Association of a homozygous GCK missense mutation with mild diabetes

Background: Homozygous inactivating GCK mutations have been repeatedly reported to cause severe hyperglycemia, presenting as permanent neonatal diabetes mellitus (PNDM). Conversely, only two cases of GCK homozygous mutations causing mild hyperglycemia have been so far described. We here report a novel GCK mutation (c.1116G>C, p.E372D), in a family with one homozygous member showing mild hyperglycemia. Methods: GCK mutational screening was carried out by Sanger sequencing. Computational analyses to investigate pathogenicity and molecular dynamics (MD) were performed for GCK-E372D and for previously described homozygous mutations associated with mild (n = 2) or severe (n = 1) hyperglycemia, used as references. Results: Of four mildly hyperglycemic family-members, three were heterozygous and one, diagnosed in the adulthood, was homozygous for GCK-E372D. Two nondiabetic family members carried no mutations. Fasting glucose (p = 0.016) and HbA1c (p = 0.035) correlated with the number of mutated alleles (0–2). In-silico predicted pathogenicity was not correlated with the four mutations’ severity. At MD, GCK-E372D conferred protein structure flexibility intermediate between mild and severe GCK mutations. Conclusions: We present the third case of homozygous GCK mutations associated with mild hyperglycemia, rather than PNDM. Our in-silico analyses support previous evidences suggesting that protein stability plays a role in determining clinical severity of GCK mutations

Strontium substituted hydroxyapatite with β-lactam integrin agonists to enhance mesenchymal cells adhesion and to promote bone regeneration

Multi-functionalization of calcium phosphates to get delivery systems of therapeutic agents is gaining increasing relevance for the development of functional biomaterials aimed to solve problems related to disorders of the muscolo-skeletal system. In this regard, we functionalized Strontium substituted hydroxyapatite (SrHA) with some β-lactam integrin agonists to develop materials with enhanced properties in promoting cell adhesion and activation of intracellular signaling as well as in counteracting abnormal bone resorption. For this purpose, we selected two monocyclic β-lactams on the basis of their activities towards specific integrins on promoting cell adhesion and signalling. The amount of β-lactams loaded on SrHA could be modulated on changing the polarity of the loading solution, from 3.5–24 wt% for compound 1 and from 3.2–8.4 wt% for compound 2. Studies on the release of the β-lactams from the functionalized SrHA in aqueous medium showed an initial burst followed by a steady-release that ensures a small but constant amount of the compounds over time. The new composites were fully characterized. Co-culture of human primary mesenchymal stem cells (hMSC) and human primary osteoclast (OC) demonstrated that the presence of β-lactams on SrHA favors hMSC adhesion and viability, as well as differentiation towards osteoblastic lineage. Moreover, the β-lactams were found to enhance the inhibitory role of Strontium on osteoclast viability and differentiation

Multicentre randomised controlled trial comparing standard and high resolution optical technologies in colorectal cancer screening.

Background and objectives: The UK bowel cancer screening programme (BCSP) has been established for the early detection of colorectal cancer offering colonoscopy to patients screened positive by faecal occult blood tests. In this multisite, prospective, randomised controlled trial, we aimed to compare the performance of Standard Definition Olympus Lucera (SD-OL) with Scope Guide and the High Definition Pentax HiLine (HD-PHL). Patients and methods: Subjects undergoing a colonoscopy as part of the UK National BCSP at four UK sites were randomised to an endoscopy list run using either SD-OL or HD-PHL. Primary endpoints were polyp and adenoma detection rate (PDR and ADR, respectively) as well as polyp size, morphology and histology characteristics. Results: 262 subjects (168 males, mean age 66.3±4.3 years) were colonoscoped (133 patients with HD-PHL while 129 with SD-OL). PDR and ADR were comparable within the two optical systems. The HD-PHL group resulted in a PDR 55.6% and ADR 43.6%; the SD-OL group had PDR 56.6% and ADR 45.7%. HD-PHL was significantly superior to SD-OL in detection of flat adenomas (18.6% vs 5.2%, p<0.001), but not detection of pedunculated or sessile polyps. Patient comfort, use of sedation and endoscopist perception of procedural difficulty resulted similar despite the use of Scope Guide with SD-OL. Conclusion: PDR and ADR were not significantly different between devices. The high-resolution colonoscopy system HD-PHL may improve polyp detection as compared with standard resolution technology in detecting flat adenomas. This advantage may have clinically significant implications for missed lesion rates and post-colonoscopy interval colorectal cancer rates

Linguistic markers of processing the first months of the pandemic COVID-19: a psycholinguistic analysis of Italian university students' diaries

A longitudinal psycholinguistic study was conducted with 107 students from different Italian universities that produced daily photo-diary entries for two weeks, one at the beginning and the other at the end of the first Italian lockdown period, imposed in view of the rapid dissemination of COVID -19. The task was to take a daily photo accompanied by a short description (text). The texts accompanying the photos were analysed using Linguistic Inquiry and Word Count (LIWC) software to analyze linguistic markers representing psychological processes related to the experience of the pandemic and the lockdown, identifying potential changes in psycholinguistic variables useful for understanding the psychological impact of such harsh and extended restricted living conditions on Italian students. LIWC categories related to negation, anger, cognitive mechanisms, tentative discourse, past, and future increased statistically significantly between the two time points, while word count, prepositions, communication, leisure, and home decreased statistically significantly. While male participants used more articles at both time points, females used more words related to anxiety, social processes, past, and present at T1 and more related to insight at T2. Participants who lived with their partner showed higher scores on negative emotions, affect, positive feelings, anger, optimism, and certainty. Participants from southern Italy tended to describe their experiences from a collective and social perspective rather than an individual perspective. By identifying, discussing, and comparing these phenomena with the broader literature, a spotlight is shed for the first time on the psycholinguistic analysis of students at the national level who faced the first COVID -19 lockdown in Italy

Contribution of the HMPID detector to the high-pT physics at LHC

The LHC will deliver unexplored energy regimes for proton-proton and heavy-ion collisions. As shown by the RHIC experiments, particle identification over a large momentum range is essential to disentangle physics processes, especially in the intermediate p$_T$ (1 $<p_{T}<5$ GeV/c) region. The novel design of the High-Momentum Particle Identification Detector (HMPID), based on large surface CsI photocathodes, is able to identify $\pi^{\pm}$, $K^{\pm}$, $p$ and $\bar{p}$ in the momentum region where bulk medium properties and hard scatterings interplay. Furthermore, measurement of resonance particles such as the $\phi \to K^+K^-$ could provide information on the system evolution. The HMPID layout and segmentation are optimized to study particle correlations at high momenta describing the early phase and the dynamical evolution of the collision. At LHC, the increased hard cross section will significantly be enhanced compared to RHIC. Jet reconstruction via Deterministic Annealing can address jet quenching and detailed measurements of jet properties. In this paper, we present these selected topics from the possible HMPID contributions to the physics goals of LHC.Comment: 6 pages, 7 figures, Contribution to QCD @ Work 2007: International Workshop on Quantum Chromodynamics Theory and Experiment, Martina Franca, Italy, 16-20 June 200

Prospect for Charge Current Neutrino Interactions Measurements at the CERN-PS

Tensions in several phenomenological models grew with experimental results on neutrino/antineutrino oscillations at Short-Baseline (SBL) and with the recent, carefully recomputed, antineutrino fluxes from nuclear reactors. At a refurbished SBL CERN-PS facility an experiment aimed to address the open issues has been proposed [1], based on the technology of imaging in ultra-pure cryogenic Liquid Argon (LAr). Motivated by this scenario a detailed study of the physics case was performed. We tackled specific physics models and we optimized the neutrino beam through a full simulation. Experimental aspects not fully covered by the LAr detection, i.e. the measurements of the lepton charge on event-by-event basis and their energy over a wide range, were also investigated. Indeed the muon leptons from Charged Current (CC) (anti-)neutrino interactions play an important role in disentangling different phenomenological scenarios provided their charge state is determined. Also, the study of muon appearance/disappearance can benefit of the large statistics of CC muon events from the primary neutrino beam. Results of our study are reported in detail in this proposal. We aim to design, construct and install two Spectrometers at "NEAR" and "FAR" sites of the SBL CERN-PS, compatible with the already proposed LAr detectors. Profiting of the large mass of the two Spectrometers their stand-alone performances have also been exploited.Comment: 70 pages, 38 figures. Proposal submitted to SPS-C, CER

A progress report on the development of the CsI-RICH detector for the ALICE experiment at LHC

The particle identification in ALICE (A Large Ion Collider Experiment) at LHC will be achieved by two complementary systems based on time of flight measurement, at low $p_t$, and on the Ring Imaging Cherenkov (RICH) technique, at $p_t$ ranging from 2 to 5 GeV/$c$, respectively. The High Momentum PID (HMPID) system will cover $\sim$5\% of the phase space, the single arm detector array beeing composed by seven 1.3$\times$1.3 m$^2$ CsI-RICH modules placed at 4.7 m from the interaction point where a density of about 50 particles/m$^2$ is expected.\\ A 1 m$^2$ prototype, 2/3 of HMPID module size, has been successfully tested at the CERN/PS beam where 18 photoelectrons per event have been obtained with 3 GeV/c pions and 10 mm liquid $\mathrm{C}_6\mathrm{F}_{14}$ radiator. Mechanical problems related to the liquid radiator vessel construction have been solved and the prototype, fully equipped, will be tested at the CERN/SPS to investigate the PID capability in high particle density events.\\ In this report, after an introductory discussion on the requirements for PID in ALICE, the HMPID prototype is described and the main results of beam tests on large area CsI photocathodes, operated in RICH detectors, are given