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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.

Introduction Recipients of solid organ transplant (SOT) are at risk of viral infection and development of viral-driven malignancy (EBV-PTLD) due to immunosuppressive medications to prevent organ rejection. Treatments are limited by poor efficacy and organ toxicity, and reduction in immunosuppression to enable the patient's immune system fight the infection risks organ rejection. Allogeneic viral specific T-cells (VST) have been used to treat viral infections after stem cell transplant, and here we evaluated VST for the treatment of CMV, ADV, EBV-PTLD and BK in six SOT (heart, liver, kidney, lung) recipients. Methods Clinical descriptors of diagnosis, therapy and viral load in patients are presented. Results At the time of VST infusion, patients were a median of 16 years of age (range 2 - 69 years) with an average of 5 years post-SOT. Patients were on one or more immunosuppressive medications, including on Tacrolimus (3), prednisolone (4) and hydrocortisone (2). The majority of patients have received multiple monthly infusions to treat viral disease (range of 1-8). The HLA match between the VST unit and recipient ranged from 4/10 to 6/10. Class I matches were from 0/6 to 3/6, and Class II matches from 1/4 to 4/4. The treatment was safe with no serious adverse events observed. All patients had stable viral disease or a clinical response following VST infusion. The response was sustained over multiple infusions except one patient who showed a response to CMV after the first infusion but not after the second. This patient had a 5/10 match (3 class I and 2 class II match), liver transplant, and Tacrolimus treatment. Other patients with the same degree of match, virus infection, or immunosuppressant had continued responses and were not likely the cause of the loss of response and therefore could be immune mediated rejection of the VST. The presence of cells responding to viral peptides was evaluated in PBMC from five patients using IFNg ELIspot. Compared to pre-infusion, there was a higher number of responding cells circulating at up to 4 weeks post-VST infusion for CMV and ADV with 129 to 852 spots 1 × 105 peripheral blood mononuclear cells in response to viral peptide. Neither of the 2 kidney recipients treated for BK and EBV, or EBV-PTDL had an increase spots over background despite showing a clinical response suggesting that the cells contributing to the clinical response were in the tissues or still active despite being below the level of detection of 10 spots per 1 × 105 peripheral blood mononuclear cells. Conclusion Infusion of allogeneic VST to SOT recipients suffering from viral infections was safe and resulted in clinical responses in recipients and may offer additional treatment options to this group of patients. Further data are needed to correlate clinical response with VST activity and persistence to optimize future infusion schedules and allow for optimal dosing.

Travel halted. Consumer habits changed. Marketing strategies adjusted. Restaurants closed. Future projections deleted. All of this occurred in the food industry, and many others like it, once COVID-19 spread. As the leading brand of Angus beef, it shifted what it needed to in order to offer more support to its foodservice distribution, retail, restaurant and international partners. The Certified Angus Beef ® brand’s purpose has always been to promote high-quality beef brought to tables by family farmers and ranchers. While that still rings true, the pandemic has shed a light on how every link in the chain strengthens what those cattle caregivers do and what consumers have come to expect.

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.

A SNP (IGF2 G3072A) within intron 3 of disrupts a binding site for the repressor zinc finger BED-type containing 6 (ZBED6), leading to increased carcass lean yields in pigs. However, the relative contributions of prenatal as opposed to postnatal increased IGF2 expression are unclear. As muscle fiber number is set at birth, prenatal and neonate skeletal muscle development is critical in determining mature growth potential. Therefore, the objectives of this study were to determine the contributions of hyperplasia and hypertrophy to increased muscle mass and to delineate the effect of the mutation on the expression of myogenic genes during prenatal and postnatal growth. Sows (IGF2 A/A) were bred to a single heterozygous (IGF2 A/G) boar. For fetal samples, sows were euthanized at 60 and 90 d of gestation (d60 and d90) to obtain fetuses. Male and female offspring were also euthanized at birth (0d), weaning (21d), and market weight of approximately 130 kg (176d). At each sampling time, the LM, psoas major (PM), and semitendinosus (ST) muscles were weighed. Samples of the LM were used to quantify the expression of IGF family members, myogenic regulatory factors (MRF), myosin heavy chain isoforms, and growth factors, myostatin, and . Liver samples were used to quantify and expression. At 176d, weights of LM, PM, and ST muscles were all increased approximately 8% to 14% (P < 0.01) in pigs with paternal A (A(Pat)) alleles compared with those with paternal G (G(Pat)) alleles. Additionally, total muscle fiber number in the ST at 176d tended to be greater (P = 0.10), whereas muscle fiber cross-sectional area tended to be reduced ( P= 0.08) in A(Pat) pigs compared with G(Pat) pigs. In addition to the expected 2.7- to 4.5-fold increase (P ≤ 0.02) in expression in the LM in A(Pat) compared with G(Pat) pigs at postnatal sampling times (21d and 176d), IGF2 expression was also increased (P ≤ 0.06) 1.4- to 1.5-fold at d90 of gestation and at birth. At d90, expression of myogenic factor 5 (MYF5), a MRF expressed in proliferating myoblasts, in the LM was greater (P = 0.01) in A (Pat) pigs than in G(Pat) pigs. Interestingly, at 21d hepatic expression was greater (P = 0.01), whereas expression decreased (P = 0.01) in A(Pat) pigs compared with G(Pat) pigs; however, there were no differences (P ≥ 0.18) in hepatic expression between genotypes at 0d and 176d. These data suggest that prenatal hyperplasia of muscle fibers stimulated by increased IGF2 expression may contribute to increased muscle mass of A(Pat) pigs.

Fathali M MoghaddamAmerican Psychological Association, 2018A simple definition of radicalisation is when an individual or group reacts to a perceived threat by adopting progressively excessive meas...

The political theorist Hannah Arendt observed in her 1963 book Eichmann in Jerusalem: A Report on the Banality of Evil, that ‘No punishment has ever possessed enough power of deterrence to prevent ...

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.

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.

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 (0d), 7days (7d), weaning (21d), sexual maturity (42d), and 70d. For the neonatal periods, 0d and 7d, all muscles from the hind limbs were compiled for RNA extraction. At 21d, 42d, and 70d, 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 21d, 42d and 70d. However, Igf1 expression was reduced ( P ≤0.04) at 7d and 21d in MN mice compared to WT mice. Expression of Igf2 did not differ between genotypes at 0d and 7d, but, at 21d, 42d and 70d in BF and TB muscles, Igf2 expression was 1.9–2.9 fold greater ( P 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 21d MN mice compared with WT mice. Though male mice were heavier than females starting at 21d 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.

Myostatin inhibits while insulin-like growth factors (IGF) 1 and 2 increase pre- and postnatal skeletal muscle growth. However, the contribution of altered IGF expression to the hypermuscular pheno...

Prenatal muscle development is altered by maternal nutrition, the effect of maternal infection during pregnancy on offspring muscle growth and development is less clear. We assessed muscle developm...

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.

A detailed morphometric study of the basilar membrane was made from serial sections and graphic reconstructions of the cochlea of three little brown bats. Four distinct morphometric changes were observed within the basilar membrane. First, between 0-1.4 mm from the basal end of the cochlea, there is a rapid increase in width and cross-sectional area of the basilar membrane. Secondly, between 1.4-2.5 mm, there is little change in width of the basilar membrane (its cross-sectional area is at its greatest in this region). Thirdly, between 2.7-3.1 mm, there is a sudden decrease in cross-sectional area concomitant with an increase in the width of the basilar membrane. Finally, between 3.1 mm and the apex, there is a gradual decrease in cross-sectional area concomitant with an increase in the width of the basilar membrane. The magnitudes of the cross-sectional areas of the scalae media and vestibuli decrease from base to apex, but this is not true for the scala tympani. The cross-sectional area of the scala tympani appears to decrease from the base to 0.7 mm, then it increases up to 1.4 mm, and then it decreases to the apex. These morphometric changes in the basilar membrane of the little brown bat are compared to those in other echolocating and non-echolocating mammals. The significance of these changes is discussed in relation to the range of hearing in the little brown bat.

This study of psychiatric personnel involved with admissions procedures at a leading New England mental health center demonstrates on a small scale that the psychiatric community is generally unaware of patients' legal rights at the time of their admission and during subsequent hospitalization. The hospital staff's awareness of these rights can mean the difference between incarceration and freedom for the patient. The authors conclude that there is a need for educational programs on law for psychiatric personnel; they suggest possible approaches.