Emergency preparedness.
The Boy Scout motto is "be prepared," but can your home health agency abide by this standard? The post-9/11 days of 2001 and the natural disasters that have threatened people and plagued our home and countries abroad illustrate the heightened level of awareness and preparedness home healthcare agencies must achieve to satisfactorily meet emergency preparedness standards. Community-based nurses often are on the front line of response to a man-made, biological, or naturally occurring event. You may have been assigned to work on a plan for your agency's response or have had questions asked about preparedness by your clients and family members. Here are six Web sites to get you started on the answers to those questions and concerns.


Inhibition of Mycobacterium tuberculosis PknG by non-catalytic rubredoxin domain specific modification: reaction of an electrophilic nitro-fatty acid with the Fe-S center.
PknG from Mycobacterium tuberculosis is a Ser/Thr protein kinase that regulates key metabolic processes within the bacterial cell as well as signaling pathways from the infected host cell. This multidomain protein has a conserved canonical kinase domain with N- and C-terminal flanking regions of unclear functional roles. The N-terminus harbors a rubredoxin-like domain (Rbx), a bacterial protein module characterized by an iron ion coordinated by four cysteine residues. Disruption of the Rbx-metal binding site by simultaneous mutations of all the key cysteine residues significantly impairs PknG activity. This encouraged us to evaluate the effect of a nitro-fatty acid (9- and 10-nitro-octadeca-9-cis-enoic acid; OA-NO2) on PknG activity. Fatty acid nitroalkenes are electrophilic species produced during inflammation and metabolism that react with nucleophilic residues of target proteins (i.e., Cys and His), modulating protein function and subcellular distribution in a reversible manner. Here, we show that OA-NO2 inhibits kinase activity by covalently adducting PknG remote from the catalytic domain. Mass spectrometry-based analysis established that cysteines located at Rbx are the specific targets of the nitroalkene. Cys-nitroalkylation is a Michael addition reaction typically reverted by thiols. However, the reversible OA-NO2-mediated nitroalkylation of the kinase results in an irreversible inhibition of PknG. Cys adduction by OA-NO2 induced iron release from the Rbx domain, revealing a new strategy for the specific inhibition of PknG. These results affirm the relevance of the Rbx domain as a target for PknG inhibition and support that electrophilic lipid reactions of Rbx-Cys may represent a new drug strategy for specific PknG inhibition.


Lack of association between dopamine D4 receptor gene and personality traits.
Personality traits have shown considerable heritable components. Association between alleles of a polymorphism in the third exon of the dopamine D4 receptor gene (DRD4) and the personality trait Novelty Seeking has been reported. Recently, in a sample of Swedish non-psychiatric subjects we could not detect any significant relationships between the same polymorphism and Novelty Seeking related scales in the Karolinska Scales of Personality (KSP). However, there was a tendency in the direction of the proposed association. There were also tentative associations between an exon I 13 bp deletion polymorphism and the personality traits Socialization and Guilt. We investigated a new Swedish population-based sample (N = 167) investigated with the KSP for three DRD4 polymorphisms. Neither of the previous results were replicated. Combining the previous and the present samples did not give rise to any significant association between DRD4 polymorphisms and personality scales. The dopamine D4 receptor gene is probably not of importance to the different personality dimensions as measured by the Karolinska Scales of Personality.


Predictors of Problem Gambling in the U.S.
In this article we examine data from a national U.S. adult survey of gambling to determine correlates of problem gambling and discuss them in light of theories of the etiology of problem gambling. These include theories that focus on personality traits, irrational beliefs, anti-social tendencies, neighborhood influences and availability of gambling. Results show that males, persons in the 31-40 age range, blacks, and the least educated had the highest average problem gambling symptoms. Adults who lived in disadvantaged neighborhoods also had the most problem gambling symptoms. Those who attended religious services most often had the fewest problem gambling symptoms, regardless of religious denomination. Respondents who reported that it was most convenient for them to gamble had the highest average problem gambling symptoms, compared to those for whom gambling was less convenient. Likewise, adults with the personality traits of impulsiveness and depression had more problem gambling symptoms than those less impulsive or depressed. Respondents who had friends who approve of gambling had more problem gambling symptoms than those whose friends did not approve of gambling. The results for the demographic variables as well as for impulsiveness and religious attendance are consistent with an anti-social/impulsivist pathway to problem gambling. The results for depression are consistent with an emotionally vulnerable pathway to problem gambling.


Effects of oxytocin administration and conditioned oxytocin on brain activity: An fMRI study.
It has been demonstrated that secretion of several hormones can be classically conditioned, however, the underlying brain responses of such conditioning have never been investigated before. In this study we aimed to investigate how oxytocin administration and classically conditioned oxytocin influence brain responses. In total, 88 females were allocated to one of three groups: oxytocin administration, conditioned oxytocin, or placebo, and underwent an experiment consisting of three acquisition and three evocation days. Participants in the conditioned group received 24 IU of oxytocin together with a conditioned stimulus (CS) during three acquisition days and placebo with the CS on three evocation days. The oxytocin administration group received 24 IU of oxytocin and the placebo group received placebo during all days. On the last evocation day, fMRI scanning was performed for all participants during three tasks previously shown to be affected by oxytocin: presentation of emotional faces, crying baby sounds and heat pain. Region of interest analysis revealed that there was significantly lower activation in the right amygdala and in two clusters in the left superior temporal gyrus in the oxytocin administration group compared to the placebo group in response to observing fearful faces. The activation in the conditioned oxytocin group was in between the other two groups for these clusters but did not significantly differ from either group. No group differences were found in the other tasks. Preliminary evidence was found for brain activation of a conditioned oxytocin response; however, despite this trend in the expected direction, the conditioned group did not significantly differ from other groups. Future research should, therefore, investigate the optimal timing of conditioned endocrine responses and study whether the findings generalize to other hormones as well.


Concurrent assessment of epidemiological and operational uncertainties for optimal outbreak control: Ebola as a case study.
Determining how best to manage an infectious disease outbreak may be hindered by both epidemiological uncertainty (i.e. about epidemiological processes) and operational uncertainty (i.e. about the effectiveness of candidate interventions). However, these two uncertainties are rarely addressed concurrently in epidemic studies. We present an approach to simultaneously address both sources of uncertainty, to elucidate which source most impedes decision-making. In the case of the 2014 West African Ebola outbreak, epidemiological uncertainty is represented by a large ensemble of published models. Operational uncertainty about three classes of interventions is assessed for a wide range of potential intervention effectiveness. We ranked each intervention by caseload reduction in each model, initially assuming an unlimited budget as a counterfactual. We then assessed the influence of three candidate cost functions relating intervention effectiveness and cost for different budget levels. The improvement in management outcomes to be gained by resolving uncertainty is generally high in this study; appropriate information gain could reduce expected caseload by more than 50%. The ranking of interventions is jointly determined by the underlying epidemiological process, the effectiveness of the interventions and the size of the budget. An epidemiologically effective intervention might not be optimal if its costs outweigh its epidemiological benefit. Under higher-budget conditions, resolution of epidemiological uncertainty is most valuable. When budgets are tight, however, operational and epidemiological uncertainty are equally important. Overall, our study demonstrates that significant reductions in caseload could result from a careful examination of both epidemiological and operational uncertainties within the same modelling structure. This approach can be applied to decision-making for the management of other diseases for which multiple models and multiple interventions are available.


Validation of the 5-Item Medication Adherence Report Scale in Older Stroke Patients in Iran.
There is a lack of feasible and validated measures to self-assess medication adherence for older patients with stroke. In addition, the potential determinants of medication adherence for older patients with stroke remain unclear. The aims of this study were to (1) examine the psychometric properties of a 5-item questionnaire on medication adherence, specifically the 5-item Medication Adherence Report Scale (MARS-5), and (2) explore the determinants of medication adherence. Stroke patients older than 65 years (N = 523) filled out the MARS-5 and the Hospital Anxiety and Depression Scale. The medication possession rate (MPR) was calculated to measure the objective medication adherence. Several clinical characteristics (stroke types, blood pressure, comorbidity, HbA1c, quantity of prescribed drugs, fasting blood glucose, and total cholesterol) and background information were collected. We used Rasch analysis with a differential item functioning test to examine psychometric properties. All 5 items in the MARS-5 fit in the same construct (ie, medication adherence), no differential item functioning items were displayed in the MARS-5 across gender, and the MARS-5 total score was strongly correlated with the MPR (r = 0.7). Multiple regression models showed that the MARS-5 and the MPR shared several similar determinants. In addition, the variance of the MARS-5 (R = 0.567) was more than that of the MPR (R = 0.300). The MARS-5 is a feasible and valid self-assessed medication adherence for older patients with stroke. In addition, several determinants were found to be related to medication adherence for older patients with stroke. Healthcare providers may want to take heed of these determinants to improve medication adherence for this population.


Pyranicin, a non-classical annonaceous acetogenin, is a potent inhibitor of DNA polymerase, topoisomerase and human cancer cell growth.
This report describes the inhibitory activities of the natural and non-natural acetogenins [mucocin (compound 1), jimenezin (compound 2), 19-epi jimenezin (compound 3), muconin (compound 4), pyranicin (compound 5), pyragonicin (compound 6), 10-epi pyragonicin (compound 7), and a gamma-lactone (compound 8)], which were synthesized by us, against DNA polymerase (pol), DNA topoisomerase (topo), and human cancer cell growth. Among the compounds tested, compound 5 was revealed to be the strongest inhibitor of the animal pols and human topos tested, and the IC50 values for pols and topos were 2.3-15.8 and 5.0-7.5 microM, respectively. The compound also suppressed human cancer cell (promyelocytic leukemia cell line, HL-60) growth with the same tendency as the inhibition of pols and topos and the LD50 value was 9.4 microM. Compound 5 arrested the cells at G2/M and G1 phases, and prevented the incorporation of thymidine into the cells, indicating that it blocks DNA replication by inhibiting the activity of pols and topos. This compound also induced apoptosis of the cells. Based on these results, the action mode of compound 5 is discussed.


HIV Infection and HIV-Associated Behaviors Among Persons Who Inject Drugs - 23 Metropolitan Statistical Areas, United States, 2018.
In the United States, 10% of HIV infections diagnosed in 2018 were attributed to unsafe injection drug use or male-to-male sexual contact among persons who inject drugs (PWID) (1). In 2017, among PWID or men who have sex with men and who inject drugs (MSM-ID), 76% of those who received a diagnosis of HIV infection lived in urban areas* (2). To monitor the prevalence of HIV infection and associated behaviors among persons who reported injecting drugs in the past 12 months, including MSM-ID, CDC's National HIV Behavioral Surveillance (NHBS) conducts interviews and HIV testing among populations of persons at high risk for HIV infection (MSM, PWID, and heterosexually active adults at increased risk for HIV infection) in selected metropolitan statistical areas (MSAs) (3). The estimated HIV infection prevalence among PWID in 23 MSAs surveyed in 2018 was 7%. Among HIV-negative PWID, an estimated 26% receptively shared syringes and 68% had condomless vaginal sex during the preceding 12 months. During the same period, 57% had been tested for HIV infection, and 55% received syringes from a syringe services program (SSP). While overall SSP use did not significantly change since 2015, a substantial decrease in SSP use occurred among Black PWID, and HIV prevalence among Black PWID was higher than that among Hispanic and White PWID. These findings underscore the importance of continuing and expanding HIV prevention programs and community-based strategies for PWID, such as those provided by SSPs, especially following service disruptions created by the COVID-19 pandemic (4). Efforts are needed to ensure that PWID have low-barrier access to comprehensive and integrated needs-based SSPs (where legally permissible) that include provision of sterile syringes and safe syringe disposal, HIV and hepatitis C virus (HCV) testing and referrals to HIV and HCV treatment, HIV preexposure prophylaxis, and treatment for substance use and mental health disorders.


Tricarboxylic acid cycle intermediates accumulate at the onset of intense exercise in man but are not essential for the increase in muscle oxygen uptake.
It was proposed that a contraction-induced increase in tricarboxylic acid cycle intermediates (TCAI) is obligatory for the increase in muscle oxygen uptake at the start of exercise. To test this hypothesis, we measured changes in muscle TCAI during the initial seconds of intense exercise and used dichloroacetate (DCA) in an attempt to alter the level of TCAI. Five men performed strenuous leg kicking exercise (64+/-8 W) under noninfused control (CON) and DCA-supplemented conditions; biopsies (vastus lateralis) were obtained at rest and after 5, 15, and 180 s of exercise. In CON, the total concentration of three measured TCAI (SigmaTCAI: citrate, malate, and fumarate) increased (p<0.05) by 71% during the first 15 s of exercise. The SigmaTCAI was lower (p<0.05) in DCA than in CON at rest [0.18+/-0.02 vs 0.64+/-0.09 mmol kg(-1) dry weight (d.w.)], after 5 s (0.30+/-0.07 vs 0.85+/-0.14 mmol kg(-1) d.w.), and 15 s of exercise (0.60+/-0.07 vs 1.09+/-0.16 mmol kg(-1) d.w.), but not different after 3 min (3.12+/-0.53 vs 3.23+/-0.55 mmol kg(-1) d.w.). Despite differences in the level of muscle TCAI, muscle phosphocreatine degradation was similar in DCA and CON during the first 15 s of exercise (17.5+/-3.3 vs 25.6+/-4.1 mmol kg(-1) d.w.). Taken together with our previous observation that DCA does not alter muscle oxygen uptake during the initial phase of intense leg kicking exercise (Bangsbo et al. Am J Physiol 282:R273-R280, 2002), the present data suggest that muscle TCAI accumulate during the initial seconds of exercise; however, this increase is not essential for the contraction-induced increase in mitochondrial respiration.


Quercetin ameliorates oxidative stress, inflammation and apoptosis in the heart of streptozotocin-nicotinamide-induced adult male diabetic rats.
Quercetin is known to possess beneficial effects in ameliorating diabetic complications, however the mechanisms underlying cardioprotective effect of this compound in diabetes is not fully revealed. In this study, quercetin effect on oxidative stress, inflammation and apoptosis in the heart in diabetes were investigated. Normal and streptozotocin-nicotinamide induced adult male diabetic rats received quercetin (10, 25 and 50mg/kg/bw) orally for 28days were anesthetized and hemodynamic parameters i.e. systolic blood pressure (SBP), diastolic blood pressure (DBP) and heart rate (HR) were measured. Blood was collected for analyses of fasting glucose (FBG), insulin and cardiac injury marker levels (troponin-C, CK-MB and LDH). Following sacrificed, heart was harvested and histopathological changes were observed. Heart was subjected for analyses of oxidative stress marker i.e. lipid peroxidation and activity and expression levels of anti-oxidative enzymes i.e. SOD, CAT and GPx. Levels of inflammation in the heart were determined by measuring nuclear factor (p65-NF-κB), tumor necrosis factor (TNF-α), interleukins (IL)-1β and IL-6 levels by using enzyme-linked immunoassay (ELISA). Distribution and expression levels of TNF-α and Ikk-β (inflammatory markers), caspase-3, caspase-9, Blc-2 and Bax (apoptosis markers) in the heart were identified by immunohistochemistry and Western blotting respectively. Administration of quercetin to diabetic rats caused significant decrease in FBG and cardiac injury marker levels with increased in insulin levels. In diabetic rat heart, lesser histopathological changes were observed with oxidative stress, inflammation and apoptosis levels markedly decreased. Quercetin could potentially be used to ameliorate myocardial damage due to oxidative stress, inflammation and apoptosis in diabetes.


Age Group Comparisons of TENS Response Among Individuals With Chronic Axial Low Back Pain.
Chronic low back pain (CLBP) is a highly prevalent and disabling musculoskeletal pain condition among older adults. Transcutaneous electrical nerve stimulation (TENS) is commonly used to treat CLBP, however response to TENS in older adults compared with younger adults is untested. In a dose-response study stratified by age, 60 participants with axial CLBP (20 young, 20 middle-aged, 20 older) received four 20-minute sessions of high-frequency high-intensity TENS over a 2- to 3-week period in a laboratory-controlled setting. Experimental measures of pain sensitivity (mechanical pressure pain detection threshold) and central pain excitability (phasic heat temporal summation and heat aftersensations) were assessed before and after TENS. Episodic or immediate axial CLBP relief was assessed after TENS via measures of resting pain, movement-evoked-pain, and self-reported disability. Cumulative or prolonged axial CLBP relief was assessed by comparing daily pain reports across sessions. Independent of age, individuals experienced episodic increase in the pressure pain detection threshold and reduction in aftersensation after TENS application. Similarly, all groups, on average, experienced episodic axial CLBP relief via improved resting pain, movement-evoked pain, and disability report. Under this design, no cumulative effect was observed as daily pain did not improve for any age group across the 4 sessions. However, older adults received higher TENS amplitude across all sessions to achieve TENS responses similar to those in younger adults. These findings suggest that older adults experience similar episodic axial CLBP relief to that of younger individuals after high-frequency, high-intensity TENS when higher dose parameters are used. This study examined age group differences in experimental and axial CLBP response to TENS, delivered under the current recommended parameters of strong, but tolerable amplitude. Older adults had comparable TENS response although at higher TENS amplitude than younger adults, which may have important mechanistic and clinical implications.


Obesity as a disease: has the AMA resolution had an impact on how physicians view obesity?
In 2013, the American Medical Association (AMA) passed a resolution characterizing obesity as a disease. It is unclear whether primary care physicians (PCPs) agree with this characterization and how their agreement or lack thereof affects their treatment of patients with obesity. We sought to understand PCP opinions about the AMA obesity resolution and how it has affected management of patients with obesity. Small, medium, and large communities in Wisconsin METHODS: Focus groups were conducted with PCPs in Wisconsin. PCPs were asked whether they considered obesity a disease and what they factored into this consideration, including the AMA decision. A directed approach to content analysis was used to analyze the data. A taxonomy of consensus codes was developed, coding summaries were generated, and representative quotes were identified. Three focus groups comprising a total of 16 PCP participants were conducted. Not all PCPs were aware of the AMA resolution. PCPs held divergent opinions on whether obesity represented a disease, primarily focusing their considerations on obesity as a risk factor versus a disease. They also discussed how considering obesity as a disease affects the patient-doctor relationship, insurance coverage, physician reimbursement, and research. The AMA resolution did not appear to have made a significant impact on PCP opinions or management practices in our focus groups in Wisconsin. Follow-up surveys that quantify the prevalance of these opinions and practices at the state and national levels would be highly informative.


Premorbid adjustment profiles in psychosis and the role of familial factors.
Disease heterogeneity in patients with psychotic disorder may be explained by distinct profiles of premorbid adjustment. The current study explored premorbid adjustment profiles in patients with psychotic disorders, associations with cognitive and clinical characteristics after disease onset, and the role of familial factors. A total of 666 patients with psychosis (predominantly schizophrenia), 673 siblings, 575 parents, and 585 controls were included in this study. Cluster analyses were performed on the patients' scores of the Premorbid Adjustment Scale (PAS), using information on domains (social, academic) and age epochs (childhood, early adolescence, late adolescence). Resulting profiles were compared with characteristics in patients and their unaffected relatives. Six clusters, labeled normal, social intermediate, academic decline, overall decline, overall intermediate, and overall impaired adjustment, were identified in patients. Patients in different clusters differed from each other on cognitive, clinical, and functional characteristics after disease onset. Heterogeneity in the patient population may be explained in part by the adjustment profile prior to disease onset. This is in line with theories that propose different etiologies in the development of psychosis. Patient profiles were expressed in unaffected siblings, suggesting a role for familial factors.


Physical function in ankylosing spondylitis is independently determined by both disease activity and radiographic damage of the spine.
To study the relationship between disease activity, radiographic damage and physical function in patients with ankylosing spondylitis (AS) PATIENTS AND METHODS: Baseline and 2-year data of the Outcome in Ankylosing Spondylitis International Study (OASIS)(217 patients) were used. Physical function was expressed by the Bath Ankylosing Spondylitis Functional Index (BASFI) and the Dougados Functional Index (DFI); disease activity by the Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) and by erythrocyte sedimentation rate and C-reactive protein; and structural damage by the modified Stoke Ankylosing Spondylitis Spine Score (mSASSS). Syndesmophyte- and non-syndesmophyte sum cores, and numbers of affected (bridged) vertebral units were derived from the mSASSS. Univariate correlations were calculated on baseline values using the Spearman rank correlation. Multivariate associations were investigated by generalised estimating equations (GEE) on baseline and 2-year data. mSASSS correlated moderately well with BASFI (Spearman's r = 0.45) and DFI (r = 0.38). BASDAI correlated well with BASFI (r = 0.66) and DFI (r = 0.59). Correlation coefficients for mSASSS versus BASFI and DFI decreased by increasing levels of BASDAI, being zero at the highest quintile of BASDAI. GEE showed that both BASDAI and mSASSS independently and significantly helped to explain either BASFI or DFI. Results were similar for syndesmophyte sum score, non-syndesmophyte sum score, number of affected VUs or number of VUs with bridging. The lumbar part of the mSASSS contributed similarly to the cervical part in explaining BASFI/DFI. Physical function impairment in AS is independently caused by patient-reported disease activity and the level of structural damage of the lumbar and cervical spine. Syndesmophytes and other radiographic abnormalities contribute to physical function impairment.


A novel topology for representing protein folds.
Various topologies for representing 3D protein structures have been advanced for purposes ranging from prediction of folding rates to ab initio structure prediction. Examples include relative contact order, Delaunay tessellations, and backbone torsion angle distributions. Here, we introduce a new topology based on a novel means for operationalizing 3D proximities with respect to the underlying chain. The measure involves first interpreting a rank-based representation of the nearest neighbors of each residue as a permutation, then determining how perturbed this permutation is relative to an unfolded chain. We show that the resultant topology provides improved association with folding and unfolding rates determined for a set of two-state proteins under standardized conditions. Furthermore, unlike existing topologies, the proposed geometry exhibits fine scale structure with respect to sequence position along the chain, potentially providing insights into folding initiation and/or nucleation sites.


Genetic characterization of ABT-199 sensitivity in human AML.
Acute myeloid leukemias (AML) with mutations in the NPM1 gene (NPM1c+) represent a large AML subgroup with varying response to conventional treatment, highlighting the need to develop targeted therapeutic strategies for this disease. We screened a library of clinical drugs on a cohort of primary human AML specimens and identified the BCL2 inhibitor ABT-199 as a selective agent against NPM1c+ AML. Mutational analysis of ABT-199-sensitive and -resistant specimens identified mutations in NPM1, RAD21, and IDH1/IDH2 as predictors of ABT-199 sensitivity. Comparative transcriptome analysis further uncovered BCL2A1 as a potential mediator of ABT-199 resistance in AML. In line with our observation that RAD21 mutation confers sensitivity to ABT-199, we provide functional evidence that reducing RAD21 levels can sensitize AML cells to BCL2 inhibition. Moreover, we demonstrate that ABT-199 is able to produce selective anti-AML activity in vivo toward AML with mutations associated with compound sensitivity in PDX models. Overall, this study delineates the contribution of several genetic events to the response to ABT-199 and provides a rationale for the development of targeted therapies for NPM1c+ AML.


Health technology assessment in Italy.
The aim of this study was to review the history of health technology assessment (HTA) in Italy. Founded in 1978, the Italian National Health Service (NHS) has been strongly regionalized mainly after a constitutional reform, which started a devolution process. HTA started in the 1980s at the National Institute of Health and in a few University Hospitals, with a focus on big ticket technology: that process was driven by clinical engineers. In recent years, HTA is becoming an important tool for decision-making processes at central, regional, and local levels. In particular, the National Agency for Regional Health Services (AGENAS) and five regions (of twenty-one) are strongly committed to develop HTA initiatives connected with the planning process. At the local level, the hospital-based HTA activity is probably the most important peculiarity of the country and the real driver of the HTA movement.


Desert Beetle-Inspired Superwettable Patterned Surfaces for Water Harvesting.
With the impacts of climate change and impending crisis of clean drinking water, designing functional materials for water harvesting from fog with large water capacity has received much attention in recent years. Nature has evolved different strategies for surviving dry, arid, and xeric conditions. Nature is a school for human beings. In this contribution, inspired by the Stenocara beetle, superhydrophilic/superhydrophobic patterned surfaces are fabricated on the silica poly(dimethylsiloxane) (PDMS)-coated superhydrophobic surfaces using a pulsed laser deposition approach with masks. The resultant samples with patterned wettability demonstrate water-harvesting efficiency in comparison with the silica PDMS-coated superhydrophobic surface and the Pt nanoparticles-coated superhydrophilic surface. The maximum water-harvesting efficiency can reach about 5.3 g cm-2 h-1 . Both the size and the percentage of the Pt-coated superhydrophilic square regions on the patterned surface affect the condensation and coalescence of the water droplet, as well as the final water-harvesting efficiency. The present water-harvesting strategy should provide an avenue to alleviate the water crisis facing mankind in certain arid regions of the world.


Living with oropharyngeal dysphagia: effects of bolus modification on health-related quality of life--a systematic review.
Difficulty swallowing, oropharyngeal dysphagia, is widespread among many patient populations (such as stroke and cancer groups) and aged community-dwelling individuals. It is commonly managed with bolus modification: altering food (usually cutting, mashing or puréeing) or fluids (typically thickening) to make them easier or safer to swallow. Although this treatment is ubiquitous, anecdotal evidence suggests patients dislike this management, and this may affect compliance and well-being. This review aimed to examine the impact of bolus modification on health-related quality of life. A systematic review of the literature was conducted by speech pathologists with experience in oropharyngeal dysphagia. The literature search was completed with electronic databases, PubMed and Embase, and all available exclusion dates up to September 2012 were used. The search was limited to English-language publications which were full text and appeared in peer-reviewed journals. Eight studies met the inclusion criteria. Generally, bolus modification was typically associated with worse quality of life. Modifications to foods appeared to be more detrimental than modifications to fluids, but this may be due to the increased severity of dysfunction that is implied by the necessity for significant alterations to foods. The number of studies retrieved was quite small. The diverse nature of methodologies, terminologies and assessment procedures found in the studies makes the results difficult to generalise. Overall, even though the severity of dysphagia may have been a confounding factor, the impact of bolus modification on health-related quality of life in patients with oropharyngeal dysphagia appears to be negative, with increased modification of food and fluids often correlating to a decreased quality of life. Further, associated disease factors, such as decreased life expectancy, may also have affected health-related quality of life. More research is needed.


Effects of dexamethasone on host innate and adaptive immune responses and parasite development in rainbow trout Oncorhynchus mykiss infected with Loma salmonae.
The effects of dexamethasone (dex) treatment on infections with the microsporidian parasite, Loma salmonae and the effects of dex on initiation of the adaptive immune response were investigated in rainbow trout, Oncorhynchus mykiss experimentally infected with the parasite. Dex treatment resulted in significantly higher infections with the parasite in the gills and other internal organs, suggesting that dex inhibits aspects of the innate immune response to L. salmonae; the heavier infections in the gills and organs of rainbow trout resembled infections seen in Chinook salmon. Mean xenoma counts per microscope field in the gills of fish infected with L. salmonae treated with dex or left untreated were 169 and 30, respectively. Although higher numbers of xenomas were observed in dex treated fish, the xenomas were generally smaller in size than in infected control fish. The xenomas in dex treated fish showed morphological signs of degeneration including loss and degeneration of early parasite stages, accumulation of amorphous material in xenomas, and infiltration with phagocytic cells containing degenerated parasites. The xenomas in infected untreated fish had larger xenomas with a more uniform size and contained identifiable parasite stages in the cytoplasm. According to this study, once fish have developed an adaptive immune response to the parasite by previous exposure, then fish have 100% protection to reinfection even when treated with heavy doses of dex. L. salmonae immune fish treated or untreated with dex during reinfection with the parasite developed no xenomas in the gills 6 weeks post reinfection. These results indicate that once the cellular response is primed to L. salmonae, then dex related immunosuppression does not reduce the effectiveness of the adaptive immune response.


Effect of vibration on a canine cutaneous artery.
Vibration of rings of isolated canine saphenous arteries depressed contractions induced by potassium chloride, prostaglandin F2 alpha, and activation of the adrenergic nerve endings by electrical stimulation. Peak contractions to exogenous norepinephrine were not significantly affected by vibration, being augmented, unchanged, or depressed, whereas contractions during the stable plateau phase were depressed. The calcium entry blocker diltiazem reduced the peak response but not the stable plateau phase of the contraction to norepinephrine; in the presence of diltiazem, vibration still depressed the latter. When vibration was applied during the steady state of contractions evoked by electrical stimulation, the depression was immediate, and its extent increased with both the amplitude (0.025-0.10 mm) and the frequency (30-150 Hz) of vibration. In arteries labeled with [3H]norepinephrine, vibration (120 Hz, 0.1 mm amplitude) during electrical stimulation induced a slight but significant increase in the release of labeled transmitter. It is suggested that the depression of contractions to potassium ions, prostaglandin F2 alpha, sympathetic nerve stimulation, and the plateau phase of the response to exogenous norepinephrine are caused by vibration depressing the force-generating process in vascular smooth muscle. Failure of vibration to significantly depress the peak contraction to norepinephrine may be explained by the facilitation by vibration of the influx of extracellular calcium ions.


Ginsenoside Rg3 (Shenyi Capsule) Combined with Chemotherapy for Digestive System Cancer in China: A Meta-Analysis and Systematic Review.
In China, ginsenoside Rg3 is often used in combination with chemotherapy to treat digestive system cancer. We here performed a meta-analysis and systematic review to provide a much needed high-quality evaluation of the efficacy and safety of ginsenoside Rg3 combined with chemotherapy in these cancers. The PubMed, EMBASE, Cochrane Library, China National Knowledge Infrastructure (CNKI), Wanfang, and Weipu (VIP) databases were searched. All randomized controlled trials (RCTs) concerning ginsenoside Rg3 combined with chemotherapy for digestive system cancer were selected. Dichotomous data were expressed as odds ratios (ORs) with 95% confidence intervals (CI). The methodological quality of the included studies was evaluated according to the Cochrane evidence-based medicine system, and the statistical analyses were performed with Review Manager 5.3 and STATA 12.0 software. In addition, the Grades of Recommendation Assessment, Development and Evaluation (GRADE) approach was used to rate the quality of the evidence. Trial sequential analysis (TSA) was used to evaluate information size and treatment benefits. A total of 18 trials comprising 1531 patients were included in this study. The results revealed that the trials were of sufficient standard to draw reliable conclusions that ginsenoside Rg3 combined with chemotherapy could improve the objective response rate (ORR; OR 2.17, 95% CI 1.72-2.73), disease control rate (DCR; OR 2.83, 95% CI 2.02-3.96), 1-year survival rate (SR; OR = 2.33, 95% CI = 1.24-4.37), Karnofsky Performance Scale (KPS; OR 2.67, 95% CI 1.76-4.03), gastrointestinal dysfunction (OR 0.44, 95% CI 0.31-0.61), and the decline of leucocyte count (OR 0.28, 95% CI 0.21-0.38). Ginsenoside Rg3 combined with chemotherapy can improve the clinical efficacy and alleviate treatment-induced side effects for digestive system cancer.


Human immunodeficiency virus infection in pregnancy.
The incidence and prevalence of human immunodeficiency virus (HIV) infection in women of child-bearing age continue to increase both internationally and in Canada. The care of HIV-infected pregnant women is complex, and multiple issues must be addressed, including the current and future health of the woman, minimization of the risk of maternal-infant HIV transmission, and maintenance of the well-being of the fetus and neonate. Vertical transmission of HIV can occur in utero, intrapartum and postpartum, but current evidence suggests that the majority of transmission occurs toward end of term, or during labour and delivery. Several maternal and obstetrical factors influence transmission rates, which can be reduced by optimal medical and obstetrical care. Zidovudine therapy has been demonstrated to reduce maternal-infant transmission significantly, but several issues, including the short and long term safety of antiretrovirals and the optimal use of combination antiretroviral therapy in pregnancy, remain to be defined. It is essential that health care workers providing care to these women fully understand the natural history of HIV disease in pregnancy, the factors that affect vertical transmission and the management issues during pregnancy. Close collaboration among a multidisciplinary team of knowledgeable health professionals and, most importantly, the woman herself can improve both maternal and infant outcomes.


Awareness of forensic odontology among police personnel: A new ray of hope in forensic odontology.
Police personnel play an important role in collecting and producing evidence. Knowledge about the various aspects of forensic as well as dental sciences and related evidence in them provide a golden opportunity to forensic odontologists to actively participate in the identification of the accused or victim. They can also act as an expert witness in court to produce forensic dental evidence. To evaluate the awareness and knowledge about the utilization of forensic odontology during evidence collection by the crime scene investigation (CSI) officers. Four hundred police officers were included in this survey. A questionnaire was designed to assess the awareness and knowledge about forensic odontology and application of the known knowledge in identifying and considering the dental evidences. Data were analyzed using the software Statistical Package for Social Sciences (SPSS, Chicago, Il, USA) version 17.0 by comparing the overall awareness of forensic odontology among the trained SI officers and trainee police personnel. The collected results showed that there is a requirement for changes in the current practice of evidence collection and highlighted the need for better communication between the police personnel and forensic odontologists. A significantly higher number of police officers in both the trained and trainee groups reported knowledge about the subject (P < 0.001) through newspapers and mass media as the sources of knowledge. Even though the respondents have knowledge about forensic odontology, there is a lack of communication and facilities in their system; hence, steps must be taken to educate the police personnel about the application of forensic odontology.


Chronic cannabis abuse raises nerve growth factor serum concentrations in drug-naive schizophrenic patients.
Long-term cannabis abuse may increase the risk of schizophrenia. Nerve growth factor (NGF) is a pleiotropic neurotrophic protein that is implicated in development, protection and regeneration of NFG-sensitive neurones. We tested the hypothesis that damage to neuronal cells in schizophrenia is precipitated by the consumption of cannabis and other neurotoxic substances, resulting in raised NGF serum concentrations and a younger age for disease onset. The NGF serum levels of 109 consecutive drug-naive schizophrenic patients were measured and compared with those of healthy controls. The results were correlated with the long-term intake of cannabis and other illegal drugs. Mean (+/- SD) NGF serum levels of 61 control persons (33.1 +/- 31.0 pg/ml) and 76 schizophrenics who did not consume illegal drugs (26.3 +/- 19.5 pg/ml) did not differ significantly. Schizophrenic patients with regular cannabis intake (> 0.5 g on average per day for at least 2 years) had significantly raised NGF serum levels of 412.9 +/- 288.4 pg/ml (n = 21) compared to controls and schizophrenic patients not consuming cannabis (p < 0.001). In schizophrenic patients who abused not only cannabis, but also additional substances, NGF concentrations were as high as 2336.2 +/- 1711.4 pg/ml (n = 12). On average, heavy cannabis consumers suffered their first episode of schizophrenia 3.5 years (n = 21) earlier than schizophrenic patients who abstained from cannabis. These results indicate that cannabis is a possible risk factor for the development of schizophrenia. This might be reflected in the raised NGF-serum concentrations when both schizophrenia and long-term cannabis abuse prevail.


Are pollinating hawk moths declining in the Northeastern United States? An analysis of collection records.
Increasing attention to pollinators and their role in providing ecosystem services has revealed a paucity of studies on long-term population trends of most insect pollinators in many parts of the world. Because targeted monitoring programs are resource intensive and unlikely to be performed on most insect pollinators, we took advantage of existing collection records to examine long-term trends in northeastern United States populations of 26 species of hawk moths (family Sphingidae) that are presumed to be pollinators. We compiled over 6,600 records from nine museum and 14 private collections that spanned a 112-year period, and used logistic generalized linear mixed models (GLMMs) to examine long-term population trends. We controlled for uneven sampling effort by adding a covariate for list length, the number of species recorded during each sampling event. We found that of the 22 species for which there was sufficient data to assess population trends, eight species declined and four species increased in detection probability (the probability of a species being recorded during each year while accounting for effort, climate, and spatial effects in the GLMMs). Of the four species with too few records to statistically assess, two have disappeared from parts of their ranges. None of the four species with diurnal adults showed a trend in detection probability. Two species that are pests of solanaceous crops declined, consistent with a seven-fold drop in the area planted in tobacco and tomato crops. We found some evidence linking susceptibility to parasitoidism by the introduced fly Compsilura concinnata (Tachinidae) to declines. Moths with larvae that feed on vines and trees, where available evidence indicates that the fly is most likely to attack, had a greater propensity to decline than species that use herbs and shrubs as larval host plants. Species that develop in the spring, before Compsilura populations have increased, did not decline. However, restricting the analysis to hawk moth records from areas outside of a "refuge" area where Compsilura does not occur did not significantly increase the intensity of the declines as would be predicted if Compsilura was the primary cause of declines. Forests have recovered over the study period across most of the northeastern U.S., but this does not appear to have been a major factor because host plants of several of the declining species have increased in abundance with forest expansion and maturation. Climate variables used in the GLMMs were not consistently related to moth detection probability. Hawk moth declines may have ecological effects on both the plants pollinated by these species and vertebrate predators of the moths.


Spinal but not general anesthesia increases the ratio of T helper 1 to T helper 2 cell subsets in patients undergoing transurethral resection of the prostate.
Surgical stress and anesthesia cause immunosuppression that may predispose patients to postoperative infections. T helper lymphocytes play a major role in the immune response by controlling cell-mediated and humoral immunity. The type of immune response generated is determined by the differentiation of precursor T helper cells into Th1 or Th2 cells. Each cell subset secretes a particular array of cytokines that further augment the differentiation into that subset. Th1 cells produce interferon gamma and are responsible for cell-mediated immunity. Th2 cells produce interleukin-4 and are more effective in inducing humoral immunity. Cytokine concentrations are altered during surgery and anesthesia, which may effect Th cell predominance and, therefore, subsequent immune responses. We determined Th1 to Th2 cell ratios in patients undergoing transurethral resection of the prostate (TURP) using either spinal or general anesthesia. Mononuclear cells were isolated before anesthesia, immediately after surgery, and after 24 h from patients undergoing TURP, 10 under general anesthesia and 9 under spinal anesthesia. T helper cell subsets were quantified by using flow cytometry, and the ratio of Th1 to Th2 cells was calculated. Th1 to Th2 ratios in patients receiving spinal anesthesia increased over the three time points studied (P = 0.029) but did not change in patients who had general anesthesia (P = 0.11). At 24 h, Th1 to Th2 ratios were significantly higher in the spinal group than in patients who received general anesthesia (P = 0.0157). Total T helper cell numbers remained constant. These data suggest that, from an immunological viewpoint, spinal anesthesia, but not general anesthesia, benefits the patient by maintaining Th1 cell numbers, thereby promoting cellular immunity. Spinal anesthesia may result in less immunosuppression after surgery. We found that the ratio of T helper 1 to T helper 2 cells was higher in patients undergoing prostate surgery by spinal rather than general anesthesia. Th1 cells promote protective immune responses that may result in fewer postoperative infections.


A case of relapsed autoimmune hypothalamitis successfully treated with methylprednisolone and azathioprine.
Autoimmune hypothalamitis is a rare autoimmune neuroendocirne disease. A case of a 70-year-old female with autoimmune hypothalamitis was reported. The chief clinical characteristics were diabetes insipidus and adenopituitary function deficiency. Cranial magnetic resonance imaging (MRI) scan indicated a mass in the hypothalamus. The diagnosis of autoimmune hypothalamitis was presumed. After treatment with prednisone, there was a marked reduction in the mass and the hypothalamus-adenopituitary function partially improved. However, after glucocorticoid therapy was withdrawn, the hypothalamic lesion relapsed progressively. High dose methylprednisolone pulse therapy (HDMPT) in combination with azathioprine was initiated thereafter. During follow-up, MRI scan indicated the lesion shrank strikingly, and the patient's clinical condition improved as well. In view of the good response of the hypothalamic lesion to glucocorticoid and immunodepressant, the putative diagnosis of autoimmune hypothalamitis was confirmed. This case report suggested that HDMPT in combination with azathioprine therapy might be an effective trial for autoimmune hypothalamitis treatment.


Dual versus single vessel normothermic ex vivo perfusion of rat liver grafts using metamizole for vasodilatation.
Normothermic ex vivo liver perfusion (NEVLP) is a promising strategy to increase the donor pool in liver transplantation. Small animal models are essential to further investigate questions regarding organ preservation and reconditioning by NEVLP. A dual vessel small animal NEVLP (dNEVLP) model was developed using metamizole as a vasodilator and compared to conventional portovenous single vessel NEVLP (sNEVLP). Livers of male Wistar rats were perfused with erythrocyte-supplemented culture medium for six hours by either dNEVLP via hepatic artery and portal vein or portovenous sNEVLP. dNEVLP was performed either with or without metamizole treatment. Perfusion pressure and flow rates were constantly monitored. Transaminase levels were determined in the perfusate at the start and after three and six hours of perfusion. Bile secretion was monitored and bile LDH and GGT levels were measured hourly. Histopathological analysis was performed using liver and bile duct tissue samples after perfusion. Hepatic artery pressure was significantly lower in dNEVLP with metamizole administration. Compared to sNEVLP, dNEVLP with metamizole treatment showed higher bile production, lower levels of transaminases during and after perfusion as well as significantly lower necrosis in liver and bile duct tissue. Biochemical markers of bile duct injury showed the same trend. Our miniaturized dNEVLP system enables normothermic dual vessel rat liver perfusion. The administration of metamizole effectively ameliorates arterial vasospasm allowing for six hours of dNEVLP, with superior outcome compared to sNEVLP.


Predicting Adsorption Properties of Catalytic Descriptors on Bimetallic Nanoalloys with Site-Specific Precision.
Bimetallic nanoparticles present a vastly tunable structural and compositional design space rendering them promising materials for catalytic and energy applications. Yet it remains an enduring challenge to efficiently screen candidate alloys with atomic level specificity while explicitly accounting for their inherent stabilities under reaction conditions. Herein, by leveraging correlations between binding energies of metal adsorption sites and metal-adsorbate complexes, we predict adsorption energies of typical catalytic descriptors (OH*, CH3*, CH*, and CO*) on bimetallic alloys with site-specific resolution. We demonstrate that our approach predicts adsorption energies on top and bridge sites of bimetallic nanoparticles having generic morphologies and chemical environments with errors between 0.09 and 0.18 eV. By forging a link between the inherent stability of an alloy and the adsorption properties of catalytic descriptors, we can now identify active site motifs in nanoalloys that possess targeted catalytic descriptor values while being thermodynamically stable under working conditions.


Maternal smoking during pregnancy and infant stress response: test of a prenatal programming hypothesis.
Maternal smoking during pregnancy (MSDP) is associated with early and long-term neurobehavioral deficits; however mechanisms remain unknown. We tested the hypothesis that MSDP programs the hypothalamic pituitary adrenocortical (HPA) axis of the offspring leading to adverse outcomes. In an intensive, prospective study, we investigated associations between MSDP and infant cortisol stress response and explored whether alterations in cortisol response were mediated by epigenetic modulation of the placental glucocorticoid receptor gene (NR3C1). Participants were 100 healthy mother-infant pairs (53% MSDP-exposed; 42% female) from a low income, racially/ethnically diverse sample (55% minorities). MSDP was assessed by timeline followback interview verified by saliva and meconium cotinine. Infant cortisol responses to a neurobehavioral exam were assessed seven times over the first postnatal month. Methylation of placental NR3C1 promoter exon 1F was assessed using bisulfite pyrosequencing in a subsample (n=45). MSDP-exposed infants showed significantly and persistently attenuated basal and reactive cortisol levels over the first postnatal month vs. unexposed infants. Exploratory analyses revealed that MSDP was associated with altered methylation of the placental NR3C1 promoter; degree of methylation of the placental NR3C1 was associated with infant basal and reactive cortisol over the first postnatal month and mediated effects of MSDP on infant basal cortisol. Results provide initial support for our hypothesis that MSDP programs offspring HPA (dys)regulation. Epigenetic regulation of placental GR may serve as a novel underlying mechanism. Results may have implications for delineating pathways to adverse outcomes from MSDP.


Health-related social control and relationship interdependence among gay couples.
How gay partners influence each other to promote health and prevent human immunodeficiency virus (HIV) is poorly understood. The present study combined qualitative and quantitative methods to examine the experience of health-related social control and relationship processes among a sample of 60 gay male couples. Couples completed semistructured interviews and separate self-administered questionnaires. Findings suggest that partners attempt to change a variety of behaviors, many of which are not HIV related, that they use a variety of social control tactics, some of which are specific to HIV prevention, and that their care and concern for each other and their relationship motivate social control to change health behaviors. The implications for health behavior change research and intervention are discussed.


Can we normalise developmentally appropriate health care for young people in UK hospital settings? An ethnographic study.
The WHO has argued that adolescent-responsive health systems are required. Developmentally appropriate healthcare (DAH) for young people is one approach that could underpin this move. The aim of this study was to explore the potential for DAH to become normalised, to become a routine, taken-for-granted, element of clinical practice. Qualitative ethnographic study. Analyses were based on procedures from first-generation grounded theory and theoretically informed by normalisation process theory. Two tertiary and one secondary care hospital in England. 192 participants, health professionals (n=121) and managers (n=71) were recruited between June 2013 and January 2015. Approximately 1600 hours of non-participant observations in clinics, wards and meeting rooms were conducted, alongside 65 formal qualitative interviews. We observed diverse values and commitments towards the care of young people and provision of DAH, including a distributed network of young person-orientated practitioners. Informal networks of trust existed, where specific people, teams or wards were understood to have the right skill-mix, or mindset, or access to resources, to work effectively with young people. As young people move through an organisation, the preference is to direct them to other young person-orientated practitioners, so inequities in skills and experience can be self-sustaining. At two sites, initiatives around adolescent and young adult training remained mostly within these informal networks of trust. At another, through support by wider management, we observed a programme that sought to make the young people's healthcare visible across the organisation, and to get people to reappraise values and commitment. To move towards normalisation of DAH within an organisation, we cannot solely rely on informal networks and cultures of young person-orientated training, practice and mutual referral and support. Organisation-wide strategies and training are needed, to enable better integration and consistency of health services for all young people.


Collection of language data and services provided by health plans.
Key stakeholders agree better data on patients' language are needed to effectively address language-related barriers to timely, highquality healthcare. Our objective was to describe health plan efforts to collect language data from its members, provide language services, and improve the provision of culturally and linguistically appropriate services (CLAS). National surveys in 2003, 2006, and 2008. Surveys were administered to health plans offering commercial, Medicaid, and/or Medicare Advantage products. 123 health plans responded to the 2008 survey (50% response rate), including 65 commercial (50%), 46 Medicaid (53%), and 12 Medicare plans (44%), representing a total enrollment of 133.8 million Americans. In 2008, 74.0% of health plans collected language data (commercial 60.0%, Medicaid 89.1%, Medicare 91.7%), which is an increase for each plan type since 2003. Health plans used direct and indirect collection methods. Nearly all health plans reported offering language services, the most common being telephonic interpreting, multilingual member materials, and access to bilingual providers. A variety of strategies for improving CLAS were cited by health plans, including improving health plan communication materials, health literacy initiatives for members, and targeted training for providers and staff. Health plans have made substantial progress in the collection of language data and many are offering options for language services. With the rapid growth in Medicaid participation and newly insured individuals anticipated under the Affordable Care Act, health plans may be uniquely positioned to implement and test interventions that aim to improve appropriate utilization of language services by providers and patients.


The National Children's Study: a 21-year prospective study of 100,000 American children.
Prospective, multiyear epidemiologic studies have proven to be highly effective in discovering preventable risk factors for chronic disease. Investigations such as the Framingham Heart Study have produced blueprints for disease prevention and saved millions of lives and billions of dollars. To discover preventable environmental risk factors for disease in children, the US Congress directed the National Institute of Child Health and Human Development, through the Children's Health Act of 2000, to conduct the National Children's Study. The National Children's Study is hypothesis-driven and will seek information on environmental risks and individual susceptibility factors for asthma, birth defects, dyslexia, attention-deficit/hyperactivity disorder, autism, schizophrenia, and obesity, as well as for adverse birth outcomes. It will be conducted in a nationally representative, prospective cohort of 100,000 US-born children. Children will be followed from conception to 21 years of age. Environmental exposures (chemical, physical, biological, and psychosocial) will be assessed repeatedly during pregnancy and throughout childhood in children's homes, schools, and communities. Chemical assays will be performed by the Centers for Disease Control and Prevention, and banks of biological and environmental samples will be established for future analyses. Genetic material will be collected on each mother and child and banked to permit study of gene-environment interactions. Recruitment is scheduled to begin in 2007 at 7 Vanguard Sites and will extend to 105 sites across the United States. The National Children's Study will generate multiple satellite studies that explore methodologic issues, etiologic questions, and potential interventions. It will provide training for the next generation of researchers and practitioners in environmental pediatrics and will link to planned and ongoing prospective birth cohort studies in other nations. Data from the National Children's Study will guide development of a comprehensive blueprint for disease prevention in children.


Is atrial fibrillation associated with pulmonary embolism?
A pulmonary embolism (PE) is thought to be associated with atrial fibrillation (AF). Nevertheless, this association is based on weak data. To assess whether the presence of AF influences the clinical probability of PE in a cohort of patients with suspected PE and to confirm the association between PE and AF. We retrospectively analyzed the data from two trials that included 2449 consecutive patients admitted for a clinically suspected PE. An electrocardiography (ECG) was systematically performed and a PE was diagnosed by computer tomography (CT). The prevalence of AF among patients with or without a PE was compared in a multivariate logistic regression model. The prevalence of PE was 22.8% (519/2272) in patients without AF and 18.8% (25/133) in patients with AF (P = 0.28). After adjustment for confounding factors, AF did not significantly modify the probability of PE (odds ratio [OR] 0.68, 95% confidence interval [CI] 0.42-1.11). However, when PE suspicion was based on new-onset dyspnea, AF significantly decreased the probability of PE (OR 0.47, 95% CI 0.26-0.84). If isolated chest pain without dyspnea was the presenting complaint, AF tended to increase the probability of PE (OR 2.42, 95% CI 0.97-6.07). Overall, the presence of AF does not increase the probability of PE when this diagnosis is suspected. Nevertheless, when PE suspicion is based on new-onset dyspnea, AF significantly decreases the probability of PE, as AF may mimic its clinical presentation. However, in patients with chest pain alone, AF tends to increase PE probability.


Effects of a drag-reducing polyelectrolyte of microscopic linear dimension (Separan AP-273) on rat hemodynamics.
Separan AP-273, a polydisperse, high molecular weight (10(5)-10(7) dalton range), anionic polyacrylamide, demonstrates polymer drag reduction (Toms effect) in the flows of several substances including blood. That is, under appropriate conditions, pipe flow can be increased markedly for a given pressure gradient, sometimes threefold or more, by nanomolar concentrations of linear macropolymers. The effect of intact and degraded Separan was tested in the open-chest, anesthetized rat, and left ventricular and carotid pressures, aortic blood flow (electromagnetic flow probe on ascending aorta), and the electrocardiogram were recorded. The results indicate that aortic flow, which in control animals was about half the flow reported for conscious rats, increases markedly after injection of Separan. The effect on blood pressure after an initial fall was variable, but the slope of arterial diastolic pressure was consistently steepened. Electrocardiographic changes were unremarkable except for a slow decline in heart rate. Although secondary reflexes undoubtedly influenced the results, the primary mechanism of the polymer appears to involve a reduced resistance to flow. The results are compatible with the proposal that the Toms effect, or some variant of it, is operative in vivo under favorable conditions. If this view is correct, then Separan and two other chemically different macropolymers with similar hemodynamic effects and physical attributes, i.e., linearity and molecular lengths approaching 100 micron, might be prototypes of a novel category of cardiovascular drugs.


Diffusion and precipitation processes in iron-based silica gardens.
Silica gardens are tubular structures that form along the interface of multivalent metal salts and alkaline solutions of sodium silicate, driven by a complex interplay of osmotic and buoyant forces together with chemical reaction. They display peculiar plant-like morphologies and thus can be considered as one of the few examples for the spontaneous biomimetic self-ordering of purely inorganic materials. Recently, we could show that silica gardens moreover are highly dynamic systems that remain far from equilibrium for considerable periods of time long after macroscopic growth is completed. Due to initial compartmentalisation, drastic concentration gradients were found to exist across the tube walls, which give rise to noticeable electrochemical potential differences and decay only slowly in a series of coupled diffusion and precipitation processes. In the present work, we extend these studies and investigate the effect of the nature of the used metal cations on the dynamic behaviour of the system. To that end, we have grown single macroscopic silica garden tubes by controlled addition of sodium silicate sol to pellets of iron(ii) and iron(iii) chloride. In the following, the concentrations of ionic species were measured as a function of time on both sides of the formed membranes, while electrochemical potentials and pH were monitored online by immersing the corresponding sensors into the two separated solution reservoirs. At the end of the experiments, the solid tube material was furthermore characterised with respect to composition and microstructure by a combination of ex situ techniques. The collected data are compared to the previously reported case of cobalt-based silica gardens and used to shed light on ion diffusion through the inorganic membranes as well as progressive mineralisation at both surfaces of the tube walls. Our results reveal important differences in the dynamics of the three studied systems, which can be explained based on the acidity of the metal cations and the porosity of the membranes, leading to substantially dissimilar time-dependent solution chemistry as well as distinct final mineral structures. The insight gained in this work may help to better understand the diffusion properties and precipitation patterns in tubular iron (hydr)oxide/silicate structures observed in geological environments and during steel corrosion.


Increased capacity for circulatory fatty acid transport in a highly aerobic mammal.
Plasma fatty acid (FA) and albumin concentrations, cardiac output, and hematocrit of dogs and goats [dog-to-goat ratio of maximal oxygen consumption (VO2max) = 2.2] were measured to determine rates of circulatory FA delivery during exercise. Our goals were 1) to characterize the mechanism(s) used by the endurance-adapted species (dog) to support higher rates of FA delivery to working muscles than the sedentary species (goat) and 2) to determine whether circulatory transport is scaled with VO2max. Lipid oxidation was 2.5 times higher in dogs than in goats. Dogs had higher cardiac outputs than goats, but this positive effect on their FA delivery was canceled by higher hematocrit. Dogs always had higher plasma FA concentrations than goats. In contrast, albumin was steady and identical in both species, showing that dogs transport FA at higher rates than goats only because they load more FA on their albumin. Average dog-to-goat ratios for FA delivery (1.5-2.0) were lower than would be expected if this rate were scaled with VO2max. In vitro experiments showed that dog albumin is designed for high rates of FA transport because it can bind 50% more FA than goat albumin. All endurance-adapted species may possess such "aerobic albumins" to supply more circulating FA to their working muscles than sedentary species.


Thermally reversible nanoparticle gels with tuneable porosity showing structural colour.
We present colloidal gels formed from dispersions of PEG- and PEG+DNA-coated silica nanoparticles showing structural colour. The PEG- and PEG+DNA-coated silica colloids are functionalized using exclusively covalent bonds in aqueous conditions. Both sets of colloids self-assemble into thermally-reversible colloidal gels with porosity that can be tuned by changing the colloid volume fraction, although the interaction potentials of the colloids in the two systems are different. Confocal microscopy and image analysis tools are used to characteraize the gels' microstructures. Optical reflection spectroscopy is employed to study the underlying gel nanostructure and to characterize the optical response of the gels. X-ray nanotomography is used to visualize the nanoscale phase separation between the colloid-rich gel branches and the colloid-free gel pores. These nanoparticle gels open new routes for creating structural colour where the gel structure is decoupled from the form factor of the individual colloids. This approach can be extended to create unexplored three dimensional macroscale materials with length scales spanning hundreds of nanometers, which has been difficult to achieve using other methods.


Maturation of hydrogenases.
Enzymes possessing the capacity to oxidize molecular hydrogen have developed convergently three class of enzymes leading to: [FeFe]-, [NiFe]-, and [FeS]-cluster-free hydrogenases. They differ in the composition and the structure of the active site metal centre and the sequence of the constituent structural polypeptides but they show one unifying feature, namely the existence of CN and/or CO ligands at the active site Fe. Recent developments in the analysis of the maturation of [FeFe]- and [NiFe]- hydrogenases have revealed a remarkably complex pattern of mostly novel biochemical reactions. Maturation of [FeFe]-hydrogenases requires a minimum of three auxiliary proteins, two of which belong to the class of Radical-SAM enzymes and other to the family of GTPases. They are sufficient to generate active enzyme when their genes are co-expressed with the structural genes in a heterologous host, otherwise deficient in [FeFe]-hydrogenase expression. Maturation of the large subunit of [NiFe]-hydrogenases depends on the activity of at least seven core proteins that catalyse the synthesis of the CN ligand, have a function in the coordination of the active site iron, the insertion of nickel and the proteolytic maturation of the large subunit. Whereas this core maturation machinery is sufficient to generate active hydrogenase in the cytoplasm, like that of hydrogenase 3 from Escherichia coli, additional proteins are involved in the export of the ready-assembled heterodimeric enzyme to the periplasm via the twin-arginine translocation system in the case of membrane-bound hydrogenases. A series of other gene products with intriguing putative functions indicate that the minimal pathway established for E. coli [NiFe]-hydrogenase maturation may possess even higher complexity in other organisms.


Chimpanzee Personality and the Arginine Vasopressin Receptor 1A Genotype.
Polymorphisms of the arginine vasopressin receptor 1a (AVPR1a) gene have been linked to various measures related to human social behavior, including sibling conflict and agreeableness. In chimpanzees, AVPR1a polymorphisms have been associated with traits important for social interactions, including sociability, joint attention, dominance, conscientiousness, and hierarchical personality dimensions named low alpha/stability, disinhibition, and negative emotionality/low dominance. We examined associations between AVPR1a and six personality domains and hierarchical personality dimensions in 129 chimpanzees (Pan troglodytes) living in Japan or in a sanctuary in Guinea. We fit three linear and three animal models. The first model included genotype, the second included sex and genotype, and the third included genotype, sex, and sex × genotype. All personality phenotypes were heritable. Chimpanzees possessing the long form of the allele were higher in conscientiousness, but only in models that did not include the other predictors; however, additional analyses suggested that this may have been a consequence of study design. In animal models that included sex and sex × genotype, chimpanzees homozygous for the short form of the allele were higher in extraversion. Taken with the findings of previous studies of chimpanzees and humans, the findings related to conscientiousness suggest that AVPR1a may be related to lower levels of impulsive aggression. The direction of the association between AVPR1a genotype and extraversion ran counter to what one would expect if AVPR1a was related to social behaviors. These results help us further understand the genetic basis of personality in chimpanzees.


Development and Validation of a High Anatomical Fidelity FE Model for the Buttock and Thigh of a Seated Individual.
Current practices for designing new cushions for seats depend on superficial measurements, such as pressure mapping, which do not provide sufficient information about the condition of sub-dermal tissues. Finite element (FE) modelling offers a unique alternative to integrate assessment of sub-dermal tissue condition into seat/cushion design and development processes. However, the development and validation of such FE models for seated humans requires accurate representation of the anatomy and material properties, which remain challenges that are yet to be addressed. This paper presents the development and validation of a detailed 3D FE model with high anatomical fidelity of the buttock and thigh, for a specific seated subject. The developed model consisted of 28 muscles, the pelvis, sacrum, femur, and one layer of inter-muscular fat, subcutaneous fat and skin. Validation against in vivo measurements from MRI data confirmed that the FE model can simulate the deformation of soft tissues under sitting loads with an accuracy of (mean ± SD) 4.7 ± 4.4 mm. Simulation results showed that the maximum strains (compressive, shear and von-Mises) on muscles (41, 110, 79%) were higher than fat tissues (21, 62, 41%). The muscles that experienced the highest mechanical loads were the gluteus maximus, adductor magnus and muscles in the posterior aspect of the thighs (biceps femoris, semitendinosus and semimembranosus muscles). The developed FE model contributes to the progression towards bio-fidelity in modelling the human body in seated postures by providing insight into the distribution of stresses/strains in individual muscles and inter-muscular fat in the buttock and thigh of seated individuals. Industrial applications for the developed FE model include improving the design of office and household furniture, automotive and airplane seats and wheelchairs as well as customisation and assessment of sporting and medical equipment to meet individual requirements.


Cognitive, educational, and behavioural outcomes at 7 to 8 years in a national very low birthweight cohort.
To examine cognitive, behavioural, and educational outcomes in middle childhood among a birth cohort of very low birthweight children. Two hundred and ninety eight survivors from a national birth cohort of 413 New Zealand very low birthweight (VLBW) children born in 1986 were assessed at 7 to 8 years of age on measures of behaviour, cognitive ability, school performance and the need for special education. These outcomes were compared with the same measures in a general population sample of over 1000 children studied at a similar age. The VLBW children had significantly higher rates of problems and poorer levels of functioning across all outcome measures than the general child sample. These differences persisted even after control for variability in social, family, and other characteristics of the two samples and for the degree of sensorineural disability. There was evidence of a gradient of risk with birthweight, with extremely low birthweight children having generally higher rates of problems and difficulties than other VLBW children after covariate control. The findings are consistent with a growing body of research evidence which suggests that premature and VLBW infants are at increased risk of longer term morbidity and functional impairment in middle childhood.


Effect on hematologic risk factors for coronary heart disease of a cholesterol reducing diet.
A dietary portfolio of cholesterol-lowering ingredients has proved effective in reducing serum cholesterol. However, it is not known whether this dietary combination will also affect hematologic risk factors for coronary heart disease (CHD). Reductions in hematocrit and polymorphonuclear leukocytes have been reported to improve cardiovascular risk. We, therefore, report changes in hematological indices, which have been linked to cardiovascular health, in a 1-year assessment of subjects taking an effective dietary combination (portfolio) of cholesterol-lowering foods. For 12 months, 66 hyperlipidemic subjects were prescribed diets high in plant sterols (1.0 g/1000 kcal), soy protein (22.5 g/1000 kcal), viscous fibers (10 g/1000 kcal) and almonds (23 g/1000 kcal). Fifty-five subjects completed the study. Over the 1 year, data on completers indicated small but significant reductions in hemoglobin (-1.5+/-0.6 g/l, P=0.013), hematocrit (-0.007+/-0.002 l/l, P<0.001), red cell number (-0.07+/-0.02 10(9)/l, P<0.001) and neutrophils (-0.34+/-0.13 10(9)/l, P=0.014). Mean platelet volume was also increased (0.16+/-0.07 fl, P=0.033). The increase in red cell osmotic fragility (0.05+/-0.03 g/l, P=0.107) did not reach significance. These small changes in hematological indices after a cholesterol-lowering diet are in the direction, which would be predicted to reduce CHD risk. Further research is needed to clarify whether the changes observed will contribute directly or indirectly to cardiovascular benefits beyond those expected from reductions previously seen in serum lipids and blood pressure.


How confident are general dental practitioners in their decision to administer antibiotic prophylaxis? A questionnaire study.
Common dental procedures induce bacteremia. To prevent infectious complications from bacteremia in patients with specific medical conditions, antibiotic prophylaxis is considered. Recommendations are often unclear and ambiguous. In a previous study we reported wide variations in general dental practitioners' (GDPs') administrations of antibiotic prophylaxis. We hypothesized that within such a conflicting clinical area, decisions are made with a high level of personal uncertainty. This study examined GDPs' confidence in their decisions and analyzed the extent to which case-related factors might explain individual variations in confidence. Postal questionnaires in combination with telephone interviews were used. The response rate was 51% (101/200). There were no significant differences between respondents and non-respondents regarding sex, age, or place of work. The GDPs were presented to patient cases of different medical conditions, where some should receive antibiotic prophylaxis according to recommendations when performing dental procedures that could cause gingival bleeding. The GDPs assessed on visual analogue scales how confident they were in their decisions. The extent to which case-related factors, medical condition and dental procedure, could explain individual variation in confidence was analyzed. Overall the GDPs exhibited high confidence in their decisions regardless of whether they administered antibiotic prophylaxis or not, or whether their decisions were in accordance with recommendations or not. The case-related factors could explain between 30-100% of the individual variation in GDPs' confidence. For 46%, the medical condition significantly explained the individual variation in confidence. However, for most of these GDPs, lower confidence was not presented for conditions where recommendations are unclear and higher confidence was not presented for conditions where recommendations are more clear. For 8% the dental procedure significantly explained the variation, although all procedures could cause bacteremia. For 46% neither the medical condition nor the dental procedure could significantly explain the individual variation in confidence. The GDPs presented high confidence in their decisions, and the majority of GDPs did not present what could be considered a justified varied level of confidence according to the clarity of recommendations. Clinicians who are overconfident in their decisions may be less susceptible to modifications of their behavior to more evidence-based strategies.


Intramachine and intermachine variability in transesophageal color Doppler images of pulsatile jets. In vitro studies.
Color Doppler flow mapping is widely used as a marker of severity of valvular regurgitation, and the transesophageal approach has provided high-quality images in patients with poor acoustic windows. However, different instruments produce significantly variable images. Techniques that use jet spatial information to determine the severity of the lesion may need to be derived specifically for the instrument used. Given a lack of standardization of the many commonly used instruments, the goal of this study was to quantify variability between instruments by imaging well-defined jet flow fields created in vitro. Pulsatile jets were created in vitro using a blood analogue fluid through physiological orifice diameters and imaged from a distal window using six commonly used color Doppler instruments. Transesophageal transducers (5.0 MHz) were used with all instruments studied. Peak jet areas were planimetered and averaged with systematic variations in Nyquist limit, color filter, and sector angle (which produced variations in frame rate). Changes in instrument settings produced significant variation in jet size for all instruments studied. Comparisons within instruments and among instruments were difficult because of preset and ambiguous setting levels. When comparisons were possible between similar settings, variability was dramatic (eg, 57% variability between instruments with very similar Nyquist limits). A lack of standardized color Doppler instrument settings prohibits translation of jet area techniques from one instrument to another. This should be taken into consideration when using different machines for clinical study.


[Alterations in social reciprocity in attention-deficit hyperactivity disorder].
Social interactions in children with attention deficit-hyperactivity disorder (ADHD) are inappropriate and such social problems may originate from a failure to attend to the appropriate cues of affect. The present study aimed to determine the factors predictive of social reciprocity in ADHD and their relationship to sociodemographics. Participants were required to interpret emotional cues depicted in pictures of facial expressions with a test that was adopted from the Reading Mind in the Eyes Test (RMET). Diagnoses were established based on the Kiddie Schedule for Affective Disorders and Schizophrenia (K-SADS-PL). Moreover, a detailed sociodemographic form, the Child Behavior Checklist (CBCL), and the Social Reciprocity Scale (SRS) were used for assessment. This study included 133 children; 64 in the ADHD group and 69 in the control group. There wasn't a significant difference in mean age between the ADHD group (13.22 ± 1.28 years) and control group (12.97 ± 1.27 years). In all, 50% of the ADHD group and 49.3% of the control group were male. The mean RMET score was significantly lower in the ADHD group than in the control group (ADHD group: 20.52 ± 3.95; control group: 23.70 ± 3.55) and the mean SRS score was significantly higher in the ADHD group than in the control group (ADHD group: 65.84 ± 18.83; control group: 36.04 ± 16.32). In the ADHD group attention problems and lower level of ability to interpret emotional facial expressions were predictive of impaired social reciprocity. The findings show that both the ability to decode facial expressions and social reciprocity were impaired in the ADHD group. These findings highlight the difficulty children with ADHD have with social functioning and interpretation of emotions based on facial expressions.


Dissecting metabolism using zebrafish models of disease.
Zebrafish (Danio rerio) are becoming an increasingly powerful model organism to study the role of metabolism in disease. Since its inception, the zebrafish model has relied on unique attributes such as the transparency of embryos, high fecundity and conservation with higher vertebrates, to perform phenotype-driven chemical and genetic screens. In this review, we describe how zebrafish have been used to reveal novel mechanisms by which metabolism regulates embryonic development, obesity, fatty liver disease and cancer. In addition, we will highlight how new approaches in advanced microscopy, transcriptomics and metabolomics using zebrafish as a model system have yielded fundamental insights into the mechanistic underpinnings of disease.


Characteristics of extended-spectrum β-lactamase- and carbapenemase-producing Enterobacteriaceae Isolates from rivers and lakes in Switzerland.
One of the currently most relevant resistance mechanisms in Enterobacteriaceae is the production of enzymes that lead to modern expanded-spectrum cephalosporin and even carbapenem resistance, mainly extended-spectrum β-lactamases (ESBLs) and carbapenemases. A worrisome aspect is the spread of ESBL and carbapenemase producers into the environment. The aim of the present study was to assess the occurrence of ESBL- and carbapenemase-producing Enterobacteriaceae and to further characterize ESBL- and carbapenemase-producing Enterobacteriaceae in rivers and lakes in Switzerland. ESBL-producing Enterobacteriaceae were detected in 21 (36.2%) of the 58 bodies of water sampled. One river sample tested positive for a carbapenemase-producing Klebsiella pneumoniae subsp. pneumoniae strain. Seventy-four individual strains expressing an ESBL phenotype were isolated. Species identification revealed 60 Escherichia coli strains, seven Klebsiella pneumoniae subsp. pneumoniae strains, five Raoultella planticola strains, one Enterobacter cloacae strain, and one Enterobacter amnigenus strain. Three strains were identified as SHV-12 ESBL producers, and 71 strains carried genes encoding CTX-M ESBLs. Of the 71 strains with CTX-M ESBL genes, 8 isolates expressed CTX-M-1, three produced CTX-M-3, 46 produced CTX-M-15, three produced CTX-M-55, one produced CTX-M-79, six produced CTX-M-14, and four produced CTX-M-27. Three of the four CTX-M-27 producers belonged to the multiresistant pandemic sequence type E. coli B2:ST131 that is strongly associated with potentially severe infections in humans and animals.


Use of a criteria-based audit to optimize uptake of cesarean delivery in a low-resource setting.
To evaluate the impact of a criteria-based audit (CBA) of obstructed labor and fetal distress on cesarean delivery and perinatal outcomes. A cross-sectional study was performed at a tertiary referral hospital in Tanzania. Data were collected before and after CBA (January 2013-November 2013 and July 2015-June 2016). Outcomes of fetal distress (baseline CBA, n=248; re-audit, n=251) and obstructed labor (baseline CBA, n=260; re-audit n=250) were assessed using a checklist. Additionally, 27 960 parturients were assessed using the Robson classification. Perinatal morbidity and mortality decreased from 42 of 260 (16.2%) to 22 of 250 (8.8%) among patients with obstructed labor after CBA (P=0.012). Cesarean delivery rate decreased for referred term multiparas with induced labor or prelabor cesarean delivery (odds ratio [OR] 0.28, 95% confidence interval [CI] 0.09-0.82). Cesarean delivery rate for preterm pregnancies increased among both referred (OR 1.28, 95% CI 1.02-1.63) and non-referred (OR 2.78, 95% CI 1.98-3.90) groups. Neonatal distress rate decreased for referred term multiparas (OR 0.72, 95% CI 0.56-0.92), referred preterm pregnancies (OR 0.32, 95% CI 0.25-0.39), and non-referred preterm pregnancies (OR 0.26, 95% CI 0.18-0.36). Use of CBA reduced poor perinatal outcomes of obstructed labor and increased uptake of cesarean delivery.


Efficacy of night-time compression for breast cancer related lymphedema (LYNC): protocol for a multi-centre, randomized controlled efficacy trial.
Lymphedema is a prevalent long-term effect of breast cancer treatment that is associated with reduced quality of life. More recent observational data suggest that the addition of night-time compression to day-time use of a compression garment results in better long-term control of arm lymphedema. The primary objectives of the randomized controlled phase of the trial are to determine the efficacy of night-time compression on arm lymphedema volume maintenance and quality of life in breast cancer survivors who have completed intensive reduction treatment for their lymphedema. The study will be a parallel 3-arm, multi-centre randomized fast-track trial. A total of 120 women with breast cancer related lymphedema will be recruited from 3 centres in Canada and randomized to group 1: Day-time compression garment alone or Group 2: Day-time compression garment + night-time compression bandaging or Group 3: Day-time compression garment + use of a night-time compression system garment. The duration of the primary intervention period will be 12 weeks. The follow-up period after the intervention (weeks 13 to 24) will follow a longitudinal observational design. The primary outcome variables: differences from baseline to week 12 in arm volume and quality of life (Lymphoedema Functioning, Disability and Health Questionnaire: Lymph-ICF). Secondary outcomes include bioimpedance analysis, sleep disturbance and self-efficacy. All measurements are standardized and will be performed prior to randomization, and at weeks 6, 12, 18 and 24. The use of night-time compression as a self-management strategy for chronic breast cancer related lymphedema is seen as an innovative approach to improve long-term control over the condition. This trial aims to advance the knowledge on self-management strategies for lymphedema. This trial was registered at clinicaltrials.gov on July 9(th), 2014 ( NCT02187289 ).


Clinical effectiveness of cardiac resynchronization and implantable cardioverter-defibrillator therapy in men and women with heart failure: findings from IMPROVE HF.
Many clinical trials have demonstrated a benefit for cardiac resynchronization (CRT) and implantable cardioverter-defibrillator (ICD) therapies in patients with heart failure and reduced ejection fraction, yet questions have been raised with regard to the benefit of ICDs for women. The purpose of this study was to determine the clinical effectiveness of CRT and ICD therapy as a function of sex in outpatients with heart failure and reduced ejection fraction (≤35%). Data from the Registry to Improve the Use of Evidence-Based Heart Failure Therapies in the Outpatient Setting (IMPROVE HF) were analyzed by device status and sex among guideline-eligible patients for vital status (alive/dead) at 24 months. Multivariate generalized estimating equation analyses were conducted adjusting for baseline patient and practice characteristics. In the ICD/CRT-defibrillator (CRT-D) eligible cohort (n=7748), there were 5485 (71%) men and 2261 (29%) women. In the CRT-pacemaker (CRT-P)/CRT-D eligible cohort (n=1188), there were 824 (69%) men and 364 (31%) women. The clinical benefit associated with ICD/CRT-D therapy was similar in both men and women (men adjusted odds ratio, 0.71; 95% confidence interval, 0.57-0.87; P=0.0012; and women adjusted odds ratio, 0.65; 95% confidence interval, 0.49-0.85; P=0.0019). For CRT-P/CRT-D, the associated benefits showed no significant heterogeneity (men adjusted odds ratio, 0.59; 95% confidence interval, 0.33-1.06; P=0.0793; and women adjusted odds ratio, 0.44; 95% confidence interval, 0.22-0.90; P=0.0243). The device-by-sex interactions were not significant (P=0.4441 for CRT-P/CRT-D and P=0.5966 for ICD/CRT-D). The use of guideline-directed CRT and ICD therapy was associated with substantially reduced 24-month mortality in eligible men and women with heart failure and reduced ejection fraction. Device therapies should be offered to all eligible patients with heart failure, without modification based on sex.


Influence of polydopamine-mediated surface modification on oxygen-release capacity of haemoglobin-based oxygen carriers.
Oxidative toxicity has impeded the development of haemoglobin-based oxygen carriers (HBOCs) by causing methaemoglobin (MetHb) formation and inducing oxidative stress. In our previous work, polydopamine-coated haemoglobin (Hb-PDA) nanoparticles have been designed and synthesized with the capacity to reduce oxidative toxicity. In this investigation, the mass ratio of dopamine (DA) to haemoglobin (Hb) and the pH value are found to be the primary factors that influence preparation of Hb-PDA nanoparticles. X-ray photoelectron spectroscopy showed that the catechol groups of DA play a crucial role in the modification of Hb surface. Hb-PDA nanoparticles were found to exhibit oxidative protection from hydrogen peroxide (H2O2) and the change of mitochondrial membrane potential showed that the Hb-PDA nanoparticles reduced H2O2-induced apoptosis. It is demonstrated that modification of PDA could maintain the oxygen-release capacity of Hb. These findings confirm that Hb-PDA nanoparticles possess restrained oxidative toxicity and preserve oxygen-release capacity.


Impact of frequency of denture cleaning on microbial and clinical parameters - a bench to chairside approach.
Objective: Robust scientific and clinical evidence of how to appropriately manage denture plaque is lacking. This two-part study (i) developed an in vitro model of denture plaque removal, and (ii) assessed effectiveness of these approaches in a randomised clinical trial. Method: (i) a complex denture plaque model was developed using the dominant microbial genera from a recent microbiome analyses. Biofilms formed on polymethylmethacrylate were brushed daily with a wet toothbrush, then either treated daily for 5 days or only on Days 1 and 5 with Polident® denture cleanser tablets (3 min soaking). Quantitative and qualitative microbiological assessments were performed. (ii), an examiner-blind, randomised, crossover study of complete maxillary denture wearers was performed (n = 19). Either once-daily for 7 days or on Day 7 only, participants soaked dentures for 15 min using Corega® denture cleansing tables, then brushed. Denture plaque microbiological assessment used sterilized filter paper discs. Results: The in vitro model showed daily cleaning with denture cleanser plus brushing significantly reduced microbial numbers compared to intermittent denture cleaning with daily brushing (p < 0.001). The clinical component of the study showed a statistically significant reduction in denture plaque microbial numbers in favour of daily versus weekly treatment (aerobic bacteria p = 0.0144). Both in vitro and in vivo studies showed that denture plaque biofilm composition were affected by different treatment arms. Conclusions: This study demonstrated that daily denture cleansing regimens are superior to intermittent denture cleansing, and that cleansing regimens can induce denture plaque compositional changes. Clinicaltrials.gov registration: NCT02780661.


Hydrogen-rich saline protects against oxidative damage and cognitive deficits after mild traumatic brain injury.
Oxidative stress is the principal factor in traumatic brain injury (TBI) that initiates events that result in protracted neuronal dysfunction and remodeling. Importantly, antioxidants can protect the brain against oxidative damage and modulate the capacity of the brain to cope with synaptic dysfunction and cognitive impairment. However, no studies have investigated the effects of hydrogen-rich saline on cognitive deficits after TBI. In the present study, rats with fluid percussion injury (FPI) were used to investigate the protective effects of hydrogen-rich saline. The results showed that hydrogen-rich saline reduced the level of malondialdehyde (MDA) and elevated the level of silent information regulator 2 (Sir2). In addition, treatment with hydrogen-rich saline, which elevated the levels of molecules associated with brain-derived neurotropic factor (BDNF)-mediated synaptic plasticity, improved cognitive performance in the Morris water maze after mild TBI. These results suggest that hydrogen-rich saline can protect the brain against the deleterious effects of mild TBI on synaptic plasticity and cognition and that hydrogen-rich saline could be an effective therapeutic strategy for patients with cognitive deficits after TBI.


A comprehensive survey of the approaches for pathway analysis using multi-omics data integration.
Pathway analysis has been widely used to detect pathways and functions associated with complex disease phenotypes. The proliferation of this approach is due to better interpretability of its results and its higher statistical power compared with the gene-level statistics. A plethora of pathway analysis methods that utilize multi-omics setup, rather than just transcriptomics or proteomics, have recently been developed to discover novel pathways and biomarkers. Since multi-omics gives multiple views into the same problem, different approaches are employed in aggregating these views into a comprehensive biological context. As a result, a variety of novel hypotheses regarding disease ideation and treatment targets can be formulated. In this article, we review 32 such pathway analysis methods developed for multi-omics and multi-cohort data. We discuss their availability and implementation, assumptions, supported omics types and databases, pathway analysis techniques and integration strategies. A comprehensive assessment of each method's practicality, and a thorough discussion of the strengths and drawbacks of each technique will be provided. The main objective of this survey is to provide a thorough examination of existing methods to assist potential users and researchers in selecting suitable tools for their data and analysis purposes, while highlighting outstanding challenges in the field that remain to be addressed for future development.