Novel strategies for the characterization of cancellous bone morphology: Virtual isolation and analysis

Objectives: The advent of micro-computed tomography (μCT) made cancellous bone more accessible than ever before. Nevertheless, the characterization of cancellous bone is made difficult by its inherent complexity and the difficulties in defining homology across datasets. Here we propose novel virtual methodological approaches to overcome those issues and complement existing methods. Materials and methods: We present a protocol for the isolation of the whole cancellous region within a μCT scanned bone. This method overcomes the subsampling issues and allows studying cancellous bone as a single unit. We test the protocol on a set of primate bones. In addition, we describe a set of morphological indices calculated on the topological skeleton of the cancellous bone: node density, node connectivity, trabecular angle, trabecular tortuosity, and fractal dimension. The usage of the indices is shown on a small comparative sample of primate femoral heads. Results: The isolation protocol proves reliable in isolating cancellous structures from several different bones, regardless of their shape. The indices seem to detect some functional differences, although further testing on comparative samples is needed to clarify their potential for the study of cancellous architecture. Conclusions: The approaches presented overcome some of the difficulties of trabecular bone studies. The methods presented here represent an alternative or supporting method to the existing tools available to address the biomechanics of cancellous bone

Genetic Features of Metachronous Esophageal Cancer Developed in Hodgkin's Lymphoma or Breast Cancer Long-Term Survivors: An Exploratory Study.

Background Development of novel therapeutic drugs and regimens for cancer treatment has led to improvements in patient long-term survival. This success has, however, been accompanied by the increased occurrence of second primary cancers. Indeed, patients who received regional radiotherapy for Hodgkin's Lymphoma (HL) or breast cancer may develop, many years later, a solid metachronous tumor in the irradiated field. Despite extensive epidemiological studies, little information is available on the genetic changes involved in the pathogenesis of these solid therapy-related neoplasms. Methods Using microsatellite markers located in 7 chromosomal regions frequently deleted in sporadic esophageal cancer, we investigated loss of heterozygosity (LOH) and microsatellite instability (MSI) in 46 paired (normal and tumor) samples. Twenty samples were of esophageal carcinoma developed in HL or breast cancer long-term survivors: 14 squamous cell carcinomas (ESCC) and 6 adenocarcinomas (EADC), while 26 samples, used as control, were of sporadic esophageal cancer (15 ESCC and 11 EADC). Results We found that, though the overall LOH frequency at the studied chromosomal regions was similar among metachronous and sporadic tumors, the latter exhibited a statistically different higher LOH frequency at 17q21.31 (p = 0.018). By stratifying for tumor histotype we observed that LOH at 3p24.1, 5q11.2 and 9p21.3 were more frequent in ESCC than in EADC suggesting a different role of the genetic determinants located nearby these regions in the development of the two esophageal cancer histotypes. Conclusions Altogether, our results strengthen the genetic diversity among ESCC and EADC whether they occurred spontaneously or after therapeutic treatments. The presence of histotype-specific alterations in esophageal carcinoma arisen in HL or breast cancer long-term survivors suggests that their transformation process, though the putative different etiological origin, may retrace sporadic ESCC and EADC carcinogenesis

Serological survey for mycoplasma hyopneumoniae in free-living wild boars from Campos Gerais region, Paraná, Brasil.

The south region of Brazil was responsible for 80.3% of total pork meat export in the country in 2015 (2), with the state of Paraná accountable for 21% of the total pork meat production in that year. Pig farming represented 5.7% of the agricultural gross income of the state in 2016, and the Campos Gerais region accounted for 13.2% of that amount (2). Wild boars are the result of crossbreeding between boars (Sus scrofa scrofa) and domestic pigs (Sus scrofa domesticus). The total population of free-living wild boars in Brazil is unknown (11), but sightings are common in the crop fields and near livestock farms of different regions of Paraná state, including in Campos Gerais (9). The health status of pig herds is important in terms of maintenance and growth of pork production and exports and there are evidences that domestic pigs and wild boars share vulnerabilities in certain viral and bacterial pathogen infections (12). Mycoplasma hyopneumoniae (Mhyo) is a bacterial pathogen that causes porcine enzootic pneumonia, an economically important disease that affects both domestic pigs and wild boars. Mhyo was first isolated in 1965, simultaneously in the United Kingdom (UK) and in the United States of America (USA) (3; 7). Economic losses related to this pathogen and mycoplasmal pneumonia in pig herds are associated with decreased feed efficiency, reduced average of the daily weight gain, and increased medication costs. Thus, knowing the health status of free-living wild boars in the regards of this pathogen is important for the biosecurity of the pork production. The aim of this study was to investigate antibodies against Mhyo in serum samples of free-living wild boars in Campos Gerais region

Agroecosystem Performances of Livestock Farms in a Mountain Area of Sicily

Agroecosystem performance indicators (APIs) represent instruments for studying agroecosystem performance via an input/output approach and a knowledge base, with the aim of improving the sustainability level of the farm\u27s activity (Tellarini & Caporali, 2000). This research used APIs to evaluate the influence of stocking rate on the performance (in terms of energy) of farms in a mountainous area of northern Sicily, Italy

Managing Dynamic User Communities in a Grid of Autonomous Resources

One of the fundamental concepts in Grid computing is the creation of Virtual Organizations (VO's): a set of resource consumers and providers that join forces to solve a common problem. Typical examples of Virtual Organizations include collaborations formed around the Large Hadron Collider (LHC) experiments. To date, Grid computing has been applied on a relatively small scale, linking dozens of users to a dozen resources, and management of these VO's was a largely manual operation. With the advance of large collaboration, linking more than 10000 users with a 1000 sites in 150 counties, a comprehensive, automated management system is required. It should be simple enough not to deter users, while at the same time ensuring local site autonomy. The VO Management Service (VOMS), developed by the EU DataGrid and DataTAG projects[1, 2], is a secured system for managing authorization for users and resources in virtual organizations. It extends the existing Grid Security Infrastructure[3] architecture with embedded VO affiliation assertions that can be independently verified by all VO members and resource providers. Within the EU DataGrid project, Grid services for job submission, file- and database access are being equipped with fine- grained authorization systems that take VO membership into account. These also give resource owners the ability to ensure site security and enforce local access policies. This paper will describe the EU DataGrid security architecture, the VO membership service and the local site enforcement mechanisms Local Centre Authorization Service (LCAS), Local Credential Mapping Service(LCMAPS) and the Java Trust and Authorization Manager.Comment: Talk from the 2003 Computing in High Energy and Nuclear Physics (CHEP03), La Jolla, Ca, USA, March 2003, 7 pages, LaTeX, 5 eps figures. PSN TUBT00

Advanced hybrid closed-loop system: first successful clinical case after total pancreatectomy

A 64-year-old woman has undergone in February 2019 total spleen-preserving pancreatectomy for cystic pancreatic neoplasia. In her medical history, in 2010 she also underwent total thyroidectomy because of thyroid cancer. She is a former smoker who quitted smoking in 2014. From February 2019, she assumes pancrelipase 10.000 UI daily as pancreatic replacement therapy and from 2010 levotiroxine for thyroid replacement. At the discharge, insulin therapy with multiple daily injections, supported by advanced educational therapeutic plan about carbohydrates counting, was started, but, after a severe hypoglycemic event, she developed an important fear of hypoglycemia with a consequent wrong approach to the insulin therapy, preferring to maintain glycemic values higher than 200 mg/dL in order to avoid hypoglycemia. Insulin therapy with continuous subcutaneous insulin infusion (CSII) was suggested, but she refused mainly because of discomfort. Yearly mean glycated hemoglobin (HbA1c) was 74 mmol/mol (8.9%). In December 2019, she was admitted to emergency room because of another severe hypoglycemia with loss of consciousness due to inappropriate insulin administration. After this event, patient started real-time continuous glucose monitoring (CGM—Medtronic Guardian Connect, Northridge California)

Gut microbiota and nutrient interactions with skin in psoriasis : a comprehensive review of animal and human studies

The intestinal tract (i.e., the gut), is where the body's nutrients are absorbed, and is simultaneously inhabited by numerous microbes. An increasing body of literature suggests a crucial role for the gut microbiome in modulating systemic inflammatory disease. Psoriasis is a chronic systemic inflammatory disease and its pathogenesis is related to the interaction between genetic susceptibility, immune response and environmental triggers. The omics era has allowed physicians to assess different aspects of psoriasis pathogenesis such as the microbiome, infectome, and autoinfectome. Furthermore, diet appears to play an important role in modulating disease activity, perhaps by influencing gut microbes. Given these observations, we aimed to summarize the current knowledge regarding skin-microbiome-gut-nutrients and psoriasis

Simultaneous Combination of the CDK4/6 Inhibitor Palbociclib With Regorafenib Induces Enhanced Anti-tumor Effects in Hepatocarcinoma Cell Lines

Advanced hepatocarcinoma (HCC) is an aggressive malignancy with poor prognosis and limited treatment options. Alterations of the cyclin D-CDK4/6-Rb pathway occur frequently in HCC, providing the rationale for its targeting at least in a molecular subset of HCC. In a panel of HCC cell lines, we investigated whether the CDK4/6 inhibitor palbociclib might improve the efficacy of regorafenib, a powerful multi-kinase inhibitor approved as second-line treatment for advanced HCC after sorafenib failure and currently under clinical investigation as first-line therapy in combination with immunotherapy. In Rb-proficient cells, the simultaneous drug combination, but not the sequential schedules, inhibited cell proliferation, either in short or in long-term experiments, and induced cell death more strongly than individual treatments. Moreover, the combination significantly reduced spheroid cell growth and inhibited cell migration/invasion. The superior efficacy of palbociclib plus regorafenib emerged also under hypoxia and was associated with a significant down-regulation of CDK4/6-Rb-myc and mTORC1/p70S6K signaling. Moreover, regorafenib suppressed palbociclib-induced expression of cyclin D1 contributing to the cytotoxic effects of the combination. Besides these inhibitory effects on cell viability/proliferation, palbociclib and regorafenib reduced glucose uptake, although this effect was dependent on the cell model and on the oxygen availability (normoxia or hypoxia). Palbociclib and regorafenib combination impaired glucose uptake and utilization, down-regulating basal and hypoxia-induced expression of HIF-1α, HIF-2α, GLUT-1, and MCT4 proteins as well as the activity/expression of glycolytic enzymes (HK2, PFKP, aldolase A, PKM2). In addition, regorafenib alone reduced mitochondrial respiration. The combined treatment impaired glucose metabolism and respiration without enhancing the effects of the single agents. Our findings provide pre-clinical evidence for the effectiveness of palbociclib and regorafenib combination in HCC cell models

Pancreaticoduodenectomy model demonstrates a fundamental role of dysfunctional β cells in predicting diabetes

BACKGROUND. The appearance of hyperglycemia is due to insulin resistance, functional deficits in the secretion of insulin, and a reduction of β cell mass. There is a long-standing debate as to the relative contribution of these factors to clinically manifesting β cell dysfunction. The aim of this study was to verify the acute effect of one of these factors, the reduction of β cell mass, on the subsequent development of hyperglycemia. METHODS. To pursue this aim, nondiabetic patients, scheduled for identical pancreaticoduodenectomy surgery, underwent oral glucose tolerance tests (OGTT) and hyperglycemic clamp (HC) procedures, followed by arginine stimulation before and after surgery. Based on postsurgery OGTT, subjects were divided into 3 groups depending on glucose tolerance: normal glucose tolerance (post-NGT), impaired glucose tolerance (post-IGT), or having diabetes mellitus (post-DM). RESULTS. At baseline, the 3 groups showed similar fasting glucose and insulin levels; however, examining the various parameters, we found that reduced first-phase insulin secretion, reduced glucose sensitivity, and rate sensitivity were predictors of eventual postsurgery development of IGT and diabetes. CONCLUSION. Despite comparable functional mass and fasting glucose and insulin levels at baseline and the very same 50% mass reduction, only reduced first-phase insulin secretion and glucose sensitivity predicted the appearance of hyperglycemia. These functional alterations could be pivotal to the pathogenesis of type 2 diabetes (T2DM)