Interrater reliability of the functional movement screen.
The Functional Movement Screen (FMS) is a series of 7 tests that categorize fundamental movement. Each test is scored on an ordinal scale with 4 categories. The purpose of this study was to determine the interrater reliability of the FMS. Forty healthy subjects were videotaped while performing the FMS. The videos were independently scored by 4 raters, including 2 experts who instruct FMS training courses and 2 novices who completed a standardized training course on the FMS. Interrater reliability was analyzed using the weighted kappa statistic. The novice raters demonstrated excellent or substantial agreement on 14 of the 17 tests, whereas the expert raters did the same on 13 of the 17 tests. When the novice raters were paired with the expert raters, all 17 components demonstrated excellent or substantial agreement. These data indicate that the FMS can confidently be applied by trained individuals. This would suggest that the FMS can be confidently used to assess the movement patterns of athletes and to make decisions related to interventions for performance enhancement, and the FMS may assist in identifying athletes at risk for injury.


Steady-state stiffness of utricular hair cells depends on macular location and hair bundle structure.
Spatial and temporal properties of head movement are encoded by vestibular hair cells in the inner ear. One of the most striking features of these receptors is the orderly structural variation in their mechanoreceptive hair bundles, but the functional significance of this diversity is poorly understood. We tested the hypothesis that hair bundle structure is a significant contributor to hair bundle mechanics by comparing structure and steady-state stiffness of 73 hair bundles at varying locations on the utricular macula. Our first major finding is that stiffness of utricular hair bundles varies systematically with macular locus. Stiffness values are highest in the striola, near the line of hair bundle polarity reversal, and decline exponentially toward the medial extrastriola. Striolar bundles are significantly more stiff than those in medial (median: 8.9 μN/m) and lateral (2.0 μN/m) extrastriolae. Within the striola, bundle stiffness is greatest in zone 2 (106.4 μN/m), a band of type II hair cells, and significantly less in zone 3 (30.6 μN/m), which contains the only type I hair cells in the macula. Bathing bundles in media that break interciliary links produced changes in bundle stiffness with predictable time course and magnitude, suggesting that links were intact in our standard media and contributed normally to bundle stiffness during measurements. Our second major finding is that bundle structure is a significant predictor of steady-state stiffness: the heights of kinocilia and the tallest stereocilia are the most important determinants of bundle stiffness. Our results suggest 1) a functional interpretation of bundle height variability in vertebrate vestibular organs, 2) a role for the striola in detecting onset of head movement, and 3) the hypothesis that differences in bundle stiffness contribute to diversity in afferent response dynamics.


Differential control of U1 small nuclear RNA expression during mouse development.
During normal mouse development the relative amounts of two types of U1 small nuclear RNA's (U1 RNA) change significantly. Fetal tissues have comparable levels of the two major types of mouse U1 RNA's, mU1a and mU1b, whereas most differentiated adult tissues contain only mU1a RNA's. Those adult tissues that also accumulate detectable amounts of embryonic (mU1b) RNA's (for example, testis, spleen, and thymus) contain a significant proportion of stem cells capable of further differentiation. Several strains of mice express minor sequence variants of U1 RNA's that are subject to the same developmental controls as the major types of adult and embryonic U1 RNA. The differential accumulation of embryonic U1 RNA's may influence the pattern of gene expression during early development and differentiation.


Comparing two methods to measure preferred listening levels of personal listening devices.
The potential risk to hearing that mass-storage personal listening devices (PLDs) pose remains unclear. Previous research in this area has either focused on maximum outputs of these devices or on ear-canal measurements of listening levels that could not be compared to standards of occupational noise exposure. The purpose of this study was to compare two standard measurement protocols [ISO 11904-1 (2002), Switzerland; ISO 11904-2 (2004), Switzerland] for the measurement of preferred listening levels of PLD. Noise measurements, behavioral thresholds, and oral interviews were obtained from 30 (18-30 years) PLD users. Preferred listening levels for self-selected music were determined in quiet and background noise using a probe microphone, as well as in the DB-100 ear simulator mounted in KEMAR. The ear-canal measurements were compensated for diffuse-field. Only one of the subjects was found to be listening at hazardous levels once their reported daily usage was accounted for using industrial workplace standards. The variance across subjects was the smallest in the ear-canal measurements that were compensated for diffuse-field equivalence [ISO 11904-1 (2002), Switzerland]. Seven subjects were found to be listening at levels above 85 dBA based on measurements obtained in the KEMAR and then compensated for diffuse-field equivalence.


Collective helping and bystander effects in coevolving helping networks.
We study collective helping behavior and bystander effects in a coevolving helping network model. A node and a link of the network represents an agent who renders or receives help and a friendly relation between agents, respectively. A helping trial of an agent depends on relations with other involved agents and its result (success or failure) updates the relation between the helper and the recipient. We study the network link dynamics and its steady states analytically and numerically. The full phase diagram is presented with various kinds of active and inactive phases and the nature of phase transitions are explored. We find various interesting bystander effects, consistent with the field study results, of which the underlying mechanism is proposed.


The Effect of propolis on Th1/Th2 cytokine expression and production by melanoma-bearing mice submitted to stress.
Since propolis possesses immunomodulatory and antitumoral activities, this work aimed to evaluate its effect on Th1 (IL-2 and IFN-γ) and Th2 (IL-4 and IL-10) cytokines mRNA expression and production by melanoma-bearing mice submitted to immobilization stress. C57BL/6 male mice were inoculated with B16F10 cells, treated with propolis and submitted to stress for 14 days. Spleen cells were assessed for Th1/Th2 cytokine expression and production. Stress induced a higher tumor area, while propolis-treated mice, stressed or not, showed a melanoma development similar to the control. In groups without melanoma, stress or propolis treatment did not affect IL-2, IL-4 and IL-10 gene expression. On the other hand, IL-2 and IL-10 expression was inhibited in melanoma-bearing mice, stressed or not. Th1 cytokine production was also inhibited in melanoma-bearing mice. Propolis administration to melanoma-bearing mice submitted to stress stimulated IL-2 expression, as well as Th1 cytokine (IL-2 and IFN-γ) production, indicating the activation of antitumor cell-mediated immunity. Propolis also stimulated IL-10 expression and production, which may be related to immunoregulatory effects. The data indicate that propolis exerted an immunomodulatory activity in this assay, which may be related to its antitumoral action in vivo.


Primary Malignant Deciduoid Mesothelioma: A Challenging Diagnosis.
Primary malignant deciduoid mesothelioma is a rare subtype of epithelioid mesothelioma that was first described in the peritoneum in young women without a history of asbestos exposure. It was thought to be a distinct clinicopathologic entity with ominous prognosis; recent studies have better characterized this entity. On morphology, primary malignant deciduoid mesothelioma is characterized by cytomorphologic features resembling decidualized tissue. Pleomorphism is variable. The immunoprofile is similar to other epithelioid mesotheliomas. The prognosis is the same as other epithelioid mesotheliomas and seems to depend on histological grade.


Psychosis: an autoimmune disease?
Psychotic disorders are common and disabling. Overlaps in clinical course in addition to epidemiological and genetic associations raise the possibility that autoimmune mechanisms may underlie some psychoses, potentially offering novel therapeutic approaches. Several immune loci including the major histocompatibility complex and B-cell markers CD19 and CD20 achieve genome-wide significance in schizophrenia. Emerging evidence suggests a potential role via neurodevelopment in addition to classical immune pathways. Additionally, lymphocyte biology is increasingly investigated. Some reports note raised peripheral CD19+ and reduced CD3+ lymphocyte counts, with altered CD4 : CD8 ratios in acute psychosis. Also, post-mortem studies have found CD3+ and CD20+ lymphocyte infiltration in brain regions that are of functional relevance to psychosis. More specifically, the recent paradigm of neuronal surface antibody-mediated (NSAb) central nervous system disease provides an antigen-specific model linking adaptive autoimmunity to psychopathology. NSAbs bind extracellular epitopes of signalling molecules that are classically implicated in psychosis such as NMDA and GABA receptors. This interaction may cause circuit dysfunction leading to psychosis among other neurological features in patients with autoimmune encephalitis. The detection of these cases is crucial as autoimmune encephalitis is ameliorated by commonly available immunotherapies. Meanwhile, the prevalence and relevance of these antibodies in people with isolated psychotic disorders is an area of emerging scientific and clinical interest. Collaborative efforts to achieve larger sample sizes, comparison of assay platforms, and placebo-controlled randomized clinical trials are now needed to establish an autoimmune contribution to psychosis.


A vestige of Earth's oldest ophiolite.
A sheeted-dike complex within the approximately 3.8-billion-year-old Isua supracrustal belt (ISB) in southwest Greenland provides the oldest evidence of oceanic crustal accretion by spreading. The geochemistry of the dikes and associated pillow lavas demonstrates an intraoceanic island arc and mid-ocean ridge-like setting, and their oxygen isotopes suggest a hydrothermal ocean-floor-type metamorphism. The pillows and dikes are associated with gabbroic and ultramafic rocks that together make up an ophiolitic association: the Paleoarchean Isua ophiolite complex. These sheeted dikes offer evidence for remnants of oceanic crust formed by sea-floor spreading of the earliest intact rocks on Earth.


Insight into the mechanism of inactivation and pH sensitivity in potassium channels from molecular dynamics simulations.
Potassium (K (+)) channels can regulate ionic conduction through their pore by a mechanism, involving the selectivity filter, known as C-type inactivation. This process is rapid in the hERG K (+) channel and is fundamental to its physiological role. Although mutations within hERG are known to remove this process, a structural basis for the inactivation mechanism has yet to be characterized. Using MD simulations based on homology modeling, we observe that the carbonyl of the filter aromatic, Phe627, forming the S 0 K (+) binding site, swiftly rotates away from the conduction axis in the wild-type channel. In contrast, in well-characterized non-inactivating mutant channels, this conformational change occurs less frequently. In the non-inactivating channels, interactions with a water molecule located behind the selectivity filter are critical to the enhanced stability of the conducting state. We observe comparable conformational changes in the acid sensitive TASK-1 channel and propose a common mechanism in these channels for regulating efflux of K (+) ions through the selectivity filter.


Bone-microarchitecture and bone-strength in a sample of adults with hypophosphatasia and a matched reference population assessed by HR-pQCT and impact microindentation.
Hypophosphatasia (HPP) is an autosomal recessive or dominate disease affecting bone mineralization, and adults with HPP are in risk to develop metatarsal stress fractures and femoral pseudofractures. Given to the scarce data on the bone quality and its association to the fracture risk in adults with HPP, this study aimed to evaluate bone turnover, bone strength and structure in adults with HPP. In this cross-sectional study, we included 14 adults with genetically verified HPP and 14 sex-, age-, BMI-, and menopausal status-matched reference individuals. We analyzed bone turnover markers, and measured bone material strength index (BMSi) by impact microindentation. Bone geometry, volumetric density and bone microarchitecture as well as failure load at the distal radius and tibia were evaluated using a second-generation high-resolution peripheral quantitative computed tomography system. Bone turnover markers did not differ between patients with HPP and reference individuals. BMSi did not differ between the groups (67.90 [63.75-76.00] vs 65.45 [58.43-69.55], p = 0.149). Parameters of bone geometry and volumetric density did not differ between adults with HPP and the reference group. Patients with HPP had a tendency toward higher trabecular separation (0.664 [0.613-0.724] mm vs 0.620 [0.578-0.659] mm, p = 0.054) and inhomogeneity of trabecular network (0.253 [0.235-0.283] mm vs 0.229 [0.208-0.252] mm, p = 0.056) as well as lower trabecular bone volume fraction (18.8 [16.4-22.7] % vs 22.8 [20.6-24.7] %, p = 0.054) at the distal radius. In addition, compound heterozygous adults with HPP had a significantly higher cortical porosity at the distal radius than reference individuals (1.5 [0.9-2.2] % vs 0.7 [0.6-0.7] %, p = 0.041). BMSi is not reduced in adults with HPP. Increased cortical porosity may contribute to the occurrence of femoral pseudofractures in compound heterozygous adults with HPP. However, further studies investigating larger cohorts of adults with HPP using methods of bone histomorphometry are recommended to adequately assess the bone quality in adults with HPP.


Daily physical activities and sports in adult survivors of childhood cancer and healthy controls: a population-based questionnaire survey.
Healthy lifestyle including sufficient physical activity may mitigate or prevent adverse long-term effects of childhood cancer. We described daily physical activities and sports in childhood cancer survivors and controls, and assessed determinants of both activity patterns. The Swiss Childhood Cancer Survivor Study is a questionnaire survey including all children diagnosed with cancer 1976-2003 at age 0-15 years, registered in the Swiss Childhood Cancer Registry, who survived ≥5 years and reached adulthood (≥20 years). Controls came from the population-based Swiss Health Survey. We compared the two populations and determined risk factors for both outcomes in separate multivariable logistic regression models. The sample included 1058 survivors and 5593 controls (response rates 78% and 66%). Sufficient daily physical activities were reported by 52% (n = 521) of survivors and 37% (n = 2069) of controls (p<0.001). In contrast, 62% (n = 640) of survivors and 65% (n = 3635) of controls reported engaging in sports (p = 0.067). Risk factors for insufficient daily activities in both populations were: older age (OR for ≥35 years: 1.5, 95CI 1.2-2.0), female gender (OR 1.6, 95CI 1.3-1.9), French/Italian Speaking (OR 1.4, 95CI 1.1-1.7), and higher education (OR for university education: 2.0, 95CI 1.5-2.6). Risk factors for no sports were: being a survivor (OR 1.3, 95CI 1.1-1.6), older age (OR for ≥35 years: 1.4, 95CI 1.1-1.8), migration background (OR 1.5, 95CI 1.3-1.8), French/Italian speaking (OR 1.4, 95CI 1.2-1.7), lower education (OR for compulsory schooling only: 1.6, 95CI 1.2-2.2), being married (OR 1.7, 95CI 1.5-2.0), having children (OR 1.3, 95CI 1.4-1.9), obesity (OR 2.4, 95CI 1.7-3.3), and smoking (OR 1.7, 95CI 1.5-2.1). Type of diagnosis was only associated with sports. Physical activity levels in survivors were lower than recommended, but comparable to controls and mainly determined by socio-demographic and cultural factors. Strategies to improve physical activity levels could be similar as for the general population.


Competitive trait anxiety, success-failure and sex as determinants of motor performance.
Two experiments determined the effects of competitive trait anxiety, success-failure, and sex on the performance of 10- to 12 yr.-old children competing on a complex motor maze. Competitive trait anxiety was assessed by the Sport Competition Anxiety Test and success-failure was induced by giving bogus win-loss feedback. High and low competitive trait-anxiety children were randomly assigned to one of three conditions: winning 80%, 50% or 20% of 20 contests. The average completion time and the variability of times within each of two blocks of 10 contests were the two performance measures. State-anxiety was assessed with Spielberger's State Anxiety Inventory for Children as an indicant of arousal prior to and during competition. The findings of Exp. 1 yielded no significant performance differences. In Exp. 2 a significant interaction of competitive trait anxiety X success-failure X sex for performance time and variability was obtained. This interaction was largely attributed to sex differences.


Nut Consumption in Relation to Cardiovascular Disease Incidence and Mortality Among Patients With Diabetes Mellitus.
The evidence regarding the potential health benefits of nut consumption among individuals with type 2 diabetes mellitus is limited. To examine intake of total and specific types of nuts, including tree nuts and peanuts, in relation to subsequent risk of cardiovascular disease (CVD), including coronary heart disease and stroke, and all-cause and cause-specific mortality among individuals with diabetes mellitus. This prospective analysis included 16 217 men and women with diabetes mellitus at baseline or diagnosed during follow-up (Nurses' Health Study: 1980-2014, Health Professionals Follow-Up Study: 1986-2014). Nut consumption was assessed using a validated food frequency questionnaire and updated every 2 to 4 years. During 223 682 and 254 923 person-years of follow-up, there were 3336 incident CVD cases and 5682 deaths, respectively. Higher total nut consumption was associated with a lower risk of CVD incidence and mortality. The multivariate-adjusted hazard ratios (95% CIs) for participants who consumed 5 or more servings of total nuts per week (1 serving=28 g), compared with those who consumed <1 serving per month, were 0.83 (0.71-0.98; P trend=0.01) for total CVD incidence, 0.80 (0.67-0.96; P trend=0.005) for coronary heart disease incidence, 0.66 (0.52-0.84; P trend <0.001) for CVD mortality, and 0.69 (0.61-0.77; P trend <0.001) for all-cause mortality. Total nut consumption was not significantly associated with risk of stroke incidence or cancer mortality. For specific types of nuts, higher tree nut consumption was associated with lower risk of total CVD, coronary heart disease incidence, and mortality because of CVD, cancer, and all causes, whereas peanut consumption was associated with lower all-cause mortality only (all P trend <0.001). In addition, compared with participants who did not change the consumption of total nuts from pre- to post-diabetes mellitus diagnosis, participants who increased consumption of total nuts after diabetes mellitus diagnosis had an 11% lower risk of CVD, a 15% lower coronary heart disease risk, a 25% lower CVD mortality, and a 27% lower all-cause mortality. The associations persisted in subgroup analyses stratified by sex/cohort, body mass index at diabetes mellitus diagnosis, smoking status, diabetes mellitus duration, nut consumption before diabetes mellitus diagnosis, or diet quality. Higher consumption of nuts, especially tree nuts, is associated with lower CVD incidence and mortality among participants with diabetes mellitus. These data provide novel evidence that supports the recommendation of incorporating nuts into healthy dietary patterns for the prevention of CVD complications and premature deaths among individuals with diabetes mellitus.


Effect of computerised prescribing on use of antibiotics.
To examine whether the use of current prescribing software systems might raise rates of repeat prescribing, with a consequent increase in use of antibiotics in the community. A prospective audit of consecutive prescriptions for amoxycillin, cefaclor, roxithromycin and amoxycillin/clavulanate presented to community pharmacies in the Hunter region of New South Wales and a follow-up survey of people who received a repeat prescription, October to November 2000. The frequency of repeat prescription ordering on computer-generated and handwritten prescriptions; the proportion of people who filled their repeat prescription. Data were collected for 1667 prescriptions presented to 35 pharmacies; 126 people who received repeat prescriptions completed the survey. The rate of repeat prescription ordering on computer-generated prescriptions was 69%, compared with 40% for handwritten prescriptions (odds ratio, 3.3; 95% CI, 2.6-4.2). Computer-generated repeat prescriptions were as likely to be filled as hand-written prescriptions (61% and 69%, respectively). The default settings on computerised prescribing packages result in a significant increase in the use of antibiotics. We estimate these settings result in about 500 000 additional prescriptions being filled annually in Australia for the four antibiotics in the study.


Identifying drivers of forest resilience in long-term records from the Neotropics.
Here, we use 30 long-term, high-resolution palaeoecological records from Mexico, Central and South America to address two hypotheses regarding possible drivers of resilience in tropical forests as measured in terms of recovery rates from previous disturbances. First, we hypothesize that faster recovery rates are associated with regions of higher biodiversity, as suggested by the insurance hypothesis. And second, that resilience is due to intrinsic abiotic factors that are location specific, thus regions presently displaying resilience in terms of persistence to current climatic disturbances should also show higher recovery rates in the past. To test these hypotheses, we applied a threshold approach to identify past disturbances to forests within each sequence. We then compared the recovery rates to these events with pollen richness before the event. We also compared recovery rates of each site with a measure of present resilience in the region as demonstrated by measuring global vegetation persistence to climatic perturbations using satellite imagery. Preliminary results indeed show a positive relationship between pre-disturbance taxonomic richness and faster recovery rates. However, there is less evidence to support the concept that resilience is intrinsic to a region; patterns of resilience apparent in ecosystems presently are not necessarily conservative through time.


Barriers and drivers to service delivery in global mental health projects.
Research in global mental health (GMH) has previously documented how contextual factors like political instability, poverty and poorly-funded health infrastructure continue to compromise effective and equitable mental health service delivery. There is a need to develop more feasible and evidence-based solutions through implementation research. This paper, one in a series pertaining to implementation in GMH projects worldwide, focuses on implementation factors influencing mental health service delivery. This is a qualitative study carried out as part of a Theory of Change-driven evaluation of Grand Challenges Canada's (GCC's) Global Mental Health portfolio. Purposive sampling was used to recruit twenty-nine GCC grantees for interviews. A semi-structured interview schedule was used to guide the interviews which were recorded and subsequently transcribed. Transcripts were double-coded and analyzed in NVivo 11 using framework analysis. This paper reports results related to detection and treatment of mental illness, mental health promotion and prevention of mental illness. Key barriers included: lack of appropriate human resources and expertise for service delivery; lack of culturally appropriate screening tools and interventions; and difficulties integrating services with the existing mental health system. Formative research was a key driver facilitating the cultural adaptation of mental health detection, treatment, promotion and preventative approaches. Recruiting local providers and utilizing mHealth for improving screening, monitoring and data management were also found to be successful approaches in reducing workforce burden, improving sustainability, mental health literacy, participant engagement and uptake. The study identifies a number of key barriers to and drivers of successful service delivery from the perspective of grantees implementing GMH projects. Findings highlight several opportunities to mitigate common challenges, providing recommendations for strengthening systems- and project-level approaches for delivering mental health services. Further, more inclusive research is required to inform guidance around service delivery for successful implementation, better utilization of funding and improving mental health outcomes among vulnerable populations in low-resource settings.


Biliary liver flukes (Opisthorchiasis and Clonorchiasis) in immigrants in the United States: often subtle and diagnosed years after arrival.
Biliary liver flukes are extremely common parasites in some regions of the world where consumption of raw fresh-water fish is a cultural practice. Clonorchis sinensis and Opisthorchis spp. are the major biliary liver flukes associated with human disease. Some of these parasites are highly associated with cholangiocarcinoma. It was noted that several cases presenting at our center had been in the US for prolonged periods. This prompted us to retrospectively review cases of liver fluke infection diagnosed at our facility. All cases of biliary liver fluke infection over a 6-year period were retrospectively investigated at a clinic serving international patients, to determine the prevalence and risk factors for infection in a nonendemic area. Cases were identified through review of stool ova and parasite (O&P) records maintained at Regions Hospital/HealthPartners microbiology laboratory. All O&P samples positive for Opisthorchis spp. or Clonorchis sinensis were included in the review. Seventeen cases were identified during the study period. Our center performed approximately 1,800 stool O&P examinations per year on approximately 1,100 individuals per year during the study period. Biliary liver flukes were uncommon, accounting for 1.3% of individuals infected with organisms considered to be potentially pathogenic. Infections were predominantly found in migrants from Laos, Cambodia and Thailand. Cases were also identified in migrants from the former Soviet Union and South America. It is of note that 25% of patients were detected after 5 years of residence in the US. Often, the only clinical clue to infection was a mild absolute eosinophilia (500 to 1000 microL). Although biliary liver fluke is an infrequent cause of infection in immigrants to the US, because of the potential long-term consequences of chronic infection, educational information highlighting routes of infection and the fact that asymptomatic infection is common and may eventually lead to cancer should be aimed at high-risk community members and those who have been visiting friends and relatives in endemic areas.


Thrombolytic therapy for the treatment of acute pulmonary embolism.
To determine whether thrombolytic therapy reduces the rate of death or complications in patients with acute pulmonary embolism and whether a particular thrombolytic regimen is more effective than others. The key words "fibrinolytic agents," "plasminogen activators," "streptokinase," "urokinase" and "pulmonary embolism" were used to search MEDLINE for relevant articles in English; the bibliographies of these articles were reviewed for additional publications. Articles were included if they were of a randomized controlled design; 10 such articles were found. Ten trials were appraised with the use of the following methodologic criteria: a clear description of the study population; use of objective criteria to diagnose pulmonary embolism and to assess outcomes; use of clinically relevant outcomes; and blinded outcome assessments. In the nine trials that met the methodologic criteria thrombolytic therapy led to a more rapid resolution of the radiographic and hemodynamic abnormalities associated with acute pulmonary embolism than did anticoagulant therapy alone, although these benefits were short-lived. No difference was detected in the death rate or the resolution of symptoms between patients receiving thrombolytic therapy and those receiving anticoagulant therapy alone. In addition, bleeding complications were more frequent and serious in patients who received lytic therapy, although these events were related to the use of invasive procedures. There is a lack of evidence that thrombolytic therapy improves clinically relevant outcomes of patients with acute pulmonary embolism. This may be a reflection of the small sample size of the clinical trials. Further research is required to define the role of thrombolytic therapy in the management of patients with acute pulmonary embolism.


Parenting stress in families with very low birth weight preterm infants in early infancy.
Taking care of a premature infant adds an extra burden to already stressed parents. Previous studies have shown that parental stress occurs during the initial hospitalization. However, there is little information on parental stress over time, and the few existing results are conflicting. In addition, many studies have focused on maternal stress but there is little information about a father's long-term adaptation to stress. The purpose of this study was to examine the degree and type of parenting stress in the families of very low birth weight (VLBW) preterm infants over the first two years of life. We compared parenting stress in families with preterm infants with control families, while also comparing the stress in mothers to that in fathers. Furthermore, we explored the relationship between parenting stress in the preterm group with identified factors that included the infant's age, medical complications, and parents' perceived feeding issues after they had been discharged from the hospital. This was an exploratory study with a cross sectional design. Participants included a total of 505 mothers from Tainan, Taiwan; 297 with preterm children (239 mothers, 58 fathers) and 208 with full-term children (181 mothers, 27 fathers). Assessments including the Parenting Stress Index, Neonatal Medical Index and Behavior-based Feeding Questionnaire were used to measure parental distress, infants' medical complications and parents' perceived feeding issues, respectively. Results of the study, though not statistically significant, indicated the presence of increased parenting stress in parents of preterm infants as compared to parents of full-term infants. 13.1% of mothers with preterm infants demonstrated total stress levels that warranted clinical intervention. We also found that mothers of preterm infants presented different parenting stress patterns than fathers of preterm infants. Fathers of preterm infants tended to have overall higher stress scores than mothers. On the other hand, mothers of preterm infants tended to report more health related difficulties, more depression, higher social isolation and role restriction, and less support from their spouses, than reported by fathers. Moreover, as time went on, parents with preterm infants continued to experience greater parenting stress than those with full-term infants. Understanding the experiences of parents with preterm children is important for health care providers while interviewing parents for information regarding their children and designing intervention programs to improve children's outcomes.


Inonotus obliquus polysaccharides induces apoptosis of lung cancer cells and alters energy metabolism via the LKB1/AMPK axis.
The present study explores the mechanisms underlying the anti-cancer action of Inonotus obliquus polysaccharides (IOP). Thus, we characterized the IOP components extracted from Chaga sclerotium and, found that the extracts contained 70% polysaccharides with an average molecular weight of 4.5 × 104 Da consisting of 75% glucose. We then showed that IOP extract activated AMPK in lung cancer cells expressing LKB1, suppressed cell viability, colony-formation, and triggered cell apoptosis. In conjunction, IOP downregulated Bcl-2, upregulated Bax, and enhanced cleavage of Caspase-3 and PARP. All of these effects were prevented by treatment with Compound C, a chemical inhibitor of AMPK. IOP diminished mitochondrial membrane potential (MMP), concurrent with decreases in oxidative phosphorylation and glycolysis, which was dependent on LKB1/AMPK. Finally, IOP at a dosage of 50 mg/kg significantly inhibited allograft tumor growth of the LLC1 cells in association with increased apoptosis. Collectively, our results demonstrate that IOP acts on cancer cells through a mechanism by which AMPK triggers the apoptotic pathway via the opening of mitochondrial permeability transition pore, and reducing MMP, leading to an inhibition of ATP production. Therefore, our study provides a solid foundation for the use of IOP as a promising alternative or supplementary medicine for cancer therapy.


Argonaute proteins are key determinants of RNAi efficacy, toxicity, and persistence in the adult mouse liver.
shRNA overexpression from viral gene therapy vectors can trigger cytotoxicity leading to organ failure and lethality in mice and rats. This process likely involves saturation of endogenous cellular RNAi factors including exportin-5 (Xpo-5). Here, we have shown that Xpo-5 overexpression enhanced shRNA efficiency in the liver of adult mice but increased hepatotoxicity. We identified the 4 members of the human Argonaute (Ago) protein family as downstream factors involved in saturation of endogenous cellular RNAi, all of which were able to interact with shRNAs in cells and mice. In Ago/shRNA coexpression studies, Ago-2 (Slicer) was the primary rate-limiting determinant of both in vitro and in vivo RNAi efficacy, toxicity, and persistence. In adult mice, vector-based Ago-2/Xpo-5 coexpression enhanced U6-driven shRNA silencing of exogenous and endogenous hepatic targets, reduced hepatotoxicity, and extended RNAi stability by more than 3 months. Use of weaker RNA polymerase III promoters to minimize shRNA expression likewise alleviated in vivo toxicity and permitted greater than 95% persistent knockdown of hepatitis B virus and other transgenes in mouse liver for more than 1 year. Our studies substantiate that abundant small RNAs can overload the endogenous RNAi pathway and reveal possible strategies for reducing hepatotoxicity of short- and long-term clinical gene silencing in humans.


Critical role of the fifth domain of E-cadherin for heterophilic adhesion with alpha E beta 7, but not for homophilic adhesion.
The integrin alpha(E)beta(7) is expressed on intestinal intraepithelial T lymphocytes and CD8(+) T lymphocytes in inflammatory lesions near epithelial cells. Adhesion between alpha(E)beta(7)(+) T and epithelial cells is mediated by the adhesive interaction of alpha(E)beta(7) and E-cadherin; this interaction plays a key role in the damage of target epithelia. To explore the structure-function relationship of the heterophilic adhesive interaction between E-cadherin and alpha(E)beta(7), we performed cell aggregation assays using L cells transfected with an extracellular domain-deletion mutant of E-cadherin. In homophilic adhesion assays, L cells transfected with wild-type or a domain 5-deficient mutant formed aggregates, whereas transfectants with domain 1-, 2-, 3-, or 4-deficient mutants did not. These results indicate that not only domain 1, but domains 2, 3, and 4 are involved in homophilic adhesion. When alpha(E)beta(7)(+) K562 cells were incubated with L cells expressing the wild type, 23% of the resulting cell aggregates consisted of alpha(E)beta(7)(+) K562 cells. In contrast, the binding of alpha(E)beta(7)(+) K562 cells to L cells expressing a domain 5-deficient mutant was significantly decreased, with alpha(E)beta(7)(+) K562 cells accounting for only 4% of the cell aggregates, while homophilic adhesion was completely preserved. These results suggest that domain 5 is involved in heterophilic adhesion with alpha(E)beta(7), but not in homophilic adhesion, leading to the hypothesis that the fifth domain of E-cadherin may play a critical role in the regulation of heterophilic adhesion to alpha(E)beta(7) and may be a potential target for treatments altering the adhesion of alpha(E)beta(7)(+) T cells to epithelial cells in inflammatory epithelial diseases.


CHD6 regulates the topological arrangement of the CFTR locus.
The control of transcription is regulated through the well-coordinated spatial and temporal interactions between distal genomic regulatory elements required for specialized cell-type and developmental gene expression programs. With recent findings CFTR has served as a model to understand the principles that govern genome-wide and topological organization of distal intra-chromosomal contacts as it relates to transcriptional control. This is due to the extensive characterization of the DNase hypersensitivity sites, modification of chromatin, transcription factor binding sites and the arrangement of these sites in CFTR consistent with the restrictive expression in epithelial cell types. Here, we identified CHD6 from a screen among several chromatin-remodeling proteins as a putative epigenetic modulator of CFTR expression. Moreover, our findings of CTCF interactions with CHD6 are consistent with the role described previously for CTCF in CFTR regulation. Our results now reveal that the CHD6 protein lies within the infrastructure of multiple transcriptional complexes, such as the FACT, PBAF, PAF1C, Mediator, SMC/Cohesion and MLL complexes. This model underlies the fundamental role CHD6 facilitates by tethering cis-acting regulatory elements of CFTR in proximity to these multi-subunit transcriptional protein complexes. Finally, we indicate that CHD6 structurally coordinates a three-dimensional stricture between intragenic elements of CFTR bound by several cell-type specific transcription factors, such as CDX2, SOX18, HNF4α and HNF1α. Therefore, our results reveal new insights into the epigenetic regulation of CFTR expression, whereas the manipulation of CFTR gene topology could be considered for treating specific indications of cystic fibrosis and/or pancreatitis.


Effects of tapering tumor necrosis factor inhibitor on the achievement of inactive disease in patients with axial spondyloarthritis: a nationwide cohort study.
To investigate the association between the extent of tapering tumor necrosis factor inhibitor (TNFi) and the likelihood of achieving inactive disease in patients with axial spondyloarthritis (axSpA) METHODS: We analyzed 1575 1-year follow-up interval data of 776 axSpA patients treated with TNFi for more than 1 year in a nationwide observational cohort. The decision on tapering TNFi was made by patients and their physicians. We quantified TNFi used during interval as a dose quotient (DQ). The intervals were classified into the heavy-tapering (DQ < 50), mild-tapering (DQ 50-99), and control groups (DQ = 100). Outcome variables included achieving Ankylosing Spondylitis Disease Activity Score-inactive disease (ASDAS-ID) and major clinical response of Bath Ankylosing Spondylitis Disease Activity Index (BASDAI50) in the follow-up visit. The effects of TNFi tapering on the outcome were analyzed using the generalized estimating equation. At the baseline visit, 91.1% of the patients showed a high disease activity (ASDAS-CRP ≥ 2.1). DQ of each interval was significantly influenced by the ASDAS-CRP measure in the prior follow-up (P < 0.001). ASDAS-ID was observed in 42.3% of the intervals. A multivariable analysis showed that the likelihood of outcome achievement was comparable between the control and mild-tapering groups, but significantly decreased in the heavy-tapering group (vs. the control group, adjusted OR = 0.28, [95% CI, 0.08-0.94]). In contrast, the likelihood to achieve BASDAI50 response was not different among the groups. In the subgroup of patients who reached ASDAS-ID 1 year after TNFi treatment (n = 327), ASDAS-ID was observed in 66.1% of the subsequent intervals, and only the mild-tapering group showed a likelihood of target maintenance comparable with that of the control group (adjusted OR = 1.25 [0.41-3.80]). This likelihood decreased with an increase in ASDAS-CRP. Mild tapering of TNFi has efficacy comparable with that of the standard-dose treatment for ASDAS-ID achievement in patients with axSpA.


Paternal support and preterm birth, and the moderation of effects of chronic stress: a study in Los Angeles county mothers.
Maternal psychosocial stress is an important risk factor for preterm birth, but support interventions have largely been unsuccessful. The objective of this study is to assess how support during pregnancy influences preterm birth risk and possibly ameliorates the effects of chronic stress, life event stress, or pregnancy anxiety in pregnant women. We examined 1,027 singleton preterm births and 1,282 full-term normal weight controls from a population-based retrospective case-control study of Los Angeles County, California women giving birth in 2003, a mostly Latina population (both US-born and immigrant). We used logistic regression to assess whether support from the baby's father during pregnancy influences birth outcomes and effects of chronic stress, pregnancy anxiety, and life event stress. Adjusted odds of preterm birth decreased with better support (OR 0.73 [95%CI 0.52, 1.01]). Chronic stress (OR 1.46 [95%CI 1.11, 1.92]), low confidence of a normal birth (OR 1.57 [95% CI 1.17, 2.12]), and fearing for the baby's health (OR 1.67 [95%CI 1.30, 2.14]) increased preterm birth risk, but life events showed no association. Our data also suggested that paternal support may modify the effect of chronic stress on the risk of preterm birth, such that among mothers lacking support, those with moderate-to-high stress were at increased odds of delivering preterm (OR 2.15 [95%CI 0.92, 5.03]), but women with greater support had no increased risk with moderate-to-high chronic stress (OR 1.13 [95%CI 0.94, 1.35]). Paternal support may moderate the effects of chronic stress on the risk of preterm delivery.


Prospective study of methylenetetrahydrofolate reductase (MTHFR) variant C677T and risk of all-cause and cardiovascular disease mortality among 6000 US adults.
The association between blood homocysteine concentration and the risk of cardiovascular disease (CVD) remains controversial, but few studies have examined the association between MTHFR C677T (a proxy for high homocysteine concentration) and death from CVD. The objective was to examine associations of MTHFR C677T, a proxy for high homocysteine concentrations, with CVD mortality and with all-cause mortality in a national representative prospective cohort of the US adult population before the introduction of mandatory folic acid fortification of flour. We used Mendelian randomization to examine the association of MTHFR C677T with cause-specific mortality in 5925 participants by accessing the NHANES III (1991-1994) Linked Mortality File (through 2006). A comparison of homozygotes at baseline showed that individuals with a TT genotype had a 2.2-μmol/L higher homocysteine and a 1.4-ng/mL lower folate concentration, respectively, than did those with a CC genotype. The TT genotype frequency varied from 1.2% (95% CI: 0.7, 2.0) in non-Hispanic blacks and 11.6% (95% CI: 9.6, 14.0) in non-Hispanic whites to 19.4% (95% CI: 16.7, 22.3) in Mexican Americans. After adjustment for ethnic group and other CVD risk factors, the MTHFR C677T TT genotype was associated with significantly lower CVD mortality (HR: 0.69; 95% CI: 0.50, 0. 95) but had no significant effect on all-cause mortality (HR: 0.79; 95% CI: 0.59, 1.05). After stratification by period of follow-up, the inverse association of MTHFR with CVD mortality was significant only in the period after introduction of mandatory folic acid fortification. The inverse association of MTHFR with CVD mortality was unexpected and highlights the need for caution in interpretation of Mendelian randomization studies, which, like other observational studies, can be influenced by chance, bias, or confounding.


Associations between quality of life and marital status in cancer patients and survivors.
The cancer survival rate in Korea has substantially increased, necessitating the management of not only patients with cancer but also longer term survivors. Although the divorce rate has drastically increased in Korea, there is not sufficient research regarding the relationship between changes in marital status and quality of life (QOL) in cancer patients and survivors. Thus, we aimed to examine the relationship between marital status and QOL in such cases. This study was performed using the Community Health Survey of 2008 administered by the Korea Centers for Disease Control and Prevention (N=169,328). We used t-tests and Chi-square tests to compare demographic variables between men and women, and analysis of variance (ANOVA) to compare QOL scores among comparison groups. We also performed a multilevel analysis on the relationship between QOL and marital status while accounting for provincial differences. Decline of EuroQOL five dimensions (EQ-5D) in single patients with cancer was greater than in any other marital status group, but there was no statistically significant decline in survivors of cancer with regard to marital status. In the general population, the decline of EQ-5D was higher among single people than married people. Using the EuroQOL visual analog scale (EQ-VAS), single people had higher values than those of other marital status among both patients with cancer and survivors of cancer. In the general population, EQ-VAS values were higher for single people compared to married people. There may be a significant relationship between marital status and QOL in cancer patients and survivors. Policy interventions to manage patients with cancer who experience a decline in QOL as well as marital problems should be conducted.


Differential proteomic responses of selectively bred and wild-type Sydney rock oyster populations exposed to elevated CO2.
Previous work suggests that larvae from Sydney rock oysters that have been selectively bred for fast growth and disease resistance are more resilient to the impacts of ocean acidification than nonselected, wild-type oysters. In this study, we used proteomics to investigate the molecular differences between oyster populations in adult Sydney rock oysters and to identify whether these form the basis for observations seen in larvae. Adult oysters from a selective breeding line (B2) and nonselected wild types (WT) were exposed for 4 weeks to elevated pCO2 (856 μatm) before their proteomes were compared to those of oysters held under ambient conditions (375 μatm pCO2 ). Exposure to elevated pCO2 resulted in substantial changes in the proteomes of oysters from both the selectively bred and wild-type populations. When biological functions were assigned, these differential proteins fell into five broad, potentially interrelated categories of subcellular functions, in both oyster populations. These functional categories were energy production, cellular stress responses, the cytoskeleton, protein synthesis and cell signalling. In the wild-type population, proteins were predominantly upregulated. However, unexpectedly, these cellular systems were downregulated in the selectively bred oyster population, indicating cellular dysfunction. We argue that this reflects a trade-off, whereby an adaptive capacity for enhanced mitochondrial energy production in the selectively bred population may help to protect larvae from the effects of elevated CO2 , whilst being deleterious to adult oysters.


Prospective study of Clostridium difficile intestinal colonization and disease following single-dose antibiotic prophylaxis in surgery.
A total of 108 volunteers undergoing an elective surgical procedure were randomly given a single 2-g intravenous prophylactic dose of either a cephalosporin or mezlocillin. Stool samples were cultured for Clostridium difficile the day before the operation and later on postoperative days 4, 7, and 14. C. difficile was detected in 23.0% of patients who received a cephalosporin (cefoxitin, 8.3%; cefazolin, 14.3%; cefotetan, 20.0%; ceftriaxone, 25.0%; cefoperazone, 43.7%), in 3.3% of patients given mezlocillin, and in none of 15 control volunteers given no antimicrobial agent. No patient experienced diarrhea.


Oral immunotherapy for treatment of egg allergy in children.
For egg allergy, dietary avoidance is the only currently approved treatment. We evaluated oral immunotherapy using egg-white powder for the treatment of children with egg allergy. In this double-blind, randomized, placebo-controlled study, 55 children, 5 to 11 years of age, with egg allergy received oral immunotherapy (40 children) or placebo (15). Initial dose-escalation, build-up, and maintenance phases were followed by an oral food challenge with egg-white powder at 10 months and at 22 months. Children who successfully passed the challenge at 22 months discontinued oral immunotherapy and avoided all egg consumption for 4 to 6 weeks. At 24 months, these children underwent an oral food challenge with egg-white powder and a cooked egg to test for sustained unresponsiveness. Children who passed this challenge at 24 months were placed on a diet with ad libitum egg consumption and were evaluated for continuation of sustained unresponsiveness at 30 months and 36 months. After 10 months of therapy, none of the children who received placebo and 55% of those who received oral immunotherapy passed the oral food challenge and were considered to be desensitized; after 22 months, 75% of children in the oral-immunotherapy group were desensitized. In the oral-immunotherapy group, 28% (11 of 40 children) passed the oral food challenge at 24 months and were considered to have sustained unresponsiveness. At 30 months and 36 months, all children who had passed the oral food challenge at 24 months were consuming egg. Of the immune markers measured, small wheal diameters on skin-prick testing and increases in egg-specific IgG4 antibody levels were associated with passing the oral food challenge at 24 months. These results show that oral immunotherapy can desensitize a high proportion of children with egg allergy and induce sustained unresponsiveness in a clinically significant subset. (Funded by the National Institutes of Health; ClinicalTrials.gov number, NCT00461097.).


Lactobacillus casei abundance is associated with profound shifts in the infant gut microbiome.
Colonization of the infant gut by microorganisms over the first year of life is crucial for development of a balanced immune response. Early alterations in the gastrointestinal microbiota of neonates has been linked with subsequent development of asthma and atopy in older children. Here we describe high-resolution culture-independent analysis of stool samples from 6-month old infants fed daily supplements of Lactobacillus casei subsp. Rhamnosus (LGG) or placebo in a double-blind, randomized Trial of Infant Probiotic Supplementation (TIPS). Bacterial community composition was examined using a high-density microarray, the 16S rRNA PhyloChip, and the microbial assemblages of infants with either high or low LGG abundance were compared. Communities with high abundance of LGG exhibited promotion of phylogenetically clustered taxa including a number of other known probiotic species, and were significantly more even in their distribution of community members. Ecologically, these aspects are characteristic of communities that are more resistant to perturbation and outgrowth of pathogens. PhyloChip analysis also permitted identification of taxa negatively correlated with LGG abundance that have previously been associated with atopy, as well as those positively correlated that may prove useful alternative targets for investigation as alternative probiotic species. From these findings we hypothesize that a key mechanism for the protective effect of LGG supplementation on subsequent development of allergic disease is through promotion of a stable, even, and functionally redundant infant gastrointestinal community.


Interrelation between donor and recipient heart rates during exercise after heterotopic cardiac transplantation.
The interrelation between the rates of the innervated recipient heart and the denervated donor heart at rest, on standing, and during the different phases of maximal exercise was studied in nine patients 1-6 months after heterotopic cardiac transplantation. The resting heart rate was significantly higher in the donor heart compared with the recipient heart. Eight of the nine recipient hearts and none of the donor hearts showed an increase in heart rate on standing up. All patients were exercised using a Bruce protocol until fatigued. The increase in heart rate during the first three minutes of exercise was lower in the donor hearts (10.7(6) beats/min) than in the recipient hearts (30(4.8) beats/min) but the peak heart rates were almost identical (donor hearts 152.7(2.9) and recipient hearts 152(2.8) beats/min). Five of the nine donor hearts and none of the recipient hearts showed a significant increase in heart rate after cessation of exercise. Three minutes after exercise heart rate had decreased by only 0.2(5.7) beats/min in the donor hearts compared with 33.6(6) beats/min in the recipient hearts. In spite of these differences in response between the donor hearts and recipient hearts, there were significant correlations between the two heart rates in the same patient at rest, after the first three minutes of exercise, at peak exercise, and during recovery.


Destruction of Myc by ubiquitin-mediated proteolysis: cancer-associated and transforming mutations stabilize Myc.
The human proto-oncogene c-myc encodes a highly unstable transcription factor that promotes cell proliferation. Although the extreme instability of Myc plays an important role in preventing its accumulation in normal cells, little is known about how Myc is targeted for rapid destruction. Here, we have investigated mechanisms regulating the stability of Myc. We show that Myc is destroyed by ubiquitin-mediated proteolysis, and define two elements in Myc that oppositely regulate its stability: a transcriptional activation domain that promotes Myc destruction, and a region required for association with the POZ domain protein Miz-1 that stabilizes Myc. We also show that Myc is stabilized by cancer-associated and transforming mutations within its transcriptional activation domain. Our data reveal a complex network of interactions regulating Myc destruction, and imply that enhanced protein stability contributes to oncogenic transformation by mutant Myc proteins.


[Reflux disease and eating disorders--a case for teamwork].
The term erosion describes tooth wear caused by acids. Erosions can be a consequence of medical problems like gastroesophageal reflux disease or eating disorders which lead to a regular contact of gastric acid with teeth. These, so called intrinsic erosions occur in such typical locations within the dental arches that even in the absence of other symptoms gastric acid can be assumed to be the cause. Dental professionals may thus be the first to discover and diagnose the underlying medical problem. A good cooperation between the physician and the dentist is consequently necessary for a causal treatment of the patient. Parallel to the therapy of the underlying disease practical dental prophylactic measures like chewing gum und fluoride rinses are recommended.


Personal Health Information Recommender: implementing a tool for the empowerment of cancer patients.
Nowadays, patients have a wealth of information available on the Internet. Despite the potential benefits of Internet health information seeking, several concerns have been raised about the quality of information and about the patient's capability to evaluate medical information and to relate it to their own disease and treatment. As such, novel tools are required to effectively guide patients and provide high-quality medical information in an intelligent and personalised manner. With this aim, this paper presents the Personal Health Information Recommender (PHIR), a system to empower patients by enabling them to search in a high-quality document repository selected by experts, avoiding the information overload of the Internet. In addition, the information provided to the patients is personalised, based on individual preferences, medical conditions and other profiling information. Despite the generality of our approach, we apply the PHIR to a personal health record system constructed for cancer patients and we report on the design, the implementation and a preliminary validation of the platform. To the best of our knowledge, our platform is the only one combining natural language processing, ontologies and personal information to offer a unique user experience.


Cloning and analysis of an actin-encoding cDNA from the dimorphic pathogenic fungus Histoplasma capsulatum.
We have cloned an actin-encoding cDNA from the dimorphic fungus Histoplasma capsulatum, an important pathogen of humans. The predicted amino acid sequence as well as the general codon pattern of Histoplasma actin revealed the highest degree of similarity to the actin of the filamentous ascomycete Aspergillus nidulans. Southern blot analysis determined that actin was encoded by a single copy in the Histoplasma genome. Northern blot analysis showed a single 1700 nt transcript in yeast and mould cells as well as in cells undergoing the temperature induced mould-to-yeast conversion. Actin mRNA levels normalized to 18 S rRNA were found to be equivalent in all the stages examined, except for a sharp four-fold transient decrease 4 h into the mould-to-yeast conversion. These data suggest that actin mRNA would not be a suitable internal marker for expression studies during Histoplasma mould-to-yeast morphogenesis.


Adaptive sampling of information in perceptual decision-making.
In many perceptual and cognitive decision-making problems, humans sample multiple noisy information sources serially, and integrate the sampled information to make an overall decision. We derive the optimal decision procedure for two-alternative choice tasks in which the different options are sampled one at a time, sources vary in the quality of the information they provide, and the available time is fixed. To maximize accuracy, the optimal observer allocates time to sampling different information sources in proportion to their noise levels. We tested human observers in a corresponding perceptual decision-making task. Observers compared the direction of two random dot motion patterns that were triggered only when fixated. Observers allocated more time to the noisier pattern, in a manner that correlated with their sensory uncertainty about the direction of the patterns. There were several differences between the optimal observer predictions and human behaviour. These differences point to a number of other factors, beyond the quality of the currently available sources of information, that influences the sampling strategy.


Fatigue and Sleep Disturbance in Arabic Cancer Patients After Completion of Therapy: Prevalence, Correlates, and Association With Quality of Life.
Fatigue and sleep disturbance are 2 of the most common and distressing cancer symptoms that negatively affect quality of life. The aim of this study was to assess the prevalence of, and factors contributing to, fatigue and sleep disturbance in Arabic-speaking cancer patients in Oman after completion of their cancer treatment. A cross-sectional and descriptive correlational design was used. Data were collected using the Pittsburgh Sleep Quality Index where a score of >5 indicated as poorer sleep, the Functional Assessment of Cancer Therapy-Fatigue a score of ≤34 indicating clinically significant fatigue, and the Functional Assessment of Cancer Therapy-General. Of the 369 patients who participated, 77.5% (n = 286) reported clinically significant fatigue, and 78% (n = 288) reported poor sleep. Fatigue (P < .05) was significantly associated with age, cancer site, months since diagnosis, type of treatment received, and comorbidity. Those experiencing fatigue and poor sleep had the lowest quality of life among the cancer patients studied. Fatigue and sleep disturbance are significant problems for the Arabic patients diagnosed with cancer. Both fatigue and sleep disturbance should be routinely assessed in the case of such patients. Routine assessments of fatigue and sleep disturbance are recommended so that appropriate interventions and treatment management plans can be introduced to reduce fatigue and improve sleep quality among patients with cancer.


Selective gene-expression profiling of migratory tumor cells in vivo predicts clinical outcome in breast cancer patients.
Metastasis of breast cancer is the main cause of death in patients. Previous genome-wide studies have identified gene-expression patterns correlated with cancer patient outcome. However, these were derived mostly from whole tissue without respect to cell heterogeneity. In reality, only a small subpopulation of invasive cells inside the primary tumor is responsible for escaping and initiating dissemination and metastasis. When whole tissue is used for molecular profiling, the expression pattern of these cells is masked by the majority of the noninvasive tumor cells. Therefore, little information is available about the crucial early steps of the metastatic cascade: migration, invasion, and entry of tumor cells into the systemic circulation. In the past, we developed an in vivo invasion assay that can capture specifically the highly motile tumor cells in the act of migrating inside living tumors. Here, we used this assay in orthotopic xenografts of human MDA-MB-231 breast cancer cells to isolate selectively the migratory cell subpopulation of the primary tumor for gene-expression profiling. In this way, we derived a gene signature specific to breast cancer migration and invasion, which we call the Human Invasion Signature (HIS). Unsupervised analysis of the HIS shows that the most significant upregulated gene networks in the migratory breast tumor cells include genes regulating embryonic and tissue development, cellular movement, and DNA replication and repair. We confirmed that genes involved in these functions are upregulated in the migratory tumor cells with independent biological repeats. We also demonstrate that specific genes are functionally required for in vivo invasion and hematogenous dissemination in MDA-MB-231, as well as in patient-derived breast tumors. Finally, we used statistical analysis to show that the signature can significantly predict risk of breast cancer metastasis in large patient cohorts, independent of well-established prognostic parameters. Our data provide novel insights into, and reveal previously unknown mediators of, the metastatic steps of invasion and dissemination in human breast tumors in vivo. Because migration and invasion are the early steps of metastatic progression, the novel markers that we identified here might become valuable prognostic tools or therapeutic targets in breast cancer.


In conversation with Nigel Scrutton.
Nigel Scrutton FRS is Professor of Molecular Enzymology and Biophysical Chemistry at the University of Manchester and former Director of the Manchester Institute of Biotechnology (MIB). He obtained a first degree in Biochemistry from King's College London and followed this with a PhD at the University of Cambridge. His doctoral research, undertaken in Richard Perham's laboratory, yielded fundamental breakthroughs in enzyme redesign that have stood the test of time. Nigel was awarded a ScD degree by the University of Cambridge in 2003. After faculty positions at the University of Leicester, Nigel was appointed Professor at the University of Manchester in 2005. Over the last 15 years, he has cemented his reputation as a world leader in the fields of enzyme engineering and biocatalysis, synthetic biology, biophysics and biomanufacturing, notably by establishing and directing the Synthetic Biology Research Centre 'SYNBIOCHEM' and UK Future Biomanufacturing Research Hub. In recognition of his scientific contributions, he has received many academic awards and accolades, including being elected as Fellow of the Royal Society earlier this year. In this interview, he highlights how fundamental studies of enzymatic catalysis and mechanisms are driving key advances in biotechnology and biomanufacturing, and describes how the experiences and mentors of his formative years helped to shape his successful career at the interface between discovery and application-focused science.


Photojournalism-Based Intervention Reduces Caregiver Burden and Depression in Alzheimer's Disease Family Caregivers.
Purpose: Art interventions have demonstrated holistic benefits for persons living with dementia and their caregivers. In this article, we describe the results of a pilot photojournalism program for 10 unpaid caregivers of persons living with dementia, with respect to caregivers' experience in the program and their psychological well-being. Design: Caregivers participated in four sessions led by a professional photojournalist who taught principles of photography. Between the sessions, caregivers took photographs that represented what caregiving meant to them using digital cameras provided in the program. During the sessions, instruction was interspersed with discussion of caregivers' photographs. Method: Caregiver burden and depressive symptoms were measured pre- and postprogram. Qualitative exploration included sessions' observations, viewing caregivers' photographs, and recording caregivers' accompanying comments. Findings: For participants with pre- and postprogram data, caregiver burden decreased significantly (p = .037). For caregivers with pre- and postprogram data, depressive symptoms decreased nonsignificantly (p = .066). Clinically meaningful reductions in caregiver burden and depressive symptoms were attained. Qualitative findings highlighted caregivers' strong engagement with the project, the facilitator, and other participants, and reflection on multiple aspects of their experience. Conclusions: This intervention helped caregivers creatively communicate their experience and demonstrated efficacy in the improvement of caregivers' psychological well-being.


Single-molecule binding experiments on long time scales.
We describe an approach for performing single-molecule binding experiments on time scales from hours to days, allowing for the observation of slower kinetics than have been previously investigated by single-molecule techniques. Total internal reflection fluorescence microscopy is used to image the binding of labeled ligand to molecules specifically coupled to the surface of an optically transparent flow cell. Long-duration experiments are enabled by ensuring sufficient positional, chemical, thermal, and image stability. Principal components of this experimental stability include illumination timing, solution replacement, and chemical treatment of solution to reduce photodamage and photobleaching; and autofocusing to correct for spatial drift.


Polymorphisms in human soluble epoxide hydrolase.
Human soluble epoxide hydrolase (hsEH) metabolizes a variety of epoxides to the corresponding vicinal diols. Arachidonic and linoleic acid epoxides are thought to be endogenous substrates for hsEH. Enzyme activity in humans shows high interindividual variation (e.g., 500-fold in liver) suggesting the existence of regulatory and/or structural gene polymorphisms. We resequenced each of the 19 exons of the hsEH gene (EPHX2) from 72 persons representing black, Asian, and white populations. A variety of polymorphisms was found, six of which result in amino acid substitutions. Amino acid variants were localized on the crystal structure of the mouse sEH, resulting in the prediction that at least two of these (Arg287Gln and Arg103Cys) might significantly affect enzyme function. The six variants of the hsEH cDNA corresponding to each single polymorphism and one corresponding to a double polymorphism were then constructed by site-directed mutagenesis and expressed in insect cells. As predicted, Arg287Gln and the double mutant Arg287Gln/Arg103Cys showed decreased enzyme activity using trans-stilbene oxide, trans-diphenylpropene oxide, and 14,15-epoxyeicosatrienoic acid as substrates. Lys55Arg and Cys154Tyr mutants had elevated activity for all three substrates. Detailed kinetic studies revealed that the double mutant Arg287Gln/Arg103Cys showed significant differences in Km and Vmax. In addition, stability studies showed that the double mutant was less stable than wild-type protein when incubated at 37 degrees C. These results suggest that at least six hsEH variants exist in the human population and that at least four of these may influence hsEH-mediated metabolism of exogenous and endogenous epoxide substrates in vivo.


Lentiviral vector-mediated genetic modification of human neural progenitor cells for ex vivo gene therapy.
Human neural progenitor cells (hNPC) hold great potential as an ex vivo system for delivery of therapeutic proteins to the central nervous system. When cultured as aggregates, termed neurospheres, hNPC are capable of significant in vitro expansion. In the current study, we present a robust method for lentiviral vector-mediated gene delivery into hNPC that maintains the differentiation and proliferative properties of neurosphere cultures while minimizing the amount of viral vector used and controlling the number of insertion sites per population. This method results in long-term, stable expression even after differentiation of the hNPC to neurons and astrocytes and allows for generation of equivalent transgenic populations of hNPC. In addition, the in vitro analysis presented predicts the behavior of transgenic lines in vivo when transplanted into a rodent model of Parkinson's disease. The methods presented provide a powerful tool for assessing the impact of factors such as promoter systems or different transgenes on the therapeutic utility of these cells.


Innovative interactive flexible docking method for multi-scale reconstruction elucidates dystrophin molecular assembly.
At present, our molecular knowledge of dystrophin, the protein encoded by the DMD gene and mutated in myopathy patients, remains limited. To get around the absence of its atomic structure, we have developed an innovative interactive docking method based on the BioSpring software in combination with Small-angle X-ray Scattering (SAXS) data. BioSpring allows interactive handling of biological macromolecules thanks to an augmented Elastic Network Model (aENM) that combines the spring network with non-bonded terms between atoms or pseudo-atoms. This approach can be used for building molecular assemblies even on a desktop or a laptop computer thanks to code optimizations including parallel computing and GPU programming. By combining atomistic and coarse-grained models, the approach significantly simplifies the set-up of multi-scale scenarios. BioSpring is remarkably efficient for the preparation of numeric simulations or for the design of biomolecular models integrating qualitative experimental data restraints. The combination of this program and SAXS allowed us to propose the first high-resolution models of the filamentous central domain of dystrophin, covering repeats 11 to 17. Low-resolution interactive docking experiments driven by a potential grid enabled us to propose how dystrophin may associate with F-actin and nNOS. This information provides an insight into medically relevant discoveries to come.


Diet in the etiology of oral and pharyngeal cancer among women from the southern United States.
A case-control interview study involving 227 women in North Carolina with oral cavity or pharyngeal cancer and 405 matched controls showed a protective effect of a usual adult diet high in fruits and vegetables. The relative risks of 0.65 for moderate and 0.52 for high (relative to 1.0 for infrequent) consumption of fruits and vegetables were statistically significant and remained after controlling for demographic characteristics, tobacco and alcohol use, relative weight, and intake of other food groups. Risks were lower with higher bread and cereal intake but higher for those women with the lightest weights, adjusted for height. The inverse associations between oral and pharyngeal cancer and intake of fruits and vegetables and intake of breads and cereals could not be attributed to an association with general nutritional status, since meat and fish consumption was related to an increased risk of oral and pharynx cancer. Moreover, dairy and egg consumption was generally unrelated to cancer risk. The reduction in risk with greater fruit and vegetable consumption is consistent with the hypothesis that vitamin C and/or beta-carotene intake is associated with a reduced risk of oral and pharyngeal cancer.


Nurses' experiences of practice and political reform in long-term aged care in Australia: implications for the retention of nursing personnel.
The aim of the study was to explore registered nurses' experiences in long-term aged care in light of the political reform of aged care services in Australia. In Australia, the aged care industry has undergone a lengthy period of political and structural reform. Despite reviews into various aspects of these reforms, there has been little consideration of the effect these are having on the practice experiences and retention of nursing staff in long-term care. In this critical hermeneutic study, 14 nurses from long-term care facilities in Australia were interviewed about their experiences during the reform period. The data revealed a sense of tension and conflict between nurses' traditional values, roles and responsibilities and those supported by the reforms. Nurses struggled to re-negotiate both their practice roles and values as the reforms were implemented and the system evolved. Nursing management support was an important aspect in mediating the effect of reforms on nursing staff. This research highlights both the tensions experienced by nurses in long-term aged care in Australia and the need to re-negotiate nursing roles, responsibilities and values within an evolving care system. This research supports a role for sensitive and proactive nursing management during periods of industry reform as a retention strategy for qualified nursing personnel.


International project for producing reference values for concentrations of trace elements in human blood and urine--TRACY.
In assessing the concentrations of toxic metals, such as cadmium, chromium, and mercury, in human blood and urine samples to determine whether they are abnormal or not, reliable reference values are needed from populations of nonoccupationally exposed subjects. Numerous publications present concentrations claimed to be typical for the study populations, but they can differ by up to an order of magnitude for a particular element. This is the consequence of general problems that are related to the definition of the reference groups, and the sampling and analytical procedures used, and that make it difficult to define typical and unbiased values. An international group of experts now establishes criteria and procedures to evaluate publications containing information on the concentrations of metals in tissues and body fluids for reference populations. These evaluations have been compiled in a data base (TRACY).


Nanoparticle-imprinted polymers for size-selective recognition of nanoparticles.
Citrate-stabilized gold nanoparticles 15 nm and 33 nm in diameter were transferred concomitantly with a monolayer of positively charged polyaniline by Langmuir-Blodgett transfer at pH 5 onto a conducting indium-doped tin oxide (ITO) support. Films consisting of one to three layers of polyaniline with thicknesses of 1-3 nm were prepared and characterized by scanning electron microscopy (SEM), atomic force microscopy (AFM), and X-ray photoelectron spectroscopy. After electro-oxidation of the Au nanoparticles in 0.1 M KCl, cavities were left behind in the film that could be analyzed by SEM. These cavities were able to recapture analyte nanoparticles from a solution of pH 10 and showed size-exclusion properties. The amount of nanoparticles taken up by the cavities was conveniently analyzed by measuring the charge associated with the electro-oxidation of these particles in 0.1 M KCl after the film had been rinsed with water. The size-exclusion properties improved with the number of Langmuir-Blodgett layers transferred.


Human resources for mental health care: current situation and strategies for action.
A challenge faced by many countries is to provide adequate human resources for delivery of essential mental health interventions. The overwhelming worldwide shortage of human resources for mental health, particularly in low-income and middle-income countries, is well established. Here, we review the current state of human resources for mental health, needs, and strategies for action. At present, human resources for mental health in countries of low and middle income show a serious shortfall that is likely to grow unless effective steps are taken. Evidence suggests that mental health care can be delivered effectively in primary health-care settings, through community-based programmes and task-shifting approaches. Non-specialist health professionals, lay workers, affected individuals, and caregivers with brief training and appropriate supervision by mental health specialists are able to detect, diagnose, treat, and monitor individuals with mental disorders and reduce caregiver burden. We also discuss scale-up costs, human resources management, and leadership for mental health, particularly within the context of low-income and middle-income countries.


Tetrahymena alpha-type DNA polymerase A: purification and subunit analysis.
DNA polymerase A (an alpha-type polymerase) from the ciliate, Tetrahymena pyriformis, has been purified 260,000-fold (40,000 units/mg protein). The polymerase A did not show any heterogeneity in terms of size and charge during purification. Enzymatic properties of the DNA polymerase A remained unchanged during the purification. Two-dimensional gel electrophoresis revealed that in the first dimension (isoelectric focusing agarose gel), the activity of the purified enzyme was focused at around pH 5.5 and that in the second dimension (sodium dodecyl sulfate-polyacrylamide gel), 135,000- and 66,000-dalton polypeptides emerged from the activity peak at a stoichiometric ratio of about 1:3. The native molecular weight of the DNA polymerase A estimated from the stoichiometric subunit ratio approximately coincided with that estimated from gel filtration on Sephadex G-200 under low ionic strength conditions. The present results strongly suggest the existence of a common high-molecular-weight catalytic core subunit in alpha-type polymerases of eukaryotes.


The effect of seasons on Brazilian red propolis and its botanical source: chemical composition and antibacterial activity.
The aim of this study was to evaluate the effect of seasons on the chemical composition and antibacterial activity of Brazilian red propolis (BRP) and its plant source. BRP was collected from Maceio, Alagoas state, north-east of Brazil, during one year. Chemical composition was determined by physicochemical analyses and HPLC while antimicrobial activity was assessed against Streptococcus mutans, Streptococcus sobrinus, Staphylococcus aureus and Actinomyces naeslundii by determining the minimal inhibitory and bactericidal concentrations (MIC and MBC, respectively). The comparative chemical profiles varied quantitatively according to the collection period. Formononetin was the most abundant compound in both propolis and resin, while isoliquiritigenin, (3S)-neovestitol, (3S)-vestitol are suggested to be responsible for antimicrobial activity of Brazilian red propolis. MIC varied from 15.6 to 125 μg/mL, whereas MBC varied from 31.2 to 500 μg/mL. Therefore, season in which propolis and its botanical source are collected indeed influences their chemical compositions, resulting in variations in their antibacterial activity.


Neuroimaging of cerebral venous thrombosis.
Early and accurate diagnosis of cerebral venous thrombosis (CVT) is possible with the help of computed tomography (CT) scan and magnetic resonance imaging (MRI). Empty delta sign on postcontrast CT is present in only up to 30% of the cases. The role of CT venography is not yet established, but it is emerging as an effective modality for diagnosis of CVT. T2* MRI sequence is superior to spin echo in detecting CVT and small hemor rhages. MR venography is considered the technique of choice for diagnosis and follow-up of CVT, but in certain cases, MRI could be superior as it shows the thrombus itself and not just the absence of signal as seen on MR venography. Diffusion-weighted imaging is a relatively new MRI technique that is extremely sensitive in detecting acute arterial strokes and can distinguish cytotoxic and vasogenic edema. The presence of hyperintense signal on diffusion-weighted imaging in the occluded veins or sinuses at the time of diagnosis may predict a low rate of vessel recanalization. Contrast angiography should be strongly considered if isolated cortical vein thrombosis is suspected.


Mitral valve dysfunction and repair following orthotopic heart transplantation: a case report.
Mitral valve dysfunction after orthotopic heart transplantation may cause symptoms refractory to medical therapy. In this report, we present a patient who underwent mitral annuloplasty for severe symptomatic mitral valve insufficiency 9 years after heart transplantation, and we critically appraise the literature available for mitral valve dysfunction in this setting. Mitral valve repair, when feasible, should be considered for mitral insufficiency after transplantation to improve functional status and reduce the risk of retransplantation--this is particularly prudent in view of chronic donor shortage.


Solving the Opioid Epidemic in Ohio.
On May 31, 2017, Ohio Attorney General Mike DeWine took a step in fighting Ohio's opioid epidemic, bringing the first of many lawsuits against five top pharmaceutical companies. However, under Federal and State law, there is an exception called the Learned Intermediary Doctrine, which can absolve drug manufacturers of liability from any misconduct that might be found and transfer that liability to a treating physician. This exception is the way many drug manufacturers were able to avoid being held responsible in the past. This Note proposes that with the current pending lawsuit in the State of Ohio, an exception to the Learned Intermediary Doctrine should be introduced. This Note begins with a discussion of opioids and how these drugs have become such an aggressive problem in a very short amount of time in Ohio. Part II talks about the role the government can play and the drug manufacturers have played and continue to play in the availability of opioids. It discusses the effect these pharmaceutical companies have had on this problem and in increasing this problem. Part II also discusses why this is a problem and why this problem matters. Further, it talks about the steps that have already been taken by the Ohio Legislature to combat the opioid problems. Finally, it delves into a discussion of what this current lawsuit means for fighting and decreasing the opioid problem and how it will directly affect the heroin epidemic in Ohio.


Mycobacterium genavense infections: a retrospective multicenter study in France, 1996-2007.
Mycobacterium genavense, a nontuberculous mycobacterium, led to devastating infections in patients with acquired immunodeficiency syndrome (AIDS) before highly active antiretroviral therapy (HAART) was available, as well as in other immunocompromised patients. We conducted the current study to describe the features of this infection in patients infected with human immunodeficiency virus (HIV) in the HAART era and in non HIV-infected patients.We conducted a retrospective cohort survey in France. All patients with M. genavense infection diagnosed from 1996 to 2007 at the National Reference Center, Institut Pasteur, Paris, were identified and their clinical, laboratory, and microbiologic data were centralized in a single database. Twenty-five cases of M. genavense infection originating from 19 centers were identified. Twenty patients had AIDS, 3 had solid organ transplantation, and 2 had sarcoidosis. Sixty-four percent (n = 16) were male, mean age was 42 years, and median CD4 count was 13/mm (range, 0-148/mm) in patients with AIDS. Twenty-four patients had disseminated infection with fever (75%, n = 18), weight loss (79%, n = 19), abdominal pain (71%, n = 17), diarrhea (62.5%, n = 15), splenomegaly (71%, n = 17), hepatomegaly (62.5%, n = 15), or abdominal adenopathy (62.5%, n = 15). M. genavense was isolated from the lymph node (n = 13), intestinal biopsy (n = 9), blood (n = 6), sputum (n = 3), stool (n = 3), and bone marrow (n = 5). Eleven patients (44%) died, 8 (32%) were considered cured with no residual symptoms, and 6 (24%) had chronic symptoms. The 1-year survival rate was 72%.The prognosis of M. genavense infection in HIV-infected patients has dramatically improved with HAART. Clinical presentations in HIV and non-HIV immunocompromised patients were similar.


Favored Conformations of Carbonyl Compounds: A Structural Study of n-Octanal.
We report on the molecular structures of the two most abundant conformers of n-octanal observed by molecular beam Fourier transform microwave spectroscopy. Next to limonene, which is the main component of citrus-oil, octanal and other n-alkyl aldehydes strongly enhance the typical fresh smell of lemon-oil. Due to the high flexibility of its n-alkyl chain and the high number of possible conformers, different semi-empirical methods (AM1, PM3, MMFF94) were used to sample the conformational space of octanal before performing more sophisticated quantum chemical calculations at the MP2 level of theory. This technique has previously been shown to be an ideal tool to characterize relevant odorant structures in fragrance chemistry. The structure of octanal and structurally related molecules is discussed in the context of the most abundant chain conformations and the potential use of the microwave validated structures for further studies in biological media.


Effects of acetabular rim trimming on hip joint contact pressures: how much is too much?
In patients with femoroacetabular impingement (FAI), acetabular rim trimming removes the offending area of the acetabular deformity in patients with pincer-type and mixed-type FAI to improve hip joint kinematics. Although the rationale for arthroscopic acetabular rim trimming in patients with FAI is well established, the amount of rim resection has not been quantified, and the threshold at which excessive rim resection results in abnormal hip contact pressures has not been described. To investigate the changes in contact areas, contact pressures, and peak forces within the hip joint with sequential acetabular rim trimming. Controlled laboratory study. Six fresh-frozen, nondysplastic, human cadaveric hemipelvises were analyzed utilizing thin-film piezoresistive load sensors to measure the contact area, contact pressure, and peak force after anterosuperior acetabular rim trimming at depths of 0 mm (intact), 2 mm, 4 mm, 6 mm, and 8 mm. Each specimen was examined at 20° of extension and 60° of flexion. Analysis was performed on 2 regions of interest: the acetabular rim and the acetabular base (deep part of the acetabulum). After each experimental condition, the acetabulum was normalized with respect to the intact state to account for specimen variability. Statistical analysis was conducted through 1-way analysis of variance with post hoc Games-Howell tests. At the acetabular base, there were significant increases in the contact area after 4-mm resection (60°: 169.12% ± 30.64%; P = .0138), contact pressure after 6-mm resection (60°: 292.76% ± 79.07%; P = .009), and peak force after 6-mm resection (60°: 166.00% ± 34.40%; P = .027). At the acetabular rim, there were significant decreases in the contact area after 6-mm resection (60°: 66.32% ± 18.80%; P = .0354) (20°: 65.47% ± 15.87%; P = .0127), contact pressure after 6-mm resection (60°: 50.77% ± 11.49%; P < .001) (20°: 58.01% ± 23.10%; P = .0335), and peak force after 6-mm resection (60°: 60.67% ± 9.29%; P < .001) (20°: 74.44% ± 9.84%; P = .007). Resecting more than 4 to 6 mm of the acetabular rim during hip arthroscopic surgery to address a pincer deformity may dramatically increase contact pressures by 3-fold at the acetabular base. The study suggests that excessive rim resection may lead to increased loads in the hip joint and may predispose to premature joint degeneration. Resecting more than 4 to 6 mm of the acetabular rim may significantly alter hip joint biomechanics, increasing joint reactive forces and subsequent chondrolabral degeneration.


An audit of reporting of conflict of interest policies among three stakeholders in Indian biomedical journals.
A conflict of interest (COI) in publication exists when the primary interest of publication is influenced by a secondary interest (financial or non-financial). International guidelines are available that can be used by journal editors to formulate their own COI policies. The present study was carried out with the objective of evaluating COI policies existing among Indian biomedical journals. MEDLINE/PubMed and MedIND/IndMed databases were searched. Inclusions were journals that were active and indexed. Outcome measures were proportion of journals: (a) mentioning COI disclosure statement for authors, reviewers, and editors, (b) adequately explaining COI, (c) referring to three international guidelines, and (d) the proportion of PubMed/other than PubMed indexed journals mentioning COI policy for authors, reviewers, and editors and providing an adequate explanation for COI. Apart from descriptive statistics, associations between indexing and COI Policy for all three stakeholders were evaluated. A total of n = 106 journals formed the final sample. Among them, 82 (77%) were PubMed and 24 (23%) were MedIND/IndMed indexed. COI disclosure statement was mentioned in 93 (87.7%) journals for authors, 10 (9.4%) for reviewers, and 06 (5.6%) for editors. Only 35 (33%) journals adequately explained COI. A total of 61 (57.5%) journals endorsed all the three international guidelines. PubMed indexing was found to be associated with approximately 19 times the odds of COI policies being present on the journal's home page relative to the journals indexed with other indexing agencies (crude odds ratio - 18.8, 95% confidence interval [4.6, 77],P < 0.0001). Very few Indian biomedical journals have COI policies for reviewers and editors and most did not explain it adequately. Nearly, a fifth of the journals we evaluated did not follow any guideline for disclosing COI.


Assessment of visuo-attentional abilities in young children with or without visual disorder: toward a systematic screening in the general population.
In young children, visual attention, analysis or memory is only rarely evaluated. Moreover, tools to test for such higher-order visual capacities in children are limited. In an attempt to develop and refine such tools, we selected nine tests to assess visuo-attentional abilities before formal reading education (grade 1). The battery consisted of gaze fixation, visual field, visual extinction, binocular visual pursuit, visual memory, "A" cancellation, Teddy bears cancellation, embedded figures, and matching tasks. This battery was used in the general population (n=110) to calculate cut-off scores identifying the lower 5% of the general population to obtain a screening measure for neurovisual disabilities in children. To evaluate our battery's sensitivity and specificity to neurovisual disorders over ophthalmological diseases, a neurovisual group (n=9) and an ophthalmologic group (n=13) also completed the tests. Overall, all but three tests of the battery could be used to discriminate between neurovisual and ophthalmologic children. The ophthalmologic children failed the visual field extent examination and the cancellation tasks, consistent with deleterious effects of ophthalmologic disease on visual perception as well as higher-order vision. Using the cut-off scores, the battery identified only 2 out of 13 ophthalmologic patients, but 5 out of 9 neurovisual patients. In the general population, these cut-off scores identified seven children. These children were previously undiagnosed with any disability (i.e., no diagnosis of ophthalmological, neurological, or psychiatric disease) and thus did not receive any rehabilitation. This preliminary study highlights the necessity for a neurovisual disorder screening tool for young children.


Assessment of the CHA2DS2-VASc Score in Predicting Ischemic Stroke, Thromboembolism, and Death in Patients With Heart Failure With and Without Atrial Fibrillation.
The CHA2DS2-VASc score (congestive heart failure, hypertension, age ≥75 years [doubled], diabetes, stroke/transient ischemic attack/thromboembolism [doubled], vascular disease [prior myocardial infarction, peripheral artery disease, or aortic plaque], age 65-75 years, sex category [female]) is used clinically for stroke risk stratification in atrial fibrillation (AF). Its usefulness in a population of patients with heart failure (HF) is unclear. To investigate whether CHA2DS2-VASc predicts ischemic stroke, thromboembolism, and death in a cohort of patients with HF with and without AF. Nationwide prospective cohort study using Danish registries, including 42 987 patients (21.9% with concomitant AF) not receiving anticoagulation who were diagnosed as having incident HF during 2000-2012. End of follow-up was December 31, 2012. Levels of the CHA2DS2-VASc score (based on 10 possible points, with higher scores indicating higher risk), stratified by concomitant AF at baseline. Analyses took into account the competing risk of death. Ischemic stroke, thromboembolism, and death within 1 year after HF diagnosis. In patients without AF, the risks of ischemic stroke, thromboembolism, and death were 3.1% (n = 977), 9.9% (n = 3187), and 21.8% (n = 6956), respectively; risks were greater with increasing CHA2DS2-VASc scores as follows, for scores of 1 through 6, respectively: (1) ischemic stroke with concomitant AF: 4.5%, 3.7%, 3.2%, 4.3%, 5.6%, and 8.4%; without concomitant AF: 1.5%, 1.5%, 2.0%, 3.0%, 3.7%, and 7% and (2) all-cause death with concomitant AF: 19.8%, 19.5%, 26.1%, 35.1%, 37.7%, and 45.5%; without concomitant AF: 7.6%, 8.3%, 17.8%, 25.6%, 27.9%, and 35.0%. At high CHA2DS2-VASc scores (≥4), the absolute risk of thromboembolism was high regardless of presence of AF (for a score of 4, 9.7% vs 8.2% for patients without and with concomitant AF, respectively; overall P<.001 for interaction). C statistics and negative predictive values indicate that the CHA2DS2-VASc score performed modestly in this HF population with and without AF (for ischemic stroke, 1-year C statistics, 0.67 [95% CI, 0.65-0.68] and 0.64 [95% CI, 0.61-0.67], respectively; 1-year negative predictive values, 92% [95% CI, 91%-93%] and 91% [95% CI, 88%-95%], respectively). Among patients with incident HF with or without AF, the CHA2DS2-VASc score was associated with risk of ischemic stroke, thromboembolism, and death. The absolute risk of thromboembolic complications was higher among patients without AF compared with patients with concomitant AF at high CHA2DS2-VASc scores. However, predictive accuracy was modest, and the clinical utility of the CHA2DS2-VASc score in patients with HF remains to be determined.


Effects of remote ischemic preconditioning in high-risk patients undergoing cardiac surgery (Remote IMPACT): a randomized controlled trial.
Remote ischemic preconditioning is a simple therapy that may reduce cardiac and kidney injury. We undertook a randomized controlled trial to evaluate the effect of this therapy on markers of heart and kidney injury after cardiac surgery. Patients at high risk of death within 30 days after cardiac surgery were randomly assigned to undergo remote ischemic preconditioning or a sham procedure after induction of anesthesia. The preconditioning therapy was three 5-minute cycles of thigh ischemia, with 5 minutes of reperfusion between cycles. The sham procedure was identical except that ischemia was not induced. The primary outcome was peak creatine kinase-myocardial band (CK-MB) within 24 hours after surgery (expressed as multiples of the upper limit of normal, with log transformation). The secondary outcome was change in creatinine level within 4 days after surgery (expressed as log-transformed micromoles per litre). Patient-important outcomes were assessed up to 6 months after randomization. We randomly assigned 128 patients to remote ischemic preconditioning and 130 to the sham therapy. There were no significant differences in postoperative CK-MB (absolute mean difference 0.15, 95% confidence interval [CI] -0.07 to 0.36) or creatinine (absolute mean difference 0.06, 95% CI -0.10 to 0.23). Other outcomes did not differ significantly for remote ischemic preconditioning relative to the sham therapy: for myocardial infarction, relative risk (RR) 1.35 (95% CI 0.85 to 2.17); for acute kidney injury, RR 1.10 (95% CI 0.68 to 1.78); for stroke, RR 1.02 (95% CI 0.34 to 3.07); and for death, RR 1.47 (95% CI 0.65 to 3.31). Remote ischemic precnditioning did not reduce myocardial or kidney injury during cardiac surgery. This type of therapy is unlikely to substantially improve patient-important outcomes in cardiac surgery. ClinicalTrials.gov, no. NCT01071265.