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The Ca2+-binding protein sorcin regulates intracellular calcium homeostasis and plays a role in the induction of drug resistance in human cancers. Recently, an 18 kDa mitochondrial isoform of sorcin was reported to participate in antiapoptosis in human colorectal cancer (CRC), but information remains lacking about the functional role of the more abundant 22 kDa isoform of sorcin expressed in CRC. We found the 22 kDa isoform to be widely expressed in human CRC cells, whether or not they were drug resistant. Its upregulation in drug-sensitive cells induced resistance to 5-fluorouracil, oxaliplatin, and irinotecan, whereas its downregulation sensitized CRC cells to these chemotherapeutic agents. Sorcin enhances the accumulation of Ca2+ in the endoplasmic reticulum (ER), preventing ER stress, and, in support of this function, we found that the 22 kDa isoform of sorcin was upregulated under conditions of ER stress. In contrast, RNAi-mediated silencing of sorcin activated caspase-3, caspase-12, and GRP78/BiP, triggering apoptosis through the mitochondrial pathway. Our findings establish that CRC cells overexpress sorcin as an adaptive mechanism to prevent ER stress and escape apoptosis triggered by chemotherapeutic agents, prompting its further investigation as a novel molecular target to overcome MDR. Cancer Res; 71(24); 7659–69. ©2011 AACR.

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Flow Energy Harvesters (FEHs), equipped with piezoelectric active layers, are designed to extract energy from non-pulsating flows. FEHs featuring cantilevers with tip-mounted Vibration Inducers (VIs) are designed to develop a galloping motion. In this paper, we present the modelling of a recently introduced VI shape, featuring semitubular-shaped winglets, which do not produce a wake interacting with the cantilever. Such peculiarity allows (i) to exploit the contribution of the wake to the formation of the lift, therefore opening to a more compact design; (ii) its performance to be analyzed by means of simple two-dimensional Computational Fluid Dynamics (CFD) simulations. By comparison with experimental data, we show that the minimal framework for the modelling of such new class of VIs needs to account for both the direct action of the fluid onto the cantilever and the drag on the VI, which are usually negligible for other VI shapes.

Aim of this study was to compare early clinical and hemodynamic outcomes of Intuity and ME bioprostheses. A propensity score weighting approach was performed. Preoperative variables were defined according to EuroSCORE criteria and postoperative complications according to VARC-2 definitions. We evaluated 375 patients who underwent SAVR with the 2 study devices. Intuity and ME were implanted in 252 (67.2%) and in 123 (32.8%) patients, respectively. There were no differences in terms of postoperative complications, including mortality (1% in each group; OR 0.46[0.05;4.21]). The incidence of pace-maker implantation was 6% and 5% in Intuity and ME groups, respectively (OR 0.53[0.27;1.07]). Intuity showed significantly lower gradients (Median mean gradients: 9mmHg vs 14mmHg, P0.001), larger effective orifice area index (1.13cm2/m2 vs 1cm2/m2, P=0.007) and lower incidence of patient-prosthesis mismatch (7.1% vs 22.8%, P=0.006). The RD Intuity provides similar early clinical outcomes but shows significantly better hemodynamic performance compared to the ME valve.

Vitamin D is known to modulate immune response and its deficiency was associated with respiratory distress in patients hospitalized for pneumonia. Nevertheless, numerous reviews on vitamin D in COVID-19 patients have shown conflicting results, as previously reported also for other respiratory diseases (e.g., influenza).This umbrella review aims to assess whether low serum 25-OHD is associated with susceptibility to COVID 19, their severity, and mortality. A total of 1559 studies were excluded after the title, abstract and full-text articles screening and 9 papers were included in this review: 2 systematic reviews and 7 metanalysis.The findings of this review that summarized studies from 5 WHO regions (European Region, Region of the Americas, South-East Asia Region, Eastern Mediterranean Region, Western Pacific Region) to exclusion only African region, show that low serum 25-OHD levels are associated with higher infection risks for COVID-19.Although the umbrella findings indicate a potential role of vitamin D deficiency in COVID-19 severity in hospitalized patients and showing an association between Vitamin D supplementation and COVID-19 severity, however, more robust data from randomized controlled trials are further needed to confirm a possible association with the mortality rates.

Background In Italy the Law 9/2012 prescribed the total closure of forensic psychiatric hospitals (OPGs) and the conversion to a care model based on residential units in the community employing only clinical personnel (Residenze per l'Esecuzione delle Misure di Sicurezza – REMS) and fully integrated in public mental health services. The aim of this study is to report sociodemographic, clinical and criminological characteristics of patients admitted in Volterra REMS since it opened on 01/12/15 up to 31/12/17. Methods Sociodemographic and clinical information was collected from official documents (clinical files, ward reports) and from patients' personal health records. Psychiatric diagnoses were made by REMS psychiatrists according to the DSM-5 criteria. Criminological information was obtained from patients' criminal records. Results Volterra REMS patients' characteristics are similar to those of samples of OPGs patients (unmarried socially disadvantaged males with an average age of 40, no offsprings, low education, high rates of Schizophrenia Spectrum Disorders and medical comorbidity). However, the REMS model presents a very high turnover rate: during the study period 61 patients were admitted while 32 were discharged. Being assisted by public mental health services before committing the crime increased the probability of discharge. In non-EU patients long acting injectable antipsychotics were used more frequently than in community ones. Substance-Related Disorders are the main psychiatric comorbidity and resulted as being more frequent in bipolar patients than in other patients. Conclusions Due to the high patients' turnover, we expect a progressive change in sociodemographic, clinical and criminological features of the REMS population. The REMS model provides a return for mentally disordered criminals to the care of local public mental health services which are recovering after many years some of their most challenging patients ensuring their deinstitutionalization and reintegration into society.

Abstract Time resolved PIV encompassing moving and/or deformable objects interfering with the light source requires the employment of dynamic masking (DM). A few DM techniques have been recently developed, mainly in microfluidics and multiphase flows fields. Most of them require ad-hoc design of the experimental setup, and may spoil the accuracy of the resulting PIV analysis. A new DM technique is here presented which envisages, along with a dedicated masking algorithm, the employment of fluorescent coating to allow for accurate tracking of the object. We show results from measurements obtained through a validated PIV setup demonstrating the need to include a DM step even for objects featuring limited displacements. We compare the proposed algorithm with both a no-masking and a static masking solution. In the framework of developing low cost, flexible and accurate PIV setups, the proposed algorithm is made available through a freeware application able to generate masks to be used by an existing, freeware PIV analysis package. Graphic abstract

The dynamics of unconfined gravity currents generated by a lock-exchange with different lock widths is considered. The gravity currents were generated by density differences caused by a salinity gradient and were realized both numerically and experimentally. Several runs were carried out in order to study the role played by the lock width in the current dynamics. Numerical simulations were performed with a new single-layer, 2D, shallow-water model, which accounts for the dilution of the gravity current due to the entrained ambient fluid. By the comparison between experimental and numerical results, the relevant role played by the entrainment in the propagation velocity of the front emerges, mainly for the cases with a narrow lock. The effect of the lock width on the current dynamics is also highlighted: the lock chocks the flow causing a localized loss of mechanical energy and a consequent deceleration of the flow. Results show that the smaller is the lock, the larger is the loss of energy.

In the field of sleep disorders, the quality of couple relationship is arousing increasing attention, given its implications for quality of life and treatment adherence. The aim of the present study was to evaluate relationship quality in a sample of treated or untreated patients with Obstructive Sleep Apnoea Syndrome. Eighty-seven patients were recruited in a hospital-based Centre for Sleep Medicine. Subjects were administered the Dyadic Adjustment Scale (DAS) to evaluate relationship quality, and the Epworth Sleepiness Scale (ESS). Apnoea-hypopnoea indexes (AHI) were collected through nocturnal polysomnography or home testing with a portable monitoring device. Although the DAS average scores were similar to local normative values, relationship quality was significantly lower in the untreated patients when compared with the ones treated. The ESS scores showed a negative correlation with many DAS scores, whereas no significant correlation emerged for AHI. Such data suggest a significant impact of perceived sleep apnoea symptoms on marital satisfaction, even though in the absence of striking differences between the whole sample and the general population.

The Lattice Boltzmann Method has been successfully applied to solve Multilayer Shallow Water models for the simulation of gravity currents generated by laboratory lock exchange experiments in regular geometries. When complex boundaries are to be modelled, several approaches are feasible. In this work two types of boundary conditions are analyzed and compared in the simulation of lock exchange gravity currents impacting on vertical obstacles. The first one belongs to the common group of bounce back approaches; the second one is an adaptation of the immersed boundary technique to the Shallow Water dynamics. The analysis is carried out comparing accuracy against experimental data. Efficiency is also taken into account. Results show that the computational overhead introduced by the Immersed Boundary technique is not counterbalanced by a gain in accuracy for the considered kind of obstacles.

A new front condition for gravity currents in a two-layer shallow water framework with a free surface is developed by applying the theory of the weak formulation to a first order system of four partial differential equations written in conservation form. The Rankine–Hugoniot jump conditions are applied and a relation between the velocity and the height of the shock is obtained. Laboratory experiments on lock-release non-Boussinesq gravity currents are performed and the front propagation and the free surface displacement are evaluated. Front velocities, predicted by the present mathematical model, are compared to both laboratory measurements and the predictions of the Benjamin formula, which is based on the rigid lid approximation. The new jump condition is in a good agreement with the laboratory measurements, while the Benjamin formula exhibits an overestimation of the shock velocity in the non-Boussinesq cases. In addition, the free surface displacement near the shock predicted by the new model is in agreement with the laboratory measurements.

SUMMARY In this paper the dynamics of a two-layered liquid, made of two immiscible shallow-layers of different density, has been investigated within the framework of the lattice Boltzmann method (LBM). The LBM developed in this paper for the two-layered, shallow-water flow has been obtained considering two separate sets of LBM equations, one for each layer. The coupling terms between the two sets have been defined as external forces, acted on one layer by the other. Results obtained from the LBM developed in this paper are compared with numerical results obtained solving the two-layered, shallow-water equations, with experimental and other numerical results published in literature. The results are interesting. First, the numerical results obtained by the LBM and by the shallow-water model can be considered as equivalent. Second, the LBM developed in this paper is able to simulate motion conditions on nonflat topography. Third, the agreement between the LBM (and also shallow-water model) numerical results and the experimental results is good when the evolution of the flow does not depend on the viscosity, that is, during the initial phase of the flow, dominated by gravity and inertia forces. When the viscous forces dominate the evolution of the flow the agreement between numerical and experimental results depends strongly on the viscosity; it is good if the numerical LBM viscosity has the same order of magnitude of the liquid's kinematic viscosity. Copyright © 2012 John Wiley & Sons, Ltd.

Background: Nevirapine (NVP) is a nonnucleoside reverse transcriptase inhibitor used in HIV patients and recently evaluated as a differentiating and antiproliferative agent in human malignancies. However, while NVP is a safe treatment in immunocompromised patients, NVP-containing regimens have been associated with severe immune-mediated toxicities in non-HIV individuals. Methods and Results: We describe the toxicity profile of single-agent NVP in 6 non-HIV cancer patients treated for a median period of 7.3 months (range 1–24), reporting only a reversible grade III increase in glutamyl transpeptidase and glutamic pyruvic transaminase serum values. Interestingly, NVP treatment correlates with either a decrease in CD8+ T cell counts or a parallel increase in CD4/CD8 ratio, antithyroglobulin and antithyroid peroxidase autoantibody titers. Conclusions: These results, although obtained in a small cohort of patients, suggest that the toxicity profile of single-agent NVP may be worth testing in a phase I/II study in non-HIV cancer patients and that NVP toxicity may depend on its capacity to trigger autoimmune responses in susceptible individuals.

This paper investigates the dynamics of lock-release gravity currents propagating upslope by laboratory experiments and shallow-water simulations. Both the interface between the dense and the ambient fluid and the instantaneous velocity field were measured by image analysis. Different runs were carried out by varying the initial density of the lock fluid and the bed upslope. As a gravity current moves upslope, the dense layer becomes thinner, and an accumulation region of dense fluid in the initial part of the tank occurs. The current speed decreases as the bed upslope increases, and for the highest up sloping angles, the gravity current stops before reaching the end of the tank. A new two-layer shallow-water model is developed and benchmarked against laboratory experiments. The present model accounts for the mixing between the two layers, the free surface, and the space-time variations of the density. The effect of the horizontal density gradient in the simulation of gravity currents is investigated by comparing the numerical results of both the present model and the model proposed by Adduce et al. [“Gravity currents produced by lock-exchange: Experiments and simulations with a two layer shallow-water model with entrainment,” J. Hydraul. Eng. 138, 111-121 (2012)] with laboratory measurements. The comparison shows that the present model reproduces both the current shape and the front position better than the Adduce et al. model, in particular, for gravity currents flowing up a slope. For these currents, the presence of a backflow near the lock is shown by the analysis of the streamwise depth-averaged velocity predicted by the present model and the velocity measured by particle image velocimetry as well.

In the last few years, not many studies on the use of robot-assisted therapy to recover hand function in acute stroke patients have been carried out. This randomized-controlled observer trial is aimed at evaluating the effects of intensive robot-assisted hand therapy compared with intensive occupational therapy in the early recovery phases after stroke with a 3-month follow-up. Twenty acute stroke patients at their first-ever stroke were enrolled and randomized into two groups. The experimental treatment was performed using the Amadeo Robotic System. Control treatment, instead, was carried out using occupational therapy executed by a trained physiotherapist. All participants received 20 sessions of treatment for 4 consecutive weeks (5 days/week). The following clinical scales, Fugl-Meyer Scale (FM), Medical Research Council Scale for Muscle Strength (hand flexor and extensor muscles) (MRC), Motricity Index (MI) and modified Ashworth Scale for wrist and hand muscles (MAS), were performed at baseline (T0), after 20 sessions (end of treatment) (T1) and at the 3-month follow-up (T2). The Barthel Index was assessed only at T0 and T1. Evidence of a significant improvement was shown by the Friedman test for the FM [experimental group (EG): P=0.0039, control group (CG): P

In the literature there are some case reports of hypoxemia due to right to left blood shunting [2–4]. Most causes of right to left shunting through a patent foramen ovale are attributed to right atrial pressure exceeding that of the left, forcing open a potentially patent foramen ovale. A patent foramen ovale is present in 25–30% of healthy subjects [5], and is responsible for a right to left shunt when pulmonary hypertension is present. In the absence of pulmonary hypertension there are three main pathophysiologic mechanisms [6]: extrinsic compression of the right atrium (right hydrothorax or a localized pericardial effusion) causing an increase in the right heart pressure; a decrease in the compliance of the right ventricle (due to right ventricle ischemia or after pneumonectomy); and an abnormal anatomic relationship between the vena cava and the atrial septum or an anatomic distortion of the heart with downward displacement of the right atrium due to the enlargement of the thoracic aorta with distortion of the position of the atrial septum relative to caval inflow and favouring interatrial flow.

Background. No strongly clinical evidence about the use of hand robot-assisted therapy in stroke patients was demonstrated. This preliminary observer study was aimed at evaluating the efficacy of intensive robot-assisted therapy in hand function recovery, in the early phase after a stroke onset.Methods. Seven acute ischemic stroke patients at their first-ever stroke were enrolled. Treatment was performed using Amadeo robotic system (Tyromotion GmbH Graz, Austria). Each participant received, in addition to inpatients standard rehabilitative treatment, 20 sessions of robotic treatment for 4 consecutive weeks (5 days/week). Each session lasted for 40 minutes. The exercises were carried out as follows: passive modality (5 minutes), passive/plus modality (5 minutes), assisted therapy (10 minutes), and balloon (10 minutes). The following impairment and functional evaluations, Fugl-Meyer Scale (FM), Medical Research Council Scale for Muscle Strength (hand flexor and extensor muscles) (MRC), Motricity Index (MI), and modified Ashworth Scale for wrist and hand muscles (AS), were performed at the beginning (T0), after 10 sessions (T1), and at the end of the treatment (T2). The strength hand flexion and extension performed by Robot were assessed at T0 and T2. The Barthel Index and COMP (performance and satisfaction subscale) were assessed at T0 and T2.Results. Clinical improvements were found in all patients. No dropouts were recorded during the treatment and all subjects fulfilled the protocol. Evidence of a significant improvement was demonstrated by the Friedman test for the MRC (P<0.0123). Evidence of an improvement was demonstrated for AS, FM, and MI.Conclusions. This original rehabilitation treatment could contribute to increase the hand motor recovery in acute stroke patients. The simplicity of the treatment, the lack of side effects, and the first positive results in acute stroke patients support the recommendations to extend the clinical trial of this treatment, in association with physiotherapy and/or occupational therapy.

The Ca2+-binding protein sorcin regulates intracellular calcium homeostasis and plays a role in the induction of drug resistance in human cancers. Recently, an 18 kDa mitochondrial isoform of sorcin was reported to participate in antiapoptosis in human colorectal cancer (CRC), but information remains lacking about the functional role of the more abundant 22 kDa isoform of sorcin expressed in CRC. We found the 22 kDa isoform to be widely expressed in human CRC cells, whether or not they were drug resistant. Its upregulation in drug-sensitive cells induced resistance to 5-fluorouracil, oxaliplatin, and irinotecan, whereas its downregulation sensitized CRC cells to these chemotherapeutic agents. Sorcin enhances the accumulation of Ca2+ in the endoplasmic reticulum (ER), preventing ER stress, and, in support of this function, we found that the 22 kDa isoform of sorcin was upregulated under conditions of ER stress. In contrast, RNAi-mediated silencing of sorcin activated caspase-3, caspase-12, and GRP78/BiP, triggering apoptosis through the mitochondrial pathway. Our findings establish that CRC cells overexpress sorcin as an adaptive mechanism to prevent ER stress and escape apoptosis triggered by chemotherapeutic agents, prompting its further investigation as a novel molecular target to overcome MDR. Cancer Res; 71(24); 7659–69. ©2011 AACR.

The simultaneous finding of submandibular ectopic thyroid tissue and functional orthotopic thyroid gland is an extremely rare event. The present report describes the case of a woman presenting with a left submandibular mass, distant from a palpable multinodular goitre. Ultrasonography showed an ovoidal solid mass adjacent to the lower margin of the left submandibular gland. Cytological specimens showed colloid material and thyroid follicular cells with no malignant features. A preoperative CT scan demonstrated a very thin connection between the thyroid and the submandibular mass. The patient underwent total thyroidectomy and excision of the submandibular mass. The histopathological diagnosis of the thyroid tissue was multinodular goitre, and the submandibular mass was ectopic thyroid tissue showing a hyperplastic pattern. The main differential diagnosis of the submandibular mass was a metastasis from a well differentiated cancer. This case illustrates that an ectopic thyroid off the midline may not necessarily be a metastasis from a thyroid cancer.

Patients suffering from Alzheimer’s disease, Parkinson disease with dementia, and diffuse cerebrovascular dementia show different features of cortical sources of resting state electroencephalographic (EEG) rhythms (Babiloni et al., 2004, 2011). Here, we tested the hypothesis that stroke patients are characterized by peculiar abnormalities of these rhythms. Resting state eyes-closed EEG data were recorded in 29 acute stroke, 29 Alzheimer’s disease, 29 mild cognitive impairment patients, and 29 cognitively intact elderly subjects. Stroke patients were age matched with the other groups, they showed a mild cognitive decline. EEG recordings were performed from the 20th to 30th days from the first ischemic or hemorrhagic acute event. LORETA was used for source estimation. Compared to the other groups, the stroke patients were characterized by a greater power of widespread cortical sources of delta (1–4 Hz) and theta (4–8 Hz) rhythms (p

TRAP1, a mitochondrial chaperone with antiapoptotic functions, is involved in drug-resistance in human CRC. TRAP1 is a component of the HSP90 mitochondrial survival pathway, which antagonizes the proapoptotic activity of cyclophilin D. Interestingly, novel agents are able to disassemble this pathway and are under clinical evaluation. GST-pulldown experiments and mass spectrometry assays led us to the identification of several TRAP1 ligands and, among others, Sorcin, a Ca2+-binding protein involved in the MDR phenotype of human tumors. We functionally characterized the cooperation between TRAP1 and Sorcin in favoring survival of CRC cells and investigated the expression levels of the two proteins in human CRCs. We demonstrated the mitochondrial localization of a 18kDa isoform of Sorcin that specifically interacts with TRAP1 in human CRC cells. The overexpression or down-regulation of Sorcin and/or TRAP1 allowed us to demonstrate a reciprocal regulation between the two proteins and to show that their interaction is required for Sorcin mitochondrial localization and TRAP1 protein stability. Furthermore, the upregulation of either TRAP1 and/or Sorcin induced resistance to 5-fluoruracil (FU), irinotecan (IRI) and oxaliplatin (l-OHP) in CRC cells. Of note, the knock-down of TRAP1 and/or Sorcin expression by siRNAs as well as the pharmacological inhibition of TRAP1 ATPase re-established a phenotype sensitive to FU, IRI and l-OHP. Consistently with these in vitro observations, gene expression analysis showed that TRAP1 and Sorcin are up-regulated, respectively, in 28/41 and 18/41 CRCs and a significant correlation between the expression of TRAP1 and the p22 isoform of Sorcin was observed (Sperman rank test p = 0.003; Kendal Tau test p = 0.003). Finally, the two proteins are also co-upregulated in CRC cells resistant to FU, IRI and l-OHP. Sorcin and TRAP1 are functionally linked in a survival network responsible for resistance to chemotherapy in CRCs. Thus, TRAP1 pathway deserves to be further evaluated as molecular target to overcome drug resistance in human CRC.