Non-surgical management for air injection injury to the hand, a case report.

We present a case a high pressure air injection injury to the index finger with air extension proximal to the elbow. This patient was treated non-surgically with close observation. At 3 year follow-up, no lasting deficits or complications were noted and radiographs revealed complete resolution of the air tissue dissection.

The pesticide chlorpyrifos promotes obesity by inhibiting diet-induced thermogenesis in brown adipose tissue.

Obesity results from a caloric imbalance between energy intake, absorption and expenditure. In both rodents and humans, diet-induced thermogenesis contributes to energy expenditure and involves the activation of brown adipose tissue (BAT). We hypothesize that environmental toxicants commonly used as food additives or pesticides might reduce BAT thermogenesis through suppression of uncoupling protein 1 (UCP1) and this may contribute to the development of obesity. Using a step-wise screening approach, we discover that the organophosphate insecticide chlorpyrifos suppresses UCP1 and mitochondrial respiration in BAT at concentrations as low as 1 pM. In mice housed at thermoneutrality and fed a high-fat diet, chlorpyrifos impairs BAT mitochondrial function and diet-induced thermogenesis, promoting greater obesity, non-alcoholic fatty liver disease (NAFLD) and insulin resistance. This is associated with reductions in cAMP; activation of p38MAPK and AMPK; protein kinases critical for maintaining UCP1 and mitophagy, respectively in BAT. These data indicate that the commonly used pesticide chlorpyrifos, suppresses diet-induced thermogenesis and the activation of BAT, suggesting its use may contribute to the obesity epidemic.

Glass surface evolution following gas adsorption and particle deposition from indoor cooking events as probed by microspectroscopic analysis.

Indoor surfaces are extremely diverse and their interactions with airborne compounds and aerosols influence the lifetime and reactivity of indoor emissions. Direct measurements of the physical and chemical state of these surfaces provide insights into the underlying physical and chemical processes involving surface adsorption, surface partitioning and particle deposition. Window glass, a ubiquitous indoor surface, was placed vertically during indoor activities throughout the House Observations of Microbial and Environmental Chemistry (HOMEChem) campaign and then analyzed to measure changes in surface morphology and surface composition. Atomic force microscopy-infrared (AFM-IR) spectroscopic analyses reveal that deposition of submicron particles from cooking events is a contributor to modifying the chemical and physical state of glass surfaces. These results demonstrate that the deposition of glass surfaces can be an important sink for organic rich particles material indoors. These findings also show that particle deposition contributes enough organic matter from a single day of exposure equivalent to a uniform film up to two nanometers in thickness, and that the chemical distinctness of different indoor activities is reflective of the chemical and morphological changes seen in these indoor surfaces. Comparison of the experimental results to physical deposition models shows variable agreement, suggesting that processes not captured in physical deposition models may play a role in the sticking of particles on indoor surfaces.

Development of a non-radioactive screening assay to detect chemicals disrupting the human sodium iodide symporter activity.

Adequate concentration of iodide ions within thyroid epithelial cells, which is mediated by the sodium iodide symporter (NIS), is essential for proper thyroid hormone synthesis. Inhibition of NIS activity represents a potential mechanism by which goitrogens/toxicants can disrupt thyroid hormone physiology. It is necessary to develop a rapid, simple, inexpensive and sensitive screening assay to identify chemicals affecting NIS function. The current study compares the sensitivities of non-radioactive Sandell-Kolthoff (SK) reaction and radioactive iodide uptake (RAIU) in a previously described NIS assay. The EPAhNIS cell line (HEK293T stably transfected to over-express the human NIS) was tested with the reference NIS inhibitor (sodium perchlorate) across multiple log concentration range. The results from SK reaction in EPAhNIS cells showed similar performance to published RAIU results from the same cell line, in terms of assay screening coefficient (Z') and variability (CV). Results from the reference chemicals tested in EPAhNIS cells revealed that SK reaction yielded IC50 and selectivity scores consistent with those observed for RAIU. However, RAIU seems marginally more sensitive than the SK reaction, as RAIU consistently detected weaker NIS inhibitors among the test chemicals. We developed a second hNIS assay based on the MCF-7 cell line. Applying reference anions and chemicals to MCF7hNIS cells, we found that in comparison with results from EPAhNIS cells, the SK reaction with MCF7hNIS: 1) yielded similar Z' and CV; 2) had similar IC50 and selectivity scores for reference chemicals; 3) identified more NIS inhibitors among reference chemicals than SK reaction, but less than the RAIU assay in EPAhNIS cells. In conclusion, the SK reaction can be used with both EPAhNIS and MCF7hNIS cells to measure iodide uptake and identify NIS inhibitors, except for those presenting an extremely weak potency.

Opportunities to improve measurement-based care practices in mental health care systems: A case example of electronic mental health screening and measurement.

INTRODUCTION: Measurement-based care (MBC) involves the systematic collection of data to inform clinical decision-making and monitor treatment outcomes. In addition to benefitting patients and providers, data on MBC implementation can also be used to inform quality improvement efforts within existing health care systems. METHOD: The method was retrospective chart review. We collected data on electronic mental health (MH) screens and symptom measures recorded by MH providers. Patients were 28,376 veterans who received MH services in a northeastern region. RESULTS: Although rates varied by MH condition and clinic type, screening for alcohol misuse, depression, and posttraumatic stress disorder appeared to occur with regularity. MH symptom measurement was less frequent than screening but included measures of alcohol and substance use, posttraumatic stress disorder, depression, and suicidal ideation. Patient demographics (e.g., age, military service era, sex, MH diagnosis) and frequency of clinic contact emerged as significant predictors of symptom measurement. DISCUSSION: In this article, we illustrate how data on MH screening and measurement can be organized, analyzed, and interpreted to identify opportunities to enhance MBC practices in MH care. We conclude with a discussion of how large data set analyses can contribute to programmatic MBC initiatives. (PsycINFO Database Record (c) 2018 APA, all rights reserved).

Ingested foreign body mimicking acute appendicitis.

INTRODUCTION: The incidence of acute appendicitis is approximately 250,000 cases per year in the United States with a lifetime risk of 7% (Gupta & Dupuy, 1997). However, despite strongly associated clinical signs, diagnostic accuracy based on history and physical exam alone is only 70% (Jess et al., 1981). This is in large part due to the multitude of mimics found in the differential diagnosis of appendicitis. As a result highly sensitive imaging such as computed tomography scan has become standard of care. PRESENTATION OF CASE: We present a case of an otherwise healthy 20year old male presenting to the emergency department with acute onset of right lower quadrant pain and leukocytosis consistent with a diagnosis of appendicitis. Ultrasonography was grossly negative as was a computed tomography scan. Given the peritoneal nature of the patient's abdominal exam, general surgery was consulted. The patient was taken for exploratory laparoscopy where a long, thin, metallic foreign body was found to have perforated the small intestine. DISCUSSION: Discussion includes a literature review of computed tomography negative appendicitis, as well as the frequency of foreign body mimicking appendicitis. This case demonstrates the importance of the clinical exam even in the face of negative highly sensitive imaging modalities. CONCLUSION: In conclusion, there are several mimics of acute appendicitis and we present an unusual case of a foreign body mimicking this disorder in a young person. Highly sensitive imaging coupled with history and physical examination remains the standard of care for diagnosing appendicitis; however, clinical acumen must be utilized to formulate a broad differential.

Innervation of the Long Head of the Triceps Brachii in Humans-A Fresh Look.

The triceps brachii muscle occupies the posterior compartment of the arm in humans and has three heads. The lateral and medial heads originate from the humerus and the long head arises from the infraglenoid tubercle of the scapula. All heads form a common tendon that inserts onto the olecranon and the deep antebrachial fascia on each side of it. Each head receives its own motor branch, which all are thought to originate from the radial nerve. However, several studies reported that the motor branch of the long head of the triceps (LHT) arises from the axillary nerve or the posterior cord. Here, we dissected 27 triceps in 15 cadavers to analyze the innervation of the LHT and found only radial innervation, which contradicts those studies. We examined studies reporting that the motor branch to the LHT in humans does not arise from the radial nerve as well as studies of the triceps in primates. Occasional variations of the innervation of skeletal muscles are normal, but a change of principal motor innervation from radial to axillary nerve has important implications. This is because the axillary nerve is often involved during shoulder injuries. The precise identification of the prevalence of axillary versus radial innervation is therefore clinically relevant for surgery, nerve drafting, and occupational and physical therapy. We conclude that the primary motor branch to the LHT arises from the radial nerve but axillary/posterior cord innervations occur occasionally. We suggest the development of a standard methodology for further studies. Anat Rec, 301:473-483, 2018. © 2018 Wiley Periodicals, Inc.

Improving Readiness and Reducing Costs: An Analysis of Factors That Influence Site Selection for Army Outpatient Surgical Services.

EXECUTIVE SUMMARY: The variable costs of providing surgical procedures for military beneficiaries are greater when care is rendered in the civilian purchased care network than when provided at a direct care military treatment facility (MTF). To reduce healthcare-related costs, retaining surgical services is a priority at MTFs across the U.S. Army Medical Command. This study is the first to identify factors significantly associated with outpatient surgical service site selection in the military health system (MHS). We analyzed 1,000,305 patient encounters in fiscal year 2014, of which 970,367 were direct care encounters and 29,938 were purchased care encounters. We used multiple binomial logistic regression to assess and compare the odds of site selection at a purchased care facility and an MTF. We found that an increase in provider administrative time (OR = 1.024, p < .001) and an increase in case complexity (OR = 1.334, p < .001) were associated with increased odds that an outpatient surgical service was provided in a purchased care setting. The increased odds that highly complex cases were seen in purchased care has the potential to affect the medical readiness of military providers and the efficacy of graduate medical education programs. Healthcare administrators can use the results of this study to develop and implement MTF level policies to enhance outpatient surgical service practices in the Army medical system. These efforts may reduce costs and increase military provider medical readiness.

Hepatic miRNA profiles and thyroid hormone homeostasis in rats exposed to dietary potassium perfluorooctanesulfonate (PFOS).

Perfluorooctanesulfonate (PFOS) has been widely used in a variety of industrial and commercial applications as a surfactant and stain repellent. PFOS causes liver damage (including liver tumors) in experimental animals, primarily via interaction with PPARα and CAR/PXR. We investigated the involvement of microRNAs (miRNAs) in PFOS-induced hepatotoxicity, and mechanisms involved in abnormal thyroid hormone (TH) homeostasis, in the livers of adult male rats exposed in feed to 50mg PFOS/kg diet for 28 days. PFOS-treated rats exhibited expected histopathological and clinical chemistry changes, and global gene expression changes consistent with the involvement of PPARα and CAR/PXR. Thirty-eight miRNAs were significantly altered. Three members of the miR-200 family were the most increased, while miR-122-5p and miR-21-5p were the most decreased, in PFOS-treated rats. Expression of the miR-23b-3p/27b-3p/24-3p cluster also decreased in PFOS-treated animals. Pathway analysis of miRNAs and associated gene expression changes suggests involvement of epithelial to mesenchymal transition (EMT), which is a primary process of tumor cell motility and cancer metastasis. Our analysis also revealed transcripts that may mediate PFOS-induced effects on TH homeostasis including: activation of the CAR/PXR pathway, phase II/III enzymes, and deiodinase. These changes are consistent with low serum TH due to enhanced metabolic clearance of TH. However, most TH hepatic target genes were not altered in a manner consistent with reduced TH signaling, suggesting that PFOS exposure did not induce functional hypothyroidism. Collectively, the study suggests an important role for miRNAs in PFOS-induced hepatotoxicity and provides insight into the effects of PFOS on TH homeostasis.

Toxicogenomic assessment of liver responses following subchronic exposure to furan in Fischer F344 rats.

Furan is a widely used industrial chemical and a contaminant in heated foods. Chronic furan exposure causes cholangiocarcinoma and hepatocellular tumors in rats at doses of 2 mg/kg bw/day or greater, with gender differences in frequency and severity. The hepatic transcriptional alterations induced by low doses of furan (doses below those previously tested for induction of liver tumors) and the potential mechanisms underlying gender differences are largely unexplored. We used DNA microarrays to examine the global hepatic mRNA and microRNA transcriptional profiles of male and female rats exposed to 0, 0.03, 0.12, 0.5 or 2 mg/kg bw/day furan over 90 days. Marked gender differences in gene expression responses to furan were observed, with many more altered genes in exposed males than females, confirming the increased sensitivity of males even at the low doses. Pathway analysis supported that key events in furan-induced liver tumors in males include gene expression changes related to oxidative stress, apoptosis and inflammatory response, while pathway changes in females were consistent with primarily adaptive responses. Pathway benchmark doses (BMDs) were estimated and compared to relevant apical endpoints. Transcriptional pathway BMDs could only be examined in males. These median BMDs ranged from 0.08 to 1.43 mg/kg bw/day and approximated those derived from traditional histopathology. MiR-34a (a P53 target) was the only microRNA significantly increased at the 2 mg/kg bw/day, providing evidence to support the importance of apoptosis and cell proliferation in furan hepatotoxicity. Overall, this study demonstrates the use of transcriptional profiling to discern mode of action and mechanisms involved in gender differences.

A novel angiotensin I-converting enzyme mutation (S333W) impairs N-domain enzymatic cleavage of the anti-fibrotic peptide, AcSDKP.

BACKGROUND: Angiotensin I-converting enzyme (ACE) has two functional N- and C-domain active centers that display differences in the metabolism of biologically-active peptides including the hemoregulatory tetrapeptide, Ac-SDKP, hydrolysed preferentially by the N domain active center. Elevated Ac-SDKP concentrations are associated with reduced tissue fibrosis. RESULTS: We identified a patient of African descent exhibiting unusual blood ACE kinetics with reduced relative hydrolysis of two synthetic ACE substrates (ZPHL/HHL ratio) suggestive of the ACE N domain center inactivation. Inhibition of blood ACE activity by anti-catalytic mAbs and ACE inhibitors and conformational fingerprint of blood ACE suggested overall conformational changes in the ACE molecule and sequencing identified Ser333Trp substitution in the N domain of ACE. In silico analysis demonstrated S333W localized in the S1 pocket of the active site of the N domain with the bulky Trp adversely affecting binding of ACE substrates due to steric hindrance. Expression of mutant ACE (S333W) in CHO cells confirmed altered kinetic properties of mutant ACE and conformational changes in the N domain. Further, the S333W mutant displayed decreased ability (5-fold) to cleave the physiological substrate AcSDKP compared to wild-type ACE. CONCLUSIONS AND SIGNIFICANCE: A novel Ser333Trp ACE mutation results in dramatic changes in ACE kinetic properties and lowered clearance of Ac-SDKP. Individuals with this mutation (likely with significantly increased levels of the hemoregulatory tetrapeptide in blood and tissues), may confer protection against fibrosis.

Iron deficiency modifies gene expression variation induced by augmented hypoxia sensing.

In congenital Chuvash polycythemia (CP), VHL(R200W) homozygosity leads to elevated hypoxia inducible factor (HIF) levels at normoxia. CP is often treated by phlebotomy resulting in iron deficiency, permitting us to examine the separate and synergistic effects of iron deficiency and HIF signaling on gene expression. We compared peripheral blood mononuclear cell gene expression profiles of eight VHL(R200W) homozygotes with 17 wildtype individuals with normal iron status and found 812 up-regulated and 2120 down-regulated genes at false discovery rate of 0.05. Among differential genes we identified three major gene regulation modules involving induction of innate immune responses, alteration of carbohydrate and lipid metabolism, and down-regulation of cell proliferation, stress-induced apoptosis and T-cell activation. These observations suggest molecular mechanisms for previous observations in CP of lower blood sugar without increased insulin and low oncogenic potential. Studies including 16 additional VHL(R200W) homozygotes with low ferritin indicated that iron deficiency enhanced the induction effect of VHL(R200W) for 50 genes including hemoglobin synthesis loci but suppressed the effect for 107 genes enriched for HIF-2 targets. This pattern is consistent with potentiation of HIF-1α protein stability by iron deficiency but a trend for down-regulation of HIF-2α translation by iron deficiency overriding an increase in HIF-2α protein stability.

A program to improve detection of undiagnosed dementia in primary care and its association with healthcare utilization.

OBJECTIVE: Alzheimer's disease and related dementias are common and costly, with increased healthcare utilization for patients with these disorders. The current study describes a novel dementia detection program for veterans and examines whether program-eligible patients have higher healthcare utilization than age-matched comparison patients. DESIGN: Using a telephone-based case-finding approach, the detection program used risk factors available in the electronic medical record (EMR) and telephone-based brief cognitive screening. Holding illness severity constant, dementia detection and healthcare utilization were compared across age-matched groups with and without program risk factors. SETTING: Five Veterans Affairs Healthcare Network Upstate New York primary care clinics. PARTICIPANTS: Veterans aged 70 years and older. MEASUREMENTS: EMR data and the Charlson comorbidity index. RESULTS: Program-eligible patients (n = 5,333) demonstrated significantly greater levels of medical comorbidity relative to comparison patients and were on average more than twice as likely to be admitted to the hospital. They also had nearly double the number of outpatient visits to several services. Similar patterns were seen in those who screened positive on a brief cognitive measure, compared with those who screened negative. CONCLUSIONS: A novel program using EMR data to assist in the detection of newly diagnosed dementia in a clinical setting was found to be useful in identifying older veterans with multiple comorbid medical conditions and increased utilization of hospital and clinic services. Results suggest undetected cognitive impairment and dementia may significantly contribute to healthcare utilization and costs of care in older veterans.

Ultraporous ß-tricalcium phosphate alone or combined with bone marrow aspirate for benign cavitary lesions: comparison in a prospective randomized clinical trial.

BACKGROUND: Ultraporous ß-tricalcium phosphate (TCP) synthetic graft material (Vitoss; Orthovita) persists for a year or longer in some cases. In this study, we prospectively examined healing of cavitary defects filled with TCP versus TCP and bone marrow aspirate (TCP/BM) with the hypothesis that bone-marrow aspirate speeds incorporation of bone graft substitute. METHODS: Fifty-five patients with a benign bone lesion undergoing surgical curettage were randomized to receive TCP (N = 26; mean duration of follow-up [and standard deviation], 20.2 ± 7.2 months) or TCP/BM (N = 29; mean duration of follow-up, 18.0 ± 7.7 months). There were no significant differences between the groups with regard to demographic or defect parameters. Clinical and radiographic evaluations were done at 1.5, three, six, twelve, eighteen, and twenty-four months, and computed tomography [CT] scans were performed at twelve months. An independent radiographic review was done to evaluate six parameters. RESULTS: There was a significant (p < 0.001) increase in trabeculation through the defect and graft resorption with decreases in the persistence of the graft in both soft tissue and the defect as well as a decreased radiolucent rim around the graft over time. No significant differences were observed between the TCP and TCP/BM groups in terms of any radiographic parameter. No complications related to the graft material or BM were identified. CONCLUSIONS: While significant improvements in radiographic parameters were observed in both TCP groups over two years of follow-up, the addition of BM was not found to provide any significant benefit. Results should not be extrapolated to other bone graft substitutes used for this purpose.

Genetic variants associated with idiopathic pulmonary fibrosis susceptibility and mortality: a genome-wide association study.

BACKGROUND: Idiopathic pulmonary fibrosis (IPF) is a devastating disease that probably involves several genetic loci. Several rare genetic variants and one common single nucleotide polymorphism (SNP) of MUC5B have been associated with the disease. Our aim was to identify additional common variants associated with susceptibility and ultimately mortality in IPF. METHODS: First, we did a three-stage genome-wide association study (GWAS): stage one was a discovery GWAS; and stages two and three were independent case-control studies. DNA samples from European-American patients with IPF meeting standard criteria were obtained from several US centres for each stage. Data for European-American control individuals for stage one were gathered from the database of genotypes and phenotypes; additional control individuals were recruited at the University of Pittsburgh to increase the number. For controls in stages two and three, we gathered data for additional sex-matched European-American control individuals who had been recruited in another study. DNA samples from patients and from control individuals were genotyped to identify SNPs associated with IPF. SNPs identified in stage one were carried forward to stage two, and those that achieved genome-wide significance (p<5 × 10(-8)) in a meta-analysis were carried forward to stage three. Three case series with follow-up data were selected from stages one and two of the GWAS using samples with follow-up data. Mortality analyses were done in these case series to assess the SNPs associated with IPF that had achieved genome-wide significance in the meta-analysis of stages one and two. Finally, we obtained gene-expression profiling data for lungs of patients with IPF from the Lung Genomics Research Consortium and analysed correlation with SNP genotypes. FINDINGS: In stage one of the GWAS (542 patients with IPF, 542 control individuals matched one-by-one to cases by genetic ancestry estimates), we identified 20 loci. Six SNPs reached genome-wide significance in stage two (544 patients, 687 control individuals): three TOLLIP SNPs (rs111521887, rs5743894, rs5743890) and one MUC5B SNP (rs35705950) at 11p15.5; one MDGA2 SNP (rs7144383) at 14q21.3; and one SPPL2C SNP (rs17690703) at 17q21.31. Stage three (324 patients, 702 control individuals) confirmed the associations for all these SNPs, except for rs7144383. Linkage disequilibrium between the MUC5B SNP (rs35705950) and TOLLIP SNPs (rs111521887 [r(2)=0·07], rs5743894 [r(2)=0·16], and rs5743890 [r(2)=0·01]) was low. 683 patients from the GWAS were included in the mortality analysis. Individuals who developed IPF despite having the protective TOLLIP minor allele of rs5743890 carried an increased mortality risk (meta-analysis with fixed-effect model: hazard ratio 1·72 [95% CI 1·24-2·38]; p=0·0012). TOLLIP expression was decreased by 20% in individuals carrying the minor allele of rs5743890 (p=0·097), 40% in those with the minor allele of rs111521887 (p=3·0 × 10(-4)), and 50% in those with the minor allele of rs5743894 (p=2·93 × 10(-5)) compared with homozygous carriers of common alleles for these SNPs. INTERPRETATION: Novel variants in TOLLIP and SPPL2C are associated with IPF susceptibility. One novel variant of TOLLIP, rs5743890, is also associated with mortality. These associations and the reduced expression of TOLLIP in patients with IPF who carry TOLLIP SNPs emphasise the importance of this gene in the disease. FUNDING: National Institutes of Health; National Heart, Lung, and Blood Institute; Pulmonary Fibrosis Foundation; Coalition for Pulmonary Fibrosis; and Instituto de Salud Carlos III.

Peripheral blood gene expression as a novel genomic biomarker in complicated sarcoidosis.

Sarcoidosis, a systemic granulomatous syndrome invariably affecting the lung, typically spontaneously remits but in ~20% of cases progresses with severe lung dysfunction or cardiac and neurologic involvement (complicated sarcoidosis). Unfortunately, current biomarkers fail to distinguish patients with remitting (uncomplicated) sarcoidosis from other fibrotic lung disorders, and fail to identify individuals at risk for complicated sarcoidosis. We utilized genome-wide peripheral blood gene expression analysis to identify a 20-gene sarcoidosis biomarker signature distinguishing sarcoidosis (n = 39) from healthy controls (n = 35, 86% classification accuracy) and which served as a molecular signature for complicated sarcoidosis (n = 17). As aberrancies in T cell receptor (TCR) signaling, JAK-STAT (JS) signaling, and cytokine-cytokine receptor (CCR) signaling are implicated in sarcoidosis pathogenesis, a 31-gene signature comprised of T cell signaling pathway genes associated with sarcoidosis (TCR/JS/CCR) was compared to the unbiased 20-gene biomarker signature but proved inferior in prediction accuracy in distinguishing complicated from uncomplicated sarcoidosis. Additional validation strategies included significant association of single nucleotide polymorphisms (SNPs) in signature genes with sarcoidosis susceptibility and severity (unbiased signature genes - CX3CR1, FKBP1A, NOG, RBM12B, SENS3, TSHZ2; T cell/JAK-STAT pathway genes such as AKT3, CBLB, DLG1, IFNG, IL2RA, IL7R, ITK, JUN, MALT1, NFATC2, PLCG1, SPRED1). In summary, this validated peripheral blood molecular gene signature appears to be a valuable biomarker in identifying cases with sarcoidoisis and predicting risk for complicated sarcoidosis.

A novel molecular signature for elevated tricuspid regurgitation velocity in sickle cell disease.

RATIONALE: An increased tricuspid regurgitation jet velocity (TRV > 2.5 m/s) and pulmonary hypertension defined by right heart catheterization both independently confer increased mortality in sickle cell disease (SCD). OBJECTIVES: We explored the usefulness of peripheral blood mononuclear cell-derived gene signatures as biomarkers for an elevated TRV in SCD. METHODS: Twenty-seven patients with SCD underwent echocardiography and peripheral blood mononuclear cell isolation for expression profiling and 112 patients with SCD were genotyped for single-nucleotide polymorphisms. MEASUREMENTS AND MAIN RESULTS: Genome-wide gene and miRNA expression profiles were correlated against TRV, yielding 631 transcripts and 12 miRNAs. Support vector machine analysis identified a 10-gene signature including GALNT13 (encoding polypeptide N-acetylgalactosaminyltransferase 13) that discriminates patients with and without increased TRV with 100% accuracy. This finding was then validated in a cohort of patients with SCD without (n = 10) and with pulmonary hypertension (n = 10, 90% accuracy). Increased TRV-related miRNAs revealed strong in silico binding predictions of miR-301a to GALNT13 corroborated by microarray analyses demonstrating an inverse correlation between their expression. A genetic association study comparing patients with an elevated (n = 49) versus normal (n = 63) TRV revealed five significant single-nucleotide polymorphisms within GALNT13 (P < 0.005), four trans-acting (P < 2.1 × 10(-7)) and one cis-acting (P = 0.6 × 10(-4)) expression quantitative trait locus upstream of the adenosine-A2B receptor gene (ADORA2B). CONCLUSIONS: These studies validate the clinical usefulness of genomic signatures as potential biomarkers and highlight ADORA2B and GALNT13 as potential candidate genes in SCD-associated elevated TRV.

Group diabetes education administered through telemedicine: tools used and lessons learned.

OBJECTIVE: To describe the use of telemedicine for teaching group diabetes education classes to individuals with diabetes mellitus in a rural medically underserved area. SUBJECTS AND METHODS: Adults with diabetes from a rural area served by Oswego Hospital in upstate New York were asked to participate in this study. Volunteers received diabetes education through real-time teleconferencing (n=27) by joining age- and sex-matched patients from the Joslin Diabetes Center, Syracuse, NY, in our "Living with Diabetes Class" (n=39). The two 3-h sessions offered comprehensive diabetes education by a diabetes nurse educator, dietitian, and exercise physiologist. These sessions were followed in 3 months by a 3-h follow-up class. Each group receiving tele-education consisted of two or three patients with diabetes. RESULTS: The hemoglobin A1c test (a blood test that estimates the overall average glucose levels over the past 3 months) improved in the face-to-face and the telemedicine groups. There was no significant change in weight between groups. Each group had significant improvements in scores on the Problem Areas In Diabetes survey, which is a measure of emotional functioning in diabetes. Diabetes treatment satisfaction as measured in the Diabetes Treatment Satisfaction Questionnaire improved in the face-to-face group but not in the telemedicine group. Although the face-to-face group had significantly higher scores in the Diabetes Treatment Satisfaction Questionnaire, the telemedicine group was highly satisfied with the services provided. CONCLUSIONS: Telemedicine offers an effective alternative approach for providing group diabetes education to individuals with poor access to diabetes education programs.

Diabetes prevention and control in the workplace: a pilot project for county employees.

OBJECTIVES: To improve nutrition and physical activity of county employees and promote weight loss. DESIGN: Random assignment to begin the program when first offered or after 3 months ("wait control" group). SETTING: Worksite. PARTICIPANTS: Onondaga County employees (n = 45) at risk for diabetes (n = 35) or with diabetes (n = 10). Mean (±SD) age = 51.2 (± 8.0) years and body mass index (BMI) = 37.3 ± (6.8 kg/m). INTERVENTION: Twelve weekly healthy lifestyle sessions based on the Diabetes Prevention Program curriculum, followed by monthly sessions for up to 12 months. OUTCOMES: Medical: Weight, BMI, waist circumference, blood pressure, fasting glucose, lipid, and hemoglobin A1c levels. Psychosocial/behavioral: Health-related quality of life Short Form-12, Impact of Weight on Quality of Life Scale), physical activity (International Physical Activity Questionnaire), eating behavior (3-Factor Eating Questionnaire, National Cancer Institute Fat Screener), job satisfaction. RESULTS: The intervention group lost significant weight compared to the wait control group over the first 3 months (mean [95% CI], -2.23 kg [-3.5 to 0.97]) vs [+ 0.73 kg (+0.17 to +1.28)], with a decrease in BMI (P < .001) and waist circumference (P = .004), an increase in physical activity (International Physical Activity Questionnaire, P = .011) and lower dietary fat intake (P = .018). Over 12 months, 22.5% (9/40) lost more than 5% body weight and 12.5% (5/40) lost more than 7% body weight. After the first 3 months, there was gradual partial weight regain but reduction in waist circumference was maintained. The intervention group demonstrated significant improvement in Impact of Weight on Quality of Life Scale (P < .001), 3-Factor Eating (cognitive restraint P < .001, uncontrolled eating P = .003, and emotional eating P = .001), International Physical Activity Questionnaire (P = .011), and Short Form-12 Physical Component Summary (P = .048). No improvements were observed in blood pressure, lipid, hemoglobin A1c, or glucose levels. Job satisfaction was inversely related to BMI at baseline (P = .001) with a trend for improvement with the modest weight loss. CONCLUSIONS: A worksite intervention program can help government employees adopt healthier lifestyles and achieve modest weight loss.

Low levels of the herbicide atrazine alter sex ratios and reduce metamorphic success in Rana pipiens tadpoles raised in outdoor mesocosms.

BACKGROUND: There are conflicting reports regarding the effects of atrazine (ATZ) on amphibian development. Therefore, further studies are needed to examine the potential mechanisms of action of ATZ in amphibians. OBJECTIVES: Our aim in this study was to determine whether low concentrations of ATZ affect gonadal development and metamorphosis in the Northern leopard frog, Rana pipiens. METHODS: Tadpoles were exposed in outdoor mesocosms to nominal concentrations of 0.1 and 1.8 microg/L of formulated ATZ from Gosner stage 27 (G27) to metamorphic climax (G42). Exposure to 17alpha-ethinylestradiol (EE2; 1.5 microg/L) provided a positive control for induction of testicular oocytes in males. Endocrine-related gene expression and gonadal histopathology were examined at G42 and in a subset of premetamorphic G34 tadpoles that failed to metamorphose. RESULTS: Gonadal gross morphology revealed that the 1.8-microg/L ATZ treatment produced 20% more females compared with the control. Histologic analysis revealed that 22% of EE2-treated males had testicular oocytes, whereas none were observed in any animals from the control or either ATZ groups. ATZ increased brain estrogen receptor alpha mRNA to 2.5 times that of the control at premetamorphosis and altered liver levels of 5beta-reductase activity at metamorphosis. In contrast, brain aromatase mRNA level and activity did not change. ATZ treatments significantly reduced metamorphic success (number of animals reaching metamorphosis) without affecting body weight, snout-vent length, or age at metamorphosis. Gene expression analysis indicated that ATZ decreased the expression of deiodinase type 3 in the tail at premetamorphosis. CONCLUSIONS: Our study indicates that exposure to low concentrations of ATZ in experimental mesocosms alters gonadal differentiation and metamorphosis in developing R. pipiens.