Single Gene Deletions of Orexin, Leptin, Neuropeptide Y, and Ghrelin Do Not Appreciably Alter Food Anticipatory Activity in Mice

Timing activity to match resource availability is a widely conserved ability in nature. Scheduled feeding of a limited amount of food induces increased activity prior to feeding time in animals as diverse as fish and rodents. Typically, food anticipatory activity (FAA) involves temporally restricting unlimited food access (RF) to several hours in the middle of the light cycle, which is a time of day when rodents are not normally active. We compared this model to calorie restriction (CR), giving the mice 60% of their normal daily calorie intake at the same time each day. Measurement of body temperature and home cage behaviors suggests that the RF and CR models are very similar but CR has the advantage of a clearly defined food intake and more stable mean body temperature. Using the CR model, we then attempted to verify the published result that orexin deletion diminishes food anticipatory activity (FAA) but observed little to no diminution in the response to CR and, surprisingly, that orexin KO mice are refractory to body weight loss on a CR diet. Next we tested the orexigenic neuropeptide Y (NPY) and ghrelin and the anorexigenic hormone, leptin, using mouse mutants. NPY deletion did not alter the behavior or physiological response to CR. Leptin deletion impaired FAA in terms of some activity measures, such as walking and rearing, but did not substantially diminish hanging behavior preceding feeding time, suggesting that leptin knockout mice do anticipate daily meal time but do not manifest the full spectrum of activities that typify FAA. Ghrelin knockout mice do not have impaired FAA on a CR diet. Collectively, these results suggest that the individual hormones and neuropepetides tested do not regulate FAA by acting individually but this does not rule out the possibility of their concerted action in mediating FAA

Automated Home-Cage Behavioural Phenotyping of Mice

Neurobehavioral analysis of mouse phenotypes requires the monitoring of mouse behavior over long periods of time. Here, we describe a trainable computer vision system enabling the automated analysis of complex mouse behaviors. We provide software and an extensive manually annotated video database used for training and testing the system. Our system performs on par with human scoring, as measured from ground-truth manual annotations of thousands of clips of freely behaving mice. As a validation of the system, we characterized the home-cage behaviors of two standard inbred and two non-standard mouse strains. From this data we were able to predict in a blind test the strain identity of individual animals with high accuracy. Our video-based software will complement existing sensor based automated approaches and enable an adaptable, comprehensive, high-throughput, fine-grained, automated analysis of mouse behavior.McGovern Institute for Brain ResearchCalifornia Institute of Technology. Broad Fellows Program in Brain CircuitryNational Science Council (China) (TMS-094-1-A032

Numerical simulation of blood flow and pressure drop in the pulmonary arterial and venous circulation

A novel multiscale mathematical and computational model of the pulmonary circulation is presented and used to analyse both arterial and venous pressure and flow. This work is a major advance over previous studies by Olufsen et al. (Ann Biomed Eng 28:1281–1299, 2012) which only considered the arterial circulation. For the first three generations of vessels within the pulmonary circulation, geometry is specified from patient-specific measurements obtained using magnetic resonance imaging (MRI). Blood flow and pressure in the larger arteries and veins are predicted using a nonlinear, cross-sectional-area-averaged system of equations for a Newtonian fluid in an elastic tube. Inflow into the main pulmonary artery is obtained from MRI measurements, while pressure entering the left atrium from the main pulmonary vein is kept constant at the normal mean value of 2 mmHg. Each terminal vessel in the network of ‘large’ arteries is connected to its corresponding terminal vein via a network of vessels representing the vascular bed of smaller arteries and veins. We develop and implement an algorithm to calculate the admittance of each vascular bed, using bifurcating structured trees and recursion. The structured-tree models take into account the geometry and material properties of the ‘smaller’ arteries and veins of radii ≥ 50 μ m. We study the effects on flow and pressure associated with three classes of pulmonary hypertension expressed via stiffening of larger and smaller vessels, and vascular rarefaction. The results of simulating these pathological conditions are in agreement with clinical observations, showing that the model has potential for assisting with diagnosis and treatment for circulatory diseases within the lung

Increasing incidence of skin disorders in children? A comparison between 1987 and 2001

BACKGROUND: The increasing proportion of skin diseases encountered in general practice represents a substantial part of morbidity in children. Only limited information is available about the frequency of specific skin diseases. We aimed to compare incidence rates of skin diseases in children in general practice between 1987 and 2001. METHODS: We used data on all children aged 0–17 years derived from two consecutive surveys performed in Dutch general practice in 1987 and 2001. Both surveys concerned a longitudinal registration of GP consultations over 12 months. Each disease episode was coded according to the International Classification of Primary Care. Incidence rates of separate skin diseases were calculated by dividing all new episodes for each distinct ICPC code by the average study population at risk. Data were stratified for socio-demographic characteristics. RESULTS: The incidence rate of all skin diseases combined in general practice decreased between 1987 and 2001. Among infants the incidence rate increased. Girls presented more skin diseases to the GP. In the southern part of the Netherlands children consulted their GP more often for skin diseases compared to the northern part. Children of non-Western immigrants presented relatively more skin diseases to the GP. In general practice incidence rates of specific skin diseases such as impetigo, dermatophytosis and atopic dermatitis increased in 2001, whereas warts, contact dermatitis and skin injuries decreased. CONCLUSION: The overall incidence rate of all skin diseases combined in general practice decreased whereas the incidence rates of bacterial, mycotic and atopic skin diseases increased

Inhibition of Reactive Gliosis Attenuates Excitotoxicity-Mediated Death of Retinal Ganglion Cells

Reactive gliosis is a hallmark of many retinal neurodegenerative conditions, including glaucoma. Although a majority of studies to date have concentrated on reactive gliosis in the optic nerve head, very few studies have been initiated to investigate the role of reactive gliosis in the retina. We have previously shown that reactive glial cells synthesize elevated levels of proteases, and these proteases, in turn, promote the death of retinal ganglion cells (RGCs). In this investigation, we have used two glial toxins to inhibit reactive gliosis and have evaluated their effect on protease-mediated death of RGCs. Kainic acid was injected into the vitreous humor of C57BL/6 mice to induce reactive gliosis and death of RGCs. C57BL/6 mice were also treated with glial toxins, alpha-aminoadipic acid (AAA) or Neurostatin, along with KA. Reactive gliosis was assessed by immunostaining of retinal cross sections and retinal flat-mounts with glial fibrillary acidic protein (GFAP) and vimentin antibodies. Apoptotic cell death was assessed by TUNEL assays. Loss of RGCs was determined by immunostaining of flat-mounted retinas with Brn3a antibodies. Proteolytic activities of matrix metalloproteinase-9 (MMP-9), tissue plasminogen activator (tPA), and urokinase plasminogen activator (uPA) were assessed by zymography assays. GFAP-immunoreactivity indicated that KA induced reactive gliosis in both retinal astrocytes and in Muller cells. AAA alone or in combination with KA decreased GFAP and vimentin-immunoreactivity in Mϋller cells, but not in astrocytes. In addition AAA failed to decrease KA-mediated protease levels and apoptotic death of RGCs. In contrast, Neurostatin either alone or in combination with KA, decreased reactive gliosis in both astrocytes and Mϋller cells. Furthermore, Neurostatin decreased protease levels and prevented apoptotic death of RGCs. Our findings, for the first time, indicate that inhibition of reactive gliosis decreases protease levels in the retina, prevents apoptotic death of retinal neurons, and provides substantial neuroprotection

Darwin Core: An Evolving Community-Developed Biodiversity Data Standard

Biodiversity data derive from myriad sources stored in various formats on many distinct hardware and software platforms. An essential step towards understanding global patterns of biodiversity is to provide a standardized view of these heterogeneous data sources to improve interoperability. Fundamental to this advance are definitions of common terms. This paper describes the evolution and development of Darwin Core, a data standard for publishing and integrating biodiversity information. We focus on the categories of terms that define the standard, differences between simple and relational Darwin Core, how the standard has been implemented, and the community processes that are essential for maintenance and growth of the standard. We present case-study extensions of the Darwin Core into new research communities, including metagenomics and genetic resources. We close by showing how Darwin Core records are integrated to create new knowledge products documenting species distributions and changes due to environmental perturbations

A prospective study of mental health care for comorbid depressed mood in older adults with painful osteoarthritis

<p>Abstract</p> <p>Background</p> <p>Comorbid depression is common among adults with painful osteoarthritis (OA). We evaluated the relationship between depressed mood and receipt of mental health (MH) care services.</p> <p>Methods</p> <p>In a cohort with OA, annual interviews assessed comorbidity, arthritis severity, and MH (SF-36 mental health score). Surveys were linked to administrative health databases to identify mental health-related visits to physicians in the two years following the baseline interview (1996-98). Prescriptions for anti-depressants were ascertained for participants aged 65+ years (eligible for drug benefits). The relationship between MH scores and MH-related physician visits was assessed using zero-inflated negative binomial regression, adjusting for confounders. For those aged 65+ years, logistic regression examined the probability of receiving <it>any </it>MH-related care (physician visit or anti-depressant prescription).</p> <p>Results</p> <p>Analyses were based on 2,005 (90.1%) individuals (mean age 70.8 years). Of 576 (28.7%) with probable depression (MH score < 60/100), 42.5% experienced one or more MH-related physician visits during follow-up. The likelihood of a physician visit was associated with sex (adjusted OR women vs. men = 5.87, p = 0.005) and MH score (adjusted OR per 10-point decrease in MH score = 1.63, p = 0.003). Among those aged 65+, 56.7% with probable depression received <it>any </it>MH care. The likelihood of receiving <it>any </it>MH care exhibited a significant interaction between MH score and self-reported health status (p = 0.0009); with good general health, worsening MH was associated with increased likelihood of MH care; as general health declined, this effect was attenuated.</p> <p>Conclusions</p> <p>Among older adults with painful OA, more than one-quarter had depressed mood, but almost half received no mental health care, suggesting a care gap.</p

Supporting Goal-Oriented Primary Health Care for Seniors with Complex Care Needs Using Mobile Technology:Evaluation and Implementation of the Health System Performance Research Network, Bridgepoint Electronic Patient Reported Outcome Tool

BACKGROUND: Older adults experiencing multiple chronic illnesses are at high risk of hospitalization and health decline if they are unable to manage the significant challenges posed by their health conditions. Goal-oriented care approaches can provide better care for these complex patients, but clinicians find the process of ascertaining goals “too complex and too-time consuming,” and goals are often not agreed upon between complex patients and their providers. The electronic patient reported outcomes (ePRO) mobile app and portal offers an innovative approach to creating and monitoring goal-oriented patient-care plans to improve patient self-management and shared decision-making between patients and health care providers. The ePRO tool also supports proactive patient monitoring by the patient, caregiver(s), and health care provider. It was developed with and for older adults with complex care needs as a means to improve their quality of life. OBJECTIVE: Our proposed project will evaluate the use, effectiveness, and value for money of the ePRO tool in a 12-month multicenter, randomized controlled trial in Ontario; targeting individuals 65 or over with two or more chronic conditions that require frequent health care visits to manage their health conditions. METHODS: Intervention groups using the ePRO tool will be compared with control groups on measures of quality of life, patient experience, and cost-effectiveness. We will also evaluate the implementation of the tool. RESULTS: The proposed project presented in this paper will be funded through the Canadian Institute for Health Research (CIHR) eHealth Innovation Partnerships Program (eHIPP) program (CIHR–143559). The expected completion date of the study is November, 2019. CONCLUSIONS: We anticipate our program of work will support improved quality of life and patient self-management, improved patient-centered primary care delivery, and will encourage the adoption of goal-oriented care approaches across primary health care systems. We have partnered with family health teams and quality improvement organizations in Ontario to ensure that our research is practical and that findings are shared widely. We will work with our established international network to develop an implementation framework to support continued adaptation and adoption across Canada and internationally

How to Exploit the Digitalization Potential of Business Processes

Process improvement is the most value-adding activity in the business process management (BPM) lifecycle. Despite mature knowledge, many approaches have been criticized to lack guidance on how to put process improvement into practice. Given the variety of emerging digital technologies, organizations not only face a process improvement black box, but also high uncertainty regarding digital technologies. This paper thus proposes a method that supports organizations in exploiting the digitalization potential of their business processes. To achieve this, action design research and situational method engineering were adopted. Two design cycles involving practitioners (i.e., managers and BPM experts) and end-users (i.e., process owners and participants) were conducted. In the first cycle, the method’s alpha version was evaluated by interviewing practitioners from five organizations. In the second cycle, the beta version was evaluated via real-world case studies. In this paper, detailed results of one case study, which was conducted at a semiconductor manufacturer, are included

The effectiveness of computerized clinical guidelines in the process of care: a systematic review

<p>Abstract</p> <p>Background</p> <p>Clinical practice guidelines have been developed aiming to improve the quality of care. The implementation of the computerized clinical guidelines (CCG) has been supported by the development of computerized clinical decision support systems.</p> <p>This systematic review assesses the impact of CCG on the process of care compared with non-computerized clinical guidelines.</p> <p>Methods</p> <p>Specific features of CCG were studied through an extensive search of scientific literature, querying electronic databases: Pubmed/Medline, Embase and Cochrane Controlled Trials Register. A multivariable logistic regression was carried out to evaluate the association of CCG's features with positive effect on the process of care.</p> <p>Results</p> <p>Forty-five articles were selected. The logistic model showed that Automatic provision of recommendation in electronic version as part of clinician workflow (Odds Ratio [OR]= 17.5; 95% confidence interval [CI]: 1.6-193.7) and Publication Year (OR = 6.7; 95%CI: 1.3-34.3) were statistically significant predictors.</p> <p>Conclusions</p> <p>From the research that has been carried out, we can conclude that after implementation of CCG significant improvements in process of care are shown. Our findings also suggest clinicians, managers and other health care decision makers which features of CCG might improve the structure of computerized system.</p