ITA-MNGIE: an Italian regional and national survey for mitochondrial neuro-gastro-intestinal encephalomyopathy

Mitochondrial neuro-gastro-intestinal encephalomyopathy (MNGIE) is a rare and unavoidably fatal disease due to mutations in thymidine phosphorylase (TP). Clinically it is characterized by gastrointestinal dysfunction, malnutrition/cachexia and neurological manifestations. MNGIE diagnosis remains a challenge mainly because of the complexity and rarity of the disease. Thus, our purposes were to promote a better knowledge of the disease in Emilia-Romagna region (ERR) by creating an accurate and dedicated network; to establish the minimal prevalence of MNGIE in Italy starting from ERR. Blood TP activity level was used as screening test to direct candidates to complete diagnostic work-up. During the study period of 1 year, only 10/71 units of ERR recruited 14 candidates. Their screening did not show TP activity changes. An Italian patient not resident in ERR was actually proved to have MNGIE. At the end of study in Italy there were nine cases of MNGIE; thus, the Italian prevalence of the disease is ~0.15/1,000,000 as a gross estimation. Our study confirms that MNGIE diagnosis is a difficult process which reflects the rarity of the disease and, as a result, a low level of awareness among specialists and physicians. Having available novel therapeutic options (e.g., allogenic hematopoietic stem cell transplantation and, more recently, liver transplantation) and an easy screening test, an early diagnosis should be sought before tissue damage occurs irreversibly

Real-world effectiveness and persistence of golimumab as second-line anti-TNFα drug in rheumatoid arthritis, psoriatic arthritis, and axial spondyloarthritis patients in Italy: GO-BEYOND, a 12-month prospective observational study

A high proportion of patients may fail a first-line anti-TNF drug, necessitating the switch to another anti-TNF treatment. After 12 months of GLM treatment, 80% of RA patients achieved low disease activity (LDA), 37.1% with PsA achieved minimal disease activity and 55.3% with axSpA achieved LDA while persistence at 12 months in all patients was 77.7%. In this 1-year analysis of the GO-BEYOND study in Italy, GLM had a favorable benefit: risk profile and high retention rate in patients with PsA, RA and axSpA

Performance of the CMS Cathode Strip Chambers with Cosmic Rays

The Cathode Strip Chambers (CSCs) constitute the primary muon tracking device in the CMS endcaps. Their performance has been evaluated using data taken during a cosmic ray run in fall 2008. Measured noise levels are low, with the number of noisy channels well below 1%. Coordinate resolution was measured for all types of chambers, and fall in the range 47 microns to 243 microns. The efficiencies for local charged track triggers, for hit and for segments reconstruction were measured, and are above 99%. The timing resolution per layer is approximately 5 ns

Neutralising antibodies after COVID-19 vaccination in UK haemodialysis patients

Vaccination against COVID-19 induces highly protective immune responses in most people. As some countries switch from suppression to acceptance of transmission of SARS-CoV-2 within a largely vaccinated adult population, vulnerable patient groups that have not mounted adequate immune responses to vaccination might experience significant morbidity and mortality. There is an urgent need to identify such patient groups and to optimise medical advice and vaccination strategies for them

Measurement of the D+ and Ds+ decays into K+K-K+

We present the first clear observation of the doubly Cabibbo suppressed decay D+ --> K-K+K+ and the first observation of the singly Cabibbo suppressed decay Ds+ --> K-K+K+. These signals have been obtained by analyzing the high statistics sample of photoproduced charm particles of the FOCUS(E831) experiment at Fermilab. We measure the following relative branching ratios: Gamma(D+ --> K-K+K+)/Gamma(D+ --> K-pi+pi+) = (9.49 +/- 2.17(statistical) +/- 0.22(systematic))x10^-4 and Gamma(Ds+ --> K-K+K+)/Gamma(Ds+ --> K-K+pi+) = (8.95 +/- 2.12(statistical) +2.24(syst.) -2.31(syst.))x10^-3

Measurement of the Ωc0\Omega_c^0 Lifetime

The FOCUS experiment(FNAL-E831) has used two channels, $\Omega^- \pi^+$ and $\Xi^-K^- \pi^+ \pi^+$,to measure the lifetime of the $\Omega_c^0$ charmed baryon. From a sample of $64 \pm 14$ signal events at a mass of 2.698 GeV/$c^2$, we measure an $\Omega_c^0$ lifetime of $72 \pm 11$ (stat.) $\pm 11$ (sys.) fs, substantially improving upon the current world average.Comment: 12 pages and 5 figure

Contribution of Cerebellar Sensorimotor Adaptation to Hippocampal Spatial Memory

Complementing its primary role in motor control, cerebellar learning has also a bottom-up influence on cognitive functions, where high-level representations build up from elementary sensorimotor memories. In this paper we examine the cerebellar contribution to both procedural and declarative components of spatial cognition. To do so, we model a functional interplay between the cerebellum and the hippocampal formation during goal-oriented navigation. We reinterpret and complete existing genetic behavioural observations by means of quantitative accounts that cross-link synaptic plasticity mechanisms, single cell and population coding properties, and behavioural responses. In contrast to earlier hypotheses positing only a purely procedural impact of cerebellar adaptation deficits, our results suggest a cerebellar involvement in high-level aspects of behaviour. In particular, we propose that cerebellar learning mechanisms may influence hippocampal place fields, by contributing to the path integration process. Our simulations predict differences in place-cell discharge properties between normal mice and L7-PKCI mutant mice lacking long-term depression at cerebellar parallel fibre-Purkinje cell synapses. On the behavioural level, these results suggest that, by influencing the accuracy of hippocampal spatial codes, cerebellar deficits may impact the exploration-exploitation balance during spatial navigation

Mitochondrial Neurogastrointestinal Encephalomyopathy (MNGIE): Position Paper on Diagnosis, Prognosis and Treatment by the MNGIE International Network

Mitochondrial Neurogastrointestinal Encephalomyopathy (MNGIE) is a rare autosomal recessive disease caused by TYMP mutations and thymidine phosphorylase (TP) deficiency. Thymidine and deoxyuridine accumulate impairing the mitochondrial DNA maintenance and integrity. Clinically, patients show severe and progressive gastrointestinal and neurological manifestations. The onset typically occurs in the second decade of life and mean age at death is 37 years. Signs and symptoms of MNGIE are heterogeneous and confirmatory diagnostic tests are not routinely performed by most laboratories, accounting for common misdiagnosis. Factors predictive of progression and appropriate tests for monitoring are still undefined. Several treatment options showed promising results in restoring the biochemical imbalance of MNGIE. The lack of controlled studies with appropriate follow‐up accounts for the limited evidence informing diagnostic and therapeutic choices. The International Consensus Conference (ICC) on MNGIE, held in Bologna, Italy, on March 30th‐31st, 2019, aimed at an evidence‐based consensus on diagnosis, prognosis and treatment of MNGIE among experts, patients, caregivers and other stakeholders involved in caring the condition. The conference was conducted according to the National Institute of Health Consensus Conference methodology. A consensus development panel formulated a set of statements and proposed a research agenda. Specifically, the ICC produced recommendations on: (1) diagnostic pathway; (2) prognosis and the main predictors of disease progression; (3) efficacy and safety of treatments; and (4) research priorities on diagnosis, prognosis and treatment. The Bologna ICC on diagnosis, management and treatment of MNGIE provided evidence‐based guidance for clinicians incorporating patients' values and preferences