Health-related quality of life and functional changes in DMD:A 12-month longitudinal cohort study

Family caregivers of people with amyotrophic lateral sclerosis (ALS) live stressful lives in which they spend most of their time caring for their loved ones and managing difficult situations, thereby reducing the time spent in taking care of themselves. This situation may last several years. Previous literature has widely highlighted that this situation reduces caregivers' quality of life and increases their psychological distress and risk of health problems, but there is a lack of studies that focus on psychological interventions for these situations. This qualitative study examined a pilot experience of two mutual support groups for family caregivers of people with ALS. The aim was to identify caregivers' needs, the prominent aspects of their experience, and to understand whether and how this intervention strategy might help them. Six partners (four men and two women) and six adult children (five women and one man) participated in the groups, which were conducted in northern Italy. After the support groups finished, participants underwent semi-structured interviews. The authors conducted a content analysis of the transcripts of the interviews and the 20 group sessions. The thematic areas identified were "caregiving," "being the son/daughter of a person with ALS," "being the partner of a person with ALS," "group experience" and "group evaluation." The caregiving experience was profoundly different depending on whether the caregiver was a son/daughter or a partner of a patient with ALS. Moreover, comparison with peers and mutual support helped participants to better cope with ALS and its consequences, to improve their care for their relatives and to overcome typical caregiver isolation. These results suggest the usefulness of involving communities in caregiver support in order to create new networks and activate personal and social resources for well-being

Economic consequences of investing in anti-HCV antiviral treatment from the Italian NHS perspective : a real-world-based analysis of PITER data

OBJECTIVE: We estimated the cost consequence of Italian National Health System (NHS) investment in direct-acting antiviral (DAA) therapy according to hepatitis C virus (HCV) treatment access policies in Italy. METHODS: A multistate, 20-year time horizon Markov model of HCV liver disease progression was developed. Fibrosis stage, age and genotype distributions were derived from the Italian Platform for the Study of Viral Hepatitis Therapies (PITER) cohort. The treatment efficacy, disease progression probabilities and direct costs in each health state were obtained from the literature. The break-even point in time (BPT) was defined as the period of time required for the cumulative costs saved to recover the Italian NHS investment in DAA treatment. Three different PITER enrolment periods, which covered the full DAA access evolution in Italy, were considered. RESULTS: The disease stages of 2657 patients who consecutively underwent DAA therapy from January 2015 to December 2017 at 30 PITER clinical centres were standardized for 1000 patients. The investment in DAAs was considered to equal €25 million, €15 million, and €9 million in 2015, 2016, and 2017, respectively. For patients treated in 2015, the BPT was not achieved, because of the disease severity of the treated patients and high DAA prices. For 2016 and 2017, the estimated BPTs were 6.6 and 6.2 years, respectively. The total cost savings after 20 years were €50.13 and €55.50 million for 1000 patients treated in 2016 and 2017, respectively. CONCLUSIONS: This study may be a useful tool for public decision makers to understand how HCV clinical and epidemiological profiles influence the economic burden of HCV

Vertebral fractures in patients on dialysis : a clinically relevant problem with insufficient investigation

Sir, Chronic kidney disease mineral and bone disorder (CKD-MBD), previously denominated renal osteodystrophy [1], is a major clinical problem, with increasing prevalence and adverse outcomes, including high bone turnover associated with secondary hyperparathyroidism, low bone turnover or adynamic bone disease, cardiovascular calcifications and bone fractures. The impact of such outcomes on patient morbidity and mortality has not been fully elucidated. We would like to point out a poorly investigated subject, which we feel is of great clinical importance: .

MoVES: a Framework for Parallel and Distributed Simulation of Wireless Vehicular Ad Hoc Networks

In this paper, we illustrate a Mobile Wireless Vehicular Environment Simulation (MoVES) framework for the parallel and distributed simulation of vehicular wireless ad hoc networks (VANETs). The proposed framework supports extensible, module-based and layered modeling, and scalable, accurate and efficient simulation of vehicular scenarios integrated with wireless communication and mobile services/applications. The vehicular layer includes models for vehicles, synthetic and trace-driven mobility, driver behavior, GPS-based street maps, intersection policies and traffic lights. The wireless communication layer currently includes models for physical propagation, and a network protocol stack including IEEE 802.11 Medium Access Control, up to the Application layer. MoVES provides a platform for microscopic modeling and simulation-based analysis of wireless vehicular scenarios and communication-based services and applications, like Intelligent Transportation Systems, communication-based monitoring/control and info-mobility services. The framework includes design solutions for scalable, accurate and efficient parallel and distributed simulation of complex, vehicular communication scenarios executed over cost-effective, commercial-off-the-shelf (COTS) simulation architectures. Dynamic model partition and adaptation-based load balancing solutions have been designed by exploiting common assumptions and model characteristics, in a user-transparent way. Test-bed performance evaluation for realistic scenarios has shown the effectiveness of MoVES in terms of simulation efficiency, scalability, adaptation and simulation accuracy

Alnus glutinosa (L.) Gaertn. and Alnus cordata (Loisel) Duby as new sources of safe cosmetic and pharmacological anti-melanogenic agents

The genus Alnus (Betulaceae) comprises many species with a long history in traditional medicines. The crude extracts and isolated compounds from Alnus species exhibit a wide spectrum of in vitro and in vivo pharmacological activities (1). Phytochemical investigations revealed the presence of diarylheptanoids, a class of natural products typically found in Alnus genus with two aryl groups joined by a heptane chain in the main skeleton that have drawn attention due to their multiple biological properties and their therapeutic potential (2). A previous study reported that oregonin and other structurally analogous diarylheptanoids isolated from the bark of A. hirsuta showed inhibitory effects on melanogenesis in B16 melanoma cells.(3). Nowadays the discovery of new whitening agents from natural sources is increasing, due to the weak effectiveness and unwanted side effects of currently available compounds. In this context, the aim of this study was to evaluate the skin whitening capabilities of crude extracts (80% aqueous MeOH) obtained from the fresh bark of Alnus glutinosa (L.) Gaertn. and Alnus cordata (Loisel) Duby, an endemic species in the Mediterranean areas (4). As tyrosinase is the rate-limiting enzyme in melanin biosynthesis, the inhibitory effects of A. glutinosa and A. cordata extracts (AGE and ACE, respectively) on mushroom tyrosinase activity were preliminary evaluated. In addition, the anti-melanogenic ability of AGE and ACE was further investigated on the pigmentation of early stage zebrafish at 72 hours post fertilization (hpf) to find new skin whitening agents without cytotoxic concerns. Results of the enzymatic assay showed that ACE was capable to inhibit dose dependently L-DOPA oxidation catalyzed by tyrosinase (IC50 = 77.44 \ub1 0.54 \u3bcg/mL) as compared to the reference inhibitor kojic acid (2.24 \ub1 0.18 \u3bcg/mL). Unlike, AGE exhibited a lower anti-tyrosinase activity (100 \u3bcg/mL reached 28% of inhibition while higher doses showed pro-oxidative effects). Moreover, the zebrafish in vivo assay revealed that ACE (50 \u3bcg/mL) has equivalent inhibitory effects on the pigmentation (76.57%) to that of phenylthiourea (PTU, 30 \u3bcg/mL), used as the reference inhibitor (77.80%), as compared to control, while they did not affect the embryos development and survival. Conversely, the depigmenting effects of AGE were about 10 fold less than ACE (45.28% at 500 \u3bcg/mL). A mild anti-melanogenic activity was also evidenced for the diarylheptanoid oregonin (10% of inhibition at 20 \u3bcg/mL). A preliminary phytochemical screening evidenced that ACE and AGE have a high phenolic content (399.27 \ub1 14.30 and 534.17 \ub1 20.60 mg GAE/g of extract, respectively). However, despite AGE showed the highest phenolic content, the quali-quantitative RP-HPLC-DAD analysis highlighted as it is predominantly composed by oregonin (418.45 \u3bcg/mg of AGE vs 1.23 \u3bcg/mg of ACE) that exhibited a mild anti-melanogenic activity both in vitro and in vivo assays. Further phytochemical investigations are still in progress to identify the bioactive compounds of ACE as to be considered a potential candidate for the treatment of skin disorders due to its bleaching properties and favorable safety profiles

Friction and lubrication of pleural tissues

The frictional behaviour of rabbit\u2019s visceral pleura sliding against parietal pleura was assessed in vitro while oscillating at physiological velocities and amplitudes under physiological normal forces. For sliding velocities up to 3 cm s 121 and normal compressive loads up to 12 cm H2O, the average value of the coefficient of kinetic friction (\u3bc) was constant at 0.019\ub10.002 (S.E.) with pleural liquid as lubricant. With Ringer-bicarbonate solution, \u3bc was still constant, but significantly increased (\u394\u3bc=0.008\ub10.001; P < 0.001). Under these conditions, no damage of the sliding pleural surfaces was found on light and electron microscopy. Additional measurements, performed also on peritoneum, showed that changes in nominal contact area or strain of the mesothelia, temperature in the range 19\u201339 \ub0C, and prolonged sliding did not affect \u3bc. Gentle application of filter paper increased \u3bc 10-fold and irreversibly, suggesting alteration of the mesothelia. With packed the red blood cells (RBC) between the sliding mesothelia, \u3bc increased appreciably but reversibly on removal of RBC suspension, whilst no ruptures of RBC occurred. In conclusion, the results indicate a low value of sliding friction in pleural tissues, partly related to the characteristics of the pleural liquid, and show that friction is independent of velocity, normal load, and nominal contact area, consistent with boundary lubrication

Development of various forms of lung injury with increasing tidal volume in normal rats

Background: Mechanical ventilation (MV) with large tidal volumes (VT) causes lung edema, mechanical alterations, tissue lesions, and release of inflammatory markers. Objective: The aim of the present study is to explore the dependence of these events on tissue strain-stress. Methods: Sixty-three, normal, open-chest, normal rats were ventilated for 2-4 hours with VT from 7.5 (baseline ventilation) to 39.5ml\uf0d7kg-1 and PEEP ~2.5cmH2. Arterial blood gasses and mean pressure, and lung mechanics were measured during baseline ventilation before and after test ventilation, when cytokine, von Willebrand Factor (vWF), and albumin concentration in serum and broncho-alveolar lavage fluid (BALF), lung wet-to-dry ratio (W/D), and histologic injury scores were assessed. Main results: Elevation of W/D and serum vWF and cytokine concentration occurred with VT>25ml\uf0d7kg-1 and peak inflation pressure (Ppeak) >25cmH2O, whereas with VT>30ml\uf0d7kg-1 and Ppeak>30cmH2O, cytokine and albumin concentration increased also in BALF, arterial oxygen tension decreased, and lung mechanics and histology deteriorated, while W/D and serum vWF and cytokine concentration increased further. Conclusions: In normal rats, lung injury occurs once a definite volume and/or pressure threshold is overcome. Microvascular stress-strain failure leading to interstitial edema is the initial manifestation of injurious MV, as shown by elevated vWF and cytokine levels in serum only. Failure of the epithelial barrier with alveolar flooding occurs only at higher stress-strain levels, with inflammatory reaction, mechanical and histologic damage proportional to the concomitant edema formation