Behavioral medicine, clinical health psychology, and cost offset.

The use of medical services is a function of several interacting psychological and social variables as well as a function of physical malfunction. The clinical significance of addressing patients' psychosocial issues has only occasionally been considered. However, the shift in health care economics toward health care maintenance is responsible for the increased interest in interventions in the domain of behavioral medicine and health psychology. Evidence is reviewed for 6 mechanistic pathways by which behavioral interventions can maximize clinical care and result in significant economic benefits. The rationale for further integration of behavioral and biomedicine interventions is also reviewed. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Near-Complete Remission of Glioblastoma in a Patient Treated with an Allogenic Dendritic Cell-Based Vaccine: The Role of Tumor-Specific CD4+T-Cell Cytokine Secretion Pattern in Predicting Response and Recurrence

Immunotherapy has brought hope to the fight against glioblastoma, but its efficacy remains unclear. We present the case of CST, a 25-year-old female patient with a large right-hemisphere glioblastoma treated with a dendritic–tumor cell fusion vaccine. CST showed a near-complete tumor response, with a marked improvement in her functional status and simultaneous increases in tumor-specific CD8+ and CD4+ T cells. Two months before recurrence, the frequency of tumor-specific T cells decreased, while that of IL-17 and CD4+ T cells increased. CST passed away 15 months after enrollment. In this illustrative case, the tumor-specific CD4+ T-cell numbers and phenotype behaved as treatment efficacy biomarkers, highlighting the key role of the latter in glioblastoma immunotherapy.     

Impact of Zinc on Oxidative Signaling Pathways in the Development of Pulmonary Vasoconstriction Induced by Hypobaric Hypoxia

Hypobaric hypoxia is a condition that occurs at high altitudes (>2500 m) where the partial pressure of gases, particularly oxygen (PO₂), decreases. This condition triggers several physiological and molecular responses. One of the principal responses is pulmonary vascular contraction, which seeks to optimize gas exchange under this condition, known as hypoxic pulmonary vasoconstriction (HPV); however, when this physiological response is exacerbated, it contributes to the development of high-altitude pulmonary hypertension (HAPH). Increased levels of zinc (Zn²⁺) and oxidative stress (known as the “ROS hypothesis”) have been demonstrated in the vasoconstriction process. Therefore, the aim of this review is to determine the relationship between molecular pathways associated with altered Zn²⁺ levels and oxidative stress in HPV in hypobaric hypoxic conditions. The results indicate an increased level of Zn²⁺, which is related to increasing mitochondrial ROS (mtROS), alterations in nitric oxide (NO), metallothionein (MT), zinc-regulated, iron-regulated transporter-like protein (ZIP), and nicotinamide adenine dinucleotide phosphate (NADPH) oxidase-induced protein kinase C epsilon (PKCε) activation in the development of HPV. In conclusion, there is an association between elevated Zn²⁺ levels and oxidative stress in HPV under different models of hypoxia, which contribute to understanding the molecular mechanism involved in HPV to prevent the development of HAPH.     

Modeling the behavior of persons with mild cognitive impairment or Alzheimer’s for intelligent environment simulation

User Modeling and User-Adapted Interaction - Intelligent environments may improve the independence and quality of life of persons with mild cognitive impairment (MCI) or Alzheimer’s disease...     

Improving Scalability of Application-Level Checkpoint-Recovery by Reducing Checkpoint Sizes

The execution times of large-scale parallel applications on nowadays multi/many-core systems are usually longer than the mean time between failures. Therefore, parallel applications must tolerate hardware failures to ensure that not all computation done is lost on machine failures. Checkpointing and rollback recovery is one of the most popular techniques to implement fault-tolerant applications. However, checkpointing parallel applications is expensive in terms of computing time, network utilization and storage resources. Thus, current checkpoint-recovery techniques should minimize these costs in order to be useful for large scale systems. In this paper three different and complementary techniques to reduce the size of the checkpoints generated by application-level checkpointing are proposed and implemented. Detailed experimental results obtained on a multicore cluster show the effectiveness of the proposed methods to reduce checkpointing cost.     

Altered Distribution and Expression of Syndecan-1 and -4 as an Additional Hallmark in Psoriasis

Syndecans act as independent co-receptors to exert biological activities and their altered function is associated with many pathophysiological conditions. Here, syndecan-1 and -4 were examined in lesional skin of patients with psoriasis. Immunohistochemical staining confirmed altered syndecan-1 distribution and revealed absence of syndecan-4 expression in the epidermis. Fibronectin (FN)—known to influence inflammation and keratinocyte hyperproliferation via α5β1 integrin in psoriasis—was also decreased. Syndecan-1 and -4 expression was analyzed in freshly isolated lesional psoriatic human keratinocytes (PHK) characterized based on their proliferation and differentiation properties. mRNA levels of syndecan-1 were similar between healthy and PHK, while syndecan-4 was significantly decreased. Cell growth and release of the pro-inflammatory Tumor Necrosis Factor-alpha (TNFα) were selectively and significantly induced in PHKs plated on FN. Results from co-culture of healthy keratinocytes and psoriatic fibroblasts led to the speculation that at least one factor released by fibroblasts down-regulate syndecan-1 expression in PHK plated on FN. To assay if biological treatments for psoriasis target keratinocyte proliferation, gelatin-based patches enriched with inteleukin (IL)-17α or TNFα blockers were prepared and tested using a full-thickness healthy epidermal model (Phenion^®). Immunohistochemistry analysis showed that both blockers impacted the localisation of syndecan-1 within the refined epidermis. These results provide evidence that syndecans expression are modified in psoriasis, suggesting that they may represent markers of interest in this pathology.     

Enapotamab Vedotin,an AXL-Specific Antibody-Drug Conjugate,Demonstrates Antitumor Efficacy in Patient-Derived Xenograft Models of Soft Tissue Sarcoma

Doxorubicin (doxo) remains the standard of care for patients with advanced soft tissue sarcoma (STS), even though response rates to doxo are only around 14% to 18%. We evaluated enapotamab vedotin (EnaV), an AXL-specific antibody-drug conjugate (ADC), in a panel of STS patient-derived xenografts (PDX). Eight models representing multiple STS subtypes were selected from our STS PDX platform (n = 45) by AXL immunostaining on archived passages. Models were expanded by unilateral transplantation of tumor tissue into the left flank of 20 NMRI nu/nu mice. Once tumors were established, mice were randomized into an EnaV treatment group, or a group treated with isotype control ADC. Treatment efficacy was assessed by tumor volume evaluation, survival analysis, and histological evaluation of tumors, and associated with AXL expression. EnaV demonstrated significant tumor growth delay, regression, and/or prolonged survival compared to isotype control ADC in 5/8 STS PDX models investigated. Experimental passages of responding models were all found positive for AXL at varying levels, but no linear relationship could be identified between the level of expression and level of response to EnaV. One model was found negative for AXL on experimental passage and did not respond to EnaV. This study provides a preclinical rationale for the evaluation of AXL-targeting ADCs in the treatment of AXL-expressing sarcomas.     

Thermo-Metallurgical Modeling of Nodular Cast Iron Cooling Process

A new numerical model to describe the microstructural evolution of a eutectic nodular cast iron during its cooling is presented. In particular, equiaxial solidification assuming an independent nucleation of austenite and graphite nodules is considered. In this context, the austenite has dendritic growth whereas the graphite grows with a spherical shape. After solidification occurs, the model assumes that the graphite nodules present in the cast iron continue growing since the carbon content in austenite decreases. Once the stable eutectoid temperature is reached, the alloy undergoes the austenite-ferrite transformation. The nucleation of the ferrite takes place at the contour of the spherical graphite nodules where austenite has low carbon concentration. A ferrite shell surrounding the graphite nodules is formed afterward by means of a process governed by carbon diffusion. Then, a ferrite-pearlite competitive transformation occurs when the temperature is below the metastable temperature. This thermo-metallurgical model is discretized and solved by means of the finite element method. The model allows the computation of cooling curves, fraction evolution for each component, and size and distribution of graphite nodules. The present numerical results are compared with experiments using standardized Quick-cup-type cups, and satisfactory numerical predictions of the final microstructure and cooling curves are achieved.