Demand for the quality conservation of Venice, Italy, according to different nationalities.

This paper focuses on visitor demand for the quality conservation of Venice according to different nationalities. The vast majority of visitors to Venice are foreigners (both tourists and day-visitors) who come from all over the world. In this research they are mainly categorized as non-Italian Europeans or non-Europeans. A specific theoretical model, in which quality conservation is provided publicly and also privately through donations, is presented for nationals and for foreigners. The data are obtained from a contingent valuation survey carried out in Venice, the aim of which was to estimate visitors' willingness to donate (WTD) to the Venice flood defence programme. Demand functions are estimated by applying a twostage regression model. The authors show that the majority of visitors are willing to donate. On average, Italians and non-Europeans would donate more than non-Italian Europeans. As expected, these visitor categories have different mean WTD and different behavioural functions which are affected by attitudinal and economic variables. Bequest value is the main donation motive. Those who identify this as a donation motive, on average, state the highest WTD and the highest degree of certainty to donate. This result seems to confirm empirically the validity of the sustainable development principle applied to the management of Venice as a cultural tourist site

Acute inactivation of the medial forebrain bundle imposes oscillations in the SNr: a challenge for the 6-OHDA model?

It has been recently shown that the substantia nigra pars reticulata (SNr) of 6-hydroxydopamine (6-OHDA)-lesioned rats, under urethane anaesthesia, manifests a prominent low frequency oscillation (LFO) of around 1Hz, synchronized with cortical slow wave activity (SWA). Nevertheless, it is poorly understood whether these electrophysiological alterations are correlated only with severe dopamine depletion or may also play a relevant pathogenetic role in the early stages of the dopamine denervation. Hence, here we recorded SNr single units and electrocorticogram (ECoG) in two models of dopamine denervation: (i) acute dopamine denervated rats, obtained by injection of tetrodotoxin (TTX), (ii) chronic dopamine depleted rats, 2 weeks after 6-OHDA lesioning. Both TTX and 6-OHDA were infused into the medial forebrain bundle (MFB). The acute TTX-mediated dopamine depletion caused a fast developing occurrence of a SNr/ECoG coherence, peaking between 0.48 and 1.22 Hz, parallel with a consistent decrease of firing rate (from 22.61 \ub1 7.04 to 15.35 \ub1 9.04 Hz) homolateraly to the infusion. Strikingly, this abnormal 1 Hz synchronization, TTX-mediated was qualitatively similar to the ECoG/SNr synchronization detectable in the 6-OHDA lesioned hemisphere (LH). In addition, TTX infusion in the un-lesioned hemispheres (UH) of 6-OHDA treated rats, produced ECoG/SNr synchronization qualitatively similar to that recordable in the LH. Hence, our data support the proposition that LFO, is tightly correlated to cortex, and represent a critical hallmark of a basal ganglia (BG) failure from the early stages of dopamine denervation

Successful subthalamic stimulation, but levodopa-induced dystonia, in a genetic Parkinson's disease

Recently, it is under scrutiny the possibility to anticipate the stereotactic implantation of the subthalamic nucleus (STN) even in relatively mild Parkinson's disease (PD) patients with an unsatisfying response to drugs. In addition, it is debated whether levodopa (LD) and deep brain stimulation (DBS) are congruent or, instead, mutually exclusive. A 56-year-old LRRK2-positive PD patient, with 7 years of disease history, dominated by severe left resting tremor, was submitted to bilateral implantation of the subthalamic nucleus (STN). Before surgery, the combination of LD and dopamine agonists failed to handle tremor unless administered at doses, which induced undesirable adverse events. STN deep brain stimulation (DBS) abolished tremor but did not provide satisfying control of hypokinetic-rigid symptoms. The condition STIM-ON plus LD, albeit transiently beneficial, installed a painful dystonia developing slowly after 24-36 h. Only a chronic therapy combining rotigotine plus STN-DBS proved effective without side effects. This case report, based upon the surprising difference between the therapeutic response to the combination of LD and dopamine agonist (before surgery) and the combination of DBS and agonist after surgery, emphasizes how STIM and LD target different motor domains through mechanisms with differential plasticity and confirms the efficacy of STN-DBS in LRKK2 patient

Four-Step Co-Designing of the Reablement Strategies Targeting Sarcopenia (ReStart-S): An Exercise-Based Multicomponent Program for Older Adults Residing in Long-Term Care Settings

Prabal Kumar,1 Shashikiran Umakanth,2 Emanuele Marzetti,3,4 Sanjay Kalra,5,6 Girish N1 1Department of Physiotherapy, Manipal College of Health Professions, Manipal Academy of Higher Education, Manipal, Karnataka, India; 2Department of Medicine, Dr. TMA Pai Hospital, Manipal Academy of Higher Education, Manipal, Karnataka, India; 3Fondazione Policlinico Universitario “Agostino Gemelli” IRCCS, Rome, Italy; 4Department of Geriatrics, Orthopedics and Rheumatology, Università Cattolica Del Sacro Cuore, Rome, Italy; 5Department of Endocrinology, Bharti Hospital, Karnal, India; 6University Center for Research & Development, Chandigarh University, Mohali, IndiaCorrespondence: Girish N, Department of Physiotherapy, Manipal College of Health Professions, Manipal Academy of Higher Education, Manipal, Karnataka, India, Tel +91 9886782114, Email [email protected]; [email protected]: The prevalence of sarcopenia is concerningly high in long-term care settings (LTCS); yet, no exercise programs specifically targeting older adults living in residential care are available.Objective: The goal of the present study was to co-design and validate a program named Reablement Strategies targeting Sarcopenia (ReStart-S) for older long-term care residents.Design: Cross-sectional study with an exploratory phase.Settings: LTCS in Udupi, Karnataka, India.Participants: Sarcopenic older adults diagnosed using Asian Working Group for Sarcopenia 2019 criteria.Material and Methods: The program was designed using a four-step intervention mapping technique involving systematic progression after completing each step. The steps included 1) identifying the appropriate exercise-based intervention for sarcopenia, 2) determining objectives and expected outcomes, 3) seeking expert views through a Delphi consensus approach, and 4) assessing the feasibility of ReStart-S program among older adults living in LTCS.Results: A comprehensive literature review appraised existing exercise programs for managing sarcopenia. A workshop held with six older adults and one caretaker, decided on morning exercise sessions, recommended 2– 7 days/week. The results of the review and workshop were compiled for the Delphi process that had seven experts from 5 countries, achieving a 71% response rate after four rounds. In the last step, a pilot study on eight LTCS residents, two males and six females with a mean age of 78.3 ± 8.3 years, was conducted and the program was found to be feasible.Conclusion: The ReStart-S program for managing sarcopenia among older adults residing in LTCS incorporates evidence from the literature and the engagement of older adults, caregivers, and experts, making it a contextually appropriate intervention. Our study also provides researchers and healthcare professionals insight into co-designing an intervention program for vulnerable older adults. Finally, the program evaluation indicates that a full-scale trial testing the efficacy of the ReStart-S program is feasible.Keywords: reablement, sarcopenia, intervention mapping, older adults, long-term care setting

Diet enrichment with a specific essential free amino acid mixture improves healing of undressed wounds in aged rats

Chronic wounds are a major, often underestimated, health problem for the elderly. Standard wound care products are not usuallymanufactured tomeet the increased demand of nutrients by skin cells in order to regenerate new tissue and accelerate healing. This work was therefore undertaken to establish whether wound healing could be accelerated by nutritional supplementation with a specific mixture tailored to human need of essential amino acids (EAAs) without topical medication. To this end, using a skin full-thickness excisional model in aged rats,we compared the closure dynamics of undressing wounds in animals fed an EAAs-enriched diet or standard diet. We assessed the degree of fibrosis and inflammation, as well as relevant signaling molecules such as COL1A1, iNOS and TGFβ1. The results showed wound healing was accelerated in EAAs-fed rats, which was accompanied by reduced inflammation and changes in TGFβ1 and COL1A1 expression. Collectively, our findings indicate that dietary supplementation with balanced EAAs diet could serve as a strategy to accelerate wound healing without inducing fibrosis and could therefore be a simple but pivotal therapeutic approach in human also

Skeletal Muscle Apoptotic Signaling Predicts Thigh Muscle Volume and Gait Speed in Community-Dwelling Older Persons: An Exploratory Study

Preclinical studies strongly suggest that accelerated apoptosis in skeletal myocytes may be involved in the pathogenesis of sarcopenia. However, evidence in humans is sparse. In the present study, we investigated whether apoptotic signaling in the skeletal muscle was associated with indices of muscle mass and function in older persons.Community-dwelling older adults were categorized into high-functioning (HF) or low-functioning (LF) groups according to their short physical performance battery (SPPB) summary score. Participants underwent an isokinetic knee extensor strength test and 3-dimensional magnetic resonance imaging of the thigh. Vastus lateralis muscle samples were obtained by percutaneous needle biopsy and assayed for the expression of a set of apoptotic signaling proteins. Age, sex, number of comorbid conditions and medications as well as knee extensor strength were not different between groups. HF participants displayed greater thigh muscle volume compared with LF persons. Multivariate partial least squares (PLS) regressions showed significant correlations between caspase-dependent apoptotic signaling proteins and the muscular percentage of thigh volume (R(2) = 0.78; Q(2) = 0.61) as well as gait speed (R(2) = 0.81; Q(2) = 0.56). Significant variables in the PLS model of percent muscle volume were active caspase-8, cleaved caspase-3, cytosolic cytochrome c and mitochondrial Bak. The regression model of gait speed was mainly described by cleaved caspase-3 and mitochondrial Bax and Bak. PLS predictive apoptotic variables did not differ between functional groups. No correlation was determined between apoptotic signaling proteins and muscle strength or quality (strength per unit volume).Data from this exploratory study show for the first time that apoptotic signaling is correlated with indices of muscle mass and function in a cohort of community-dwelling older persons. Future larger-scale studies are needed to corroborate these preliminary findings and determine if down-regulation of apoptotic signaling in skeletal myocytes will provide improvements in the muscle mass and functional status of older persons

Disease activity and damage in juvenile idiopathic arthritis: Methotrexate era versus biologic era

Objective: To compare the long-term disease state, in terms of activity and damage, of children with juvenile idiopathic arthritis (JIA) who had their disease onset in methotrexate (MTX) or biologic eras. Methods: Patients were included in MTX or biologic era cohort depending on whether their disease presentation occurred before or after January 2000. All patients had disease duration 65 5 years and underwent a prospective cross-sectional assessment, which included measurement of disease activity and damage. Inactive disease (ID) and low disease activity (LDA) states were defined according to Wallace, JADAS10, and cJADAS10 criteria. Articular and extraarticular damage was assessed with the Juvenile Arthritis Damage Index (JADI). Results: MTX and biologic era cohorts included 239 and 269 patients, respectively. Patients were divided in the "functional phenotypes" of oligoarthritis and polyarthritis. At cross-sectional visit, patients in the biologic era cohort with either oligoarthritis or polyarthritis had consistently higher frequencies of ID and LDA by all criteria. The measurement of disease damage at cross-sectional visit revealed that the frequency of impairment of > 1 JADI-Articular items was higher in MTX than in biologic era cohort (17.6% versus 11% in oligoarthritis and 52.6% versus 21.8% in polyarthritis). Likewise, frequency of involvement of > 1 JADI-Extraarticular items was higher in the MTX than in the biologic era cohort (26.5% versus 16.2% in oligoarthritis and 31.4% versus 13.5% in polyarthritis). Conclusion: Our study provides evidence of the remarkable outcome improvement obtained with the recent therapeutic advance in JIA