Reconstruction of Radiation Dose Received by Diagnostic Radiologic Technologists in Korea.
Diagnostic medical radiation workers in Korea have been officially monitored for their occupational radiation doses since 1996. The purpose of this study was to design models for reconstructing unknown individual radiation doses to which diagnostic radiation technologists were exposed before 1996. Radiation dose reconstruction models were developed by using cross-sectional survey data and the personal badge doses of 8167 radiologic technologists. The models included calendar year and age as predictors, and the participants were grouped into six categories according to their sex and facility type. The annual doses between 1971 and 1995 for those who were employed before 1996 were estimated using these models. The calendar year and age were inversely related to the estimated radiation doses in the models of all six groups. The annual median estimated doses decreased from 9.45 mSv in 1971 to 1.26 mSv in 1995, and the associated dose variation also decreased with time. The estimated median badge doses from 1996 (1.22 mSv) to 2011 (0.30 mSv) were similar to the measured doses (1.68 mSv to 0.21 mSv) for the same years. Similar results were observed for all six groups. The reconstruction models developed in this study may be useful for estimating historical occupational radiation doses received by medical radiologic technologists in Korea.


Reaction time and critical duration for lines' detection and identification of their orientation.
Reaction time (RT) and duration of complete temporal summation (tc) were studied for both detection of lines and identification of their orientation. The RT was studied as a function of stimulus intensity, number of orientations and angular difference between them. The temporal summation was studied for detection and identification at several angular differences. It was found that the intensity-dependent part of RT for identification at angular difference of 22 degrees equaled that for detection but considerably lengthened at smaller angular differences (10 degrees). The intensity-independent part of RT was minimal for detection and maximal for identification with eight alternatives. The tc increased from 30 msec for detection and identification with the accuracy of 22 degrees to 100 msec for identification with the accuracy of 5 degrees. The results support the conclusion that detection and coarse identification differ only in their later stages and that accurate identification involves additional processes with longer time-constants compared to coarse identification.


Rural-urban disparities in age trajectories of depression caseness in later life: The China Health and Retirement Longitudinal Study.
No consensus has been reached on whether depression decreases or increases with age in later life. Majority of the evidence comes from Western societies, while little is known about this relationship and its rural-urban disparities in the Chinese context. Three waves of data from 15,501 Chinese adults aged 45-85 years from the China Health and Retirement Longitudinal Study, Chinese sister study of Health and Retirement Study, were used. Depression caseness was identified using the 10-item Center for Epidemiologic Studies Depression Scale (score ≥12). Urbanisation levels were determined by combining rural-urban residence and rural-urban Hukou (a household registration system). Odds ratios and predicted probabilities of depression caseness were estimated using generalised linear mixed models. For both men and women and across all ages, the crude predicted probability of depression caseness was the highest in the rural group, followed by the semi-urban group, and the lowest in the urban group. The probability was stable over age among urban men (around 0.05), but it increased at an accelerated rate with age among semi-urban men (0.25 at age 85, 95% confidence interval [CI]: 0.13-0.44) and rural men (0.29 at age 85, 95% CI: 0.22-0.39). Among women the age pattern was similar between the urbanisation groups: the probability increased with age, reached a peak at ages 75-80 (urban women: 0.16, 95% CI: 0.13-0.20; semi-urban women: 0.28, 95% CI: 0.20-0.39; rural women: 0.41, 95% CI: 0.36-0.46), and decreased slightly afterwards. These differences were significantly attenuated when socio-demographic characteristics and physical disability, but not when behaviour-related factors, were controlled for. The age trajectories of later-life depression caseness varied by gender and urbanisation levels, and were not U-shaped as in many Western societies. The increasing depression caseness with age and the large rural disadvantage were substantially driven by socio-demographic characteristics and physical disability.


Treatment of dental complications in sickle cell disease.
Sickle cell disease is the most common single gene disorder and the commonest haemoglobinopathy found with high prevalence in many populations across the world. Management of dental complications in people with sickle cell disease requires special consideration for three main reasons. Firstly, dental and oral tissues are affected by the blood disorder resulting in several oro-facial abnormalities. Secondly, living with a haemoglobinopathy and coping with its associated serious consequences may result in individuals neglecting their oral health care. Finally, the treatment of these oral complications must be adapted to the systemic condition and special needs of these individuals, in order not to exacerbate or deteriorate their general health.Guidelines for the treatment of dental complications in this population who require special care are unclear and even unavailable in many aspects. Hence this review was undertaken to provide a basis for clinical care by investigating and analysing the existing evidence in the literature for the treatment of dental complications in people with sickle cell disease. To assess methods of treating dental complications in people with sickle cell disease. We searched the Cochrane Haemoglobinopathies Trials Register, compiled from electronic database searches and handsearching of journals and conference abstract books.Date of last search: 11 April 2016.Additionally, we searched nine online databases (PubMed, Google Scholar, ClinicalTrials.gov, WHO International Clinical Trials Registry Platform, Literature in the Health Sciences in Latin America and the Caribbean database, African Index Medicus, Index Medicus for South East Asia Region, Index Medicus for the Eastern Mediterranean Region, Indexing of Indian Medical Journals). We also searched the reference lists of relevant articles and reviews and contacted haematologists, experts in fields of dentistry, organizations, pharmaceutical companies and researchers working in this field.Date of last search: 03 March 2016. We searched for published or unpublished randomised controlled studies of treatments for dental complications in people with sickle cell disease. Two review authors intended to independently extract data and assess the risk of bias of the included studies using standard Cochrane methodologies; however, no studies were identified for inclusion in the review. No randomised controlled studies were identified. This Cochrane review did not identify any randomised controlled studies assessing interventions for the treatment of dental complications in people with sickle cell disease. There is an important need for randomised controlled studies in this area, so as to identify the most effective and safe method for treating dental complications in people with sickle cell disease.


Characterization of the 23S and 5S rRNA genes and 23S-5S intergenic spacer region (ITS-2) of Photobacterium damselae.
The 23S ribosomal RNA (rRNA) gene has been sequenced in strains of the fish pathogens Photobacterium damselae subsp. damselae (ATCC 33539) and subsp. piscicida (ATCC 29690), showing that 3 nucleotide positions are clearly different between subspecies. In addition, the 5S rRNA gene plus the intergenic spacer region between the 23S and 5S rRNA genes (ITS-2) were amplified, cloned and sequenced for the 2 reference strains as well as the field isolates RG91 (subsp. damselae) and DI21 (subsp. piscicida). A 100% similarity was found for the consensus 5S rRNA gene sequence in the 2 subspecies, although some microheterogeneity was detected as inter-cistronic variability within the same chromosome. Sequence analysis of the spacer region between the 23S and 5S rRNA genes revealed 2 conserved and 3 variable nucleotide sequence blocks, and 4 different modular organizations were found. The ITS-2 spacer region exhibited both inter-subspecies and intercistronic polymorphism, with a mosaic-like structure. The EMBL accession numbers for the 23S, 5S and ITS-2 sequences are: P. damselae subsp. piscicida 5S gene (AJ274379), P. damselae subsp. damselae 23S gene (Y18520), subsp. piscicida 23S gene (Y17901), P. damselae subsp. piscicida ITS-2 (AJ250695, AJ250696), P. damselae subsp. damselae ITS-2 (AJ250697, AJ250698).


Synergistic Effect of Artificial Tears Containing Epigallocatechin Gallate and Hyaluronic Acid for the Treatment of Rabbits with Dry Eye Syndrome.
Dry eye syndrome (DES) is a common eye disease. Artificial tears (AT) are used to treat DES, but they are not effective. In this study, we assessed the anti-inflammatory effect of AT containing epigallocatechin gallate (EGCG) and hyaluronic acid (HA) on DES. Human corneal epithelial cells (HCECs) were used in the WST-8 assay to determine the safe dose of EGCG. Lipopolysaccharide-stimulated HCECs showing inflammation were treated with EGCG/HA. The expression of IL-1ß, IL-6, IL-8, and TNF-α was assessed by real-time PCR and AT physical properties such as the viscosity, osmolarity, and pH were examined. AT containing EGCG and HA were topically administered in a rabbit DES model established by treatment with 0.1% benzalkonium chloride (BAC). Tear secretion was assessed and fluorescein, H&E, and TUNEL staining were performed. Inflammatory cytokine levels in the corneas were also examined. The non-toxic optimal concentration of EGCG used for the treatment of HCECs in vitro was 10 μg/mL. The expression of several inflammatory genes, including IL-1ß, IL-6, IL-8, and TNF-α, was significantly inhibited in inflamed HCECs treated with 10 μg/mL EGCG and 0.1% (w/v) HA (E10/HA) compared to that in inflamed HCECs treated with either EGCG or HA alone. AT containing E10/HA mimic human tears, with similar osmolarity and viscosity and a neutral pH. Fluorescence examination of the ocular surface of mouse eyes showed that HA increased drug retention on the ocular surface. Topical treatment of DES rabbits with AT plus E10/HA increased tear secretion, reduced corneal epithelial damage, and maintained the epithelial layers and stromal structure. Moreover, the corneas of the E10/HA-treated rabbits showed fewer apoptotic cells, lower inflammation, and decreased IL-6, IL-8, and TNF-α levels. In conclusion, we showed that AT plus E10/HA had anti-inflammatory and mucoadhesive properties when used as topical eye drops and were effective for treating DES in rabbits.


ATXN2 and its neighbouring gene SH2B3 are associated with increased ALS risk in the Turkish population.
Expansions of the polyglutamine (polyQ) domain (≥ 34) in Ataxin-2 (ATXN2) are the primary cause of spinocerebellar ataxia type 2 (SCA2). Recent studies reported that intermediate-length (27-33) expansions increase the risk of Amyotrophic Lateral Sclerosis (ALS) in 1-4% of cases in diverse populations. This study investigates the Turkish population with respect to ALS risk, genotyping 158 sporadic, 78 familial patients and 420 neurologically healthy controls. We re-assessed the effect of ATXN2 expansions and extended the analysis for the first time to cover the ATXN2 locus with 18 Single Nucleotide Polymorphisms (SNPs) and their haplotypes. In accordance with other studies, our results confirmed that 31-32 polyQ repeats in the ATXN2 gene are associated with risk of developing ALS in 1.7% of the Turkish ALS cohort (p=0.0172). Additionally, a significant association of a 136 kb haplotype block across the ATXN2 and SH2B3 genes was found in 19.4% of a subset of our ALS cohort and in 10.1% of the controls (p=0.0057, OR: 2.23). ATXN2 and SH2B3 encode proteins that both interact with growth receptor tyrosine kinases. Our novel observations suggest that genotyping of SNPs at this locus may be useful for the study of ALS risk in a high percentage of individuals and that ATXN2 and SH2B3 variants may interact in modulating the disease pathway.


QT interval dispersion in chronic heart failure and left ventricular hypertrophy: relation to autonomic nervous system and Holter tape abnormalities.
To study QT dispersion in left ventricular hypertrophy and chronic heart failure and to determine the relation to ventricular arrhythmias. Investigational laboratory of a tertiary referral centre. Patients with left ventricular hypertrophy and normal systolic function (n = 14) and patients with chronic heart failure (n = 18) were matched with controls (n = 17). The QT dispersion was examined in relation to abnormalities in resting mechanical and autonomic function and to the findings of 24 hour Holter monitoring. QT dispersion is the difference between the maximum and the minimum QT values from the 12 lead electrocardiogram. Mean(SD) QT dispersion from the 10 lead electrocardiogram was also examined once the 12 lead minimum and maximum values had been removed. The QT distribution is the curve describing the distance from the mean for all QT intervals (ms). All measures of QT dispersion were increased significantly in left ventricular hypertrophy and tended to increase in those with heart failure. The QT distribution was abnormal in both heart failure and left ventricular hypertrophy. There was no relation between the degree of change in QT dispersion and the incidence of ventricular arrhythmia on 24 hour Holter monitoring. Also there was no relation between QT dispersion and autonomic or mechanical abnormalities. The QT dispersion was related to QRS duration. Though QT dispersion and distribution are abnormal in left ventricular hypertrophy these findings do not support the hypothesis that QT dispersion reflects arrhythmic risk in either hypertrophy or heart failure.


Non-photopic and photopic visual cycles differentially regulate immediate, early, and late phases of cone photoreceptor-mediated vision.
Cone photoreceptors in the retina enable vision over a wide range of light intensities. However, the processes enabling cone vision in bright light (i.e. photopic vision) are not adequately understood. Chromophore regeneration of cone photopigments may require the retinal pigment epithelium (RPE) and/or retinal Müller glia. In the RPE, isomerization of all-trans-retinyl esters to 11-cis-retinol is mediated by the retinoid isomerohydrolase Rpe65. A putative alternative retinoid isomerase, dihydroceramide desaturase-1 (DES1), is expressed in RPE and Müller cells. The retinol-isomerase activities of Rpe65 and Des1 are inhibited by emixustat and fenretinide, respectively. Here, we tested the effects of these visual cycle inhibitors on immediate, early, and late phases of cone photopic vision. In zebrafish larvae raised under cyclic light conditions, fenretinide impaired late cone photopic vision, while the emixustat-treated zebrafish unexpectedly had normal vision. In contrast, emixustat-treated larvae raised under extensive dark-adaptation displayed significantly attenuated immediate photopic vision concomitant with significantly reduced 11-cis-retinaldehyde (11cRAL). Following 30 min of light, early photopic vision was recovered, despite 11cRAL levels remaining significantly reduced. Defects in immediate cone photopic vision were rescued in emixustat- or fenretinide-treated larvae following exogenous 9-cis-retinaldehyde supplementation. Genetic knockout of Des1 (degs1) or retinaldehyde-binding protein 1b (rlbp1b) did not eliminate photopic vision in zebrafish. Our findings define molecular and temporal requirements of the nonphotopic or photopic visual cycles for mediating vision in bright light.


Effects of green tea extracts on gene expression in HepG2 and Cal-27 cells.
Green tea extract is known to contain compounds that are able to produce antioxidant effects in many types of living cells. Treatment of cultured human hepatoma (HepG2) cells with green tea extract resulted in dramatically increased expression of at least 15 genes that are present on a commercial human drug metabolism gene array. RT-PCR was used to confirm the microarray results, and analysis of the 5'-flanking region of each of these genes revealed potential electrophile/antioxidant response elements. Members of the acetyl transferase, epoxide hydrolase, sulfotransferase and glutathione transferase gene families were strongly induced. In addition, the human tongue carcinoma cell line Cal-27 did not respond to green tea extract in the same way, as none of the induced genes in the HepG2 cells were induced in the Cal-27 cells. The lack of induction of detoxification enzymes in the Cal-27 cell line may help to explain the previously observed increased cytotoxicity of green tea catechins on this cell line.


Isolated facial diplegia in Guillain-Barré syndrome: Bifacial weakness with paresthesias.
Bifacial weakness with paresthesias (BFP) is a subtype of Guillain-Barré syndrome defined by rapidly progressive bilateral facial weakness in the absence of other cranial neuropathies, ataxia, or limb weakness. Many patients also complain of distal limb paresthesias and display diminished or absent deep tendon reflexes. BFP is a localized form of Guillain-Barré syndrome and is thought to be caused exclusively by demyelinating- rather than axonal-type neuropathy. Patients with BFP do not display anti-ganglioside IgG antibodies. Since it is rare, many physicians are unfamiliar with BFP, as bilateral facial weakness is more commonly associated with sarcoidosis, Lyme disease, or meningeal pathology. Many patients diagnosed with bilateral Bell palsy may instead have BFP. In this review, we highlight the clinical features of BFP and outline diagnostic criteria.


Fibromyalgia and obesity: the hidden link.
Fibromyalgia is a chronic disorder of uncertain etiology, characterized by widespread pain, muscle tenderness, and decreased pain threshold to pressure and other stimuli. Obesity is a well-known aggravating factor for certain rheumatologic conditions, such as knee osteoarthritis. Emerging evidences are exploring the link between obesity and other rheumatic diseases, such as fibromyalgia. Epidemiological data show that fibromyalgia patients have higher prevalence of obesity (40%) and overweight (30%) in multiple studies compared with healthy patients. Several mechanisms have been proposed to explain "the hidden link", but at this time is not possible to ascertain whether obesity is cause or consequence of fibromyalgia. Among mechanisms proposed, there are the following: impaired physical activity, cognitive and sleep disturbances, psychiatric comorbidity and depression, dysfunction of thyroid gland, dysfunction of the GH/IGF-1 axis, impairment of the endogenous opioid system. In this article, we review the scientific evidence supporting a possible link between obesity and fibromyalgia, how obesity influences fibromyalgia symptoms and how fibromyalgia severity can be improved by weight loss. In addition, we analyze the possible mechanisms by which fibromyalgia and obesity interrelate.


Selective augmentation of striatal functional connectivity following NMDA receptor antagonism: implications for psychosis.
The psychotomimetic effect of the N-methyl-D-aspartate receptor (NMDAR) antagonist ketamine is thought to arise from a functional modulation of the brain's fronto-striato-thalamic (FST) circuits. Animal models suggest a pronounced effect on ventral 'limbic' FST systems, although recent work in patients with psychosis and high-risk individuals suggests specific alterations of dorsal 'associative' FST circuits. Here, we used functional magnetic resonance imaging to investigate the effects of a subanesthetic dose of ketamine on measures of functional connectivity as indexed by the temporal coherence of spontaneous neural activity in both dorsal and ventral FST circuits, as well as their symptom correlates. We adopted a placebo-controlled, double-blind, randomized, repeated-measures design in which 19 healthy participants received either an intravenous saline infusion or a racemic mixture of ketamine (100 ng/ml) separated by at least 1 week. Compared with placebo, ketamine increased functional connectivity between the dorsal caudate and both the thalamus and midbrain bilaterally. Ketamine additionally increased functional connectivity of the ventral striatum/nucleus accumbens and ventromedial prefrontal cortex. Both connectivity increases significantly correlated with the psychosis-like and dissociative symptoms under ketamine. Importantly, dorsal caudate connectivity with the ventrolateral thalamus and subthalamic nucleus showed inverse correlation with ketamine-induced symptomatology, pointing to a possible resilience role to disturbances in FST circuits. Although consistent with the role of FST in mediating psychosis, these findings contrast with previous research in clinical samples by suggesting that acute NMDAR antagonism may lead to psychosis-like experiences via a mechanism that is distinct from that implicated in frank psychotic illness.


The molecular biology of Bluetongue virus replication.
The members of Orbivirus genus within the Reoviridae family are arthropod-borne viruses which are responsible for high morbidity and mortality in ruminants. Bluetongue virus (BTV) which causes disease in livestock (sheep, goat, cattle) has been in the forefront of molecular studies for the last three decades and now represents the best understood orbivirus at a molecular and structural level. The complex nature of the virion structure has been well characterised at high resolution along with the definition of the virus encoded enzymes required for RNA replication; the ordered assembly of the capsid shell as well as the protein and genome sequestration required for it; and the role of host proteins in virus entry and virus release. More recent developments of Reverse Genetics and Cell-Free Assembly systems have allowed integration of the accumulated structural and molecular knowledge to be tested at meticulous level, yielding higher insight into basic molecular virology, from which the rational design of safe efficacious vaccines has been possible. This article is centred on the molecular dissection of BTV with a view to understanding the role of each protein in the virus replication cycle. These areas are important in themselves for BTV replication but they also indicate the pathways that related viruses, which includes viruses that are pathogenic to man and animals, might also use providing an informed starting point for intervention or prevention.


Memory trace replay: the shaping of memory consolidation by neuromodulation.
The consolidation of memories for places and events is thought to rely, at the network level, on the replay of spatially tuned neuronal firing patterns representing discrete places and spatial trajectories. This occurs in the hippocampal-entorhinal circuit during sharp wave ripple events (SWRs) that occur during sleep or rest. Here, we review theoretical models of lingering place cell excitability and behaviorally induced synaptic plasticity within cell assemblies to explain which sequences or places are replayed. We further provide new insights into how fluctuations in cholinergic tone during different behavioral states might shape the direction of replay and how dopaminergic release in response to novelty or reward can modulate which cell assemblies are replayed.


Resveratrol Attenuates Copper and Zinc Homeostasis and Ameliorates Oxidative Stress in Type 2 Diabetic Rats.
Diabetes is a common metabolic disorder characterized by elevated blood glucose level. Trace element homeostasis causes disturbances in diabetes due to hyperglycemia. Superoxide dismutase (SOD), an antioxidant enzyme, contains zinc and copper ions as its cofactors. Defects in SOD level and activity have been observed in diabetes. Resveratrol (RSV) has displayed hypoglycemic effects and is proven to improve oxidative stress. The aim of the present study was to examine the possible effects of RSV on blood glucose level, serum copper and zinc levels, SOD, and a number of other oxidative markers in type 2 diabetic rats. Diabetes was induced in male Wistar rats with administration of streptozotocin and nicotine amide. The studied groups containing six animals per group were as follows: group 1 normal control group; group 2 diabetic control group; groups 3, 4, and 5 diabetic rats that received 1, 5, and 10 mg/kg body weight of RSV, respectively for 30 days. Serum glucose, copper, zinc, SOD activity, total oxidant status (TOS) as well as thiol groups were all measured. Blood glucose in RSV treated groups significantly decreased. Similarly, copper significantly decreased in diabetic groups treated with RSV. Treatment with 10 mg/kg RSV resulted in significantly increased serum zinc. Furthermore, Cu/Zn ratio was observed to decrease in treated groups compared with untreated diabetic control group. RSV treated groups revealed an increased level of SOD activity as well as improved oxidative status. In summary, the results showed that RSV has potential hypoglycemic effect, attenuates trace element homeostasis, and consequently increases SOD activity level.


Does estrogen prevent skin aging? Results from the First National Health and Nutrition Examination Survey (NHANES I)
To evaluate the relation between noncontraceptive estrogen use and skin wrinkling, dryness, and atrophy. Cross-sectional analysis of a national probability sample-based cohort study. Multiple community sites throughout the United States. Postmenopausal women (n = 3875) aged 40 years and older at baseline. Skin conditions (wrinkling, dryness, and atrophy) were ascertained using a uniform clinical examination by trained dermatology resident physicians. Self-reported use of estrogen before the baseline examination, sunlight exposure, and smoking history were obtained by standardized interview. Body mass index, a measure of weight in kilograms divided by the square of the height in meters, was evaluated in uniform examination clothing. Mean (+/-SD) age of the participants was 61.6 (+/-9.0) years and mean (+/-SD) number of years since menopause was 15.6 (+/-9.4). Most were white (83.7%), the remainder being African American (15.9%) or another race (0.4%). Atrophy was present in 499 (16.2%), dry skin in 1132 (36.2%), and wrinkled skin in 880 women (28.2%). The prevalence of all 3 skin conditions was lower in African American women compared with white women. Information on hormone use was available for 3403 participants (88%). Among all women, after adjustment for age, body mass index, and sunlight exposure, estrogen use was associated with a statistically significant decrease in the likelihood of senile dry skin (odds ratio, 0.76; 95% confidence interval, 0.60-0.97). The odds of wrinkling were substantially lower in estrogen users, adjusted for age, body mass index, and sun exposure (odds ratio, 0.68; 95% confidence interval, 0.52-0.89) and additionally for smoking (odds ratio, 0.67; 95% confidence interval, 0.44-1.01). In multivariable models, estrogen use was not associated with skin atrophy. These results strongly suggest that estrogen use prevents dry skin and skin wrinkling, thus extending the potential benefits of postmenopausal estrogen therapy to include protection against selected age- and menopause-associated dermatologic conditions.


High-refined carbohydrate diet leads to polycystic ovary syndrome-like features and reduced ovarian reserve in female rats.
Obesity is associated with several female reproductive complications, such as polycystic ovary syndrome (PCOS). The exact mechanism of this relationship remains unclear. Few previous studies using diet containing refined carbohydrate (HCD) leading to obesity have been performed and it is unclear if HCD is linked with reproductive dysfunctions. In this investigation, we assessed whether subchronic HCD exposure results in reproductive and other irregularities. Female rats were fed with HCD for 15 days and metabolic outcomes and reproductive tract morphophysiology were assessed. We further assessed reproductive tract inflammation, oxidative stress (OS) and fibrosis. HCD rats displayed metabolic impairments, such as an increase in body weight/adiposity, adipocyte hypertrophic, abnormal lipid profile, glucose tolerance and insulin resistance (IR) and hyperleptinemia. Improper functioning of the HCD reproductive tract was observed. Specifically, irregular estrous cyclicity, high LH levels and abnormal ovarian morphology coupled with reduction in primordial and primary follicle numbers was observed, suggesting ovarian reserve depletion. Improper follicular development and a reduction in antral follicles, corpora lutea and granulosa layer area together with an increase in cystic follicles were apparent. Uterine atrophy and reduction in endometrial gland (GE) number was observed in HCD rats. Reproductive tract inflammation, OS and fibrosis were seen in HCD rats. Further, strong positive correlations were observed between body weight/adiposity and IR with estrous cycle length, cystic follicles, ovarian reserve, GE and other abnormalities. Thus, these data suggest that the subchronic HCD exposure led to PCOS-like features, impaired ovarian reserve, GE number, and other reproductive abnormalities in female rats.


A review of enzymatic transesterification of microalgal oil-based biodiesel using supercritical technology.
Biodiesel is considered a promising replacement to petroleum-derived diesel. Using oils extracted from agricultural crops competes with their use as food and cannot realistically satisfy the global demand of diesel-fuel requirements. On the other hand, microalgae, which have a much higher oil yield per hectare, compared to oil crops, appear to be a source that has the potential to completely replace fossil diesel. Microalgae oil extraction is a major step in the overall biodiesel production process. Recently, supercritical carbon dioxide (SC-CO(2)) has been proposed to replace conventional solvent extraction techniques because it is nontoxic, nonhazardous, chemically stable, and inexpensive. It uses environmentally acceptable solvent, which can easily be separated from the products. In addition, the use of SC-CO(2) as a reaction media has also been proposed to eliminate the inhibition limitations that encounter biodiesel production reaction using immobilized enzyme as a catalyst. Furthermore, using SC-CO(2) allows easy separation of the product. In this paper, conventional biodiesel production with first generation feedstock, using chemical catalysts and solvent-extraction, is compared to new technologies with an emphasis on using microalgae, immobilized lipase, and SC-CO(2) as an extraction solvent and reaction media.


A CAF-1-PCNA-mediated chromatin assembly pathway triggered by sensing DNA damage.
Sensing DNA damage is crucial for the maintenance of genomic integrity and cell cycle progression. The participation of chromatin in these events is becoming of increasing interest. We show that the presence of single-strand breaks and gaps, formed either directly or during DNA damage processing, can trigger the propagation of nucleosomal arrays. This nucleosome assembly pathway involves the histone chaperone chromatin assembly factor 1 (CAF-1). The largest subunit (p150) of this factor interacts directly with proliferating cell nuclear antigen (PCNA), and critical regions for this interaction on both proteins have been mapped. To isolate proteins specifically recruited during DNA repair, damaged DNA linked to magnetic beads was used. The binding of both PCNA and CAF-1 to this damaged DNA was dependent on the number of DNA lesions and required ATP. Chromatin assembly linked to the repair of single-strand breaks was disrupted by depletion of PCNA from a cell-free system. This defect was rescued by complementation with recombinant PCNA, arguing for role of PCNA in mediating chromatin assembly linked to DNA repair. We discuss the importance of the PCNA-CAF-1 interaction in the context of DNA damage processing and checkpoint control.


Genetic variants associated with severe retinopathy of prematurity in extremely low birth weight infants.
To determine genetic variants associated with severe retinopathy of prematurity (ROP) in a candidate gene cohort study of US preterm infants. Preterm infants in the discovery cohort were enrolled through the Eunice Kennedy Shriver National Institute of Child Health and Human Development Neonatal Research Network, and those in the replication cohort were from the University of Iowa. All infants were phenotyped for ROP severity. Because of differences in the durations of enrollment between cohorts, severe ROP was defined as threshold disease in the discovery cohort and as threshold disease or type 1 ROP in the replication cohort. Whole genome amplified DNA from stored blood spot samples from the Neonatal Research Network biorepository was genotyped using an Illumina GoldenGate platform for candidate gene single nucleotide polymorphisms (SNPs) involving angiogenic, developmental, inflammatory, and oxidative pathways. Three analyses were performed to determine significant epidemiologic variables and SNPs associated with levels of ROP severity. Analyses controlled for multiple comparisons, ancestral eigenvalues, family relatedness, and significant epidemiologic variables. Single nucleotide polymorphisms significantly associated with ROP severity from the discovery cohort were analyzed in the replication cohort and in meta-analysis. Eight hundred seventeen infants in the discovery cohort and 543 in the replication cohort were analyzed. Severe ROP occurred in 126 infants in the discovery and in 14 in the replication cohort. In both cohorts, ventilation days and seizure occurrence were associated with severe ROP. After controlling for significant factors and multiple comparisons, two intronic SNPs in the gene BDNF (rs7934165 and rs2049046, P < 3.1 × 10(-5)) were associated with severe ROP in the discovery cohort and were not associated with severe ROP in the replication cohort. However, when the cohorts were analyzed together in an exploratory meta-analysis, rs7934165 increased in associated significance with severe ROP (P = 2.9 × 10(-7)). Variants in BDNF encoding brain-derived neurotrophic factor were associated with severe ROP in a large candidate gene study of infants with threshold ROP.


Determinants of immunization coverage in lucknow district.
Immunization remains one of the most important public health interventions and a cost-effective strategy to reduce both the morbidity and mortality associated with infectious diseases. Over two million deaths are delayed through immunization each year worldwide. This study sought to identify specific factors associated with immunization coverage in order to advance improved intervention, policies/strategies therefore raising overall immunization coverage. A cross-sectional study was conducted among a total of 198 children aged 12-23 months at Urban Health and Training Centre (UHTC), Era's Lucknow Medical College, Lucknow, over a period of 6 months i.e., from July 2012-December 2012. Data were collected, compiled and tabulated using Microsoft Excel and analyzed using SPSS 17.0 version. A total of 198 children of age 12-23 months were included in this study, of which 74.7% of children were fully immunized, 11.1% were partially immunized and 14.1% were not immunized at all. The most common reason for partial or non-immunization was family problems (24%) of the respondents followed by lack of knowledge of immunization (20%), and fear of side effects (16%). The odds of risk of partial/non-immunization in illiterate women is 5.78 more than the graduate women (P = 0.039). Although in the present study, majority of the children were immunized, it is still not up to the mark. We have to make it 100%, so that we can reduce mortality due to vaccine-preventable diseases. Increasing awareness and reducing fear of side effects of immunization among parents through health education, counseling, etc. can increase the percentage of immunized children.


Effectiveness of a nurse-led intensive home-visitation programme for first-time teenage mothers (Building Blocks): a pragmatic randomised controlled trial.
Many countries now offer support to teenage mothers to help them to achieve long-term socioeconomic stability and to give a successful start to their children. The Family Nurse Partnership (FNP) is a licensed intensive home-visiting intervention developed in the USA and introduced into practice in England that involves up to 64 structured home visits from early pregnancy until the child's second birthday by specially recruited and trained family nurses. We aimed to assess the effectiveness of giving the programme to teenage first-time mothers on infant and maternal outcomes up to 24 months after birth. We did a pragmatic, non-blinded, randomised controlled, parallel-group trial in community midwifery settings at 18 partnerships between local authorities and primary and secondary care organisations in England. Eligible participants were nulliparous and aged 19 years or younger, and were recruited at less than 25 weeks' gestation. Field-based researchers randomly allocated mothers (1:1) via remote randomisation (telephone and web) to FNP plus usual care (publicly funded health and social care) or to usual care alone. Allocation was stratified by site and minimised by gestation (<16 weeks vs ≥16 weeks), smoking status (yes vs no), and preferred language of data collection (English vs non-English). Mothers and assessors (local researchers at baseline and 24 months' follow-up) were not masked to group allocation, but telephone interviewers were blinded. Primary endpoints were biomarker-calibrated self-reported tobacco use by the mother at late pregnancy, birthweight of the baby, the proportion of women with a second pregnancy within 24 months post-partum, and emergency attendances and hospital admissions for the child within 24 months post-partum. Analyses were by intention to treat. This trial is registered with ISRCTN, number ISRCTN23019866. Between June 16, 2009, and July 28, 2010, we screened 3251 women. After enrolment, 823 women were randomly assigned to receive FNP and 822 to usual care. All follow-up data were retrieved by April 25, 2014. 304 (56%) of 547 women assigned to FNP and 306 (56%) of 545 assigned to usual care smoked at late pregnancy (adjusted odds ratio [AOR] 0·90, 97·5% CI 0·64-1·28). Mean birthweight of 742 babies with mothers assigned to FNP was 3217·4 g (SD 618·0), whereas birthweight of 768 babies assigned to usual care was 3197·5 g (SD 581·5; adjusted mean difference 20·75 g, 97·5% CI -47·73 to 89·23. 587 (81%) of 725 assessed children with mothers assigned to FNP and 577 (77%) of 753 assessed children assigned to usual care attended an emergency department or were admitted to hospital at least once before their second birthday (AOR 1·32, 97·5% CI 0·99-1·76). 426 (66%) of 643 assessed women assigned to FNP and 427 (66%) 646 assigned to usual care had a second pregnancy within 2 years (AOR 1·01, 0·77-1·33). At least one serious adverse event (mainly clinical events associated with pregnancy and infancy period) was reported for 310 (38%) of 808 participants (mother-child) in the usual care group and 357 (44%) of 810 in the FNP group, none of which were considered related to the intervention. Adding FNP to the usually provided health and social care provided no additional short-term benefit to our primary outcomes. Programme continuation is not justified on the basis of available evidence, but could be reconsidered should supportive longer-term evidence emerge. Department of Health Policy Research Programme.


Suppressing the dissolution of polysulfides with cosolvent fluorinated diether towards high-performance lithium sulfur batteries.
The dissolution and shuttle of polysulfides in electrolytes cause severe anode corrosion, low coulombic efficiency, and a rapid fading of the capacity of lithium-sulfur batteries. Fluorinated diether (FDE) was selected as a cosolvent in traditional ether electrolytes to suppress the dissolution of polysulfides. The modified electrolytes lead to a negligible solubility of polysulfides, as well as decreased corrosion of the lithium anode. In an optimal system, the cells show improved cycling performance with an average coulombic efficiency of above 99% and a highly stable reversible discharge capacity of 701 mA h g-1 after 200 cycles at a 0.5C rate. A combination of electrochemical studies and X-ray photoelectron spectroscopy demonstrates the sulfur reduction mechanism with three voltage plateaus.


The impact of hearing loss on the quality of life of elderly adults.
Hearing loss is the most common sensory deficit in the elderly, and it is becoming a severe social and health problem. Especially in the elderly, hearing loss can impair the exchange of information, thus significantly impacting everyday life, causing loneliness, isolation, dependence, and frustration, as well as communication disorders. Due to the aging of the population in the developed world, presbycusis is a growing problem that has been reported to reduce quality of life (QoL). Progression of presbycusis cannot be remediated; therefore, optimal management of this condition not only requires early recognition and rehabilitation, but it also should include an evaluation of QoL status and its assessment.


Mechanisms of thermal stability during flight in the honeybee apis mellifera
Thermoregulation of the thorax allows honeybees (Apis mellifera) to maintain the flight muscle temperatures necessary to meet the power requirements for flight and to remain active outside the hive across a wide range of air temperatures (Ta). To determine the heat-exchange pathways through which flying honeybees achieve thermal stability, we measured body temperatures and rates of carbon dioxide production and water vapor loss between Ta values of 21 and 45 degrees C for honeybees flying in a respirometry chamber. Body temperatures were not significantly affected by continuous flight duration in the respirometer, indicating that flying bees were at thermal equilibrium. Thorax temperatures (Tth) during flight were relatively stable, with a slope of Tth on Ta of 0.39. Metabolic heat production, calculated from rates of carbon dioxide production, decreased linearly by 43 % as Ta rose from 21 to 45 degrees C. Evaporative heat loss increased nonlinearly by over sevenfold, with evaporation rising rapidly at Ta values above 33 degrees C. At Ta values above 43 degrees C, head temperature dropped below Ta by approximately 1-2 degrees C, indicating that substantial evaporation from the head was occurring at very high Ta values. The water flux of flying honeybees was positive at Ta values below 31 degrees C, but increasingly negative at higher Ta values. At all Ta values, flying honeybees experienced a net radiative heat loss. Since the honeybees were in thermal equilibrium, convective heat loss was calculated as the amount of heat necessary to balance metabolic heat gain against evaporative and radiative heat loss. Convective heat loss decreased strongly as Ta rose because of the decrease in the elevation of body temperature above Ta rather than the variation in the convection coefficient. In conclusion, variation in metabolic heat production is the dominant mechanism of maintaining thermal stability during flight between Ta values of 21 and 33 degrees C, but variations in metabolic heat production and evaporative heat loss are equally important to the prevention of overheating during flight at Ta values between 33 and 45 degrees C.


Risk factors for recurrence of shoulder instability after arthroscopic Bankart repair.
The higher failure rates reported with arthroscopic stabilization of traumatic, recurrent anterior shoulder instability compared with open stabilization remain a concern. The purpose of this study was to evaluate the outcomes of arthroscopic Bankart repairs with the use of suture anchors and to identify risk factors related to postoperative recurrence of shoulder instability. Ninety-one consecutive patients underwent arthroscopic stabilization for recurrent anterior traumatic shoulder instability. The mean age (and standard deviation) at the time of surgery was 26.4 +/- 5.4 years. Seventy-one patients were male. Seventy-nine patients were involved in sports (forty, in high-risk sports). Capsulolabral reattachment and capsule retensioning was performed with use of absorbable suture anchors (mean, 4.3 anchors; range, two to seven anchors). All patients were prospectively followed, and, at the time of the last review, the patients were examined and assessed functionally by independent observers. At a mean follow-up of thirty-six months, fourteen patients (15.3%) experienced recurrent instability: six sustained a frank dislocation and eight reported a subluxation. The mean delay to recurrence was 17.6 months. The risk of postoperative recurrence was significantly related to the presence of a bone defect, either on the glenoid side (a glenoid compression-fracture; p = 0.01) or on the humeral side (a large Hill-Sachs lesion; p = 0.05). By contrast, a glenoid separation-fracture was not associated with postoperative recurrent dislocation or subluxation. Recurrence of instability was significantly higher in patients with inferior shoulder hyperlaxity (p = 0.03) and/or anterior shoulder hyperlaxity (p = 0.01). On multivariate analysis, the presence of glenoid bone loss and inferior hyperlaxity led to a 75% recurrence rate (p < 0.001). Lastly, the number of suture-anchors was critical: patients who had three anchors or fewer were at higher risk for recurrent instability (p = 0.03). In the treatment of traumatic recurrent anterior shoulder instability, patients with bone loss or with shoulder hyperlaxity are at risk for recurrent instability after arthroscopic Bankart repair. At least four anchor points should be used to obtain secure shoulder stabilization.


The geographical region of origin determines the phagocytic vulnerability of Lichtheimia strains.
Mucormycoses are life-threatening infections that affect patients suffering from immune deficiencies. We performed phagocytosis assays confronting various strains of Lichtheimia species with alveolar macrophages, which form the first line of defence of the innate immune system. To investigate 17 strains from four different continents in a comparative fashion, transmitted light and confocal fluorescence microscopy was applied in combination with automated image analysis. This interdisciplinary approach enabled the objective and quantitative processing of the big volume of image data. Applying machine-learning supported methods, a spontaneous clustering of the strains was revealed in the space of phagocytic measures. This clustering was not driven by measures of fungal morphology but rather by the geographical origin of the fungal strains. Our study illustrates the crucial contribution of machine-learning supported automated image analysis to the qualitative discovery and quantitative comparison of major factors affecting host-pathogen interactions. We found that the phagocytic vulnerability of Lichtheimia species depends on their geographical origin, where strains within each geographic region behaved similarly, but strongly differed amongst the regions. Based on this clustering, we were able to also classify clinical isolates with regard to their potential geographical origin.


From an executive network to executive control: a computational model of the n-back task.
A paradigmatic test of executive control, the n-back task, is known to recruit a widely distributed parietal, frontal, and striatal "executive network," and is thought to require an equally wide array of executive functions. The mapping of functions onto substrates in such a complex task presents a significant challenge to any theoretical framework for executive control. To address this challenge, we developed a biologically constrained model of the n-back task that emergently develops the ability to appropriately gate, bind, and maintain information in working memory in the course of learning to perform the task. Furthermore, the model is sensitive to proactive interference in ways that match findings from neuroimaging and shows a U-shaped performance curve after manipulation of prefrontal dopaminergic mechanisms similar to that observed in studies of genetic polymorphisms and pharmacological manipulations. Our model represents a formal computational link between anatomical, functional neuroimaging, genetic, behavioral, and theoretical levels of analysis in the study of executive control. In addition, the model specifies one way in which the pFC, BG, parietal, and sensory cortices may learn to cooperate and give rise to executive control.


Fine mapping and candidate gene analysis of Brtri1, a gene controlling trichome development in Chinese cabbage (Brassica rapa L. ssp pekinensis).
Trichomes are derived from the epidermis and constitute an ideal system for studying cell division in plants. Here, a Chinese cabbage doubled haploid (DH) line (FT) without trichomes was crossed with another DH line (PurDH-1) with trichomes to develop an F2 population for fine mapping of trichome control genes. Genetic analysis showed that the trichome phenotype was controlled by a single dominant gene, Brtri1. Using 1226 glabrous individuals in the F2 segregation population, Brtri1 was localized to a 16.84 kb region between markers Pur6-31 and Pur6-39 on chromosome A06. One of the four complete open reading frames within the mapping region, Bra025311, encodes a MYB transcription factor and is highly homologous to the trichome regulatory gene GL1 in Arabidopsis thaliana. It was thus regarded as a candidate gene for Brtri1. Comparative sequencing showed a 5-bp deletion in the third exon of Bra025311 in FT, resulting in a frame-shift mutation. No expression of Bra025311 was detected in FT. A co-dominant indel marker close to this mutation site was developed for marker-assisted selection in Chinese cabbage breeding.


Hepatocellular Carcinoma Mechanisms Associated with Chronic HCV Infection and the Impact of Direct-Acting Antiviral Treatment.
Hepatitis C virus (HCV) infection is the major risk factor for liver cirrhosis and hepatocellular carcinoma (HCC). The mechanisms of HCC initiation, growth, and metastasis appear to be highly complex due to the decade-long interactions between the virus, immune system, and overlapping bystander effects of host metabolic liver disease. The lack of a readily accessible animal model system for HCV is a significant obstacle to understand the mechanisms of viral carcinogenesis. Traditionally, the primary prevention strategy of HCC has been to eliminate infection by antiviral therapy. The success of virus elimination by antiviral treatment is determined by the SVR when the HCV is no longer detectable in serum. Interferon-alpha (IFN-α) and its analogs, pegylated IFN-α (PEG-IFN-α) alone with ribavirin (RBV), have been the primary antiviral treatment of HCV for many years with a low cure rate. The cloning and sequencing of HCV have allowed the development of cell culture models, which accelerated antiviral drug discovery. It resulted in the selection of highly effective direct-acting antiviral (DAA)-based combination therapy that now offers incredible success in curing HCV infection in more than 95% of all patients, including those with cirrhosis. However, several emerging recent publications claim that patients who have liver cirrhosis at the time of DAAs treatment face the risk of HCC occurrence and recurrence after viral cure. This remains a substantial challenge while addressing the long-term benefit of antiviral medicine. The host-related mechanisms that drive the risk of HCC in the absence of the virus are unknown. This review describes the multifaceted mechanisms that create a tumorigenic environment during chronic HCV infection. In addition to the potential oncogenic programming that drives HCC after viral clearance by DAAs, the current status of a biomarker development for early prediction of cirrhosis regression and HCC detection post viral treatment is discussed. Since DAAs treatment does not provide full protection against reinfection or viral transmission to other individuals, the recent studies for a vaccine development are also reviewed.


Inhibition of human immunodeficiency virus Rev and human T-cell leukemia virus Rex function, but not Mason-Pfizer monkey virus constitutive transport element activity, by a mutant human nucleoporin targeted to Crm1.
The hypothesis that the cellular protein Crm1 mediates human immunodeficiency virus type 1 (HIV-1) Rev-dependent nuclear export posits that Crm1 can directly interact both with the Rev nuclear export signal (NES) and with cellular nucleoporins. Here, we demonstrate that Crm1 is indeed able to interact with active but not defective forms of the HIV-1 Rev NES and of NESs found in other retroviral nuclear export factors. In addition, we demonstrate that Crm1 can bind the Rev NES when Rev is assembled onto the Rev response element RNA target and that Crm1, like Rev, is a nucleocytoplasmic shuttle protein. Crm1 also specifically binds the Rev NES in vitro, although this latter interaction is detectable only in the presence of added Ran . GTP. Overexpression of a truncated, defective form of the nucleoporin Nup214/CAN, termed DeltaCAN, that retains Crm1 binding ability resulted in the effective inhibition of HIV-1 Rev or human T-cell leukemia virus Rex-dependent gene expression. In contrast, DeltaCAN had no significant affect on Mason-Pfizer monkey virus constitutive transport element (MPMV CTE)-dependent nuclear RNA export or on the expression of RNAs dependent on the cellular mRNA export pathway. As a result, DeltaCAN specifically blocked late, but not early, HIV-1 gene expression in HIV-1-infected cells. These data strongly validate Crm1 as a cellular cofactor for HIV-1 Rev and demonstrate that the MPMV CTE nuclear RNA export pathway uses a distinct, Crm1-independent mechanism. In addition, these data identify a novel and highly potent inhibitor of leucine-rich NES-dependent nuclear export.


Physical qualification of drivers; medical examination; certificate. Federal Motor Carrier Safety Administration (FMCSA), DOT. Final rule.
This document updates and simplifies the medical examination form that is currently used to determine the physical qualification of commercial motor vehicle (CMV) drivers operating in interstate commerce. The FMCSA takes this action in response to numerous requests from medical examiners to update and simplify the medical examination form that is currently used. This action is intended to reduce the incidence of errors on such forms and to provide more uniform medical examinations of CMV drivers engaged in interstate commerce. The current Federal physical qualification standards tested by medical examiners and recorded on the form will not be revised in this rulemaking.


Impact of Wheat/Faba Bean Mixed Cropping or Rotation Systems on Soil Microbial Functionalities.
Cropping systems based on carefully designed species mixtures reveal many potential advantages in terms of enhancing crop productivity, reducing pest and diseases, and enhancing ecological services. Associating cereals and legume production either through intercropping or rotations might be a relevant strategy of producing both type of culture, while benefiting from combined nitrogen fixed by the legume through its symbiotic association with nitrogen-fixing bacteria, and from a better use of P and water through mycorrhizal associations. These practices also participate to the diversification of agricultural productions, enabling to secure the regularity of income returns across the seasonal and climatic uncertainties. In this context, we designed a field experiment aiming to estimate the 2 years impact of these practices on wheat yield and on soil microbial activities as estimated through Substrate Induced Respiration method and mycorrhizal soil infectivity (MSI) measurement. It is expected that understanding soil microbial functionalities in response to these agricultural practices might allows to target the best type of combination, in regard to crop productivity. We found that the tested cropping systems largely impacted soil microbial functionalities and MSI. Intercropping gave better results in terms of crop productivity than the rotation practice after two cropping seasons. Benefits resulting from intercrop should be highly linked with changes recorded on soil microbial functionalities.


Vitamin D deficiency and course of frailty in a depressed older population.
Objective: To study the association between vitamin D levels and frailty, its components and course in a depressed sample.Methods: Baseline and two-year follow-up data from the depressed sample of the Netherlands Study of Depression in Older persons (NESDO), a prospective observational cohort study, were analyzed. The 378 participants (aged 60-93) had a diagnosis of depression according to DSM-IV criteria. Frailty was defined according to Fried's physical phenotype. 25-OH vitamin D measurement was performed by liquid chromatography - tandem mass spectrometry. Linear and logistic regression analyses were performed, adjusted for covariates.Results: Higher vitamin D levels were cross-sectionally associated with lower prevalence of frailty (OR 0.64 [95%-CI 0.45 - 0.90], p = .010), predicted a lower incidence of frailty among non-frail depressed patients (OR 0.51 [95%-CI 0.26 - 1.00], p=.050), and, surprisingly, the persistence of frailty among frail depressed patients (OR 2.82 [95%-CI 1.23 - 6.49], p=.015).Conclusions: In a depressed population, higher vitamin D levels were associated with lower prevalence and incidence of frailty. Future studies should examine whether the favorable effect of low vitamin D levels on the course of frailty can be explained by confounding or whether unknown pathophysiological mechanisms may exert protective effects.


Relationships between Motor and Executive Functions and the Effect of an Acute Coordinative Intervention on Executive Functions in Kindergartners.
There is growing evidence indicating positive, causal effects of acute physical activity on cognitive performance of school children, adolescents, and adults. However, only a few studies examined these effects in kindergartners, even though correlational studies suggest moderate relationships between motor and cognitive functions in this age group. One aim of the present study was to examine the correlational relationships between motor and executive functions among 5- to 6-year-olds. Another aim was to test whether an acute coordinative intervention, which was adapted to the individual motor functions of the children, causally affected different executive functions (i.e., motor inhibition, cognitive inhibition, and shifting). Kindergartners (N = 102) were randomly assigned either to a coordinative intervention (20 min) or to a control condition (20 min). The coordination group performed five bimanual exercises (e.g., throwing/kicking balls onto targets with the right and left hand/foot), whereas the control group took part in five simple activities that hardly involved coordination skills (e.g., stamping). Children's motor functions were assessed with the Movement Assessment Battery for Children 2 (Petermann, 2009) in a pre-test (T1), 1 week before the intervention took place. Motor inhibition was assessed with the Simon says task (Carlson and Wang, 2007), inhibition and shifting were assessed with the Hearts and Flowers task (Davidson et al., 2006) in the pre-test and again in a post-test (T2) immediately after the interventions. Results revealed significant correlations between motor functions and executive functions (especially shifting) at T1. There was no overall effect of the intervention. However, explorative analyses indicated a three-way interaction, with the intervention leading to accuracy gains only in the motor inhibition task and only if it was tested directly after the intervention. As an unexpected effect, this result needs to be treated with caution but may indicate that the effect of acute coordinative exercise is temporally limited and emerges only for motor inhibition, but not for cognitive inhibition or shifting. More generally, in contrast to other studies including older participants and endurance exercises, no general effect of an acute coordinative intervention on executive functions was revealed for kindergartners.


Improving qPCR telomere length assays: Controlling for well position effects increases statistical power.
Telomere length (TL) is commonly measured using quantitative PCR (qPCR). Although, easier than the southern blot of terminal restriction fragments (TRF) TL measurement method, one drawback of qPCR is that it introduces greater measurement error and thus reduces the statistical power of analyses. To address a potential source of measurement error, we consider the effect of well position on qPCR TL measurements. qPCR TL data from 3,638 people run on a Bio-Rad iCycler iQ are reanalyzed here. To evaluate measurement validity, correspondence with TRF, age, and between mother and offspring are examined. First, we present evidence for systematic variation in qPCR TL measurements in relation to thermocycler well position. Controlling for these well-position effects consistently improves measurement validity and yields estimated improvements in statistical power equivalent to increasing sample sizes by 16%. We additionally evaluated the linearity of the relationships between telomere and single copy gene control amplicons and between qPCR and TRF measures. We find that, unlike some previous reports, our data exhibit linear relationships. We introduce the standard error in percent, a superior method for quantifying measurement error as compared to the commonly used coefficient of variation. Using this measure, we find that excluding samples with high measurement error does not improve measurement validity in our study. Future studies using block-based thermocyclers should consider well position effects. Since additional information can be gleaned from well position corrections, rerunning analyses of previous results with well position correction could serve as an independent test of the validity of these results.


Clinical interventions for treatment non-adherence in psychosis: meta-analysis.
Studies investigating the efficacy of clinical interventions for reducing treatment non-adherence have generated contrasting findings, and treatment non-adherence remains common in clinical practice. To systematically review whether there are effective clinical interventions that community psychiatric services can implement to reduce non-adherence. Systematic review and meta-regression analysis of randomised controlled trials (RCTs) and controlled clinical trials (CCTs) were used to assess the efficacy of interventions to enhance adherence. We reviewed 24 studies, more than half of which were RCTs. In 14 studies the experimental intervention was an educational programme. Five studies evaluated pre-discharge educational sessions, three studies explored the benefit of psychotherapeutic interventions and two studies looked at the effect of telephone prompts. The overall estimate of the efficacy of these interventions produced an odds ratio of 2.59 (95% CI 2.21-3.03) for dichotomous outcomes, and a standardised mean difference of 0.36 (95% CI 0.06-0.66) for continuous outcomes. Community psychiatric services can potentially use effective clinical interventions, backed by scientific evidence, for reducing patient non-adherence.


Vanin-1 licenses inflammatory mediator production by gut epithelial cells and controls colitis by antagonizing peroxisome proliferator-activated receptor gamma activity.
Colitis involves immune cell-mediated tissue injuries, but the contribution of epithelial cells remains largely unclear. Vanin-1 is an epithelial ectoenzyme with a pantetheinase activity that provides cysteamine/cystamine to tissue. Using the 2,4,6-trinitrobenzene sulfonic acid (TNBS)-colitis model we show here that Vanin-1 deficiency protects from colitis. This protection is reversible by administration of cystamine or bisphenol A diglycidyl ether, a peroxisome proliferator-activated receptor (PPAR)gamma antagonist. We further demonstrate that Vanin-1, by antagonizing PPARgamma, licenses the production of inflammatory mediators by intestinal epithelial cells. We propose that Vanin-1 is an epithelial sensor of stress that exerts a dominant control over innate immune responses in tissue. Thus, the Vanin-1/pantetheinase activity might be a new target for therapeutic intervention in inflammatory bowel disease.


Busulfan-mediated oxidative stress and genotoxicity decrease in sperm of Satureja Khuzestanica essential oil-administered mice.
Here, we studied the protective effects of Satureja Khuzestanica essential oil (SKEO) as a potent anti-oxidant, against damage caused by chemotherapy with busulfan in testis and epididymal sperm of adult mice. The NMRI adult mice were assigned: G1: control, G2: was treated with busulfan (4 days, 3.2 mg/kg), G3: was treated with busulfan (4 days, 3.2 mg/kg) and SKEO (28 days, 225 mg/kg) at the same time, and G4: was pre-treated with SKEO (7 days, 225 mg/kg) and subsequently co-treated with busulfan (4 days, 3.2 mg/kg) and SKEO (28 days, 225 mg/kg). Apoptosis and Bcl-2 family gene expression were evaluated in sperm by the terminal deoxynucleotidyl transferase-mediated dUTP-biotin nick end labeling (TUNEL) assay and Real-Time PCR, respectively. The level of oxidative stress was studied in sperm and testis by Superoxide Dismutase (SOD) and Glutathione Peroxidase (GPx) assays. Lactate Dehydrogenase (LDH), and Thiobarbituric assays were used for analyzing cytotoxicity and lipid peroxidation in testis and sperm of mice, (TBA) respectively. The results showed a significant decrease in the percentage of apoptotic sperm in G4 versus G2 and G3 (p < 0.05). SKEO pre-treatment potentially increased Bcl-2 expression and decreased BAX expression in sperm of G4 compared with G2 and G3. The activities of SOD and GPx were increased, also, LDH and TBA decreased significantly in testis and sperm of G4 compared with G2 and G3 (p < 0.05). SKEO pre-treatment had a notable role in reducing oxidative stress, apoptosis, cytotoxicity, and genotoxicity in sperm of busulfan-treated mice. In addition, cytotoxicity and oxidative stress were decreased significantly in testes of this group. Thereby, SKEO may inhibit busulfan-mediated apoptosis in sperm via decreasing oxidative stress and regulating Bcl-2 family genes expression. In conclusion, the beneficial properties of SKEO pre-treatment and co-treatment by its herbal potent anti-oxidants may reduce adverse effects of chemotherapy in the reproductive system in a rodent system. SKEO: Satureja Khuzestanica essential oil; SOD: superoxide dismutase; GPx: glutathione peroxidase; LDH: lactate dehydrogenase; GC-MS: gas chromatography/mass spectrometry; TdT: terminal deoxynucleotidyl transferase; TUNEL: terminal deoxynucleotidyl transferase-mediated dUTP-biotin nick end labeling; ROS: reactive oxygen species.


Development, validation, and performance of a scale to measure community mobilization.
Community mobilization approaches (CMAs) are increasingly becoming key components of health programming. However, CMAs have been ill defined and poorly evaluated, largely due to the lack of measurement tools to assess mobilization processes and impact. We developed the Community Mobilization Measure (CMM), composed of a set of scales to measure mobilization domains hypothesized to operate at the community-level. The six domains include: shared concerns, critical consciousness, leadership, collective action, social cohesion, and organizations and networks. We also included the domain of social control to explore synergies with the related construct of collective efficacy. A survey instrument was developed and pilot tested, then revised and administered to 1181 young people, aged 18-35, in a community-based survey in rural South Africa. Item response modeling and exploratory factor analyses were conducted to assess model fit, dimensionality, reliability, and validity. Results indicate the seven-dimensional model, with linked domains but no higher order construct, fit the data best. Internal consistency reliability of the factors was strong, with ρ values ranging from 0.81 to 0.93. Six of seven scales were sufficiently correlated to represent linked concepts that comprise community mobilization; social control was less related to the other components. At the village level, CMM sub-scales were correlated with other metrics of village social capital and integrity, providing initial evidence of higher-level validity, however additional evaluation of the measure at the community-level is needed. This is the first effort to develop and validate a comprehensive measure for community mobilization. The CMM was designed as an evaluation tool for health programming and should facilitate a more nuanced understanding of mechanisms of change associated with CM, ultimately making mobilizing approaches more effective.


Use of insulin pump therapy at nighttime only for children 7-10 years of age with type 1 diabetes.
Because of age-related developmental and cognitive issues, children <10 years of age may not be able to wear an insulin pump safely when they are not under direct parental supervision. The purpose of this study was to determine if insulin pump therapy at nighttime only, when children are at home, could improve fasting and nighttime blood glucose levels without adverse effects. The study cohort consisted of 10 children aged 7-10 years. A randomized crossover design was used to compare nighttime-only pump usage from dinner and throughout the night, combined with a prebreakfast injection of intermediate-acting NPH and rapid-acting lispro insulin, with 3 insulin injections per day. Comparisons were made among mean blood glucose values and percentage of blood glucose levels within the target range (70-150 mg/dl) before meals, at bedtime, and at 3:00 A.M.; serum fructosamine levels; and scores on measures of adherence and fear of hypoglycemia. Compared with baseline levels, the use of the pump resulted in a significant decrease in the mean average (P < 0.001), breakfast (P < 0.0001), and 3:00 A.M. (P < 0.003) blood glucose levels. There was a decrease in the percentage of blood glucose values less than the target range (P < 0.01) and in fructosamine (P < 0.01) values and an increase in the percentage of blood glucose levels within the target range (P < 0.03). Nighttime-only insulin pump therapy may be a viable alternative that young children can use to improve glycemia when they are not capable of independently managing an insulin pump.


Colonization of barley (Hordeum vulgare) with Salmonella enterica and Listeria spp.
Colonization of barley plants by the food-borne pathogens Salmonella enterica serovar typhimurium and three Listeria spp. (L. monocytogenes, L. ivanovii, L. innocua) was investigated in a monoxenic system. Herbaspirillum sp. N3 was used as a positive control and Escherichia coli HB101 as a negative control for endophytic root colonization. Colonization of the plants was tested 1-4 weeks after inoculation by determination of CFU, specific PCR assays and fluorescence in situ hybridization (FISH) with fluorescently labelled oligonucleotide probes in combination with confocal laser scanning microscopy (CLSM). Both S. enterica strains were found as endophytic colonizers of barley roots and reached up to 2.3 x 10(6) CFU per g root fresh weight after surface sterilization. The three Listeria strains had 10-fold fewer cell numbers after surface sterilization on the roots and therefore were similar to the results of nonendophytic colonizers, such as E. coli HB101. The FISH/CSLM approach demonstrated not only high-density colonization of the root hairs and the root surface by S. enterica but also a spreading to subjacent rhizodermis layers and the inner root cortex. By contrast, the inoculated Listeria spp. colonized the root hair zone but did not colonize other parts of the root surface. Endophytic colonization of Listeria spp. was not observed. Finally, a systemic spreading of S. enterica to the plant shoot (stems and leaves) was demonstrated using a specific PCR analysis and plate count technique.


The Dorsomedial Prefrontal Cortex Plays a Causal Role in Integrating Social Impressions from Faces and Verbal Descriptions.
Several neuroimaging studies point to a key role of the dorsomedial prefrontal cortex (dmPFC) in the formation of socially relevant impressions. In 3 different experiments, participants were required to form socially relevant impressions about other individuals on the basis of text descriptions of their social behaviors, and to decide whether a face alone, a trait adjective (e.g., "selfish"), or a face presented with a trait adjective was consistent or inconsistent with the impression they had formed. Before deciding whether the target stimulus matched the impression they had previously formed, participants received transcranial magnetic stimulation (TMS) over the dmPFC, the inferior frontal gyrus (IFG, also implicated in social impression formation), or over a control site (vertex). Results from the 3 experiments converged in showing that interfering with dmPFC activity significantly delayed participants in responding whether a face-adjective pair was consistent with the impression they had formed. No effects of TMS were observed following stimulation of the IFG or when evaluations had to be made on faces or trait adjectives presented alone. Our findings critically extend previous neuroimaging evidence by indicating a causal role of the dmPFC in creating coherent impressions based on the integration of face and verbal description of social behaviors.


Epidemiological evaluation of acute gastroenteritis and therapeutic approaches in Middle East Countries.
Gastroenteritis represents with respiratory tract infection the most common infectious disease syndrome of humans in developing countries. Gut microbiota regional variation and dysbiosis play a crucial role in triggering and worsening this devastating GI disease. With this manuscript, we want to explore and emphasize the critical aspect of acute gastroenteritis in Middle-East Countries and its correlation with the clinical aspect of gut microbiota modification and intestinal homeostasis. Approximately 1 of 50 children born each year in developed nations is hospitalized for acute gastroenteritis sometime during childhood. The highest rate of illness occurs in children between 3 and 24 months of age. The common causes of diarrhea are infections with viruses and bacteria, diarrhea due to a systemic infection other than gastrointestinal, diarrhea associated with antibiotic administration, and feeding related diarrhea. The single most common diarrheal disorder observed in the Emergency Department and general practice is viral gastroenteritis. In particular, Rotavirus is the cause of more than 2 million hospitalizations and over half a million deaths from acute GE in infants and young children. This burden produces also direct and indirect economic costs. The use of probiotics to counterbalance commensal dysbiosis is emerging as a standard medical practice in these countries. In this scenario, one of the most interesting aspects is that probiotics and gut microbiota modulation could deeply improve the prevention and treatment of this devastating GI pathology. At the same time, vaccination might represent a cost-effective strategy to reduce the health and economic burden of some pathogens, such as rotavirus.


Developing an Intervention for Fall-Related Injuries in Dementia (DIFRID): an integrated, mixed-methods approach.
Falls in people with dementia can result in a number of physical and psychosocial consequences. However, there is limited evidence to inform how best to deliver services to people with dementia following a fall. The aim of the DIFRID study was to determine the feasibility of developing and implementing a new intervention to improve outcomes for people with dementia with fall-related injuries; this encompasses both short-term recovery and reducing the likelihood of future falls. This paper details the development of the DIFRID intervention. The intervention was designed using an integrated, mixed-methods approach. This involved a realist synthesis of the literature and qualitative data gathered through interviews and focus groups with health and social care professionals (n = 81). An effectiveness review and further interviews and observation were also conducted and are reported elsewhere. A modified Delphi panel approach with 24 experts was then used to establish a consensus on how the findings should translate into a new intervention. After feedback from key stakeholders (n = 15) on the proposed model, the intervention was manualised and training developed. We identified key components of a new intervention covering three broad areas: • Ensuring that the circumstances of rehabilitation are optimised for people with dementia • Compensating for the reduced ability of people with dementia to self-manage • Equipping the workforce with the necessary skills and information to care for this patient group Consensus was achieved on 54 of 69 statements over two rounds of the Delphi surveys. The statements were used to model the intervention and finalise the accompanying manual and protocol for a feasibility study. Stakeholder feedback was generally positive and the majority of suggested intervention components were approved. The proposed outcome was a 12-week complex multidisciplinary intervention primarily based at the patient's home. A new intervention has been developed to improve outcomes for people with dementia following a fall requiring healthcare attention. The feasibility of this intervention is currently being tested. ISRCTN41760734 (16/11/2015).


Genetic and nongenetic factors associated with milk color in dairy cows.
Milk color is one of the sensory properties that can influence consumer choice of one product over another and it influences the quality of processed dairy products. This study aims to quantify the cow-level genetic and nongenetic factors associated with bovine milk color traits. A total of 136,807 spectra from Irish commercial and research herds (with multiple breeds and crosses) were used. Milk lightness (Lˆ*), red-green index (aˆ*) and yellow-blue index (bˆ*) were predicted for individual milk samples using only the mid-infrared spectrum of the milk sample. Factors associated with milk color were breed, stage of lactation, parity, milking-time, udder health status, pasture grazing, and seasonal calving. (Co)variance components for Lˆ*,aˆ*, and bˆ* were estimated using random regressions on the additive genetic and within-lactation permanent environmental effects. Greater bˆ* value (i.e., more yellow color) was evident in milk from Jersey cows. Milk Lˆ* increased consistently with stage of lactation, whereas aˆ* increased until mid lactation to subsequently plateau. Milk bˆ* deteriorated until 31 to 60 DIM, but then improved thereafter until the end of lactation. Relative to multiparous cows, milk yielded by primiparae was, on average, lighter (i.e., greater Lˆ*), more red (i.e., greater aˆ*), and less yellow (i.e., lower bˆ*). Milk from the morning milk session had lower Lˆ*,aˆ*, and bˆ* Heritability estimates (±SE) for milk color varied between 0.15 ± 0.02 (30 DIM) and 0.46 ± 0.02 (210 DIM) for Lˆ*, between 0.09 ± 0.01 (30 DIM) and 0.15 ± 0.02 (305 DIM) for aˆ*, and between 0.18 ± 0.02 (21 DIM) and 0.56 ± 0.03 (305 DIM) for bˆ* For all the 3 milk color features, the within-trait genetic correlations approached unity as the time intervals compared shortened and were generally <0.40 between the peripheries of the lactation. Strong positive genetic correlations existed between bˆ* value and milk fat concentration, ranging from 0.82 ± 0.19 at 5 DIM to 0.96 ± 0.01 at 305 DIM and confirming the observed phenotypic correlation (0.64, SE = 0.01). Results of the present study suggest that breeding strategies for the enhancement of milk color traits could be implemented for dairy cattle populations. Such strategies, coupled with the knowledge of milk color traits variation due to nongenetic factors, may represent a tool for the dairy processors to reduce, if not eliminate, the use of artificial pigments during milk manufacturing.


Effect of anaerobic phases length on denitrifying dephosphatation biocenosis - a case study of IFAS-MBSBBR.
The study aimed to evaluate the influence of the duration times of anaerobic phases on the bacterial biocenosis characterisation while denitrifying dephosphatation in the Integrated Fixed-Film Activated Sludge - Moving-Bed Sequencing Batch Biofilm Reactor (IFAS-MBSBBR). The experiment was conducted in a laboratory model. The study consisted of four series, which differed in terms of the ratio of the anaerobic phases. duration concerning the overall reaction time in the cycle. The anaerobic phases covered from 18 to 30% of the whole cycle duration. During the reactor performance that took 9 months, the influent and effluent were monitored by analysis of COD, TKN, NH4-N, NO2-N, NO3-N, TP, PO4-P, pH, alkalinity and the phosphorus uptake batch tests. Characterisation of the activated sludge and the biofilm biocenosis was based on fluorescent in situ hybridisation (identification of PAO and GAO) and the denaturing gradient gel electrophoresis patterns. The organic compounds removal was high (more than 95.7%) independently of cycle configuration. The best efficiency for nitrogen (91.1%) and phosphorus (98.8%) removal was achieved for the 30% share of the anaerobic phases in the reaction time. Denitrifying PAO (DPAO) covered more than 90% of PAO in the biofilm and usually around 70% of PAO in the activated sludge. A substantial part of the polyphosphate accumulating organisms (PAO) community were Actinobacteria. The denitrifying dephosphatation activity was performed mainly by Accumulibacter phosphatis. High nutrient removal efficiencies may be obtained in IFAS-MBSBBR using the denitrifying dephosphatation process. It was found that the length of anaerobic phases influenced denitrification and the biological phosphorus removal. The extension of the anaerobic phases duration time in the reaction time caused an increase in the percentage share of denitrifying PAO (DPAO) in PAO. The biocenosis of the biofilm and the activated sludge reveal different species patterns and domination of the EBPR community.


Evaluation of z-axis resolution and image noise for nonconstant velocity spiral CT data reconstructed using a weighted 3D filtered backprojection (WFBP) reconstruction algorithm.
To determine the constancy of z-axis spatial resolution, CT number, image noise, and the potential for image artifacts for nonconstant velocity spiral CT data reconstructed using a flexibly weighted 3D filtered backprojection (WFBP) reconstruction algorithm. A WFBP reconstruction algorithm was used to reconstruct stationary (axial, pitch=0), constant velocity spiral (pitch = 0.35-1.5) and nonconstant velocity spiral CT data acquired using a 128 x 0.6 mm acquisition mode (38.4 mm total detector length, z-flying focal spot technique), and a gantry rotation time of 0.30 s. Nonconstant velocity scans used the system's periodic spiral mode, where the table moved in and out of the gantry in a cyclical manner. For all scan types, the volume CTDI was 10 mGy. Measurements of CT number, image noise, and the slice sensitivity profile were made for all scan types as a function of the nominal slice width, table velocity, and position within the scan field of view. A thorax phantom was scanned using all modes and reconstructed transverse and coronal plane images were compared. Negligible differences in slice thickness, CT number, noise, or artifacts were found between scan modes for data taken at two positions within the scan field of view. For nominal slices of 1.0-3.0 mm, FWHM values of the slice sensitivity profiles were essentially independent of the scan type. For periodic spiral scans, FWHM values measured at the center of the scan range were indistinguishable from those taken 5 mm from one end of the scan range. All CT numbers were within +/- 5 HU, and CT number and noise values were similar for all scan modes assessed. A slight increase in noise and artifact level was observed 5 mm from the start of the scan on the first pass of the periodic spiral. On subsequent passes, noise and artifact level in the transverse and coronal plane images were the same for all scan modes. Nonconstant velocity periodic spiral scans can achieve z-axis spatial resolution, CT number accuracy, image noise and artifact level equivalent to those for stationary (axial), and constant velocity spiral scans. Thus, periodic spiral scans are expected to allow assessment of four-dimensional CT data for scan lengths greater than the detector width without sacrificing image quality.


Regulation of Hoxa2 in cranial neural crest cells involves members of the AP-2 family.
Hoxa2 is expressed in cranial neural crest cells that migrate into the second branchial arch and is essential for proper patterning of neural-crest-derived structures in this region. We have used transgenic analysis to begin to address the regulatory mechanisms which underlie neural-crest-specific expression of Hoxa2. By performing a deletion analysis on an enhancer from the Hoxa2 gene that is capable of mediating expression in neural crest cells in a manner similar to the endogenous gene, we demonstrated that multiple cis-acting elements are required for neural-crest-specific activity. One of these elements consists of a sequence that binds to the three transcription factor AP-2 family members. Mutation or deletion of this site in the Hoxa2 enhancer abrogates reporter expression in cranial neural crest cells but not in the hindbrain. In both cell culture co-transfection assays and transgenic embryos AP-2 family members are able to trans-activate reporter expression, showing that this enhancer functions as an AP-2-responsive element in vivo. Reporter expression is not abolished in an AP-2(alpha) null mutant embryos, suggesting redundancy with other AP-2 family members for activation of the Hoxa2 enhancer. Other cis-elements identified in this study critical for neural-crest-specific expression include an element that influences levels of expression and a conserved sequence, which when multimerized directs expression in a broad subset of neural crest cells. These elements work together to co-ordinate and restrict neural crest expression to the second branchial arch and more posterior regions. Our findings have identified the cis-components that allow Hoxa2 to be regulated independently in rhombomeres and cranial neural crest cells.


Studies on steroid receptors in human and rabbit skeletal muscle - clues to the understanding of the mechanism of action of anabolic steroids.
The mechanism of action of steroid hormones in target tissues include the binding of the steroid molecule to specific receptors in the cytoplasm. Steroid receptors may therefore be regarded as mediators of hormone action. The presence of such receptors in tissues reflects their hormone-sensitivity and the receptor levels are indicative of the relative potential for a direct hormonal action on the tissue in question. Using 3H-labeled synthetic ligands and a charcoal adsorption assay, the presence of specific androgen, glucocorticoid and estrogen (in rabbits only) receptors was demonstrated in human and rabbit skeletal muscle cytosol. These tissues can therefore be regarded as targets for these steroids. Scatchard analysis was then used to quantitate the receptors in muscle in different conditions. In back muscle of scoliotic patients, the concentrations of androgen and glucocorticoid receptors were similar on the convex and concave sides, except the concentration of glucocorticoid receptors (per g of wet weight), which was higher on the convex side. The tissue concentration (per g of wet weight) of glucocorticoid and estrogen receptors (but not of androgen receptor) was higher in rabbit soleus (slow-twitch) muscle than in the gastrocnemius/plantaris (fast-twitch) muscle complex. When the concentrations were related to the number of nuclei (i.e. expressed per mg of DNA), however, only the estrogen receptor concentration differed between the muscles (higher in soleus). Muscle atrophy in rabbit gastrocnemius muscle was induced by tenotomy or denervation and led to similar changes with an increase with time in androgen and glucocorticoid receptor levels (expressed per g of wet weight or per mg of protein) and a concomitant loss of muscle weight and protein. The total muscle content of receptors or the receptor concentration expressed per mg of DNA were also increased, but to a lesser extent. Synthetic anabolic-androgenic steroids can act directly on skeletal muscle in view of their capacity to bind to the androgen receptor as shown in the present study. Relative binding affinities of anabolic-androgenic steroids to the androgen receptor were similar in rabbit and rat skeletal muscle and in rat prostate. The protein/DNA ratio in the muscle samples was used as an estimation of the size of the "functional DNA-unit". The results indicate that slow-twitch fibers have smaller "DNA units", but also that muscle atrophy causes a decrease of the size of the "DNA unit".(ABSTRACT TRUNCATED AT 400 WORDS)


Independent effects of imageability and grammatical class in synonym judgement in aphasia.
The grammatical class effect in aphasia, i.e. dissociated processing of words according to their respective grammatical class, has been attributed to either grammatical, lexical or semantic (i.e., imageability) deficits. This study explores the hypotheses of impaired semantic treatment as the source of the grammatical class effect in aphasia. A synonym judgement task that includes nouns and verbs of high and low imageability has been administered to 30 Spanish-speaking patients suffering from receptive or productive aphasia and 30 controls. Normal controls performed significantly better than aphasic patients. Although globally the productive aphasics performed significantly better than the receptive aphasics, grammatical class (nouns better than verbs) and imageability (high imageability better than low imageability) affected performance in both subgroups. No significant interaction emerged between these two factors. The results suggest that the grammatical class effect may emerge from semantic impairment and that it is -at least partially- independent of the imageability of words.


Human telomeres that carry an integrated copy of human herpesvirus 6 are often short and unstable, facilitating release of the viral genome from the chromosome.
Linear chromosomes are stabilized by telomeres, but the presence of short dysfunctional telomeres triggers cellular senescence in human somatic tissues, thus contributing to ageing. Approximately 1% of the population inherits a chromosomally integrated copy of human herpesvirus 6 (CI-HHV-6), but the consequences of integration for the virus and for the telomere with the insertion are unknown. Here we show that the telomere on the distal end of the integrated virus is frequently the shortest measured in somatic cells but not the germline. The telomere carrying the CI-HHV-6 is also prone to truncations that result in the formation of a short telomere at a novel location within the viral genome. We detected extra-chromosomal circular HHV-6 molecules, some surprisingly comprising the entire viral genome with a single fully reconstituted direct repeat region (DR) with both terminal cleavage and packaging elements (PAC1 and PAC2). Truncated CI-HHV-6 and extra-chromosomal circular molecules are likely reciprocal products that arise through excision of a telomere-loop (t-loop) formed within the CI-HHV-6 genome. In summary, we show that the CI-HHV-6 genome disrupts stability of the associated telomere and this facilitates the release of viral sequences as circular molecules, some of which have the potential to become fully functioning viruses.


Learning-induced plasticity in human audition: objects, time, and space.
The human auditory system is comprised of specialized but interacting anatomic and functional pathways encoding object, spatial, and temporal information. We review how learning-induced plasticity manifests along these pathways and to what extent there are common mechanisms subserving such plasticity. A first series of experiments establishes a temporal hierarchy along which sounds of objects are discriminated along basic to fine-grained categorical boundaries and learned representations. A widespread network of temporal and (pre)frontal brain regions contributes to object discrimination via recursive processing. Learning-induced plasticity typically manifested as repetition suppression within a common set of brain regions. A second series considered how the temporal sequence of sound sources is represented. We show that lateralized responsiveness during the initial encoding phase of pairs of auditory spatial stimuli is critical for their accurate ordered perception. Finally, we consider how spatial representations are formed and modified through training-induced learning. A population-based model of spatial processing is supported wherein temporal and parietal structures interact in the encoding of relative and absolute spatial information over the initial ~300 ms post-stimulus onset. Collectively, these data provide insights into the functional organization of human audition and open directions for new developments in targeted diagnostic and neurorehabilitation strategies.


[Tumor necrosis factor blocking agents: a review. Part I: Clinical efficacy evaluation].
Blockade of tumor necrosis factor with monoclonal antibodies, has emerged as one of the most promising therapies in some autoimmune conditions as rheumatoid arthritis, ankylosing spondylitis, psoriatic arthritis and Crohn s disease. They have shown effectiveness on reducing symptoms and modifying the progression of the disease. However, they disrupt the balance of inflammatory and immune responses and some risks associated with TNF-blockers have become apparent. The purpose of this article is to review the evidence about benefits and risk associated with the use of TNF-blockers in approved indications and to provide practical recommendations for its use in the management of these conditions.


High Intensity Interval- vs Resistance or Combined- Training for Improving Cardiometabolic Health in Overweight Adults (Cardiometabolic HIIT-RT Study): study protocol for a randomised controlled trial.
Although evidence shows the positive health effects of physical activity, most of the adult population in Colombia are sedentary. It is, therefore, important to implement strategies that generate changes in lifestyle behaviours. This protocol describes a study in which we will compare the effects of 12 weeks of high-intensity interval training (HIIT), resistance training (RT) or combined training (HIIT + RT) on the improvement of body composition, endothelial function, blood pressure, blood lipids, and cardiorespiratory fitness in a cohort of sedentary, overweight adults (aged 30-50 years). Sixty sedentary, overweight adults attending primary care in Bogotá, Colombia will be included in a factorial randomised controlled trial. Participants will be randomly assigned to the following intervention groups: (1) non-exercise group: usual care with dietary support, (2) HIIT group: 4 × 4-min intervals at 85-95 % maximum heart rate (HRmax) (with the target zone maintained for at least 2 minutes), interspersed with a 4-min recovery period, at 65 % HRmax, (3) RT group: completing a resistance circuit (including upper and lower muscle groups) as many times as needed according to subject's weight until an expenditure of 500 kcal at 40-80 % of one-rep max (1RM) has been achieved, and (4) combined group: HIIT + RT. The primary end point for effectiveness is vascular function as measured by flow-mediated vasodilatation 1 week after the end of exercise training. The results of this study will provide new information about the possible effect of the programme in improving the cardiometabolic health of overweight adults, making a more efficient use of an adult's resources over time. ClinicalTrials.gov ID: NCT02715063 . Registered on 8 March 2016.


Correspondences between the binding characteristics of a non-natural peptide, Lei-Dab7, and the distribution of SK subunits in the rat central nervous system.
Small-conductance calcium-activated potassium channels (SK1-SK3 channels) are responsible for long-lasting hyperpolarization following action potential and contribute to the neuronal firing and integration signal. Two peptide toxins: apamin and Leiurotoxin 1, block this SK channels with high affinities. We generated a modified Leiurotoxin 1 (Lei-Dab7) that inhibits SK2 channels with a high selectivity. Competitive binding of radio-iodinated apamin to different rat brain structures, in the presence of native apamin and Lei-Dab7, has shown that dissociation constants differ by a factor of 1000 and thus demonstrated that ligand affinity is as important as ligand selectivity for a specific receptor. However, the lack of ligands discriminating between SK channel subunits is impeding the understanding of the role of each heteromeric SK channel type in different tissues. Our study aims to better understand the molecular combinations of SK channels and their association with specific functional implications. On this purpose, a clustering technique allows us to identify five groups of brain structures reflecting singular profiles of affinity and selectivity of Lei-Dab7 in comparison with apamin. The analysis of correspondences between Lei-Dab7 binding and distribution of SK subunits in these groups of brain structures suggests that functional heteromeric SK channels are involved in specific information processes.