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Political Efficacy and Political Participation of Nurse Practitioners: A Dissertation

Wed, 02/08/2017 - 1:55pm

In many states, outdated rules and regulations restrict nurse practitioners (NPs) from practicing to their full potential, often limiting patients’ access to primary care. Modernizing NP state scope of practice laws and allowing patients greater access to NPs services is a priority. Unlike other professions, nurse practitioners have been unable to consistently influence legislative changes to health policy. This study examined the political efficacy and participation of nurse practitioners in the United States today (N=632). A descriptive cross sectional design, in conjunction with a political efficacy framework, evaluated nurse practitioners’ participation in political activities and their internal and external political efficacy. Increased internal political efficacy was significantly (p < 0.001) associated with NPs who were older, had specific health policy education, and have been mentored in health policy. Our findings show that NPs vote at consistently higher rates (94%) than the general population and almost 50% report contacting legislators via mail/email/phone. As a group however, NPs report limited participation in other political activities, especially grassroots efforts. These findings hold significant implications for the profession as we strive to make policy changes across the country. It is important that educators assess our current methods of educating NPs about politics and health policy. Professional organizations and policy makers must reexamine outreach and strategies to inspire greater grassroots engagement of NPs.

Macrocognition in the Health Care Built Environment (m-HCBE): A Focused Ethnographic Study of 'Neighborhoods' in a Pediatric Intensive Care Unit: A Dissertation

Wed, 02/08/2017 - 1:55pm

Objectives: The objectives of this research were to describe the interactions (formal and informal) in which macrocognitive functions occur and their location on a pediatric intensive care unit (PICU); describe challenges and facilitators of macrocognition using three constructs of space syntax (openness, connectivity, and visibility); and analyze the health care built environment (HCBE) using those constructs to explicate influences on macrocognition.

Background: In high reliability, complex industries, macrocognition is an approach to develop new knowledge among interprofessional team members. Although macrocognitive functions have been analyzed in multiple health care settings, the effect of the HCBE on those functions has not been directly studied. The theoretical framework, “Macrocognition in the Health Care Built Environment” (m-HCBE) addresses this relationship.

Methods: A focused ethnographic study was conducted, including observation and focus groups. Architectural drawing files used to create distance matrices and isovist field view analyses were compared to panoramic photographs and ethnographic data.

Results: Neighborhoods comprised of corner configurations with maximized visibility enhanced team interactions as well as observation of patients, offering the greatest opportunity for informal situated macrocognitive interactions (SMIs).

Conclusions: Results from this study support the intricate link between macrocognitive interactions and space syntax constructs within the HCBE. These findings help to advance the m-HCBE theory for improving physical space by designing new spaces or refining existing spaces, or for adapting IPT practices to maximize formal and informal SMI opportunities; this lays the groundwork for future research to improve safety and quality for patient and family care.

The DREAMers Study: Undocumented College Students and Their Mental Health Needs

Tue, 02/07/2017 - 4:36pm

Undocumented college students face several barriers that may place them at high risk of poor mental health. Despite growing up and receiving primary and secondary (K-12) education in the U.S., many undocumented young adults cannot legally work, vote or drive in most states. Their illegal status interferes with their ability to accumulate relevant/ practical work experience leading to the inability to develop the necessary job skills before graduating high school, which can limit their employment opportunities.

Ipsilateral Lower Limb Weakness After Sarcoma Treatment: A Case Report

Mon, 02/06/2017 - 1:25pm

Case Diagnosis: Our patient experienced worsening left foot neuropathy following chemotherapy and radiation treatment for sarcoma.

Case Description: A 24-year-old man underwent local resection of a 12cm x 8cm x 14.5cm rhabdomyosarcoma in the left vastus lateralis. Then, he was treated with vincristine for 40 weeks and radiation to the left lateral thigh with a maximum dose of 50.4 Gy. The sciatic nerve was outside the target area and received a lower dose. While undergoing chemotherapy, the patient experienced bilateral dysesthesias in his fingertips and feet. He had no history of neuropathy prior to treatment. After chemotherapy was completed, these symptoms subsided in all extremities except the left foot, which developed atraumatic plantar flexion and dorsiflexion weakness, great toe extensor and flexor weakness, decreased sensation in the distal left toe to the metatarsal. Electromyography and needle conduction studies demonstrated left worse than right polyneuropathy mainly affecting the tibial and peroneal motor nerves. There was no clear evidence of a single nerve compressive lesion and repeat scans of the thigh showed no new lesion. Given the presence of milder nerve abnormalities on the right in addition to left sided weakness, the cause is likely multifactorial and temporally related to cancer treatments.

Discussions: Persistent or worsening features may appear in patients who received vincristine despite termination of treatment. The pattern is typically sensorimotor; however, this patient demonstrates mainly motor abnormalities. The left worse than right pattern could suggest radiation-induced neuropathy, but no myokymic potentials were seen. Myokymic potentials are common in radiation neuropathy, although their absence does not rule it out. Treatment included physical therapy, gabapentin, and an ankle foot orthosis.

Conclusions: Fourteen months after completing radiation and seven months after completing chemotherapy (seven months after symptom onset), the patient’s symptoms are markedly improved. This case demonstrates that neuropathy after treatment in sarcoma patients may be multifactorial.

Total Joint Replacement Prehabilitation: A Feasibility Study

Mon, 02/06/2017 - 1:25pm

Objectives: Pre-operative physical therapy has been shown to reduce post-acute care service utilization. Shifting rehabilitation to the presurgical period, referred to as prehabilitation, could result in reduced recovery time and cost. Limited access to physical therapy may prevent patients from achieving the benefits, and a standard set of independent exercises may be an alternative. We aim to assess the feasibility of an independent exercise program as a pre-surgical intervention for total hip and knee replacement.

Design: Participants were taught two exercises for hip or knee arthritis at least one week prior to surgery and instructed to perform them independently at home. Subjects were contacted three days to one month post-operatively and surveyed about discharge, frequency of exercise, and living status of alone or with others. No adverse effects were reported. Additional information was collected from the subjects’chart including age, BMI, and sex. Discharge outcomes were compared with pre-existing independent factors using univariate and multivariate analyses.

Results: A total of 80 subjects were followed with a home discharge rate of 78.75%. Univariate analyses showed that the presence of other people in the home showed a slight, but non-significant, association with differences of discharge destination. 82.1%-83.3% of patients who live with others were discharged home versus 57.1% of patients living alone (LR chi-square: 3.84, p=0.15). Multivariate analyses showed a slight, but non-significant, association between frequency of prehabilitation and discharge destination (OR=1.212; 95% CI, 0.960-1.530). BMI showed no associated difference in discharge destination.

Conclusions: Increased frequency of prehabilitation and presence of others at home showed slight associations with increased discharges to home, but were non-significant. Increased exposure to prehabilitation (duration times frequency) trends toward more frequent home discharge. Independently performed prehabilitation may be offered as an alternative pre-surgical intervention with likely little to no adverse effect. Larger numbers are needed to determine likelihood of discharge home.

Two Cases of Lyme Arthritis in Winter In New England: A Case Series

Mon, 02/06/2017 - 1:25pm

Case Diagnosis: Lyme Arthritis

Case Description: Patient 1 is a 26 year old male who presented in March with severe right knee pain and swelling for two weeks. He had a similar episode a month prior, but it resolved. The second episode progressed with pain from knee to foot and numbness on top of the foot. He had no known history of tick bites, travel, or trauma, but endorsed contact with a dog. On physical exam, he had a right knee effusion with limited ROM, diffuse joint line tenderness, positive McMurray’s, and pain with ligamentous testing. Synovial fluid of the joint showed WBC count 44,467 and was positive for Lyme. He was treated with doxycycline. MRI findings were limited to ACL laxity and inflammation.

Patient 2 is a 24 year old male who presented in December with progressive right knee and calf pain for one week. He had been fishing in the woods a few weeks prior with no trauma. Joint aspiration showed a positive Lyme PCR and WBC count 37,520, and he was treated with doxycycline. Aspiration was repeated for recurrent effusion, and an MRI was done due to persistent pain. MRI showed bone contusion, ACL laxity, and inflammation.

Discussions: Lyme disease is transmitted by Ixodes scapularis ticks, which appear in late spring and early summer; however,Lyme arthritis may occur during any season. Ticks infected with the spirochete B. burgdorferi are primarily found in the Northeastern and upper Midwestern US. B. burgdorferi strains of Lyme often disseminate to joints, tendons, or bursae early in infection.Lyme arthritis presents later, with an adaptive immune response that results in spirochetal killing.

Conclusions: Lyme arthritis can present at any time of year, and clinical suspicion in endemic regions should remain high even without a known history of tick exposure or erythema migrans rash.

Fresh Start, a postpartum weight loss intervention for diverse low-income women: design and methods for a randomized clinical trial

Thu, 02/02/2017 - 3:44pm

BACKGROUND: Overweight and obesity are prevalent among young women and are greater among minority and low-income women. The postpartum period is critical in women's weight trajectories as many women do not lose their pregnancy weight, and others lose some and then plateau or experience weight gain. Excess weight puts women at greater risk of chronic disease and thus weight loss in the postpartum period may be key to the long-term health of young women. This paper describes the design and methods of a randomized clinical trial of Fresh Start, an innovative narrative-based group intervention aimed at promoting postpartum weight loss among low-income, diverse women.

METHODS/DESIGN: Study participants were recruited from the five sites of the Women, Infants and Children (WIC) program in central Massachusetts. Participants were English-speaking, age > /= 18 years, 6 weeks to 6 months postpartum, with a body mass index (BMI) > /= 27 kg/m(2). The Fresh Start postpartum weight loss intervention, adapted from the Diabetes Prevention Program (DPP) in collaboration with WIC staff and clients, consisted of an 8-week group-based curriculum followed by nine monthly telephone calls. It included a narrative component (i.e., storytelling), group discussions, print materials and access to exercise facilities. The study is a two-arm randomized controlled trial. The control condition included print materials and access to exercise facilities. In-person assessments were conducted at baseline and at 6 and 12 months following the eight-week intervention phase.

DISCUSSION: The Fresh Start intervention translated key elements of an evidence-based weight loss protocol into a format that is hypothesized to be relevant, acceptable and effective for the target audience of low-SES postpartum women. This novel intervention was developed in collaboration with WIC to be sustainable within the context of its clinics, which reach approximately 9 million individuals per year across the U.S. via 10,000 clinics. TRIAL

REGISTRATION: clinicaltrials.gov NCT02176915. Registered 25 June 2014.

Longitudinal changes in neurodevelopmental outcomes between 18 and 36 months in children with prenatal triptan exposure: findings from the Norwegian Mother and Child Cohort Study

Thu, 02/02/2017 - 3:44pm

OBJECTIVE: This study sought to determine whether changes in neurodevelopmental outcomes between 18 and 36 months of age were associated with prenatal exposure to triptan medications, a class of 5-HT receptor agonists used in the treatment of migraine.

METHOD: Using data from the Norwegian Mother and Child Cohort Study, a prospective birth cohort that includes nearly 40% of all pregnancies in Norway from 1999 to 2008, we identified 50 469 mother-child dyads who met inclusion criteria and were present for at least one follow-up assessment at 18 or 36 months postpartum. Neurodevelopment was assessed using the Child Behaviour Checklist, the Emotionality, Activity, and Shyness Questionnaire, and the Ages and Stages Questionnaire. We used generalised estimating equations to evaluate change from 18 to 36 months for children prenatally exposed to triptans, relative to contrast groups, and used marginal structural models with inverse probability of treatment and censoring weights to address time-varying exposure and confounding as well as loss to follow-up.

RESULTS: Among eligible participants (n=50 469), 1.0% used a triptan during pregnancy, 2.0% used triptans prior to pregnancy only, 8.0% reported migraine without triptan use and 89.0% had no history of migraine. Children with prenatal triptan exposure had greater increases in emotionality (r-RR 2.18, 95% CI 1.03 to 4.53) and activity problems (r-RR 1.70, 95% CI 1.02 to 2.8) compared to children born to mothers who discontinued triptan use prior to pregnancy.

CONCLUSION: Prenatal triptan exposure was associated with changes over time in externalising-type behaviours such as emotionality and activity, but not with internalising-type behaviours.

Neighborhood environment correlates of physical activity and sedentary behavior among Latino adults in Massachusetts

Thu, 02/02/2017 - 3:44pm

BACKGROUND: U.S. Latinos experience high rates of cardio-metabolic diseases and have high rates of physical inactivity and sedentary behavior. Understanding the environmental factors associated with physical activity and sedentary behaviors among Latinos could inform future interventions. The purpose of this study is to explore the neighborhood environment correlates of physical activity and sedentary behavior in a sample of U.S. Latino adults.

METHODS: Cross-sectional study of 602 Latino adults in Lawrence, MA. Survey assessments of physical activity, sedentary behavior, and neighborhood environment were verbally administered. The neighborhood environment scale assessed violence, safety, aesthetic quality, walkability, availability of healthy foods, social cohesion, and activities with neighbors.

RESULTS: After controlling forage, gender, education, body mass index (BMI), and smoking status, two variables were associated with the outcomes of interest. Living in more walkable neighborhoods was associated with an increased likelihood of engaging in adequate levels of physical activity ( > 150 min per week, as recommended by the American College of Sports Medicine (ACSM)) (OR = 1.403, p = .018); and greater frequency of activities with neighbors was associated with greater sedentary behavior (beta = .072, p = .05).

CONCLUSIONS: There were different neighborhood environment correlates of physical activity and sedentary behavior in this Latino community. Focusing on a greater understanding of the distinct social and physical environmental correlates of physical activity and sedentary behavior may provide important insights for reducing CVD risk and health disparities among Latinos.

Multimodal Learning and Intelligent Prediction of Symptom Development in Individual Parkinson's Patients

Thu, 02/02/2017 - 3:44pm

We still do not know how the brain and its computations are affected by nerve cell deaths and their compensatory learning processes, as these develop in neurodegenerative diseases (ND). Compensatory learning processes are ND symptoms usually observed at a point when the disease has already affected large parts of the brain. We can register symptoms of ND such as motor and/or mental disorders (dementias) and even provide symptomatic relief, though the structural effects of these are in most cases not yet understood. It is very important to obtain early diagnosis, which can provide several years in which we can monitor and partly compensate for the disease's symptoms, with the help of various therapies. In the case of Parkinson's disease (PD), in addition to classical neurological tests, measurements of eye movements are diagnostic. We have performed measurements of latency, amplitude, and duration in reflexive saccades (RS) of PD patients. We have compared the results of our measurement-based diagnoses with standard neurological ones. The purpose of our work was to classify how condition attributes predict the neurologist's diagnosis. For n = 10 patients, the patient age and parameters based on RS gave a global accuracy in predictions of neurological symptoms in individual patients of about 80%. Further, by adding three attributes partly related to patient 'well-being' scores, our prediction accuracies increased to 90%. Our predictive algorithms use rough set theory, which we have compared with other classifiers such as Naive Bayes, Decision Trees/Tables, and Random Forests (implemented in KNIME/WEKA). We have demonstrated that RS are powerful biomarkers for assessment of symptom progression in PD.

Patient-Specific MRI-Based Right Ventricle Models Using Different Zero-Load Diastole and Systole Geometries for Better Cardiac Stress and Strain Calculations and Pulmonary Valve Replacement Surgical Outcome Predictions

Thu, 02/02/2017 - 3:44pm

BACKGROUND: Accurate calculation of ventricular stress and strain is critical for cardiovascular investigations. Sarcomere shortening in active contraction leads to change of ventricular zero-stress configurations during the cardiac cycle. A new model using different zero-load diastole and systole geometries was introduced to provide more accurate cardiac stress/strain calculations with potential to predict post pulmonary valve replacement (PVR) surgical outcome.

METHODS: Cardiac magnetic resonance (CMR) data were obtained from 16 patients with repaired tetralogy of Fallot prior to and 6 months after pulmonary valve replacement (8 male, 8 female, mean age 34.5 years). Patients were divided into Group 1 (n = 8) with better post PVR outcome and Group 2 (n = 8) with worse post PVR outcome based on their change in RV ejection fraction (EF). CMR-based patient-specific computational RV/LV models using one zero-load geometry (1G model) and two zero-load geometries (diastole and systole, 2G model) were constructed and RV wall thickness, volume, circumferential and longitudinal curvatures, mechanical stress and strain were obtained for analysis. Pairwise T-test and Linear Mixed Effect (LME) model were used to determine if the differences from the 1G and 2G models were statistically significant, with the dependence of the pair-wise observations and the patient-slice clustering effects being taken into consideration. For group comparisons, continuous variables (RV volumes, WT, C- and L- curvatures, and stress and strain values) were summarized as mean +/- SD and compared between the outcome groups by using an unpaired Student t-test. Logistic regression analysis was used to identify potential morphological and mechanical predictors for post PVR surgical outcome.

RESULTS: Based on results from the 16 patients, mean begin-ejection stress and strain from the 2G model were 28% and 40% higher than that from the 1G model, respectively. Using the 2G model results, RV EF changes correlated negatively with stress (r = -0.609, P = 0.012) and with pre-PVR RV end-diastole volume (r = -0.60, P = 0.015), but did not correlate with WT, C-curvature, L-curvature, or strain. At begin-ejection, mean RV stress of Group 2 was 57.4% higher than that of Group 1 (130.1+/-60.7 vs. 82.7+/-38.8 kPa, P = 0.0042). Stress was the only parameter that showed significant differences between the two groups. The combination of circumferential curvature, RV volume and the difference between begin-ejection stress and end-ejection stress was the best predictor for post PVR outcome with an area under the ROC curve of 0.855. The begin-ejection stress was the best single predictor among the 8 individual parameters with an area under the ROC curve of 0.782.

CONCLUSION: The new 2G model may be able to provide more accurate ventricular stress and strain calculations for potential clinical applications. Combining morphological and mechanical parameters may provide better predictions for post PVR outcome.

Alcohol Consumption, Left Atrial Diameter, and Atrial Fibrillation

Thu, 02/02/2017 - 3:44pm

BACKGROUND: Alcohol consumption has been associated with atrial fibrillation (AF) in several epidemiologic studies, but the underlying mechanisms remain unknown. We sought to test the hypothesis that an atrial myopathy, manifested by echocardiographic left atrial enlargement, explains the association between chronic alcohol use and AF.

METHODS AND RESULTS: We evaluated the relationship between cumulative alcohol consumption and risk of incident AF in 5220 Offspring and Original Framingham Heart Study participants (mean age 56.3 years, 54% women) with echocardiographic left atrial size measurements. The incidence of AF was 8.4 per 1000 person-years, with 1088 incident AF cases occurring over a median 6.0 years (25th-75th percentiles 4.0-8.7 years) of follow-up. After multivariable adjustment for potential confounders, every additional 10 g of alcohol per day (just under 1 drink per day) was associated with a 0.16 mm (95% CI, 0.10-0.21 mm) larger left atrial dimension. Also in multivariable adjusted analysis, every 10 g per day of alcohol consumed was associated with a 5% higher risk of developing new-onset AF (hazard ratio, 1.05; 95% CI, 1.01-1.09). An estimated 24% (95% CI, 8-75) of the association between alcohol and AF risk was explained by left atrial enlargement.

CONCLUSIONS: Our study of a large, community-based sample identified alcohol consumption as a predictor of left atrial enlargement and subsequent incident AF. Left atrial enlargement may be an intermediate phenotype along the causal pathway linking long-term alcohol consumption to AF.

Dental Calculus Stimulates Interleukin-1beta Secretion by Activating NLRP3 Inflammasome in Human and Mouse Phagocytes

Thu, 02/02/2017 - 3:44pm

Dental calculus is a mineralized deposit associated with periodontitis. The bacterial components contained in dental calculus can be recognized by host immune sensors, such as Toll-like receptors (TLRs), and induce transcription of proinflammatory cytokines, such as IL-1beta. Studies have shown that cellular uptake of crystalline particles may trigger NLRP3 inflammasome activation, leading to the cleavage of the IL-1beta precursor to its mature form. Phagocytosis of dental calculus in the periodontal pocket may therefore lead to the secretion of IL-1beta, promoting inflammatory responses in periodontal tissues. However, the capacity of dental calculus to induce IL-1beta secretion in human phagocytes has not been explored. To study this, we stimulated human polymorphonuclear leukocytes (PMNs) and peripheral blood mononuclear cells (PBMCs) with dental calculus collected from periodontitis patients, and measured IL-1beta secretion by ELISA. We found that calculus induced IL-1beta secretion in both human PMNs and PBMCs. Calculus also induced IL-1beta in macrophages from wild-type mice, but not in macrophages from NLRP3- and ASC-deficient mice, indicating the involvement of NLRP3 and ASC. IL-1beta induction was inhibited by polymyxin B, suggesting that LPS is one of the components of calculus that induces pro-IL-1beta transcription. To analyze the effect of the inorganic structure, we baked calculus at 250 degrees C for 1 h. This baked calculus failed to induce pro-IL-1beta transcription. However, it did induce IL-1beta secretion in lipid A-primed cells, indicating that the crystalline structure of calculus induces inflammasome activation. Furthermore, hydroxyapatite crystals, a component of dental calculus, induced IL-1beta in mouse macrophages, and baked calculus induced IL-1beta in lipid A-primed human PMNs and PBMCs. These results indicate that dental calculus stimulates IL-1beta secretion via NLRP3 inflammasome in human and mouse phagocytes, and that the crystalline structure has a partial role in the activation of NLRP3 inflammasome.

Regulation of X-linked gene expression during early mouse development by Rlim

Thu, 02/02/2017 - 3:44pm

Mammalian X-linked gene expression is highly regulated as female cells contain two and male one X chromosome (X). To adjust the X gene dosage between genders, female mouse preimplantation embryos undergo an imprinted form of X chromosome inactivation (iXCI) that requires both Rlim (also known as Rnf12) and the long non-coding RNA Xist. Moreover, it is thought that gene expression from the single active X is upregulated to correct for bi-allelic autosomal (A) gene expression. We have combined mouse genetics with RNA-seq on single mouse embryos to investigate functions of Rlim on the temporal regulation of iXCI and Xist. Our results reveal crucial roles of Rlim for the maintenance of high Xist RNA levels, Xist clouds and X-silencing in female embryos at blastocyst stages, while initial Xist expression appears Rlim-independent. We find further that X/A upregulation is initiated in early male and female preimplantation embryos.

Tuberculosis Susceptibility and Vaccine Protection Are Independently Controlled by Host Genotype

Thu, 02/02/2017 - 3:44pm

The outcome of Mycobacterium tuberculosis infection and the immunological response to the bacillus Calmette-Guerin (BCG) vaccine are highly variable in humans. Deciphering the relative importance of host genetics, environment, and vaccine preparation for the efficacy of BCG has proven difficult in natural populations. We developed a model system that captures the breadth of immunological responses observed in outbred individual mice, which can be used to understand the contribution of host genetics to vaccine efficacy. This system employs a panel of highly diverse inbred mouse strains, consisting of the founders and recombinant progeny of the "Collaborative Cross" project. Unlike natural populations, the structure of this panel allows the serial evaluation of genetically identical individuals and the quantification of genotype-specific effects of interventions such as vaccination. When analyzed in the aggregate, our panel resembled natural populations in several important respects: the animals displayed a broad range of susceptibility to M. tuberculosis, differed in their immunological responses to infection, and were not durably protected by BCG vaccination. However, when analyzed at the genotype level, we found that these phenotypic differences were heritable. M. tuberculosis susceptibility varied between lines, from extreme sensitivity to progressive M. tuberculosis clearance. Similarly, only a minority of the genotypes was protected by vaccination. The efficacy of BCG was genetically separable from susceptibility to M. tuberculosis, and the lack of efficacy in the aggregate analysis was driven by nonresponsive lines that mounted a qualitatively distinct response to infection. These observations support an important role for host genetic diversity in determining BCG efficacy and provide a new resource to rationally develop more broadly efficacious vaccines.

IMPORTANCE: Tuberculosis (TB) remains an urgent global health crisis, and the efficacy of the currently used TB vaccine, M. bovis BCG, is highly variable. The design of more broadly efficacious vaccines depends on understanding the factors that limit the protection imparted by BCG. While these complex factors are difficult to disentangle in natural populations, we used a model population of mice to understand the role of host genetic composition in BCG efficacy. We found that the ability of BCG to protect mice with different genotypes was remarkably variable. The efficacy of BCG did not depend on the intrinsic susceptibility of the animal but, instead, correlated with qualitative differences in the immune responses to the pathogen. These studies suggest that host genetic polymorphism is a critical determinant of vaccine efficacy and provide a model system to develop interventions that will be useful in genetically diverse populations.

Adipocyte-specific Hypoxia-inducible gene 2 promotes fat deposition and diet-induced insulin resistance

Thu, 02/02/2017 - 3:44pm

OBJECTIVE: Adipose tissue relies on lipid droplet (LD) proteins in its role as a lipid-storing endocrine organ that controls whole body metabolism. Hypoxia-inducible Gene 2 (Hig2) is a recently identified LD-associated protein in hepatocytes that promotes hepatic lipid storage, but its role in the adipocyte had not been investigated. Here we tested the hypothesis that Hig2 localization to LDs in adipocytes promotes adipose tissue lipid deposition and systemic glucose homeostasis.

METHOD: White and brown adipocyte-deficient (Hig2fl/fl x Adiponection cre+) and selective brown/beige adipocyte-deficient (Hig2fl/fl x Ucp1 cre+) mice were generated to investigate the role of Hig2 in adipose depots. Additionally, we used multiple housing temperatures to investigate the role of active brown/beige adipocytes in this process.

RESULTS: Hig2 localized to LDs in SGBS cells, a human adipocyte cell strain. Mice with adipocyte-specific Hig2 deficiency in all adipose depots demonstrated reduced visceral adipose tissue weight and increased glucose tolerance. This metabolic effect could be attributed to brown/beige adipocyte-specific Hig2 deficiency since Hig2fl/fl x Ucp1 cre+ mice displayed the same phenotype. Furthermore, when adipocyte-deficient Hig2 mice were moved to thermoneutral conditions in which non-shivering thermogenesis is deactivated, these improvements were abrogated and glucose intolerance ensued. Adipocyte-specific Hig2 deficient animals displayed no detectable changes in adipocyte lipolysis or energy expenditure, suggesting that Hig2 may not mediate these metabolic effects by restraining lipolysis in adipocytes.

CONCLUSIONS: We conclude that Hig2 localizes to LDs in adipocytes, promoting adipose tissue lipid deposition and that its selective deficiency in active brown/beige adipose tissue mediates improved glucose tolerance at 23 degrees C. Reversal of this phenotype at thermoneutrality in the absence of detectable changes in energy expenditure, adipose mass, or liver triglyceride suggests that Hig2 deficiency triggers a deleterious endocrine or neuroendocrine pathway emanating from brown/beige fat cells.

Common Statistical Pitfalls in Basic Science Research

Thu, 02/02/2017 - 3:44pm

In this review, we focused on common sources of confusion and errors in the analysis and interpretation of basic science studies. The issues addressed are seen repeatedly in the authors' editorial experience, and we hope this article will serve as a guide for those who may submit their basic science studies to journals that publish both clinical and basic science research. We have discussed issues related to sample size and power, study design, data analysis, and presentation of results. We then illustrated these issues using a set of examples from basic science research studies.

Relationship between Massachusetts Youth Screening Instrument-second version and psychiatric disorders in youths in welfare and juvenile justice institutions in Switzerland

Thu, 02/02/2017 - 3:44pm

BACKGROUND: There is growing evidence that it is important to have well-standardized procedures for identifying the mental health needs of youths in welfare and juvenile justice institutions. One of the most widely used tools for mental health screening in the juvenile justice system is the Massachusetts Youth Screening Instrument-second version (MAYSI-2). To contribute to the body of research examining the utility of the MAYSI-2 as a mental health screening tool; the first objective of the current study was to examine the relationship between the MAYSI-2 and the Schedule for Affective Disorders and Schizophrenia for School-Age Children, Present and Lifetime version (K-SADS-PL) in a sample of Swiss youths in welfare and juvenile justice institutions using a cross-sectional design. Secondly, as the sample was drawn from the French-, German- and Italian-speaking parts of Switzerland, the three languages were represented in the total sample and consequently differences between the language regions were analyzed as well. The third objective was to examine gender differences in this relationship.

METHODS: Participants were 297 boys and 149 girls (mean age = 16.2, SD = 2.5) recruited from 64 youth welfare and juvenile justice institutions in Switzerland. The MAYSI-2 was used to screen for mental health or behavioral problems that could require further evaluation. Psychiatric classification was based on the Schedule for Affective Disorders and Schizophrenia for School-Age Children, Present and Lifetime version (K-SADS-PL). Binomial logistic regression analysis was used to predict (cluster of) psychiatric disorders from MAYSI-2 scales.

RESULTS: The regression analyses revealed that the MAYSI-2 scales generally related well to their corresponding homotypic (cluster of) psychiatric disorders. For example, the alcohol/drug use scale identified the presence of any substance use disorder and the suicide ideation scale identified youths reporting suicide ideation or suicide attempts. Several MAYSI-2 scales were also related to heterotypic (cluster of) psychiatric disorders. For example, the MAYSI-2 scale alcohol/drug use, was positively related to any disruptive disorder. Furthermore, the results revealed gender differences in the relationship between the MAYSI-2 and K-SADS-PL (e.g., in the boys' subsample no MAYSI-2 scale was significantly related to any affective disorder; whereas, in the girls' subsample the MAYSI-2 scales depressed-anxious and somatic complaints were significantly related to any affective disorder).

CONCLUSIONS: Overall, The MAYSI-2 seems to serve well as a first-stage screen to identify service needs for youths in welfare and juvenile justice institutions in Switzerland. Its effectiveness to identify the presence of (cluster of) psychiatric disorders differs between genders.

Diagnostic Prevalence of Ankylosing Spondylitis Using Computerized Health Care Data, 1996 to 2009: Underrecognition in a US Health Care Setting

Thu, 02/02/2017 - 3:44pm

INTRODUCTION: Few studies have assessed the prevalence and features of axial spondyloarthritis (axSpA) and ankylosing spondylitis in diverse, population-based, community settings.

OBJECTIVES: We used computerized diagnoses to estimate the prevalence of axSpA and ankylosing spondylitis in Kaiser Permanente Northern California (KPNC).

METHODS: We identified persons aged 18 years or older with 1 or more International Classification of Diseases, Ninth Revision (ICD-9) diagnosis Code 720.X (ankylosing spondylitis and other inflammatory spondylopathies) in clinical encounter data from 1996 through 2009 to estimate the prevalence of axSpA and ankylosing spondylitis. We reviewed medical records to confirm the diagnosis in a random sample and estimated the positive predictive value of computerized data to identify confirmed cases using various case definitions.

RESULTS: In the computerized data, 5568 adults had diagnostic codes indicating axSpA. On the basis of our case-finding approach using a single physician diagnosis code for ICD-9 720.X, the point prevalence of these conditions, standardized to the 2000 US Census, was 2.26 per 1000 persons for axSpA and 1.07 per 1000 for ankylosing spondylitis. Less than half of suspected cases saw a rheumatologist. The most specific algorithm for confirmed ankylosing spondylitis required 2 or more computerized diagnoses assigned by a rheumatologist, with 67% sensitivity (95% confidence interval, 64%-69%) and 81% positive predictive value (95% confidence interval, 79%-83%).

CONCLUSIONS: Observed prevalence in the KPNC population, compared with national estimates for axSpA and ankylosing spondylitis, suggests there is substantial underrecognition of these conditions in routine clinical practice. However, use of computerized data is able to identify true cases of ankylosing spondylitis, facilitating population-based research.