Measurement of the

^{140}Ce(n,γ) is a key reaction for slow neutron-capture (s-process) nucleosynthesis due to being a bottleneck in the reaction flow. For this reason, it was measured with high accuracy (uncertainty ≈5%) at the n_TOF facility, with an unprecedented combination of a high purity sample and low neutron-sensitivity detectors. The measured Maxwellian averaged cross section is up to 40% higher than previously accepted values. Stellar model calculations indicate a reduction around 20% of the s-process contribution to the Galactic cerium abundance and smaller sizeable differences for most of the heavier elements. No variations are found in the nucleosynthesis from massive stars.

A new digital health tool for the telemonitoring of patients with scleroderma during iloprost administration: a feasibility and acceptability study.

OBJECTIVE: To assess the feasibility of a new device for telemonitoring vital parameters during iloprost infusion. MATERIALS AND METHODS: In a pilot study, patients with systemic sclerosis received iloprost infusion while being telemonitored with Umana T1 Heart Monitor, within the hospital, under the supervision of family/community nurses and rheumatologists. Patients were administered a questionnaire to obtain information on satisfaction, practicability, and compliance with the new monitoring device. RESULTS: Data recorded by the device for blood pressure, heart rate, and oximetry were concordant with those registered directly by nurses. Most patients found the device useful and thought it could be used at home, even while working. CONCLUSIONS: Umana Heart Monitor T1 could be a valuable aid in at-home iloprost therapy in patients with systemic sclerosis.

Ingested versus inhaled limonene in sheep: A pilot study to explore potential different transfer to the mammary gland and effects on milk and Caciotta cheese aroma.

Concentration is a key determinant in the overall positive impact of terpenes on milk and cheese aroma; additionally, route of intake may affect the achievable concentrations of dietary terpenes in milk and cheese. In this study, we explored the possibility that the amount of the monoterpene limonene transferred to sheep milk and its corresponding cheese could differ depending on the route of intake and that the aroma profile of these products could also differ. To this aim, 12 lactating dairy ewes were repeatedly exposed to limonene by the oral or respiratory route during a 48-h test period, according to a 3 × 3 Latin square experimental design. Limonene content was measured in individual and bulk milk samples, in 1-d-old and 15-d-old Caciotta cheese obtained from that milk, in the related whey and curd, and in the air inhaled by the ewes in the respiratory treatment group (to obtain an estimate of the dose actually supplied by this route). Bulk milk and fresh (1-d-old) cheese underwent sensory analysis by ortho-olfactory evaluation. Both intake routes demonstrated transfer of limonene to milk, but the respiratory route transferred limonene with greater efficiency than the oral route. Moreover, according to the protocol used in this study, a short period of respiratory exposure induced a slightly higher limonene content in milk compared with oral exposure. As to the fate of limonene during cheesemaking, an important part of it was lost into the whey, perhaps through volatilization. The differences between milk and cheese tended to dissipate in curd and fresh cheese and disappeared completely after 15 d of ripening. Finally, it was possible to distinguish between the 2 routes of limonene intake using sensory analysis, even though no direct relationship was identified between the different aroma profiles of milks and cheeses from the oral and respiratory groups and their respective limonene contents. Overall, our results expand current knowledge on the biological pathways of terpene transfer from feed to sheep milk and cheese, as well as on the role played by terpenes in the formation of aroma in these products. Our observations may contribute to future development of strategies for external control and better standardization of the presence of odor compounds in milk and cheese from dairy ruminants.

Clinical characteristics, management and outcome of patients with invasive candidiasis hospitalized in Internal Medicine Units: findings from a registry by the Italian Scientific Society FADOI.

PURPOSE: Invasive candidiasis (IC) is a challenging clinical condition, burdened by relevant mortality and morbidity. There is limited knowledge on the occurrence and management of IC in Internal Medicine Units (IMUs). Aim of this study was to provide real-world data on this topic. METHODS: Consecutive objectively diagnosed cases of IC were collected in this prospective registry, which involved 18 IMUs in Italy. Patients were followed-up to 90 days from the diagnosis of candidemia. RESULTS: A total of 111 patients were observed (median age 78, IQR 67-83) for an overall incidence of infection of 1.89 cases/1000 hospital admissions. Candida albicans was the most frequent isolated species (62%), followed by Candida parapsilosis (17%) and Candida glabrata (13%). Echinocandins and fluconazole were used as initial therapy in 56.8 and 43.2% of patients, respectively. Antifungal therapy was started within 24 h in 18.9% of patients, in 40.6% in the period 1-3 days, and in 40.5% of patients more than 3 days after blood cultures. Death rate was 19.8% at 30 days and 40.5% at 90 days. At multivariable analysis concomitant bacteremia (i.e. polymicrobial sepsis), and fluconazole as the initial therapy were associated with an increased risk of death at 90 days. CONCLUSIONS: The incidence of IC is not negligible, and our registry confirmed that these patients have a relevant mortality rate at 90 days. Concomitant bacteremia, featuring polymicrobial sepsis, and starting antifungal treatment with fluconazole instead of echinocandins independently increase the risk of death. Efforts are needed to improve the awareness and management of IC in IMUs.

The SonicHand Protocol for Rehabilitation of Hand Motor Function: A Validation and Feasibility Study.

Musical sonification therapy is a new technique that can reinforce conventional rehabilitation treatments by increasing therapy intensity and engagement through challenging and motivating exercises. The aim of this paper is to evaluate the feasibility and validity of the SonicHand protocol, a new training and assessment method for the rehabilitation of hand function. The study was conducted in 15 healthy individuals and 15 stroke patients. The feasibility of implementation of the training protocol was tested in stroke patients only, who practiced a series of exercises concurrently to music sequences produced by specific movements. The assessment protocol evaluated hand motor performance during pronation/supination, wrist horizontal flexion/extension, and hand grasp without sonification. From hand position data, 15 quantitative parameters were computed evaluating mean velocity, movement smoothness, and angular excursions of hand/fingers. We validated this assessment in terms of its ability to discriminate between patients and healthy subjects, test-retest reliability and concurrent validity with the upper limb section of the Fugl-Meyer scale (FM), the functional independence measure (FIM), and the Box and Block Test (BBT). All patients showed a good understanding of the assigned tasks and were able to correctly execute the proposed training protocol, confirming its feasibility. A moderate-to-excellent intraclass correlation coefficient was found in 8/15 computed parameters. The moderate-to-strong correlation was found between the measured parameters and the clinical scales. The SonicHand training protocol is feasible and the assessment protocol showed good to excellent between-group discrimination ability, reliability, and concurrent validity, thus enabling the implementation of new personalized and motivating training programs employing sonification for the rehabilitation of hand function.

Early alert from the microbiology laboratory improves the outcome of elderly patients with Enterococcus spp. bloodstream infection: Results from a multicentre prospective study.

OBJECTIVES: This study describes the clinical features and outcomes of patients with bloodstream infection (BSI) due to Enterococcus spp. and identified factors predictive of mortality. METHODS: This analysis is part of a prospective multicentre observational study of consecutive hospitalised patients with BSI conducted from March 2012 to December 2012 in 31 internal medicine wards in Italy. Patients with enterococcal BSI were selected from the entire cohort. Patient characteristics, therapeutic interventions and outcome were reviewed. Cox regression analysis was performed to identify factors associated with in-hospital mortality. Hazard ratios (HRs) and 95% interval confidences (CIs) were calculated. RESULTS: Among 533 patients with BSI, 41 (7.7%) had BSI by Enterococcus spp. (28 Enterococcus faecalis, 4 Enterococcus faecium and 3 each of Enterococcus avium, Enterococcus casseliflavus and Enterococcus gallinarum). Six BSIs (14.6%) were polymicrobial. Median (IQR) patient age was 73 (66-85.5) years. In-hospital mortality was 24.4%. Polymicrobial infection (HR = 9.100, 95% CI 1.295-63.949; P = 0.026), age (HR = 1.261, 95% CI 1.029-1.546; P = 0.025) and SOFA score (HR = 1.244, 95% CI 1.051-1.474; P = 0.011) were risk factors for in-hospital mortality. Conversely, receiving an alert from the microbiology laboratory before obtaining final antimicrobial susceptibility results was associated with survival (HR = 0.073, 95% CI 0.007-0.805; P = 0.033). CONCLUSION: BSI due to Enterococcus spp. in elderly patients is associated with high mortality. Polymicrobial infection, age and SOFA score are factors associated with poor outcome. Conversely, early alert from the microbiology laboratory improves patient survival.

Ultrasound elastography is useful to distinguish acute and chronic deep vein thrombosis.

Essentials Ultrasound elastography uses tissue deformation to assess the relative quantification of its elasticity. Compression and duplex ultrasonography may be unable to correctly determine the thrombus age. Ultrasound elastography may be useful to distinguish between acute and chronic deep vein thrombosis. The exact determination of the thrombus age could have both therapeutic and prognostic implications. BACKGROUND: Background Ultrasound elastography (UE) imaging is a novel sonographic technique that is commonly employed for relative quantification of tissue elasticity. Its applicability to venous thromboembolic events has not yet been fully established; in particular, it is unclear whether this technique may be useful in determining the age of deep vein thrombosis (DVT). Thus, the aim of this study was to assess the role of UE in distinguishing acute from chronic DVT. Methods Consecutive patients with a first unprovoked acute and chronic (3 months old) DVT of the lower limbs were analyzed. Patients with recurrent DVT or with a suspected recurrence were excluded. The mean elasticity index (EI) values of acute and chronic popliteal and femoral vein thrombosis were compared. The accuracy of the EI in distinguishing acute from chronic DVT was also assessed by measuring the sensitivity, specificity, positive and negative predictive values, and likelihood ratios. Results One-hundred and forty-nine patients (mean age 63.9 years, standard deviation 13.6; 73 males) with acute and chronic DVT were included. The mean EI of acute femoral DVT was higher than that of chronic femoral DVT (5.09 versus 2.46), and the mean EI of acute popliteal DVT was higher than that of chronic popliteal DVT (4.96 versus 2.48). An EI value of > 4 resulted in a sensitivity of 98.9% (95% confidence interval [CI] 93.3-99.9), a specificity of 99.1% (95% CI 94.8-99.9), a positive predictive value of 91.1% (95% CI 77.9-97.1), a negative predictive value of 98.6% (95% CI 91.3-99.9), a positive likelihood ratio of 13.23 (95% CI 93-653) and a negative likelihood ratio of 0.001 (95% CI 0.008-0.05) for acute DVT. Conclusions UE appears to be a promising technique for distinguishing between acute and chronic DVT. Larger prospective studies are warranted to confirm our preliminary findings.

Evaluation of the threshold value for the modified early warning score (MEWS) in medical septic patients: a secondary analysis of an Italian multicentric prospective cohort (SNOOPII study).

BACKGROUND: Due to aging and resources limitation, septic patients are often admitted to medical wards (MWs). Early warning deterioration is a relevant issue in this setting. Unfortunately, a suitable prognostic score has not been identified, yet. AIM: To explore the ability of Modified Early Warning Score (MEWS) to predict the in-hospital mortality in septic patients admitted to MWs. DESIGN: Secondary analysis of a multicentric prospective study. METHODS: Consecutive septic patients with positive blood culture admitted to 31 Italian MWs were included. Baseline characteristics, clinics, isolates, rate of transfer to ICU, MEWS was collected on admission according to the study protocol. The accuracy of MEWS in predicting the in-hospital mortality was assessed with the area under the receiver-operating characteristic curves. Sensitivity, specificity, positive and negative predictive value (PPV and NPV), likelihood ratio (LR) were calculated for different MEWS cut-offs and age/comorbidities subgroups. RESULTS: In total 526 patients were included in this analysis. Median MEWS was (range 0-11). In-hospital mortality was 14.8% and transfer to ICU 1.3%. Mortality progressively increased according to MEWS (3% in MEWS 0 vs. 27% in MEWS >5; Chi square for trend P < 0.05). The AUC of MEWS in predicting in-hospital mortality was 0.596 (95% CI, 0.524, 0.669). MEWS did not appear to have an adequate sensitivity, sensibility, PPV, NPV and LR both in the whole population and in the pre-specified subgroups. CONCLUSIONS: Our findings do not seem to support the use of MEWS to predict the in-hospital mortality risk of sepsis in MWs.

The role of comprehensive geriatric assessment and functional status in evaluating the patterns of antithrombotic use among older people with atrial fibrillation.

Aim of the study is to investigate the use of antithrombotic drugs in older patients with atrial fibrillation (AF) at the time of hospital discharge. We enrolled 399 ≥65 years old patients with AF consecutively admitted to our acute geriatric unit from September 2012 to February 2014. Utilization of antithrombotic drugs, comorbidities, functional, mental and nutritional status were evaluated through a comprehensive geriatric assessment (CGA). A Logistic regression model was used to assess variables associated with antithrombotic use. On admission, 198 patients (49.6%) used oral anticoagulants (OAC), 125 (21.3%) antiplatelets, 32 (8%) low weight molecular heparin (LMWH) and 44 (11%) none of them. At discharge the proportion of patients on OAC increased to 55.7%. Age>90years (OR=2.57, CI=1.28-5.16, p-value=0.008), severe functional impairment (OR=3.38, CI=1.63-7.01, p-value=0.001), polypharmacy (OR=2.07, CI=1.1-3.86, p-value=0.023), HAS-BLED score (OR=1.64, CI=1.09-2.47, p-value=0.019) and ≥1 OAC contraindication (OR=5.01, CI=2.68-9.34, p-value<0.001) were all associated with OAC underuse. In conclusion, OAC is underused in geriatric patients with AF, while antiplatelet, LMWH and no antithrombotic therapy are relatively overused. Factors associated with the decision to not prescribe OAC lie on a mix of clinical and geriatric variables, among which functional status is particularly relevant.

The prognostic value of baseline (18)F-FDG PET/CT in steroid-naïve large-vessel vasculitis: introduction of volume-based parameters.

PURPOSE: The aim of this study was to analyse if the result of a baseline (18)F-fluorodeoxyglucose (FDG) positron emission tomography (PET)/CT scan, in large-vessel vasculitis (LVV) patients, is able to predict the course of the disease, not only in terms of presence/absence of final complications but also in terms of favourable/complicated progress (response to steroid therapy, time to steroid suspension, relapses, etc.). METHODS: A total of 46 consecutive patients, who underwent (18)F-FDG PET/CT between May 2010 and March 2013 for fever of unknown origin (FUO) or suspected vasculitis (before starting corticosteroid therapy), were enrolled. The diagnosis of LVV was confirmed in 17 patients. Considering follow-up results, positive LVV patients were divided into two groups, one characterized by favourable (nine) and the other by complicated progress (eight), on the basis of presence/absence of vascular complications, presence/absence of at least another positive PET/CT during follow-up and impossibility to comply with the tapering schedule of the steroid due to biochemical/symptomatic relapse. Vessel uptake in subjects of the two groups was compared in terms of intensity and extension. To evaluate the extent of active disease, we introduced two volume-based parameters: "volume of increased uptake" (VIU) and "total lesion glycolysis" (TLG). The threshold used to calculate VIU on vessel walls was obtained by the "vessel to liver" ratio by means of receiver-operating characteristic analysis and was set at 0.92 × liver maximum standardized uptake value in each patient. RESULTS: Measures of tracer uptake intensity were significantly higher in patients with complicated progress compared to those with a favourable one (p < 0.05). Measures of disease extension were even more significant and TLG emerged as the best parameter to separate the two groups of patients (p = 0.01). CONCLUSION: This pilot study shows that, in LVV patients, the combined evaluation of the intensity and the extension of FDG vessel uptake at diagnosis can predict the clinical course of the disease, separating patients with favourable or complicated progress.

Improving proprioceptive deficits after stroke through robot-assisted training of the upper limb: a pilot case report study.

The purpose of this study was to determine whether a conventional robot-assisted therapy of the upper limb was able to improve proprioception and motor recovery of an individual after stroke who exhibited proprioceptive deficits. After robotic sensorimotor training, significant changes were observed in kinematic performance variables. Two quantitative parameters evaluating position sense improved after training. Range of motion during shoulder and wrist flexion improved, but only wrist flexion remained improved at 3-month follow-up. These preliminary results suggest that intensive robot-aided rehabilitation may play an important role in the recovery of sensory function. However, further studies are required to confirm these data.

Expression and function of the Scn5a-encoded voltage-gated sodium channel NaV 1.5 in the rat jejunum.

BACKGROUND: The SCN5A-encoded voltage-gated sodium channel NaV 1.5 is expressed in human jejunum and colon. Mutations in NaV 1.5 are associated with gastrointestinal motility disorders. The rat gastrointestinal tract expresses voltage-gated sodium channels, but their molecular identity and role in rat gastrointestinal electrophysiology are unknown. METHODS: The presence and distribution of Scn5a-encoded NaV 1.5 was examined by PCR, Western blotting and immunohistochemistry in rat jejunum. Freshly dissociated smooth muscle cells were examined by whole cell electrophysiology. Zinc finger nuclease was used to target Scn5a in rats. Lentiviral-mediated transduction with shRNA was used to target Scn5a in rat jejunum smooth muscle organotypic cultures. Organotypic cultures were examined by sharp electrode electrophysiology and RT-PCR. KEY RESULTS: We found NaV 1.5 in rat jejunum and colon smooth muscle by Western blot. Immunohistochemistry using two other antibodies of different portions of NaV 1.5 revealed the presence of the ion channel in rat jejunum. Whole cell voltage-clamp in dissociated smooth muscle cells from rat jejunum showed fast activating and inactivating voltage-dependent inward current that was eliminated by Na(+) replacement by NMDG(+) . Constitutive rat Scn5a knockout resulted in death in utero. NaV 1.5 shRNA delivered by lentivirus into rat jejunum smooth muscle organotypic culture resulted in 57% loss of Scn5a mRNA and several significant changes in slow waves, namely 40% decrease in peak amplitude, 30% decrease in half-width, and 7 mV hyperpolarization of the membrane potential at peak amplitude. CONCLUSIONS & INFERENCES: Scn5a-encoded NaV 1.5 is expressed in rat gastrointestinal smooth muscle and it contributes to smooth muscle electrophysiology.

Under-detection of delirium and impact of neurocognitive deficits on in-hospital mortality among acute geriatric and medical wards.

BACKGROUND: Delirium is a neuropsychiatric disorder, triggered by medical precipitants causes. Study aims were to describe the prevalence and impact on in-hospital mortality of delirium identified through ICD-9 codes as well as evidence of neurocognitive deficits demonstrated in a population of older patients admitted to acute medical wards. METHODS: This was a prospective cohort multicenter study of 2521 older patients enrolled in the "Registro Politerapie SIMI (REPOSI)" during the years 2010 and 2012. The diagnosis of delirium was obtained by ICD-9 codes. Cognitive function was evaluated with the Short Blessed Test (SBT) and single SBT items were used as measures of deficits in attention, orientation and memory. Combination of deficits in SBT items was used as a proxy for delirium. Logistic regression was used to evaluate the association with in-hospital mortality of delirium and combined deficits in SBT items. RESULTS: Delirium was coded in 2.9%, while deficits in attention, orientation, and memory were found in 35.4%, 29.7% and 77.5% of patients. Inattention and either disorientation or memory deficits were found in 14.1%, while combination of the 3 deficits in 19.8%. Delirium, as per ICD-9 codes, was not a predictor of in-hospital mortality. In contrast, objective deficits of inattention, in combination with orientation and memory disorders, were stronger predictors after adjusting for covariates. CONCLUSIONS: The documentation of delirium is poor in medical wards of Italian acute hospitals. Neurocognitive deficits on objective testing (in a pattern suggestive of undiagnosed delirium) should be used to raise awareness of delirium, given their association with in-hospital mortality.

Pain management in internal medicine and effects of a standardised educational intervention: the FADOI-DOMINO study.

PURPOSE: Few real-world data are available on the frequency and management of pain in Internal Medicine (IM). Aims of our study were to assess the prevalence of pain in IM, and to evaluate the effects on pain management of a standardised educational programme. MATERIALS AND METHODS: The study was performed in 26 IM Units in Italy, with two cross-sectional surveys (PRE phase and POST phase) interspersed with an educational programme. In PRE phase each Centre reviewed the hospital charts of the last 100 consecutive patients hospitalised for any cause. An educational programme was conducted in each Centre by means of the 'outreach visit', a face-to-face meeting between health personnel and a trained external expert. Six months after, each Centre repeated the data collection (POST phase), specular to the PRE. RESULTS: A total of 5200 medical charts were analysed. Pain was documented in 37.5% of the patients. After the educational intervention, the intensity of pain was appropriately assessed in a higher percentage of patients (77.4% vs. 47.8%, p = 0.0001), and it was more frequently monitored during hospitalisation. Qualitative definition of pain (pathogenesis, duration, etc.) increased in POST phase (75.4% vs. 62.7%, p = 0.0001). A 73.3% increase in the use of strong opioids was detected following educational programme. CONCLUSIONS: Pain affects 4 out of 10 patients hospitalised in IM. According to our large real-world study, to implement a standardised one-shot educational programme may persistently improve the attitude of health personnel towards the characterisation and management of pain.

Evaluation of upper limb sense of position in healthy individuals and patients after stroke.

The aims of this study were to develop and evaluate reliability of a quantitative assessment tool for upper limb sense of position on the horizontal plane. We evaluated 15 healthy individuals (controls) and 9 stroke patients. A robotic device passively moved one arm of the blindfolded participant who had to actively move his/her opposite hand to the mirror location in the workspace. Upper-limb's position was evaluated by a digital camera. The position of the passive hand was compared with the active hand's 'mirror' position. Performance metrics were then computed to measure the mean absolute errors, error variability, spatial contraction/expansion, and systematic shifts. No significant differences were observed between dominant and non-dominant active arms of controls. All performance parameters of the post-stroke group differed significantly from those of controls. This tool can provide a quantitative measure of upper limb sense of position, therefore allowing detection of changes due to rehabilitation.

Robot-aided neurorehabilitation in sub-acute and chronic stroke: does spontaneous recovery have a limited impact on outcome?

BACKGROUND: Robotic neurorehabilitation, thanks to high dosage/intensity training protocols, has the potential for a greater impact on impairment. OBJECTIVE: We aimed to analyze how time since the acute event may influence the motor recovery process during robot-assisted rehabilitation of the upper limb. METHODS: A total of 41 patients after stroke were enrolled: 20 in subacute phase, i.e. ≤ 6 months elapsed since their unilateral cerebrovascular accident (CVA), and 21 at chronic stage, i.e. > 6 months since CVA. All subjects underwent 30 minutes of robot-aided rehabilitation twice a day, 5 days a week for at least three weeks of training. Patients were evaluated at the start and end of treatment using the Fugl-Meyer and Modified Ashworth clinical scales and by a set of robot measured kinematic parameters. The time interval from stroke was considered as a grouping factor to analyze its impact on time course of recovery. RESULTS: After training both groups significantly improved their impairment (F = 44.25, p < 0.001) but sub-acute patients showed a greater improvement on the Fugl-Meyer scale than chronic patients. The time course of recovery of the kinematic variables showed higher time constants of motor improvement in the sub-acute than chronic group, but they were one order lower than spontaneous recovery time constants. CONCLUSIONS: Spontaneous recovery seems to have a limited impact on the improvement of sub-acute patients, most of their changes being likely due to re-learning during rehabilitation. In addition, a longer recovery time was required to maximize outcome in sub-acute than in chronic patients.

A new interpretation of the σA parameter.

A new study of the σA parameter has been undertaken to understand its behaviour when the diffraction amplitude distributions are far from the standard Wilson distributions. The study has led to the formulation of a new statistical interpretation of σA, expressed in terms of a correlation factor. The new formulas allow a more accurate use of σA in electron-density modification procedures.