Janus kinase (JAK) 2 V617F mutation as the cause of primary thrombocythemia in acromegaly with severe visceromegaly and divergence between growth hormone and insulin-like growth factor-1 concentrations during the follow-up: causal or casual association?

OBJECTIVE: An increased prevalence of hematological abnormalities is reported in acromegaly, but to date no reports about the presence of the Janus Kinase (JAK) 2 mutation in acromegalic patients have been described. DESIGN: We report the complex clinical presentation of the unique case, never described, of acromegaly due to GH-secreting pituitary adenoma associated with JAK2 V617F mutation. RESULTS: The patient shows primary thrombocythemia and myelofibrosis, due to JAK2 V617F mutation, severe visceromegaly and a peculiar clinical course of the disease characterized by discrepant values of GH and IGF-1 during somatostatin analog (SA) treatment despite a significant reduction in pituitary adenoma size and therapeutic resistance both to SA and pegvisomant. CONCLUSIONS: The presence of JAK2 V617F mutation is a cause of primary thrombocythemia and myelofibrosis in acromegaly. In this patient, a peculiar clinical course of acromegaly was observed, with the difficulty in controlling the disease. More data, on a larger cohort of patients, could clarify whether JAK2 V617F mutation has a serious impact on the clinical features and course of acromegaly.OBJECTIVE: An increased prevalence of hematological abnormalities is reported in acromegaly, but to date no reports about the presence of the Janus Kinase (JAK) 2 mutation in acromegalic patients have been described. DESIGN: We report the complex clinical presentation of the unique case, never described, of acromegaly due to GH-secreting pituitary adenoma associated with JAK2 V617F mutation. RESULTS: The patient shows primary thrombocythemia and myelofibrosis, due to JAK2 V617F mutation, severe visceromegaly and a peculiar clinical course of the disease characterized by discrepant values of GH and IGF-1 during somatostatin analog (SA) treatment despite a significant reduction in pituitary adenoma size and therapeutic resistance both to SA and pegvisomant. CONCLUSIONS: The presence of JAK2 V617F mutation is a cause of primary thrombocythemia and myelofibrosis in acromegaly. In this patient, a peculiar clinical course of acromegaly was observed, with the difficulty in controlling the disease. More data, on a larger cohort of patients, could clarify whether JAK2 V617F mutation has a serious impact on the clinical features and course of acromegaly

Multi-level analysis of on-chip optical wireless links

Networks-on-chip are being regarded as a promising solution to meet the on-going requirement for higher and higher computation capacity. In view of future kilo-cores architectures, electrical wired connections are likely to become inefficient and alternative technologies are being widely investigated. Wireless communications on chip may be therefore leveraged to overcome the bottleneck of physical interconnections. This work deals with wireless networks-on-chip at optical frequencies, which can simplify the network layout and reduce the communication latency, easing the antenna on-chip integration process at the same time. On the other end, optical wireless communication on-chip can be limited by the heavy propagation losses and the possible cross-link interference. Assessment of the optical wireless network in terms of bit error probability and maximum communication range is here investigated through a multi-level approach. Manifold aspects, concurring to the final system performance, are simultaneously taken into account, like the antenna radiation properties, the data-rate of the core-to core communication, the geometrical and electromagnetic layout of the chip and the noise and interference level. Simulations results suggest that communication up to some hundreds of \u3bcm can be pursued provided that the antenna design and/or the target data-rate are carefully tailored to the actual layout of the chip

A genome wide association study for backfat thickness in Italian Large White pigs highlights new regions affecting fat deposition including neuronal genes.

BACKGROUND: Carcass fatness is an important trait in most pig breeding programs. Following market requests, breeding plans for fresh pork consumption are usually designed to reduce carcass fat content and increase lean meat deposition. However, the Italian pig industry is mainly devoted to the production of Protected Designation of Origin dry cured hams: pigs are slaughtered at around 160 kg of live weight and the breeding goal aims at maintaining fat coverage, measured as backfat thickness to avoid excessive desiccation of the hams. This objective has shaped the genetic pool of Italian heavy pig breeds for a few decades. In this study we applied a selective genotyping approach within a population of ~ 12,000 performance tested Italian Large White pigs. Within this population, we selectively genotyped 304 pigs with extreme and divergent backfat thickness estimated breeding value by the Illumina PorcineSNP60 BeadChip and performed a genome wide association study to identify loci associated to this trait. RESULTS: We identified 4 single nucleotide polymorphisms with P 645.0E-07 and additional 119 ones with 5.0E-07<P 645.0E-05. These markers were located throughout all chromosomes. The largest numbers were found on porcine chromosomes 6 and 9 (n=15), 4 (n=13), and 7 (n=12) while the most significant marker was located on chromosome 18. Twenty-two single nucleotide polymorphisms were in intronic regions of genes already recognized by the Pre-Ensembl Sscrofa10.2 assembly. Gene Ontology analysis indicated an enrichment of Gene Ontology terms associated with nervous system development and regulation in concordance with results of large genome wide association studies for human obesity. CONCLUSIONS: Further investigations are needed to evaluate the effects of the identified single nucleotide polymorphisms associated with backfat thickness on other traits as a pre-requisite for practical applications in breeding programs. Reported results could improve our understanding of the biology of fat metabolism and deposition that could also be relevant for other mammalian species including humans, confirming the role of neuronal genes on obesity

Usefulness of glycated albumin as a biomarker for glucose control and prognostic factor in chronic kidney disease patients on dialysis (CKD-G5D)

In chronic kidney disease patients on dialysis (CKD-G5D) accurate assessment of glycemic control is vital to improve their outcome and survival. The best glycemic marker for glucose control in these patients is still debated because several clinical and pharmacological factors may affect the ability of the available biomarkers to reflect the patient's glycemic status properly. This review discusses the role of glycated albumin (GA) both as a biomarker for glucose control and as a prognostic factor in CKD-G5D; it also looks at the pros and cons of GA in comparison to the other markers and its usefulness in hemodialysis and peritoneal dialysis

A multi-scale regional landslide susceptibility assessment approach: the SUFRA_SICILIA (SUscettibilit\ue0 da FRAna in Sicilia) project

The SUFRA project is based on a three level susceptibility mapping. According to the availability of more detailed data, the three scale for susceptibility mapping are increased respect to the ones suggested by the TIER group to 1:100,000, 1:50,000 and 1:25,000/1:10,000. The mapping levels exploit climatic, soil use (CORINE2009) and seismic informative layers, differentiating in the details of the core data (geology and topography), in the quality and resolution of the landslide inventory and in the modelling approach (Tab. 1). SUFRA_100 is based on a heuristic approach which is applied by processing a geologic layer (produced by ARTA integrating pre-CARG 1:100,000 geologic maps); the DEM exploited are IGMI 250m and the mapping units are 1km side square cells. Models are validated with respect to the PAI LIPs (Landslide Identification Points) which are reclassified adopting a simplified scheme. Output cuts of SUFRA100 will be referred to administrative boundaries (provinces). SUFRA50 is based on statistical analysis of new CARG geologic maps and 20m (ITA2000) - 2m (ATA2007) DEM. The mapping units are 500m and 50m cells, hydrographic and hydro-morphometric units. The landslide inventory is the IFFI2012_LIPs (first level) which is the result of the conversion in IFFI format of the PAI archive, which will be supported by remote landslide mapping (exploiting the ATA2007 aerial photos), according to the IFFI first level approach. Validation of the models will be performed exploiting both random spatial partition and temporal partition methods. Output cuts of SUFRA50 will be based on physiographic (basin) and administrative (municipalities) boundaries. SUFRA10/25 is based on statistical analysis of new CARG geologic maps (remotely and field adapted) and 2m (ATA2007) DEM. The mapping units are the slope units (SLUs) which are derived by further partitioning the hydro-morphometric units so to obtain closed morphodynamic units. The landslide inventories is the IFFI2012 which is the results of a field supported (on focus) landslide remote systematic mapping, according to the IFFI full level approach. Examples of SUFRA_100, SUFRA_50 and SUFRA_10 are presented for some representative key sector of Sicily. First results attest for the feasibility and goodness of the proposed protocol. The SUFRA program aims at enabling the regional governmental administration to cope with landslide prevision, which is the required operational concept in land management and planning. PAI has been a great advance with respect to the \u201cpre-SARNO\u201d conditions, but it is very exposed to fail: it is a blind approach for new activations; it is critically dependent on the quality of the landslide inventories; it cannot project the susceptibility outside the landslide area

Dielectric and plasmonic vivaldi antennas for on-chip wireless communication

In this paper, different technologies enabling wireless on-chip communication are investigated. In particular, plasmonic Vivaldi antennas coupled to silicon waveguides and all-dielectric Vivaldi antennas are proposed. The design criteria and the performances of the two antenna configurations are also discussed

Molecular analysis of TP53, Ki-Ras and P16 methylation status in tissue and plasma of subjects affected by gastrointestinal cancer (GIC)

BACKGROUND: Despite the improvement in detection and surgical therapy in the last years, the outcome of patients affected by colorectal carcinoma (CRC) remains limited by metastatic relapse. The aim of this study was to investigate the presence of free tumor DNA in the plasma of CRC patients in order to understand its possible prognostic role. PATIENTS AND METHODS: Ki-Ras, TP53 mutations and p16(INK4A) methylation status were prospectively evaluated in tumor tissues and plasma of 66 CRC patients. RESULTS: In 50 of the 66 primitive tumor cases (76%) at least one significant alteration was identified in Ki-Ras and/or TP53 and/or p16(INK4A) genes. Eighteen of the 50 patients presented the same alteration both in the plasma and in the tumor tissue. At univariate analysis, Ki-Ras mutations proved to be significantly related to quicker relapse (P <0.01), whereas only a trend towards statistical significance (P = 0.083) was observed for the TP53 mutations CONCLUSIONS: Detection of Ki-Ras and TP53 mutation in plasma should be significantly related to disease recurrence. These data suggest that patients with a high risk of recurrence can be identified by means of the analysis of tumor-derived plasma DNA with the use of fairly non-invasive techniques

Effectiveness of polymyxin B-immobilized fiber column in sepsis: a systematic review

INTRODUCTION: Severe sepsis and septic shock are common problems in the intensive care unit and carry a high mortality. Endotoxin, one of the principal components on the outer membrane of gram-negative bacteria, is considered important to their pathogenesis. Polymyxin B bound and immobilized to polystyrene fibers (PMX-F) is a medical device that aims to remove circulating endotoxin by adsorption, theoretically preventing the progression of the biological cascade of sepsis. We performed a systematic review to describe the effect in septic patients of direct hemoperfusion with PMX-F on outcomes of blood pressure, use of vasoactive drugs, oxygenation, and mortality reported in published studies. METHODS: We searched PubMed, the Cochrane Collaboration Database, and bibliographies of retrieved articles and consulted with experts to identify relevant studies. Prospective and retrospective observational studies, pre- and post-intervention design, and randomized controlled trials were included. Three authors reviewed all citations. We identified a total of 28 publications - 9 randomized controlled trials, 7 non-randomized parallel studies, and 12 pre-post design studies - that reported at least one of the specified outcome measures (pooled sample size, 1,425 patients: 978 PMX-F and 447 conventional medical therapy). RESULTS: Overall, mean arterial pressure (MAP) increased by 19 mm Hg (95% confidence interval [CI], 15 to 22 mm Hg; p < 0.001), representing a 26% mean increase in MAP (range, 14% to 42%), whereas dopamine/dobutamine dose decreased by 1.8 microg/kg per minute (95% CI, 0.4 to 3.3 microg/kg per minute; p = 0.01) after PMX-F. There was significant intertrial heterogeneity for these outcomes (p < 0.001), which became non-significant when analysis was stratified for baseline MAP. The mean arterial partial pressure of oxygen/fraction of inspired oxygen (PaO2/FiO2) ratio increased by 32 units (95% CI, 23 to 41 units; p < 0.001). PMX-F therapy was associated with significantly lower mortality risk (risk ratio, 0.53; 95% CI, 0.43 to 0.65). The trials assessed had suboptimal method quality. CONCLUSION: Based on this critical review of the published literature, direct hemoperfusion with PMX-F appears to have favorable effects on MAP, dopamine use, PaO2/FiO2 ratio, and mortality. However, publication bias and lack of blinding need to be considered. These findings support the need for further rigorous study of this therapy