantly lower in the KP group during the first 30 days. The serum corticosterone levels in the KP group were lower than those in the controls throughout the study period and were significantly low on days 20 and 30. There were no significant changes in mating behavior in the rats treated with KP. Although KP affected the body weight and serum corticosterone level, it did not affect mating behavior, reproductive and non-reproductive organ weights or hormones related to the reproductive system in the adult male rats. Therefore, we conclude that the testosterone-like effect of KP did not disturb the hypothalamic-pituitary-testicular axis or male reproduction.


Procollagen type I N-terminal propeptide (PINP) is a marker for fibrogenesis in bile duct ligation-induced fibrosis in rats.
Fibrosis can be described as the excess deposition of extracellular matrix (ECM) components, such as collagens and proteoglycans. Fibrosis of the liver, which eventually leads to cirrhosis, is a major global health problem. Being able to measure fibrosis progression may enable timely preventative intervention. The aim of the current study was to investigate the utility of serum procollagen type I N-terminal propeptide (PINP) as a marker of hepatic fibrosis, as distinct from bone formation, during three different periods of fibrosis development following hepatic injury induced by bile duct ligation (BDL) in rats. BDL was performed on 30 female Sprague-Dawley rats aged 6 months, and sham operations on 30 controls. Animals were killed after 14, 28, or 35 days. The extent of liver fibrosis was evaluated by quantitative histology after Sirus Red staining. Levels of serum PINP and osteocalcin (a marker solely for osteoblastic bone formation) were determined using ELISA at baseline and post termination. Collagen formation increased by 30% compared to 3% in sham-operated animals (P < 0.0001). PINP levels increased significantly in all BDL groups compared with baseline (14 days: baseline 13.9 ng/ml, termination 17.7 ng/ml, P = 0.047; 28 days: baseline 17.9 ng/ml, termination 26.2 ng/ml, P = 0.005; 35 days: baseline 18.0 ng/ml, termination 27.4 ng/ml P = 0.015, an increase of 52%). PINP levels did not change from baseline in the sham-operated rats, indicating that the increased PINP levels were due to hepatic injury. The bone-specific marker, osteocalcin, did not increase in either BDL or sham-operated rats. PINP measured in serum correlated to the extent of liver fibrosis as evaluated by quantitative histology (R2 = 0.42, P < 0.001). PINP was associated with the development of liver fibrosis, but not bone formation, in mature rats subjected to BDL. Thus, PINP may be useful in studying the pathogenesis of liver fibrosis. However, caution should be applied when interpreting PINP levels in other disease states.


Novel High-Temperature-Resistant Phosphates: Thermal Ablation Behavior of La-Al System Phosphates at 2000 °C.
The saturation-free and directionless cross-linking and interpenetration processes between La3+ and [(H2PO4)2Al(HPO4)]-plasma in La-Al phosphate by mixing Al(OH)3, CrO3, and H2O2 dissolved in H3PO4 and La2O3 as a curing accelerator, as well as the thermal stability of the La-Al phosphate bulk materials and the evolutions of the phase composition and morphology at different temperatures were studied using thermogravimetric/differential scanning calorimetry under different temperatures in a muffle furnace. The La-Al phosphates showed good thermal stability, and the thermal weight loss rate of the materials decreased from 18% before heat treatment to ∼2% after heat treatment. In addition, the La-Al phosphate bulk material showed excellent resistance to ablation when subjected to ablation by an oxyacetylene flame at 2000 °C for 30 s. It evolved into a dense LaPO4 and AlPO4 high-temperature phase layer on the sample surface, which prevented further ablation damage to the sample and significantly improved the temperature resistance of the La-Al phosphate bulk material.


Effects of Sublethal Doses of Imidacloprid on Young Adult Honeybee Behaviour.
Imidacloprid (IMI), a neonicotinoid used for its high selective toxicity to insects, is one of the most commonly used pesticides. However, its effect on beneficial insects such as the honeybee Apis mellifera L is still controversial. As young adult workers perform in-hive duties that are crucial for colony maintenance and survival, we aimed to assess the effect of sublethal IMI doses on honeybee behaviour during this period. Also, because this insecticide acts as a cholinergic-nicotinic agonist and these pathways take part in insect learning and memory processes; we used IMI to assess their role and the changes they suffer along early adulthood. We focused on appetitive behaviours based on the proboscis extension response. Laboratory reared adults of 2 to 10 days of age were exposed to sublethal IMI doses (0.25 or 0.50ng) administered orally or topically prior to behavioural assessment. Modification of gustatory responsiveness and impairment of learning and memory were found as a result of IMI exposure. These outcomes differed depending on age of evaluation, type of exposure and IMI dose, being the youngest bees more sensitive and the highest oral dose more toxic. Altogether, these results imply that IMI administered at levels found in agroecosystems can reduce sensitivity to reward and impair associative learning in young honeybees. Therefore, once a nectar inflow with IMI traces is distributed within the hive, it could impair in-door duties with negative consequences on colony performance.


[Surgical treatment of coronary circulation disorders].
The objectives of aorto-coronary bypass surgery are threefold: relief of angina pectoris, increase in exercise performance and prolongation of life. The effect of surgery on ischemic pain and exercise tolerance is widely accepted, but the influence of bypass grafting on life expectancy is still controversial. Recent results of prospective randomized trials, however, have shown significantly better survival for surgically treated patients with specific anatomic characteristics such as left main disease and three-vessel disease. Among the operative risks, hospital mortality (1% in our experience) and incidence of perioperative myocardial infarction (around 5%, usually asymptomatic clinical course) have decreased with growing surgical practice and application of cold cardioplegia. Postoperative angiographic studies reveal 85% to 90% graft patency rate at one year; later the mean annual occlusion rate is reported to be less than 3%. The aorto-coronary bypass operation is indicated mainly for the following two groups of patients: 1. those in whom angina or drug therapy results in a restriction of working capacity or an undesirable change in lifestyle despite appropriate medical treatment; 2. the two subsets of patients being exposed to a particularly high risk of myocardial infarction or sudden death: patients with left main disease and patients with three-vessel disease. The benefits of coronary bypass surgery depend on several conditions: major determinants are completeness of revascularization, suitability of distal coronary segments for bypass grafting, and degree of ventricular impairment.


Hydrogen-bond vibrational and energetic dynamical properties in sI and sII clathrate hydrates and in ice Ih: Molecular dynamics insights.
Equilibrium molecular dynamics (MD) simulations have been performed on cubic (sI and sII) polymorphs of methane hydrate, and hexagonal ice (ice Ih), to study the dynamical properties of hydrogen-bond vibrations and hydrogen-bond self-energy. It was found that hydrogen-bond energies are greatest in magnitude in sI hydrates, followed by sII, and their energies are least in magnitude in ice Ih. This is consistent with recent MD-based findings on thermal conductivities for these various materials [N. J. English and J. S. Tse, Phys. Rev. Lett. 103, 015901 (2009)], in which the lower thermal conductivity of sI methane hydrate was rationalised in terms of more strained hydrogen-bond arrangements. Further, modes for vibration and energy-transfer via hydrogen bonds in sI hydrate were found to occur at higher frequencies vis-à-vis ice Ih and sII hydrate in both the water-librational and OH⋯H regions because of the more strained nature of hydrogen bonds therein.


[Hepatocyte growth factor (HGF) and atherosclerosis].
Hepatocyte growth factor (HGF) takes part in tissue regeneration after injury. It is a potent survival and regeneration factor after severe tissue damage. It promotes cell growth and protection from apoptosis, regulates the cell migration and differentiation. HGF is a subject of intensive investigations in order to apply it in the future in gene therapy to improve treatment of angina pectoris or intermittent claudication. The aim of this review is discussion about the role of HGF in pathogenesis and treatment of atherosclerosis. Angiogenetic activity of HGF was proven in vivo as well as in vitro. In patients with collaterals increased HGF plasma concentration was revealed. It is possible to determine with high probability the risk of cardiovascular event on the basis of HGF concentration. Plasma concentration of this factor increases dramatically after heparin injection, particularly after unfractionated heparin. Also other drugs (ACE-inhibitors) may take part in regulation of HGF synthesis.


Direct monitoring of absorption in solution by cavity ring-down spectroscopy.
Cavity ring-down spectroscopy is applied to the liquid phase by placing the target solution directly into the optical cavity. We demonstrate that solutions in the cavity can be stirred and more importantly monitored in a flow. We report a minimum detectable absorption of 10(-6) cm(-1) for a range of organic solvents. This detection limit corresponds to picomolar concentrations for strong absorbers.


The role of science in international trade law.
While the General Agreement on Tariffs and Trade addressed overt barriers to international trade, the current focus of international trade rules has shifted to less obvious, but in many cases no less restrictive, barriers to trade, such as protectionist measures adopted under the guise of health and safety standards. The new agreements established under the World Trade Organization ("WTO"), including the Agreement on the Application of Sanitary and Phytosanitary Measures ("SPS Agreement"), the Agreement on Technical Barriers to Trade ("TBT Agreement"), provide important tools that can be invoked by governments and used by stakeholders to address regulatory barriers that were once thought outside the purview of international trade rules. Non-science based regulations can be and have been successfully challenged under the SPS and TBT Agreements, which prohibit WTO Members from maintaining laws or regulations that adversely affect trade unless such measures are scientifically justified. Stakeholders should use to the fullest extent possible international trade rules to eliminate non-science based regulations that adversely affect trade in the goods that they produce.


Yang-Lee zeros of the two- and three-state Potts model defined on phi3 Feynman diagrams.
We present both analytical and numerical results on the position of partition function zeros on the complex magnetic field plane of the q=2 state (Ising) and the q=3 state Potts model defined on phi(3) Feynman diagrams (thin random graphs). Our analytic results are based on the ideas of destructive interference of coexisting phases and low temperature expansions. For the case of the Ising model, an argument based on a symmetry of the saddle point equations leads us to a nonperturbative proof that the Yang-Lee zeros are located on the unit circle, although no circle theorem is known in this case of random graphs. For the q=3 state Potts model, our perturbative results indicate that the Yang-Lee zeros lie outside the unit circle. Both analytic results are confirmed by finite lattice numerical calculations.


Chemical compositions and biological activities of Serevenia buxifolia essential oil leaves cultivated in Vietnam (Thua Thien Hue).
Serevenia buxifolia is an evergreen citrus plant and has attracted considerable attention due to its bioactive components and biological activities. In the present study, the essential oil (EO) from S. buxifolia cultivated in Vietnam was demonstrated to exhibit the in vitro antioxidant, thrombolytic, anti-hemolysis, anti-inflammatory, and antidiabetic activities. Briefly, the gas chromatography coupled to mass spectrometry analysis revealed that the leaf EO of S. buxifolia was composed of 33 components, with the main constituents being β-carypphyllene (32.5%), and elixene (9.8%). The extracted oil possessed a fairly high free radical scavenging activity against 2, 2-diphenyl-1-picrylhydrazyl (DPPH), with an IC50 value of 190.7 μg/mL compared with positive control, α-tocopherol, IC50 value of 42.6 μg/mL. The EO also exhibited thrombolytic activity: the percentage of inhibition was found to be 70.75% at 100 μL, in comparison with 87.2% for the positive control, streptokinase. For hemolytic activity, the percentage of inhibition of the EO was from 27.4% to 59.6% at concentrations from 10 to 100 μg/mL, respectively. The results of in vitro anti-inflammatory activity indicated that the EO of S. buxifolia leaves effectively protects the heat-induced denaturation, with an IC50 value of 40.25 μg/mL. The EO also exhibited antidiabetic potential, with IC50 values of 87.8 and 134.9 μg/mL against α-amylase and α-glucosidase, respectively. It is noteworthy that the potent biological activities of the obtained S. buxifolia oil increased in a dose-dependent manner. The results achieved show that the EO of S. buxifolia leaves can be a potential source for oxidative stress, inflammatory, and diabetic management.


Patterns of and reasons for electronic cigarette use in primary care patients.
Electronic cigarette (e-cigarette) use is rising in both the general and clinical populations. Little is known about e-cigarette use in primary care, where physicians report discussing e-cigarette use with patients. Identify how and why smokers in primary care use e-cigarettes. Cross-sectional secondary data analysis from a randomized controlled trial of a tablet intervention to deliver the 5As for smoking cessation in primary care. Current smokers aged 18 and older in three primary care clinics in San Francisco, CA (N = 788). Patients reported sociodemographics, cigarette smoking habits, quitting readiness, and ever and current use of e-cigarettes. We also asked reasons they have used or would use e-cigarettes. ICD-9 codes from the medical record determined comorbidities. Fifty-two percent (n = 408) of patients reported ever using an e-cigarette, and 20% (n = 154) reported past-30-day use. Ever e-cigarette use was associated with younger age and negatively associated with being seen at practices at a public safety-net hospital compared to a practice at University-affiliated hospital. The most common reason for having used e-cigarettes among ever e-cigarette users, and for interest in future use of e-cigarettes among never e-cigarette users, was to cut down cigarette use. The mean number of days of e-cigarette use in the past 30 increased with duration of e-cigarette use. Most current e-cigarette users did not know the nicotine content of their e-cigarettes. Over half of smokers in primary care have ever used e-cigarettes, and one-fifth are currently using them. Most reported using e-cigarettes to cut down or quit cigarettes. Primary care providers should be prepared to discuss e-cigarettes with patients. Screening for e-cigarette use may help identify and treat patients interested in changing their cigarette smoking habits.


Insect inspired vision-based velocity estimation through spatial pooling of optic flow during linear motion.
Insects rely on the perception of image motion, or optic flow, to estimate their velocity relative to nearby objects. This information provides important sensory input for avoiding obstacles. However, certain behaviors, such as estimating the absolute distance to a landing target, accurately measuring absolute distance traveled, and estimating the ambient wind speed require decoupling optic flow into its component parts: absolute ground velocity and distance to nearby objects. Behavioral experiments suggest that insects perform these calculations, but their mechanism for doing so remains unknown. Here we present a novel algorithm that combines the geometry of dynamic forward motion with known features of insect visual processing to provide a hypothesis for how insects mightdirectlyestimate absolute ground velocity from a combination of optic flow and acceleration information. Our robotics-inspired-biology approach reveals three critical requirements. First, absolute ground velocity can only be directly estimated from optic flow during times of active acceleration and deceleration. Second, spatial pooling of optic flow across a receptive field helps to alleviate the effects of noise and/or low resolution visual systems. Third, averaging velocity estimates from multiple receptive fields further helps to reject noise. Our algorithm provides a hypothesis for how insects might estimate absolute velocity from vision during active maneuvers, and also provides a theoretical framework for designing fast analog circuitry for efficient state estimation that can be applied to insect-sized robots.


Orthotic management in patients with stroke.
Orthotic management for the individual with a hemiplegic gait pattern secondary to a stroke is an important consideration for any treatment plan for this patient population. Patient evaluation, gait analysis, previous management, medical team cohesion, and patient expectations are elements necessary to establish the orthotic goals for the patient. These goals are the basis by which an orthotic treatment plan can be established as well as a measure for future outcome. Therefore, the purpose of this discussion is to describe the steps necessary to determine the most effective method of orthotic management and to identify orthotic design indications and contraindications.


An unusual RNA tertiary interaction has a role for the specific aminoacylation of a transfer RNA.
The nucleotides in a tRNA that specifically interact with the cognate aminoacyl-tRNA synthetase have been found largely located in the helical stems, the anticodon, or the discriminator base, where they vary from one tRNA to another. The conserved and semiconserved nucleotides that are responsible for the tRNA tertiary structure have been shown to have little role in synthetase recognition. Here we report that aminoacylation of Escherichia coli tRNA(Cys) depends on the anticodon, the discriminator base, and a tertiary interaction between the semiconserved nucleotides at positions 15 and 48. While all other tRNAs contain a purine at position 15 and a complementary pyrimidine at position 48 that establish the tertiary interaction known as the Levitt pair, E. coli tRNA(Cys) has guanosine -15 and -48. Replacement of guanosine -15 or -48 with cytidine virtually eliminates aminoacylation. Structural analyses with chemical probes suggest that guanosine -15 and -48 interact through hydrogen bonds between the exocyclic N-2 and ring N-3 to stabilize the joining of the two long helical stems of the tRNA. This tertiary interaction is different from the traditional base pairing scheme in the Levitt pair, where hydrogen bonds would form between N-1 and O-6. Our results provide evidence for a role of RNA tertiary structure in synthetase recognition.


Silver stains in the study of endocrine cells of the gut and pancreas.
The usefulness of argentaffin (Masson) and argyrophil (Davenport, Sevier-Munger and Grimelius) staining methods for identification of endocrine cell types in the gastrointestinal tract and pancreas is discussed and comments are made on the techniques themselves. The applicability of silver impregnation methods in the histopathological investigations of endocrine tumours in the above-mentioned organs is outlined, and the chemical background of the silver reactions is briefly reviewed.


Fabrication of Nanoyttria by Method of Solution Combustion Synthesis.
In the work the research on properties of an yttria nanopowder obtained by solution combustion synthesis (SCS) in terms of its application in ceramic technology is presented. In order to characterize the SCS reaction the decomposition of yttrium nitrate, glycine and their solution was investigated using differential thermal analysis coupled with FT-IR spectrometry of the gases emitted during the measurements. The product obtained in the SCS process was characterized in terms of its microstructure, particle size distribution and BET specific surface. Although the obtained powders showed nanoscaled structures, only after calcination at a temperature of 1100 °C nanosized particles were revealed. The calcined powder occurred in an agglomerated state (cumulants mean Zave = 1.3 µm). After milling particle size was successfully decreased to Zave = 0.28 µm. The deagglomerated powder was isostatically densified and tested for sintering ability. The obtained nanopowder showed very high sintering activity as the shrinkage onset was detected already at a temperature of about 1150 °C.


Chemokines involved in tumor promotion and dissemination in patients with renal cell cancer.
Chemokines play a critical role in tumor initiation, progression, and metastasis and have been associated with poor prognosis in diverse malignancies. The prognostic impact of chemokines for renal cell cancer (RCC) remains to be defined. Patients diagnosed with RCC and operated between 07/07 and 05/11 were differentially assessed for expression profiles of a series of chemokines and their receptors by RT-qPCR and Western Blot analysis (tumor and adjacent normal tissue, n=37) and by Luminex for corresponding serum expression levels. Results were statistically correlated with clinicopathologic parameters. Gene expression of CCL2, CCR7, CXCL12, CXCR3, CXCR5 and CX3CL1 chemokines was significantly down-regulated in tumor compared to normal tissue. The gene profile for CCR6 was positively correlated with tumor size and stage. A positive linear correlation was found between CXCL12 and tumor stage as well as between CX3CR1 and C-reactive protein. In contrast to clear cell RCCs those of a chromophobe type showed a significantly down-regulated gene expression for CCR6, CCL20, and CXCL12. The CXCR7 serum level was significantly increased in patients with tumor-related mortality during postoperative follow-up. Chemokines may serve as novel diagnostic and prognostic biomarkers for RCC. Studies on larger collectives are required for further assessment of potential clinical application.


Neurogenetic asymmetries in the catshark developing habenulae: mechanistic and evolutionary implications.
Analysis of the establishment of epithalamic asymmetry in two non-conventional model organisms, a cartilaginous fish and a lamprey, has suggested that an essential role of Nodal signalling, likely to be ancestral in vertebrates, may have been largely lost in zebrafish. In order to decipher the cellular mechanisms underlying this divergence, we have characterised neurogenetic asymmetries during habenular development in the catshark Scyliorhinus canicula and addressed the mechanism involved in this process. As in zebrafish, neuronal differentiation starts earlier on the left side in the catshark habenulae, suggesting the conservation of a temporal regulation of neurogenesis. At later stages, marked, Alk4/5/7 dependent, size asymmetries having no clear counterparts in zebrafish also develop in neural progenitor territories, with a larger size of the proliferative, pseudostratified neuroepithelium, in the right habenula relative to the left one, but a higher cell number on the left of a more lateral, later formed population of neural progenitors. These data show that mechanisms resulting in an asymmetric, preferential maintenance of neural progenitors act both in the left and the right habenulae, on different cell populations. Such mechanisms may provide a substrate for quantitative variations accounting for the variability in size and laterality of habenular asymmetries across vertebrates.


Degenerative myelopathy in a family of Siberian Husky dogs.
Three closely related, Siberian Husky dogs had chronic progressive paresis and ataxia with muscle atrophy in the hindlimbs. Radiologic and myelographic examination of the spine revealed no abnormalities. On histologic examination, disseminated degeneration of the white matter, particularly in the thoracic segments, was seen. The clinical and pathological findings were similar to those described in aging large dogs with so-called degenerative myelopathy. The cause of this disease is unknown but the fact that these 3 Huskies were closely related suggest that hereditary factors may play a role.


Cycloheximide reduces infarct volume when administered up to 6 h after mild focal ischemia in rats.
We have previously described a rodent model of brief (30 min) middle cerebral artery occlusion followed by reperfusion, in which infarction develops gradually, reaching completion more than 3 days after ischemia, accompanied by morphological, biochemical, and pharmacological evidence of apoptosis. In the present study, we tested the hypotheses that delayed administration of a protein synthesis inhibitor would be effective in reducing tissue injury in this slowly evolving ischemic infarction, and that efficacy of this treatment would wane with more prolonged ischemia. Focal cerebral ischemia was induced in Long-Evans rats by occlusion of the right middle cerebral artery. Infarction volume was analyzed using triphenyl tetrazolium chloride staining, and morphology was studied using hematoxylin and eosin stained sections. Following 30 min middle cerebral artery occlusion and reperfusion, the core ischemic region exhibited vacuolization in the neuropil by 36 h after ischemia, and infarction reached full size by 7 days after ischemia. Cycloheximide reduced infarct volume when given up to 6 h after ischemia. If the duration of ischemic insult was increased to 90 min, the therapeutic window for delayed cycloheximide was only 30 min. In permanent middle cerebral artery occlusion, cycloheximide was ineffective even when given prior to ischemia onset. After mild, but not severe, ischemic insults, cerebral infarction develops slowly and may be treatable with protein synthesis inhibitors, even when treatment is delayed for up to 6 h after the onset of ischemia.


[Osteoporosis: a risk factor for periodontal disease (literature review)].
Osteoporosis is a major public health problem all over the world. Caucasian women have the highest risk. Osteoporosis affects about 10% of the total population but the prevalence among postmenopausal women is more than 30%. It had long been stated that general osteoporosis played no role in the etiology of destructive periodontitis with inflammatory nature. Nevertheless a substantial number of publications in recent years indicated just an opposite relationship. It has been shown that total body calcium and bone density was closely associated with mandibular bone density and several studies have demonstrated close relationship between edentulism and systemic osteopenia. Certain data showed clear relationship between osteoporosis and periodontal disease, and osteoporosis is considered as one of the risk factors for periodontal bone loss. Both osteoporosis and periodontal disease are chronic multifactorial diseases with many genetic and behavioral risk factors and determinants. Both diseases can be successfully controlled by eliminating several risk factors. Estrogen replacement therapy can be protective against both postmenopausal osteoporosis and severe periodontitis in postmenopausal women. Tobacco smoking and diet are also important risk factors for both diseases and genetic factors have also been identified as important risk factors in the etiology of both diseases. Recent epidemiological and clinical data provides limited but convincing evidence suggesting an association between osteoporosis and periodontal disease, and many common risk factors could have been detected in the etiology of both diseases.


Analysis of RTEL1 and PCDHGB6 promoter methylation in circulating-free DNA of lung cancer patients using liquid biopsy: A pilot study.
Analysis of epigenetic alterations such as methylation of circulating-free DNA (cf-DNA) expression significantly broadened perspectives of lung cancer (LC) screening. Moreover, methylation of tumor suppressor genes may be analyzed with non-invasive manner in patients' blood samples (liquid biopsy), what underline necessity of detailed investigation of tumor cf-DNA. The purpose of current study was to assess methylation of RTEL1 and PCDHGB6 promoter regions in cf-DNA of 70 LC patients and 80 healthy individuals using qMSP-PCR technique. Methylation status of both genes has not been investigated in cf-DNA of LC patients before. PCDHGB6 promoter methylation was found in 41.4% of LC patients and in 1.3% of healthy individuals, whereas promoter of RTEL1 was found methylated in 51.4% of LC patients and in 8.8% of healthy individuals. Combined analysis of two markers improved test sensitivity up to 62.9% and specificity up to 90% with area under the curve (AUC) in receiver operating curve (ROC) of 0.755. The evaluation of RTEL1 and PCDHGB6 promoter methylation may be an useful tool for non-invasive diagnosis of LC in liquid biopsy.


Screening for mild cognitive impairment among older Albanian patients by clinical pharmacists.
To assess the prevalence of mild cognitive impairment (MCI) and its correlated factors among elderly Albanian patients using different screening tools applied by clinical pharmacists. Patients aged 60 years old or more from two primary care centers located in two Albanian cities were included in the study. Two clinical pharmacists applied the MoCA/MoCA B (Montreal Cognitive Assessment/Basic) and the Mini-Cog in Albanian. A predictive multivariate logistic regression analysis and Kappa statistic were conducted. The prevalence of MCI using MoCA/MoCA B and Mini-Cog scales was 75.73 and 20.39%, respectively. There was a poor degree of agreement between them (Kappa 2.38). Older men had an increased risk of MCI. The involvement of clinical pharmacists in screening for MCI might help in selecting vulnerable individuals for more specialized examination. The MoCA/MoCA B tool is recommended for higher sensitivity.


Neuroketotherapeutics: A modern review of a century-old therapy.
Neuroketotherapeutics represent a class of bioenergetic medicine therapies that feature the induction of ketosis. These therapies include medium-chain triglyceride supplements, ketone esters, fasting, strenuous exercise, the modified Atkins diet, and the classic ketogenic diet. Extended experience reveals persons with epilepsy, especially pediatric epilepsy, benefit from ketogenic diets although the mechanisms that underlie its effects remain unclear. Data indicate ketotherapeutics enhance mitochondrial respiration, promote neuronal long-term potentiation, increase BDNF expression, increase GPR signaling, attenuate oxidative stress, reduce inflammation, and alter protein post-translational modifications via lysine acetylation and β-hydroxybutyrylation. These properties have further downstream implications involving Akt, PLCγ, CREB, Sirtuin, and mTORC pathways. Further studies of neuroketotherapeutics will enhance our understanding of ketone body molecular biology, and reveal novel central nervous system therapeutic applications.


CeO2-based Pd(Pt) nanoparticles grafted onto Fe3O4/graphene: a general self-assembly approach to fabricate highly efficient catalysts with magnetic recyclable capability.
New Pd(Pt) catalysts have been fabricated by assembling multicomponents of Fe3O4 and CeO2/Pd(Pt) on the surface of reduced graphene oxide (RGO) nanosheets in layers. The as-obtained Pd(Pt) catalysts exhibit extremely high catalytic activity in the selective hydrogenation reaction of nitrobenzene. Owing to the presence of Fe3O4, the catalysts can be easily recycled from the catalytic system through magnetic separation. Their high activity, stability, and magnetic recyclability make the as-obtained hybrids very promising as catalysts in catalytic applications. Compared to other traditional multishell magnetic catalysts that were prepared by means of layer-by-layer technology, our process is much more facile and more easily controlled.


Violent injuries to the upper ureter.
Frequently traumatic injury to the renal pelvis or upper ureter is overshadowed by multiple associated injuries. The diagnosis may be particularly difficult, due to the lack of hematuria and absence of pathognomonic findings. All too frequently the delayed manifestations of urinary wound drainage, retroperitoneal mass, or urinary ascites and sepsis first draw attention to the ureteral injury. A review of the problem and our experience with 16 such injuries is presented. As with other infrequent injuries the single and most important diagnostic factor is the prepared mind of the examiner. We feel all patients who have penetrating abdominal trauma, have fractured lumbar processes, or are involved in accidents where deceleration or extension occur should have infusion pyelography even in the absence of hematuria.


Spectral characteristics of chromatic confocal imaging systems.
We present signal-generation models for chromatic confocal imaging systems with illumination and detection pinholes of finite size: a collinear model that considers neither aberrations nor diffraction effects, a geometrical model that accounts for aberrations, and a wave optical model covering both aberrations and diffraction effects. These models are aimed at describing the spectral response of multipoint sensor systems with field-dependent aberrations and vignetting effects. They are suitable for single- and double-pass systems with either diffusely or specularly reflecting surfaces under test. We show experimental results to verify our models.


MTDL-EPDCLD: A Multi-Task Deep-Learning-Based System for Enhanced Precision Detection and Diagnosis of Corn Leaf Diseases.
Corn leaf diseases lead to significant losses in agricultural production, posing challenges to global food security. Accurate and timely detection and diagnosis are crucial for implementing effective control measures. In this research, a multi-task deep learning-based system for enhanced precision detection and diagnosis of corn leaf diseases (MTDL-EPDCLD) is proposed to enhance the detection and diagnosis of corn leaf diseases, along with the development of a mobile application utilizing the Qt framework, which is a cross-platform software development framework. The system comprises Task 1 for rapid and accurate health status identification (RAHSI) and Task 2 for fine-grained disease classification with attention (FDCA). A shallow CNN-4 model with a spatial attention mechanism is developed for Task 1, achieving 98.73% accuracy in identifying healthy and diseased corn leaves. For Task 2, a customized MobileNetV3Large-Attention model is designed. It achieves a val_accuracy of 94.44%, and improvements of 4-8% in precision, recall, and F1 score from other mainstream deep learning models. Moreover, the model attains an area under the curve (AUC) of 0.9993, exhibiting an enhancement of 0.002-0.007 compared to other mainstream models. The MTDL-EPDCLD system provides an accurate and efficient tool for corn leaf disease detection and diagnosis, supporting informed decisions on disease management, increased crop yields, and improved food security. This research offers a promising solution for detecting and diagnosing corn leaf diseases, and its continued development and implementation may substantially impact agricultural practices and outcomes.


The Invertebrate Life of New Zealand: A Phylogeographic Approach.
Phylogeography contributes to our knowledge of regional biotas by integrating spatial and genetic information. In New Zealand, comprising two main islands and hundreds of smaller ones, phylogeography has transformed the way we view our biology and allowed comparison with other parts of the world. Here we review studies on New Zealand terrestrial and freshwater invertebrates. We find little evidence of congruence among studies of different taxa; instead there are signatures of partitioning in many different regions and expansion in different directions. A number of studies have revealed unusually high genetic distances within putative species, and in those where other data confirm this taxonomy, the revealed phylogeographic structure contrasts with northern hemisphere continental systems. Some taxa show a signature indicative of Pliocene tectonic events encompassing land extension and mountain building, whereas others are consistent with range expansion following the last glacial maximum (LGM) of the Pleistocene. There is some indication that montane taxa are more partitioned than lowland ones, but this observation is obscured by a broad range of patterns within the sample of lowland/forest taxa. We note that several geophysical processes make similar phylogeographic predictions for the same landscape, rendering confirmation of the drivers of partitioning difficult. Future multi-gene analyses where applied to testable alternative hypotheses may help resolve further the rich evolutionary history of New Zealand's invertebrates.


BAY-6096: A Potent, Selective, and Highly Water-Soluble Adrenergic α2B Antagonist.
After acute myocardial infarction, early reperfusion is the most effective strategy for reducing cardiac damage and improving clinical outcome. However, restoring blood flow to the ischemic myocardium can paradoxically induce injury by itself (reperfusion injury), with microvascular dysfunction being one contributing factor. α2B adrenergic receptors have been hypothesized to be involved in this process. To assess α2B-related pharmacology, we identified a novel α2B antagonist by HTS. The HTS hit showed limited α2A selectivity as well as low solubility and was optimized toward BAY-6096, a potent, selective, and highly water-soluble α2B antagonist. Key aspects of the optimization were the introduction of a permanently charged pyridinium moiety to achieve very good aqueous solubility and the inversion of an amide to prevent genotoxicity. BAY-6096 dose-dependently reduced blood pressure increases in rats induced by an α2B agonist, demonstrating the role of α2B receptors in vascular constriction in rats.


Role of adrenocorticotropic hormone in the modulation of pollinosis induced by pollen antigens.
A mild restraint stressor suppressed an increase in the levels of Th2-dependent cytokines and IgE, thereby reducing the symptoms of pollinosis. In the present study, to clarify the mechanism of action of adrenocorticotropic hormone (ACTH) in improving the symptoms of pollinosis, we studied the effects of ACTH on the plasma level of histamine, mast cell number in nasal-associated lymphoid tissue (NALT) and the T cell differentiation in splenocytes. The role of ACTH in the development of pollen antigen-induced pollinosis was studied in mice. Allergic symptoms and parameters were measured on day 17 after sensitization. To investigate the effects of ACTH on T cell differentiation, we stimulated splenocytes obtained from control mice with ACTH and CD3/CD28 in vitro, and measured the cytokine production in the culture supernatant. The plasma levels of IL-10, IgE and histamine and mast cell number in NALT were increased in the sensitized animals in association with a concomitant increase in the incidence of sneezing and nasal rubbing. The intraperitoneal administration of ACTH decreased the IL-10, IgE and histamine levels in the plasma and mast cell number in NALT, while increasing the IFN-γ level and suppressing the incidence of nasal rubbing. Furthermore, the production of IFN-γ increased, while the IL-4 level was suppressed after 2 days in culture. The present findings showed that ACTH directly affects T cell differentiation and promotes Th1-type reactions. The regulation of the Th1/Th2 balance by ACTH may result in a decrease in the pathological features of pollinosis.


The Effects of microRNA-515-5p on the Toll-Like Receptor 4 (TLR4)/JNK Signaling Pathway and WNT1-Inducible-Signaling Pathway Protein 1 (WISP-1) Expression in Rheumatoid Arthritis Fibroblast-Like Synovial (RAFLS) Cells Following Treatment with Receptor Activator of Nuclear Factor-kappa-B Ligand (RANKL).
BACKGROUND This study aimed to investigate the effects of microRNA-515-5p (miR-515-5p) on the expression of the WNT1-inducible-signaling pathway protein 1 (WISP-1) gene in rheumatoid arthritis fibroblast-like synovial (RAFLS) cells following treatment with the receptor activator of nuclear factor-kappa-B ligand (RANKL). MATERIAL AND METHODS RAFLS cells were cultured in vitro and were divided into six study groups: a normal control group; a miR-515-5p mimic group; a miR-515-5p inhibitor group; a RANKL (50 ng/ml) treatment group; a miR-515-5p mimic+RANKL treatment group; and a miR-515-5p inhibitor+RANKL treatment group. The luciferase assay was used to determine the effects of miR-515-5p on the WISP1 expression. Cell proliferation, cell apoptosis, the cell cycle, and protein expression were determined using the Cell Counting Kit-8 (CCK-8) assay, flow cytometry, Western blot, and real-time polymerase chain reaction (RT-PCR). RESULTS The luciferase assay showed that the effects of miR-515-on the 3'-UTR of WISP1 inhibited the gene expression. The miR-515-5p mimics promoted cell proliferation, reduced apoptosis, and promoted the cell cycle. The miR-515-5p mimics reduced, the expression of TLR4, WISP1, and JNK at the mRNA level, while the miR-515-5p inhibitor promoted the expression of TLR4, WISP1, and JNK. Both the miR-515-5p inhibitor and mimic promoted the phosphorylation of AKT in RAFLS cells treated with or without RANKL compared with the control, and the miR-515-5p inhibitor promoted the phosphorylation of JNK in the RAFLS cells. CONCLUSIONS In RAFLS cells, miR-515-5p inhibited the expression of the WISP1 gene, and treatment with RANKL inhibited the TLR4/JNK signaling pathway.


Interstrand Crosslink Repair as a Target for HDAC Inhibition.
DNA interstrand crosslinks (ICLs) covalently connect complementary DNA strands. Consequently, DNA replication and transcription are hampered, DNA damage responses (DDR) are initiated, and cell death is triggered. Therefore, drugs inducing ICLs are effective against rapidly growing cancer cells. However, tumors engage a complicated enzymatic machinery to repair and survive ICLs. Several factors, including the post-translational acetylation/deacetylation of lysine residues within proteins, control this network. Histone deacetylases (HDACs) modulate the expression and functions of DNA repair proteins which remove ICLs and control the accessibility of chromatin. Accordingly, histone deacetylase inhibitors (HDACi) are small, pharmacologically and clinically relevant molecules that sensitize cancer cells to ICL inducers. We discuss the mechanism of ICL repair and targets of HDACi within this pathway.


[Molecular and serological diagnosis of a dengue outbreak in Coro, Falcón state, Venezuela].
Dengue virus (DV) is responsible for a spectrum of diseases, from a self-limited fever disease (DF, dengue fever) to the more severe forms of hemorrhagic fever/dengue shock syndrome (DHF/DSS). The aim of this study was the serological and molecular confirmation of an outbreak of dengue in Falcon state, Venezuela. A total of 54 sera from patients with clinical diagnosis of DV infection were analyzed by an enzyme immunoassays developed in Venezuela (ELISA -IgM e -IgG) and by PCR. From them, 78% exhibited DV infection (PCR+ y/o IgM+), 48% exhibited viremia by PCR and 57% were positive to IgM. An interesting observation was the high percent (76%) of patients with past or secondary infection (IgG positive), which included all the patients exhibiting clinical symptoms of DHF (n = 8). From the PCR positive sera, serotype 1 was found in 27%, serotype 2 in 54% and serotype 4 in 19%. No serotype 3 was found circulating in this population, although this serotype was already circulating in the nearby island of Aruba. The combination of serological and molecular methods allow us to obtain a fairly precise information of this outbreak.


Normal bone turnover in transient hyperphosphatasemia.
Transient hyperphosphatasemia of infancy and early childhood (THI) is characterized by a temporary isolated elevation of serum alkaline phosphatase activity (ALP), predominantly its bone or liver isoform, in either sick or healthy children under 5 years of age. Return to normal ALP levels usually occurs within four months. Spontaneous rise of ALP might concern the physician, especially when treating seriously ill children. However, THI is considered a benign biochemical disorder with no clinical consequences. Some existing reports support the hypothesis that THI is a result of increased bone turnover. We present evidence of normal bone turnover in two children with THI. In a one-year-old girl and a boy of the same age, high ALP levels (31 and 109 µkat/L, respectively) were accidentally detected. The children had no signs of metabolic bone disease or of liver disease. The high ALP levels returned to normal in two months, thus fulfilling the diagnosis of THI. In both patients, serum parathyroid hormone and bone turnover markers, serum CrossLaps, and serum osteocalcin were neither elevated, nor did these markers follow the ALP dynamics, thus reflecting normal bone turnover in THI. Children with THI should be spared from extensive investigations and unnecessary vitamin D treatment.


Childhood Disorder: Dysregulated Self-Conscious Emotions? Psychopathological Correlates of Implicit and Explicit Shame and Guilt in Clinical and Non-clinical Children and Adolescents.
This study examined psychopathological correlates of implicit and explicit shame and guilt in 30 clinical and 129 non-clinical youths aged 8-17 years. Shame and guilt were measured explicitly via two self-reports and a parent report, and implicitly by means of an Implicit Association Test (IAT), while a wide range of psychopathological symptoms were assessed with questionnaires completed by children, parents, and teachers. The results showed no differences of implicit and explicit shame and guilt between the clinical and non-clinical group, implying that dysregulation of these self-conscious emotions is not per definition associated with psychopathology. Correlational analyses indicated that self-reported explicit shame was positively associated with a broad range of internalizing psychopathology, while self-reported explicit guilt was associated with higher levels of anxiety and to some extent lower levels of externalizing psychopathology. Correlations with parent-rated shame and guilt revealed the same pattern of results but were in general weaker. Furthermore, implicit shame and guilt did not show significant correlations with the various measures of psychopathology. It can be concluded that the link between shame and guilt and psychopathology is complex, and partly dependent on the disorder under study and context-related factors defining the maladaptive nature of these self-conscious emotions.


Role of the transcription activator virF and the histone-like protein YmoA in the thermoregulation of virulence functions in yersiniae.
The chromosome of Y. enterocolitica encodes a heat-stable enterotoxin, Yst, being related to STI. The capacity to produce Yst generally disappears during storage of the strains. In these strains, the yst gene is intact but remains silent. The pYV plasmid encodes the eleven secreted antihost proteins called Yops as well as the outer membrane protein YadA. The Yops are secreted by a novel, pYV-encoded secretion mechanism. This mechanism which does not involve the removal of an N-terminal signal sequence, is encoded by the pYV virA and virC loci. The virC locus contains 13 genes called yscA-M. The virA locus encodes the LcrD membrane protein. The yop, yadA and ysc genes form the yop regulon controlled by transcriptional activator VirF. Transcription of the yop, yadA, ysc and virF genes is controlled by temperature. A chromosome-encoded histone-like protein, called YmoA, is involved in the thermoregulation of the yop regulon, which suggests that this thermoregulation could result from temperature-induced changes in DNA topology. The phenotype of ymoA mutants resembles that of osmZ or drdX mutants of E. coli but YmoA is not the Yersinia homologue of the E. coli histone H1. The YmoA histone is also involved in the silencing of the yst gene.


Methylation regulates HEY1 expression in glioblastoma.
Glioblastoma (GBM) remains one of the most lethal and difficult-to-treat cancers of the central nervous system. The poor prognosis in GBM patients is due in part to its resistance to available treatments, which calls for identifying novel molecular therapeutic targets. In this study, we identified a mediator of Notch signaling, HEY1, whose methylation status contributes to the pathogenesis of GBM. Datamining studies, immunohistochemistry and immunoblot analysis showed that HEY1 is highly expressed in GBM patient specimens. Since methylation status of HEY1 may control its expression, we conducted bisulphite sequencing on patient samples and found that the HEY1 promoter region was hypermethylated in normal brain when compared to GBM specimens. Treatment on 4910 and 5310 xenograft cell lines with sodium butyrate (NaB) significantly decreased HEY1 expression with a concomitant increase in DNMT1 expression, confirming that promoter methylation may regulate HEY1 expression in GBM. NaB treatment also induced apoptosis of GBM cells as measured by flow cytometric analysis. Further, silencing of HEY1 reduced invasion, migration and proliferation in 4910 and 5310 cells. Furthermore, immunoblot and q-PCR analysis showed the existence of a potential positive regulatory loop between HEY1 and p53. Additionally, transcription factor interaction array with HEY1 recombinant protein predicted a correlation with p53 and provided various bonafide targets of HEY1. Collectively, these studies suggest HEY1 may be an important predictive marker for GBM and potential target for future GBM therapy.


Advances in Electrocatalysis for Energy Conversion and Synthesis of Organic Molecules.
Ubiquitous electrochemistry is expected to play a major role for reliable energy supply as well as for production of sustainable fuels and chemicals. The fundamental understanding of organics-based electrocatalysis in alkaline media at the solid-liquid interface involves complex mechanisms and performance descriptors (from the electrolyte and reaction intermediates), which undermine the roads towards advance and breakthroughs. Here, we review and diagnose recently designed strategies for the electrochemical conversion of organics into electricity and/or higher-value chemicals. To tune the mysterious workings of nanocatalysts in electrochemical devices, we examine the guiding principles by which the performance of a particular electrode material is governed, thus highlighting various tactics for the development of synthesis methods for nanomaterials with specific properties. We end by examining the production of chemicals by using electrochemical methods, from selective oxidation to reduction reactions. The intricate relationship between electrode and selectivity encourages both of the communities of electrocatalysis and organic synthesis to move forward together toward the renaissance of electrosynthesis methods.


A press-through-pack in the larynx.
A case of a 96-year-old male with a foreign body in the larynx is reported. The foreign body was a press-through-pack (PTP), a plastic packing for medicine, 16 mm x 16 mm x 3 mm in size. The PTP was safely removed from the larynx under general anesthesia.


Role of Different CD40 Polymorphisms in Graves' Disease and Hashimoto's Thyroiditis.
Genome-wide association studies have led to the discovery of several susceptibility genes related to autoimmune thyroid diseases (AITDs). However, controversial results have been reported regarding the role of single-nucleotide polymorphism (SNP) of CD40 in the disease susceptibility. The objective of this study was to identify the relationship of the polymorphisms of three sites of CD40 with the susceptibility to AITD in the Chinese population. We genotyped three polymorphisms of CD40: C/T -1 SNP, 58038T site of the third exon and C64610G site of the ninth exon in 196 GD cases, 121 HT cases and 122 control subjects. The three putative polymorphism sites were amplified by PCR for sequencing and analysis. The genotype frequencies of CD40 -1 C/C genotype and C allele were significantly higher in the GD group than those in normal control. For the C64610G polymorphism, the C/G genotype was significantly more frequent in HT group than in control group, and the G allele frequencies in the GD and HT group were both higher than those in control group. These results indicated that there exist different susceptibility loci for AITD within CD40, each contributing a different effect in the onset and development of AITDs.


[Intramuscular myxoma. Apropos of a case].
Intramuscular myxoma is a relatively unusual benign tumor of soft tissues. Clinical examination is non specific and the definitive diagnosis can only be established on histology. The treatment consists of excision of the tumor. The prognosis is very good and recurrence is very rare. No cases of metastasis have been described.


Interdisciplinary paleovegetation study in the Fernando de Noronha Island (Pernambuco State), northeastern Brazil.
The aim of this research was to reconstruct vegetation changes (with climate inferences) that occurred during the Holocene in the Fernando de Noronha Island, Pernambuco State, northeastern Brazil. The research approach included the use of geochemical (mineralogy, elemental), carbon isotopes (delta13C, 14C) and pollen analyses in soil organic matter (SOM) and sediments collected in Lagoa da Viração and Manguezal do Sueste. The carbon isotopes data of SOM indicated that there was no significant vegetation changes during the last 7400 BP, suggesting that the climate was not the determinant factor for the vegetation dynamics. The pollen analysis of the sediment of a core collected in the Lagoa da Viração showed the absence of Quaternary material in the period between 720 BP and 90 BP. The mineralogical analysis of deeper layer showed the presence of diopside indicating this material was developed "in situ". Only in the shallow part of the core were found pollen of similar plant species of the modern vegetation. The geochemistry and isotope results, in association with the sediment type and pollen analyses of sediment samples of Manguezal do Sueste, indicated variations in the vegetation and in its location since the middle Holocene. Such variations can be associated with climatic events and sea level oscillations and also with anthropogenic events considering the last five hundred years.


Species-specific diversity in the anatomical and physiological organisation of the BNST-VTA pathway.
The anteromedial part of the bed nucleus of the stria terminalis (amBNST) is a limbic structure innervating the ventral tegmental area (VTA) that is remarkably constant across species. The amBNST modulates fear and anxiety, and activation of VTA dopamine (DA) neurons by amBNST afferents seems to be the way by which stress controls motivational states associated with reward or aversion. Because fear learning and anxiety states can be expressed differently between rats and mice, we compared the functional connectivity between amBNST and the VTA-DA neurons in both species using consistent methodological approaches. Using a combination of in vivo electrophysiological, neuroanatomical tracing and laser capture approaches we explored the BNST influences on VTA-DA neuron activity. First, we characterised in rats the molecular phenotype of the amBNST neurons projecting to the VTA. We found that this projection is complex, including both GABAergic and glutamatergic neurons. Then, VTA injections of a conventional retrograde tracer, the β-sub-unit of the cholera toxin (CTB), revealed a stronger BNST-VTA projection in mice than in rats. Finally, electrical stimulations of the BNST during VTA-DA neuron recording demonstrated a more potent excitatory influence of the amBNST on VTA-DA neuron activity in rats than in mice. These data illustrate anatomically, but also functionally, a significant difference between rats and mice in the amBNST-VTA pathway. More generally, together with previous findings, our research highlights the importance of species differences for the interpretation and the generalisation of research data.


A New Recall of Alcohol Marketing Scale for Youth: Measurement Properties and Associations With Youth Drinking Status.
Adolescents are exposed to alcohol marketing through traditional advertising and through newer digital media channels. Cumulative marketing exposure across channels is of concern but has been insufficiently studied. This study explores the measurement of alcohol marketing exposure across channels and whether cumulative recalled exposure is independently associated with underage drinking. Two hundred two New England adolescents (ages 12-17 years) were recruited from a general pediatrics clinic and completed an online survey. Recall of alcohol marketing across channels (e.g., Internet, magazines) was assessed, along with drinking behavior and relevant covariates (i.e., demographics, parental/peer drinking, smoking status, sensation seeking, Internet use, social media use, television use, and parental Internet monitoring). Confirmatory factor analysis was used to establish a latent construct of alcohol marketing exposure recall. Logistic regression tested associations between alcohol marketing recall and adolescent drinking, with covariates controlled for. Adolescents reported recall of alcohol marketing across all marketing channels. Alcohol marketing recall items were significantly correlated, with α = .83. The latent measurement model of alcohol marketing recall provided excellent fit to the data, χ2(17, n = 202) = 27.402, p = .052; root mean square error of approximation (.000-.092) = .055; Tucker-Lewis Index = .960; comparative fit index = .976; standardized root mean square residual = .037). Adjusted cross-sectional logistic regression analyses demonstrated that the latent alcohol marketing recall construct was significantly associated with underage drinking (adjusted odds ratio = 4.08, 95% CI [1.15, 14.46]) when relevant covariates were accounted for. The final measurement model provided support for construct validity of a novel alcohol marketing recall construct assessing cumulative cross-channel marketing exposure. Adolescent recall of alcohol marketing across channels was significantly associated with underage drinking, while associated factors such as peer/parental drinking were accounted for.


Protein kinase Calpha controls the adhesion but not the antiproliferative response of human colon carcinoma cells to transforming growth factor beta1: identification of two distinct branches of post-protein kinase Calpha adhesion signal pathway.
Transforming growth factor beta1 (TGFbeta1) inhibits cellular proliferation and induces the expression of the matrix adhesion molecules fibronectin (FN) and laminin (LM) in a concurrent manner, followed by the induction of the intercellular adhesion molecule carcinoembryonic antigen (CEA) (collectively designated as adhesion responses) in TGFbeta1-responsive human colon carcinoma cells. Exactly how TGFbeta1 controls cellular adhesion and proliferation is poorly understood. In the present report, we showed that down-regulating protein kinase Calpha (PKCalpha) expression blocked the induction of these adhesion responses by TGFbeta1, showing that PKCalpha is a postreceptor focal point controlling the induction of these molecules. Down-regulating PKCalpha expression, however, had minimal effect on the antiproliferative response to TGFbeta1 or the induction of p21/WAF1, a marker associated with the antiproliferative effect of TGFbeta1, demonstrating that the adhesion signal pathway is distinct from that of antiproliferation. Blockade of FN induction blocked the induction of CEA but not the induction of LM. Blockade of LM induction, on the other hand, had no effect on the induction of FN and CEA. These results established the existence of two distinct and parallel postPKCalpha adhesion signal pathways, one leading to the induction of LM and the other leading to the induction of FN and CEA.


Nose to brain delivery in rats: Effect of surface charge of rhodamine B labeled nanocarriers on brain subregion localization.
Nose to brain delivery and nanotechnology are the combination of innovative strategies for molecules to reach the brain and to bypass blood brain barriers. In this work we investigated the fate of two rhodamine B labeled polymeric nanoparticles (Z-ave <250nm) of opposite surface charge in different areas of the brain after intranasal administration in rats. A preliminary screening was carried out to select the suitable positive (chitosan/poly-l-lactide-co-glycolide) nanocarrier through photon correlation spectroscopy and turbiscan. Physico-chemical and technological characterizations of poly-l-lactide-co-glycolide (negative) and chitosan/poly-l-lactide-co-glycolide (positive) fluorescent labeled nanoparticles were performed. The animals were allocated to three groups receiving negative and positive polymeric nanoparticles via single intranasal administration or no treatment. The localization of both nanocarriers in different brain areas was detected using fluorescent microscopy. Our data revealed that both nanocarriers reach the brain and are able to persist in the brain up to 48h after intranasal administration. Surface charge influenced the involved pathways in their translocation from the nasal cavity to the central nervous system. The positive charge of nanoparticles slows down brain reaching and the trigeminal pathway is involved, while the olfactory pathway may be responsible for the transport of negatively charged nanoparticles, and systemic pathways are not excluded.


Bovine quantitative trait loci analysis for growth, carcass, and meat quality traits in an F2 population from a cross between Japanese Black and Limousin.
A genome-wide scan for QTL affecting economically important traits in beef production was performed using an F(2) resource family from a Japanese Black x Limousin cross, where 186 F(2) animals were measured for growth, carcass, and meat-quality traits. All family members were genotyped for 313 informative microsatellite markers that spanned 2,382 cM of bovine autosomes. The centromeric region of BTA2 contained significant QTL (i.e., exceeding the genome-wide 5% threshold) for 5 carcass grading traits [LM area, beef marbling standards (BMS) number, luster, quality grade, and firmness), 8 computer image analysis (CIA) traits [LM lean area, ratio of fat area (RFA) to LM area, LM area, RFA to musculus (M.) trapezius area, M. trapezius lean area, M. semispinalis lean area, RFA to M. semispinalis area, and RFA to M. semispinalis capitis area], and 5 meat quality traits (contents of CP, crude fat, moisture, C16:1, and C18:2 of LM). A significant QTL for withers height was detected at 80.3 cM on BTA5. We detected significant QTL for the C14:0 content in backfat and C14:0 and C14:1 content in intermuscular fat around the 62.3 to 71.0 cM region on BTA19 and for C14:0, C14:1, C18:1, and C16:0 content and ratio of total unsaturated fatty acid content to total SFA content in intramuscular fat at 2 different regions on BTA19 (41.1 cM for C14:1 and 62.3 cM for the other 4 traits). Overall, we identified 9 significant QTL regions controlling 27 traits with genome-wide significance of 5%; of these, 22 traits exceeded the 1% genome-wide threshold. Some of the QTL affecting meat quality traits detected in this study might be the same QTL as previously reported. The QTL we identified need to be validated in commercial Japanese Black cattle populations.


Early transposition of the sartorius muscle for exposed patent infrainguinal bypass grafts.
The traditional approach for patent and exposed and infected infrainguinal bypass grafts in the groin has included wide operative debridement and secondary or delayed primary closure. However, this has been associated with significant risk of further contamination and length of stay. The authors reviewed their experience using the wide debridement, sartorius muscle flap transposition, and primary wound closure as an alternative. During the past 5 years, they have had 50 patients with major wound necrosis or infection in the groin or thigh with the graft or native artery being exposed after debridement. This group included 28 men; 74% of the patients had hypertension, 58% had diabetes, and 20% had renal failure. The grafts were split evenly between native vein and prosthetic material. After wide debridement, closure was performed by the vascular surgeon using the sartorius muscle flap. Postoperatively, there was an 8% major amputation rate and a 12% mortality rate in the first 30 days. One patient developed a pseudoaneurysm 5 weeks after placement of the flap. This patient underwent removal of the infected polytetrafluoroethylene graft with ligation of the common femoral artery. None of the procedures have resulted in further systemic or graft sepsis. None have resulted in arterial or graft blowout. Follow-up was for an average of 18 months. Closure of groin and thigh wounds with exposed bypass graft or native artery can be safely performed with the sartorius muscle flap with excellent results. The length of stay of these patients compared to historical controls is acceptable. Furthermore, the chance of infection of the native artery or bypass may be reduced. Familiarity with this simple technique can be a valuable tool for the vascular surgeon.


Spermatogonial stem cell biology in the bull: development of isolation, culture, and transplantation methodologies and their potential impacts on cattle production.
Widespread adoption of artificial insemination as a breeding practice has allowed for expanded use of desirable genetics from specific sires and greatly influenced production traits in dairy cattle populations worldwide. In fact, the average dairy cow in the US in 2009 produced 4.5 times more milk than in 1940 when commercialization of artificial insemination began. While many factors have contributed to this rapid increase in levels of milk production, genetic gain through expanded utilization of germlines from specific sires has been a major contribution. In comparison, use of artificial insemination in beef cattle populations has been limited due to challenges with implementing intensive management strategies required for success. Thus, there is need for alternative reproductive tools to expand use of desirable male genetics in the beef cattle industry. The process of sperm production, termed spermatogenesis, is supported by a tissue-specific stem cell population referred to as spermatogonial stem cells (SSCs). These unique cells have the capacity for infinite self-renewal and long-term regeneration of spermatogenesis following transplantation. In rodents, methods for isolating, culturing, and transplanting SSCs have been devised. For beef cattle, transplanting SSCs isolated from a donor male into the testes of recipient males in which donor-derived spermatogenesis occurs and offspring with donor genetics are produced from natural breeding has great potential as an alternative to artificial insemination. This potential reproductive strategy would allow for expansive use of genetics from desirable sires that overcomes the logistical challenges of artificial insemination. Translation of the methods devised for rodents to cattle is at the forefront of development. Devising means for isolating an SSC-enriched cell fraction from donor testes and identifying conditions that support long-term maintenance and proliferation of bovine SSCs in vitro are two tools that would greatly accelerate the pace at which transplantation will become a commercially viable option for cattle industries. Recent studies showed that expression of THY1 by SSCs is a conserved phenotype between rodents and cattle, and selection of the THY1 + fraction from donor testes can be used for isolating an SSC-enriched germ cell population. In addition, the conditions devised for expanding the number of rodent SSCs in vitro continues to serve as the basis for developing conditions that support bovine SSCs. With these tools in hand major advances in developing implementable reproductive tools with SSCs for commercial cattle production will be made in the coming decade.


Rhodium-Catalyzed Enantioselective Isomerization of Secondary Allylic Alcohols.
The first catalytic enantioselective isomerization of secondary allylic alcohols to access ketones with a α-tertiary stereocenter is presented. The racemic allylic alcohol substrates can be converted to the enantioenriched ketone products in a stereoconvergent fashion. The use of commercially available catalysts and mild reaction conditions makes this an attractive method in stereoselective synthesis.


Expression and purification of recombinant polyomavirus VP2 protein and its interactions with polyomavirus proteins.
Recombinant polyomavirus VP2 protein was expressed in Escherichia coli (RK1448), using the recombinant expression system pFPYV2. Recombinant VP2 was purified to near homogeneity by sodium dodecyl sulfate-polyacrylamide gel electrophoresis, electroelution, and Extracti-Gel chromatography. Polyclonal serum to this protein which reacted specifically with recombinant VP2 as well as polyomavirus virion VP2 and VP3 on Western blots (immunoblots) was produced. Purified VP2 was used to establish an in vitro protein-protein interaction assay with polyomavirus structural proteins and purified recombinant VP1. Recombinant VP2 interacted with recombinant VP1, virion VP1, and the four virion histones. Recombinant VP1 coimmunoprecipitated with recombinant VP2 or truncated VP2 (delta C12VP2), which lacked the carboxy-terminal 12 amino acids. These experiments confirmed the interaction between VP1 and VP2 and revealed that the carboxyterminal 12 amino acids of VP2 and VP3 were not necessary for formation of this interaction. In vivo VP1-VP2 interaction study accomplished by cotransfection of COS-7 cells with VP2 and truncated VP1 (delta N11VP1) lacking the nuclear localization signal demonstrated that VP2 was capable of translocating delta N11VP1 into the nucleus. These studies suggest that complexes of VP1 and VP2 may be formed in the cytoplasm and cotransported to the nucleus for virion assembly to occur.


Therapeutic potential of erythropoietin in cardiovascular disease: erythropoiesis and beyond.
Erythropoietin (EPO) is a glycoprotein hormone implicated in the regulation of red blood cell production. Anemia is common in chronic heart failure (CHF) patients and associated with an inappropriately low EPO-production, suggesting a role for its recombinant human form (rhEPO) in treatment. Although safety concerns have been raised regarding treatment with rhEPO in patients with chronic kidney disease, treatment with rhEPO in patients with CHF has so far been safe and well tolerated. The effect of rhEPO on outcome in anemic CHF patients is under investigation in a phase III clinical trial. In addition to its erythropoietic effects, EPO has been detected in the cardiovascular system, fueling intense research into possible non-hematopoietic effects. EPO has been shown to exert protective effects on the heart during acute myocardial ischemia and improve cardiac function in experimental CHF. Acute protection is mediated through reduction of apoptotic cell death. Improvement of cardiac function in CHF is related to myocardial neovascularization. EPO exhibits a vast array of beneficial effects in cardiovascular disease. In addition to the correction of anemia in CHF, rhEPO might benefit patients with cardiovascular disease.


Correlation Between Histological Diagnosis and Mutational Panel Testing of Thyroid Nodules: A Two-Year Institutional Experience.
Indeterminate thyroid fine-needle aspiration (FNA) cytology, including atypia of undetermined significance (AUS/FLUS) and suspicious for follicular neoplasm (SFN), continues to generate uncertainty about the presence of malignancy, resulting in repeated follow-up, repeat FNA, or diagnostic surgery. Mutational panel testing may improve the malignancy risk prediction in indeterminate nodules, but the general application of such testing has not been investigated extensively. A retrospective review was performed of all patients undergoing thyroidectomy at a tertiary care facility over a two-year period. Mutational panel test results, when present, were analyzed relative to FNA cytologic result and surgical histopathologic diagnosis. Malignancy rates, sensitivity, specificity, positive predictive values (PPV), negative predictive values (NPV) and positive and negative likelihood ratios (LR) were calculated. A total of 261 operated thyroid nodules had the following initial FNA cytology results: 2% non-diagnostic, 23% benign, 28% AUS/FLUS, 11% SFN, 9% suspicious for malignancy (SUSP), and 27% malignant. The histopathologic malignancy rate was 48%, subcategorized by cytology into benign 7%, AUS/FLUS 30%, SFN 38%, and SUSP 83%. Mutations were more frequent in indeterminate nodules that were histologically malignant versus benign (p < 0.0001) or versus adenoma (p = 0.001). Mutational analysis in 44 AUS/FLUS nodules resulted in a malignancy detection sensitivity of 85%, a specificity of 65%, a PPV of 50%, a NPV of 91%, and a positive LR of 2.4. In 12 SFN nodules analyzed with ThyroSeq(®) testing, sensitivity was 100%, specificity 57%, PPV 63%, NPV 100%, and LR 2.3. Performance of the seven-gene mutational panel was not significantly different from the ThyroSeq(®) panel in the AUS/FLUS group. The malignancy yield, comparing the mutation positive AUS/FLUS group with the untested AUS/FLUS surgical cohort, did not reach statistical significance (p = 0.17). In a surgical cohort, a similar NPV but a lower PPV was found with the use of mutational panel testing compared to the published literature. Following the identification of a mutation, the prevalence of malignancy in the AUS/FLUS or SFN category was increased by nearly 15% to 45% and 53%, respectively. Further study is needed to confirm these results and to analyze clinical outcome subcategories relative to the utility of mutational testing.


Effect of adhesive application methods on bond strength to bovine enamel.
Single-step self-etch adhesive systems have been developed to simplify and shorten bonding procedures. With the gain in popularity of these simplified systems, their reliability has become a focus of interest. The purpose of this study was to determine the effect of adhesive application method on enamel bond strength. Two commercial single-step self-etch adhesive systems, Clearfil tri-S Bond, and G-Bond, were used. Bovine mandibular incisors were mounted in self-curing resin and the facial enamel surfaces were ground wet on 600-grit SiC paper. Adhesives were only applied without agitation (inactive) or were agitated by a brush (active), and resin composites were condensed into the mold on the enamel surface and light-activated. Ten specimens per test group were stored in water at 37 degrees C for 24 h, then shear-tested at a cross-head speed of 1.0 mm/min. Two-way ANOVA followed by the Tukey HSD test were used. The bond strengths for active application were higher than those for inactive application. Significant differences were found for both adhesive systems. From the results of this study, active application of single-step self-etch adhesive may help to ensure the creation of a roughened enamel surface and enhance the penetration of resin monomer into the subsurface demineralized enamel.


Biallelic polymorphism in the intron region of beta-tubulin gene of Cryptosporidium parasites.
Nucleotide sequencing of polymerase chain reaction amplified intron region of the Cryptosporidium parvum beta-tubulin gene in 26 human and 15 animal isolates revealed distinct genetic polymorphism between the human and bovine genotypes. The separation of 2 genotypes of C. parvum is in agreement with our previous genotyping data based on the thrombospondin-related adhesion protein (TRAP-C2) gene, indicating these genotype characteristics are linked at 2 genetic loci. Characterization of Cryptosporidium muris and Cryptosporidium serpentis has further shown that non-parvum Cryptosporidium parasites have beta-tubulin intron sequences identical to bovine genotype of C. parvum. Thus, results of this study confirm the lineage of 2 genotypes of C. parvum at 2 genetic loci and suggest a need for extensive characterization of various Cryptosporidium spp.


Auditory evoked responses in postmenopausal women on hormone replacement therapy.
The effect of hormone replacement therapy (HRT) was studied in 32 postmenopausal women on their auditory Evoked Potentials i.e. auditory brainstem response (ABR), Middle latency response (MLR) & slow vertex response (SVR). Recordings were done on computerized evoked potential recorder using 10/20 system of electrode placement and standard click stimuli. A significant improvement in neural transmission was observed as was evidenced by decrease in the ABR wave latencies I, III, IV & V and interpeak latency III-V and I-V after 6 months of HRT. A similar significant decrease was observed in MLR wave latencies of Po, Na & Pa. The SVR wave latencies although found to be decreased after HRT, could not reach the level of statistical significance. There was a significant inverse correlation obtained between latencies of wave I in ABR, Po in MLR and serum estradiol. The results indicate the effect of sex hormone in improving transmission in auditory pathway from periphery through brainstem, thalamus upto cortex. However slow vertex responses indicate that auditory association areas are not much affected. This might have bearing on improvement of neuropsychological functions in postmenopausal women on HRT.


Coexpression of growth arrest-specific gene 6 and receptor tyrosine kinases, Axl and Sky, in human uterine endometrium and ovarian endometriosis.
We demonstrated the expression of Gas6, the protein product of the growth arrest-specific gene 6 (gas6) and a member of the vitamin K-dependent protein family, and its receptor tyrosine kinases, Axl and Sky, in human uterine and ovarian endometriotic endometria using RT-PCR-Southern blot analysis and immunohistochemistry. Gas6, Axl and Sky mRNA were detected in all samples analysed. There was no significant difference between the levels of Sky mRNA in normal uterine and endometriotic endometria; however, the levels of Gas6 and Axl mRNA in endometriotic endometria were significantly higher than in normal endometria. These mRNA levels showed no significant alteration during the menstrual cycle. In the immunohistochemical study, Gas6, Axl and Sky were found in endometrial glandular cells and stromal cells in all samples analysed. This study demonstrates the coexpression of receptor tyrosine kinases and their ligand, Gas6, in normal uterine and ovarian endometriotic endometria, and the overexpression of Axl and Gas6 in endometriotic endometria. It is suggested that Gas6 and Axl signal transduction is aberrantly stimulated in endometriotic endometria, and is plausibly related to its growth potential.


Requirement for, and patterns of, pyruvate and glutamine metabolism in the domestic dog oocyte in vitro.
Supplementation of energy substrates to culture medium is essential for resumption and completion of meiosis in vitro for many mammalian species. Objectives were to study the dog oocyte, specifically the influences of pyruvate and glutamine on maturation and the utilization of these two substrates at various developmental stages and incubation times. Ovarian oocytes (n=681) were obtained from spayed bitches and cultured for 48 hr in TCM 199 medium containing various concentrations of pyruvate (0-2.5 mM) and glutamine (0-4 mM) before being assessed for nuclear status. For analyzing metabolic activity, 259 dog oocytes were cultured for 0, 12, 24, 36, or 48 hr, assessed for pyruvate and glutamine metabolism using the hanging drop method and then evaluated for nuclear status. Neither pyruvate nor glutamine had influence (P > 0.05) on oocyte maturation in vitro (IVM). However, both culture interval and meiotic status influenced pyruvate uptake (P < 0.05). Specifically, pyruvate uptake declined as the oocyte progressed from the germinal vesicle (GV) to metaphase II (MII) stage. Glutamine oxidation decreased as culture duration progressed (P < 0.05). In summary, pyruvate or glutamine is not required to promote successful IVM of dog oocytes. But, both substrates are being metabolized, and in patterns different to the domestic cat, another carnivore species. Pyruvate played an important role earlier in the maturational process, and less glutamine was oxidized as the oocyte neared nuclear maturation. These variations emphasize the importance of defining species specificities in carnivores before expecting consistently successful IVM/IVF.


Simplified phase-recovery method in temporal speckle pattern interferometry.
A simplified method for object phase recovering is implemented in temporal speckle pattern interferometry when the employed interferometer admits the introduction of a temporal carrier, and the well-known two-beam interferometry equation is verified. The spatiotemporal evolution of the object phase is isolated by modulating the acquired interferometric intensity signals with a known temporal carrier in order to carry out its analysis by using a bivariate empirical mode decomposition framework that avoids the application of the Hilbert transform, which is not suitable for intensity signals with abrupt fluctuations. The advantages and limitations of this technique are analyzed and discussed by comparing computation time and phase recovery capability with well-known phase-retrieval methods by means of numerical simulations and experimental data.


The Role of Mutation Rates of GNAQ or GNA11 in Cases of Uveal Melanoma in Japan.
GNAQ and GNA11 mutations are thought to be important for the tumorigenesis of uveal melanoma. Although previous studies have reported on mutation rates in cases of uveal melanoma, presently, no such report for the Japanese population exists. In this study, we examined the frequency of GNAQ and GNA11 somatic mutations in cases of uveal melanoma in Japan and their relationship with clinicopathologic features or Ki-67-positive cell rates (Ki-67 labeling index: Ki-67 LI) using immunofluorescence methods. The study involved 19 cases of uveal melanoma. We extracted the template DNA from formalin-fixed, paraffin-embedded specimens using a DNA extraction kit. We amplified the DNA sequences of GNAQ and GNA11 using polymerase chain reaction and analyzed mutations by direct sequencing. We evaluated Ki-67 LI using immunofluorescence methods. The frequencies of GNAQ and GNA11 somatic mutations were 26.3% (5/19) and 31.6% (6/19), respectively. The GNAQ and GNA11 mutations were mutually exclusive, as indicated in previous reports. The frequency of GNA11 mutations was significantly higher in epithelioid cells; however, no significant association between GNAQ mutations and cell type was evident, and there was no significant difference in Ki-67 LI between the mutation-positive and mutation-negative tumors. GNAQ and GNA11 mutations were identified in cases of uveal melanoma in Japan, although at lower frequencies than in white counterparts. The mutation frequency of GNA11 was significantly higher in epithelioid cells.


Wellness and Impairment Content in Schools of Medicine Curricula in the United States and Canada.
Medical students experience numerous stressors, ranging from academic demands to financial strain. These stressors contribute to medical students having a substantial incidence of psychological problems, substance abuse, and seeking of mental health treatment. Left untreated, these problems can result in dysfunctional habit development and subsequent professional impairment. Research has demonstrated the benefits of wellness-impairment educational programs in medical education, but it is unknown to what degree the topics of wellness and impairment are included in medical school curricula. To assess this, a 13-item survey instrument was sent to associate deans in 142 schools of allopathic medicine; 71 (50.0%) responded. The majority of respondents reported that physician impairment (95.8%) and wellness (77.5%) are addressed in their school of medicine curricula, although the degree to which these topics were included varied. Access to other health-promoting resources on campus was also assessed and is discussed. Results suggested that there is a disparity between primary and secondary prevention approaches on school of medicine campuses. Implications for curricula and directions for future research are discussed.


[Research progress on chemical constituents, pharmacological mechanism and clinical application of Guizhi decoction].
Guizhi Decoction was one of the most commonly used traditional Chinese Medicine which possesses the effects of "jie-ji-fa-biao, regulating Ying and Wei". It was mainly used to treat mind-cold due to exogenous evils such as fever, headache, sweating, hate the wind, et al. Modern studies indicated that the chemical constituents of Guizhi decoction mainly include phenylpropanoid, monoterpenes, organic acids, flavonoids, triterpenoid saponins and so on. Pharmacological experimental studies had shown that Guizhi decoction could play a big role in dual-directional regulation on sweat gland, body temperature, immune function, gastrointestinal peristalsis, and blood pressure, and could also play the role of anti-inflammatory, antibacterial, antiviral, anti-allergic, analgesic, hypoglycemic, and cardiovascular protection. Many diseases such as internal, external, gynecological and pediatric diseases were treated in the clinical by using Guizhi decoction and its analogous formulae involving circulatory, immune, urinary, reproductive, endocrine, digestive, nervous and other systems. This article reviews the latest research progress of Guizhi decoction from three aspects: chemical constituents, pharmacological mechanism and clinical application. It will provide reference for further research and development of Guizhi decoction.