Oral contraceptives and venous thromboembolism: a systematic review and meta-analysis.
An association between oral contraceptive (OC) use and venous thromboembolism (VTE) has long been recognized. However, no summary estimates of the increase in VTE risk associated with OC use have been available since 1995, and no meta-analyses have evaluated the VTE risk of new preparations containing drospirenone. The aim of the study was to carry out a meta-analysis to summarize existing evidence on the association between venous VTE and OC use, and to investigate how such an association may vary according to the type of OC, OC user characteristics, study characteristics and biases. Relevant cohort or case-control studies were searched in MEDLINE and other electronic databases up to May 2010, with no language restriction. Data were combined using a generic inverse-variance approach. Meta-regression in addition to stratification was used to explore potential predictors of the summary estimate of risk. Sixteen cohort and 39 case-control studies were included in at least one comparison. Overall, the odds ratio (OR) of OC users versus non-users was 3.41 (95% CI 2.98, 3.92). This estimate was based upon nine cohort studies evaluating approximately 12 000 000 person-years, and 23 case-control studies including approximately 45 000 women. VTE risk for OC users was significantly lower in studies evaluating 'all VTE cases' than in those evaluating 'idiopathic VTE only' (OR 3.09 and 4.94, respectively). Among the carriers of genetic mutations G20210A and Factor V Leiden (FVL), OC users showed a significantly increased VTE risk compared with non-users (OR 1.63; 95% CI 1.01, 2.65, and OR 1.80; 95% CI 1.20, 2.71, respectively). When the newest OCs containing drospirenone were compared with non-drospirenone-containing OCs (except those containing levonorgestrel only), VTE risk did not significantly increase (OR 1.13; 95% CI 0.94, 1.35). This meta-analysis confirms that OC use significantly increases VTE risk. The strength of this association, however, varies according to the generation of OC, type of outcome and presence of a genetic mutation, with ORs ranging from 3 to 5.


Phylogenetic framework and molecular signatures for the class Chloroflexi and its different clades; proposal for division of the class Chloroflexia class. nov. [corrected] into the suborder Chloroflexineae subord. nov., consisting of the emended family Oscillochloridaceae and the family Chloroflexaceae fam. nov., and the suborder Roseiflexineae subord. nov., containing the family Roseiflexaceae fam. nov.
The phylum "Chloroflexi" contains highly divergent groups of bacteria. To understand the evolutionary relationships among these bacteria, phylogenetic trees were constructed based upon concatenated sequences for 20 conserved proteins and comparative genomic analyses were carried out to identify molecular markers (conserved signature indels or CSIs) that are specific for different clades of Chloroflexi. In phylogenetic trees based upon either concatenated protein sequences or the 16S rRNA gene, species from the class Chloroflexi and the order Chloroflexales formed strongly supported clades. The species from these clades are also clearly distinguished from other bacteria based upon 5 and 9 identified CSIs, respectively, in important proteins that were specific for these clades. Additionally, three CSIs that were specific for the genus Chloroflexus and four CSIs specific for the genus Roseiflexus were also identified. In phylogenetic trees, the species Oscillochloris trichoides (family Oscillochloridaceae) formed a strongly supported clade with the species from the genus Chloroflexus (and with Chloronema in the 16S rRNA gene tree). A specific relationship of O. trichoides to the Chloroflexus spp. is also strongly supported by 7 CSIs that are uniquely shared by the species from these genera but not found in Roseiflexus or any other bacteria. In addition to their phylogenetic clustering and shared presence of many novel CSIs, the species from the genera Chloroflexus and Oscillochloris (and also Chloronema) also differ from species of the genera Roseiflexus (and Heliothrix) by their green color, shared presence of the chlorosomes and Bchl c (in addition to Bchl a and d in some species), by their fatty acid profiles, and by the presence of β- and γ-carotenes and quinone MK-10. Based upon these observations, we propose division of the order Chloroflexales into two suborders: the first of these suborders Chloroflexineae subord. nov. is comprised of the family Oscillochloridaceae (emended to include the genus Chloronema) and a new family Chloroflexaceae fam. nov. consisting of the genus Chloroflexus. The second suborder Roseiflexineae subord. nov. contains a new family Roseiflexaceae fam. nov. comprised of the genera Roseiflexus and Heliothrix; orange-red bacteria lacking chlorosomes and Bchl c and differing from the Chloroflexineae in their carotenoids, quinones and fatty acid profiles. Additionally, we also provide here formal descriptions of the class Chloroflexia class. nov. [corrected], and of the orders Chloroflexales ord. nov. and Herpetosiphonales ord. nov. Lastly, our phylogenetic and comparative analyses provide either no or very weak support for a grouping together of the different classes (viz. Chloroflexi, Thermomicrobia, Dehalococcoidetes, Anaerolineae, Caldilineae and Ktedonobacteria) that are currently part of the phylum Chloroflexi. However, a specific grouping of the classes Chloroflexi and Thermomicrobia (as well as 'Thermobaculum') is supported by both phylogenetic means and the identified CSIs. Based upon these results, it is suggested that the phylum Chloroflexi "sensu stricto" should be comprised only of the classes Chloroflexi and Thermomicrobia and the other four classes (viz. Dehalococcoidetes, Anaerolineae, Caldilineae and Ktedonobacteria), which are at present part of this "superphylum" should be regarded as taxa related to the phylum Chloroflexi "sensu stricto", awaiting more detailed investigations to clarify their relationships to each other and other phyla of bacteria.


Caffeine and opening the eyes have additive effects on resting arousal measures.
Studies indicate that the change from closed to open eyes in a resting condition results in an increase in skin conductance level (SCL) and a global decrease in EEG alpha activity, both indicative of increased arousal. Other studies show that ingestion of caffeine also produces SCL increase and alpha reduction. This study investigated the additivity of the effects of these two independent arousing variables. EEG activity and SCL were recorded from 22 university students during both eyes-closed and eyes-open resting conditions, under the action of both caffeine and placebo, in a counterbalanced randomised double-blind study. SCL increased significantly from eyes-closed to eyes-open conditions, and from placebo to caffeine, with no interaction. Global reductions in EEG alpha amplitude were apparent with opening of the eyes and caffeine ingestion; again, there was no interaction. Caffeine had a larger effect than opening the eyes on SCL, but their relative effect sizes were reversed in alpha. The two dependent measures showed the predicted negative correlation in both eyes-closed placebo and eyes-open caffeine conditions, with the latter substantially reduced relative to the former. Caffeine and opening the eyes have additive effects on two measures of arousal, increasing SCL and reducing global EEG alpha. However, the independent variable effects are not equivalent, suggesting that one or both measures reflect additional non-arousal processes. As caffeine is widely used by both children and adults, knowledge of the additivity of arousal effects of caffeine and opening the eyes is important in controlling participant state in EEG studies. The current results confirm the use of mean global alpha amplitude as a measure of resting-state arousal, but also point to non-arousal effects of visual input.


Asymptomatic Bile Duct Dilatation in Children: Is It a Disease?
Bile duct dilatation is a relatively common sonographic finding; nevertheless, its clinical significance in children is controversial because little research has been done in the area. Therefore, we investigated the natural course and clinical significance of biliary duct dilatation in children. We performed a retrospective study of 181 children (range, 1-day-old to 17-year-old) in whom dilatation of the intrahepatic duct and/or common hepatic duct and/or common bile duct was detected by abdominal ultrasonography at the Severance Children's Hospital between November 2005 and March 2014. We reviewed and analyzed laboratory test results, clinical manifestations, and clinical course in these patients. Pediatric patients (n=181) were enrolled in the study and divided into two groups. The first group included 59 subjects, without definitive cause of bile duct dilatation, who did not require treatment; the second group included 122 subjects, with definitive cause of bile duct dilatation or underlying biliary disease, who did require treatment. In the first group, 24 patients (40.7%) showed spontaneous resolution of bile duct dilatation, 20 patients (33.9%) showed no change, and 15 patients (25.4%) were lost to follow-up. In the second group, 31 patients were diagnosed with choledochal cysts, and 91 patients presented with biliary tract dilatations due to secondary causes, such as gallbladder or liver disease, post-operative complications, or malignancy. Biliary dilatation in pediatric patients without symptoms, and without laboratory and other sonographic abnormalities, showed a benign clinical course. No pathologic conditions were noted on follow-up ultrasonography.


The molecular pathogenesis of hepatic encephalopathy.
Hepatic encephalopathy (HE) incorporates a spectrum of neuropsychiatric abnormalities seen in patients with liver dysfunction with a potential for full reversibility. Distinct syndromes are identified in acute liver failure and cirrhosis. Rapid deterioration in consciousness level and increased intracranial pressure that may result in brain herniation and death are a feature of acute liver failure whereas manifestations of HE in cirrhosis include psychomotor dysfunction, impaired memory, increased reaction time, sensory abnormalities, poor concentration and in severe forms, coma. For over a 100 years ammonia has been considered central to its pathogenesis. In the brain, the astrocyte is the main site for ammonia detoxification, during the conversion of glutamate to glutamine. An increased ammonia level raises the amount of glutamine within astrocytes, causing an osmotic imbalance resulting in cell swelling and ultimately brain oedema. The present review focuses upon the molecular mechanisms involved in the pathogenesis of HE. Therapy of HE is directed primarily at reducing ammonia generation and increasing its detoxification.


Algorithmic stability and sanity-check bounds for leave-one-out cross-validation.
In this article we prove sanity-check bounds for the error of the leave-one-out cross-validation estimate of the generalization error: that is, bounds showing that the worst-case error of this estimate is not much worse than that of the training error estimate. The name sanity check refers to the fact that although we often expect the leave-one-out estimate to perform considerably better than the training error estimate, we are here only seeking assurance that its performance will not be considerably worse. Perhaps surprisingly, such assurance has been given only for limited cases in the prior literature on cross-validation. Any nontrivial bound on the error of leave-one-out must rely on some notion of algorithmic stability. Previous bounds relied on the rather strong notion of hypothesis stability, whose application was primarily limited to nearest-neighbor and other local algorithms. Here we introduce the new and weaker notion of error stability and apply it to obtain sanity-check bounds for leave-one-out for other classes of learning algorithms, including training error minimization procedures and Bayesian algorithms. We also provide lower bounds demonstrating the necessity of some form of error stability for proving bounds on the error of the leave-one-out estimate, and the fact that for training error minimization algorithms, in the worst case such bounds must still depend on the Vapnik-Chervonenkis dimension of the hypothesis class.


Drug efflux mediated by the human multidrug resistance P-glycoprotein is inhibited by cell swelling.
P-glycoprotein (P-gp), the product of the human multidrug resistance (MDR1) gene, confers multidrug resistance on cells by acting as an ATP-dependent drug transporter. A method using confocal microscopy was developed to measure the transport activity of P-gp from the rate of movement of doxorubicin, a fluorescent substrate of P-gp, across the membrane of a single cell. Recent work has shown that expression of P-gp enhances the activation of chloride channels in response to cell swelling, suggesting that membrane stretch might switch P-gp from a drug-transporting mode to a mode in which it activates chloride channels. In agreement with this idea, we find that cell swelling inhibits drug efflux in cells expressing P-gp but is without effect on the slower background efflux in cells not expressing P-gp and in cells transiently transfected with a mutated MDR1 in which the ATP hydrolysis sites had been inactivated. The identification of a novel means for inhibiting P-gp-mediated drug transport may have implications for the reversal of multidrug resistance during chemotherapy.


A Landscape-Scale, Applied Fire Management Experiment Promotes Recovery of a Population of the Threatened Gouldian Finch, Erythrura gouldiae, in Australia's Tropical Savannas.
Fire is an integral part of savanna ecology and changes in fire patterns are linked to biodiversity loss in savannas worldwide. In Australia, changed fire regimes are implicated in the contemporary declines of small mammals, riparian species, obligate-seeding plants and grass seed-eating birds. Translating this knowledge into management to recover threatened species has proved elusive. We report here on a landscape-scale experiment carried out by the Australian Wildlife Conservancy (AWC) on Mornington Wildlife Sanctuary in northwest Australia. The experiment was designed to understand the response of a key savanna bird guild to fire, and to use that information to manage fire with the aim of recovering a threatened species population. We compared condition indices among three seed-eating bird species--one endangered (Gouldian finch) and two non-threatened (long-tailed finch and double-barred finch)--from two large areas (> 2,830 km2) with initial contrasting fire regimes ('extreme': frequent, extensive, intense fire; versus 'benign': less frequent, smaller, lower intensity fires). Populations of all three species living with the extreme fire regime had condition indices that differed from their counterparts living with the benign fire regime, including higher haematocrit levels in some seasons (suggesting higher levels of activity required to find food), different seasonal haematocrit profiles, higher fat scores in the early wet season (suggesting greater food uncertainty), and then lower muscle scores later in the wet season (suggesting prolonged food deprivation). Gouldian finches also showed seasonally increasing stress hormone concentrations with the extreme fire regime. Cumulatively, these patterns indicated greater nutritional stress over many months for seed-eating birds exposed to extreme fire regimes. We tested these relationships by monitoring finch condition over the following years, as AWC implemented fire management to produce the 'benign' fire regime throughout the property. The condition indices of finch populations originally living with the extreme fire regime shifted to resemble those of their counterparts living with the benign fire regime. This research supports the hypothesis that fire regimes affect food resources for savanna seed-eating birds, with this impact mediated through a range of grass species utilised by the birds over different seasons, and that fire management can effectively moderate that impact. This work provides a rare example of applied research supporting the recovery of a population of a threatened species.


Affinity of recombinant antibody and antibody fragment binding to human thyroglobulin: potential applications in gene therapy.
Recombinant antibodies and antibody fragments are currently being produced. They can be used in vitro for the structural study of antigen-antibody interactions for instance, but their in vivo production may have applications for gene therapy of certain cancers and severe viral diseases and in developing new animal models of autoimmune disease. We report here these two types of applications using a recombinant antihuman thyroglobulin (hTg) antibody.


The Potential Protective Effects of Polyphenols in Asbestos-Mediated Inflammation and Carcinogenesis of Mesothelium.
Malignant Mesothelioma (MM) is a tumor of the serous membranes linked to exposure to asbestos. A chronic inflammatory response orchestrated by mesothelial cells contributes to the development and progression of MM. The evidence that: (a) multiple signaling pathways are aberrantly activated in MM cells; (b) asbestos mediated-chronic inflammation has a key role in MM carcinogenesis; (c) the deregulation of the immune system might favor the development of MM; and (d) a drug might have a better efficacy when injected into a serous cavity thus bypassing biotransformation and reaching an effective dose has prompted investigations to evaluate the effects of polyphenols for the therapy and prevention of MM. Dietary polyphenols are able to inhibit cancer cell growth by targeting multiple signaling pathways, reducing inflammation, and modulating immune response. The ability of polyphenols to modulate the production of pro-inflammatory molecules by targeting signaling pathways or ROS might represent a key mechanism to prevent and/or to contrast the development of MM. In this review, we will report the current knowledge on the ability of polyphenols to modulate the immune system and production of mediators of inflammation, thus revealing an important tool in preventing and/or counteracting the growth of MM.


Family structure and children's health in the United States: findings from the National Health Interview Survey, 2001-2007.
This report presents statistics from the 2001-2007 National Health Interview Survey (NHIS) on selected measures of physical health and limitations, access to or utilization of health care, and behavior or emotional well-being for children under age 18 by family structure, sex, age, race, Hispanic origin, parent's education, family income, poverty status, home tenure status, health insurance coverage, place of residence, and region. NHIS is a multistage probability sample survey conducted annually by interviewers of the U.S. Census Bureau for the Centers for Disease Control and Prevention's National Center for Health Statistics, and is representative of the civilian noninstitutionalized population of the United States. Information about one randomly selected child per family is collected in a face-to-face interview with an adult proxy respondent familiar with the child's health. Children in nuclear families were generally less likely than children in nonnuclear families to be in good, fair, or poor health; to have a basic action disability; to have leaming disabilities or attention deficit hyperactivity disorder; to lack health insurance coverage; to have had two or more emergency room visits in the past 12 months; to have receipt of needed prescription medication delayed during the past 12 months due to lack of affordability; to have gone without needed dental care due to cost in the past 12 months; to be poorly behaved; and to have definite or severe emotional or behavioral difficulties during the past 6 months. Children living in single-parent families had higher prevalence rates than children in nuclear families for the various health conditions and indicators examined in this report. However, when compared with children living in other nonnuclear families, children in single-parent families generally exhibited similar rates with respect to child health, access to care, and emotional or behavioral difficulties.


Statistical learning and spelling: Evidence from an incidental learning experiment with children.
Statistical learning processes-akin to those seen in spoken language acquisition (Saffran et al., 1996)-may be important for the development of literacy, particularly spelling development. One previous study provides direct evidence for this process: Samara and Caravolas (2014) demonstrated that 7-year-olds generalize over permissible letter contexts (graphotactics) in novel word-like stimuli under incidental learning conditions. However, unlike in actual orthography, conditioning contexts in Samara and Caravolas' (2014) stimuli comprised perfectly correlated, redundant cues in both word-initial and word-final positions. The current study explores whether 7-year-olds can extract such constraints in the absence of redundant cues. Since theories of literacy development predict greater sensitivity to restrictions within word-final units, we also contrast learning in word-initial and word-final units. We demonstrate that-for 7-year-old learners in two linguistic contexts (English and Turkish)-there is substantial evidence for the learning of both types of restriction.


Automatic Segmentation of Human Cortical Layer-Complexes and Architectural Areas Using Ex vivo Diffusion MRI and Its Validation.
Recently, several magnetic resonance imaging contrast mechanisms have been shown to distinguish cortical substructure corresponding to selected cortical layers. Here, we investigate cortical layer and area differentiation by automatized unsupervised clustering of high-resolution diffusion MRI data. Several groups of adjacent layers could be distinguished in human primary motor and premotor cortex. We then used the signature of diffusion MRI signals along cortical depth as a criterion to detect area boundaries and find borders at which the signature changes abruptly. We validate our clustering results by histological analysis of the same tissue. These results confirm earlier studies which show that diffusion MRI can probe layer-specific intracortical fiber organization and, moreover, suggests that it contains enough information to automatically classify architecturally distinct cortical areas. We discuss the strengths and weaknesses of the automatic clustering approach and its appeal for MR-based cortical histology.


A tonic heat test stimulus yields a larger and more reliable conditioned pain modulation effect compared to a phasic heat test stimulus.
The interest in conditioned pain modulation (CPM) as a clinical tool for measuring endogenously induced analgesia is increasing. There is, however, large variation in the CPM methodology, hindering comparison of results across studies. Research comparing different CPM protocols is needed in order to obtain a standardized test paradigm. The aim of the study was to assess whether a protocol with phasic heat stimuli as test-stimulus is preferable to a protocol with tonic heat stimulus as test-stimulus. In this experimental crossover study, we compared 2 CPM protocols with different test-stimulus; one with tonic test-stimulus (constant heat stimulus of 120-second duration) and one with phasic test-stimuli (3 heat stimulations of 5 seconds duration separated by 10 seconds). Conditioning stimulus was a 7°C water bath in parallel with the test-stimulus. Twenty-four healthy volunteers were assessed on 2 occasions with minimum 1 week apart. Differences in the magnitude and test-retest reliability of the CPM effect in the 2 protocols were investigated with repeated-measures analysis of variance and by relative and absolute reliability indices. The protocol with tonic test-stimulus induced a significantly larger CPM effect compared to the protocol with phasic test-stimuli (P < 0.001). Fair and good relative reliability was found with the phasic and tonic test-stimuli, respectively. Absolute reliability indices showed large intraindividual variability from session to session in both protocols. The present study shows that a CPM protocol with a tonic test-stimulus is preferable to a protocol with phasic test-stimuli. However, we emphasize that one should be cautious to use the CPM effect as biomarker or in clinical decision making on an individual level due to large intraindividual variability.


A Risk-Based Strategy for Evaluating Mitigation Options for Process-Formed Compounds in Food: Workshop Proceedings.
Processing (eg, cooking, grinding, drying) has changed the composition of food throughout the course of human history; however, awareness of process-formed compounds, and the potential need to mitigate exposure to those compounds, is a relatively recent phenomenon. In May 2015, the North American Branch of the International Life Sciences Institute (ILSI North America) Technical Committee on Food and Chemical Safety held a workshop on the risk-based process for mitigation of process-formed compounds. This workshop aimed to gain alignment from academia, government, and industry on a risk-based process for proactively assessing the need for and benefit of mitigation of process-formed compounds, including criteria to objectively assess the impact of mitigation as well as research needed to support this process. Workshop participants provided real-time feedback on a draft framework in the form of a decision tree developed by the ILSI North America Technical Committee on Food and Chemical Safety to a panel of experts, and they discussed the importance of communicating the value of such a process to the larger scientific community and, ultimately, the public. The outcome of the workshop was a decision tree that can be used by the scientific community and could form the basis of a global approach to assessing the risks associated with mitigation of process-formed compounds.


Control of sexually transmitted infections and prevention of HIV transmission: mending a fractured paradigm.
Control of sexually transmitted infections (STIs) is feasible, leads to improved sexual and reproductive health and contributes to preventing HIV transmission. The most advanced HIV epidemics have developed under conditions of poor STI control, particularly where ulcerative STIs were prevalent. Several countries that have successfully controlled STIs have documented stabilization or reversal of their HIV epidemics. STI control is a public health outcome measured by reduced incidence and prevalence. The means to achieve this include: (i) targeting and outreach to populations at greatest risk; (ii) promoting and providing condoms and other means of prevention; (iii) effective clinical interventions; (iv) an enabling environment; and (v) reliable data. Clinical services include STI case management, screening and management of STIs in sex partners. Syndromic case management is effective for most symptomatic curable STIs and screening strategies exist to detect some asymptomatic infections. Presumptive epidemiologic treatment of sex partners and sex workers complement efforts to interrupt transmission and reduce prevalence. Clinical services alone are insufficient for control since many people with STIs do not attend clinics. Outreach and peer education have been effectively used to reach such populations. STI control requires effective interventions with core populations whose rates of partner change are high enough to sustain transmission. Effective, appropriate targeting is thus necessary and often sufficient to reduce prevalence in the general population. Such efforts are most effective when combined with structural interventions to ensure an enabling environment for prevention. Reliable surveillance and related data are critical for designing and evaluating interventions and for assessing control efforts.


Glucocorticoid-induced leucine zipper (GILZ) promotes the nuclear exclusion of FOXO3 in a Crm1-dependent manner.
GILZ (glucocorticoid-induced leucine zipper) is an ubiquitous protein whose expression is induced by glucocorticoids in lymphoid cells. We previously showed that GILZ expression is rapidly induced upon interleukin 2 deprivation in T-cells, protecting cells from apoptosis induced by forkhead box subgroup O3 (FOXO3). The aim of this work is to elucidate the molecular mechanism of FOXO factor inhibition by GILZ. We show in the myeloid cell line HL-60 and the lymphoid CTLL-2 T-cell line that GILZ down-regulates the expression of p27(KIP1) and Bim, two FOXO targets involved in cell cycle regulation and apoptosis, respectively. GILZ inhibits FOXO1, FOXO3, and FOXO4 transcriptional activities measured with natural or synthetic FOXO-responsive promoters in HL-60 cells. This inhibitory effect is independent of protein kinase B and IkappaB kinase phosphorylation sites. GILZ does not hinder FOXO3 DNA-binding activity and does not physically interact with FOXO3. However, using fluorescence microscopy, we observe that GILZ expression provokes a Crm-1-dependent nuclear exclusion of FOXO3 leading to its relocalization to the cytoplasm. Moreover, GILZ exclusive cytoplasmic localization is a prerequisite for FOXO3 inhibition and relocalization. We propose that GILZ is a general inhibitor of FOXO factors acting through an original mechanism by preventing them from reaching target genes within the nucleus.


Factors contributing to sex differences in functional outcomes and participation after stroke.
To examine factors contributing to the sex differences in functional outcomes and participation restriction after stroke. Individual participant data on long-term functional outcome or participation restriction (i.e., handicap) were obtained from 11 stroke incidence studies (1993-2014). Multivariable log-binomial regression was used to estimate the female:male relative risk (RR) of poor functional outcome (modified Rankin Scale score >2 or Barthel Index score <20) at 1 year (10 studies, n = 4,852) and 5 years (7 studies, n = 2,226). Multivariable linear regression was used to compare the mean difference (MD) in participation restriction by use of the London Handicap Scale (range 0-100 with lower scores indicating poorer outcome) for women compared to men at 5 years (2 studies, n = 617). For each outcome, study-specific estimates adjusted for confounding factors (e.g., sociodemographics, stroke-related factors) were combined with the use of random-effects meta-analysis. In unadjusted analyses, women experienced worse functional outcomes after stroke than men (1 year: pooled RRunadjusted 1.32, 95% confidence interval [CI] 1.18-1.48; 5 years: RRunadjusted 1.31, 95% CI 1.16-1.47). However, this difference was greatly attenuated after adjustment for age, prestroke dependency, and stroke severity (1 year: RRadjusted 1.08, 95% CI 0.97-1.20; 5 years: RRadjusted 1.05, 95% CI 0.94-1.18). Women also had greater participation restriction than men (pooled MDunadjusted -5.55, 95% CI -8.47 to -2.63), but this difference was again attenuated after adjustment for the aforementioned factors (MDadjusted -2.48, 95% CI -4.99 to 0.03). Worse outcomes after stroke among women were explained mostly by age, stroke severity, and prestroke dependency, suggesting these potential targets to improve the outcomes after stroke in women.


The Dutch Objective Burden Inventory: validity and reliability in a Canadian population of caregivers for people with heart failure.
Evidence suggests that caregivers of people with heart failure (HF) often experience caregiver burden and emotional distress. However, these studies measured the caregiving experience using generic tools since a disease-specific tool was not available. Recently, the Dutch Objective Burden Inventory (DOBI) was developed as a disease-specific tool measuring objective caregiver burden in a Dutch HF population of caregivers. Using a cross-sectional design, caregivers of HF patients attending an outpatient HF clinic completed the DOBI, the Hosptial Anxiety and Depression Scale (HADS) and the Caregiver Reaction Assessment (CRA). Caregivers (n=47) were mainly female (72%) and spouses (72%) of the HF patients with a mean age of 63.1 (±10.4) years. Patients were older (mean age 72.7; ±10.6), 64% male and had advanced HF. Feasibility for the objective portion of the DOBI was excellent with <10% missing values. The subjective component of the DOBI was incomplete and could not be used in the analyses. Seven items had minimal variability. Significant relationships emerged between the DOBI, CRA and HADS revealing construct validity for all subscales of the DOBI. Cronbach's alpha was >.80 for all DOBI subscales. The DOBI is the only disease-specific tool that measures burden for caregivers of HF patients. The objective portion of the DOBI showed evidence of adequate internal consistency and construct validity in a Canadian population of caregivers of HF patients attending a HF Clinic. Further testing is needed to determine floor and ceiling effects for DOBI items and responsiveness of this tool.


'Mixed blessings': parental religiousness, parenting, and child adjustment in global perspective.
Most studies of the effects of parental religiousness on parenting and child development focus on a particular religion or cultural group, which limits generalizations that can be made about the effects of parental religiousness on family life. We assessed the associations among parental religiousness, parenting, and children's adjustment in a 3-year longitudinal investigation of 1,198 families from nine countries. We included four religions (Catholicism, Protestantism, Buddhism, and Islam) plus unaffiliated parents, two positive (efficacy and warmth) and two negative (control and rejection) parenting practices, and two positive (social competence and school performance) and two negative (internalizing and externalizing) child outcomes. Parents and children were informants. Greater parent religiousness had both positive and negative associations with parenting and child adjustment. Greater parent religiousness when children were age 8 was associated with higher parental efficacy at age 9 and, in turn, children's better social competence and school performance and fewer child internalizing and externalizing problems at age 10. However, greater parent religiousness at age 8 was also associated with more parental control at age 9, which in turn was associated with more child internalizing and externalizing problems at age 10. Parental warmth and rejection had inconsistent relations with parental religiousness and child outcomes depending on the informant. With a few exceptions, similar patterns of results held for all four religions and the unaffiliated, nine sites, mothers and fathers, girls and boys, and controlling for demographic covariates. Parents and children agree that parental religiousness is associated with more controlling parenting and, in turn, increased child problem behaviors. However, children see religiousness as related to parental rejection, whereas parents see religiousness as related to parental efficacy and warmth, which have different associations with child functioning. Studying both parent and child views of religiousness and parenting are important to understand the effects of parental religiousness on parents and children.


Beliefs about Fighting and Their Relations to Urban Adolescents' Frequency of Aggression and Victimization: Evaluation of the Beliefs about Fighting Scale.
This study investigated the structure and concurrent validity of the Beliefs About Fighting Scale (BAFS). Participants were 2,118 students from three urban middle schools who completed measures of their beliefs, frequency of physical aggression, victimization, and nonviolent intentions. Ratings of students' frequency of physical aggression, physical victimization, and nonviolent behavior were also obtained from their teachers. The majority of the sample was African American (81%). Confirmatory factor analyses supported a model with separate factors representing beliefs against fighting, beliefs that fighting is sometimes necessary, beliefs supporting reactive aggression, and beliefs supporting proactive aggression. Support was also found for strong measurement invariance across sex, grade, and groups that differed in whether a violence prevention program was being implemented at their school. The four BAFS factors were associated with adolescents' frequency of aggression, victimization, and nonviolent behavior. This study underscores the importance of assessing multiple aspects of beliefs associated with aggressive behavior.


Differential responses of collagen and glycosaminoglycan syntheses and cell proliferation to exogenous transforming growth factor beta 1 in the developing mouse skin fibroblasts in culture.
Skin fibroblast cultures were established from mouse foetuses at days 14, 15, 16 and 18 of gestation and from newborn mice. Modulations of mitotic and biosynthetic phenotypes of the fibroblasts by transforming growth factor beta1 (TGFbeta1) were studied. Treatment of the fibroblasts with TGFbeta1 at doses of 1 and 10 ng/ml for 48 h resulted in significant stimulation of cell proliferation in the 15-, 16- and 18-day foetal fibroblasts and a slight stimulation in the 14-day foetal fibroblasts. Treatment with TGFbeta1 resulted in stimulation of collagen synthesis approximately 2-fold in the 18-day foetal and newborn fibroblasts, but failed to stimulate it in the 14-, 15- and 16-day foetal fibroblasts. TGFbeta1 stimulated glycosaminoglycan (GAG) synthesis throughout all developmental stages approximately 1.8-2.6 fold. Histological study demonstrated that skin wounds made at day 16 of gestation were replaced with normal-appearing dermis, but at day 18 the wounds left dermal fibrosis and lack of hair follicles. These results indicate that the modulations of fibroblast phenotypes (proliferation and syntheses of collagen and GAG) in response to TGFbeta1 occur at different stages of gestation. Ontogenic transitions of skin wound healing and collagen synthetic phenotype with TGFbeta1 treatment in cultured fibroblasts occurred between days 16 and 18 of gestation, suggesting that the unresponsiveness of collagen synthesis to exogenous TGFbeta1 in cell culture may be related to the phenomenon of scarless wounds in the foetus.


Quantitative measures of motor development in Angelman syndrome.
Angelman Syndrome is a rare neurodevelopmental disorder characterized by developmental delay, lack of speech, seizures, intellectual disability, characteristic behavior, and movement disorders. Clinical gait analysis provides the opportunity for movement quantification to investigate an observed maladaptive change in gait pattern and offers an objective outcome of change. Pressure-sensor-based technology, inertial and activity monitoring, and instrumented gait analysis (IGA) were employed to define motor abnormalities in Angelman syndrome. Temporal-spatial gait parameters of persons with Angelman Syndrome (pwAS) show deficiencies in gait performance through walking speed, step length, step width, and walk ratio. pwAS walk with reduced step lengths, increased step width, and greater variability. Three-dimensional motion kinematics showed increased anterior pelvic tilt, hip flexion, and knee flexion. PwAS have a walk ratio more than two standard deviations below controls. Dynamic electromyography showed prolonged activation of knee extensors, which was associated with a decreased range of motion and the presence of hip flexion contractures. Use of multiple gait tracking modalities revealed that pwAS exhibit a change in gait pattern to a flexed knee gait pattern. Cross-sectional studies of individuals with AS show a regression toward this maladaptive gait pattern over development in pwAS ages 4-11. PwAS unexpectedly did not have spasticity associated with change in gait pattern. Multiple quantitative measures of motor patterning may offer early biomarkers of gait decline consistent with critical periods of intervention, insight into appropriate management strategies, objective primary outcomes, and early indicators of adverse events.


A Mycobacterium tuberculosis Dormancy Antigen Differentiates Latently Infected Bacillus Calmette-Guérin-vaccinated Individuals.
IFN-γ release assays (IGRAs) are better indicators of Mycobacterium tuberculosis infection than the tuberculin skin test (TST) in Bacillus Calmette-Guérin (BCG)-vaccinated populations. However, IGRAs do not discriminate active and latent infections (LTBI) and no gold standard for LTBI diagnosis is available. Thus, since improved tests to diagnose M. tuberculosis infection are required, we assessed the efficacy of several M. tuberculosis latency antigens. BCG-vaccinated healthy donors (HD) and tuberculosis (TB) patients were recruited. QuantiFERON-TB Gold In-Tube, TST and clinical data were used to differentiate LTBI. IFN-γ production against CFP-10, ESAT-6, Rv2624c, Rv2626c and Rv2628 antigens was tested in peripheral blood mononuclear cells. LTBI subjects secreted significantly higher IFN-γ levels against Rv2626c than HD. Additionally, Rv2626c peptide pools to which only LTBI responded were identified, and their cumulative IFN-γ response improved LTBI discrimination. Interestingly, whole blood stimulation with Rv2626c allowed the discrimination between active and latent infections, since TB patients did not secrete IFN-γ against Rv2626c, in contrast to CFP-10 + ESAT-6 stimulation that induced IFN-γ response from both LTBI and TB patients. ROC analysis confirmed that Rv2626c discriminated LTBI from HD and TB patients. Therefore, since only LTBI recognizes specific epitopes from Rv2626c, this antigen could improve LTBI diagnosis, even in BCG-vaccinated people.


Responsibility for Canada's healthcare quality agenda: interviews with Canadian health leaders.
Canadian healthcare is under increased scrutiny to improve quality and performance, and for good reason. The proliferation of provincial-level quality councils underscores the urgency to establish an aligned national quality agenda. Patient safety has long been held as a critical element of a high-quality healthcare system; with the inexorable growth in spending, efficiency has more recently been introduced. Efficiency and quality are both factors in Ontario's Excellent Care for All legislation introduced in June of 2010, and Quebec's l'Institut national d'excellence en santé et en services sociaux (INESSS) arising from the Castonguay report. These associations of quality and efficiency are also echoed in the US, Australian and UK public debates. The development of a quality agenda has concurrently precipitated discussion regarding responsibility for quality, particularly but not exclusively with the emergence of quality issues in the technical and interpretive pathology arena. The discussion and debate on responsibility have become preoccupations at the national, provincial, institutional and individual profession levels.


Interaction of the BKCa channel gating ring with dendrotoxins.
Two classes of small homologous basic proteins, mamba snake dendrotoxins (DTX) and bovine pancreatic trypsin inhibitor (BPTI), block the large conductance Ca(2+)-activated K(+) channel (BKCa, KCa1.1) by production of discrete subconductance events when added to the intracellular side of the membrane. This toxin-channel interaction is unlikely to be pharmacologically relevant to the action of mamba venom, but as a fortuitous ligand-protein interaction, it has certain biophysical implications for the mechanism of BKCa channel gating. In this work we examined the subconductance behavior of 9 natural dendrotoxin homologs and 6 charge neutralization mutants of δ-dendrotoxin in the context of current structural information on the intracellular gating ring domain of the BKCa channel. Calculation of an electrostatic surface map of the BKCa gating ring based on the Poisson-Boltzmann equation reveals a predominantly electronegative surface due to an abundance of solvent-accessible side chains of negatively charged amino acids. Available structure-activity information suggests that cationic DTX/BPTI molecules bind by electrostatic attraction to site(s) on the gating ring located in or near the cytoplasmic side portals where the inactivation ball peptide of the β2 subunit enters to block the channel. Such an interaction may decrease the apparent unitary conductance by altering the dynamic balance of open versus closed states of BKCa channel activation gating.


COAGULATION IN EMBRYONIC BLOOD.
1. In pig embryos of 100 to 270 mm. the average coagulation time of the blood was found to be about 23 minutes. This represents a coagulation time six to eight times greater than that obtained for the adult. 2. The first evidence of coagulation in the blood of these embryos consisted in the appearance of small masses of fibrin deposited almost invariably at the side of the test-tube. The ensuing coagulum was, as a rule, in the nature of a sliding clot, never attaining any marked degree of density or firmness. 3. In an analysis of the possible factors involved in this greater coagulation time of embryonic blood, it was found that numerically the blood platelets varied from 415,000 to 800,000 per c.mm., a content not differing in any significant degree from that of the adult, in which the average was found to be about 588,000 with a variation from 544,000 to 932,000. 4. The addition of platelet material obtained from adult pig blood reduced the coagulation time for embryonic blood to an average of 8.4 minutes, a decrease of 75 per cent. 5. The addition of two drops of 0.5 per cent calcium chloride reduced the coagulation time for embryonic blood to an average of 10.3 minutes, a reduction of over 50 per cent. 6. The addition of tissue extract to embryonic blood reduced the coagulation time to an average of 3.7 minutes, a time essentially equivalent to that obtained for adult blood. The clot was of a much firmer character than that obtained either in the normal coagulation or in the calcium experiments. 7. Chemical analysis demonstrated a calcium content in embryonic blood in excess of that of the adult, in the proportion of 7 : 5. 8. In view of the results indicated above, it became evident that the calcium in embryonic blood must be present in some combined form. This conclusion is supported by experiments in which barium and magnesium brought about a reduction in coagulation time in non-oxalated embryonic blood, but did not have this effect when added to oxalated blood, indicating in the former case, on the basis of the specificity of calcium, a liberation of free calcium ions. With oxalated blood, it was also found that under certain conditions coagulation could be brought about by the addition of tissue extract. 9. That the fibrinogen content plays no important part in coagulation time is shown by the fact that whereas the maximum amount of fibrin obtained by defibrinating embryonic blood was about 12 per cent of that obtained from the adult, nevertheless upon the addition of tissue extract the coagulation time of embryonic blood becomes equivalent to that of the adult. 10. The presence of bile was demonstrated in the circulating blood of these embryos. Since it was further demonstrated that by the addition of bile to adult blood conditions could be produced essentially identical with those of embryonic blood, and since in the preceding analysis of the factors involved in coagulation no significant differences could be demonstrated between the blood of the embryos and that of the adult other than the presence of bile in the former, the data justify the conclusion that the bile content in the circulation of 100 to 270 mm. pig embryos constitutes the primary factor accounting for the greater coagulation time in the blood of these embryos. A condition in embryonic blood in some respects comparable with that of icterus is also indicated. 11. In the calcium experiments the results are apparently due primarily to the introduction of calcium ions in excess of the amount which enters into chemical combination with the bile present. With tissue extract it appears that the free calcium ions essential for the initiation of coagulation must be liberated through some interaction with the constituents of bile. 12. The results of this study suggest that the normal coagulation of embryonic blood, as far as bile is concerned, involves a process comparable with that obtained after the addition of tissue extract or cephalin, but on a smaller scale. In the embryonic blood in vitro, through the gradual disintegration of cellular elements, a certain amount of tissue substance (cephalin (?)) is slowly set free in the plasma, neutralizing the bile and ultimately liberating a sufficient amount of calcium to bring about coagulation.


Directed evolution of the substrate specificity of biotin ligase.
We have developed selection scheme for directing the evolution of Escherichia coli biotin protein ligase (BPL) via in vitro compartmentalization, and have used this scheme to alter the substrate specificity of the ligase towards the utilization of the biotin analogue desthiobiotin. In this scheme, a peptide substrate (BAP) was conjugated to a DNA library encoding BirA, emulsified such that there was a single template per compartment, and protein variants were transcribed and translated in vitro. Those variants that could efficiently desthiobiotinylate their corresponding peptide:DNA conjugate were subsequently captured and amplified. Following just six rounds of selection and amplification several variants that demonstrated higher activity with desthiobiotin were identified. The best variants from Round 6, BirA6-40 and BirA6-47 , showed 17-fold and 10-fold higher activity, respectively, their abilities to use desthiobiotin as a substrate. While selected enzymes contained a number of substitutions, a single mutation, M157T, proved sufficient to provide much greater activity with desthiobiotin. Further characterization of BirA6-40 and the single substitution variant BirAM157T revealed that they had twoto threefold higher kcat values for desthiobiotin. These variants had also lost much of their ability to utilize biotin, resulting in orthogonal enzymes that in conjunction with streptavidin variants that can utilize desthiobiotin may prove to be of great use in developing additional, robust conjugation handles for a variety of biological and biotechnological applications.


Rare infections mimicking MS.
The diagnosis of multiple sclerosis (MS), despite well defined clinical criteria is not always simple. On many occasions it is difficult to differentiate MS from various non-MS idiopathic demyelinating disorders, specific and infectious inflammatory diseases or non-inflammatory demyelinating diseases. Clinicians should be aware of various clinical and MRI "red flags" that may point to the other diagnosis and demand further diagnostic evaluation. It is generally accepted that atypical clinical symptoms or atypical neuroimaging signs determine necessity for broad differential diagnostic work up. Of the infectious diseases that are most commonly mistaken for MS the clinician should take into account Whipple's disease, Lyme disease, Syphilis, HIV/AIDS, Brucellosis, HHV-6 infection, Hepatitis C, Mycoplasma and Creutzfeld-Jacob disease, among others. Cat scratch disease caused by Bartonella hensellae, Mediterranean spotted fever caused by Riketssia connore and Leptospirosis caused by different Leptospira serovars rarely cause focal neurological deficit and demyelinating MRI changes similar to MS. When atypical clinical and neuroimaging presentations are present, serology on rare infectious diseases that may mimic MS may be warranted. This review will focus on the infectious diseases mimicking MS with presentation of rare illustrative cases.


Image guided stereotactic radiosurgery for lesions in proximity to the anterior visual pathways: a preliminary report.
The incidence of optic neuropathy after stereotactic radiosurgery (SRS) is related to the total dose, fraction size, and treatment volume. Theoretically, fractionated SRS can decrease this risk. In this paper, we report our technique for fractionated SRS and assess its potential role in the management of tumors located adjacent to the anterior visual pathways. Since 1997, thirteen patients (median age: 50, range 21-76) with lesions in close proximity to the anterior visual pathways were treated on the CyberKnife image guided SRS system (Accuray, Inc., Sunnyvale, CA). The CyberKnife is a 6MV linear accelerator mounted on a robotic arm which can monitor and adjust to changes in the target position in real time thus eliminating skeletal frame immobilization and allowing for convenient multi-fraction SRS treatments. Magnetic Resonance Imaging (MRI) and computerized tomography (CT) imaging for treatment planning were obtained with the patients head immobilized in an aquaplast mask. After image fusion, the target and critical structures were delineated. Two to five fractions were prescribed with approximately a 24-hour interfraction interval. The patients received 25 Gy in 5 fractions (n=5), 21 Gy in 3 fractions (n=5), or 20 Gy in 2 fractions (n=3) to the 75-95% isodose line. Ten of the thirteen patients had good pretreatment vision. In nearly all instances, the volume of the optic nerve that received 80% of the prescribed dose was < 0.05 cm3. In all instances, the volume of the optic nerve that received 50% of the prescribed dose was </= 0.5 cm3. Only one patient received more than a 5 Gy daily dose to > 0.03 cm3 of optic nerve. With median follow up of 18 months (range 12 to 54), four patients have had improvement in their vision. No visual deterioration has been observed in any of the other patients. In addition, there has been no tumor progression within the treated field. Fractionated SRS using the CyberKnife is technically feasible and may decrease the risk of optic neuropathy. Greater patient accrual and longer follow up will be necessary to further determine the clinical benefit of this approach.


Persons with Alzheimer's disease make phone calls independently using a computer-aided telephone system.
This study assessed whether four patients with a diagnosis of Alzheimer's disease could make independent phone calls via a computer-aided telephone system. The study was carried out according to a non-concurrent multiple baseline design across participants. All participants started with baseline during which the telephone system was not available, and continued with intervention in which such system was used. It involved a net-book computer provided with specific software, a global system for mobile communication modem (GSM), a microswitch, and photos of the persons available for the phone calls. All participants learned to use the system and made phone calls independently to a variety of partners such as family members, friends and staff personnel. The positive implications of the system were discussed in relation to previous data in this area and the possibility of helping persons with Alzheimer's disease restore an important, instrumental daily ability and engage in communication with distant partners.


Description of Streptococcus pneumoniae infections in burn patients.
Longer survival in burn patients has resulted in more infectious complications, typically with Klebsiella pneumoniae, Pseudomonas aeruginosa, Acinetobacter baumannii, and Staphylococcus aureus. Although Streptococcus pneumoniae infections are common in the community and can cause nosocomial infections, the incidence and risk factors for pneumococcal infections in burn patients is unclear. We performed an electronic retrospective chart review to collect rates of and risk factors for S. pneumoniae infections in patients with thermal burns from March 2003 through June 2008. Of the 1838 patients admitted to the burn center, 10 were infected (0.54% incidence). Patients presented with pneumonia (seven patients, 0.38% incidence) and bacteremia (three patients, 0.16% incidence) within a week of initial burn (median 1 day, range 0-8), often in the setting of bacterial co-infection (five patients). This group was mainly young males with median 28.8% total body surface area burns; 60% had concomitant inhalational injury. Most did not have traditional risk factors for pneumococcal infection but had objective signs of infection at time of positive culture and were treated with appropriate antibiotics. Two patients in this series died, although no mortality was attributed to S. pneumoniae. Pneumococcal disease is not common in burn patients and generally occurs early on in hospitalization after burn making it more likely to be a community-acquired pathogen rather than nosocomial in the burn population. It should be considered in the setting of sepsis or new pulmonary infiltrates within a week after burn, but typical empiric antibiotics against the usual burn pathogens should be adequate to also treat for pneumococcal infection.


On impact and volcanism across the Cretaceous-Paleogene boundary.
The cause of the end-Cretaceous mass extinction is vigorously debated, owing to the occurrence of a very large bolide impact and flood basalt volcanism near the boundary. Disentangling their relative importance is complicated by uncertainty regarding kill mechanisms and the relative timing of volcanogenic outgassing, impact, and extinction. We used carbon cycle modeling and paleotemperature records to constrain the timing of volcanogenic outgassing. We found support for major outgassing beginning and ending distinctly before the impact, with only the impact coinciding with mass extinction and biologically amplified carbon cycle change. Our models show that these extinction-related carbon cycle changes would have allowed the ocean to absorb massive amounts of carbon dioxide, thus limiting the global warming otherwise expected from postextinction volcanism.


Mechanistic Links Between Obesity, Diabetes, and Blood Pressure: Role of Perivascular Adipose Tissue.
Obesity is increasingly prevalent and is associated with substantial cardiovascular risk. Adipose tissue distribution and morphology play a key role in determining the degree of adverse effects, and a key factor in the disease process appears to be the inflammatory cell population in adipose tissue. Healthy adipose tissue secretes a number of vasoactive adipokines and anti-inflammatory cytokines, and changes to this secretory profile will contribute to pathogenesis in obesity. In this review, we discuss the links between adipokine dysregulation and the development of hypertension and diabetes and explore the potential for manipulating adipose tissue morphology and its immune cell population to improve cardiovascular health in obesity.


Comment on "Cell type regulates selective segregation of mouse chromosome 7 DNA strands in mitosis".
Armakolas and Klar (Reports, 24 February 2006, p. 1146) suggested that segregation of mouse chromosome 7, after induction of a site-specific crossover between homologous chromosomes, is driven by a preferential inheritance of the old Watson and the old Crick DNA strands. However, this interpretation only considered half of the possible outcomes. The conjecture fails when all possible outcomes are examined.


Regional asynchronicity in dairy production and processing in early farming communities of the northern Mediterranean.
In the absence of any direct evidence, the relative importance of meat and dairy productions to Neolithic prehistoric Mediterranean communities has been extensively debated. Here, we combine lipid residue analysis of ceramic vessels with osteo-archaeological age-at-death analysis from 82 northern Mediterranean and Near Eastern sites dating from the seventh to fifth millennia BC to address this question. The findings show variable intensities in dairy and nondairy activities in the Mediterranean region with the slaughter profiles of domesticated ruminants mirroring the results of the organic residue analyses. The finding of milk residues in very early Neolithic pottery (seventh millennium BC) from both the east and west of the region contrasts with much lower intensities in sites of northern Greece, where pig bones are present in higher frequencies compared with other locations. In this region, the slaughter profiles of all domesticated ruminants suggest meat production predominated. Overall, it appears that milk or the by-products of milk was an important foodstuff, which may have contributed significantly to the spread of these cultural groups by providing a nourishing and sustainable product for early farming communities.


Sleep quality and perceived health in college undergraduates with adverse childhood experiences.
Research demonstrates that poor sleep quality is a predictor of chronic mental and physical health problems. The link between adverse childhood experiences (ACEs) and poor health outcomes is also well established; however, few studies have examined the relationships between ACEs, sleep quality, and physical and mental health. The current study used structural equation modeling to assess the direct and indirect relationships between ACEs, sleep quality, symptoms of depression and anxiety, and general health perception in a sample of college undergraduates (N = 399), a group of individuals whose age is notable for only recently transitioning out of childhood. Indirect (ie, mediation) effects indicated with 95% confidence that sleep quality mediated the relationship between ACEs and general health perception, depressive symptoms, and symptoms of anxiety. Sleep quality did not account for the entire relationship between ACE score and these health outcomes, indicating partial mediation. When reversing the mediator and outcome variables, depression and anxiety fully mediated the relationship between ACE score and sleep quality. The results of this study suggest that sleep quality may be an important intermediary mechanism by which ACEs might contribute to poor health outcomes and especially poor general health perception. Prospective longitudinal research is needed to examine the directionality of the relationships between ACEs, sleep quality, and physical and mental health outcomes over time.


Full-length transcriptome sequences and the identification of putative genes for flavonoid biosynthesis in safflower.
The flower of the safflower (Carthamus tinctorius L.) has been widely used in traditional Chinese medicine for the ability to improve cerebral blood flow. Flavonoids are the primary bioactive components in safflower, and their biosynthesis has attracted widespread interest. Previous studies mostly used second-generation sequencing platforms to survey the putative flavonoid biosynthesis genes. For a better understanding of transcription data and the putative genes involved in flavonoid biosynthesis in safflower, we carry our study. High-quality RNA was extracted from six types of safflower tissue. The RNAs of different tissues were mixed equally and used for multiple size-fractionated libraries (1-2, 2-3 and 3-6 k) library construction. Five cells were carried (2 cells for 1-2 and for 2-3 k libraries and 1 cell for 3-6 k libraries). 10.43Gb clean data and 38,302 de-redundant sequences were captured. 44 unique isoforms were annotated as encoding enzymes involved in flavonoid biosynthesis. The full length flavonoid genes were characterized and their evolutional relationship and expressional pattern were analyzed. They can be divided into eight families, with a large differences in the tissue expression. The temporal expressions under MeJA treatment were also measured, 9 genes are significantly up-regulated and 2 genes are significantly down-regulated. The genes involved in flavonoid synthesis in safflower were predicted in our study. Besides, the SSR and lncRNA are also analyzed in our study. Full-length transcriptome sequences were used in our study. The genes involved in flavonoid synthesis in safflower were predicted in our study. Combined the determination of flavonoids, CtC4H2, CtCHS3, CtCHI3, CtF3H3, CtF3H1 are mainly participated in MeJA promoting the synthesis of flavonoids. Our results also provide a valuable resource for further study on safflower.


MMP/TIMP imbalance in amniotic fluid during PROM: an indirect support for endogenous pathway to membrane rupture.
We theorize that excessive degradation of the fetal membrane extracellular matrix (ECM) by specific matrix metalloproteinases (MMPs) results in preterm premature rupture of the membranes (PROM). Active, inhibitor free MMP2 and 9 (gelatinase A and B respectively) can degrade the amniochorion basement membrane Type IV collagen to initiate rupture. This study examines the levels of the gelatinases and their natural inhibitors (tissue inhibitor of matrix metalloproteinases-TIMPs) in the amniotic fluid during PROM, preterm labor (PTL) and at term. A total of 51 AF samples were collected from the following groups of patients. Group 1: Women with PTL and no ROM (n = 16) Group 2: Women with PROM (n = 16) irrespective of labor status Group 3: Women at term with intact membranes undergoing cesarean delivery irrespective of labor status (n = 19). ELISA was used to assay MMP2, MMP9, TIMP1 and TIMP2 levels in the amniotic fluid. The active, TIMP free levels of MMP2 were quantitated by zymography followed by computerized densitometry. Active MMP9 was measured using a bioassay that specifically detects MMP9 activity. Statistical analysis was performed by Tukey-Kramer multiple comparison method. PROM is associated with increased MMP2 levels (mean 2125 ng/ml;) when compared with term (mean 1455 ng/ml; p < 0.01) or PTL where a non significant increase was seen (mean 1862 ng/ml; p = ns). MMP9 levels were higher in PROM (mean 15.03 ng/ml) than at term (mean 1.14 ng/ml; p < 0.001) or PTL (mean 3.75 ng/ml; p < 0.01). TIMP1 levels were slightly increased during PROM (mean 3143 ng/ml) compared to term (mean 1892 ng/ml; p < 0.05) pr PTL where a non significant change was seen (mean 2406 ng/ml; p = ns). TIMP2 levels were decreased in PROM (mean 98 ng/ml) compared with term (mean 176 ng/ml; p < 0.05) and PTL (mean 236 ng/ml; p < 0.001). Active, TIMP free MMP2 levels were increased during PROM (mean 233 pg/ml) compared to those at term (mean 132 pg/ml; p < 0.05) or PTL (mean 132 pg/ml; p < 0.05). Active forms of MMP9 were seen only during PROM (mean 632 pg/ml). Active, TIMP free forms of MMP2 and 9 are increased in the amniotic fluid of women with PROM. These MMPs can degrade the amniochorion basement membranes and other ECM components resulting in PROM.


Trehalose Recycling Promotes Energy-Efficient Biosynthesis of the Mycobacterial Cell Envelope.
The mycomembrane layer of the mycobacterial cell envelope is a barrier to environmental, immune, and antibiotic insults. There is considerable evidence of mycomembrane plasticity during infection and in response to host-mimicking stresses. Since mycobacteria are resource and energy limited under these conditions, it is likely that remodeling has distinct requirements from those of the well-characterized biosynthetic program that operates during unrestricted growth. Unexpectedly, we found that mycomembrane remodeling in nutrient-starved, nonreplicating mycobacteria includes synthesis in addition to turnover. Mycomembrane synthesis under these conditions occurs along the cell periphery, in contrast to the polar assembly of actively growing cells, and both liberates and relies on the nonmammalian disaccharide trehalose. In the absence of trehalose recycling, de novo trehalose synthesis fuels mycomembrane remodeling. However, mycobacteria experience ATP depletion, enhanced respiration, and redox stress, hallmarks of futile cycling and the collateral dysfunction elicited by some bactericidal antibiotics. Inefficient energy metabolism compromises the survival of trehalose recycling mutants in macrophages. Our data suggest that trehalose recycling alleviates the energetic burden of mycomembrane remodeling under stress. Cell envelope recycling pathways are emerging targets for sensitizing resource-limited bacterial pathogens to host and antibiotic pressure.IMPORTANCE The glucose-based disaccharide trehalose is a stress protectant and carbon source in many nonmammalian cells. Mycobacteria are relatively unique in that they use trehalose for an additional, extracytoplasmic purpose: to build their outer "myco" membrane. In these organisms, trehalose connects mycomembrane biosynthesis and turnover to central carbon metabolism. Key to this connection is the retrograde transporter LpqY-SugABC. Unexpectedly, we found that nongrowing mycobacteria synthesize mycomembrane under carbon limitation but do not require LpqY-SugABC. In the absence of trehalose recycling, compensatory anabolism allows mycomembrane biosynthesis to continue. However, this workaround comes at a cost, namely, ATP consumption, increased respiration, and oxidative stress. Strikingly, these phenotypes resemble those elicited by futile cycles and some bactericidal antibiotics. We demonstrate that inefficient energy metabolism attenuates trehalose recycling mutant Mycobacterium tuberculosis in macrophages. Energy-expensive macromolecule biosynthesis triggered in the absence of recycling may be a new paradigm for boosting host activity against bacterial pathogens.


Deletion of haematopoietic Dectin-2 or CARD9 does not protect from atherosclerosis development under hyperglycaemic conditions.
C-type lectin receptors, including Dectin-2, are pattern recognition receptors on monocytes and macrophages that mainly recognize sugars and sugar-like structures present on fungi. Activation of C-type lectin receptors induces downstream CARD9 signalling, leading to the production of cytokines. We hypothesized that under hyperglycaemic conditions, as is the case in diabetes mellitus, glycosylated protein (sugar-like) structures activate C-type lectin receptors, leading to immune cell activation and increased atherosclerosis development. Low-density lipoprotein receptor-deficient mice were lethally irradiated and transplanted with bone marrow from control wild-type, Dectin-2-/- or Card9-/- mice. After 6 weeks of recovery, mice received streptozotocin injections (50 mg/g BW; 5 days) to induce hyperglycaemia. After an additional 2 weeks, mice were fed a Western-type diet (0.1% cholesterol) for 10 weeks. Deletion of haematopoietic Dectin-2 reduced the number of circulating Ly6Chi monocytes, increased pro-inflammatory cytokine production, but did not affect atherosclerosis development. Deletion of haematopoietic CARD9 tended to reduce macrophage and collagen content in atherosclerotic lesions, again without influencing the lesion size. Deletion of haematopoietic Dectin-2 did not influence atherosclerosis development under hyperglycaemic conditions, despite some minor effects on inflammation. Deletion of haematopoietic CARD9 induced minor alterations in plaque composition under hyperglycaemic conditions, without affecting lesion size.


Empathy and emotion recognition in people with autism, first-degree relatives, and controls.
Empathy is the lens through which we view others' emotion expressions, and respond to them. In this study, empathy and facial emotion recognition were investigated in adults with autism spectrum conditions (ASC; N=314), parents of a child with ASC (N=297) and IQ-matched controls (N=184). Participants completed a self-report measure of empathy (the Empathy Quotient [EQ]) and a modified version of the Karolinska Directed Emotional Faces Task (KDEF) using an online test interface. Results showed that mean scores on the EQ were significantly lower in fathers (p<0.05) but not mothers (p>0.05) of children with ASC compared to controls, whilst both males and females with ASC obtained significantly lower EQ scores (p<0.001) than controls. On the KDEF, statistical analyses revealed poorer overall performance by adults with ASC (p<0.001) compared to the control group. When the 6 distinct basic emotions were analysed separately, the ASC group showed impaired performance across five out of six expressions (happy, sad, angry, afraid and disgusted). Parents of a child with ASC were not significantly worse than controls at recognising any of the basic emotions, after controlling for age and non-verbal IQ (all p>0.05). Finally, results indicated significant differences between males and females with ASC for emotion recognition performance (p<0.05) but not for self-reported empathy (p>0.05). These findings suggest that self-reported empathy deficits in fathers of autistic probands are part of the 'broader autism phenotype'. This study also reports new findings of sex differences amongst people with ASC in emotion recognition, as well as replicating previous work demonstrating empathy difficulties in adults with ASC. The use of empathy measures as quantitative endophenotypes for ASC is discussed.


Close proximity interactions support transmission of ESBL-K. pneumoniae but not ESBL-E. coli in healthcare settings.
Antibiotic-resistance of hospital-acquired infections is a major public health issue. The worldwide emergence and diffusion of extended-spectrum β-lactamase (ESBL)-producing Enterobacteriaceae, including Escherichia coli (ESBL-EC) and Klebsiella pneumoniae (ESBL-KP), is of particular concern. Preventing their nosocomial spread requires understanding their transmission. Using Close Proximity Interactions (CPIs), measured by wearable sensors, and weekly ESBL-EC-and ESBL-KP-carriage data, we traced their possible transmission paths among 329 patients in a 200-bed long-term care facility over 4 months. Based on phenotypically defined resistance profiles to 12 antibiotics only, new bacterial acquisitions were tracked. Extending a previously proposed statistical method, the CPI network's ability to support observed incident-colonization episodes of ESBL-EC and ESBL-KP was tested. Finally, mathematical modeling based on our findings assessed the effect of several infection-control measures. A potential infector was identified in the CPI network for 80% (16/20) of ESBL-KP acquisition episodes. The lengths of CPI paths between ESBL-KP incident cases and their potential infectors were shorter than predicted by chance (P = 0.02), indicating that CPI-network relationships were consistent with dissemination. Potential ESBL-EC infectors were identified for 54% (19/35) of the acquisitions, with longer-than-expected lengths of CPI paths. These contrasting results yielded differing impacts of infection control scenarios, with contact reduction interventions proving less effective for ESBL-EC than for ESBL-KP. These results highlight the widely variable transmission patterns among ESBL-producing Enterobacteriaceae species. CPI networks supported ESBL-KP, but not ESBL-EC spread. These outcomes could help design more specific surveillance and control strategies to prevent in-hospital Enterobacteriaceae dissemination.


Genetic stratification in myeloid diseases: from risk assessment to clinical decision support tool.
Genetic aberrations have become a dominant factor in the stratification of myeloid malignancies. Cytogenetic and a few mutation studies are the backbone of risk assessment models of myeloid malignancies which are a major consideration in clinical decisions, especially patient assignment for allogeneic stem cell transplantation. Progress in our understanding of the genetic basis of the pathogenesis of myeloid malignancies and the growing capabilities of mass sequencing may add new roles for the clinical usage of genetic data. A few recently identified mutations recognized to be associated with specific diseases or clinical scenarios may soon become part of the diagnostic criteria of such conditions. Mutational studies may also advance our capabilities for a more efficient patient selection process, assigning the most effective therapy at the best timing for each patient. The clinical utility of genetic data is anticipated to advance further with the adoption of deep sequencing and next-generation sequencing techniques. We herein suggest some future potential applications of sequential genetic data to identify pending deteriorations at time points which are the best for aggressive interventions such as allogeneic stem cell transplantation. Genetics is moving from being mostly a prognostic factor to becoming a multitasking decision support tool for hematologists. Physicians must pay attention to advances in molecular hematology as it will soon be accessible and influential for most of our patients.


Imaging of the trachea.
Numerous benign and malignant tracheal diseases may affect the trachea primarily and secondarily. While the posterior anterior (PA) and lateral chest radiograph is the conventional study for initial evaluation of the trachea and central airways, findings may not always be apparent on conventional radiographs, and further evaluation with cross sectional imaging is usually necessary. Computed tomography (CT) is the imaging modality of choice for imaging the trachea and bronchi. Familiarity with the imaging appearances of the normal and diseased trachea will enhance diagnostic evaluation.


Preparation of two recombinant crustacean hyperglycemic hormones from the giant freshwater prawn, Macrobrachium rosenbergii, and their hyperglycemic activities.
Crustacean hyperglycemic hormone (CHH) is released from the X-organ/sinus gland complex located in the eyestalks, and regulates glucose levels in the hemolymph. In the giant freshwater prawn (Macrobrachium rosenbergii), two cDNAs encoding different CHH molecules were previously cloned by other workers. One of these (Mar-CHH-2) was expressed only in the eyestalks, whereas the other (Mar-CHH-L) was expressed in the heart, gills, antennal gland, and thoracic ganglion, but not in the eyestalks. However, their biological activities had not yet been characterized. Therefore, in this study, recombinant Mar-CHH-2 (rMar-CHH-2) and Mar-CHH-L (rMar-CHH-L) were produced using an E. coli expression system, by expression in bacterial cells and recovery in the insoluble fraction. Thereafter, rMar-CHH-2 and rMar-CHH-L were subjected to refolding and were subsequently purified by reversed-phase HPLC. The rMar-CHH-2 and rMar-CHH-L thus obtained exhibited the same disulfide bond arrangements as those of other CHHs reported previously, indicative of natural conformation. In in vivo bioassay, rMar-CHH-2 showed significant hyperglycemic activity, whereas rMar-CHH-L had no effect. These results indicate that Mar-CHH-L does not function as a CHH, but may have some other, unknown function.


Intrathecal baclofen versus selective dorsal rhizotomy for children with cerebral palsy who are nonambulant: a systematic review.
Cerebral palsy (CP) is the most common childhood physical disability. Historically, children with hypertonia who are nonambulatory (Gross Motor Function Classification System [GMFCS] level IV or V) were considered candidates for intrathecal baclofen (ITB) therapy to facilitate care and mitigate discomfort. Selective dorsal rhizotomy (SDR) was often reserved for ambulant children to improve gait. Recently, case series have suggested SDR as an alternative to ITB in selected children functioning at GMFCS level IV/V. The objective for this study was to systematically review the evidence for ITB and SDR in GMFCS level IV or V children. Medline, Embase, Web of Science, and Cochrane databases were systematically searched. Articles were screened using the following inclusion criteria: 1) peer-reviewed articles reporting outcomes after SDR or ITB; 2) outcomes reported using a quantifiable scale or standardized outcome measure; 3) patients were < 19 years old at the time of operation; 4) patients had a diagnosis of CP; 5) patients were GMFCS level IV/V or results were reported based on GMFCS status and included some GMFCS level IV/V patients; 6) article and/or abstract in English; and 7) primary indication for surgery was hypertonia. Included studies were assessed with the Risk of Bias in Non-Randomized Studies - of Interventions (ROBINS-I) tool. Twenty-seven studies met inclusion criteria. The most commonly reported outcomes were spasticity (on the Mean Ashworth Scale) and gross motor function (using the Gross Motor Function Measure), although other outcomes including frequency of orthopedic procedures and complications were also reported. There is evidence from case series that suggests that both ITB and SDR can lower spasticity and improve gross motor function in this nonambulatory population. Complication rates are decidedly higher after ITB due in part to the ongoing risk of device-related complications. The heterogeneity among study design, patient selection, outcome selection, and follow-up periods was extremely high, preventing meta-analysis. There are no comparative studies, and meaningful health-related quality of life outcomes such as care and comfort are lacking. This review is limited by the high risk of bias among included studies. Studies of SDR or ITB that did not clearly describe patients as being GMFCS level IV/V or nonambulatory were excluded. There is a lack of evidence comparing the outcomes of ITB and SDR in the nonambulatory CP population. This could be overcome with standardized prospective studies using more robust methodology and relevant outcome measures.


Can differences in obstetric outcomes be explained by differences in the care provided? The MFMU Network APEX study.
The purpose of this study was to determine whether hospital differences in the frequency of adverse obstetric outcomes are related to differences in care. The Assessment of Perinatal EXcellence cohort comprises 115,502 women and their neonates who were born in 25 hospitals in the United States between March 2008 and February 2011. Hierarchical logistic regression was used to quantify the amount of variation in postpartum hemorrhage, peripartum infection, severe perineal laceration, and a composite adverse neonatal outcome among hospitals that is explained by differences in patient characteristics, hospital characteristics, and obstetric care provided. The study included 115,502 women. For most outcomes, 20-40% of hospital differences in outcomes were related to differences in patient populations. After adjusting for patient-, provider-, and hospital-level factors, multiple care processes were associated with the predefined adverse outcomes; however, these care processes did not explain significant variation in the frequency of adverse outcomes among hospitals. Ultimately, 50-100% of the interhospital variation in outcomes was unexplained. Hospital differences in the frequency of adverse obstetric outcomes could not be explained by differences in frequency of types of care provided.


Interconnected V2O5 nanoporous network for high-performance supercapacitors.
Vanadium pentoxide (V(2)O(5)) has attracted attention for supercapcitor applications because of its extensive multifunctional properties. In the present study, V(2)O(5) nanoporous network was synthesized via simple capping-agent-assisted precipitation technique and it is further annealed at different temperatures. The effect of annealing temperature on the morphology, electrochemical and structural properties, and stability upon oxidation-reduction cycling has been analyzed for supercapacitor application. We achieved highest specific capacitance of 316 F g(-1) for interconnected V(2)O(5) nanoporous network. This interconnected nanoporous network creates facile nanochannels for ion diffusion and facilitates the easy accessibility of ions. Moreover, after six hundred consecutive cycling processes the specific capacitance has changed only by 24%. A simple cost-effective preparation technique of V(2)O(5) nanoporous network with excellent capacitive behavior, energy density, and stability encourages its possible commercial exploitation for the development of high-performance supercapacitors.


Newly discovered Neanderthal remains from Shanidar Cave, Iraqi Kurdistan, and their attribution to Shanidar 5.
The Neanderthal remains from Shanidar Cave, excavated between 1951 and 1960, have played a central role in debates concerning diverse aspects of Neanderthal morphology and behavior. In 2015 and 2016, renewed excavations at the site uncovered hominin remains from the immediate area where the partial skeleton of Shanidar 5 was found in 1960. Shanidar 5 was a robust adult male estimated to have been aged over 40 years at the time of death. Comparisons of photographs from the previous and recent excavations indicate that the old and new remains were directly adjacent to one another, while the disturbed arrangement and partial crushing of the new fossils is consistent with descriptions and photographs of the older discoveries. The newly discovered bones include fragments of several vertebrae, a left hamate, part of the proximal left femur, a heavily crushed partial pelvis, and the distal half of the right tibia and fibula and associated talus and navicular. All these elements were previously missing from Shanidar 5, and morphological and metric data are consistent with the new elements belonging to this individual. A newly discovered partial left pubic symphysis indicates an age at death of 40-50 years, also consistent with the age of Shanidar 5 estimated previously. Thus, the combined evidence strongly suggests that the new finds can be attributed to Shanidar 5. Ongoing analyses of associated samples, including for sediment morphology, palynology, and dating, will therefore offer new evidence as to how this individual was deposited in the cave and permit new analyses of the skeleton itself and broader discussion of Neanderthal morphology and variation.


[Recent developments in the modeling and psychological management of persecutory ideation].
Persecutory ideas are a major clinical problem and are associated with impaired functioning, reduced compliance with medication and increased risk of hospitalization. Persecutory ideation is defined as the false conviction that others are threatening or conspiring against one. Although persecutory delusions are mainly described and experienced in schizophrenia spectrum disorders, they also occur in other neurological and psychiatric diagnoses including Alzheimer disease, epilepsy, depression, mania, dementia and post-traumatic stress disorder. Moreover, epidemiological data from general and clinical populations indicated that paranoid beliefs occur on a hierarchy of severity and are present to a lesser degree in the general population, with paranoid delusions representing the severe end of a continuum. In this review we focus on the important advances following a decade of research from psychological sciences, and more particularly the work of Daniel Freeman and Philippa Garety in England. Their work has demonstrated that a range of causal factors are involved in the development and maintenance of delusions beyond the traditional cognitive and behavioural models. Indeed, there is now well-validated evidence that sleep disturbances, worry proneness, reasoning biases, such as failure to consider alternative explanations or belief confirmation bias, abnormal experiences such as hallucinations, negative self-beliefs, and safety behaviours, are central factors that contribute to the paranoid phenomenon. In this review, we describe each of these causal factors in detail as well as the clinical interventions developed by Freeman and his collaborators, including the integrative and modular "Feeling Safe" intervention. Broadly speaking, the aim of this psychological intervention is for patients to relearn safety by exposing them to situations they consider as potentially dangerous after reduction of the influence of the maintenance factors described above. A recent publication showed that the Feeling Safe program led to recovery in persecutory delusions for 50% of patients having poor response to antipsychotic medication, making the intervention as the most effective psychological treatment for persecutory delusions. Finally, we will critically discuss the efficacy data from the numerous clinical studies validating its effectiveness. Prospects for the implementation of the Feeling Safe program in France also is discussed.


Maintenance of the engrailed expression pattern by Polycomb group genes in Drosophila.
The stable maintenance of expression patterns of homeotic genes depends on the function of a number of negative trans-regulators, termed the Polycomb (Pc) group of genes. We have examined the pattern of expression of the Drosophila segment polarity gene, engrailed (en), in embryos mutant for several different members of the Pc group. Here we report that embryos mutant for two or more Pc group genes show strong ectopic en expression, while only weak derepression of en occurs in embryos mutant for a single Pc group gene. This derepression is independent of two known activators of en expression: en itself and wingless. Additionally, in contrast to the strong ectopic expression of homeotic genes observed in extra sex combs- (esc-) mutant embryos, the en expression pattern is nearly normal in esc- embryos. This suggests that the esc gene product functions in a pathway independent of the other genes in the group. The data indicate that the same group of genes is required for stable restriction of en expression to a striped pattern and for the restriction of expression of homeotic genes along the anterior-posterior axis, and support a global role for the Pc group genes in stable repression of activity of developmental selector genes.


Intensive Care Unit death and factors influencing family satisfaction of Intensive Care Unit care.
Family satisfaction of Intensive Care Unit (FS-ICU) care is believed to be associated with ICU survival and ICU outcomes. A review of literature was done to determine factors influencing FS-ICU care in ICU deaths. Factors that positively influenced FS-ICU care were (a) communication: Honesty, accuracy, active listening, emphatic statements, consistency, and clarity; (b) family support: Respect, compassion, courtesy, considering family needs and wishes, and emotional and spiritual support; (c) family meetings: Meaningful explanation and frequency of meetings; (d) decision-making: Shared decision-making; (e) end of life care support: Support during foregoing life-sustaining interventions and staggered withdrawal of life support; (f) ICU environment: Flexibility of visiting hours and safe hospital environment; and (g) other factors: Control of pain and physical symptoms, palliative care consultation, and family-centered care. Factors that negatively influenced FS-ICU care were (a) communication: Incomplete information and unable to interpret information provided; (b) family support: Lack of emotional and spiritual support; (c) family meetings: Conflicts and short family meetings; (d) end of life care support: Resuscitation at end of life, mechanical ventilation on day of death, ICU death of an elderly, prolonged use of life-sustaining treatment, and unfamiliar technology; and (e) ICU environment: Restrictive visitation policies and families denied access to see the dying loved ones. Families of the patients admitted to ICU value respect, compassion, empathy, communication, involvement in decision-making, pain and symptom relief, avoiding futile medical interventions, and dignified end of life care.


Dental Fluorosis and Dental Caries Prevalence among 12 and 15-Year-Old School Children in Nalgonda District, Andhra Pradesh, India.
Fluoride is a double edged sword. The assessment of dental caries and fluorosis in endemic fluoride areas will facilitate in assessing the relation between fluoride concentrations in water with dental caries, dental fluorosis simultaneously. The objective of the following study is to assess the dental caries and dental fluorosis prevalence among 12 and 15-year-old school children in Nalgonda district, Andhra Pradesh, India. This was a cross-sectional study. Two stage cluster sampling technique was employed to select 20 schools from Nalgonda district. The oral examination of available 12 and 15-year-old children fulfilling the inclusion and exclusion criteria was carried out to assess dental caries and fluorosis. The examination was conducted by a single trained and calibrated examiner using the mouth mirror and community periodontal index probe under natural daylight. These areas were divided into four categories, low, medium, high and very high fluoride areas based on the fluoride concentration at the time of statistical analysis. The data was analyzed using Statistical Package for the Social Sciences version 16 (IBM, Chicago, USA). The caries prevalence was less among 12-year-old children (39.9% [369/924]) compared with 15-years-old children (46.7% [444/951]). The prevalence was more among females (50.4% [492/977]) than males (35.8% [321/898]). The prevalence was more in low fluoride area (60.5% [300/496]) followed by very high fluoride area (54.8% [201/367]), high fluoride area (32.4% [293/904]) and medium fluoride area (17.6% [19/108]) in the descending order. The fluorosis prevalence increased with increasing fluoride concentration with no difference in gender and age distribution. Low fluoride areas require fluoridation or alternate sources of fluoride, whereas high fluoride areas require defluoridation. Defluoridation of water is an immediate requirement in areas with fluoride concentration of 4 parts per million and above as dental fluorosis is a public health problem in these areas with 100% prevalence.


Cimicifuga racemosa treatment and health related quality of life in post-menopausal Spanish women.
The effect of Cimicifuga racemosa (CR) treatment was evaluated in healthy symptomatic post-menopausal women using the Cervantes health-related quality of life (HR-QoL) scale. A prospective observational study was carried out in 122 healthy symptomatic post-menopausal Spanish women with elevated body weight, aged between 45 and 59 years. Three groups were formed according to age intervals. Each patient completed the Cervantes HR-QoL scale before and after CR treatment (20 mg, twice a day for 3 months). Changes in Cervantes scale global quality of life scores as well as in their domains (menopause and health, psychic, sexuality and couple relationship) were analysed. The CR treatment ameliorated global quality of life in both the whole group of patients and when women were analysed by age subgroups. There were significant positive changes in Z scores for the Cervantes HR-QoL scale 'menopause and health', and 'psychic' domains in both the entire population and by age groups. The 'sexuality domain' significantly improved when the entire population was assessed, but not when each age-group was separately analysed; while there were no changes in 'couple relationship domain' scores. CR treatment increased both global quality of life and the four domains of the Cervantes HR-QoL scale, being an effective treatment to reduce symptoms in post-menopausal woman with elevated body weight.


Cross-linguistic similarity norms for Japanese-English translation equivalents.
Formal and semantic overlap across languages plays an important role in bilingual language processing systems. In the present study, Japanese (first language; L1)-English (second language; L2) bilinguals rated 193 Japanese-English word pairs, including cognates and noncognates, in terms of phonological and semantic similarity. We show that the degree of cross-linguistic overlap varies, such that words can be more or less "cognate," in terms of their phonological and semantic overlap. Bilinguals also translated these words in both directions (L1-L2 and L2-L1), providing a measure of translation equivalency. Notably, we reveal for the first time that Japanese-English cognates are "special," in the sense that they are usually translated using one English term (e.g., コール /kooru/ is always translated as "call"), but the English word is translated into a greater variety of Japanese words. This difference in translation equivalency likely extends to other non-etymologically related, different-script languages in which cognates are all loanwords (e.g., Korean-English). Norming data were also collected for L1 age of acquisition, L1 concreteness, and L2 familiarity, because such information had been unavailable for the item set. Additional information on L1/L2 word frequency, L1/L2 number of senses, and L1/L2 word length and number of syllables is also provided. Finally, correlations and characteristics of the cognate and noncognate items are detailed, so as to provide a complete overview of the lexical and semantic characteristics of the stimuli. This creates a comprehensive bilingual data set for these different-script languages and should be of use in bilingual word recognition and spoken language research.


Genetically modified clostridium for gene therapy of tumors.
Many murine and human tumors contain hypoxic or necrotic regions in which the oxygen tension is abnormally low. For example,>50% of primary tumors of the breast, cervix, and head and neck contain areas that are hypoxic. Because hypoxic regions are not present in normal tissue, this provides the potential for selectively targeting gene therapy to tumor cells.


Effect of a carbohydrate-protein supplement on endurance performance during exercise of varying intensity.
Increasing the plasma glucose and insulin concentrations during prolonged variable intensity exercise by supplementing with carbohydrate has been found to spare muscle glycogen and increase aerobic endurance. Furthermore, the addition of protein to a carbohydrate supplement will enhance the insulin response of a carbohydrate supplement. The purpose of the present study was to compare the effects of a carbohydrate and a carbohydrate-protein supplement on aerobic endurance performance. Nine trained cyclists exercised on 3 separate occasions at intensities that varied between 45% and 75% VO2max for 3 h and then at 85% VO2max until fatigued. Supplements (200 ml) were provided every 20 min and consisted of placebo, a 7.75% carbohydrate solution, and a 7.75% carbohydrate/1.94% protein solution. Treatments were administered using a double-blind randomized design. Carbohydrate supplementation significantly increased time to exhaustion (carbohydrate 19.7 +/- 4.6 min vs. placebo 12.7 +/- 3.1 min), while the addition of protein enhanced the effect of the carbohydrate supplement (carbohydrate-protein 26.9 +/- 4.5 min, p < .05). Blood glucose and plasma insulin levels were elevated above placebo during carbohydrate and carbohydrate-protein supplementation, but no differences were found between the carbohydrate and carbohydrate-protein treatments. In summary, we found that the addition of protein to a carbohydrate supplement enhanced aerobic endurance performance above that which occurred with carbohydrate alone, but the reason for this improvement in performance was not evident.