Browsing by Subject "Carbohydrates"

Now showing 1 - 9 of 9
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    Innovative Designs and Logistical Considerations for Expedited Clinical Development of Combination Disease-Modifying Treatments for Type 1 Diabetes
    (American Diabetes Association, 2022) Anderson, Randy L.; DiMeglio, Linda A.; Mander, Adrian P.; Dayan, Colin M.; Linsley, Peter S.; Herold, Kevan C.; Marinac, Marjana; Ahmed, Simi T.; Pediatrics, School of Medicine
    It has been 100 years since the life-saving discovery of insulin, yet daily management of type 1 diabetes (T1D) remains challenging. Even with closed-loop systems, the prevailing need for persons with T1D to attempt to match the kinetics of insulin activity with the kinetics of carbohydrate metabolism, alongside dynamic life factors affecting insulin requirements, results in the need for frequent interventions to adjust insulin dosages or consume carbohydrates to correct mismatches. Moreover, peripheral insulin dosing leaves the liver underinsulinized and hyperglucagonemic and peripheral tissues overinsulinized relative to their normal physiologic roles in glucose homeostasis. Disease-modifying therapies (DMT) to preserve and/or restore functional β-cell mass with controlled or corrected autoimmunity would simplify exogenous insulin need, thereby reducing disease mortality, morbidity, and management burdens. However, identifying effective DMTs for T1D has proven complex. There is some consensus that combination DMTs are needed for more meaningful clinical benefit. Other complexities are addressable with more innovative trial designs and logistics. While no DMT has yet been approved for marketing, existing regulatory guidance provides opportunities to further "de-risk" development. The T1D development ecosystem can accelerate progress by using more innovative ways for testing DMTs for T1D. This perspective outlines suggestions for accelerating evaluation of candidate T1D DMTs, including combination therapies, by use of innovative trial designs, enhanced logistical coordination of efforts, and regulatory guidance for expedited development, combination therapies, and adaptive designs.
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    Protein function prediction by integrating sequence, structure and binding affinity information
    (2014-02-03) Zhao, Huiying; Zhou, Yaoqi; Liu, Yunlong; Meroueh, Samy; Janga, Sarath Chandra
    Proteins are nano-machines that work inside every living organism. Functional disruption of one or several proteins is the cause for many diseases. However, the functions for most proteins are yet to be annotated because inexpensive sequencing techniques dramatically speed up discovery of new protein sequences (265 million and counting) and experimental examinations of every protein in all its possible functional categories are simply impractical. Thus, it is necessary to develop computational function-prediction tools that complement and guide experimental studies. In this study, we developed a series of predictors for highly accurate prediction of proteins with DNA-binding, RNA-binding and carbohydrate-binding capability. These predictors are a template-based technique that combines sequence and structural information with predicted binding affinity. Both sequence and structure-based approaches were developed. Results indicate the importance of binding affinity prediction for improving sensitivity and precision of function prediction. Application of these methods to the human genome and structure genome targets demonstrated its usefulness in annotating proteins of unknown functions and discovering moon-lighting proteins with DNA,RNA, or carbohydrate binding function. In addition, we also investigated disruption of protein functions by naturally occurring genetic variations due to insertions and deletions (INDELS). We found that protein structures are the most critical features in recognising disease-causing non-frame shifting INDELs. The predictors for function predictions are available at http://sparks-lab.org/spot, and the predictor for classification of non-frame shifting INDELs is available at http://sparks-lab.org/ddig.
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    Some aspects on the control of lipid synthesis
    (1971) Shinohara, Naomi
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    A study of the effect of dietary habits and refined carbohydrate intake on the dental caries experience in 200 children
    (1957) Zita, Alegria C., 1928-
    Previous studies have suggested a positive relationship between the amount of readily fermentable carbohydrate and the dental caries experience. The frequency of eating and the amount of carbohydrate consumed between meals have also been considered in previous studies but the results have been controversial and contradictory. From 7 day diet records of 200 children the frequency of eating was determined, and the total sugar intake and the between meal sugar was calculated as to its carbohydrate equivalent of teaspoons of sugar. The dental caries experience of these children was determined from the clinical examination records and periapical and bite wing radiographs and recorded as DMFS. The average total sugar intake of these children was 164 teaspoons while the average between meal sugar was 55 teaspoons. A correlation between the total sugar consumed and the DMFS showed that the relationship was not statistically significant. The total between meal sugar intake showed the highest correlation with the DMFS. The frequency of between meal eating did not show a statistically significant effect on the dental caries experience. A slight negative relationship was obtained between the total sugar intake and the milk intake, indicating that as the milk intake tends to increase, the sugar tends to decrease and vice versa. A multiple correlation between DMFS and the total sugar and total milk intake showed a negative correlation coefficient. The children residing in the city had a higher DMFS than the rural children of comparable ages.
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    The Association of Dietary Fluoride Intake and Diet Variables with Dental Caries in Adolescents from the ELEMENT Cohort Study
    (Karger, 2021) Cantoral, Alejandra; Muñoz-Rocha, Teresa V.; Luna-Villa, Lynda; Mantilla-Rodriguez, Andres; Ureña-Cirett, José L.; Castiblanco, Gina A.; Solano, Maritsa; Howard, Hu H.; Peterson, Karen E.; Téllez-Rojo, Martha M.; Martínez-Mier, Esperanza A.; Cariology, Operative Dentistry and Dental Public Health, School of Dentistry
    To examine the association of dietary fluoride intake, total carbohydrate consumption and other key dietary variables with dental caries experience among adolescents, a cross-sectional analysis was conducted in a sample of 402 participants from the Early Life Exposures in Mexico to Environmental Toxicants cohort. The presence and severity of dental caries were assessed using the Caries Detection and Assessment System (ICDAS) to calculate the number of Decayed, Missing, and Filled Teeth or Surfaces (D1MFT/D4MFT). Dietary intake of fluoride, energy, carbohydrates and food groups was estimated using a validated Food Frequency Questionnaire (FFQ). Multivariate zero-inflated negative binomial regression models and negative binomial regression models were run to estimate the association of fluoride intake (mg/d) and total carbohydrate intake (g/d) with the D1MFT/D4MFT index. We found that 80% of adolescents experienced dental caries (D1MFT>0), with 30% presenting cavitated lesions (D4MFT>0). Mean scores for D1MFT and D4MFT were 6.2 (SD 5.3) and 0.67 (SD 1.3), respectively. The median intake of fluoride estimated by the FFQ was 0.015 mg/d, this intake was statistically higher in those participants with a D4MFT=0 than those with a D4MFT>0 (0.90 vs 0.82 mg/d; 0.016 mg/Kg/d vs 0.014 mg/Kg/d, p<0.05). For D1MFT, D1MFS, D4MFT and D4MFS scores, there was a statistically significant reduction in the number of lesions with higher fluoride consumption (mg/d) from foods and beverages. The reported frequency of consumption of sugary foods in a whole day was statistically higher in those with D1MFT>0 than those with D1MFT=0 (p<0.05). Total carbohydrate intake (g/d) was positively associated with dental caries experience. We conclude that higher fluoride intake through foods and beverages was associated with lower dental caries experience among adolescents; this effect was seen even when the dietary intake of fluoride was 0.015mg/kg/d, which is lower than the average intake recommendation. In contrast, a higher amount of total carbohydrate intake and the frequency of intake of sugary foods were associated with higher dental caries experience, with no apparent threshold for the effects.