Multitarget visual tracking based effective surveillance with cooperation of multiple active cameras.
This paper presents a tracking-based surveillance system that is capable of tracking multiple moving objects, with almost real-time response, through the effective cooperation of multiple pan-tilt cameras. To construct this surveillance system, the distributed camera agent, which tracks multiple moving objects independently, is first developed. The particle filter is extended with target depth estimate to track multiple targets that may overlap with one another. A strategy to select the suboptimal camera action is then proposed for a camera mounted on a pan-tilt platform that has been assigned to track multiple targets within its limited field of view simultaneously. This strategy is based on the mutual information and the Monte Carlo method to maintain coverage of the tracked targets. Finally, for a surveillance system with a small number of active cameras to effectively monitor a wide space, this system is aimed to maximize the number of targets to be tracked. We further propose a hierarchical camera selection and task assignment strategy, known as the online position strategy, to integrate all of the distributed camera agents. The overall performance of the multicamera surveillance system has been verified with computer simulations and extensive experiments.


Blind trials of computer-assisted structure elucidation software.
One of the largest challenges in chemistry today remains that of efficiently mining through vast amounts of data in order to elucidate the chemical structure for an unknown compound. The elucidated candidate compound must be fully consistent with the data and any other competing candidates efficiently eliminated without doubt by using additional data if necessary. It has become increasingly necessary to incorporate an in silico structure generation and verification tool to facilitate this elucidation process. An effective structure elucidation software technology aims to mimic the skills of a human in interpreting the complex nature of spectral data while producing a solution within a reasonable amount of time. This type of software is known as computer-assisted structure elucidation or CASE software. A systematic trial of the ACD/Structure Elucidator CASE software was conducted over an extended period of time by analysing a set of single and double-blind trials submitted by a global audience of scientists. The purpose of the blind trials was to reduce subjective bias. Double-blind trials comprised of data where the candidate compound was unknown to both the submitting scientist and the analyst. The level of expertise of the submitting scientist ranged from novice to expert structure elucidation specialists with experience in pharmaceutical, industrial, government and academic environments. Beginning in 2003, and for the following nine years, the algorithms and software technology contained within ACD/Structure Elucidator have been tested against 112 data sets; many of these were unique challenges. Of these challenges 9% were double-blind trials. The results of eighteen of the single-blind trials were investigated in detail and included problems of a diverse nature with many of the specific challenges associated with algorithmic structure elucidation such as deficiency in protons, structure symmetry, a large number of heteroatoms and poor quality spectral data. When applied to a complex set of blind trials, ACD/Structure Elucidator was shown to be a very useful tool in advancing the computer's contribution to elucidating a candidate structure from a set of spectral data (NMR and MS) for an unknown. The synergistic interaction between humans and computers can be highly beneficial in terms of less biased approaches to elucidation as well as dramatic improvements in speed and throughput. In those cases where multiple candidate structures exist, ACD/Structure Elucidator is equipped to validate the correct structure and eliminate inconsistent candidates. Full elucidation can generally be performed in less than two hours; this includes the average spectral data processing time and data input.


Health indicator recording in UK primary care electronic health records: key implications for handling missing data.
Clinical databases are increasingly used for health research; many of them capture information on common health indicators including height, weight, blood pressure, cholesterol level, smoking status, and alcohol consumption. However, these are often not recorded on a regular basis; missing data are ubiquitous. We described the recording of health indicators in UK primary care and evaluated key implications for handling missing data. We examined the recording of health indicators in The Health Improvement Network (THIN) UK primary care database over time, by demographic variables (age and sex) and chronic diseases (diabetes, myocardial infarction, and stroke). Using weight as an example, we fitted linear and logistic regression models to examine the associations of weight measurements and the probability of having weight recorded with individuals' demographic characteristics and chronic diseases. In total, 6,345,851 individuals aged 18-99 years contributed data to THIN between 2000 and 2015. Women aged 18-65 years were more likely than men of the same age to have health indicators recorded; this gap narrowed after age 65. About 60-80% of individuals had their height, weight, blood pressure, smoking status, and alcohol consumption recorded during the first year of registration. In the years following registration, these proportions fell to 10%-40%. Individuals with chronic diseases were more likely to have health indicators recorded, particularly after the introduction of a General Practitioner incentive scheme. Individuals' demographic characteristics and chronic diseases were associated with both observed weight measurements and missingness in weight. Missing data in common health indicators will affect statistical analysis in health research studies. A single analysis of primary care data using the available information alone may be misleading. Multiple imputation of missing values accounting for demographic characteristics and disease status is recommended but should be considered and implemented carefully. Sensitivity analysis exploring alternative assumptions for missing data should also be evaluated.


Supramolecular self-assemblies as functional nanomaterials.
In this review, we survey the diversity of structures and functions which are encountered in advanced self-assembled nanomaterials. We highlight their flourishing implementations in three active domains of applications: biomedical sciences, information technologies, and environmental sciences. Our main objective is to provide the reader with a concise and straightforward entry to this broad field by selecting the most recent and important research articles, supported by some more comprehensive reviews to introduce each topic. Overall, this compilation illustrates how, based on the rules of supramolecular chemistry, the bottom-up approach to design functional objects at the nanoscale is currently producing highly sophisticated materials oriented towards a growing number of applications with high societal impact.


Emerging Pharmacological Treatments to Prevent Abdominal Aortic Aneurysm Growth and Rupture.
Abdominal aortic aneurysm (AAA) is a local expansion of the abdominal aorta wall caused by a complex multifactorial maladaptive vascular remodeling. Despite recent advances in the management of cardiovascular diseases, there currently is no established drug therapy for AAA. Since the probability of death from a ruptured AAA still remains high, preventive elective repair of AAAs larger than 5.5 cm in luminal diameter is considered the best treatment option. However, perioperative complications are problematic as elective AAA repair comes with numerous intrinsic risks. Impelled by the need of improving AAA therapy, significant efforts have been made to identify pharmacological tools that would slow down AAA enlargement and lower the risk of rupture, thereby reducing the necessity of surgical intervention. In this review, we discuss recent findings addressing molecular targets that could potentially treat AAA, particularly addressing: statins, classical renin angiotensin system (RAS) blockers, the protective arm of RAS, renin inhibitors, tetracyclines, interleukin-1β inhibition, anti-angiogenic agents and urocortins.


Chlortetracycline Enhances Tonsil Colonization and Fecal Shedding of Multidrug-Resistant Salmonella enterica Serovar Typhimurium DT104 without Major Alterations to the Porcine Tonsillar and Intestinal Microbiota.
Salmonella spp. are estimated to cause 1.2 million cases of human foodborne illness each year in the United States, and pigs can often be asymptomatically colonized with Salmonella spp. (>50% of farms). Recent reports state that 18.3% of Salmonella enterica serovar Typhimurium isolates are resistant to ≥3 antimicrobial classes, and multidrug-resistant (MDR) strains are associated with an increased hospitalization rate and other complications. Chlortetracycline is commonly used in swine production to prevent/treat various diseases; therefore, chlortetracycline treatment of pigs unknowingly colonized with MDR Salmonella may have collateral effects on Salmonella spp. (and other gut bacteria). In this study, we determined the effect of in-feed chlortetracycline (400 g/ton) on shedding and colonization of pigs challenged with the MDR S Typhimurium strain DT104 (n = 11/group). We also assessed the impact on the fecal microbiota over the 12-day experimental period and on the ileum, cecum, and tonsil microbiota at 7 days postinoculation (dpi). In MDR S Typhimurium-inoculated pigs, chlortetracycline administration significantly increased fecal shedding at 2 dpi (+1.4 log10 CFU/g; P < 0.001) and enhanced tonsil colonization (+3.1 log10 CFU/g; P < 0.001). There were few major alterations detected in the gut or tonsillar microbiota of pigs treated with MDR S Typhimurium and/or chlortetracycline. The tonsillar transcriptome was largely unaffected despite increased colonization by MDR S Typhimurium following inoculation of the chlortetracycline-treated pigs. These results highlight the idea that chlortetracycline administration can enhance shedding and colonization of MDR S Typhimurium in pigs, which could increase the risk of environmental dissemination of MDR Salmonella strains.IMPORTANCESalmonella spp. are an important cause of foodborne illness in North America, and pork products are associated with sporadic cases and outbreaks of human salmonellosis. Isolates of Salmonella may be resistant to multiple antibiotics, and infections with multidrug-resistant (MDR) Salmonella spp. are more difficult to treat, leading to increased hospitalization rates. Swine operations commonly use antimicrobials, such as chlortetracycline, to prevent/treat infections, which may have collateral effects on pig microbial populations. Recently, we demonstrated that chlortetracycline induces the expression of genes associated with pathogenesis and invasion in MDR Salmonella enterica serovar Typhimurium in vitro In our current study, we show increased tonsillar colonization and fecal shedding of the MDR S Typhimurium strain DT104 from pigs administered chlortetracycline. Therefore, pigs unknowingly colonized with multidrug-resistant Salmonella spp. and receiving chlortetracycline for an unrelated infection may be at a greater risk for disseminating MDR Salmonella spp. to other pigs and to humans through environmental or pork product contamination.


Dissociable effects of cannabis with and without cannabidiol on the human brain's resting-state functional connectivity.
Two major constituents of cannabis are Δ9-tetrahydrocannabinol (THC) and cannabidiol (CBD). THC is the main psychoactive component; CBD may buffer the user against the harmful effects of THC. We examined the effects of two strains of cannabis and placebo on the human brain's resting-state networks using fMRI. Seventeen healthy volunteers (experienced with cannabis, but not regular users) underwent three drug treatments and scanning sessions. Treatments were cannabis containing THC (Cann-CBD; 8 mg THC), cannabis containing THC with CBD (Cann+CBD; 8 mg THC + 10 mg CBD), and matched placebo cannabis. Seed-based resting-state functional connectivity analyses were performed on three brain networks: the default mode (DMN; defined by positive connectivity with the posterior cingulate cortex: PCC+), executive control (ECN; defined by negative connectivity with the posterior cingulate cortex: PCC-) and salience (SAL; defined by positive connectivity with the anterior insula: AI+) network. Reductions in functional connectivity (relative to placebo) were seen in the DMN (PCC+) and SAL (AI+) networks for both strains of cannabis, with spatially dissociable effects. Across the entire salience network (AI+), Cann-CBD reduced connectivity relative to Cann+CBD. The PCC in the DMN was specifically disrupted by Cann-CBD, and this effect correlated with subjective drug effects, including feeling 'stoned' and 'high'. THC disrupts the DMN, and the PCC is a key brain region involved in the subjective experience of THC intoxication. CBD restores disruption of the salience network by THC, which may explain its potential to treat disorders of salience such as psychosis and addiction.


[Clinical value of inflammatory biomarkers after stent implantation].
The introduction of coronary stents into clinical practice has revolutionized the treatment of coronary artery disease. However, in-stent restenosis (ISR) and stent thrombosis represent the main adverse reactions following stent implantation. Along with procedural and technical factors, individual susceptibility, in particular the inflammatory response, play an important role in the development of these complications. C-reactive protein, one of the most extensively studied inflammatory biomarkers, was found to predict the risk of ISR but not of stent thrombosis in bare-metal stent (BMS)-treated patients. On the contrary, C-reactive protein failed to predict the occurrence of ISR in drug-eluting stent (DES)-treated patients, but it appeared to predict the risk of stent thrombosis. Important differences in the pathophysiological mechanisms of adverse reactions to BMS and DES account for the differences in the prognostic value of inflammatory biomarkers. Moreover, DES polymers are responsible for late hypersensitivity allergic reactions that may lead to late ISR and stent thrombosis. Notably, a correct employment of inflammatory biomarkers may become a useful tool for identification and management of high-risk patients. In this review, the evolving role of inflammatory biomarkers in predicting adverse reactions after stent implantation is discussed, underlying therapeutic and clinical consequences for the management of patients receiving a BMS or a DES.


Investigation into potential transmission sources of Giardia duodenalis in a threatened marsupial (Petrogale penicillata).
Assemblages of the protozoan parasite Giardia duodenalis common in humans and domestic species are increasingly identified in wildlife species, raising concern about the spill-over of pathogens from humans and domestic animals into wildlife. Here, the identity and prevalence of G. duodenalis in populations of a threatened marsupial, the brush-tailed rock-wallaby (Petrogale penicillata), was investigated. Identification of G. duodenalis isolates, across three loci (18S rRNA, β-giardin and gdh), from rock-wallaby fecal samples (n = 318) identified an overall detection rate of 6.3%. No significant difference in G. duodenalis detection was found among captive, wild and supplemented populations. Isolates were assigned to the zoonotic assemblages A and B at 18S rRNA, with sub-assemblages AI and BIV identified at the β-giardin and gdh loci, respectively. Assemblages AI and BIV have previously been identified in human clinical cases, but also in domestic animals and wildlife. The identification of these assemblages in brush-tailed rock-wallabies suggests there are transmission routes of G. duodenalis from humans or other animals to Australian wildlife, both in captivity and in the wild.


Preconditioning of Cardiosphere-Derived Cells With Hypoxia or Prolyl-4-Hydroxylase Inhibitors Increases Stemness and Decreases Reliance on Oxidative Metabolism.
Cardiosphere-derived cells (CDCs), which can be isolated from heart explants, are a promising candidate cell source for infarcted myocardium regeneration. However, current protocols used to expand CDCs require at least 1 month in vitro to obtain sufficient cells for transplantation. We report that CDC culture can be optimized by preconditioning the cells under hypoxia (2% oxygen), which may reflect the physiological oxygen level of the stem cell niche. Under hypoxia, the CDC proliferation rate increased by 1.4-fold, generating 6 × 10(6) CDCs with higher expression of cardiac stem cell and pluripotency gene markers compared to normoxia. Furthermore, telomerase (TERT), cytokines/ligands involved in stem cell trafficking (SDF/CXCR-4), erythropoiesis (EPO), and angiogenesis (VEGF) were increased under hypoxia. Hypoxic preconditioning was mimicked by treatment with two types of hypoxia-inducible factor (HIF) prolyl-4-hydroxylase inhibitors (PHDIs): dimethyloxaloylglycine (DMOG) and 2-(1-chloro-4-hydroxyisoquinoline-3-carboxamido) acetic acid (BIC). Despite the difference in specificity, both PHDIs significantly increased c-Kit expression and activated HIF, EPO, and CXCR-4. Furthermore, treatment with PHDIs for 24 h increased cell proliferation. Notably, all hypoxic and PHDI-preconditioned CDCs had decreased oxygen consumption and increased glycolytic metabolism. In conclusion, cells cultured under hypoxia could have potentially enhanced therapeutic potential, which can be mimicked, in part, by PHDIs.


Discussing issues of health promotion and research in the context of primary care during the ongoing austerity period: an exploratory analysis from two regions in Greece.
In Greece, both Primary Health Care (PHC) system and National Health System (NHS) in general, were plagued by several inefficiencies even prior to the financial crisis; the imposed austerity measures dramatically worsened the level of health provision and access, especially for vulnerable social groups, resulting in an exacerbation of existing disparities and access gaps. The current branch study was conducted in two regions of Greece, namely Crete and Epirus, with the main aim of eliciting responses to gather baseline information regarding crucial PHC-related aspects, using questionnaires with dichotomous questions. Directors or managers (physicians who have been assigned administrative/governance duties), of the Primary Health Care Centres (PHCCs) in two Greek geographic and administrative regions of Crete and Epirus, were invited to participate and to contribute to the investigation of issues on the provision of prevention and health promotion services, e-health topics and primary care research. Thirty directors/managers were approached and twenty-eight agreed to participate. Data processing and analysis of the responses was performed for the completed questionnaires. Data analysis did not demonstrate a surprisingly substantial deviation in the average score of positive responses of directors/managers in the PHCCs of Crete in comparison to those of directors/managers in the PHCCs of Epirus. The findings show that several gaps exist in terms of prevention and health promotion resources and activities in both regions, while e-health, electronic health record (EHR) and telemedicine services are poorly developed. The study confirms that the Greek PHC is characterized by several inefficiencies, which may affect the quality of the services provided. An overall deficit has been emerged for PHCCs in both regions, a fact that indicates crucial points lacking in terms of overall PHC provision, thus adversely impacting upon living conditions, health quality and prevention.


The utility of CAD in recovering Gondwanan vicariance events and the evolutionary history of Aciliini (Coleoptera: Dytiscidae).
Aciliini presently includes 69 species of medium-sized water beetles distributed on all continents except Antarctica. The pattern of distribution with several genera confined to different continents of the Southern Hemisphere raises the yet untested hypothesis of a Gondwana vicariance origin. The monophyly of Aciliini has been questioned with regard to Eretini, and there are competing hypotheses about the intergeneric relationship in the tribe. This study is the first comprehensive phylogenetic analysis focused on the tribe Aciliini and it is based on eight gene fragments. The aims of the present study are: 1) to test the monophyly of Aciliini and clarify the position of the tribe Eretini and to resolve the relationship among genera within Aciliini, 2) to calibrate the divergence times within Aciliini and test different biogeographical scenarios, and 3) to evaluate the utility of the gene CAD for phylogenetic analysis in Dytiscidae. Our analyses confirm monophyly of Aciliini with Eretini as its sister group. Each of six genera which have multiple species are also supported as monophyletic. The origin of the tribe is firmly based in the Southern Hemisphere with the arrangement of Neotropical and Afrotropical taxa as the most basal clades suggesting a Gondwana vicariance origin. However, the uncertainty as to whether a fossil can be used as a stem-or crowngroup calibration point for Acilius influenced the result: as crowngroup calibration, the 95% HPD interval for the basal nodes included the geological age estimate for the Gondwana break-up, but as a stem group calibration the basal nodes were too young. Our study suggests CAD to be the most informative marker between 15 and 50 Ma. Notably, the 2000 bp CAD fragment analyzed alone fully resolved the tree with high support. 1) Molecular data confirmed Aciliini as a monophyletic group. 2) Bayesian optimizations of the biogeographical history are consistent with an influence of Gondwana break-up history, but were dependent on the calibration method. 3) The evaluation using a method of phylogenetic signal per base pair indicated Wnt and CAD as the most informative of our sampled genes.


Structural and physiological MRI correlates of occult cerebrovascular disease in late-onset epilepsy.
Late-onset epilepsy (LOE), with onset after 50 years of age, is often attributed to underlying occult cerebrovascular disease. LOE is associated with a three-fold increase in subsequent stroke risk, therefore it is important to improve our understanding of pathophysiology. In this exploratory study, we aimed to determine whether established structural magnetic resonance imaging markers and novel physiological imaging markers of occult cerebrovascular disease were more common in patients with LOE than age-matched controls. Sixteen patients with LOE (mean age ± SD: 67.6 ± 6.5 years) and 15 age-matched control subjects (mean age: 65.1 ± 3.9 years) underwent a 3 T MRI scan protocol. T1-weighted images and T2-weighted fluid attenuated inversion recovery (FLAIR) images were used to determine cortical grey matter volume and white matter hyperintensity (WMH) volume respectively, whilst multiple delay time arterial spin labelling (ASL) images were collected at rest and during a hypercapnic challenge. Cerebral blood flow (CBF) and arterial arrival time (AAT) were calculated from ASL data under both normocapnic and hypercapnic conditions. Cerebrovascular reactivity was also calculated for both CBF and AAT relative to the change in end-tidal CO2. Patients with LOE were found to have significantly lower cortical volume than control subjects (33.8 ± 3.8% of intracranial volume vs. 38.0 ± 5.5%, p = 0.02) and significantly higher WMH volume (1339 ± 1408 mm3 vs. 514 ± 481 mm3, p = 0.047). Baseline whole brain AAT was found to be significantly prolonged in patients with LOE in comparison to control subjects (1539 ± 129 ms vs. 1363 ± 167 ms, p = 0.005). Voxel-based analysis showed the significant prolongation of AAT to be predominantly distributed in the frontal and temporal lobes. Voxel-based morphometry showed the lower cortical volume to be localised primarily to temporal lobes. No significant differences in CBF or cerebrovascular reactivity were found between the two groups. Baseline whole brain AAT and cortical volume differences persisted upon further analysis to take account of differences in smoking history between patients and control subjects. These findings suggest that occult cerebrovascular disease is relevant to the pathophysiology of LOE.


Differences in the angiographic evaluation of coiled cerebral aneurysms between a core laboratory reader and operators: results of the Cerecyte Coil Trial.
Independent evaluation of angiographic images is becoming widely applied in the assessment of treatment outcomes of cerebral aneurysms. In the current study, we assessed the agreement between an independent core laboratory and the operators regarding angiographic appearance in a recent randomized, controlled trial. Data were derived from the Cerecyte Coil Trial. Angiographic images of each coiled aneurysm, taken immediately after embolization and at 5- to 7-month follow-up, were evaluated by the operator at the treating center and by an independent neuroradiologist at the core laboratory. For the purpose of this study, images were interpreted on a 3-point scale to provide uniformity for analysis; grade 1: complete occlusion, grade 2: neck remnant; and grade 3: sac filling. "Unfavorable angiographic appearance" was defined as grade 3 at follow-up or interval worsening of grade between the 2 time points. The study included 434 aneurysms. Immediately after embolization, grade 3 was reported by operators in 39 (9%) compared with 52 (12%) by the core laboratory (P = .159). On follow-up, grade 3 was reported by operators in 44 (10%) compared with 81 (19%) by the core laboratory (P < .0001). Overall, operators noted unfavorable angiographic appearance in 78 (18%) compared with 134 (31%) by the core laboratory (P < .0001). At every time point, agreement between the core laboratory and the operators was slight. Unfavorable angiographic appearance was noted almost twice as frequently by an independent core laboratory as compared with the operators. Planning of trials and interpretation of published studies should be done with careful attention to the mode of angiographic appearance interpretation.


Threonine requirement of pigs weighing 5 to 15 kg.
Weanling crossbred pigs (avg initial wt 6.4 kg) were fed diets containing six levels of threonine to determine the threonine requirement of young pigs fed diets somewhat similar to those used in commercial swine production. The diets (16% crude protein) were composed primarily of grain sorghum, oat groats and soybean meal supplemented with minerals, vitamins, lysine, tryptophan, methionine and isoleucine, and were calculated to be adequate in all nutrients except threonine and crude protein. Threonine levels were .53, .57, .62, .68, .75 and .83% of the diet. There were two trials, each with 96 pigs. The pigs were fed the experimental diets for 28 d. The addition of threonine increased weight gain (P less than .02) and feed efficiency (P less than .001), with most of the response occurring between .53 and .68% threonine. There was little further response when threonine was increased above .68%. Plasma threonine concentrations increased as dietary threonine increased, with a sharp rise when dietary threonine exceeded .68%. Concentrations of most other essential amino acids in the plasma declined in response to increasing dietary threonine, and reached minimum values at either .68 or .75% threonine. Plasma urea concentrations decreased as threonine was increased in the diet, reaching a plateau at .68% dietary threonine. The data indicate the young pigs weaned at 3 to 4 wk of age require approximately .70% threonine.


The novel lupus antigen related protein acheron enhances the development of human breast cancer.
Acheron (Achn) is a new member of the Lupus antigen family of RNA binding proteins. Previous studies have shown that Achn controls developmental decisions in neurons and muscle. In the human mammary gland, Achn expression is restricted to ductal myoepithelial cells. Microarray analysis and immunohistochemistry have shown that Achn expression is elevated in some basal-like ductal carcinomas. To study the possible role of Achn in breast cancer, we engineered human MDA-MB-231 cells to stably express enhanced green fluorescent protein-tagged wild-type Achn (AchnWT), as well as Achn lacking either its nuclear localization signal (AchnNLS) or its nuclear export signal (AchnNES). In in vitro assays, AchnWT and AchnNES, but not AchnNLS, enhanced cell proliferation, lamellipodia formation, and invasive activity and drove expression of the elevated expression of the metastasis-associated proteins MMP-9 and VEGF. To determine if Achn could alter the behavior of human breast cancer cells in vivo, Achn-engineered MDA-MB-231 cells were injected into athymic SCID/Beige mice. AchnWT and AchnNES-expressing tumors displayed enhanced angiogenesis and an approximately 5-fold increase in tumor size relative to either control cells or those expressing AchnNLS. These data suggest that Achn enhances human breast tumor growth and vascularization and that this activity is dependent on nuclear localization.


Guideline summary review: An evidence-based clinical guideline for the diagnosis and treatment of degenerative lumbar spondylolisthesis.
The North American Spine Society's (NASS) Evidence-Based Clinical Guideline for the Diagnosis and Treatment of Degenerative Lumbar Spondylolisthesis features evidence-based recommendations for diagnosing and treating degenerative lumbar spondylolisthesis. The guideline updates the 2008 guideline on this topic and is intended to reflect contemporary treatment concepts for symptomatic degenerative lumbar spondylolisthesis as reflected in the highest quality clinical literature available on this subject as of May 2013. The NASS guideline on this topic is the only guideline on degenerative lumbar spondylolisthesis included in the Agency for Healthcare Research and Quality's National Guideline Clearinghouse (NGC). The purpose of this guideline is to provide an evidence-based educational tool to assist spine specialists when making clinical decisions for patients with degenerative lumbar spondylolisthesis. This article provides a brief summary of the evidence-based guideline recommendations for diagnosing and treating patients with this condition. A systematic review of clinical studies relevant to degenerative spondylolisthesis was carried out. This NASS spondyolisthesis guideline is the product of the Degenerative Lumbar Spondylolisthesis Work Group of NASS' Evidence-Based Guideline Development Committee. The methods used to develop this guideline are detailed in the complete guideline and technical report available on the NASS website. In brief, a multidisciplinary work group of spine care specialists convened to identify clinical questions to address in the guideline. The literature search strategy was developed in consultation with medical librarians. Upon completion of the systematic literature search, evidence relevant to the clinical questions posed in the guideline was reviewed. Work group members used the NASS evidentiary table templates to summarize study conclusions, identify study strengths and weaknesses, and assign levels of evidence. Work group members participated in webcasts and in-person recommendation meetings to update and formulate evidence-based recommendations and incorporate expert opinion when necessary. The draft guidelines were submitted to an internal peer review process and ultimately approved by the NASS Board of Directors. Upon publication, the Degenerative Lumbar Spondylolisthesis guideline was accepted into the NGC and will be updated approximately every 5 years. Twenty-seven clinical questions were addressed in this guideline update, including 15 clinical questions from the original guideline and 12 new clinical questions. The respective recommendations were graded by strength of the supporting literature, which was stratified by levels of evidence. Twenty-one new or updated recommendations or consensus statements were issued and 13 recommendations or consensus statements were maintained from the original guideline. The clinical guideline was created using the techniques of evidence-based medicine and best available evidence to aid practitioners in the care of patients with degenerative lumbar spondylolisthesis. The entire guideline document, including the evidentiary tables, literature search parameters, literature attrition flow chart, suggestions for future research, and all of the references, is available electronically on the NASS website at https://www.spine.org/Pages/ResearchClinicalCare/QualityImprovement/ClinicalGuidelines.aspx and will remain updated on a timely schedule.


Characterizations of a quality certified athletic trainer.
Didactic proficiency does not ensure clinical aptitude. Quality athletic health care requires clinical knowledge and affective traits. To develop a grounded theory explaining the constructs of a quality certified athletic trainer (AT). Delphi study. Interviews in conference rooms or business offices and by telephone. Thirteen ATs (men = 8, women = 5) stratified across the largest employment settings (high school, college, clinical) in the 4 largest districts of the National Athletic Trainers? Association (2, 3, 4, 9). Open-ended interview questions were audio recorded, transcribed, and reviewed before condensing. Two member checks ensured trustworthiness. Open coding reduced text to descriptive adjectives. We grouped adjectives into 5 constructs (care, communication, commitment, integrity, knowledge) and grouped these constructs into 2 higher-order constructs (affective traits, effective traits). According to participants, ATs who demonstrate the ability to care, show commitment and integrity, value professional knowledge, and communicate effectively with others can be identified as quality ATs. These abilities facilitate the creation of positive relationships. These relationships allow the quality AT to interact with patients and other health care professionals on a knowledgeable basis that ultimately improves health care delivery. Our resulting theory supported the examination of characteristics not traditionally assessed in an athletic training education program. If researchers can show that these characteristics develop ATs into quality ATs (eg, those who work better with others, relate meaningfully with patients, and improve the standard of health care), they must be cultivated in the educational setting.


Interval training at 95% and 100% of the velocity at VO2 max: effects on aerobic physiological indexes and running performance.
The objective of this study was to analyze the effect of two different high-intensity interval training (HIT) programs on selected aerobic physiological indices and 1500 and 5000 m running performance in well-trained runners. The following tests were completed (n=17): (i) incremental treadmill test to determine maximal oxygen uptake (VO2 max), running velocity associated with VO2 max (vVO2 max), and the velocity corresponding to 3.5 mmol/L of blood lactate concentration (vOBLA); (ii) submaximal constant-intensity test to determine running economy (RE); and (iii) 1500 and 5000 m time trials on a 400 m track. Runners were then randomized into 95% vVO2 max or 100% vVO2 max groups, and undertook a 4 week training program consisting of 2 HIT sessions (performed at 95% or 100% vVO2 max, respectively) and 4 submaximal run sessions per week. Runners were retested on all parameters at the completion of the training program. The VO2 max values were not different after training for both groups. There was a significant increase in post-training vVO2 max, RE, and 1500 m running performance in the 100% vVO2 max group. The vOBLA and 5000 m running performance were significantly higher after the training period for both groups. We conclude that vOBLA and 5000 m running performance can be significantly improved in well-trained runners using a 4 week training program consisting of 2 HIT sessions (performed at 95% or 100% vVO2 max) and 4 submaximal run sessions per week. However, the improvement in vVO2 max, RE, and 1500 m running performance seems to be dependent on the HIT program at 100% vVO2 max.


Feasibility and Effect of a Multidimensional Support Program to Improve Gerotranscendence Perception and Depression for Older Adults: A Pragmatic Cluster-Randomized Control Study.
Improving perception of gerotranscendence can increase life satisfaction in older adults to achieve successful aging. The purpose of this study was to evaluate the feasibility and effect of a multidimensional support program (MSP) on gerotranscendence and depression in community-dwelling older adults. Using a cluster-randomized control trial design, four sites (98 participants) were randomly assigned to a MSP or control group. The Gerotranscendence Scale and Geriatric Depression Scale were administered pre- and postintervention. A total of 91 participants completed the study. The mean attendance rates in the MSP and control groups were 85.5% and 84.3%, respectively. The MSP was found to significantly enhance the perception of gerotranscendence in older adults but not their level of depression. This study demonstrated the MSP is a feasible and effective program to improve perception of gerotranscendence and may potentially lead to positive psychological well-being for older adults. [Res Gerontol Nurs. 2019; 12(3):148-158.].


Abnormal Localization of STK17A in Bile Canaliculi in Liver Allografts: An Early Sign of Chronic Rejection.
The biological significance of STK17A, a serine/threonine kinase, in the liver is not known. We analyzed STK17A expression in HepG2 cells and human liver tissue. Accordingly, we investigated whether STK17A could help in identifying earlier changes during the evolution of chronic rejection (CR) after liver transplantation. RT-PCR and immunofluorescence were used to analyze STK17A expression in HepG2 cells. Antibody microarray was performed using human liver samples from CR and healthy donors. Immunohistochemistry was used to verify the clinical utility of STK17A on sequential biopsies for the subsequent development of CR. A novel short isoform of STK17A was found in HepG2 cells. STK17A was localized in the nuclei and bile canaliculi in HepG2 cells and human livers. Microarray of STK17A revealed its decrease in failed liver allografts by CR. During the evolution of CR, the staining pattern of bile canalicular STK17A gradually changed from diffuse linear to focal intermittent. The focal intermittent staining pattern was observed before the definite diagnosis of CR. In conclusion, the present study was the first to find localization of STK17A in normal bile canaliculi. Abnormal expression and localization of STK17A were associated with CR of liver allografts since the early stage of the rejection process.


Contrasting growth phenology of native and invasive forest shrubs mediated by genome size.
Examination of the significance of genome size to plant invasions has been largely restricted to its association with growth rate. We investigated the novel hypothesis that genome size is related to forest invasions through its association with growth phenology, as a result of the ability of large-genome species to grow more effectively through cell expansion at cool temperatures. We monitored the spring leaf phenology of 54 species of eastern USA deciduous forests, including native and invasive shrubs of six common genera. We used new measurements of genome size to evaluate its association with spring budbreak, cell size, summer leaf production rate, and photosynthetic capacity. In a phylogenetic hierarchical model that differentiated native and invasive species as a function of summer growth rate and spring budbreak timing, species with smaller genomes exhibited both faster growth and delayed budbreak compared with those with larger nuclear DNA content. Growth rate, but not budbreak timing, was associated with whether a species was native or invasive. Our results support genome size as a broad indicator of the growth behavior of woody species. Surprisingly, invaders of deciduous forests show the same small-genome tendencies of invaders of more open habitats, supporting genome size as a robust indicator of invasiveness.


Unique mechanism of action of the thiourea drug isoxyl on Mycobacterium tuberculosis.
The thiourea isoxyl (thiocarlide; 4,4'-diisoamyloxydiphenylthiourea) is known to be an effective anti-tuberculosis drug, active against a range of multidrug-resistant strains of Mycobacterium tuberculosis and has been used clinically. Little was known of its mode of action. We now demonstrate that isoxyl results in a dose-dependent decrease in the synthesis of oleic and, consequently, tuberculostearic acid in M. tuberculosis with complete inhibition at 3 microg/ml. Synthesis of mycolic acid was also affected. The anti-bacterial effect of isoxyl was partially reversed by supplementing growth medium with oleic acid. The specificity of this inhibition pointed to a Delta9-stearoyl desaturase as the drug target. Development of a cell-free assay for Delta9-desaturase activity allowed direct demonstration of the inhibition of oleic acid synthesis by isoxyl. Interestingly, sterculic acid, a known inhibitor of Delta9-desaturases, emulated the effect of isoxyl on oleic acid synthesis but did not affect mycolic acid synthesis, demonstrating the lack of a relationship between the two effects of the drug. The three putative fatty acid desaturases in the M. tuberculosis genome, desA1, desA2, and desA3, were cloned and expressed in Mycobacterium bovis BCG. Cell-free assays and whole cell labeling demonstrated increased Delta9-desaturase activity and oleic acid synthesis only in the desA3-overexpressing strain and an increase in the minimal inhibitory concentration for isoxyl, indicating that DesA3 is the target of the drug. These results validate membrane-bound Delta9-desaturase, DesA3, as a new therapeutic target, and the thioureas as anti-tuberculosis drugs worthy of further development.


The role of migration in the evolution of phenotypic switching.
Stochastic switching is an example of phenotypic bet hedging, where an individual can switch between different phenotypic states in a fluctuating environment. Although the evolution of stochastic switching has been studied when the environment varies temporally, there has been little theoretical work on the evolution of phenotypic switching under both spatially and temporally fluctuating selection pressures. Here, we explore the interaction of temporal and spatial change in determining the evolutionary dynamics of phenotypic switching. We find that spatial variation in selection is important; when selection pressures are similar across space, migration can decrease the rate of switching, but when selection pressures differ spatially, increasing migration between demes can facilitate the evolution of higher rates of switching. These results may help explain the diverse array of non-genetic contributions to phenotypic variability and phenotypic inheritance observed in both wild and experimental populations.


Distinctive Clinical Profile of Blacks Versus Whites Presenting With Sudden Cardiac Arrest.
Sudden cardiac arrest (SCA) is a major contributor to mortality, but data are limited among nonwhites. Identification of differences in clinical profile based on race may provide opportunities for improved SCA prevention. In the ongoing Oregon Sudden Unexpected Death Study (SUDS), individuals experiencing SCA in the Portland, OR, metropolitan area were identified prospectively. Patient demographics, arrest circumstances, and pre-SCA clinical profile were compared by race among cases from 2002 to 2012 (for clinical history, n=126 blacks, n=1262 whites). Incidence rates were calculated for cases from the burden assessment phase (2002-2005; n=1077). Age-adjusted rates were 2-fold higher among black men and women (175 and 90 per 100 000, respectively) compared with white men and women (84 and 40 per 100 000, respectively). Compared with whites, blacks were >6 years younger at the time of SCA and had a higher prearrest prevalence of diabetes mellitus (52% versus 33%; P<0.0001), hypertension (77% versus 65%; P=0.006), and chronic renal insufficiency (34% versus 19%; P<0.0001). There were no racial differences in previously documented coronary artery disease or left ventricular dysfunction, but blacks had more prevalent congestive heart failure (43% versus 34%; P=0.04) and left ventricular hypertrophy (77% versus 58%; P=0.02) and a longer QTc interval (466±36 versus 453±41 milliseconds; P=0.03). In this US community, the burden of SCA was significantly higher in blacks compared with whites. Blacks with SCA had a higher prearrest prevalence of risk factors beyond established coronary artery disease, providing potential targets for race-specific prevention.


DNA-free genome editing for ZmPLA1 gene via targeting immature embryos in tropical maize.
Doubled haploid (DH) production accelerates the development of homozygous lines in a single generation. In maize, haploids are widely produced by the use of haploid inducer Stock 6, earlier reported in 1959. Three independent studies reported haploid induction in maize which is triggered due to a 4 bp frame-shift mutation in matrilineal (ZmPLA1) gene. The present study was focused on the generation of mutants for ZmPLA1 gene in maize inbred line LM13 through site-directed mutagenesis via CRISPR/Cas9-mediated ribonucleoprotein (RNP) complex method to increase the haploid induction rate. Three single guide RNAs (sgRNAs) for the ZmPLA1 gene locus were used for transforming the 14 days old immature embryos via bombardment. 373 regenerated plants were subjected to mutation detection followed by Sanger's sequencing. Out of three putative mutants identified, one mutant depicted one base pair substitution and one base pair deletion at the target site.


Relation between the hypothalamic-pituitary-thyroid (HPT) axis and the hypothalamic-pituitary-adrenal (HPA) axis during repeated stress.
Previous work has indicated that acute and repeated stress can alter thyroid hormone secretion. Corticosterone, the end product of hypothalamic-pituitary-adrenal (HPA) axis activation and strongly regulated by stress, has been suggested to play a role in hypothalamic-pituitary-thyroid (HPT) axis regulation. In the current study, we sought to further characterize HPT axis activity after repeated exposure to inescapable foot-shock stress (FS), and to examine changes in proposed regulators of the HPT axis, including plasma corticosterone and hypothalamic arcuate nucleus agouti-related protein (AGRP) mRNA levels. Adult male Sprague-Dawley rats were subjected to one daily session of inescapable FS for 14 days. Plasma corticosterone levels were determined during and after the stress on days 1 and 14. Animals were killed on day 15, and trunk blood and brains were collected for measurement of hormone and mRNA levels. Repeated exposure to FS led to a significant decrease in serum levels of 3,5,3'-triiodothyronine (T3) and 3,5,3',5'-tetraiodothyronine (T4). Stress-induced plasma corticosterone levels were not altered by repeated exposure to the stress. Despite the decrease in peripheral hormone levels, thyrotropin-releasing hormone (TRH) mRNA levels within the paraventricular nucleus of the hypothalamus were not altered by the stress paradigm. Arcuate nucleus AGRP mRNA levels were significantly increased in the animals exposed to repeated FS. Additionally, we noted significant correlations between stress-induced plasma corticosterone levels and components of the HPT axis, including TRH mRNA levels and free T4 levels. Additionally, there was a significant correlation between AGRP mRNA levels and total T3 levels. Changes in body weight were also correlated with peripheral corticosterone and TRH mRNA levels. These results suggest that repeated exposure to mild-electric foot-shock causes a decrease in peripheral thyroid hormone levels, and that components of the HPA axis and hypothalamic AGRP may be involved in stress regulation of the HPT.


Tumor proteomics by multivariate analysis on individual pathway data for characterization of vulvar cancer phenotypes.
Vulvar squamous cell carcinoma (VSCC) is the fourth most common gynecological cancer. Based on etiology VSCC is divided into two subtypes; one related to high-risk human papilloma virus (HPV) and one HPV negative. The two subtypes are proposed to develop via separate intracellular signaling pathways. We investigated a suggested link between HPV infection and relapse risk in VSCC through in-depth protein profiling of 14 VSCC tumor specimens. The tumor proteomes were analyzed by liquid-chromatography tandem mass spectrometry. Relative protein quantification was performed by 8-plex isobaric tags for relative and absolute quantification. Labeled peptides were fractionated by high-resolution isoelectric focusing prior to liquid-chromatography tandem mass spectrometry to reduce sample complexity. In total, 1579 proteins were regarded as accurately quantified and analyzed further. For classification of clinical groups, data analysis was performed by comparing protein level differences between tumors defined by HPV and/or relapse status. Further, we performed a biological analysis on individual tumor proteomes by matching data to known biological pathways. We here present a novel analysis approach that combines pathway alteration data on individual tumor level with multivariate statistics for HPV and relapse status comparisons. Four proteins (signal transducer and activator of transcription-1, myxovirus resistance protein 1, proteasome subunit alpha type-5 and legumain) identified as main classifiers of relapse status were validated by immunohistochemistry (IHC). Two of the proteins are interferon-regulated and on mRNA level known to be repressed by HPV. By both liquid-chromatography tandem mass spectrometry and immunohistochemistry data we could single out a subgroup of HPV negative/relapse-associated tumors. The pathway level data analysis confirmed three of the proteins, and further identified the ubiquitin-proteasome pathway as altered in the high risk subgroup. We show that pathway fingerprinting with resolution on individual tumor level adds biological information that strengthens a generalized protein analysis.


Domain combinations in archaeal, eubacterial and eukaryotic proteomes.
There is a limited repertoire of domain families that are duplicated and combined in different ways to form the set of proteins in a genome. Proteins are gene products, and at the level of genes, duplication, recombination, fusion and fission are the processes that produce new genes. We attempt to gain an overview of these processes by studying the evolutionary units in proteins, domains, in the protein sequences of 40 genomes. The domain and superfamily definitions in the Structural Classification of Proteins Database are used, so that we can view all pairs of adjacent domains in genome sequences in terms of their superfamily combinations. We find 783 out of the 859 superfamilies in SCOP in these genomes, and the 783 families occur in 1307 pairwise combinations. Most families are observed in combination with one or two other families, while a few families are very versatile in their combinatorial behaviour; 209 families do not make combinations with other families. This type of pattern can be described as a scale-free network. We also study the N to C-terminal orientation of domain pairs and domain repeats. The phylogenetic distribution of domain combinations is surveyed, to establish the extent of common and kingdom-specific combinations. Of the kingdom-specific combinations, significantly more combinations consist of families present in all three kingdoms than of families present in one or two kingdoms. Hence, we are led to conclude that recombination between common families, as compared to the invention of new families and recombination among these, has also been a major contribution to the evolution of kingdom-specific and species-specific functions in organisms in all three kingdoms. Finally, we compare the set of the domain combinations in the genomes to those in the RCSB Protein Data Bank, and discuss the implications for structural genomics.


Cylindrical luminescent solar concentrators with near-infrared quantum dots.
We investigate the performance of cylindrical luminescent solar concentrators (CLSCs) with near-infrared lead sulfide quantum dots (QDs) in the active region. We fabricate solid and hollow cylinders from a composite of QDs in polymethylmethacrylate, prepared by radical polymerization, and characterize sample homogeneity and optical properties using spectroscopic techniques. We additionally measure photo-stability and photocurrent outputs under both laboratory and external ambient conditions. The experimental results are in good agreement with theoretical calculations which demonstrate that the hollow CLSCs have higher absorption of incident radiation and lower self-absorption compared to solid cylindrical and planar geometries with similar geometric factors, resulting in a higher optical efficiency.


Acute oxygen sensing in cellular models: relevance to the physiology of pulmonary neuroepithelial and carotid bodies.
The combination of studies in native tissues and immortalised model systems during the last decade has made possible a deeper understanding of the physiology and functional morphology of arterial and airway oxygen sensors. Complementary and overlapping information from these earlier studies has allowed a detailed description of the cellular events that link decreased environmental oxygen to the release of physiologically important vasoactive transmitters. Since these basic pathways have now been defined functionally, what remains to be determined is the molecular identity of the specific proteins involved in the signal transduction pathways, and how these proteins interact to produce a full physiological response. With these goals clearly in sight, we have embarked upon a strategy that is a novel combination of proteomics and functional genomics. It is hoped this strategy will enable us to develop and refine the initial models in order to understand more completely the process of oxygen sensing in health and disease.


Comprehensive radionuclide esophagogastrointestinal transit study: methodology, reference values, and initial clinical experience.
A radionuclide methodology and reference values have been developed for a single gastrointestinal transit study including esophageal transit, liquid and solid gastric emptying, and small- and large-bowel transit, using (111)In-diethylenetriaminepentaacetic acid (DTPA) with the standardized (99m)Tc-labeled solid meal. Eighteen healthy subjects and 18 patients were investigated. The esophageal transit study was performed with 3.7 MBq (0.1 mCi) of (111)In-DTPA in 15 mL of water. A liquid-only 30-min gastric-emptying study followed, with ingestion of 3.7 MBq (0.1 mCi) of (111)In-DTPA in 300 mL of water. Then, a simultaneous solid-liquid emptying study was acquired after ingestion of a solid (99m)Tc-sulfur colloid-labeled meal and 7.4 MBq (0.2 mCi) of (111)In-DTPA in 120 mL of water. Images were acquired intermittently for 4 h. Additional (111)In images were acquired at 5 and 6 h to measure small-bowel transit, and at 24, 48, and 72 h for large-bowel transit. Reference values were determined for esophageal transit (transit time, percentage emptying at 10 s), liquid-only gastric emptying (emptying half-time), liquid and solid emptying in a dual-phase solid-liquid study (emptying half-time and percentage emptying at 1, 2, 3, and 4 h), small-bowel transit index (percentage transit to ileocecal valve at 6 h), and colonic transit (geometric center and percentage colonic emptying) at 24, 48, and 72 h. Results from the first 18 patients found abnormal transit in 72% (13/18); clinical management changed in 61% (11/18). We have developed a radionuclide methodology and derived reference values for a comprehensive gastrointestinal transit study using (111)In-DTPA with the standardized (99m)Tc-labeled solid meal. Our initial clinical experience suggests clinical value.


Improving patient handovers from hospital to primary care: a systematic review.
Evidence shows that suboptimum handovers at hospital discharge lead to increased rehospitalizations and decreased quality of health care. To systematically review interventions that aim to improve patient discharge from hospital to primary care. PubMed, CINAHL, PsycInfo, the Cochrane Library, and EMBASE were searched for studies published between January 1990 and March 2011. Randomized, controlled trials of interventions that aimed to improve handovers between hospital and primary care providers at hospital discharge. Two reviewers independently abstracted data on study objectives, setting and design, intervention characteristics, and outcomes. Studies were categorized according to methodological quality, sample size, intervention characteristics, outcome, statistical significance, and direction of effects. Of the 36 included studies, 25 (69.4%) had statistically significant effects in favor of the intervention group and 34 (94.4%) described multicomponent interventions. Effective interventions included medication reconciliation; electronic tools to facilitate quick, clear, and structured summary generation; discharge planning; shared involvement in follow-up by hospital and community care providers; use of electronic discharge notifications; and Web-based access to discharge information for general practitioners. Statistically significant effects were mostly found in reducing hospital use (for example, rehospitalizations), improvement of continuity of care (for example, accurate discharge information), and improvement of patient status after discharge (for example, satisfaction). Heterogeneity of the interventions and study characteristics made meta-analysis impossible. Most studies had diffuse aims and poor descriptions of the specific intervention components. Many interventions have positive effects on patient care. However, given the complexity of interventions and outcome measures, the literature does not permit firm conclusions about which interventions have these effects. The European Union, the Framework Programme of the European Commission.


The effect of substrate and surface plasmons on symmetry breaking at the substrate interface of the topological insulator Bi2Te3.
A pressing challenge in engineering devices with topological insulators (TIs) is that electron transport is dominated by the bulk conductance, and so dissipationless surface states account for only a small fraction of the conductance. Enhancing the surface-to-volume ratio is a common method to enhance the relative contribution of such states. In thin films with reduced thickness, the confinement results in symmetry-breaking and is critical for the experimental observation of topologically protected surface states. We employ micro-Raman and tip-enhanced Raman spectroscopy to examine three different mechanisms of symmetry breaking in Bi2Te3 TI thin films: surface plasmon generation, charge transfer, and application of a periodic strain potential. These mechanisms are facilitated by semiconducting and insulating substrates that modify the electronic and mechanical conditions at the sample surface and alter the long-range interactions between Bi2Te3 and the substrate. We confirm the symmetry breaking in Bi2Te3 via the emergence of the Raman-forbidden [Formula: see text] mode. Our results suggest that topological surface states can exist at the Bi2Te3/substrate interface, which is in a good agreement with previous theoretical results predicting the tunability of the vertical location of helical surface states in TI/substrate heterostructures.


Redox-sensitive up-regulation of eNOS by purple grape juice in endothelial cells: role of PI3-kinase/Akt, p38 MAPK, JNK, FoxO1 and FoxO3a.
The vascular protective effect of grape-derived polyphenols has been attributable, in part, to their direct action on blood vessels by stimulating the endothelial formation of nitric oxide (NO). The aim of the present study was to determine whether Concord grape juice (CGJ), which contains high levels of polyphenols, stimulates the expression of endothelial NO synthase (eNOS) in porcine coronary artery endothelial cells and, if so, to determine the signaling pathway involved. CGJ dose- and time-dependently increased eNOS mRNA and protein levels and this effect is associated with an increased formation of NO in endothelial cells. The stimulatory effect of CGJ on eNOS mRNA is not associated with an increased eNOS mRNA stability and inhibited by antioxidants such as MnTMPyP, PEG-catalase, and catalase, and by wortmannin (an inhibitor of PI3-kinase), SB 203580 (an inhibitor of p38 MAPK), and SP 600125 (an inhibitor of JNK). Moreover, CGJ induced the formation of reactive oxygen species (ROS) in endothelial cells and this effect is inhibited by MnTMPyP, PEG-catalase, and catalase. The CGJ-induced the phosphorylation of p38 MAPK and JNK kinases is abolished by MnTMPyP. CGJ induced phosphorylation of transcription factors FoxO1 and FoxO3a, which regulate negatively eNOS expression, and this effect is prevented by MnTMPyP, PEG-catalase, wortmannin, SB203580 and SP600125. Moreover, chromatin immunoprecipitation assay indicated that the FoxO3a protein is associated with the eNOS promoter in control cells and that CGJ induced its dissociation. Thus, the present study indicates that CGJ up-regulates the expression of eNOS mRNA and protein leading to an increased formation of NO in endothelial cells. The stimulatory effect of CGJ is a redox-sensitive event involving PI3-kinase/Akt, p38 MAPK and JNK pathways, and the inactivation of the FoxO transcription factors, FoxO1 and FoxO3a, thereby preventing their repression of the eNOS gene.


Body weight and risk of breast cancer in BRCA1/2 mutation carriers.
Obesity is an established risk factor for postmenopausal breast cancer in the general population. However, it is still unclear whether this association also exists in BRCA1/2 mutation carriers. We investigated the association between self-reported anthropometric measures and breast cancer risk in a nationwide retrospective cohort study, including 719 BRCA1/2 carriers, of whom 218 had been diagnosed with breast cancer within 10 years prior to questionnaire completion. All time-varying Cox proportional hazards analyses were stratified by menopausal status. For premenopausal breast cancer, no statistically significant associations were observed for any of the anthropometric measures. The association between body mass index (BMI) at age 18 and premenopausal breast cancer risk suggested a trend of decreasing risk with increasing BMI (HR(22.50-24.99 vs. 18.50-22.49) = 0.83, 95% CI = 0.47-1.44 and HR(≥ 25.00 vs. 18.50-22.49) = 0.41, 95% CI = 0.13-1.27). For postmenopausal breast cancer, being 1.67 m and taller increased the risk 1.7-fold (HR = 1.67, 95% CI = 1.01-2.74) when compared to a height <1.67 m. Compared with a current body weight < 72 kg, a current body weight of ≥ 72 kg increased the risk of postmenopausal breast cancer 2.1-fold (95% CI = 1.23-3.59). A current BMI of ≥ 25.0 kg/m², an adult weight gain of 5 kg or more, and a relative adult weight gain of 20% or more were all non-significantly associated with a 50-60% increased risk of postmenopausal breast cancer [HR = 1.46 (0.86-2.51), HR = 1.56 (95% CI = 0.85-2.87), and HR = 1.60 (95% CI = 0.97-2.63), respectively], when compared with having a healthy or stable weight. No associations for body weight or BMI at age 18 were observed. In conclusion, menopausal status seemed to modify the association between body weight and breast cancer risk among BRCA1/2 carriers. We observed no clear association between body weight and premenopausal breast cancer, while overweight and weight gain increased postmenopausal breast cancer risk. Carriers may reduce their risk of postmenopausal breast cancer by maintaining a healthy body weight throughout life.


Can sleep quality and wellbeing be improved by changing the indoor lighting in the homes of healthy, elderly citizens?
The study investigated the effect of bright blue-enriched versus blue-suppressed indoor light on sleep and wellbeing of healthy participants over 65 years. Twenty-nine participants in 20 private houses in a uniform settlement in Copenhagen were exposed to two light epochs of 3 weeks with blue-enriched (280 lux) and 3 weeks blue-suppressed (240 lux) indoor light or vice versa from 8 to 13 pm in a randomized cross-over design. The first light epoch was in October, the second in November and the two light epochs were separated by one week. Participants were examined at baseline and at the end of each light epoch. The experimental indoor light was well tolerated by the majority of the participants. Sleep duration was 7.44 (95% CI 7.14-7.74) hours during blue-enriched conditions and 7.31 (95% CI 7.01-7.62) hours during blue-suppressed conditions (p = 0.289). Neither rest hours, chromatic pupillometry, nor saliva melatonin profile showed significant changes between blue-enriched and blue-suppressed epochs. Baseline Pittsburgh Sleep Quality Index (PSQI) was significantly worse in females; 7.62 (95% CI 5.13-10.0) versus 4.06 (95% CI 2.64-5.49) in males, p = 0.009. For females, PSQI improved significantly during blue-enriched light exposure (p = 0.007); no significant changes were found for males. The subjective grading of indoor light quality doubled from participants habitual indoor light to the bright experimental light, while it was stable between light epochs, although there were clear differences between blue-enriched and blue-suppressed electrical light conditions imposed. Even though the study was carried out in the late autumn at northern latitude, the only significant difference in Actiwatch-measured total blue light exposure was from 8 to 9 am, because contributions from blue-enriched, bright indoor light were superseded by contributions from daylight.


Assessment of parental perception of malaria vaccine in Tanzania.
Clinical trials of the RTS,S malaria vaccine have completed Phase III and the vaccine is on track for registration. Before making decisions about implementation, it is essential to prepare the ground for introducing the vaccine by assessing awareness and willingness to use malaria vaccines and to provide policy makers with evidence-based information on the best strategies to engage communities to manage the introduction of malaria vaccine in Tanzania. In November 2011, as part of a large cross-sectional study of all 23 regions of Tanzania (mainland Tanzania and Zanzibar) was conducted during Tanzanian Integrated Measles Campaign (IMC) survey. In this study, the variables of interests were awareness and willingness to use a malaria vaccine. The main outcome measure was willingness to use a malaria vaccine. Logistic regression was used to examine the influence of predictive factors. A representative sample of 5502 (out of 6210) women, aged 18 years or older and with children under 11 months old, was selected to participate, using random sampling probability. Awareness of the forthcoming malaria vaccine, 11.8 % of participants in mainland Tanzania responded affirmatively, compared to 3.4 % in Zanzibar (p value <0.0001). 94.5 % of all respondents were willing to vaccinate their children against malaria, with a slight difference between mainland Tanzania (94.3 %) and Zanzibar (96.8 %) (p value = 0.0167). Although mothers had low awareness and high willingness to use malaria vaccine, still availability of malaria vaccine RTS,S will compliment other existing malaria interventions and it will be implemented through the Immunization, Vaccines and Biologicals (IVB) programme (formerly EPI). The information generated from this study can aid policy makers in planning and setting priorities for introducing and implementing the malaria vaccine.


Circulating chemerin level is independently correlated with arterial stiffness.
Adipokines have been implicated in the pathogenesis of obesity and obesity-related disorders, including atherosclerosis. Chemerin is a recently discovered adipokine which is closely correlated with various metabolic phenotypes in humans. We examined the association between circulating chemerin levels and arterial stiffness, as represented by the brachial ankle pulse wave velocity (baPWV). Fifty-eight obese and 62 non-obese individuals participated in the study. We measured the serum chemerin and high sensitivity C-reactive protein (hsCRP) levels, and the homeostasis model assessment of insulin resistance (HOMA-IR), as well as other cardiovascular risk factors. Vascular health was assessed by the baPWV and carotid intima-media thickness (IMT). The serum chemerin level was significantly increased in obese individuals compared with lean controls (120.14±19.43 ng/mL vs. 106.81±23.39 ng/mL, p = 0.001). The circulating chemerin level had a significant positive correlation with the body mass index, waist circumference, HOMA-IR, and low-density lipoprotein-cholesterol, triglycerides, and hsCRP levels. The serum chemerin level was significantly associated with the baPWV (r= 0.280, p= 0.002), but not the carotid IMT (r= 0.065, p= 0.504). Multiple stepwise regression analysis showed that age (p < 0.001), waist circumference (p= 0.038), systolic blood pressure (p < 0.001), and serum fasting glucose (p= 0.003) and chemerin levels (p= 0.017) were definitive risk factors for arterial stiffness (r(2)=0.457). The circulating chemerin level was an independent risk factor for arterial stiffness even after adjusting for other cardiovascular risk factors.


Aminopeptidase activity in seminal plasma and effect of dilution rate on rabbit reproductive performance after insemination with an extender supplemented with buserelin acetate.
Ovulation induction in artificially inseminated rabbits by adding GnRH synthetic analogues in the seminal doses is a welfare-orientated method to induce ovulation in rabbits and could have some advantages in field practice. This study was conducted to determine the effect of male genotype on the aminopeptidase activity in rabbit seminal plasma and the effects of dilution rate of semen on availability and reproductive performance when buserelin acetate is added to the seminal dose. To study the aminopeptidase activity, 12 mature bucks belonging to a paternal line and 12 from a maternal line were used. The bucks from the paternal line were used to study the effect of dilution rate on the availability of buserelin acetate after 2 hours of dilution and on the reproductive performance of the doses after artificial insemination of 389 commercial crossbreed does. Aminopeptidase activity in seminal plasma is dependent on the male genotype. The paternal line resulted 27% more aminopeptidase activity than the maternal line (P < 0.05). On the other hand, semen diluted 1:20 exhibited a marked increase in the availability of buserelin acetate and the fertility in this group was significantly higher than females from dilution rate 1:5 group, which showed similar results to that of the negative control group (does inseminated with semen diluted 1:20 in non-GnRH-supplemented extender). We conclude that the bioavailability of buserelin acetate when added to the seminal dose appears to be determined by the activity of the existing aminopeptidases and is consequently affected by the dilution rate used to prepare the artificial insemination doses.


Variations on the Hermann grid: an extinction illusion.
When the white disks in a scintillating grid are reduced in size, and outlined in black, they tend to disappear. One sees only a few of them at a time, in clusters which move erratically on the page. Where they are not seen, the grey alleys seem to be continuous, generating grey crossings that are not actually present. Some black sparkling can be seen at those crossings where no disk is seen. The illusion also works in reverse contrast.


Testicular microlithiasis and dyspermia: is there any correlation?
Testicular microlithiasis (MT) is an uncommon sonographic finding (prevalence in the literature: 0.7 to 6%). Several studies have highlighted its possible correlation with an increased risk of testicular cancer, but few studies have investigated its possible link with dyspermia. The aim of our study was to investigate in our series the number of patients with microlithiasis, diagnosed by ultrasound, and compare the quality of their sperm with that of patients in a control group with normal testicular ultrasound exam. We performed 277 consecutive testicular ultrasound examinations from January 2012 to July 2012. Among all these, we selected 86 patients that showed no pathological elements at echography and 11 patients affected by MT, to one or both testicles. Each patient was also submitted to a short-term semen analysis using the WHO2010 parameters for sperm evaluation. Among 11 patients with MT, 7 (63.63%) were dyspermic and 4 (36.36%) were normospermic. Among the 86 patients with normal testicular ultrasound 51 (59.3%) were dyspermic, 4 (4.65%) were azoospermic, while the remaining 31 (36.05%) were normospermic. Comparing the results of the two groups we obtained an odds ratio of 0.99 (95% CI: 0.27 to 3.64, p: 0.98). This study, although preliminary, with a low number of participants, shows that sperm quality is not affected by the presence of testicular microlithiasis, because the results of spermiograms are almost comparable between the two groups.


A proposed approach may help systematic reviews retain needed expertise while minimizing bias from nonfinancial conflicts of interest.
Groups such as the Institute of Medicine emphasize the importance of attention to financial conflicts of interest. Little guidance exists, however, on managing the risk of bias for systematic reviews from nonfinancial conflicts of interest. We sought to create practical guidance on ensuring adequate clinical or content expertise while maintaining independence of judgment on systematic review teams. Workgroup members built on existing guidance from international and domestic institutions on managing conflicts of interest. We then developed practical guidance in the form of an instrument for each potential source of conflict. We modified the Institute of Medicine's definition of conflict of interest to arrive at a definition specific to nonfinancial conflicts. We propose questions for funders and systematic review principal investigators to evaluate the risk of nonfinancial conflicts of interest. Once risks have been identified, options for managing conflicts include disclosure followed by no change in the systematic review team or activities, inclusion on the team along with other members with differing viewpoints to ensure diverse perspectives, exclusion from certain activities, and exclusion from the project entirely. The feasibility and utility of this approach to ensuring needed expertise on systematic reviews and minimizing bias from nonfinancial conflicts of interest must be investigated.


Going back to nature: the benefits of wood enrichment.
Environmental enrichment can be defined as altering the living environment of captive animals in order to provide them with opportunities to express more of their natural behavioral repertoire. The challenge of providing effective enrichment in laboratory species is to ensure that it allows for normal behavioral opportunities. For many animals, these behaviors include foraging, sheltering, exploring, nest building and gnawing. In the wild, many species use wood and bark to satisfy these behaviors, thereby maintaining physiological and behavioral health. For laboratory animals, various wood enrichment products are available that will provide appropriate environmental enrichment and satisfy those same needs.


Korean American health insurance and health services utilization.
The purpose of this ethnic group study was to describe the unique pattern of Korean Americans, as compared with the aggregate of Asian Americans, for: (a) the predisposing, enabling, and need factors for health service utilization, focusing specifically on the role of health insurance coverage; and (b) predictors of health insurance coverage. Using the behavioral model for health service utilization, data were selected from the 1992 National Health Insurance Survey (NHIS, 1994) for Korean Americans (n = 345) and Asian Americans (n = 3,059). Results differed between the Korean American group and the Asian American group. Health insurance coverage was the strongest predictor of Korean American utilization, and need factors lacked significance, suggesting that uninsured Korean Americans have less access regardless of need. For the aggregate Asian American group, need factors tempered the influence of health insurance on utilization. Results of this type of study may be helpful for designing and implementing health care services tailored for specific ethnic at-risk markets.


Trypanosoma cruzi trans-sialidase operates through a covalent sialyl-enzyme intermediate: tyrosine is the catalytic nucleophile.
Modified sialic acid substrates have been used to label Trypanosoma cruzi trans-sialidase, demonstrating that the enzyme catalyses the transfer of sialic acid through a covalent glycosyl-enzyme intermediate, a mechanism common to most retaining glycosidases. Peptic digestion of labeled protein, followed by LC-MS/MS analysis of the digest, identified Tyr342 as the catalytic nucleophile. This is the first such example of a retaining glycosidase utilizing an aryl glycoside intermediate. It is suggested that this alternative choice of nucleophile is a consequence of the chemical nature of sialic acid. A Tyr/Glu couple is invoked to relay charge from a remote glutamic acid, thereby avoiding electrostatic repulsion with the sialic acid carboxylate group.


(6S*)-6-[(1S*,2R*)-1,2-Di-hydroxy-pent-yl]-4-meth-oxy-5,6-di-hydro-2H-pyran-2-one.
The title compound, C11H18O5, was isolated from a liquid culture of Pestalotiopsis sp. In the mol-ecule, the pyran-2-one ring assumes a half-chair conformation. The two terminal C atoms of the pentyl group were refined as disordered over two sets of sites, with refined occupancies of 0.881 (10) and 0.119 (10). In the crystal, mol-ecules are linked via O-H⋯O hydrogen bonds forming a three-dimensional network.


Positive feedback in the transition from sexual reproduction to parthenogenesis.
Understanding how new phenotypes evolve is challenging because intermediate stages in transitions from ancestral to derived phenotypes often remain elusive. Here we describe and evaluate a new mechanism facilitating the transition from sexual reproduction to parthenogenesis. In many sexually reproducing species, a small proportion of unfertilized eggs can hatch spontaneously ('tychoparthenogenesis') and develop into females. Using an analytical model, we show that if females are mate-limited, tychoparthenogenesis can result in the loss of males through a positive feedback mechanism whereby tychoparthenogenesis generates female-biased sex ratios and increasing mate limitation. As a result, the strength of selection for tychoparthenogenesis increases in concert with the proportion of tychoparthenogenetic offspring in the sexual population. We then tested the hypothesis that mate limitation selects for tychoparthenogenesis and generates female-biased sex ratios, using data from natural populations of sexually reproducing Timema stick insects. Across 41 populations, both the tychoparthenogenesis rates and the proportions of females increased exponentially as the density of individuals decreased, consistent with the idea that low densities of individuals result in mate limitation and selection for reproductive insurance through tychoparthenogenesis. Our model and data from Timema populations provide evidence for a simple mechanism through which parthenogenesis can evolve rapidly in a sexual population.


Paternal diet defines offspring chromatin state and intergenerational obesity.
The global rise in obesity has revitalized a search for genetic and epigenetic factors underlying the disease. We present a Drosophila model of paternal-diet-induced intergenerational metabolic reprogramming (IGMR) and identify genes required for its encoding in offspring. Intriguingly, we find that as little as 2 days of dietary intervention in fathers elicits obesity in offspring. Paternal sugar acts as a physiological suppressor of variegation, desilencing chromatin-state-defined domains in both mature sperm and in offspring embryos. We identify requirements for H3K9/K27me3-dependent reprogramming of metabolic genes in two distinct germline and zygotic windows. Critically, we find evidence that a similar system may regulate obesity susceptibility and phenotype variation in mice and humans. The findings provide insight into the mechanisms underlying intergenerational metabolic reprogramming and carry profound implications for our understanding of phenotypic variation and evolution.


Correlation Between mMINDS and CIWA-Ar Scoring Tools in Patients With Alcohol Withdrawal Syndrome.
Many alcohol withdrawal scoring tools are used in hospitalized patients to assess the severity of alcohol withdrawal and guide treatment. The revised Clinical Institute Withdrawal Assessment (CIWA-Ar) and the modified Minnesota Detoxification Scale (mMINDS) are commonly used but have never been correlated. To determine the strength of correlation between the CIWA-Ar and mMINDS scoring tools in patients with alcohol withdrawal syndrome. A single-center, prospective correlation study conducted at a large academic medical center. Patients treated for alcohol withdrawal syndrome according to the Yale Alcohol Withdrawal Protocol were identified daily, and both the CIWA-Ar and mMINDS were administered at each time point required by the protocol. Clinical data were obtained from the electronic medical records. A total of 185 CIWA-Ar and mMINDS scores were collected in 30 patients. The Pearson correlation coefficient across all scores was 0.82, indicating a strong correlation. The Pearson correlation coefficient was 0.87 for CIWA-Ar scores of 10 or less and 0.52 for CIWA-Ar scores above 10. Strong correlations were also shown for tremor (0.98), agitation (0.84), and orientation (0.87). The correlation between the CIWA-Ar and mMINDS tools is strong and appears to be most robust in patients with CIWA-Ar scores of 10 or less.


Altered properties of volume-sensitive osmolyte and anion channels (VSOACs) and membrane protein expression in cardiac and smooth muscle myocytes from Clcn3-/- mice.
ClC-3, a member of the large superfamily of ClC voltage-dependent Cl(-) channels, has been proposed as a molecular candidate responsible for volume-sensitive osmolyte and anion channels (VSOACs) in some cells, including heart and vascular smooth muscle. However, the reported presence of native VSOACs in at least two cell types from transgenic ClC-3 disrupted (Clcn3(-/-)) mice casts considerable doubt on this proposed role for ClC-3. We compared several properties of native VSOACs and examined mRNA transcripts and membrane protein expression profiles in cardiac and pulmonary arterial smooth muscle cells from Clcn3(+/+) and Clcn3(-/-) mice to: (1) test the hypothesis that native VSOACs are unaltered in cells from Clcn3(-/-) mice, and (2) test the possibility that targeted inactivation of the Clcn3 gene using a conventional murine global knock-out approach may result in compensatory changes in expression of other membrane proteins. Our experiments demonstrate that VSOAC currents in myocytes from Clcn3(+/+) and Clcn3(-/-) mice are remarkably similar in terms of activation and inactivation kinetics, steady-state current densities, rectification, anion selectivity (I(-) > Cl(-)>> Asp(-)) and sensitivity to block by glibenclamide, niflumic acid, DIDS and extracellular ATP. However, additional experiments revealed several significant differences in other fundamental properties of native VSOACs recorded from atrial and smooth muscle cells from Clcn3(-/-) mice, including: differences in regulation by endogenous protein kinase C, differential sensitivity to block by anti-ClC-3 antibodies, and differential sensitivities to [ATP](i) and free [Mg(2+)](i). These results suggest that in response to Clcn3 gene deletion, there may be compensatory changes in expression of other proteins that alter VSOAC channel subunit composition or associated regulatory subunits that give rise to VSOACs with different properties. Consistent with this hypothesis, in atria from Clcn3(-/-) mice compared to Clcn3(+/+) mice, quantitative analysis of ClC mRNA expression levels revealed significant increases in transcripts for ClC-1, ClC-2, and ClC-3, and protein expression profiles obtained using two-dimensional polyacrylamide gel electrophoresis revealed complex changes in at least 35 different unidentified membrane proteins in cells from Clcn3(-/-) mice. These findings emphasize that caution needs to be exercised in simple attempts to interpret the phenotypic consequences of conventional global Clcn3 gene inactivation.


Rape Beyond Crime.
Public health experts agree that sexual violence constitutes a significant public health issue. Yet criminal law dominates rape law almost completely, with public health law playing at best a small supporting role. Recent civil law developments, such as university disciplinary proceedings, similarly fixate on how best to find and penalize perpetrators. As a result, rape law continues to spin its wheels in the same arguments and obstacles. This Article argues that, without broader cultural changes, criminal law faces a double bind: rape laws will either be ineffective or neglect the importance of individual culpability. Public health law provides more promising terrain for rape prevention because it is a strong legal framework that can engage the complex causes of rape, including the social norms that promote sexual aggression. While criminal law can only punish bad behavior, public health interventions can use the more effective prevention strategy of promoting positive behaviors and relationships. They can also address the myriad sexual behaviors and social determinants that increase the risk of rape but are outside the scope of criminal law. Perhaps most importantly, public health law relies on evidence-based interventions and the expertise of public health authorities to ensure that laws and policies are effective. Transforming rape law in this way provides a framework for legal feminism to undertake the unmet challenge of "theorizing yes," that is, moving beyond how to protect women's right to refuse sex and toward promoting and exploring positive models of sex. Criminal law is simply incapable of meeting this challenge because it concerns only what sex should not be. A public health framework can give the law a richer role in addressing the full spectrum of sexual attitudes and behaviors.


High-salt diet elevates baroreceptor pressure thresholds in normal and Dahl rats.
Dahl Salt Sensitive (DS) rats rapidly develop high blood pressure when exposed to a high-salt diet. Recent studies suggest that DS rats have poorly functioning baroreceptor afferents and baroreflexes even when salt intake is restricted. This study examines baroreceptor pressure- and mechano-transduction in DS, Dahl Resistant (DR), and Sprague-Dawley (SD) rats during low- and high-salt conditions. Single unit, regularly discharging baroreceptors were studied using an in vitro aortic arch-aortic nerve preparation. Pressure thresholds and suprathreshold pressure sensitivities were determined from responses to slow ramps of pressure. Pressure-diameter relations measured in each rat were used to transform pressure threshold and pressure sensitivity values to their mechanical equivalents in terms of aortic wall strain. A total of 407 unit baroreceptors were studied from 49 rats. Tail systolic blood pressures were significantly higher only in DS during high salt. Pressure threshold was similar for all groups on low salt. Exposure to a high-salt diet increased the mean pressure threshold for all three groups. Pressure threshold for high-salt diet was highest in DS and lowest in DR. Pressure sensitivities were lowest in DS and highest in DR on low salt. High salt had no significant effect on pressure sensitivity. The differences in threshold apparent when expressed in terms of pressure were eliminated by conversion to their mechanical equivalents (strain threshold and strain sensitivity). The results suggest that baroreceptors in the two Dahl rat strains represent two extremes from normal baroreceptor function. DS tend to be less pressure responsive than normal (SD), and DR tend to be somewhat more responsive to pressure.(ABSTRACT TRUNCATED AT 250 WORDS)


Human cystinosis: intracellular deposition of cystine.
Membrane-limited inclusions were found in the cytoplasm of cells of the rectal mucosa, leukocytes, and cultured fibroblasts from two humans with cystinosis. Most of the inclusions contained amorphous material, presumably cystine. In cells of the rectal mucosa the material appeared frequently crystallized. This was rarely seen in leukocytes, and never in cultured fibroblasts. The fact that acid phosphatase could be demonstrated consistently in the organelles responsible for sequestration of cystine indicates that they are lysosomes.


Neuromuscular effects of three phospholipases A2 from the venom of the Australian king brown snake Pseudechis australis.
Three single chain phospholipases A2 (Pa-10A, Pa-11 and Pa-13) isolated from Australian king brown snake (Pseudechis australis) venom were tested for effects on neuromuscular transmission and muscle contractility on chick biventer cervicis and mouse diaphragm preparations. At 1 microgram/ml (about 85 nM) and higher, Pa-10A and Pa-11 reduced responses of both preparations to indirect stimulation in a concentration-dependent manner. Responses to direct muscle stimulation were generally reduced more slowly. Pa-11 also decreased membrane potentials of chick biventer muscle fibres and caused damage visible by light microscopy. Pa-13, which is about 50 times less active as a phospholipase A2, was also less potent in its pharmacological effects: 20 micrograms Pa-13 per ml were required to reduce responses of either preparation. The phospholipases A2 also caused a slow contracture. After block of responses to nerve stimulation, responses of the chick preparation to acetylcholine, carbachol and KCl could be obtained, although they were smaller than control and highly variable in different preparations. It is concluded that Pa-10A and Pa-11 produce muscle paralysis by reducing acetylcholine release and by a direct blockade of muscle fibre contractility. Pa-13 has similar, though less pronounced, activities.


Prevalence of erosive tooth wear in Chilean adults, 2016: A cross-sectional study.
To determine the prevalence, severity and distribution of erosive tooth wear lesions in adult patients at the Universidad de los Andes Health Center in the San Bernardo Metropolitan Region, Chile, during a period of 4 months in 2016. A cross-sectional study was conducted. A consecutive sample of patients from 18 to 46 years old who were receiving care at the Universidad de los Andes Health Center during a period from September 2016 to January 2017 was analysed. Basic erosive wear examinations (BEWEs) were performed by two calibrated examiners. A total of 535 adults were included in this study. An erosive tooth wear prevalence of 97.9% was found in which at least one surface had a BEWE score of 2 or 3 as the highest score (98.56% for females and 95.8% for males). In the sample, 75.70% and 74.77% of individuals had at least one surface with a BEWE score of 3 at the second and fifth sextant, respectively. The median of cumulative BEWE scores was 12. The median by individual of the affected percentage of tooth surfaces with BEWE scores 2 or 3 was 19.70%. We found a high prevalence of erosive tooth wear, mainly in the anterior group of teeth. No differences were found between the sexes, but a positive correlation with age was found. The percentage of surfaces affected was low or moderate.


Hinge-like structure induced unusual properties of black phosphorus and new strategies to improve the thermoelectric performance.
We systematically investigated the geometric, electronic and thermoelectric (TE) properties of bulk black phosphorus (BP) under strain. The hinge-like structure of BP brings unusual mechanical responses such as anisotropic Young's modulus and negative Poisson's ratio. A sensitive electronic structure of BP makes it transform among metal, direct and indirect semiconductors under strain. The maximal figure of merit ZT of BP is found to be 0.72 at 800 K that could be enhanced to 0.87 by exerting an appropriate strain, revealing BP could be a potential medium-high temperature TE material. Such strain-induced enhancements of TE performance are often observed to occur at the boundary of the direct-indirect band gap transition, which can be attributed to the increase of degeneracy of energy valleys at the transition point. By comparing the structure of BP with SnSe, a family of potential TE materials with hinge-like structure are suggested. This study not only exposes various novel properties of BP under strain, but also proposes effective strategies to seek for better TE materials.


mSin3A/histone deacetylase 2- and PRMT5-containing Brg1 complex is involved in transcriptional repression of the Myc target gene cad.
The role of hSWI/SNF complexes in transcriptional activation is well characterized; however, little is known about their function in transcriptional repression. We have previously shown that subunits of the mSin3A/histone deacetylase 2 (HDAC2) corepressor complex copurify with hSWI/SNF complexes. Here we show that the type II arginine-specific methyltransferase PRMT5, which is involved in cyclin E repression, can be found in association with Brg1 and hBrm-based hSWI/SNF complexes. We also show that hSWI/SNF-associated PRMT5 can methylate hypoacetylated histones H3 and H4 more efficiently than hyperacetylated histones H3 and H4. Protein-protein interaction studies indicate that PRMT5 and mSin3A interact with the same hSWI/SNF subunits as those targeted by c-Myc. These observations prompted us to examine the expression profile of the c-Myc target genes, carbamoyl-phosphate synthase-aspartate carbamoyltransferase-dihydroorotase (cad) and nucleolin (nuc). We found that cad repression is altered in cells that express inactive Brg1 and in cells treated with the HDAC inhibitor depsipeptide. Using chromatin immunoprecipitation assays, we found that Brg1, mSin3A, HDAC2, and PRMT5 are directly recruited to the cad promoter. These results suggest that hSWI/SNF complexes, through their ability to interact with activator and repressor proteins, control expression of genes involved in cell growth and proliferation.


A cluster-randomised controlled trial of values-based training to promote autonomously held recovery values in mental health workers.
The implementation and use of evidence-based practices is a key priority for recovery-oriented mental health service provision. Training and development programmes for employees continue to be a key method of knowledge and skill development, despite acknowledged difficulties with uptake and maintenance of behaviour change. Self-determination theory suggests that autonomy, or a sense that behaviour is self-generated, is a key motivator to sustained behaviour change, in this case practices in mental health services. This study examined the utility of values-focused staff intervention as a specific, reproducible method of autonomy support. Mental health workers (n = 146) were assigned via cluster randomisation to either a values clarification condition or an active problem-solving control condition. Results demonstrated that a structured values clarification exercise was useful in promoting integrated motivation for the changed practice and resulted in increased implementation planning. Structured values clarification intervention demonstrates utility as a reproducible means of autonomy support within the workplace. We discuss future directions for the study of autonomous motivation in the field of implementation science. ACTRN12613000353796.


Reconciling migration models to the Americas with the variation of North American native mitogenomes.
In this study we evaluated migration models to the Americas by using the information contained in native mitochondrial genomes (mitogenomes) from North America. Molecular and phylogeographic analyses of B2a mitogenomes, which are absent in Eskimo-Aleut and northern Na-Dene speakers, revealed that this haplogroup arose in North America ∼11-13 ka from one of the founder Paleo-Indian B2 mitogenomes. In contrast, haplogroup A2a, which is typical of Eskimo-Aleuts and Na-Dene, but also present in the easternmost Siberian groups, originated only 4-7 ka in Alaska, led to the first Paleo-Eskimo settlement of northern Canada and Greenland, and contributed to the formation of the Na-Dene gene pool. However, mitogenomes also show that Amerindians from northern North America, without any distinction between Na-Dene and non-Na-Dene, were heavily affected by an additional and distinctive Beringian genetic input. In conclusion, most mtDNA variation (along the double-continent) stems from the first wave from Beringia, which followed the Pacific coastal route. This was accompanied or followed by a second inland migratory event, marked by haplogroups X2a and C4c, which affected all Amerindian groups of Northern North America. Much later, the ancestral A2a carriers spread from Alaska, undertaking both a westward migration to Asia and an eastward expansion into the circumpolar regions of Canada. Thus, the first American founders left the greatest genetic mark but the original maternal makeup of North American Natives was subsequently reshaped by additional streams of gene flow and local population dynamics, making a three-wave view too simplistic.