Do films about mentally disturbed characters promote ineffective coping in vulnerable youth?
Suicidal youth tend to doubt the effectiveness of professional mental health treatment. This study examined whether exposure to films about suicidal and mentally disturbed persons supports this lack of belief. Exposure to three popular films featuring suicides or the mentally ill was compared to films that featured a heroic suicide unrelated to mental illness as well as to films with violent and comedic content in a nationally representative survey of youth ages 14-22 (N=900). Exposure to films about mental disturbance among "vulnerable" respondents who had experienced recent depressive and suicidal symptoms (24% of sample) was compared to those without these symptoms. Increasing exposure to films with mentally disturbed characters was related to belief in the treatment inefficacy of mental disorders. The findings suggest that exposure to fictional depictions of characters failing to get help for mental disorders may have long-term effects on depressed and suicidal youth.


Endoscopic treatment of early leaks and strictures after laparoscopic one anastomosis gastric bypass.
Laparoscopic one anastomosis gastric bypass has become a prominent bariatric procedure. Yet, early and late complications, primarily leaks and strictures, are not uncommon. This study summarizes our experience with endoscopic treatment of laparoscopic one anastomosis gastric bypass complications. This is a retrospective study of consecutive patients referred to our hospital from 2015 to 2017 with post laparoscopic one anastomosis gastric bypass complications. Therapy was tailored to each case, including fully covered self-expandable metal stents, fibrin glue, septotomy, internal drainage with pigtail stents, through-the-scope and pneumatic dilation. Success was defined as resuming oral nutrition without enteral or parenteral support or further surgical intervention. Nine patients presented with acute or early leaks: 5 (56%) had staple-line leaks, 3 (33%) had anastomotic leaks and 1 (11%) had both. All were treated with stents. Adjunctive endoscopic drainage was applied in 4 patients (44%). Overall 5 patients (56%) with acute/ early leaks recovered completely, including all 3 patients with anastomotic leak and the patient with both leaks but only 1/5 with staple line leak (20%). Complication rate in the leak group reached 22%. Eight patients presented with strictures, 7 at the anastomosis and one due to remnant stomach misalignment. All anastomotic strictures were dilated successfully. However, the patient with the pouch stricture required conversion to Roux-en-Y gastric bypass after 3 failed attempts of dilation. Endoscopic treatments of laparoscopic one anastomosis gastric bypass complications are relatively effective and safe. Anastomosis-related complications are more amenable to endoscopic treatment compared to staple line leaks.


International multicentre psychometric evaluation of patient-reported outcome data for the treatment of Peyronie's disease.
To compare patient-reported outcomes (PROs) of surgical correction of Peyronie's disease (PD) with the Nesbit procedure, plaque incision and grafting, and the insertion of a malleable penile implant after surgical correction of penile curvature. We performed a retrospective review of men who underwent surgical correction of PD between January 2010 and December 2012 at six international centres. Treatment-related PROs and satisfaction were evaluated with a non-validated questionnaire. The response rate to the questionnaire was 70.9%, resulting in a study cohort of 206 patients. The Nesbit procedure, plaque incision with grafting, or implantation of a malleable penile prosthesis was performed in 50, 48, and 108 patients, respectively. Overall, 79.1% reported a subjective loss of penile length due to PD preoperatively (range 2.1-3.2 cm). Those patients treated with a malleable penile implant reported the greatest subjective penile length loss, due to PD. A subjective loss of penile length of >2.5 cm resulted in reduced preoperative sex ability. Postoperatively, 78.0%, 29.2% and 24.1% patients in the Nesbit, grafting, and implant groups reported a postoperative, subjective loss of penile length (range 0.4-1.2 cm), with 86.3%, 78.6%, and 82.1% of the patients in each group, respectively, being bothered by the loss of length. Penile length loss due to PD affects most patients. Further penile length loss due to the surgical correction leads to bother among the affected patients, irrespective of the magnitude of the loss. The Nesbit procedure was associated with the highest losses in penile length. In patients with PD and severe erectile dysfunction, a concomitant lengthening procedure may be offered to patients to help overcome the psychological burden caused by the loss of penile length.


A survey of surgical team members' perceptions of near misses and attitudes towards Time Out protocols.
Medical errors are inherently of concern in modern health care. Although surgical errors as incorrect surgery (e.g., wrong patient, wrong site, or wrong procedure) are infrequent, they are devastating events to experience. To gain insight about incidents that could lead to incorrect surgery, we surveyed how surgical team members perceive near misses and their attitudes towards the use of Time Out protocols in the operating room. We hypothesised that perceptions of near-miss experiences and attitudes towards Time Out protocols vary widely among surgical team members. This cross-sectional study (N = 427) included surgeons, anaesthetists, nurse anaesthetists, and operating room nurses. The questionnaire consisted of 14 items, 11 of which had dichotomous responses (0 = no; 1 = yes) and 3 of which had responses on an ordinal scale (never = 0; sometimes = 1; often = 2; always = 3). Items reflected team members' experience of near misses or mistakes; their strategies for verifying the correct patient, site, and procedure; questions about whether they believed that these mistakes could be avoided using the Time Out protocol; and how they would accept the implementation of the protocol in the operating room. In the operating room, 38% of respondents had experienced uncertainty of patient identity, 81% had experienced uncertainty of the surgical site or side, and 60% had prepared for the wrong procedure. Sixty-three per cent agreed that verifying the correct patient, site, and procedure should be a team responsibility. Thus, only nurse anaesthetists routinely performed identity checks prior to surgery (P ≤ 0.001). Of the surgical team members, 91% supported implementation of a Time Out protocol in their operating rooms. The majority of our surgical personnel experienced near misses with regard to correct patient identity, surgical site, or procedure. Routines for ensuring the correct patient, site, and surgical procedure must involve all surgical team members. We find that the near-miss experiences are a wake-up call for systematic risk reducing efforts and the use of checklists in surgery.


Multilevel psychometric properties of the AHRQ hospital survey on patient safety culture.
The Agency for Healthcare Research and Quality (AHRQ) Hospital Survey on Patient Safety Culture was designed to assess staff views on patient safety culture in hospital settings. The purpose of this study was to examine the multilevel psychometric properties of the survey. Survey data from 331 U.S. hospitals with 2,267 hospital units and 50,513 respondents were analyzed to examine the psychometric properties of the survey's items and composites. Item factor loadings, intraclass correlations (ICCs), design effects, internal consistency reliabilities, and multilevel confirmatory factor analyses (MCFA) were examined as well as intercorrelations among the survey's composites. Psychometric analyses confirmed the multilevel nature of the data at the individual, unit and hospital levels of analysis. Results provided overall evidence supporting the 12 dimensions and 42 items included in the AHRQ Hospital Survey on Patient Safety Culture as having acceptable psychometric properties at all levels of analysis, with a few exceptions. The Staffing composite fell slightly below cutoffs in a number of areas, but is conceptually important given its impact on patient safety. In addition, one hospital-level model fit indicator for the Supervisor/Manager Expectations & Actions Promoting Patient Safety composite was low (CFI = .82), but all other psychometrics for this scale were good. Average dimension intercorrelations were moderate at .42 at the individual level, .50 at the unit level, and .56 at the hospital level. Psychometric analyses conducted on a very large database of hospitals provided overall support for the patient safety culture dimensions and items included in the AHRQ Hospital Survey on Patient Safety Culture. The survey's items and dimensions overall are psychometrically sound at the individual, unit, and hospital levels of analysis and can be used by researchers and hospitals interested in assessing patient safety culture. Further research is needed to study the criterion-related validity of the survey by analysing the relationship between patient safety culture and patient outcomes and studying how to improve patient safety culture.


Contextualizing nativity status, Latino social ties, and ethnic enclaves: an examination of the 'immigrant social ties hypothesis'.
Researchers have posited that one potential explanation for the better-than-expected health outcomes observed among some Latino immigrants, vis-à-vis their US-born counterparts, may be the strength of social ties and social support among immigrants. We examined the association between nativity status and social ties using data from the Chicago Community Adult Health Study's Latino subsample, which includes Mexicans, Puerto Ricans, and other Latinos. First, we used ordinary least squares (OLS) regression methods to model the effect of nativity status on five outcomes: informal social integration; social network diversity; network size; instrumental support; and informational support. Using multilevel mixed-effects regression models, we estimated the association between Latino/immigrant neighborhood composition and our outcomes, and whether these relationships varied by nativity status. Lastly, we examined the relationship between social ties and immigrants' length of time in the USA. After controlling for individual-level characteristics, immigrant Latinos had significantly lower levels of social ties than their US-born counterparts for all the outcomes, except informational support. Latino/immigrant neighborhood composition was positively associated with being socially integrated and having larger and more diverse social networks. The associations between two of our outcomes (informal social integration and network size) and living in a neighborhood with greater concentrations of Latinos and immigrants were stronger for US-born Latinos than for immigrant Latinos. US-born Latinos maintained a significant social ties advantage over immigrants - regardless of length of time in the USA - for informal social integration, network diversity, and network size. At the individual level, our findings challenge the assumption that Latino immigrants would have larger networks and/or higher levels of support and social integration than their US-born counterparts. Our study underscores the importance of understanding the contexts that promote the development of social ties. We discuss the implications of these findings for understanding Latino and immigrant social ties and health outcomes.


A Prospective Observational Survey on the Long-Term Effect of LDL Apheresis on Drug-Resistant Nephrotic Syndrome.
LDL apheresis (LDL-A) is used for drug-resistant nephrotic syndrome (NS) as an alternative therapy to induce remission by improvement of hyperlipidemia. Several clinical studies have suggested the efficacy of LDL-A for refractory NS, but the level of evidence remains insufficient. A multicenter prospective study, POLARIS (Prospective Observational Survey on the Long-Term Effects of LDL Apheresis on Drug-Resistant Nephrotic Syndrome), was conducted to evaluate its clinical efficacy with high-level evidence. Patients with NS who showed resistance to primary medication for at least 4 weeks were prospectively recruited to the study and treated with LDL-A. The long-term outcome was evaluated based on the rate of remission of NS 2 years after treatment. Factors affecting the outcome were also examined. A total of 58 refractory NS patients from 40 facilities were recruited and enrolled as subjects of the POLARIS study. Of the 44 subjects followed for 2 years, 21 (47.7%) showed remission of NS based on a urinary protein (UP) level <1.0 g/day. The UP level immediately after LDL-A and the rates of improvement of UP, serum albumin, serum creatinine, eGFR, and total and LDL cholesterol after the treatment session significantly affected the outcome. Almost half of the cases of drug-resistant NS showed remission 2 years after LDL-A. Improvement of nephrotic parameters at termination of the LDL-A treatment was a predictor of a favorable outcome.


Solid phase syntheses of polyamine toxins HO-416b and PhTX-433. Use of an efficient polyamide reduction strategy that facilitates access to branched analogues.
[structure--se text] Polyamine toxins HO-416b (1) and PhTX-433 (2) isolated from the venom of insects are important lead compounds in neuropharmacology. Their total synthesis has been achieved on a trityl derivatized resin in good yield and purity using a mild borane reduction protocol to access the polyamine chains from polyamide precursors. The synthesis of PhTX isomer 3 demonstrates the potential of this strategy for the generation of branched analogues.


The total synthesis of immunostimulant α-galactosylceramides from naturally configured α-galactoside raffinose.
The total synthesis of absolute anomeric confirmation α-galactosylceramide analogues from raffinose is described. Using the naturally occurring α-galactoside raffinose as the starting material, the easily maneuverable protocol without glycosylation reactions ensured the critical α-linkage in the product and simplified the synthetic procedures. The immunostimulatory activities of the new α-galactosylceramides were validated by both in vitro and in vivo NKT cell stimulation assays.


Conversion of biosynthetic human proinsulin to partially cleaved intermediates by collagenase proteinases adsorbed to isolated rat adipocytes.
Studies of the biological activity of proinsulin have resulted in widely varying conclusions. Relative to insulin, the biological activity of proinsulin has been reported from less than 1% to almost 20%. Many of the assays in vitro for the biological potency of proinsulin have utilized isolated rat adipocytes. To examine further the interaction of proinsulin with rat adipocytes, we prepared specifically-labelled proinsulin isomers that were iodinated on tyrosine residues corresponding to the A14, A19, B16 or B26 residue of insulin. These were incubated with rat adipocytes and their metabolism was examined by trichloroacetic acid precipitation, by Sephadex G-50 chromatography, and by h.p.l.c. chromatography. By trichloroacetic acid-precipitation assay, there was little or no proinsulin degradation. By G-50 chromatography and subsequent h.p.l.c. analysis, however, we found that the labelled proinsulin isomers were converted rapidly and almost completely to materials which eluted differently on h.p.l.c. from intact proinsulin. This conversion was due primarily to proteolytic activity which adsorbed to the fat cells from the crude collagenase used to isolate the cells. Two primary conversion intermediates were found: one with a cleavage at residues 23-24 of proinsulin (the B-chain region of insulin), and one at residues 55-56 in the connecting peptide region. These intermediates had receptor binding properties equivalent to or less than intact proinsulin. These findings show that isolated fat cells can degrade proinsulin to intermediates due to their contamination with proteolytic activity from the collagenase used in their preparation. Thus the previously reported range in biological activities of proinsulin in fat cells may have arisen from such protease contamination. Finally, the present findings demonstrate that a sensitive assay for degradation of hormones is required to examine biological activities in isolated cells.


Metagenomic analysis of double-stranded DNA viruses in healthy adults.
The Human Microbiome Project (HMP) was undertaken with the goal of defining microbial communities in and on the bodies of healthy individuals using high-throughput, metagenomic sequencing analysis. The viruses present in these microbial communities, the 'human virome', are an important aspect of the human microbiome that is particularly understudied in the absence of overt disease. We analyzed eukaryotic double-stranded DNA (dsDNA) viruses, together with dsDNA replicative intermediates of single-stranded DNA viruses, in metagenomic sequence data generated by the HMP. 706 samples from 102 subjects were studied, with each subject sampled at up to five major body habitats: nose, skin, mouth, vagina, and stool. Fifty-one individuals had samples taken at two or three time points 30 to 359 days apart from at least one of the body habitats. We detected an average of 5.5 viral genera in each individual. At least 1 virus was detected in 92% of the individuals sampled. These viruses included herpesviruses, papillomaviruses, polyomaviruses, adenoviruses, anelloviruses, parvoviruses, and circoviruses. Each individual had a distinct viral profile, demonstrating the high interpersonal diversity of the virome. Some components of the virome were stable over time. This study is the first to use high-throughput DNA sequencing to describe the diversity of eukaryotic dsDNA viruses in a large cohort of normal individuals who were sampled at multiple body sites. Our results show that the human virome is a complex component of the microbial flora. Some viruses establish long-term infections that may be associated with increased risk or possibly with protection from disease. A better understanding of the composition and dynamics of the virome may hold important keys to human health.


The NIFTY study: a multicentre randomised double-blind placebo-controlled trial of nifedipine maintenance tocolysis in fetal fibronectin-positive women in threatened preterm labour.
In an unselected group of women with signs of preterm labour, maintenance tocolysis is not effective in the prevention of preterm birth and does not improve neonatal outcome. Among women with signs of preterm labour, those who are fetal fibronectin positive have an increased risk of preterm birth. We investigated whether maintenance tocolysis with nifedipine would delay delivery and improve neonatal outcome in women with threatened preterm labour and a positive fetal fibronectin status. Women with a singleton pregnancy in threatened preterm labour (24(+0) to 33(+6) weeks) with a positive fetal fibronectin test were randomised to nifedipine or placebo. Study medication was continued until 36 completed weeks' gestation. The primary endpoint was prolongation of pregnancy of seven days. Secondary endpoints were gestational age at delivery and length of NICU admission. Of the 60 participants, 29 received nifedipine and 31 placebo. Prolongation of pregnancy by >7 days occurred in 22/29 (76%) in the nifedipine group and 25/31 (81%) in the placebo group (relative risks, RR 0.94 [0.72-1.2]). Gestational age at delivery was 36.1 ± 5.1 weeks for nifedipine and 36.8 ± 3.6 weeks for placebo (P = 0.027). Length of NICU admission [median (interquartile ranges, IQR)] was 27 (24-41) days and 16 (8-37) days in nifedipine and placebo groups, respectively (P = 0.17). In women with threatened preterm labour who are fetal fibronectin positive, maintenance tocolysis with nifedipine does not seem to prolong pregnancy, nor reduce length of NICU admission.


Muscle involvement in systemic sclerosis: points to consider in clinical trials.
SSc is clinically and pathogenetically heterogeneous. Consensus standards for trial design and outcome measures are needed. International experts experienced in SSc clinical trial design and a researcher experienced in systematic literature review screened the PubMed and Cochrane Central Register of Controlled Trials in order to develop points to consider when planning a clinical trial for muscle involvement in SSc. The experts conclude that SSc-associated muscle involvement is heterogeneous and lacks a universally accepted gold-standard for measuring therapeutic response. Although outcome studies are currently limited by the inability to clearly distinguish active, reversible muscle inflammation from irreversible muscle damage and extramuscular organ involvement, strong consideration should be given to enrolling patients with a myopathy that features several elements of likely reversibility such as muscle weakness, biopsy-proven active inflammation, an MRI indicating muscle inflammation and a baseline serum creatinine kinase above three times the upper limit of normal to prevent floor effect. Randomized controlled trials are preferred, with a duration of at least 24 weeks. Outcome measures should include a combination of elements that are likely to be reversible, such as muscle weakness, biopsy-proven active inflammation, creatinine kinase/aldolase and a quality of life questionnaire. The individual measurements might require a short pre-study for further validation. A biological sample repository is recommended.


Evidence for a Diagenetic Origin of Vera Rubin Ridge, Gale Crater, Mars: Summary and Synthesis of Curiosity's Exploration Campaign.
This paper provides an overview of the Curiosity rover's exploration at Vera Rubin ridge (VRR) and summarizes the science results. VRR is a distinct geomorphic feature on lower Aeolis Mons (informally known as Mount Sharp) that was identified in orbital data based on its distinct texture, topographic expression, and association with a hematite spectral signature. Curiosity conducted extensive remote sensing observations, acquired data on dozens of contact science targets, and drilled three outcrop samples from the ridge, as well as one outcrop sample immediately below the ridge. Our observations indicate that strata composing VRR were deposited in a predominantly lacustrine setting and are part of the Murray formation. The rocks within the ridge are chemically in family with underlying Murray formation strata. Red hematite is dispersed throughout much of the VRR bedrock, and this is the source of the orbital spectral detection. Gray hematite is also present in isolated, gray-colored patches concentrated toward the upper elevations of VRR, and these gray patches also contain small, dark Fe-rich nodules. We propose that VRR formed when diagenetic event(s) preferentially hardened rocks, which were subsequently eroded into a ridge by wind. Diagenesis also led to enhanced crystallization and/or cementation that deepened the ferric-related spectral absorptions on the ridge, which helped make them readily distinguishable from orbit. Results add to existing evidence of protracted aqueous environments at Gale crater and give new insight into how diagenesis shaped Mars' rock record.


Quantitation of circulating DNA in the serum of breast cancer patients by real-time PCR.
The purpose of this study was to quantify the level of serum DNA in different groups of primary breast cancer patients and in healthy controls using real-time quantitative PCR in order to determine whether such measurements have diagnostic or prognostic value. A total of 96 serum samples of patients with primary breast cancer before surgery (with positive or negative lymph nodes and with high or low relapse-free survival) as well as 24 healthy controls were analysed. DNA concentrations in the serum of the patients differed significantly from the concentration of serum DNA in the controls (medians were 221 and 63 ng x ml(-1), respectively, P<0.001 M-W test). However, no statistically significant difference was observed between the patient groups (P=0.87, M-W test). The serum DNA levels were elevated independently of the size of primary tumour or lymph node metastases. The overall survival of patients with serum DNA concentrations >221 ng x ml(-1) was better than patients with serum DNA concentration <or=221 ng ml(-1) (Kaplan-Meier, P=0.028).


Does ureteral access sheat usage lead to permanent damage in the ureter? A placebo controlled trial in a rabbit model.
To evaluate the clinical stenosis or precursor histological changes that ureteral access sheaths commonly used in ureteroscopic surgeries may cause in the long term in ureter. In this study, the animals were divided into 9 groups and according to their groups, ureters of the rabbits were endoscopically fitted with 2F and 3F ureter catheters. The catheters were left in place and withdrawn after a specified period of time. All the ureters were excised and evaluated macroscopically, microscopically and histologically. Ureter diameters were measured and FGF-2 (+) labeled fibroblasts were counted in connective tissue as stenosis precursors. Macroscopically or microscopically, no stenosis was found in any group. The ureter diameter of the group that were catheterized for the longest time with the catheter that had the widest diameter was significantly lower than the group with the shorter duration and the catheter with the narrower diameter and the control group. When the groups were compared in terms of their FGF values, there was a significant difference in FGF-2 counts at all three ureter levels (p <0.05). The use of ureteral access sheath may lead to histological changes, as its diameter and duration increase.


Bad-deficient mice develop diffuse large B cell lymphoma.
The proapoptotic activity of the "BH3-only" molecule BAD can be differentially regulated by survival factor signaling. Bad-deficient mice lacking both BAD long and BAD short proteins proved viable, and most cell types appeared to develop normally. BAD did not exclusively account for cell death after withdrawal of survival factors, but it was an intermediate for epidermal growth factor- or insulin-like growth factor I-countered apoptosis, consistent with a "sensitizing" BH3-only molecule. Lymphocytes developed normally with no premalignant hyperplasia, but they displayed subtle abnormalities in proliferation and IgG production. Despite the minimal phenotype, Bad-deficient mice progressed, with aging, to diffuse large B cell lymphoma of germinal center origin. Exposure of Bad-null mice to sublethal gamma-irradiation resulted in an increased incidence of pre-T cell and pro-/pre-B cell lymphoblastic leukemia/lymphoma. Thus, proapoptotic BAD suppresses tumorigenesis in the lymphocyte lineage.


Regulation of adiponectin secretion by adipocytes in the polycystic ovary syndrome: role of tumor necrosis factor-{alpha}.
Adipose tissue dysfunction associated with low-grade chronic inflammation and dysregulation of adipokine secretion might significantly contribute to the pathogenesis of polycystic ovary syndrome (PCOS). The objective of the study was to determine whether the effect of TNF-alpha, IL-6, monocyte chemoattractant protein-1, or coculture of adipocytes and adipose tissue macrophages (ATMs), on the secretion of adiponectin by adipocytes, differs in PCOS compared with controls. Primary cultures of sc adipocytes and coculture of adipocytes and ATMs from overweight and obese patients with PCOS and healthy control women were used. Adiponectin secretion by adipocytes was measured. The baseline secretion of adiponectin by isolated adipocytes did not differ between PCOS and control samples. The net change in adiponectin secretion in response to IL-6, monocyte chemoattractant protein-1, and TNF-alpha differed between PCOS (decreasing) and control (increasing) adipocytes, although the difference reached significance only for TNF-alpha (P < 0.04). Coculture of isolated adipocytes and ATMs resulted in a decrease in adiponectin secretion by PCOS (P < 0.05) but not control adipocytes, and the difference between the net change in adiponectin secretion in PCOS vs. control samples was significant (P < 0.03). Our results suggest that adiponectin secretion by adipocytes in response to cytokines/chemokines and most notably in response to coculturing with ATMs differs between PCOS and control women, favoring greater suppression of adiponectin in PCOS. The mechanisms underlying these defects and the role of concurrent obesity remain to be determined.


Ameliorating effect of lyophilized extract of Butea frondosa leaves on scopolamine-induced amnesia in rats.
Butea frondosa (BF) Roxb. & Koen. (syn. B. monosperma Lam.) (Fabaceae) leaves have been used in folklore medicine for the treatment of diabetes, conjunctivitis, gastrointestinal tract, and central nervous system disorders such as anxiety, amnesia, etc. To evaluate the effect of lyophilized hydroalcoholic extract of BF leaves (BFLE) at 100, 200 and 400 mg/kg, p.o., for its memory enhancing activity against scopolamine-induced amnesia in rats. Antiamnesic effect of the BFLE was evaluated using Morris water maze and object recognition test models. The effect of BFLE on acetylcholinesterase activity and malondialdehyde and glutathione levels were also evaluated in brain homogenate. BFLE ameliorates scopolamine-induced amnesia in both the models with maximum effect at 400 mg/kg. BFLE (400 mg/kg) decreased escape latency and increased time spent in target quadrant (24.2 and 42.5 s, respectively) in comparison to scopolamine (82 and 18.2 s, respectively) in the Morris water maze task. In the object recognition test, BFLE produced significant increase in ability to discriminate between novel and familiar objects. The highest investigated dose of BFLE (400 mg/kg), produced a significant decrease in acetylcholinesterase activity and malondialdehyde levels, and improves glutathione levels in comparison to scopolamine. Moreover, this effect of BFLE at 400 mg/kg was comparable to that of standard, donepezil. BFLE exhibited significant antiamnesic activity in rats thereby validating its folklore use.


Decomposing demographic contributions to the effective population size with moose as a case study.
Levels of random genetic drift are influenced by demographic factors, such as mating system, sex ratio and age structure. The effective population size (Ne ) is a useful measure for quantifying genetic drift. Evaluating relative contributions of different demographic factors to Ne is therefore important to identify what makes a population vulnerable to loss of genetic variation. Until recently, models for estimating Ne have required many simplifying assumptions, making them unsuitable for this task. Here, using data from a small, harvested moose population, we demonstrate the use of a stochastic demographic framework allowing for fluctuations in both population size and age distribution to estimate and decompose the total demographic variance and hence the ratio of effective to total population size (Ne /N) into components originating from sex, age, survival and reproduction. We not only show which components contribute most to Ne /N currently, but also which components have the greatest potential for changing Ne /N. In this relatively long-lived polygynous system we show that Ne /N is most sensitive to the demographic variance of older males, and that both reproductive autocorrelations (i.e., a tendency for the same individuals to be successful several years in a row) and covariance between survival and reproduction contribute to decreasing Ne /N (increasing genetic drift). These conditions are common in nature and can be caused by common hunting strategies. Thus, the framework presented here has great potential to increase our understanding of the demographic processes that contribute to genetic drift and viability of populations, and to inform management decisions.


A High-Protein, Low Glycemic Index Diet Suppresses Hunger but Not Weight Regain After Weight Loss: Results From a Large, 3-Years Randomized Trial (PREVIEW).
Background: Previous studies have shown an increase in hunger during weight-loss maintenance (WLM) after diet-induced weight loss. Whether a combination of a higher protein, lower glycemic index (GI) diet and physical activity (PA) can counteract this change remains unclear. Aim: To compare the long-term effects of two diets [high protein (HP)-low GI vs. moderate protein (MP)-moderate GI] and two PA programs [high intensity (HI) vs. moderate intensity (MI)] on subjective appetite sensations during WLM after ≥8% weight loss (WL). Methods: Data derived from the 3-years PREVIEW randomized intervention study. An 8-weeks WL phase using a low-energy diet was followed by a 148-weeks randomized WLM phase. For the WLM phase, participants were assigned to one of the four groups: HP-MI, HP-HI, MP-MI, and MP-HI. Available data from 2,223 participants with overweight or obesity (68% women; BMI ≥ 25 kg/m2). Appetite sensations including satiety, hunger, desire to eat, and desire to eat something sweet during the two phases (at 0, 8 weeks and 26, 52, 104, and 156 weeks) were assessed based on the recall of feelings during the previous week using visual analogue scales. Differences in changes in appetite sensations from baseline between the groups were determined using linear mixed models with repeated measures. Results: There was no significant diet × PA interaction. From 52 weeks onwards, decreases in hunger were significantly greater in HP-low GI than MP-moderate GI (P time × diet = 0.018, P dietgroup = 0.021). Although there was no difference in weight regain between the diet groups (P time × diet = 0.630), hunger and satiety ratings correlated with changes in body weight at most timepoints. There were no significant differences in appetite sensations between the two PA groups. Decreases in hunger ratings were greater at 52 and 104 weeks in HP-HI vs. MP-HI, and greater at 104 and 156 weeks in HP-HI vs. MP-MI. Conclusions: This is the first long-term, large-scale randomized intervention to report that a HP-low GI diet was superior in preventing an increase in hunger, but not weight regain, during 3-years WLM compared with a MP-moderate GI diet. Similarly, HP-HI outperformed MP-HI in suppressing hunger. The role of exercise intensity requires further investigation. Clinical Trial Registration: www.ClinicalTrials.gov, identifier: NCT01777893.


Programmed assembly of polymer-DNA conjugate nanoparticles with optical readout and sequence-specific activation of biorecognition.
Soft micellar nanoparticles can be prepared from DNA conjugates designed to assemble via base pairing such that strands containing a polymer corona and a cholesterol tail generate controlled supramolecular architecture. Functionalization of one DNA conjugate strand with a biorecognition ligand results in shielding of the ligand when in the micelle, while encoding of the DNA sequences with overhangs allows supramolecular unpacking by addition of a complementary strand and sequence-specific unshielding of the ligand. The molecular assembly/disassembly and 'on-off' switch of the recognition signal is visualized by FRET pair signalling, PAGE and a facile turbidimetric binding assay, allowing direct and amplified readout of nucleic acid sequence recognition.


Conditioned Media From Glial Cells Promote a Neural-Like Connexin Expression in Human Adipose-Derived Mesenchymal Stem Cells.
The expression of neuronal and glial connexins (Cxs) has been evaluated in adipose-derived mesenchymal stem cells (ASCs) whose neural differentiation was promoted by a conditioned medium (CM) obtained from cultures of olfactory ensheathing cells (OECs) or Schwann cells (SCs). By immunocytochemistry and flow cytometer analysis it was found that Cx43 was already considerably expressed in naïve ASCs and further increased after 24 h and 7 days from CM exposition. Cx32 and Cx36 were significantly improved in conditioned cultures compared to control ASCs, whereas a decreased expression was noticed in the absence of CM treatments. Cx47 was virtually absent in any conditions. Altogether, high basal levels and induced increases of Cx43 expression suggest a potential attitude of ASCs toward an astrocyte differentiation, whereas the lack of Cx47 would indicate a poor propensity of ASCs to become oligodendrocytes. CM-evoked Cx32 and Cx36 increases showed that a neuronal- or a SC-like differentiation can be promoted by using this strategy. Results further confirm that environmental cues can favor an ASC neural differentiation, either as neuronal or glial elements. Of note, the use of glial products present in CM rather than the addition of chemical agents to achieve such differentiation would resemble "more physiological" conditions of differentiation. As a conclusion, the overexpression of typical neural Cxs would indicate the potential capability of neural-like ASCs to interact with neighboring neural cells and microenvironment.


Aging effects on passive resistive torque in the rat ankle joint after lengthening contractions.
The aim of this study was to evaluate whether aging affects (1) the sensation of joint stiffness after lengthening contractions (LCs); (2) passive resistive torque (PRT) of the ankle joint; (3) and the connectin (titin) isoform composition in the medial gastrocnemius (MG) muscle. Anesthetized young (9 weeks) and adult (35 weeks) Wistar rats (n = 6 per group) were used in the present study. A single bout of LCs was performed on the MG muscle with a combination of electrically induced tetanic contractions via a skin electrode and simultaneous forced dorsiflexion of the ankle joint (angular velocity 15 degrees /s, 0 degrees -45 degrees ). Static PRT of the ankle joint (at 30 degrees and 45 degrees ) was measured to evaluate joint stiffness. These parameters were measured until 10 days after treatment. The connectin isoform was measured as muscle extensibility employing low-porosity 2% polyacrylamide gel electrophoresis. The averaged static PRT was significantly higher in adult rats than in young rats. Connectin isoform analysis revealed that the adult group contained larger amounts of beta-connectin than did the young rats. After the LCs, static PRT of the ankle joint gradually increased until day 4 in the young group, whereas the adult group did not show a significant change during the experimental period. We concluded that (1) joint stiffness of adult rats is greater than in young rats, similar to human studies; (2) the increased joint stiffness may be due to connectin isoform composition; and (3) joint stiffness after MG muscle LCs is more apparent in young rats.


Inter-dog aggression in a UK owner survey: prevalence, co-occurrence in different contexts and risk factors.
Aggression between dogs is common and can result in injury. The aims of this study were to estimate prevalence, evaluate co-occurrence with human-directed aggression, and investigate potential risk factors, using a cross-sectional convenience sample of dog owners. Aggression (barking, lunging, growling or biting) towards unfamiliar dogs was reported to currently occur, by 22 per cent of owners, and towards other dogs in the household, by 8 per cent. A low level of concordance between dog and human-directed aggression suggested most dogs were not showing aggression in multiple contexts. Aggression towards other dogs in the household was associated with increasing dog age, use of positive punishment/negative reinforcement training techniques, and attending ring-craft classes. Aggression towards other dogs on walks was associated with location of questionnaire distribution, owner age, age of dog, origin of dog, dog breed type, use of positive punishment/negative reinforcement training techniques and attending obedience classes for more than four weeks. In both, the amount of variance explained by models was low (<15 per cent), suggesting that unmeasured factors mostly accounted for differences between groups. These results suggest general characteristics of dogs and owners which contribute to intraspecific aggression, but also highlight that these are relatively minor predictors.


Interactions in the ionic liquid [EMIM][FAP]: a coupled experimental and computational analysis.
Gas-phase electronic and structural properties of the room temperature ionic liquid 1-ethyl-3-methylimidazolium tris(perfluoroethyl)trifluorophosphate ([EMIM][FAP]) were studied using density functional theory, and confirmed with results from infrared spectroscopy. A conformational analysis allowed the identification of several plausible conformers of the ion pairs. For the detected conformers, the infrared spectra were predicted and their thermodynamic properties were evaluated. The topology of the electronic density of the most stable conformers of [EMIM][FAP] ion pairs were characterised using the quantum theory of atoms in molecules. A number of possible hydrogen bonds between the cations and anions of the ionic liquid were identified. Excellent correspondence was found between the predicted spectra of gas-phase [EMIM][FAP] conformers and the experimental infrared spectrum, which in turn allowed a clear attribution of the vibration modes of [EMIM][FAP]. Finally, the contribution of the various conformers of both isomers of the [FAP](-) anion to the ionic liquid macro-properties is shown.


Retained Foreign Body in a Diabetic Patient's Hand.
Diabetic peripheral neuropathy puts patients at increased risk of acute injury by foreign bodies and also contributes to delayed presentation and diagnosis. We describe a 57-year-old patient with poorly controlled type 1 diabetes who presented with a three-week history of worsening swelling and erythema in the metacarpophalangeal joint of his left thumb. He denied any previous trauma or injury and was initially treated with intravenous antibiotics. Subsequent imaging revealed septic arthritis and osteomyelitis secondary to a retained foreign body, which was surgically removed in theatre. This is the first reported case of a retained foreign body in the hand of a diabetic patient, and demonstrates the importance of early radiological imaging of peripheral limb injuries in high-risk patients.


Patient and Family Engagement in Designing and Implementing a Weaning Trial: A Novel Research Paradigm in Critical Care.
The call for meaningful patient and family engagement in research has recently gained considerable momentum. This article defines patient and family engagement broadly and specifically in clinical research. Using a multicenter, North American weaning trial as an exemplar, we describe our early experiences as clinical researchers with patient and family engagement. The role of our Patient and Family Advisory Committee in trial design and implementation is illustrated. Through our experiences, we share our insights regarding the perceived opportunities and also highlight some challenges associated with engaging patients and family engagement in critical care research. Although "engagement science" is in its infancy, engaging patients and families in research holds promise as a novel research paradigm that will not only provide new insights into the questions, methods, and outcomes used in ICU research, but it will also make investments in research more accountable and ensure a strong "patient- and family-centered focus" of our research.


Risk of cardiovascular disease among teachers in Cape Town: Findings of the South African PaCT pilot study.
The accelerating epidemic of cardiovascular disease (CVD) and other non-communicable diseases (NCDs) highlights the need to establish long-term cohort studies in Africa. The Partnership for Cohort Research and Training (PaCT) seeks to study NCDs in South Africa (SA), Uganda, Tanzania and Nigeria on a long-term basis. Pilot studies at each site have tested feasibility. The SA site additionally studied the prevalence of CVD risk factors and categorised participants' 10-year predicted risk of a cardiovascular event. We enrolled teachers from 111 public schools in the Metro South Education District in Cape Town, SA, between January 2011 and May 2012. Participants completed a self-administered questionnaire and biological measurements, and chose post or email for 6-month follow-up. The participation of schools was permitted by 53.2% of principals, and 489 of 1 779 teachers agreed to participate. Of teachers willing to participate in the follow-up, 52% were retained, three-quarters by post and a quarter by email. Their mean age was 46.3 years and 70.3% were female. The prevalence of CVD risk factors was high and featured hypertension (48.5%), hypercholesterolaemia (20.5%), smoking (18.0%), diabetes (10.1%) and chronic kidney disease (10.4%), while 84.7% were overweight or obese. Of the participants, 18.7% were at high risk of a heart attack or stroke within 10 years. Establishing a cohort study among teachers has challenges but also opportunities for addressing CVD, which will soon impose a substantial burden on Cape Town's education system.


Dynamic speckle multiplexing scheme in volume holographic data storage and its realization.
Dynamic speckle multiplexing scheme in volume holographic data storage is proposed, since it offers a novel multiplexing geometry, and could be combined with other schemes to make the full use of the dynamic ranges. In this scheme, a random diffuser is added in the original reference path of the classical 90 masculine setup. In this paper, we analyzed the propagation of the speckle field in the holographic system and established the related theoretical model based on the dynamic speckle auto-correlation function and diffraction theory. We successfully realized the dynamic speckle multiplexing in our experimental system and reached a storage density of 4.6 Gigapixels/cm3 based on the DPL laser source.


Insulin resistance versus insulin secretion in the hypertension of obesity.
We measured the degree of association between obesity, blood pressure, insulin resistance, and insulin secretion in 72 male and female obese hypertensive, obese nonhypertensive, and normal weight control subjects. Baseline weight, body mass index, percent body fat, waist/hip ratio, and systolic and diastolic blood pressures were obtained. Insulin sensitivity was assessed according to Bergman's minimal model. Twelve-hour urinary c-peptide was measured after a standard liquid meal. Insulin action was inversely associated with blood pressure status, obesity status, and age. Meal-stimulated c-peptide excretion significantly correlated with systolic blood pressure and percent fat but not with body mass index or age. Multivariate regression analysis indicated that, of the measures of body composition, percent fat and waist/hip ratio had the strongest correlation with insulin action either alone or in combination with c-peptide excretion. Obese hypertensive patients had an index of insulin action (10(-4).min-1/[microunits/ml]) of 1.34 +/- 0.19, which was significantly (p less than 0.003) lower than in the obese nonhypertensive patients (index, 2.26 +/- 0.10) or the nonobese subjects (index, 5.41 +/- 0.26, p less than 0.001). Meal-stimulated c-peptide excretion (nmol/kg lean body mass) was increased only in the obese hypertensive group (0.32 +/- 0.01) and was significantly higher (p less than 0.001) than in the obese nonhypertensive (0.16 +/- 0.01) or the nonobese subjects (0.14 +/- 0.01). These results support the hypothesis that abnormalities in blood pressure regulation, insulin-stimulated glucose uptake, and insulin secretion coexist.


Toll-like receptors 2 and 4 mediate the capacity of mesenchymal stromal cells to support the proliferation and differentiation of CD34⁺ cells.
Bone marrow derived-mesenchymal stromal cells (BM-MSCs) are multipotent, nonhematopoietic progenitors in a hematopoietic microenvironment and indispensable for regulating hematopoiesis. Several studies have reported that toll-like receptors (TLRs) are expressed in mesenchymal stromal cells (MSCs) to modulate their biological functions. In this study, we investigated the possible role(s) of TLRs in mediating the hematopoiesis-supporting role of human BM-MSCs. Human BM-MSCs were analyzed for mRNA expression of TLR1-10 by reverse transcription-polymerase chain reaction. TLR1-6, but not TLR7-10 were expressed by BM-MSCs. The protein expression of TLR2 and TLR4 was also confirmed by flow cytometry. We further explored the role of TLR2 and TLR4 in mediating the capacity of BM-MSCs to support the proliferation and differentiation of CD34(+) hematopoietic stem/progenitor cells obtained from cord blood. BM-MSCs increased proliferation of CD34(+) cells and promoted the differentiation towards the myeloid lineage 7 or 14days after co-culture, as well as colony formation by those cells and the production of interleukin 1 (IL-1), IL-8, IL-11, stem cell factor (SCF), granulocyte colony-stimulating factor (CSF), macrophage CSF and granulocyte-macrophage CSF, if MSCs had been stimulated with TLR2 agonist (PAM(3)CSK(4)) or TLR4 agonist (LPS). Interestingly, although these effects were elevated in a different degree, a synergistic effect was not observed in BM-MSCs co-stimulated with PAM(3)CSK(4) and LPS. Together, our findings suggest that TLR2 and TLR4 signaling may indirectly regulate hematopoiesis by modulating BM-MSCs' functions. The increased hematopoietic proliferation and differentiation could be mediated, at least in part, by augmented hematopoiesis-related cytokine production of BM-MSCs.


The effects of climate change and land-use change on demographic rates and population viability.
Understanding the processes that lead to species extinctions is vital for lessening pressures on biodiversity. While species diversity, presence and abundance are most commonly used to measure the effects of human pressures, demographic responses give a more proximal indication of how pressures affect population viability and contribute to extinction risk. We reviewed how demographic rates are affected by the major anthropogenic pressures, changed landscape condition caused by human land use, and climate change. We synthesized the results of 147 empirical studies to compare the relative effect size of climate and landscape condition on birth, death, immigration and emigration rates in plant and animal populations. While changed landscape condition is recognized as the major driver of species declines and losses worldwide, we found that, on average, climate variables had equally strong effects on demographic rates in plant and animal populations. This is significant given that the pressures of climate change will continue to intensify in coming decades. The effects of climate change on some populations may be underestimated because changes in climate conditions during critical windows of species life cycles may have disproportionate effects on demographic rates. The combined pressures of land-use change and climate change may result in species declines and extinctions occurring faster than otherwise predicted, particularly if their effects are multiplicative.


Cognitive functioning in subjects with recent-onset psychosis from a low-middle-income environment: multiple-domain deficits and longitudinal evaluation.
Cognitive deficits are a key feature of recent-onset psychosis, but there is no consensus on whether such deficits are generalized or confined to specific domains. Besides, it is unclear whether cognitive deficits: a) are found in psychotic patients in samples from outside high-income countries; and b) whether they progress uniformly over time in schizophrenia and affective psychoses. We applied 12 tests organized into eight cognitive domains, comparing psychosis patients (n = 56, time from initial contact = 677.95+/-183.27 days) versus healthy controls (n=70) recruited from the same area of São Paulo, Brazil. Longitudinal comparisons (digit span and verbal fluency) were conducted between a previous assessment of the subjects carried out at their psychosis onset, and the current follow-up evaluation. Psychosis patients differed significantly from controls on five domains, most prominently on verbal memory. Cognitive deficits remained detectable in separate comparisons of the schizophrenia subgroup and, to a lesser extent, the affective psychosis subjects against controls. Longitudinal comparisons indicated significant improvement in schizophrenia, affective psychoses, and control subjects, with no significant group-by-time interactions. Our results reinforce the view that there are generalized cognitive deficits in association with recent-onset psychoses, particularly of non-affective nature, which persist over time.


Profile and geographic distribution of reported cases of visceral leishmaniasis in Campo Grande, State of Mato Grosso do Sul, Brazil, from 2002 to 2009.
This study sought to describe the profile and geographic distribution of reported cases of visceral leishmaniasis (VL) in the City of Campo Grande, State of Mato Grosso do Sul (MS), Brazil, from 2002 to 2009. Human data were collected from the Brazilian National Information System for Notifiable Diseases. Canine cases and entomological data were obtained from the Information Service for Canine Visceral Leishmaniasis Control/Campo Grande, MS. A total of 951 records from 2002 to 2009 were investigated. The number of reported cases of VL in males was significantly higher (p < 0.0001) than that in females. The higher frequency observed among males was associated with age (p < 0.0001), which increased in individuals aged 40 years and older. The overall fatality rate was 7.4%. Entomological surveys conducted in 2006, 2007, and 2009 showed the insect vector Lutzomyia longipalpis to be present in all urban regions of the county. VL cases in humans and dogs, as well as in vectors, occurs in all urban regions of Campo Grande. Despite not observing tendencies of increase or reduction in the incidence of the disease due to aging, the major incidence in men is higher in those aged 40 years or above.


MYH9 is a major-effect risk gene for focal segmental glomerulosclerosis.
The increased burden of chronic kidney and end-stage kidney diseases (ESKD) in populations of African ancestry has been largely unexplained. To identify genetic variants predisposing to idiopathic and HIV-1-associated focal segmental glomerulosclerosis (FSGS), we carried out an admixture-mapping linkage-disequilibrium genome scan on 190 African American individuals with FSGS and 222 controls. We identified a chromosome 22 region with a genome-wide logarithm of the odds (lod) score of 9.2 and a peak lod of 12.4 centered on MYH9, a functional candidate gene expressed in kidney podocytes. Multiple MYH9 SNPs and haplotypes were recessively associated with FSGS, most strongly a haplotype spanning exons 14 through 23 (OR = 5.0, 95% CI = 3.5-7.1; P = 4 x 10(-23), n = 852). This association extended to hypertensive ESKD (OR = 2.2, 95% CI = 1.5-3.4; n = 433), but not type 2 diabetic ESKD (n = 476). Genetic variation at the MYH9 locus substantially explains the increased burden of FSGS and hypertensive ESKD among African Americans.


Information flow, opinion polling and collective intelligence in house-hunting social insects.
The sharing and collective processing of information by certain insect societies is one of the reasons that they warrant the superlative epithet 'super-organisms' (Franks 1989, Am. Sci. 77, 138-145). We describe a detailed experimental and mathematical analysis of information exchange and decision-making in, arguably, the most difficult collective choices that social insects face: namely, house hunting by complete societies. The key issue is how can a complete colony select the single best nest-site among several alternatives? Individual scouts respond to the diverse information they have personally obtained about the quality of a potential nest-site by producing a recruitment signal. The colony then deliberates over (i.e. integrates) different incoming recruitment signals associated with different potential nest-sites to achieve a well-informed collective decision. We compare this process in honeybees and in the ant Leptothorax albipennis. Notwithstanding many differences - for example, honeybee colonies have 100 times more individuals than L. albipennis colonies - there are certain similarities in the fundamental algorithms these societies appear to employ when they are house hunting. Scout honeybees use the full power of the waggle dance to inform their nest-mates about the distance and direction of a potential nest-site (and they indicate the quality of a nest-site indirectly through the vigour of their dance), and yet individual bees perhaps only rarely make direct comparisons of such sites. By contrast, scouts from L. albipennis colonies often compare nest-sites, but they cannot directly inform one another of their estimation of the quality of a potential site. Instead, they discriminate between sites by initiating recruitment sooner to better ones. Nevertheless, both species do make use of forms of opinion polling. For example, scout bees that have formerly danced for a certain site cease such advertising and monitor the dances of others at random. That is, they act without prejudice. They neither favour nor disdain dancers that advocate the site they had formerly advertised or the alternatives. Thus, in general the bees are less well informed than they would be if they systematically monitored dances for alternative sites rather than spending their time reprocessing information they already have. However, as a result of their lack of prejudice, less time overall will be wasted in endless debate among stubborn and potentially biased bees. Among the ants, the opinions of nest-mates are also pooled effectively when scouts use a threshold population of their nest-mates present in a new nest-site as a cue to switch to more rapid recruitment. Furthermore, the ants' reluctance to begin recruiting to poor nest-sites means that more time is available for the discovery and direct comparison of alternatives. Likewise, the retirement of honeybee scouts from dancing for a given site allows more time for other scouts to find potentially better sites. Thus, both the ants and the bees have time-lags built into their decision-making systems that should facilitate a compromise between thorough surveys for good nest-sites and relatively rapid decisions. We have also been able to show that classical mathematical models can illuminate the processes by which colonies are able to achieve decisions that are relatively swift and very well informed.


Low-frequency electronic noise in superlattice and random-packed thin films of colloidal quantum dots.
We report measurements of low-frequency electronic noise in ordered superlattice, weakly-ordered and random-packed thin films of 6.5 nm PbSe quantum dots prepared using several different ligand chemistries. For all samples, the normalized noise spectral density of the dark current revealed a Lorentzian component, reminiscent of the generation-recombination noise, superimposed on the 1/f background (f is the frequency). An activation energy of ∼0.3 eV was extracted from the temperature dependence of the noise spectra in the ordered and random quantum dot films. The noise level in the ordered films was lower than that in the weakly-ordered and random-packed films. A large variation in the magnitude of the noise spectral density was also observed in samples with different ligand treatments. The obtained results are important for application of colloidal quantum dot films in photodetectors.


Plasma soluble corin in patients with heart failure.
Corin is a transmembrane protease that processes natriuretic peptides in the heart. Like many membrane proteins, corin is shed from the cell surface. In this study, we obtained plasma samples from healthy controls and patients with heart failure (HF) and acute myocardial infarction. Soluble corin levels in plasma were measured by an ELISA method. In healthy adults (n=198), plasma corin levels were 690 pg/mL (SD, 260 pg/mL). The corin levels did not differ significantly among different age groups. In patients with HF (n=291), plasma corin levels were significantly lower compared with that of healthy controls (365 pg/mL [SD, 259]; P<0.001). The reduction in plasma corin levels seemed to correlate with the severity of HF. In patients of New York Heart Association classes II, III, and IV, plasma corin levels were 450 pg/mL (SD, 281 pg/mL; n=69), 377 pg/mL (SD, 270 pg/mL; n=132), and 282 pg/mL (SD, 194 pg/mL; n=90), respectively (P<0.001 class II vs class IV; P<0.05 class III vs class IV). In contrast, plasma corin levels in patients with acute myocardial infarction (n=73) were similar to that of healthy controls (678 pg/mL [SD, 285 pg/mL]; P>0.05). Soluble corin was detected in human plasma. Plasma corin levels were reduced significantly in patients with HF but not in those with acute myocardial infarction. Our results indicate that corin deficiency may contribute to the pathogenesis of HF and that plasma corin may be used as a biomarker in the diagnosis of HF.


Lower dimensional kernels for video discriminators.
This work presents an analysis of the discriminators used in Generative Adversarial Networks (GANs) for Video. We show that unconstrained video discriminator architectures induce a loss surface with high curvature which make optimization difficult. We also show that this curvature becomes more extreme as the maximal kernel dimension of video discriminators increases. With these observations in hand, we propose a methodology for the design of a family of efficient Lower-Dimensional Video Discriminators for GANs (LDVD-GANs). The proposed methodology improves the performance and efficiency of video GAN models it is applied to and demonstrates good performance on complex and diverse datasets such as UCF-101. In particular, we show that LDVDs can double the performance of Temporal-GANs and provide for state-of-the-art performance on a single GPU using the proposed methodology.


Detecting cognitive impairment in clients with mild stroke or transient ischemic attack attending a stroke prevention clinic.
Twenty clients diagnosed with probable transient ischemic attack (TIA) or stroke attending a stroke prevention clinic (SPC) were screened for cognitive function, as one inclusion criteria for a pilot study examining medication adherence and hypertension management. The Mini Mental State Examination (MMSE) was administered at study admission followed by a second screening within two weeks using the Montreal Cognitive Assessment (MoCA) tool. Individual scores for the MMSE and MoCA were compared. Results demonstrated that the majority (90%) of participants scored in the normal range (> or = 26) on the MMSE (m = 27.9 sd 2.15). However, more than half (55%) of participants had some degree of cognitive impairment based on MoCA scores of < 26 (m = 23.65 sd = 4.082). MoCA scores demonstrated a wider range (Range = 16) compared to the range of MMSE scores (Range = 8). MoCA scores were significantly (p = < 0.05) lower than the MMSE scores. Findings from this pilot study suggest that the MoCA test will identify more deficits in cognition among SPC clients diagnosed with cerebrovascular disease. Further investigation is underway to determine the implications of these deficits on SPC clients' abilities to follow medication and other treatment regimens.


"Developing good taste in evidence": facilitators of and hindrances to evidence-informed health policymaking in state government.
Policymaking is a highly complex process that is often difficult to predict or influence. Most of the scholarship examining the role of research evidence in policymaking has focused narrowly on characteristics of the evidence and the interactions between scientists and government officials. The real-life context in which policymakers are situated and make decisions also is crucial to the development of evidence-informed policy. This qualitative study expands on other studies of research utilization at the state level through interviews with twenty-eight state legislators and administrators about their real-life experiences incorporating evidence into policymaking. The interviews were coded inductively into the following categories: (1) the important or controversial issue or problem being addressed, (2) the information that was used, (3) facilitators, and (4) hindrances. Hindrances to evidence-informed policymaking included institutional features; characteristics of the evidence supply, such as research quantity, quality, accessibility, and usability; and competing sources of influence, such as interest groups. The policymakers identified a number of facilitators to the use of evidence, including linking research to concrete impacts, costs, and benefits; reframing policy issues to fit the research; training to use evidence-based skills; and developing research venues and collaborative relationships in order to generate relevant evidence. Certain hindrances to the incorporation of research into policy, like limited budgets, are systemic and not readily altered. However, some of the barriers and facilitators of evidence-informed health policymaking are amenable to change. Policymakers could benefit from evidence-based skills training to help them identify and evaluate high-quality information. Researchers and policymakers thus could collaborate to develop networks for generating and sharing relevant evidence for policy.


The mediational role of panic self-efficacy in cognitive behavioral therapy for panic disorder: a systematic review and meta-analysis.
Cognitive models of panic disorder (PD) with or without agoraphobia have stressed the role of catastrophic beliefs of bodily symptoms as a central mediating variable of the efficacy of cognitive behavioral therapy (CBT). Perceived ability to cope with or control panic attacks, panic self-efficacy, has also been proposed to play a key role in therapeutic change; however, this cognitive factor has received much less attention in research. The aim of the present review is to evaluate panic self-efficacy as a mediator of therapeutic outcome in CBT for PD using descriptive and meta-analytic procedures. We performed systematic literature searches, and included and evaluated 33 studies according to four criteria for establishing mediation. Twenty-eight studies, including nine randomized waitlist-controlled studies, showed strong support for CBT improving panic self-efficacy (criterion 1); ten showed an association between change in panic self-efficacy and change in outcome during therapy (criterion 2); three tested, and one established formal statistical mediation of panic self-efficacy (criterion 3); while four tested and three found change in panic self-efficacy occurring before the reduction of panic severity (criterion 4). Although none of the studies fulfilled all of the four criteria, results provide some support for panic self-efficacy as a mediator of outcome in CBT for PD, generally on par with catastrophic beliefs in the reviewed studies.


High Prevalence of Gestational Diabetes Mellitus in Beijing: Effect of Maternal Birth Weight and Other Risk Factors.
Gestational diabetes mellitus (GDM) is associated with both short- and long-term adverse health consequences for both the mother and her offspring. The aim was to study the prevalence and risk factors for GDM in Beijing. The study population consisted of 15,194 pregnant women attending prenatal care in 15 hospitals in Beijing, who delivered between June 20, 2013, and November 30, 2013, after 28 weeks of gestation. The participants were selected by cluster sampling from the 15 hospitals identified through random systematic sampling based on the number of deliveries in 2012. A questionnaire was designed to collect information. A total of 2987 (19.7%) women were diagnosed with GDM and 208 (1.4%) had diabetes in pregnancy (DIP). Age (OR: 1.053, 95% CI: 1.033-1.074, P < 0.01), family history of diabetes mellitus (OR: 1.481, 95% CI: 1.254-1.748, P < 0.01), prepregnancy body mass index (BMI) (OR: 1.481, 95% CI: 1.254-1.748, P < 0.01), BMI gain before 24 weeks (OR: 1.126, 95% CI: 1.075-1.800, P < 0.01), maternal birth weight (P < 0.01), and fasting plasma glucose at the first prenatal visit (P < 0.01) were identified as risk factors for GDM. In women with birth weight <3000 g, GDM rate was significantly higher. One out of every five pregnant women in Beijing either had GDM or DIP and this constitutes a huge health burden for health services. Prepregnancy BMI and weight gain before 24th week are important modifiable risk factors for GDM. Ensuring birth weight above 3000 g may help reduce risk for future GDM among female offsprings.


Interactions of Brf1 peptides with the tetratricopeptide repeat-containing subunit of TFIIIC inhibit and promote preinitiation complex assembly.
The binding of Brf1 to the tetratricopeptide repeat (TPR)-containing transcription factor IIIC (TFIIIC) subunit (Tfc4) represents a rate-limiting step in the ordered assembly of the RNA polymerase III initiation factor TFIIIB. Tfc4 contains multiple binding sites for Brf1 within its amino terminus and adjacent TPR arrays, but the access of Brf1 to these sites is limited by autoinhibition. Moreover, the Brf1 binding sites in Tfc4 overlap with sites important for the subsequent recruitment of another TFIIIB subunit, Bdp1, implying that repositioning of Brf1 is required after its initial interaction with Tfc4. As a starting point for dissecting the steps in TFIIIC-directed assembly of TFIIIB, we conducted yeast two-hybrid screens of Brf1 peptide libraries against different TPR-containing Tfc4 fragments. Short, biochemically active peptides were identified in three distinct regions of Brf1. Two peptides defined conserved but distal regions of Brf1 that participate in stable binding of Brf1 to TFIIIC-DNA. Remarkably, a third peptide that binds specifically to TPR6-9 of Tfc4 was found to promote the formation of both TFIIIC-DNA and Brf1-TFIIIC-DNA complexes and to reduce the mobility of these complexes in native gels. The data are consistent with this peptide causing a conformational change in TFIIIC that overcomes Tfc4 autoinhibition of Brf1 binding and suggest a structural model for the Brf1-Tfc4 interaction.


2-Aminothiazoles as therapeutic leads for prion diseases.
2-Aminothiazoles are a new class of small molecules with antiprion activity in prion-infected neuroblastoma cell lines (J. Virol. 2010, 84, 3408). We report here structure-activity studies undertaken to improve the potency and physiochemical properties of 2-aminothiazoles, with a particular emphasis on achieving and sustaining high drug concentrations in the brain. The results of this effort include the generation of informative structure-activity relationships (SAR) and the identification of lead compounds that are orally absorbed and achieve high brain concentrations in animals. The new aminothiazole analogue (5-methylpyridin-2-yl)-[4-(3-phenylisoxazol-5-yl)-thiazol-2-yl]-amine (27), for example, exhibited an EC(50) of 0.94 μM in prion-infected neuroblastoma cells (ScN2a-cl3) and reached a concentration of ∼25 μM in the brains of mice following three days of oral administration in a rodent liquid diet. The studies described herein suggest 2-aminothiazoles as promising new leads in the search for effective therapeutics for prion diseases.


Chaperone-mediated hierarchical control in targeting misfolded proteins to aggresomes.
Protein misfolding is a common event in living cells. Molecular chaperones not only assist protein folding; they also facilitate the degradation of misfolded polypeptides. When the intracellular degradative capacity is exceeded, juxtanuclear aggresomes are formed to sequester misfolded proteins. Despite the well-established role of chaperones in both protein folding and degradation, how chaperones regulate the aggregation process remains controversial. Here we investigate the molecular mechanisms underlying aggresome formation in mammalian cells. Analysis of the chaperone requirements for the fate of misfolded proteins reveals an unexpected role of heat shock protein 70 (Hsp70) in promoting aggresome formation. This proaggregation function of Hsp70 relies on the interaction with the cochaperone ubiquitin ligase carboxyl terminal of Hsp70/Hsp90 interacting protein (CHIP). Disrupting Hsp70-CHIP interaction prevents the aggresome formation, whereas a dominant-negative CHIP mutant sensitizes the aggregation of misfolded protein. This accelerated aggresome formation also relies on the stress-induced cochaperone Bcl2-associated athanogene 3. Our results indicate that a hierarchy of cochaperone interaction controls different aspects of the intracellular protein triage decision, extending the function of Hsp70 from folding and degradation to aggregation.


Potency of positive gamma-aminobutyric acid(A) modulators to substitute for a midazolam discriminative stimulus in untreated monkeys does not predict potency to attenuate a flumazenil discriminative stimulus in diazepam-treated monkeys.
In monkeys discriminating midazolam (0.56 mg/kg s.c.) from saline, substitution for midazolam was elicited by various positive gamma-aminobutyric acid(A) (GABA(A)) modulators, including the benzodiazepines (BZs) triazolam, midazolam, and diazepam; the BZ(1)-selective ligands zaleplon and zolpidem; the barbiturates amobarbital and pentobarbital; and the neuroactive steroid pregnanolone. In another group of diazepam (5.6 mg/kg/day p.o.)-treated monkeys discriminating flumazenil (0.32 mg/kg s.c.) from vehicle, these positive GABA(A) modulators shifted the flumazenil dose-effect function to the right, i.e., attenuated diazepam withdrawal. The potency of positive GABA(A) modulators to substitute for midazolam in untreated monkeys did not predict their potency to attenuate the flumazenil stimulus in diazepam-treated monkeys. For instance, larger doses of BZs and BZ(1)-selective ligands were required to attenuate the flumazenil stimulus than to substitute for midazolam. The opposite relationship was revealed for non-BZ ligands, i.e., smaller doses of barbiturates and a neuroactive steroid were required to attenuate the flumazenil stimulus than to substitute for midazolam. The greater potency of non-BZ site ligands to attenuate diazepam withdrawal might be due to actions at a subtype of GABA(A) receptor not modulated by BZ site ligands, to the development of BZ tolerance without cross-tolerance to non-BZ site ligands, or to noncompetitive interactions at the GABA(A) receptor complex. Thus, interactions among GABA(A) modulators in BZ-dependent subjects are not predicted by their acute actions in nondependent subjects. It is not clear whether attenuation of BZ withdrawal is determined by subunit specificity or site of action on the GABA(A) receptor complex.


Liquid-based cytology: evaluation of effectiveness, cost-effectiveness, and application to present practice.
This article reviews the data available as of 2004 on the effectiveness and cost-effectiveness of cervical screening with the two available cytologic methods, the conventional Papanicolaou (Pap; CP) smear and liquid-based cytology (LBC), and discusses the application of LBC to current practice. The majority of LBC studies are on the ThinPrep Pap Test (CYTYC, Boxsborough, MA) and the remainder are on SurePath (TriPath, Burlington, NC), which was previously known as AutoCyte Prep. LBC identified more low-grade squamous intraepithelial lesion (LSIL) Pap test results compared with paired conventional cytology in 17 of 21 ThinPrep and 9 of 12 SurePath "split-sample" studies considered to fulfill the criteria for inclusion in the British NHS Health Technology Assessment (HTA) evaluation of cervical cytology. In four of the six recent ThinPrep and one of two SurePath split-sample studies, more high-grade squamous intraepithelial lesion-positive (HSIL+) results were identified by LBC than by CP. All 15 "direct-to vial studies" meeting HTA criteria reported more LSIL+ results for LBC compared with CP, and all eight of the direct-to-vial studies reporting HSIL+ results separately showed increased detection of high-grade cytology interpretations. Fifteen studies met the criteria for evaluating sensitivity and specificity. Aggregate sensitivity for the CP was 71.5% and for LBC was 80.1%. Indirect comparisons of the two LBC methods did not detect a difference in sensitivity, and a meta-analysis of the six studies comparing specificity between CP and LBC found no difference. Other capabilities of LBC are improved specimen adequacy and the ability to do ancillary testing out of the liquid-based vial. In cost-effective analyses based on models of disease natural history and/or the clinical effectiveness of each screening modality, screening with CP was always dominated by screening with LBC. Primary cervical screening guidelines issued by the American Cancer Society in 2002 recommend repeating the cytology biannually if liquid-based and annually if conventional. The gain in sensitivity, apparent cost-effectiveness, and advantage of having a representative specimen for ancillary testing, support the use of LBC.


Recovery of normal autologous myelopoiesis after graft rejection following allogeneic bone marrow transplant for agnogenic myeloid metaplasia.
Allogeneic hematopoietic transplantation is the only currently available therapy that has the potential to cure agnogenic myeloid metaplasia (AMM) or primary myelofibrosis (PMF). Amelioration of fibrosis and eradication of the abnormal clone is thought to occur through the repopulation of marrow by donor-derived hematopoiesis and graft-vs.-host reaction leading to graft vs. tumor effect. We report here a 50-year-old female with AMM/PMF, conditioned with busulfan and cyclophosphamide, who rejected a single locus (HLA-B) mismatched bone marrow transplant from her daughter, but recovered normal autologous hematopoiesis with disappearance of marrow fibrosis and extramedullary hematopoiesis. Variable number tandem repeats (VNTR) analysis showed a gradual loss of donor-derived hematopoietic cells with recovery of autologous hematopoiesis. This case therefore illustrates that eradication of AMM/PMF in this patient with myeloablative chemotherapy combined with a transient allogeneic effect was sufficient to suppress the abnormal stem cell clone associated with AMM/PMF with subsequent cure.


Pseudospectral versus finite-difference schemes in the numerical integration of stochastic models of surface growth.
We present a comparison between finite differences schemes and a pseudospectral method applied to the numerical integration of stochastic partial differential equations that model surface growth. We have studied, in 1+1 dimensions, the Kardar, Parisi, and Zhang model (KPZ) and the Lai, Das Sarma, and Villain model (LDV). The pseudospectral method appears to be the most stable for a given time step for both models. This means that the time up to which we can follow the temporal evolution of a given system is larger for the pseudospectral method. Moreover, for the KPZ model, a pseudospectral scheme gives results closer to the predictions of the continuum model than those obtained through finite difference methods. On the other hand, some numerical instabilities appearing with finite difference methods for the LDV model are absent when a pseudospectral integration is performed. These numerical instabilities give rise to an approximate multiscaling observed in earlier numerical simulations. With the pseudospectral approach no multiscaling is seen in agreement with the continuum model.


Effect of habitual knuckle cracking on hand function.
The relation of habitual knuckle cracking to osteoarthrosis with functional impairment of the hand has long been considered an old wives' tale without experimental support. The mechanical sequelae of knuckle cracking have been shown to produce the rapid release of energy in the form of sudden vibratory energy, much like the forces responsible for the destruction of hydraulic blades and ship propellers. To investigate the relation of habitual knuckle cracking to hand function 300 consecutive patients aged 45 years or above and without evidence of neuromuscular, inflammatory, or malignant disease were evaluated for the presence of habitual knuckle cracking and hand arthritis/dysfunction. The age and sex distribution of the patients (74 habitual knuckle crackers, 226 non-knuckle crackers) was similar. There was no increased preponderance of arthritis of the hand in either group; however, habitual knuckle crackers were more likely to have hand swelling and lower grip strength. Habitual knuckle cracking was associated with manual labour, biting of the nails, smoking, and drinking alcohol. It is concluded that habitual knuckle cracking results in functional hand impairment.


Influence of landscape factors and management decisions on spatial and temporal patterns of the transmission of chronic wasting disease transmission in white-tailed deer.
Chronic wasting disease (CWD) has been reported in white-tailed deer at the border of the US states of Illinois and Wisconsin since 2002. Transmission of infectious prions between animals and from the environment has resulted in spatial and temporal structure observable in the spatio-temporal patterns of reported cases. Case locations of 382 positive cases from 28,954 deer tested between 2002 and 2009 provided insight into the potential risk factors and landscape features associated with transmission using a combination of clustering, generalised linear modelling and descriptive evaluations of a risk map of predicted cases of CWD. A species distribution map of white-tailed deer developed using MaxEnt provided an estimate of deer locations. We found that deer probability increased in areas with larger forests and less urban and agricultural lands. Spatial clustering analysis revealed a core area of persistent CWD transmission in the northern part of the region. The regression model indicated that larger and more compact forests were associated with higher risk for CWD. High risk areas also had soils with less clay and more sand than other parts of the region. The transmission potential was higher where landscape features indicated the potential for higher deer concentrations. The inclusion of spatial lag variables improved the model. Of the 102 cases reported in the study area in the two years following the study period, 89 (87%) of those were in the 32% of the study area with the highest 50% of predicted risk of cases.


A patient questionnaire to identify bowel disease.
Although functional gastrointestinal symptoms are seen frequently by internists and are the commonest reason for patients to be referred to gastroenterologists, no validated self-report questionnaire is available for their diagnosis. To differentiate among non-ulcer dyspepsia, the irritable bowel syndrome, organic gastrointestinal disease, and health, we developed a self-report questionnaire. Our bowel disease questionnaire, which evaluated 46 symptom-related items was completed prospectively by 361 subjects before their clinical evaluation as outpatients. Of these subjects, 115 were categorized ultimately as having functional bowel disease (non-ulcer dyspepsia or the irritable bowel syndrome), 101 were categorized ultimately as having organic gastrointestinal disease, and 145 were healthy persons having routine periodic examinations for whom no additional diagnoses were made. All diagnoses were based on independent clinical evaluations, not on the patients' responses to the questionnaire. The bowel disease questionnaire was acceptable and easily completed; it elicited symptoms in a highly reliable manner and was shown to be a valid measure of functional bowel complaints. Our questionnaire discriminated non-ulcer dyspepsia from irritable bowel syndrome with a sensitivity of 75% and a specificity of 72%, and it discriminated functional bowel disease from organic disease and health with sensitivities of 85% and 83%, and specificities of 60% and 76%, respectively. We believe that this questionnaire is an additional and useful diagnostic tool for identifying patients with functional gastrointestinal symptoms.


In-vitro activity of fosfomycin against Escherichia coli and Klebsiella pneumoniae bloodstream isolates and frequency of OXA-48, NDM, KPC, VIM, IMP types of carbapenemases in the carbapenem-resistant groups.
The aim of this study was to determine the in-vitro activity of fosfomycin against Escherichia coli (E. coli) and Klebsiella pneumoniae (K. pneumoniae) isolates and the frequency of OXA-48, NDM, KPC, VIM, IMP types of carbapenemases in the carbapenem-resistant (CR) groups. A total of 346 isolates (126 E. coli and 220 K. pneumoniae) from nosocomial bloodstream infections were included. Carbapenem and fosfomycin susceptibility were tested by Etest (bioMerieux, France) and agar dilution methods, respectively and evaluated in accordance with EUCAST criteria. The presence of OXA-48, NDM, KPC, VIM, IMP types of carbapenemases were conducted by using PCR method. Of the total 346 isolates, 185 (41 E. coli, 144 K. pneumoniae) were CR. Fosfomycin susceptibility of E. coli was higher than 95% and was not statistically significant between the CR and carbapenem-susceptible (CS) groups. Fosfomycin susceptibility of CS and CR K. pneumoniae was 90.7% and 69.4%, respectively, and statistically significantly lower in CR group. Of the total 185 CR isolates, 163 (32 E. coli, 131 K. pneumoniae) were producing carbapenemases. OXA-48 was the prominent carbapenemase type produced by E. coli (96.8%) and K. pneumoniae (70.9%). The frequency of NDM and KPC types produced by K. pneumoniae was 20.6% and 15.2%, respectively. Fosfomycin has substantial in-vitro activity against nosocomial CS and CR E. coli and CS K. pneumoniae bloodstream isolates. However, due to the risk of emerging resistance with fosfomycin monotherapy, combination therapy should be considered to obtain the possible additive or synergistic activity. Emerging fosfomycin resistance of CR K. pneumoniae isolates is alarming and OXA-48 is still the prominent carbapenemase type in Turkey.


PHYLOGENETIC ANALYSIS OF BRACHIDINIUM CAPITATUM (DINOPHYCEAE) FROM THE GULF OF MEXICO INDICATES MEMBERSHIP IN THE KARENIACEAE(1).
Brachidinium capitatum F. J. R. Taylor, typically considered a rare oceanic dinoflagellate, and one which has not been cultured, was observed at elevated abundances (up to 65 cells · mL(-1) ) at a coastal station in the western Gulf of Mexico in the fall of 2007. Continuous data from the Imaging FlowCytobot (IFCB) provided cell images that documented the bloom during 3 weeks in early November. Guided by IFCB observations, field collection permitted phylogenetic analysis and evaluation of the relationship between Brachidinium and Karenia. Sequences from SSU, LSU, internal transcribed spacer (ITS), and cox1 regions for B. capitatum were compared with five other species of Karenia; all B. capitatum sequences were unique but supported its placement within the Kareniaceae. From a total of 71,487 images, data on the timing and frequency of dividing cells was also obtained for B. capitatum, allowing the rate of division for B. capitatum to be estimated. The maximum daily growth rate estimate was 0.22 d(-1) . Images showed a range in morphological variability, with the position of the four major processes highly variable. The combination of morphological features similar to the genus Karenia and a phylogenetic analysis placing B. capitatum in the Karenia clade leads us to propose moving the genus Brachidinium into the Kareniaceae. However, the lack of agreement among individual gene phylogenies suggests that the inclusion of different genes and more members of the genus Karenia are necessary before a final determination regarding the validity of the genus Brachidinium can be made.


Genomic and transcriptomic evidence for scavenging of diverse organic compounds by widespread deep-sea archaea.
Microbial activity is one of the most important processes to mediate the flux of organic carbon from the ocean surface to the seafloor. However, little is known about the microorganisms that underpin this key step of the global carbon cycle in the deep oceans. Here we present genomic and transcriptomic evidence that five ubiquitous archaeal groups actively use proteins, carbohydrates, fatty acids and lipids as sources of carbon and energy at depths ranging from 800 to 4,950 m in hydrothermal vent plumes and pelagic background seawater across three different ocean basins. Genome-enabled metabolic reconstructions and gene expression patterns show that these marine archaea are motile heterotrophs with extensive mechanisms for scavenging organic matter. Our results shed light on the ecological and physiological properties of ubiquitous marine archaea and highlight their versatile metabolic strategies in deep oceans that might play a critical role in global carbon cycling.


Movement Sonification: Effects on Motor Learning beyond Rhythmic Adjustments.
Motor learning is based on motor perception and emergent perceptual-motor representations. A lot of behavioral research is related to single perceptual modalities but during last two decades the contribution of multimodal perception on motor behavior was discovered more and more. A growing number of studies indicates an enhanced impact of multimodal stimuli on motor perception, motor control and motor learning in terms of better precision and higher reliability of the related actions. Behavioral research is supported by neurophysiological data, revealing that multisensory integration supports motor control and learning. But the overwhelming part of both research lines is dedicated to basic research. Besides research in the domains of music, dance and motor rehabilitation, there is almost no evidence for enhanced effectiveness of multisensory information on learning of gross motor skills. To reduce this gap, movement sonification is used here in applied research on motor learning in sports. Based on the current knowledge on the multimodal organization of the perceptual system, we generate additional real-time movement information being suitable for integration with perceptual feedback streams of visual and proprioceptive modality. With ongoing training, synchronously processed auditory information should be initially integrated into the emerging internal models, enhancing the efficacy of motor learning. This is achieved by a direct mapping of kinematic and dynamic motion parameters to electronic sounds, resulting in continuous auditory and convergent audiovisual or audio-proprioceptive stimulus arrays. In sharp contrast to other approaches using acoustic information as error-feedback in motor learning settings, we try to generate additional movement information suitable for acceleration and enhancement of adequate sensorimotor representations and processible below the level of consciousness. In the experimental setting, participants were asked to learn a closed motor skill (technique acquisition of indoor rowing). One group was treated with visual information and two groups with audiovisual information (sonification vs. natural sounds). For all three groups learning became evident and remained stable. Participants treated with additional movement sonification showed better performance compared to both other groups. Results indicate that movement sonification enhances motor learning of a complex gross motor skill-even exceeding usually expected acoustic rhythmic effects on motor learning.


Impact of the penalty points system on severe road traffic injuries in Kuwait.
This study aimed to examine the effect of a penalty points system (PPS) implemented in early July 2006 on the number of severe road traffic injuries (RTIs) in Kuwait. Monthly counts of RTIs that occurred between January 2003 and December 2009 were analyzed. We used an interrupted seasonal autoregressive integrated moving average model (SARIMA) to estimate the intervention parameter along with its 95 percent confidence interval (CI) after accounting for seasonal and trend components in the data series. Based on the SARIMA model, we computed the number of RTIs that would have occurred post-PPS for 42 months after July 1, 2006, if it had not been implemented. During the study period, a total of 4696 RTIs occurred. The Poisson rates of injuries (per 10 million of mean mid-year population and per 10 million of annual mean number of registered vehicles) were significantly (P < .001) lower in the post-PPS (λ(post-PPS) = 7 and 16, respectively) than the pre-PPS (λ(pre-PPS) = 9 and 23, respectively) implementation period. The intervention parameter's estimate was -7.68 (95% CI: -14.77, -0.60), suggesting that 322 (95% CI: 25, 620) individuals would have had RTIs in the 42 months post-PPS enactment, had it not been implemented. This translates to a 14.6 percent (95% CI: 1.1%, 28.0%) reduction. These findings suggest that PPS implementation in Kuwait appears to have resulted in a significant reduction in the number of RTIs in the ensuing period. Therefore, PPS seems a feasible and effective approach in reducing RTIs in Kuwait and other countries in the region, if adequately implemented. Future studies may focus on evaluating the long-term effects of PPS implementation.


Single-molecule imaging of electroporated dye-labelled CheY in live Escherichia coli.
For the past two decades, the use of genetically fused fluorescent proteins (FPs) has greatly contributed to the study of chemotactic signalling in Escherichia coli including the activation of the response regulator protein CheY and its interaction with the flagellar motor. However, this approach suffers from a number of limitations, both biological and biophysical: for example, not all fusions are fully functional when fused to a bulky FP, which can have a similar molecular weight to its fused counterpart; they may interfere with the native interactions of the protein and the chromophores of FPs have low brightness and photostability and fast photobleaching rates. A recently developed technique for the electroporation of fluorescently labelled proteins in live bacteria has enabled us to bypass these limitations and study the in vivo behaviour of CheY at the single-molecule level. Here we show that purified CheY proteins labelled with organic dyes can be internalized into E. coli cells in controllable concentrations and imaged with video fluorescence microscopy. The use of this approach is illustrated by showing single CheY molecules diffusing within cells and interacting with the sensory clusters and the flagellar motors in real time.This article is part of the themed issue 'The new bacteriology'.


Participatory Design of a Personalized Genetic Risk Tool to Promote Behavioral Health.
Despite major advancements in genomic medicine, research to optimize the design and communication of genetically informed interventions in behavioral health has lagged. The goal of this study was to engage potential end users in participatory codesign of a personalized genetically informed risk tool to intervene on high-risk health behaviors. We used structured interviews to examine end-user attitudes and interest in personalized genetics, qualitative interviews to guide iterative design of a genetically informed tool, and questionnaires to assess acceptability and potential utility of the tool. Participants expressed strong demand for using personal genetics to inform smoking and alcohol-related disease risk and guide treatment (78%-95% agreed). Via iterative design feedback, we cocreated a genetically informed risk profile featuring (i) explanation of genetic and phenotypic markers used to construct a risk algorithm, (ii) personalized risks and benefits of healthy behavior change, and (iii) recommended actions with referral to freely available resources. Participants demonstrated sufficient understanding and cited motivating behavior change as the most useful purpose of the tool. In three phases, we confirmed strong desire for personalized genetics on high-risk health behaviors; codesigned a genetically informed profile with potential end users; and found high acceptability, comprehensibility, and perceived usefulness of the profile. As scientific discovery of genomic medicine advances in behavioral health, we must develop the tools to communicate these discoveries to consumers who stand to benefit. The potential of genomic medicine to engage populations and personalize behavioral health treatment depends, in part, on preparatory studies to design for the future implementation of genetically informed interventions.


Targeting high-performance liquid chromatography-high-resolution mass spectrometry-solid-phase extraction-nuclear magnetic resonance analysis with high-resolution radical scavenging profiles-Bioactive secondary metabolites from the endophytic fungus Penicillium namyslowskii.
The high-resolution radical scavenging profile of an extract of the endophytic fungus Penicillium namyslowskii was used to target analysis by high-performance liquid chromatography-high-resolution mass spectrometry-solid-phase extraction-nuclear magnetic resonance spectroscopy, i.e., HPLC-HRMS-SPE-NMR, for identification of anti-oxidative secondary metabolites. This revealed the two chromatographic peaks with the highest relative response in the radical scavenging profile to be griseophenone C and peniprequinolone. The HPLC-HRMS-SPE-NMR analysis was performed in the tube-transfer mode using a cryogenically cooled NMR probe designed for 1.7mm NMR tubes. To further explore the potential of the above HPLC-HRMS-SPE-NMR platform for analysis of endophytic extracts, six peaks displaying no radical scavenging activity were also analyzed. This allowed unambiguous identification of six metabolites, i.e., dechlorogriseofulvin, dechlorodehydrogriseofulvin, griseofulvin, dehydrogriseofulvin, mevastatin acid, and mevastatin. The high mass sensitivity of the 1.7mm cryogenically cooled NMR probe allowed for the first time acquisition of direct detected (13)C NMR spectra of fungal metabolites, i.e., dechlorogriseofulvin and griseofulvin, directly from crude extract via HPLC-HRMS-SPE-NMR. Dechlorodehydrogriseofulvin was reported for the first time from nature.