Diurnally Entrained Anticipatory Behavior in Archaea

By sensing changes in one or few environmental factors biological systems can anticipate future changes in multiple factors over a wide range of time scales (daily to seasonal). This anticipatory behavior is important to the fitness of diverse species, and in context of the diurnal cycle it is overall typical of eukaryotes and some photoautotrophic bacteria but is yet to be observed in archaea. Here, we report the first observation of light-dark (LD)-entrained diurnal oscillatory transcription in up to 12% of all genes of a halophilic archaeon Halobacterium salinarum NRC-1. Significantly, the diurnally entrained transcription was observed under constant darkness after removal of the LD stimulus (free-running rhythms). The memory of diurnal entrainment was also associated with the synchronization of oxic and anoxic physiologies to the LD cycle. Our results suggest that under nutrient limited conditions halophilic archaea take advantage of the causal influence of sunlight (via temperature) on O2 diffusivity in a closed hypersaline environment to streamline their physiology and operate oxically during nighttime and anoxically during daytime

Large‐Scale Characterization of Systemic Sclerosis Serum Protein Profile: Comparison to Peripheral Blood Cell Transcriptome and Correlations With Skin/Lung Fibrosis

OBJECTIVE: To provide a large-scale assessment of serum protein dysregulations in diffuse cutaneous systemic sclerosis (dcSSc) and to investigate serum protein correlates of SSc fibrotic features. METHODS: Baseline serum protein profile of 66 participants with dcSSc enrolled in the Scleroderma: Cyclophosphamide Or Transplant trial and 66 healthy, age- and gender-matched controls was investigated. A panel of 230 proteins, including several cytokines and chemokines was determined. Whole blood gene expression profiling in concomitantly collected samples was performed. RESULTS: Mean disease duration was 2.3 years, all had interstitial lung disease (ILD), and none were treated with immunosuppressive agents at baseline visit. Ninety proteins were differentially expressed compared to controls. Similar to previous global skin transcript results, hepatic fibrosis, granulocyte and agranulocyte adhesion and diapedesis were the top over-represented pathways. Eighteen proteins correlated with modified Rodnan Skin Score (mRSS). Soluble EGFR was significantly down-regulated in dcSSc and showed the strongest negative correlation with mRSS and predicted its course, whereas Alpha 1 Antichymotrypsin was significantly up-regulated in dcSSc and showed the strongest positive correlation with mRSS. Furthermore, higher CA15.3 correlated with more severe ILD, based on lower forced vital capacity and higher high-resolution CT scores. Only 14 genes showed significant differential expression in the same direction in serum protein and whole blood RNA gene expression analyses. CONCLUSIONS: dcSSc has a distinct serum protein profile with prominent dysregulation of proteins related to fibrosis and immune cell adhesion/diapedesis. The differential expression for most serum proteins in SSc is likely to originate outside the peripheral blood cells

APACHE II Predicts Long-term Survival in COPD Patients Admitted to a General Medical Ward

OBJECTIVE: The Acute Physiology and Chronic Health Evaluation II (APACHE II) was developed to predict intensive-care unit (ICU) resource utilization. This study tested APACHE II's ability to predict long-term survival of patients with chronic obstructive pulmonary disease (COPD) admitted to general medical floors. DESIGN: We performed a retrospective cohort study of patients admitted for COPD exacerbation outside the ICU. APACHE II scores were calculated by chart review. Mortality was determined by the Social Security Death Index. We tested the association between APACHE II scores and long-term mortality with Cox regression and logistic regression. PATIENTS: The analysis included 92 patients admitted for COPD exacerbation in two Burlington, Vermont hospitals between January 1995 and June 1996. MEASUREMENTS AND MAIN RESULTS: In Cox regression, APACHE II score (hazard ratio [HR] 1.76 for each increase in a 3-level categorization, 95% confidence interval [CI] 1.16 to 2.65) and comorbidity (HR 2.58; 95% CI, 1.36 to 4.88) were associated with long-term mortality (P < .05) in the univariate analysis. After controlling for smoking history, comorbidity, and admission pCO(2), APACHE II score was independently associated with long-term mortality (HR 2.19; 95% CI, 1.27 to 3.80). In univariate logistic regression, APACHE II score (odds ratio [OR] 2.31; 95% confidence internal [CI] 1.24 to 4.30) and admission pCO(2) (OR 4.18; 95% CI, 1.15 to 15.21) were associated with death at 3 years. After controlling for smoking history, comorbidity, and admission pCO(2), APACHE II score was independently associated with death at 3 years (OR 2.62; 95% CI, 1.12 to 6.16). CONCLUSION: APACHE II score may be useful in predicting long-term mortality for COPD patients admitted outside the ICU

Integrating Behavioral Health and Primary Care (IBH-PC) to improve patient-centered outcomes in adults with multiple chronic medical and behavioral health conditions: study protocol for a pragmatic cluster-randomized control trial.

BackgroundChronic diseases that drive morbidity, mortality, and health care costs are largely influenced by human behavior. Behavioral health conditions such as anxiety, depression, and substance use disorders can often be effectively managed. The majority of patients in need of behavioral health care are seen in primary care, which often has difficulty responding. Some primary care practices are providing integrated behavioral health care (IBH), where primary care and behavioral health providers work together, in one location, using a team-based approach. Research suggests there may be an association between IBH and improved patient outcomes. However, it is often difficult for practices to achieve high levels of integration. The Integrating Behavioral Health and Primary Care study responds to this need by testing the effectiveness of a comprehensive practice-level intervention designed to improve outcomes in patients with multiple chronic medical and behavioral health conditions by increasing the practice's degree of behavioral health integration.MethodsForty-five primary care practices, with existing onsite behavioral health care, will be recruited for this study. Forty-three practices will be randomized to the intervention or usual care arm, while 2 practices will be considered "Vanguard" (pilot) practices for developing the intervention. The intervention is a 24-month supported practice change process including an online curriculum, a practice redesign and implementation workbook, remote quality improvement coaching services, and an online learning community. Each practice's degree of behavioral health integration will be measured using the Practice Integration Profile. Approximately 75 patients with both chronic medical and behavioral health conditions from each practice will be asked to complete a series of surveys to measure patient-centered outcomes. Change in practice degree of behavioral health integration and patient-centered outcomes will be compared between the two groups. Practice-level case studies will be conducted to better understand the contextual factors influencing integration.DiscussionAs primary care practices are encouraged to provide IBH services, evidence-based interventions to increase practice integration will be needed. This study will demonstrate the effectiveness of one such intervention in a pragmatic, real-world setting.Trial registrationClinicalTrials.gov NCT02868983 . Registered on August 16, 2016