Bone Mineral Density,Body Composition,and Metabolic Health of Very Low Birth Weight Infants Fed in Hospital Following Current Macronutrient Recommendations during the First 3 Years of Life

The present study longitudinally evaluated growth, bone mineral density, body composition, and metabolic health outcome in very low birth weight (VLBW) infants whose in-hospital target nutrient intake was within recent recommendations. From six months to three years, bone mineral density (dual-energy X-ray absorptiometry, DXA), body composition, and metabolic health outcome were compared with a reference group of term infants. The aim was to test whether in-hospital achieved weight gain until 36 weeks of gestation (light or appropriate for term equivalent age; LTEA or ATEA) predicts later growth, bone mineral density (BMD), abdominal obesity, or metabolic health outcomes such as insulin resistance, relative to term infants, during the first three years of life. Target in-hospital energy and protein intake was not achieved. Growth in weight, length and head circumference, mid arm circumference, adiposity, fat free mass (FFM), and bone mineralization in VLBW infants was less than those in term infants and influenced by nutritional status at discharge. Preterm infants had poorer motor and cognitive outcomes. Post-discharge body composition patterns indicate FFM proportional to height but lower fat mass index in LTEA preterm infants than term infants, with no evidence of increased truncal fat in preterm infants. The hypothesis of early BMD catch-up in VLBW infants after discharge was not supported by the present data. The clinical significance of these findings is unclear. The data may suggest a reduced obesity risk but an increased osteoporosis risk. Since postnatal growth restriction may have permanent negative health effects, LTEA VLBW infants would especially appear to benefit from targeted preventive interventions. Further follow-up of the infants is required.     

Relationship between minimal residual disease measured by multiparametric flow cytometry prior to allogeneic hematopoietic stem cell transplantation and outcome in children with acute lymphoblastic leukemia

Background

The presence of minimal residual disease detected by polymerase chain reaction techniques prior to allogeneic hematopoietic stem cell transplantation has proven to be an independent prognostic factor for poor outcome in children with acute lymphoblastic leukemia.

Design and Methods

The aim of this study was to ascertain whether the presence of minimal residual disease detected by multiparametric flow cytometry prior to allogeneic hematopoietic stem cell transplantation is related to outcome in children acute lymphoblastic leukemia. Minimal residual disease was quantified by multiparametric flow cytometry at a median of 10 days prior to hematopoietic stem cell transplantation in 31 children (age range, 10 months to 16 years) with acute lymphoblastic leukemia. Thirteen patients were transplanted in first remission. Stem cell donors were HLA-identical siblings in 8 cases and matched unrelated donors in 23. Twenty-six children received a total body irradiation-containing conditioning regimen. According to the level of minimal residual disease, patients were divided into two groups: minimal residual disease-positive (≥0.01%) (n=10) and minimal residual disease-negative (<0.01%) (n=21).

Results

Estimated event-free survival rates at 2 years for the minimal residual disease-negative and -positive subgroups were 74% and 20%, respectively (P=0.004) and overall survival rates were 80% and 20%, respectively (P=0.005). Bivariate analysis identified pre-transplant minimal residual disease as the only significant factor for relapse and also for death (P<0.01).

Conclusions

The presence of minimal residual disease measured by multiparametric flow cytometry identified a group of patients with a 9.5-fold higher risk of relapse and a 3.2-fold higher risk of death than those without minimal residual disease. This study supports the strong relationship between pre-transplantation minimal residual disease measured by multiparametric flow cytometry and outcome following allogeneic hematopoietic stem cell transplantation and concur with the results of previous studies using polymerase chain reaction techniques.     

In vivo depletion of DC impairs the anti‐tumor effect of agonistic anti‐CD137 mAb

Anti‐CD137 mAb are capable of inducing tumor rejection in several syngeneic murine tumor models and are undergoing clinical trials for cancer. The anti‐tumor effect involves co‐stimulation of tumor‐specific CD8⁺ T cells. Whether antigen cross‐presenting DC are required for the efficacy of anti‐CD137 mAb treatment has never been examined. Here we show that the administration of anti‐CD137 mAb eradicates EG7‐OVA tumors by a strictly CD8β⁺ T‐cell‐dependent mechanism that correlates with increased CTL activity. Ex vivo analyses to determine the identity of the draining lymph node cell type responsible for tumor antigen cross‐presentation revealed that CD11c⁺ cells, most likely DC, are the main players in this tumor model. A minute number of tumor cells, revealed by the presence of OVA cDNA, reach tumor‐draining lymph nodes. Direct antigen presentation by tumor cells themselves also participates in anti‐OVA CTL induction. Using CD11c diphtheria toxin receptor‐green fluorescent protein→C57BL/6 BM chimeric mice, which allow for sustained ablation of DC with diphtheria toxin, we confirmed the involvement of DC in tumor antigen cross‐presentation in CTL induction against OVA_257–264 epitope and in the antitumor efficacy induced by anti‐CD137 mAb.     

Developmental increase in postsynaptic alpha-amino-3-hydroxy-5-methyl-4 isoxazolepropionic acid receptor compartmentalization at the calyx of Held synapse

The pattern of expression of ionotropic glutamate receptor (GluR) subunits 1-4 in the medial nucleus of the trapezoid body (MNTB) has been reported to change during development. The aim of this study was to compare the distribution of the GluR1-4 subunits in the MNTB at postnatal day (P) 9, before high-frequency signal transmission in the auditory system has developed, with that observed in mature adult rats. GluR1-4 subunits were studied by preembedding and postembedding immunocytochemical methods. Increased levels of GluR1, 2/3, and 4 associated with development were evident only at postsynaptic sites of MNTB principal cell bodies receiving calyces of Held synapses, whereas receptor density at nonsynaptic sites was found to remain unaltered. Taken together, the expression pattern of GluR subunits and the density of immunoparticles in postsynaptic specializations are indicative of a compartmentalization of alpha-amino-3-hydroxy-5-methyl-4 isoxazolepropionic acid (AMPA) subunits upon development. These developmental changes provide a morphological basis for establishment of the postsynaptic properties needed for high-frequency synaptic transmission of auditory signals to MNTB principal neurons.     

Neuroprotective effect of melatonin against ischemia is partially mediated by alpha‐7 nicotinic receptor modulation and HO‐1 overexpression

Melatonin has been widely studied as a protective agent against oxidative stress. However, the molecular mechanisms underlying neuroprotection in neurodegeneration and ischemic stroke are not yet well understood. In this study, we evaluated the neuroprotective/antioxidant mechanism of action of melatonin in organotypic hippocampal cultures (OHCs) as well as in photothrombotic stroke model in vivo. Melatonin (0.1, 1, and 10 μm ) incubated postoxygen and glucose deprivation (OGD) showed a concentration‐dependent protection; maximum protection was achieved at 10 μm (90% protection). Next, OHCs were exposed to 10 μm melatonin at different post‐OGD times; the protective effect of melatonin was maintained at 0, 1, and 2 hr post‐OGD treatment, but it was lost at 6 hr post‐OGD. The protective effect of melatonin and the reduction in OGD‐induced ROS were prevented by luzindole (melatonin antagonist) and α‐bungarotoxin (α‐Bgt, a selective α7 nAChR antagonist). In Nrf2 knockout mice, the protective effect of melatonin was reduced by 40% compared with controls. Melatonin, incubated 0, 1, and 2 hr post‐OGD, increased the expression of heme oxygenase‐1 (HO‐1), and this overexpression was prevented by luzindole and α‐bungarotoxin. Finally, administration of 15 mg/kg melatonin following the induction of photothrombotic stroke in vivo, reduced infarct size (50%), and improved motor skills; this effect was partially lost in 0.1 mg/kg methyllycaconitine (MLA, selective α7 nAChR antagonist)‐treated mice. Taken together, these results demonstrate that postincubation of melatonin provides a protective effect that, at least in part, depends on nicotinic receptor activation and overexpression of HO‐1.     

Brooding rumination as a mediator in the relation between early maladaptive schemas and symptoms of depression and social anxiety in adolescents

Theory states that different cognitive constructs can be included in an integrated sequential model. This 3-wave longitudinal study assessed whether schema domains predict brooding rumination and brooding in turn predict depression and social anxiety symptoms among adolescents. A total of 1170 adolescents (M_age = 13.44 years old, SD_age = 1.30) completed measures of schema domains, brooding rumination, depression and social anxiety symptoms at baseline, 6- and 12-month follow-up (T1, T2, T3, respectively). Results revealed that the Disconnection and Rejection schema domain at T1 predicted prospective depression symptoms at T3 directly but not through brooding rumination. However, this schema domain did not predict social anxiety symptoms. The Other-Directedness schema domain at T1 predicted social anxiety symptoms at T3 both directly and through brooding at T2. Furthermore, this schema domain also predicted depression symptoms at T3 through brooding at T2. Identifying specific schema domains and the mechanisms through which these domains predict psychological symptoms has implications for interventions with adolescents.     

Lichen sclerosus et atrophicus in a surgical scar treated with fractional laser

Lichen sclerosus et atrophicus (LSA) is a chronic inflammatory disease of unknown cause that typically affects the genital area (1). It has been reported in post-traumatic areas as a result of Koebner phenomenon. LSA responds poorly to treatment making it a therapeutic challenge (2). Laser therapy has been described for LSA with variable results (3,4).