New insight into the genomic structure of dog T cell receptor beta (TRB) locus inferred from expression analysis

Here is an updated report on the genomic organization of T cell receptor beta (TRB) locus in the domestic dog (Canis lupus familiaris) as inferred from comparative genomics and expression analysis. The most interesting results we found were a second TRBD–J–C cluster, which is absent from the reference genome sequence, and the annotation of two additional TRBV genes. In dogs, TRB locus consists of a library of 37 TRBV genes positioned at the 50 end of two in tandem aligned D–J–C gene clusters, each composed of a single TRBD, 6 TRBJ and one TRBC genes, followed by a single TRBV gene with an inverted transcriptional orientation. The TRB genes are distributed in less than 300 kb, making the canine locus, one of the smaller mammalian TRB locus studied so far. The small size may be ascribed to reduced gene duplication occurrences and a lower density of total interspersed repeats compared to humans and mice. Despite the low TRBV gene content, a large and diversified beta chain repertoire is displayed in the dog peripheral blood. A full usage of TRBV and TRBJ genes, including pseudogenes, and a high level of allelic polymorphism contribute to generate diversity. Finally, this study suggests that the overall TRB locus organization is evolutionarily conserved supporting the dog as a highly suited model system for immune development and diseases

NIGER-DELTA: ENVIRONMENT, OGONI CRISIS AND THE STATE

Among the well agreed-on benefits of a guideline computerisation, with respect to the traditional text format, there are the disambiguation, the possibility of looking at the guideline at different levels of detail and the possibility of generating patient-tailored suggestions. Nevertheless, the connection of guidelines with patient records is still a challenging problem, as well as their effective integration into the clinical workflow. In this paper, we describe the evolution of our environment for representing and running guidelines. The main new features concern the choice of a commercial product as the middle layer with the electronic patient record, the consequent possibility of gathering information from different legacy systems, and the extension of this "virtual medical record" to the storage of process data. This last feature allows managing exceptions, i.e. decisions that do not comply with guidelines

Nabilone for the treatment of medication overuse headache: results of a preliminary double-blind, active-controlled, randomized trial.

Medication overuse headache (MOH) is a severe burden to sufferers and its treatment has few evidence-based indications. The aim of this study is to evaluate efficacy and safety of nabilone in reducing pain and frequency of headache, the number of analgesic intake and in increasing the quality of life on patients with long-standing intractable MOH. Thirty MOH patients were enrolled at the University of Modena's Interdepartmental Centre for Research on Headache and Drug Abuse (Italy) in a randomized, double-blind, active-controlled, crossover study comparing nabilone 0.5 mg/day and ibuprofen 400 mg. The patients received each treatment orally for 8 weeks (before nabilone and then ibuprofen or vice versa), with 1 week wash-out between them. Randomization and allocation (ratio 1:1) were carried out by an independent pharmacy through a central computer system. Participants, care givers, and those assessing the outcomes were blinded to treatment sequence. Twenty-six subjects completed the study. Improvements from baseline were observed with both treatments. However, nabilone was more effective than ibuprofen in reducing pain intensity and daily analgesic intake (p < 0.05); moreover, nabilone was the only drug able to reduce the level of medication dependence (-41 %, p < 0.01) and to improve the quality of life (p < 0.05). Side effects were uncommon, mild and disappeared when nabilone was discontinued. This is the first randomized controlled trial demonstrating the benefits of nabilone on headache, analgesic consumption and the quality of life in patients with intractable MOH. This drug also appears to be safe and well-tolerated. Larger scale studies are needed to confirm these preliminary finding

Detecting Recent Dynamics in Large-Scale Landslides via the Digital Image Correlation of Airborne Optic and LiDAR Datasets: Test Sites in South Tyrol (Italy)

Large-scale slow-moving deep-seated landslides are complex and potentially highly damaging phenomena. The detection of their dynamics in terms of displacement rate distribution is therefore a key point to achieve a better understanding of their behavior and support risk management. Due to their large dimensions, ranging from 1.5 to almost 4 km(2), in situ monitoring is generally integrated using satellite and airborne remote sensing techniques. In the framework of the EFRE-FESR SoLoMon project, three test-sites located in the Autonomous Province of Bolzano (Italy) were selected for testing the possibility of retrieving significant slope displacement data from the analysis of multi-temporal airborne optic and light detection and ranging (LiDAR) surveys with digital image correlation (DIC) algorithms such as normalized cross-correlation (NCC) and phase correlation (PC). The test-sites were selected for a number of reasons: they are relevant in terms of hazard and risk; they are representative of different type of slope movements (earth-slides, deep seated gravitational slope Deformation and rockslides), and different rates of displacement (from few cm/years to some m/years); and they have been mapped and monitored with ground-based systems for many years (DIC results can be validated both qualitatively and quantitatively). Specifically, NCC and PC algorithms were applied to high-resolution (5 to 25 cm/px) airborne optic and LiDAR-derived datasets (such as hillshade and slope maps computed from digital terrain models) acquired during the 2019-2021 period. Qualitative and quantitative validation was performed based on periodic GNSS surveys as well as on manual homologous point tracking. The displacement maps highlight that both DIC algorithms succeed in identifying and quantifying slope movements of multi-pixel magnitude in non-densely vegetated areas, while they struggle to quantify displacement patterns in areas characterized by movements of sub-pixel magnitude, especially if densely vegetated. Nonetheless, in all three landslides, they proved to be able to differentiate stable and active parts at the slope scale, thus representing a useful integration of punctual ground-based monitoring systems

MICROPILES TRIPODS SHIELDS (MTS) AS UNCONVENTIONAL BREAKERS FOR THE CONTROL OF MODERATELY RAPID EARTHFLOWS (SASSI NERI LANDSLIDE, NORTHERN APENNINES)

The paper deals with the idea, design and implementation of unconventional one-of-a-kind Micropiles Tripods Shields (MTS) intended to break and decelerate moderately rapid earthflows surges in the track zone of the Sassi Neri landslide (Nure Valley, Northern Apennines, Province of Piacenza, Italy). The MTS are inspired to floating anchors and “chevaux de fries” used in wartime. The basic elements are tripods of 193 mm diameter steel micropiles laid out at triangle, driven into the stable bedrock and emerging some meters aboveground. Each tripod consists of a vertical upslope central pile and two lateral oblique piles, linked by two transversal beams and connection plates aboveground. Multiple tripods are spaced along transversal rows to form Micropiles Tripods Shields (MTS) to advancing earthflows. The design of MTS has been based on field investigations such as boreholes and geophysics, that indicated a limited thickness of landslide deposits in the track zone where MTS have been installed. The forces resulting from active earthflows fronts have been estimated both with geotechnical and hydraulic computations. The analysis of vertical and transversal forces as well as bending moments acting on a single tripod versus the characteristic resistances was carried out using a bi-dimensional scheme with finite-elements software Plaxis, that indicated that the stress levels were compatible with the structural resistance of the tripods. The construction of MTS took place in 2018, involving working site preparation with partial lime-treatment of the surficial layers, underground micropiles drilling and installation, aboveground micropiles welding, tripods completion with connection beams and plates. Some tripods have been instrumented with load cells for monitoring earth pressures against micropiles, electric transducers for groundwater monitoring next to the piles, tiltmeters for tripods rotations and a total station for slope and tripods movements monitoring. Results show that the acceleration of slope movements corresponds to a generalized increase of pore water pressure at all the monitored tripods and to temporary slight tilting of the tripods which has so far being fully recovered when the landside slowed down and pressure decreased. This pioneering application indicates that once the characteristics of the earthflows are carefully considered, the depth to the bedrock in the installation zone is limited, and the logistical conditions in the field during construction are adequate, the MTS can be taken into consideration as a possible unconventional solution to break down and control moderately rapid earthflow

Evolution of the T-cell receptor (TR) Loci in the adaptive immune response: The tale of the TRG locus in mammals

T lymphocytes are the principal actors of vertebrates’ cell-mediated immunity. Like B cells, they can recognize an unlimited number of foreign molecules through their antigen-specific heterodimer receptors (TRs), which consist of αβ or γδ chains. The diversity of the TRs is mainly due to the unique organization of the genes encoding the α, β, γ, and δ chains. For each chain, multi-gene families are arranged in a TR locus, and their expression is guaranteed by the somatic recombination process. A great plasticity of the gene organization within the TR loci exists among species. Marked structural differences affect the TR γ (TRG) locus. The recent sequencing of multiple whole genome provides an opportunity to examine the TR gene repertoire in a systematic and consistent fashion. In this review, we report the most recent findings on the genomic organization of TRG loci in mammalian species in order to show differences and similarities. The comparison revealed remarkable diversification of both the genomic organization and gene repertoire across species, but also unexpected evolutionary conservation, which highlights the important role of the T cells in the immune response

Inside the 2016 American Society of Clinical Oncology Genitourinary Cancers Symposium: Part 1 - Kidney cancer

The American Society of Clinical Oncology Genitourinary Cancers Symposium, Moscone West Building, San Francisco, CA, USA, 7-9 January 2016 The American Society of Clinical Oncology (ASCO) Genitourinary Cancers Symposium, held in San Francisco (CA, USA), from 7 to 9 January 2016, focused on 'patient-centric care: translating research to results'. Every year, this meeting is a must for anyone studying genitourinary tumors to keep abreast of the most recent innovations in this field, exchange views on behaviors customarily adopted in daily clinical practice, and discuss future topics of scientific research. This two-part report highlights the key themes presented at the 2016 ASCO Genitourinary Cancers Symposium, with part 1 reporting the main novelties of kidney cancer and part 2 discussing the most relevant issues which have emerged for bladder and prostate tumors

SAT0461 SHORT-TERM MONITORING OF DENOSUMAB EFFECT IN BREAST CANCER PATIENTS RECEIVING AROMATASE INHIBITORS USING REMS TECHNOLOGY ON LUMBAR SPINE

Background:Aromatase inhibitor (AI) therapy in women with estrogen receptor-positive (ER+) breast cancer (BC) causes accelerated bone loss and increased risk of osteoporosis and fractures as side effects. Denosumab (i.e. 60 mg twice a year) is a viable therapy against bone resorption, but the short-term monitoring of bone mineral density (BMD) change with time is still an unmet clinical need, since the current techniques (including dual-energy X-ray absorptiometry, DXA) require 1-2 years between two consecutive measurements [1]. Radiofrequency Echographic Multi Spectrometry (REMS), with high performance in terms of precision and repeatability [2], might be used in this setting of patients for short-term monitoring of bone health-related parameters.Objectives:The objective is the short-term monitoring of the effect of AIs with/without denosumab on bone health in BC patients using REMS and DXA scans at lumbar spine.Methods:Post-menopausal ER+ BC patients treated with adjuvant AIs were recruited. Two subgroups were identified, whether receiving also 60 mg of denosumab therapy every 6 months or not (named Group A and Group B, respectively). All patients underwent baseline DXA and REMS lumbar spine scans at time T0, previous to the first AI therapy, and after 12 months (time T1). REMS scan only was repeated also at 18 months (T2), since a 6-month interval between two consecutive scans is not recommended for DXA. The bone mineral density (BMD) was measured with both techniques.Results:Overall, 254 ER+ BC patients were enrolled (127 per group). The effect of denosumab on BMD is reported in Table. The BMD values obtained by DXA and REMS were not significantly different at T0 and T1, whereas the difference between Group A and B at T1 was statistically significant (p<0.001) both for REMS and DXA. At T2, REMS confirmed the increasing trend of BMD for Group A and the decreasing one for Group B, and the difference between groups was statistically significant (p<0.001). For each time point and each group, there were not statistically significant differences between DXA and REMS.Conclusion:Several studies have shown the effect of denosumab on BMD over a period not less than 2 years from the start of treatment. This study showed the feasibility of short-term follow-up using REMS lumbar spine scans at 6-month time steps.References:[1]Diez-Perez A et al, Aging Clin Exp Res 2019;31(10):1375–89[2]Di Paola M et al, Osteoporos Int 2018;30:391–402Table 1.BMD values, expressed as g/cm2, measured by DXA and REMS for Group A (patients receiving AIs only) and Group B (patients receiving AIs and denosumab) at baseline (T0), 12 months (T1) and 18 months (T2) from the start of therapy. Results are presented as median values with 25thand 75thpercentiles. P-values are obtained with a Mann-Whitney test.DXAREMSScan timeGroup AGroup BpGroup AGroup BpT00.840 (0.719-0.959)0.867 (0.723-0.958)0.990.833 (0.708-0.949)0.855 (0.714-0.973)0.77T10.823 (0.702-0.944)0.889 (0.749-0.990)0.0030.819 (0.691-0.927)0.887 (0.740-1.018)<0.001T2---0.801 (0.679-0.909)0.899 (0.754-1.020)<0.001Note:The authorsD. Ciardo, M. Ciccarese, F. Conversano, M. Di Paola, R. Forcignanò, A. Grimaldi, F.A. Lombardi, M. Muratore and P. Pisaniare listed in alphabetical orderDisclosure of Interests:None declare

Multiparametric magnetic resonance imaging for the differential diagnosis between granulomatous prostatitis and prostate cancer: a literature review to an intriguing diagnostic challenge

Multiparametric magnetic resonance imaging (mpMRI) is currently the most effective diagnostic tool for detecting prostate cancer (PCa) and evaluating adenocarcinoma-mimicking lesions of the prostate gland, among which granulomatous prostatitis (GP) represents the most interesting diagnostic challenge. GP consists of a heterogeneous group of chronic inflammatory lesions that can be differentiated into four types: idiopathic, infective, iatrogenic, and associated with systemic granulomatous disease. The incidence of GP is growing due to the increase in endourological surgical interventions and the adoption of intravesical instillation of Bacillus Calmette-Guerin in patients with non-muscle invasive bladder cancer; therefore, the difficulty lies in identifying specific features of GP on mpMRI to avoid the use of transrectal prostate biopsy as much as possible