AAV-mediated and pharmacological induction of Hsp70 expression stimulates survival of retinal ganglion cells following axonal injury.

We evaluated the effect of AAV2- and 17-AAG (17-N-allylamino-17-demethoxygeldanamycin)-mediated upregulation of Hsp70 expression on the survival of retinal ganglion cells (RGCs) injured by optic nerve crush (ONC). AAV2-Hsp70 expression in the retina was primarily observed in the ganglion cell layer. Approximately 75% of all transfected cells were RGCs. RGC survival in AAV2-Hsp70-injected animals was increased by an average of 110% 2 weeks after the axonal injury compared with the control. The increase in cell numbers was not even across the retinas with a maximum effect of approximately 306% observed in the inferior quadrant. 17-AAG-mediated induction of Hsp70 expression has been associated with cell protection in various models of neurodegenerative diseases. We show here that a single intravitreal injection of 17-AAG (0.2 ug ul(-1)) results in an increased survival of ONC-injured RGCs by approximately 49% compared with the vehicle-treated animals. Expression of Hsp70 in retinas of 17-AAG-treated animals was upregulated approximately by twofold compared with control animals. Our data support the idea that the upregulation of Hsp70 has a beneficial effect on the survival of injured RGCs, and the induction of this protein could be viewed as a potential neuroprotective strategy for optic neuropathies

Principles of primary survey and resuscitation in cases of pediatric trauma

Trauma is a common cause of death and disability in children. Proper approach to pediatric trauma involves adherence to ABCDE sequence in the primary survey and resuscitation in order to promptly recognize and manage life-threatening conditions immediately. This readily reviewed sequence includes A: establishment and maintenance of a patent airway while maintaining cervical spine immobilization; B: evaluation of breathing, ventilation and oxygenation, immediate treatment of tension pneumothorax, open pneumothorax and massive hemothorax; C: evaluation and treatment of circulatory compromise and shock; D: Disability and Neurologic Status, assessment of signs of increased intracranial pressure and impending cerebral herniation; and E: Exposure while preventing hypothermia. Implementing these assessment and management priorities can result in more favorable outcomes. © 2015 Tehran University of Medical Sciences. All rights reserve

Bone mineral density is lower in male than female patients with plaque-type psoriasis in Iran

Background There are many similarities with regard to contributing cytokines in patients with psoriasis and osteoporosis. A theory of probable relationship between these two entities has been proposed but there is no concordant consensus. The aim of this study was to evaluate bone mineral density (BMD) in patients with psoriasis. Method and materials This cross-sectional study of BMD was conducted with 64 eligible patients with psoriasis who were referred to the dermatology clinic of Razi hospital in Tehran, Iran in between 2011 and 2012. Results The mean T score of femoral neck was �1.17 and �0.49 in men and women, respectively, which was statistically significant (p =.047). The mean T score of the lumbar spine was �0.93 and �0.30 in men and women, respectively, but not statistically significant (p =.058). In total except with the exclusion of the study site (femur or lumbar), men and women did not have a statistically significant difference with regard to osteoporosis or osteopenia in BMD (p =.114). The Pearson correlation coefficient demonstrated a moderate inverse relationship between age and T score of the femoral neck and lumbar spine (r = �0.419 and �.406, respectively), which was statistically significant (p =.001). Although there was no statistically significant relationship between the Psoriasis Area and Severity Index (PASI) and T scores of the femoral neck (p =.596), a positive and weak correlation was observed between the PASI and T scores for the lumbar spine, which was statistically significant (r = 0.269; p =.03). Conclusion Patients with psoriasis had decreased bone density, which was more significant in men. Prevalence of osteoporosis showed no statistically significant difference when compared with the healthy population in Iran. © 201

Bone mineral density is lower in male than female patients with plaque-type psoriasis in Iran

Background There are many similarities with regard to contributing cytokines in patients with psoriasis and osteoporosis. A theory of probable relationship between these two entities has been proposed but there is no concordant consensus. The aim of this study was to evaluate bone mineral density (BMD) in patients with psoriasis. Method and materials This cross-sectional study of BMD was conducted with 64 eligible patients with psoriasis who were referred to the dermatology clinic of Razi hospital in Tehran, Iran in between 2011 and 2012. Results The mean T score of femoral neck was �1.17 and �0.49 in men and women, respectively, which was statistically significant (p =.047). The mean T score of the lumbar spine was �0.93 and �0.30 in men and women, respectively, but not statistically significant (p =.058). In total except with the exclusion of the study site (femur or lumbar), men and women did not have a statistically significant difference with regard to osteoporosis or osteopenia in BMD (p =.114). The Pearson correlation coefficient demonstrated a moderate inverse relationship between age and T score of the femoral neck and lumbar spine (r = �0.419 and �.406, respectively), which was statistically significant (p =.001). Although there was no statistically significant relationship between the Psoriasis Area and Severity Index (PASI) and T scores of the femoral neck (p =.596), a positive and weak correlation was observed between the PASI and T scores for the lumbar spine, which was statistically significant (r = 0.269; p =.03). Conclusion Patients with psoriasis had decreased bone density, which was more significant in men. Prevalence of osteoporosis showed no statistically significant difference when compared with the healthy population in Iran. © 201

A role for SETD2 loss in tumorigenesis through DNA methylation dysregulation

SETD2-dependent H3 Lysine-36 trimethylation (H3K36me3) has been recently linked to the deposition of de-novo DNA methylation. SETD2 is frequently mutated in cancer, however, the functional impact of SETD2 loss and depletion on DNA methylation across cancer types and tumorigenesis is currently unknown. Here, we perform a pan-cancer analysis and show that both SETD2 mutation and reduced expression are associated with DNA methylation dysregulation across 21 out of the 24 cancer types tested. In renal cancer, these DNA methylation changes are associated with altered gene expression of oncogenes, tumour suppressors, and genes involved in neoplasm invasiveness, including TP53, FOXO1, and CDK4. This suggests a new role for SETD2 loss in tumorigenesis and cancer aggressiveness through DNA methylation dysregulation. Moreover, using a robust machine learning methodology, we develop and validate a 3-CpG methylation signature which is sufficient to predict SETD2 mutation status with high accuracy and correlates with patient prognosis

Interrogation of the Microenvironmental Landscape in Brain Tumors Reveals Disease-Specific Alterations of Immune Cells

Brain malignancies encompass a range of primary and metastatic cancers, including low-grade and high-grade gliomas and brain metastases (BrMs) originating from diverse extracranial tumors. Our understanding of the brain tumor microenvironment (TME) remains limited, and it is unknown whether it is sculpted differentially by primary versus metastatic disease. We therefore comprehensively analyzed the brain TME landscape via flow cytometry, RNA sequencing, protein arrays, culture assays, and spatial tissue characterization. This revealed disease-specific enrichment of immune cells with pronounced differences in proportional abundance of tissue-resident microglia, infiltrating monocyte-derived macrophages, neutrophils, and T cells. These integrated analyses also uncovered multifaceted immune cell activation within brain malignancies entailing converging transcriptional trajectories while maintaining disease- and cell-type-specific programs. Given the interest in developing TME-targeted therapies for brain malignancies, this comprehensive resource of the immune landscape offers insights into possible strategies to overcome tumor-supporting TME properties and instead harness the TME to fight cancer

MM-wave cavity/klystron developments using deep x-ray lithography at the Advanced Photon Source.

Recent microfabrication technologies based on LIGA (German acronym for Li thographe, G alvanoformung, und A bformung) have been applied to build high-aspect-ratio, metallic or dielectric, planar structures suitable for high frequency rf cavity structures. The cavity structures would be used as parts of linear accelerators, microwave undulators, and mm-wave amplifiers. The microfabrication process includes manufacturing of precision x-ray masks, exposure of positive resist by x-rays through the mask, resist development, and electroforming of the final microstructure. Prototypes of a 32-cell, 108-GHz constant impedance cavity and a 66-cell, 94-GHz constant-gradient cavity were fabricated using the synchrotron radiation sources at APS. Preliminary design parameters for a 91- GHz modulator klystron along with an overview of the new technology are discussed