A Review of Psychosocial Risk Factors for Pediatric Atopy

Pediatric atopy is increasing in prevalence and creates a significant financial and quality of life burden for children and families (e.g., frequent clinic visits, academic, and social challenges). Thus, it is important to understand modifiable risk factors related to disease onset or exacerbation in young children. The existing research base suggests that while a genetic link has been identified, specific family psychological factors (e.g., parent stress) also appear to play a significant role in the development of pediatric atopy. The function of psychological stress in the clinical expression and exacerbation of allergic diseases in young children is hypothesized to be due to neuroendocrine and immunologic systems. Specifically, stress-related activation of the sympathetic and adrenomedullary (SAM) system as well as the hypothalamic-pituitary-adrenocortical (HPA) axis from both the intrauterine environment and early childhood experiences may increase risk of childhood atopy above and beyond genetic risk. Consequently, prevention and intervention strategies aimed at reducing children's early exposure to stress and psychological difficulties in parents may prove beneficial in preventing or reducing the likelihood that their children will develop atopy

Concise Review: Stem Cell Therapies for Amyotrophic Lateral Sclerosis: Recent Advances and Prospects for the Future

Amyotrophic lateral sclerosis (ALS) is a lethal disease involving the loss of motor neurons. Although the mechanisms responsible for motor neuron degeneration in ALS remain elusive, the development of stem cell‐based therapies for the treatment of ALS has gained widespread support. Here, we review the types of stem cells being considered for therapeutic applications in ALS, and emphasize recent preclinical advances that provide supportive rationale for clinical translation. We also discuss early trials from around the world translating cellular therapies to ALS patients, and offer important considerations for future clinical trial design. Although clinical translation is still in its infancy, and additional insight into the mechanisms underlying therapeutic efficacy and the establishment of long‐term safety are required, these studies represent an important first step toward the development of effective cellular therapies for the treatment of ALS. S tem C ells 2014;32:1099–1109Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/106861/1/stem1628.pd

Stem cell technology for neurodegenerative diseases

Over the past 20 years, stem cell technologies have become an increasingly attractive option to investigate and treat neurodegenerative diseases. In the current review, we discuss the process of extending basic stem cell research into translational therapies for patients suffering from neurodegenerative diseases. We begin with a discussion of the burden of these diseases on society, emphasizing the need for increased attention toward advancing stem cell therapies. We then explain the various types of stem cells utilized in neurodegenerative disease research, and outline important issues to consider in the transition of stem cell therapy from bench to bedside. Finally, we detail the current progress regarding the applications of stem cell therapies to specific neurodegenerative diseases, focusing on Parkinson disease, Huntington disease, Alzheimer disease, amyotrophic lateral sclerosis, and spinal muscular atrophy. With a greater understanding of the capacity of stem cell technologies, there is growing public hope that stem cell therapies will continue to progress into realistic and efficacious treatments for neurodegenerative diseases. Ann Neurol 2011;70: 353–361.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/86937/1/22487_ftp.pd

Sleep Duration Mediates the Relationship Between Health Behavior Patterns and Obesity

Objective: To examine associations between health behavior patterns and childhood obesity, and the mediating effect of sleep duration. Design: Population-based survey. Participants: Secondary analysis of data from the Infant Feeding Practices Study (age 6 years, n = 1073). Measurements: Mothers self-reported their child’s health behaviors including physical activity (PA), screen time, sleep duration, and diet. Latent class analysis determined the child’s patterns based on health behaviors. Sleep was examined as a mediator between the class membership variable and %BMIp95. Results: A 3-class model fit the data best, with classes labeled as “Poorest eaters” (low fruit/vegetable consumption, high fast food), “Healthy” (low screen time, highest fruit/vegetable consumption) and “Active, super-eaters, highest screen time” (highest PA and screen time, ate the most). “Poorest eaters” had an increased %BMIp95 (β = 4.11, P = .006) relative to the “Healthy” class. The “Poorest eaters” and “Active, super-eaters, highest screen time” classes had shorter sleep duration (β = −0.51, P \u3c .001; β = −0.38, P \u3c .001; respectively) relative to the “Healthy” class. Independent of class membership, each additional hour of sleep was associated with a %BMIp95 that was 2.93 U lower (P \u3c .001). Conclusions: Our results indicate that health behavior patterns mediated by sleep duration may influence a child’s %BMIp95. The bi-directionality of the relationship between health behaviors and sleep remains unclear. Our findings suggest the importance of a constellation of health behaviors on childhood obesity. Interventions should include a multitude of health behaviors and consider the possibility that improving diet and activity behaviors may facilitate improved sleep and lowered obesity risk among children

Autocrine Production of IGF‐I Increases Stem Cell‐Mediated Neuroprotection

Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disorder resulting in motor neuron (MN) loss. There are currently no effective therapies; however, cellular therapies using neural progenitor cells protect MNs and attenuate disease progression in G93A‐SOD1 ALS rats. Recently, we completed a phase I clinical trial examining intraspinal human spinal stem cell (HSSC) transplantation in ALS patients which demonstrated our approach was safe and feasible, supporting the phase II trial currently in progress. In parallel, efforts focused on understanding the mechanisms underlying the preclinical benefit of HSSCs in vitro and in animal models of ALS led us to investigate how insulin‐like growth factor‐I (IGF‐I) production contributes to cellular therapy neuroprotection. IGF‐I is a potent growth factor with proven efficacy in preclinical ALS studies, and we contend that autocrine IGF‐I production may enhance the salutary effects of HSSCs. By comparing the biological properties of HSSCs to HSSCs expressing sixfold higher levels of IGF‐I, we demonstrate that IGF‐I production augments the production of glial‐derived neurotrophic factor and accelerates neurite outgrowth without adversely affecting HSSC proliferation or terminal differentiation. Furthermore, we demonstrate that increased IGF‐I induces more potent MN protection from excitotoxicity via both indirect and direct mechanisms, as demonstrated using hanging inserts with primary MNs or by culturing with organotypic spinal cord slices, respectively. These findings support our theory that combining autocrine growth factor production with HSSC transplantation may offer a novel means to achieve additive neuroprotection in ALS. Stem Cells 2015;33:1480–1489Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/111155/1/stem1933.pd

Variation in renal responses to exercise in the heat with progressive acclimatisation

Objectives To investigate changes in renal status from exercise in the heat with acclimatisation and to evaluate surrogates markers of Acute Kidney Injury. Design Prospective observational cohort study. Methods 20 male volunteers performed 60 min standardised exercise in the heat, at baseline and on four subsequent occasions during a 23-day acclimatisation regimen. Blood was sampled before and after exercise for serum creatinine, copeptin, interleukin-6, normetanephrine and cortisol. Fractional excretion of sodium was calculated for corresponding urine samples. Ratings of Perceived Exertion were reported every 5 min during exercise. Acute Kidney Injury was defined as serum creatinine rise ≥26.5 μmol L−1 or fall in estimated glomerular filtration rate >25%. Predictive values of each candidate marker for developing Acute Kidney Injury were determined by ROC analysis. Results From baseline to Day 23, serum creatinine did not vary at rest, but showed a significant (P < 0.05) reduction post-exercise (120 [102, 139] versus 102 [91, 112] μmol L−1). Acute Kidney Injury was common (26/100 exposures) and occurred most frequently in the unacclimatised state. Log-normalised fractional excretion of sodium showed a significant interaction (exercise by acclimatization day), with post-exercise values tending to rise with acclimatisation. Ratings of Perceived Exertion predicted AKI (AUC 0.76, 95% confidence interval 0.65–0.88), performing at least as well as biochemical markers. Conclusions Heat acclimatization is associated with reduced markers of renal stress and AKI incidence, perhaps due to improved regional perfusion. Acclimatisation and monitoring Ratings of Perceived Exertion are practical, non-invasive measures that could help to reduce renal injury from exercise in the heat

TH17 cells require ongoing classic IL-6 receptor signaling to retain transcriptional and functional identity

Acting in concert with TGF-b, IL-6 signaling induces Th17 cell development by programming Th17-related genes via STAT3. A role for IL-6 signaling beyond the inductive phase of Th17 cell development has not been defined, as IL-23 signaling downstream of Th17 cell induction also activates STAT3 and is thought responsible for Th17 cell maintenance. Here, we find that IL-6 signaling is required for both induction and maintenance of Th17 cells; IL-6Ra–deficient Th17 cells rapidly lost their Th17 phenotype and did not cause disease in two models of colitis. Cotransfer of WT Th17 cells with IL-6Ra–deficient Th17 cells induced colitis but was unable to rescue phenotype loss of the latter. High IL-6 in the colon promoted classic, or cis, rather than trans receptor signaling that was required for maintenance of Th17 cells. Thus, ongoing classic IL6 signaling underpins the Th17 program and is required for Th17 cell maintenance and function

Human Cortical Neural Stem Cells Expressing Insulin‐Like Growth Factor‐I: A Novel Cellular Therapy for Alzheimer’s Disease

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/135291/1/sct3201653379.pd

The Protective Effects of CD39 Overexpression in Multiple Low-Dose Streptozotocin–Induced Diabetes in Mice

Islet allograft survival limits the long-term success of islet transplantation as a potential curative therapy for type 1 diabetes. A number of factors compromise islet survival, including recurrent diabetes. We investigated whether CD39, an ectonucleotidase that promotes the generation of extracellular adenosine, would mitigate diabetes in the T cell–mediated multiple low-dose streptozotocin (MLDS) model. Mice null for CD39 (CD39KO), wild-type mice (WT), and mice overexpressing CD39 (CD39TG) were subjected to MLDS. Adoptive transfer experiments were performed to delineate the efficacy of tissue-restricted overexpression of CD39. The role of adenosine signaling was examined using mutant mice and pharmacological inhibition. The susceptibility to MLDS-induced diabetes was influenced by the level of expression of CD39. CD39KO mice developed diabetes more rapidly and with higher frequency than WT mice. In contrast, CD39TG mice were protected. CD39 overexpression conferred protection through the activation of adenosine 2A receptor and adenosine 2B receptor. Adoptive transfer experiments indicated that tissue-restricted overexpression of CD39 conferred robust protection, suggesting that this may be a useful strategy to protect islet grafts from T cell–mediated injury

Body mass index and variability in meal duration and association with rate of eating

BackgroundA fast rate of eating is associated with a higher risk for obesity but existing studies are limited by reliance on self-report and the consistency of eating rate has not been examined across all meals in a day. The goal of the current analysis was to examine associations between meal duration, rate of eating, and body mass index (BMI) and to assess the variance of meal duration and eating rate across different meals during the day.MethodsUsing an observational cross-sectional study design, non-smoking participants aged 18–45 years (N = 29) consumed all meals (breakfast, lunch, and dinner) on a single day in a pseudo free-living environment. Participants were allowed to choose any food and beverages from a University food court and consume their desired amount with no time restrictions. Weighed food records and a log of meal start and end times, to calculate duration, were obtained by a trained research assistant. Spearman's correlations and multiple linear regressions examined associations between BMI and meal duration and rate of eating.ResultsParticipants were 65% male and 48% white. A shorter meal duration was associated with a higher BMI at breakfast but not lunch or dinner, after adjusting for age and sex (p = 0.03). Faster rate of eating was associated with higher BMI across all meals (p = 0.04) and higher energy intake for all meals (p &lt; 0.001). Intra-individual rates of eating were not significantly different across breakfast, lunch, and dinner (p = 0.96).ConclusionShorter beakfast and a faster rate of eating across all meals were associated with higher BMI in a pseudo free-living environment. An individual's rate of eating is constant over all meals in a day. These data support weight reduction interventions focusing on the rate of eating at all meals throughout the day and provide evidence for specifically directing attention to breakfast eating behaviors