[Home care and place of death for elderly people living in the remote islands of Japan. An examination on the presence of inpatient facilities].
The purpose of this study was to clarify the actual status of end-of-life care for elderly people living in the remote islands of Japan, and whether the presence of inpatient facilities was related to the place of death, so as to obtain suggestions for constructing a system of end-of-life care. The survey targeted caregivers (85 people) who cared for elderly people (aged 65 and over), who had been legally certified for long-term care, and who had died between April 2009 and July 2011 in five islands of Japan. Islands were selected from a list of remote islands specified in the Remote Islands Development Act and related laws. Using a mixed method embedded design, we conducted semi-structured interviews using a questionnaire that assessed the place and cause of the elderly patient's death, age at death, gender, and whether the patient or family members had requested that the patient be allowed to die at home. The proportion of elderly people who died at home in the group living on remote islands with no inpatient facilities was 39.0% (16 of 41 people), compared with 18.2% (8 of 44 people) living on islands with inpatient facilities. The difference was significant (P=0.029). Among the 24 elderly people who died at home, 6 died of cancer. Terminally ill cancer patients were released to die at home under three conditions: the caregivers could provide sufficient care, the visiting physician was present, and pain control was provided. It was also possible for elderly cancer patients to receive end-of-life care in remote islands that did not have inpatient facilities. In addition, among the elderly people who died at home in the remote islands, home care had been recommended by medical staff. It is important for professionals coordinating home care to understand the characteristics of diseases, perform early assessment of caregiver situations, and collaborate with medical staff.


Effects of operational and environmental factors on evolution of resistance to pyriproxyfen in the sweetpotato whitefly (Hemiptera: Aleyrodidae).
Pyriproxyfen has been an important insecticide used as part of an integrated pest management (IPM) program for the sweetpotato whitefly, Bemisia tabaci (Gennadius) (B biotype), in Arizona cotton. We used a simulation model to examine the effects of pyriproxyfen concentration, insecticide action thresholds, crop diversity, planting date, and pyriproxyfen decay on evolution of resistance to pyriproxyfen in B. tabaci. In the model, pyriproxyfen use was restricted to cotton with a limit of one application per season. Other model parameters were based on data from laboratory and field experiments. Whitefly population densities and the number of insecticide applications per year increased as resistance evolved. Resistance evolved slowest with a low pyriproxyfen concentration. Lower action thresholds for pyriproxyfen and higher action thresholds for insecticides other than pyriproxyfen also slowed the evolution of resistance. However, lower action thresholds for pyriproxyfen resulted in more insecticide sprays per year with a high pyriproxyfen concentration. Resistance to pyriproxyfen evolved fastest in cotton-intensive regions and slowest in multicrop regions. In regions with noncotton crops, increasing immigration to cotton slowed resistance. Resistance evolved faster with earlier planting dates, although fewer insecticide sprays were needed compared with fields planted later in the year. Faster rates of pyriproxyfen decay slowed resistance. In some cases, strategies that delayed resistance were effective from an IPM perspective. However, some strategies that delayed resistance resulted in higher population densities. Results suggest that modification of operational and environmental factors, which can be controlled by growers, could prolong the efficacy of pyriproxyfen.


A wake-based correlate of swimming performance and foraging behavior in seven co-occurring jellyfish species.
It is generally accepted that animal-fluid interactions have shaped the evolution of animals that swim and fly. However, the functional ecological advantages associated with those adaptations are currently difficult to predict on the basis of measurements of the animal-fluid interactions. We report the identification of a robust, fluid dynamic correlate of distinct ecological functions in seven jellyfish species that represent a broad range of morphologies and foraging modes. Since the comparative study is based on properties of the vortex wake--specifically, a fluid dynamical concept called optimal vortex formation--and not on details of animal morphology or phylogeny, we propose that higher organisms can also be understood in terms of these fluid dynamic organizing principles. This enables a quantitative, physically based understanding of how alterations in the fluid dynamics of aquatic and aerial animals throughout their evolution can result in distinct ecological functions.


An Integrative Model of Physiological Traits Can be Used to Predict Obstructive Sleep Apnea and Response to Non Positive Airway Pressure Therapy.
Both anatomical and nonanatomical traits are important in obstructive sleep apnea (OSA) pathogenesis. We have previously described a model combining these traits, but have not determined its diagnostic accuracy to predict OSA. A valid model, and knowledge of the published effect sizes of trait manipulation, would also allow us to predict the number of patients with OSA who might be effectively treated without using positive airway pressure (PAP). Fifty-seven subjects with and without OSA underwent standard clinical and research sleep studies to measure OSA severity and the physiological traits important for OSA pathogenesis, respectively. The traits were incorporated into a physiological model to predict OSA. The model validity was determined by comparing the model prediction of OSA to the clinical diagnosis of OSA. The effect of various trait manipulations was then simulated to predict the proportion of patients treated by each intervention. The model had good sensitivity (80%) and specificity (100%) for predicting OSA. A single intervention on one trait would be predicted to treat OSA in approximately one quarter of all patients. Combination therapy with two interventions was predicted to treat OSA in ∼50% of patients. An integrative model of physiological traits can be used to predict population-wide and individual responses to non-PAP therapy. Many patients with OSA would be expected to be treated based on known trait manipulations, making a strong case for the importance of non-anatomical traits in OSA pathogenesis and the effectiveness of non-PAP therapies.


Avoiding and identifying errors in health technology assessment models: qualitative study and methodological review.
Health policy decisions must be relevant, evidence-based and transparent. Decision-analytic modelling supports this process but its role is reliant on its credibility. Errors in mathematical decision models or simulation exercises are unavoidable but little attention has been paid to processes in model development. Numerous error avoidance/identification strategies could be adopted but it is difficult to evaluate the merits of strategies for improving the credibility of models without first developing an understanding of error types and causes. The study aims to describe the current comprehension of errors in the HTA modelling community and generate a taxonomy of model errors. Four primary objectives are to: (1) describe the current understanding of errors in HTA modelling; (2) understand current processes applied by the technology assessment community for avoiding errors in development, debugging and critically appraising models for errors; (3) use HTA modellers' perceptions of model errors with the wider non-HTA literature to develop a taxonomy of model errors; and (4) explore potential methods and procedures to reduce the occurrence of errors in models. It also describes the model development process as perceived by practitioners working within the HTA community. A methodological review was undertaken using an iterative search methodology. Exploratory searches informed the scope of interviews; later searches focused on issues arising from the interviews. Searches were undertaken in February 2008 and January 2009. In-depth qualitative interviews were performed with 12 HTA modellers from academic and commercial modelling sectors. All qualitative data were analysed using the Framework approach. Descriptive and explanatory accounts were used to interrogate the data within and across themes and subthemes: organisation, roles and communication; the model development process; definition of error; types of model error; strategies for avoiding errors; strategies for identifying errors; and barriers and facilitators. There was no common language in the discussion of modelling errors and there was inconsistency in the perceived boundaries of what constitutes an error. Asked about the definition of model error, there was a tendency for interviewees to exclude matters of judgement from being errors and focus on 'slips' and 'lapses', but discussion of slips and lapses comprised less than 20% of the discussion on types of errors. Interviewees devoted 70% of the discussion to softer elements of the process of defining the decision question and conceptual modelling, mostly the realms of judgement, skills, experience and training. The original focus concerned model errors, but it may be more useful to refer to modelling risks. Several interviewees discussed concepts of validation and verification, with notable consistency in interpretation: verification meaning the process of ensuring that the computer model correctly implemented the intended model, whereas validation means the process of ensuring that a model is fit for purpose. Methodological literature on verification and validation of models makes reference to the Hermeneutic philosophical position, highlighting that the concept of model validation should not be externalized from the decision-makers and the decision-making process. Interviewees demonstrated examples of all major error types identified in the literature: errors in the description of the decision problem, in model structure, in use of evidence, in implementation of the model, in operation of the model, and in presentation and understanding of results. The HTA error classifications were compared against existing classifications of model errors in the literature. A range of techniques and processes are currently used to avoid errors in HTA models: engaging with clinical experts, clients and decision-makers to ensure mutual understanding, producing written documentation of the proposed model, explicit conceptual modelling, stepping through skeleton models with experts, ensuring transparency in reporting, adopting standard housekeeping techniques, and ensuring that those parties involved in the model development process have sufficient and relevant training. Clarity and mutual understanding were identified as key issues. However, their current implementation is not framed within an overall strategy for structuring complex problems. Some of the questioning may have biased interviewees responses but as all interviewees were represented in the analysis no rebalancing of the report was deemed necessary. A potential weakness of the literature review was its focus on spreadsheet and program development rather than specifically on model development. It should also be noted that the identified literature concerning programming errors was very narrow despite broad searches being undertaken. Published definitions of overall model validity comprising conceptual model validation, verification of the computer model, and operational validity of the use of the model in addressing the real-world problem are consistent with the views expressed by the HTA community and are therefore recommended as the basis for further discussions of model credibility. Such discussions should focus on risks, including errors of implementation, errors in matters of judgement and violations. Discussions of modelling risks should reflect the potentially complex network of cognitive breakdowns that lead to errors in models and existing research on the cognitive basis of human error should be included in an examination of modelling errors. There is a need to develop a better understanding of the skills requirements for the development, operation and use of HTA models. Interaction between modeller and client in developing mutual understanding of a model establishes that model's significance and its warranty. This highlights that model credibility is the central concern of decision-makers using models so it is crucial that the concept of model validation should not be externalized from the decision-makers and the decision-making process. Recommendations for future research would be studies of verification and validation; the model development process; and identification of modifications to the modelling process with the aim of preventing the occurrence of errors and improving the identification of errors in models.


Sculpturing wafer-scale nanofluidic devices for DNA single molecule analysis.
We present micro- and nanofluidic devices with 3D structures and nanochannels with multiple depths for the analysis of single molecules of DNA. Interfacing the nanochannels with graded and 3D inlets allows the improvement of the flow and controls not only the translocation speed of the DNA but also its conformation inside the nanochannels. The complex, multilevel, multiscale fluidic circuits are patterned in a simple, two-minute imprinting step. The stamp, the key of the technology, is directly milled by focused ion beam, which allows patterning nanochannels with different cross sections and depths, together with 3D transient inlets, all at once. Having such a variety of structures integrated in the same sample allows studying, optimizing and directly comparing their effect on the DNA flow. Here, DNA translocation is studied in long (160 µm) and short (5-40 µm) nanochannels. We study the homogeneity of the stretched molecules in long, meander nanochannels made with this technology. In addition, we analyze the effect of the different types of inlet structures interfacing short nanochannels. We observe pre-stretching and an optimal flow, and no hairpin formation, when the inlets have gradually decreasing widths and depths. In contrast, when the nanochannels are faced with an abrupt transition, we observe clogging and hairpin formation. In addition, 3D inlets strongly decrease the DNA molecules' speed before they enter the nanochannels, and help capturing more DNA molecules. The robustness and versatility of this technology and DNA testing results evidence the potential of imprinted devices in biomedical applications as low cost, disposable lab-on-a-chip devices.


A treatment-based classification approach to low back syndrome: identifying and staging patients for conservative treatment.
We present a treatment-based classification approach to the conservative management of low back syndrome. The approach has three levels of classification based on historical information, behavior of symptoms, and clinical signs. We first distinguish patients whose conservative care can be managed predominantly and independently by physical therapists versus patients who require consultation with other services (eg, psychology) or who require referral because of possible serious nonmusculoskeletal pathology. Once patients who can be managed by physical therapists are identified, the next level of classification is to stage their condition with regard to severity. We propose three stages: stage I for patients in the acute phase where the therapeutic goal is symptom relief, stage II for patients in a subacute phase where symptom relief and quick return to normal function are encouraged, and stage III for selected patients who must return to activities requiring high physical demands and who demonstrate a lack of physical conditioning necessary to perform the desired activities safely. The remainder of the article focuses on a third level of classification for stage I only in which patients are classified into distinct categories that are treatment-based and that specifically guide conservative management. The entire approach is diagnosis based, with specific algorithms and decision rules as well as examples presented.


Ecosystem impacts of geoengineering: a review for developing a science plan.
Geoengineering methods are intended to reduce climate change, which is already having demonstrable effects on ecosystem structure and functioning in some regions. Two types of geoengineering activities that have been proposed are: carbon dioxide (CO(2)) removal (CDR), which removes CO(2) from the atmosphere, and solar radiation management (SRM, or sunlight reflection methods), which reflects a small percentage of sunlight back into space to offset warming from greenhouse gases (GHGs). Current research suggests that SRM or CDR might diminish the impacts of climate change on ecosystems by reducing changes in temperature and precipitation. However, sudden cessation of SRM would exacerbate the climate effects on ecosystems, and some CDR might interfere with oceanic and terrestrial ecosystem processes. The many risks and uncertainties associated with these new kinds of purposeful perturbations to the Earth system are not well understood and require cautious and comprehensive research.


The Medical School of the Catholic University of Croatia: Principles, Goals, Standards and Organization.
The aim of the study was to present the concept on which the School of Medicine at the Catholic University of Croatia (CUC) will be established. The new School will alleviate the shortage of physicians in Croatia and introduce an innovative form of medical education focused on principles of patient-centered care and social accountability. At the same time, the students will acquire all relevant competencies and levels of knowledge, skills and attitudes that are required by current evidence in medical education, European standards and guidelines for quality assurance at higher education institutions. The four pillars of the CUC Medical School are: 1) distributed medical education that involves health institutions outside major medical centers, 2) the concept of transformative learning, 3) teaching and practicing evidence-based medicine, and 4) implementation of quality management principles supported by information technology solutions for effective management of learning, research and practice. The overall aim of the CUC School of Medicine is to educate and train physicians capable of using best available medical evidence to deliver economically sustainable healthcare that can improve equity and health outcomes in the communities they serve, particularly those that are currently underserved. The proposed programme is introducing an original system of modern medical education that insists on developing humanistic aspects of medicine, patient-centred care and social accountability, while maintaining all competencies and knowledge levels that a physician should have according to the current understanding of medical education.


Clinical effectiveness of first and repeat influenza vaccination in adult and elderly diabetic patients.
Influenza vaccine uptake remains low among the high-risk group of patients with diabetes, partly because of conflicting evidence regarding its potential benefits. We assessed the clinical effectiveness of influenza vaccination in adults with diabetes and specifically examined potential modification of effect by age and prior influenza vaccine uptake. The study was part of the Prevention of Influenza, Surveillance and Management (PRISMA) study, a nested case-control study conducted during the 1999-2000 influenza A epidemic, among 75,235 patients from primary care of any age recommended for vaccination. Among 9,238 adult patients with diabetes, 131 cases arose who were either hospitalized for diabetes dysregulation, acute respiratory disease, or cardiovascular disease and 61 cases who died, and we compared them with 1,561 control subjects. We evaluated the effect of (prior) influenza vaccination by means of logistic regression analysis controlling for age, sex, health insurance coverage, prior health care use, medication use, and comorbid conditions. Vaccination was associated with a 56% reduction in any complication (95% CI 36-70%), a 54% reduction in hospitalizations (26-71%), and 58% reduction in deaths (13-80%). Among study subjects aged 18-64 years, we observed somewhat higher reductions in the occurrence of any complication than among those aged >65 years (72 vs. 39%). In first-time vaccinated subjects, the primary end point was reduced by 47% (0.2-72%), and in those who received vaccination in the year before, the reduction was 58% (4-81%). Adults with type 2 diabetes, like other individuals from recognized risk groups, benefit considerably from influenza vaccination, and no difference in vaccine effectiveness was observed between first-time and repeat vaccination.


Incidence and clinical consequence of the purple glove syndrome in patients receiving intravenous phenytoin.
To determine the incidence, risk factors, and long-term sequelae of the purple glove syndrome (PGS) in hospital patients receiving IV phenytoin. PGS is a poorly understood, potentially serious local complication of IV phenytoin administration characterized by progressive distal limb edema, discoloration, and pain. The pharmacologic records of the Mayo Foundation hospitals were reviewed to identify 179 consecutive patients who had IV phenytoin ordered during a 3-month period. Their hospital records were then reviewed to confirm IV phenytoin treatment, the frequency of PGS (defined as the progressive development of edema, discoloration, and pain in the limb after administration of IV phenytoin), and the outcome of PGS. A total of 152 patients received IV phenytoin, and nine (5.9%) developed PGS. PGS patients received a greater median initial dose of phenytoin, total 24-hour dose, and total number of doses (all p < 0.05). In addition, the median age of the PGS patients was older, their infusion was more often given for acute seizures, it was less likely to be administered in the operating room, and the length of their hospital stay was longer (all p < 0.05). One patient required surgical therapy, and all other patients resolved within 3 weeks with conservative management. PGS is not rare and elderly patients and individuals receiving large, multiple doses are particularly at risk. This iatrogenic complication may be preventable by substituting fosphenytoin for IV phenytoin.


Assessment of respondent driven sampling for recruiting female sex workers in two Vietnamese cities: reaching the unseen sex worker.
Respondent driven sampling (RDS) is a relatively new method to sample hard-to-reach populations. Until this study, female sex workers (FSWs) in Vietnam were sampled using a variety of methods, including time location sampling (TLS), which may not access the more hidden types of FSWs. This paper presents an analysis from an HIV biological and behavioral surveillance survey to assess the feasibility and effectiveness of RDS to sample FSWs, to determine if RDS can reach otherwise inaccessible FSWs in Vietnam and to compare RDS findings of HIV risk factors with a theoretical TLS. Through face-to-face interviews with FSWs in Ho Chi Minh City (HCMC) and Hai Phong (HP), data were collected about the venues where they most often solicit their clients. These data were used to create three variables to assess whether FSWs solicit their clients in locations that are visible, semi-visible and non-visible. For this analysis, the visible group simulates a sample captured using TLS. Survey results in HIV prevalence and related risk factors and service utilization, adjusted for sampling methodology, were compared across each of the three FSW visibility groups to assess potential bias in TLS relative to RDS. The number of self-reported visible FSWs (HCMC: n=311; HP: n=162) was much larger than those of the semi-visible (HCMC: n=65; HP: n=43) and non-visible (HCMC: n=37; HP: n=10) FSWs in HCMC and HP. Non-visible FSWs in both cities were just as likely as visible and semi-visible FSWs to be HIV positive (HCMC: visible 14.5%, semi-visible 13.8%, non-visible 13.5%, p value = 0.982; HP: visible 35.2%, semi-visible 30.2%, non-visible 30.0%, p value = 0.801), to practice behaviors that put them at risk for contracting and transmitting HIV (injecting drug use-HCMC: visible 13.8%, semi-visible 12.3%, non-visible 5.4%, p value = 0.347; HP: visible 38.9%, semi-visible 23.3%, non-visible 30.0%, p value = 0.378, to have no condom use in the past month -HCMC only: visible 52.7%, semi-visible 63.1%, non-visible 48.6%, p value = 0.249) and to have symptoms of a sexually transmitted infection (STI) in the past year (HCMC: visible 16.1%, semi-visible 12.3%, non-visible 16.2%, p value = 0.742; HP: visible 13.6%, semi-visible 18.6%, non-visible 20.0%, p value = 0.640). There was a difference found among the visible, semi-visible and non-visible groups in HP for no past month condom use (visible 53.1%, semi-visible 79.1%, non-visible 60.0%, p value = 0.009). This study found that RDS was successful at recruiting hidden types of FSWs in Vietnam. Past reports of FSWs in Vietnam have assessed the more visible FSWs as being the most vulnerable and at risk for HIV. Although the number of visible FSWs is much higher than those of the semi and non-visible groups, this study found that the non-visible FSWs are very vulnerable to HIV infection. If prevention programs are targeting and responding to those who are most likely to be assessed (e.g., more visible types of FSWs) then this analysis indicates that a significant proportion of the FSW population at risk for HIV may not be receiving optimal HIV information and services.


Chronic fibrous sheath mistaken for retained pacemaker product.
A 71-year-old man underwent implantation of a single-chamber system in 1988 for sinoatrial disease, which was then upgraded to dual-chamber 7 years later following recurrent syncope. He presented with pacemaker erosion but without clinical or laboratory evidence of infective endocarditis. The pacemaker system was uneventfully extracted 5 days later via a transfemoral approach using a needle-eye snare. A post-procedure trans-thoracic echocardiogram was performed, which demonstrated an echogenic structure in the right atrium-this was initially felt to be a retained fragment of pacing lead. A short-axis view of the tricuspid valve with a bright linear echo crossing is shown in Figure 1. However, a post-procedural chest X-ray confirmed the absence of any retained intra-cardiac lead. The reverberant cast-like structure noted is a heavily calcified fibrous sheath as the pacing leads were confirmed to be intact at the time of removal.


Characteristics of epilepsy patients and caregivers who either have or have not heard of SUDEP.
Describe the characteristics of persons with epilepsy (PWEs) and caregivers that have or have not heard of sudden unexpected death in epilepsy (SUDEP) prior to completing a survey through the Internet or in the clinical setting. An online survey for adult PWEs and caregivers was solicited by e-mail and newsletter to Epilepsy Therapy Project members. A similar survey was implemented in a clinic setting of a community hospital. The survey asked about seizure characteristics, epilepsy management, fear of death, and familiarity with the term SUDEP. Respondents that never heard of SUDEP read a definition and responded to questions about their initial reactions. Surveys from 1,392 PWEs and 611 caregivers recruited through an epilepsy Website and a clinic demonstrated that Internet respondents were much more likely to have heard about SUDEP than the clinic population (71.1% vs. 38.8%; p < 0.001), and caregivers of PWEs were more likely to have heard about SUDEP than PWEs (76.2% vs. 65.2%; p < 0.001). Prior awareness was related to an increased level of education, more severe and longer duration of epilepsy, and having an epileptologist as the primary care provider. Although most PWEs and caregivers reported feelings of fear, anxiety, and sadness after first hearing of SUDEP, they wanted to discuss it with their doctor. Persons with epilepsy, and especially their caregivers, often worry that the PWEs may die of epilepsy or seizures. This worry escalated with knowledge of SUDEP and increased epilepsy severity. Approximately half of PWEs and caregivers believed that knowledge about SUDEP would influence their epilepsy management. Our results may help epilepsy care providers determine when to facilitate a discussion about epilepsy-related mortality and SUDEP among patients and caregivers, and to educate those at high risk about the importance of seizure control as well as reduce fears about death in patients with well-controlled and nonconvulsive epilepsies.


Physiology of dark fermentative growth of Rhodopseudomonas capsulata.
The photosynthetic bacterium Rhodopseudomonas capsulata can grow under anaerobic conditions with light as the energy source or, alternatively, in darkness with D-fructose or certain other sugars as the sole source of carbon and energy. Growth in the latter mode requires an "accessory oxidant" such as trimethylamine-N-oxide, and the resulting cells contain the photosynthetic pigments characteristic of R. capsulata (associated with intracytoplasmic membranes) and substantial deposits of poly-beta-hydroxybutyrate. In dark anaerobic batch cultures in fructose plus trimethylamine-N-oxide medium, trimethylamine formation parallels growth, and typical fermentation products accumulate, namely, CO2 and formic, acetic, and lactic acids. These products are also found in dark anaerobic continuous cultures of R. capsulata; acetic acid and CO2 predominate when fructose is limiting, whereas formic and lactic acids are observed at elevated concentrations when trimethylamine-N-oxide is the limiting nutrient. Evidence is presented to support the conclusions that ATP generation during anaerobic dark growth of R. capsulata on fructose plus trimethylamine-N-oxide occurs by substrate level phosphorylations associated with classical glycolysis and pyruvate dissimilation, and that the required accessory oxidant functions as an electron sink to permit the management of fermentative redox balance, rather than as a terminal electron acceptor necessary for electron transport-driven phosphorylation.


Effects of a Stroke Primary Prevention Program on Risk Factors for At-Home Elderly.
BACKGROUND To prevent stroke from occurring, stroke risk factors in at-risk subjects should be controlled and the diseases causing stroke should be managed. This study evaluated a nursing intervention to prevent stroke in at-risk elderly living at home. The program consisted of stroke and nutrition education as well as exercise guidance. MATERIAL AND METHODS This study targeted 93 elderly people living at home residing in E province with 1 or more stroke risk factors, including high blood pressure, diabetes, hyperlipidemia, obesity, smoking, or drinking alcohol. The 12-week program included a stroke education class once a week, a nutrition management class once a week, and exercise guidance 3 times a week. Each session lasted 50-70 min. Each disease education and nutrition management session lasted for 20 min and each exercise session lasted for 30-50 min. RESULTS The experimental group's body mass index (BMI) (t=8.27, p<.001), systolic blood pressure (t=2.39, p=.021), fasting blood sugar (t=0.39, p=.700), total cholesterol (t=4.18, p<.001), triglyceride levels (t=2.50, p=.016), and depression scores (t=5.48, p<.001) were significantly reduced and high-density phospholipid protein levels increased significantly by the end of the program (t=-2.94, p=.005). CONCLUSIONS Based on the results of this study, participating in a stroke prevention program enabled at-risk elderly participants who lived at home in rural areas to perform health-promoting behaviors. This program may reduce the incidence of stroke by reducing risk factors and managing stroke precursor diseases.


Exploring the Point-of-Sale Among Vape Shops Across the United States: Audits Integrating a Mystery Shopper Approach.
Vape shops represent prominent, unique retailers, subject to Food and Drug Administration (FDA) regulation in the United States. This study assessed compliance of US vape shop retail marketing strategies with new regulations (eg, required age verification, prohibited free samples) and pre-implementation conditions for other regulations (eg, health warning labels on all nicotine products, required disclosures of e-liquid contents). 95.0% of shops displayed minimum-age signage; however, mystery shoppers were asked for age verification at 35.6% upon entry and at 23.4% upon purchase. Although 85.5% of shops had some evidence of implementing FDA health warnings, 29.1% had signage indicating prohibited health claims, 16.3% offered free e-liquid samples, 27.4% had signage with cartoon imagery, and 33.3% were within two blocks of schools. All shops sold open-system devices, 64.8% sold closed-system devices, 68.2% sold their own brand of e-liquids, 42.5% sold e-liquids containing cannabidiol, 83.2% offered price promotions of some kind, and 89.9% had signage for product and price promotions. Results indicated that most shops complied with some implementation of FDA health warnings and with free sampling bans and minimum-age signage. Other findings indicated concerns related to underage access, health claims, promotional strategies, and cannabidiol product offerings, which call for further FDA and state regulatory/enforcement efforts.


[Current peritoneal dialysis compared with haemodialysis: medium-term survival analysis of incident dialysis patients in the Canary Islands in recent years].
Important differences in patient survival exist between peritoneal dialysis (PD) and haemodialysis (HD). Several different studies have shown that PD yields a better survival rate than HD in the first and second years of treatment, especially in younger patients and non-diabetic patients with low comorbidity, whereas HD produces better results in diabetic patients, elderly patients, and in patients with greater comorbidity. In recent years, interesting changes have occurred in PD units in the Canary Islands, such as the introduction of peritoneal dialysis solutions with bicarbonate dialysate and low content of glucose degradation products, extended use of automated dialysis, and continuity of physicians and nurses in PD units, in addition to enhancing visits for advanced chronic kidney disease (ACKD). This situation led us to perform our study with the primary objective of comparing medium-term survival among incident dialysis patients on HD versus PD in recent years in the Canary Islands, and as a secondary objective, to compare survival between these two types of dialysis by subgroups as defined by age, sex and diabetes. This was a retrospective cohort study comparing survival between HD and PD patients starting dialysis in the Canary Islands between 01/01/2006 and 31/12/2009, with adjustment based on the propensity score analysis. We analysed data from the RERCAN database, which collects data on demographic variables, changes in type of dialysis, province and hospital of the patient, and mortality and its causes. We calculated Kaplan-Meier estimates of survival based on the overall population and stratified by age, sex and diabetes. We applied a Cox proportional hazards model for survival to estimate the relative mortality risk of PD compared with HD, using as independent variables: age, sex, quartiles of propensity score, the province of the patient, and diabetes. Finally, we applied a Cox model with time-dependent effects, using as a fixed risk factor the initial type of dialysis in order to assess the effect of PD versus HD on short and medium-term survival. The cohort included 1469 patients (173 PD and 1296 HD), with a mean age of 62.5 years, 65% male. Mean follow-up was 16.2±12.4 months. Factors associated with greater probability of choosing PD were younger age and living in the province of Las Palmas. The cumulative mortality in the intention to treat (ITT) analysis was 27.1% in the HD group and 8.7% in the PD group, P<.0001. The cumulative probability of survival by ITT using PD vs HD was 96.6% versus 89% at 6 months (P<.001), 96% versus 80% at 12 months (P<.001), 90% versus 65% at 24 months (P<.001), 82% versus 58% at 36 months (P<.001) and 73% versus 45% at 46 months (P<.001). In the subgroup analysis, survival was also higher in PD patients compared to HD patients both over and under 65 years old, in both diabetic and non-diabetic patients, and in both genders. The same analysis from the 90th day onward produced similar results. In the ITT analysis, the Cox-adjusted mortality risk for PD was 61% lower than for HD (RR: 0.398, 95% CI 0.237-0.669, P=.001), adjusted for age, diabetes, sex, patient's province and propensity score. Broken down by years of survival on the technique used, the relative risk of death for PD compared with HD in the first year was also significantly lower (RR 0.509, 95% CI: 0.259-0.999, P=.049). From year 2 onwards, only age was a risk factor for mortality (RR: 2.785, 95% CI: 1.525-5.086, P=.001) and no differences were shown between the two dialysis techniques. In the Canary Islands, PD has demonstrated survival advantages over HD in the short and medium term. It is remarkable that this benefit was found in young and old patients, men and women, and diabetic and non-diabetic patients, and that this advantage was maintained even after years of being on dialysis.


Myocardial interstitial fibrosis in the era of precision medicine. Biomarker-based phenotyping for a personalized treatment.
Myocardial interstitial fibrosis is a constant pathological finding in structural heart diseases of various etiologies that evolve with heart failure. Although fibrosis facilitates heart failure progression, until now no therapeutic strategy has been developed that ensures its reversal. A possible explanation for this may lie in the vision of myocardial interstitial fibrosis as a homogeneous lesion instead of a heterogeneous lesion in which different phenotypes can be distinguished using appropriate criteria. In addition, the notion that the heterogeneity of myocardial interstitial fibrosis may be cardiac disease-specific must be also considered when approaching this entity. Therefore, we propose that myocardial interstitial fibrosis represents a true challenge for transitioning from usual care to biomarker-based personalized treatment and precision medicine in heart failure. As a proof-of-concept, in this review we discuss the phenotyping of myocardial interstitial fibrosis in patients with heart failure attributable to hypertensive heart disease based on its histomolecular alterations and provide evidence of the prognostic relevance of the resulting stratification. Furthermore, we discuss the available information on some circulating biomarkers and certain pharmacological agents useful for noninvasive identification and personalized treatment, respectively, of those phenotypes.


Allopurinol for chronic gout.
Allopurinol, a xanthine oxidase inhibitor, is considered one of the most effective urate-lowering drugs and is frequently used in the treatment of chronic gout. To assess the efficacy and safety of allopurinol compared with placebo and other urate-lowering therapies for treating chronic gout. We searched the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE and EMBASE on 14 January 2014. We also handsearched the 2011 to 2012 American College of Rheumatology (ACR) and European League against Rheumatism (EULAR) abstracts, trial registers and regulatory agency drug safety databases. All randomised controlled trials (RCTs) or quasi-randomised controlled clinical trials (CCTs) that compared allopurinol with a placebo or an active therapy in adults with chronic gout. We extracted and analysed data using standard methods for Cochrane reviews. The major outcomes of interest were frequency of acute gout attacks, serum urate normalisation, pain, function, tophus regression, study participant withdrawal due to adverse events (AE) and serious adverse events (SAE). We assessed the quality of the body of evidence for these outcomes using the GRADE approach. We included 11 trials (4531 participants) that compared allopurinol (various doses) with placebo (two trials); febuxostat (four trials); benzbromarone (two trials); colchicine (one trial); probenecid (one trial); continuous versus intermittent allopurinol (one trial) and different doses of allopurinol (one trial). Only one trial was at low risk of bias in all domains. We deemed allopurinol versus placebo the main comparison, and allopurinol versus febuxostat and versus benzbromarone as the most clinically relevant active comparisons and restricted reporting to these comparisons here.Moderate-quality evidence from one trial (57 participants) indicated allopurinol 300 mg daily probably does not reduce the rate of gout attacks (2/26 with allopurinol versus 3/25 with placebo; risk ratio (RR) 0.64, 95% confidence interval (CI) 0.12 to 3.52) but increases the proportion of participants achieving a target serum urate over 30 days (25/26 with allopurinol versus 0/25 with placebo, RR 49.11, 95% CI 3.15 to 765.58; number needed to treat for an additional beneficial outcome (NNTB) 1). In two studies (453 participants), there was no significant increase in withdrawals due to AE (6% with allopurinol versus 4% with placebo, RR 1.36, 95% CI 0.61 to 3.08) or SAE (2% with allopurinol versus 1% with placebo, RR 1.93, 95% CI 0.48 to 7.80). One trial reported no difference in pain reduction or tophus regression, but did not report outcome data or measures of variance sufficiently and we could not calculate the differences between groups. Neither trial reported function.Low-quality evidence from three trials (1136 participants) indicated there may be no difference in the incidence of acute gout attacks with allopurinol up to 300 mg daily versus febuxostat 80 mg daily over eight to 24 weeks (21% with allopurinol versus 23% with febuxostat, RR 0.89, 95% CI 0.71 to 1.1); however more participants may achieve target serum urate level (four trials; 2618 participants) with febuxostat 80 mg daily versus allopurinol 300 mg daily (38% with allopurinol versus 70% with febuxostat, RR 0.56, 95% CI 0.48 to 0.65, NNTB with febuxostat 4). Two trials reported no difference in tophus regression between allopurinol and febuxostat over a 28- to 52-week period; but as the trialists did not provide variance, we could not calculate the mean difference between groups. The trials did not report pain reduction or function. Moderate-quality evidence from pooled data from three trials (2555 participants) comparing allopurinol up to 300 mg daily versus febuxostat 80 mg daily indicated no difference in the number of withdrawals due to AE (7% with allopurinol versus 8% with febuxostat, RR 0.89, 95% CI 0.62 to 1.26) or SAE (4% with allopurinol versus 4% with febuxostat, RR 1.13, 95% CI 0.71 to 1.82) over a 24- to 52-week period.Low-quality evidence from one trial (65 participants) indicated there may be no difference in the incidence of acute gout attacks with allopurinol up to 600 mg daily compared with benzbromarone up to 200 mg daily over a four-month period (0/30 with allopurinol versus 1/25 with benzbromarone, RR 0.28, 95% CI 0.01 to 6.58). Based on the pooled results of two trials (102 participants), there was moderate-quality evidence of no probable difference in the proportion of participants achieving a target serum urate level with allopurinol versus benzbromarone (58% with allopurinol versus 74% with benzbromarone, RR 0.79, 95% CI 0.56 to 1.11). Low-quality evidence from two studies indicated there may be no difference in the number of participants who withdrew due to AE with allopurinol versus benzbromarone over a four- to nine-month period (6% with allopurinol versus 7% with benzbromarone, pooled RR 0.80, 95% CI 0.18 to 3.58). There were no SAEs. They did not report tophi regression, pain and function.All other comparisons were supported by small, single studies only, limiting conclusions. Our review found low- to moderate-quality evidence indicating similar effects on withdrawals due to AEs and SAEs and incidence of acute gout attacks when allopurinol (100 to 600 mg daily) was compared with placebo, benzbromarone (100 to 200 mg daily) or febuxostat (80 mg daily). There was moderate-quality evidence of little or no difference in the proportion of participants achieving target serum urate when allopurinol was compared with benzbromarone. However, allopurinol seemed more successful than placebo and may be less successful than febuxostat (80 mg daily) in achieving a target serum urate level (6 mg/dL or less; 0.36 mmol/L or less) based on moderate- to low-quality evidence. Single studies reported no difference in pain reduction when allopurinol (300 mg daily) was compared with placebo over 10 days, and no difference in tophus regression when allopurinol (200 to 300 mg daily) was compared with febuxostat (80 mg daily). None of the trials reported on function, health-related quality of life or participant global assessment of treatment success, where further research would be useful.


Practicing governance towards equity in health systems: LMIC perspectives and experience.
The unifying theme of the papers in this series is a concern for understanding the everyday practice of governance in low- and middle-income country (LMIC) health systems. Rather than seeing governance as a normative health system goal addressed through the architecture and design of accountability and regulatory frameworks, these papers provide insights into the real-world decision-making of health policy and system actors. Their multiple, routine decisions translate policy intentions into practice - and are filtered through relationships, underpinned by values and norms, influenced by organizational structures and resources, and embedded in historical and socio-political contexts. These decisions are also political acts - in that they influence who accesses benefits and whose voices are heard in decision-making, reinforcing or challenging existing institutional exclusion and power inequalities. In other words, the everyday practice of governance has direct impacts on health system equity.The papers in the series address governance through diverse health policy and system issues, consider actors located at multiple levels of the system and draw on multi-disciplinary perspectives. They present detailed examination of experiences in a range of African and Indian settings, led by authors who live and work in these settings. The overall purpose of the papers in this series is thus to provide an empirical and embedded research perspective on governance and equity in health systems.


A Review of the Current Challenges Associated with the Development of an Artificial Pancreas by a Double Subcutaneous Approach.
Patients with diabetes type 1 (DM1) struggle daily to achieve good glucose control. The last decade has seen a rush of research groups working towards an artificial pancreas (AP) through the application of a double subcutaneous approach, i.e., subcutaneous (SC) continuous glucose monitoring (CGM) and continuous subcutaneous insulin infusion. Few have focused on the fundamental limitations of this approach, especially regarding outcome measures beyond time in range. Based on insulin physiology, the limitations of CGM, SC insulin absorption, meal challenge, and physical activity in DM1 patients, we discuss the limitations of the double SC approach. Finally, we discuss safety measures and the achievements reported in some recent AP studies that have utilized the double SC approach. Most studies show that a double SC AP increases the time in range compared to a sensor-augmented insulin pump and shortens the time in hypoglycemia. Despite these achievements, the proportion of time spent in hyperglycemia is still roughly 20-40%, and hypoglycemia is still present 1-4% of the time. The main factors limiting further progress are the latency of SC CGM (at least 5-10 min) and the slow pharmacokinetics of SC-delivered fast-acting insulin. The maximum blood insulin level is reached after 45 min and the maximum glucose-lowering effect is observed after 1.5-2 h, while the glucose-lowering effect lasts for at least 5 h. Although using a double SC AP leads to significant improvements in glucose control, the SC approach has severe limitations that hamper further progress towards a robust AP.


Cannabis and schizophrenia.
Schizophrenia is a mental illness causing disordered beliefs, ideas and sensations. Many people with schizophrenia smoke cannabis, and it is unclear why a large proportion do so and if the effects are harmful or beneficial. It is also unclear what the best method is to allow people with schizophrenia to alter their cannabis intake. To assess the effects of specific psychological treatments for cannabis reduction in people with schizophrenia.To assess the effects of antipsychotics for cannabis reduction in people with schizophrenia.To assess the effects of cannabinoids (cannabis related chemical compounds derived from cannabis or manufactured) for symptom reduction in people with schizophrenia. We searched the Cochrane Schizophrenia Group Trials Register, 12 August 2013, which is based on regular searches of BIOSIS, CINAHL, EMBASE, MEDLINE, PUBMED and PsycINFO.We searched all references of articles selected for inclusion for further relevant trials. We contacted the first author of included studies for unpublished trials or data. We included all randomised controlled trials involving cannabinoids and schizophrenia/schizophrenia-like illnesses, which assessed:1) treatments to reduce cannabis use in people with schizophrenia;2) the effects of cannabinoids on people with schizophrenia. We independently inspected citations, selected papers and then re-inspected the studies if there were discrepancies, and extracted data. For dichotomous data we calculated risk ratios (RR) and for continuous data, we calculated mean differences (MD), both with 95% confidence intervals (CI) on an intention-to-treat basis, based on a fixed-effect model. We excluded data if loss to follow-up was greater than 50%. We assessed risk of bias for included studies and used GRADE to rate the quality of the evidence. We identified eight randomised trials, involving 530 participants, which met our selection criteria.For the cannabis reduction studies no one treatment showed superiority for reduction in cannabis use. Overall, data were poorly reported for many outcomes of interest. Our main outcomes of interest were medium-term data for cannabis use, global state, mental state, global functioning, adverse events, leaving the study early and satisfaction with treatment. 1. Reduction in cannabis use: adjunct psychological therapies (specifically about cannabis and psychosis) versus treatment as usualResults from one small study showed people receiving adjunct psychological therapies specifically about cannabis and psychosis were no more likely to reduce their intake than those receiving treatment as usual (n = 54, 1 RCT, MD -0.10, 95% CI -2.44 to 2.24, moderate quality evidence). Results for other main outcomes at medium term were also equivocal. No difference in mental state measured on the PANSS positive were observed between groups (n = 62, 1 RCT, MD -0.30 95% CI -2.55 to 1.95, moderate quality evidence). Nor for the outcome of general functioning measured using the World Health Organization Quality of Life BREF (n = 49, 1 RCT, MD 0.90 95% CI -1.15 to 2.95, moderate quality evidence). No data were reported for the other main outcomes of interest 2. Reduction in cannabis use: adjunct psychological therapy (specifically about cannabis and psychosis) versus adjunct non-specific psychoeducation One study compared specific psychological therapy aimed at cannabis reduction with general psychological therapy. At three-month follow-up, the use of cannabis in the previous four weeks was similar between treatment groups (n = 47, 1 RCT, RR 1.04 95% CI 0.62 to 1.74, moderate quality evidence). Again, at a medium-term follow-up, the average mental state scores from the Brief Pscychiatric Rating Scale-Expanded were similar between groups (n = 47, 1 RCT, MD 3.60 95% CI - 5.61 to 12.81, moderate quality evidence). No data were reported for the other main outcomes of interest: global state, general functioning, adverse events, leaving the study early and satisfaction with treatment. 3. Reduction in cannabis use: antipsychotic versus antipsychotic In a small trial comparing effectiveness of olanzapine versus risperidone for cannabis reduction, there was no difference between groups at medium-term follow-up (n = 16, 1 RCT, RR 1.80 95% CI 0.52 to 6.22, moderate quality evidence). The number of participants leaving the study early at medium term was also similar (n = 28, 1 RCT, RR 0.50 95% CI 0.19 to 1.29, moderate quality evidence). Mental state data were reported, however they were reported within the short term and no difference was observed. No data were reported for global state, general functioning, and satisfaction with treatment.With regards to adverse effects data, no study reported medium-term data. Short-term data were presented but overall, no real differences between treatment groups were observed for adverse effects. 4. Cannabinoid as treatment: cannabidiol versus amisulprideAgain, no data were reported for any of the main outcomes of interest at medium term. There were short-term data reported for mental state using the BPRS and PANSS, no overall differences in mental state were observed between treatment groups. Results are limited and inconclusive due to the small number and size of randomised controlled trials available and quality of data reporting within these trials. More research is needed to a) explore the effects of adjunct psychological therapy that is specifically about cannabis and psychosis as currently there is no evidence for any novel intervention being better than standard treatment,for those that use cannabis and have schizophrenia b) decide the most effective drug treatment in treating those that use cannabis and have schizophrenia, and c) assess the effectiveness of cannabidiol in treating schizophrenia. Currently evidence is insufficient to show cannabidiol has an antipsychotic effect.


Roles of chromosomal and episomal dinB genes encoding DNA pol IV in targeted and untargeted mutagenesis in Escherichia coli.
DNA polymerase IV (pol IV) in Escherichia coli is a member of a novel family of DNA polymerases (the DinB/UmuC/Rad30/Rev1 super-family or the DNA polymerase Y family). Although expression of the dinB gene encoding DNA pol IV is known to result in an enhancement of untargeted mutagenesis, it remains uncertain whether DNA pol IV is involved in a variety of lesion-induced mutagenesis (targeted mutagenesis), and the relationship between expression levels of dinB and the mutagenesis that DNA pol IV promotes has not been investigated thoroughly. Here, we report that DNA pol IV is involved in -1 frameshift mutagenesis induced by 4-nitroquinoline N-oxide (4-NQO) and that the expression level of the chromosomal pol IV gene is 6-12 times higher than those for other SOS-inducible DNA polymerases in E. coli, i.e., DNA pol II (PolB) or DNA pol V (UmuDC), respectively. Interestingly, the dinB gene is present not only on the chromosome but also on the F' plasmid in the E. coli CC108 strain. In this strain, 750 molecules of DNA pol IV are expressed from the F' dinB gene in the uninduced state and 250 molecules are expressed from the chromosomal gene. These cellular expression levels strongly affect -1 frameshifts induced by 4-NQO in runs of six guanine bases: mutagenicity was highest in the strain CC108, followed by strains YG2242 (chromosome deltadinB/F' dinB+), YG2247 (chromosome dinB+/F' deltadinB) and FC1243 (chromosome deltadinB/F' deltadinB). The incidence of untargeted -1 frameshifts was reduced by two-thirds on deletion of dinB from the F' episome. The chromosomal dinB gene appeared to have little or no effect on the untargeted mutagenesis. These results suggest that DNA pol IV efficiently mediates targeted mutagenesis by 4-NQO, and that the cellular levels of expression substantially affect targeted and untargeted mutagenesis.


Changing perspectives on palliative care.
In the United States, hospice and palliative care are two distinct expressions of the hospice interdisciplinary team approach to end-of-life care, which originated in Great Britain in the 1960s. The hospice movement developed largely as a home-care program and alternative to conventional care. Hospice regulations and reimbursement allowances limit services to patients who are expected to die within 6 months and who forego many common oncologic treatments. On the other hand, palliative care is a more recent academic, medically mainstream discipline that attempts to integrate the hospice approach into oncology and other areas of clinical medicine from the earliest phases of diagnosis and treatment. Palliative care entertains all appropriate forms of care at any phase of an illness. In this review, we describe the key goals of palliative care, which include excellent pain and symptom control, psychosocial and spiritual support for the patient and family, informed decision-making, and coordinated services across the continuum of care. We focus on selected recent developments that are important to oncology practice: the role of artificial nutrition; management of malignant small bowel obstruction; communication tasks, such as information sharing, recognition of patient preferences, advanced-care planning, and bereavement care; and ethical principles related to the hastening of death.


Simultaneous ranging and velocimetry of fast moving targets using oppositely chirped pulses from a mode-locked laser.
A lidar system based on the coherent detection of oppositely chirped pulses generated using a 20 MHz mode locked laser and chirped fiber Bragg gratings is presented. Sub millimeter resolution ranging is performed with > 25 dB signal to noise ratio. Simultaneous, range and Doppler velocity measurements are experimentally demonstrated using a target moving at > 330 km/h inside the laboratory.


Cellular retinoic acid- and cellular retinol-binding proteins: complementary deoxyribonucleic acid cloning, chromosomal assignment, and tissue specific expression.
Both cellular retinoic acid-binding protein (CRABP) and cellular retinol-binding protein (CRBP) are widely distributed in mammalian tissues and display different patterns of tissue distribution. We have isolated cDNA clones for bovine CRABP and for human CRBP from a bovine adrenal gland cDNA library and from a human liver cDNA library, respectively, by probing with synthetic oligonucleotides. The primary structures of the two proteins inferred from the DNA sequences were identical to the previously reported amino acid sequences. The cDNA probes were used to obtain some information about the genes for CRABP and CRBP, including their chromosomal localization, and about the tissue specific expression of these two genes. Southern blot analyses under highly stringent conditions, of genomic DNA from both the bovine and the mouse, showed that for each retinoid-binding protein, specific DNA sequences are sufficiently conserved across species to allow cross-hybridization to occur. Under the same conditions, however, the DNA sequences for CRABP and CRBP within each species appear to be sufficiently different that cross-hybridization was not observed between the two cDNA probes. Using mouse-hamster somatic cell hybrids, it was demonstrated that these genes map to mouse chromosome 9 or 10. Northern blot analyses of RNA from six tissues from both the bovine and the mouse showed marked differences in the levels of the specific transcript for each binding protein among the different tissues, and in the tissue distribution of CRABP mRNA as compared to that of CRBP mRNA. In both species, CRBP mRNA was detected in more tissues than was CRABP mRNA. For both proteins, the relative tissue distribution of the mRNAs appeared to both resemble and to differ from the reported distribution of the binding proteins themselves. The factors that regulate the tissue specific expression of the genes for CRABP and CRBP remain to be determined.


Recurrent dendrodendritic inhibition of accessory olfactory bulb mitral cells requires activation of group I metabotropic glutamate receptors.
Metabotropic glutamate receptors (mGluRs) modulate neural excitability and network tone in many brain regions. Expression of mGluRs is particularly high in the accessory olfactory bulb (AOB), a CNS structure critical for detecting chemicals that identify kin and conspecifics. Because of its relative simplicity and its direct projection to the hypothalamus, the AOB provides a model system for studying how mGluRs affect the flow of encoded sensory information to downstream areas. We investigated the role of group I mGluRs in synaptic processing in AOB slices and found that under control conditions, recurrent inhibition of principal neurons (mitral cells) was completely eliminated by the mGluR1 antagonist LY367385 [(S)-(+)-alpha-amino-4-carboxy-2 methylbenzeneacetic acid]. In addition, the group I mGluR agonist DHPG [(S)-3,5-dihydroxyphenylglycine; 20 microM] induced a dramatic increase in the rate of spontaneous IPSCs. This increase was dependent on voltage-gated calcium channels but persisted even after blockade of ionotropic glutamatergic transmission and sodium channels. Together, these results indicate that mGluR1 plays a critical role in controlling information flow through the AOB and suggest that mGluR1 may be an important locus for experience-dependent changes in synaptic function.


Genome-wide translational changes induced by the prion [PSI+].
Prions are infectious proteins that can adopt a structural conformation that is then propagated among other molecules of the same protein. [PSI(+)] is an aggregated conformation of the translational release factor eRF3. [PSI(+)] modifies cellular fitness, inducing various phenotypes depending on genetic background. However, the genes displaying [PSI(+)]-controlled expression remain unknown. We used ribosome profiling in isogenic [PSI(+)] and [psi(-)] strains to identify the changes induced by [PSI(+)]. We found 100 genes with stop codon readthrough events and showed that many stress-response genes were repressed in the presence of [PSI(+)]. Surprisingly, [PSI(+)] was also found to affect reading frame selection independently of its effect on translation termination efficiency. These results indicate that [PSI(+)] has a broader impact than initially anticipated, providing explanations for the phenotypic differences between [psi(-)] and [PSI(+)] strains.


Identification of New Fungal Pathogens of Coast Live Oak in California.
A decline of coast live oak (Quercus agrifolia) has been observed throughout southern California. In this study, the identity and pathogenicity of non-Botryosphaeriaceae fungal species consistently recovered from necrotic tissues of branch and bleeding trunk canker samples from these locations were assessed. Species were identified morphologically and by comparison of the complete sequence of the internal transcribed spacer (ITS) of the ribosomal DNA to sequences available in GenBank. Phylogenetic analyses were then conducted using ITS and partial sequences of the β-tubulin and mitochondrial small ribosomal subunit genes for unknown species. Fungi recovered and identified included Fusarium solani, Phaeoacremonium mortoniae, Diatrypella verrucaeformis, and a fungus described herein as Cryptosporiopsis querciphila sp. nov. One-year-old coast live oak seedlings were wound inoculated under controlled conditions to test pathogenicity of the fungal species. Each fungal species was successfully reisolated from necrotic tissue at 70 and 100% for P. mortoniae and all other species, and xylem necrosis was significantly different between all treatments and controls (P < 0.0001 at α = 0.05). Isolates of F. solani were the most aggressive tested. These species represent new records of fungal pathogens of coast live oak in California. Results from the pathogenicity test suggest that these fungi play a role in the decline of southern California coast live oak trees.


Quantitative molecular assessment of chimerism across tissues in marmosets and tamarins.
Marmosets are playing an increasingly large and important role in biomedical research. They share genetic, anatomical, and physiological similarities with humans and other primate model species, but their smaller sizes, reproductive efficiency, and amenability to genetic manipulation offer an added practicality. While their unique biology can be exploited to provide insights into disease and function, it is also important that researchers are aware of the differences that exist between marmosets and other species. The New World monkey family Callitrichidae, containing both marmoset and tamarin species, typically produces dizygotic twins that show chimerism in the blood and other cells from the hematopoietic lineage. Recently, a study extended these findings to identify chimerism in many tissues, including somatic tissues from other lineages and germ cells. This has raised the intriguing possibility that chimerism may play an increasingly pervasive role in marmoset biology, ranging from natural behavioral implications to increased variability and complexity in biomedical studies. Using a quantitative PCR based methodology, Y-chromosomes can be reliably detected in the females with male fraternal twins allowing for a relative quantification of chimerism levels between individuals and tissues. With this approach in common marmosets (Callithrix jacchus) and cotton-top tamarins (Saguinus oedipus), chimerism was detected across a broad array of tissues. Chimerism levels were significantly higher in tissues primarily derived from the hematopoietic lineage, while they were lower, though still detectable, in tissues with other origins. Interestingly, animals with a characteristic marmoset wasting disease show higher levels of chimerism in those tissues affected. Fibroblast cell lines from chimeric individuals, however, are not found to be chimeric themselves. Taken together, the levels of chimerism in tissues of different origins coupled with other lines of evidence suggest that indeed only hematopoietic cell lineages are chimeric in callitrichids. The chimerism detected in other tissues is likely the result of blood or lymphocytic infiltration. Using molecular methods to detect chimerism in a tissue sample seems to have allowed a substantial increase in the ability to detect these minor cell populations.


Human-mouse quantitative trait locus concordance and the dissection of a human neuroticism locus.
Exploiting synteny between mouse and human disease loci has been proposed as a cost-effective method for the identification of human susceptibility genes. Here we explore its utility in an analysis of a human personality trait, neuroticism, which can be modeled in mice by tests of emotionality. We investigated a mouse emotionality locus on chromosome 1 that contains no annotated genes but abuts four regulators of G protein signaling, one of which (rgs2) has been previously identified as a quantitative trait gene for emotionality. This locus is syntenic with a human region that has been consistently implicated in the genetic aetiology of neuroticism. The functional candidacy of 29 murine sequence variants was tested by a combination of gel shift and transient transfection assays. Murine sequences that contained functional variants and exhibited significant cross-species conservation were prioritized for investigation in humans. Genetic association with neuroticism was tested in 1869 high and 2032 low unrelated individuals scored for neuroticism, selected from the extremes of 88,141 people from southwest England. Fifteen sequence variants contributed to variation in the expression of rgs18, the gene lying at the edge of the quantitative trait loci (QTL) interval. There was no evidence of association between neuroticism and single nucleotide polymorphisms (SNPs) lying in the human regions homologous to those of mouse functional variants. One SNP, rs6428058, in a region of sequence conservation 644 kb upstream of RGS18, showed significant association (p = .000631). It is unlikely that a single variant is responsible for the mouse emotionality locus on chromosome 1. This level of underlying genetic complexity means that although cross-species QTL concordance may be invaluable for the identification of human disease loci, it is unlikely to be as informative in the identification of human disease-causing variants.


Prospective pilot study of high-dose (10 mg/kg/day) liposomal amphotericin B (L-AMB) for the initial treatment of mucormycosis.
Mucormycosis incidence is increasing and is associated with a high rate of mortality. Although lipid-based formulations of amphotericin B are the recommended first-line treatment, only one prospective trial in a limited number of patients has been performed to evaluate this regimen. Patients with proven or probable mucormycosis were included between June 2007 and March 2011. Patients were scheduled to receive 10 mg/kg/day liposomal amphotericin B (L-AMB) monotherapy for 1 month and surgery was performed when appropriate. The primary outcome was response rate at week 4 or at the end of treatment (EOT) if before week 4, evaluated by an independent committee. ClinicalTrials.gov Identifier: NCT00467883. Forty patients were enrolled. Response was analysed in 33 patients at week 4. Most patients had a haematological malignancy as their primary underlying disease (53%). Seventy-one percent of patients underwent therapeutic surgery. The response rate at week 4 or at EOT was 36%, with 18% partial responses and 18% complete responses. The response rate at week 12 was 45%, with 13% partial responses and 32% complete responses. Overall mortality was 38% at week 12 and 53% at week 24. Serum creatinine doubled in 16 (40%) patients and returned to normal levels within 12 weeks in 10/16 (63%). High-dose L-AMB for mucormycosis, in combination with surgery in 71% of cases, was associated with an overall response rate of 36% at week 4 and 45% at week 12 and creatinine level doubling in 40% of patients (transient in 63%). These results may serve as the basis for future clinical trials.


[DNA analysis of retroposon-like genetic LINE elements in blood plasma of rats exposed to radio-diapason electromagnetic waves].
The elevation of LINE-elements' DNA level was revealed in blood plasma of rats exposed to electromagnetic waves. The amount of full-size 5'-containing LINE-elements copies was increased especially. Connection of this effect with retrotransposon activation and genetic instability condition of organism development is supposed.


Lipase incorporated ionic liquid polymers as active, stable and reusable biocatalysts.
The aim of this study was to develop ionic liquid (IL) polymer materials incorporating enzymes that can be used as active, stable and reusable biocatalysts. To this goal, Candida rugosa lipase has been microencapsulated in surfactant aggregates formed in an IL monomer or the solution of an IL monomer/IL and then incorporated into polymer frameworks through the free radical polymerization of an IL (1-vinyl-3-ethylimidazolium bis(trifluoromethyl-sulfonyl) amide) ([veim][Tf(2)N]). The activity, stability and reusability of such IL polymer materials containing lipase were evaluated using lipase-catalyzed hydrolysis of p-nitrophenyl butyrate (p-PNB) as a model reaction. Lipase encapsulated within ionic liquid polymer materials remained active and exhibited excellent stability in aqueous solutions. More importantly, these biopolymer materials retained most of their activity after five reaction cycles, in which biopolymers were recovered from the reaction mixture simply by centrifugation. This study promulgates a direction toward the design of IL - an interesting class of tunable and designable solvents - based polymer materials containing biomolecules via a combination of polymer and supramolecular chemistry for diverse applications.


[The challenge of the peripheral Nephrological Center: an Italian story].
In small peripheral nephrological hospitals it can sometimes be difficult to obtain an early diagnosis and to ensure a state-of-the-art treatment. In the most complex cases, in fact, patients must be transferred to the closest Nephrological Referral Center in order to recover kidney function or improve the chance of survival. Other challenges are represented by the progressive ageing of the population and by the management of oncological patients developing kidney complications, for which it would be desirable to create dedicated clinics. However, small hospitals also offer many advantages, such as better work management, the opportunity to attend many training initiatives and congresses, and the ability to better balance career with family needs. Cooperating in smaller teams and the harmony that develops with the other physicians and nurses allows us to offer the best healthcare to nephropathic patients who live far away from the major Referral Centers. Each peripheral Center can also represent an essential resource for the major Center because it acts as the first point of contact with patients, taking care of identifying the situations that need the attention of the Referral Center and, subsequently, taking charge of the follow-up in conservative or replacement therapy.


Validation of the Functional Status II questionnaire in the assessment of extremely-low-birthweight infants.
The increased survival of infants born at extremely low birthweight (ELBW) has been associated with significant morbidity, including higher rates of neurodevelopmental disability. However, formalized testing to evaluate these problems is both time-consuming and costly. The revised Functional Status questionnaire (FS-II) was designed to assess caregivers' perceptions of the functional status of children with chronic diseases. We evaluated the reliability and validity of the FS-II for ELBWinfants at 18 to 22 months corrected age using data from the US Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD) Neonatal Research Network (NRN). Exploratory factor analyses were conducted using data from the network's first follow-up study of 1080 children born in 1993 to 1994 (508 males, 572 females [53%]), and results were confirmed using data from the next network follow-up of 4022 children born in 1995 to 2000 (1864 males, 2158 females [54%]). Results suggest that a two-factor solution comprising measures of general health and independence is most appropriate for ELBW infants. These factors differed from those found among chronically ill children, and new, more appropriate scales are presented for screening ELBWsurvivors. Both scales demonstrated good internal consistency: Cronbach's a=0.87 for general health and a=0.75 for independence. Construct validity of the scales was assessed by comparing mean scores on the scales according to scores on the Bayley Scales of Infant Development, second edition (BSID-II), and medical conditions. As hypothesized, infants with greater functional impairments according to their BSID-II scores or medical conditions had lower scores on the general health and independence scales, supporting the validity of the scales.


Designing the CGM Experience: An App Design Process Overview.
Users of continuous glucose monitors (CGMs) experience the product in part through software. Smartphone and watch apps empower people affected by diabetes to make real-time treatment decisions based on glucose readings and aggregate data such as medication, nutrition, and activity information. As CGMs evolve and gain greater market adoption, there's opportunity for these apps to play a greater role in users' lives and diabetes management. To do so, designers should follow the best practices established by the broader technology community and apply them to the needs of this community. The process of thorough discovery research, clear problem definition, iterative design, and testing can lower barriers toward broader adoption, and favorably influence the health of users through their mobile apps.


Primary pulmonary hypertension in HIV infection.
A prospective evaluation of 74 human immunodeficiency virus (HIV)-infected patients with cardiopulmonary complaints revealed six patients (8.1 percent) with pulmonary hypertension with elevated right ventricular systolic over right atrial pressure of 58 +/- 8 mm Hg (range, 49 to 66 mm Hg), as documented by Doppler echocardiography. A thromboembolic cause was excluded by normal lung perfusion scans. Electrocardiographic and roentgenographic features of pulmonary hypertension were present in five patients. Two patients died three and nine months after diagnosis of pulmonary hypertension. Autopsy revealed plexogenic pulmonary arteriopathy in both. The observation of six patients with primary pulmonary hypertension (PPH) in a cohort of 1,200 HIV-infected subjects corresponding to an incidence of 0.5 percent is striking and suggests a possible association of PPH with HIV infection.


Clinical significance of early recurrences of atrial tachycardia after atrial fibrillation ablation.
atrial tachycardia (AT) commonly recurs within 3 months after radiofrequency catheter ablation for atrial fibrillation (AF). However, it remains unclear whether early recurrence of atrial tachycardia (ERAT) predicts late recurrence of AF or AT. of 352 consecutive patients who underwent circumferential pulmonary vein isolation with or without linear ablation(s) for AF, 56 patients (15.9%) with ERAT were identified by retrospective analysis. ERAT was defined as early relapse of AT within a 3-month blanking period after ablation. during 21.7 ± 12.5 months, the rate of late recurrence was higher in patients with ERAT (41.1%) compared with those without ERAT (11.8%, P < 0.001). In a multivariable model, positive inducibility of AF or AT immediately after ablation (65.2% vs 36.4%, P = 0.046; odd ratio, 3.9; 95% confidence interval, 1.0-14.6) and the number of patients who underwent cavotricuspid isthmus (CTI) ablation (73.9% vs 42.4%, P = 0.042; odd ratio, 4.5; 95% confidence interval, 1.1-19.5) were significantly related to late recurrence in the ERAT group. The duration of ablation (174.3 ± 62.3 vs 114.7 ± 39.5 minutes, P = 0.046) and the procedure time (329.3 ± 83.4 vs 279.2 ± 79.7 minutes, P = 0.027) were significantly longer in patients with late recurrence than in those without late recurrence following ERAT. the late recurrence rate is higher in the patients with ERAT compared with those without ERAT following AF ablation, and is more often noted in the patients who underwent CTI ablation and had a prolonged procedure time. Furthermore, inducibility of AF or AT immediately after ablation independently predicts late recurrence in patients with ERAT.


Post-traumatic stress disorder after childbirth: the phenomenon of traumatic birth.
CHILDBIRTH CAN BE A VERY PAINFUL EXPERIENCE, often associated with feelings of being out of control. It should not, therefore, be surprising that childbirth may be traumatic for some women. Most women recover quickly post partum; others appear to have a more difficult time. The author asserts that post-traumatic stress disorder (PTSD) may occur after childbirth. He calls this variant of PTSD a "traumatic birth experience." There is very little literature on this topic. The evidence available is from case series, qualitative research and studies of women seeking elective cesarean section for psychologic reasons. Elective cesarean section exemplifies the avoidance behaviour typical of PTSD. There are many ways that health care professionals, including physicians, obstetric nurses, midwives, psychologists, psychiatrists and social workers, can address this phenomenon. These include taking a careful history to determine whether a woman has experienced trauma that could place her at risk for a traumatic birth experience; providing excellent pain control during childbirth and careful postpartum care that includes understanding the woman's birth experience; and ruling out postpartum depression. Much more research is needed in this area.


Prevalence and correlates of sexual and gender-based violence against Chinese adolescent women who are involved in commercial sex: a cross-sectional study.
Despite the vast quantity of research among Chinese female sex workers (FSWs) to address concerns regarding HIV/sexually transmitted infection (STI) risk, there is a paucity of research on issues of sexual and gender-based violence (SGBV) and the missed opportunity for sexual and reproductive health (SRH) promotion among young FSWs. Our research aimed to assess the prevalence and correlates of SGBV among Chinese adolescent FSWs, and to explore SRH service utilisation. A cross-sectional study using a one-stage cluster sampling method was employed. A semistructured questionnaire was administered by trained peer educators or health workers. Multivariable logistic regression was conducted to determine individual and structural correlates of SGBV. Between July and September 2012, 310 adolescent women aged 15-20 years, and who self-reported having received money or gifts in exchange for sex in the past 6 months were recruited and completed their interview in Kunming, Yunnan Province, China. Findings confirm the high prevalence of SGBV against adolescent FSWs in China, with 38% (118/310) of participants affected in the past year. Moreover, our study demonstrated the low uptake of public health services and high rates of prior unwanted pregnancy (52%; 61/118), abortion (53%; 63/118) and self-reported STI symptoms (84%; 99/118) in participants who were exposed to SGBV. Forced sexual debut was reported by nearly a quarter of FSWs (23%; 70/310) and was independently associated with having had a drug-using intimate partner and younger age (<17 years old) at first abortion. When controlling for potential confounders, having experienced SGBV was associated with frequent alcohol use, having self-reported symptoms of STI, having an intimate partner and having an intimate partner with illicit drug use. This study calls for effective and integrated interventions addressing adolescent FSWs' vulnerability to SGBV and broader SRH consequences.


Boys have not caught up, family influences still continue: Influences on executive functioning and behavioral self-regulation in elementary students in Germany.
The development of self-regulation is influenced by various child-level and family-level characteristics. Previous research focusing on the preschool period reported a female advantage in self-regulation and negative effects of various adverse features of the family environment on self-regulation. The present study aimed to investigate growth in self-regulation (i.e., executive functioning and behavioral self-regulation) over 1 school year during early elementary school and to explore the influences of child sex, the level of home chaos, and family educational resources on self-regulation. Participants were 263 German children (51% girls; mean age 8.59 years, SD = 0.56 years). Data were collected during the fall and spring of the school year. A computer-based standardized test battery was used to assess executive functioning. Caregiver ratings assessed children's behavioral self-regulation and information on the family's home environment (chaotic home environment and educational resources). Results suggest growth in elementary school children's executive functioning over the course of the school year. However, there were no significant changes in children's behavioral self-regulation between the beginning and the end of Grade 3. Sex differences in inhibitory control/cognitive flexibility and behavioral self-regulation were found, suggesting an advantage for girls. Educational resources in the family but not chaotic family environment were significantly related to self-regulation at both time-points. Children from families with more educational resources scored higher on self-regulation measures compared to their counterparts from less advantaged families. We did not find evidence for child-level or family-level characteristics predicting self-regulation growth over time. Findings add to the evidence of a gender gap in self-regulation skills, but suggest that it might not further widen towards the end of elementary school age. Adequate self-regulation skills should be fostered in both girls and boys. Results also add to the importance of supporting self-regulation development in children from disadvantaged family backgrounds early in life.


Informed Consent to Vaccination: Theoretical, Legal, and Empirical Insights.
Informed consent matters - so does protecting people from infectious diseases. This paper examines what the appropriate informed consent process for vaccines should look like and how the process is conceptualized by law and health authorities. Drawing on the extensive theoretical and empirical literature on informed consent and vaccination, this article sets out what an ideal informed consent process for vaccination would consist of, highlighting the need for autonomous decisions. To be autonomous, decisions need to be based on full, accessible information and reached without coercion. We suggest that the information provided must address the nature of the procedure - including benefits to the child, benefits to society, and risks. Parents should have their concerns and misconceptions addressed. The information needs to be accessible and include an opportunity to ask questions. Based on this ideal model we examined in detail the legal framework surrounding informed consent to vaccination and the process as conceptualized by health authorities in two countries, Israel and the United States, to assess whether they meet the requirements. These two countries are similar in some of their values, for example, the importance of individual autonomy, and face similar problems related to vaccine hesitancy. At the same time, there are meaningful differences in their vaccine policies and the current structures of their informed consent processes, allowing for a meaningful comparison. We found neither country met our ideal informed consent process, and suggested improvements both to the materials and to the processes used to obtain informed consent.


Experience Developing a Community Pharmacy Practice-based Research Network.
In 2010, the Purdue University College of Pharmacy established the Medication Safety Research Network of Indiana (Rx-SafeNet), the first practice-based research network (PBRN) in Indiana comprised solely of community pharmacies. In the development of Rx-SafeNet and through our early project experiences, we identified several "lessons learned." We share our story and what we learned in an effort to further advance the work of the greater PBRN community. We have formed the infrastructure for Rx-SafeNet, including an Executive Committee, Advisory Board, member pharmacies/site coordinators, and Project Review Team. To date, 22 community pharmacies have joined and we have recently completed data collection for the network's first project. Lessons learned during the development of Rx-SafeNet may benefit PBRNs nationally. Although community pharmacy PBRNs are not yet commonplace in the U.S., we believe their development and subsequent research efforts serve as an important avenue for investigating medication use issues.


Perisynaptic barrier of proteoglycans in the mature brain and spinal cord.
Cell bodies and their dendrites of motor neurons, motor-related neurons, and certain other subsets of neurons such as GABAergic interneurons in the mature brain and spinal cord possess intensely negatively charged perineuronal or perisynaptic nets of proteoglycans which are linked to the nerve cell surface glycoproteins. These perineuronal nets of proteoglycans are digested by chondroitinase ABC, hyaluronidase, or collagenase, but not by endo-alpha-N-acetylgalactosaminidase, which is reactive to the nerve cell surface glycoproteins. Aggrecan, versican, neurocan, and brevican are members of a family of chondroitin sulfate proteoglycans that bind to hyaluronan. Neurocan- or brevican-deficient mice showed a regionally heterogeneous composition of proteoglycans in perineuronal nets. Aggrecan glycoforms contribute to the molecular heterogeneity of the perineuronal nets. Proteoglycans such as phosphacan are included in matrix-associated proteoglycans. The extracellular matrix glycoprotein tenascin-R is accumulated in the perineuronal nets. The perineuronal proteoglycans are produced by associated satellite astrocytes just before weaning, while the nerve cell surface glycoproteins are produced by the associated nerve cells at earlier stages after birth. The perineuronal proteoglycans may entrap the tissue fluid and form a perineuronal gel layer which protects the synapses as a "perisynaptic barrier". Degradation of the perineuronal proteoglycans or perisynaptic barrier by treatment with chondroitinase ABC or hyaluronidase reactivates the neuronal plasticity or promotes the functional recovery of a severed nervous system. Another set of perineuronal nets occurs, which are intensely positively charged and contain guanidino compounds. It is considered that these intensely positively charged nets are intermingled with the intensely negatively charged ones of proteoglycans.


Analysis of a low-finesse Fabry-Perot sensing interferometer illuminated by a multimode optical fiber.
A model of the reflected fringe system for an ideal plane-parallel, low-finesse Fabry-Perot (FP) cavity illuminated by a multimode optical fiber has been developed and experimentally validated. This showed that the phase dispersion within the cavity arising from the divergent nature of the incident illumination significantly degrades the visibility of the reflected fringes. Departures from the ideal FP cavity are also examined. The effect on fringe visibility when the plane of the FP cavity is tilted with respect to the fiber axis and when the cavity surfaces are no longer perfectly parallel to each other has been explored. The analysis described is relevant to the design and the optimization of multimode optical-fiber sensors that use FP sensing cavities.


Genotype-phenotype correlation in a novel ABHD12 mutation underlying PHARC syndrome.
PHARC syndrome is a rare neurodegenerative disorder caused by mutations in the ABHD12 gene. It is a genetically heterogeneous and clinically variable disease, which is characterized by demyelinating polyneuropathy, hearing loss, cerebellar ataxia, retinitis pigmentosa, and early-onset cataract and can easily be misdiagnosed as other neurologic disorders with a similar clinical picture, such as Charcot-Marie-Tooth disease and Refsum disease. We describe the genotype-phenotype correlation of two siblings with a novel genotype underlying PHARC syndrome. The genotype was identified using next-generation sequencing. We examined both patients by means of thorough history taking and clinical examination, nerve conduction studies (NCS), brain imaging, and optical coherence tomography to establish a genotype-phenotype correlation. We identified a novel homozygous point mutation (c.784C > T, p.Arg262*) in the ABHD12 gene. This mutation was detected in both siblings, who had bilateral hearing loss and cataracts, signs of cerebellar ataxia, and neuropathy with a primarily demyelinating pattern in NCS. In one case, retinitis pigmentosa was also evident. As PHARC syndrome is a rare autosomal recessive disorder, our findings highlight the importance of an interdisciplinary diagnostic workup with clinical and molecular genetic testing to avoid a misdiagnosis as Charcot-Marie-Tooth disease or Refsum disease.


Body composition and cardiometabolic disease risk factors in captive baboons (Papio hamadryas sp.): sexual dimorphism.
Baboons (Papio hamadryas sp.) exhibit significant sexual dimorphism in body size. Sexual dimorphism is also exhibited in a number of circulating factors associated with risk of cardiometabolic disease. We investigated whether sexual dimorphism in body size and composition underlie these differences. We examined data from 28 male and 24 female outdoor group-housed young adult baboons enrolled in a longitudinal observational study of cardiometabolic disease risk factors. Animals were sedated with ketamine HCl (10 mg/kg) before undergoing venous blood draws, basic body measurements, and dual-energy X-ray absorptiometry body composition scans. Percentage glycated hemoglobin A1c (%HbA1c ) was measured in whole blood. Serum samples were analyzed for glucose, insulin, C-peptide, high-density lipoprotein, and triglyceride concentrations. Males were heavier and had greater body length and lean tissue mass than females. Females had a greater body fat percentage relative to males (10.8 ± 6.4 vs. 6.9 ± 4.0, P = 0.01). Although C-peptide, fasting glucose, and %HbA1c did not differ between the sexes, females had greater fasting insulin and triglyceride compared to their male counterparts. Insulin and percentage body fat were significantly correlated in males (r = 0.61, P = 0.001) and to a lesser extent in females (r = 0.43, P = 0.04). Overall, relations between adiposity and fasting insulin and fasting triglyceride were stronger in males. After accounting for differences in percentage body fat, fasting insulin and triglyceride were no longer statistically different between males and females. Despite stronger correlations between relative adiposity and insulin and triglyceride in males, the higher fasting insulin and triglyceride of female baboons may be underlain by their greater relative body fat masses.


The failure in NGF maturation and its increased degradation as the probable cause for the vulnerability of cholinergic neurons in Alzheimer's disease.
This short review discusses the arguments to consider the dismetabolism of the pathway responsible for both the maturation and degradation of NGF as the culprit of vulnerability of the forebrain cholinergic system to the Alzheimer's disease neuropathology. This summary includes information regarding a novel metabolic cascade converting Pro-NGF to mature NGF in the extracellular space and its ultimate degradation by a metalloprotease. It also describes how this pathway is altered in Alzheimer's disease with the consequential CNS accumulation of proNGF and impairment in the formation of NGF along with increased degradation of this key trophic factor. This metabolic scenario in Alzheimer's disease should result in the failure of NGF trophic support to forebrain cholinergic neurons and thus explaining the vulnerability of these neurons in this neurodegenerative condition.


The use of mechanisms and modes of toxic action in integrated testing strategies: the report and recommendations of a workshop held as part of the European Union OSIRIS Integrated Project.
This report on The Potential of Mode of Action (MoA) Information Derived from Non-testing and Screening Methodologies to Support Informed Hazard Assessment, resulted from a workshop organised within OSIRIS (Optimised Strategies for Risk Assessment of Industrial Chemicals through Integration of Non-test and Test Information), a project partly funded by the EU Commission within the Sixth Framework Programme. The workshop was held in Liverpool, UK, on 30 October 2008, with 35 attendees. The goal of the OSIRIS project is to develop integrated testing strategies (ITS) fit for use in the REACH system, that would enable a significant increase in the use of non-testing information for regulatory decision making, and thus minimise the need for animal testing. One way to improve the evaluation of chemicals may be through categorisation by way of mechanisms or modes of toxic action. Defining such groups can enhance read-across possibilities and priority settings for certain toxic modes or chemical structures responsible for these toxic modes. Overall, this may result in a reduction of in vivo testing on organisms, through combining available data on mode of action and a focus on the potentially most-toxic groups. In this report, the possibilities of a mechanistic approach to assist in and guide ITS are explored, and the differences between human health and environmental areas are summarised.


Regional Odontodysplasia with Generalised Enamel Defect.
Regional odontodysplasia (ROD) is uncommon developmental anomaly, which tends to be localised and involves the ectodermal and mesodermal tooth components. A five-year-old female was referred to Department of Child Dental Health at the Leeds Dental Institute regarding malformed primary teeth. On examination 64, 74, and 72 had localised hypomineralized enamel defect. The crown of 55 was broken down with only the root remaining below the gingival level. 54 has a yellowish brown discolouration with rough irregular surface. The upper anterior teeth show mild enamel opacity. Radiographically, 55 and 54 had thin radioopaque contour, showing poor distinction between the enamel and dentine and the classic feature of a wide pulp chamber. 15, 16, and 17 were developmentally delayed and were displaying the characteristic "ghost appearance." Comprehensive dental care was done under local anaesthesia and it included extraction of the primary molars affected by ROD, stainless steel crown on 64, and caries prevention program. Fifteen months following the initial assessment the patient's oral condition remains stable and she is under regular follow-up at the department. Paediatric dentists should be aware of this anomaly as it involves both dentitions and usually requires multidisciplinary care.