20 research outputs found
MambaFoley: Foley Sound Generation using Selective State-Space Models
No full textRecent advancements in deep learning have led to widespread use of techniques for audio content generation, notably employing Denoising Diffusion Probabilistic Models (DDPM) across various tasks. Among these, Foley Sound Synthesis is of particular interest for its role in applications for the creation of multimedia content. Given the temporal-dependent nature of sound, it is crucial to design generative models that can effectively handle the sequential modeling of audio samples. Selective State-Space Models (SSMs) have recently been proposed as a valid alternative to previously proposed techniques, demonstrating competitive performance with lower computational complexity. In this paper, we introduce MambaFoley, a diffusion-based model that, to the best of our knowledge, is the first to leverage the recently proposed SSM known as Mamba for the Foley sound generation task. To evaluate the effectiveness of the proposed method, we compare it with a state-of-the-art Foley sound generative model using both objective and subjective analyses
Dietary intakes in infertile women a pilot study
No full textAbstract Background The reproductive axis is closely linked to nutritional status. The purpose of this study was to compare the nutritional status in two groups of young infertile women, without clinically overt eating disorders: hypothalamic amenorrhea (HA) and polycystic ovary syndrome (PCOS). Methods Eighteen young infertile women (10 HA, 8 PCOS) attending an outpatient gynecological endocrinology unit, underwent evaluation of anthropometry, body composition, dietary intakes by means of a food frequency questionnaire (FFQ) and a seven-day food diary (7DD), and psychological characteristics by means of EDI2 and SCL90 tests. Results HA women had lower BMI and body fat compared to PCOS women. Habitual intake derived from FFQs showed a similar macronutrient distribution between groups (about 16% protein, 33% fat, 52% carbohydrates). The psychometric profiles of the two groups did not differ significantly. The underreporting of dietary intakes (measured as habitual energy intake by FFQs/basal metabolic rate) was found to be negatively correlated with the interpersonal sensitivity SCL-90 subscale scores (r = -0.54, p = 0.02). Conclusion Our study identified differences in body composition but not in dietary habits between HA and PCOS infertile women. We documented, for the first time, a relationship between the accuracy of dietary surveys and the psychological characteristics of subjects with anovulation. This finding suggests that it may be important to be aware of the psychological terrain when planning a dietary survey in infertile women.</p
Antiproliferative effect of ASC-J9 delivered by PLGA nanoparticles against estrogen-dependent breast cancer cells
No full textAmong polymeric nanoparticles designed for cancer therapy, PLGA nanoparticles have become one of the most popular polymeric devices for chemotherapeutic-based nanoformulations against several kinds of malignant diseases. Promising properties, including long-circulation time, enhanced tumor localization, interference with "multidrug" resistance effects, and environmental biodegradability, often result in an improvement of the drug bioavailability and effectiveness. In the present work, we have synthesized 1,7-bis(3,4-dimethoxyphenyl)-5-hydroxyhepta-1,4,6-trien-3-one (ASC-J9) and developed uniform ASC-J9-loaded PLGA nanoparticles of about 120 nm, which have been prepared by a single-emulsion process. Structural and morphological features of the nanoformulation were analyzed, followed by an accurate evaluation of the in vitro drug release kinetics, which exhibited Fickian law diffusion over 10 days. The intracellular degradation of ASC-J9-bearing nanoparticles within estrogen-dependent MCF-7 breast cancer cells was correlated to a time- and dose-dependent activity of the released drug. A cellular growth inhibition associated with a specific cell cycle G2/M blocking effect caused by ASC-J9 release inside the cytosol allowed us to put forward a hypothesis on the action mechanism of this nanosystem, which led to the final cell apoptosis. Our study was accomplished using Annexin V-based cell death analysis, MTT assessment of proliferation, radical scavenging activity, and intracellular ROS evaluation. Moreover, the intracellular localization of nanoformulated ASC-J9 was confirmed by a Raman optical imaging experiment designed ad hoc. PLGA nanoparticles and ASC-J9 proved also to be safe for a healthy embryo fibroblast cell line (3T3-L1), suggesting a possible clinical translation of this potential nanochemotherapeutic to expand the inherently poor bioavailability of hydrophobic ASC-J9 that could be proposed for the treatment of malignant breast cancer. © 2014 American Chemical Society
Cream formulation impact on topical administration of engineered colloidal nanoparticles.
No full textIn order to minimize the impact of systemic toxicity of drugs in the treatment of local acute and chronic inflammatory reactions, the achievement of reliable and efficient delivery of therapeutics in/through the skin is highly recommended. While the use of nanoparticles is now an established practice for drug intravenous targeted delivery, their transdermal penetration is still poorly understood and this important administration route remains almost unexplored. In the present study, we have synthesized magnetic (iron oxide) nanoparticles (MNP) coated with an amphiphilic polymer, developed a water-in-oil emulsion formulation for their topical administration and compared the skin penetration routes with the same nanoparticles deposited as a colloidal suspension. Transmission and scanning electron microscopies provided ultrastructural evidence that the amphiphilic nanoparticles (PMNP) cream formulation allowed the efficient penetration through all the skin layers with a controllable kinetics compared to suspension formulation. In addition to the preferential follicular pathway, also the intracellular and intercellular routes were involved. PMNP that crossed all skin layers were quantified by inductively coupled plasma mass spectrometry. The obtained data suggests that combining PMNP amphiphilic character with cream formulation improves the intradermal penetration of nanoparticles. While PMNP administration in living mice via aqueous suspension resulted in preferential nanoparticle capture by phagocytes and migration to draining lymph nodes, cream formulation favored uptake by all the analyzed dermis cell types, including hematopoietic and non-hematopoietic. Unlike aqueous suspension, cream formulation also favored the maintenance of nanoparticles in the dermal architecture avoiding their dispersion and migration to draining lymph nodes via afferent lymphatics
Population aging and the labor market : the case of Sri Lanka
No full textSri Lanka's population is predicted to age vary fast during the next 50 years, bringing a slowdown of labor force growth and after 2030its contraction. Based on a 2006 representative survey of old people in Sri Lanka, the paper examines labor market consequences of this process, focusing on retirement pathways and the determinants of labor market withdrawal. The paper finds that a vast majority of Sri Lankan old workers are engaged in the informal sector, work long hours, and are paid less than younger workers. Moreover, the paper shows that labor market duality carries over to old age: (i) previous employment is the most important predictor of the retirement pathway; (ii) older workers fall into two categories: civil servants and formal private sector workers, who generally stop working before they reach 60 because they are forced to do so by mandatory retirement regulations, and casual workers and the self-employed, who work until very old age (or death) due to poverty and insufficient income and who stop working primarily because of poor health; and (iii) the option of part-time work is used primarily by workers who held regular jobs in their prime age employment, but not by casual workers and self-employed.Labor Markets,Health Monitoring&Evaluation,Labor Policies,Work&Working Conditions,
High-sensitivity analysis of clonal hematopoiesis reveals increased clonal complexity of potential-driver mutations in severe COVID-19 patients
No full textWhether Clonal Hematopoiesis (CH) represents a risk factor for severity of the COVID-19 disease remains a controversial issue. We report the first high- sensitivity analysis of CH in COVID-19 patients (threshold of detection at 0.5% vs 1 or 2% in previous studies). We analyzed 24 patients admitted to ICU for COVID-19 (COV-ICU) and 19 controls, including healthy subjects and asymptomatic SARS-CoV2-positive individuals. Despite the significantly higher numbers of CH mutations identified (80% mutations with <2% variant allele frequency, VAF), we did not find significant differences between COV-ICU patients and controls in the prevalence of CH or in the numbers, VAF or functional categories of the mutated genes, suggesting that CH is not overrepresented in patients with COVID-19. However, when considering potential drivers CH mutations (CH-PD), COV-ICU patients showed higher clonal complexity, in terms of both mutation numbers and VAF, and enrichment of variants reported in myeloid neoplasms. However, we did not score an impact of increased CH-PD on patient survival or clinical parameters associated with inflammation. These data suggest that COVID-19 influence the clonal composition of the peripheral blood and call for further investigations addressing the potential long-term clinical impact of CH on people experiencing severe COVID-19. We acknowledge that it will indispensable to perform further studies on larger patient cohorts in order to validate and generalize our conclusions. Moreover, we performed CH analysis at a single time point. It will be necessary to consider longitudinal approaches with long periods of follow-up in order to assess if the COVID-19 disease could have an impact on the evolution of CH and long-term consequences in patients that experienced severe COVID-19
Treatment of low bone density in young people with cystic fibrosis: a multicentre, prospective, open-label observational study of calcium and calcifediol followed by a randomised placebo-controlled trial of alendronate.
No full textSummary Background Long-term complications of cystic fibrosis include osteoporosis and fragility fractures, but few data are available about effective treatment strategies, especially in young patients. We investigated treatment of low bone mineral density in children, adolescents, and young adults with cystic fi brosis. Methods We did a multicentre trial in two phases. We enrolled patients aged 5-30 years with cystic fi brosis and low bone mineral density, from ten cystic fi brosis regional centres in Italy. The fi rst phase was an open-label, 12-month observational study of the eff ect of adequate calcium intake plus calcifediol. The second phase was a 12-month, double-blind, randomised, placebo-controlled, parallel group study of the effi cacy and safety of oral alendronate in patients whose bone mineral apparent density had not increased by 5% or more by the end of the observational phase. Patients were randomly assigned to either alendronate or placebo. Both patients and investigators were masked to treatment assignment. We used dual x-ray absorptiometry at baseline and every 6 months thereafter, corrected for body size, to assess lumbar spine bone mineral apparent density. We assessed bone turnover markers and other laboratory parameters every 3-6 months. The primary endpoint was mean increase of lumbar spine bone mineral apparent density, assessed in the intention-totreat population. This study is registered with ClinicalTrials.gov, number NCT01812551. Findings We screened 540 patients and enrolled 171 (mean age 13.8 years, SD 5.9, range 5-30). In the observational phase, treatment with calcium and calcifediol increased bone mineral apparent density by 5% or more in 43 patients (25%). 128 patients entered the randomised phase. Bone mineral apparent density increased by 16.3% in the alendronate group (n=65) versus 3·1% in the placebo group (n=63; p=0.0010). 19 of 57 young people (33.3%) receiving alendronate attained a normal-for-age bone mineral apparent density Z score. In the observational phase, fi ve patients had moderate episodes of hypercalciuria, which resolved after short interruption of calcifediol treatment. During the randomised phase, one patient taking alendronate had mild fever versus none in the placebo group; treatment groups did not diff er signifi cantly for other adverse events. Interpretation Correct calcium intake plus calcifediol can improve bone mineral density in some young patients with cystic fi brosis. In those who do not respond to calcium and calcifediol alone, alendronate can safely and eff ectively increase bone mineral density. Funding Telethon Foundation (Italy)
Tempo das figuras: Agambem, Virno, Cacciari, Rella
No full textTese (doutorado) - Universidade Federal de Santa Catarina, Centro de Comunicação e Expressão, Programa de Pós-Graduação em Literatura, Florianópolis, 2009Este trabalho tem como objetivo analisar quatro figuras da crítica italiana contemporânea que antagonizam e protagonizam o debate sobre estética e política: Giorgio Agamben, Paolo Virno, Massimo Cacciari e Franco Rella. A análise passa, principalmente, pelos materiais esparsos produzidos a partir dos anos 1970 até a entrada do novo século, a fim de observar a montagem das categorias que movimentam as articulações desses pensamentos. Categorias que, carregadas de tempo e de ética, permitem chegar à hipótese de que o pensar filosófico e o fazer poético, artístico e crítico operam de maneira polarmente conjugada na inoperância constituída entre as quatro figuras, de modo a perceber que: pela profanação, Agamben monta as imagens que transitam entre as diversas disciplinas do saber e a arte; pela ambivalência, Virno rearticula a conduta da esquerda, a partir de considerações marxinianas; pelo paradoxo do pensamento, Cacciari explicita filosofia estética e filosofia política; pela noção de figura, Rella passeia pelas imagens da modernidade. Diante das divergências e das semelhanças há algo que os toca: a tarefa dada ao tempo
Antiproliferative Effect of ASC-J9 Delivered by PLGA Nanoparticles against Estrogen-Dependent Breast Cancer Cells
No full textAmong polymeric nanoparticles designed
for cancer therapy, PLGA
nanoparticles have become one of the most popular polymeric devices
for chemotherapeutic-based nanoformulations against several kinds
of malignant diseases. Promising properties, including long-circulation
time, enhanced tumor localization, interference with “multidrug”
resistance effects, and environmental biodegradability, often result
in an improvement of the drug bioavailability and effectiveness. In
the present work, we have synthesized 1,7-bis(3,4-dimethoxyphenyl)-5-hydroxyhepta-1,4,6-trien-3-one
(ASC-J9) and developed uniform ASC-J9-loaded PLGA nanoparticles of
about 120 nm, which have been prepared by a single-emulsion process.
Structural and morphological features of the nanoformulation were
analyzed, followed by an accurate evaluation of the in vitro drug release kinetics, which exhibited Fickian law diffusion over
10 days. The intracellular degradation of ASC-J9-bearing nanoparticles
within estrogen-dependent MCF-7 breast cancer cells was correlated
to a time- and dose-dependent activity of the released drug. A cellular
growth inhibition associated with a specific cell cycle G2/M blocking
effect caused by ASC-J9 release inside the cytosol allowed us to put
forward a hypothesis on the action mechanism of this nanosystem, which
led to the final cell apoptosis. Our study was accomplished using
Annexin V-based cell death analysis, MTT assessment of proliferation,
radical scavenging activity, and intracellular ROS evaluation. Moreover,
the intracellular localization of nanoformulated ASC-J9 was confirmed
by a Raman optical imaging experiment designed ad hoc. PLGA nanoparticles and ASC-J9 proved also to be safe for a healthy
embryo fibroblast cell line (3T3-L1), suggesting a possible clinical
translation of this potential nanochemotherapeutic to expand the inherently
poor bioavailability of hydrophobic ASC-J9 that could be proposed
for the treatment of malignant breast cancer
Registro Italiano Fibrosi Cistica : Rapporto 2011-2014 = Italian Cystic Fibrosis Registry : Report 2011-2014
No full textINTRODUCTION
The Italian Cystic Fibrosis Registry (ICFR) is based on a new agreement about the data flow towards the Registry signed on October, 4th 2016 by the Centre for Rare Diseases of the Italian National Institute of Health (NIH), the clinicians of the Italian National Referral and Support Centres for Cystic Fibrosis, the Paediatric Hospital "Bambino Gesu" (Rome), the Italian Cystic Fibrosis Society, and the Italian League for Cystic Fibrosis.
OBJECTIVES
The aim of the present Report is to improve the knowledge on cystic fibrosis (CF) through the epidemiological description of Italian patients.
The members of the Scientific and Technical Committee have to write a report on data collected by ICFR, in order to contribute to achieve the aims of ICFR itself, i.e., to improve the care of CF patients. In particular, the Report should contribute to the following objectives:
to analyze the medium and long-term clinical and epidemiological trends of the disease;
to identify the main healthcare needs at regional and national level in order to contribute to the healthcare programmes and to the distribution of resources;
to compare Italian data with the international ones.
DESIGN
Analyses and results described in the present Report are referred to patients in charge to the Italian National Referral and Support Centres for Cystic Fibrosis in the period 2011-2014. Data were sent by Centres by means of a specific software (Camilla, Ibis Informatica) and has undergone a double quality control (QC): the first by NIH and the second at a European level (before the inclusion of the Italian data within the European Cystic Fibrosis Registry). These QCs assure the completeness and accuracy of data as well as their consistency with European core data.
SETTING AND PARTICIPANTS
A total of 29 different CF centres (referral, support, and Paediatric Hospital "Bambino Gesu") sent their data to ICFR; data referred to the period 2011-2014. Data regarding Sardinia Region (Southern Italy) are missing; data from Molise (Southern Italy) CF centre refer only to 2014.
RESULTS
The present Report has been organized into 10 sections.
1. Demography: number of Italian patients with cystic fibrosis (CF) in 2014 was 4,981 and their median age was 20.4 years; estimated 2014 CF prevalence was 8.2/100,000 residents in Italy; on average, 52.1% of the patients were male and CF distribution showed higher frequency in patients aged from 7 to 35 years. On average, 53.7% of CF patients are aged more than 18 years.
2. Diagnoses: most of the CF patients were diagnosed before two years of age (around 66%); a significant proportion of patients (on average, 12%) was diagnosed in adult age.
3. New diagnoses: new diagnoses were 187 in 2011, 200 in 2012, 160 in 2013, and 135 in 2014. Estimated incidence was 1/4,052 live births in 2011; 1/4,313 in 2012; 1/5,189 in 2013 and 1/8,243 in 2014.
4. Genetics: 99.5% of patients was studied at the molecular level, with identification of 90.1% of Cystic Fibrosis Transmembrane Regulator CFTR mutations; [delta] 508F was the most frequent mutation (44.8% in 2014).
5. Lung function: FEV 1 (Forced Expiratory Volume in the first second) scores progressively decreased shortly before the start of adult age, in accordance with the natural history of the disease. Most of the patients between 6 and 17 years of age reported a FEV 1 % >= 70% of the predicted value, while the proportion of patients with severe lung disease (FEV 1 % < 40% of the predicted value) is < 2% over the period 2011-2014.
6. Nutrition: most critical periods come out during the first 6 months of life and during adolescence. Prevalence of malnourished male aged 12-17 years decreases over the period 20112014; an increasing percentage of patient (both male and female) with a suboptimal body mass index value is observed among patients aged more than 18 years
7. Complications: the presence of missing data represents an obstacle in the correct evaluation of prevalence value of complications related to Italian patients within ICFR. Nevertheless, it was estimated that, in 2014, the principal complication in patients aged < 18 years was hepatopathies (15%), while in patients aged more than 18 years the principal complications were due to hepatopathies (25%) and diabetes (22%).
8. Transplantation: during the period 2011-2014, 135 patients ageed between 7 and 53 years received a double lung transplant; median age at transplantation was 32.5 years. Median duration of waiting list for transplantation is estimated in 11 months.
9. Microbiology: analyses were referred to test performed in 2014. Prevalence of adult patients with Pseudomonas aeruginosa chronic infection is 49.4% compared to 14.5% of paediatric patients; Staphylococcus aureus chronic infection is present in 48% of adult patients and 45.6% of paediatric patients; Burkholderia Cepacia complex is present almost exclusively in adult patients (4.9%); Nontuberculous mycobacteria is present in 0.9% and 0.3% of adult and paediatric patients, respectively; Stenotrophomonas maltophilia infection is present in 4.6% of patients (both adults and paediatric).
10. Mortality: RIFC data show that 176 patients (median age 32 years; 81 males and 95 females) died in the period 2011-2014.
CONCLUSIONS The present Report shows that CF population is growing (median age), so paediatric mortality is decreasing. A very low percentage of paediatric population is characterized by complication of pulmonary functions; adult patients are characterized by an increase of age at death (more than 30 years of age). ICFR Report may represent an important tool to analyze clinical and epidemiological trends of the disease as well as to identify the main healthcare needs at regional and national level to contribute to the healthcare programmes and to the distribution of the resources
