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Recently Published

  • POINT-OF-CARE TECHNOLOGY CLINICIAN-FACING SURVEY Dataset for Sampling of Healthcare Professionals’ Perspective on Point-of-Care Technologies from 2019-2021: a survey of benefits, concerns, and development

    Orwig, Taylor; Sutaria, Shiv; Wang, Ziyue; Howard-Wilson, Sakeina; Dunlap, Denise; Lilly, Craig M; Buchholz, Bryan; McManus, David D.; Hafer, Nathaniel (2023-11-27)
    Point-of-care technology (POCT) plays a vital role in modern healthcare by providing a fast diagnosis, improving patient management, and extending healthcare access to remote and resource-limited areas. The objective of this study was to understand how healthcare professionals in the United States perceived POCTs during 2019-2021 to assess the decision-making process of implementing these newer technologies into everyday practice.
  • Data from LGBTQ+ Health Research Guides: A Multi-Institutional Analysis of Usage Patterns and User Information Needs

    Stevens, Gregg A.; Morris, Martin; Parker, Robin M. N.; Fajardo, Francisco J.; Brody, Erica R.; McLean, Katie D. (2023-06-09)
    Data and documentation from LGBTQ+ Health Research Guides: A Multi-Institutional Analysis of Usage Patterns and User Information Needs research study.
  • Data and Code from "Show me the data! Data sharing practices demonstrated in published research at the University of Massachusetts Chan Medical School"

    Grynoch, Tess; MacKenzie, Kimberly (2022-07-11)
    Data extracted from articles published by UMass Chan researchers to determine where and how data was being shared. Code from the analysis is also included.
  • Dataset from: COVID-19: A Gray Swan’s Impact on the Adoption of Novel Medical Technologies

    Dunlap, Denise; Santos, Roberto S.; Lilly, Craig M; Teebagy, Sean; Hafer, Nathaniel; Buchholz, Bryan; McManus, David D. (2021-12-20)
    This dataset is used to examine how the COVID-19 pandemic has shifted many providers and patient perspectives related to healthcare and offers an opportunity to investigate potential changes in provider perceptions towards the adoption of novel point-of-care technologies (POCTs).
  • Supplementary materials for: Ergocalciferol in New-onset Type 1 diabetes: A Randomized Controlled Trial

    Nwosu, Benjamin U.; Parajuli, Sadichchha; Jasmin, Gabrielle; Fleshman, Jody; Sharma, Rohit B.; Alonso, Laura C.; Lee, Austin F.; Barton, Bruce A. (2021-09-15)
    This document consists of supplementary materials, including the 2021 Investigational Study Protocol, for a published manuscript. Manuscript abstract: Context: The effect of the anti-inflammatory and immunomodulatory actions of vitamin D on the duration of partial clinical remission (PR) in youth with type 1 diabetes (T1D) is unclear. Objective: This work aimed to determine the effect of adjunctive ergocalciferol on residual β-cell function (RBCF) and PR in youth with newly diagnosed T1D who were maintained on a standardized insulin treatment protocol. The hypothesis was that ergocalciferol supplementation increases RBCF and prolongs PR. Methods: A 12-month, randomized, double-blind, placebo-controlled trial was conducted of 50 000 IU of ergocalciferol per week for 2 months, and then once every 2 weeks for 10 months, vs placebo in 36 individuals aged 10 to 21 years, with T1D of less than 3 months and a stimulated C-peptide (SCP) level greater than or equal to 0.2 nmol/L (≥ 0.6 ng/mL). The ergocalciferol group had 18 randomly assigned participants (10 male/8 female), mean age 13.3 ± 2.8 years, while the control group had 18 participants (14 male/4 female), aged 14.3 ± 2.9 years. Results: The ergocalciferol treatment group had statistically significantly higher serum 25-hydroxyvitamin D at 6 months (P = .01) and 9 months (P = .02) than the placebo group. At 12 months, the ergocalciferol group had a statistically significantly lower serum tumor necrosis factor α (TNF-α) concentration (P = .03). There were no statistically significant differences between the groups at each time point from baseline to 12 months for SCP concentration (P = .08), glycated hemoglobin A1c (HbA1c) (P = .09), insulin dose-adjusted A1c (IDAA1c), or total daily dose of insulin. Temporal trends for rising HbA1c (P = .04) and IDAA1c (P = .02) were statistically significantly blunted in the ergocalciferol group. Conclusion: Ergocalciferol statistically significantly reduced serum TNF-α concentration and the rates of increase both in A1c and IDAA1c, suggesting a protection of RBCF and PR in youth with newly diagnosed T1D.
  • TRACE-CORE Dataset on Religious Practices and Long-Term Survival after Hospital Discharge for an Acute Coronary Syndrome

    Abu, Hawa O.; Lapane, Kate L.; Waring, Molly E.; Ulbricht, Christine M.; Devereaux, Randolph S.; McManus, David D.; Allison, Jeroan J.; Kiefe, Catarina I.; Goldberg, Robert J. (2019-08-13)
    Manuscript abstract: Background: Prior studies of healthy populations have found religious practices to be associated with survival. However, no contemporary studies have examined whether religiosity influences survival among patients discharged from the hospital after an acute coronary syndrome (ACS). The present study examined the relationship between religious practices and 2-year all-cause mortality among hospital survivors of an ACS. Methods: Patients hospitalized for an ACS were recruited from 6 medical centers in Massachusetts and Georgia between 2011 and 2013. Study participants self-reported three items assessing religiosity: strength/comfort from religion, petition prayers for health, and awareness of intercessory prayers by others. All cause-mortality within 2-years of hospital discharge was ascertained by review of medical records at participating study hospitals and from death certificates. Cox proportional hazards models were used to estimate the multivariable adjusted risk of 2-year all-cause mortality. Results: Participants (n=2,068) were on average 61 years old, 34% were women, and 81% were non-Hispanic White. Approximately 85% derived strength/comfort from religion, 61% prayed for their health, and 89% were aware of intercessions. Overall, 6% died within 2 years post-discharge. After adjusting for sociodemographic variables (age, sex, and race/ethnicity), petition prayers were associated with an increased risk of 2-year all-cause mortality (HR: 1.64; 95% CI: 1.01-2.66). With further adjustment for several clinical and psychosocial measures, this association was no longer statistically significant. Strength/comfort from religion and intercessory prayers were not significantly associated with mortality. Conclusions: Most ACS survivors acknowledge deriving strength and comfort from religion, praying for their health, and intercessions made by others for their health. Although the reported religious practices were not associated with post-discharge survival after multivariable adjustment, acknowledging that patients utilize their religious beliefs and practices as strategies to improve their health would ensure a more holistic approach to patient management.
  • Data from: The Institutional Repository Landscape in Medical Schools and Academic Health Centers: A 2018 Snapshot View and Analysis

    Kipnis, Daniel G.; Palmer, Lisa A.; Kubilius, Ramune K. (2019-04-25)
    This dataset supports a research study where we used survey research methods to gain a deeper understanding of the institutional repository (IR) landscape in medical schools and academic health centers. The dataset is composed of a set of comma-delimited (.csv) files and a text README file. Information about the dataset, including a file list, can be found in the README file.
  • Data from: Tobacco smoke exposure is an independent predictor of vitamin D deficiency in US children

    Nwosu, Benjamin U.; Kum-Nji, Philip (2018-06-26)
    Manuscript abstract: IMPORTANCE: The role of tobacco-smoke exposure on serum vitamin D concentration in US pediatric population is not known. We hypothesized that tobacco smoke exposure would increase the prevalence of vitamin D deficiency in US children. METHODS: Representative national data were accessed from the National Health and Nutrition Examination Survey (NHANES) 2009-2010 databank on 2,263 subjects of ages 3 to 17 years. Subjects were categorized into two groups based on their age: children, ifyears; and youth if 10 to 17 years. Descriptive and multiple logistic regression analyses were conducted to determine the effect of serum cotinine-verified tobacco smoke exposure on vitamin D status after controlling for key sociodemographic confounders. Vitamin D deficiency was defined as 25(OH)D/mL, insufficiency as 25(OH)D of 20-29.9 ng/mL, and sufficiency as 25(OH)D of ≥30 ng/mL. Tobacco smoke exposure status was defined by serum cotinine concentration as follows: unexposed and non-smoking ( RESULTS: The prevalence of second-hand smoke exposure was 42.0% (95%CI, 36.7%-47.5%); while the prevalence of active smoking among teenagers was 9.0% (95%CI, 6.2%-12.5%). Vitamin D deficiency occurred at a frequency of 15.1% in children unexposed to tobacco smoke, 20.9% in children exposed to passive tobacco smoke, and 18.0% among actively smoking youth (p CONCLUSIONS: This analysis of a nationwide database reports that tobacco smoke exposure is an independent predictor of vitamin D deficiency in US children.
  • Data from: Children with type 1 diabetes who experienced a honeymoon phase had significantly lower LDL cholesterol 5 years after diagnosis

    Nwosu, Benjamin U.; Zhang, Bo; Ayyoub, Sanaa S.; Choi, Stephanie; Villalobos-Ortiz, Tony R.; Alonso, Laura C.; Barton, Bruce A. (2018-02-06)
    Manuscript abstract: Importance: Landmark studies showed that partial clinical remission in new-onset type 1 diabetes is associated with reduced prevalence of long-term complications, but early clinical indicators of this favorable outcome are poorly characterized. Aim: To determine if there were any differences in lipid parameters, especially LDL-cholesterol, between remitters and non-remitters 4 to 5 years after the diagnosis of type 1 diabetes after controlling for hemoglobin A1c, body mass index, and pubertal status. Subjects and Methods: A longitudinal retrospective cohort study of 123 subjects of mean age 11.9 ± 2.9 years, [male 11.7 ± 2.9 years, (n=55); female 12.0 ± 2.9 years, (n=68), p=0.60] with type 1 diabetes of 4-5 years duration. Anthropometric and biochemical data were collected at the 4th or 5th year after diagnosis in line with the American Diabetes Association recommendation to initiate screening for complications in children either at the beginning of puberty or 4-5 years after diagnosis. Puberty was defined by Tanner stages II-V. Partial clinical remission was defined by the gold-standard insulin-dose adjusted hemoglobin A1c (IDAA1c) of ≤9. Results: There were 44 (35.8%) remitters (age 13.0 ± 2.5y; male 52.3%). Both the total cholesterol and LDL-cholesterol were significantly lower in remitters compared to non-remitters: LDL-C: 78.8 ± 28.7 mg/dL vs. 91.6 ± 26.5 mg/dL, p=0.023; and total cholesterol: 151.5 ± 32.6 mg/dL vs. 167.0 ± 29.6 mg/dL, p=0.015. Other lipid fractions were similar between the groups. There were no differences between the groups for glycemic control, body mass index z score, thyroid function, celiac disease occurrence, or vitamin D status. Though a greater number of remitters were in puberty compared to non-remitters (86.4% vs. 60.8%, p=0.006), LDL-C concentration was similar in prepubertal remitters vs. non-remitters (p=0.93), but was significantly lower in remitters in puberty compared to non-remitters in puberty (p=0.018) after adjusting for age and duration of diabetes. Conclusions: Children with type 1 diabetes who underwent a honeymoon phase had significantly lower LDL cholesterol 5 years after diagnosis regardless of their age, glycemic control, adiposity, or pubertal status. This early divergence in lipidemia may explain the dichotomy in the prevalence of long-term complication in type 1 diabetes between remitters and non-remitters. It also offers a pathway for targeted lipid monitoring in type 1 diabetes, by establishing non-remission as a non-modifiable risk factor for vascular complication in type 1 diabetes.
  • Data from: A Predictive Model for Lack of Partial Clinical Remission in New-onset Pediatric Type 1 Diabetes

    Marino, Katherine R.; Lundberg, Rachel L.; Jasrotia, Aastha; Maranda, Louise S.; Thompson, Michael J.; Barton, Bruce A.; Alonso, Laura C.; Nwosu, Benjamin U. (2017-02-09)
    Manuscript abstract: IMPORTANCE: >50% of patients with new-onset type 1 diabetes (T1D) do not enter partial clinical remission (PCR); early identification of these patients may improve initial glycemic control and reduce long-term complications. AIM: To determine whether routinely obtainable clinical parameters predict non-remission in children and adolescents with new-onset T1D. SUBJECTS AND METHODS: Data on remission were collected for the first 36 months of disease in 204 subjects of ages 2-14 years with new-onset type 1 diabetes. There were 86 remitters (age 9.1±3.0y; male 57%), and 118 non-remitters (age 7.0±3.1y; male 40.7%). PCR was defined as insulin-dose adjusted hemoglobin A1c of ≤9. RESULTS: Non-remission occurred in 57.8% of subjects. Univariable analysis showed that the risk for non-remission was increased 9-fold in patients with 4 diabetes-associated auto-antibodies (OR = 9.90, p = 0.010); 5-fold in patients(odds ratio = 5.38, p = 0.032), 3-fold in those with bicarbonate of/dL at diagnosis (OR = 3.71, p = 0.008). Combined estimates of risk potential for HC03 and the number of autoantibodies by multivariable analysis, adjusted for BMI standard deviation score, showed HC03/dL with a clinically significant 10-fold risk (OR = 10.1, p = 0.074); and the number of autoantibodies with a 2-fold risk for non-remission (OR = 1.9, p = 0.105). Male sex and older age were associated with decreased risk for non-remission. A receiver-operating characteristic curve model depicting sensitivity by 1-specificity for non-remission as predicted by bicarbonate/dL, age3 diabetes-associated autoantibodies had an area under the curve of 0.73. CONCLUSIONS: More than 50% of children and adolescents with new-onset T1D do not undergo partial clinical remission and are thus at an increased risk for long-term complications of diabetes mellitus. A predictive model comprising of bicarbonate/dL, age3 diabetes-associated autoantibodies has 73% power for correctly predicting non-remission in children and adolescents with new-onset T1D. Early identification of these non-remitters may guide the institution of targeted therapy to limit dysglycemia and reduce the prevalence of long-term deleterious complications.
  • Data from: Vitamin D Status in Pediatric Irritable Bowel Syndrome

    Nwosu, Benjamin U.; Maranda, Louise S.; Candela, Ninfa (2016-10-29)
    Manuscript abstract: IMPORTANCE: Irritable bowel syndrome (IBS) is associated with significant morbidity in children and adolescents, and the therapeutic efficacy of available treatment options is limited. The role of vitamin D supplementation in pediatric IBS is unclear as the vitamin D status of pediatric patients with IBS is unknown. Equally, the relationship of vitamin D status with psychosomatic symptoms in children and adolescents is unclear. AIM: To characterize the vitamin D status of pediatric patients with IBS using a case-control study design. HYPOTHESIS: Serum 25-hydroxyvitamin D [25(OH)D] concentration will be similar between patients with IBS and controls. SUBJECTS AND METHODS: A retrospective case-controlled study of 116 controls (age 14.6 ± 4.3 y), female (n = 67; 58%) and 55 subjects with IBS (age 16.5 ± 3.1y), female (n = 44; 80%). Overweight was defined as BMI of ≥85th butpercentile, and obesity as BMI ≥95th percentile. Vitamin D deficiency was defined as 25(OH)D of/L, while seasons of vitamin D draw were categorized as summer, winter, spring, and fall. Major psychosomatic manifestations included in the analysis were depression, anxiety, and migraine. RESULTS: More than 50% of IBS subjects had vitamin D deficiency at a cut-off point of/L (53% vs. 27%, p = 0.001); and >90% of IBS subjects had vitamin D deficiency at a cut-off point of/L (93% vs. 75%, p = 0.006). IBS subjects had significantly lower mean 25(OH)D: 53.2 ± 15.8 nmol/L vs. 65.2 ± 28.0 nmol/L, p = 0.003; and albumin: 6.2 ± 0.6 vs. 6.5 ± 0.6 μmol/L, p = 0.0.01. IBS subjects with migraine had significantly lower mean 25(OH)D concentration compared to controls (p = 0.01). BMI z-score was similar between the controls and IBS subjects (0.5 ± 1.4 vs. 1.2 ± 2.9, p = 0.11). CONCLUSIONS: Pediatric patients with IBS had significantly lower 25(OH)D concentration compared to controls despite having similar mean BMI values as controls. Only 7% of the children and adolescents with IBS were vitamin D sufficient, and >50% of the subjects with IBS had vitamin D deficiency. This is a much higher prevalence of vitamin D deficiency compared to IBD and other malabsorption syndromes. Monitoring for vitamin D deficiency should be part of the routine care for patients with IBS. Randomized control trials are warranted to determine the role of adjunctive vitamin D therapy in pediatric IBS.
  • Data from: A Higher Activation Threshold of Memory CD8+ T Cells Has a Fitness Cost That Is Modified by TCR Affinity during Tuberculosis

    Carpenter, Stephen M.; Nunes-Alves, Claudio; Booty, Matthew G.; Way, Sing Sing; Behar, Samuel M. (2015-12-15)
    Manuscript abstract: T cell vaccines against Mycobacterium tuberculosis (Mtb) and other pathogens are based on the principle that memory T cells rapidly generate effector responses upon challenge, leading to pathogen clearance. Despite eliciting a robust memory CD8+ T cell response to the immunodominant Mtb antigen TB10.4 (EsxH), we find the increased frequency of TB10.4-specific CD8+ T cells conferred by vaccination to be short-lived after Mtb challenge. To compare memory and naïve CD8+ T cell function during their response to Mtb, we track their expansions using TB10.4-specific retrogenic CD8+ T cells. We find that the primary (naïve) response outnumbers the secondary (memory) response during Mtb challenge, an effect moderated by increased TCR affinity. To determine whether the expansion of polyclonal memory T cells is restrained following Mtb challenge, we used TCRβ deep sequencing to track TB10.4-specific CD8+ T cells after vaccination and subsequent challenge in intact mice. Successful memory T cells, defined by their clonal expansion after Mtb challenge, express similar CDR3β sequences suggesting TCR selection by antigen. Thus, both TCR-dependent and -independent factors affect the fitness of memory CD8+ responses. The impaired expansion of the majority of memory T cell clonotypes may explain why some TB vaccines have not provided better protection.
  • Data from: The Cardiovascular Effects of Adjunctive Metformin Therapy in Overweight/obese Youth with Type 1 Diabetes: A Randomized, Double-Blind, Placebo-Controlled Trial

    Nwosu, Benjamin U.; Maranda, Louise S.; Cullen, Karen; Greenman, Lisa; Fleshman, Jody; McShea, Nancy; Barton, Bruce A.; Lee, Mary M. (2015-10-08)
    This dataset is the primary data source for a manuscript submitted for publication. Manuscript abstract: Context: The cardiovascular effect of adjunctive metformin therapy in overweight/obese youth with type 1 diabetes (T1D) is unknown. Objective: To compare the effect of prolonged, adjunctive metformin vs. placebo therapy on markers of cardiovascular risk in overweight/obese youth with T1D based on differences in total cholesterol (TC)/ high-density lipoprotein (HDL) ratio, triglycerides (TG)/HDL ratio, Atherogenic Index of Plasma (AIP) log [TG/HDL] ratio, adiponectin/leptin ratio, and 25-hydroxyvitamin D [25(OH)D] concentration. Hypothesis: Adjunctive metformin therapy will improve markers of cardiovascular health in overweight/obese youth with T1D. Setting: University outpatient facility. Design and Participants: A 9-mo randomized, double-blind, placebo-controlled trial of metformin (1000 mg daily) and placebo in 28 subjects (13m/15f) of ages 10-20years (y), with HbA1c >8%, BMI >85%, and T1D > 12 months. The metformin group consisted of 15 subjects (8 m/7f), of age 15.0±2.5 y; while the control group consisted of 13 subjects (5m/8f), of age 14.5±3.1y. Participants employed a self-directed treat-to-target insulin regimen based on a titration algorithm of (-2)-0-(+2) units to adjust long-acting insulin dose every 3rd day from -3 mo through +9 mo to maintain fasting plasma glucose between 90-120 mg/dL. Results: After adjusting for age, gender, BMI, and baseline values, the metformin group had a clinically significant reduction in TC/HDL of 0.5 unit: 3.5[3.0-4.1] vs. 4.0 [3.3-4.4] (p=0.578); and TG/HDL of 1.0 unit, 2.6 [1.1-4.3] vs. 3.6 [2.0-5.2] (p=0.476); and AIP of 0.44 unit: -0.23 ± 0.9 vs. 0.21 ± 0.8 (p=0.251). Conversely, the metformin group had a clinically significant elevation in adiponectin/leptin ratio of 0.8 unit: 2.0[0.84-3.2] vs. 1.2[0.11-2.3], (p=0.057); and a mean serum 25(OH)D in the vitamin D sufficiency range, 31.3 ng/mL [22.3-40.4] compared to the placebo group's lower mean 25(OH)D of 25.8 ng/mL [14.1-35.9], (p=0.337). Conclusions: Prolonged adjunctive metformin therapy may be cardio-protective in overweight/obese youth with T1D.
  • Data from: A Randomized, Double-Blind, Placebo-Controlled Trial of Adjunctive Metformin Therapy in Overweight/Obese Youth with Type 1 Diabetes

    Nwosu, Benjamin U.; Maranda, Louise; Cullen, Karen; Greenman, Lisa; Fleshman, Jody; McShea, Nancy; Barton, Bruce A.; Lee, Mary M. (2015-07-01)
    Manuscript abstract: CONTEXT: Insulin resistance has been proposed as one of the causes of poor glycemic control in overweight/obese youth with type 1 diabetes (T1D). However, the role of adjunctive metformin, an insulin sensitizer, on glycemic control in these patients is unclear. OBJECTIVE: To compare the effect of metformin vs. placebo on hemoglobin A1c (HbA1c), total daily dose (TDD) of insulin, and other parameters in overweight/obese youth with T1D. HYPOTHESIS: Adjunctive metformin therapy will improve glycemic control in overweight/obese youth with T1D. DESIGN, SETTING, AND PARTICIPANTS: A 9-mo randomized, double-blind, placebo controlled trial of metformin and placebo in 28 subjects (13m/15f) of ages 10-20years (y), with HbA1c >8% (64 mmol/mol), BMI >85%, and T1D > 12 months was conducted at a university outpatient facility. The metformin group consisted of 15 subjects (8 m/ 7f), of age 15.0 ± 2.5 y; while the control group was made up of 13 subjects (5m/ 8f), of age 14.5 ± 3.1y. All participants employed a self-directed treat-to-target insulin regimen based on a titration algorithm of (-2)-0-(+2) units to adjust their long-acting insulin dose every 3rd day from -3 mo through +9 mo to maintain fasting plasma glucose (FPG) between 90-120 mg/dL (5.0-6.7 mmol/L). Pubertal maturation was determined by Tanner stage. RESULTS: Over the course of the 9 months of observation, the between-treatment differences in HbA1c of 0.4% (9.85% [8.82 to 10.88] for placebo versus 9.46% [8.47 to 10.46] for metformin) was not significant (p = 0.903). There were non-significant reduction in fasting plasma glucose (189.4 mg/dL [133.2 to 245.6] for placebo versus 170.5 mg/dL [114.3 to 226.7] for metformin), (p = 0.927); total daily dose (TDD) of short-acting insulin per kg body weight/day(p = 0.936); and the TDD of long-acting insulin per kg body weight per day (1.15 units/kg/day [0.89 to 1.41] for placebo versus 0.90 units/kg/day [0.64 to 1.16] for metformin) (p = 0.221). There was no difference in the occurrence of hypoglycemia between the groups. CONCLUSIONS: This 9-month RCT of adjunctive metformin therapy in overweight and obese youth with T1D resulted in a 0.4% lower HbA1c value in the metformin group compared to the placebo group.
  • Data from: Human and Murine Clonal CD8+ T Cell Expansions Arise during Tuberculosis Because of TCR Selection

    Nunes-Alves, Claudio; Booty, Matthew G.; Carpenter, Stephen; Rothchild, Alissa C.; Martin, Constance J.; Desjardins, Danielle; Steblenko, Katherine; Kloverpris, Henrik; Madansein, Rajhmun; Ramsuran, Duran; et al. (2015-04-07)
    Manuscript abstract: The immune system can recognize virtually any antigen, yet T cell responses against several pathogens, including Mycobacterium tuberculosis, are restricted to a limited number of immunodominant epitopes. The host factors that affect immunodominance are incompletely understood. Whether immunodominant epitopes elicit protective CD8+ T cell responses or instead act as decoys to subvert immunity and allow pathogens to establish chronic infection is unknown. Here we show that anatomically distinct human granulomas contain clonally expanded CD8+ T cells with overlapping T cell receptor (TCR) repertoires. Similarly, the murine CD8+ T cell response against M. tuberculosis is dominated by TB10.44-11-specific T cells with extreme TCRβ bias. Using a retrogenic model of TB10.44-11-specific CD8+ T cells, we show that TCR dominance can arise because of competition between clonotypes driven by differences in affinity. Finally, we demonstrate that TB10.4-specific CD8+ T cells mediate protection against tuberculosis, which requires interferon-γ production and TAP1-dependent antigen presentation in vivo. Our study of how immunodominance, biased TCR repertoires, and protection are inter-related, provides a new way to measure the quality of T cell immunity, which if applied to vaccine evaluation, could enhance our understanding of how to elicit protective T cell immunity.
  • Data from: The Vitamin D Status in Inflammatory Bowel Disease

    Veit, Lauren; Maranda, Louise S.; Fong, Jay G.; Nwosu, Benjamin U. (2014-05-22)
    Manuscript abstract: Context: There is no consensus on the vitamin D status of children and adolescents with inflammatory bowel disease (IBD). Aim: To determine the vitamin D status of patients with IBD by comparing their serum 25(OH)D concentration to that of healthy controls. Hypothesis: Serum 25(OH)D concentration will be lower in patients with IBD compared to controls. Subjects and Methods: A case-controlled retrospective study of subjects with IBD (n=58) of 2-20 years (male n=31, age 16.38 ± 2.21 years; female n=27, age16.56 ± 2.08 years) and healthy controls (n=116; male n=49, age 13.90 ± 4.59 years; female n=67, age 15.04 ± 4.12years). Study subject inclusion criteria: diagnosis of Crohn’s disease (CD) or ulcerative colitis (UC). Vitamin D deficiency was defined as 25(OH)D of (/mL) ( /L), overweight as BMI of ≥85th but <95th percentile, and obesity as BMI ≥95th percentile. Data were expressed as mean ± SD. Results: Patients with CD, UC, and their controls had mean serum 25(OH)D concentrations of 61.69 ± 24.43 nmol/L, 53.26 ± 25.51, and 65.32 ± 27.97 respectively (ANOVA, p=0.196). The overweight/obese controls had significantly lower 25(OH)D concentration compared to the normal-weight controls (p=0.031); whereas 25(OH)D concentration was similar between the normal-weight and overweight/obese IBD patients (p=0.883). There was no difference in 25(OH)D between patients with UC and CD, or between subjects with active IBD and controls. However, IBD subjects with elevated ESR had significantly lower 25(OH)D than IBD subjects with normal ESR (p=0.025), as well as controls (65.3 ± 28.0 nmol/L vs. 49.5 ± 25.23, p = 0.045). Conclusion: There is no difference in mean serum 25(OH)D concentration between children and adolescents with IBD and controls. However, IBD subjects with elevated ESR have significantly lower 25(OH)D than controls. Therefore, IBD subjects with elevated ESR should be monitored for vitamin D deficiency.
  • Data from: The Effects of Vitamin D Supplementation on Hepatic Dysfunction, Vitamin D Status, and Glycemic Control in Children and Adolescents with Vitamin D Deficiency and Either Type 1 or Type 2 Diabetes Mellitus

    Nwosu, Benjamin U.; Maranda, Louise S. (2014-05-05)
    Background: The effects of vitamin D supplementation on mild hepatic dysfunction and glycemic control are unclear in children and adolescents with either type 1 (T1D) or type 2 diabetes (T2D). Hypothesis: Vitamin D supplementation will improve hepatic dysfunction and glycemic control. Aim: To determine the effect of vitamin D supplementation on alanine transaminase (ALT), hemoglobin A1c (HbA1c), and serum 25-hydroxyvitamin D [25(OH)D] concentration. Subjects and Methods: A retrospective study of 131 subjects with either T1D (n=88: 46 females, 42 males), or T2D ( n=43: 26 females, 17 males) of ages 3-18 years between 2007-2013. All subjects had (1) a diagnosis of diabetes for >12 mo, (2) received vitamin D supplementation for the management of vitamin D deficiency (3) had baseline and subsequent simultaneous measurements of HbA1c, ALT, and 25(OH)D. Vitamin D deficiency was defined as 25(OH)D concentration of <50nmol/L (20 ng/mL). Results: At baseline, vitamin D deficiency occurred in 72.1% of patients with T2D and in 37.5% of T1D patients (p Conclusions: Vitamin D supplementation in subjects with T2D was associated with statistically significant decreases in BMI SDS, ALT, and a clinically-significant decrease in HbA1c.
  • Data from: Lactose Intolerance: Lack of Evidence for Short Stature or Vitamin D Deficiency in Prepubertal Children

    Setty-Shah, Nithya; Maranda, Louise S.; Candela, Ninfa; Fong, Jay G.; Dahod, Idris; Rogol, Alan D.; Nwosu, Benjamin U. (2013-08-07)
    Background: The health consequences of lactose intolerance (LI) are unclear. Aims: To investigate the effects of LI on stature and vitamin D status. Hypotheses: LI subjects will have similar heights and vitamin D status as controls. Subjects and Methods: Prepubertal children of ages 3-12 years with LI (n=38, age 8.61 ± 3.08y, male/female 19/19) were compared to healthy, age- and gender-matched controls (n=49, age 7.95±2.64, male/female 28/21). Inclusion criteria: prepubertal status (boys: testicular volume Results: There was no significant difference in 25(OH)D between the LI and non-LI subjects (60.1±21.1, vs. 65.4 ± 26.1 nmol/L, p = 0.29). Upon stratification into normal weight (BMI percentile) vs. overweight/obese (BMI ≥85th percentile), the normal weight controls had significantly higher 25(OH)D level than both the normal weight LI children (78.3 ± 32.6 vs. 62.9 ± 23.2, p = 0.025), and the overweight/obese LI children (78.3±32.6 vs. 55.3±16.5, p = 0.004). Secondly, there was no overall difference in height z-score between the LI children and controls. The normal weight LI patients had similar height as normal controls (-0.46 ± 0.89 vs. -0.71 ± 1.67, p = 0.53), while the overweight/obese LI group was taller than the normal weight controls (0.36 ± 1.41 vs. -0.71 ± 1.67, p = 0.049), and of similar height as the overweight/obese controls (0.36 ± 1.41 vs. 0.87 ± 1.45, p = 0.28). MPTH z-score was similar between the groups. Conclusion: Short stature and vitamin D deficiency are not features of LI in prepubertal children.
  • Data from: PTC124 Targets Genetic Disorders Caused by Nonsense Mutations

    Jacobson, Allan; Spatrick, Phyllis; He, Feng (2007-05-03)
    Manuscript abstract: Nonsense mutations promote premature translational termination and cause anywhere from 5-70% of the individual cases of most inherited diseases. Studies on nonsense-mediated cystic fibrosis have indicated that boosting specific protein synthesis from less than 1% to as little as 5% of normal levels may greatly reduce the severity or eliminate the principal manifestations of disease. To address the need for a drug capable of suppressing premature termination, we identified PTC124-a new chemical entity that selectively induces ribosomal readthrough of premature but not normal termination codons. PTC124 activity, optimized using nonsense-containing reporters, promoted dystrophin production in primary muscle cells from humans and mdx mice expressing dystrophin nonsense alleles, and rescued striated muscle function in mdx mice within 2-8 weeks of drug exposure. PTC124 was well tolerated in animals at plasma exposures substantially in excess of those required for nonsense suppression. The selectivity of PTC124 for premature termination codons, its well characterized activity profile, oral bioavailability and pharmacological properties indicate that this drug may have broad clinical potential for the treatment of a large group of genetic disorders with limited or no therapeutic options.