The Role of Glutathione and Its Precursors in Type 2 Diabetes.

Type 2 diabetes (T2D) is a major worldwide health crisis affecting about 6.2% of the world's population. Alarmingly, about one in five children in the USA have prediabetes. Glutathione (GSH) and its precursors play a promising role in the prevention and management of type T2D. Oxidative stress (OxS) is a probable factor in both T2D initiation and progression. GSH is the major cytosolic water-soluble chemical antioxidant and emerging evidence supports its role in improving T2D outcomes. Dietary supplementation with N-acetyl-cysteine (NAC) and/or glycine (GLY), which are GSH precursors, has also been studied for possible beneficial effects on T2D. This review will focus on the underlying pathophysiological and molecular mechanisms linking GSH and its precursors with T2D and OxS. In addition to their traditional antioxidant roles, the in vivo effects of GSH/NAC/GLY supplements will be evaluated for their potential abilities to modulate the complex pro-oxidant pathophysiological factors (e.g., hyperglycemia) driving T2D progression. Positive feedback loops that amplify OxS over long time intervals are likely to result in irreversible T2D micro- and macro-vascular damage. Most clinical studies with GSH/NAC/GLY have focused on adults or the elderly. Future research with pediatric populations should be a high priority since early intervention is critical.

The Role of Natural Antioxidant Products That Optimize Redox Status in the Prevention and Management of Type 2 Diabetes.

The worldwide prevalence of type 2 diabetes (T2D) and prediabetes is rapidly increasing, particularly in children, adolescents, and young adults. Oxidative stress (OxS) has emerged as a likely initiating factor in T2D. Natural antioxidant products may act to slow or prevent T2D by multiple mechanisms, i.e., (1) reducing mitochondrial oxidative stress, (2) preventing the damaging effects of lipid peroxidation, and (3) acting as essential cofactors for antioxidant enzymes. Natural antioxidant products should also be evaluated in the context of the complex physiological processes that modulate T2D-OxS such as glycemic control, postprandial OxS, the polyol pathway, high-calorie, high-fat diets, exercise, and sleep. Minimizing processes that induce chronic damaging OxS and maximizing the intake of natural antioxidant products may provide a means of preventing or slowing T2D progression. This "optimal redox" (OptRedox) approach also provides a framework in which to discuss the potential benefits of natural antioxidant products such as vitamin E, vitamin C, beta-carotene, selenium, and manganese. Although there is a consensus that early effective intervention is critical for preventing or reversing T2D progression, most research has focused on adults. It is critical, therefore, that future research include pediatric populations.

Oxidative Stress in Type 2 Diabetes: The Case for Future Pediatric Redoxomics Studies.

Considerable evidence supports the role of oxidative stress in adult type 2 diabetes (T2D). Due to increasing rates of pediatric obesity, lack of physical activity, and consumption of excess food calories, it is projected that the number of children living with insulin resistance, prediabetes, and T2D will markedly increase with enormous worldwide economic costs. Understanding the factors contributing to oxidative stress and T2D risk may help develop optimal early intervention strategies. Evidence suggests that oxidative stress, triggered by excess dietary fat consumption, causes excess mitochondrial hydrogen peroxide emission in skeletal muscle, alters redox status, and promotes insulin resistance leading to T2D. The pathophysiological events arising from excess calorie-induced mitochondrial reactive oxygen species production are complex and not yet investigated in children. Systems medicine is an integrative approach leveraging conventional medical information and environmental factors with data obtained from "omics" technologies such as genomics, proteomics, and metabolomics. In adults with T2D, systems medicine shows promise in risk assessment and predicting drug response. Redoxomics is a branch of systems medicine focusing on "omics" data related to redox status. Systems medicine with a complementary emphasis on redoxomics can potentially optimize future healthcare strategies for adults and children with T2D.

Preferences for peer-reviewed versus other publication sources: a survey of general dentists in the National Dental PBRN.

BACKGROUND: Medical professionals have access to a broad range of resources to address clinical information needs. While much attention is given to new sources of data such as those available on the internet, it is less clear how clinicians choose between peer-reviewed research literature and other publication-based sources. This analysis distinguishes between possible drivers of publication type preference (namely, practice setting, advanced training, professional development experiences). Dentists enrolled in the National Dental Practice-Based Research Network (PBRN) are the population for this study. Theories of human and intellectual capital and institutional logics theory are used to understand how advanced training and other clinical experiences may explain the choices that dentists make when faced with clinical questions. METHODS: An online questionnaire was implemented with general dentists in the US National Dental PBRN. A series of logistic and Ordinary Least Squares (OLS) regression models were used to explain the use of peer-reviewed and other publications. Measures of knowledge-based human capital distinctions (advanced clinical training and research engagement, advanced professional status, personal motivation for professional advancement) were used to explain preferences for research literature as a clinical resource. RESULTS: General dentists with advanced training, as well as those with a skill advancement motivation, show a preference for peer-reviewed materials. General dentists who have been practicing longer tend to favor other dental publications, preferring those sources as a resource when faced with clinical challenges. Human capital and professional motivation distinguish the information preferences among general dentists. Further, these factors explain more variance in use of peer-reviewed materials than practice setting does. Few differences by demographic groups were evident. CONCLUSIONS: Results point to a distinct variation in the general dentistry professional community. Advanced training among general dentists, as well as the types of procedures typically conducted in their practice, distinguishes their information preferences from other general dentists, including those with more years of clinical experience.

Transient versus Permanent Congenital Hypothyroidism after the Age of 3 Years in Infants Detected on the First versus Second Newborn Screening Test in Oregon, USA.

BACKGROUND/AIMS: The newborn screening (NBS) program in Oregon, USA, collects two routine specimens in all infants. The aim of our study was to determine the incidence of permanent versus transient congenital hypothyroidism (CH) in infants detected on the first versus second screening test. METHODS: Thyroid function was determined in infants after the age of 3 years diagnosed with CH and born in Oregon between 2005 and 2011. Permanent hypothyroidism was defined as a TSH rise >10 mIU/ml after the first year on treatment or a TSH rise >6 mIU/ml with temporary discontinuation of l-thyroxine after the age of 3 years. RESULTS: Of the cases detected on the first test, 72 of 87 (83%) were permanent and 15 of 87 (17%) were transient, while of the cases detected on the second test, 5 of 22 (23%) were permanent and 17 of 22 (77%) were transient (OR 16.3, p < 0.001). There was a female preponderance detected on the first screen versus a male preponderance on the second screen. Blood spot and serum thyroid function tests at diagnosis, before treatment, were not meaningfully different between the two groups. The mean l-thyroxine dose at the age of 3 years was greater on the first screen: 61.2 versus 36.6 µg/day. CONCLUSIONS: Infants detected on the second NBS specimen have a higher incidence of transient CH. © 2016 S. Karger AG, Basel.

Internet use and depression among retired older adults in the United States: a longitudinal analysis.

OBJECTIVES: The purpose of this study is to examine the association between Internet use among retired older adults in the United States and changes in a commonly used predictor of depression (the CES-D). METHOD: Analyzing data from four waves (2002-2008) of the Health and Retirement Survey, we assess whether an available and commonly used index of a depression state was affected by prior values of the index and Internet use. The sample includes 3,075 respondents observed over 4 waves of data, yielding a total of 12,300 observations. We analyzed the effect on depression of Internet use and past depression in a full sample and a matched sample. We also conducted informal tests for confounders. Finally, we tested a basic mediation model to determine whether Internet use affected depression through its relationship with loneliness and social isolation. RESULTS: Across methods, we found a positive contribution of Internet use to mental well-being of retired older adults in the United States, where Internet use reduced the probability of a depression state by one third. We found no evidence of confounding. Some evidence of mediation was found. DISCUSSION: Our dynamic probit model indicates that for retired older adults in the United States, Internet use was found to reduce the probability of a depressed state by about 33%. Number of people in the household partially mediates this relationship, with the reduction in depression largest for people living alone. This provides some evidence that the mechanism linking Internet use to depression is the remediation of social isolation and loneliness. Encouraging older adults to use the Internet may help decrease isolation and depression.

Screening for congenital hypothyroidism: a worldwide view of strategies.

Detection by newborn screening (NBS) and treatment of babies with congenital hypothyroidism (CH) has largely eliminated the intellectual disability caused by this disorder. Lowering of the screening TSH cutoff and changes in birth demographics have been associated with an approximate doubling of the incidence of CH, from 1:3500 to 1:1714. The additional cases detected by lowering of the TSH cutoff tend to have milder hypothyroidism, with imaging often demonstrating a eutopic, "gland in-situ", and some cases turn out to have transient CH. Based on our search for current screening programs, approximately 71 percent of babies worldwide are not born in an area with an established NBS program, despite the existence of screening for over five decades in developed countries. Thus, the majority of babies with CH worldwide are not detected and treated early, such that the economic burden of retardation owing to CH remains a significant public health challenge.

Prolonged unintended brain cooling may inhibit recovery from brain injuries: case study and literature review.

BACKGROUND: Tracheal intubation of comatose patients is common, but contrary to most standards for respiratory care, heated nebulizers are not always used. This deviation from recommendations appears to be widespread. CASE REPORT: In the case examined, a tracheotomized patient suffering from severe anoxic brain injury was unintentionally exposed to chilled air, 17 degrees C (63 degrees F) at the cannula, for a period of 31 months. A month after upper respiratory tract warming was restored the vegetative state lifted, as marked by the patient's ability to verbalize responses to questions. CONCLUSIONS: This clinical experience led us to a review of the literature. Among other findings, we learned that brain temperature is strongly affected by the temperature of arterial blood flow. Arterial blood, in turn, is strongly affected by the air temperature in the lungs. Experiments have shown that the introduction of colder air in the lungs will produce rapid cooling of at least some surface brain tissues. Chilled aortic blood is also more viscous and less efficient in transfer of oxygen. Hypothermia of brain tissue may significantly affect the endocrine system and neurochemistry. Through inferences from the literature, we also identify other possible effects. We hypothesize that intubated delivery of air into the lungs at a temperature significantly below body temperature, especially over a prolonged period, is likely to inhibit recovery and may even produce iatrogenic effects. We recommend the use of heated nebulizers. Research strategies are recommended.

Thromboxane mediates neutrophil superoxide production in pregnancy.

OBJECTIVE: We recently reported that activation of neutrophils obtained from pregnant women resulted in production of tumor necrosis factor-alpha by a thromboxane- and cyclooxygenase-2- dependent mechanism. Activated neutrophils also generate reactive oxygen species such as the superoxide anion, which can lead to oxidative damage of biomolecules. In this study, we tested the possibility that thromboxane plays a role in neutrophil superoxide generation in pregnancy via cyclooxygenase-2 by inhibiting key enzymes in the pathway leading to its synthesis. STUDY DESIGN: Neutrophils were isolated from normal pregnant women and incubated for 2 hours in phosphate-buffered saline with glucose alone or with treatments. Experiment 1 treatments were: (1) indomethacin at a dose sufficient to inhibit phospholipase A2 (100 microM); (2) aspirin (100 microM), a cyclooxygenase-1 and cyclooxygenase-2 inhibitor; (3) NS-398 (10 microM), a specific cyclooxygenase-2 inhibitor; (4) nordihydroguaiaretic acid (10 microM), a lipoxygenase inhibitor; and (5) pinane thromboxane, a thromboxane synthase inhibitor. Experiment 2 treatments were arachidonic acid (50 microM and 100 microM) and arachidonic acid (100 microM) alone or in combination with phorbol myristic acid plus varying doses of pinane thromboxane (5 microM to 100 microM). RESULTS: Indomethacin inhibited superoxide production to one fourth of control. Aspirin, NS-398, and pinane thromboxane also significantly decreased neutrophil superoxide production. Nordihydroguaiaretic acid had no significant affect on neutrophil superoxide generation. Arachidonic acid stimulated superoxide generation by neutrophils, and this was inhibited by pinane thromboxane in a dose-dependent manner. Pinane thromboxane also significantly inhibited superoxide production by neutrophils exposed to arachidonic acid plus phorbol myristic acid, a known activator of neutrophils. CONCLUSION: These data demonstrate that thromboxane is involved in the production of superoxide by neutrophils obtained from pregnant women. Neutrophil superoxide generation is significantly decreased by inhibition of thromboxane synthase, cyclooxygenase-2, or phospholipase A2. NS-398 inhibits neutrophil superoxide generation as effectively as aspirin, suggesting that cyclooxygenase-2 plays an important role in neutrophil superoxide production mediated by thromboxane.

Stroboscopic vision as a treatment for motion sickness: strobe lighting vs. shutter glasses.

INTRODUCTION: Countermeasures (e.g., drugs, training, etc.) designed to combat the problem of space motion sickness (SMS) have had only limited successes. A possible solution for SMS and terrestrial motion sickness may rest in preventing retinal slip via stroboscopic vision. METHODS: There were 32 subjects who participated in a study to investigate the effect of stroboscopic illumination on motion sickness using either a strobe light or liquid crystal display (LCD) shutter glasses. There were 19 subjects who read text and made +/- 20 degrees head movements in the horizontal plane (yaw) at 0.2 Hz while wearing left-right reversing prisms and exposed to 4-Hz stroboscopic or normal room illumination (control condition). Motion sickness was scored using the Miller and Graybiel scale and subjective self-ratings. In a crossover design, testing was repeated using stroboscopic LCD shutter glasses with an additional 13 subjects and 6 subjects from the first condition. RESULTS: During the experiment with a strobe light, motion sickness scores were significantly lower than in the control condition (chi 0.32 strobe vs. chi 3.79 light = p < 0.003). Results with the LCD shutter glasses corresponded with those when the environment was strobed in an otherwise dark room (chi 1.0 glasses vs. chi 4.1 light = p < 0.001). CONCLUSIONS: Stroboscopic illumination reduced the severity of motion sickness symptoms, and shutter glasses with a flash frequency of 4 Hz are as effective as a strobe light. Stroboscopic illumination appears to be an effective countermeasure where retinal slip is a significant factor in eliciting motion sickness due to either self- or surround-motion.