RIscoper: a tool for RNA-RNA interaction extraction from the literature.
Numerous experimental and computational studies in the biomedical literature have provided considerable amounts of data on diverse RNA-RNA interactions (RRIs). However, few text mining systems for RRIs information extraction are available. RNA Interactome Scoper (RIscoper) represents the first tool for full-scale RNA interactome scanning and was developed for extracting RRIs from the literature based on the N-gram model. Notably, a reliable RRI corpus was integrated in RIscoper, and more than 13 300 manually curated sentences with RRI information were recruited. RIscoper allows users to upload full texts or abstracts, and provides an online search tool that is connected with PubMed (PMID and keyword input), and these capabilities are useful for biologists. RIscoper has a strong performance (90.4% precision and 93.9% recall), integrates natural language processing techniques and has a reliable RRI corpus. The standalone software and web server of RIscoper are freely available at www.rna-society.org/riscoper/. Supplementary data are available at Bioinformatics online.


Cost-effectiveness of superabsorbent wound dressing versus standard of care in patients with moderate-to-highly exuding leg ulcers.
To determine the cost-effectiveness/utility of a superabsorbent wound dressing (Zetuvit Plus Silicone) versus the current standard of care (SoC) dressings, from the NHS perspective in England, in patients with moderate-to-high exudating leg ulcers. A model-based economic evaluation was conducted to analyse the cost-effectiveness/utility of a new intervention. We used a microsimulation state-transition model with a time horizon of six months and a cycle length of one week. The model uses a combination of incidence base and risk prediction approach to inform transition probabilities. All clinical efficiency, health-related quality of life (HRQoL), cost and resource use inputs were informed by conducting a systematic review of UK specific literature. Treatment with the superabsorbent dressing leads to a total expected cost per patient for a six month period of £2887, associated with 15.933 expected quality adjusted life weeks and 10.9% healing rate. When treated with SoC, the total expected cost per patient for a six month period is £3109, 15.852 expected quality adjusted life weeks and 8% healing rate. Therefore, the superabsorbent dressing leads to an increase in quality-adjusted life weeks, an increase in healing rate by 2.9% and a cost-saving of £222 per single average patient over six months. Results of several scenario analyses, one-way deterministic sensitivity analysis, and probabilistic sensitivity analysis confirmed the robustness of base-case results. The probabilistic analysis confirmed that, in any combination of variable values, the superabsorbent dressing leads to cost saving results. According to the model prediction, the superabsorbent dressing leads to an increase in health benefits and a decrease in associated costs of treatment.


The geometry of the occluding contour and its effect on motion interpretation.
Form information related to occlusion is needed to correctly interpret image motion. This work describes one of a series of investigations into the form constraints on motion perception. In the present study, we focus specifically on the geometry of the occluding contour, and in particular on whether its influence on motion can be accounted for merely by its effect on perceived occlusion. We used an occluded square moving in a circle, holding the T-junctions at points of occlusion constant while manipulating the occluding contour. We found evidence for two main influences of occluding contour geometry on motion interpretation and occlusion: the convexity of the occluding contour and additional static T-junctions that are formed elsewhere on the occluding contour. Our results suggest that convex occluding contours are more occlusive than concave ones, and that T-junctions along the contour increase or decrease the strength of occlusion depending on their orientation. Motion interpretation is influenced by both factors, but their effect on motion appears to be dominated by interactions occurring at an intermediate "semilocal" scale, which is larger than the scale at which junctions are defined, but smaller than the scale of the whole moving figure. We propose that these computations are related to occlusion but are not identical to the computations that mediate static occlusion judgments.


Chinese herbal medicine for acute upper respiratory tract infections and reproductive safety: A systematic review.
Acute upper respiratory tract infections (AURTIs) are common and self-limited in people with normal immunity but sometimes lead to poor clinical outcomes under specific conditions such as pregnancy if not treated appropriately. Chinese herbal medicines (CHM), which are widely used to treat AURTIs, have proven to be effective in preclinical and clinical studies. This review focuses on the bioactivities of typical CHM and the adverse reactions they cause, and especially issues with reproductive safety when treating AURTIs. The main mechanisms for clinical efficacy may include anti-viral, anti-bacterial, anti-inflammatory, antipyretic, and immunomodulatory action as indicated by preclinical evidence. Most clinical trials indicate that CHM shortens the natural course of AURTIs and that it relieves related symptoms such as a fever, headaches, coughing, myalgia, a cold, sore throat, and a nasal obstruction. However, some CHM have a range of adverse effects and potentially affect reproduction from endocrinal secretion to embryo development while others do not. Therefore, clinical adverse reactions and preclinical studies on the toxicity of CHM are discussed. More reliable evidence is required to conclude that CHM are efficacious and safe for pregnant women with AURTIs. This review should help to promote advances in the research on and development of CHM as alternative treatments for AURTIs and offer insight into strategies to manage the safety of CHM during clinical use.


Longitudinal associations between body mass index, physical activity, and healthy dietary behaviors in adults: A parallel latent growth curve modeling approach.
Physical activity (PA) and healthy dietary behaviors (HDB) are two well-documented lifestyle factors influencing body mass index (BMI). This study examined 7-year longitudinal associations between changes in PA, HDB, and BMI among adults using a parallel latent growth curve modeling (LGCM). We used prospective cohort data collected by a private company (SimplyWell LLC, Omaha, NE, USA) implementing a workplace health screening program. Data from a total of 2,579 adults who provided valid BMI, PA, and HDB information for at least 5 out of 7 follow-up years from the time they entered the program were analyzed. PA and HDB were subjectively measured during an annual online health survey. Height and weight measured during an annual onsite health screening were used to calculate BMI (kg·m2). The parallel LGCMs stratified by gender and baseline weight status (normal: BMI<25, overweight BMI 25-29.9, and obese: BMI>30) were fitted to examine the longitudinal associations of changes in PA and HDB with change in BMI over years. On average, BMI gradually increased over years, at rates ranging from 0.06 to 0.20 kg·m2·year, with larger increases observed among those of normal baseline weight status across genders. The increases in PA and HDB were independently associated with a smaller increase in BMI for obese males (b = -1.70 and -1.98, respectively), and overweight females (b = -1.85 and -2.46, respectively) and obese females (b = -2.78 and -3.08, respectively). However, no significant associations of baseline PA and HDB with changes in BMI were observed. Our study suggests that gradual increases in PA and HDB are independently associated with smaller increases in BMI in overweight and obese adults, but not in normal weight individuals. Further study is warranted to address factors that check increases in BMI in normal weight adults.


Survival lotteries reconsidered.
In 1975 John Harris envisaged a survival lottery to redistribute organs from one to a greater number in order to reduce number of deaths as a consequence of organ failure. In this paper I reach a conclusion about when running a survival lottery is permissible by looking at the reason prospective participants have for allowing the procedure from a contractual perspective. I identify three versions of the survival lottery. In a National Lottery, everyone within a jurisdiction is a candidate for being a donor for everyone else, disregarding all differences between individuals' eventual possibility of needing an organ. In a Group Specific Lottery, it is a question of running a lottery among members of a specific group who share the same probability of getting organ failure. In a Local Lottery one randomises among individuals who are already in need of a new organ but who happen to be compatible and in need of different organs. While the first is vulnerable to considerations of fairness, it is difficult to perceive a feasible way to implement the second option that does not come with a host of unwelcome consequences. I argue, however, that it is permissible to run Local Lotteries.


Isolation and characterization of Chinese hamster ovary cell variants defective in adhesion to fibronectin-coated collagen.
Variant clones of Chinese hamster ovary (CHO) cells were selected for reduced adhesion to serum-coated tissue culture plates. These clones also displayed reduced adhesion to substrata composed of collagen layers coated with bovine serum or with fibronectin (cold-insoluble globulin). Wild-type (WT) and adhesion variant (ADv) cells grew at comparable rates in suspension culture, but the adhesion variants could not be grown in monolayer culture because of their inability to attach to the substratum. The adhesion deficit in these cells was not corrected by raising the concentration of divalent cations or of serum to levels 10-fold greater than those normally utilized in cell culture. However, both WT and ADv clones could adhere, spread, and attain a normal CHO morphology on substrata coated with concanavalin A or poly-L-lysine. In addition, the adhesion variants could attach to substrata coated with "footpad" material (substratum-attached material) derived from monolayers of human diploid fibroblasts or WT CHO cells. These observations suggest that the variant clones may have a cell surface defect that prevents them from utilizing exogeneous fibronectin as an adhesion-promoting ligand; however the variants seem to have normal cytoskeletal and metabolic capacities that allow them to attach and spread on substrata coated with alternative ligands. These variants should be extremely useful in studying the molecular basis of cell adhesion.


Delayed repair for blunt thoracic aortic injury: is it really equivalent to early repair?
Blunt thoracic aortic injury (BTAI) is a severe injury that traditionally has mandated immediate surgical repair. Delaying operative intervention for BTAI can allow other life-threatening injuries to be managed first, but potentially increases the risk of aortic rupture and death. The objective of this study was to evaluate the outcome of delayed repair (DR) compared with early repair (ER) for BTAI and to assess the effectiveness of a protocol for medical control of systolic blood pressure and heart rate in those patients whose repairs were delayed. This study is a retrospective review of University of Michigan Health System (UMHS) data from January 1, 1992, through March 1, 2003. ER was defined as operative repair within 16 hours from the time of injury. A similar analysis was conducted for patients with BTAI selected from the National Trauma Data Bank. For the UMHS data, there were 45 patients in the DR group and 33 patients in the ER group. Mortality in the ER group versus the DR group was 9% versus 20%. Multivariate analysis adjusting for age, Injury Severity Score, abdominal Abbreviated Injury Scale score, Glasgow Coma Scale score, and intubation status demonstrated an odds ratio for death from ER compared with DR of 1.72 (p = 0.57). Patients undergoing DR had an absolute increase in hospital length of stay (33.1 vs. 20.9 days) and complication rate (2.1 vs. 1.5 incidents per patient). A similar result was obtained for multivariate analysis of the National Trauma Data Bank data, with an odds ratio of 1.40 (p = 0.51) for death from ER versus DR. UMHS patients whose repairs were delayed achieved target systolic blood pressure and heart rate for 76% and 74% of the hourly measurements recorded, respectively. Patients with BTAI can safely undergo delayed aortic repair if other injuries warrant a higher treatment priority without increasing their overall risk of mortality. Delayed repair is, however, associated with a higher complication rate.


Nocturnal violence: implications for resident trauma operative experiences.
Trauma centers face novel challenges in resource allocation in an era of cost consciousness and work-hour restrictions. Studies have shown that time of day and day of week affect trauma admission volume; however, these studies were performed in cold climates. Data from 2000 to 2010 at a Level I trauma center were reviewed. Demographic, injury severity, and injury timing from 23,827 trauma patients were analyzed along with their emergency department disposition (operating room, intensive care unit, ward) and final outcome. Nighttime arrivals (NAs) accounted for 56.6 per cent and daytime arrivals accounted for 43.4 per cent of total admissions. The increase in NAs was most pronounced during the period from midnight to 6 am on weekends (P < 0.05). Also, the period from midnight to 6 am on weekends showed a significantly increased proportion of penetrating trauma (P < 0.01). Similarly, there was an increased rate of trauma arrivals needing emergent operative intervention in the period between midnight and 6 am on weekends when compared with any other time period (P < 0.01). In a southern Level I trauma center, patient volume varies nonrandomly with time. Emergent operative intervention is more likely between midnight and 6 am, the peak time for penetrating trauma. Because resident operative experience is maximized at night and on weekends, coverage during these periods should remain a priority for residency programs.


Development of an evidence evaluation and synthesis system for drug-drug interactions, and its application to a systematic review of HIV and malaria co-infection.
In all settings, there are challenges associated with safely treating patients with multimorbidity and polypharmacy. The need to characterise, understand and limit harms resulting from medication use is therefore increasingly important. Drug-drug interactions (DDIs) are prevalent in patients taking antiretrovirals (ARVs) and if unmanaged, may pose considerable risk to treatment outcome. One of the biggest challenges in preventing DDIs is the substantial gap between theory and clinical practice. There are no robust methods published for formally assessing quality of evidence relating to DDIs, despite the diverse sources of information. We defined a transparent, structured process for developing evidence quality summaries in order to guide therapeutic decision making. This was applied to a systematic review of DDI data with considerable public health significance: HIV and malaria. This was a systematic review of DDI data between antiretrovirals and drugs used in prophylaxis and treatment of malaria. The data comprised all original research in humans that evaluated pharmacokinetic data and/or related adverse events when antiretroviral agents were combined with antimalarial agents, including healthy volunteers, patients with HIV and/or malaria, observational studies, and case reports. The data synthesis included 36 articles and conference presentations published via PubMed and conference websites/abstract books between 1987-August 2016. There is significant risk of DDIs between HIV protease inhibitors, or NNRTIs and artemesinin-containing antimalarial regimens. For many antiretrovirals, DDI studies with antimalarials were lacking, and the majority were of moderate to very low quality. Quality of evidence and strength of recommendation categories were defined and developed specifically for recommendations concerning DDIs. There is significant potential for DDIs between antiretrovirals and antimalarials. The application of quality of evidence and strength of recommendation criteria to DDI data is feasible, and allows the assessment of DDIs to be robust, consistent, transparent and evidence-based.


Patterns of gestational weight gain and its association with birthweight in Nigeria.
Despite the increasing global importance of gestational weight gain (GWG) and its impact on birthweight, little is known about the patterns of GWG in African populations. To determine the pattern of GWG and its association with birthweight in Nigeria. It was a longitudinal study of 200 pregnant women receiving antenatal care at two tertiary hospitals in Enugu, south eastern Nigeria. The women were consecutively recruited at <14 weeks gestation and their body mass indexes recorded upon recruitment. Thereafter, weight measurements were taken at each visit until 38-39 weeks. Mean total GWG was 10.7 ± 3.4 kg, while mean birthweight was 3.3 ± 0.6 kg. GWG in second trimester had positive correlation with birthweight (r = 0.164, P = 0.02). Obese women gained above the recommended limits by the "institute of medicine" while underweight women gained below the limits. Excessive total GWG was associated with higher risk of macrosomia [8/21 (38.1%) vs. 7/179; RR: 9.74; 95% CI: 3.9-24.2; P < 0.001] while inadequate total GWG was associated with higher risk of low birth weight [7/72 (9.7%) vs. 3/128 (2.3%; RR: 4.15; 95% CI: 1.1-15.4; P = 0.03]. Maternal age of <35 years, high social class, nulliparity, and regular antenatal care were associated with normal GWG while maternal age <35 years and regular antenatal care were associated with normal birthweight (P < 0.05). Women should be counseled on the factors that influence GWG and birthweight. Interventions to assist women achieve appropriate GWG may need to include components related to improved dietary intake for the underweight and increased physical activity for the obese.


Allergic disease and autoimmune effectors pathways.
Allergy and autoimmunity result from dysregulation of the immune system. Until recently, it was generally accepted that the mechanisms that govern these disease processes are quite disparate; however, new discoveries suggest possible common pathogenetic effector pathways. This review illustrates the concomitant presentation of these conditions and the potential relationship or common mechanism in some cases, by looking at the key elements that regulate the immune response in both allergic and autoimmunite conditions: mast cells, antibodies, T cells, cytokines, and genetic determinants. The parallel appearance of allergic and autoimmune conditions in the some patients may reveal that such aberrations of the immune system have a common pathophysiologic mechanism. Mast cells, which play a key role in allergic reactions, and the wealth of inflammatory mediators they express, make it likely that they have profound effects on many autoimmune processes. Activation of protein kinases by inflammatory cytokines and environmental stresses may contribute to both allergic and autoimmune diseases. The presence of autoantibodies in some allergic conditions suggests an autoimmune basis for these conditions. Because of the central role T cells play in immune reactivity, the T-cell receptor (TCR) loci have long been considered important candidates for common disease susceptibility within the immune system such as asthma, atopy, and autoimmunity. Immunomodulation is the key to a successful treatment of allergic and autoimmune conditions.


Promotion of corneal allograft survival by the induction of oxidative macrophages.
A Th1-type immune response was detected in allotransplanted, rejected corneas. Because the intracellular thiol redox status of antigen-presenting cells (APCs) reportedly regulates the Th1/Th2 balance through distinctive cytokine production by APCs, this study was conducted to investigate the effect of the intracellular thiol redox status of macrophages (Mps) on corneal allograft survival. N,N'-diacetyl-L-cystine dimethylester (NACOMe)(2) was injected intraperitoneally into BALB/c (H-2(d)) mice to induce Mps with a low intracellular glutathione content (icGSH). Corneal grafts from C57BL/10 (H-2(b)), B10.D2 (H-2(d)), and DBA/2 (H-2(d)) donor mice were placed on neovascularized BALB/c graft beds for assessment. B10.D2-grafted recipients were evaluated for donor-specific delayed-type hypersensitivity (DTH), and the cytokines produced by their lymphocytes were examined (IFN-gamma, IL-4, and IL-10). In other experiments, naïve BALB/c mice, injected intravenously with Mps of low icGSH content, received B10.D2 corneal grafts. In (NACOMe)(2)-treated mice, 13 of 20 B10.D2 grafts and 6 of 10 DBA/2 grafts survived indefinitely. No grafts survived in the control mice (P < 0.0001). (NACOMe)(2) treatment did not enhance C57BL/10 graft survival. At 2 weeks after B10.D2 grafting, control mice exhibited DTH, but (NACOMe)(2)-treated mice did not (P < 0.01). Lymphocytes from (NACOMe)(2)-treated mice did not respond to donor splenocytes. Those of control mice showed Th1-type cytokine secretion. The intravenous transfer of peritoneal Mps from (NACOMe)(2)-treated mice prolonged corneal allograft survival (P < 0.003). The observed enhanced graft acceptance may be due to the suppression of alloantigen-induced Th1 polarization through the induction of Mps with reduced icGSH levels.


Perioperative Diagnosis and Treatment of Serotonin Syndrome Following Administration of Methylene Blue.
Serotonin syndrome (SS) involves serotonergic hyperactivity caused by excessive activation of 5-HT2A receptors. As the use of antidepressants increases, so does the population of patients at risk for developing this complication. The diagnosis is made based on current serotonergic medication use in conjunction with certain clinical signs. The severity of the clinical presentation may vary, especially when the complication occurs while the patient is under general anesthesia. As a result, the incidence of SS is likely underreported and treatment may be delayed, leading to life-threatening complications. A 67-year-old, American Society of Anesthesiologist physical status 3 male with multiple medical comorbidities, including anxiety/depression and chronic neck pain, presented for an elective laparoscopic total abdominal colectomy for colonic inertia. His intraoperative course was significant for SS likely triggered by the administration of methylene blue, which only became clinically apparent during anesthetic emergence. We considered and systematically ruled out other potential causes of his clinical condition. His management was primarily supportive, using hydration and benzodiazepine administration, and resulted in full neurologic recovery. SS is an underdiagnosed condition with limited treatment options beyond symptom management. Thus, vigilance, early diagnosis, and cessation of offending medications are of utmost importance. Anesthesiologists managing at-risk surgical patients must have a high clinical suspicion of perioperative SS if their patients exhibit tachycardia, hypertension, and hyperthermia together with clonus, agitation, diaphoresis, or hypertonia. These signs may be masked by general anesthesia and may only manifest themselves upon anesthetic emergence.


Personality and physiological traits predict contest interactions in Kryptolebias marmoratus.
Personality and physiological traits often have close relationships with dominance status, but the significance and/or direction of the relationships vary between studies. This study examines whether two personality traits (aggressiveness and boldness) and three physiological traits (testosterone and cortisol levels and oxygen consumption rates) are associated with contest decisions/performance using a mangrove killifish Kryptolebias marmoratus. The results show that individuals that attacked their own mirror images (an aggressiveness index) at higher rates or had higher levels of testosterone were more likely to attack their opponent and win non-escalated contests, while individuals that had higher levels of cortisol were more likely to lose. After the contests, (1) individuals that had attacked their opponents or won had higher post-contest oxygen consumption rates, and (2) individuals that had attacked their opponents also had higher post-contest levels of cortisol. Although no significant correlations were detected among pre-contest physiological traits, post-contest levels of cortisol were positively correlated with oxygen consumption rates. Overall, personality and physiological traits provide useful predictors for the fish's contest decisions/performance. Contest interactions subsequently modified post-contest physiological traits and potentially also promoted associations between them. Nevertheless, the fish's physiological traits remained rather consistent over the entire study period.


Drug abuse treatment success among needle exchange participants.
Although lowering incidence rates of human immunodeficiency virus (HIV) transmission is the primary goal of needle exchange programs (NEPs), other desirable outcomes are possible. Referring exchange participants to more comprehensive drug abuse treatment programs has the potential to reduce or eliminate the use of drugs. This possibility was evaluated by comparing the treatment responses of new admissions with an outpatient opioid agonist treatment program in Baltimore, Maryland. New admissions (1994 - 1997) to an opioid agonist treatment program were first grouped by referral source (needle exchange, n = 82 vs. standard referrals, n = 243) and then compared on admission demographic and clinical variables and response to treatment during the first three months. Outcome measures included retention rates, self-reported drug use and injecting frequencies, self-reported illegal activities for profit, and results from weekly urinalysis testing for opioids and cocaine. Patients from the NEP were significantly older and more likely to be male, African American, and unemployed than standard referral patients. Needle exchange patients also had a greater baseline severity of drug use than patients in the standard referral group. Despite these baseline differences, both groups achieved comparably good short-term treatment outcomes (including reduced drug use and criminal activity for profit); treatment retention was also good, although slightly better in the standard referral group (88% vs. 76%). These data demonstrate the feasibility and merits of creating strong linkages between NEPs and more comprehensive drug abuse treatment clinics.


Use of brachytherapy to preserve function in children with soft-tissue sarcomas.
Pediatric soft-tissue sarcomas are managed with a multimodality treatment program that includes surgery, chemotherapy, and external-beam radiotherapy (teletherapy). The use of teletherapy in young children can result in significant long-term toxicities (especially growth retardation of bones and organs). Brachytherapy, if feasible, is an attractive alternative for the treatment of pediatric soft-tissue sarcomas, since it irradiates small volumes and, thus, may potentially minimize complications. Aggressive chemotherapy is used to achieve systemic control and tumor shrinkage, thereby facilitating conservative surgery and brachytherapy. The brachytherapy techniques used in children are similar to those employed in adults. Low-dose-rate (LDR) brachytherapy with manually afterloaded removable iridium-192 is commonly used, although it is associated with some radiation exposure hazards. Low-energy radionuclides (e.g., iodine-125) and remote afterloading technology have been used to reduce radiation exposure hazards. Brachytherapy, in conjunction with chemotherapy and surgery but without supplementary teletherapy, has produced good local control with acceptable late complications in selected patients with localized tumors. Brachytherapy can also be used as a boost to moderate dose external-beam radiotherapy for more extensive tumors. The use of newer modalities, such as high-dose-rate, pulsed-dose-rate, and intraoperative brachytherapy, has allowed brachytherapy to be given to younger children and infants, but the long-term morbidities of these modalities need to be established.


Solvent Exchange Leading to Nanobubble Nucleation: A Molecular Dynamics Study.
The solvent exchange procedure has become the most-used protocol to produce surface nanobubbles, while the molecular mechanisms behind the solvent exchange are far from being fully understood. In this paper, we build a simple model and use molecular dynamics simulations to investigate the dynamic characteristics of solvent exchange for producing nanobubbles. We find that at the first stage of solvent exchange, there exists an interface between interchanging solvents of different gas solubility. This interface moves toward the substrate gradually as the exchange process proceeds. Our simulations reveal directed diffusion of gas molecules against the gas concentration gradient, driven by the solubility gradient of the liquid composition across the moving solvent-solvent interface. It is this directed diffusion that causes gas retention and produces a local gas oversaturation much higher near the substrate than far from it. At the second stage of solvent exchange, the high local gas oversaturation leads to bubble nucleation either on the solid surface or in the bulk solution, which is found to depend on the substrate hydrophobicity and the degree of local gas oversaturation. Our findings suggest that solvent exchange could be developed into a standard procedure to produce oversaturation and used to a variety of nucleation applications other than generating nanobubbles.


Emergency management of dental trauma: knowledge of Hong Kong primary and secondary school teachers.
OBJECTIVES. To investigate the level of knowledge about emergency management of dental trauma among Hong Kong primary and secondary school teachers. DESIGN. Questionnaire survey. SETTING. A teachers' union that unites 90% of teachers in Hong Kong. PARTICIPANTS. Randomly selected primary and secondary school teachers. RESULTS. Only 32.8% of respondents correctly stated that a person sustaining dental trauma should go to dentists directly. In all, 73.1% of teachers correctly stated that a dental trauma patient should go for treatment immediately. Only 32.5% knew that a fractured tooth should be put in liquid. Even fewer (23.2%) realised that the displaced tooth should be repositioned back to the original position. Relatively more respondents (74.7%) understood that an avulsed baby tooth should not be put back. Disappointingly, only 16.3% of teachers knew that an avulsed permanent tooth should be replanted. Furthermore, only 29.6% of teachers thought that they were able to distinguish between deciduous teeth and permanent teeth, whilst 20.4% correctly identified at least one of the appropriate mediums: milk, physiological saline or saliva, for storing an avulsed tooth. Teachers who previously received first-aid training with dental content or acquired dental injury information from other sources, scored significantly higher than teachers without such training or acquired information. CONCLUSION. The knowledge on emergency management of dental trauma among primary and secondary school teachers in Hong Kong is insufficient, particularly on the handling of permanent tooth avulsion and the appropriate storage medium for avulsed teeth. Receipt of first-aid training with dental contents and acquisition of dental injury information from other sources were positively correlated with knowledge in managing dental trauma.


Active site plasticity and possible modes of chemical inhibition of the human DNA deaminase APOBEC3B.
The single-stranded DNA cytosine deaminase APOBEC3B (A3B) functions in innate immunity against viruses, but it is also strongly implicated in eliciting mutations in cancer genomes. Because of the critical role of A3B in promoting virus and tumor evolution, small molecule inhibitors are desirable. However, there is no reported structure for any of the APOBEC3-family enzymes in complex with a small molecule bound in the active site, which hampers the development of small molecules targeting A3B. Here we report high-resolution structures of an active A3B catalytic domain chimera with loop 7 residues exchanged with those from the corresponding region of APOBEC3G (A3G). The structures reveal novel open conformations lacking the catalytically essential zinc ion, with the highly conserved active site residues extensively rearranged. These inactive conformations are stabilized by 2-pyrimidone or an iodide ion bound in the active site. Molecular dynamics simulations corroborate the remarkable plasticity of the engineered active site and identify key interactions that stabilize the native A3B active site. These data provide insights into A3B active site dynamics and suggest possible modes of its inhibition by small molecules, which would aid in rational design of selective A3B inhibitors for constraining virus and tumor evolution.


The aging of America. Impact on health care costs.
The rapid growth of the oldest age groups will have a major impact on future health care costs. We use current US Census Bureau projections for the growth of our oldest age groups to project future costs for Medicare, nursing homes, dementia, and hip fractures. Without major changes in the health of our older population, these health care costs will escalate enormously, in large part as a result of the projected growth of the "oldest old," those aged 85 years and above. Medicare costs for the oldest old may increase sixfold by the year 2040 (in constant 1987 dollars). It is unlikely that these projected increases in health care costs will be restrained solely by cost-containment strategies. Successful containment of these health care costs will be related to our ability to prevent and/or cure those age-dependent diseases and disorders that will produce the greatest needs for long-term care.


The Arabidopsis RNA-directed DNA methylation argonautes functionally diverge based on their expression and interaction with target loci.
Argonaute (AGO) effectors of RNA silencing bind small RNA (sRNA) molecules and mediate mRNA cleavage, translational repression, or epigenetic DNA modification. In many organisms, these targeting mechanisms are devolved to different products of AGO multigene families. To investigate the basis of AGO functional diversification, we characterized three closely related Arabidopsis thaliana AGOs (AGO4, AGO6, and AGO9) implicated in RNA-directed DNA methylation. All three AGOs bound 5' adenosine 24-nucleotide sRNAs, but each exhibited different preferences for sRNAs from different heterochromatin-associated loci. This difference was reduced when AGO6 and AGO9 were expressed from the AGO4 promoter, indicating that the functional diversification was partially due to differential expression of the corresponding genes. However, the AGO4-directed pattern of sRNA accumulation and DNA methylation was not fully recapitulated with AGO6 or AGO9 expressed from the AGO4 promoter. Here, we show that sRNA length and 5' nucleotide do not account for the observed functional diversification of these AGOs. Instead, the selectivity of sRNA binding is determined by the coincident expression of the AGO and sRNA-generating loci, and epigenetic modification is influenced by interactions between the AGO protein and the different target loci. These findings highlight the importance of tissue specificity and AGO-associated proteins in influencing epigenetic modifications.


Construction and characterization of a Streptomyces rimosus recA mutant: the RecA-deficient strain remains viable.
Although previously reported attempts to construct recA null mutants in Streptomyces spp. have been unsuccessful, we have used the suicide plasmid pErmdeltaRecA to inactivate the recA gene in Streptomyces rimosus by gene disruption. pErmdeltaRecA carries the erythromycin resistance gene ermE and a 451-bp fragment of the S. rimosus recA gene (encoding amino acids 2-151). An erythromycin-resistant clone with single plasmid integration into the recA gene on the chromosome was analyzed in detail. This clone possesses one inactive copy of recA which lacks the entire promoter region and the ATG start codon, and a second, truncated gene that encodes only first 151 amino acids of the RecA protein. This S. rimiosus rec A mutant can therefore be considered a completely RecA-deficient strain. The mutant strain is highly sensitive to UV light. Introduction of a plasmid carrying the wild type S. rimosus recA gene completely restored the UV resistance of the recA mutant to wild-type levels. recA genes encoding RecA proteins with short deletions at the C-terminus (21 and 51 amino acids) could not fully rescue the UV sensitivity of the S. rimosus recA strain, when introduced in the same way.


The landscape of genomic alterations across childhood cancers.
Pan-cancer analyses that examine commonalities and differences among various cancer types have emerged as a powerful way to obtain novel insights into cancer biology. Here we present a comprehensive analysis of genetic alterations in a pan-cancer cohort including 961 tumours from children, adolescents, and young adults, comprising 24 distinct molecular types of cancer. Using a standardized workflow, we identified marked differences in terms of mutation frequency and significantly mutated genes in comparison to previously analysed adult cancers. Genetic alterations in 149 putative cancer driver genes separate the tumours into two classes: small mutation and structural/copy-number variant (correlating with germline variants). Structural variants, hyperdiploidy, and chromothripsis are linked to TP53 mutation status and mutational signatures. Our data suggest that 7-8% of the children in this cohort carry an unambiguous predisposing germline variant and that nearly 50% of paediatric neoplasms harbour a potentially druggable event, which is highly relevant for the design of future clinical trials.


Plant-derived cannabinoids modulate the activity of transient receptor potential channels of ankyrin type-1 and melastatin type-8.
The plant cannabinoids (phytocannabinoids), cannabidiol (CBD), and Delta(9)-tetrahydrocannabinol (THC) were previously shown to activate transient receptor potential channels of both vanilloid type 1 (TRPV1) and ankyrin type 1 (TRPA1), respectively. Furthermore, the endocannabinoid anandamide is known to activate TRPV1 and was recently found to antagonize the menthol- and icilin-sensitive transient receptor potential channels of melastatin type 8 (TRPM8). In this study, we investigated the effects of six phytocannabinoids [i.e., CBD, THC, CBD acid, THC acid, cannabichromene (CBC), and cannabigerol (CBG)] on TRPA1- and TRPM8-mediated increase in intracellular Ca2+ in either HEK-293 cells overexpressing the two channels or rat dorsal root ganglia (DRG) sensory neurons. All of the compounds tested induced TRPA1-mediated Ca2+ elevation in HEK-293 cells with efficacy comparable with that of mustard oil isothiocyanates (MO), the most potent being CBC (EC(50) = 60 nM) and the least potent being CBG and CBD acid (EC(50) = 3.4-12.0 microM). CBC also activated MO-sensitive DRG neurons, although with lower potency (EC(50) = 34.3 microM). Furthermore, although none of the compounds tested activated TRPM8-mediated Ca2+ elevation in HEK-293 cells, they all, with the exception of CBC, antagonized this response when it was induced by either menthol or icilin. CBD, CBG, THC, and THC acid were equipotent (IC(50) = 70-160 nM), whereas CBD acid was the least potent compound (IC(50) = 0.9-1.6 microM). CBG inhibited Ca2+ elevation also in icilin-sensitive DRG neurons with potency (IC(50) = 4.5 microM) similar to that of anandamide (IC(50) = 10 microM). Our findings suggest that phytocannabinoids and cannabis extracts exert some of their pharmacological actions also by interacting with TRPA1 and TRPM8 channels, with potential implications for the treatment of pain and cancer.


Genetics of auditory mechano-electrical transduction.
The hair bundles of cochlear hair cells play a central role in the auditory mechano-electrical transduction (MET) process. The identification of MET components and of associated molecular complexes by biochemical approaches is impeded by the very small number of hair cells within the cochlea. In contrast, human and mouse genetics have proven to be particularly powerful. The study of inherited forms of deafness led to the discovery of several essential proteins of the MET machinery, which are currently used as entry points to decipher the associated molecular networks. Notably, MET relies not only on the MET machinery but also on several elements ensuring the proper sound-induced oscillation of the hair bundle or the ionic environment necessary to drive the MET current. Here, we review the most significant advances in the molecular bases of the MET process that emerged from the genetics of hearing.


Evaluation of electropositive filtration for recovering norovirus in water.
The virus adsorption-elution (VIRADEL) technique has been widely used in the recovery of various enteric viruses in water, and an electropositive filter such as 1 MDS has been commonly applied. However, effective methods of monitoring waterborne norovirus (NoV) have not yet been well characterized and optimized. Hence, in this study, the VIRADEL technique was evaluated and optimized for effectively detecting NoV in water by two commonly used electropositive filters (1MDS and NanoCeram filter). Various elution and concentration methods were evaluated by using both murine norovirus (MNV) and human NoV. Among the tested elution buffers, the most effective was 1.5% beef extract plus 0.01% Tween 80 for both 1MDS (67.5%) and NanoCeram (85.7%) microfilters. The recovery rate of GII-4 human NoV was higher by organic flocculation (86.6%) than by polyethylene glycol (PEG) precipitations (11.6~73.6%). When both 1MDS and NanoCeram filters were tested to detect NoV in surface and groundwater, the sensitivity of NoV recovered by these filters appeared to depend on the types and conditions of environmental water. The results of this study will help to set a standard of detection method for NoV in water.


Beyond audiofacial morbidity after vestibular schwannoma surgery.
Outcomes following vestibular schwannoma (VS) surgery have been extensively described; however, complication rates reported in the literature vary markedly. In addition, the majority of reports have focused on outcomes related to cranial nerves (CNs) VII and VIII. The objective of this study was to analyze reported morbidity unrelated to CNs VII and VIII following the resection of VS. The authors performed a comprehensive search of the English language literature, identifying and aggregating morbidity and death data from patients who had undergone microsurgical removal of VSs. A subgroup analysis based on surgical approach and tumor size was performed to compare rates of CSF leakage, vascular injury, neurological deficit, and postoperative infection. One hundred articles met the inclusion criteria, providing data for 32,870 patients. The overall mortality rate was 0.2% (95% CI 0.1-0.3%). Twenty-two percent of patients (95% CI 21-23%) experienced at least 1 surgically attributable complication unrelated to CNs VII or VIII. Cerebrospinal fluid leakage occurred in 8.5% of patients (95% CI 6.9-10.0%). This rate was markedly increased with the translabyrinthine approach but was not affected by tumor size. Vascular complications, such as ischemic injury or hemorrhage, occurred in 1% of patients (95% CI 0.75-1.2%). Neurological complications occurred in 8.6% of cases (95% CI 7.9-9.3%) and were less likely with the resection of smaller tumors (p < 0.0001) and the use of the translabyrinthine approach (p < 0.0001). Infections occurred in 3.8% of cases (95% CI 3.4-4.3%), and 78% of these infections were meningitis. This study provides statistically powerful data for practitioners to advise patients about the published risks of surgery for VS unrelated to compromised CNs VII and VIII.


A nested model for visualization design and validation.
We present a nested model for the visualization design process with four layers: characterize the problem domain, abstract into operations on data types, design visual encoding and interaction techniques, and create algorithms to execute techniques efficiently. The output from a level above is input to the level below, bringing attention to the design challenge that an upstream error inevitably cascades to all downstream levels. This model provides prescriptive guidance for determining appropriate evaluation approaches by identifying threats to validity unique to each level. We call attention to specific steps in the design and evaluation process that are often given short shrift. We also provide three recommendations motivated by this model:authors should distinguish between these levels when claiming contributions at more than one of them, authors should explicitly state upstream assumptions at levels above the focus of a paper, and visualization venues should accept more papers on domain characterization.


A clinical guide to periodontology: pathology of periodontal disease.
An appreciation of dental plaque and the host response provides an essential basis from which to understand the disease process and treatment rationale. This information will help the reader to understand not only the way that plaque may have an impact on oral tissues but also why regular effective cleaning may improve periodontal health and why some individuals appear to have a greater susceptibility to periodontitis than others, either intrinsically or in relation to various systemic factors.


Nobiletin exerts anti-diabetic and anti-inflammatory effects in an in vitro human model and in vivo murine model of gestational diabetes.
Gestational diabetes mellitus (GDM) is a global health issue, whereby pregnant women are afflicted with carbohydrate intolerance with first onset during pregnancy. GDM is characterized by maternal peripheral insulin resistance, thought to be driven by low-grade maternal inflammation. Nobiletin, a polymethoxylated flavonoid, possesses potent glucose-sensitizing and anti-inflammatory properties; however, its effects in GDM have not been assessed. The present study aimed to determine the effects of nobiletin on glucose metabolism and inflammation associated with GDM in both in vitro human tissues and an in vivo animal model of GDM. In vitro, treatment with nobiletin significantly improved TNF-impaired glucose uptake in human skeletal muscle, and suppressed mRNA expression and protein secretion of pro-inflammatory cytokines and chemokines in human placenta and visceral adipose tissue (VAT). Mechanistically, nobiletin significantly inhibited Akt and Erk activation in placenta, and NF-κB activation in VAT. In vivo, GDM mice treated with 50 mg/kg nobiletin daily via oral gavage from gestational day (gd) 1-17 or via i.p. injections from gd 10-17 significantly improved glucose tolerance. Pregnant GDM mice treated with nobiletin from either gd 1-17 or gd 10-17 exhibited significantly suppressed mRNA expression of pro-inflammatory cytokines and chemokines in placenta, VAT and subcutaneous adipose tissue (SAT). Using a quantitative mass spectrometry approach, we identified differentially abundant proteins associated with the effect of nobiletin in vivo. Together, these studies demonstrate that nobiletin improves glucose metabolism and reduces inflammation associated with GDM and may be a novel therapeutic for the prevention of GDM.


Is baseline aerobic fitness associated with illness and attrition rate in military training?
Respiratory illnesses are a leading cause of morbidity and medical discharge in the military. This study aimed to investigate the effects of baseline aerobic fitness on haematological, salivary and mood variables, and simultaneously, in a novel approach, to identify factors precipitating illness and attrition rate in recruits during military training. Thirty-five healthy male recruits from an Army Training Regiment undertaking 12 weeks of training were prospectively investigated. Their 2.4 km run time (RT) was used as a surrogate of baseline aerobic fitness. Saliva and venous blood samples were analysed for secretory IgA, full blood counts and cell cytokine production (interleukin (IL) 6 and IL-8), respectively. Each recruit completed questionnaires on mood profile, and gastrointestinal and upper respiratory tract symptoms (URTS). Significant salivary and haematological perturbations were observed and coincided with increased duration of URTS/week and mood disturbance over this military training period. From Start to End: leucocyte count decreased by 28% (p<0.001); neutrophil percentage (%) decreased by 13% (p<0.01); lymphocyte % increased by 17% (p<0.05); the neutrophil:lymphocyte ratio decreased by 22% (p<0.01); eosinophil% increased by 71% (p<0.01). From Start to Mid to End: monocyte% increased by 68% at Mid (p<0.01) but only by 30% at End (p<0.01); IL-6 increased by 39% at Mid (p<0.01) and a further 61% by End. The 2.4 km RT was significantly associated with URTS duration (p<0.01). In addition, a 1-min increase in 2.4 km RT increased a recruit's risk 9.8-fold of developing URTS lasting, on average, 3.36 days/week. In recruits ranked with high-URTS duration their RT was 48 s slower (p<0.01) than those with low-URTS, and their attrition rate reached 45%. The least fit recruits may have found training more physically demanding as reflected in the higher URTS duration, which may have led to a high attrition rate from the Army. It is worth considering that baseline aerobic fitness might be an important factor in illness development and attrition rate in recruits during this type of military training.


SATB1 targets chromatin remodelling to regulate genes over long distances.
Eukaryotic chromosomes are organized inside the nucleus in such a way that only a subset of the genome is expressed in any given cell type, but the details of this organization are largely unknown. SATB1 ('special AT-rich sequence binding 1'), a protein found predominantly in thymocytes, regulates genes by folding chromatin into loop domains, tethering specialized DNA elements to an SATB1 network structure. Ablation of SATB1 by gene targeting results in temporal and spatial mis-expression of numerous genes and arrested T-cell development, suggesting that SATB1 is a cell-type specific global gene regulator. Here we show that SATB1 targets chromatin remodelling to the IL-2Ralpha ('interleukin-2 receptor alpha') gene, which is ectopically transcribed in SATB1 null thymocytes. SATB1 recruits the histone deacetylase contained in the NURD chromatin remodelling complex to a SATB1-bound site in the IL-2Ralpha locus, and mediates the specific deacetylation of histones in a large domain within the locus. SATB1 also targets ACF1 and ISWI, subunits of CHRAC and ACF nucleosome mobilizing complexes, to this specific site and regulates nucleosome positioning over seven kilobases. SATB1 defines a class of transcriptional regulators that function as a 'landing platform' for several chromatin remodelling enzymes and hence regulate large chromatin domains.


Interaction of severe acute respiratory syndrome-coronavirus and NL63 coronavirus spike proteins with angiotensin converting enzyme-2.
Although in different groups, the coronaviruses severe acute respiratory syndrome-coronavirus (SARS-CoV) and NL63 use the same receptor, angiotensin converting enzyme (ACE)-2, for entry into the host cell. Despite this common receptor, the consequence of entry is very different; severe respiratory distress in the case of SARS-CoV but frequently only a mild respiratory infection for NL63. Using a wholly recombinant system, we have investigated the ability of each virus receptor-binding protein, spike or S protein, to bind to ACE-2 in solution and on the cell surface. In both assays, we find that the NL63 S protein has a weaker interaction with ACE-2 than the SARS-CoV S protein, particularly in solution binding, but the residues required for contact are similar. We also confirm that the ACE-2-binding site of NL63 S lies between residues 190 and 739. A lower-affinity interaction with ACE-2 might partly explain the different pathological consequences of infection by SARS-CoV and NL63.


Choices enhance punching performance of competitive kickboxers.
While self-controlled practice has been shown to enhance motor learning with various populations and novel tasks, it remains unclear if such effects would be found with athletes completing familiar tasks. Study 1 used a single case-study design with a world-champion kickboxer. We investigated whether giving the athlete a choice over the order of punches would affect punching velocity and impact force. Separated by 1 min of rest, the athlete completed 2 rounds of 12 single, maximal effort punches (lead straight, rear straight, lead hook and rear hook) delivered to a punching integrator in a counterbalanced order over six testing days. In one round the punches were delivered in a predetermined order while in the second round the order was self-selected by the athlete. In the choice condition, the world champion punched with greater velocities (6-11 %) and impact forces (5-10 %). In Study 2, the same testing procedures were repeated with 13 amateur male kickboxers over 2 testing days. Similar to Study 1, the athletes punched with significantly greater velocities (6 %, p < 0.05) and normalised impact forces (2 %, p < 0.05) in the choice condition. These findings complement research on autonomy support in motor learning by demonstrating immediate advantages in force production and velocity with experienced athletes.


An administrative data validation study of the accuracy of algorithms for identifying rheumatoid arthritis: the influence of the reference standard on algorithm performance.
We have previously validated administrative data algorithms to identify patients with rheumatoid arthritis (RA) using rheumatology clinic records as the reference standard. Here we reassessed the accuracy of the algorithms using primary care records as the reference standard. We performed a retrospective chart abstraction study using a random sample of 7500 adult patients under the care of 83 family physicians contributing to the Electronic Medical Record Administrative data Linked Database (EMRALD) in Ontario, Canada. Using physician-reported diagnoses as the reference standard, we computed and compared the sensitivity, specificity, and predictive values for over 100 administrative data algorithms for RA case ascertainment. We identified 69 patients with RA for a lifetime RA prevalence of 0.9%. All algorithms had excellent specificity (>97%). However, sensitivity varied (75-90%) among physician billing algorithms. Despite the low prevalence of RA, most algorithms had adequate positive predictive value (PPV; 51-83%). The algorithm of "[1 hospitalization RA diagnosis code] or [3 physician RA diagnosis codes with ≥1 by a specialist over 2 years]" had a sensitivity of 78% (95% CI 69-88), specificity of 100% (95% CI 100-100), PPV of 78% (95% CI 69-88) and NPV of 100% (95% CI 100-100). Administrative data algorithms for detecting RA patients achieved a high degree of accuracy amongst the general population. However, results varied slightly from our previous report, which can be attributed to differences in the reference standards with respect to disease prevalence, spectrum of disease, and type of comparator group.


Generation of Phase-Modulated Periodic Optical Signals by use of a Polarization Interferometer.
Polarization phase-shifting interferometry is an established technique in optical metrology. In the present study it is shown that, by use of this technique, not only is it possible to realize any discrete magnitude of a predetermined phase difference (from 0 to 2pi) between two light beams but also phase-modulated periodic optical signals can be generated simply by rotation of a polarizer or a retarder or both placed at the input of a conventional two-beam interferometer. Some representative linear and nonlinear periodic polarization-induced phase-modulated optical signals are shown. A linear phase modulation of 0-2pi with constant output intensity is obtained in some cases. The Poincaré sphere representation is introduced as a convenient tool for visualizing the dynamics involved in the generation of polarization-phase-modulated waveforms and as a possible aid to intelligent modification of the generated waveform as required. This all-optical technique of continuous and periodic phase variation should prove useful for introducing phase modulation without the need for electro-optic devices.


Analysis of 81 genes from 64 plastid genomes resolves relationships in angiosperms and identifies genome-scale evolutionary patterns.
Angiosperms are the largest and most successful clade of land plants with >250,000 species distributed in nearly every terrestrial habitat. Many phylogenetic studies have been based on DNA sequences of one to several genes, but, despite decades of intensive efforts, relationships among early diverging lineages and several of the major clades remain either incompletely resolved or weakly supported. We performed phylogenetic analyses of 81 plastid genes in 64 sequenced genomes, including 13 new genomes, to estimate relationships among the major angiosperm clades, and the resulting trees are used to examine the evolution of gene and intron content. Phylogenetic trees from multiple methods, including model-based approaches, provide strong support for the position of Amborella as the earliest diverging lineage of flowering plants, followed by Nymphaeales and Austrobaileyales. The plastid genome trees also provide strong support for a sister relationship between eudicots and monocots, and this group is sister to a clade that includes Chloranthales and magnoliids. Resolution of relationships among the major clades of angiosperms provides the necessary framework for addressing numerous evolutionary questions regarding the rapid diversification of angiosperms. Gene and intron content are highly conserved among the early diverging angiosperms and basal eudicots, but 62 independent gene and intron losses are limited to the more derived monocot and eudicot clades. Moreover, a lineage-specific correlation was detected between rates of nucleotide substitutions, indels, and genomic rearrangements.


Use of morphometry to quantify osteolysis after total hip arthroplasty.
Progressive osteolysis threatens the longevity of hip arthroplasties and radiographic review is recommended. Measurement of osteolytic lesions in a clinical setting has not been achieved easily in the past. Other radiologic investigations provide accurate information but cost and risk to the patient prohibit their use in routine review. We developed a simple, reliable tool to be used in hip arthroplasty review to quantify osteolytic changes seen on plain film radiographs. A morphometric grid was developed and tested on simulated and actual osteolytic lesions. Four health professionals measured lesions on each of two occasions. Intraclass correlation coefficients (ICC) for interobserver and intraobserver reliabilities were calculated and Bland-Altman plots were constructed for graphic analysis. The ICCs for interobserver reliability on the simulated and actual osteolytic lesions were in the range 0.90 to 0.96. The values for intraobserver (test-retest) reliability were 0.97 to 0.98. The Bland-Altman plots confirmed agreement and in each case, proximity of the mean to zero indicated no significant bias. The data show a morphometric grid is reliable for measuring osteolytic changes after hip arthroplasty. This tool has potential to improve monitoring processes for hip arthroplasty and to be useful in future research studies. Additional work is needed to test for validity and clinical importance of the measurements obtained.


Effect of Areca Nut on Helicobacter pylori-Induced Gastric Diseases in Mice.
Areca nut (AN) chewing is a habit in many countries in Central, Southern, and Southeast Asia. It is strongly associated with the occurrence of oral, pharyngeal, and esophageal cancer as well as systemic inflammation. However, the association between AN intake and the development of gastric lesions has not yet been identified. The aim of this study was to investigate the effect of AN on gastric diseases using a mouse model for Helicobacter pylori infection. We studied four groups of mice: those fed a normal diet (ND), those fed a diet containing 2.5% AN (AD), those fed ND and infected with H. pylori PMSS1 strain (ND/HP), and those fed AD and infected with H. pylori PMSS1 strain (AD/HP). Food intake and body weight were monitored weekly during the experiments. At 10 weeks, the mice were sacrificed, and the stomach weight, H. pylori colonization, and gastric inflammation were evaluated. The stomach weight had increased significantly in the ND/HP and AD/HP groups along with increases in H. pylori colonization; however, there was no significant difference between these two groups with respect to stomach weight and colonization. On histological grading, mononuclear cell infiltration was severer in the AD/HP group than in the ND/HP group. These data suggest that chronic gastric inflammation was aggravated by AN treatment in the mice with H. pylori-induced gastric lesions. Furthermore, as previously suggested, this animal model is useful to determine the effect of potential carcinogens on gastric lesions induced by H. pylori infection.


Heritability of Psychotic Experiences in Adolescents and Interaction With Environmental Risk.
Genetic risk factors are known to play a role in the etiology of psychotic experiences in the general population. Little is known about whether these risk factors interact with environmental risks for psychotic experiences. To assess etiological heterogeneity and exposure to environmental risks associated with psychotic experiences in adolescence using the twin design. This twin study, conducted from December 1, 2014, to August 31, 2020, included a UK-based sample of twin pairs aged 16 years. This investigation evaluated the extent to which the genetic variance underlying psychotic experiences and the magnitude of the heritability of psychotic experiences was moderated by exposure to 5 environmental risk factors (bullying, dependent life events, cannabis use, tobacco use, and low birth weight). Psychotic experiences were assessed by 5 self-reported measures and 1 parent-reported measure. Participants' exposure to environmental risks was assessed at birth and age 12 to 16 years. Structural equation models were used to assess differences in the variance in and heritability of psychotic experiences across these exposures, while controlling for gene-environment correlation effects. Analyses were repeated in an independent Swedish sample. Data analyses were performed from September 1, 2018, to August 31, 2020. Primary outcome measures were exposure to environmental factors, as measured by a composite score, and psychotic experiences. A total of 4855 twin pairs (1926 female same-sex pairs, 1397 male same-sex pairs, and 1532 opposite-sex pairs) were included from the Twins Early Development Study (TEDS), and 6435 twin pairs (2358 female same-sex pairs, 1861 male same-sex pairs, and 2216 opposite-sex pairs) were included from the Child and Adolescent Twin Study in Sweden (CATSS). Mean age of twins from TEDS was 16.5 years. Mean age of twins from CATSS was 18.6 years. More exposure to environmental risk factors was associated with having more psychotic experiences. The relative contribution of genetic influences to psychotic experiences was lower with increasing environmental exposure for paranoia (44%; 95% CI, 33%-53% to 38%; 95% CI, 14%-58%), cognitive disorganization (47%; 95% CI, 38%-51% to 32%; 95% CI, 11%-45%), grandiosity (41%; 95% CI, 29%-52% to 32%; 95% CI, 9%-48%), and anhedonia (49%; 95% CI, 42%-53% to 37%; 95% CI, 15%-54%). This pattern was replicated for the measure of psychotic experiences in the independent Swedish replication sample. The heritability of hallucinations and parent-rated negative symptoms remained relatively constant. Findings of this twin study suggest that environmental factors play a greater role in the etiology of psychotic experiences than genetic factors. The relative importance of environmental factors is even higher among individuals exposed to environmental risks for psychotic experiences, highlighting the importance of a diathesis-stress or bioecological framework for understanding adolescent psychotic experiences.


People carrying excess weight have an increased risk of severe covid-19.
The studyGao M, Piernas C, Astbury NM, et al. Associations between body-mass index and COVID-19 severity in 6.9 million people in England: a prospective, community-based cohort study. Lancet Diabetes Endocrinol 2021;9:6.To read the full NIHR Alert, go to: https://evidence.nihr.ac.uk/alert/excess-weight-increases-risks-of-severe-covid-19/.


Axes of alienation: applying an intersectional lens on the social contract during the pandemic response to protect sexual and reproductive rights and health.
While economic inequalities have been a key focus of attention through the COVID 19 pandemic, gendered relations of power at every level have undermined health rights of women, girls and gender diverse individuals. Sexual and reproductive health rights (SRHR) have always been sites of power contestations within families, societies, cultures, and politics; these struggles are exacerbated by economic, racial, religious, caste, citizenship status, and other social inequities, especially in times of crisis such as these. Policy responses to the COVID pandemic such as lockdown, quarantine, contact tracing and similar measures are premised on the existence of a social contract between the government and the people and among people, with the health sector playing a key role in preventive and curative care.We propose the use of an intersectional lens to explore the impact of the COVID-19 pandemic on the social contract, drawing on our field experiences from different continents particularly as related to SRHR. Along with documenting the ways in which the pandemic hinders access to services, we note that it is essential to interrogate state-society relations in the context of vulnerable and marginalized groups, in order to understand implications for SRHR. Intersectional analysis takes on greater importance now than in non-pandemic times as the state exercises more police or other powers and deploys myriad ways of 'othering'.We conclude that an intersectional analysis should not limit itself to the cumulative disadvantages and injustices posed by the pandemic for specific social groups, but also examine the historical inequalities, structural drivers, and damaged social contract that underlie state-society relationships. At the same time, the pandemic has questioned the status quo and in doing so it has provided opportunities for disruption; for re-imagining a social contract that reaches across sectors, and builds community resilience and solidarities while upholding human rights and gender justice. This must find place in future organizing and advocacy around SRHR.


What evidence is there for the homology of protein-protein interactions?
The notion that sequence homology implies functional similarity underlies much of computational biology. In the case of protein-protein interactions, an interaction can be inferred between two proteins on the basis that sequence-similar proteins have been observed to interact. The use of transferred interactions is common, but the legitimacy of such inferred interactions is not clear. Here we investigate transferred interactions and whether data incompleteness explains the lack of evidence found for them. Using definitions of homology associated with functional annotation transfer, we estimate that conservation rates of interactions are low even after taking interactome incompleteness into account. For example, at a blastp E-value threshold of 10(-70), we estimate the conservation rate to be about 11 % between S. cerevisiae and H. sapiens. Our method also produces estimates of interactome sizes (which are similar to those previously proposed). Using our estimates of interaction conservation we estimate the rate at which protein-protein interactions are lost across species. To our knowledge, this is the first such study based on large-scale data. Previous work has suggested that interactions transferred within species are more reliable than interactions transferred across species. By controlling for factors that are specific to within-species interaction prediction, we propose that the transfer of interactions within species might be less reliable than transfers between species. Protein-protein interactions appear to be very rarely conserved unless very high sequence similarity is observed. Consequently, inferred interactions should be used with care.


Analysis of intra-specific variation in the fatty acid profiles of Borrelia burgdorferi.
Analysis of the fatty acid methyl esters (FAMEs) of bacteria is a commonly used chemotaxonomic technique. Application of this methodology to spirochaetes associated with Lyme borreliosis revealed distinct clusters corresponding to three genetically distinguished groups: Borrelia burgdorferi sensu stricto, B. garinii, and the VS461 group. However, B. garinii formed a common group with B. hermsii, a relapsing fever spirochaete, and VS461 grouped with B. turicatae and B. parkeri, two other relapsing fever spirochaetes. The diversity in fatty acid profiles of Lyme disease spirochaetes has implications for the protean clinical manifestations of the disease.


Heterogeneity within the PF-EPN-B ependymoma subgroup.
Posterior fossa ependymoma comprise three distinct molecular variants, termed PF-EPN-A (PFA), PF-EPN-B (PFB), and PF-EPN-SE (subependymoma). Clinically, they are very disparate and PFB tumors are currently being considered for a trial of radiation avoidance. However, to move forward, unraveling the heterogeneity within PFB would be highly desirable. To discern the molecular heterogeneity within PFB, we performed an integrated analysis consisting of DNA methylation profiling, copy-number profiling, gene expression profiling, and clinical correlation across a cohort of 212 primary posterior fossa PFB tumors. Unsupervised spectral clustering and t-SNE analysis of genome-wide methylation data revealed five distinct subtypes of PFB tumors, termed PFB1-5, with distinct demographics, copy-number alterations, and gene expression profiles. All PFB subtypes were distinct from PFA and posterior fossa subependymomas. Of the five subtypes, PFB4 and PFB5 are more discrete, consisting of younger and older patients, respectively, with a strong female-gender enrichment in PFB5 (age: p = 0.011, gender: p = 0.04). Broad copy-number aberrations were common; however, many events such as chromosome 2 loss, 5 gain, and 17 loss were enriched in specific subtypes and 1q gain was enriched in PFB1. Late relapses were common across all five subtypes, but deaths were uncommon and present in only two subtypes (PFB1 and PFB3). Unlike the case in PFA ependymoma, 1q gain was not a robust marker of poor progression-free survival; however, chromosome 13q loss may represent a novel marker for risk stratification across the spectrum of PFB subtypes. Similar to PFA ependymoma, there exists a significant intertumoral heterogeneity within PFB, with distinct molecular subtypes identified. Even when accounting for this heterogeneity, extent of resection remains the strongest predictor of poor outcome. However, this biological heterogeneity must be accounted for in future preclinical modeling and personalized therapies.


Apixaban versus warfarin in patients with atrial fibrillation according to prior warfarin use: results from the Apixaban for Reduction in Stroke and Other Thromboembolic Events in Atrial Fibrillation trial.
Patients with atrial fibrillation who are vitamin K antagonist (VKA)-naive may have a higher risk of thrombosis and/or bleeding than VKA-experienced patients. Using data from ARISTOTLE, we assessed baseline characteristics and the treatment effect of apixaban versus warfarin in the VKA-naive and VKA-experienced cohorts. We compared rates of study drug discontinuation and time-in-therapeutic range. Overall, 7,800 (43%) were VKA naive, and 10,401 were VKA experienced. At baseline, both groups were similar with respect to age and congestive heart failure, hypertension, age, diabetes, stroke score (CHADS2). Fewer VKA-naive patients had a history of prior stroke (18% vs 21%) or prior bleeding (10% vs 22%) and were more often female (39% vs 33%). The effect of apixaban on the primary efficacy and safety outcomes was similar in VKA-naive (stroke/systemic embolism: hazard ratio [HR] 0.86, 95% CI 0.67-1.11 and major bleeding: HR 0.73, 95% CI 0.59-0.91) and VKA-experienced populations (stroke/systemic embolism: HR 0.73, 95% CI 0.57-0.95, P value for interaction = 0.39 and major bleeding: HR 0.66, 95% CI 0.55-0.80, P value for interaction = 0.50). Permanent study drug discontinuation was numerically less likely in patients receiving apixaban whether they were VKA naive (HR for discontinuation: 0.87, 95% CI 0.79-0.95) or VKA experienced (HR for discontinuation: 0.93, 95% CI 0.85-1.02). Among patients receiving warfarin, the mean/median times in therapeutic range were lower in the VKA-naive group (VKA-naive: 57.5/61.4, VKA-experienced: 66.0/69.1, P < .001). The treatment effects of apixaban (vs warfarin) were not modified by VKA naivety. The rates of stroke/systemic embolism and major bleeding were numerically lower among the patients assigned to apixaban, irrespective of prior VKA use.


Trait anxiety and impoverished prefrontal control of attention.
Many neurocognitive models of anxiety emphasize the importance of a hyper-responsive threat-detection system centered on the amygdala, with recent accounts incorporating a role for prefrontal mechanisms in regulating attention to threat. Here we investigated whether trait anxiety is associated with a much broader dysregulation of attentional control. Volunteers performed a response-conflict task under conditions that posed high or low demands on attention. High trait-anxious individuals showed reduced prefrontal activity and slower target identification in response to processing competition when the task did not fully occupy attentional resources. The relationship between trait anxiety and prefrontal recruitment remained after controlling for state anxiety. These findings indicate that trait anxiety is linked to impoverished recruitment of prefrontal attentional control mechanisms to inhibit distractor processing even when threat-related stimuli are absent. Notably, this deficit was observed when ongoing task-related demands on attention were low, potentially explaining the day-to-day difficulties in concentration that are associated with clinical anxiety.


Guidelines for application of meta-analysis in environmental epidemiology. ISLI Risk Science Institute.
The use of meta-analysis in environmental epidemiology can enhance the value of epidemiologic data in debates about environmental health risks. Meta-analysis may be particularly useful to formally examine sources of heterogeneity, to clarify the relationship between environmental exposures and health effects, and to generate information beyond that provided by individual studies or a narrative review. However, meta-analysis may not be useful when the relationship between exposure and disease is obvious, when there are only a few studies of the key health outcomes, or when there is substantial confounding or other biases which cannot be adjusted for in the analysis. Recent increases in the use of meta-analysis in environmental epidemiology have highlighted the need for guidelines for the application of the technique. Guidelines, in the form of desirable and undesirable attributes, are presented in this paper for various components of a meta-analysis including study identification and selection; data extraction and analysis; and interpretation, presentation, and communication of results. Also discussed are the appropriateness of the use of meta-analysis in environmental health studies and when meta-analysis should or should not be used.


Marine natural products.
Covering: 2010. Previous review: Nat. Prod. Rep., 2011, 28, 196. This review covers the literature published in 2010 for marine natural products, with 895 citations (590 for the period January to December 2010) referring to compounds isolated from marine microorganisms and phytoplankton, green, brown and red algae, sponges, cnidarians, bryozoans, molluscs, tunicates, echinoderms, mangroves and other intertidal plants and microorganisms. The emphasis is on new compounds (1003 for 2010), together with the relevant biological activities, source organisms and country of origin. Biosynthetic studies, first syntheses, and syntheses that lead to the revision of structures or stereochemistries, have been included.


Zn(2+) induces stimulation of the c-Jun N-terminal kinase signaling pathway through phosphoinositide 3-Kinase.
Zn(2+), one of the most abundant trace metal ions in mammalian cells, modulates the functions of many regulatory proteins associated with a variety of cellular activities. In the central nervous system, Zn(2+) is highly localized in the cerebral cortex and hippocampus. It has been proposed to play a role in normal brain function as well as in the pathophysiology of certain neurodegenerative disorders. We here report that Zn(2+) induced stimulation of the c-Jun N-terminal kinase (JNK) pathway in mouse primary cortical cells and in various cell lines. Exposure of cells to Zn(2+) resulted in the stimulation of JNK and its upstream kinases including stress-activated protein kinase kinase and mitogen-activated protein kinase kinase kinase. Zn(2+) also induced stimulation of phosphoinositide 3-kinase (PI3K) The Zn(2+)-induced JNK stimulation was blocked by LY294002, a PI3K inhibitor, or by a dominant-negative mutant of PI3Kgamma. Furthermore, overexpression of Rac1N17, a dominant negative mutant of Rac1, suppressed the Zn(2+)- and PI3Kgamma-induced JNK stimulation. The stimulatory effect of Zn(2+) on both PI3K and JNK was repressed by the free-radical scavenging agent N-acetylcysteine. Taken together, our data suggest that Zn(2+) induces stimulation of the JNK signaling pathway through PI3K-Rac1 signals and that the free-radical generation may be an important step in the Zn(2+) induction of the JNK stimulation.


Tumor profiling of co-regulated receptor tyrosine kinase and chemoresistant genes reveal different targeting options for lung and gastroesophageal cancers.
The expression of a number of genes can influence the response rates to chemotherapy while genes encoding receptor tyrosine kinases (RTKs) determine the response to most targeted cancer therapies currently used in clinics. In this study, we evaluated seven genes known to influence chemotherapeutic response (ERCC1, BRCA1, RRM1, TUBB3, STMN1, TYMS, and TOP2A) and five RTKs (EGFR, ERBB2, PDGFRB, VEGFR1 and VEGFR2) in non-small cell lung cancer (NSCLC) and esophagus cancer (EC) and the data are compared to gastric cancer (GC) data reported previously. We demonstrate significant differences in the expression profiles between different cancer types as well as heterogeneity among patients within the same cancer type. In all three cancer types, five chemoresistant genes (TOP2A, STMN1, TYMS, BRCA1 and RRM1) are coordinately up-regulated in almost all EC, approximately 90% of NSCLC and one third of GC patients. Most EC and nearly half of GC patients have increased expression of the three RTKs critical to angiogenesis (PDGFR, VEGFR1 and VEGFR2), while almost none of the NSCLC patients have elevated expression of angiogenic RTKs. A variable percentage of patients in the three cancer types show upregulation of the EGFR family RTKs, EGFR and/or ERBB2. It is of interest to note that approximately 10% of the NSCLC and GC patients are triple-negative for the chemosensitivity genes, angiogenic and EGFR RTK genes. The results suggest significant gene expression differences between different cancer types as well as heterogeneity within each cancer type and therefore different molecules should be targeted for future drug development and clinical trials.


Reactive oxygen species in oncogenic transformation.
Ever since ROS (reactive oxygen species) were shown to meet the criteria of true signalling molecules, such as regulated production and a specific biological function, many efforts have been made to understand the precise role of ROS. The function of ROS in pathological mechanisms is taking a more and more central role in various fields of biomedical research, including neurobiology, cardiology and cancer. An elevated oxidative status has been found in many types of cancer cells, and the introduction of chemical and enzymological antioxidants can inhibit tumour cell proliferation, pointing to a critical role of ROS in mediating loss of growth control. The present review describes ROS-regulated mechanisms that are associated with cancer and tumour invasiveness. The cellular processes that are linked to these ROS functions are mitogenic signalling and cell motility, while ROS have also been implicated in apoptosis and cellular senescence, two mechanisms regarded as being anti-tumorigenic. This "two-faced" character of free radicals will be discussed and placed in the context of the physiological conditions of the tumour cell, the different molecular backgrounds, and the specific ROS. More detailed understanding of the signalling pathways regulated by ROS in tumour cells will open up new prospects for chemo- or gene-therapeutic interventions.


The role of brain MRI in mitochondrial neurogastrointestinal encephalomyopathy.
Leukoencephalopathy is a hallmark of mitochondrial neurogastrointestinal encephalomyopathy (MNGIE) a devastating disorder characterized by ptosis, ophthalmoparesis, gastrointestinal dysfunction and polyneuropathy. To characterize MNGIE-associated leukoencephalopathy and to correlate it with clinical, biochemical and molecular data, four MNGIE patients with heterogeneous clinical phenotypes (enteropathic arthritis, exercise intolerance, CIDP-like phenotype and typical presentation) were studied by magnetic resonance imaging (MRI) and magnetic resonance spectroscopy (MRS). Diffusion weighted imaging (DWI) with apparent diffusion coefficient (ADC) maps were also obtained. In two patients we also investigated the role of brain MRI in monitoring the evolution of leukoencephalopathy by performing follow-up imaging studies at an interval of one and two years. The extension and distribution of leukoencephalopathy were not clearly linked with age, phenotype or disease severity, and did not seem to be related to TYMP mutations, enzyme activity or pyrimidine levels. In the studied patients MRS revealed reduced N-acetyl-aspartate and increased choline signals. Although DWI appeared normal in all patients but one, ADC maps always showed moderate increased diffusivity. Leukoencephalopathy worsened over a two-year period in two patients, regardless of the clinical course, indicating a lack of correlation between clinical phenotype, size and progression of white matter abnormalities during this period. Brain MRI should be considered a very useful tool to diagnose both classical and atypical MNGIE. Serial MRIs in untreated and treated MNGIE patients will help to establish whether the leukoencephalopathy is a reversible condition or not.


Lower incidence of Bronchiolitis obliterans in allogeneic hematopoietic stem cell transplantation with reduced-intensity conditioning compared with myeloablative conditioning.
Bronchiolitis obliterans (BO) is one of the most devastating complications after allogeneic stem cell transplantation (HSCT). However, its true pathogenesis is still to be elucidated. We conducted this study to find whether tissue damage due to high-dose chemo-radiotherapy is related to its pathogenesis. In all, 144 patients who received allogeneic HSCT between May 1999 and October 2001, and survived more than 80 days after transplant, were analyzed. Clinical course, pulmonary function tests, imaging studies including CT scan, and pathology results were reviewed. The overall incidence of BO was 9.7% (14/144). The cumulative incidence of BO at 2 years after transplant was 17% with myeloablative conditioning, and 2.3% with reduced intensity conditioning (P=0.024). Multivariate analysis showed that myeloablative conditioning was the only factor which affected the incidence of BO. Development of BO did not significantly affect the overall survival of patients. However, if they developed BO earlier than 200 days post transplant, the prognosis was significantly worse than if they developed it later than 200 days post transplant (P=0.003) or if they did not develop BO (P=0.002). Our results imply that tissue damage secondary to intensive chemo-radiotherapy may contribute to the pathogenesis of BO.


Suppression of thromboxane A2 but not of systemic prostacyclin by controlled-release aspirin.
The antithrombotic efficacy of aspirin is attributed to its inhibition of the enzyme prostaglandin G/H synthase, which is necessary for the formation of thromboxane A2 in platelets. Thromboxane A2 is a potent vasoconstrictor and platelet agonist. However, the formation of prostacyclin by vascular endothelium also requires prostaglandin G/H synthase, and prostacyclin exerts opposite effects on platelet function and vascular tone. We wanted to see whether controlled-release aspirin would affect the formation of thromboxane A2 but not prostacyclin by reducing the aspirin concentration that reaches the posthepatic circulation. A controlled-release formulation containing 75 mg of aspirin, designed to release 10 mg per hour, was developed to inhibit prostaglandin G/H synthase in platelets in the prehepatic circulation. The effects of the controlled-release preparation on plasma levels of aspirin and salicylate, serum levels of thromboxane B2, and urinary dinor metabolites of prostacyclin and thromboxane B2 (measured by gas chromatography-mass spectrometry) were compared with those of conventional immediate-release aspirin in normal volunteers. Prostacyclin release was stimulated by intravenous bradykinin. Steady-state inhibition of serum thromboxane B2 required two to four days and appeared slower with 75 mg of controlled-release than with the same amount of immediate-release aspirin. Maximal inhibition was achieved rapidly by adding a single loading dose of 162.5 mg of immediate-release aspirin to the regimen. Over a 28-day period, suppression of thromboxane A2 with this regimen was comparable to that with immediate-release aspirin taken either as 162.5 mg daily or as 325 mg on alternate days, despite the minimal systemic bioavailability of controlled-release aspirin. Bleeding time was prolonged to a similar degree with each of the three regimens. The five- to sixfold increase in the prostacyclin metabolite induced by bradykinin was depressed by pretreatment for four days with 75 mg of immediate-release aspirin, but not by 75 mg of controlled-release aspirin. Maximal inhibition of platelet thromboxane A2 production was sustained during long-term dosing with controlled-release aspirin, whereas basal prostacyclin biosynthesis fell only slightly and systemic synthesis of prostacyclin stimulated by bradykinin was preserved. Controlled-release aspirin may facilitate determination of the clinical importance of preserving prostacyclin during platelet inhibition in humans.


Are different stoichiometries feasible for complexes between lymphotoxin-alpha and tumor necrosis factor receptor 1?
Tumor necrosis factors, TNF and lymphotoxin-α (LT), are cytokines that bind to two receptors, TNFR1 and TNFR2 (TNF-receptor 1 and 2) to trigger their signaling cascades. The exact mechanism of ligand-induced receptor activation is still unclear. It is generally assumed that three receptors bind to the homotrimeric ligand to trigger a signaling event. Recent evidence, though, has raised doubts if the ligand:receptor stoichiometry should indeed be 3:3 for ligand-induced cellular response. We used molecular dynamics simulations, elastic network models, as well as MM/PBSA to analyze this question. Applying MM/PBSA methodology to different stoichiometric complexes of human LT-(TNFR1)n=1,2,3 the free energy of binding in these complexes has been estimated by single-trajectory and separate-trajectory methods. Simulation studies rationalized the favorable binding energy in the LT-(TNFR1)1 complex, as evaluated from single-trajectory analysis to be an outcome of the interaction of cysteine-rich domain 4 (CRD4) and the ligand. Elastic network models (ENMs) help to associate the difference in the global fluctuation of the receptors in these complexes. Functionally relevant transformation associated with these complexes reveal the difference in the dynamics of the receptor when free and in complex with LT. MM/PBSA predicts complexes with a ligand-receptor molar ratio of 3:1 and 3:2 to be energetically favorable. The high affinity associated with LT-(TNFR1)1 is due to the interaction between the CRD4 domain with LT. The global dynamics ascertained from ENMs have highlighted the differential dynamics of the receptor in different states.


Help-seeking behavior for erectile dysfunction: a clinic-based survey in China.
The behavior of Chinese patients seeking help for erectile dysfunction (ED) has not been described in detail. This was an observational study conducted using an outpatient clinic-based questionnaire survey of ED patients. From 2008 to 2009, physicians in 10 medical centers in China enrolled 2693 men (aged 25-70 years) diagnosed with ED. The diagnosis was based on the International Index of Erectile Function 5 (IIEF-5) Questionnaire. The men completed a survey that asked questions about demographics, marital status, education level and household income as well as help-seeking behavior and awareness of medical therapy. The mean age of the 2693 men was 43.4 ± 5.3 years; 73% were <50-years-old and 49% had a high household income. The mean time between noticing ED and taking the first treatment was 4.3 ± 2.1 months. Of the 2577 respondents, physicians (54%) and the internet (52%) were most frequently consulted sources for information about ED. Young ED patients preferred using the internet and older patients preferred consulting with physicians. Western medicine (19%) and traditional Chinese medicine (16%) were most frequently used for treatment. Young ED patients preferred to first search the internet for information, whereas older patients first asked physicians for help. Side effects of treatment were the greatest concern, especially for older patients. Physicians and the internet are frequently consulted for ED information and therapy. On the basis of these survey results, we believe that physicians in China should enhance health education about ED, especially via the internet.


Estimates of state-level chronic hepatitis C virus infection, stratified by race and sex, United States, 2010.
Hepatitis C virus (HCV) is the most common blood-borne viral infection in the United States. Previously, we used data from the National Health and Nutrition Examination Survey (NHANES) and mortality data from the National Vital Statistics System (NVSS) to estimate the prevalence of HCV antibodies (anti-HCV) and HCV RNA among all U.S. states. However, demographic differences in HCV burden at the state-level have not been systematically described. This analysis quantified the HCV burden stratified by sex and race (and associated disparities) for each U.S. state. Building on our previous method, we used three publicly available data sources to estimate HCV RNA prevalence among noninstitutionalized adults stratified by sex and race group. We used a small-area estimation approach that included direct standardization of NHANES demographic data with logistic regression modeling of HCV-related mortality data as an adjustment factor to estimate the state-level prevalence and total persons with chronic HCV infection for sex and race groups in all U.S. states. Nationally, males had an estimated HCV RNA prevalence of 1.56% (95% CI: 1.37-1.84%) and females had a prevalence of 0.75% (95% CI: 0.63-0.96%). Stratified by race, national estimated prevalence of HCV RNA was highest among non-Hispanic black (2.43, 95% CI: 2.10-2.90%), followed by non-Hispanic white (1.05, 95% CI: 0.90-1.27%) and Hispanic/other (0.74, 95% CI: 0.59-1.04%). Males in most jurisdictions (41/51) have an HCV RNA prevalence that is between 1.5 and 2.5 times higher than their female counterparts. HCV infection disparities by sex are mostly consistent across the country. However, race differences in HCV infection differ by state and tailored prevention and treatment efforts specific to the local HCV epidemic are needed to reduce race disparities.


Real-time kinetic binding studies at attomolar concentrations in solution phase using a single-stage opto-biosensing platform based upon infrared surface plasmons.
Here we present a new generic opto-bio-sensing platform combining immobilised aptamers on an infrared plasmonic sensing device generated by nano-structured thin film that demonstrates amongst the highest index spectral sensitivities of any optical fibre sensor yielding on average 3.4 × 104 nm/RIU in the aqueous index regime (with a figure of merit of 330) This offers a single stage, solution phase, atto-molar detection capability, whilst delivering real-time data for kinetic studies in water-based chemistry. The sensing platform is based upon optical fibre and has the potential to be multiplexed and used in remote sensing applications. As an example of the highly versatile capabilities of aptamer based detection using our platform, purified thrombin is detected down to 50 attomolar concentration using a volume of 1mm3 of solution without the use of any form of enhancement technique. Moreover, the device can detect nanomolar levels of thrombin in a flow cell, in the presence of 4.5% w/v albumin solution. These results are important, covering all concentrations in the human thrombin generation curve, including the problematic initial phase. Finally, selectivity is confirmed using complementary and non-complementary DNA sequences that yield performances similar to those obtained with thrombin.


Monitoring policy and actions on food environments: rationale and outline of the INFORMAS policy engagement and communication strategies.
The International Network for Food and Obesity/non-communicable diseases Research, Monitoring and Action Support (INFORMAS) proposes to collect performance indicators on food policies, actions and environments related to obesity and non-communicable diseases. This paper reviews existing communications strategies used for performance indicators and proposes the approach to be taken for INFORMAS. Twenty-seven scoring and rating tools were identified in various fields of public health including alcohol, tobacco, physical activity, infant feeding and food environments. These were compared based on the types of indicators used and how they were quantified, scoring methods, presentation and the communication and reporting strategies used. There are several implications of these analyses for INFORMAS: the ratings/benchmarking approach is very commonly used, presumably because it is an effective way to communicate progress and stimulate action, although this has not been formally evaluated; the tools used must be trustworthy, pragmatic and policy-relevant; multiple channels of communication will be needed; communications need to be tailored and targeted to decision-makers; data and methods should be freely accessible. The proposed communications strategy for INFORMAS has been built around these lessons to ensure that INFORMAS's outputs have the greatest chance of being used to improve food environments.


Self-adaptive hydrogels to mineralization.
Mineralized biological tissues, whose behavior can range from rigid to compliant, are an essential component of vertebrates and invertebrates. Little is known about how the behavior of mineralized yet compliant tissues can be tuned by the degree of mineralization. In this work, a synthesis route to tune the structure and mechanical response of agarose gels via ionic crosslinking and mineralization has been developed. A combination of experimental techniques demonstrates that crosslinking via cooperative hydrogen bonding in agarose gels is disturbed by calcium ions, but they promote ionic crosslinking that modifies the agarose network. Further, it is shown that the rearrangement of the hydrogel network helps to accommodate precipitated minerals into the network -in other words, the hydrogel self-adapts to the precipitated mineral- while maintaining the viscoelastic behavior of the hydrogel, despite the reinforcement caused by mineralization. This work not only provides a synthesis route to design biologically inspired soft composites, but also helps to understand the change of properties that biomineralization can cause to biological tissues, organisms and biofilms.