Medicine and Health Sciences Commons^™

Site-Specific Mutation Of The Sensor Kinase Gras In Staphylococcus Aureus Alters The Adaptive Response To Distinct Cationic Antimicrobial Peptides, Ambrose L. Cheung, Arnold S. Bayer, Michael R. Yeaman, Yan Q. Xiong, Alan J. Waring, Guido Memmi, Niles Donegan

Dartmouth Scholarship

The Staphylococcus aureus two-component regulatory system, GraRS, is involved in resistance to killing by distinct host defense cationic antimicrobial peptides (HD-CAPs). It is believed to regulate downstream target genes such as mprF and dltABCD to modify the S. aureus surface charge. However, the detailed mechanism(s) by which the histidine kinase, GraS, senses specific HD-CAPs is not well defined. Here, we studied a well-characterized clinical methicillin-resistant S. aureus (MRSA) strain (MW2), its isogenic graS deletion mutant (ΔgraS strain), a nonameric extracellular loop mutant (ΔEL strain), and four residue-specific ΔEL mutants (D37A, P39A, P39S, and D35G D37G D41G strains). The ΔgraS and …

Wordless Intervention For Epilepsy In Learning Disabilities (Wield): Study Protocol For A Randomized Controlled Feasibility Trial, Marie-Anne Durand, Bob Gates, Georgina Parkes, Asif Zia

Dartmouth Scholarship

Epilepsy is the most common neurological problem that affects people with learning disabilities. The high seizure frequency, resistance to treatments, associated skills deficit and co-morbidities make the management of epilepsy particularly challenging for people with learning disabilities. The Books Beyond Words booklet for epilepsy uses images to help people with learning disabilities manage their condition and improve quality of life. Our aim is to conduct a randomized controlled feasibility trial exploring key methodological, design and acceptability issues, in order to subsequently undertake a large-scale randomized controlled trial of the Books Beyond Words booklet for epilepsy.

Blood Levels Of S-100 Calcium-Binding Protein B, High-Sensitivity C-Reactive Protein, And Interleukin-6 For Changes In Depressive Symptom Severity After Coronary Artery Bypass Grafting: Prospective Cohort Nested Within A Randomized, Controlled Trial, Daniel M. Pearlman, Jeremiah R. R. Brown, Todd A. Mackenzie, Felix Hernandez, Souhel Najjar

Dartmouth Scholarship

Background: Cross-sectional and retrospective studies have associated major depressive disorder with glial activation and injury as well as blood–brain barrier disruption, but these associations have not been assessed prospectively. Here, we aimed to determine the relationship between changes in depressive symptom severity and in blood levels of S-100 calcium- binding protein B (S-100B), high-sensitivity C-reactive protein, and interleukin-6 following an inflammatory challenge.

Methods: Fifty unselected participants were recruited from a randomized, controlled trial comparing coronary artery bypass grafting procedures performed with versus without cardiopulmonary bypass for the risk of neurocognitive decline. Depressive symptom severity was measured at baseline, discharge, and …

Role Of A Genetic Variant On The 15q25.1 Lung Cancer Susceptibility Locus In Smoking-Associated Nasopharyngeal Carcinoma, Xuemei Ji, Weidong Zhang, Jiang Gui, Xia Fan, Weiwei Zhang, Yafang Li, Guangyu An, Dakai Zhu, Qiang Hu

Dartmouth Scholarship

Background: The 15q25.1 lung cancer susceptibility locus, containing CHRNA5, could modify lung cancer susceptibility and multiple smoking related phenotypes. However, no studies have investigated the association between CHRNA5 rs3841324, which has been proven to have the highest association with CHRNA5 mRNA expression, and the risk of other smoking-associated cancers, except lung cancer. In the current study we examined the association between rs3841324 and susceptibility to smoking-associated nasopharyngeal carcinoma (NPC).

Methods: In this case-control study we genotyped the CHRNA5 rs3841324 polymorphism with 400 NPC cases and 491 healthy controls who were Han Chinese and frequency-matched by age (±5 years), gender, and …

Calcium Supplementation Increases Blood Creatinine Concentration In A Randomized Controlled Trial, Elizabeth L. L. Barry, Leila A. A. Mott, Michal L. L. Melamed, Judith R. Rees, Anastasia Ivanova, Robert S. Sandler, Dennis J. Ahnen, Robert S. Bresalier, Robert W. Summers, Roberd M. Bostick, John A. Baron

Dartmouth Scholarship

Background: Calcium supplements are widely used among older adults for osteoporosis prevention and treatment. However, their effect on creatinine levels and kidney function has not been well studied.

Methods: We investigated the effect of calcium supplementation on blood creatinine concentration in a randomized controlled trial of colorectal adenoma chemoprevention conducted between 2004–2013 at 11 clinical centers in the United States. Healthy participants (N=1,675) aged 45–75 with a history of colorectal adenoma were assigned to daily supplementation with calcium (1200 mg, as carbonate), vitamin D3 (1000 IU), both, or placebo for three or five years. Changes in blood creatinine and total …

Successful Mdr-Tb Treatment Regimens Including Amikacin Are Associated With High Rates Of Hearing Loss, Chawangwa Modongo, Rafal S. Sobota, Boikobo Kesenogile, Ronald Ncube

Dartmouth Scholarship

Aminoglycosides are a critical component of multidrug-resistant tuberculosis (MDR-TB) treatment but data on their efficacy and adverse effects in Botswana is scarce. We determined the effect of amikacin on treatment outcomes and development of hearing loss in MDR-TB patients. Patients started on MDR-TB treatment between 2006 and 2012 were included. Multivariate analysis was used to determine the effect of amikacin on treatment outcomes and development of hearing loss.

The Impact Of Waist Circumference On Function And Physical Activity In Older Adults: Longitudinal Observational Data From The Osteoarthritis Initiative, John A. Batsis, Alicia J. Zbehlik, Laura K. Barre, Todd A. Mackenzie, Stephen J. Bartels

Dartmouth Scholarship

Background: We previously demonstrated that BMI is associated with functional decline and reduced quality of life. While BMI in older adults is fraught with challenges, waist circumference (WC) is a marker of visceral adiposity that can also predict mortality. However, its association with function and quality of life in older adults is not well understood and hence we sought to examine the impact of WC on six-year outcomes.

Methods: We identified adults aged ≥60 years from the longitudinal Osteoarthritis Initiative and stratified the cohort into quartiles based on WC. Our primary outcome measures of function at six year follow-up included: …

Performance Of The Oraquick Hcv Rapid Antibody Test For Screening Exposed Patients In A Hepatitis C Outbreak Investigation, Fengxiang Gao, Elizabeth A. Talbot, Carol H. Loring, Jill J. Power, Jodie Dionne-Odom

Dartmouth Scholarship

During a nosocomial hepatitis C outbreak, emergency public clinics employed the OraQuick HCV rapid antibody test on site, and all results were verified by a standard enzyme immunoassay (EIA). Of 1,157 persons, 1,149 (99.3%) exhibited concordant results between the two tests (16 positive, 1,133 negative). The sensitivity, specificity, positive predictive value, and negative predictive value were 94.1%, 99.5%, 72.7%, and 99.9%, respectively. OraQuick performed well as a screening test during an outbreak investigation and could be integrated into future hepatitis C virus (HCV) outbreak testing algorithms.

Why 'Down Under' Is A Cut Above: A Comparison Of Rates Of And Reasons For Caesarean Section In England And Australia, Samantha J. Prosser, Yvette D. Miller, Rachel Thompson, Maggie Redshaw

Dartmouth Scholarship

Background: Most studies examining determinants of rising rates of caesarean section have examined patterns in documented reasons for caesarean over time in a single location. Further insights could be gleaned from cross-cultural research that examines practice patterns in locations with disparate rates of caesarean section at a single time point.

Methods: We compared both rates of and main reason for pre-labour and intrapartum caesarean between England and Queensland, Australia, using data from retrospective cross-sectional surveys of women who had recently given birth in England (n = 5,250) and Queensland (n = 3,467).

An Imaging-Based Platform For High-Content, Quantitative Evaluation Of Therapeutic Response In 3d Tumour Models, Jonathan P. Celli, Imran Rizvi, Adam R. Blanden, Iqbal Massodi, Iqbal Massodi, Michael D. Glidden, Brian Pogue, Tayyaba Hasan

Dartmouth Scholarship

While it is increasingly recognized that three-dimensional (3D) cell culture models recapitulate drug responses of human cancers with more fidelity than monolayer cultures, a lack of quantitative analysis methods limit their implementation for reliable and routine assessment of emerging therapies. Here, we introduce an approach based on computational analysis of fluorescence image data to provide high-content readouts of dose-dependent cytotoxicity, growth inhibition, treatment-induced architectural changes and size-dependent response in 3D tumour models. We demonstrate this approach in adherent 3D ovarian and pancreatic multiwell extracellular matrix tumour overlays subjected to a panel of clinically relevant cytotoxic modalities and appropriately designed controls …

Birth Control: To What Extent Do Women Report Being Informed And Involved In Decisions About Pregnancy And Birth Procedures?, Rachel Thompson, Yvette D. Miller

Dartmouth Scholarship

Background: Health policy, guidelines, and standards advocate giving patients comprehensive information and facilitating their involvement in health-related decision-making. Routine assessment of patient reports of these processes is needed. Our objective was to examine decision-making processes, specifically information provision and consumer involvement in decision-making, for nine pregnancy, labour, and birth procedures, as reported by maternity care consumers in Queensland, Australia.

Methods: Participants were women who had a live birth in Queensland in a specified time period and were not found to have had a baby that died since birth, who completed the extended Having a Baby in Queensland Survey, 2010 about …