Treatment response with sirolimus for a pediatric patient with an EBV‐associated smooth‐muscle tumor after bone marrow transplantation

Epstein–Barr virus–associated smooth‐muscle tumors (EBV‐SMTs) are unique and rare neoplasms described in immunocompromised patients. The case describes a nine‐year‐old female with a history of acute lymphoblastic leukemia with relapse and subsequent allogeneic bone marrow transplantation who presented with multiple EBV‐SMTs of the liver. EBV utilizes the mammalian target of rapamycin (mTOR) pathway for tumor growth, and sirolimus, a mTOR inhibitor, has shown to result in a short‐term response. We now report an extended treatment response with sirolimus in a pediatric patient with an EBV‐SMT.     

Role of Adhesion in Electrostatic Precipitation

Human subjects ingested daily 5- to 20-mg doses of technical DDT, p,p′-DDE, or p,p′-DDD for 81 to 183 days. Serum and adipose concentrations of DDT and DDT metabolites in response to these dosings have indicated that the initial dechlorination of DDT is of critical importance to its metabolic fate. Conversion to the saturated p,p′-DDD makes possible further degradation to the readily excreted p,p′-DDA. Dehydrochlorination, on the other hand, yields p,p′-DDE, a stable metabolite that is avidly retained in adipose storage. In two subjects ingesting technical DDT, conversion to DDE has been extremely limited, while conversion to DDD has been regularly demonstrable during and after dosing. Tissue stores of p,p′-DDE in general population probably originate mainly from preformed dietary p,p′-DDE in the diet, rather than from p,p′-DDT.     

Compartmentalization of excitatory amino acid receptors in human striatum.

Division of the mammalian neostriatum into two intermingled compartments called striosomes and matrix has been established by analysis of enzyme activity, neuropeptide distribution, nucleic acid hybridization, and neurotransmitter receptor binding. Striosomes and matrix are distinct with respect to afferent and efferent connections, and these regions provide the potential for modulation and integration of information flow within basal ganglia circuitry. The primary neurotransmitters of corticostriatal afferents are excitatory amino acids, but to date no correlation of excitatory amino acid receptors and striatal compartments has been described. We examined binding to the three pharmacologically distinct ionotropic excitatory amino acid receptors, N-methyl-D-aspartate, alpha-amino-3-hydroxy-5-methylisoxazole-4-propionic acid, and kainate, in human striatum using in vitro receptor autoradiography and compared the binding to striosomes and matrix histochemically defined by acetylcholinesterase activity. Our findings reveal increased binding to N-methyl-D-aspartate receptors and alpha-amino-3-hydroxy-5-methylisoxazole-4-propionic acid receptors in matrix relative to striosomes and increased kainate receptor binding in striosomes relative to matrix. These results suggest that afferent input to the two striatal compartments may be mediated by pharmacologically distinct excitatory amino acid receptor subtypes.     

Tissues of MSH2-deficient mice demonstrate hypermutability on exposure to a DNA methylating agent

The mutational response of mismatch repair-deficient animals to the alkylating agent N-methyl-N-nitrosourea was evaluated by using a transgenic lacI reporter system. Although the mutations detected in MSH2 heterozygotes were similar to those of controls, MSH2^−/− animals demonstrated striking increases in mutation frequency in response to this agent. G:C to A:T transitions at GpG sites, as opposed to CpG sites, dominated the mutational spectrum of both MSH2^+/+ and MSH2^−/− N-methyl-N-nitrosourea -treated animals. Extrapolating to humans with hereditary non-polyposis colorectal cancer, the results suggest that MSH2 heterozygotes are unlikely to be at increased risk of mutation, even when exposed to potent DNA methylating agents. In contrast, mismatch repair-deficient cells spontaneously arising within individuals with hereditary non-polyposis colorectal cancer would likely exhibit hypermutability in response to such mutagens, an outcome predicted to accelerate the pace of tumorigenesis.     

Changes in physical activity,diet, and body weight across the education and employment transitions of early adulthood: A systematic review and meta‐analysis

Early adulthood is a time when individuals go through important life transitions, such as moving from high school into higher education or employment, but the impact of these life transitions on changes in body weight, diet, and physical activity is not known. We searched six electronic databases to July 2019 for longitudinal observational studies providing data on adiposity, diet, and/or physical activity across education or employment transitions in young people aged between 15 and 35 years. We found 19 studies, of which 17 assessed changes in physical activity, three body weight, and five diet or eating behaviours. Meta‐analysis (n=9) found that leaving high school was associated with a decrease of ?7.04 (95% CI, ?11.26, ?2.82) min/day of moderate‐to‐vigorous physical activity. Three studies reported increases in body weight on leaving high school. A small number of studies suggested decreases in diet quality on leaving high school (n=2/4 papers) and leaving university (n=1) but not on starting employment (n=1). Studies suggested no change in physical activity on leaving university (n=4) but decreases in physical activity on starting employment (n=2/3). The transition of leaving high school is an important time to support individuals to prevent decreases in physical activity and gains in body weight.