Publications

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

Masterson TD, Bobak C, Rapuano KM, Shearrer GE, Gilbert-Diamond D

2019;14(9):e0221995doi: 10.1371/journal.pone.0221995

Associations between brain region volume and weight status have been observed in children cross-sectionally. However, it is unclear if differences in brain region volume precede weight gain.

PLoS One|2019

Morris JP 4th, Yashinskie JJ, Koche R, Chandwani R, Tian S, Chen CC, Baslan T, Marinkovic ZS, Sánchez-Rivera FJ, Leach SD, Carmona-Fontaine C, Thompson CB, Finley LWS, Lowe SW

2019 Sep 18;doi: 10.1038/s41586-019-1577-5

The tumour suppressor TP53 is mutated in the majority of human cancers, and in over 70% of pancreatic ductal adenocarcinoma (PDAC). Wild-type p53 accumulates in response to cellular stress, and regulates gene expression to alter cell fate and prevent tumour development. Wild-type p53 is also known to modulate cellular metabolic pathways, although p53-dependent metabolic alterations that constrain cancer progression remain poorly understood. Here we find that p53 remodels cancer-cell metabolism to enforce changes in chromatin and gene expression that favour a premalignant cell fate. Restoring p53 function in cancer cells derived from KRAS-mutant mouse models of PDAC leads to the accumulation of α-ketoglutarate (αKG, also known as 2-oxoglutarate), a metabolite that also serves as an obligate substrate for a subset of chromatin-modifying enzymes. p53 induces transcriptional programs that are characteristic of premalignant differentiation, and this effect can be partially recapitulated by the addition of cell-permeable αKG. Increased levels of the αKG-dependent chromatin modification 5-hydroxymethylcytosine (5hmC) accompany the tumour-cell differentiation that is triggered by p53, whereas decreased 5hmC characterizes the transition from premalignant to de-differentiated malignant lesions that is associated with mutations in Trp53. Enforcing the accumulation of αKG in p53-deficient PDAC cells through the inhibition of oxoglutarate dehydrogenase-an enzyme of the tricarboxylic acid cycle-specifically results in increased 5hmC, tumour-cell differentiation and decreased tumour-cell fitness. Conversely, increasing the intracellular levels of succinate (a competitive inhibitor of αKG-dependent dioxygenases) blunts p53-driven tumour suppression. These data suggest that αKG is an effector of p53-mediated tumour suppression, and that the accumulation of αKG in p53-deficient tumours can drive tumour-cell differentiation and antagonize malignant progression.

Nature|2019 Sep 18

Rak KJ, Kuza CC, Ashcraft LE, Morrison PK, Angus DC, Barnato AE, Hravnak M, Hershey TB, Kahn JM

2017 Jan-Dec;16(1)doi: 10.1177/1609406917733387

Telemedicine, the use of audiovisual technology to provide health care from a remote location, is increasingly used in intensive care units (ICUs). However, studies evaluating the impact of ICU telemedicine show mixed results, with some studies demonstrating improved patient outcomes, while others show limited benefit or even harm. Little is known about the mechanisms that influence variation in ICU telemedicine effectiveness, leaving providers without guidance on how to best use this potentially transformative technology. The Contributors to Effective Critical Care Telemedicine (ConnECCT) study aims to fill this knowledge gap by identifying the clinical and organizational factors associated with variation in ICU telemedicine effectiveness, as well as exploring the clinical contexts and provider perceptions of ICU telemedicine use and its impact on patient outcomes, using a range of qualitative methods. In this report, we describe the study protocol, data collection methods, and planned future analyses of the ConnECCT study. Over the course of 1 year, the study team visited purposefully sampled health systems across the United States that have adopted telemedicine. Data collection methods included direct observations, interviews, focus groups, and artifact collection. Data were collected at the ICUs that provide in-person critical care as well as at the supporting telemedicine units. Iterative thematic content analysis will be used to identify and define key constructs related to telemedicine effectiveness and describe the relationship between them. Ultimately, the study results will provide a framework for more effective implementation of ICU telemedicine, leading to improved clinical outcomes for critically ill patients.

Int J Qual Methods|2017 Jan-Dec

Leary JC, Walsh KE, Morin RA, Schainker EG, Leyenaar JK

2019 Sep 18;14:E1-E10doi: 10.12788/jhm.3268

Although the majority of children are hospitalized in nonchildren's hospitals, little is known about the quality and safety of pediatric care in community hospitals.

J Hosp Med|2019 Sep 18

Fraze TK, Brewster AL, Lewis VA, Beidler LB, Murray GF, Colla CH

2019 Sep 4;2(9):e1911514doi: 10.1001/jamanetworkopen.2019.11514

Social needs, including food, housing, utilities, transportation, and experience with interpersonal violence, are linked to health outcomes. Identifying patients with unmet social needs is a necessary first step to addressing these needs, yet little is known about the prevalence of screening.

JAMA Netw Open|2019 Sep 4

Dwan D, Baker CM, Zhang SC, Black CC, Zuurbier RA, diFlorio-Alexander RM

2019 Sep 17;doi: 10.1111/tbj.13581

Breast J|2019 Sep 17

Louie CE, Hong J, Bauer DF

2019;10:135doi: 10.25259/SNI-305-2019

Bertolotti's syndrome is defined by back pain and/or radicular symptoms attributed to a congenital lumbosacral transitional vertebra (LSTV). There are few studies that discuss the surgical management of Bertolotti's syndrome. Here, we report long-term outcomes after resecting a pseudoarthrosis between the sacrum and L5 in two teenage patients, along with a review of literature.

Surg Neurol Int|2019

D'Agostino EN, Calnan DR, Makler VI, Khan I, Kanter JH, Bauer DF

2019;10:90doi: 10.25259/SNI-66-2019

In a split cord malformation (SCM), the spinal cord is divided longitudinally into two distinct hemicords that later rejoin. This can result in a tethered cord syndrome (TCS). Rarely, TCS secondary to SCM presents in adulthood. Here, we present an adult female with Type I SCM resulting in TCS and a review of literature.

Surg Neurol Int|2019

Schartz D, D'Agostino E, Makler V, Hickey WF, Bauer DF

2019;10:73doi: 10.25259/SNI-90-2019

Third ventricular meningiomas are exceedingly rare intracranial tumors that may present with intraventricular hemorrhage.

Surg Neurol Int|2019

Crocker AW, Harty CE, Hammond JH, Willger SD, Salazar P, Botelho NJ, Jacobs NJ, Hogan DA

2019 Sep 16;pii: JB.00393-19. doi: 10.1128/JB.00393-19

has a broad metabolic repertoire that facilitates its co-existence with different microbes. Many microbes secrete products that can then catabolize, including ethanol, a common fermentation product. Here, we show that under oxygen limiting conditions utilizes AdhA, an NAD-linked alcohol dehydrogenase, as a previously undescribed means for ethanol catabolism. In a rich medium containing ethanol, AdhA, but not the previously described PQQ-linked alcohol dehydrogenase, ExaA, oxidizes ethanol and leads to the accumulation of acetate in culture supernatants. AdhA-dependent acetate accumulation, and the accompanying decrease in pH, promotes survival in LB-grown stationary phase cultures. The transcription of is elevated by hypoxia and in anoxic conditions, and we show that it is regulated by the Anr transcription factor. We have shown that mutants, which lack an important quorum sensing regulator, have higher levels of Anr-regulated transcripts in low oxygen conditions compared to their wild type counterparts. Here, we show that a mutant, when grown with ethanol, has an even larger decrease in pH than WT that is dependent on both and The large increase in AdhA activity is similar to that of a strain expressing a hyperactive Anr-D149A variant. Ethanol catabolism in by AdhA supports growth on ethanol as a sole carbon source and electron donor in oxygen-limited settings and in cells growing by denitrification in anoxic conditions. This is the first demonstration of a physiological role for AdhA in ethanol oxidation in Ethanol is a common product of microbial fermentation, and the response to and utilization of ethanol is relevant to our understanding of its role in microbial communities. Here, we report that the putative alcohol dehydrogenase, AdhA, is responsible for ethanol catabolism and acetate accumulation in low oxygen conditions and that it is regulated by Anr.

J Bacteriol|2019 Sep 16

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