Reviewer Acknowledgments

We offer these reviewers our heartfelt thanks for a task that usually goes unrewarded in the academic environment. This year, we are especially grateful for those people listed below. They have assisted us in reaching the start of our 4th year, by guiding our decisions with your knowledge and capabilities

Delivering health knowledge and wisdom from the hills and hollows of Appalachia

There is knowledge in the pages of Appalachia’s hills. This journal is positioned to find and publish those translations. It grows from a need to provide an outlet for scholarship about Appalachia’s health so that knowledge, and occasionally wisdom, is shared with those who care about and are committed to improving the region’s health

Reviewer Acknowledgments for 2019

The Editorial Team extends a heart-felt “thank you” to those who have given their time and expertise in the past year to participate in this process with the Journal of Appalachian Health. We know that you have many competing pressures on your time, and that you are not financially compensated for the time you spend reviewing manuscripts. We hope that there are other forms of compensation that make the sacrifice worth the effort

letter to tHe eDitor

Bhat M, Lu Y, Marcil V, et al. Tumour necrosis factor-alpha polymorphism increases the risk for nonvariceal upper gastrointestinal bleeding in patients taking proton pump inhibitors. Can J Gastroenterol Hepatol 2014;28(9):488. To the Editor: Nonvariceal upper gastrointestinal bleeding (NVUGIB) is associated with significant morbidity, affecting 50 to 150 per 100,000 adults annually (1). Patients with NVUGIB may present with melena, hematochezia or coffee-ground emesis, often accompanied by a decrease in hemoglobin levels and even hemodynamic instability. Nonsteroidal anti-inflammatory drugs (NSAIDs) and Helicobacter pylori infection are the principal risk factors for NVUGIB, accounting for >95% of cases. Taking proton pump inhibitors (PPIs) is a known protective factor against NVUGIB. There has recently been growing interest in a possible genetic predisposition to NVUGIB, with investigation of single nucleotide polymorphisms (SNPs) associated with bleeding events. Of particular interest have been mutations in proinflammatory genes or genes that regulate NSAID/PPI metabolism, which may contribute to excessive inflammation and ulceration in the context of H pylori infection and NSAID use. A recent pharmacogenomic study The above literature describing a genetic predisposition for bleeding events applies principally to East Asian patient populations. Therefore, we decided to study whether such genetic associations could be elicited in the Canadian context. We performed a pilot study to assess the association of SNPs involved in NSAID metabolism (CYP2C9) and inflammatory response (TNF-α) with NVUGIB events. Patients who were part of the REASON-II NVUGIB study population at the McGill University Health Centre (Montreal, Quebec) were recruited (5). Study controls were asymptomatic patients undergoing screening colonoscopy, and excluded if there was any history of NVUGIB. DNA extracted from serum was genotyped for SNPs in the proinflammatory TNF-α (rs1799724, rs1800630, rs1799964) and NSAID-metabolizing CYP2C9 genes (rs1799853, rs1057910). Using STATA version 10, we assessed for any association between SNPs and NVUGIB events using logistic regression analysis and stratifying according to H pylori status, NSAID and PPI use. Our study included 23 patients and 46 controls of comparable age and sex, with NSAID (26.1% versus 6.7%) and PPI use (21.7% versus 13.0%) being more prevalent among patients. The TNFα1031C SNP, a proinflammatory cytokine polymorphism, was more common among patients with NVUGIB (OR 2.2 [95% CI 0.9 to 5.1]; P=0.084), particularly among those using PPIs (OR 20.0 [95% CI 0.9 to 429.9]; P=0.056) or not taking NSAIDs (OR 3.2 [95% CI 1.1 to 9.0]; P=0.027) at the time of the bleeding event. There was a trend in association of the TNF-α863A SNP with NVUGIB in patients not taking NSAIDs (OR 2.7 [95% CI 0.9 to 8.6]; P=0.071). We did not detect an association between CYP2C9 polymorphisms and NVUGIB, a result similar to that obtained in the study by Musumba et al (2). In conclusion, our pilot study demonstrates that TNF-α1031C SNP confers a risk for NVUGIB events among patients taking PPIs, a finding compatible with previous studies showing increased risk for peptic ulceration with this particular SNP (3

Modeling the Measurements of Cochlear Microcirculation and Hearing Function after Loud Noise

Objective: Recent findings support the crucial role of microcirculatory disturbance and ischemia for hearing impairment especially after noise-induced hearing loss (NIHL). The aim of this study was to establish an animal model for in vivo analysis of cochlear microcirculation and hearing function after a loud noise to allow precise measurements of both parameters in vivo. Study Design: Randomized controlled trial. Setting: Animal study. Subjects and Methods: After assessment of normacusis (0 minutes) using evoked auditory brainstem responses (ABRs), noise (106-dB sound pressure level [SPL]) was applied to both ears in 6 guinea pigs for 30 minutes while unexposed animals served as controls. In vivo fluorescence microscopy of the stria vascularis capillaries was performed after surgical exposure of 1 cochlea. ABR measurements were derived from the contralateral ear. Results: After noise exposure, red blood cell velocity was reduced significantly by 24.3% (120 minutes) and further decreased to 44.5% at the end of the observation (210 minutes) in contrast to stable control measurements. Vessel diameters were not affected in both groups. A gradual decrease of segmental blood flow became significant (38.1%) after 150 minutes compared with controls. Hearing thresholds shifted significantly from 20.0 ± 5.5 dB SPL (0 minutes) to 32.5 ± 4.2dB SPL (60 minutes) only in animals exposed to loud noise. Conclusion: With regard to novel treatments targeting the stria vascularis in NIHL, this standardized model allows us to analyze in detail cochlear microcirculation and hearing function in vivo

Lack of asthma and rhinitis control in general practitioner-managed patients prescribed fixed-dose combination therapy in Australia

Peer reviewedPublisher PD

Influence of wiring cost on the large-scale architecture of human cortical connectivity

In the past two decades some fundamental properties of cortical connectivity have been discovered: small-world structure, pronounced hierarchical and modular organisation, and strong core and rich-club structures. A common assumption when interpreting results of this kind is that the observed structural properties are present to enable the brain's function. However, the brain is also embedded into the limited space of the skull and its wiring has associated developmental and metabolic costs. These basic physical and economic aspects place separate, often conflicting, constraints on the brain's connectivity, which must be characterized in order to understand the true relationship between brain structure and function. To address this challenge, here we ask which, and to what extent, aspects of the structural organisation of the brain are conserved if we preserve specific spatial and topological properties of the brain but otherwise randomise its connectivity. We perform a comparative analysis of a connectivity map of the cortical connectome both on high- and low-resolutions utilising three different types of surrogate networks: spatially unconstrained (‘random’), connection length preserving (‘spatial’), and connection length optimised (‘reduced’) surrogates. We find that unconstrained randomisation markedly diminishes all investigated architectural properties of cortical connectivity. By contrast, spatial and reduced surrogates largely preserve most properties and, interestingly, often more so in the reduced surrogates. Specifically, our results suggest that the cortical network is less tightly integrated than its spatial constraints would allow, but more strongly segregated than its spatial constraints would necessitate. We additionally find that hierarchical organisation and rich-club structure of the cortical connectivity are largely preserved in spatial and reduced surrogates and hence may be partially attributable to cortical wiring constraints. In contrast, the high modularity and strong s-core of the high-resolution cortical network are significantly stronger than in the surrogates, underlining their potential functional relevance in the brain

Vinorelbine plus trastuzumab combination as first-line therapy for HER 2-positive metastatic breast cancer patients: an international phase II trial

The aim of this international phase II trial was to determine the efficacy and safety profile of weekly vinorelbine plus trastuzumab as first-line chemotherapy for women with HER 2-overexpressing metastatic breast cancer. Sixty-nine patients with tumours overexpressing HER 2 received vinorelbine: 30 mg m−2 week−1 and trastuzumab: 4 mg kg−1 on day 1 as a loading dose followed by 2 mg kg−1 week−1 starting on day 8. Sixty-two patients were evaluable for response and 69 patients were evaluable for toxicity. The overall response rate was 62.9%. The median time to response was 8.4 weeks, the median duration of response was 17.5 months, the median progression-free survival was 9.9 months (95% CI, 5.6–12.1) and the one-year progression-free survival was 39.1%. The median survival for all patients was 23.7 months (95% CI, 18.4–32.6). This regimen was safe: grade 3–4 neutropenia were observed over 17.7% of courses in 83.8% of patients, with only two episodes of febrile neutropenia (0.1%) in two patients (2.9%). Only one patient discontinued treatment due to grade 3 symptomatic cardiac dysfunction that resolved with therapy. Vinorelbine plus trastuzumab is one of the most active treatment regimens for patients with HER 2-positive metastatic breast cancer and demonstrates a very favourable safety profile allowing prolonged treatment with long-term survival. This study has been presented in part at the following conferences: The San Antonio Breast Cancer Symposium, San Antonio, TX, USA, 2003; The American Society of Clinical Oncology, Orlando, FL, USA, 2005