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Polymorphisms in mitochondrial DNA (mtDNA) are used to group individuals into haplogroups reflecting human global migration and are associated with multiple diseases, including cancer. Here, we evaluate the association between mtDNA haplogroup and risk of myelodysplastic syndromes (MDS). Cases were identified by the Minnesota Cancer Surveillance System. Controls were identified through the Minnesota State driver's license/identification card list. Because haplogroup frequencies vary by race and ethnicity, we restricted analyses to non‐Hispanic whites. We genotyped 15 mtSNPs that capture common European mitochondrial haplogroup variation. We used SAS v.9.3 (SAS Institute, Cary, NC) to calculate odds ratios (OR) and 95% confidence intervals (CI) overall and stratified by MDS subtype and IPSS‐R risk category. We were able to classify 215 cases with confirmed MDS and 522 controls into one of the 11 common European haplogroups. Due to small sample sizes in some subgroups, we combined mt haplogroups into larger bins based on the haplogroup evolutionary tree, including HV (H + V), JT (J + T), IWX (I + W + X), UK (U + K), and Z for comparisons of cases and controls. Using haplogroup HV as the reference group, we found a statistically significant association between haplogroup JT and MDS (OR = 0.58, 95% CI 0.36, 0.92, P = 0.02). No statistically significant heterogeneity was observed in subgroup analyses. In this population‐based study of MDS, we observed an association between mtDNA haplogroup JT and risk of MDS. While previously published studies provide biological plausibility for the observed association, further studies of the relationship between mtDNA variation and MDS are warranted in larger sample sizes. © 2016 Wiley Periodicals, Inc.

Background Antiepileptic drugs (AED) are often considered first line for monotherapy in treatment of patients with migraines, and also those with comorbid migraine and epilepsy. Topiramate, a newer generation AED, has broad mechanism of action and evidence of benefit in patients with either episodic or chronic migraine along with epilepsy, both generalized and focal. Methods Our goal is to review the relevant mechanisms of action along with any supportive evidence published to date on the use of topiramate (TPM) in patients with both migraine headache and epilepsy. Conclusions There has been very little published to date on the use of TPM in patients diagnosed with both disorders. Despite this, TPM has been adopted as first line therapy in this patient population. Future studies investigating the effectiveness of this treatment strategy are warranted in order to determine the most effective use of this medication in patients diagnosed with migraine headaches and epilepsy.

ABSTRACT The objective of this study was to investigate the effects of 2% L-glutamine supplementation on myenteric innervation in the ileum of diabetic rats, grouped as follows: normoglycemic (N); normoglycemic supplemented with L-glutamine (NG); diabetic (D); and diabetic supplemented with L-glutamine (DG). The ileums were subjected to immunohistochemical techniques to localize neurons immunoreactive to HuC/D protein (HuC/D-IR) and neuronal nitric oxide synthase enzyme (nNOS-IR) and to analyze varicosities immunoreactive to vasoactive intestinal polypeptide (VIP-IR) and calcitonin gene-related peptide (CGRP-IR). L-Glutamine in the DG group (i) prevented the increase in the cell body area of nNOS-IR neurons, (ii) prevented the increase in the area of VIP-IR varicosities, (iii) did not prevent the loss of HuC/D-IR and nNOS-IR neurons per ganglion, and (iv) reduced the size of CGRP-IR varicosities. L-Glutamine in the NG group reduced (i) the number of HuC/D-IR and nNOS-IR neurons per ganglion, (ii) the cell body area of nNOS-IR neurons, and (iii) the size of VIP-IR and CGRP-IR varicosities. 2% L-glutamine supplementation exerted differential neuroprotective effects in experimental diabetes neuropathy that depended on the type of neurotransmitter analyzed. However, the effects of this dose of L-glutamine on normoglycemic animals suggests there are additional actions of this beyond its antioxidant capacity.

Summary Background Patients with Crohn's disease ( CD ) have serologic responses to various microbial antigens. Serologic markers are associated with aggressive forms of disease and can be detected before onset of symptoms. Their utility in pre‐clinical disease or prediction of complicated disease course before diagnosis is unclear. Aim To evaluate the pattern of serologic anti‐microbial antibodies long prior to diagnosis and the subsequent risk of complicated Crohn's disease at diagnosis. Methods Sera from 100 US military personnel with Crohn's disease were obtained from the Department of Defense Serum Repository. For each patient, four samples were obtained at different time points before and around diagnosis, and were tested for 6 microbiota‐directed antibodies ( ASCA ‐IgA, ASCA ‐IgG, anti‐OmpC, anti‐ CB ir1, anti‐A4‐Fla2 and anti‐FlaX). Associations between the presence and accumulation of Crohn's disease anti‐microbial antibodies before diagnosis and with the later development of complications were evaluated. Results Overall, 65 patients were positive for at least one Crohn's disease associated anti‐microbial antibody in the earliest available sample, at a median of 6 years before Crohn's disease diagnosis (interquartile range, 5.6–8.2). The number of positive anti‐microbial antibodies increased up to the time of Crohn's disease diagnosis. Complicated disease developed around the time of diagnosis in 24 patients. The proportion of positive antimicrobial antibodies before diagnosis was higher in patients with complicated vs. noncomplicated Crohn's disease. There was an inverse relationship between the time to first complication and the magnitude of serologic response before diagnosis. Conclusion The presence and accumulation of circulating anti‐microbial antibodies years before Crohn's disease diagnosis was associated with complicated Crohn's disease at or shortly after diagnosis.

This paper describes the goals of the American Society of Health‐System Pharmacists' Pharmacy Practice Model Initiative (PPMI) and its recommendations for health‐system pharmacy practice transformation to meet future patient care needs and elevate the role of pharmacists as patient care providers. PPMI envisions a future in which pharmacists have greater responsibility for medication‐related outcomes and technicians assume greater responsibility for product‐related activities. Although the PPMI recommendations have elevated the level of practice in many settings, they also potentially affect existing clinical pharmacists, in general, and clinical pharmacy specialists, in particular. Moreover, although more consistent patient care can be achieved with an expanded team of pharmacist providers, the role of clinical pharmacy specialists must not be diminished, especially in the care of complex patients and populations. Specialist practitioners with advanced training and credentials must be available to model and train pharmacists in generalist positions, residents, and students. Indeed, specialist practitioners are often the innovators and practice leaders. Negotiation between hospitals and pharmacy schools is needed to ensure a continuing role for academic clinical pharmacists and their contributions as educators and researchers. Lessons can be applied from disciplines such as nursing and medicine, which have developed new models of care involving effective collaboration between generalists and specialists. Several different pharmacy practice models have been described to meet the PPMI goals, based on available personnel and local goals. Studies measuring the impact of these new practice models are needed.

Earlier reports showed that hyperplasia of sympathoadrenal cell precursors during embryogenesis in Nf1-deficient mice is independent of Nf1’s role in down-modulating RAS-MAPK signaling. We demonstrate in zebrafish that nf1 loss leads to aberrant activation of RAS signaling in MYCN-induced neuroblastomas that arise in these precursors, and that the GTPase-activating protein (GAP)-related domain (GRD) is sufficient to suppress the acceleration of neuroblastoma in nf1-deficient fish, but not the hypertrophy of sympathoadrenal cells in nf1 mutant embryos. Thus, even though neuroblastoma is a classical “developmental tumor”, NF1 relies on a very different mechanism to suppress malignant transformation than it does to modulate normal neural crest cell growth. We also show marked synergy in tumor cell killing between MEK inhibitors (trametinib) and retinoids (isotretinoin) in primary nf1a-/- zebrafish neuroblastomas. Thus, our model system has considerable translational potential for investigating new strategies to improve the treatment of very high-risk neuroblastomas with aberrant RAS-MAPK activation.

The author, a physician living with lymphoma for five years, relates the details of the lived experience. He reflects on the impact of his illness on aspects of his life: personal health, professional work as a physician, and his journey in faith.