Factors Associated with Bovine Neonatal Pancytopenia (BNP) in Calves: A Case-Control Study

Bovine neonatal pancytopenia (BNP; previously known as idiopathic haemorrhagic diathesis and commonly known as bleeding calf syndrome) is a novel haemorrhagic disease of young calves which has emerged in a number of European countries during recent years. Data were retrospectively collected during June to November 2010 for 56 case calves diagnosed with BNP between 17 March and 7 June of the same year. These were compared with 58 control calves randomly recruited from herds with no history of BNP. Multivariable logistic regression analysis showed that increased odds of a calf being a BNP case were associated with its dam having received PregSure® BVD (Pfizer Animal Health) vaccination prior to the birth of the calf (odds ratio (OR) 40.78, p<0.001) and its herd of origin being located in Scotland (OR 9.71, p = 0.006). Decreased odds of a calf being a BNP case were associated with the calf having been kept outside (OR 0.11, p = 0.006). The longer that a cattle herd had been established on the farm was also associated with decreased odds of a calf in that herd being a BNP case (OR 0.97, p = 0.011)

Effects of tryptophan depletion and tryptophan loading on the affective response to high-dose CO2 challenge in healthy volunteers

It has been reported that in panic disorder (PD), tryptophan depletion enhances the vulnerability to experimentally induced panic, while the administration of serotonin precursors blunts the response to challenges. Using a high-dose carbon dioxide (CO2) challenge, we aimed to investigate the effects of acute tryptophan depletion (ATD) and acute tryptophan loading (ATL) on CO2-induced panic response in healthy volunteers. Eighteen healthy volunteers participated in a randomized, double-blind placebo-controlled study. Each subject received ATD, ATL, and a balanced condition (BAL) in separate days, and a double-breath 35% CO2 inhalation 4.5 h after treatment. Tryptophan (Trp) manipulations were obtained adding 0 g (ATD), 1.21 g (BAL), and 5.15 g (ATL) of l-tryptophan to a protein mixture lacking Trp. Assessments consisted of a visual analogue scale for affect (VAAS) and panic symptom list. A separate analysis on a sample of 55 subjects with a separate-group design has also been performed to study the relationship between plasma amino acid levels and subjective response to CO2. CO2-induced subjective distress and breathlessness were significantly lower after ATD compared to BAL and ATL (p &lt;0.05). In the separate-group analysis, Delta VAAS scores were positively correlated to the ratio Trp:I LNAA pound after treatment (r = 0.39; p &lt;0.05). The present results are in line with preclinical data indicating a role for the serotonergic system in promoting the aversive respiratory sensations to hypercapnic stimuli (Richerson, Nat Rev Neurosci 5(6):449-461, 2004). The differences observed in our study, compared to previous findings in PD patients, might depend on an altered serotonergic modulatory function in patients compared to healthy subjects

An experimental study of low-level laser therapy in rat Achilles tendon injury

The aim of this controlled animal study was to investigate the effect of low-level laser therapy (LLLT) administered 30 min after injury to the Achilles tendon. The study animals comprised 16 Sprague Dawley male rats divided in two groups. The right Achilles tendons were injured by blunt trauma using a mini guillotine, and were treated with LLLT or placebo LLLT 30 min later. The injury and LLLT procedures were then repeated 15 hours later on the same tendon. One group received active LLLT (λ = 904 nm, 60 mW mean output power, 0.158 W/cm2 for 50 s, energy 3 J) and the other group received placebo LLLT 23 hours after LLLT. Ultrasonographic images were taken to measure the thickness of the right and left Achilles tendons. Animals were then killed, and all Achilles tendons were tested for ultimate tensile strength (UTS). All analyses were performed by blinded observers. There was a significant increase in tendon thickness in the active LLLT group when compared with the placebo group (p < 0.05) and there were no significant differences between the placebo and uninjured left tendons. There were no significant differences in UTS between laser-treated, placebo-treated and uninjured tendons. Laser irradiation of the Achilles tendon at 0.158 W/cm2 for 50 s (3 J) administered within the first 30 min after blunt trauma, and repeated after 15 h, appears to lead to edema of the tendon measured 23 hours after LLLT. The guillotine blunt trauma model seems suitable for inflicting tendon injury and measuring the effects of treatment on edema by ultrasonography and UTS. More studies are needed to further refine this model

Health impact of US military service in a large population-based military cohort: findings of the Millennium Cohort Study, 2001-2008

<p>Abstract</p> <p>Background</p> <p>Combat-intense, lengthy, and multiple deployments in Iraq and Afghanistan have characterized the new millennium. The US military's all-volunteer force has never been better trained and technologically equipped to engage enemy combatants in multiple theaters of operations. Nonetheless, concerns over potential lasting effects of deployment on long-term health continue to mount and are yet to be elucidated. This report outlines how findings from the first 7 years of the Millennium Cohort Study have helped to address health concerns related to military service including deployments.</p> <p>Methods</p> <p>The Millennium Cohort Study was designed in the late 1990s to address veteran and public concerns for the first time using prospectively collected health and behavioral data.</p> <p>Results</p> <p>Over 150 000 active-duty, reserve, and National Guard personnel from all service branches have enrolled, and more than 70% of the first 2 enrollment panels submitted at least 1 follow-up survey. Approximately half of the Cohort has deployed in support of operations in Iraq and Afghanistan.</p> <p>Conclusion</p> <p>The Millennium Cohort Study is providing prospective data that will guide public health policymakers for years to come by exploring associations between military exposures and important health outcomes. Strategic studies aim to identify, reduce, and prevent adverse health outcomes that may be associated with military service, including those related to deployment.</p

Network-Based Integration of GWAS and Gene Expression Identifies a HOX-Centric Network Associated with Serous Ovarian Cancer Risk

BACKGROUND: Genome-wide association studies (GWAS) have so far reported 12 loci associated with serous epithelial ovarian cancer (EOC) risk. We hypothesized that some of these loci function through nearby transcription factor (TF) genes and that putative target genes of these TFs as identified by coexpression may also be enriched for additional EOC risk associations. METHODS: We selected TF genes within 1 Mb of the top signal at the 12 genome-wide significant risk loci. Mutual information, a form of correlation, was used to build networks of genes strongly coexpressed with each selected TF gene in the unified microarray dataset of 489 serous EOC tumors from The Cancer Genome Atlas. Genes represented in this dataset were subsequently ranked using a gene-level test based on results for germline SNPs from a serous EOC GWAS meta-analysis (2,196 cases/4,396 controls). RESULTS: Gene set enrichment analysis identified six networks centered on TF genes (HOXB2, HOXB5, HOXB6, HOXB7 at 17q21.32 and HOXD1, HOXD3 at 2q31) that were significantly enriched for genes from the risk-associated end of the ranked list (P < 0.05 and FDR < 0.05). These results were replicated (P < 0.05) using an independent association study (7,035 cases/21,693 controls). Genes underlying enrichment in the six networks were pooled into a combined network. CONCLUSION: We identified a HOX-centric network associated with serous EOC risk containing several genes with known or emerging roles in serous EOC development. IMPACT: Network analysis integrating large, context-specific datasets has the potential to offer mechanistic insights into cancer susceptibility and prioritize genes for experimental characterization

Variants in genes encoding small GTPases and association with epithelial ovarian cancer susceptibility

Epithelial ovarian cancer (EOC) is the fifth leading cause of cancer mortality in American women. Normal ovarian physiology is intricately connected to small GTP binding proteins of the Ras superfamily (Ras, Rho, Rab, Arf, and Ran) which govern processes such as signal transduction, cell proliferation, cell motility, and vesicle transport. We hypothesized that common germline variation in genes encoding small GTPases is associated with EOC risk. We investigated 322 variants in 88 small GTPase genes in germline DNA of 18,736 EOC patients and 26,138 controls of European ancestry using a custom genotype array and logistic regression fitting log-additive models. Functional annotation was used to identify biofeatures and expression quantitative trait loci that intersect with risk variants. One variant, ARHGEF10L (Rho guanine nucleotide exchange factor 10 like) rs2256787, was associated with increased endometrioid EOC risk (OR=1.33, p=4.46 x 10-6). Other variants of interest included another in ARHGEF10L, rs10788679, which was associated with invasive serous EOC risk (OR=1.07, p=0.00026) and two variants in AKAP6 (A-kinase anchoring protein 6) which were associated with risk of invasive EOC (rs1955513, OR=0.90, p=0.00033; rs927062, OR =0.94, p=0.00059). Functional annotation revealed that the two ARHGEF10L variants were located in super-enhancer regions and that AKAP6 rs927062 was associated with expression of GTPase gene ARHGAP5 (Rho GTPase activating protein 5). Inherited variants in ARHGEF10L and AKAP6, with potential transcriptional regulatory function and association with EOC risk, warrant investigation in independent EOC study populations

Adolescent Brain Development and the Risk for Alcohol and Other Drug Problems

Dynamic changes in neurochemistry, fiber architecture, and tissue composition occur in the adolescent brain. The course of these maturational processes is being charted with greater specificity, owing to advances in neuroimaging and indicate grey matter volume reductions and protracted development of white matter in regions known to support complex cognition and behavior. Though fronto-subcortical circuitry development is notable during adolescence, asynchronous maturation of prefrontal and limbic systems may render youth more vulnerable to risky behaviors such as substance use. Indeed, binge-pattern alcohol consumption and comorbid marijuana use are common among adolescents, and are associated with neural consequences. This review summarizes the unique characteristics of adolescent brain development, particularly aspects that predispose individuals to reward seeking and risky choices during this phase of life, and discusses the influence of substance use on neuromaturation. Together, findings in this arena underscore the importance of refined research and programming efforts in adolescent health and interventional needs

PALB2, CHEK2 and ATM rare variants and cancer risk: data from COGS

Background: The rarity of mutations in PALB2, CHEK2 and ATM make it difficult to estimate precisely associated cancer risks. Population-based family studies have provided evidence that at least some of these mutations are associated with breast cancer risk as high as those associated with rare BRCA2 mutations. We aimed to estimate the relative risks associated with specific rare variants in PALB2, CHEK2 and ATM via a multicentre case-control study.Methods: We genotyped 10 rare mutations using the custom iCOGS array: PALB2 c.1592delT, c.2816T&gt;G and c.3113G&gt;A, CHEK2c.349A&gt;G, c.538C&gt;T, c.715G&gt;A, c.1036C&gt;T, c.1312G&gt;T, and c.1343T&gt;G and ATM c.7271T&gt;G. We assessed associations with breast cancer risk (42 671 cases and 42 164 controls), as well as prostate (22 301 cases and 22 320 controls) and ovarian (14 542 cases and 23 491 controls) cancer risk, for each variant.Results: For European women, strong evidence of association with breast cancer risk was observed for PALB2 c.1592delT OR 3.44 (95% CI 1.39 to 8.52, p=7.1×10−5), PALB2 c.3113G&gt;A OR 4.21 (95% CI 1.84 to 9.60, p=6.9×10−8) and ATM c.7271T&gt;G OR 11.0 (95% CI 1.42 to 85.7, p=0.0012). We also found evidence of association with breast cancer risk for three variants in CHEK2, c.349A&gt;G OR 2.26 (95% CI 1.29 to 3.95), c.1036C&gt;T OR 5.06 (95% CI 1.09 to 23.5) and c.538C&gt;T OR 1.33 (95% CI 1.05 to 1.67) (p≤0.017). Evidence for prostate cancer risk was observed for CHEK2 c.1343T&gt;G OR 3.03 (95% CI 1.53 to 6.03, p=0.0006) for African men and CHEK2 c.1312G&gt;T OR 2.21 (95% CI 1.06 to 4.63, p=0.030) for European men. No evidence of association with ovarian cancer was found for any of these variants.Conclusions: This report adds to accumulating evidence that at least some variants in these genes are associated with an increased risk of breast cancer that is clinically important.</p

A cluster randomized trial of a transition intervention for adolescents with congenital heart disease: rationale and design of the CHAPTER 2 study

BACKGROUND: The population of adolescents and young adults with congenital heart disease (CHD) is growing exponentially. These survivors are at risk of late cardiac complications and require lifelong cardiology care. However, there is a paucity of data on how to prepare adolescents to assume responsibility for their health and function within the adult health care system. Evidence-based transition strategies are required. METHODS: The Congenital Heart Adolescents Participating in Transition Evaluation Research (CHAPTER 2) Study is a two-site cluster randomized clinical trial designed to evaluate the efficacy of a nurse-led transition intervention for 16–17 year olds with moderate or complex CHD. The primary endpoint is excess time to adult CHD care, defined as the time interval between the final pediatric cardiology appointment and the first adult CHD appointment, minus the recommended time interval between these appointments. Secondary endpoints include the MyHeart score (CHD knowledge), Transition Readiness Assessment Questionnaire score, and need for catheter or surgical re-intervention. Participants are enrolled in clusters based on week of attendance in the pediatric cardiology clinic. The intervention consists of two one-hour individualized sessions between a cardiology nurse and study participant. Session One focuses on knowledge of the participant’s CHD, review of their cardiac anatomy and prior interventions, and potential late cardiac complications. Session Two focuses on self-management and communication skills through review and discussion of videos and role-play. The study will recruit 120 participants. DISCUSSION: Many adolescents and young adults experience a gap in care predisposing them to late cardiac complications. The CHAPTER 2 Study will investigate the impact of a nurse-led transition intervention among adolescents with CHD. Fidelity of the intervention is a major focus and priority. This study will build on our experience by (i) enrolling at two tertiary care programs, (ii) including a self-management intervention component, and (iii) evaluating the impact of the intervention on time to ACHD care, a clinically relevant outcome. The results of this study will inform pediatric cardiology programs, patients and policy makers in judging whether a structured intervention program provides clinically meaningful outcomes for adolescents and young adults living with CHD. TRIAL REGISTRATION: ClinicalTrials.gov ID NCT0172333