Differences in telomere length between sporadic and familial cutaneous melanoma

BACKGROUND: Several pieces of evidence indicate that a complex relationship exists between constitutional telomere length (TL) and the risk of cutaneous melanoma. Although the general perception is that longer telomeres increase melanoma risk, some studies do not support this association. We hypothesise that discordant data are due to the characteristics of the studied populations. OBJECTIVES: To evaluate the association of telomere length with familial and sporadic melanoma. METHODS: TL was measured by multiplex quantitative PCR in leukocytes from 310 melanoma patients according to familial/sporadic and single/multiple cancers and 216 age-matched controls. RESULTS: Patients with sporadic melanoma were found to have shorter telomeres as compared to those with familial melanoma. In addition, shorter telomeres, while tending to reduce the risk of familial melanoma regardless of single or multiple tumors, nearly trebled the risk of single sporadic melanoma. CONCLUSIONS: This is the first time that TL has been correlated to opposite effects on melanoma risk according to the presence or absence of familial predisposition. Individual susceptibility to melanoma should be taken into account when assessing the role of TL as a risk factor. This article is protected by copyright. All rights reserved

Luminescent protein staining with Re(i) tetrazolato complexes

Within the general framework of our past and current studies dealing with the investigation of the photophysical properties and the biological behavior of the family of tetrazolato and tetrazole Re(i) complexes, we have endeavored to investigate their potential in the luminescent staining of proteins purified by acrylamide gel electrophoresis. With the aim to provide the first examples of luminescent Re(i) complexes to be exploited for this specific purpose, we have designed and prepared four new Re(i)-based species with the general formula fac-[Re(CO)3(N^N)(Tph)]2-/0, where Tph is the 5-(phenyl)tetrazolato anion and N^N is in turn represented by bathophenanthroline disulfonate (BPS), bathocuproine disulfonate (BCS) or by the SO3-free bathocuproine (BC). In this latter case, the neutral complex fac-[Re(CO)3(BC)(Tph)] served as a model species for the characterization of the former disulfonate complexes. Its cationic analogue fac-[Re(CO)3(BC)(Tph-Me)]+was also prepared by a straightforward methylation reaction. All complexes displayed bright phosphorescence in organic media and, relative to their water solubility, the dianionic species fac-[Re(CO)3(BPS)(Tph)]2-and fac-[Re(CO)3(BCS)(Tph)]2-were also highly emissive in aqueous solution. The sulfonate groups played a key role in promoting and significantly enhancing the luminescent staining performances of both the Re(i) complexes fac-[Re(CO)3(BPS)(Tph)]2-and fac-[Re(CO)3(BCS)(Tph)]2-for proteins. Highlighting a response superior to that of Coomassie Blue and comparable to the one obtained by the well-known silver staining method, these dianionic Re(i)-complexes could efficiently detect up to 50 ng of pure Bovine Serum Albumin (BSA), as well as all proteins found in a Standard Protein Marker mix and from a total protein extract. A lower but still good response for luminescent protein staining was surprisingly obtained by employing the-SO3-free neutral and cationic complexes fac-[Re(CO)3(BC)(Tph)] and fac-[Re(CO)3(BC)(Tph-Me)]+, respectively. These preliminary results open up new possibilities for the further widening of the use of Re(i)-based complexes as luminescent protein staining agents

Comparison of a fast track protocol and standard care after hip arthroplasty in the reduction of the length of stay and the early weight-bearing resumption: study protocol for a randomized controlled trial

Background: To date, hip arthroplasty is one of the most commonly performed surgical procedures, with growing worldwide demand. In recent decades, major progress made in terms of surgical technique, biomechanics, and tribology knowledge has contributed to improve the medical and functional management of the patient. This study aims to assess if the application of a fast track protocol, consisting of a preoperative educational intervention, adequate postoperative pain control, and intensive rehabilitation intervention, reduces the length of stay (LOS) and allows the early functional recovery compared to standard clinical practice for patients undergoing hip arthroplasty. Methods: The study population consists of 90 patients with primary arthrosis of the hip with an anterior indication of hip arthroplasty. The exclusion criteria are older than 70 years, a contraindication to performing spinal anesthesia, and bone mass index (BMI) greater than 32. Participants, 45 for each group, are randomly allocated to one of two arms: fast track clinical pathway or standard care protocol. During allocation, baseline parameters such as Harris Hip Score (HHS) and Western Ontario and McMaster Universities (WOMAC) index are collected. On the third postoperative day, the functional autonomy for each patient is assessed by the Iowa Level of Assistance (ILOA) scale, and it is expected the discharge for patients in the fast track group (primary outcome). On the other hand, standard care patient discharge is expected after 5–7 days after surgery. During follow-up fixed at 6 weeks and 3, 6, and 12 months, HHS and WOMAC scores are collected for each patient (secondary outcomes). Discussion: Although total hip replacement has become a widespread standardized procedure, to the authors’ knowledge, only few randomized controlled trials were performed to evaluate the effectiveness of fast track pathway vs. standard care procedure in the reduction of the LOS after hip arthroplasty. It is expected that our results collected by the application of minimally invasive surgical interventions with concomitant management of perioperative pain and bleeding and early functional rehabilitation will contribute to enriching the understanding of clinical and organizational aspects linked to fast track arthroplasty. Trial registration: ClinicalTrials.gov NCT03875976. Registered on 15 March 2019—“retrospectively registered”

Long-term effect of neonatal inhibition of APP gamma-secretase on hippocampal development in the Ts65Dn mouse model of Down syndrome

Neurogenesis impairment is considered a major determinant of the intellectual disability that characterizes Down syndrome (DS), a genetic condition caused by triplication of chromosome 21. Previous evidence obtained in the Ts65Dn mouse model of DS showed that the triplicated gene APP (amyloid precursor protein) is critically involved in neurogenesis alterations. In particular, excessive levels of AICD (amyloid precursor protein intracellular domain) resulting from APP cleavage by gamma-secretase increase the transcription of Ptch1, a Sonic Hedgehog (Shh) receptor that keeps the mitogenic Shh pathway repressed. Previous evidence showed that neonatal treatment with ELND006, an inhibitor of gamma-secretase, reinstates the Shh pathway and fully restores neurogenesis in Ts65Dn pups. In the framework of potential therapies for DS, it is extremely important to establish whether the positive effects of early intervention are retained after treatment cessation. Therefore, the goal of the current study was to establish whether early treatment with ELND006 leaves an enduring trace in the brain of Ts65Dn mice. Ts65Dn and euploid pups were treated with ELND006 in the postnatal period P3-P15 and the outcome of treatment was examined at ~ one month after treatment cessation. We found that in treated Ts65Dn mice the pool of proliferating cells in the hippocampal dentate gyrus (DG) and total number of granule neurons were still restored as was the number of pre- and postsynaptic terminals in the stratum lucidum of CA3, the site of termination of the mossy fibers from the DG. Accordingly, patch-clamp recording from field CA3 showed functional normalization of the input to CA3. Unlike in field CA3, the number of pre- and postsynaptic terminals in the DG of treated Ts65Dn mice was no longer fully restored. The finding that many of the positive effects of neonatal treatment were retained after treatment cessation provides proof of principle demonstration of the efficacy of early inhibition of gamma-secretase for the improvement of brain development in DS

Fully-resolved simulations of coal particle combustion using a detailed multi-step approach for heterogeneous kinetics

Fully-resolved simulations of the heating, ignition, volatile flame combustion and char conversion of single coal particles in convective gas environments are conducted and compared to experimental data (Molina and Shaddix, 2007). This work extends a previous computational study (Tufano et al., 2016) by adding a significant level of model fidelity and generality, in particular with regard to the particle interior description and hetero- geneous kinetics. The model considers the elemental analysis of the given coal and interpolates its properties by linear superposition of a set of reference coals. The improved model description alleviates previously made assumptions of single-step pyrolysis, fixed volatile composition and simplified particle interior properties, and it allows for the consideration of char conversion. The results show that the burning behavior is affected by the oxygen concentration, i.e. for enhanced oxygen levels ignition occurs in a single step, whereas decreasing the oxygen content leads to a two-stage ignition process. Char conversion becomes dominant once the volatiles have been depleted, but also causes noticeable deviations of temperature, released mass, and overall particle con- version during devolatilization already, indicating an overlap of the two stages of coal conversion which are usually considered to be consecutive. The complex pyrolysis model leads to non-monotonous profiles of the combustion quantities which introduce a minor dependency of the ignition delay time $τ_{ign}$ on its definition. Regardless of the chosen extraction method, the simulations capture the measured values of $τ_{ign}$ very well

Obstructive sleep apneas naturally occur in mice during REM sleep and are highly prevalent in a mouse model of Down syndrome

Study objectives: The use of mouse models in sleep apnea study is limited by the belief that central (CSA) but not obstructive sleep apneas (OSA) occur in rodents. We aimed to develop a protocol to investigate the presence of OSAs in wild-type mice and, then, to apply it to a validated model of Down syndrome (Ts65Dn), a human pathology characterized by a high incidence of OSAs. Methods: In a pilot study, nine C57BL/6J wild-type mice were implanted with electrodes for electroencephalography (EEG), neck electromyography (nEMG), and diaphragmatic activity (DIA), and then placed in a whole-body-plethysmographic (WBP) chamber for 8 h during the rest (light) phase to simultaneously record sleep and breathing activity. CSA and OSA were discriminated on the basis of WBP and DIA signals recorded simultaneously. The same protocol was then applied to 12 Ts65Dn mice and 14 euploid controls. Results: OSAs represented about half of the apneic events recorded during rapid-eye-movement-sleep (REMS) in each experimental group, while the majority of CSAs were found during non-rapid eye movement sleep. Compared with euploid controls, Ts65Dn mice had a similar total occurrence rate of apneic events during sleep, but a significantly higher occurrence rate of OSAs during REMS, and a significantly lower occurrence rate of CSAs during NREMS. Conclusions: Mice physiologically exhibit both CSAs and OSAs. The latter appear almost exclusively during REMS, and are highly prevalent in Ts65Dn. Mice may, thus, represent a useful model to accelerate the understanding of the pathophysiology and genetics of sleep-disordered breathing and to help the development of new therapies

Interim [18F] Fluorodeoxyglucose Positron Emission Tomography (Pet) for Early Metabolic Assessment of Response to Peb Chemotherapy for Metastatic Seminoma: Preliminary Findings

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Digitatio and Scientific Exploitation of the Italian and Vatican Astronomical Plate Archives

There is a widespread interest to digitize the precious information contained in the astronomical plate archives, both for the preservation of their content and for its fast distribution to all interested researchers in order to achieve their better scientific exploitation. This paper presents the first results of our large-scale project to digitize the archive of plates of the Italian Astronomical Observatories and of the Specola Vaticana. Similar systems, composed by commercial flat-bed retro-illuminated scanners plus dedicated personal computers and acquisition and analysis software, have been installed in all participating Institutes. Ad-hoc codes have been developed to acquire the data, to test the suitability of the machines to our scientific needs, and to reduce the digital data in order to extract the astrometric, photometric and spectroscopic content. Two more elements complete the overall project: the provision of high quality BVRI CCD sequences in selected fields with the Campo Imperatore telescopes, and the distribution of the digitized information to all interested researchers via the Web. The methods we have derived in the course of this project have been already applied successfully to plates taken by other Observatories, for instance at Byurakan and at Hamburg.Comment: To appear in Experimental Astronom