Adolescent chronic variable social stress influences exploratory behavior and nicotine responses in male, but not female, BALB/cJ mice.

Anxiety disorders and nicotine use are significant contributors to global morbidity and mortality as independent and comorbid diseases. Early-life stress, potentially via stress-induced hypothalamic-pituitary-adrenal axis (HPA) dysregulation, can exacerbate both. However, little is known about the factors that predispose individuals to the development of both anxiety disorders and nicotine use. Here, we examined the relationship between anxiety-like behaviors and nicotine responses following adolescent stress. Adolescent male and female BALB/cJ mice were exposed to either chronic variable social stress (CVSS) or control conditions. CVSS consisted of repeated cycles of social isolation and social reorganization. In adulthood, anxiety-like behavior and social avoidance were measured using the elevated plus-maze (EPM) and social approach-avoidance test, respectively. Nicotine responses were assessed with acute effects on body temperature, corticosterone production, locomotor activity, and voluntary oral nicotine consumption. Adolescent stress had sex-dependent effects on nicotine responses and exploratory behavior, but did not affect anxiety-like behavior or social avoidance in males or females. Adult CVSS males exhibited less exploratory behavior, as indicated by reduced exploratory locomotion in the EPM and social approach-avoidance test, compared to controls. Adolescent stress did not affect nicotine-induced hypothermia in either sex, but CVSS males exhibited augmented nicotine-induced locomotion during late adolescence and voluntarily consumed less nicotine during adulthood. Stress effects on male nicotine-induced locomotion were associated with individual differences in exploratory locomotion in the EPM and social approach-avoidance test. Relative to controls, adult CVSS males and females also exhibited reduced corticosterone levels at baseline and adult male CVSS mice exhibited increased corticosterone levels following an acute nicotine injection. Results suggest that the altered nicotine responses observed in CVSS males may be associated with HPA dysregulation. Taken together, adolescent social stress influences later-life nicotine responses and exploratory behavior. However, there is little evidence of an association between nicotine responses and prototypical anxiety-like behavior or social avoidance in BALB/cJ mice.

Acute West Nile Virus Meningoencephalitis Diagnosed Via Metagenomic Deep Sequencing of Cerebrospinal Fluid in a Renal Transplant Patient.

Solid organ transplant patients are vulnerable to suffering neurologic complications from a wide array of viral infections and can be sentinels in the population who are first to get serious complications from emerging infections like the recent waves of arboviruses, including West Nile virus, Chikungunya virus, Zika virus, and Dengue virus. The diverse and rapidly changing landscape of possible causes of viral encephalitis poses great challenges for traditional candidate-based infectious disease diagnostics that already fail to identify a causative pathogen in approximately 50% of encephalitis cases. We present the case of a 14-year-old girl on immunosuppression for a renal transplant who presented with acute meningoencephalitis. Traditional diagnostics failed to identify an etiology. RNA extracted from her cerebrospinal fluid was subjected to unbiased metagenomic deep sequencing, enhanced with the use of a Cas9-based technique for host depletion. This analysis identified West Nile virus (WNV). Convalescent serum serologies subsequently confirmed WNV seroconversion. These results support a clear clinical role for metagenomic deep sequencing in the setting of suspected viral encephalitis, especially in the context of the high-risk transplant patient population.

Improving colon cancer screening rates in primary care: a pilot study emphasising the role of the medical assistant.

BACKGROUND: Colorectal cancer (CRC) is the third-leading cause of cancer death for both men and women in the USA. Despite consensus recommendations for screening, just over half of eligible adults nationally have undergone screening. We therefore implemented a programme to improve the rate of CRC screening. METHODS: This study was conducted in the Utah Health Research Network and the University of Utah Community Clinics, a 100 000 patient, seven-practice, university-owned system offering primary and secondary care and ancillary services including endoscopy. We focused on patients aged >or=50 who were seen between 1 January 2003 and 31 October 2006, and who were not current for CRC screening at the time of the visit. The study included a three-phase INTERVENTION: electronic medical record (EMR) reminders, physician and medical assistant (MA) education about CRC screening guidelines, and redesign of patient visit workflow with an expanded role for MAs to review patients' CRC screening status and recommend testing when appropriate. With patient agreement, the MA entered a preliminary order in the EMR, and the physician confirmed or rejected the order. The primary outcome measure was the rate of screening colonoscopy ordered for eligible patients. RESULTS: The baseline colonoscopy referral rate was 6.0%. Provider education and electronic reminders had minimal immediate impact on screening rates. Addition of the expanded MA role was associated with a sustained increase in colonoscopy referral order rate to 13.4%, a relative improvement of 123%. CONCLUSIONS: The MA can play a key role in improving CRC screening rates as part of a redesigned system of primary care.

XIAP-mediated neuroprotection in retinal ischemia.

Retinal ischemia results in the loss of vision in a number of ocular diseases including acute glaucoma, diabetic retinopathy, hypertensive retinopathy and retinal vascular occlusion. Recent studies have shown that most of the neuronal death that leads to loss of vision results from apoptosis. XIAP-mediated gene therapy has been shown to protect a number of neuronal types from apoptosis but has never been assessed in retinal neurons following ischemic-induced cell death. We injected an adeno-associated viral vector expressing XIAP or GFP into rat eyes and 6 weeks later, rendered them ischemic by raising intraocular pressure. Functional analysis revealed that XIAP-treated eyes retained larger b-wave amplitudes than GFP-treated eyes up to 4 weeks post-ischemia. The number of cells in the inner nuclear layer (INL) and the thickness of the inner retina were significantly preserved in XIAP-treated eyes compared to GFP-treated eyes. Similarly, there was no significant reduction in optic nerve axon numbers in XIAP-treated eyes. There were also significantly fewer TUNEL (TdT-dUTP terminal nick end labeling) positive cells in the INL of XIAP-treated retinas at 24 h post-ischemia. Thus, XIAP-mediated gene therapy imparts both functional and structural protection to the retina after a transient ischemic episode.

The reliability of cryoSEM for the observation and quantification of xylem embolisms and quantitative analysis of xylem sap in situ.

The reliability of cryoSEM for visualizing gas embolisms in xylem vessels of intact, functioning roots is examined and discussed. The possibility that these embolisms form as a result of freezing water columns under tension is discounted by a double-freeze experiment. Two regions of the same root, one frozen under tension, the other isolated from the tension by the first freeze, had the same percentage of embolisms, as did also long pieces of root frozen simultaneously along their length. The reliability of energy-dispersive X-ray analysis to measure xylem sap concentration in situ in frozen tissue was established by measurement of KCl standard solution frozen on stubs, and within xylem vessels. Solute heterogeneity within the vessels varied with freezing procedure; deep-freeze > LN2 > cryopliers > liquid ethane, but only the deep-freeze method gave unsatisfactory estimates of concentration for the standard solution. It is concluded that cryoanalytical SEM is useful for direct observation of gas and liquid-filled compartments, and for solute analyses at depth within intact plant organs.