Cerenkov Radiation Energy Transfer (CRET) Imaging: A Novel Method for Optical Imaging of PET Isotopes in Biological Systems

Positron emission tomography (PET) allows sensitive, non-invasive analysis of the distribution of radiopharmaceutical tracers labeled with positron (β(+))-emitting radionuclides in small animals and humans. Upon β(+) decay, the initial velocity of high-energy β(+) particles can momentarily exceed the speed of light in tissue, producing Cerenkov radiation that is detectable by optical imaging, but is highly absorbed in living organisms.To improve optical imaging of Cerenkov radiation in biological systems, we demonstrate that Cerenkov radiation from decay of the PET isotopes (64)Cu and (18)F can be spectrally coupled by energy transfer to high Stokes-shift quantum nanoparticles (Qtracker705) to produce highly red-shifted photonic emissions. Efficient energy transfer was not detected with (99m)Tc, a predominantly γ-emitting isotope. Similar to bioluminescence resonance energy transfer (BRET) and fluorescence resonance energy transfer (FRET), herein we define the Cerenkov radiation energy transfer (CRET) ratio as the normalized quotient of light detected within a spectral window centered on the fluorophore emission divided by light detected within a spectral window of the Cerenkov radiation emission to quantify imaging signals. Optical images of solutions containing Qtracker705 nanoparticles and [(18)F]FDG showed CRET ratios in vitro as high as 8.8±1.1, while images of mice with subcutaneous pseudotumors impregnated with Qtracker705 following intravenous injection of [(18)F]FDG showed CRET ratios in vivo as high as 3.5±0.3.Quantitative CRET imaging may afford a variety of novel optical imaging applications and activation strategies for PET radiopharmaceuticals and other isotopes in biomaterials, tissues and live animals

Adult attention deficit hyperactivity disorder symptom profiles and concurrent problems with alcohol and cannabis: Sex differences in a representative, population survey

Background: Adult attention deficit hyperactivity disorder (ADHD) shows a robust association with alcohol and cannabis misuse, and these relationships are expressed differently in males and females. Manifestation of specific ADHD symptom profiles, even in the absence of the full disorder, may also be related to problems with alcohol and cannabis, although these relationships have not been investigated in epidemiological studies. To address this question, we studied the sex-specific associations of ADHD symptomatology with problematic alcohol and cannabis use in a representative sample of adults aged 18 years and older residing in Ontario, Canada. Methods: Data were obtained from the Centre for Addiction and Mental Health Monitor, an ongoing cross-sectional telephone survey, between January 2011 and December 2013. Respondents (n = 5080) reported on current ADHD symptomatology, measured using the Adult ADHD Self-Report Version 1.1 Screener (ASRS-V1.1) and four additional items, and alcohol and cannabis use, which were measured using the Alcohol Use Disorders Identification Test (AUDIT) and the Alcohol, Smoking and Substance Involvement Screening Test (ASSIST), respectively. Logistic regression analyses were conducted in men and women to test the association of each ADHD symptom cluster (hyperactivity, inattentiveness, impulsivity) with problematic alcohol and cannabis use. Results: After controlling for age, education, and comorbid internalizing and externalizing psychopathology, hyperactive symptoms were associated with problematic alcohol use in both men and women and with problematic cannabis use in men. Impulsive symptoms were independently associated with problematic cannabis use in men. By contrast, inattentive symptomatology predicted problems with alcohol and cannabis only in women. In all models, age was negatively associated with substance misuse and externalizing behavior was positively correlated and the strongest predictor of hazardous alcohol and cannabis use. Conclusions: ADHD symptom expression in adulthood is related to concurrent hazardous use of alcohol and cannabis. Distinctive ADHD symptom profiles may confer increased risk for substance misuse in a sex-specific manner

Risk of caesarean section after induced labour: do hospitals make a difference

Background: There is a well-known relationship between induced labour and caesarean rates. However, it remains unknown whether this relationship reflects the impact of more complex obstetric conditions or the variability in obstetric practices. We sought to quantify the independent role of the hospital as a variable that can influence the occurrence of caesarean section after induced labour. Methods: As part of the Portuguese Generation XXI birth cohort, we evaluated 2041 consecutive women who underwent singleton pregnancies with labour induction, at five public level III obstetric units (April 2005-August 2006). The indications for induction were classified according to the guidelines of the American and the Royal Colleges of Obstetricians and Gynaecologists. Poisson regression models were adjusted to estimate the association between the hospital and surgical delivery after induction. Crude and adjusted prevalence ratios (PR) and a 95% confidence interval (95% CI) were computed. Results: The proportion of women who were induced without formal clinical indications varied among hospitals from 20.3% to 45.5% (p < 0.001). After adjusting for confounders, the risk of undergoing a caesarean section after induced labour remained significantly different between the hospitals, for the cases in which there was no evident indication for induction [the highest PR reaching 1.86 (95% CI, 1.23–2.82)] and also when at least one such indication was present [1.53 (95% CI, 1.12–2.10)]. This pattern was also observed among the primiparous cephalic term induced women [the highest PR reaching 2.06 (95% CI, 1.23–2.82) when there was no evident indication for induction and 1.61 (95% CI, 1.11–2.34) when at least one such indication was present]. Conclusions:Caesarean section after induced labour varied significantly across hospitals where similar outcomes were expected. The effect was more evident when the induction was not based on the unequivocal presence of commonly accepted indications

Palliative care: End-of-life symptoms

Gregory B. Crawford, Katherine A. Hauser, and Wendy I. Janse