Timely Questions Emerging in Chronobiology: The Circadian Clock Keeps on Ticking.

Chronobiology investigations have revealed much about cellular and physiological clockworks but we are far from having a complete mechanistic understanding of the physiological and ecological implications. Here we present some unresolved questions in circadian biology research as posed by the editorial staff and guest contributors to the Journal of Circadian Rhythms. This collection of ideas is not meant to be comprehensive but does reveal the breadth of our observations on emerging trends in chronobiology and circadian biology. It is amazing what could be achieved with various expected innovations in technologies, techniques, and mathematical tools that are being developed. We fully expect strengthening mechanistic work will be linked to health care and environmental understandings of circadian function. Now that most clock genes are known, linking these to physiological, metabolic, and developmental traits requires investigations from the single molecule to the terrestrial ecological scales. Real answers are expected for these questions over the next decade. Where are the circadian clocks at a cellular level? How are clocks coupled cellularly to generate organism level outcomes? How do communities of circadian organisms rhythmically interact with each other? In what way does the natural genetic variation in populations sculpt community behaviors? How will methods development for circadian research be used in disparate academic and commercial endeavors? These and other questions make it a very exciting time to be working as a chronobiologist.

Factors associated with ciprofloxacin-resistant Escherichia coli urinary tract infections in discharged ED patients.

BACKGROUND: We sought to identify factors associated with Escherichia coli resistance to ciprofloxacin among discharged emergency department (ED) patient visits treated for a urinary tract infection (UTI). We hypothesized that specific historical factors available upon ED presentation would be associated with increased odds of ciprofloxacin resistance in this population. METHODS: We conducted a retrospective, observational cohort study of consecutive discharged adult ED patient visits with a primary diagnosis of UTI caused by E coli to a single center from 2011 to 2014. Two investigators separately abstracted to a preconstructed data collection form the following independent variables on each included visit: patient age, sex, residence, active immunosuppressive condition or medication, chronic indwelling Foley catheter, hospitalization or antibiotic use within 90 days prior to presentation, and history of recurrent UTIs. We used multivariable logistic regression after taking into account colinearity to identify those independent variables associated with increased odds of ciprofloxacin resistance and report descriptive characteristics of the study cohort, odds ratios (ORs) with 95% confidence interval (CI) and model strength. RESULTS: Age at least 65 years (OR, 3.15; 95% CI, 1.44-6.87; P=.004), recurrent UTI (OR, 6.23; 95% CI, 2.38-16.30; P<.001), and recent hospitalization (OR, 3.99; 95% CI, 1.56-10.23; P=.004) were significantly associated with ciprofloxacin-resistant E coli UTIs in relevant visits. CONCLUSION: In this single-center study, age at least 65 years, recurrent UTI, and recent hospitalization were most clearly associated with increased odds of ciprofloxacin-resistant UTIs in discharged adult ED patient visits. If validated, these factors should suggest that alternative antimicrobial agents should be considered in the treatment of this condition among discharged adult ED patients.

Pharmacist addition to the post-ED visit review of discharge antimicrobial regimens.

OBJECTIVE: Our objective was to evaluate whether pharmacist addition to the postvisit review of discharged adult emergency department (ED) visits' prescriptions/cultures would reduce the prevalence of revised antimicrobial regimen inappropriateness. METHODS: We conducted a retrospective observational study of discharged adult ED visits to a single center with positive cultures requiring antimicrobial regimen revision (May 1 to October 31, 2012, nurse process; February 1 to July 31, 2013, nurse/pharmacist process). Investigators abstracted cohorts' medical records for demographic, ED diagnosis, original/revised antibiotic regimen, culture result, medical history, medications, and patient instruction data and determined whether the revised regimen was inappropriate based on Infectious Diseases Society of America/Centers for Disease Control and Prevention and clinical guidelines. We used the large sample z-test to compare the prevalence of revised antimicrobial regimen inappropriateness between the 2 cohorts. RESULTS: In the prepharmacist cohort, there were 411 positive ED discharge cultures. Seventy-three (17.8%; 95% confidence interval [CI], 14.1%-21.5%) required antimicrobial regimen revision; 34 of these met 1 or more level of inappropriateness (46.6%; 95% CI, 35.1%-58.0%). In the postpharmacist cohort, there were 459 positive ED discharge cultures. Seventy-five (16.3%; 95% CI, 13.0%-19.7%) required revision; 11 of these met 1 or more level of inappropriateness (14.7%; 95% CI, 6.7%-22.7%; z = 4.2; P < .0001 for comparison). CONCLUSION: In this single-center study, pharmacist addition to the postvisit review of discharged adult ED patients' prescriptions/cultures reduced the prevalence of revised antimicrobial regimen inappropriateness.

Development and validation of a food-frequency questionnaire for the determination of detailed fatty acid intakes.

OBJECTIVE: To validate a fat intake questionnaire (FIQ) developed to assess habitual dietary intake while focusing on the assessment of detailed fatty acid intake including total trans unsaturated fatty acids (TUFA). DESIGN: An 88 food item/food group FIQ was developed using a meal pattern technique. Validation was achieved by comparison with dietary intake assessed by a modified diet history (DH) in a cross-over design. Eighty-four individuals supplied adipose tissue biopsies for linoleic acid and total TUFA analysis as an independent validation of the FIQ and DH. SETTING: Medical Centre, Dublin Airport, Republic of Ireland. SUBJECTS: One hundred and five healthy volunteers (43 females and 62 males aged 23-63 years). RESULTS: Significant correlations (P<0.0005) were achieved for intakes of energy (0.78), total fat (0.77), saturated fat (0.77), monounsaturated fat (0.63), polyunsaturated fat (0.73), TUFA (0.67) and linoleic acid (0.71) assessed by the FIQ compared with the DH. Linoleic acid intake assessed by the FIQ and the DH was significantly correlated with adipose tissue concentrations (r=0.58 and 0.49, respectively; P<0.005); however, total TUFA intake was poorly correlated with adipose tissue concentrations (r=0.17 and 0.10 for FIQ and DH, respectively). CONCLUSIONS: The FIQ compared favourably with the DH in assessing habitual diet, in particular fatty acid intake. In addition, the FIQ was successfully validated against the linoleic acid composition of adipose tissue, an independent biomarker of relative fatty acid status. The FIQ could therefore be used as an alternative to the DH as it is a shorter, less labour-intensive method.