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Hypochondroplasia (HCH) is a rare autosomal dominant skeletal dysplasia condition caused by FGFR3 mutations leading to disproportionate short stature. Classically HCH presents in toddlers or school-age children, as limb-to-trunk disproportion and is often mild and easily overlooked during infancy. We report experiences from a single-center UK HCH-cohort of 31 patients, the rate of antenatal HCH detection in our cohort (13/31, 41.9%) and describe relevant case-data for this subset of 13 patients. Inclusion criteria were patients with confirmed molecular HCH diagnosis (by age 3 years) and presenting with short long-bones or large head size on antenatal ultrasound scan. We then conducted a systematic literature review using PUBMED and MEDLINE, analyzing patients with HCH and related antenatal findings. Antenatally suspected (with subsequent molecular confirmation) HCH has been reported 15 times in the literature (2004-2019). Key markers (consistent in both groups) included reduced; femur length, humeral length and increased; biparietal diameter and head circumference. HCH is increasingly detected both antenatally and in infancy, contrary to previous descriptions. This is likely due to greater HCH awareness, improved imaging, and easier molecular testing. Thus, one should consider HCH outside the classical presenting period. Studying the natural history of younger patients with HCH is important with the advent of several targeted FGFR3 therapies currently in trials for Achondroplasia, that may soon be trialed in HCH.

OBJECTIVE: To document the appearance of artifacts created by commonly encountered surgical conditions and instrumentation on optical coherence tomography (OCT) and to compare these findings with histopathology. STUDY DESIGN: Ex vivo study. ANIMALS: Five canine cadavers. METHODS: Skin, subcutaneous fat, skeletal muscle, and fascia samples were obtained from fresh canine cadavers. Blood pooling, hemostatic crushing, scalpel blade cut, monopolar electrosurgery, bipolar vessel sealing device, and ultrasonic energy surgical artifacts were induced on each tissue type. Each specimen was imaged with OCT and subsequently histologically processed. RESULTS: Most surgical instrumentation used for tumor excision created a high-scattering region with local architectural disruption. Blood pooling was visible as a high-scattering layer overlying tissue with normal architecture. Only the scalpel blade created a focal, low-scattering area representing a sharply demarcated cut within the tissue distinct from the appearance of other instrumentation. CONCLUSION: Common surgical instruments and conditions encountered during tumor excision produced high-scattering OCT artifacts in tissues commonly seen at surgical margins. CLINICAL SIGNIFICANCE: The clinical value of OCT hinges on the ability of personnel to interpret this novel imaging and recognize artifacts. Defining and describing the appearance of common surgical artifacts provides a foundation to create image libraries with known histological and OCT interpretation, ultimately improving the diagnostic accuracy of OCT for assessment of surgical margins.

Approximately 30% of healthy volunteers (HVs) show dilated intercellular spaces in the esophageal epithelium suggesting a functionally reduced epithelial integrity. We aimed to evaluate the presence of an altered epithelial integrity in HVs and whether physiological acid could explain such a difference.Biopsies for Ussing chamber experiments were taken between 3 cm and 5 cm proximal to the gastroesophageal junction. Twenty-four-hour impedance-pH (MII-pH) monitoring was performed in the same 15 HVs. MII-pH tracings from 24 HVs before and after treatment with esomeprazole (40 mg b.i.d., two weeks), a proton pump inhibitor, were analyzed. Reflux parameters and impedance baseline (IB) at different levels of the esophagus were calculated.Epithelial integrity in the distal esophagus presents a large variability in vivo and in vitro (transepithelial electrical resistance 196.9 ± 16.27Ω. cmA subgroup of HVs presents a low epithelial integrity in the distal esophagus probably due to the increased presence of physiological acid reflux. Whether these individuals have a higher chance to develop gastroesophageal reflux disease is unknown. The role of epithelial integrity in symptom perception needs to be further explored.

Consolidation and protection are among the most important treatments usually carried out in conservation of stone artifacts and monuments. In this paper, portable unilateral NMR and conventional techniques were used for investigating new multifunctional treatments based on tetraethoxysilane, silica, and polytetrafluoroethylene nanoparticles. The study was carried out on a very complex and heterogeneous porous stone such as tuff. NMR study allowed to obtain detailed information on the penetration depth of treatments, the hydrophobic effect, and changes in the open porosity caused by treatments. Physical and chemical inhomogeneities between the impregnated layers of tuff and the layers underneath were also detected. The average pores radius and pores interconnection obtained from NMR diffusion measurements were used for the first time to compare effects of different consolidating and/or protective treatments on stone. Because unilateral NMR technique is neither destructive nor invasive, investigation of treatments can be also carried out and optimized directly on buildings and monuments of interest for Cultural Heritage. Copyright © 2014 John Wiley & Sons, Ltd.

Oxidative challenge is an important factor affecting the adaptive strategies of Antarctic fish, but data on antioxidant defenses in these organisms remain scarce. In this context, a key role could be played by acylpeptide hydrolase (APEH), which was recently hypothesized to participate in the degradation of oxidized and cytotoxic proteins, although its physiological function is still not fully clarified. This study represents the first report on piscine members of this enzyme family, specifically from the Antarctic teleost Trematomus bernacchii. The cDNAs corresponding to two apeh genes were isolated, and the respective proteins were functionally and structurally characterized with the aim of understanding the biological significance of these proteases in Antarctic fish. Both APEH isoforms (APEH-1Tb and APEH-2Tb ) showed distinct temperature-kinetic behavior, with significant differences in the Km values. Moreover, beside the typical acylpeptide hydrolase activity, APEH-2Tb showed remarkable oxidized protein endohydrolase activity towards oxidized BSA, suggesting that this isoform could play a homeostatic role in removing oxidatively damaged proteins, sustaining the antioxidant defense systems. The 3D structures of both APEHs were predicted, and a possible relationship was found between the substrate specificity/affinity and the marked changes in the number of charged residues and hydrophobicity properties surrounding their catalytic sites. Our results demonstrated the occurrence of two APEH isoforms in T. bernacchii, belonging to different phylogenetic clusters, identified for the first time, and showing distinct molecular and temperature-kinetic behaviors. In addition, we suggest that the members of the new cluster 'APEH-2' could participate in reactive oxygen species detoxification as phase 3 antioxidant enzymes, enhancing the protein degradation machinery.

Scattone A, Serio G, Marzullo A, Nazzaro P, Corsi F, Cocca M P, Mattoni M, Punzi A, Gentile M, Buonadonna A L & Pennella A (2012) Histopathology60, 472–481 High Wilms’ tumour gene (WT1) expression and low mitotic count are independent predictors of survival in diffuse peritoneal mesothelioma Aims: To evaluate the use of the Wilms’ tumour gene (WT1) marker and histomorphological parameters as indicators of prognosis in malignant peritoneal mesothelioma (MPM). Methods and results: Histological samples of 31 MPM were stained immunohistochemically for the WT1 protein. The results were quantified by recording the number of stained nuclei, and then correlated with patient survival. Statistical correlation was evaluated for tumour histotype, mitotic count (MC), nuclear grade (NG), necrosis, lymphoid response (grade of inflammation) and desmoplasia with regard to survival. High-grade histology (solid epithelioid, pure sarcomatoid or biphasic tumours), high NG, MC more than five per 10 per high-power field (HPF), necrosis and desmoplasia were associated with a significantly worse prognosis. Patients with MPM with low WT1 expression (≤25% of positive cells) survived for a significantly shorter time compared to those with high WT1 expression (>25% of positive cells) (P = 0.0001). The 50% survival time of subjects with low WT1 expression was 2.9 months [95% confidence interval (CI): 2.05–3.71] versus 31.5 months (95% CI: 20.4–42.5) for those with high WT1 expression. On multivariate analysis, WT1 and MC were found to be associated independently with survival (P = 0.002; P = 0.005, respectively). Conclusions: Our study suggests that low WT1 expression and high MC may be indicative of an unfavourable prognosis in patients with advanced malignant peritoneal mesothelioma.

We report the synthesis and characterization of two new meso-ferrocenylporphyrins, with the ferrocenyl unit attached at the para position of a C6F4 group by a CN bond with NH(CH2)2NH (2a) and NH(CH2)4NH (2b) spacers. Compounds 2a and 2b were characterized through elemental analyses, electrospray ionization high-resolution mass spectrometry, 1H NMR, UV–visible and fluorescence spectroscopies, electrochemistry and spectroelectrochemistry. The free base porphyrin 2 was included for comparison purposes. The binding ability of 2 and the porphyrin derivatives 2a and 2b with calf thymus DNA was determined using UV–visible and fluorescence spectroscopies. The results suggest that the interaction of these systems most probably occurs through π-stacking by non-classical modes involving the partial insertion of the C6F5 ring between adjacent base pairs on DNA and possible hydrogen interaction with the aliphatic NH(CH2)nNH (n = 2 or 4) groups with calf thymus DNA. Moreover, we also demonstrate that porphyrins generate singlet oxygen species and show good photostability after irradiation.

Anaplastic large cell lymphoma (ALCL) is characterized by preferential paracortical and intrasinusoidal lymph node involvement by large anaplastic tumor cells expressing the CD30 antigen. Up to 80% of pediatric patients with ALCL can be cured with multi-agent chemotherapeutic regimens. Patients resistant to chemotherapy or suffering from early relapse have a poor prognosis and a poor chance of survival. In these cases, the highly aggressive clinical course of ALCL, associated with systemic symptoms and extranodal involvement, has been treated with different approaches in various cooperative trials, including conventional chemotherapy and human stem cell transplantation (HSCT). However, the optimal treatment has not yet been defined, in particular in cases of relapse. More recently, radioimmunotherapy has been studied with encouraging results in cancer patients, including non-Hodgkin's lymphoma. Here we describe the case of a pediatric ALCL, relapsing after HSCT, treated with pretargeted antibody-guided radioimmunotherapy, obtaining a complete remission, with excellent quality of life over the past 10 months.

Background Elevated liver enzymes are associated with cardiovascular disease, while their relationship with cancer-related mortality has not been assessed so far in diabetic patients. Methods An observational cohort study was performed on a consecutive series of 1952 type 2 diabetic patients. The association of liver enzymes with all-cause and cause-specific mortality was assessed. Information on all-cause mortality was obtained by the City of Florence Registry Office. Results The average duration of follow-up was 6.4 ± 2.7 years. Over that period, 362 deaths were recorded (26.9%), with a yearly mortality rate of 4.2%. Age- and sex-adjusted HR of all-cause mortality for gamma glutamyl-transpeptidase (γ-GT) γ-GT > 40 U/l was 1.610 [1.245–2.082]. An increased cardiovascular mortality rate was observed in patients with elevation of γ-GT, and γ-GT and/or alanine aminotransferase (ALT), when compared with the rest of the sample (15.3 vs 10.8%, p < 0.05; and 15.2 vs 10.7%, p < 0.05, respectively). Similar results were observed when considering cancer-related mortality. The association of higher γ-GT levels with all-cause, cardiovascular, and cancer-related mortality was confirmed at a multivariate analysis after adjustment for potential confounders. Conclusions The present study shows that, in type 2 diabetic patients, higher γ-GT, but not ALT, is associated with increased mortality for cardiovascular disease and malignancies. Copyright © 2007 John Wiley & Sons, Ltd.

two different diisocyanates were investigated as co-monomers for in situ polymerisation of poly(urethane-urea) into Neapolitan yellow tuff for conservation and restoration purpose. The obtained copolymers were characterised by means of FTIR spectroscopy, whereas the protective and consolidating efficiency of the performed treatments was evaluated through water capillary absorption, water vapour permeability and abrasion resistance measurements. The distribution and the penetration depth of the synthesized copolymer were also analysed applying micro-FTIR. The morphology of treated tuff was investigated by SEM. It was shown that comparatively higher protective and consolidating properties are achieved by using 1,6-diisocyanatohexane as monomer for in situ polymerisation.

The blood of Channichthyidae, the most phyletically derived notothenioid family, is devoid of haemoglobin (Hb). Three of the 15 channichthyid species retain inactive genomic remnants of the major adult notothenioid a-globin gene, but have lost the gene encoding adult β-globin. In an attempt to understand the mutational events leading to loss of globin expression in channichthyds, the organisation of globin genes in red-blooded notothenioid species was examined. Globin genes in fish are often organised as alβ pairs linked in 5' to 5' orientation, and the major adult α- and β-globins of the Antarctic yellowbelly rockcod Notothenia coriiceps have this organisation. A second globin gene cluster from N. coriiceps contains two sets of linked α- and β-globin genes but the deduced amino acid sequences of the globins differ from those of the adult globins. To test the hypothesis that the globins may be expressed at different stages of ontogenesis. total RNA from head kidney and erythrocytes of adult and juvenile N. coriiceps were probed for transcripts corresponding to the four globin genes. The data suggest that the globin genes of this cluster are transcribed maximally in the early phase of development. Southern analysis of the genomes of red- and white-blooded notothenioids revealed that the genes of this complex are absent in Hb-less icefish.

Isothermal and non-isothermal crystallization kinetics of poly(l-lactic acid)/poly(butylene terephthalate) (PLLA/PBT) blends containing PLLA as major component is detailed in this contribution. PLLA and PBT are not miscible, but compatibility of the polymer pair is ensured by interactions between the functional groups of the two polyesters, established upon melt mixing. Crystal polymorphism of the two polyesters is not influenced by blending, as probed by wide-angle X-ray analysis. The addition of PLLA does not affect the temperature range of crystallization kinetics of PBT, nor the crystallinity level attained when the blends are cooled from the melt at constant rate. Conversely, PBT favors crystallization of the biodegradable polyester. The addition of PBT results in an anticipated onset of crystallization of PLLA during cooling at a fixed rate, with a sizeable enhancement of the crystal fraction. Isothermal crystallization analysis confirmed the faster crystallization rate of PLLA in the presence of PBT. © 2014 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2014, 131, 40372.