Elliottskriver2566

The purpose of this work was to identify parameters influencing the risk of late radiation side effects, fair or poor cosmetic outcomes (COs) and pain in breast cancer patients after breast-conserving therapy (BCT) and three-dimensional conformal radiotherapy (3D-CRT).

Between 2006 and 2013, 159 patients were treated at the Hannover Medical School. Physician-rated toxicity according to the LENT-SOMA criteria, CO and pain were assessed by multivariate analysis.

LENT-SOMA grade 1-4 toxicity was observed as follows fibrosis 10.7 %, telangiectasia 1.2 %, arm oedema 8.8 % and breast oedema 5.0 %. In addition, 15.1 % of patients reported moderate or severe breast pain, and 21.4 % complained about moderate or severe pain in the arm or shoulder. In multivariate analysis, axillary clearing (AC) was significantly associated with lymphoedema of the arm [odds ratio (OR) 4.37, p = 0.011, 95 % confidence interval (CI) 1.4-13.58]. Breast oedema was also highly associated with AC (OR 10.59, p = 0.004, 95 % CI 2.1-53.36reast oedema. Late toxicities exclusive breast pain were not associated with radiotherapy parameters.

To examine the cross-sectional and inter-temporal validity of the Household Food Insecurity Access Scale (HFIAS) for rural households in Burundi.

Longitudinal survey about food security and agricultural production, individually administered by trained interviewers in June 2007 and 2012.

Ngozi, north of Burundi.

Three hundred and fourteen household heads were interviewed.

Tobit models showed that the HFIAS was significantly correlated with objective measures of food security, in this case total annual food production (P<0·01), livestock keeping (P<0·01) and coffee production (P<0·01) in both 2007 and 2012. This confirms that the HFIAS is cross-sectionally valid and corroborates the findings of previous studies. However, while total food production decreased by more than 25 % in terms of energy between 2007 and 2012, households reported an improvement in their perceived food security over the same period, with the HFIAS decreasing from 13·9 to 10·8 (P<0·001). This finding questions the inter-temporal validity of the HFIAS. It may be partly explained through response shifts, in which households assess their own food security status in comparison to that of their peers.

The evidence from our study suggests that the HFIAS is cross-sectionally valid, but may not be inter-temporally valid, and should not be used as a single indicator to study temporal trends in food security.

The evidence from our study suggests that the HFIAS is cross-sectionally valid, but may not be inter-temporally valid, and should not be used as a single indicator to study temporal trends in food security.

To identify determinants of fruit and vegetable (F&V) consumption among school-aged children.

A survey study was conducted in October 2010. The questionnaire contained questions concerning social and demographic data, lifestyle and dietary habits, particularly the frequency of F&V consumption, availability of F&V and knowledge about recommended amounts of F&V intake.

Polish primary schools.

Children (n 1255) aged 9 years from randomly selected primary schools and their parents.

The children's consumption of fruit and of vegetables was influenced by the fruit consumption and vegetable consumption of their parents (r=0·333 and r=0·273, respectively; P=0·001), parents encouraging their children to eat F&V (r=0·259 and r=0·271, respectively; P=0·001), giving children F&V to take to school (r=0·338 and r=0·321, respectively; P=0·001) and the availability of F&V at home (r=0·200 and r=0·296, respectively; P=0·001). Parental education influenced only the frequency of fruit consumption (r=0·074; P=0·01). A correlation between parents' knowledge of the recommended intakes and the frequency of vegetable and fruit consumption by children was noticed (r=0·258 and r=0·192, respectively, P=0·001).

Factors within the family environment such as parents' dietary habits and F&V availability had the greatest influence on the F&V consumption by children. Educational activities aimed at parents are crucial to increase the consumption of F&V among children.

Factors within the family environment such as parents' dietary habits and F&V availability had the greatest influence on the F&V consumption by children. Educational activities aimed at parents are crucial to increase the consumption of F&V among children.A major key to improvement of cancer therapy is the combination of drugs. Mixing drugs that already exist on the market may offer an attractive alternative. Here we report on a new model-based streamlined feedback system control (s-FSC) method, based on a design of experiment approach, for rapidly finding optimal drug mixtures with minimal experimental effort. We tested combinations in an in vitro assay for the viability of a renal cell adenocarcinoma (RCC) cell line, 786-O. An iterative cycle of in vitro testing and s-FSC analysis was repeated a few times until an optimal low dose combination was reached. Starting with ten drugs that target parallel pathways known to play a role in the development and progression of RCC, we identified the best overall drug combination, being a mixture of four drugs (axitinib, erlotinib, dasatinib and AZD4547) at low doses, inhibiting 90% of cell viability. The removal of AZD4547 from the optimized drug combination resulted in 80% of cell viability inhibition, while still maintaining the synergistic interaction. PGE2 chemical structure These optimized drug combinations were significantly more potent than monotherapies of all individual drugs (p  less then  0.001, CI  less then  0.3).The preparation of microcapsules consisting of poly(D,L-lactide-co-glycolide) (PLGA) polymer shell and aqueous core is a clear challenge and hence has been rarely addressed in literature. Herein, aqueous core-PLGA shell microcapsules have been prepared by internal phase separation from acetone-water in oil emulsion. The resulting microcapsules exhibited mean particle size of 1.1 ± 0.39 μm (PDI = 0.35) with spherical surface morphology and internal poly-nuclear core morphology as indicated by scanning electron microscopy (SEM). The incorporation of water molecules into PLGA microcapsules was confirmed by differential scanning calorimetry (DSC). Aqueous core-PLGA shell microcapsules and the corresponding conventional PLGA microspheres were prepared and loaded with risedronate sodium as a model drug. Interestingly, aqueous core-PLGA shell microcapsules illustrated 2.5-fold increase in drug encapsulation in comparison to the classical PLGA microspheres (i.e., 31.6 vs. 12.7%), while exhibiting sustained release behavior following diffusion-controlled Higuchi model. The reported method could be extrapolated to encapsulate other water soluble drugs and hydrophilic macromolecules into PLGA microcapsules, which should overcome various drawbacks correlated with conventional PLGA microspheres in terms of drug loading and release.Previously, we demonstrated that CD28 and CTLA-4 signaling control Casitas-B-lineage lymphoma (Cbl)-b protein expression, which is critical for T cell activation and tolerance induction. However, the molecular mechanism(s) of this regulation remains to be elucidated. In this study, we found that Cbl-b fails to undergo tyrosine phosphorylation upon CD3 stimulation because SHP-1 is recruited to and dephosphorylates Cbl-b, whereas CD28 costimulation abrogates this interaction. In support of this finding, T cells lacking SHP-1 display heightened tyrosine phosphorylation and ubiquitination of Cbl-b upon TCR stimulation, which correlates with decreased levels of Cbl-b protein. The aberrant Th2 phenotype observed in T cell-specific Shp1(-/-) mice is reminiscent of heightened Th2 response in Cblb(-/-) mice. Indeed, overexpressing Cbl-b in T cell-specific Shp1(-/-) T cells not only inhibits heightened Th2 differentiation in vitro, but also Th2 responses and allergic airway inflammation in vivo. Therefore, SHP-1 regulates Cbl-b-mediated T cell responses by controlling its tyrosine phosphorylation and ubiquitination.Understanding the mechanisms of host macrophage responses to Mycobacterium tuberculosis is essential for uncovering potential avenues of intervention to boost host resistance to infection. Macrophage transcriptome profiling revealed that M. tuberculosis infection strongly induced the expression of several enzymes controlling tryptophan catabolism. These included IDO1 and tryptophan 2,3-dioxygenase, which catalyze the rate-limiting step in the kynurenine pathway, producing ligands for the aryl hydrocarbon receptor (AHR). The AHR and heterodimeric partners AHR nuclear translocator and RELB are robustly expressed, and AHR and RELB levels increased further during infection. Infection enhanced AHR/AHR nuclear translocator and AHR/RELB DNA binding and stimulated the expression of AHR target genes, including that encoding the inflammatory cytokine IL-1β. AHR target gene expression was further enhanced by exogenous kynurenine, and exogenous tryptophan, kynurenine, or synthetic agonist indirubin reduced mycobacterial viability. Comparative expression profiling revealed that AHR ablation diminished the expression of numerous genes implicated in innate immune responses, including several cytokines. Notably, AHR depletion reduced the expression of IL23A and IL12B transcripts, which encode subunits of IL-23, a macrophage cytokine that stimulates production of IL-22 by innate lymphoid cells. AHR directly induced IL23A transcription in human and mouse macrophages through near-upstream enhancer regions. Taken together, these findings show that AHR signaling is strongly engaged in M. tuberculosis-infected macrophages and has widespread effects on innate immune responses. Moreover, they reveal a cascade of AHR-driven innate immune signaling, because IL-1β and IL-23 stimulate T cell subsets producing IL-22, another direct target of AHR transactivation.Aging is associated with gradual deterioration of adaptive immune function, a hallmark of which is the profound loss of naive T cells (TN) associated with decline in thymic output and export of new cells into the peripheral T cell pool. Because the lymphotropic cytokine IL-7 plays crucial roles in both development of TN in the thymus and TN homeostasis in the periphery, we sought to determine the extent to which therapeutic administration of IL-7 could reverse TN deficiency in aging rhesus macaques (RM), either by enhancement of the demonstrably reduced thymopoiesis or by peripheral TN expansion. Our results indicate that treatment of both adult (8-15 y) and old (>20 y) RM with recombinant simian IL-7 (rsIL-7) results in only transient increases in peripheral CD4(+) and CD8(+) TN numbers with no long-term benefit, even with repeated therapy. This transient effect was due to peripheral TN expansion and not enhanced thymic function, and appeared to be limited by induction of IL-7 nonresponsiveness. However, rsIL-7 therapy had a more promising effect on the central memory T cell (TCM) population (both CD4(+) and CD8(+)) in adult and old RM, doubling the numbers of these cells in circulation and maintaining this larger population long term. IL-7 therapy did not reduce TCR diversity of the memory T cell compartment, suggesting that rsIL-7-induced expansion was symmetrical. Thus, although rsIL-7 failed to counter age-associated TN loss, the ability of this therapy to expand clonotypically diverse CD4(+) and CD8(+) TCM populations might potentially improve adaptive immune responsiveness in the elderly.