Medicine and Health Sciences Commons^™

Metabolic Acidosis After Sodium Thiosulfate Infusion And The Role Of Hydrogen Sulfide, Guenola M. Hunt, Hilary F. Ryder

Dartmouth Scholarship

Sodium thiosulfate (STS), first-line treatment for calcific uremic arteriolopathy, causes a mild asymptomatic acidosis in many patients. However, severe, life-threatening acidosis out of proportion with the expected acid load of STS may occur, potentially due to metabolism of STS to hydrogen sulfide.

Can Novel Technologies Improve Breast Conserving Surgery?, Brian W. Pogue

Dartmouth Scholarship

The practice of breast conserving surgery has been transformative for management of women’s breast cancer, and yet the current practice remains in a situation where approximately one-third of all patients have incomplete surgical resection. This is measured by the finding of clear margins on the surgical specimen, as measured by pathology sampling. This is a very active area of professional debate and research study, and the solutions are not as obvious as one might guess. Still, reviews of the status of the field suggest that technical solutions should be available to help mitigate this issue, and the tools for molecular …

The Workingwell Smartphone App For Individuals With Serious Mental Illnesses: A Proof-Of-Concept, Mixed Methods Feasibility Study (Preprint), Joanne Nicholson, Spenser M. Wright, Alyssa M. Carlisle, Mary Ann Greene Sweeney, Gregory J. Mchugo

Dartmouth Scholarship

Background: The disparities in employment for individuals with serious mental illnesses (SMI) have been well documented, as have the benefits of work. The benefits of mobile technology in providing accessible, in-the-moment support for these individuals has been demonstrated. The WorkingWell mobile app was developed to meet the need for accessible follow-along supports for individuals with SMI in the workplace. Objective: We explore the usability, usage, usefulness and overall feasibility of the WorkingWell mobile app with individuals with SMI receiving community-based services and actively employed. Methods: In this proof-of-concept, mixed methods, two-month feasibility study (N=40), employed individuals with SMI were recruited …

Clinical Effectiveness Of Family Therapeutic Interventions In The Prevention And Treatment Of Perinatal Depression: A Systematic Review And Meta-Analysis, Fallon Cluxton-Keller, Martha L. Bruce

Dartmouth Scholarship

Background:

Family therapy is a potential strategy to increase family support for those suffering from perinatal depression. Family therapeutic interventions for this population typically target depressed women and their adult family members to improve family functioning and reduce depressive symptoms.

Objective:

This systematic review and meta-analysis is a synthesis of the current evidence on the usefulness of family therapy interventions in the prevention and treatment of perinatal depression and impacts on maternal depressive symptoms and family functioning.

Methods:

This study used the Cochrane Collaboration guidelines for systematic reviews and meta-analyses. Six electronic databases were searched for randomized controlled trials and …

Workshop On Emerging Technology And Data Analytics For Behavioral Health, David Kotz, Sarah E. Lord, A. James O'Malley, Luke Stark, Lisa Marsch

Dartmouth Scholarship

Wearable and portable digital devices can support self-monitoring for patients with chronic medical conditions, individuals seeking to reduce stress, and people seeking to modify health-related behaviors such as substance use or overeating. The resulting data may be used directly by a consumer, or shared with a clinician for treatment, a caregiver for assistance, or a health coach for support. The data can also be used by researchers to develop and evaluate just-in-time interventions that leverage mobile technology to help individuals manage their symptoms and behavior in real time and as needed. Such wearable systems have huge potential for promoting delivery …

Daily Associations Between Objective Sleep And Consumption Of Highly Palatable Food In Free-Living Conditions, W. S. Chan

Dartmouth Scholarship

Objectives:

Prior studies have shown that individuals with shorter sleep duration and later sleep timing consume more highly palatable food (HPF). It is unclear if this relationship exists at the within‐individual level, e.g. if sleeping less or later on one night is associated with greater HPF consumption in the following day in naturalistic environments. This study examined the daily associations between naturalistic sleep and HPF consumption.

Methods:

Data were obtained from 78 healthy young adults (age = 20.38 [SD = 2.40] years). Participants carried a wrist actigraph and completed daily diaries tracking food consumption and covariates for seven consecutive days. …

Continue, Adjust, Or Stop Antipsychotic Medication: Developing And User Testing An Encounter Decision Aid For People With First-Episode And Long-Term Psychosis, Yaara Zisman-Ilani, David Shern, Patricia Deegan, Julie Kreyenbuhl, Lisa Dixon, Robert Drake, William Torrey, Manish Mishra, Ksenia Gorbenko, Glyn Elwyn

Dartmouth Scholarship

Background:

People with psychosis struggle with decisions about their use of antipsychotics. They often want to reduce the dose or stop, while facing uncertainty regarding the effects these decisions will have on their treatment and recovery. They may also fear raising this issue with clinicians. The purpose of this study was to develop and test a shared decision making (SDM) tool to support patients and clinicians in making decisions about antipsychotics.

Methods:

A diverse editorial research team developed an Encounter Decision Aid (EDA) for patients and clinicians to use as part of the psychiatric consultation. The EDA was tested using …

Neural Responses To Naturalistic Clips Of Behaving Animals Under Two Different Task Contexts, Samuel A. Nastase, Yaroslav O. Halchenko, Andrew C. Connolly, M. Ida Gobbini, James V. Haxby

Dartmouth Scholarship

The human brain rapidly deploys semantic information during perception to facilitate our interaction with the world. These semantic representations are encoded in the activity of distributed populations of neurons (Haxby et al., 2001; McClelland and Rogers, 2003; Kriegeskorte et al., 2008b) and command widespread cortical real estate (Binder et al., 2009; Huth et al., 2012). The neural representation of a stimulus can be described as a location (i.e., response vector) in a high-dimensional neural representational space (Kriegeskorte and Kievit, 2013; Haxby et al., 2014). This resonates with behavioral and theoretical work describing mental representations of objects and actions as being …

Too Important To Ignore: Leveraging Digital Technology To Improve Chronic Illness Management Among Black Men, Stuart W. Grande, Ledric D. Sherman

Dartmouth Scholarship

Health disparities associated with chronic illness experiences of black men demonstrate widespread, systematic failures to meet an urgent need. Well-established social and behavioral determinants that have led to health disparities among black men include racism, discrimination, and stress. While advocacy work that includes community-engagement and tailoring health promotion strategies have shown local impact, evidence shows the gaps are increasing. We suspect that failure to reduce current disparities may be due to conventional public health interventions and programs; therefore, we submit that innovative interventions, ones that embrace digital technologies and their ability to harness naturally occurring social networks within groups, like …

Altruism, Scepticism, And Collective Decision-Making In Foreign-Born U.S. Residents In A Tuberculosis Vaccine Trial, Sienna R. Craig, Timothy Lahey, Apoorva Dixit, C. Fordham Von Reyn

Dartmouth Scholarship

Background:

The current vaccine against tuberculosis, BCG, is effective when given in most TB-endemic countries at birth but has diminished efficacy against pulmonary TB after 15–20 years. As a result, new booster vaccines for adolescents and adults are being developed to realize the World Health Organization target of global elimination of TB by 2035. Multiple TB candidates thus are in active clinical development.

Methods:

One of these, DAR-901, is advancing in human clinical trials. These clinical trials are conducted in BCG immunized adults with and without HIV infection in order to assess safety and efficacy among the people most in …

Diagnostic Value Of Lingual Tonsillectomy In Unknown Primary Head And Neck Carcinoma Identification After A Negative Clinical Workup And Positron Emission Tomography-Computed Tomography, Chad K. Sudoko, Marc A. Polacco, Benoit J. Gosselin, Joseph A. Paydarfar

Dartmouth Scholarship

Objective: Diagnostic rates of unknown primary head and neck carcinoma (UPHNC) using lingual tonsillectomy (LT) are highly variable. This study sought to determine the diagnostic value of LT in UPHNC identification using strict inclusion criteria and definitions to produce a more accurate estimate of diagnosis rate.

Methods: In this retrospective chart review, records of patients who underwent LT for UPHNC were reviewed. Inclusion criteria included absence of suspicious findings on physical exam and positron emission tomography-computed tomography as well as negative biopsies after panendoscopy and palatine tonsillectomy. Following inclusion criteria, 16 patients were reviewed. A systematic literature review on LT …

Impact Of Prenatal Stress On Offspring Glucocorticoid Levels: A Phylogenetic Meta-Analysis Across 14 Vertebrate Species, Zaneta M. Thayer, Meredith A. Wilson, Andrew W. Kim, Adrian V. Jaeggi

Dartmouth Scholarship

Prenatal exposure to maternal stress is commonly associated with variation in Hypothalamic Pituitary Adrenal (HPA)-axis functioning in ofspring. However, the strength or consistency of this response has never been empirically evaluated across vertebrate species. Here we meta-analyzed 114 results from 39 studies across 14 vertebrate species using Bayesian phylogenetic mixed-efects models. We found a positive overall efect of prenatal stress on ofspring glucocorticoids (d’=0.43) though the 95% Highest Posterior Density Interval overlapped with 0 (−0.16–0.95). Meta-regressions of potential moderators highlighted that phylogeny and life history variables predicted relatively little variation in efect size. Experimental studies (d’=0.64) produced stronger efects than …

Architecting A System Model For Personalized Healthcare Delivery And Managed Individual Health Outcomes, Inas S. Khayal, Amro M. Farid

Dartmouth Scholarship

In recent years, healthcare needs have shifted from treating acute conditions to meeting an unprecedented chronic disease burden. The healthcare delivery system has structurally evolved to address two primary features of acute care: the relatively short time period, on the order of a patient encounter, and the siloed focus on organs or organ systems, thereby operationally fragmenting and providing care by organ specialty. Much more so than acute conditions, chronic disease involves multiple health factors with complex interactions between them over a prolonged period of time necessitating a healthcare delivery model that is personalized to achieve individual health outcomes. Using …

Pre-Post, Mixed Methods Feasibility Study Of The Workingwell Mobile Support Tool For Individuals With Serious Mental Illness In The United States, Johanne Nicholson, Spenser M. Wright, Alyssa M. Carlisle

Dartmouth Scholarship

Successful competitive employment has been found to be related to enhanced self-esteem, higher quality of life and reduced mental health service use for individuals living with serious mental illnesses (SMIs) including schizophrenia, bipolar disorder and major depression. The effectiveness of the individual placement and support model has been demonstrated in multiple randomised controlled trials in many countries. The management of stress, depression and anxiety in the workplace may be effectively enhanced through digital mental health interventions. The WorkingWell mobile support tool (‘app’) is specifically designed to meet the need for illness management support for individuals with SMI in the workplace, …

Closed-Loop Stimulation Of Temporal Cortex Rescues Functional Networks And Improves Memory, Yousseff Ezzyat, Paul A. Wanda, Deborah F. Levy, Allison Kadel, Ada Aka, Isaac Pedisich, Michael R. Sperling, Ashwini D. Sharan, Bradley C. Lega, Alexis Burks, Robert E. Gross, Cory S. Inman, Barbara C. Jobst, Mark A. Gorenstein

Dartmouth Scholarship

Memory failures are frustrating and often the result of ineffective encoding. One approach to improving memory outcomes is through direct modulation of brain activity with electrical stimulation. Previous efforts, however, have reported inconsistent effects when using open-loop stimulation and often target the hippocampus and medial temporal lobes. Here we use a closed-loop system to monitor and decode neural activity from direct brain recordings in humans. We apply targeted stimulation to lateral temporal cortex and report that this stimulation rescues periods of poor memory encoding. This system also improves later recall, revealing that the lateral temporal cortex is a reliable target …

Similar Neural Responses Predict Friendship, Carolyn Parkinson, Adam M. Kleinbaum, Thalia Wheatley

Dartmouth Scholarship

Human social networks are overwhelmingly homophilous: individuals tend to befriend others who are similar to them in terms of a range of physical attributes (e.g., age, gender). Do similarities among friends reflect deeper similarities in how we perceive, interpret, and respond to the world? To test whether friendship, and more generally, social network proximity, is associated with increased similarity of real-time mental responding, we used functional magnetic resonance imaging to scan subjects’ brains during free viewing of naturalistic movies. Here we show evidence for neural homophily: neural responses when viewing audiovisual movies are exceptionally similar among friends, and that similarity …

Application Of Fluorescence-Guided Surgery To Subsurface Cancers Requiring Wide Local Excision: Literature Review And Novel Developments Toward Indirect Visualization., Kimberly S. Samkoe, Brent D. Bates, Jonathan T. Elliott, Ethan Larochelle, Jason R. Gunn, Kayla Marra, Joachim Feldwisch, Dipak B. Ramkumar, David F. Bauer, Keith D. Paulsen, Brian W. Pogue, Eric R. Henderson

Dartmouth Scholarship

The excision of tumors by wide local excision is challenging because the mass must be removed entirely without ever viewing it directly. Positive margin rates in sarcoma resection remain in the range of 20% to 35% and are associated with increased recurrence and decreased survival. Fluorescence-guided surgery (FGS) may improve surgical accuracy and has been utilized in other surgical specialties. ABY-029, an anti-epidermal growth factor receptor Affibody molecule covalently bound to the near-infrared fluorophore IRDye 800CW, is an excellent candidate for future FGS applications in sarcoma resection; however, conventional methods with direct surface tumor visualization are not immediately applicable. A …

Algorithm Development For Intrafraction Radiotherapy Beam Edge Verification From Cherenkov Imaging., Clare Snyder, Brian W. Pogue, Michael Jermyn, Irwin Tendler

Dartmouth Scholarship

Imaging of Cherenkov light emission from patient tissue during fractionated radiotherapy has been shown to be a possible way to visualize beam delivery in real time. If this tool is advanced as a delivery verification methodology, then a sequence of image processing steps must be established to maximize accurate recovery of beam edges. This was analyzed and developed here, focusing on the noise characteristics and representative images from both phantoms and patients undergoing whole breast radiotherapy. The processing included temporally integrating video data into a single, composite summary image at each control point. Each image stack was also median filtered …

Machine Learning Based Classification Of Deep Brain Stimulation Outcomes In A Rat Model Of Binge Eating Using Ventral Striatal Oscillations, Wilder Doucette, Lucas Dwiel, Jared E. Boyce, Amanda A. Simon, Jibran Y. Khokhar, Alan I. Green

Dartmouth Scholarship

Neuromodulation-based interventions continue to be evaluated across an array of appetitive disorders but broader implementation of these approaches remains limited due to variable treatment outcomes. We hypothesize that individual variation in treatment outcomes may be linked to differences in the networks underlying these disorders. Here, Sprague-Dawley rats received deep brain stimulation separately within each nucleus accumbens (NAc) sub-region (core and shell) using a within-animal crossover design in a rat model of binge eating. Significant reductions in binge size were observed with stimulation of either target but with significant variation in effectiveness across individuals. When features of local field potentials (LFPs) …

Impact Of Numeracy On Understanding Of Prostate Cancer Risk Reduction In Psa Screening, Kevin Koo, Charles D. Brackett, Ellen H. Eisenburg, Kelly A. Kieffer, Elias S. Hyams

Dartmouth Scholarship

Prostate-specific antigen (PSA) screening for prostate cancer in men of average risk remains controversial. Patients’ ability to incorporate risk reduction data into their decision-making may depend on their numeracy. We assessed the impact of patients’ numeracy on their understanding of the risk reduction benefits of PSA screening. Men attending a general internal medicine clinic were invited to complete a survey. Four versions of the survey each included a three-item numeracy test and PSA risk reduction data, framed one of four ways: absolute (ARR) versus relative risk reduction (RRR), with or without baseline risk (BR). Respondents were asked to adjust their …

Iron Reduction Response And Demographic Differences Between Diabetics And Non-Diabetics With Cardiovascular Disease Entered To A Controlled Clinical Trial, Leo Zacharski, Galina Shamayeva, Bruce Chow

Dartmouth Scholarship

Iron-catalyzed oxygen free radical-induced oxidative stress mediates the pathogenesis of diabetes and cardiovascular disease (CVD). Diabetics (n=473) and non-diabetics (n=804) with CVD entered to a randomized trial of iron (ferritin) reduction by calibrated phlebotomy (www.clinicaltrials.gov, Identifier NCT00032357) had comparable iron measures at entry but diabetics had greater burden of CVD and comorbidities, lower hemoglobin and hematocrit levels, and higher glucose levels than non-diabetics. Entry iron measures were lower in diabetics on hypoglycemic therapy compared to diabetics untreated previously. Diabetics and non-diabetics had comparable iron measures during follow-up. Loess analysis of paired ferritin and hemoglobin, and paired ferritin and glucose levels …

Vista Deficiency Attenuates Antibody-Induced Arthritis And Alters Macrophage Gene Expression In Response To Simulated Immune Complexes, Sabrina Ceeraz, Susan K. Eszterhas, Petra Sergent, David A. Armstrong, Alix Ashare, Thomas Broughton, Li Wang, Dov Pechenick, Christopher M. Burns, Randolph J. Noelle, Matthew P. Vincenti, Roy A. Fava

Dartmouth Scholarship

In addition to activated T cells, the immune checkpoint inhibitor “V domain-containing Ig suppressor of T-cell activation” (VISTA) is expressed by myeloid cell types, including macrophages and neutrophils. The importance of VISTA expression by myeloid cells to antibody-induced arthritis and its potential for relevance in human disease was evaluated. Methods: VISTA was immunolocalized in normal and arthritic human synovial tissue sections and synovial tissue lysates were subjected to western blot analysis. The collagen antibody-induced arthritis model (CAIA) was performed with DBA/1 J mice treated with antibodies against VISTA and with VISTA-deficient mice (V-KO). Total mRNA from arthritic joints, spleens, and …

Lung Malignancy In Prostate Cancer: A Report Of Both Metastatic And Primary Lung Lesions, Lael Reinstatler, Jonathan Dupuis, Jessica L. Dillon, Candace C. Black, Joseph D. Phillips, Elias S. Hyams

Dartmouth Scholarship

Prostate cancer is the most common non-cutaneous malignancy diagnosed in men. When it metastasizes, it usually spreads to bone and/or lymph nodes. A handful of cases have described prostatic metastases to the lung; however, this is usually in the setting of existing bone lesions. Here we describe a unique case in which a patient was found to have both metastatic prostate cancer to the lung and a primary lung cancer in the absence of any other evidence of extra-prostatic disease.

Small Rna Teg49 Is Derived From A Sara Transcript And Regulates Virulence Genes Independent Of Sara In Staphylococcus Aureus, Adhar Manna, Samin Kim, Liviu Cengher, Anna Corvaglia, Stefano Leo, Patrice Francois, Ambrose L. Cheung

Dartmouth Scholarship

Expression of virulence factors in Staphylococcus aureus is regulated by a wide range of transcriptional regulators, including proteins and small RNAs (sRNAs), at the level of transcription and/or translation. The sarA locus consists of three overlapping transcripts generated from three distinct promoters, all containing the sarA open reading frame (ORF). The 5= untranslated regions (UTRs) of these transcripts contain three separate regions 711, 409, and 146 nucleotides (nt) upstream of the sarA translation start, the functions of which remain unknown. Re- cent transcriptome-sequencing (RNA-Seq) analysis and subsequent characterization indicated that two sRNAs, teg49 and teg48, are processed and likely produced …

Patient-Predicted Sleep Position Vs. Hst Data: A Tendency To Underestimate Supine Sleep, Adam J. Sorscher, Anthony P. Anzivino, Todd Mackenzie

Dartmouth Scholarship

Purpose The purpose of this study is to measure people’s accuracy when they estimate what proportion of their nightly sleep at home is supine vs. non-supine. Methods A series of patients referred for obstructive sleep apnea (OSA) evaluation were asked if they Bknew with confidence^ how they slept with regard to their body position. BYes^ responders were then asked to estimate what percentage of their sleep was supine vs. non-supine. This value was compared with the actual proportion of supine vs. non-supine sleep that they exhibited in a home sleep test (HST) that followed. Results We obtained data from 49 …

Addition Of T2-Guided Optical Tomography Improves Noncontrast Breast Magnetic Resonance Imaging Diagnosis., Jinchao Feng, Junqing Xu, Shudong Jiang, Hong Yin, Yan Zhao, Jiang Gui, Ke Wang, Xiuhua Lv, Fang Ren, Brian W. Pogue, Keith D. Paulsen

Dartmouth Scholarship

BACKGROUND:

While dynamic contrast-enhanced magnetic resonance imaging (DCE MRI) is recognized as the most sensitive examination for breast cancer detection, it has a substantial false positive rate and gadolinium (Gd) contrast agents are not universally well tolerated. As a result, alternatives to diagnosing breast cancer based on endogenous contrast are of growing interest. In this study, endogenous near-infrared spectral tomography (NIRST) guided by T2 MRI was evaluated to explore whether the combined imaging modality, which does not require contrast injection or involve ionizing radiation, can achieve acceptable diagnostic performance.

METHODS:

Twenty-four subjects-16 with pathologically confirmed malignancy and 8 with benign …

Intrinsic And Innate Defenses Of Neurons: Détente With The Herpesviruses, Lynn Enquist, David A. Leib

Dartmouth Scholarship

Neuroinvasive herpesviruses have evolved to efficiently infect and establish latency in neurons. The nervous system has limited capability to regenerate, so immune responses therein are carefully regulated to be nondestructive, with dependence on atypical intrinsic and innate defenses. In this article we review studies of some of these noncanonical defense pathways and how herpesvirus gene products counter them, highlighting the contributions that primary neuronal in vitro models have made to our understanding of this field.

Optimizing Fresh Specimen Staining For Rapid Identification Of Tumor Biomarkers During Surgery., Connor W. Barth, Jasmin M. Schaefer, Vincent M. Rossi, Scott C. Davis, Summer L. Gibbs

Dartmouth Scholarship

Rationale: Positive margin status due to incomplete removal of tumor tissue during breast conserving surgery (BCS) is a prevalent diagnosis usually requiring a second surgical procedure. These follow-up procedures increase the risk of morbidity and delay the use of adjuvant therapy; thus, significant efforts are underway to develop new intraoperative strategies for margin assessment to eliminate re-excision procedures. One strategy under development uses topical application of dual probe staining and a fluorescence imaging strategy termed dual probe difference specimen imaging (DDSI). DDSI uses a receptor-targeted fluorescent probe and an untargeted, spectrally-distinct fluorescent companion imaging agent topically applied to fresh resected …

Assessing Daylight & Low-Dose Rate Photodynamic Therapy Efficacy, Using Biomarkers Of Photophysical, Biochemical And Biological Damage Metrics In Situ., Ana Luiza Ribeiro De Souza, Ethan Larochelle, Kayla Marra, Jason Gunn, Scott C. Davis, Kimberley S. Samoke, M. Shane Chapman, Edward V. Maytin, Tayyaba Hasan, Brian W. Pogue

Dartmouth Scholarship

Background

Sunlight can activate photodynamic therapy (PDT), and this is a proven strategy to reduce pain caused by conventional PDT treatment, but assessment of this and other alternative low dose rate light sources, and their efficacy, has not been studied in an objective, controlled pre-clinical setting. This study used three objective assays to assess the efficacy of different PDT treatment regimens, using PpIX fluorescence as a photophysical measure, STAT3 cross-linking as a photochemical measure, and keratinocyte damage as a photobiological measure.

Methods

Nude mouse skin was used along with in vivo measures of photosensitizer fluorescence, keratinocyte nucleus damage from pathology, …

Anthropometric Factors And Cutaneous Melanoma: Prospective Data From The Population-Based Janus Cohort, Jo S. Stenehjem, Marit B. Veierød, Lill Tove Nilsen, Reza Ghiasvand, Bjørn Johnsen, Tom K. Grimsrud, Ronnie Babigumira, Judy R. Rees, Trude E. Robsahm

Dartmouth Scholarship

The aim of the present study was to prospectively examine risk of cutaneous melanoma (CM) according to measured anthropometric factors, adjusted for exposure to ultraviolet radiation (UVR), in a large population-based cohort in Norway. The Janus Cohort, including 292,851 Norwegians recruited 1972–2003, was linked to the Cancer Registry of Norway and followed for CM through 2014. Cox regression was used to estimate hazard ratios (HRs) of CM with 95% confidence intervals (CIs). Restricted cubic splines were incorporated into the Cox models to assess possible non-linear relationships. All analyses were adjusted for attained age, indicators of UVR exposure, education, and smoking …