The association of anthropometric measurements and lipid profiles in Turkish hypertensive adults.
Few studies have associated anthropometric measurements and lipid profile with hypertension in adult populations and to the best of our knowledge none has been done in Turkey To relate anthropometric derivatives of overweight/obesity with hyperlipidemia status in a group of Turkish hypertensive adults. Six hundred forty nine (307 male, 342 female) hypertensive adults aged between 20 and 64 years were included in the study. The mean systolic and diastolic blood pressure (BP) of participants were measured as 147.6 ± 17.2 and 91.4 ± 10.4 mmHg for males and 149.9 ± 16.3 and 91.1 ± 9.4 mmHg for females, respectively. With respect to BMI classification systolic BP was significantly higher in obese males and females, and diastolic BP was only higher in obese females (p<0.05). According to BMIs for lipid profile, high-density lipoprotein-cholesterol (HDL-C), total cholesterol (TC) levels were found to be lower in normal females than other BMI groups. Age and waist circumference (WC) in particular was the most related factor for systolic and diastolic BP in both genders (p<0.05). This study indicates most hypertensive adults surveyed were overweight and obese. Furthermore, age and WC were the important factors that affects the systolic and diastolic BP in both genders.


Naturally Occurring Microbiota in Dengue Vector Mosquito Breeding Habitats and Their Use as Diet Organisms by Developing Larvae in the Kandy District, Sri Lanka.
Naturally occurring microbiota in mosquito larval habitats are among biotic factors which affect the population dynamics of developing larvae. Many microbiota species serve as food items for vector mosquito larvae, and food limitations within habitats adversely affect larval survival, developmental rate, adult fitness, and thereby vector competence. Therefore, identification of microbiota as associates with larvae reveals their relationship between each other as parasites, pathogens, epibionts, or diet organisms. Analysis of associated microbiota species in the dengue vector larval breeding habitats (n = 40) and the mosquito larval gut content were conducted in Kandy District in Sri Lanka. Study revealed that a total of 22 microbiota species belong to nine phyla (Amoebozoa, Bacillariophyta, Ciliophora, Chlorophyta, Sarcodina, Cyanobacteria/Cyanophyta, Euglenozoa, Ochrophyta/Heterokontophyta, and Rotifera) were encountered from different Ae. aegypti mosquito breeding habitats while 26 microbiota species that belonged to ten phyla were recorded from Ae. albopictus mosquito breeding habitats with one additional phylum Arthropoda. Considering Ae. aegypti breeding habitats, only Philodina citrina in low roof gutters existed as constant species. Considering Aedes albopictus breeding habitats, Volvox aureus in plastic containers, Lecane luna in coconut shells, Phacus pleuronectes in concrete slabs, and Pinnularia sp. in tree holes existed as constant species. The rest of the microbiota existed as common or accidental/rare species in a variety of habitat types. The Shannon-Weiner diversity (21.01 and 19.36) and gamma diversity (eight and eight) of the microbiota associated with Ae. aegypti and Ae. albopictus larvae, respectively, in ponds were found to be higher than other types of breeding habitats recorded during the study. Twelve microbiota species were recorded from larval gut analysis as food organisms of both species of mosquito larvae. However, the distribution of gut microbiota species differed between Ae. aegypti and Ae. albopictus (Chi - square = 21.294, P = 0.002). Identification of microbiota as food items of vector mosquito larvae led to a focus on larval food limitation by introducing food competitors, which could be a potential additional tool for integrated vector control approaches within the country.


A randomized trial of a nursing intervention for HIV disease management among persons with serious mental illness.
The heightened risk of persons with serious mental illness to contract and transmit HIV is recognized as a public health problem. Persons with HIV and mental illness may be at risk for poor treatment adherence, development of treatment-resistant virus, and worse outcomes. The objective of this study was to test the effectiveness of a community-based advanced practice nurse (APN) intervention (PATH, Preventing AIDS Through Health) to promote adherence to HIV and psychiatric treatment regimens. Community-dwelling HIV-positive participants with co-occurring serious mental illnesses (N=238) were recruited from community HIV provider agencies from 2004 to 2008 to participate in the randomized controlled trial. Participants in the intervention group (N=128) were assigned an APN who provided community-based care management at a minimum of one visit per week and coordinated clients' medical and mental health care for one year. Viral load and CD4 cell count were evaluated at baseline and 12 months. Longitudinal models for continuous log viral load showed that compared with the control group, the intervention group exhibited a significantly greater reduction in log viral load at 12 months (d=-.361 log 10 copies per milliliter, p<.001). Differences in CD4 counts from baseline to 12 months were not statistically significant. This project demonstrated the effectiveness of community-based APNs in delivering a tailored intervention to improve outcomes of individuals with HIV and co-occurring serious mental illnesses. Persons with these co-occurring conditions can be successfully treated; with appropriate supportive services, their viral loads can be reduced.


Frontal atrophy correlates with behavioural changes in progressive supranuclear palsy.
Regional brain volumes were measured in 21 patients with progressive supranuclear palsy (PSP), 17 patients with Parkinson's disease and 23 controls using 3D MRI-based volumetry. Cortical, subcortical and ventricular volume measures were correlated with global indices of motor disability and cognitive disturbance. All MRI measures, including hippocampal volume, were preserved in Parkinson's disease. Patients with PSP could be distinguished from both Parkinson's disease and controls by whole brain volume loss, ventricular dilatation and disproportionate atrophy of the frontal cortex. Caudate nucleus volume loss additionally differentiated PSP from controls, but was modest in severity and proportionate to whole brain volume loss. The present study identifies disease-specific differences in the topography of brain atrophy between PSP and Parkinson's disease, and has potential implications for the in vivo radiological differentiation of these two disorders. In PSP, the variance in frontal grey matter volume related to measures of behavioural disturbance, confirming the use of behavioural tests for ante-mortem case differentiation and suggesting that intrinsic cortical deficits contribute to these clinical disturbances.


Quantitative inference of cellular parameters from microfluidic cell culture systems.
Microfluidic cell culture systems offer a convenient way to measure cell biophysical parameters in conditions close to the physiological environment. We demonstrate the application of a mathematical model describing the spatial distribution of nutrient and growth factor concentrations in inferring cellular oxygen uptake rates from experimental measurements. We use experimental measurements of oxygen concentrations in a poly(dimethylsiloxane) (PDMS) microreactor culturing human hepatocellular liver carcinoma cells (HepG2) to infer quantitative information on cellular oxygen uptake rates. We use a novel microchannel design to avoid the parameter correlation problem associated with simultaneous cellular uptake and diffusion of oxygen through the PDMS surface. We find that the cellular uptake of oxygen is dependent on the cell density and can be modeled using a logistic term in the Michaelis-Menten equation. Our results are significant not only for the development of novel assays to quantitatively infer cell response to stimuli, but also for the development, design, and optimization of novel in vitro systems for drug discovery and tissue engineering.


Performance of a new symptom checker in patient triage: Canadian cohort study.
Computerized algorithms known as symptom checkers aim to help patients decide what to do should they have a new medical concern. However, despite widespread implementation, most studies on symptom checkers have involved simulated patients. Only limited evidence currently exists about symptom checker safety or accuracy when used by real patients. We developed a new prototype symptom checker and assessed its safety and accuracy in a prospective cohort of patients presenting to primary care and emergency departments with new medical concerns. A prospective cohort study was done to assess the prototype's performance. The cohort consisted of adult patients (≥16 years old) who presented to hospital emergency departments and family physician clinics. Primary outcomes were safety and accuracy of triage recommendations to seek hospital care, seek primary care, or manage symptoms at home. Data from 281 hospital patients and 300 clinic patients were collected and analyzed. Sensitivity to emergencies was 100% (10/10 encounters). Sensitivity to urgencies was 90% (73/81) and 97% (34/35) for hospital and primary care patients, respectively. The prototype was significantly more accurate than patients at triage (73% versus 58%, p<0.01). Compliance with triage recommendations in this cohort using this iteration of the symptom checker would have reduced hospital visits by 55% but cause potential harm in 2-3% from delay in care. The prototype symptom checker was superior to patients in deciding the most appropriate treatment setting for medical issues. This symptom checker could reduce a significant number of unnecessary hospital visits, with accuracy and safety outcomes comparable to existing data on telephone triage.


Experiment research on inhibition of glioma with sTRAIL in vitro.
We report that adenovirus mediated TNF-related apoptosis-inducing ligand (TRAIL) influenced the cell growth and cell cycle in the glioma cells in vitro. After being infected with the Ad-sTRAIL, U251 cell growth was inhibited. The expression of sTRAIL was detected using immunofluorescence. The higher rate of apoptosis was demonstrated using short-term microculture tetrazoliun (MTT) assay and flow cytometry. The rate of Ad-sTRAIL-inducing U251 cell apoptosis was increased depending on the dosage and the time. The apoptosis of G0/G1 and S phase cells was more significant than that of the control groups. The growth and proliferation of U251 cell line was inhibited after the infection of Ad-sTRAIL. It is dose- and time dependent.


Neonatal CPAP for Respiratory Distress Across Malawi and Mortality.
Our aim in this observational study was to monitor continuous positive airway pressure (CPAP) usage and outcomes in newborn wards at 26 government hospitals in Malawi after the introduction of CPAP as part of a quality-improvement initiative. CPAP was implemented in 3 phases from 2013 through 2015. Survival to discharge was analyzed for neonates treated with nasal oxygen and/or CPAP with admission weights of 1 to 2.49 kg at 24 government hospitals with transfer rates <15%. This analysis includes neonates admitted with respiratory illness for 5.5 months before (621 neonates) and 15 months immediately after CPAP implementation (1836 neonates). A follow-up data analysis was completed for neonates treated with CPAP at all hospitals during an additional 11 months (194 neonates). On implementation of CPAP, survival to discharge improved for all neonates admitted with respiratory distress (48.6% vs 54.5%; P = .012) and for those diagnosed with respiratory distress syndrome (39.8% vs 48.3%; P = .042). There were no significant differences in outcomes for neonates treated with CPAP during the implementation and follow-up periods. Hypothermia on admission was pervasive and associated with poor outcomes. Neonates with normal mean temperatures during CPAP treatment experienced the highest survival rates (65.7% for all neonates treated with CPAP and 60.0% for those diagnosed with respiratory distress syndrome). A nurse-led CPAP service can improve outcomes for neonates in respiratory distress in low-resource settings. However, the results show that real-world improvements in survival may be limited without access to comprehensive newborn care, especially for small and sick infants.


Sassafras tea and diaphoresis.
A patient whose main symptom is sweating can present a diagnostic challenge. Dr Haines describes a case in which diaphoresis was caused not by a conventional medication or illness but rather by a life-style change in which the patient began consuming sassafras tea.


Models and corrections: Range separation for electronic interaction-Lessons from density functional theory.
Model Hamiltonians with long-range interaction yield energies are corrected taking into account the universal behavior of the electron-electron interaction at a short range. Although the intention of this paper is to explore the foundations of using density functionals combined with range separation, the approximations presented can be used without them, as illustrated by a calculation on harmonium. In the regime, when the model system approaches the Coulomb system, they allow the calculation of ground states, excited states, and properties, without making use of the Hohenberg-Kohn theorem. Asymptotically, the technique is improvable and allows for error estimates that can validate the results. Some considerations for correcting the errors of finite basis sets in this spirit are also presented. Being related to the present understanding of density functional approximations, the results are comparable to those obtained with the latter, as long as these are accurate.


High body mass index and risk of exacerbations and pneumonias in individuals with chronic obstructive pulmonary disease: observational and genetic risk estimates from the Copenhagen General Population Study.
In the clinic, the combination of obesity and chronic obstructive pulmonary disease (COPD) has been increasing. However, whether high body mass index (BMI) affects the risk of exacerbations and pneumonias in individuals with COPD is presently unknown. Genetics can be used to assess the causal role of high BMI in exacerbations and pneumonias in individuals with COPD. We tested the hypothesis that high BMI is associated with an increased risk of exacerbations and pneumonias in individuals with COPD, both observationally and genetically. We genotyped 93 894 individuals of Danish descent, aged 20-100 years, from the Copenhagen General Population Study, for FTO (rs9939609), MC4R (rs17782313) and TMEM18 (rs6548238), and created an allele score. A total of 10 883 individuals had spirometric COPD with forced expiratory volume in 1 s (FEV1) / forced vital capacity (FVC) < lower limit of normal (LLN). In these individuals, we observed 1453 exacerbations and 3390 pneumonias during 4.7 years of follow-up. For each increase in allele score, BMI was 0.28 kg/m2 [95% confidence interval (CI): 0.25-0.30) higher. Age- and sex-adjusted genetic hazard ratios (HRs) per one allele score increase in individuals with COPD were 1.13 (1.01-1.27) for exacerbations, 1.10 (1.03-1.19) for pneumonias and 1.12 (1.04-1.21) for exacerbations and/or pneumonias. Corresponding multivariable adjusted observational HRs per unit (kg/m2) BMI increase were 0.98 (0.95-1.01), 0.99 (0.96-1.03) and 0.99 (0.96-1.01), respectively. Genetically determined high BMI was associated with an increased risk of recurrent exacerbations and pneumonias in individuals with COPD, whereas this was not the case for observationally determined high BMI. The genetic data are compatible with the notion that high BMI leads to increased risk of exacerbations and pneumonias in individuals with COPD.


Achieving sub-100 ps time-of-flight resolution in thick LSO positron emission tomography while reducing system cost: a Monte Carlo study.
Evaluating the time-of-flight (TOF) resolution improvement that could be obtained using an easy crystal block modification which enables depth of interaction (DOI) assessment and simplifies the detector assembling process. A fast optical Monte Carlo (MC) code was developed. The code was evaluated versus measurements of the energy resolution, number of detected scintillation photons and TOF resolution (TOFr) reported for different crystal photodetector setups. Then, MC simulations were performed for a modified crystal block section of 8 × 8 mm2 in which two partial saw cuts allow light sharing between four detector pixels with a strong dependence on the DOI. Relative differences between MC simulations and reported measurements were always below 10% for any quantities. The simulations showed that the best TOFr was obtained by leaving the partial saw cuts empty. This feature results from the fact that for a slant angle lower than 56 degrees, the scintillation photons undergo a lossless total reflection at the L[Y]SO → air boundary, which is hardly achievable using a reflector material. According to the simulations, this approach allows a TOFr improvement from 163 ps to 90 ps full width at half-maximum using a 22 mm thick LSO 0.2%Ca:Ce crystal coupled to a FBK-NUV-HD silicon photomultiplier. Sub-100 ps TOFr using thick LSO crystal appears achievable using this simple crystal block modification. The method reduces by a factor of 4 the number of crystal pixels to be covered by a reflective material and afterwards joined together. As clinical positron emission tomography contains about 60 000 crystal pixels, this benefit would reduce the assembling cost.


Extracellular Vesicles in Rheumatoid Arthritis and Systemic Lupus Erythematosus: Functions and Applications.
In the last two decades, extracellular vesicles (EVs) have aroused wide interest among researchers in basic and clinical research. EVs, small membrane vesicles are released by almost all kinds of cells into the extracellular environment. According to many recent studies, EVs participate in immunomodulation and play an important role in the pathogenesis of autoimmune diseases. In addition, EVs have great potential in the diagnosis and therapy of autoimmune diseases. Here, we reviewed the latest research advances on the functions and mechanisms of EVs and their roles in the pathogenesis, diagnosis, and treatment of rheumatoid arthritis and systemic lupus erythematosus.


Challenges in making a business case for effective pain management in nursing homes.
The lack of a systematic and comprehensive pain management program is a common quality problem in nursing homes. The purpose of this article is to address the business case for effective pain management in this setting, including the conceptual domains and processes that should be considered in improving quality and reducing costs. Unfortunately, the literature contains very little to inform those working to implement effective and efficient pain management programs in nursing homes. This article suggests several strategies for establishing an internal business case to support the implementation of a comprehensive pain management program in a nursing home setting.


Evaluation, by a statistically designed experiment, of an experimental grade of microcrystalline cellulose, Avicel 955, as a technology to aid the production of pellets with high drug loading.
A statistically designed experiment has been undertaken to evaluate an experimental grade of microcrystalline cellulose (Avicel 955) as a technology to aid the production of pellets by extrusion spheronization of formulations with high drug load. An attempt has been made to relate the properties of the drugs to the ability to produce spherical pellets which have a narrow size distribution and are round, as assessed by a 2-dimensional shape factor by the process of extrusion/spheronization. Twenty drugs were tested at a level of 80%, and in all cases pellets could be produced. In some cases in terms of either size distribution or shape they were not of the highest quality. Nevertheless, a best level of water was identified for each drug. Principal component analysis did allow structuring of the data characterizing the process and the pellets, identifying a relationship between the water content and the steady state extrusion force as one component with the median pellet size and its interquartile range as the other. When multivariate analysis was used with the whole data set, it was not possible to relate the drug properties of pKa, freezing point depression, or solubility to the water content, steady state extrusion force, median pellet diameter, its interquartile range, and its shape satisfactorily. Thus other properties of the drug must be involved in the extrusion/spheronization process. Prediction of the best water content to use in a formulation was possible for 50% of the formulations by using a nonlinear model to relate the above drug properties to the water content.


Biotin sulfoxide reductase contributes to oxidative stress tolerance and virulence in Salmonella enterica serovar Typhimurium.
Oxidative stress converts sulfur residues of molecules like biotin and methionine into their oxidized forms. Here we show that the biotin sulfoxide reductase BisC of Salmonella enterica serovar Typhimurium (S. Typhimurium) repairs both oxidized biotin and oxidized methionine. Exposure to H2O2 in vitro reduced survival of a S. Typhimurium ΔbisC mutant. Furthermore, replication of the ΔbisC mutant inside IFN-γ activated macrophages was reduced. In vitro tolerance of the mutant to H2O2 was restored by plasmids carrying either bisC or msrA; the latter encodes a methioinine sulfoxide reductase. In contrast, the proliferation defect inside IFN-γ activated macrophages was rescued by bisC but not by msrA. Thus growth of the ΔbisC mutant in IFN-γ activated macrophages required repair of oxidized biotin. Both the ΔbisC and a biotin auxotrophic (ΔbioB) mutant were attenuated in mice, suggesting that besides biotin biosynthesis, biotin repair was essential for virulence of S. Typhimurium in vivo. Attenuation of the ΔbisC mutant was more pronounced in 129 mice that produce a stronger oxidative response. These results show that BisC is essential for full virulence of Salmonella by contributing to the defence of S. Typhimurium against host-derived stress, and provides an attractive drug target since it is not present in mammals.


Gene delivery of cytochrome p450 epoxygenase ameliorates monocrotaline-induced pulmonary artery hypertension in rats.
Pulmonary arterial hypertension (PAH) is a life-threatening disease that leads to progressive pulmonary hypertension, right heart failure, and death. Endothelial dysfunction and inflammation were implicated in the pathogenesis of PAH. Epoxyeicosatrienoic acids (EETs), products of the cytochrome P450 epoxygenase metabolism of arachidonic acid, are potent vasodilators that possess anti-inflammatory and other protective properties in endothelial cells. We investigated whether gene delivery with the human cytochrome P450 epoxygenase 2J2 (CYP2J2) ameliorates monocrotaline (MCT)-induced pulmonary hypertension in rats. Significant pulmonary hypertension developed 3 weeks after the administration of MCT, but gene therapy with CYP2J2 significantly attenuated the development of pulmonary hypertension and pulmonary vascular remodeling, without causing changes in systemic arterial pressure or heart rate. These effects were associated with increased pulmonary endothelial NO synthase (eNOS) expression and its activity, inhibition of inflammation in the lungs, and transforming growth factor (TGF)-β/type II bone morphogenetic protein receptor (BMPRII)-drosophila mothers against decapentaplegic proteins (Smads) signaling. Collectively, these data suggest that gene therapy with CYP2J2 may have potential as a novel therapeutic approach to this progressive and oftentimes lethal disorder.


Isolation and bicarbonate transport of chloroplast envelope membranes from species of differing net photosynthetic efficiency.
A three-phase discontinuous sucrose gradient yielded two fractions of chloroplast envelope membranes from spinach (Spinacia oleracea L.), sunflower (Helianthus annuus L.), and maize (Zea mays L., mesophyll and undifferentiated chloroplasts). These species were selected to represent plants with fast photorespiration and slow net photosynthesis, fast photorespiration yet fast net photosynthesis, and slow photorespiration and fast net photosynthesis, respectively. Buoyant densities were 1.08 and 1.11 g cm(-3). The light fraction contained primarily single (incomplete) membrane vesicles and the heavy fraction double (complete) ones. Enzymic, chemical, and electron microscopic examination of the complete envelope membranes showed a lack of microbial, microsomal, mitochondrial, and lamellar membrane contamination as well as stromal contamination. Envelope membranes for all species examined were found to contain 2 to 4% of the total chloroplast protein and yields of about 0.2 to 0.4 mg of protein were obtained from 40 g leaves. An Mg(2+)-dependent nonlatent ATPase, a marker enzyme for chloroplast envelope membranes, had the following activities (mumoles of phosphate released/hr(-1) mg protein(-1)): spinach, 77; sunflower, 163; old maize, 126; and young maize, 87. Bicarbonate transport was directly correlated with levels of ATPase activity in spinach and sunflower envelope membranes. Transport of HCO(3) (-) with sunflower envelope membranes approached that of young maize.


Abnormal cerebral vasodilation in aneurysmal subarachnoid hemorrhage: use of serial 133Xe cerebral blood flow measurement plus acetazolamide to assess cerebral vasospasm.
A patient with cerebral vasospasm following subarachnoid hemorrhage (SAH) was investigated by serial measurement of cerebral blood flow (CBF) using the xenon-133 emission tomography method. The CBF was measured before and after acetazolamide injection. On Day 2 after SAH, there was early local hyperperfusion in the middle cerebral artery (MCA) territory, ipsilateral to the left posterior communicating artery aneurysm. The regional CBF of this arterial territory decreased slightly after acetazolamide injection, probably because of vasoplegia and the "steal" phenomenon, and thus surgery was delayed. A right hemiplegia with aphasia and disturbed consciousness occurred 4 days later (on Day 6 after SAH) due to arterial vasospasm, despite treatment with a calcium-channel blocker. The initial hyperemia of the left MCA territory was followed by ischemia. The vasodilation induced by acetazolamide administration was significantly subnormal until Day 13, at which time CBF and vasoreactivity amplitude returned to normal and the patient's clinical condition improved. Surgery on Day 14 and outcome were without complication. It is concluded that serial CBF measurements plus acetazolamide injection are useful for monitoring the development of cerebral vasospasm to determine the most appropriate time for aneurysm surgery.


Fulminating influenza pneumonia in the elderly: a case demonstration.
An 82-year-old male Bangkokian with hypertension, diabetes mellitus, end-stage renal disease, and coronary artery disease for many years, was hospitalized due to deterioration of a 3-day influenza-like-illness with one-day chest oppression and respiratory failure. At the emergency room, oxygen saturation was 79% on room air Chest X-ray revealed bilateral diffuse pulmonary infiltrates. He was intubated and hemodialysis was initiated. Emergency coronary angiography revealed patent coronary artery. Sputum gram stain revealed numerous leukocytes with no bacteria. On day three of hospitalization, empiric treatment with oseltamivir and clarithromycin was administered Seventy-two hours later his clinical condition began to improve and fever subsided 7 days later Rapid test of tracheal secretion with immunofluorescence assay was positive for moderate amount of influenza A virus. Viral isolation yielded influenza A virus subtype H1N1. Review of in-patient records at this hospital using ICD-10 codes as J10 and J11 during 1995-2005, discovered 32 cases with claim diagnosis of influenza. However this is the first case with proven influenza pneumonia that was given empiric oseltamivir. Rapid deterioration of influenza-like illness due to human influenza virus in the elderly and pathogenesis of pulmonary in this case are discussed to alert physicians to recognize this dreadful illness and treat it in timely fashion.


Serotonin type 3 receptors modulate the aggression-stimulating effects of adolescent cocaine exposure in Syrian hamsters (Mesocricetus auratus).
Repeated cocaine (0.5 mg/kg) exposure throughout adolescence stimulates offensive aggression in hamsters. These studies examined whether the cocaine-induced aggressive response was regulated by serotonin Type 3 (5-HT(3)) receptor activity and correlated with altered 5-HT(3) receptor expression. Cocaine-treated Syrian hamsters (Mesocricetus auratus) were tested for aggression after the administration of either the 5-HT(3) antagonist 3-tropanylindole-3-carboxylate methiodide (tropisetron; 0.01-1.20 mg/kg) or the 5-HT(3) agonist l-(m-chlorophenyl)-biguanide hydrochloride (mCPBG; 5.0-15.0 mg/kg), alone or in combination. Tropisetron alone dose dependently reduced cocaine-induced aggression, with a significant reduction at 0.3 mg/kg, whereas mCPBG was ineffective. mCPBG administered prior to tropisetron required a higher dose (1.2 mg/kg) of antagonist to block aggression, indicating a selective 5-HT(3) effect. Cocaine-treated hamsters showed altered 5-HT-sub-3 immunoreactivity in several brain areas implicated in aggression control. These data support a role for 5-HT(3) receptors in adolescent cocaine-induced aggression.


Asenapine-induced restless legs syndrome: differentiation from akathisia.
Akathisia and restless legs syndrome (RLS) share some common clinical features and a common relationship with dopamine dysfunction. However, the underlying causes and appropriate treatments for akathisia and RLS are different. Herein we describe a case of RLS that was precipitated by a single dose of asenapine, which is an atypical antipsychotic, and dissect the features that support the contention that this was indeed a case of RLS and not akathisia.


Soil Microbiomes in Apple Orchards Are Influenced by the Type of Agricultural Management but Never Match the Complexity and Connectivity of a Semi-natural Benchmark.
Conversion of natural ecosystems into agricultural land may strongly affect the soil microbiome and the functioning of the soil ecosystem. Alternative farming systems, such as organic farming, have therefore been advocated to reduce this impact, yet the outcomes of different agricultural management regimes often remain ambiguous and their evaluations mostly lack a proper more natural benchmark. We used high-throughput amplicon sequencing, linear models, redundancy analyses, and co-occurrence network analyses to investigate the effect of organic and integrated pest management (IPM) on soil fungal and bacterial communities in both the crop and drive rows of apple orchards in Belgium, and we included semi-natural grasslands as a benchmark. Fungi were strongly influenced by agricultural management, with lower diversity indices and distinct communities in IPM compared to organic orchards, whereas IPM orchards had a higher AMF abundance and the most complex and connected fungal communities. Bacterial diversity indices, community composition, and functional groups were less affected by management, with only a higher network connectivity and abundance of keystone taxa in organic drive rows. On the other hand, none of the agricultural soil microbiomes matched the complexity and connectedness of our semi-natural benchmark, demonstrating that even more nature-friendly agricultural management practices strongly affect the soil microbiome and highlighting the essential role of (semi-)natural systems as a harbor of robust and functionally diverse fungal and bacterial communities.


The effects of dietary fat and bird age on the weights of eggs and egg components in the laying hen.
1. A low-fat diet or an isoenergetic and isonitrogenous high-fat diet containing 55 g maize oil/kg were fed to laying hens at different stages during the laying year in two experiments. 2. Feeding the high-fat diet to young hens resulted in a rapid increase of 2.5 g in egg weight, made up of increases in both yolk and albumen weights. 3. Switching the diets at 50 weeks caused changes in egg weight that were accounted for entirely by changes in egg albumen weight. 4. Feeding the high-fat diet from 46 weeks in a second experiment increased egg and egg albumen weights by 1.26 and 1.34 g respectively. 5. The increase in egg weight with age was associated with a greater increase in the proportion of yolk, at the expense of albumen, compared to egg weight increases related to dietary fat. 6. It is concluded that dietary fatty acids increase egg weight by a mechanism different from that causing age-related increases in weight and that the mechanism involves a stimulation of oviduct protein synthesis.


Functionalized carriers for the improved delivery of plasminogen activators.
Various plasminogen activators have been routinely used for the treatment of thrombotic diseases. However, these agents possess various problems e.g. short half life and other bleeding complications. To improve the effectiveness as well as to reduce the side effects of these drugs, various modifications have been made. For example, fibrin specific plasminogen activators have been developed. However, these agents also demonstrated various bleeding complications, clinically. Nowadays, so many carrier systems have been explored to improve the activity of these agents. Novel carriers not only improve the effectiveness of these drugs but also reduce the side effects. In the present review, we discuss novel carrier based strategies to improve the delivery of the plasminogen activators to site of thrombus.


A Preliminary Investigation: History, Physical, and lsokinetic Exam Results versus Arthroscopic Diagnosis of Chondromalacia Patella *.
The purpose of this pilot study was to identify those clinical exam findings most often seen in patients with a positive chondromalacia patella (CMP) arthroscopic exam. Twenty patients with a clinical diagnosis of CMP or meniscal lesions (M) or both (CMP+M) were evaluated by two physical therapists using the history, physical, and Cybex(R) II isokinetic testing data. More than 50% of the patients with arthroscopically confirmed CMP complained of peripatellar pain, pain with ascending and descending stairs, and pain with prolonged flexion. At least 50% of these patients also demonstrated pain with a patellar grinding test and crepitus during the active knee extension test. Chi square analysis of the clinical exam data between the arthroscopically diagnosed CMP+M patients and 20 age- and sex-matched normal subjects revealed a significant difference in response to the three history questions analyzed. No significant differences were found on the physical exam, including Cybex II isokinetic testing results. Our findings demonstrate the significant role of the history in diagnosing symptomatic CMP.J Orthop Sports Phys Ther 1985;7(3):115-123.


Pharmacokinetic and pharmacodynamic drug interactions during treatment with vigabatrin.
Pharmacokinetic drug interactions take place when one drug interacts with another at the level of metabolism, absorption or excretion. Pharmacodynamic interactions take place at the level of receptor sites, where they may have additive or potentiating effects. Vigabatrin is relatively free of pharmacokinetic interactions, and though it is associated with about a 20% decrease in serum levels of concomitantly administered phenytoin, the reduction is of little clinical significance. The mechanism underlying this effect is unknown. Because vigabatrin increases GABA-mediated inhibition in the brain (an action that is believed to account for its anticonvulsant effects), it might be expected to potentiate the CNS effects of benzodiazepines and alcohol. However, very sensitive eye movement studies have failed to detect any evidence of such an interaction. Overall, vigabatrin appears to be remarkably free of drug interactions. As a result, it is easier to use in clinical practice than older anti-epilepsy agents. Perhaps the most important finding of the interaction studies with vigabatrin is that there is no need for patients receiving the drug to be told to avoid alcohol.


Hurricane Sandy: Shared Trauma and Therapist Self-Disclosure.
Hurricane Sandy was one of the most devastating storms to hit the United States in history. The impact of the hurricane included power outages, flooding in the New York City subway system and East River tunnels, disrupted communications, acute shortages of gasoline and food, and a death toll of 113 people. In addition, thousands of residences and businesses in New Jersey and New York were destroyed. This article chronicles the first author's personal and professional experiences as a survivor of the hurricane, more specifically in the dual roles of provider and trauma victim, involving informed self-disclosure with a patient who was also a victim of the hurricane. The general analytic framework of therapy is evaluated in the context of the shared trauma faced by patient and provider alike in the face of the hurricane, leading to important implications for future work on resilience and recovery for both the therapist and patient.


A switch of G protein-coupled receptor binding preference from phosphoinositide 3-kinase (PI3K)-p85 to filamin A negatively controls the PI3K pathway.
Frequent oncogenic alterations occur in the phosphoinositide 3-kinase (PI3K) pathway, urging identification of novel negative controls. We previously reported an original mechanism for restraining PI3K activity, controlled by the somatostatin G protein-coupled receptor (GPCR) sst2 and involving a ligand-regulated interaction between sst2 with the PI3K regulatory p85 subunit. We here identify the scaffolding protein filamin A (FLNA) as a critical player regulating the dynamic of this complex. A preexisting sst2-p85 complex, which was shown to account for a significant basal PI3K activity in the absence of ligand, is disrupted upon sst2 activation. FLNA was here identified as a competitor of p85 for direct binding to two juxtaposed sites on sst2. Switching of GPCR binding preference from p85 toward FLNA is determined by changes in the tyrosine phosphorylation of p85- and FLNA-binding sites on sst2 upon activation. It results in the disruption of the sst2-p85 complex and the subsequent inhibition of PI3K. Knocking down FLNA expression, or abrogating FLNA recruitment to sst2, reversed the inhibition of PI3K and of tumor growth induced by sst2. Importantly, we report that this FLNA inhibitory control on PI3K can be generalized to another GPCR, the mu opioid receptor, thereby providing an unprecedented mechanism underlying GPCR-negative control on PI3K.


Effects of Sink Removal on Photosynthesis and Senescence in Leaves of Soybean (Glycine max L.) Plants.
Photosynthetic rate, ribulose 1,5-bisphosphate carboxylase activity, specific leaf weight, and leaf concentrations of carbohydrates, proteins, chlorophyll, and inorganic phosphate were determined periodically from midbloom until maturity in leaves of soybean plants (Glycine max L., var. Hodgson) from which reproductive and vegetative sinks had been removed 32 hours before measurement, or continuously since midbloom.Leaf photosynthesis, measured in the top of the canopy, was partially inhibited by both sink removal treatments. This inhibition was of constant magnitude from midbloom until maturity.Leaf photosynthesis in the top of the canopy declined from midbloom until maturity in the control as well as in the desinked plants. The decline in photosynthesis was gradual at first, but later became more abrupt. The photosynthetic decline was equally evident in the yellowing leaves of control plants and in the dark green leaves of the continuously desinked plants.Neither the inhibition of photosynthesis by sink removal nor the decline in photosynthetic rate with time was clearly related to any of the measured traits.


Flying triangulation--an optical 3D sensor for the motion-robust acquisition of complex objects.
Three-dimensional (3D) shape acquisition is difficult if an all-around measurement of an object is desired or if a relative motion between object and sensor is unavoidable. An optical sensor principle is presented-we call it "flying triangulation"-that enables a motion-robust acquisition of 3D surface topography. It combines a simple handheld sensor with sophisticated registration algorithms. An easy acquisition of complex objects is possible-just by freely hand-guiding the sensor around the object. Real-time feedback of the sequential measurement results enables a comfortable handling for the user. No tracking is necessary. In contrast to most other eligible sensors, the presented sensor generates 3D data from each single camera image.


Mapping Dithiobenzoate-Mediated RAFT Polymerization Products via Online Microreactor/Mass Spectrometry Monitoring.
2-cyano-2-propyl dithiobenzoates (CPDB)-mediated reversible addition-fragmentation chain transfer (RAFT) polymerization was monitored by online flow microreactor/mass spectrometry. This enabled the reactions to be followed in a time-resolved manner, closely resolving product patterns in the reaction mixtures at any point in time. RAFT polymerization was investigated for low RAFT to monomer ratios, enabling the monitoring of the early stages of a typical RAFT polymerization. The expected transition from pre- to the RAFT main equilibrium is observed. However, very high abundancies for cross-termination products were also identified, both in the pre- and main equilibrium stage. This is a somewhat surprising result as such products have always been expected, but to date have not been observed in the majority of studies. Product isolation and NMR analysis revealed that cross-termination occurs in the para position of the benzoate ring and becomes fully irreversible via re-aromatization of the ring in a H-shift reaction. The present data suggest a pronounced chain-length dependence of the cross-termination reaction, which would explain why the products are seen here, but not in other studies.


Medical indigency and inner city hospital care: patient dumping, emergency care and public policy.
This paper discusses the growing lack of private for-profit hospital care for the medically indigent. The issues of patient dumping and emergency care are examined from both judicial and public policy perspectives. The paper concludes by noting that dumping may be viewed as a most serious form of neglect and more comprehensive laws and court decisions are needed to require all hospitals, regardless of ownership, to treat all patients who arrive at their doors if they have the appropriate medical staff and facilities.


Sensitive chemiluminescent imaging for chemoselective analysis of glycan expression on living cells using a multifunctional nanoprobe.
A novel sensitive chemiluminescent (CL) imaging method was developed for in situ monitoring of cell surface glycan expression through chemoselective labeling of carbohydrate motifs and then binding to a multifunctional nanoprobe. The nanoprobe was fabricated by assembling biotin-DNA and a large amount of horseradish peroxidase (HRP) on gold nanoparticles (AuNPs). The chemoselective labeling was performed by selective oxidization of the hydroxyl sites of sialyl and galactosyl groups on cell surfaces into aldehydes by periodate and galactose oxidase, respectively, and then aniline-catalyzed hydrazone ligation with biotin hydrazide for specific recognition to avidin. With the biotin-avidin system, the multifunctional nanoprobe could conveniently be bound to the glycan sites on the cell surface. The DNA chain presenting between the AuNPs and biotin assembled on the nanoprobe could obviate the steric effect, and HRP acted to trigger the CL emission of the luminal-H(2)O(2) system. Therefore the expression of both sialyl and galactosyl groups could be selectively monitored by CL imaging with high sensitivity due to the high amount of HRP. Using human liver cancer HCCC-9810 cells as a model, this CL imaging strategy could detect HCCC cells ranging from 6 × 10(2) to 1 × 10(7) cells mL(-1) with a detection limit down to 12 cells. More importantly, this method could be used for distinguishing cancer cells from normal cells and monitoring of dynamic carbohydrate expression on living cells, providing promising application in clinical diagnosis and treatment of cancer.


[Appendicitis: yes or no to laparoscopic approach?].
Whether or not there is a benefit to laparoscopy versus open surgery in the management of acute appendicitis remains a subject of controversy despite the publication of numerous randomized studies. Operative time is longer for the laparoscopic approach. The incidence of abdominal wall abscess is decreased for laparoscopy but the incidence of deep intra-abdominal abscess may be increased, especially in the case of complicated appendicitis. Post-operative pain is diminished and resumption of normal activity is quicker with the laparoscopic approach. Hospitalization is shorter but the cost of hospital care is higher; nevertheless, the global cost may be less - particularly for patients whose return to work is hastened by a laparoscopic approach. Laparoscopy diminishes the number of normal appendectomies, particularly in women of reproductive age where the diagnosis may be unclear. Laparoscopic appendectomy is practicable and has advantages over open appendectomy under certain circumstances. These advantages are most evident in the young female, the working patient, and the obese patient. Overall, the advantages of laparoscopy are, at best, modest and clinical benefit is not always demonstrable. The risk of deep abscess, particularly in patients with perforated or gangrenous appendicitis, remains an unknown and should be evaluated by further studies.


Reactions of 4-oxalocrotonate tautomerase and YwhB with 3-halopropiolates: analysis and implications.
4-Oxalocrotonate tautomerase (4-OT) and YwhB, a 4-OT homologue found in Bacillus subtilis, exhibit a low level hydratase activity that converts trans-3-haloacrylates to acetaldehyde, presumably through a malonate semialdehyde intermediate. The mechanism for the initial transformation of the 3-haloacrylate to malonate semialdehyde involves Pro-1 as well as an arginine, two residues that play critical roles in the 4-OT-catalyzed isomerization reaction and the YwhB-catalyzed tautomerization reaction. These residues are also critical for the trans-3-chloroacrylic acid dehalogenase (CaaD)-catalyzed conversion of trans-3-haloacrylates to malonate semialdehyde. Recently, 3-bromo- and 3-chloropropiolate, the acetylene analogues of 3-haloacrylates, were characterized as potent irreversible inhibitors of CaaD due to the covalent modification of the catalytic proline. In view of these observations, an investigation of the behavior of 4-OT and YwhB with the 3-halopropiolates was undertaken. The results show that these compounds are potent irreversible inhibitors of 4-OT and YwhB with Pro-1 being the sole site of covalent modification by 3-bromopropiolate. The inactivation process could involve the enzyme-catalyzed addition of water to the 3-halopropiolate yielding an acyl halide, which would inactivate the enzyme or be initiated by the nucleophilic attack of Pro-1 at the C-3 position of the 3-halopropiolate in a Michael type reaction. The presence of the halogen along with Arg-11 could facilitate both reactions with the latter causing the polarization of the alpha,beta-unsaturated acids. The 3-halopropiolates are the first identified inhibitors of YwhB and confirm the importance of Pro-1 in its mechanism. In addition, the results set the stage for the use of these compounds as mechanistic probes of the primary as well as low level activities of 4-OT and YwhB.


Roles of Extracellular Vesicles in High-Grade Gliomas: Tiny Particles with Outsized Influence.
High-grade gliomas, particularly glioblastomas (grade IV), are devastating diseases with dismal prognoses; afflicted patients seldom live longer than 15 months, and their quality of life suffers immensely. Our current standard-of-care therapy has remained essentially unchanged for almost 15 years, with little new therapeutic progress. We desperately need a better biologic understanding of these complicated tumors in a complicated organ. One area of rejuvenated study relates to extracellular vesicles (EVs)-membrane-enclosed nano- or microsized particles that originate from the endosomal system or are shed from the plasma membrane. EVs contribute to tumor heterogeneity (including the maintenance of glioma stem cells or their differentiation), the impacts of hypoxia (angiogenesis and coagulopathies), interactions amid the tumor microenvironment (concerning the survival of astrocytes, neurons, endothelial cells, blood vessels, the blood-brain barrier, and the ensuing inflammation), and influences on the immune system (both stimulatory and suppressive). This article reviews glioma EVs and the ways that EVs manifest themselves as autocrine, paracrine, and endocrine factors in proximal and distal intra- and intercellular communications. The reader should note that there is much controversy, and indeed confusion, in the field over the exact roles for EVs in many biological processes, and we will engage some of these difficulties herein.


Historical and Current Adenosine Receptor Agonists in Preclinical and Clinical Development.
Adenosine receptors (ARs) function in the body's response to conditions of pathology and stress associated with a functional imbalance, such as in the supply and demand of energy/oxygen/nutrients. Extracellular adenosine concentrations vary widely to raise or lower the basal activation of four subtypes of ARs. Endogenous adenosine can correct an energy imbalance during hypoxia and other stress, for example, by slowing the heart rate by A1AR activation or increasing the blood supply to heart muscle by the A2AAR. Moreover, exogenous AR agonists, antagonists, or allosteric modulators can be applied for therapeutic benefit, and medicinal chemists working toward that goal have reported thousands of such agents. Thus, numerous clinical trials have ensued, using promising agents to modulate adenosinergic signaling, most of which have not succeeded. Currently, short-acting, parenteral agonists, adenosine and Regadenoson, are the only AR agonists approved for human use. However, new concepts and compounds are currently being developed and applied toward preclinical and clinical evaluation, and initial results are encouraging. This review focuses on key compounds as AR agonists and positive allosteric modulators (PAMs) for disease treatment or diagnosis. AR agonists for treating inflammation, pain, cancer, non-alcoholic steatohepatitis, angina, sickle cell disease, ischemic conditions and diabetes have been under development. Multiple clinical trials with two A3AR agonists are ongoing.


[The neurochemistry and neuropharmacology of frontotemporal dementia].
To review the neurochemical features and therapeutic options for frontotemporal dementia (FTD). The main neurochemical alterations in FTD are the serotoninergic and dopamine depletion. In contrast with Alzheimer's and diffuse Lewy bodies disease, there are not significant alterations of the cholinergic system. Cerebral perfusion and glucose metabolism studies usually show hypoperfusion or hypometabolism, with predominant involvement of temporal and frontal cortices. There have been described some alterations related with oxidative stress and apoptosis, although its pathogenetic role in FTD is not well known. Treatment of FTD is not well established, because there are only a few studies with some drugs. The most studied drugs are serotonin reuptake inhibitors, however, despite the well-known serotoninergic deficiency described in FTD, the results are not conclusive. The main neurochemical alterations of FTD are serotoninergic and dopaminergic deficiencies. The treatment is not well established, although it should be theoretically ideal to use drugs which modulate these neurotransmitter systems.


Nivolumab-induced lichenoid granulomatous stomatitis in a patient with advanced melanoma: A case report.
Lichenoid granulomatous reactions (LGR) are granulomatous inflammations of the skin and oral mucosa, also sharing features of lichenoid lesions. Thus, the present study refers to lichenoid granulomatous dermatitis (LGD) and lichenoid granulomatous stomatitis (LGS). LGR is a condition that can be triggered by drugs, diseases or environmental causes. In the present case study, anti-PD1 (nivolumab) medication had a detrimental effect on the oral mucosa, which clinicaly and histologicaly proved to be LGS. Checkpoint inhibitors consitute a cornerstone in the current treatment of several types of cancer, of which cutaneous melanoma is the best example. Oral lichenoid responses following anti-PD-1 therapy have been recorded in few case reports and small case series. To the best of our knowledhe, this is the first case of LGS being reported as a side effect of immune checkpoint inhibitor treatment.


Novel synthesis of steryl esters from phytosterols and amino Acid.
The feasibility of esterification of phytosterol with the amino acid l-glutamic acid was established. The influence of various organic solvents was investigated, and n-butanol was selected as an ideal solvent for phytosteryl esters synthesis with l-glutamic acid. The reaction conditions were further optimized by orthogonal experiments, and a 92.3% degree of esterification was obtained when optimum conditions were used. FT-IR spectral, GC-MS, and NMR analyses were adopted to determine the steryl esters of l-glutamic acid. The FT-IR spectrum indicated the presence of ester bonds in the phytosteryl esters with l-glutamic acid, and on the basis of the detailed mass spectrography analysis, GC-MS and NMR offered an efficient and reliable way to confirm the steryl esters. This novel synthesis approach of phytosteryl esters with amino acid supplied a promising alternative to the substrate on esterification of phytosterols and thus can be readily applied to further studies of functional food ingredients of phytosteryl esters.


A cDNA clone highly expressed in ripe banana fruit shows homology to pectate lyases.
A cDNA clone (Ban17), encoding a protein homologous to pectate lyase, has been isolated from a cDNA library from climacteric banana fruit by means of differential screening. Northern analysis showed that Ban17 mRNA is first detected in early climacteric fruit, reaches a steady-state maximum at the climacteric peak, and declines thereafter in overripe fruit. Accumulation of the Ban17 transcript can be induced in green banana fruit by exogenous application of ethylene. The demonstrates that expression of this gene is under hormonal control, its induction being regulated by the rapid increase in ethylene production at the onset of ripening. The deduced amino acid sequence derived from the Ban17 cDNA shares significant identity with pectate lyases from pollen and plant pathogenic bacteria of the genus Erwinia. Similarity to bacterial pectate lyases that were proven to break down the pectic substances of the plant cell wall suggest that Ban17 might play a role in the loss of mesocarp firmness during fruit ripening.


Key Odorants from the American Matsutake, Tricholoma magnivelare.
The American Matsutake, Tricholoma magnivelare (Peck) Redhead, is an edible wild mushroom with a distinctive aroma described as mushroom and spice with subtle floral and citrus nuances. In this study, a total of 36 odorants were identified from T. magnivelare using solvent-assisted flavor evaporation and aroma extract dilution analysis. Stable isotope dilution assays were performed to quantitate 14 odorants with flavor dilution factors ≥64. Odorants with high odor activity values (OAVs) included 1-octen-3-one (OAV 2125), linalool (OAV 650), (2E,4E)-nona-2,4-dienal (OAV 304), and 1-octen-3-ol (OAV 206). An odor simulation model matched the odor profile of the fresh mushroom. Omission studies showed that linalool, hexanal, (2E,4E)-nona-2,4-dienal, methyl (E)-3-phenylprop-2-enoate, and 1-octen-3-one or 1-octen-3-ol were essential to the aroma of T. magnivelare. Chiral chromatography showed that α-pinene was a scalemic mixture of 34% (R)-(+) to 66% (S)-(-), while 1-octen-3-ol was present as 95% (R)-(-) to 5% (S)-(+), and linalool was 96% (R)-(-) to 4% (S)-(+). These results establish the base for future investigations into the aroma chemistry of other members of the genus Tricholoma.


Modeling the 1,3-dipolar cycloaddition of nitrones to vinylboranes in competition with boration, cyclization, and oxidation reactions.
Structures and energetics of reactants, reactant complexes, concerted transition structures, and products of the cycloaddition of the prototypical nitrone with vinylborane have been produced and discussed. Structure optimizations have been performed at the B3LYP/6-31G(d) and B3LYP/AUG-cc-pVDZ levels of approximation, and single-point calculations on the B3LYP geometries have been carried out at the MP4(SDTQ) level with the same basis sets. Kinetic contributions to standard enthalpies, entropies, and free enthalpies have been computed at the same levels of geometry optimizations. The effects of methyl and chloro substitution on the BH2 group and of methyl substitution on the vinyl moiety has been also explicitly considered. The most striking theoretical features of this cycloaddition are (i) the formation of reactant complexes where the nitrone oxygen is strictly bound up to the boron atom (B...O interactions), (ii) their persistence in the endo/exo transition structures, and (iii) energy profiles suggesting very high reaction rates, regiospecificity (5-borylisoxazolidines) and complete endo-stereoselectivity. The BH2 (BX2) substituent appears to induce a sort of intramolecular catalysis which is also largely selective in favor of the endo reaction path. Possible competitive reaction paths such as cyclization, organoboration, and oxidation have equally been investigated, on the same grounds, both with prototypical reagents and with dimethylvinylborane, dichlorovinylborane, 2-methyl-1-propenylborane, and 2-methyl-1-propenyldichloroborane. The transition structures for these reaction paths are significantly higher in energy than those of the corresponding 1,3-dipolar cycloadditions in the sequence oxidation >> cyclization > boration > cycloaddition, whereas the resulting reaction products show the reversed sequence. Polar solvents appear to increase the competition of boration although maintaining its character of secondary reaction. As expected, the reaction rate of 1,3-dipolar cycloaddition is lowered by dimethyl substitution on the vinyl CH2 reacting center (i.e., for the reaction of 2-methyl-1-propenylborane and 2-methyl-1-propenyldichloroborane) whereas the reaction rate of boration is increased, the boration results being significantly competitive even in the gas phase. Experiments for the control of the above predictions are not yet available.


Invasive Prediction of Ground Glass Nodule Based on Clinical Characteristics and Radiomics Feature.
Objective: To explore the diagnostic value of CT radiographic images and radiomics features for invasive classification of lung adenocarcinoma manifesting as ground-glass nodules (GGNs) in computer tomography (CT). Methods: A total of 312 GGNs were enrolled in this retrospective study. All GGNs were randomly divided into training set (n = 219) and test set (n = 93). Univariate and multivariate logistic regressions were used to establish a clinical model, while the minimum redundancy maximum relevance (mRMR) and least absolute shrinkage and selection operator (LASSO) algorithm were used to select the radiomics features and construct the radiomics model. A combined model was finally built by combining these two models. The performance of these models was assessed in both training and test set. A combined nomogram was developed based on the combined model and evaluated with its calibration curves and C-index. Results: Diameter [odds ratio (OR), 1.159; p < 0.001], lobulation (OR, 2.953; p = 0.002), and vascular changes (OR, 3.431; p < 0.001) were retained as independent predictors of the invasive adenocarcinoma (IAC) group. Eleven radiomics features were selected by mRMR and LASSO method to established radiomics model. The clinical model and radiomics mode showed good predictive ability in both training set and test set. When two models were combined, the diagnostic area under the curve (AUC) value was higher than the single clinical or radiomics model (training set: 0.86 vs. 0.83 vs. 0.82; test set: 0.80 vs. 0.78 vs. 0.79). The constructed combined nomogram could effectively quantify the risk degree of 3 image features and Rad score with a C-index of 0.855 (95%: 0.805∼0.905). Conclusion: Radiographic and radiomics features show high accuracy in the invasive diagnosis of GGNs, and their combined analysis can improve the diagnostic efficacy of IAC manifesting as GGNs. The nomogram, serving as a noninvasive and accurate predictive tool, can help judge the invasiveness of GGNs prior to surgery and assist clinicians in creating personalized treatment strategies.


Control of Pyrimidine Biosynthesis in Synchronously Dividing Cells of Helianthus tuberosus.
Factors with potential for regulating pyrimidine biosynthesis in plant tissue have been explored in quiescent cells of Helianthus tuberosus induced to divide by auxin addition. Investigations confined to the first highly synchronous cell cycle of the tuber explants revealed that the relative activity of asparate carbamoyltransferase (ACTase) to ornithinecarbamoyltransferase (OCTase) (enzymes competing for carbamoyl phosphate for the pyrimidine and arginine pathways, respectively) changes from 0.5 in quiescent cells to 3.0 by the end of the first cell cycle. This was interpreted as a change in the state of cell function from accumulation of storage arginine to cell division with a concomitant demand for pyrimidine nucleotides for nucleic acid synthesis. The rise in ACTase activity began at the same time as the initiation of DNA synthesis and was dependent on continued DNA synthesis. OCTase activity declined whether or not auxin was added to the medium, whereas ACTase activity was observed to decline only in the absence of DNA synthesis.The low cellular concentration of the shared substrate, carbamoyl phosphate (2 micromolar), favored utilization of this substrate by the pyrimidine pathway over the arginine pathway because of the low K(m) (0.08 80 micromolar) for this substrate by ACTase compared to that for OCTase (9.0 millimolar). Unexpectedly, the total concentration of the feedback inhibitor for the pyrimidine pathway, UMP, was found to have more than doubled in dividing tissue at a time when pyrimidine nucleotide demand had increased. It is concluded that compartmentation decreased UMP in the vicinity of ACTase and/or that the extra UMP stabilizes newly synthesized ACTase in preparation for an even greater demand for nucleic acid synthesis in the second and subsequent cell cycles.


Enzymatic Synthesis of Trideuterated Sialosides.
Sialic acids are a family of acidic monosaccharides often found on the termini of cell surface proteins or lipid glycoconjugates of higher animals. Herein we describe the enzymatic synthesis of the two isotopically labeled sialic acid derivatives d₃-X-Gal-α-2,3-Neu5Ac and d₃-X-Gal-α-2,3-Neu5Gc. Using deuterium oxide as the reaction solvent, deuterium atoms could be successfully introduced during the enzymatic epimerization and aldol addition reactions when the sialosides were generated. NMR and mass spectrometric analyses confirmed that the resulting sialosides were indeed tri-deuterated. These compounds may be of interest as internal standards in liquid chromatography/mass spectrometric assays for biochemical or clinical studies of sialic acids. This was further exemplified by the use of this tri-deuterated sialosides as internal standards for the quantification of sialic acids in meat and egg samples.


Cycle therapy of actinic keratoses of the face and scalp with 5% topical imiquimod cream: An open-label trial.
Preliminary studies indicate that topically applied immune response modifiers may be an effective and safe method of treating actinic keratoses (AKs). Our aim was to study the potential efficacy of topical 5% imiquimod cream in the treatment of facial or scalp AKs and improve the safety profile by using a novel "cycle" dosing regimen. This pilot study is an open-label trial that included 25 patients who had between 5 and 20 discrete AKs within a cosmetic unit of the forehead, scalp, or cheek. Treatment consisted of once-daily application of 5% imiquimod cream, 3 times a week for 4 weeks. to the entire cosmetic unit, followed by a rest period of 4 weeks. The cycle was repeated if any AKs remained after a complete 8-week cycle. A maximum of 3 cycles was permitted (24 weeks). Thirty-three sites in 25 patients were evaluated. Compliance was excellent with a very tolerable safety profile. Complete clearing of all AKs was noted in 82% (27/33) of anatomic sites in 25 study subjects. Almost half the sites (15/33) were clear at the end of the first cycle. A "therapeutic interval" was noted during the rest period wherein clinical inflammation subsided but AKs continued to clear. An added effect was the uncovering and clinical appearance and subsequent eradication of incipient (subclinical) AKs in the treatment area. There was excellent compliance with the cycle therapy regimen. The observations and hypotheses made in this pilot study will be tested in controlled, randomized trials with larger study populations. The identification of a therapeutic interval may prove to be beneficial in formulating individualized dosing regimens.


Acquisition of cross-polarized diffraction images and study of blurring effect by one time-delay-integration camera.
Blurred diffraction images acquired from flowing particles affect the measurement of fringe patterns and subsequent analysis. An imaging unit with one time-delay-integration (TDI) camera has been developed to acquire two cross-polarized diffraction images. It was shown that selected elements of Mueller matrix of single scatters can be imaged with pixel matching precision in this configuration. With the TDI camera, the effect of blurring on imaging of scattered light propagating along the side directions was found to be much more significant for biological cells than microspheres. Despite blurring, classification of MCF-7 and K562 cells is feasible since the effect has similar influence on extracted image parameters. Furthermore, image blurring can be useful for analysis of the correlations among texture parameters for characterization of diffraction images from single cells. The results demonstrate that with one TDI camera the polarization diffraction imaging flow cytometry can be significantly improved and angular distribution of selected Mueller matrix elements can be accurately measured for rapid and morphology-based assay of particles and cells without fluorescent labeling.


Molecular mechanisms of Bcr-Abl-induced oncogenesis.
The chimeric Bcr-Abl oncogene has been implicated in the pathogenesis of chronic myelogenous leukemia (CML) and Philadelphia chromosome (Ph1)-positive acute lymphocytic leukemia (ALL). The Bcr-Abl protein is a complex structure comprising discrete domains associated with specific biochemical and biological functions. These domains function through their ability to activate distinct signal transduction pathways responsible for Bcr-Abl's oncogenic behavior. This review will present our current understanding of signal transduction pathways involved in Bcr-Abl-induced pathophysiology, with particular emphasis on potential targets for therapeutic intervention.


[Characterization of the effect of analgesics on the assessment of experimental pain in man. Pethidine and tramadol in a double-blind comparison].
The effect of the opioid analgesics tramadol and pethidine on experimentally induced pain was investigated in a double blind study with healthy volunteers. Using a constant current shocker, compensating the changes of the skin resistance, a constantly increasing pain stimulus was produced. Detection-, pain-, and tolerance-thresholds were assessed before and three times after intravenous injection of either pethidine (1 mg/kg bodyweight), tramadol (2 mg/kg bodyweight) or placebo (NaCl). While the two analgesics caused an increase of all three thresholds the placebo did not cause any threshold changes. The rise of the detection threshold after application of tramadol and pethidine suggests a sedation effect. However, in relation to the analgesic effect this sedation effect is stronger with tramadol than with pethidine. With the dosage used in this experiment, there is no difference in the analgesic effect of tramadol and pethidine. Compensating for intra- and interindividual changes in skin resistance, the pain stimulation method used in this study provides a good quantification of the effects of analgesics.


Elevation of renal glutathione enhances ischemic injury.
In a previous study, we tested the hypothesis that an elevated level of renal glutathione (GSH) would protect the kidney from ischemic injury. However, prior elevation of GSH with GSH monoethylester enhanced then injury induced by 35 min of ischemia and blood reflow [Scaduto RC Jr, Gattone VH, Grotyohann LW, et al; Effect of an altered glutathione content on renal ischemic injury. Am J Physiol 1988;255:F911-F921]. Additionally, GSH monoethylester produced morphologic alterations in the absence of ischemia. Thus the greater ischemic injury observed after GSH ester pretreatment could have been due to a synergistic effect between the events caused by ischemia and the pretreatment. The present study was conducted to evaluate the utility of elevating renal GSH levels by administration of GSH. Administration of GSH (1 mmol/kg body weight) caused a 3-fold elevation of renal GSH levels and a 6-fold elevation of renal cysteine levels after 60 min without causing changes in renal morphology or GFR. After 35 min of renal artery occlusion and 90 min of blood reflow, animals pretreated with GSH had a much greater decline in GFR than untreated control animals. This enhancement of renal ischemic injury in GSH-treated animals was similar to that observed following administration of GSH monoethylester. We conclude that administration of GSH is the method of choice for elevation of renal GSH and that elevation of renal GSH leads to an enhanced ischemia-induced injury which is independent of the method employed to elevate renal GSH.


Integrating cell cycle score for precise risk stratification in ovarian cancer.
Background: Ovarian cancer (OC) is a highly heterogeneous disease, of which the mesenchymal subtype has the worst prognosis, is the most aggressive, and has the highest drug resistance. The cell cycle pathway plays a vital role in ovarian cancer development and progression. We aimed to screen the key cell cycle genes that regulated the mesenchymal subtype and construct a robust signature for ovarian cancer risk stratification. Methods: Network inference was conducted by integrating the differentially expressed cell cycle signature genes and target genes between the mesenchymal and non-mesenchymal subtypes of ovarian cancer and identifying the dominant cell cycle signature genes. Results: Network analysis revealed that two cell cycle signature genes (POLA2 and KIF20B) predominantly regulated the mesenchymal modalities of OC and used to construct a prognostic model, termed the Cell Cycle Prognostic Signature of Ovarian Cancer (CCPOC). The CCPOC-high patients showed an unfavorable prognosis in the GSE26712 cohort, consistent with the results in the seven public validation cohorts and one independent internal cohort (BL-OC cohort, qRT-PCR, n = 51). Functional analysis, drug-sensitive analysis, and survival analysis showed that CCPOC-low patients were related to strengthened tumor immunogenicity and sensitive to the anti-PD-1/PD-L1 response rate in pan-cancer (r = -0.47, OC excluded), which indicated that CCPOC-low patients may be more sensitive to anti-PD-1/PD-L1. Conclusion: We constructed and validated a subtype-specific, cell cycle-based prognostic signature for ovarian cancer, which has great potential for predicting the response of anti-PD-1/PD-L1.


Elevated concentration of cerebrospinal fluid tissue transglutaminase in Parkinson's disease indicating apoptosis.
Tissue transglutaminase (tTG) is activated during the apoptotic cell death cascade and plays a key role in the formation of apoptotic bodies. We found significant elevation of tTG concentration in the cerebrospinal fluid (CSF) of 54 patients with Parkinson's disease (PD) compared with that measured in 34 control subjects, thus showing increased neural cell apoptosis in patients with PD.


[Spiral CT reconstruction for typing of tibial plateau fracture to guide surgical therapy].
To typing of tibial plateau fracture based on spiral CT reconstruction and to explore effect of the typing method for treatment. A hundred and twenty-six cases with tibial plateau fracture (male 95, female 31, age from 23 to 58 years old), the fractures were classified based on reconstruction image of spiral CT. Including central compression type in 13 cases, split type in 8, split compression type in 79, comminution type in 26. According to the different typing the suitable incision of operation and fixed method for fracture were select. A hundred and twenty-six cases were followed up for 0.5-4 years with an average of 1.2 years. According to Hohl system score to knee joint function, there were statistical significance in the pain,active movement,active range of motion between before and after operation (P < 0.01) and there were no statistical significance in stability and self-evaluation (P < 0.01). Typing of tibial plateau fracture based on spiral CT reconstruction helpful to choose operative approach, reduction and fixed method and obviously improve clinical effect.


Physiopathology of the cochlear microcirculation.
Normal blood supply to the cochlea is critically important for establishing the endocochlear potential and sustaining production of endolymph. Abnormal cochlear microcirculation has long been considered an etiologic factor in noise-induced hearing loss, age-related hearing loss (presbycusis), sudden hearing loss or vestibular function, and Meniere's disease. Knowledge of the mechanisms underlying the pathophysiology of cochlear microcirculation is of fundamental clinical importance. A better understanding of cochlear blood flow (CoBF) will enable more effective management of hearing disorders resulting from aberrant blood flow. This review focuses on recent discoveries and findings related to the physiopathology of the cochlear microvasculature.


A Scoping Review of International Barriers to Asthma Medication Adherence Mapped to the Theoretical Domains Framework.
Internationally, adult asthma medication adherence rates are low. Studies characterizing variations in barriers by country are lacking. To conduct a scoping review to characterize international variations in barriers to asthma medication adherence among adults. MEDLINE, EMBASE, Web of Science (WOS), and CINAHL were searched from inception to February 2017. English-language studies employing qualitative methods (eg, focus groups, interviews) were selected to assess adult patient- and/or caregiver-reported barriers to asthma medication adherence. Two investigators independently identified, extracted data, and collected study characteristics, methodologic approach, and barriers. Barriers were mapped using the Theoretical Domains Framework and findings categorized according to participants' country of residence, countries' gross national income, and the presence of universal health care (World Health Organization definitions). Among 2942 unique abstracts, we reviewed 809 full texts. Among these, we identified 47 studies, conducted in 12 countries, meeting eligibility. Studies included a total of 2614 subjects, predominately female (67%), with the mean age of 19.1 to 70 years. Most commonly reported barriers were beliefs about consequences (eg, medications not needed for asthma control, N = 29, 61.7%) and knowledge (eg, not knowing when to take medication, N = 27, 57.4%); least common was goals (eg, asthma not a priority, N = 1, 2.1%). In 27 studies conducted in countries classified as high income (HIC) with universal health care (UHC), the most reported barrier was participants' beliefs about consequences (N = 17, 63.3%). However, environmental context and resources (N = 12, 66.7%) were more common in HIC without UHC. International adherence barriers are diverse and may vary with a country's sociopolitical context. Future adherence interventions should account for trends.


[Fully apply the optometry knowledge to improve the visual quality of Chinese people].
With the rapid development of modern ophthalmology and optometry, people put in higher claim for visual quality. However, the application and penetration of the optometry knowledge and research achievement in every domain of ophthalmology are bound to affect the elevation of visual quality, which is one of the highlights our future work.


Drugs and pregnancy--outcomes of women engaged with a specialist perinatal outreach addictions service.
Substance misuse during pregnancy may result in harm to both mother and child. The aims of this study were to assess changes in outcomes of women seen by a specialist perinatal addictions outreach service (1989-1991 versus 2002-2005) and compare outcomes to the local hospital maternity population (2004-2005). A cross-sectional audit of health-care records was conducted comparing the outcomes of women in 2002-2005 with earlier data from 1989-1991 and the local maternity population (2004-2005). The service was attended by 126 women, of whom 83% of opioid-dependent women started/continued opioid maintenance treatment. Of 118 babies delivered, there were two stillbirths and one early neonatal death, 20% were premature, 28% were low birth weight, 21% required the Special Care Baby Unit and 21% of babies born to opioid-dependent mothers were treated for neonatal abstinence syndrome (NAS). Fewer babies required treatment for NAS in 2002-2005 compared to 1989-1991 (21% versus 44%). There were higher rates of miscarriage (3% versus <1%), low birth weight (28% versus 9%) and premature babies (20% versus 9%) compared to the local maternity population (2004-2005). Integrated perinatal addictions treatment may deliver benefits; however, engaging women into treatment earlier and reducing substance use before conception remains the objective.


In vivo quantitative whole-brain diffusion tensor imaging analysis of APP/PS1 transgenic mice using voxel-based and atlas-based methods.
Diffusion tensor imaging (DTI) has been applied to characterize the pathological features of Alzheimer's disease (AD) in a mouse model, although little is known about whether these features are structure specific. Voxel-based analysis (VBA) and atlas-based analysis (ABA) are good complementary tools for whole-brain DTI analysis. The purpose of this study was to identify the spatial localization of disease-related pathology in an AD mouse model. VBA and ABA quantification were used for the whole-brain DTI analysis of nine APP/PS1 mice and wild-type (WT) controls. Multiple scalar measurements, including fractional anisotropy (FA), trace, axial diffusivity (DA), and radial diffusivity (DR), were investigated to capture the various types of pathology. The accuracy of the image transformation applied for VBA and ABA was evaluated by comparing manual and atlas-based structure delineation using kappa statistics. Following the MR examination, the brains of the animals were analyzed for microscopy. Extensive anatomical alterations were identified in APP/PS1 mice, in both the gray matter areas (neocortex, hippocampus, caudate putamen, thalamus, hypothalamus, claustrum, amygdala, and piriform cortex) and the white matter areas (corpus callosum/external capsule, cingulum, septum, internal capsule, fimbria, and optic tract), evidenced by an increase in FA or DA, or both, compared to WT mice (p < 0.05, corrected). The average kappa value between manual and atlas-based structure delineation was approximately 0.8, and there was no significant difference between APP/PS1 and WT mice (p > 0.05). The histopathological changes in the gray matter areas were confirmed by microscopy studies. DTI did, however, demonstrate significant changes in white matter areas, where the difference was not apparent by qualitative observation of a single-slice histological specimen. This study demonstrated the structure-specific nature of pathological changes in APP/PS1 mouse, and also showed the feasibility of applying whole-brain analysis methods to the investigation of an AD mouse model.


Development of Tyrosinase Promoter-Based Fluorescent Assay for Screening of Anti-melanogenic Agents.
For screening of skin-whitening ingredients that modulate inhibition of melanogenesis, tyrosinase promoter-based assay using a three-dimensional (3D) spheroid culture technique is a beneficial tool to improve the accuracy of raw material screening in cosmetics through mimicking of the in vivo microenvironment. Although the advantages of high-throughput screening (HTS) are widely known, there has been little focus on specific cell-based promoter assays for HTS in identifying skin-whitening ingredients that inhibit accumulation of melanin. The aim of this study was therefore to develop a large-scale compatible assay through pTyr-EGFP, an enhanced green fluorescent protein (EGFP)-based tyrosinase-specific promoter, to seek potential melanogenesis inhibitors for cosmetic use. Herein, a stably transfected human melanoma cell line expressing EGFP under the control of a 2.2-kb fragment derived from the tyrosinase gene was generated. Spontaneous induction of the tyrosinase promoter by 3D spheroid culture resulted in increased expression of EGFP, providing a significant correlation with the tyrosinase mRNA level, and subsequent inhibition of tyrosinase activity. Importantly, the pTyr-EGFP system provided successful tracking of the changes in the live image and real-time monitoring. Thus tyrosinase promoter-based fluorescent assay using a 3D spheroid culture can be useful as a screening system for exploring the efficiency of anti-melanogenesis ingredients.


Fucoidan Enhances Cisplatin-induced Effects on SCC-25 Human Oral Cancer Cells by Inhibiting the PI3K/AKT Pathway.
Cisplatin is a drug for treating oral cancer. However, several previous studies indicate that oral cancer cells can develop resistance to cisplatin, which may result in a poor prognosis for patients with oral cancer. Fucoidan, a natural health product extracted from brown seaweed, has anticancer abilities against various types of cancer cell. This study evaluated whether fucoidan can enhance the sensitivity of oral cancer cells to cisplatin and explored the underlying mechanism. SCC-25 cells were used in the present study and treated with 0.3125 mg/ml fucoidan, 12.5 μg/ml cisplatin, or 0.3125 mg/ml fucoidan plus 12.5 μg/ml cisplatin for 48 h, 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide, enzyme-linked immunosorbent, and immunoblotting assays were performed to evaluate cell survival, cytokeratin-18 fragment release, and expression of markers of apoptosis and autophagy, respectively. Cotreatment with fucoidan enhanced cisplatin-induced reduction of SCC-25 cell survival compared to cisplatin alone. In addition, cotreatment also increased the expression of apoptosis markers, including activated caspase-8, activated caspase-9, activated caspase-3, and cleaved poly(ADP-ribose) polymerase (PARP), but did not increase the expression of the two autophagy markers studied, beclin and autophagy-related 12-autophagy-related 5 conjugate. Fucoidan significantly inhibited cisplatin-induced AKT serine/threonine kinase 1 activation, which promoted PARP cleavage, caspase-3 activation, and cytokeratin-18 fragment expression in SCC-25 cells. Fucoidan promoted cisplatin-induced effects by inhibiting phosphatidylinositol 4,5 bisphosphate 3 kinase/AKT serine/threonine kinase 1 activation induced by cisplatin. The results of this study may provide a basis for the possible application of the combination of fucoidan and cisplatin in the clinical treatment of oral cancer in the future to improve the prognosis of patients with oral cancer.


Crotonaldehyde formation from decomposition of ICH2CH2OH on powdered TiO2.
Adsorption and reactions of 2-iodoethanol on TiO(2) have been studied by Fourier transform infrared spectroscopy. ICH(2)CH(2)OH possesses two reactive centers of C-I and C-OH. It is found that its decomposition leads to the formation of crotonaldehyde on TiO(2). A reaction sequence of ICH(2)CH(2)OH --> ICH(2)CH(2)O- --> CH(3)CHO --> CH(3)CH=CH-CHO is proposed. Although the decomposition routes of C(2)H(5)OH and C(2)H(5)I, both forming C(2)H(5)O- on TiO(2), suggest that -OCH(2)CH(2)O- may play a role in the crotonaldehyde formation, reaction of HOCH(2)CH(2)OH on TiO(2) shows that this is not the case. Adsorbed H(2)O is formed in the ICH(2)CH(2)OH decomposition on TiO(2); however, it is found that ICH=CH(2), possibly generated by ICH(2)CH(2)OH dehydration, is not important in the crotonaldehyde formation.


Occurrence of Bunodera sacculata Van Cleave and Mueller, 1932 in Perca flavescens from Silver Creek and Silver Lake, Michigan.
Bunodera sacculata (Trematoda: Allocreadiidae) infected 65 (54%) of 120 yellow perch collected in 1997 and 40 (50%) of 80 perch from Silver Creek in 1998. and 17 (30%) of 56 perch in 2000 from Silver Lake in lower Michigan. Gravid B. sacculata occurred in the pyloric ceca and anterior intestine. There were differences in monthly trends (July through August) in prevalences, mean intensities, and mean abundances of B. sacculata in Silver Creek between 1997 and 1998. The mean intensity +/- SD (8.2 +/- 9.1) and mean abundance (4.1 +/- 7.8) of B. sacculata were significantly higher in 1998 than in 1997 and 2000. An additional 20 perch (0+ in age) collected from the creek in July 1998 were all infected and had the highest mean intensity of 21.3 +/- 14.1.


Inhibition of growth hormone secretion by activin A in human growth hormone-secreting tumour cells.
Effect of activin A on growth hormone secretion was studied in primary culture of 8 human GH-secreting adenomas, which were responsive to TRH in vivo. When studied in vitro, basal GH secretion was reduced in all cases when cells were pre-incubated for 48 h with activin A at a concentration of 5 X 10(-9) mol/l or greater. Pretreatment of GH-secreting cells with 1 X 10(-9) mol/l activin A did not affect either basal secretion or cellular content of GH. These tumour cells also responded to TRH in vitro and the GH response to TRH was completely blocked in cells pretreated with activin A. Activin A slightly reduced the increase in cytoplasmic free calcium concentration induced by TRH. Furthermore, pretreatment of the cells with activin A attenuated GH secretion induced by A23187 or 12-O-tetradecanoyl phorbol-4-acetate, agents which bypass receptor-mediated generation of second messengers. These results indicate that activin A inhibits GH secretion by directly acting on human GH-secreting cells and that activin A inhibits the action of TRH by acting on multiple steps in the messenger system.


High frequency plant regeneration from mature seed of elite, recalcitrant Malaysian indica rice ( Oryza sativa L.) CV. MR 219.
An efficient in vitro plant regeneration system was established for elite, recalcitrant Malaysian indica rice, Oryza sativa L. CV. MR 219 using mature seeds as explant on Murashige and Skoog and Chu N6 media containing 2,4-dichlorophenoxy acetic acid and kinetin either alone or in different combinations. L-proline, casein hydrolysate and L-glutamine were added to callus induction media for enhancement of embryogenic callus induction. The highest frequency of friable callus induction (84%) was observed in N6 medium containing 2.5 mg l(-1) 2,4-dichlorophenoxy acetic acid, 0.2 mg l(-1) kinetin, 2.5 mg l(-1) L-proline, 300 mg l(-1) casein hydrolysate, 20 mg l(-1) L-glutamine and 30 g l(-1) sucrose under culture in continuous lighting conditions. The maximum regeneration frequency (71%) was observed, when 30-day-old N6 friable calli were cultured on MS medium supplemented with 3 mg l(-1) 6-benzyl aminopurine, 1 mg l(-1) naphthalene acetic acid, 2.5 mg l(-1) L-proline, 300 mg l(-1) casein hydrolysate and 3% maltose. Developed shoots were rooted in half strength MS medium supplemented with 2% sucrose and were successfully transplanted to soil with 95% survival. This protocol may be used for other recalcitrant indica rice genotypes and to transfer desirable genes in to Malaysian indica rice cultivar MR219 for crop improvement.


Analyzing diffusion tensor images with ghosting artifacts: the effects of direct and indirect normalization.
The current study aims to assess the applicability of direct or indirect normalization for the analysis of fractional anisotropy (FA) maps in the context of diffusion-weighted images (DWIs) contaminated by ghosting artifacts. We found that FA maps acquired by direct normalization showed generally higher anisotropy than indirect normalization, and the disparities were aggravated by the presence of ghosting artifacts in DWIs. The voxel-wise statistical comparisons demonstrated that indirect normalization reduced the influence of artifacts and enhanced the sensitivity of detecting anisotropy differences between groups. This suggested that images contaminated with ghosting artifacts can be sensibly analyzed using indirect normalization.


Cotton AnnGh3 encoding an annexin protein is preferentially expressed in fibers and promotes initiation and elongation of leaf trichomes in transgenic Arabidopsis.
The annexins are a multifamily of calcium-regulated phospholipid-binding proteins. To investigate the roles of annexins in fiber development, four genes encoding putative annexin proteins were isolated from cotton (Gossypium hirsutum) and designated AnnGh3, AnnGh4, AnnGh5, and AnnGh6. Quantitative reverse transcription-polymerase chain reaction (qRT-PCR) results indicated that AnnGh3, AnnGh4, and AnnGh5 were preferentially expressed in fibers, while the transcripts of AnnGh6 were predominantly accumulated in roots. During fiber development, the transcripts of AnnGh3/4/5 genes were mainly accumulated in rapidly elongating fibers. With fiber cells further developed, their expression activity was dramatically declined to a relatively low level. In situ hybridization results indicated that AnnGh3 and AnnGh5 were expressed in initiating fiber cells (0-2 DPA). Additionally, their expression in fibers was also regulated by phytohormones and [Ca(2+)]. Subcellular localization analysis discovered that AnnGh3 protein was localized in the cytoplasm. Overexpression of AnnGh3 in Arabidopsis resulted in a significant increase in trichome density and length on leaves of the transgenic plants, suggesting that AnnGh3 may be involved in fiber cell initiation and elongation of cotton.


Multifunctional-autoprocessing repeats-in-toxin (MARTX) Toxins of Vibrios.
Multifunctional-autoprocessing repeats-in-toxin (MARTX) toxins are a heterogeneous group of toxins found in a number of Vibrio species and other Gram-negative bacteria. The toxins are composed of conserved repeat regions and an autoprocessing protease domain that together function as a delivery platform for transfer of cytotoxic and cytopathic domains into target eukaryotic cell cytosol. Within the cells, the effectors can alter biological processes such as signaling or cytoskeletal structure, presumably to the benefit of the bacterium. Ten effector domains are found in the various Vibrio MARTX toxins, although any one toxin carries only two to five effector domains. The specific toxin variant expressed by a species can be modified by homologous recombination to acquire or lose effector domains, such that different strains within the same species can express distinct variants of the toxins. This review examines the conserved structural elements of the MARTX toxins and details the different toxin arrangements carried by Vibrio species and strains. The catalytic function of domains and how the toxins are linked to pathogenesis of human and animals is described.


Current trends and opportunities in the methodology of electrodermal activity measurement.
Electrodermal activity (EDA) has been measured in the laboratory since the late 1800s. Although the influence of sudomotor nerve activity and the sympathetic nervous system on EDA is well established, the mechanisms underlying EDA signal generation are not completely understood. Owing to simplicity of instrumentation and modern electronics, these measurements have recently seen a transfer from the laboratory to wearable devices, sparking numerous novel applications while bringing along both challenges and new opportunities. In addition to developments in electronics and miniaturization, current trends in material technology and manufacturing have sparked innovations in electrode technologies, and trends in data science such as machine learning and sensor fusion are expanding the ways that measurement data can be processed and utilized. Although challenges remain for the quality of wearable EDA measurement, ongoing research and developments may shorten the quality gap between wearable EDA and standardized recordings in the laboratory. In this topical review, we provide an overview of the basics of EDA measurement, discuss the challenges and opportunities of wearable EDA, and review recent developments in instrumentation, material technology, signal processing, modeling and data science tools that may advance the field of EDA research and applications over the coming years.


Clonality and HPV infection analysis of concurrent glandular and squamous lesions and adenosquamous carcinomas of the uterine cervix.
We analyzed the clonality and human papillomavirus (HPV) infection status of concurrent glandular and squamous lesions and adenosquamous carcinomas of the uterine cervix to clarify their histogenesis. The glandular and squamous components were clonally different from each other in 7 informative concurrent lesions. HPV was episomal in 2 polyclonal glandular dysplasias (GDs). HPV was in a mixed integrated-episomal form in a monoclonal GD, an adenocarcinoma in situ, and an adenocarcinoma. Both tumor components were monoclonal in origin in 6 adenosquamous carcinomas, with identical patterns of X-chromosomal inactivation and types and physical status of HPV. These results imply that the concurrent glandular and squamous lesions are formed separately, whereas adenosquamous carcinoma is more likely to be a combination tumor of monoclonal origin, and that integration of HPV has an important role in the progression from polyclonal GD through monoclonal expansion to adenocarcinoma in situ and adenocarcinoma.


Evidence for heterosynaptic pairing of the inverted segment in pericentric inversion heterozygotes of the deer mouse (Peromyscus maniculatus).
Silver-stained pachytene cells of male deer mice, Peromyscus maniculatus, which were heterozygous for a naturally occurring pericentric inversion of chromosome 6, were analyzed by light microscopy. The presence of the terminally positioned inversion, involving approximately 30% of the length of chromosome 6, was detected by G-banding. Within the inversion, C-band-positive heterochromatin was restricted to the centromeric region. Silver-staining of spermatocytes revealed the synaptonemal complexes (SCs) of the autosomal bivalents and the X-Y chromosome association. Pachytene cells were scored for the presence of inversion loops corresponding to the pericentric inversion of chromosome 6. Possible loop 6 configurations were detected in less than 1% of the cells examined, the vast majority of cells having regularly formed autosomal SCs similar to those reported for homomorphic chromosome pairs in other rodent species. It appears, therefore, that in these mice the inverted region of chromosome 6 was heterosynaptic throughout pachytene. Heterosynapsis is hypothesized as a mechanism which might obviate the production of duplication and deletion chromatids expected from crossing-over in pericentric inversion loops. The observation of heterosynaptic pairing in the inverted segment and the hypothesis of inversion heterosynapsis as a mechanism averting gametic loss are consistent with the widespread occurrence of pericentric inversion polymorphisms in P maniculatus and the apparent failure of pericentric inversions to genetically isolate populations of this species.