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Purpose: There is emerging evidence that radiomics analyses can improve detection of skeletal fragility. In this cross-sectional study, we evaluated radiomics features (RFs) on computed tomography (CT) images of the lumbar spine in subjects with or without fragility vertebral fractures (VFs). Methods: Two-hundred-forty consecutive individuals (mean age 60.4 ± 15.4, 130 males) were evaluated by radiomics analyses on opportunistic lumbar spine CT. VFs were diagnosed in 58 subjects by morphometric approach on CT or XR-ray spine (D4-L4) images. DXA measurement of bone mineral density (BMD) was performed on 17 subjects with VFs. Results: Twenty RFs were used to develop the machine learning model reaching 0.839 and 0.789 of AUROC in the train and test datasets, respectively. After correction for age, VFs were significantly associated with RFs obtained from non-fractured vertebrae indicating altered trabecular microarchitecture, such as low-gray level zone emphasis (LGLZE) [odds ratio (OR) 1.675, 95% confidence interval (CI) 1.215–2.310], gray level non-uniformity (GLN) (OR 1.403, 95% CI 1.023–1.924) and neighboring gray-tone difference matrix (NGTDM) contrast (OR 0.692, 95% CI 0.493–0.971). Noteworthy, no significant differences in LGLZE (p= 0.94), GLN (p= 0.40) and NGDTM contrast (p= 0.54) were found between fractured subjects with BMD Tscore < − 2.5 SD and those in whom VFs developed in absence of densitometric diagnosis of osteoporosis. Conclusions: Artificial intelligence-based analyses on spine CT images identified RFs associated with fragility VFs. Future studies are needed to test the predictive value of RFs on opportunistic CT scans in identifying subjects with primary and secondary osteoporosis at high risk of fracture.

A preclinical insert for small animal simultaneous SPECT and MR imaging, in particular for imaging mouse brains, is presented. It consists of ten static magnetic resonance imaging (MRI)-compatible gamma cameras based on tiles of silicon photomultipliers readout by a multichannel ASIC and coupled to 5 cm × 5 cm CsI(Tl) scintillators and to an MRI-compatible multipinhole collimator. Calibration and image reconstruction algorithm are illustrated. Mutual compatibility is demonstrated along with imaging performance that is comparable with other non-MR micro-SPECT systems: 0.9 mm tomographic spatial resolution across a transverse field of view of 15.6 mm, 12% energy resolution (at 140 keV), and 1105 cps/MBq sensitivity. Experimental results with phantoms (glass capillaries of 290 μm diameter and a mini Derenzo) are presented.

The pollutant Cadmium (Cd) is widespread in the environment and causes alterations of human health by acting as an endocrine disruptor. Bone tissue seems to be a crucial target of Cd contamination. Indeed, we have previously demonstrated that this endocrine disruptor induces osteoblast apoptosis and necrosis. Thus, aim of this study was to further evaluate the effect of Cd on osteoblasts homeostasis, investigating potential modification of the Wnt/β-catenin intracellular pathway, the intracellular process involved in programmed cellular death and the cytoskeletal alterations. To this purpose, human osteoblastic Saos-2 cells, a human osteosarcoma osteoblast-like cell line, were cultured and treated with Cd. Osteoblastic cells were treated for 6 h with 10μM Cd, which induced nuclear translocation of β-catenin and increased expression of Wnt/β-catenin target genes. Longer exposure to the same Cd concentration induced osteoblastic cell apoptosis. To better characterize the intracellular events involved in these Cd-induced alterations, we evaluated the effect of Cd exposure on actin filaments and proteins associated to cytoskeletal actin, characterized by the presence of LIM domains. Long (15, 24 h) exposure of osteoblasts to Cd reduced LIM proteins expression and induced actin filaments destruction and a significant caspase-3 activation after 24 h. In addition, to prove that Cd induces osteoblastic cells apoptosis after long exposure, we performed TUNEL assay which demonstrated increase of cell apoptosis after 24 h. In conclusion, our study shows that osteoblasts exposed to Cd for short intervals of time demonstrated an increase in cell proliferation through a Wnt/β-catenin dependent mechanism, likely as a compensatory mechanism in response to cell injury. Longer exposure to the same Cd concentration induced cells apoptosis through cytoskeleton disruption-mediated mechanisms and caspase activation.

Cadmium is a widespread environmental pollutant which induces severe toxic alterations, including osteomalacia and osteoporosis, likely by estrogen receptor-dependent mechanisms. Indeed, cadmium has been described to act as an endocrine disruptor and its toxicity is exerted both in vivoand in vitrothrough induction of apoptosis and/or necrosis by not fully clarified intracellular mechanism(s) of action. Aim of the present study was to further investigate the molecular mechanism by which cadmium might alter homeostasis of estrogen target cells, such as osteoblast homeostasis, inducing cell apoptosis and/or necrosis. Human osteoblastic cells (hFOB 1.19) in culture were used as an in vitromodel to characterize the intracellular mechanisms induced by this heavy metal. Cells were incubated in the presence/absence of 10–50 µM cadmium chloride at different times and DNA fragmentation and activation of procaspases-8 and -3 were induced upon CdCl2treatment triggering apoptotic and necrotic pathways. Addition of caspase-8 and -3 inhibitors (Z-IETD-FMK and Z-DQMD-FMK) partially blocked these effects. No activation of procaspase-9 was observed. To determine the role of mitogen-activated protein kinases (MAPK) in these events, we investigated c-jun N-terminal kinase (JNK), p38 and extracellular signal-regulated protein kinase (ERK1/2) phosphorylation which were activated by 10 µM CdCl2. Chemical inhibitors of JNK, p38, and ERK1/2, SP600125, SB202190, and PD98059, significantly reduced the phosphorylation of the kinases and blunted apoptosis. In contrast, caspase inhibitors did not reduce the cadmium-induced MAPK phosphorylation, suggesting an independent activation of these pathways. In conclusion, at least 2 pathways appear activated by cadmium in osteoblasts: a direct induction of caspase-8 followed by activation of caspase-3 and an indirect induction by phosphorylation of ERK1/2, p38, and JNK MAPK triggering activation of caspase-8 and -3.

ABSTRACTScreening of Greek nontyphoid salmonellae from 2000 to 2002 yielded three extended-spectrum ß-lactamase (ESBL)-producing human isolates. Salmonella entericaserotype Brandenburg harbored a multiresistant SHV-5 gene-carrying plasmid. S. entericaserotype Blockley and S. entericaserotype Hadar harbored a TEM-52 gene-carrying plasmid. An S. entericaserotype Virchow strain producing plasmid-mediated CTX-M-32 was isolated twice from poultry end products. All ESBL plasmids were self-transferable and carried by clones currently common in Greece.

Abstract: We describe two cases of solitary necrotic nodule of the liver, an uncommon nonmalignant lesion that can mimic a metastasis. The nodule appeared hypoechoic, or targetlike, on sonography, hypodense without contrast enhancement on computed tomography, and hypointense on magnetic resonance imaging, including diffusion-weighted images. These features, peculiar when considered together, are explained by the coagulative type of necrosis.

Horse liver phosphopantothenoylcysteine decarboxylase (EC 4.1.1.36) incorporates nonexchangeable tritium from borotritide with a decrease of the activity. Substrate prevents both tritium incorporation and the decrease in activity. Acid and base hydrolysis of the tritiated protein releases labeled lactate identified by highvoltage paper electrophoresis, paper chromatography and silicic acid chromatography. These results indicate the presence of pyruvate covalently bound through an ester linkage to phosphopantothenoylcysteine decarboxylase which is then another example of a mammalian enzyme in which pyruvate is involved in a catalytic activity.

Horse liver phosphopantothenoylcysteine decarboxylase (EC 4.1.1.36) is rapidly inactivated by N‐acetoacetylation with diketene following a pseudo‐first‐order kinetics: the presence of substrate quantitatively protects against this inactivation. Histidine photo‐oxidation with methylene blue or rose bengal brings about the total loss of activity. These results indicate the presence of functional lysyl and histidyl groups at the active site of the enzyme. The substrate sulphydryl group is essential for enzyme activity. Enzymatic decarboxylation is proposed to result from a combined action of the keto group of the enzyme‐bound pyruvate protonated by an essential histidine and a protonated amino group of a lysine.

Biogel P2 gel chromatography of ultrafiltrate from chronic uremic patients leads to better resolution of the compounds present than so far reported in the literature. Reproducibility is good. Toxicity, evaluated by cell cultures, was detected in only one chromatographic fraction. Further purification of this fraction with HPLC on a RP18 column revealed two toxic fractions, to the better defined of which a polyol structure was ascribed.

Summary Holo and apoenzyme of aspartate aminotransferase from beef kidney are 80% inactivated by photoxidation in the presence of 2 × 10-6m tetraiodofluroescein with the modification of two histidine residues per enzyme protomer. At a higher concentration (1 × 10-5m) a tyrosine residue is also modified. The keto substrates, ketoglutarate and oxalacetate, protect the enzyme from photoxidation.

Summary Cytoplasmic aspartate aminotransferase from beef kindney loses 25% of its activity on nitration with tetranitromethane while the apoenzyme about 95%. In the holoenzyme 0.5 tyrosine residue and 1.0 tyrosine residue in the apoenzyme are nitrated per enzyme protomer. In addition 1 cysteine residue per protomer is oxidized in both. The presence of substrates,a-ketoglutarate and glutamate, both at ten times their Km values, does not change these results. Mercaptoethanol does not affect the residual activity of either the nitrated holo or apoenzyme. Dithionite abolishes the activity of the nitrated holoenzyme by reducing the coenzyme moiety. It has no effect on the native holoenzyme or on either the native or nitroapoenzyme.

Horse liver phosphopantothenoylcysteine decarboxylase (EC 4.1.1.36) is rapidly inactivated by N-acetoacetylation with diketene following a pseudo-first-order kinetics: the presence of substrate quantitatively protects against this inactivation. Histidine photo-oxidation with methylene blue or rose bengal brings about the total loss of activity. These results indicate the presence of functional lysyl and histidyl groups at the active site of the enzyme. The substrate sulphydryl group is essential for enzyme activity. Enzymatic decarboxylation is proposed to result from a combined action of the keto group of the enzyme-bound pyruvate protonated by an essential histidine and a protonated amino group of a lysine.

Horse liver phosphopantothenoylcysteine decarboxylase (EC 4.1.1.36) incorporates nonexchangeable tritium from borotritide with a decrease of the activity. Substrate prevents both tritium incorporation and the decrease in activity. Acid and base hydrolysis of the tritiated protein releases labeled lactate identified by highvoltage paper electrophoresis, paper chromatography and silicic acid chromatography. These results indicate the presence of pyruvate covalently bound through an ester linkage to phosphopantothenoylcysteine decarboxylase which is then another example of a mammalian enzyme in which pyruvate is involved in a catalytic activity.