Cloning and characterization of voltage‐gated calcium channel alpha1 subunits in Xenopus laevis during development

Voltage‐gated calcium channels play a critical role in regulating the Ca²⁺ activity that mediates many aspects of neural development, including neural induction, neurotransmitter phenotype specification, and neurite outgrowth. Using Xenopus laevis embryos, we describe the spatial and temporal expression patterns during development of the 10 pore‐forming alpha1 subunits that define the channels' kinetic properties. In situ hybridization indicates that Ca_V1.2, Ca_V2.1, Ca_V2.2, and Ca_V3.2 are expressed during neurula stages throughout the neural tube. These, along with Ca_V1.3 and Ca_V2.3, beginning at early tail bud stages, and Ca_V3.1 at late tail bud stages, are detected in complex patterns within the brain and spinal cord through swimming tadpole stages. Additional expression of various alpha1 subunits was observed in the cranial ganglia, retina, olfactory epithelium, pineal gland, and heart. The unique expression patterns for the different alpha1 subunits suggests they are under precise spatial and temporal regulation and are serving specific functions during embryonic development. Developmental Dynamics 238:2891–2902, 2009. © 2009 Wiley‐Liss, Inc.     

Anthropomorphic simulations of falls,shakes, and inflicted impacts in infants

OBJECT: Rotational loading conditions have been shown to produce subdural hemorrhage and diffuse axonal injury. No experimental data are available with which to compare the rotational response of the head of an infant during accidental and inflicted head injuries. The authors sought to compare rotational deceleration sustained by the head among free falls, from different heights onto different surfaces, with those sustained during shaking and inflicted impact. METHODS: An anthropomorphic surrogate of a 1.5-month-old human infant was constructed and used to simulate falls from 0.3 m (1 ft), 0.9 m (3 ft), and 1.5 m (5 ft), as well as vigorous shaking and inflicted head impact. During falls, the surrogate experienced occipital contact against a concrete surface, carpet pad, or foam mattress. For shakes, investigators repeatedly shook the surrogate in an anteroposterior plane; inflicted impact was defined as the terminal portion of a vigorous shake, in which the surrogate's occiput made contact with a rigid or padded surface. Rotational velocity was recorded directly and the maximum (peak-peak) change in angular velocity (delta theta(max)) and the peak angular acceleration (theta(max)) were calculated. Analysis of variance revealed significant increases in the delta theta(max) and theta(max) associated with falls onto harder surfaces and from higher heights. During inflicted impacts against rigid surfaces, the delta theta(max) and theta(max) were significantly greater than those measured under all other conditions. CONCLUSIONS: Vigorous shakes of this infant model produced rotational responses similar to those resulting from minor falls, but inflicted impacts produced responses that were significantly higher than even a 1.5-m fall onto concrete. Because larger accelerations are associated with an increasing likelihood of injury, the findings indicate that inflicted impacts against hard surfaces are more likely to be associated with inertial brain injuries than falls from a height less than 1.5 m or from shaking.     

Smokeless tobacco use among United States Air Force trainees

Background: The prevalence of smokeless tobacco use in the United States Air Force (USAF) exceeds civilian use rates. The prevalence and correlates of smokeless tobacco use were assessed and evaluated in a sample of USAF trainees. Methods: We conducted a cross-sectional survey of USAF technical training school personnel at Joint Base San Antonio-Lackland and Fort Sam Houston (N = 14,810). Survey completion rate was 78%. Logistic regression was used to analyze the associations between demographic variables, tobacco use, and social factors for both regular and infrequent smokeless tobacco (e.g., chewing tobacco, snuff) users. Results: Overall, 16% of Airmen had ever used smokeless tobacco and 10% regularly used smokeless tobacco. In multivariate analyses, men had greater odds than women of regular smokeless tobacco use (adjusted odds ratio [OR] = 15.2; 95% confidence interval [CI]: 10.8–21.5) and infrequent smokeless tobacco use (adjusted OR = 4.2; 95% CI: 3.1–5.7). Smokeless tobacco use was associated with participation in high school sports (adjusted OR = 1.9; 95% CI: 1.6–2.3 for regular users; adjusted OR = 1.4; 95% CI: 1.1–1.7 for infrequent users), smoking cigarettes (adjusted OR = 4.3; 95% CI: 3.6–5.1 for regular users; adjusted OR = 4.0; 95% CI: 3.2–5.0 for infrequent users), or living with someone who used smokeless tobacco (adjusted OR = 2.2; 95% CI: 1.9–2.6 for regular users; adjusted OR = 1.4; 95% CI: 1.1–1.7 for infrequent users). Black or African Americans were less likely than whites to be regular (adjusted OR = 0.3; 95% CI: 0.1–0.4) or infrequent (adjusted OR = 0.3; 95% CI: 0.2–0.4) users of smokeless tobacco. Conclusions: Smokeless tobacco use among incoming Air Force recruits is common and negatively impacts the Air Force's goal to be tobacco-free. Understanding sociodemographic characteristics perpetuating smokeless tobacco use in the Air Force population can inform the development of health promotion interventions.     

The validity of proxy responses on patient-reported outcome measures: Are proxies a reliable alternative to stroke patients’ self-report?

Quality of Life Research - Caregivers, or proxies, often complete patient-reported outcome measures (PROMs) on behalf of patients with stroke. The objective of our study was to assess the validity...     

The relationship between autism spectrum disorders and anxiety: The moderating effect of communication

Communication skills have been shown to have differing effects on levels of anxiety depending on whether or not a child has an autism spectrum disorder (ASD) or is typically developing. This article examined whether or not communication deficits differentially affect children with ASD compared to those without ASD. Ninety-nine children with autistic disorder (n = 33), Pervasive Developmental Disorder – Not Otherwise Specified (PDD-NOS; n = 33), and no diagnosis (n = 33) were examined using the Autism Spectrum Disorders Diagnostic for Children and Comorbidity for Children scales to determine their level of anxiety and degree of communication deficits. Results indicated that anxiety decreased as communication deficits increased for those with autistic disorder compared to those with PDD-NOS or no diagnosis; however, for those with PDD-NOS anxiety increased as communication deficits increased compared to those with no diagnosis. The importance and differential impact of communication deficits on anxiety for different groups is highlighted.     

The association of salvage intravesical therapy following BCG with pathologic outcomes and survival after radical cystectomy for patients with high-grade non-muscle invasive bladder cancer: A multi-institution analysis

IntroductionWhile numerous current clinical trials are testing novel salvage therapies (ST) for patients with recurrent nonmuscle invasive bladder cancer (NMIBC) after bacillus Calmette-Guérin (BCG), the natural history of this disease state has been poorly defined to date. Herein, we evaluated oncologic outcomes in patients previously treated with BCG and ST who subsequently underwent radical cystectomy (RC).MethodsWe identified 378 patients with high-grade NMIBC who received at least one complete induction course of BCG (n = 378) with (n = 62) or without (n = 316) additional ST and who then underwent RC between 2000 and 2018. Oncologic outcomes were compared using the Kaplan-Meier method and Cox proportional hazards models. Sensitivity analyses were conducted stratifying by presenting tumor stage, matched 1:3 for receipt vs. no receipt of ST.ResultsPatients receiving ST were more likely to initially present with CIS (26% vs. 17%) and less likely with T1 disease (34% vs. 50%, P = 0.06) compared to patients not treated with ST. Receipt of ST was not associated with increased risk of adverse pathology (≥pT2 or pN+) at RC (31% vs. 41%, P = 0.14). Likewise, 5-year cancer-specific survival did not significantly differ between groups on univariable Kaplan-Meier analysis (73% for ST and 74% for no ST, P = 0.7). Moreover, on multivariable analysis, receipt of ST was not significantly associated the risk of death from bladder cancer (HR 1.12; 95% CI 0.60–2.09, P = 0.7). Results were unchanged on sensitivity analysis.ConclusionsThese data suggest that, in carefully selected patients, ST following BCG for high grade NMIBC does not compromise oncologic outcomes for patients who ultimately undergo RC.     

Common variation in cytochrome P450 epoxygenase genes and the risk of incident nonfatal myocardial infarction and ischemic stroke

OBJECTIVE: The biologically active epoxyeicosatrienoic acids have protective vascular effects. CYP2J2, CYP2C8, and CYP2C9 are known to be a source of epoxyeicosatrienoic acids in cardiac tissues. We conducted a population-based, case-control study at Group Health to determine whether common genetic variation in the CYP2J2, CYP2C8, and CYP2C9 genes was associated with the risk of myocardial infarction and ischemic stroke. METHODS: We used publicly available single nucleotide polymorphism discovery data from a mixed race panel of 90 individuals to select 30 tag-single nucleotide polymorphisms that were genotyped in 856 myocardial infarction cases, 368 stroke cases and 2688 controls. We used logistic regression to estimate additive associations. To account for multiple testing, we report q values alongside findings with P<0.05. RESULTS: Variation in CYP2J2 was associated with myocardial infarction risk (P=0.027, q=0.081). Two intronic CYP2J2 tag-single nucleotide polymorphisms, rs10889160 and rs11572325 were associated with an increased risk of myocardial infarction (odds ratio: 1.24, 95% confidence interval: 1.07-1.43, P=0.004, q=0.090, and odds ratio: 1.27, 95% confidence interval: 1.08-1.51, P=0.006, q=0.090, respectively). No evidence of an association was found between variation in CYP2J2 and stroke and there was no association between variation in CYP2C8 or CYP2C9 and myocardial infarction or stroke. CONCLUSION: Common variation in CYP2J2 is associated with the risk of myocardial infarction.