TWIK-related two-pore domain potassium channel TREK-1 in carotid endothelium of normotensive and hypertensive mice.
Potassium channels are essential elements of endothelial function. Recently, evidence emerged that the TWIK (tandem of P domains in a weak inwardly rectifying K+ channel)-related K+ channel (TREK-1) of the two-pore domain potassium channel gene family (K2P) may be involved in the regulation of vascular tone. However, the functional and molecular characterization of vascular TREK-1 is incomplete. In this study, we therefore analysed the functional expression of TREK-1 in the endothelium. Moreover, we hypothesized that changes in channel expression may contribute to altered endothelial vasodilator response under conditions of elevated blood pressure. Gene expression and function of endothelial TREK-1 were analysed by single-cell RT-PCR, the patch-clamp technique and pressure myography in murine carotid arteries (CA). K+ outward currents displaying the characteristics of TREK-1 were observed following various TREK-1-activating stimuli such as membrane stretch, intracellular acidosis, polyunsaturated fatty acids, isoflurane (ISOFL), riluzole, and acetylcholine (ACh). In K(Ca)3.1(-/-) mice exhibiting elevated blood pressure, endothelial TREK-1 currents and TREK-1 mRNA expression were enhanced as compared with normotensive control mice. TREK-1-mediated vasodilator responses to alpha-linolenic acid, ISOFL, or ACh were increased. A similar up-regulation of endothelial TREK-1 was observed in spontaneously hypertensive rats. We have found that TREK-1 is an endothelial K+ channel capable of producing hyperpolarization and vasodilation. A correlation between hypertension and up-regulation of TREK-1 was observed in two different animal models of elevated blood pressure. Thus, TREK-1 may play a protective role in the cardiovascular system by providing a novel type of endothelial hyperpolarization-mediated vasodilator response.


National estimates of occupation-related inequalities in all-cause mortality using linked Census-mortality data.
This report aims to provide national estimates of occupation-related inequalities in all-cause mortality for Australian residents aged 25-64 years. Data came from the 2016 Census linked to Deaths Registrations, available via the Multi-Agency Data Integration Project. Using negative binomial regression, we estimated age-adjusted relative and absolute inequalities in all-cause mortality rates in the 13 months following Census according to occupation, defined using the Australian and New Zealand Standard Classification of Occupations (eight major groups), using managers as the reference group. Among 10.8M people, there were 20,987 deaths. Age-adjusted mortality rates were lowest among managers and professionals and were generally highest for manual occupations, for example, among men, relative risks (RR) for labourers ranged across age groups from 1.44 (95% CI 1.19-1.75, age 54-64) to 2.99 (1.93-4.65, age 25-34); among women, the RR for machine operators and drivers were 3.95 (1.39-11.21 in age 25-24 and 2.73 (1.66-4.49) in age 45-54, but there was relatively little variation by occupation in women aged 35-44 and 55-64. Around one in five deaths (23% for men, 17% for women) were associated with being in an occupation other than manager. These findings highlight that there is benefit in documenting national mortality inequalities according to occupation in addition to other measures of socioeconomic position. They provide further insights into socioeconomic inequalities in mortality. Methods that aim to reduce mortality for those in manual occupations, particularly among young men, will reduce inequalities and improve population health.


Interethnic differences in the relevance of CYP2C9 genotype and environmental factors for diclofenac metabolism in Hispanics from Cuba and Spain.
The aims of this study were to evaluate the diclofenac metabolism in Hispanics from Cuba and Spain and its relation to ethnicity, CYP2C9 genotypes and environmental factors. Diclofenac hydroxylation capacity (concentration ratios of diclofenac/metabolites in 8-h urine) was studied in 160 Cuban (classified as 76 Cuban-Whites-CWs and 84 Cuban-Mestizos-CMs) and 148 Spaniard (SPs) healthy volunteers. Diclofenac and its main metabolites, 4'-hydroxy (OH), 3'-OH and 5-OH diclofenac, and CYP2C9*2 to *6 and *8 alleles were also determined in 132 and 128 CWs and CMs, respectively. Gender, tobacco, caffeine and ethanol consumption were also evaluated. The mean diclofenac/4'-OH diclofenac ratio was higher in CMs (0.72±0.25) than in CWs (0.64±0.20; P<0.05) and SPs (0.57±0.26; P<0.001). The mean diclofenac/4'-OH diclofenac ratio was higher (P<0.05) in subjects with CYP2C9*1/*3 (0.77±0.19; n=22) and CYP2C9*1/*8 (0.93±0.33; n=4) genotypes than with CYP2C9*1/*1 (0.65±0.24; n=90). Environmental factors did not seem to influence the diclofenac metabolism in these populations. The present findings show for the first time interethnic differences between Hispanic groups in urinary diclofenac/4'-OH diclofenac ratios, and the relevance of CYP2C9*3 and CYP2C9*8 alleles.


Host-size-dependent sex ratios among parasitoid wasps: does host growth matter?
Waage's (1982) hypothesis that host-size-dependent sex ratios will occur in parasitoids of nongrowing hosts and not in parasitoids of growing hosts is examined using published data on parasitoid wasps. Waage's hypothesis is supported as a general, but not absolute, rule: among solitary parasitoid wasps, a significantly greater proportion of parasitoids of nongrowing than of growing hosts show some evidence of host-size-dependent sex ratios (85% versus 42%, G=6.54, P< 0.05). The premise of Waage's hypothesis-that for parasitoids which develop in a growing stage, host size at oviposition is not a good predictor of the amount of resources available to the developing parasitoid-is also examined. It is suggested that across host species Waage's premise will hold for some, but not all, parasitoids of growing hosts. Likely exceptions to Waage's premise, and thus his prediction, are discussed. Parasitoids of growing hosts which are expected to have evolved hostsize-dependent sex ratios include parasitoids which utilize a narrow size range of host species, parasitoids which can distinguish among host species by some criterion other than size, and parasitoids which utilize host species whose susceptible instars do not overlap in size.


An evaluation of the cariogenic potential of baby and infant fruit drinks.
The cariogenic potential of a range of fruit drinks was assessed on the basis of plaque pH by the plaque harvesting method. In addition, the inherent pH and titratable acidity of each drink was analysed. The effects of so-called 'no sugar added' and 'sugar-free' drinks were compared with a standard 10% sucrose drink for their effect on plaque pH in vitro, on a group of volunteers, using the Cariogenic Potential Index (CPI). All drinks had a low inherent pH and some a high titratable acidity. All the drinks also depressed the plaque pH below 5.5 within 5 minutes of drinking and had a CPI equal to or greater than a standard 10% sucrose solution.


The development of a water rescue unit in an urban EMS system.
A river rescue unit was developed in Pittsburgh in March 1986. From its time of inception through December 31, 1987, the unit responded 572 times (325 times in 1987); this included 144 medical calls. Many of the other calls were police related, false alarms, routine patrols, or public service calls. We present a description of the service, type of training necessary, costs involved, and administrative aspects of running a marine emergency medical services system and its integration into an urban EMS system.


Influence of alcohol and other substances of abuse at the time of injury among patients in a Norwegian emergency department.
The presence of alcohol or other substances of abuse in blood or urine from injured patients is often used as a proxy for substance influence at the time of injury. The aim of this study was to obtain an estimate of substance influence at the time of injury based on blood concentrations of alcohol and other substances of abuse, and to explore the relationship between the substance prevalence at the time of admittance to the hospital and the actual influence at the time of the injury. The study included all adult patients admitted to the emergency department of a university hospital during 1 year (n = 996). Quantification in blood was done by an enzymatic method for alcohol, and by liquid chromatography-mass spectrometry or gas chromatography-mass spectrometry for 28 other substances of abuse. Concentrations of alcohol and other substances in blood at the time of injury were calculated. The degree of influence was assessed on the basis of the calculated blood concentrations, with a threshold of influence set at a blood alcohol concentration (BAC) of 0.05 %, or a substance concentration leading to an influence similar to that of a BAC of 0.05 %. A total of 324 patients (32.5 %) were determined to be under the influence at the time of injury. In comparison, 394 patients (39.6 %) had one or more substances above the cut-off limit in blood at the time of admittance to the hospital. Alcohol was the most prevalent substance causing influence at 25.9 %. Among patients with violence-related injuries, almost 75 % were under the influence of alcohol and/or substances. Patients under the influence were younger, and men were more often under the influence than women. More patients were under the influence at nighttime and during weekends than at daytime and on weekdays. About one third of the injured patients were determined to be under the influence at the time of injury, with alcohol being the most prevalent substance causing influence. Approximately 98 % of the patients with alcohol detected in blood at the time of admittance to the hospital were under the influence of alcohol at the time of injury.


PA-457, new kind of antiretroviral: ten-day clinical trial results.
A new kind of antiretroviral, called a maturation inhibitor, worked well in reducing viral load in a ten-day trial with HIV-positive volunteers.


The "Temporary Recommendations for Use": A dual-purpose regulatory framework for off-label drug use in France.
In 2012, following the Mediator(®) (benfluorex) scandal, France displayed the ambitious goal to implement a regulatory framework for controlling off-label drug use: the "Temporary Recommendations for Use" (RTUs). It aims to regulate the use of pharmaceuticals outside the scope of a marketing authorization (MA) by establishing a framework for patient monitoring and data collection. This is intended to ensure that the benefit/risk ratio is favorable for the indication approved by the RTU. The granting of an RTU enables the reimbursement of off-label drug use and encourages pharmaceutical companies to expand their MA. Between 2012 and 2014, the regulator framework for RTUs was amended twice in order to allow the bypassing of an MA for economic reasons, when a licensed alternative drug exists (so far, this is only illustrated by the bevacizumab (Avastin(®))/ranibizumab (Lucentis(®)) case). The primary purpose of the RTU framework is interesting by implementing an original national control for off-label uses that respond to a public health need. The secondary purpose is more controversial as it promotes off-label use. This has raised legal issues and has created a ground for litigation between pharmaceutical firms and health authorities. RTUs provide an interesting example for other countries that are exploring the possibility of regulating off-label drug use. At the same time, the processes surrounding the implementation of RTUs illustrate the difficulties of public policies to balance public health needs, safety and economic goals.


Apolipoprotein-mimetic nanodiscs reduce lipid accumulation and improve liver function in acid sphingomyelinase deficiency.
Acid sphingomyelinase deficiency (ASMD) is a severe lipid storage disorder caused by the diminished activity of the acid sphingomyelinase enzyme. ASMD is characterized by the accumulation of sphingomyelin in late endosomes and lysosomes leading to progressive neurological dysfunction and hepatosplenomegaly. Our objective was to investigate the utility of synthetic apolipoprotein A-I (ApoA-I) mimetics designed to act as lipid scavengers for the treatment of ASMD. We determined the lead peptide, 22A, could reduce sphingomyelin accumulation in ASMD patient skin fibroblasts in a dose dependent manner. Intraperitoneal administration of 22A formulated as a synthetic high-density lipoprotein (sHDL) nanodisc mobilized sphingomyelin from peripheral tissues into circulation and improved liver function in a mouse model of ASMD. Together, our data demonstrates that apolipoprotein mimetics could serve as a novel therapeutic strategy for modulating the pathology observed in ASMD.


Voluntary consumption of substances of unknown palatability by vervet monkeys: a refinement.
Pure compounds and herbal medicines, had to be administered orally to vervet monkeys for testing. A reliable method was sought to avoid daily gavaging. Substances were incorporated into the maize meal based diet of this facility for voluntary consumption. Food intake was monitored. In all but one case, consumption of the treated food was in excess of 90%. In all cases, the purpose of the study was achieved. Habituation was usually only required to the vehicle, and was accomplished by incremental increases to the desired concentration. Aversion was overcome by the addition of a small amount of honey. Plasma concentrations of a compound metabolite could be measured in one case after gavage and food consumption, and were similar for both methods. The method enables reliable voluntary consumption of diverse substances. Since stressful gavaging is avoided, it is a valuable contribution to the 3Rs.


Anatomic location and somatotopic arrangement of the corticospinal tract at the cerebral peduncle in the human brain.
Little is known about the detailed anatomic location and somatotopic arrangement at the CP. Using DTT with FSL tools, we conducted an investigation of the anatomic location and somatotopic arrangement of the CST at the CP in the human brain. We recruited 43 healthy volunteers for this study. DTI was obtained by using 1.5T, and CSTs for the hand and leg were obtained by using the FSL tool. The somatotopic location of the CST was evaluated as the highest probabilistic location at the upper and lower midbrain. The posterior boundary was determined as the line between the interpeduncular fossa and the lateral sulcus; we then drew a rectangle on the basis of the boundary of the CP. In the mediolateral direction, the highest probabilistic locations for the hand and leg were an average of 60.46% and 69.98% from the medial boundary at the upper midbrain level and 53.44% and 62.76% at the lower midbrain level, respectively. As for the anteroposterior direction, the highest probabilistic locations for the hand and leg were an average of 28.26% and 32.03% from the anterior boundary at the upper midbrain level and 30.19% and 33.59% at the lower midbrain level, respectively. We found that the hand somatotopy for the CST is located at the middle portion of the CP and the leg somatotopy is located lateral to the hand somatotopy.


Percutaneous transluminal balloon pulmonary valvoplasty--long-term results.
Thirty-two patients with isolated valvar pulmonary stenosis (21 male; 11 female, age range 4 to 53 years, mean 14 years) underwent cardiac catheterization and balloon valvoplasty. Right ventricular systolic pressure before valvoplasty ranged from 65 to 210 mm Hg (mean 120.2 +/- 44.8 mm Hg). It fell to 24-200 mm Hg (mean 73.1 +/- 42.4 mm Hg) immediately after dilation. Peak systolic gradient across the pulmonary valve before valvoplasty ranged from 42 to 193 mm Hg (mean 98 +/- 45.3 mm Hg) and decreased significantly to 5 to 182 mm Hg (mean 52.7 +/- 43.1 mm Hg) immediately after dilation. At repeat cardiac catheterization in 21 patients 3 to 6 months after valvoplasty, a further significant fall of gradient was noted in 15 patients with no change in the remaining six patients. The right ventricular systolic pressure ranged from 30 to 100 mm Hg (mean 55.1 +/- 21.8 mm Hg) while the transpulmonary gradient varied from 12 to 84 mm Hg (mean 34 +/- 23.8 mm Hg). In the four patients evaluated 1 to 1 1/2 years after valvoplasty, the gradient further reduced in 2 patients and was unchanged in the remaining two patients. Patients with isolated valvar pulmonary stenosis can be adequately and safely treated with balloon valvoplasty, without recourse to surgery with excellent immediate and long-term results.


Staphylococci planktonic and biofilm environments differentially affect osteoclast formation.
The pathophysiology of chronic implant-related bone infections is characterized by an increase in osteoclast numbers and enhanced bone resorption. Biofilms are a major reason for chronicity of such infections as the biofilm matrix protects bacteria against antibiotics and impairs the function of immune cells. Macrophages are osteoclast precursor cells and therefore linked to inflammation and bone destruction. Investigations on the impact of biofilms on the ability of macrophages to form osteoclasts are yet missing and we, therefore, analyzed the effect of Staphylococcus aureus (SA) and Staphylococcus epidermidis (SE) planktonic and biofilm environments on osteoclastogenesis using RAW 264.7 cells and conditioned media (CM). Priming with the osteoclastogenic cytokine RANKL before CM addition enabled the cells to differentiate into osteoclasts. This effect was highest in SE planktonic or SA biofilm CM. Simultaneous stimulation with CM and RANKL, however, suppressed osteoclast formation and resulted in formation of inflammation-associated multinucleated giant cells (MGCs) which was most pronounced in SE planktonic CM. Our data indicate that the biofilm environment and its high lactate levels are not actively promoting osteoclastogenesis. Hence, the inflammatory immune response against planktonic bacterial factors through Toll-like receptors seems to be the central cause for the pathological osteoclast formation. Therefore, immune stimulation or approaches that aim at biofilm disruption need to consider that this might result in enhanced inflammation-mediated bone destruction.


Bone remodelling in osteoporosis.
Bone remodelling, a highly regulated succession of events, is the temporal sequence of osteoclastic bone resorption and osteoblastic bone formation. Bone loss with age and in osteoporotic patients is due to a disequilibrium between both processus. Bone histomorphometry was the method used to measure these events. Its shows clearly that, with age, the quantity of bone formed in one remodelling unit (so called mean wall thickness) decreases. In osteoporotic women, compared to control women of the same age the amount of bone formed is also decreased. Concordant data on this point have been obtained in different laboratories. By contrast, the cellular mechanism underlying this decreased amount of bone formed is largely controversial: a decreased osteoblast recruitment or life span or capacity to synthesize collagen have been suggested. Bone loss with age is associated with an increase in the amount of bone resorbed. This observation is the result of an indirect measurement founded on the distance between trabeculae. As the decreased bone formation, this processus is exaggerated in postmenopausal osteoporosis. The respective importance of decreased bone formation and increased bone resorption is however difficult to assess. Some osteoporotic patients have increased bone resorption surfaces compared to control women on their bone biopsy; however, it does not seem that these patients form a definite subgroup of osteoporotic patients as the extent of resorption surfaces changes with time in an untreated osteoporotic. In conclusion, the observed changes in bone remodelling in osteoporotic post-menopausal women are an exaggeration of those observed during ageing. These changes should be a basis for a coherent therapy of bone loss in osteoporotic patients.


New conjunctive reagents as cross-coupling partners en route to retinoid-like polyenes.
[structure: see text] New conjunctive reagents E-2 and Z-3 can be used, after transmetalation, in Negishi couplings with vinyl and aryl iodides. The subsequently unmasked terminal alkynes can be further manipulated to arrive at retinoid-like products.


All for one: changes in mitochondrial morphology and activity during syncytial oogenesis†.
The syncytial groups of germ cells (germ-line cysts) forming in ovaries of clitellate annelids are an attractive model to study mitochondrial stage-specific changes. Using transmission electron microscopy, serial block-face scanning electron microscopy, and fluorescent microscopy, we analyzed the mitochondria distribution and morphology and the state of membrane potential in female cysts in Enchytraeus albidus. We visualized in 3D at the ultrastructural level mitochondria in cysts at successive stages: 2-celled, 4-celled, 16-celled cysts, and cyst in advanced oogenesis. We found that mitochondria form extensive aggregates-they are fused and connected into large and branched mitochondrial networks. The most extensive networks are formed with up to 10 000 fused mitochondria, whereas individual organelles represent up to 2% of the total mitochondrial volume. We classify such a morphology of mitochondria as a dynamic hyperfusion state and suggest that this can maintain their high activity and intensify the process of cellular respiration within the syncytial cysts. We found some individual mitochondria undergoing degradation, which implies that damaged mitochondria are removed from networks for their final elimination. As growing oocytes were shown to possess less active mitochondria than the nurse cells, the high activity of mitochondria in the nurse cells and their dynamic hyperfusion state are attributed to serve the needs of the growing oocyte. In addition, we measured by calorimetry the total antioxidant capacity of germ-line cysts in comparison with somatic tissue, and it suggests that antioxidative defense systems, together with mitochondrial networks, can effectively protect germ-line mitochondria from damage.


A gap-filling algorithm for prediction of metabolic interactions in microbial communities.
The study of microbial communities and their interactions has attracted the interest of the scientific community, because of their potential for applications in biotechnology, ecology and medicine. The complexity of interspecies interactions, which are key for the macroscopic behavior of microbial communities, cannot be studied easily experimentally. For this reason, the modeling of microbial communities has begun to leverage the knowledge of established constraint-based methods, which have long been used for studying and analyzing the microbial metabolism of individual species based on genome-scale metabolic reconstructions of microorganisms. A main problem of genome-scale metabolic reconstructions is that they usually contain metabolic gaps due to genome misannotations and unknown enzyme functions. This problem is traditionally solved by using gap-filling algorithms that add biochemical reactions from external databases to the metabolic reconstruction, in order to restore model growth. However, gap-filling algorithms could evolve by taking into account metabolic interactions among species that coexist in microbial communities. In this work, a gap-filling method that resolves metabolic gaps at the community level was developed. The efficacy of the algorithm was tested by analyzing its ability to resolve metabolic gaps on a synthetic community of auxotrophic Escherichia coli strains. Subsequently, the algorithm was applied to resolve metabolic gaps and predict metabolic interactions in a community of Bifidobacterium adolescentis and Faecalibacterium prausnitzii, two species present in the human gut microbiota, and in an experimentally studied community of Dehalobacter and Bacteroidales species of the ACT-3 community. The community gap-filling method can facilitate the improvement of metabolic models and the identification of metabolic interactions that are difficult to identify experimentally in microbial communities.


The clinical significance of carotid intima-media thickness in cardiovascular diseases: a survey in Beijing.
This study is to investigate the relationships between prevalent cardiovascular events (myocardial infarction, stroke and peripheral arterial disease) and carotid intima-media thickness (CIMT) in middle-aged and older adults; to assess which of the indexes, IMT in the common carotid artery (CCA), internal carotid artery (ICA) and carotid bifurcation (CB) separately or in combination, is a better correlate. IMT of the CCA, ICA and CB were measured with duplex ultrasound in 1058 individuals (aged between 37 and 86 years old) in a suburban community of Beijing. Histories of cardiovascular events as well as prevalent risk factors were obtained. CIMT were compared between groups with and without cardiovascular events. Associations of cardiovascular events with IMT measurements in CCA, CB and ICA were ascertained. The group with cardiovascular events had higher mean CIMT (0.74 (0.60-0.98) mm vs 0.65 (0.54-0.80) mm, P=0.000) and higher abnormal CIMT proportion (77.20 vs 64.45%, P=0.000). The odds ratio (OR) for myocardial infarction was 1.74 (P=0.010), for stroke 1.98 (P=0.001) and for peripheral arterial disease 1.80 (P=0.072) in abnormal CIMT. However, after adjustment of traditional risk factors, the correlations disappeared, implying that CIMT may act via other risk factors. After adjustment of age, mean CIMT correlated best with total cardiovascular events (OR: 4.39 (2.39-8.04), P=0.000) and stroke (OR: 4.98 (2.55-9.71), P=0.000) separately; mean posterior CIMT correlated with myocardial infarction best (OR: 2.97 (1.68-5.24), P=0.000). CIMT may act as an intermediate point for cardiovascular diseases. Combined CIMT might be the best index associated with cardiovascular diseases.


Plasmacytoid T-cell clusters in non-specific lymphadenitis.
The occurrence and morphology of Lymphoblastennester (clusters of lymphoblasts) were analyzed in 500 unselected cases of nonspecific lymphadenitis. Sixty-eight cases showed such clusters, which consist of uniform-looking medium-sized cells. Based on the results of recent immunologic investigations, these cells may be interpreted as T-cells with plasmacytoid features ("plasmacytoid T-cells', PTC). PTC were usually located near venules in the pulp, but not in the generally hyperplastic T-nodules. There was usually no relation to hyperplasia of B-regions (follicles). Although occasional mitotic figures and basophilic blast cells were found at the edges of PTC clusters, it is possible that PTC develop through transformation of T-lymphocytes. PTC often showed pyknotic nuclei and a tendency to perish, suggesting that they are end cells. Necrotic cells were phagocytosed by macrophages, which occasionally caused a starry sky pattern like that seen in germinal centers. Sometimes there were also a few interdigitating reticulum cells in the clusters. The function of PTC is still obscure; they might secrete lymphokines.


Human fibroblasts for large-scale "omics" investigations of ATM gene function.
ATM (gene mutated in ataxia-telangiectasia) is a critical central component of the pleiotropic responses of cells to ionizing radiation-induced stress. To gain insight into molecular mechanisms and to enhance our understanding of ATM functions, we have advanced a human model cell system, derived from genetically defined immortal fibroblasts, and we have applied high-throughput genomic, proteomic and metabolomic technologies for a systems level analysis. The cellular characterizations reported here provide the background for application of a systems analysis to integrate transcription, post-translational modifications and metabolic activity induced by exposure of cells to ionizing radiation. We present here a summary of the derivation and characterization of cells comprising this model cell system and review applications of this model to systems analysis of ATM functions.


Effects of dantrolene sodium in rodent models of cardiac arrhythmia.
Dantrolene sodium has been compared with reference antiarrhythmic agents in rodent models of cardiac arrhythmia. In a coronary-artery-ligation model in rats, dantrolene sodium (3, 10 and 20 mg/kg i.v.) significantly decreased extrasystoles, episodes of ventricular tachyarrhythmia, and frequency, duration, and total episodes of ventricular fibrillation in a dose-dependent manner. In an electrically induced fibrillation model in rats, dantrolene sodium (10 and 20 mg/kg i.v.) significantly raised ventricular fibrillation threshold in a dose- and time-dependent manner. In contrast to its activity in these models, dantrolene sodium was not active in two chemically induced models involving automaticity. Aconitine-induced arrhythmias in rats and mice and ouabain-induced arrhythmias in guinea pigs were not suppressed by i.v. (10 or 20 mg/kg) or i.p. (100-3000 mg/kg) doses of the drug. These results show that the antiarrhythmic potential of dantrolene sodium, predicted by in vitro Class III and Class IV electrophysiological effects, is expressed in whole animal models.


Cellular distribution of vascular endothelial growth factor A (VEGFA) and B (VEGFB) and VEGF receptors 1 and 2 in focal cortical dysplasia type IIB.
Members of the vascular endothelial growth factor (VEGF) family are key signaling proteins in the induction and regulation of angiogenesis, both during development and in pathological conditions. However, signaling mediated through VEGF family proteins and their receptors has recently been shown to have direct effects on neurons and glial cells. In the present study, we immunocytochemically investigated the expression and cellular distribution of VEGFA, VEGFB, and their associated receptors (VEGFR-1 and VEGFR-2) in focal cortical dysplasia (FCD) type IIB from patients with medically intractable epilepsy. Histologically normal temporal cortex and perilesional regions displayed neuronal immunoreactivity (IR) for VEGFA, VEGFB, and VEGF receptors (VEGFR-1 and VEGFR-2), mainly in pyramidal neurons. Weak IR was observed in blood vessels and there was no notable glial IR within the grey and white matter. In all FCD specimens, VEGFA, VEGFB, and both VEGF receptors were highly expressed in dysplastic neurons. IR in astroglial and balloon cells was observed for VEGFA and its receptors. VEGFR-1 displayed strong endothelial staining in FCD. Double-labeling also showed expression of VEGFA, VEGFB and VEGFR-1 in cells of the microglia/macrophage lineage. The neuronal expression of both VEGFA and VEGFB, together with their specific receptors in FCD, suggests autocrine/paracrine effects on dysplastic neurons. These autocrine/paracrine effects could play a role in the development of FCD, preventing the death of abnormal neuronal cells. In addition, the expression of VEGFA and its receptors in glial cells within the dysplastic cortex indicates that VEGF-mediated signaling could contribute to astroglial activation and associated inflammatory reactions.


Use of Tranexamic Acid in Bleeding Control of Transabdominal and Transvaginal Hysterectomy.
Hysterectomy is one of the most common gynecology surgeries. This study aimed to compare perioperative bleeding in transabdominal and transvaginal hysterectomy. This prospective, double-blind, randomized, controlled clinical trial was performed on 80 patients undergoing hysterectomy referred to Shahid Beheshti Hospital, Isfahan, Iran. Patients were divided into two groups of 40; the first group (T) received 1 g intravenous tranexamic acid (TXA) for 20 min preoperatively. The second group (S) received 10 cc normal saline as placebo. Blood samples were taken before and 12 h after surgery for assessment of hemoglobin, hematocrit, and platelet count, the prothrombin time, activated partial thromboplastin time, and serum creatinine as well as volume of blood transfusion. There were no significant differences between the two groups in heart rate, diastolic blood pressure (BP), systolic BP, and mean arterial pressure before, during, and after surgery (P > 0.05). There was no significant difference in blood variables before and after surgery (P > 0.05) except the platelet count that was in the normal range in both groups after surgery (P = 0.022). The mean volume of blood transfused in the case group was significantly lower than the control group during surgery (P = 0.008) and 12 h after surgery (P = 0.01). The prophylactic administration of TXA results in a significant reduction in need for blood transfusion and the duration of surgery. Given the lower risks of using TXA compared to the other drugs, it is recommended in hysterectomy to control bleeding.


Haemoproteus tartakovskyi (Haemoproteidae): Complete sporogony in Culicoides nubeculosus (Ceratopogonidae), with implications for avian haemoproteid experimental research.
Numerous recent studies have addressed the molecular characterization, distribution and genetic diversity of Haemoproteus spp. (Haemoproteidae). Some species of these blood parasites cause severe disease in birds, and heavy infections are often lethal in biting midges (Ceratopogonidae) and other blood-sucking insects. However, information about the vectors of haemoproteids is scarce. This presents an obstacle for better understanding the mechanisms of host-parasite interactions and the epidemiology of haemoproteosis. Here we investigated the sporogonic development of Haemoproteus tartakovskyi, a widespread bird parasite, in experimentally infected biting midges, Culicoides nubeculosus. These biting midges are widespread in the Europe. The insects were cultivated under laboratory conditions. Unfed females were allowed to take blood meals on wild caught siskins Carduelis spinus naturally infected with H. tartakovskyi (lineage hSISKIN1). Engorged females were maintained at 22-23 °C, dissected at intervals, and examined for sporogonic stages. Mature ookinetes of H. tartakovskyi were seen in the midgut content between 6 and 48 h post infection, oocysts were observed in the midgut wall 3-4 days post infection (dpi). Sporozoites were first reported in the salivary gland preparations 7 dpi. In accordance with microscopy data, polymerase chain reaction amplification and sequencing confirmed presence of the corresponding parasite lineage in experimentally infected biting midges. This study indicates that C. nubeculosus willingly takes blood meals on birds and is a vector of H. tartakovskyi. These biting midges are readily amenable to cultivation under laboratory conditions. Culicoides nubeculosus transmits Haemoproteus parasites infecting parrots, owls and siskins, birds belonging to different families and orders. Thus, this vector provides a convenient model for experimental research with avian haemoproteids.


Glucose oxidase-copper hybrid nanoflowers embedded with magnetic nanoparticles as an effective antibacterial agent.
Bacterial contamination causes various problems ranging from bacterial infection to biofouling. As an effective and non-toxic agent for bacterial de-contamination, glucose oxidase (GOx)-copper hybrid nanoflowers embedded with amine-functionalized magnetic nanoparticles (NH2-MNPs), called 'MNP-GOx NFs', are developed. Positively-charged NH2-MNPs and negatively-charged GOx molecules are first interacted via electrostatic attraction which can be controlled by changing the buffer pH, and the follow-up addition of copper(II) sulfate leads to blooming of nanoflowers (MNP-GOx NFs) after incubation at room temperature for 3 days. MNP-GOx NFs show effective antibacterial activity by generating H2O2 from GOx-catalyzed glucose oxidation. For example, 99.9% killings of Staphylococcus aureus and Escherichia coli are achieved after 3 h treatment of 106/mL cells with 0.2 and 3.0 mg/mL MNP-GOx NFs, respectively, revealing that Gram-positive S. aureus with mono-layer membrane system is more vulnerable to the treatment of MNP-GOx NFs than Gram-negative E. coli with two-layer membrane system. MNP-GOx NFs can maintain 97% of bactericidal activity even after recycled uses by magnetic separation for eight times iterative bacterial killings. Finally, MNP-GOx NFs are employed for the fabrication of antibacterial gauzes. MNP-GOx NFs have also opened up a great potential for their applications in biosensors, biofuel cells and bioconversion as well as bacterial de-contamination.


Hydroxy esters atmospheric degradation: OH and Cl reactivity, products distribution and fate of the alkoxy radicals formed.
Kinetic studies of the reaction of ethyl glycolate HOCH2C(O)OCH2CH3 with OH radicals (kOH) and Cl atoms (kCl) have been conducted by the relative method using a glass atmospheric reactor by "in situ" Fourier Transform Infrared (FTIR) and Gas Chromatography equipped with flame ionization detection by Solid Phase Micro Extraction (GC-FID/SPME) at room temperature and atmospheric pressure. The following relative rate coefficients were determined using several reference compounds and two different techniques: kEG + OH-FTIR = (4.36 ± 1.21) × 10-12; kEG + OH-GC-FID= (3.90 ± 0.74) × 10-12; and kEG + Cl-GC-FID= (6.40 ± 0.72) × 10-11 all values in units of cm3.molecule-1.s-1. Complementary product studies were performed under comparable conditions to the kinetic tests, in order to identify the reaction products and to postulate their tropospheric oxidation mechanisms. The reaction of OH radicals and Cl atoms with ethyl glycolate initiates via H-atom abstraction from alkyl groups of the molecule. Formic acid was positively identified as a reaction product by FTIR. On the other hand, formaldehyde, acetaldehyde, glycolic acid; and formic acid were identified by the GC-MS technique. The Structure-Activity Relationship, (SAR) calculations were also implemented to estimate the more favorable reaction pathways and compare them with the products identified. Tropospheric lifetimes of τOH = 34 h and τCl = 5.5 days were estimated to determine how these investigated reactions might affect the air quality. In this sense, average ozone production of [O3] = 0.75 and a Photochemical Ozone Creation Potential, POCP, of 38 were calculated for the hydroxyl ester studied.


To Compare Short and Long-Term Graft Uptake and Hearing Outcome of Type I Cartilage Tympanoplasty Between Small, Medium and Large Perforations Using Reinforced Sliced Conchal Cartilage.
To compare short and long-term graft uptake and hearing outcome of type I cartilage tympanoplasty between small, medium and large perforations using reinforced sliced conchal cartilage. A retrospective study conducted in a tertiary center. Fifty patients who under went type I tympanoplasty were enrolled. Their mean age was 29.30 years and follow-up time was 6 and 18 months. The preoperative, postoperative short-term and long-term hearing and graft uptake results were analyzed. Graft uptake rate was 96% in short-term and 98% in long-term with one residual perforation in medium size, but 100% in small and large perforations (P < 0.01). Short and long-term ABG closure was identical in small and medium size perforation (P = 0.978) (P = 0.734), but, large perforation showed significant improvement in long-term (P = 0.012). Sliced conchal cartilage reinforced with temporalis fascia is a reliable technique for tympanoplasty. In long-term, large perforations have better graft uptake rate and continuous hearing improvement and ABG closure than small and medium perforations.


The use of diaminodithiol for labeling small molecules with technetium-99m.
To investigate the labeling of small molecules with 99mTc by the bifunctional chelate approach, we have synthesized both a fatty acid and an estrone derivative containing a chelator of the N2S2 type. In the case of the fatty acid, this was a diaminodithiol (DADT) while for the estrone, a diaminodisulfide (DADS) was attached. The estrone derivative (5-(2-methylene estrone 3-methyl ether)-3,3,10,10-tetramethyl-1,2-dithia-5,8-diazacyclodecane hydrochloride, DADS-E) was prepared by alkylation of DADS while the fatty acid derivative (N-(11-undecanoic acid)-N,N'-bis(2-methyl-2-mercaptopropyl) ethylenediamine hydrochloride, DADT-FA) was synthesized by alkylation of DADS followed by reduction. DADS-E was labeled in ethanol at elevated temperatures while DADT-FA was labeled at room temperature, both by stannous reduction. Paper chromatography showed both to be labeled and reverse-phase HPLC showed multiple peaks for both. Serum stability studies were performed by incubation at 37 degrees C with aliquots removed at 1 min and 1 day for analysis by size-exclusion HPLC. Initially, little pertechnetate or binding to serum proteins was observed whereas after 1 day the majority of activity in both cases was protein bound with 20 and 38% pertechnetate appearing for DADT-FA and DADS-E respectively. In conclusion, small biologically active molecules may be labeled with 99mTc through an attached diaminodithiol or diaminodisulfide group.


Dynamic control of strand excision during human DNA mismatch repair.
Mismatch repair (MMR) is activated by evolutionarily conserved MutS homologs (MSH) and MutL homologs (MLH/PMS). MSH recognizes mismatched nucleotides and form extremely stable sliding clamps that may be bound by MLH/PMS to ultimately authorize strand-specific excision starting at a distant 3'- or 5'-DNA scission. The mechanical processes associated with a complete MMR reaction remain enigmatic. The purified human (Homo sapien or Hs) 5'-MMR excision reaction requires the HsMSH2-HsMSH6 heterodimer, the 5' → 3' exonuclease HsEXOI, and the single-stranded binding heterotrimer HsRPA. The HsMLH1-HsPMS2 heterodimer substantially influences 5'-MMR excision in cell extracts but is not required in the purified system. Using real-time single-molecule imaging, we show that HsRPA or Escherichia coli EcSSB restricts HsEXOI excision activity on nicked or gapped DNA. HsMSH2-HsMSH6 activates HsEXOI by overcoming HsRPA/EcSSB inhibition and exploits multiple dynamic sliding clamps to increase tract length. Conversely, HsMLH1-HsPMS2 regulates tract length by controlling the number of excision complexes, providing a link to 5' MMR.


Potential problems inherent in cell-based stable NF-kappaB-GFP reporter systems.
The nuclear factor-kappaB (NF-kappaB) family of transcription factors plays a central role in numerous physiological processes including development, cell survival, immunity, and inflammation. We generated a series of stable clonal lines in mouse embryonic fibroblasts carrying NF-kappaB-GFP plasmid as a reporter. These cell lines were selected by flow cytometry for their high responsiveness to tumor necrosis factor (TNFalpha) or lipopolysaccharide (LPS), two classic NF-kappaB-inducing stimuli. Although all clones were generated from the same parental cell line, they each had a distinctive pattern of response to NF-kappaB stimuli. While exhibiting distinct profiles with regard to the GFP reporter, analysis of endogenous NF-kappaB downstream targets did not always show the same variability. This suggests that in the absence of confirmation of the signaling outcomes using endogenous outputs, considerable caution must be exercised in the interpretation of data using stable reporter systems.


Alterations in nutrient digestibility and performance of heat-stressed dairy cows by dietary L-theanine supplementation.
The purpose of this study was to investigate the effects of dietary L-theanine supplementation on apparent nutrient digestibility, milk yield, milk composition, and blood biochemical indices of dairy cows under heat stress. Thirty Chinese Holstein cows (19.84 ± 2.42 kg milk/d, 192.36 ± 40.77 d in milk and 2 ± 0.93 parities) were divided into 3 groups of 10 animals each. The control group was fed a basal total mixed ration (TMR) diet, while treatment 1 (LTA16) and treatment 2 (LTA32) groups were fed a basal TMR diet supplemented with L-theanine at 16 and 32 g/cow per day, respectively. The results showed that feeding the dairy cows with LTA16 treatment decreased (P < 0.05) their rectal temperature, whereas feeding with LTA32 treatment decreased (P < 0.05) their rumen fluid ammonia nitrogen content. In comparison to the control group, the supplementation of L-theanine had no significant effect (P > 0.05) on the dry matter intake, nutrient digestibility, total volatile fatty acid (TVFA) concentration and molar proportion of volatile fatty acid, milk yield, milk composition, feed efficiency and antioxidant capacity of the dairy cows. The triglyceride (TG) content of the LTA32 group was significantly greater (P = 0.014) than that of the control group. With the increase in L-theanine dosage, the serum cholesterol (CHOL) content significantly increased (P = 0.013). The serum albumin (ALB; P = 0.067), low-density lipoprotein cholesterol (LDL-C; P = 0.053), and high-density lipoprotein cholesterol (HDL-C; P = 0.067) contents showed an upward trend as L-theanine dosage increased. Ultimately, the results of this study show that supplementing dairy cow diet with L-theanine could decrease dairy cow rectal temperature, affect lipid metabolism, and potentially relieve the heat stress of dairy cows to some extent.


Chromatin-remodeling complexes: Conserved and plant-specific subunits in Arabidopsis.
Adenosine triphosphate-dependent chromatin remodeling complexes are important for the regulation of transcription, DNA replication, and genome stability in eukaryotes. Although genetic studies have illustrated various biological functions of core and accessory subunits of chromatin-remodeling complexes in plants, the identification and characterization of chromatin-remodeling complexes in plants is lagging behind that in yeast and animals. Recent studies determined whether and how the Arabidopsis SWI/SNF, ISWI, INO80, SWR1, and CHD chromatin remodelers function in multi-subunit complexes in Arabidopsis. Both conserved and plant-specific subunits of chromatin-remodeling complexes have been identified and characterized. These findings provide a basis for further studies of the molecular mechanisms by which the chromatin-remodeling complexes function in plants.


Prevention of dopaminergic toxicity of MPTP in mice by phenylethylamine, a specific substrate of type B monoamine oxidase.
N-methyl-4-phenyl-1,2,5,6-tetrahydropyridine (MPTP) is toxic to dopaminergic neurones in several mammalian species including mice. Combined treatment with phenylethylamine prevented in mice the long-term (30 days post-treatment) dopamine depletions in striatum induced by MPTP. Phenylethylamine, a naturally-occurring specific substrate of monoamine oxidase (MAO) type B, probably protects against effects of MPTP by competitively inhibiting the oxidative conversion of MPTP to its toxic metabolite N-methyl-4-phenylpyridinium ion catalysed by MAO-B.


Quantum Polar Duality and the Symplectic Camel: A New Geometric Approach to Quantization.
We define and study the notion of quantum polarity, which is a kind of geometric Fourier transform between sets of positions and sets of momenta. Extending previous work of ours, we show that the orthogonal projections of the covariance ellipsoid of a quantum state on the configuration and momentum spaces form what we call a dual quantum pair. We thereafter show that quantum polarity allows solving the Pauli reconstruction problem for Gaussian wavefunctions. The notion of quantum polarity exhibits a strong interplay between the uncertainty principle and symplectic and convex geometry and our approach could therefore pave the way for a geometric and topological version of quantum indeterminacy. We relate our results to the Blaschke-Santaló inequality and to the Mahler conjecture. We also discuss the Hardy uncertainty principle and the less-known Donoho-Stark principle from the point of view of quantum polarity.


Effects of surgical manipulation of the intestine on peptide YY and its physiology.
PYY is a gastrointestinal hormone, mainly released from the distal intestine in response to intraluminal nutrients or via a neurohormonal pathway originating in the proximal intestine. Although there are several molecular forms of circulating PYY with different bioactivity, and further more than six subtypes of Y-receptors, the function is essentially inhibitory to digestive organs located upstream of the digestive tract. These inhibitory mechanisms are named jejunal, ileal and colonic brakes, and play an important supplementary role in adaptation following intestinal resection. When massive resection of the small intestine is performed, the release of PYY from the distal intestine increases, suppressing gastric acid secretion and motility of the gastrointestinal tract, and stimulating pancreatic secretion. After total colectomy, PYY release is reduced first due to reduction of PYY-containing cells, then gradually increases with time, contributing to adaptation of the digestive organs to the new condition.


Biliary ascariasis.
The presenting clinical features of a series of cases of biliary tract ascariasis are described, in particular the characteristic colicky pain which occurs. The term 'ascaritic biliary pain' is introduced for the symptom diagnostic of live Ascaris adult worms inside the biliary passages. Methods of diagnosis before, and in the course of, operation are discussed and seem adequate. The management of worms discovered in the bile ducts, and those in the proximal small bowel, is described.


Neuropsychological function in peripheral vascular disease amputee patients.
Approximately 75% of major lower-extremity amputations are the result of peripheral vascular disease (PVD). Factors that predispose a patient to PVD (smoking, hyperlipidemia, diabetes mellitus) are also risk factors for the development of cerebrovascular disease, which could adversely affect rehabilitation. The purpose of this study was to test the hypothesis that cognitive deficits are present in amputee patients with PVD. Fourteen patients with lower-extremity amputations secondary to PVD (4 women, 10 men; mean age = 67.4 years) were recruited from a tertiary-care center for physical rehabilitation. Fourteen community-dwelling healthy volunteers (9 women, 5 men; mean age = 69.9 years) served as age-matched and education-matched controls. To assess a broad range of cognitive function, we administered standard neuropsychological tests of memory and learning, language, praxis, visuospatial skills, and abstract reasoning. PVD patients performed significantly more poorly on certain measures of psychomotor speed (Wechsler Adult Intelligence Scale-Revised Digit Symbol subtest) and problem solving/abstract reasoning (Modified Card Sorting Test) relative to controls (using the Bonferroni correction for multiple comparisons, p < .002). There were trends toward poorer patient performance on certain measures of oral fluency, concentration, reasoning, and visuoperceptual organization and constructional skills (p < .01). We propose that these cognitive deficits may be the result of unrecognized concomitant cerebrovascular disease in PVD patients and are part of a generalized pattern of vascular disease. Future research should control affective factors such as stress or depression surrounding amputation and attempt to identify the etiologic or demographic factors that are associated with neuropsychological deficits in patients with PVD.


Total Toe Replacement in the United States: What Is Known and What Is on the Horizon.
Arthritis of the first metatarsophalangeal is a common problem of the forefoot. The gold standard surgical treatment has been fusion of the first metatarsophalangeal joint. Many patients are unwilling to accept pain relief at the expense of loss of motion and the corresponding loss of shoe wear choices and activities requiring dorsiflexion of the hallux. Early implants were plagued with loosening and continued pain but implants have evolved. Current implants use modern bearing surfaces with press-fit fixation. These implants have renewed optimism for total toe arthroplasty. This article reviews the literature for implants currently available and describes the surgical techniques.


A new assessment of the algal biomass of green tide in the Yellow Sea.
The annually recurring Yellow Sea green tide causes significant economic, social, and ecological impacts in China. Currently, the magnitude of Yellow Sea green tide is usually evaluated according to the snap shot maximum algal coverage area or artificially removed algal biomass. However, this method ignores growth of the alga Ulva prolifera and thus needs improvement. We build a model to predict algal growth in drifting from upstream and the potential muaximum biomass of green tide. The results suggest that the potential maximum biomass is significantly higher than those estimated merely from maximum algal coverage area, particularly for years with extended period of algal loading in the upstream. Our method improves the evaluation of the magnitude of green tide and provides a scientific basis for developing effective countermeasures to reduce the persistent disaster.


The adsorption, kinetics, and interaction mechanisms of various types of estrogen on electrospun polymeric nanofiber membranes.
This study focuses on the adsorption kinetics of four highly potent sex hormones (estrone (E1), 17β-estradiol (E2), 17α-ethinylestradiol (EE2), and estriol (E3)), present in water reservoirs, which are considered a major cause of fish feminization, low sperm count in males, breast and ovarian cancer in females induced by hormonal imbalance. Herein, electrospun polymeric nanostructures were produced from cellulose acetate, polyamide, polyethersulfone, polyurethanes (918 and elastollan), and polyacrylonitrile (PAN) to simultaneously adsorbing these estrogenic hormones in a single step process and to compare their performance. These nanofibers possessed an average fiber diameter in the range 174-330 nm and their specific surface area ranged between 10.2 and 20.9 m2g-1. The adsorption-desorption process was investigated in four cycles to determine the effective reusability of the adsorption systems. A one-step high-performance liquid chromatography technique was developed to detect and quantify concurrently each hormone present in the solution. Experimental data were obtained to determine the adsorption kinetics by applying pseudo-first-order, pseudo-second-order and intraparticle diffusion models. Findings showed that E1, E2 and EE2 best fitted pseudo-second-order kinetics, while E3 followed pseudo-first-order kinetics. It was found that polyurethane Elastollan nanofibers had maximum adsorption capacities of 0.801, 0.590, 0.736 and 0.382 mg g-1for E1, E2, EE2 and E3, respectively. In addition, the results revealed that polyurethane Elastollan nanofibers had the highest percentage efficiency of estrogens removal at ∼58.9% due to its strong hydrogen bonding with estrogenic hormones, while the least removal efficiency for PAN at ∼35.1%. Consecutive adsorption-desorption cycles demonstrated that polyurethane maintained the best efficiency, even after being repeatedly used four times compared to the other polymers. Overall, the findings indicate that all the studied nanostructures have the potential to be effective adsorbents for concurrently eradicating such estrogens from the environment.


Increased exercise tolerance and reduced duration of ischemia after isosorbide dinitrate oral spray in angina pectoris.
The prophylactic and therapeutic anti-ischemic efficacy of isosorbide dinitrate (ISDN) oral spray was assessed in 10 patients with coronary artery disease and stable angina pectoris. The patients entered a randomized crossover study of ISDN spray and placebo, involving bicycle exercise testing. Each patient underwent 2 exercise tests at least 4 hours apart. Immediately before initiation of exercise they received either ISDN spray or placebo and crossed over during the other test. ISDN spray delayed the onset of anginal pain by about 40%, from a mean of 5.1 +/- 1.4 minutes with placebo to 7.2 +/- 1.3 minutes with the active drug (p less than 0.001). Time of onset of ST-segment depression was also significantly prolonged, from 7.1 +/- 1.5 minutes with placebo to 10.2 +/- 1.2 minutes with ISDN (p less than 0.001). The patients achieved a higher double product at onset of pain with ISDN than with placebo. The drug also reduced the time of disappearance of pain after discontinuation of exercise from 3.2 +/- 0.7 to 2.1 +/- 0.8 minutes (p less than 0.001), and the time of disappearance of electrocardiographic changes from 4.2 +/- 0.6 to 2.5 +/- 0.8 minutes (p less than 0.005). These findings indicate that oral ISDN spray is an effective prophylactic for exercise-induced angina. Its rapid onset of action makes it especially suitable for usage immediately before exercise.


Smoking is associated with increased resting energy expenditure in the general population: The NEO study.
Animal studies and human studies in small selected populations have shown a positive association between nicotine smoking and resting energy expenditure (REE), but data in large cohorts are lacking. We aimed to investigate the association between smoking behavior and REE in a large, population-based study. Population-based cross-sectional study. In this cross-sectional analysis of baseline measurements from the Netherlands Epidemiology of Obesity (NEO) study (n=6673), we included participants with REE measurement by indirect calorimetry who were not using lipid or glucose lowering drugs (n=1189). We used linear regression analysis to examine the association of smoking status (never, former, occasional, current smoker) and smoking quantity (pack years) with REE per kilogram (kg) fat free mass (FFM) and with REE adjusted for FFM. Models were adjusted for age, sex, ethnicity, educational level, physical activity, energy intake and body mass index (BMI). Mean (standard deviation, SD) age was 55.2 (5.9) years and BMI was 26.3 (4.4) kg/m(2). 60% of the participants were women. Mean (SD) REE/FFM (kcal/day/kg FFM) was for male never smokers 25.1 (2.0), male current smokers 26.4 (2.8), female never smokers 28.9 (2.5) and female current smokers 30.1 (3.7). After adjustment, only current smokers had a higher REE/FFM (mean difference 1.28, 95% CI 0.64, 1.92), and a higher REE adjusted for FFM (mean difference 60.3 kcal/day, 95% CI 29.1, 91.5), compared with never smokers. There was no association between pack years and REE/FFM (mean difference -0.01, 95% CI -0.06, 0.04) or REE adjusted for FFM (mean difference 0.2, 95% CI -2.4, 2.8) in current smokers. Current smoking is associated with a higher resting energy expenditure compared with never smoking in a large population-based cohort.


Genital chlamydial infection: a role for social scientists.
Potential sociomedical research contributions to the understanding of genital chlamydial infections are outlined in a six-part sociomedical 'checklist'. Sociomedical research focuses on human behavior and its social, economic, cultural, and psychological determinants. Thus, the author urges sociomedical researchers--primarily medical sociologists, medical anthropologists, social psychologists, and public health economists--to explore the cultural, socioeconomic, and behavioral factors contributing to the current 'epidemic' of genital chlamydial infection, a sexually transmitted disease (STD) that is found worldwide and has now supplanted gonorrhea as the most common STD in the industrialized nations. Control of this STD is particularly important because of its grave consequences for women's and maternal/child health; these include ectopic pregnancy, infertility, and neonatal morbidity. Before effective prevention and control programs can be realized, however, beliefs and behaviors surrounding such areas as sexuality, fertility, contraception, STDs, hygiene, and health care must be discerned for widely based populations in both industrialized and nonindustrialized nations.


Activated Carbons from Hydrochars Prepared in Milk.
Hydrothermal carbonization converts organics in aqueous suspension to a mixture of liquid components and carbon-rich solids (hydrochars), which in turn can be processed into activated carbons. We investigated whether milk could be used as a medium for hydrothermal carbonization, and found that hydrochars prepared from milk, with or without an added fibrous biomass, contained more carbon (particularly aliphatic carbon), less oxygen, and more mineral components than those prepared from fibrous biomass in water. Activated carbons produced from hydrochars generated in milk had lower specific surface areas and CO2 capacities than those from hydrochars formed in water; however, these differences disappeared upon normalizing to the combustible mass of the solid. Thus, in the context of N2 and CO2 uptake on activated carbons, the primary effect of using milk rather than water to form the hydrochar precursor was to contribute inorganic mass that adsorbed little CO2. Nevertheless, some of the activated carbons generated from hydrochars formed in milk had specific CO2 uptake capacities in the normal range for activated carbons prepared by activation in CO2 (here, up to 1.6 mmol g-1 CO2 at 15 kPa and 0 °C). Thus, hydrothermal carbonization could be used to convert waste milk to hydrochars and activated carbons.


The concentration of hyaluronate in amniotic fluid.
The concentration of sodium hyaluronate has been determined in amniotic fluid by a specific radioassay. It shows a large individual variation. The mean concentration is approximately 20 micrograms/ml at Weeks 16-20 of the gestational period. It drops to approximately 1 micrograms/ml at Week 30 and is then constant until the end of the pregnancy.


[Change in the diagnosis and therapy of anxiety disorders. 1: Phenomenology of anxiety and new approaches in the classification of anxiety disorders].
The pathological states anxiety neurosis and phobias, diagnostically classified under the neuroses, are, influenced by a recent American diagnostic classification, now designated anxiety disorders in clinical psychiatry. With this approach, which is more phenomenological than etiological in orientation, new diagnostic possibilities--among other things--have arisen. In the first place, an accurate differentiation of periodic and chronic states of anxiety can be made, while the clinical phenomena can be considered from various aspects, in order to evaluate simultaneously 1. the current clinical manifestation, 2. the underlying personality traits, and 3. the physical disorders presenting.


Investments, time preferences and public transfers paid to women.
The literature suggests men and women may have different preferences. This paper exploits a social experiment in which women in treatment households were given a large public cash transfer (PROGRESA). In an effort to disentangle the effect of additional income in the household from the effect of changing the distribution of income within the household, the impact of PROGRESA income on savings and investments decisions is compared with all other income sources (after taking into account participation in the program). Additional money in the hands of women is spent on small livestock (which are traditionally managed and cared for by women), improved nutrition and on child goods (particularly clothing). Among single headed households, PROGRESA income is not treated differently from other income. Direct evidence on inter-temporal preferences gathered in the Mexican Family Live Survey indicates that women are more patient than males when thinking about the future. Taken together, the results suggest that PROGRESA income results in a shift in the balance of power within households and women allocated more resources towards investments in the future.


Social Responsibility Practices of EHR Vendors: An Analysis of Disclosures in Annual Corporate Reports and Websites.
Socially desirable outcomes within healthcare IT depend not only on the ethical behavior of individuals, but also on the actions and policies of large corporations. It is therefore important to have public accountability mechanisms that can be applied to corporations. The Sustainability Accounting Standards Board (SASB) publishes standards for assessing corporate transparency around ethical issues of broad public interest. The SASB standards and methodology were used to assess disclosures in the annual shareholder reports and websites of the top EHR vendors. The results showed a very low rate of meaningful disclosure.


Recent progress and evolution of coolant usages in conventional machining methods: a comprehensive review.
This paper reviews recent progress and applications of usage of cutting fluids in conventional machining processes. In addition to reviewing the various conventional and advanced cooling techniques during machining, the paper also discusses the use of minimum quantity lubrication (MQL) in several types on metals such as steel, aluminum, alloy, and titanium alloys. Due to the toxicity of conventional cutting fluid resulting in ecological problems, the demand for environmentally friendly cutting fluid is rising. Therefore, natural vegetable oil is chosen as potential replacement as an environmentally friendly cutting fluid which fulfills the important aspects of biodegradability and sustainability. Application of vegetable oil-based cutting fluids under MQL techniques are also discussed. Moreover, the potential of palm oil as biodegradable and environmentally friendly natural vegetable oil-based metal-working fluids in MQL are reviewed.


Tylophora compounds as Na+/K(+)-ATPase inhibitors.
1. Acetyltylophoroside (AcT) and tylogenin inhibit Na+/K(+)-ATPase in spite of having structures very different from cardiac glycosides (CGs). 2. Calculation of the lowest energy conformations of AcT and tylogenin and superpositions of these with the X-ray conformations of CGs and chlormadinone acetate led to a model for the interaction of these different types of Na+/K(+)-ATPase inhibitors with the receptor.


Identification of differentially expressed proteins in heart of mouse death from smother based on label-free proteomics.
Identification of mechanical asphyxia deaths without obvious injuries is a difficult problem for forensic medicine. This study aimed to identify molecular biological markers to predict death from mechanical asphyxia (smother). We established a smother model of mice by over the head with plastic bag tightly until the mice died and applied label-free proteomic technology to identify differentially expressed proteins (DEPs) in heart. A total of 3307 proteins were quantified, and a Fold Change (FC) > 1.2 (or <1/1.2) and Q value < 0.05 were considered as DEPs. Through comparative analysis, we identified 606 DEPs compared to the control group, comprising 219 upregulated and 387 downregulated proteins. Bioinformatics analysis (MCODE analysis) showed that the candidate proteins were mainly involved in regulation of ribosome function, myocardial contraction and calcium regulation, regulation of coagulation and regulation of mitochondrial oxidative respiration. Seven of these proteins were validated using parallel reaction monitoring (PRM), including fibrinogen alpha chain (FIBA), fibrinogen gamma chain (FIBG), Calsequestrin-2 (CASQ2), NADH dehydrogenase [ubiquinone] 1 alpha subcomplex subunit 11 (NDUAB), NADH dehydrogenase [ubiquinone] 1 alpha subcomplex subunit 3 (NDUA3), NADH dehydrogenase [ubiquinone] 1 alpha subcomplex subunit 13 (NDUAD) and Rab7 (RAB7A). CASQ2 and FIBG were further validated by immunohistochemistry. In conclusion, our results may provide some auxiliary indices for identifying the death from mechanical asphyxia.


Fibronectin inhibits platelet aggregation independently of RGD sequence.
Fibronectin binds to platelet membrane glycoprotein (GP) IIb-IIIa in Arg-Gly-Asp (RGD)-dependent and -independent manner. We have isolated and characterized the 29-kDa dispase fragment of fibronectin. Binding of 125I-fibronectin to thrombin-stimulated platelets was inhibited by the 29-kDa fragment and the GRGDSPA peptide with IC50 values of 1.5 +/- 0.4 and 8.1 +/- 0.9 microM, respectively. The NH2-terminal sequence of this fragment gave this result: Ala-Val-Thr-Thr-Ile-Pro-Ala-Pro-Thr-Asp. This established the position of this peptide within fibronectin as beginning with the residue tentatively designated 1597. Neither the RGDS sequence nor the RGD-independent binding domain of fibronectin (Bowditch, R. D., Halloran, C. E., Aota, S., Obara, M., Plow, E. F., Yamada, K. M., and Ginsberg, M. H. (1991) J. Biol. Chem. 266, 23323-23328) was contained in this fragment. The 29-kDa fragment inhibited ADP-induced aggregation of platelets and binding of fibrinogen to activated platelets. The fragment bound to immobilized GPIIb-IIIa. The 125I-labeled 29-kDa fragment directly bound to thrombin-stimulated platelets with 98,000 +/- 4,600 molecules/platelet (Kd = 4.6 +/- 0.5 x 10(-6) M). Direct binding was inhibited by the unlabeled 29-kDa fragment but was not blocked by either the GRGDSPA peptide or the monoclonal anti-GPIIb-IIIa antibody. These results indicate that the additional RGD-independent binding domain(s) to GPIIb-IIIa are present on fibronectin. This additional binding domain(s) on fibronectin may prevent thrombus formation by interfering with the interaction of fibrinogen with GPIIb-IIIa.


Glycogen-lead relationship in the earthworm Dendrobaena rubida from a heavy metal site.
Control individuals contained no lead in the chloragocytes but high alpha-glycogen rosette reserves. Starvation of contaminated earthworms for 4d caused a lead loss and the chlorgocytes possessed fewer debris vesicles than those of unstarved worms, suggesting that the debris vesicles may be the route for at least some of the lead loss. No glycogen deposits were observed in the chloragocytes of starved or unstarved earthworms from contaminated soil. Maintenance of contaminated earthworms in potting compost caused lead losses similar to those sustained by starvation, but the chloragocyte cytoplasm possessed beta-glycogen reserves. Specimens maintained in lead-spiked potting compost showed lead levels similar to those of earthworms taken directly from contaminated soil. No beta-glycogen accumulations were observed under this enriched regime. Although the possible interference of lead in carbohydrate metabolism is discussed, the results do not wholly support metabolic inhibition by lead. It is hypothesised that lead sequestration is energy-demanding and that in the absence of an energy-rich diet glycogen stores fail to accumulate. In the presence of an organic-rich medium, elevated lead levels preclude glycogen formation, because of the high sequestration-demand, but at lower lead levels beta-glycogen deposits occur if a high organic diet is available.


The mechanism of decrease in dynamic mitral regurgitation during heart failure treatment: importance of reduction in the regurgitant orifice size.
The purpose of this study was to quantify and characterize the regurgitant flow pattern and regurgitant orifice area in patients undergoing therapy for severe heart failure using contemporary echocardiographic techniques. Mitral regurgitation may be dynamic in patients with heart failure and ultimately correlate with outcome in a group of patients. Fourteen patients with severe heart failure felt to require hemodynamic monitoring for the optimization of medical therapy were enrolled. Two-dimensional and Doppler echocardiograms were performed before and following invasively guided therapy. Hemodynamics and standard echocardiographic dimensions were determined as well as regurgitant volume and regurgitant orifice area derived from color M-mode and Doppler measurements. Invasively guided therapy for heart failure was associated with a reduction in weight, filling pressures of the left and right heart, systemic vascular resistance, and echocardiographic left atrial, left ventricular and mitral annular dimensions. The mitral regurgitant volume decreased from 47+/-27 ml before therapy to 14+/-14 ml after therapy; p < 0.001. While therapy for heart failure markedly attenuated the volume of regurgitation, the pattern of regurgitant flow across the mitral valve was not significantly altered. In contrast, there was no difference in the velocity time integral of the continuous-wave Doppler spectra of mitral regurgitation with therapy (128+/-23 cm to 123+/-25 cm, p = 0.23). In all patients, the regurgitant orifice area decreased with therapy from 0.55+/-0.38 cm2 to 0.21+/-0.20 cm2 (p < 0.001). Pharmacologic reduction in filling pressure and systemic vascular resistance leads to a reduction in the dynamic mitral regurgitation of heart failure through a reduction in the regurgitant orifice area but not through a change in the gradient across the mitral valve. Reduction of the regurgitant orifice area is likely related to decreased left ventricular volumes and decreased annular distention.


Highly stereoselective synthesis of trans-alkenes via electrochemical Ni-catalyzed hydroarylation of alkynes with aryl iodides.
An electrochemical nickel catalyzed hydroarylation reaction of various alkynes is herein described. In this reaction, alkynes were coupled with aryl iodides by electrochemical Ni catalysis to obtain highly selective trans-olefins. The outstanding features of this protocol include mild reaction conditions, operational simplicity, and excellent functional group tolerance.


Alterations in the rate of lipogenesis in vivo in maternal liver and adipose tissue on premature weaning of lactating rats: a possible regulatory role of prolactin.
Removal of pups for 24 h from rats at peak lactation decreased 3H2O incorporation into lipid in vivo in mammary gland by 95%, whereas it was increased in liver (77%) and adipose tissue (330%). These increases were prevented by administration of prolactin. Plasma insulin increased 3-fold on weaning and this was partially prevented by prolactin.


The protective effect of zinc on gastric ulceration caused by ethanol treatment.
1. The present study was undertaken in order to demonstrate the protective action of zinc ions on the gastric mucosa of rats submitted to the ulcerogenic effect of ethanol. 2. Aqueous solutions of zinc sulfate (20 mg/kg) and/or ethanol/water (1:1, v/v) (10 ml/kg) were intragastrically administered to young adult rats. The fundus region of the stomach was submitted to scanning electron and light microscopy study. The control group received isotonic sodium sulfate by the same route. 3. The ulcerogenic action of ethanol was completely inhibited by intragastric pretreatment with zinc sulfate for 3 consecutive days. 4. The clinical use of zinc ions to protect the gastric mucosa merits consideration in the light of the present findings.


Finessing incivility: The professional socialisation experiences of student nurses' first clinical placement, a grounded theory.
Clinical practice is where student nurses are socialised into a professional role and acquire the distinct behaviour, attitudes and values of the nursing profession. Getting it right at the outset can maximise the development of a professional identity and the transmission of robust value systems. To explore the impact of the first clinical placement on the professional socialisation of adult undergraduate student nurses in the United Kingdom. Data of a longitudinal qualitative nature were collected and analysed using grounded theory. First year student nurses in hospital ward placements comprising a rural District General Hospital and a large inner city Hospital kept daily unstructured diaries for six weeks. A total of 26 undergraduate adult student nurses were purposefully sampled between 2008 and 2010 before undertaking their initial clinical placement. Data collection and analysis used grounded theory and the key question asked of the diarists 'tell me what it is like to be a first year nurse on a first placement' was theoretically adjusted during constant comparison and as the theory emerged. Ethical approval and consent was obtained. The theory of finessing incivility comprises a conceptual framework depicting how student nurses deal with professional incivility during their initial clinical placement and sustain a student identity. Being disillusioned with their role as worker rather than learner yields a sense of 'status dislocation'. Despite needing professional benevolence, they remain altruistic and seek recompense from significant others to negotiate for learning opportunities and relocate their student status. Despite the stressful transition into clinical practice rather than 'fit in', the student nurses want to belong as learners. His or her own resilience to learn nursing and be a professional student maintains their resolve, their altruism and strengthens their existing values to be benevolent towards an indifferent profession. This behaviour ultimately mirrors the social nature of the practice community.


Alterations in serum glucose and hepatic glycogen concentrations during octanoate administration in rabbits.
During continuous administration of sodium octanoate (0.2 M) into weanling and mature rabbits, a significant decrease in serum glucose concentration was observed within 15 minutes after onset of the infusion. This relative hypoglycemia persisted for as long as one hour, after which there was a rebound to normoglycemia. Hepatic glycogen concentrations were correspondingly reduced by one-half in octanoate-treated versus control animals. Previous studies in an octanoate model have demonstrated clinical, biochemical, and pathologic features similar to those found in Reye syndrome. The current findings may have implications for the hypoglycemia observed in children with Reye syndrome.


Enhancing spatiotemporal focusing of light deep inside scattering media with Time-Gated Reflection Matrix.
Time-gated reflection matrix (RM) has been successfully used for optical imaging deep inside scattering media. Recently, this method was extended to enhance the spatiotemporal focusing of light ultra-deep inside scattering media. This is achieved by calibrating the decomposition of the RM with the Tikhonov regularization parameter to convert multiply scattered photons that share the same time of flight with the singly scattered photons into singly scattered photons. Such a capability suggests a reshaping to the interaction mechanism between light and scattering media, which may benefit or inspire wide optical applications that desire enhanced spatiotemporal focusing of light at depths inside scattering media.


Assessing physical fitness in preschool children: Feasibility, reliability and practical recommendations for the PREFIT battery.
In childhood (>6 years-old) and adolescence, fitness testing is feasible, reliable and related to later health. The purpose of this study was to examine the feasibility and reliability of a field-based fitness-test battery in preschool children. Repeated measures. A total of 161 preschoolers aged 3 to 5 years participated in the study. Anthropometry, cardiorespiratory fitness, muscular strength and motor fitness were tested twice (2 weeks apart) using weight, height, waist circumference, PREFIT 20m shuttle run, handgrip strength, standing long jump, 4×10m shuttle run and one-leg stance tests, respectively. The main results indicated that all tests are feasible and highly reliable (mean differences, weight=0.04kg, height=0.22cm, waist circumference=-0.08cm, PREFIT 20m shuttle run=2.00 laps, handgrip strength=-0.24kg and 4×10m shuttle run=0.12s), in preschool children, except for the standing long jump test and one-leg stance test (mean differences of -7.31cm and 8.01s). After some methodological adaptations, reliability for standing long jump was improved in a replication study (i.e. from -7 to -2cm). We observed evidence of heteroscedasticity in the 4×10m shuttle run and one-leg stance tests. The PREFIT battery is a feasible and reliable tool to assess physical fitness in preschool children yet standing long jump has shown mixed findings and requires further studies. The one-leg stance test showed poor reliability in our study and if confirmed by future studies, its use in 3 to 5 years-old would not be recommended. Future studies should consider the mean differences provide in this study to explain the changes in test performance.


Urinary dysfunction in Parkinson's disease: a review.
Urinary dysfunction, primarily in the form of detrusor overactivity, is highly prevalent amongst individuals with idiopathic Parkinson's disease (IPD). There has been increasing realisation of the importance of this and other non-motor features of the condition. The presentation of, pathophysiology behind and management options for bladder dysfunction in IPD are discussed.


GLI2 induces PDGFRB expression and modulates cancer stem cell properties of gastric cancer.
In this study, we aimed to investigate the downstream effector of GLI2 in gastric cancer (GC) and their regulative effect on cancer stem cell (CSC) properties of GC. Bioinformatic data mining was performed in TCGA-Stomach Adenocarcinoma (STAD), as well as in Kaplan-Meier plotter. Moderate-differentiated GC cell line SGC-7901 and poor-differentiated GC cell line MKN-45 were used as in-vitro model to investigate the regulative effect of GLI2 on PDGFRB expression. MKN-45 cells were further used to explore the effect of GLI2 shRNA or PDGFRB shRNA on CSC properties of the cells. Bioinformatic results showed that GLI2 is usually upregulated in GC tissues than in normal tissues, and high GLI2 expression is associated with unfavorable first progression free survival (PFS) and also worse overall survival (OS) in patients with GC. PDGFRB is co-upregulated with GLI2 in GC and its promoter region contains a putative GLI2 binding site. The results of dual luciferase assay confirmed this binding site. Enforced GLI2 expression elevated PDGFRB expression at both mRNA and protein level. GLI2 or PDGFRB knockdown showed similar effect on reducing spheroid colony formation and on reducing the expression of CSC related genes, including CD44, Nanog, and Oct4 in MKN-45 cells. High GLI2 or PDGFRB expression is associated with unfavorable survival in GC patients. GLI2 can induce PDGFRB expression in GC cells via directly binding to its promoter. In addition, the GLI2-PDGFRB axis might be an important signaling pathway modulating CSC properties of GC cells.


Safety of catheter ablation for atrial fibrillation in patients with intracranial hemorrhage.
The safety of anticoagulation and radiofrequency catheter ablation (RFCA) in patients with atrial fibrillation (AF) and a history of intracranial hemorrhage (ICH) remains unclear. We investigated the risks and benefits of this approach in AF patients with a history of ICH. The ICH group included 45 AF patients with a history of ICH who underwent RFCA. Five of these patients were excluded because ICH occurred spontaneously after cerebral infarction. The control group included 80 individuals who presented for AF ablation and did not have a history of ICH. Two controls were matched for each study group patient in terms of sex, age (±2 years), type of AF, and procedure date. Patients in the ICH group had higher CHADS2 (1.7 ± 1.3 vs. 1.1 ± 1.2, p < 0.05), CHA2DS2-VASc (2.6 ± 1.7 vs. 1.9 ± 1.6, p < 0.05), and HAS-BLED scores (2.5 ± 1.0 vs. 1.1 ± 1.0, p < 0.001). All participants in both groups underwent successful RFCA. The incidence of ICH during follow-up (1 vs. 0, p = 0.333) was similar between the ICH and control groups. AF-free survival between the two groups was not significant (log-rank p = 0.283) within the first 3 months, but was significant (log-rank p = 0.011) within 48 months of RFCA. History of ICH was the only independent predictor of AF recurrence according to univariate Cox regression analysis. In AF patients with a history of ICH, AF ablation with a standard anticoagulation strategy is safe and does not seem to be associated with an increased risk of hemorrhage.


Clinical concentrations of volatile anesthetics reduce depolarization-evoked release of [3H]norepinephrine, but not [3H]acetylcholine, from rat cerebral cortex.
We compared the potencies of halothane, enflurane, and methoxyflurane in producing unconsciousness in vivo and in inhibiting the release of [3H]norepinephrine and [3H]acetylcholine in vitro. Rats were anesthetized with various concentrations of each anesthetic, and responsiveness was determined by a hemostat tail pinch. Slices of cerebral cortex were equilibrated with similar concentrations of each agent in vitro, and potassium-evoked release of [3H]norepinephrine and [3H]acetylcholine was determined. For both studies, brain concentrations of the anesthetics were determined by heptane extraction and gas chromatography. Using this method, we found that brain concentrations of all three agents which caused unconsciousness in vivo also reduced depolarization-evoked release of [3H]norepinephrine by approximately 30% in vitro. The release of [3H]acetylcholine was unaffected by similar concentrations of these anesthetics. Such selective interference with stimulus-secretion coupling in central noradrenergic, and possibly other, neurons might contribute to the depressant actions of volatile anesthetics. The differential effects on norepinephrine and acetylcholine release also suggest differences in the mechanisms by which these two transmitters are released.


Tropical pyomyositis in a temperate climate: a case report.
Pyomyositis is an abscess-forming infection of large skeletal muscles, usually with Staphylococcus aureus. Although it is common in the tropics and relatively rare in temperate climates, imported cases due to growing global mobility may be expected to increase its incidence outside tropical regions. Early diagnosis and correct management are imperative in this potentially fatal disorder, and require a high degree of clinical suspicion. A case report is presented demonstrating typical aspects of diagnosis and treatment.


Test-retest reliability of single and paired pulse transcranial magnetic stimulation parameters in healthy subjects.
To determine the influence of different factors on test-retest reliability of frequently used transcranial magnetic stimulation (TMS) parameters while controlling for potential confounders in healthy subjects. TMS was applied in 93 healthy volunteers (61% male) twice (mean retest interval of 34.0 ± 25.6 (SD) days) between 7 am and 2 pm by four investigators (sessions n investigator A=47, investigator B=95, investigator C=28, investigator D=16). Women were assessed in their follicular phase. Test stimulus (TS), resting motor threshold (RMT), short latency intracortical inhibition (SICI), intracortical facilitation (ICF) and cortical silent period (SCP) were analyzed. Good test-retest reliabilities were observed for TS (r=.880) and RMT (r=.826), moderate for visual and automated analyzed CSP durations (resp. r=.466, r=.486), and poor for ICF (r=-.159). Reliable change indexes are reported. Gender (e.g. automated CSP women: r=.538 vs. men: r=.422), re-test interval and method of CSP-analysis did not influence reliabilities. In a large sample of healthy volunteers we found good to moderate test-retest reliabilities in all but one TMS-parameter. Automated analysis of the CSP did not prove to be more reliable than visual determination. This study contains analyses of re-test reliability in TMS considering several confounding factors. For the first time it presents reliable change indices for all frequently used TMS parameters.


Lansoprazole versus famotidine in symptomatic reflux esophagitis: a randomized, multicenter study.
We compared the usefulness of lansoprazole and famotidine for treatment of reflux esophagitis. Fifty-four subjects with moderate to severe reflux esophagitis were divided into two groups. The lansoprazole group (LPZ) received lansoprazole 30 mg once daily for 4 weeks, followed by famotidine 20 mg twice daily for 4 weeks. The famotidine group (FAM) received the same medications in the reverse order. Patient evaluation was based on six factors found on endoscopy, and on patient reports of heartburn. Evaluations were done before the start of the study and at 4 and 8 weeks. The improvement rates in the grade of GI classification at 4 weeks were 57.7% in the LPZ group and 38.5% in the FAM group; there was no significant difference between the two groups. However, after drugs were switched, more patients who switched to famotidine experienced a deterioration of their condition than did those who switched to lansoprazole. The percentages of "useful" or "very useful" were not significantly different between the two groups, but the percentage of "very useful" in the LPZ group (46.2%) was significantly higher than that in the FAM group (14.3%) (p < 0.05). These results suggest that lansoprazole is the first drug of choice for treatment of moderate to severe reflux esophagitis.


Malformations, genetic abnormalities, and Wilms tumor.
Wilms Tumor (WT) can occur in association with tumor predisposition syndromes and/or with clinical malformations. These associations have not been fully characterized at a clinical and molecular genetic level. This study aims to describe clinical malformations, genetic abnormalities, and tumor predisposition syndromes in patients with WT and to propose guidelines regarding indications for clinical and molecular genetic explorations. This retrospective study analyzed clinical abnormalities and predisposition syndromes among 295 patients treated for WT between 1986 and 2009 in a single pediatric oncological center. Clinically identified malformations and predisposition syndromes were observed in 52/295 patients (17.6%). Genetically proven tumor predisposition syndromes (n = 14) frequently observed were syndromes associated with alterations of the chromosome WT1 region such as WAGR (n = 6) and Denys-Drash syndromes (n = 3), syndromes associated with alterations of the WT2 region (Beckwith-Wiedeman syndrome, n = 3), and Fanconi anemia (n = 2). Hemihypertrophy and genito-urinary malformations (n = 12 and n = 16, respectively) were the most frequently identified malformations. Other different syndromes or malformations (n = 10) were less frequent. Median age of WT diagnosis was significantly earlier for children with malformations than those without (27 months vs. 37 months, P = 0.0009). There was no significant difference in terms of 5-year EFS and OS between WT patients without or with malformations. The frequency of malformations observed in patients with WT underline the need of genetic counseling and molecular genetic explorations for a better follow-up of these patients, with a frequently good outcome. A decisional tree, based on clinical observations of patients with WT, is proposed to guide clinicians for further molecular genetic explorations.


Preferential association of nucleolar organizing human chromosomes as revealed by silver staining technique at mitosis.
The frequency of different types of satellite associations of nucleolar organizing human chromosomes (i.e. acrocentric chromosomes; 13, 14, 15, 21, and 22) is reported using 10 normal individuals by Ag-staining technique. The preferential involvement of acrocentric chromosomes in satellite association is suggested. Only acrocentric chromosomes with active NORs (i.e. Ag-stained) were found in association while unstained (inactive NORs) chromosomes were never seen in satellite association. In general as number of NORs expression increase, the frequency of association per cell was also increased. A possible mechanism and the clinical consequences of such an unusual phenophenon is described.


A kind route from grounding to fundamentality.
I offer an account of fundamentality for facts in terms of metaphysical grounding. The account does justice to the idea that whether a fact is absolutely fundamental, and whether a fact is more fundamental than, or as fundamental as, another fact, are a matter of where in a grounding-induced hierarchy of kinds of facts these facts appear.


Pharmacokinetic and pharmacodynamic comparison of epinephrine, administered intranasally and intramuscularly: An integrated analysis.
Manual intramuscular epinephrine injection is the standard of care for treating severe allergic reactions and anaphylaxis. Epinephrine autoinjectors were approved on the basis of the assumption that their pharmacokinetic and pharmacodynamic profiles are equivalent to manual intramuscular injection; however, although there is emerging evidence for product-related differences in pharmacokinetic profiles, very little is known about the comparative pharmacodynamic profiles. To compare pharmacokinetic and pharmacodynamic profiles of epinephrine delivered through manual intramuscular injection, autoinjectors, and intranasal spray. This integrated analysis was based on data from 4 randomized cross-over phase 1 trials that compared the pharmacokinetics and pharmacodynamics of epinephrine using manual intramuscular epinephrine 0.3 mg injection, epinephrine 0.3 mg autoinjectors (Symjepi and EpiPen), and epinephrine 1 mg intranasal spray (neffy). Data from 175 participants showed that although neffy (1.0 mg intranasal spray) resulted in a maximum concentration (258 pg/mL) that was lower than or comparable with manual epinephrine intramuscular injection (254 pg/mL), Symjepi (438 pg/mL) and EpiPen (503 pg/mL), it led to comparable increases in systolic blood pressure (maximum effect [Emax], 16.9, 10.9, 14.9, and 18.1 mm Hg, respectively). The effect of neffy on diastolic blood pressure was also markedly more pronounced than that of other products (Emax, 9.32, 5.51, 5.78, and 5.93 mm Hg, respectively). Intranasal delivery of epinephrine using neffy increases systolic blood pressure more efficiently than do manual intramuscular injection and epinephrine autoinjectors, despite lower maximum plasma concentrations.


A typical carcinoid tumor of the lung presenting with pure persistent ground-glass opacity on high-resolution computed tomography: a case report.
Pure ground-glass opacity nodules (p-GGN) on high-resolution computed tomography (HRCT) generally have been considering typically associated with adenocarcinoma with less invasive nature. We herein reported a patient presenting focal p-GGN on middle lobe of the right lung who underwent surgical resection with its pathological diagnosis turned out to be typical carcinoid tumor.


Acute and long-term effects of viral bronchiolitis in infancy.
About 1% of infants are admitted to hospital with acute bronchiolitis; 85% of cases are caused by infection with Respiratory Syncytial Virus (RSV). The pathophysiological changes during the acute illness are inflammatory obstruction in the small airways with submucosal cellular infiltration, epithelial necrosis and mucous plugging; FRC increases and dynamic compliance falls. Failure to respond to bronchodilator drugs suggests that muscle spasm contributes relatively little to the airway narrowing. Affected infants become increasingly dyspnoeic and hypoxic for 3-4 days then spontaneously improve. After an attack of acute bronchiolitis up to 75% of children have recurrent lower respiratory tract symptoms, many continue to have hyperinflated lungs and bronchial hyperresponsiveness. In the majority, symptoms of cough and wheezing have subsided by the time they start school, but abnormalities of small airway function are detectable at least 13 years later. Children with a genetic predisposition to atopy do not appear to have an increased risk of developing bronchiolitis. Evidence of genetic predisposition to bronchial hyperresponsiveness in those with persistent wheezing is controversial. There is little to suggest that neonatal lung damage or an adverse home environment are important factors in determining susceptibility to post-bronchiolitis wheezing. IgE antibodies to RSV, and leukotriene C4, are found more frequently in the respiratory secretions of infants who wheeze during and after bronchiolitis than in those who do not. The possibility of viral-induced alteration of the immune response at the time of infection needs further investigation.


The enhancer RNA ADCY10P1 is associated with the progression of ovarian cancer.
Emerging evidence identifies enhancer RNAs (eRNAs) as a class of regulatory ncRNAs that can contribute to the transcription of target genes. In this study, we used an integrated data analysis method to identify the important role of eRNAs in ovarian cancer (OC). Gene expression profiles and clinical information from The Cancer Genome Atlas (TCGA) database were used for this study. Based on expression analysis using GEPIA2 gene and Kaplan-Meier survival was performed to ensure the significance of the selected enhancer RNA ADCY10P1 in OC. Next, we explored the correlation and clinical significance between ADCY10P1 and target gene NFYA. Furthermore, we evaluated the effects of overexpression of ADCY10P1 on the proliferation, migration, invasion and epithelial-mesenchymal transformation (EMT) of OC cell lines. We also investigated the biological function enrichment score of ADCY10P1 and verified it with OC cell lines. Finally, external validation was conducted, and the prognostic value of the ADCY10P1 in different tumors was demonstrated. We selected the eRNA ADCY10P1 associated with OC prognosis, with NFYA as its predicted target gene. Low ADCY10P1 expression was found to be associated with poor overall survival, high histological grade, and advanced stage of OC. Additionally, overexpression of ADCY10P1 inhibited the proliferation, migration, invasion and EMT phenotype of OC cell lines. Furthermore, ADCY10P1 was observed to inhibit glycolysis and fatty acid metabolism, thereby affecting OC progression. Meanwhile, OC tissue samples were externally validated. In addition, the pan-cancer analysis revealed that ADCY10P1 had prognostic value in other cancers. This study showed that ADCY10P1 plays a key role in OC progression and may facilitate prognosis prediction.


Lipoma in the cerebellopontine angle.
A case of lipoma in the cerebellopontine angle is reported. Intracranial lipomas are very rare, especially in the cerebellopontine angle. To our knowledge, only four cases, including our own, have been operated upon. Until now, total extirpation has not been possible. The singular appearance on computed tomography scanning of this dysembryoplasia is presented together with a bibliography of this subject.