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Abstract Background Killer cell immunoglobulin-like receptors (KIRs) are a family of inhibitory and activatory receptors that are expressed by most natural killer (NK) cells. The KIR gene family is polymorphic: genomic diversity is achieved through differences in gene content and allelic polymorphism. The number of KIR loci has been reported to vary among individuals, resulting in different KIR haplotypes. In this study we report the genotypic structure of KIRs in 217 unrelated healthy Italian individuals from 22 immunogenetics laboratories, located in the northern, central and southern regions of Italy. Methods Two hundred and seventeen DNA samples were studied by a low resolution PCR-SSP kit designed to identify all KIR genes. Results All 17 KIR genes were observed in the population with different frequencies than other Caucasian and non-Caucasian populations; framework genes KIR3DL3, KIR3DP1, KIR2DL4 and KIR3DL2 were present in all individuals. Sixty-five different profiles were found in this Italian population study. Haplotype A remains the most prevalent and genotype 1, with a frequency of 28.5%, is the most commonly observed in the Italian population. Conclusion The Italian Caucasian population shows polymorphism of the KIR gene family like other Caucasian and non-Caucasian populations. Although 64 genotypes have been observed, genotype 1 remains the most frequent as already observed in other populations. Such knowledge of the KIR gene distribution in populations is very useful in the study of associations with diseases and in selection of donors for haploidentical bone marrow transplantation.

Purpose: To present a selected series of extensively occlusive thrombosis of arteriovenous graft treated with the Penumbra's Indigo System., Materials and Methods: Ten patients with acute (within 72 h) extensively occlusive thrombosis of arteriovenous graft (mean extension = 30.1 (range = 15-45) cm) were treated at our institution with the Indigo System. Of the 10 cases, thrombosis was extended to venous outflow in 7 cases and to both arterial inflow and venous outflow in 3 cases., Results: Both anatomic and clinical success were achieved in 8 of the 10 procedures (80.0%). In the 2 cases of technical failure, the patients underwent surgical thrombectomy with the finding of arteriovenous graft exhaustion, which was then replaced. The 6-month primary patency, primary-assisted patency, and secondary patency rates were 37.5% (3/8), 50.0% (4/8), and 62.5% (5/8). We reported 2 complications (one minor and one major adverse event)., Conclusion: Percutaneous mechanical thrombectomy aspiration with Indigo System is a relatively safe and effective procedure and can be used even in extensively thrombosed arteriovenous graft.

Purpose: The aim of this study is to present our personal experience using covered nitinol stent-graft in the treatment of outflow tract stenosis of arteriovenous grafts (AVGs) for hemodialysis access., Materials and Methods: Between May 2015 and October 2017, we retrospectively evaluated 36 (24 males, 12 females; mean age: 65.6 years) patients with AVGs on hemodialysis who underwent percutaneous angioplasty followed by endovascular stent-graft deployment for the treatment of stenosis of the venous outflow of the AVG. Indication for treatment included early restenosis (<3 months after previous percutaneous transluminal angioplasty [PTA]), long stenosis (stenoses >50% extending for a length >5 cm), and recoil of the stenosis after PTA performed with a noncompliant high-pressure balloon. Of 36 patients, 27 (75%) required surgical thrombectomy prior to endovascular procedure. Technical success, clinical success, primary and secondary patency, and safety were evaluated., Results: Technical success was 100%, and clinical success was 94.4%. Primary patency was 94.4%, 72.2%, 63%, 45.9%, and 45.9% at 1, 3, 6, 12, and 18 months (average: 215 days, range: 9-653 days); secondary patency was 94.4% and 86.1% at 1 and 3 months; 80.4% at 6, 12, and 18 months; and 53.6% at 24 months (average: 276.8 days, range: 9-744 days). No deaths were registered., Conclusions: In selected cases, the use of stent-graft represents an effective and safe solution for the treatment of stenotic complications of the venous outflow of AVGs, even in the setting of access thrombosis.

Purpose: To assess the diagnostic performance of diffusion-weighted imaging (DWI) for the discrimination of complete responder (CR) from the non-complete responder (n-CR) in patients with locally advanced rectal cancer (LARC) undergoing chemotherapy and radiation (CRT)., Material and Methods: Between December 2009 and January 2014, 32 patients (33 lesions: one patient had two synchronous lesions) were enrolled in this retrospective study. All patients underwent a pre- and post-CRT conventional MRI study completed with DWI. For both data sets (T2-weighted and DWI), the pre- and post-CRT tumour volume (V T2 ; V DWI ) and the tumour volume reduction ratio (ΔV%) were determined as well as pre- and post-CRT apparent diffusion coefficient (ADC) and ADC change (ΔADC%). Histopathological findings were the standard of reference. Receiver operating characteristic (ROC) curves were generated to compare performance of T2-weighted and DWI volumetry, as well as ADC., Results: The area under the ROC curve (AUC) revealed a good accuracy of pre- and post-CRT values of V T2 (0.86; 0.91) and V DWI (0.82; 1.00) as well as those of ΔV T2 % (0.84) and ΔV DWI % (1.00) for the CR assessment, with no statistical difference. The AUC of pre- and post-CRT ADC (0.53; 0.54) and that of ΔADC% (0.58) were significantly lower., Conclusions: Both post-CRT V DWI and ΔV DWI % (AUC = 1) are very accurate for the assessment of the CR, in spite of no significant differences in comparison to the conventional post-CRT V T2 (AUC = 0.91) and ΔV T2 % (AUC = 0.84). On the contrary, both ADC and ΔADC% values are not reliable., Competing Interests: The authors report no conflict of interest.

Rationale and Objectives: Total kidney volume is an important biomarker for the evaluation of autosomal dominant polycystic kidney disease progression. In this study, we present a novel approach for automated segmentation of polycystic kidneys from non-contrast-enhanced computed tomography (CT) images., Materials and Methods: Non-contrast-enhanced CT images were acquired from 21 patients with a diagnosis of autosomal dominant polycystic kidney disease. Kidney volumes obtained from the fully automated method were compared to volumes obtained by manual segmentation and evaluated using linear regression and Bland-Altman analyses. Dice coefficient was used for performance evaluation., Results: Kidney volumes from the automated method well correlated with the ones obtained by manual segmentation. Bland-Altman analysis showed a low percentage bias (-0.3%) and narrow limits of agreements (11.0%). The overlap between the three-dimensional kidney surfaces obtained with our approach and by manual tracing, expressed in terms of Dice coefficient, showed good agreement (0.91 ± 0.02)., Conclusions: This preliminary study showed the proposed fully automated method for renal volume assessment is feasible, exhibiting how a correct use of biomedical image processing may allow polycystic kidney segmentation also in non-contrast-enhanced CT. Further investigation on a larger dataset is needed to confirm the robustness of the presented approach., (Copyright © 2018 The Association of University Radiologists. Published by Elsevier Inc. All rights reserved.)

We investigated the impact of vitamin D deficiency and repletion on muscle anabolism in old rats. Animals were fed a control (1 IU vitamin D 3 /g, ctrl, n=20) or a vitamin D-depleted diet (VDD; 0 IU, n=30) for 6 months. A subset was thereafter sacrificed in the control (ctrl6) and depleted groups (VDD6). Remaining control animals were kept for 3 additional months on the same diet (ctrl9), while a part of VDD rats continued on a depleted diet (VDD9) and another part was supplemented with vitamin D (5 IU, VDS9). The ctr16 and VDD6 rats and the ctr19, VDD9 and VDS9 rats were 21 and 24 months old, respectively. Vitamin D status, body weight and composition, muscle strength, weight and lipid content were evaluated. Muscle protein synthesis rate (fractional synthesis rate; FSR) and the activation of controlling pathways were measured. VDD reduced plasma 25(OH)-vitamin D, reaching deficiency (<25 nM), while 25(OH)-vitamin D increased to 118 nM in the VDS group (P<.0001). VDD animals gained weight (P<.05) with no corresponding changes in lean mass or muscle strength. Weight gain was associated with an increase in fat mass (+63%, P<.05), intramyocellular lipids (+75%, P<.05) and a trend toward a decreased plantaris weight (-19%, P=.12). Muscle FSR decreased by 40% in the VDD group (P<.001), but was restored by vitamin D supplementation (+70%, P<.0001). Such changes were linked to an over-phosphorylation of eIF2α. In conclusion, vitamin D deficiency in old rats increases adiposity and leads to reduced muscle protein synthesis through activation of eIF2α. These disorders are restored by vitamin D supplementation., (Copyright © 2017 Elsevier Inc. All rights reserved.)

By means of the life cycle assessment methodology, the purpose of this study is to assess the environmental impact when biomethane from organic waste produced at residential level is used to supply energy to a group of dwellings in the distributed generation paradigm. Three different Combined Heat and Power systems, such as fuel cells, Stirling engine and micro gas turbine, installed at household level are assessed in two different settings: one in Northern Europe (UK) and one in Southern Europe (Italy). Different operating strategies are investigated for each technology. Moreover, marginal electricity production technologies are analysed to assess their influence on the results. This study has demonstrated that the type of bio-methane fed micro-CHP technology employed has a significantly different environmental impact: fuel cells are the most environmentally friendly solution in every category analysed; Stirling engines, although can supply heat to the largest number of dwellings are the least environmentally friendly technology. However, key factors investigated in the model presented in this paper influence the decision making on the type of technology adopted and the operating strategy to be implemented., (Copyright © 2017 Elsevier Ltd. All rights reserved.)

Purpose: The aim of our study was to apply the electrical impedance tomography (EIT) technique to the study of ventilation during wake and NREM and REM sleep in patients with obstructive sleep apneas (OSA)., Methods: This is a prospective, observational, monocentric, pilot study in a neurology department with a sleep disorder center. Inclusion criteria were age ≥18 years, both gender, and diagnosis of OSA. Exclusion criteria were the contraindications to the thoracic EIT. All patients underwent laboratory-based polysomnography (PSG) alongside thoracic EIT. Primary endpoint was to compare the global impedance (GI) among the conditions: "Wake" vs "Sleep," "NREM" vs "REM," and "OSA" vs "Non-OSA." Secondary endpoint was to measure the regional distribution of impedance in the four regions of interest (ROIs), in each condition., Results: Of the 17 consecutive patients enrolled, two were excluded because of poor-quality EIT tracings. Fifteen were analyzed, 10 men and 5 women, mean age 51.6 ± 14.4 years. GI was higher in Wake vs Sleep (Wake 13.24 ± 11.23; Sleep 12.56 ± 13.36; p < 0.01), in NREM vs REM (NREM 13.48 ± 13.43; REM 0.59 ± 0.01; p < 0.01), and in Non-OSA vs OSA (Non-OSA 10.50 ± 12.99; OSA 18.98 ± 10.06; p < 0.01). No significant differences were observed in the regional distribution of impedance between Wake and Sleep (χ 2  = 3.66; p = 0.299) and between Non-OSA and OSA (χ 2  = 1.00; p = 0.799); conversely, a significant difference was observed between NREM and REM sleep (χ 2  = 62.94; p < 0.001)., Conclusions: To our knowledge, this is the first study that addresses the issue of regional ventilation in OSA patients during sleep. Thoracic electrical impedance changes through the sleep-wake cycle and during obstructive events. The application of thoracic EIT can prove a valuable additional strategy for the evaluation of OSA patients.

Enriching oils, such as olive oil, could be one solution to tackle the worldwide epidemic of vitamin D deficiency and to better fit with omega 3 (DHA) recommendations. However, data regarding the interactions occurring at the intestinal level between vitamin D and phenols from olive oil are scarce. We first determined the effect of polyphenols from a virgin olive oil, and a virgin olive oil enriched with DHA, on vitamin D absorption in rats. We then investigated the effects of 3 main olive oil phenols (oleuropein, hydroxytyrosol and pinoresinol) on vitamin D uptake by Caco-2 cells. The presence of polyphenols in the olive oil supplemented with DHA inhibited vitamin D postprandial response in rats (-25%, p<0.05). Similar results were obtained with a mix of the 3 polyphenols delivered to Caco-2 cells. However, this inhibitory effect was due to the presence of pinoresinol only. As the pinoresinol content can highly vary between olive oils, the present results should be taken into account to formulate an appropriate oil product enriched in vitamin D., (Copyright © 2016 Elsevier Ltd. All rights reserved.)

Purpose: The aim of this study was to evaluate and compare the musculoskeletal effects induced by ovariectomy-related fat mass deposition against the musculoskeletal effects caused by a high-fat diet., Methods: A group of adult female rats was ovariectomized and fed a control diet. Two additional groups were sham-operated and fed a control or a high-fat diet for 19 weeks. Distal femur and serum bone parameters were measured to assess bone metabolism. Muscle protein metabolism, mitochondrial markers and triglyceride content were evaluated in tibialis anterior. Triglyceride content was evaluated in liver. Circulating inflammatory and metabolic markers were determined., Results: The high-fat diet and ovariectomy led to similar increases in fat mass (+36.6-56.7%; p < 0.05) but had different impacts on bone and muscle tissues and inflammatory markers. Consumption of the high-fat diet led to decreased bone formation (-38.4%; p < 0.05), impaired muscle mitochondrial metabolism, muscle lipotoxicity and a 20.9% increase in tibialis anterior protein synthesis rate (p < 0.05). Ovariectomy was associated with higher bone turnover as bone formation increased +72.7% (p < 0.05) and bone resorption increased +76.4% (p < 0.05), leading to bone loss, a 17.9% decrease in muscle protein synthesis rate (p < 0.05) and liver lipotoxicity., Conclusions: In female rats, high-fat diet and ovariectomy triggered similar gains in fat mass but had different impacts on bone and muscle metabolism. The ovariectomy-induced mechanisms affecting the musculoskeletal system are mainly caused by estrogen depletion, which surpasses the potential-independent effect of adiposity.

In the past, almost all residual municipal waste in the UK was landfilled without treatment. Recent European waste management directives have promoted the uptake of more sustainable treatment technologies, especially for biodegradable waste. Local authorities have started considering other options for dealing with residual waste. In this study, a life cycle assessment of a future 20MWe plant using an advanced two-stage gasification and plasma technology is undertaken. This plant can thermally treat waste feedstocks with different composition and heating value to produce electricity, steam and a vitrified product. The objective of the study is to analyse the environmental impacts of the process when fed with seven different feedstocks (including municipal solid waste, solid refuse fuel, reuse-derived fuel, wood biomass and commercial & industrial waste) and identify the process steps which contribute more to the environmental burden. A scenario analysis on key processes, such as oxygen production technology, metal recovery and the appropriate choice for the secondary market aggregate material, is performed. The influence of accounting for the biogenic carbon content in the waste from the calculations of the global warming potential is also shown. Results show that the treatment of the refuse-derived fuel has the lowest impact in terms of both global warming potential and acidification potential because of its high heating value. For all the other impact categories analysed, the two-stage gasification and plasma process shows a negative impact for all the waste streams considered, mainly due to the avoided burdens associated with the production of electricity from the plant. The plasma convertor, key characteristic of the thermal process investigated, although utilising electricity shows a relatively small contribution to the overall environmental impact of the plant. The results do not significantly vary in the scenario analysis. Accounting for biogenic carbon enhanced the performance of biomass and refuse-derived fuel in terms of global warming potential. The main analysis of this study has been performed from a waste management perspective, using 1ton of waste as functional unit. A comparison of the results when 1kWhe of electricity produced is used as functional unit shows similar trends for the environmental impact categories considered., (Copyright © 2015 Elsevier Ltd. All rights reserved.)

As bones are levers for skeletal muscle to exert forces, both are complementary and essential for locomotion and individual autonomy. In the past decades, the idea of a bone-muscle unit has emerged. Numerous studies have confirmed this hypothesis from in utero to aging works. Space flight, bed rest as well as osteoporosis and sarcopenia experimentations have allowed to accumulate considerable evidence. Mechanical loading is a key mechanism linking both tissues with a central promoting role of physical activity. Moreover, the skeletal muscle secretome accounts various molecules that affect bone including insulin-like growth factor-1 (IGF-1), basic fibroblast growth factor (FGF-2), interleukin-6 (IL-6), IL-15, myostatin, osteoglycin (OGN), FAM5C, Tmem119 and osteoactivin. Even though studies on the potential effects of bone on muscle metabolism are sparse, few osteokines have been identified. Prostaglandin E2 (PGE2) and Wnt3a, which are secreted by osteocytes, osteocalcin (OCN) and IGF-1, which are produced by osteoblasts and sclerostin which is secreted by both cell types, might impact skeletal muscle cells. Cartilage and adipose tissue are also likely to participate to this control loop and should not be set aside. Indeed, chondrocytes are known to secrete Dickkopf-1 (DKK-1) and Indian hedgehog (Ihh) and adipocytes produce leptin, adiponectin and IL-6, which potentially modulate bone and muscle metabolisms. The understanding of this system will enable to define new levers to prevent/treat sarcopenia and osteoporosis at the same time. These strategies might include nutritional interventions and physical exercise., (Copyright © 2015 Elsevier B.V. All rights reserved.)

As the Mediterranean diet (and particularly olive oil) has been associated with bone health, we investigated the impact of extra virgin oil as a source of polyphenols on bone metabolism. In that purpose sham-operated (SH) or ovariectomized (OVX) mice were subjected to refined or virgin olive oil. Two supplementary OVX groups were given either refined or virgin olive oil fortified with vitamin D3, to assess the possible synergistic effects with another liposoluble nutrient. After 30 days of exposure, bone mineral density and gene expression were evaluated. Consistent with previous data, ovariectomy was associated with increased bone turnover and led to impaired bone mass and micro-architecture. The expression of oxidative stress markers were enhanced as well. Virgin olive oil fortified with vitamin D3 prevented such changes in terms of both bone remodeling and bone mineral density. The expression of inflammation and oxidative stress mRNA was also lower in this group. Overall, our data suggest a protective impact of virgin olive oil as a source of polyphenols in addition to vitamin D3 on bone metabolism through improvement of oxidative stress and inflammation.