Publications

Take a deeper look into all the publications produced by researchers at The Dartmouth Institute.

Wai H, Du K, Anesini J, Kim WS, Eastman A, Micalizio GC

2018 Sep 17;doi: 10.1021/acs.orglett.8b02689

A metallacycle-centered approach to the assembly of partially aromatic synthetic steroids was investigated as a means to prepare a boutique collection of unique steroidal agents. The synthesis and discovery of estra-1,3,5(10),6,8-pentaene-2,16α-diol (VII) is described, along with structure-activity relationships related to its cytotoxic properties. Overall, VII was found to have a GI = 0.2 μg/mL (∼800 nM) in MDA-MB-231 human breast cancer cells, be an efficacious estrogen receptor agonist with potency for ERβ > ERα (ERβ EC = 21 nM), possess selective affinity to the cdc-2-like kinase CLK4 (K = 350 nM), and be phenotypically related to paclitaxel by an unbiased panel assessment.

Org Lett|2018 Sep 17

Bhatia S, Sinha VK, Harward S, Gomez C, Kava BR, Parekh DJ

2018 Sep 11;pii: S1051-0443(18)31210-7. doi: 10.1016/j.jvir.2018.05.012

To evaluate the safety and efficacy of prostate artery embolization (PAE) for the treatment of benign prostatic hyperplasia for prostates ≥ 80 mL.

J Vasc Interv Radiol|2018 Sep 11

Beck A, Pelz P, Lorenz RC, Charlet K, Geisel O, Heinz A, Wüstenberg T, Müller CA

2018 Sep 11;pii: S0924-977X(18)30811-3. doi: 10.1016/j.euroneuro.2018.08.507

Increased functional brain response towards alcohol-associated stimuli is a neural hallmark of alcohol dependence and a promising target for pharmacotherapy. For the first time, we assessed the effects of individually titrated high-dose baclofen on cue reactivity and functional connectivity in alcohol-dependent (AD) patients in a randomized controlled trial (RCT). We investigated 23 recently detoxified AD patients and 23 matched healthy controls (HC) with a cue reactivity functional magnetic resonance imaging task. Patients were further scanned at baseline without medication and during treatment with high-dose baclofen/placebo (30-270 mg/d). Analyses were conducted for alcohol cue-elicited brain response, alcohol cue-modulated and stimulus-independent functional connectivity with left ventral tegmental area (VTA) as seed region. At baseline, AD patients (N = 23) showed increased cue-elicited brain activation in the ventral striatum (VS) compared to HC (N = 23), which was decreased at the second scanning session compared to baseline. Patients receiving baclofen (N = 10) showed a significant stronger decrease in cue-elicited brain activation in left orbitofrontal cortex (OFC), bilateral amygdala and left VTA than patients receiving placebo (N = 13). Treatment with baclofen further led to a decrease in alcohol cue-modulated functional connectivity between left VTA and left anterior cingulate cortex (ACC) as well as left medial prefrontal cortex (MPFC). Regarding clinical outcome, significantly more patients of the baclofen group remained abstinent during the high-dose period. Baclofen specifically decreased cue-elicited brain responses in areas known to be involved in the processing of salient (appetitive and aversive) stimuli. Treatment with high-dose baclofen seems to provide a pharmacological relief of this neural "warning signal" evoked by alcohol-related cues, thereby possibly supporting patients in remaining abstinent. Trial Registration Identifier of the main trial [BACLAD study] at clinicaltrials.gov: NCT01266655.

Eur Neuropsychopharmacol|2018 Sep 11

Austin DC, Torchia MT, Cozzolino NH, Jacobowitz LE, Bell JE

2018 Aug 23;doi: 10.1097/BOT.0000000000001321

We sought to compare range of motion, clinical outcome scores, and complications after reverse total shoulder arthroplasty (RSA) and hemiarthroplasty (HA) in geriatric patients with acute proximal humerus fractures.

J Orthop Trauma|2018 Aug 23

Prabhat AM, Kuppusamy ML, Naidu SK, Meduru S, Reddy PT, Dominic A, Khan M, Rivera BK, Kuppusamy P

2018;5:114doi: 10.3389/fcvm.2018.00114

Myocardial infarction (MI), which occurs often due to acute ischemia followed by reflow, is associated with irreversible loss (death) of cardiomyocytes. If left untreated, MI will lead to progressive loss of viable cardiomyocytes, deterioration of cardiac function, and congestive heart failure. While supplemental oxygen therapy has long been in practice to treat acute MI, there has not been a clear scientific basis for the observed beneficial effects. Further, there is no rationale for the amount or duration of administration of supplemental oxygenation for effective therapy. The goal of the present study was to determine an optimum oxygenation protocol that can be clinically applicable for treating acute MI. Using EPR oximetry, we studied the effect of exposure to supplemental oxygen cycling (OxCy) administered by inhalation of 21-100% oxygen for brief periods (15-90 min), daily for 5 days, using a rat model of acute MI. Myocardial oxygen tension (pO), cardiac function and pro-survival/apoptotic signaling molecules were used as markers of treatment outcome. OxCy resulted in a significant reduction of infarct size and improvement of cardiac function. An optimal condition of 30-min OxCy with 95% oxygen + 5% CO under normobaric conditions was found to be effective for cardioprotection.

Front Cardiovasc Med|2018

Hodge RA, Mandle HB, Ray S, Tandon S, Peterson M, Henry A, Akter Jahan F, Bostick RM, Baron JA, Barry EL, Yacoub R, Rutherford RE, Seabrook ME, Fedirko V

2018 Sep 12;pii: canprevres.0123.2018. doi: 10.1158/1940-6207.CAPR-18-0123

Chronic inflammation in the colorectum, a significant contributor to colorectal carcinogenesis, can be triggered by the activation of pro-inflammatory signaling pathways such as those initiated by Toll-like receptors (TLRs) and nuclear factor κB (NF-κB). Although experimental evidence supports calcium and vitamin D potentially modifying these pro-inflammatory pathways in the colorectum, human data in these regards are scarce. We investigated supplemental calcium (1,200 mg daily) and/or vitamin D3 (1,000 IU daily) effects on inflammatory signaling pathway-related biomarkers in a subset of 105 participants from a colorectal adenoma recurrence chemoprevention clinical trial. We assessed expression of TLR4 and TLR5, which recognize the bacterial components lipopolysaccharides and flagellin, respectively, and phospho-IKKα/β (pIKKα/β), a biomarker of inflammation, in the normal-appearing rectal crypt epithelium and stroma using standardized, automated immunohistochemistry and quantitative image analysis. Following one year of treatment, TLR4, TLR5, and pIKKα/β expression in the rectal mucosa did not statistically significantly change with vitamin D or calcium supplementation, taken alone or in combination. Several baseline participant characteristics, including body mass index, history of sessile serrated adenomas, high red/processed meat intake, and high levels of rectal epithelial cell proliferation (as measured by MIB-1/Ki-67), were associated with higher baseline expression of TLRs or pIKKα/β. Our findings suggest that vitamin D and calcium may have no substantial effect on the investigated biomarkers. However, several modifiable lifestyle factors may be associated with TLRs and pIKKα/β expression in the normal rectal mucosa, supporting their future investigation as potentially treatable, pre-neoplastic risk factors for colorectal neoplasms.

Cancer Prev Res (Phila)|2018 Sep 12

Barr PJ, Bonasia K, Verma K, Dannenberg MD, Yi C, Andrews E, Palm M, Cavanaugh KL, Masel M, Durand MA

2018 Sep 12;20(9):e11308doi: 10.2196/11308

Few clinics in the United States routinely offer patients audio or video recordings of their clinic visits. While interest in this practice has increased, to date, there are no data on the prevalence of recording clinic visits in the United States.

J Med Internet Res|2018 Sep 12

Bobak CA, Barr PJ, O'Malley AJ

2018 Sep 12;18(1):93doi: 10.1186/s12874-018-0550-6

Intraclass correlation coefficients (ICC) are recommended for the assessment of the reliability of measurement scales. However, the ICC is subject to a variety of statistical assumptions such as normality and stable variance, which are rarely considered in health applications.

BMC Med Res Methodol|2018 Sep 12

Rovner BW, Casten RJ, Hegel MT, Leiby B

2018 Sep 10;doi: 10.1001/jamaneurol.2018.2513

Mild cognitive impairment (MCI) is a transition state between normal cognitive aging and dementia that increases the risk for progressive cognitive decline. Preventing cognitive decline is a public health priority.

JAMA Neurol|2018 Sep 10

Knapp AA, Lee DC, Borodovsky JT, Auty SG, Gabrielli J, Budney AJ

2018 Sep 8;pii: S1054-139X(18)30301-X. doi: 10.1016/j.jadohealth.2018.07.012

The legal landscape of cannabis availability and use in the United States is rapidly changing. As the heterogeneity of cannabis products and methods of use increases, more information is needed on how these changes affect use, especially in vulnerable populations such as youth.

J Adolesc Health|2018 Sep 8

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