Virus-specific T cells for adenovirus infection after stem cell transplantation are highly effective and class II HLA restricted.

Infection with adenoviruses is a common and significant complication in pediatric patients after allogeneic hematopoietic stem cell transplantation. Treatment options with traditional antivirals are limited by poor efficacy and significant toxicities. T-cell reconstitution is critical for the management of adenoviral infections, but it generally takes place months after transplantation. Ex vivo-generated virus-specific T cells (VSTs) are an alternative approach for viral control and can be rapidly generated from either a stem cell donor or a healthy third-party donor. In the context of a single-center phase 1/2 clinical trial, we treated 30 patients with a total of 43 infusions of VSTs for adenoviremia and/or adenoviral disease. Seven patients received donor-derived VSTs, 21 patients received third-party VSTs, and 2 received VSTs from both donor sources. Clinical responses were observed in 81% of patients, with a complete response in 58%. Epitope prediction and potential epitope identification for common HLA molecules helped elucidate HLA restriction in a subset of patients receiving third-party products. Intracellular interferon-γ expression in T cells in response to single peptides and response to cell lines stably transfected with a single HLA molecule demonstrated HLA-restricted CD4+ T-cell response, and these results correlated with clinical outcomes. Taken together, these data suggest that VSTs are a highly safe and effective therapy for the management of adenoviral infection in immunocompromised hosts. The trials were registered at www.clinicaltrials.gov as #NCT02048332 and #NCT02532452.

Impact of Prior Consumption on Sour, Sweet, Salty, and Bitter Tastes.

Food sensory tests generally require panelists to abstain from food or beverage consumption 30 min to an hour before a tasting session. However, investigators do not have a complete control over panelists' intentional or unintentional consumption prior to a tasting session. Currently, it is unclear how prior consumption impacts the results of the tasting session. The aim of this study was to determine the effects of temporary and lingering mouth irritation caused by the consumption of coffee, orange juice, and gum within 1, 15, or 30 min prior to the tasting session on the perception of 4 basic tastes: sweet, salty, sour, and bitter. Fifty-two panelists were served a beverage (orange juice, coffee, and water) or were asked to chew a piece of gum, and then, remained in the waiting room for 1, 15, or 30 min. They were then asked to report taste intensities using 15-cm unstructured line scales. Mean intensities of all tastes were not significantly different when orange juice was a primer at 1, 15, and 30 min when compared to water. Mean intensities of bitter were significantly lower when coffee was a primer at 1, 15, and 30 min than when water was a primer. Mean intensities of sweet were significantly lower when gum was a primer at 1 and 15 min than when water was a primer. The findings showed that it is necessary for 30 min or more waiting period of no food or beverage consumption prior to sensory testing.

Elevated insulin-like growth factor 2 expression may contribute to the hypermuscular phenotype of myostatin null mice.

OBJECTIVES: Myostatin (Mstn) inhibits while insulin-like growth factors 1 and 2 (Igf1 and Igf2) increase skeletal muscle growth. However, there is little known regarding Mstn regulation of Igf1 and Igf2 expression. Therefore, the objective of this study was to quantify the expression of IGF family members in skeletal muscle and liver throughout the growth phase of Mstn null (MN) mice. Further, differences between male and female mice were investigated. METHODS: Male and female wild type (WT) and MN mice were euthanized at birth (0 d), 7 days (7 d), weaning (21 d), sexual maturity (42 d), and 70 d. For the neonatal periods, 0 d and 7 d, all muscles from the hind limbs were compiled for RNA extraction. At 21 d, 42 d, and 70 d, biceps femoris (BF), tibialis anterior, triceps brachii (TB), and gastrocnemius-soleus complex were collected. RESULTS: As expected, muscle weights were up to 90% greater in MN mice compared with WT mice at 21 d, 42 d and 70 d. However, Igf1 expression was reduced (P ≤ 0.04) at 7d and 21 d in MN mice compared to WT mice. Expression of Igf2 did not differ between genotypes at 0 d and 7d, but, at 21 d, 42 d and 70 d in BF and TB muscles, Igf2 expression was 1.9-2.9 fold greater (P<0.01) in MN compared to WT mice. Hepatic Igf1 and Igf2 levels were minimally affected by genotype; with the exception of a 1.4-fold reduction (P=0.04) in Igf1 expression in 21 d MN mice compared with WT mice. Though male mice were heavier than females starting at 21 d of age, expression differences in Igf1, Igf2, their receptors and binding proteins do not account for growth differences. In every case, when expression was different between sexes, female expression was increased despite increased growth in male mice. CONCLUSION: This study is the first to provide evidence that Mstn may negatively regulate Igf2 expression to control postnatal skeletal muscle growth, however differences in growth between male and female mice are not readily explained by changes in expression of Igf family members.

Fructose decreases physical activity and increases body fat without affecting hippocampal neurogenesis and learning relative to an isocaloric glucose diet.

Recent evidence suggests that fructose consumption is associated with weight gain, fat deposition and impaired cognitive function. However it is unclear whether the detrimental effects are caused by fructose itself or by the concurrent increase in overall energy intake. In the present study we examine the impact of a fructose diet relative to an isocaloric glucose diet in the absence of overfeeding, using a mouse model that mimics fructose intake in the top percentile of the USA population (18% energy). Following 77 days of supplementation, changes in body weight (BW), body fat, physical activity, cognitive performance and adult hippocampal neurogenesis were assessed. Despite the fact that no differences in calorie intake were observed between groups, the fructose animals displayed significantly increased BW, liver mass and fat mass in comparison to the glucose group. This was further accompanied by a significant reduction in physical activity in the fructose animals. Conversely, no differences were detected in hippocampal neurogenesis and cognitive/motor performance as measured by object recognition, fear conditioning and rotorod tasks. The present study suggests that fructose per se, in the absence of excess energy intake, increases fat deposition and BW potentially by reducing physical activity, without impacting hippocampal neurogenesis or cognitive function.

Diamorphine for pain relief in labour : a randomised controlled trial comparing intramuscular injection and patient-controlled analgesia.

OBJECTIVES: To compare the efficacy of diamorphine administered by a patient-controlled pump (patient-controlled analgesia) with intramuscular administration for pain relief in labour. DESIGN: Randomised controlled trial. SETTING: The South Glasgow University Hospitals NHS Trust. SAMPLE: Primigravidae and multigravidae in labour at term (37-42 weeks). METHODS: Women were randomised in labour to the study (patient-controlled analgesia) or control group (intramuscular). Randomisation was achieved through a random permuted block design stratified by parity. Study group women were given a loading dose of 1.2 mg diamorphine intravenously and then attached to the pump. Control group women received intramuscular diamorphine as per hospital protocol. Participants were also given 3 mg of buccal Stemetil. Data were collected throughout labour and at six postnatal weeks. MAIN OUTCOME MEASURES: Analgesia requirements during labour and women's satisfaction with the method of pain relief. RESULTS: Women in the study group (patient-controlled analgesia) used significantly less diamorphine than women in the control group (intramuscular) but were significantly more likely to state that they were very dissatisfied with their use of diamorphine and were significantly more likely to opt out of the trial before the birth of the baby. The majority of women in both groups used other analgesia concurrent with diamorphine such as Entonox, aromatherapy or TENS. CONCLUSIONS: Patient-controlled analgesia administration of diamorphine for the relief of pain in labour offers no significant advantages over intramuscular administration. The results also suggest that diamorphine is a poor analgesic for labour pain irrespective of the mode of administration.