Prevalence of 2-year "No evidence of disease activity" (NEDA-3 and NEDA-4) in relapsing-remitting multiple sclerosis. A real-world study.

BACKGROUND: No evidence of disease activity (NEDA) is becoming a gold standard in the evaluation of disease modifying therapies (DMT) in relapsing-remitting multiple sclerosis (RRMS). NEDA-3 status is the absence of relapses, new activity on brain MRI, and disability progression. NEDA-4 meets all NEDA-3 criteria plus lack of brain atrophy. OBJECTIVE: Aim of this study was to investigate the prevalence of two-year NEDA-3, NEDA-4, six-month delayed NEDA-3 (6mdNEDA-3), and six-month delayed NEDA-4 (6mdNEDA-4) in a cohort of patients with RRMS. Six-month delayed measures were introduced to consider latency of action of drugs. METHODS: Observational retrospective monocentric study. All the patients with RRMS starting DMT between 2015 and 2018, and with 2-year of follow-up, were included. Annualized brain volume loss (a-BVL) was calculated by SIENA software. RESULTS: We included 108 patients, the majority treated with first line DMT. At 2-year follow-up, 35 % of patients were NEDA-3 (50 % 6mdNEDA-3), and 17 % NEDA-4 (28 % 6mdNEDA-4). Loss of NEDA-3 status was mainly driven by MRI activity (70 %), followed by relapses (56 %), and only minimally by disability progression (7 %). CONCLUSION: In our cohort 2-year NEDA status, especially including lack of brain atrophy, was hard to achieve. Further studies are needed to establish the prognostic value of NEDA-3 and NEDA4 in the long-term follow-up.

Effect of the manufacturing process on Fiore Sardo PDO cheese microstructure by multi-frequency NMR relaxometry.

The quality of Fiore Sardo cheese, a traditional Italian dairy product, was analyzed by means of Multi-frequency Nuclear Magnetic (NMR) relaxometry. Specifically, ten cheese wheels were purchased from different production chains, either industrial (N = 5) or artisanal (N = 5) samples. The former came from large scale productions and the latter were produced by shepherds in small quantities and in very small dairy factories. A preliminary interlaboratory proficiency testing of Time Domain - NMR (TD-NMR, 20 MHz) relaxometry by five laboratories, consistently showed that product quality is significantly different in terms of molecular mobility according to their production chain (i.e. industrial or artisanal). More detailed information about cheese microstructure was obtained by Multi-frequency Fast Field Cycling NMR (FFC-NMR) at lower magnetic fields (0.01-10 MHz). According to the interpretative model adopted to describe FFC-NMR data, industrially processed cheeses showed a higher para-casein hydration, higher protein protons to water protons ratio and a higher disorder (lower fractal dimension df) than artisanal products. It is suggested that differences between artisanal and industrial cheeses generate from the processing steps preceding cheese maturation, and are clearly reflected in the visual appearance of cheeses. This study shows that NMR relaxometry techniques can successfully discriminate Fiore Sardo cheese from different production chains, and paves the way for their implementation in quality control practices of dairy products.

Dimethyl fumarate-induced lymphocyte count drop is related to clinical effectiveness in relapsing-remitting multiple sclerosis.

BACKGROUND AND PURPOSE: Dimethyl fumarate (DMF) causes a mean lymphocyte count drop of approximately 30% in relapsing-remitting multiple sclerosis (RRMS) patients. The relationship between this reduction and DMF effectiveness is controversial. The objective was to investigate if the decrease in absolute lymphocyte count (ALC) from baseline during DMF treatment is associated with clinical and magnetic resonance imaging (MRI) disease activity. A secondary aim was to evaluate ALC variations over time in a real-life cohort of DMF-treated patients. METHODS: Demographic, laboratory, clinical and MRI data were collected in this observational multicentre study, conducted on RRMS patients treated with DMF for at least 6 months. Multivariate Cox models were performed to evaluate the impact of 6-month ALC drop on time to no evidence of disease activity (NEDA-3) status loss. NEDA-3 is defined as absence of clinical relapses, MRI disease activity and confirmed disability progression. RESULTS: In all, 476 patients (312 females, age at DMF start 38.4 ± 9.97 years) were analysed up to 5-year follow-up. A greater lymphocyte decrease was associated with a lower risk of NEDA-3 status loss (hazard ratio 0.87, P = 0.01). A worse outcome in patients with lower ALC drop (<11.5%), compared with higher tertiles (11.5%-40.5% and >40.5%), was observed (P = 0.008). The nadir of ALC drop (-33.6%) and 35% of grade III lymphopaenia cases occurred after 12 months of treatment. CONCLUSION: A higher lymphocyte count drop at 6 months is related to better outcomes in DMF-treated patients. A careful ALC monitoring should be pursued up to 24 months of treatment.

The effect of community nurse on mortality and hospi- talization in a group of over-75 older adults: a nested case-control study.

Background: Bio-psycho-social frailty can negatively affect the health status of an ageing population. The integration between community nurses and social services can emphasize community care and prevent the onset of both health and social negative outcomes in the older population. The aim of the paper is to explore the causal association through the analysis of the hospitalization and mortality rate after a pro-active social service integrated by the community nurse. Study Design: A nested case-control study comparing groups of older adults has been carried out. Methods. The paper compares data stem from a cohort followed up by the University of Rome "Tor Vergata" with data from the "Long Live the Elderly!" program (LLE) cohort. Results: One-year standardized mortality rate was 6.5%, 4.7% and 7.5% in the control group, the LLE group and the LLE group integrated by the community nurse (LLE-CN), respectively. One-year hospitalization rate was 15.4%, 15.5% and 10.8% in the control group, the LLE group and the LLE-CN group, respectively. Conclusions: According to our results a social service with a pro-active approach, integrated by the community nurse, appears to be able to reduce mortality and hospitalization in a group of older adults aged>75. The multidimensional assessment of frailty stands for the first step of a new organization of community services.

Molecular mobility changes after high-temperature, short-time pasteurization: An extended time-domain nuclear magnetic resonance screening of ewe milk.

This study presents an extensive investigation on the effect of pasteurization on raw whole ewe milk. Milk samples have been analyzed, throughout lactation (from February to July), by time-domain nuclear magnetic resonance (TD-NMR), collecting the characteristic TD-NMR relaxation parameters, proton longitudinal and transverse relaxation times (1H T1 and T2). Collected data aim at integrating previous NMR works, mainly focusing on dairy model systems (casein and whey proteins solutions and gels, reconstituted skim milk) and cheese, with specific reference to the effect of heat treatments. Whole ewe milk, from a single flock (Sarda sheep breed), was daily analyzed both as untreated (raw) and heat treated with a laboratory-scaled high-temperature, short-time treatment (72°C for 15 and 20 s). Moreover, molecular dynamics in milk were investigated by TD-NMR in different periods of lactation for the first time. As a consequence of high-temperature short-time treatment, 1H T1 and T2 consistently shifted to lower values with respect to raw counterparts. Statistical analysis indicated a significant decrease of T2 in treated samples, to an extent dependent on the heat treatment duration. A subset of dedicated experiments demonstrated that the observed T2 shift is largely ascribable to protein molecular rearrangements and, to a lesser extent, to the interaction of fat globules with proteins or other nonfat components (or both). In light of the crucial importance of detecting the application of a heat treatment to milk, the results reported here suggest TD-NMR relaxation parameters were able to describe heat-induced changes in molecular dynamics and interactions of milk components in a water-rich environment. The use of TD-NMR can be considered a potential suitable technique for quality control and assurance practices in the dairy industry. Upon statistical validation of methods, the application of TD-NMR in the dairy industry would take advantage of its low cost, reliability, and robustness.

The contribution of enhancing lesions in monitoring multiple sclerosis treatment: is gadolinium always necessary?

BACKGROUND: MRI is highly sensitive for monitoring of disease activity and treatment efficacy in MS. Patients treated with disease modifying therapy (DMT), who experience MRI activity, including contrast-enhancing lesions (CEL) or new/enlarged T2 lesions, should be evaluated for a switch to more effective treatment. Due to recent evidence of gadolinium (Gd) accumulation in the brain after repeated administration of Gd-based contrast agents, FDA recommended to limit its use. AIM: To investigate the proportion of cases in which MRI activity would be detectable only using contrast-enhanced T1-weighted sequences.Secondary aims were to assess the presence of clinical or demographic variables associated with reactivation of pre-existing lesions and to analyse therapeutic consequences of different types of MRI lesions. METHODS: We retrospectively evaluated brain MRI scans, performed between 2014 and 2018, in patients treated with DMT for at least 6 months. RESULTS: We analysed 906 scans in 255 patients. New/enlarged T2 lesions were detected in 13.7% of cases, CEL in 3.5%, CEL without new T2 lesions (old lesions reactivated) in 1.1%. No variables were associated with old lesions reactivated. CEL with T2 equivalent were at higher risk of DMT switch, compared with new/enlarged T2 lesions without corresponding CEL (OR 4.0, 95% CI 1.5-10.4, p  = 0.005). CONCLUSIONS: Reactivation of pre-existing lesions is limited to a tiny fraction of MRI studies. Gd + T1-weighted images could be omitted, in patients treated with DMT for at least 6 months, without relevant loss of information.

A low-field Nuclear Magnetic Resonance dataset of whole milk during coagulation and syneresis.

We report the relaxometric dataset obtained on renneted milk during syneresis by Time-Domain Nuclear Magnetic Resonance spectroscopy (TD-NMR). Data were obtained on cow's milk provided by two different producers in two different lactation seasons (April and October) and on a group of goat's milk samples (one season, November-December, one producer). TD-NMR data refer to spin-spin relaxation times (T2) decay curves and distributions measured at 40 °C at seven time points after rennet addition, up to 70 minutes of syneresis. Curd was cut 30 min after rennet addition without removing the NMR tube from the TD-NMR instrument. The dataset here reported is related to the research article entitled "Non invasive monitoring of curd syneresis upon renneting of raw and heat-treated cow's and goat's milk" [E. Curti, A. Pardu, S. Del Vigo, R. Sanna, R. Anedda, Non-invasive monitoring of curd syneresis upon renneting of raw and heat-treated cow's and goat's milk, Int. Dairy J. 90 (2019) 95-97].

Deciphering pore-level precipitation mechanisms.

Mineral precipitation and dissolution in aqueous solutions has a significant effect on solute transport and structural properties of porous media. The understanding of the involved physical mechanisms, which cover a large range of spatial and temporal scales, plays a key role in several geochemical and industrial processes. Here, by coupling pore scale reactive transport simulations with classical nucleation theory, we demonstrate how the interplay between homogeneous and heterogeneous precipitation kinetics along with the non-linear dependence on solute concentration affects the evolution of the system. Such phenomena are usually neglected in pure macroscopic modelling. Comprehensive parametric analysis and comparison with laboratory experiments confirm that incorporation of detailed microscale physical processes in the models is compulsory. This sheds light on the inherent coupling mechanisms and bridges the gap between atomistic processes and macroscopic observations.

The use of two-dimensional NMR relaxometry in bread staling: a valuable tool?

Staling of bread was investigated in terms of physico-chemical parameters and one (1D) and two dimensional (2D) 1H Nuclear Magnetic Resonance (NMR) relaxometry. Physico-chemical properties were consistent with those generally reported for bread staling (crumb moisture loss, decrease in frozen water content, formation of amylopectin crystals, crumb hardening). One dimensional 1H NMR investigation suggested the presence of only one T1 protons population, while T2 was representative of multiple proton populations, that well related to the observed physico-chemical changes. 1H Two dimensional NMR provided an interesting insight of 1H T1 dynamics, as it allowed to discriminate the contribution of five protons pools within the 1H T1 relaxation.

Characterization of selenium in UO2 spent nuclear fuel by micro X-ray absorption spectroscopy and its thermodynamic stability.

Direct disposal of spent nuclear fuel (SNF) in deep geological formations is the preferred option for the final storage of nuclear waste in many countries. In order to assess to which extent radionuclides could be released to the environment, it is of great importance to understand how they are chemically bound in the waste matrix. This is particularly important for long-lived radionuclides such as (79)Se, (129)I, (14)C or (36)Cl, which form poorly sorbing anionic species in water and therefore migrate without significant retardation through argillaceous repository materials and host rocks. We present here X-ray absorption spectroscopic data providing evidence that in the investigated SNF samples selenium is directly bound to U atoms as Se(-II) (selenide) ion, probably replacing oxygen in the cubic UO2 lattice. This result is corroborated by a simple thermodynamic analysis, showing that selenide is the stable form of Se under reactor operation conditions. Because selenide is almost insoluble in water, our data indirectly explain the unexpectedly low release of Se in short-term aqueous leaching experiments, compared to iodine or cesium. These results have a direct impact on safety analyses for potential nuclear waste repository sites, as they justify assuming a small fractional release of selenium in performance assessment calculations.

Physico-chemical properties of ready to eat, shelf-stable pasta during storage.

The changes in physico-chemical properties of RTE shelf stable pasta were studied during storage with a multianalytical and multidimensional approach (with special focus on water status) to understand the ageing process in this product. Pasta hardness and amylopectin recrystallisation increased, macroscopic water status indicators and proton molecular translational mobility remained constant, and significant changes were measured in the proton rotational molecular mobility indicators ((1)H FID, (1)H T2) during storage. Since the main changes observed in RTE pasta during storage were similar to those observed in other cereal-based products, it would be interesting to verify the effect of the anti-staling methods commonly used in the cereal processing industry in improving RTE pasta shelf-stability.

Effect of different air/steam convection cooking methods on turkey breast meat: physical characterization, water status and sensory properties.

Turkey breast samples were cooked using a forced convection oven at three relative humidity levels (RH=8, 35 and 88%) at 100°C. Cooking parameters (temperature, cook value, and yield), textural and sensory properties as well as water status of the samples were evaluated. The application of different RH levels resulted in different cooking performances and cooked meat quality. Low steam cooking conditions (RH=35%) significantly increased cooking yield (7% higher than the high steam cooking), moisture content and water-holding capacity and had a positive effect on perceived tenderness, as shown by sensory analysis, where steam cooked samples were perceived as the most tender. The more mobile protons of (1)H T(2) (relaxing at times longer than 1s) in low steam samples were related to the higher perceived tenderness. Low steam cooking allowed for less water consumption, making this process an attractive cooking method as compared to high steam, as it also resulted in higher quality cooked turkey meat.

Efficacy and safety of short course (5-day) moxifloxacin vs 7-day ceftriaxone in the treatment of acute exacerbations of chronic bronchitis (AECB).

The aim of this multicenter, open, randomized study was to compare the efficacy and tolerability of a 5-day treatment course with oral moxifloxacin (MXF) vs a 7-day course with i.m. ceftriaxone (CRO) in 476 patients with acute exacerbations of chronic bronchitis (AECB), and to conduct a cost minimization analysis of the two treatments from the perspectives of both the Italian National Health Service (INHS) and society. The study was conducted in Italy. Clinical success rates at test-of-cure in the 423 patients of the PP (Per Protocol) population (primary efficacy parameter) were 90.6% and 89.0% for MXF and CRO, respectively. Statistical non-inferiority of MXF vs CRO was confirmed. Similar results were found between study drugs on the secondary efficacy parameters, including success at end-of-treatment (95.3% for MXF vs 92.9% for CRO), success at test-of-cure in bacteriologically-positive patients (94.1% vs 90.7%) and eradication/presumed eradication rates (91.7% vs 93.3%). ITT (Intention-to-Treat) analysis confirmed these data. There was a low incidence of adverse events (10.8% vs 9.1%). During a 6-month follow-up period, relapse rates were lower for MXF vs CRO (23.3% vs 28.3%; p > .05). Compared with CRO, MXF was associated with cost savings per patient ranging from Euro226.57 (INHS perspective) to Euro448.23 (societal perspective), with lower hospitalization rate the major variable contributing to reduced costs. MXF appears to be an ideal candidate for AECB treatment.

The effects of generation on item and order retention in immediate and delayed recall.

Recent research has shown that generating words from fragments, relative to simply reading them, inhibits processing of order information. Nairne, Riegler, and Serra (1991) showed that this reduction in processing of order information leads to deficits in recall performance. In three experiments, we generally replicate Nairne et al.'s results and demonstrate that the deficit in recall for the generated items is dependent on the easy distractor task and the relatively short (30-sec) retention interval they used. When a difficult distractor task was used, generating produced a deficit in amount of order information processed, but actually facilitated recall when recall was delayed 80 sec. The results are consistent with the hypothesis that generating words inhibits order processing, but they do not support the contention that the reduction in order processing is responsible for the deficit in recall that is sometimes observed for the generated items. The importance of the item-order distinction in explaining the generation effect, as well as the role of the item-order distinction in the long-term-memory arena, is questioned.

[Bacterial resistance in the infections from gram-negative bacilli in a long-term hospital (author's transl)]. / La resistenza batterica nelle infezioni da bacilli Gram-negativi in un ospedale per lungodegenti.

After considering the different reasons that make the problem of bacterial resistance of Gram-negative bacilli to antibiotics of great interest in a long-term hospital, the AA. present their cases. They point out how the strains isolated by them offer an antibiotic resistance which is decidedly superior to the one described in other researches. One thing seems to be noteworthy in their opinion: the bacterial resistance of the germs isolated from the urine is bigger than the one of the germs isolated from the respiratory apparatus.