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Ru(ii) complexes featuring two π-expansive benzo[i]dipyrido[3,2-a:2′,3′-c]phenazine ligands are potent photosensitizers that can be encapsulated into cubosomes to achieve hybrid formulations with augmented biopharmaceutical properties.

BACKGROUND: Robot-assisted arm therapy (RAT) has been used mainly in stroke rehabilitation in the last 20 years with rising expectations and growing evidence summarized in systematic reviews (SRs). OBJECTIVE: The aim of this study is to provide an overview of SRs about the effectiveness, within the ICF domains, and safety of RAT in the rehabilitation of adult with stroke compared to other treatments. METHODS: The search strategy was conducted using search strings adapted explicitly for each database. A screening base on title and abstract was realized to find all the potentially relevant studies. The methodological quality of the included SRs was assessed using AMSTAR-2. A pre-determined standardized form was used to realize the data extraction. RESULTS: 18 SRs were included in this overview. Generally, positive effects from the RAT were found for motor function and muscle strength, whereas there is no agreement for muscle tone effects. No effect was found for pain, and only a SR reported the positive impact of RAT in daily living activity. CONCLUSION: RAT can be considered a valuable option to increase motor function and muscle strength after stroke. However, the poor quality of most of the included SRs could limit the certainty around the results.

Background Connected health technology can enable healthcare professionals to provide multiple solutions to meet the growing demand of care and control of COVID-19 infected patients, by optimizing economic resources and extending the scope of monitoring beyond the hospital. A connected patient has the ability to monitor his state of health with tools that remotely transmit data to his doctor, help him to perform the right therapy thanks to reminder systems or electronic alerts and identifies cardiovascular alterations predictive of a worsening of the disease. An innovative mobile device, the BioBeat System® with an APP that can be downloaded directly to the Smart Phone, is characterized by sensors already validated according to the regulations of the Food and Drug Administration for vital signs, the European Society Hypertension for the detection of blood pressure. Purpose Wearable medical devices and the BioBeat software platform are appropriate for use in different settings for the management of acute, chronic cardiovascular, respiratory and inflammatory pathology, a tool capable of early identification of the instrumental signs of deterioration even before the exclusively clinical recognition that becomes even more difficult if we consider the patients at home. The aim of this study is to test the sensitivity and specificity of the biobeat wearable system applied in patients with paucisymptomatic COVID-19 infection (group A) and in those with previous SARS-COV2 disease discharged from the hospital who still needed post-acute monitoring (group B) and compared with clinical control, managing to determine early the clinical signs of worsening. Methods The data recorded by individual patients are systolic and diastolic blood pressure, heart and respiratory rate, peripheral oxygen saturation and body temperature. Thanks to these parameters it is possible to calculate the NEWS by being able to predict any adverse events early with the automatic calculation of the score. The criteria of deterioration or worsening of the clinical condition are represented by the need to hospitalize the patient, alteration of one of the criteria grouped in the ABCDE. Results Table 1 summarises the demographic data of the cases enrolled. We calculated the sensitivity of the methodology related to the alerts detected and the outcome of the patients. Sensitivity was 86.3% with a 95% CI of 0.71 to 1.03 and a specificity of 7.7%. Conclusions Continuous monitoring with biobeat watch showed a high sensitivity in detecting early any alerts predictive of worsening of the disease.

Background: Connected health technology can enable healthcare professionals to provide multiple solutions to meet the growing demand of care and control of COVID-19 infected patients, by optimizing economic resources and extending the scope of monitoring beyond the hospital. An innovative mobile device, the BioBeat Watch®, developed in Israel, with an APP that can be downloaded directly to the Smart Phone, is characterized by sensors already validated according to the regulations of the Food and Drug Administration for vital signs, the ECG track and the European Society Hypertension for the detection of blood pressure. Purpose: Wearable medical devices and the BioBeat software platform are appropriate for use in different settings for the management of acute, chronic cardiovascular, respiratory and inflammatory pathology, a tool capable of early identification of the instrumental signs of deterioration even before the exclusively clinical recognition that becomes even more difficult if we consider the patients at home.The aim of this study is to test the sensitivity and specificity of the biobeat wearable system applied in patients with paucisymptomatic COVID-19 infection (group A) and in those with previous SARS-COV2 disease discharged from the hospital who still needed post-acute monitoring (group B) and compared with clinical control, managing to determine early the clinical signs of worsening. Methods: The data recorded by individual patients are systolic and diastolic blood pressure, heart and respiratory rate, peripheral oxygen saturation and body temperature. The criteria of deterioration or worsening of the clinical condition are represented by the need to hospitalize the patient, alteration of one of the criteria grouped in the ABCDE. Results: We calculated the sensitivity of the methodology related to the alerts detected and the outcome of the patients. Sensitivity was 86.3% with a 95% CI of 0.71 to 1.03 and a specificity of 7.7%. Conclusions: Continuous monitoring with biobeat watch showed a high sensitivity in detecting early any alerts predictive of worsening of the disease.

Background Recent clinical data suggest that early vasopressin administration may be better than secondary therapy.In current clinical practice of intensive care, catecholamines represent the first-line hemodynamic treatment for septic shock. Despite the recognized efficacy as a vasopressor, the risk / benefit ratio deriving from the use of noradrenaline, especially at medium-high dosages (higher than 0.25 μg / kg / min) is unbalanced towards side effects including respiratory distress, metabolic stress oxidative and cardiac and renal toxicity. However, its trigger differs from that of catechol-amines on several levels. Vasopressin provokes a reduction in cardiac output and its vasoconstrictor activity is heterogeneous on a topographical level. Its administration provokes vasoconstriction in skin, skeletal muscle, adipose tissue, pancreas and thyroid. This vaso-constriction is less apparent in the mesenteric, coronary and cerebral territories under physiological conditions. Its impact on digestive perfusion is under debate. Two studies conducted in patients with septic shock. demonstrated absence of impact of vasopressin on splanchnic circulation. In contrast, in a recent study conducted in animals in a state of endotoxaemic shock, a reduction in digestive perfusion with vasopressin administration was observed. In this study, the association between concomitant AVP and norepinephrine therapy with mortality was evaluated in a cohort of 10 patients suffering from severe septic shock and hospitalized in the intensive care units. We assumed the NA/ argipressin combination saves the doses of the amine and improves the patient's outcome, reducing morbidity and mortality to 28 days. Methods This analysis was designed as observational study. The primary end point of the study was the 28-day mortality rate. The secondary endpoints: the length of stay in intensive care; the number of days without the need for organ support (eg, vasopressors, ventilators, or renal replacement therapy); the time required to achieve haemodynamic stability (i.e. the time to reach a MAP of 65 mm Hg: changes in haemodynamic variables; any need for the use of dobutamine or other inotropic agents. Adverse events have been classified as arrhythmias (i.e., ventricular tachycardia, ventricular fibrillation, or atrial fibrillation), myocardial necrosis, skin necrosis, ischaemia of the limbs or distal extremities, or secondary infections. The data were recorded every 6 hours for 48 hours, every 8 hours on days 3, 4 and 5 and once daily on days 6, 7, 14, 21 and 28: vital signs, non-invasive and invasive hemodynamic variables PICCO MONITORING: Cardiac Index-CI, Indexed Stroke Volume- SVI, MAP, MIXED VENOUS O2 SATURATION, Indexed Systemic Vascular Resistance- SVRI, O2 levels in arterial and mixed venous (or central venous) blood. Results Table 1 summarises the data of the cases enrolled. Table I10 ptsMale73%Age: Average±SD; range67.0±11.43;52-81Mortality in ICU1/10Length of stay in ICU24 (20-28) Conclusions Our results demonstrate how associating a continuous infusion of AVP with NA at a dosage between 0.01 and 0.04 IU / min reduces overall NE levels, improves patient outcome, reducing morbidity and mortality at 28 days. and allows us to optimize the amine descalation and ventilatory weaning times.

Ovarian cancer recurrence is frequent and associated with chemoresistance, leading to extremely poor prognosis. Herein, we explored the potential anti-cancer effect of a series of highly charged Ru(II)-polypyridyl complexes as photosensitizers in photodynamic therapy (PDT), which were able to efficiently sensitize the formation of singlet oxygen upon irradiation (Ru12+ and Ru22+) and to produce reactive oxygen species (ROS) in their corresponding dinuclear metal complexes with the Fenton active Cu(II) ion/s ([CuRu1]4+ and [Cu2Ru2]6+). Their cytotoxic and anti-tumor effects were evaluated on human ovarian cancer A2780 cells both in the absence or presence of photoirradiation, respectively. All the compounds tested were well tolerated under dark conditions, whereas they switched to exert anti-tumor activity following photoirradiation. The specific effect was mediated by the onset of programed cell death, but only in the case of Ru12+ and Ru22+ was preceded by the loss of mitochondrial membrane potential soon after photoactivation and ROS production, thus supporting the occurrence of apoptosis via type II photochemical reactions. Thus, Ru(II)-polypyridyl-based photosensitizers represent challenging tools to be further investigated in the identification of new therapeutic approaches to overcome the innate chemoresistance to platinum derivatives of some ovarian epithelial cancers and to find innovative drugs for recurrent ovarian cancer.

Purpose: The coronavirus disease 2019 (COVID-19) pandemic forced hospitals to adopt tighter restrictions, the most impacting is no access to visitors. Disorder of consciousness (DOC) due to severe acquired brain injury is a condition needing neurorehabilitation and the role of relatives is essential, hence besides physical "disconnection" digital "re-connection" is crucial. We aimed to assess whether digital communication benefits in patients with DOC, considering the sensorial and emotional deprivation due to the COVID-19 emergency lock-down.Methods: For eleven consecutive patients with DOC admitted to our Intensive Neurorehabilitation Care (mean age: 45; females: 9), two observers registered neurobehavioral changes during a video-calls with their relatives. Heart-rate variability was measured before and during the calls. The video-call was performed by using two displays of different sizes: tablet (T-video-call) and large screen (LS-Video-call).Results: The video-calls impacted on the patients' vigilance and in the relationship with relatives. Moreover, positively impacted on their relatives. The current results showed significant greater impact on patients during the LS-video-call than when they are exposed to T-video-call.Conclusions: During the COVID-19 pandemic, besides the physical disconnection to stop the contagion spread, a "digital re-connection" is needed for all and especially for fragile population groups as patients with DOC.

Background There are few data comparing the relative effectiveness of the individual β-lactams. Objectives To quantify the reduced effectiveness, defined as switching to a different antibiotic being prescribed for the same indication, among new users of β-lactam antibiotics in primary care. Methods A retrospective cohort study was conducted using the Health Search Database, an Italian primary care data source. Patients newly prescribed with β-lactams for a specific indication between 1 January 2013 and 31 December 2017 were identified. A switch to a different antibiotic for the same indication occurring during a 30day follow-up was the study outcome. Cox regression was adopted to assess the risk of switching between the different β-lactams. Results Among 178 256 patients newly treated with β-lactam antibiotics, 1172 (0.65%) switched to a different antibiotic. Amoxicillin/clavulanate (co-amoxiclav: n = 104 891) and amoxicillin (n = 21 699) were the most frequently prescribed β-lactams. The other antibiotics showed significantly higher risk of switching when compared with co-amoxiclav for lower respiratory tract [e.g. ceftriaxone, hazard ratio (HR): 1.6, 95% CI: 1.2–2.0], dental [e.g. amoxicillin, HR: 4.2, 95% CI: 2.9–5.9], and middle ear infections [e.g. amoxicillin, HR: 1.8, 95% CI: 1.1–2.7]. The same results were gathered when parenteral formulations were excluded. Conclusions The prevalence of reduced effectiveness of newly prescribed β-lactam antibiotics was lower than 1%. Specifically, the rate of switch to another antibiotic, when it was prescribed to treat low respiratory tract, dental, and middle ear infections, was lower among users of co-amoxiclav than those prescribed with other β-lactams.

The transdermal delivery of drugs and, in more general terms, of active principles can be performed by iontophoresis and/or by electroporation. The advantages of a local treatment vs. other drugs intake methods are well known as it reduces the systemic involvement and therefore the systemic contraindications. To perform the treatment exploiting the electroporation effect there is nowadays a specific variant of a known medical device used in physiotherapy: the Medium Frequency Resistive/Capacitive contact Diathermy. The adoption of a power control exploiting Pulse Width Modulation of the applied current adds to the device also this capability of great potential in rehabilitation and aesthetic medicine treatments. The theoretic approach is discussed and applications suggestions are being given.

Purpose Older patients with brain metastases (BM) are often excluded from clinical trials. The aim of our study was to investigate the outcomes following Gamma Knife radiosurgery (GKRS) in young old (65–74 years) and very old (≥75 years) patients with BM. Methods Between October 2012 and October 2018, we treated 89 patients aged ≥65 years with GKRS. Patients were divided in two group: young old (YO) and very old (VO) patients. At baseline G8, Graded Prognostic Assessment (DS-GPA) and Basic Score for Brain Metastases (BSBM) were assessed for all patients. Survival analysis was estimated using the Kaplan-Meier (KM) method. Cox regression model was used to investigate the influence of significant factors on KM. Results Median age at the time of GKRS was 72.2 years (range 65–87). A mean of 2.52 lesions were treated per patient (range 1–14). Median overall survival (OS) for YO and VO patients was 14.2 and 15.7 months, respectively. At univariate analysis, there were no significant differences in OS between the two age groups. A high BSBM (p ≤ .0001) and a high DS-GPA score (p = .0069) were associated with longer survival. A low DS-GPA score was the most powerful independent factor for predicting short survival (HR 1.76, 95% CI 1.25–2.46, p = .001) at multivariate analysis. Conclusion GKRS is a safe approach to treat BM in elderly patients. DS-GPA score represents an important prognostic factor for survival in elderly patients undergoing GKRS.

Malgré le développement exponentiel du crowdfunding, la mobilisation de la foule pour financer un projet peut représenter un défi lorsqu’il s’agit d’une organisation temporaire comme un festival. Mobilisant la théorie du signal, cette recherche étudie les facteurs clés du succès des campagnes de crowdfunding pour les festivals à partir d’un échantillon de 368 observations. Si les résultats obtenus montrent des similitudes avec ceux observés dans d’autres secteurs concernant les informations liées aux projets, ils mettent également en évidence des spécificités du crowdfunding culturel dans le choix des projets à financer.

Impulsive-compulsive behaviors (ICB) are over-represented in Parkinson's disease (PD) patients. Neurons in the ventral subthalamic nucleus (STN) might play a predominant role in the modulation of impulsivity. We characterized the firing regularity of 742 subthalamic neurons from 24 PD patients (12 ICB+ and 12 ICB-) in an OFF medication state. We computed the firing regularity in the dorsal and ventral STN regions, and we compared their performance in discriminating ICB patients. Regularity of ventral neurons in ICB+ patients is higher and supports a significant discrimination between the two cohorts. These results substantiate a ventral location of neurons involved in impulsivity.

Background The proper identification of chronic migraine is one of the mainstays for general practitioners. This study therefore aims to assess the epidemiology and determinants of chronic migraine in primary care in Italy by testing five operational case definition algorithms. Methods Five case definition algorithms defining chronic migraine were developed to estimate the prevalence and incidence rate of chronic migraine in the Health Search database. For each algorithm, we conducted a nested case-control analysis to quantify the level of association between certain determinants and incident cases of chronic migraine. Results Considering a cohort of 1,091,032 patients (52% were females), the prevalence rate of chronic migraine increased from the first to the fifth case definition algorithm ranging from 0.03 to 0.28%. No 95% confidence interval overlapped the others, and every confidence interval reliably maintained 2% precision. Incidence rates showed a growing trend (0.008–0.056 per 100,000 person-years) as well. All case definition algorithms were able to capture sex (i.e. female) and nonsteroidal anti-inflammatory drug (NSAID) overuse as statistically significant determinants of incident cases of chronic migraine. Depression was associated with a statistically significant increase of incidence rate of chronic migraine only for two case definition algorithms. Conclusion Our findings show that prevalence and incidence rate of chronic migraine are underestimated when compared with current literature. On the other hand, we found acceptable correctness of chronic migraine definition in the light of the association with well-known determinants.

Background and purpose Rehabilitation plays a central role in stroke recovery. Besides conventional therapy, technological treatments have become available. The effectiveness and appropriateness of technological rehabilitation are not yet well defined; hence, research focused on different variables impacting recovery is needed. Results from the literature identified cognitive reserve (CR) as a variable impacting on the cognitive outcome. In this paper, the aim was to evaluate whether CR influences the motor outcome in patients after stroke treated with conventional or robotic therapy and whether it may influence one treatment rather than another. Methods Seventy-five stroke patients were enrolled in five Italian neurological rehabilitation centres. Patients were assigned either to a robotic group, rehabilitation by means of robotic devices, or to a conventional group, where a traditional approach was used. Patients were evaluated at baseline and after rehabilitation treatment of 6 weeks through the Action Research Arm Test (ARAT), the Motricity Index (MI) and the Barthel Index (BI). CR was assessed at baseline using the Cognitive Reserve Index (CRI) questionnaire. Results Considering all patients, a weak correlation was found between the CRI related to leisure time and MI evolution (r = 0.276; P = 0.02). Amongst the patients who performed a robotic rehabilitation, a moderate correlation emerged between the CRI related to working activities and MI evolution (r = 0.422; P = 0.02). Conclusions Our results suggest that CR may influence the motor outcome. For each patient, CR and its subcategories should be considered in the choice between conventional and robotic treatment.

Background The use of reclaimed dredged sediments as growing media may offer a profitable alternative to their disposal as a waste and at the same time meets the need of peat-substitute substrates in horticulture. When sediments are reused to cultivate food crops, issues related to human health rise due to potential accumulation of contaminants in the product. This pilot study aimed at verifying the suitability of a reclaimed dredged port sediment, used pure or mixed with peat, as a growing medium for lettuce cultivation. Results The pure sediment caused a reduction in crop yield, probably due to its unsuitable physical properties, whereas the mixture sediment-peat and pure peat resulted in the same yield. Although the sediment contained potentially phytotoxic heavy metals and some organic pollutants, no symptoms of plant toxicity were noted. Besides, no organic contaminants were detected in lettuce heads, and heavy metals amounts were not hazardous for consumers. Conversely, plants grown in the sediment were particularly rich in minerals like Ca, Mg and Fe, and showed higher concentrations of organic acids and antioxidants. Conclusion The use of the sediment as a growing medium for lettuce was shown to be safe for both inorganic and organic contaminants. Nevertheless, considering crop yield results, the mixture of the sediment with other materials is recommended in order to produce a substrate with more suitable physicochemical properties for vegetable cultivation. © 2019 Society of Chemical Industry.

This paper presents an original multidisciplinary (geological-structural-geomorphological and seismological) study aimed at investigating the origin of diffused seismic damages affecting several ancient buildings in the Roman port city of Ostia. We also evaluate the possibility to relate these damages to a previously hypothesized ENE-WSW trending fault, bordering the morphological height upon which the Ostia town was founded. Aimed at this scope, we performed seismic noise measures (by using 14 seismic stations) that show no significantly different response and lack of significant ground motion differential amplifications. The coexistence of (i) no local geological heterogeneities and (ii) low amplification of spectral ratios in the recorded seismic signals seems to exclude that the observed seismic damage may be the consequence of significant site effects. When also the large distance from the strongest Apennine’s seismogenic source areas is considered, the possibility that the observed damage may be the consequence of local events should be considered. We discuss the potentiality of the ENE-WSW trending fault as the source of the observed seismic damages, highlighting the supporting evidence as well as the uncertainties of such interpretation.

Background Although very common in Western countries, poor epidemiological data on diverticular disease (DD) is available from the family practice. Aims To evaluate the behavior of Italian General Practitioners (GPs) on approaching DD. Methods Health Search Database was analyzed retrospectively. Results On a population of 975,523 individuals, 33,597 patients had a registered diagnosis of DD (“lifetime” prevalence = 3.4%, M = 3.2%, F = 3.7%; higher values are found in females over-65 years old; low rates of complications: diverticulitis = 0.3%, bleeding = 0.002%). As risk factors, NSAIDs and ASA were taken by 14.8% and 26.5% respectively, opioids by 7.5%, corticosteroids by 5.2%; as protective factors, 30.4% were under statins and 17.7% under calcium-antagonists. Approximately 13% of patients were referred to specialists. Colonoscopy and abdominal CT were prescribed to 48.5% and to 13% of already diagnosed patients. Among DD sufferers, 27% experienced hospitalization, but only 3.4% of cases were for a DD-linked problem. Treatment included rifaximin (61%), mesalazine (14.7%), probiotics (12.4%), ciprofloxacin (7.6%). Conclusion DD has a large impact in general practice with a higher prevalence in the elderly. GPs are required to pay particular attention to risk factors both for disease development and for its complications in order to reduce the costs deriving from diagnostic procedures, referral and hospitalization.

A marine sediment phytoremediated and homogenized by landfarming was tested for its potential recycle as growing media in horticulture. Two strawberry cultivars, Camarosa and Monterey, were grown on remediated sediment alone (TS100), commercial peat/pumice based growing medium (TS0) and a mixture 1:1 in volume of sediment and peat (TS50). Chemical fertility and strawberry production and safety of produced food were monitored for three consecutive productive seasons on the same growing media. During the first year of cultivation, plants grown on sediment-based media showed a significantly lower biomass production and fruit yield compared with peat, mainly due to the sediment low fertility. In the subsequent two years, the plant re-cultivation improved the sediment structure and N mineralization, and on the third cultivation year both strawberry cultivars showed higher fruit productivity and no accumulation of potentially toxic trace metals. The produced fruits did non accumulate high concentrations of trace metals, and risk assessment showed no risks for human health related to the consumption of strawberry produced on sediment-based growing media. We concluded that a phytoremediated sediment could be recycled as an ingredient of soilless growing media for reducing the environmental impact of plant nursery production and posing no risks for human health. These results show that reclaimed sediments could be reconsidered as a component material category in the new EU regulation on fertilizers. (c) 2021 Elsevier B.V. All rights reserved.

Focal muscular vibration (FMV) is a non-invasive technique that showed positive effects on spasticity of the upper limb in stroke subjects but different protocols have been proposed so the studies are not comparable and, to date, it is not clear which muscles should be treated, agonist, or antagonist muscles to obtain the better result on spasticity. The objective of this study is to evaluate the effects on spasticity of FMV on the upper limb flexor spastic muscles compared to the effects of FMV on the upper limb extensor muscles in subacute stroke patients. We treated 28 subacute stroke patients (mean age 64.28±13.79) randomized into two groups: Group A and Group B. Group A was treated by applying FMV to the flexor muscles of the upper limb, while Group B was treated by applying FMV to the extensor muscles of the upper limb. The effects on spasticity were assessed by Modified Ashworth Scale (primary outcome) and the upper limb motor function by instrumental robotic outcomes; moreover, muscle strength and pain were evaluated using Motricity Index and Numerical Rating Scale, respectively (secondary outcomes). Patients were subjected to FMV for three consecutive days and were evaluated three times: before treatment (T0), after a week (T1) and after a month (T2) from the end of treatment. Within group, analysis showed statistically significant changes over time of the MAS at the three joints (shoulder, elbow and wrist) in both groups, but post-hoc analysis showed that, only in Group A, MAS was significantly lower at T2, when compared with T0 at the shoulder and elbow. NRS, significantly changed over time only in the Group B. Motricity Index, did not change over time neither in the Group A, nor in the Group B. No statistically significant differences were detected in the between group analysis. Regarding the instrumental robotic outcomes, we detected a statistically significant reduction of the time required to complete the task (Duration) in both group a T2. In conclusion, this study highlighted how the same treatment protocol can determine an improvement in muscle tone and in the Duration to perform a task, regardless of the muscles treated, while the pain improves if we treat the agonist muscles.

Although incidental brain meningiomas are becoming an increasingly common radiological finding, as yet their optimal management is still a major unknown. Numerous studies have been published on the natural course of such tumours in an attempt to understand their potential growth rate, but the choice of management strategy—whether to wait and see, or to opt for surgery or radiosurgery—must also take into account several other factors, namely the position, size and radiological appearance of the tumour; the age of the patient; and any undiscovered symptoms. From a radiological point of view, more than 63% of asymptomatic meningiomas will not grow in size. The radiological features associated with a low rate of tumour growth are the existence of calcifications and the absence of signs of surrounding oedema. However, because of their location and/or the risk of producing neurological deficits, some meningiomas, even small ones, need to be treated.

Background Impulsive-compulsive behaviors are common in Parkinson's disease (PD) patients. However, the basal ganglia dysfunctions associated with high impulsivity have not been fully characterized. The objective of this study was to identify the features associated with impulsive-compulsive behaviors in single neurons of the subthalamic nucleus (STN). Methods We compared temporal and spectral features of 412 subthalamic neurons from 12 PD patients with impulsive-compulsive behaviors and 330 neurons from 12 PD patients without. Single-unit activities were extracted from exploratory microrecordings performed during deep brain stimulation (DBS) implant surgery in an OFF medication state. Results Patients with impulsive-compulsive behaviors displayed decreased firing frequency during bursts and a larger fraction of tonic neurons combined with weaker beta coherence. Information carried by these features led to the identification of patients with impulsive-compulsive behaviors with an accuracy greater than 80%. Conclusions Impulsive-compulsive behaviors in PD patients are associated with decreased bursts in STN neurons in the OFF medication state. © 2021 International Parkinson and Movement Disorder Society.

Purpose: After regulatory restrictions for terfenadine and astemizole in ‘90s, only scarce evidence on proarrhythmic potential of antihistamines has been published. We evaluate the risk of ventricular tachyarrhythmia (VA) related to the use of individual antihistamines. Methods: A matched case-control study nested in a cohort of new users of antihistamines was conducted within the EU-funded ARITMO project. Data on 1997–2010 were retrieved from seven healthcare databases: AARHUS (Denmark), GEPARD (Germany), HSD and ERD (Italy), PHARMO and IPCI (Netherlands) and THIN (UK). Cases of VA were selected and up to 100 controls were matched to each case. The odds ratio (OR) of current use for individual antihistamines (AHs) was estimated using conditional logistic regression. Results: For agents largely used to prevent allergic symptoms, such as cetirizine, levocetirizine, loratadine, desloratadine and fexofenadine, we found no VA risk. A statistically significant, increased risk of VA was found only for current use of cyclizine in the pooled analysis (ORadj, 5.3; 3.6–7.6) and in THIN (ORadj, 5.3; 95% CI, 3.7–7.6), for dimetindene in GEPARD (ORadj, 3.9; 1.1–14.7) and for ebastine in GEPARD (ORadj, 3.3; 1.1–10.8) and PHARMO (ORadj, 4.6; 1.3–16.2). Conclusions: The risk of VA associated with a few specific antihistamines could be ascribable to heterogeneity in pattern of use or in receptor binding profile.

Cet article rend compte d’une etude d’evenement dont l’objectif est d’evaluer l’impact de l’accident nucleaire de Fukushima sur le cours des actions de l’ensemble de la filiere de production d’electricite en France. Trois groupes d’entreprises sont ainsi etudies : celles qui produisent de l’electricite d’origine non nucleaire, celles qui produisent de l’electricite d’origine nucleaire et celles qui participent a differents niveaux a la filiere de production d’electricite nucleaire. Il en ressort, d’une part, un effet de contagion sur l’ensemble de la filiere de production d’electricite d’origine nucleaire, avec des effets differencies selon la place des entreprises dans la filiere et, d’autre part, un effet de competition sur les societes productrices d’electricite renouvelable. Les enseignements de cette etude interessent aussi bien les acteurs intervenant sur les marches financiers que les entreprises du secteur de l’energie.

We retrospectively analyzed data from records of 48 patients (48 eyes) treated with gamma-knife (n = 18) or Ruthenium-106 brachytherapy (n = 30) for uveal melanoma, in our Ocular Oncology Unit between December 2013 and September 2019, with the aim to evaluate treatment outcomes, and incidence and risk factors for secondary glaucoma. Patients demographics and tumor characteristics at diagnosis were recorded. Follow-up data were collected regarding local tumor control, treatment complications, enucleation need, metastases occurrence and survival status. The median follow-up period was 33.7 months in the gamma-knife group and 26.2 months in the brachytherapy group. The mean tumor thickness, the largest basal diameter and the tumor volume were significantly higher in the gamma-knife group than in the brachytherapy group. The local tumor control rate was 100% in the brachytherapy group and 77.8% in the gamma-knife group. In the gamma-knife group, six patients were enucleated, no patient treated with brachytherapy underwent enucleation. The overall survival rate was 96.7% in the brachytherapy group and 94.44% in the gamma-knife group. Secondary glaucoma occurred in 10 patients after gamma-knife and in one patient after brachytherapy: it should be emphasized that larger lesions were treated with gamma-knife, whereas smaller tumors were selected for brachytherapy. We found a significative correlation of tumor thickness (P value = 0.043) and volume (P value = 0.040) with secondary glaucoma occurrence after gamma-knife treatment. Moreover, secondary glaucoma significantly correlated with radiation retinopathy in the gamma-knife group (P value = 0.009). This study shows preliminary clinical results that could be useful for further studies with more patients and longer follow-up.

The multidimensional prognostic index (MPI) is a sensitive and specific prognosis estimation tool that accurately predicts all-cause mortality in frail older patients. It has been validated to assess the risk of 1-month to 2-year mortality in frail older patients during hospitalization and after hospital discharge. However, whether the MPI is a valid prognostic tool for follow-up periods of different lengths remains to be validated. To this end, we followed up 80 hospitalized patients (female=37, male 43) at least 75 years of age (mean age=82.6±4.4, range=75-94 years) to assess the 3-month all-cause mortality (mean follow-up=61.0 ± 31.7 months [range 4-90 days]). Accordingly, patients were subdivided into low (MPI-1, score 0-0.33), moderate (MPI-2, score 0.34-0.66) and high (MPI-3, score 0.67-1) mortality risk classes. Moreover, baseline biochemical, inflammatory and metabolic parameters, as well as anamnestic and clinical characteristics, were obtained. Although the MPI-3 score was significantly associated with 3-month all-cause mortality in univariate analysis (HR=5.79, 95%CI=1.77-18.92, p=0.004), a multivariate model indicated that only low albumin (HR=0.33, 95%CI=0.16-0.68, p=0.003) and high IL6 (HR=1.01, 95%CI=1.00-1.02, p=0.010) levels were significantly associated with 3-month all-cause mortality. In conclusion, we suggest that measurement of IL6 as well as albumin, rather than the MPI score, may help in providing tailored therapeutic interventions to decrease short term mortality in older hospitalized individuals.

This Letter to the Editor is in response to Stevens and colleagues, who presented a study about pupillometry in patients with traumatic brain injury. They did not find any correlation between pupil diameter and intracranial pressure. We agree with the clinical importance of pupil assessment and we would like to suggest the application of transorbital ultrasound for this evaluation. This approach has been proposed in the past and, with our work, we show the possible quantification of symmetry of pupil diameter variation in response to a stimulus. This approach may represent a proficient and safe method for patients' supervision.

Background The majority of stroke survivors experiences significant hand impairments, as weakness and spasticity, with a severe impact on the activity of daily living. To objectively evaluate hand deficits, quantitative measures are needed. The aim of this study is to assess the reliability, the validity and the discriminant ability of the instrumental measures provided by a robotic device for hand rehabilitation, in a sample of patients with subacute stroke. Material and methods In this study, 120 patients with stroke and 40 controls were enrolled. Clinical evaluation included finger flexion and extension strength (using the Medical Research Council, MRC), finger spasticity (using the Modified Ashworth Scale, MAS) and motor control and dexterity during ADL performance (by means of the Frenchay Arm Test, FAT). Robotic evaluations included finger flexion and extension strength, muscle tone at rest, and instrumented MAS and Modified Tardieu Scale. Subjects were evaluated twice, one day apart, to assess the test-retest reliability of the robotic measures, using the Intraclass Correlation Coefficient (ICC). To estimate the response stability, the standard errors of measurement and the minimum detectable change (MDC) were also calculated. Validity was assessed by analyzing the correlations between the robotic metrics and the clinical scales, using the Spearman’s Correlation Coefficient (r). Finally, we investigated the ability of the robotic measures to distinguish between patients with stroke and healthy subjects, by means of Mann-Whitney U tests. Results All the investigated measures were able to discriminate patients with stroke from healthy subjects (p Discussion Finger strength (in both flexion and extension) and muscle tone, as provided by a robotic device for hand rehabilitation, are reliable and sensitive measures. Moreover, finger strength is strongly correlated with clinical scales. Changes higher than the obtained MDC in these robotic measures could be considered as clinically relevant and used to assess the effect of a rehabilitation treatment in patients with subacute stroke.

In this paper, we present archaeological evidence of seismic damage in the ancient Roman town of Ostia and we perform structural analysis on damaged buildings based on the application of the principles of arch mechanics, in order to provide an objective means to identify the seismogenic origin of the observed ruptures and collapses. We combine a review of literature reports on possible earthquake damages affecting the ancient structures with field investigations, aimed at selecting representative cases in which collapse modalities can be traced back and the seismic origin evidenced. Nine cases of failure affecting masonry structures are analysed, illustrating the collapse dynamics through the virtual arches model. Using this method we also reconstruct tentative collapse vectors for the analysed cases, highlighting iso-oriented, prevalent horizontal components, indicative of earthquake-induced ruptures.

The first synthesis of highly enantioenriched [4.3.3]propelladienes is reported. The novel bridged bicyclo[3.3.0] dienes were applied as steering ligands in the rhodium-catalyzed asymmetric arylation of cyclic enones. The catalytic system showed high catalytic activity, and the 1,4-adducts were obtained in good to excellent yields (46-99%) with enantioselectivities up to 96% ee.

From easily available aminopyran and aminooxepane derivatives and 2,5-bis(trifluoromethyl)phenyl isothiocyanate the corresponding thiourea derivatives were prepared. One compound was further modified by introducing a tertiary amino group. The four catalysts were then examined as catalysts in a Michael addition of acetylacetone to β-nitrostyrene. A 1:1 mixture of one of these thioureas with an (S)-prolinol derivative was also tested as catalyst, but no synergetic effect was found. The best yield achieved was 88% and the highest ee amounted to 39%. In a preliminary experiment, the aldol reaction of acetone with isatin was investigated. One catalyst provided the expected aldol product in low yield, but in excellent enantioselectivity.

Background The use of high heels is widespread in modern society in professional and social contests. Literature showed that wearing high heels can produce injurious effects on several structures from the toes to the pelvis. No studies considered shoe length as an impacting factor on walking with high heels. Research question The aim of this study is to evaluate walking parameters in young healthy women wearing high heels, considering not only the heel height but also the foot/shoe size. Methods We evaluate spatio-temporal, kinematic and kinetic data, collected using a 8-camera motion capture system, in a sample of 21 healthy women in three different walking conditions: 1) barefoot, 2) wearing 12 cm high heel shoes independently from shoe size, and 3) wearing shoes with heel height based on shoe size, keeping the ankles’ plantar flexion angle constant. The main outcome measures were: spatio-temporal parameters, gait harmony measurement, range of motion, flexion and extension maximal values, power and moment of lower limb joints. Results Comparing the three walking conditions, the Mixed Anova test, showed significant differences between both high heeled conditions (variable and constant height) and barefoot in spatio-temporal, kinematic and kinetic parameters. Significance Regardless of the shoe size, both heeled conditions presented a similar gait pattern and were responsible for negative effects on walking parameters. Considering our results and the relevance of the heel height, further studies are needed to identify a threshold, over which it is possible to observe that wearing high heels could cause harmful effects, independently from the foot/shoe size.

Summary Analyses of healthcare data from 30 million individuals in three countries showed that current use of bisphosphonates may be associated with a small increased risk of cardiac valvulopathy (vs. those not exposed within the previous year), although confounding cannot be entirely ruled out. The observed tendency for decreased valvulopathy risk with cumulative duration of bisphosphonate use >6 months may even indicate a protective effect with prolonged use. Further studies are still needed to evaluate whether bisphosphonates increase or decrease the risk of valvulopathy. Introduction A signal of cardiac valve disorders with use of bisphosphonates was identified in the literature and EudraVigilance database, which contains reports of suspected adverse drug reactions from worldwide sources. The aim of this study was to evaluate the association using population-based healthcare data. Methods This was a case-control study among users of bisphosphonates and other drugs for osteoporosis in six healthcare databases covering over 30 million individuals in Italy, Netherlands and the UK from 1996 to 2012. Prescriptions/dispensations were used to assess drug exposure. Newly diagnosed cases of cardiac valvulopathy were identified via disease codes/free-text search. Controls were matched to each case by age, sex, database and index date. Adjusted odds ratios (ORs) were estimated using conditional logistic regression for the pooled data and meta-analysis of individual database risk estimates. Results A small but statistically significant association was found between exposure to bisphosphonates as a class and risk of valvulopathy. Overall risk was 18 % higher (95 % CI 12–23 %) in those currently exposed to any bisphosphonate (mainly alendronate and risedronate) vs. those not exposed within the previous year. Risk of valve regurgitation was 14 % higher (95 % CI 7–22 %). Decreased valvulopathy risk was observed with longer cumulative duration of bisphosphonate use, compared to use of less than 6 months. Meta-analyses of database-specific estimates confirmed results from pooled analyses. Conclusions The observed increased risks of cardiac valvulopathy with bisphosphonate use, although statistically significant, were quite small and unlikely to be clinically significant. Further studies are still needed to evaluate whether bisphosphonates increase or decrease the risk of valvulopathy and to investigate possible mechanisms for the association. Electronic supplementary material The online version of this article (doi:10.1007/s00198-015-3441-2) contains supplementary material, which is available to authorized users.

Background: It is increasingly acknowledged that the outcomes of medical treatments are influenced by the context of the clinical encounter through the mechanisms of the placebo effect. The phenomenon of placebo analgesia might be exploited to maximize the efficacy of neurorehabilitation treatments. Since its intensity varies across neurological disorders, the Italian Consensus Conference on Pain in Neurorehabilitation (ICCP) summarized the studies on this field to provide guidance on its use. Methods: A review of the existing reviews and meta-analyses was performed to assess the magnitude of the placebo effect in disorders that may undergo neurorehabilitation treatment. The search was performed on Pubmed using placebo, pain, and the names of neurological disorders as keywords. Methodological quality was assessed using a pre-existing checklist. Data about the magnitude of the placebo effect were extracted from the included reviews and were commented in a narrative form. Results: 11 articles were included in this review. Placebo treatments showed weak effects in central neuropathic pain (pain reduction from 0.44 to 0.66 on a 0-10 scale) and moderate effects in postherpetic neuralgia (1.16), in diabetic peripheral neuropathy (1.45), and in pain associated to HIV (1.82). Moderate effects were also found on pain due to fibromyalgia and migraine; only weak short-term effects were found in complex regional pain syndrome. Confounding variables might have influenced these results. Clinical implications: These estimates should be interpreted with caution, but underscore that the placebo effect can be exploited in neurorehabilitation programs. It is not necessary to conceal its use from the patient. Knowledge of placebo mechanisms can be used to shape the doctor-patient relationship, to reduce the use of analgesic drugs and to train the patient to become an active agent of the therapy. Background: It is increasingly acknowledged that the outcomes of medical treatments are influenced by the context of the clinical encounter through the mechanisms of the placebo effect. The phenomenon of placebo analgesia might be exploited to maximize the efficacy of neurorehabilitation treatments. Since its intensity varies across neurological disorders, the Italian Consensus Conference on Pain in Neurorehabilitation (ICCP) summarized the studies on this field to provide guidance on its use. Methods: A review of the existing reviews and meta-analyses was performed to assess the magnitude of the placebo effect in disorders that may undergo neurorehabilitation treatment. The search was performed on Pubmed using placebo, pain, and the names of neurological disorders as keywords. Methodological quality was assessed using a pre-existing checklist. Data about the magnitude of the placebo effect were extracted from the included reviews and were commented in a narrative form. Results: 11 articles were included in this review. Placebo treatments showed weak effects in central neuropathic pain (pain reduction from 0.44 to 0.66 on a 0-10 scale) and moderate effects in postherpetic neuralgia (1.16), in diabetic peripheral neuropathy (1.45), and in pain associated to HIV (1.82). Moderate effects were also found on pain due to fibromyalgia and migraine; only weak short-term effects were found in complex regional pain syndrome. Confounding variables might have influenced these results. Clinical implications: These estimates should be interpreted with caution, but underscore that the placebo effect can be exploited in neurorehabilitation programs. It is not necessary to conceal its use from the patient. Knowledge of placebo mechanisms can be used to shape the doctor-patient relationship, to reduce the use of analgesic drugs and to train the patient to become an active agent of the therapy.

Background and aims Despite management guidelines advocating statin/ezetimibe use in very high cardiovascular risk (CV) conditions, adherence to this therapy is still suboptimal and LDL-C target attainment unsatisfactory. We aimed to investigate the level of adherence to statin/ezetimibe and LDL-C target achievement rates in an unselected very high CV risk population in primary care setting in Italy. Methods We performed a retrospective population-based study using the Health Search IMS Health Longitudinal Patient Database (HSD), including adult patients at very high CV risk, newly treated with statin, ezetimibe or their combination, with 3 and 6 months of follow-up. Results Although the large majority of patients had previous major CV events (99.9%), only 61% and 55.14% resulted adherent (Proportion of Days Covered, PDC≥80%) after 3 and 6 months, respectively. High adherence entailed almost a three times higher probability to reach the therapeutic LDL-C target (3 months: OR = 2.26 [95% [CI]: 1.88 to 2.72]; 6-months: OR = 2.74 [95% CI: 2.27 to 3.31]). The odds to treat to LDL-C target was greater for simvastatin-ezetimibe fixed combination, simvastatin, atorvastatin and rosuvastatin, in decreasing order. Finally, poor adherence was slightly more prevalent among patients treated with less effective statins, and at both low and maximal dosage regimens. Conclusions This population-based study showed that adherence to statin therapy is poor even among patients who have already experienced a CV event. Failure to achieve recommended LDL-C levels appears imputable to the use of moderate doses and low to standard efficacy statins.

Hyacinthacines are members of the class of polyhydroxylated pyrrolizidines exhibiting outstanding biological activity as glycosidases inhibitors. Their structural complexity is embodied in the densely functionalized core, possessing a series of contiguous stereogenic centers. In this synthetic study we report a route to the more complex congeners of this class of alkaloids exploiting the diastereoselective addition of an axially chiral lithiated alkoxyallene to an enantiopure cyclic nitrone. Our stereodivergent approach enabled the installation of the targeted configuration at the ring A by minimal synthetic manipulations and at ring B by using stage dependent selective functionalizations. The versatility and robustness of this methodology were demonstrated by the syntheses of (−)-hyacinthacine B4 and of two epimers of (+)-hyacinthacine C5, allowing a suggestion of the likely structure of the isolated natural product.

Modern method contraceptive prevalence among married women in Nigeria has jumped to 16.0% in 2016 compared with

We present the design, manufacturing, test and performance of two image slicers for high resolution spectroscopy. Based on the classical Bowen-Walraven concept, our slicers allow to make two slices of the image of the input fibre. We introduce the idea of a second fibre that can be cropped in half to reach the same width of the science target fibre and that can be used for simultaneous wavelength reference. The slicers presented are mirror and prism based, respectively. Both devices work within expectation, showing differences mainly in their efficiency. The prism based slicer is the solution that was adopted for the FIDEOS spectrograph, an instrument built by the AIUC for the ESO 1m telescope of La Silla. Test spectra obtained with this instrument are included as examples of a real application of the device.

Background Metastatic meningiomas (MMs) are rare (0.1 of 100 cases). Their treatment requires a multimodal approach, with surgery, radiotherapy, chemotherapy, and radiosurgery, which allows a long-term local control (LC) and an extension of free survival. In this study, the authors performed a review of the literature and reported 2 cases of patients affected by extracranial MMs, with long-term follow-up. Case Description Case 1: A 48-year-old woman was admitted for resection of an extra-axial falx lesion (meningioma G1). After 2 years, the lesion got a local recurrence, resected with a histologic diagnosis of meningioma G3. During the next 9 years, the patient underwent 5 Gamma Knife radiosurgery (GKRS) procedures for local recurrence. At 56 years, she was readmitted for a surgical local recurrence (histologic definition: anaplastic meningioma G3). At the age of 62, the patient underwent a right lobectomy for a lung mass (histologic diagnosis: anaplastic meningioma G3). After that, multiple lesions at soma L5 and adrenal gland were discovered and then monitored. Case 2: A 48-year-old woman was operated for a lesion involving torcular herophili (meningioma G2). After 3 years, a local recurrence requires GKRS combined with tamoxifen. In the next 7 years, she underwent 5 GKRS procedures for local recurrence. The patient also underwent chemotherapy with octreotide. At the age of 61, she discovered multiple lesions in both lungs, liver, and kidney. A hepatic biopsy showed anaplastic meningioma G3. Also this patient does not suffer from any neurologic or clinical deficits. Conclusions LC in malignant meningioma is achievable through a multimodal approach; GKRS makes possible LC, but a novel aspect of these lesions is opened to discussion: the metastases. These reports show that multimodal treatment for MMs is an effective approach with good LC and improvement of overall survival. However, a long survival may allow systemic diffusion of the disease, in particular, when sagittal sinus is involved.