692 research outputs found

    Poor Outcome in a Mitochondrial Neurogastrointestinal Encephalomyopathy Patient with a Novel TYMP Mutation: The Need for Early Diagnosis.

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    Mitochondrial neurogastrointestinal encephalomyopathy (MNGIE) is a devastating autosomal recessive disorder due to mutations in TYMP, which cause loss of function of thymidine phosphorylase (TP), nucleoside accumulation in plasma and tissues and mitochondrial dysfunction. The clinical picture includes progressive gastrointestinal dysmotility, cachexia, ptosis and ophthalmoparesis, peripheral neuropathy and diffuse leukoencephalopathy, which usually lead to death in early adulthood. Therapeutic options are currently available in clinical practice (allogeneic hematopoietic stem cell transplantation and carrier erythrocyte entrapped TP therapy) and newer, promising therapies are expected in the near future. However, successful treatment is strictly related to early diagnosis. We report on an incomplete MNGIE phenotype in a young man harboring the novel heterozygote c.199 C>T (Q67X) mutation in exon 2, and the previously reported c.866 A>C (E289A) mutation in exon 7 in TYMP. The correct diagnosis was achieved many years after the onset of symptoms and unfortunately, the patient died soon after diagnosis because of multiorgan failure due to severe malnutrition and cachexia before any therapeutic option could be tried. To date, early diagnosis is essential to ensure that patients have the opportunity to be treated. MNGIE should be suspected in all patients who present with both gastrointestinal and nervous system involvement, even if the classical complete phenotype is lacking

    Sustaining Economic Exploitation of Complex Ecosystems in Computational Models of Coupled Human-Natural Networks

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    Understanding ecological complexity has stymied scientists for decades. Recent elucidation of the famously coined "devious strategies for stability in enduring natural systems" has opened up a new field of computational analyses of complex ecological networks where the nonlinear dynamics of many interacting species can be more realistically mod-eled and understood. Here, we describe the first extension of this field to include coupled human-natural systems. This extension elucidates new strategies for sustaining extraction of biomass (e.g., fish, forests, fiber) from ecosystems that account for ecological complexity and can pursue multiple goals such as maximizing economic profit, employment and carbon sequestration by ecosystems. Our more realistic modeling of ecosystems helps explain why simpler "maxi-mum sustainable yield" bioeconomic models underpinning much natural resource extraction policy leads to less profit, biomass, and biodiversity than predicted by those simple models. Current research directions of this integrated natu-ral and social science include applying artificial intelligence, cloud computing, and multiplayer online games

    A survey experiment on information, inattention and online privacy

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    Personal data lie at the forefront of different business models and constitute the main source of revenue of several online companies. In many cases, consumers may have incomplete information or may be inattentive about the digital transactions of their data. This paper investigates whether highlighting positive or negative aspects of online privacy policies, thereby mitigating the informational problem, can affect consumers’ privacy actions and attitudes. Results of an online survey experiment indicate that participants adopt a more conservative stance on disclosing sensitive and identifiable information, even when positive attitudes of companies towards their privacy are made salient, compared to when privacy is not mentioned. On the other hand, they do not change their attitudes and social actions towards privacy. These findings suggest that privacy behavior is not necessarily sensitive to exposure to objective threats or benefits of disclosing personal information. Rather, people are inattentive and their dormant privacy concerns may manifest only when consumers are asked to think about privacy.publishersversionpublishe

    Reinforced feedback in virtual environment for rehabilitation of upper extremity dysfunction after stroke: preliminary data from a randomized controlled trial.

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    OBJECTIVES: To study whether the reinforced feedback in virtual environment (RFVE) is more effective than traditional rehabilitation (TR) for the treatment of upper limb motor function after stroke, regardless of stroke etiology (i.e., ischemic, hemorrhagic). DESIGN: Randomized controlled trial. Participants. Forty-four patients affected by stroke. Intervention. The patients were randomized into two groups: RFVE (N = 23) and TR (N = 21), and stratified according to stroke etiology. The RFVE treatment consisted of multidirectional exercises providing augmented feedback provided by virtual reality, while in the TR treatment the same exercises were provided without augmented feedbacks. Outcome Measures. Fugl-Meyer upper extremity scale (F-M UE), Functional Independence Measure scale (FIM), and kinematics parameters (speed, time, and peak). RESULTS: The F-M UE (P = 0.030), FIM (P = 0.021), time (P = 0.008), and peak (P = 0.018), were significantly higher in the RFVE group after treatment, but not speed (P = 0.140). The patients affected by hemorrhagic stroke significantly improved FIM (P = 0.031), time (P = 0.011), and peak (P = 0.020) after treatment, whereas the patients affected by ischemic stroke improved significantly only speed (P = 0.005) when treated by RFVE. CONCLUSION: These results indicated that some poststroke patients may benefit from RFVE program for the recovery of upper limb motor function. This trial is registered with NCT01955291

    Intraspecific functional trait response to advanced snowmelt suggests increase of growth potential but decrease of seed production in snowbed plant species

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    In ecological theory, it is currently unclear if intraspecific trait responses to environmental variation are shared across plant species. We use one of the strongest environmental variations in alpine ecosystems, i.e., advanced snowmelt due to climate warming, to answer this question for alpine snowbed plants. Snowbeds are extreme habitats where long-lasting snow cover represents the key environmental factor affecting plant life. Intraspecific variation in plant functional traits is a key to understanding the performance and vulnerability of species in a rapidly changing environment. We sampled snowbed species after an above-average warm winter to assess their phenotypic adjustment to advanced snowmelt, based on differences in the natural snowmelt dynamics with magnitudes reflecting predicted future warming. We measured nine functional traits related to plant growth and reproduction in seven vascular species, comparing snowbeds of early and late snowmelt across four snowbed sites in the southern Alps in Italy. The early snowbeds provide a proxy for the advanced snowmelt caused by climatic warming. Seed production was reduced under advanced snowmelt in all seed-forming snowbed species. Higher specific leaf area (SLA) and lower leaf dry matter content (LDMC) were indicative of improved growth potential in most seed-forming species under advanced snowmelt. We conclude, first, that in the short term, advanced snowmelt can improve snowbed species’ growth potential. However, in the long term, results from other studies hint at increasing competition in case of ongoing improvement of conditions for plant growth under continued future climate warming, representing a risk for snowbed species. Second, a lower seed production can negatively affect the seed rain. A reduction of propagule pressure can be crucial in a context of loss of the present snowbed sites and the formation of new ones at higher altitudes along with climate warming. Finally, our findings encourage using plant functional traits at the intraspecific level across species as a tool to understand the future ecological challenges of plants in changing environments

    Electrospinning and characterisation of silk fibroin/wool keratin blends

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    Fibroin (degummed silk) and keratin are structural biopolymers respectively from silkworm filaments and from hair, wool, feathers, nails and horns. They are candidate materials for biomediacal applications because they have several useful properties including good biocompatibility and biodegradability. Many works deal about the electrospinning of silk fibroin solutions, but few works deal about the electrospinning of keratin in blend with other polymers; moreover, keratin hasn’t been previously electrospun as pure polymer

    Efficacy and safety of pharmacological interventions for managing sickle cell disease in children and adolescents: protocol for a systematic review with network meta-analysis

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    IntroductionSickle cell disease (SCD), an inherited haemoglobinopathy, has important impact on morbidity and mortality, especially in paediatrics. Previous systematic reviews are limited to adult patients or focused only on few therapies. We aim to synthesise the evidence on efficacy and safety of pharmacological interventions for managing SCD in children and adolescents.Methods and analysisThis systematic review protocol is available at Open Science Framework (doi:10.17605/OSF.IO/CWAE9). We will follow international recommendations on conduction and report of systematic reviews and meta-analyses. Searches will be conducted in PubMed, Scopus and Web of Science (no language nor time restrictions) (first pilot searches performed in May 2022). We will include randomised controlled trials comparing the effects of disease-modifying agents in patients with SCD under 18 years old. Outcomes of interest will include: vaso-occlusive crisis, haemoglobin levels, chest syndrome, stroke, overall survival and adverse events. We will provide a narrative synthesis of the findings, and whenever possible, results will be pooled by means of pairwise or Bayesian network meta-analyses with surface under the cumulative ranking curve analyses. Different statistical methods and models will be tested. Dichotomous outcomes will be reported as OR, risk ratio or HR, while continuous data will be reported as standard mean differences, both with 95% CI/credibility interval. The methodological quality of the trials will be evaluated using the Risk of Bias 2.0 tool, and the certainty of the evidence will be assessed with the Grading of Recommendations Assessment, Development and Evaluation approach.Ethics and disseminationThis study refers to a systematic review, so no ethics approval is necessary. We intent to publish our findings in international, peer-reviewed journal. Data will also be presented to peers in scientific events. Additionally, the results obtained in this study may contribute towards the update of therapeutic guidelines and for the development of health policies for SCD.PROSPERO registration numberCRD42022328471.</jats:sec

    Implications of a defined daily dose fixed database for drug utilization research studies: The case of statins in Portugal

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    Aims Given the discrepancies between PDDs (prescribed daily doses) and DDDs (defined daily doses), we aimed to assess the extent of error in the results of an 18-year population-level study on statin utilization in Portugal. Methods The Portuguese regulatory agency provided data for the period 2000-2018 on statin dispensing (C10AA). The DDDs were gathered from the ATC/DDD database. DDDs were calculated by the DDD year-by-year approach (DDDYEAR) and by the DDD last-year approach (DDDLAST). PDDs were calculated according to the year-by-year approach (PDDYEAR). Statin annual utilization rates per 1000 inhabitants per day were also calculated. Percent errors were calculated for PDDYEAR and DDDYEAR units. Results The DDDYEAR approach revealed decreases in the consumption of atorvastatin, fluvastatin, lovastatin, pravastatin and simvastatin in 2009, when their DDD was modified. Conversely, the results from both DDDLAST and PDDYEAR approaches indicated gradual changes in the actual consumption of all statins in Portugal. Before 2009, atorvastatin, pravastatin and simvastatin utilization was greatly overestimated by DDDYEAR/1000 inhabitants/day. The average dose of lovastatin prescribed in the past 18 years (20 mg) was below the assigned DDDs during the study period, varying from 30 mg to 45 mg. Conversely, the PDD for fluvastatin was above the DDD values (ranging from 40 mg in 2000 to 70 mg in 2016). For atorvastatin, pravastatin and simvastatin, national PDDs were above the assigned DDD until the DDD modification in 2009. Conclusions A more dynamic system, based on national and annually updated DDDs, should be able to reduce discrepancies between DDDs and PDDs and the bias in utilization studies

    In Vitro Production of Calcified Bone Matrix onto Wool Keratin Scaffolds via Osteogenic Factors and Electromagnetic Stimulus

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    Pulsed electromagnetic field (PEMF) has drawn attention as a potential tool to improve the ability of bone biomaterials to integrate into the surrounding tissue. We investigated the effects of PEMF (frequency, 75 Hz; magnetic induction amplitude, 2 mT; pulse duration, 1.3 ms) on human osteoblast-like cells (SAOS-2) seeded onto wool keratin scaffolds in terms of proliferation, differentiation, and production of the calcified bone extracellular matrix. The wool keratin scaffold offered a 3D porous architecture for cell guesting and nutrient diffusion, suggesting its possible use as a filler to repair bone defects. Here, the combined approach of applying a daily PEMF exposure with additional osteogenic factors stimulated the cells to increase both the deposition of bone-related proteins and calcified matrix onto the wool keratin scaffolds. Also, the presence of SAOS-2 cells, or PEMF, or osteogenic factors did not influence the compression behavior or the resilience of keratin scaffolds in wet conditions. Besides, ageing tests revealed that wool keratin scaffolds were very stable and showed a lower degradation rate compared to commercial collagen sponges. It is for these reasons that this tissue engineering strategy, which improves the osteointegration properties of the wool keratin scaffold, may have a promising application for long term support of bone formation in vivo
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