Expression of Stretch-Activated Two-Pore Potassium Channels in Human Myometrium in Pregnancy and Labor

Background: We tested the hypothesis that the stretch-activated, four-transmembrane domain, two pore potassium channels (K2P), TREK-1 and TRAAK are gestationally-regulated in human myometrium and contribute to uterine relaxation during pregnancy until labor. Methodology: We determined the gene and protein expression of K2P channels in non-pregnant, pregnant term and preterm laboring myometrium. We employed both molecular biological and functional studies of K2P channels in myometrial samples taken from women undergoing cesarean delivery of a fetus. Principal Findings: TREK-1, but not TREK-2, channels are expressed in human myometrium and significantly up-regulated during pregnancy. Down-regulation of TREK-1 message was seen by Q-PCR in laboring tissues consistent with a role for TREK-1 in maintaining uterine quiescence prior to labor. The TRAAK channel was unregulated in the same women. Blockade of stretch-activated channels with a channel non-specific tarantula toxin (GsMTx-4) or the more specific TREK-1 antagonist L-methionine ethyl ester altered contractile frequency in a dose-dependent manner in pregnant myometrium. Arachidonic acid treatment lowered contractile tension an effect blocked by fluphenazine. Functional studies are consistent with a role for TREK-1 in uterine quiescence. Conclusions: We provide evidence supporting a role for TREK-1 in contributing to uterine quiescence during gestation an

Brain Imaging of Pain

The brain is the principal processor of internal and external sensory experiences including pain. Pain is a multidimensional experience influenced by complex interactions among multiple processes including nociception (the afferent neural activity transmitting sensory information about noxious stimuli), cognitive appraisals (expectation, attention), and emotional aspects (affect)

Risk of overdose‐related death for people with a history of incarceration

BACKGROUND AND AIMS: Reported associations between previous incarceration and the risk of overdose-related death are substantially heterogeneous, and previous studies are limited by an inability to control for confounding factors in risk assessment. This study investigated the associations of overdose-related death with previous incarceration and the number or cumulative duration of previous incarcerations, and individual or neighborhood characteristics that may potentially modify the associations. DESIGN AND SETTING: A cohort study using a 20% random sample of residents in British Columbia, Canada. PARTICIPANTS: A total of 765 690 people aged 23 years or older at baseline as of 1 January 2015. Mean age was 50 years; 49% were males. MEASUREMENTS: Previous incarcerations that occurred during the 5-year exposure period (January 2010 to December 2014) were identified using provincial incarceration records. Overdose-related deaths that occurred during the 3-year follow-up period (January 2015 to December 2017) were identified using linked administrative health data. Baseline individual and neighborhood characteristics were retrieved from the provincial health insurance data. FINDINGS: In the cohort, 5743 people had an incarceration history during the exposure period, and 634 people died from drug overdose during the follow-up period. The mortality rate was 897 and 22 per 100 000 person-years for people who did and did not have an incarceration history, respectively. After adjusting for baseline individual and neighborhood characteristics (without any interaction term), people who had an incarceration history were 4.04 times (95% confidence interval 3.23-5.06) more likely to die from drug overdose compared with people without an incarceration history. The association was stronger for females, people without diagnoses of substance use disorder and people without dispensation of opioids for pain or benzodiazepines (P < 0.001 for each interaction term). There was no discernible linear trend between the number or cumulative duration of previous incarcerations and the risk of overdose-related death. CONCLUSIONS: Previous incarceration appears to be a major risk factor for overdose-related death

Hemodynamic responses to visual stimulation in children with sickle cell anemia

Blood oxygenation level- dependent (BOLD) and cerebral blood flow (CBF)-based functional magnetic resonance imaging (fMRI) were used to measure primary visual cortex responses to photic stimulation in 23 children (12.4 ± 0.7 years old) with sickle cell anemia (SCA) and 21 clinical controls (11 ± 1.0 years old). The objectives were to investigate the effect of SCA on detection of brain activation with fMRI and to explore the relationship between fMRI responses and global cognitive function. The BOLD responses were diminished in children with SCA. Clinical indicators of disease severity were greatest in patients without detectable visual cortex activation, but blood hemoglobin concentration and resting CBF were not predictive of BOLD signal amplitude in the SCA patients. Unexpectedly, the BOLD signal amplitude was positively associated (r(s)≥0.8, p≤0.05) with Wechsler Abbreviated Scale of Intelligence scores, suggesting that fMRI may help clarify medical, hemodynamic, and neural factors that mediate adverse effects of SCA on neurocognitive function