Facilitators and barriers to adolescent participation in a TB clinical trial.

The inclusion of adolescents in TB drug trials is essential for the development of safe, child-friendly regimens for the prevention and treatment of TB. TB Trials Consortium Study 31/AIDS Clinical Trials Group A5349 (S31/A5349) enrolled adolescents as young as 12 years old. We assessed investigator and coordinator described facilitators and barriers to adolescent recruitment, enrollment, and retention.Interviews were conducted with six investigators from sites that enrolled adolescent participants and six investigators from non-enrolling sites. Additionally, two focus groups were conducted with study coordinators from enrolling sites and two focus groups with non-enrolling sites. Discussions were transcribed, analyzed, summarized, and summaries were reviewed by Community Research Advisors Group members and research group representatives for content validity.Investigators and coordinators attributed the successful enrollment of adolescents to the establishment and cultivation of external partnerships, flexibility to accommodate adolescents' schedules, staff engagement, recruitment from multiple locations, dedicated recruitment staff working onsite to access potential participants, creation of youth-friendly environments, and effective communications. Non-enrolling sites were mainly hindered by regulations. Suggestions for improvement in future trials focused on study planning and site preparations.Proactive partnerships and collaboration with institutions serving adolescents helped identify and reduce barriers to their inclusion in this trial..

Forensic investigation on a combined death by food aspiration and acute escitalopram intoxication occurred to a psychiatric subject in a nursing home.

Food aspiration is one of the major health risks for elderly people in nursing homes which could lead to death. Moreover, misconducts in pharmacotherapy may represent a potential risk of adverse drug reactions. It is reported here the toxicological evaluation of a combined death by food aspiration and acute escitalopram intoxication of a psychiatric subject, occurred in a nursing home. An 89-year-old man, suffering from dysphagia and Alzheimer's, was resident in a nursing home. He was fed with a liquid diet administered directly in mouth using a syringe. The man was also being treated with escitalopram 10 mg tablet. One evening, after receiving the meal in the usual way, the man complained of sudden illness. Carried to the emergency room, the man died about 3 h later with a diagnosis of cardiogenic shock subsequentially to ab ingestis. The histological findings revealed the presence of exogenous material, probably food, up to the finest bronchial branches. The toxicological examination revealed the presence of escitalopram and its main metabolite, desmethylcitalopram: in the blood 1972 ng/ml and 285 ng/ml, in the brain 4657 ng/g and 1025 ng/g, in the gastric content 2317 ng/g and 423 ng/g, in the lung 21,771 ng/g and 468 ng/g, respectively. The bad practice of the nurses to dissolve the escitalopram tablet in the liquefied food and to administer the therapy with a syringe directly into the mouth emerged thanks this investigation. Following food aspiration, escitalopram was absorbed by inhalation route, reaching high concentrations in blood and tissues. The death occurred due to a combined mechanism between food aspiration and the escitalopram toxic action.

Transition from pediatric to adult care in patients with Turner syndrome in Italy: a consensus statement by the TRAMITI project.

PURPOSE: Transition from pediatric to adult care is associated with significant challenges in patients with Turner syndrome (TS). The objective of the TRansition Age Management In Turner syndrome in Italy (TRAMITI) project was to improve the care provided to patients with TS by harnessing the knowledge and expertise of various Italian centers through a Delphi-like consensus process. METHODS: A panel of 15 physicians and 1 psychologist discussed 4 key domains: transition and referral, sexual and bone health and oncological risks, social and psychological aspects and systemic and metabolic disorders. RESULTS: A total of 41 consensus statements were drafted. The transition from pediatric to adult care is a critical period for patients with TS, necessitating tailored approaches and early disclosure of the diagnosis to promote self-reliance and healthcare autonomy. Fertility preservation and bone health strategies are recommended to mitigate long-term complications, and psychiatric evaluations are recommended to address the increased prevalence of anxiety and depression. The consensus also addresses the heightened risk of metabolic, cardiovascular and autoimmune disorders in patients with TS; regular screenings and interventions are advised to manage these conditions effectively. In addition, cardiac abnormalities, including aortic dissections, require regular monitoring and early surgical intervention if certain criteria are met. CONCLUSIONS: The TRAMITI consensus statement provides valuable insights and evidence-based recommendations to guide healthcare practitioners in delivering comprehensive and patient-centered care for patients with TS. By addressing the complex medical and psychosocial aspects of the condition, this consensus aims to enhance TS management and improve the overall well-being and long-term outcomes of these individuals.

The TRansition Age Management in Turner syndrome in Italy (TRAMITI) project aims to improve care for individuals with Turner Syndrome (TS) during their transition from pediatric to adult care. A team of 15 physicians and 1 psychologist collaborated to create a comprehensive set of 41 consensus statements, covering four key areas: transition and referral, sexual and bone health and oncological risks, social and psychological aspects and systemic and metabolic disorders. The consensus statements highlight the importance of patient-centered care, early intervention and long-term monitoring. They emphasize a multidisciplinary approach to address the complex medical and psychosocial aspects of TS. During the critical transition period, tailored approaches and early disclosure of the diagnosis are recommended to promote self-reliance and healthcare autonomy. To mitigate long-term complications, the consensus addresses fertility preservation and bone health strategies. It also recommends psychological or psychiatric evaluations to tackle the increased prevalence of anxiety and depression in patients with TS. In addition, strategies for addressing the heightened risk of metabolic, cardiovascular and autoimmune disorders in patients with TS are proposed. Regular screenings and interventions are advised to effectively manage these conditions. Furthermore, cardiac abnormalities, including aortic dissections, require close monitoring and early surgical intervention if specific criteria are met. Overall, the TRAMITI consensus statement provides valuable insights and evidence-based recommendations. It offers guidance for healthcare practitioners in delivering comprehensive and patient-centered care for individuals with TS. By addressing both medical and psychosocial aspects, the consensus aims to enhance TS management and improve the well-being and long-term outcomes of those affected by this genetic disorder.

The economic burden of pediatric growth hormone deficiency in Italy: a cost of illness study.

PURPOSE: Growth hormone deficiency (GHD) is a rare condition with a worldwide prevalence of 1 patient in 4000 to 10,000 live births, placing a significant economic burden on healthcare systems. The aim of this study is to generate evidence on the economic burden of children and adolescents with GHD treated with rhGH and their parents in Italy. METHODS: A cost of illness analysis, adopting the prevalence approach, has been developed, producing evidence on the total annual cost sustained by the Italian National Health System (NHS) and by the society. The study is based on original data collected from a survey conducted among Italian children and adolescents with GHD and their parents. RESULTS: 143 children/adolescents with GHD and their parents participated to the survey, conducted from May to October 2021. Patients had a mean age of 12.2 years (SD: 3.1) and were mostly males (68.5%). The average direct healthcare cost sustained by the NHS was € 8,497.2 per patient/year; adding the out-of-pocket expenses (co-payments and expenses for private healthcare service), the total expense was € 8,568.6. The indirect costs, assessed with the human capital approach, were € 847.9 per patient/year. The total of direct and indirect cost is € 9,345.1 from the NHS perspective, and € 9,416.5 from a social perspective. The total cost incurred by the Italian NHS for children with GHD (range: 5,708-8,354) was estimated in € 48.5-71.0 million, corresponding to 0.04-0.06% of the total Italian public health expense in the year 2020. CONCLUSIONS: The total annual cost for GHD children is close to € 10,000, and is mainly due to the cost of rhGH treatment. This cost is almost entirely sustained by the NHS, with negligible out-of-pocket expenses. The economic burden on the Italian NHS for the health care of established GHD children is fourfold higher than the prevalence of the disease in the overall Italian population.

ANÁLISIS DE LA ADECUACIÓN DEL APORTE NUTRICIONAL A LA META CALÓRICA Y PROTEICA EN PACIENTES CON NUTRICIÓN ENTERAL EXCLUSIVA INTERNADOS EN UN HOSPITAL PÚBLICO PEDIÁTRICO DE ALTA COMPLEJIDAD / ANALYSIS OF ADEQUACY OF THE NUTRITIONAL CONTRIBUTION TO THE CALORIE GOAL AND PROTEIN IN PATIENTS WITH ENTERAL NUTRITION EXCLUSIVE BOARDING SCHOOLS IN A PUBLIC HOSPITAL PEDIATRIC HIGH COMPLEXITY

La malnutrición en los pacientes hospitalizados representa un importante problema sanitario asociado a una mayor tasa de complicaciones con un incremento de la morbimortalidad

Malnutrition in hospitalized patients represents a significant health problem associated with an increased rate of complications and higher morbidity and mortality

Adverse events among persons with TB using in-person vs. electronic directly observed therapy.

BACKGROUND: We evaluated patient safety within a randomized crossover trial comparing electronic directly observed therapy (eDOT) to in-person DOT (ipDOT) in persons undergoing TB treatment in New York City, NY, USA.METHODS: Participant symptoms, symptom severity, and clinical management were documented. We assessed adverse event reports (AERs) by DOT method during the two-period crossover. Using Cox proportional-hazards mixed-effects models, we estimated the adjusted hazard ratio (aHR) of participants reporting an adverse event (AE) vs. not reporting an AE.RESULTS: Of 211 participants, 57 (27.0%) reported AEs during the two-period crossover; of these, 54.4% (31/57) were reported while using eDOT vs. 45.6% (26/57) while using ipDOT. Controlling for study group and period, the aHR for eDOT vs. ipDOT was 0.98 (95% CI 0.49-1.93). Although statistically not significant, the wide confidence intervals suggest that a significant association cannot be entirely ruled out. Gastrointestinal symptoms were most frequently reported (42.1%, 24/57). AER types and severity did not differ significantly by DOT method. Days from symptom onset to medical attention was similar across DOT methods (median: 1.0 day, IQR 0.0-2.0). No participants switched DOT methods due to AERs or monitoring concerns.CONCLUSION: Further evaluation to ascertain whether AERs differ when patients use eDOT vs. ipDOT is warranted.

Compacton existence and spin-orbit density dependence in Bose-Einstein condensates.

We demonstrate the existence of compactons matter waves in binary mixtures of Bose-Einstein condensates (BEC) trapped in deep optical lattices (OL) subjected to equal contributions of intraspecies Rashba and Dresselhaus spin-orbit coupling (SOC) under periodic time modulations of the intraspecies scattering length. We show that these modulations lead to a rescaling of the SOC parameters that involves the density imbalance of the two components. This gives rise to density dependent SOC parameters that strongly influence the existence and the stability of compacton matter waves. The stability of SOC-compactons is investigated both by linear stability analysis and by time integrations of the coupled Gross-Pitaevskii equations. We find that SOC restricts the parameter ranges for stable stationary SOC-compacton existence but, on the other side, it gives a more stringent signature of their occurrence. In particular, SOC-compactons should appear when the intraspecies interactions and the number of atoms in the two components are perfectly balanced (or close to being balanced for the metastable case). The possibility to use SOC-compactons as a tool for indirect measurements of the number of atoms and/or the intraspecies interactions is also suggested.

Quality of life in children and adolescents with growth hormone deficiency and their caregivers: an Italian survey.

PURPOSE: The aim of this study was to produce evidence on quality of life (QoL) among Italian growth hormone deficiency (GHD) children and adolescents treated with growth hormone (GH) and their parents. METHODS: A survey was conducted among Italian children and adolescents aged 4-18 with a confirmed diagnosis of GHD and treated with GH therapy and their parents. The European Quality of Life 5 Dimensions 3 Level Version (EQ-5D-3L) and the Quality of Life in Short Stature Youth (QoLISSY) questionnaires were administered between May and October 2021 through the Computer-Assisted Personal Interview (CAPI) method. Results were compared with national and international reference values. RESULTS: The survey included 142 GHD children/adolescents and their parents. The mean EQ-5D-3L score was 0.95 [standard deviation (SD) 0.09], while the mean visual analogue scale (VAS) score was 86.2 (SD 14.2); the scores are similar to those of a reference Italian population aged 18-24 of healthy subjects. As for the QoLISSY child-version, compared to the international reference values for GHD/ idiopathic short stature (ISS) patients, we found a significantly higher score for the physical domain, and lower scores for coping and treatment; compared to the specific reference values for GHD patients, our mean scores were significantly lower for all domains except the physical one. As for the parents, we found a significantly higher score for the physical domain, and a lower score for treatment; compared to reference values GHD-specific, we found lower score in the social, emotional, treatment, parental effects, and total score domains. CONCLUSIONS: Our results suggest that the generic health-related quality of life (HRQoL) in treated GHD patients is high, comparable to that of healthy people. The QoL elicited by a disease specific questionnaire is also good, and comparable with that of international reference values of GHD/ISS patients.

Challenges associated with electronic and in-person directly observed therapy during a randomized trial.

BACKGROUND: Electronic directly observed therapy (eDOT) has been proposed as an alternative to traditional in-person DOT (ipDOT) for monitoring TB treatment adherence. Information about the comparative performance and implementation of eDOT is limited.METHODS: The frequency of challenges during DOT, challenge type, and effect on medication observation were documented by DOT method during a crossover, noninferiority randomized controlled trial. A logistic mixed-effects model that adjusted for the study design was used to estimate the percentage of successfully observed doses when challenges occurred.RESULTS: A total of 20,097 medication doses were scheduled for observation with either eDOT (15,405/20,097; 76.7%) or ipDOT (4,692/20,097; 23.3%) for 213 study participants. In total, one or more challenges occurred during 17.3% (2,672/15,405) of eDOT sessions and 15.6% (730/4,692) of ipDOT sessions. Among 4,374 documented challenges, 27.3% (n = 1,192) were characterized as technical, 65.9% (n = 2,881) were patient-related, and 6.9% (n = 301) were program-related. Estimated from the logistic model (n = 6,782 doses, 173 participants), the adjusted percentage of doses successfully observed during problematic sessions was 21.7% (95% CI 11.2-37.8) for eDOT and 4.2% (95% CI 1.1-14.7) for ipDOT.CONCLUSION: Compared to ipDOT, challenges were encountered in a slightly higher percentage of eDOT sessions but were more often resolved to enable successful dose observation during problematic sessions.

A new DLK1 defect in a family with idiopathic central precocious puberty: elucidation of the male phenotype.

PURPOSE: We aimed to investigate a cohort of female and male patients with idiopathic central precocious puberty (CPP), negative for Makorin Ring Finger Protein 3 (MKRN3) defect, by molecular screening for Delta-like 1 homolog (DLK1) defects. DLK1 is an imprinted gene, whose mutations have been described as a rare cause of CPP in girls and adult women with precocious menarche, obesity and metabolic derangement. METHODS: We enrolled 14 girls with familial CPP and 13 boys with familial or sporadic CPP from multiple academic hospital centers. Gene sequencing of DLK1 gene was performed. Circulating levels of DLK1 were measured and clinical and biochemical characteristics were described in those with DLK1 defects. RESULTS: A novel heterozygous mutation in DLK1, c.288_289insC (p.Cys97Leufs*16), was identified in a male proband, his sister and their father. Age at onset of puberty was in line with previous reports in the girl and 8 years in the boy. The father with untreated CPP showed short stature. No metabolic derangement was present in the father except hypercholesterolemia. Undetectable Dlk1 serum levels indicated the complete lack of protein production in the three affected patients. CONCLUSION: A DLK1 defect has been identified for the first time in a boy, underscoring the importance of genetic testing in males with idiopathic or sporadic CPP. The short stature reported by his untreated father suggests the need for timely diagnosis and treatment of subjects with DLK1 defects.

Endocrine system involvement in patients with RASopathies: A case series.

Background and Objectives: Endocrine complications have been described in patients affected by RASopathies but no systematic assessment has been reported. In this study, we investigate the prevalence of endocrine disorders in a consecutive unselected cohort of patients with RASopathies. Study Design: 72 patients with a genetically confirmed RASopathy (Noonan syndrome [NS], N=53; 29 LEOPARD syndrome [LS], N=2; cardiofaciocutaneous syndrome [CFCS], N=14; subjects showing co-occurring pathogenic variants in PTPN11 and NF1, N=3) and an age- and sex-matched healthy controls were included in the study. Endocrine system involvement was investigated by assessing the thyroid function, pubertal development, auxological parameters, adrenal function and bone metabolism. Results: Short stature was detected in 40% and 64% of the NS and CFCS subcohorts, respectively. Patients showed lower Z-scores at DXA than controls (p<0.05) when considering the entire case load and both NS and CFCS groups. Vitamin D and Calcitonin levels were significantly lower (p< 0.01), Parathormone levels significantly higher (p<0.05) in patients compared to the control group (p<0.05). Patients with lower BMD showed reduced physical activity and joint pain. Finally, anti-TPO antibody levels were significantly higher in patients than in controls when considering the entire case load and both NS and CFCS groups. Conclusions: The collected data demonstrate a high prevalence of thyroid autoimmunity, confirming an increased risk to develop autoimmune disorders both in NS and CFCS. Reduced BMD, probably associated to reduced physical activity and inflammatory cytokines, also occurs. These findings are expected to have implications for the follow-up and prevention of osteopenia/osteoporosis in both NS and CFCS.

Sustainable Microbial and Heavy Metal Reduction in Water Purification Systems Based on PVA/IC Nanofiber Membrane Doped with PANI/GO.

Effective and efficient removal of both heavy metal pollutants and bacterial contamination from fresh water is an open issue, especially in developing countries. In this work, a novel eco-friendly functional composite for water treatment application was investigated. The composite consisted of electrospun nanofiber membrane from blended polyvinyl alcohol (PVA)/iota carrageenan (IC) polymers doped with equal concentrations of graphene oxide (GO) nanoparticles and polyaniline (PANI). The effectiveness of this composite as a water purification fixed-bed filter was optimized in a batch system for the removal of cadmium (Cd+2) and lead (Pb+2) ions, and additionally characterized for its antimicrobial and antifungal properties and cytotoxicity effect. The fiber nanocomposite exhibited efficient antibacterial activity, with maximum adsorption capacity of about 459 mg g-1 after 120 min for Cd+2 and of about 486 mg g-1 after 90 min for Pb+2. The optimized conditions for removal of both metals were assessed by using a response surface methodology model. The resulting scores at 25 °C were 91.4% (Cd+2) removal at 117 min contact time for 89.5 mg L-1 of initial concentration and 29.6 cm2 membrane area, and 97.19% (Pb+2) removal at contact time 105 min for 83.2 mg L-1 of initial concentration and 30.9 cm2 nanofiber composite membrane. Adsorption kinetics and isotherm followed a pseudo-second-order model and Langmuir and Freundlich isotherm model, respectively. The prepared membrane appears to be promising for possible use in domestic water purification systems.

Efficacy and safety of robotic-assisted surgery in challenging hysterectomies - a single institutional experience.

OBJECTIVE: An increasing number of robotic hysterectomies are being performed and the most common indication is fibroids. Fibroid uterus is common indication for hysterectomy for enlarged uteri. The role of robotic approach for complex pathologies as enlarged uterus is still debatable. The study aimed to analyze the feasibility of robotic hysterectomy in patients with enlarged uteri and the impact of uterine weight on surgical outcomes and on operative time length. PATIENTS AND METHODS: One hundred and thirty-eight patients who underwent robotic hysterectomy for benign indications at the 2nd Division of Obstetrics and Gynecology, Azienda Ospedaliero-Universitaria Pisana, University of Pisa were consecutively enrolled. RESULTS: Data of patients undergoing robotic surgery for benign indications were collected. Patients were stratified in two groups based on their uterine weight, to analyze the effective impact of uterine weight and dimension on surgical performance, operative time and postoperative outcomes. Conversion rate was 0%. Median uterine weight was 615 g (range 400-1900 g). Median total operating time was 131 minutes (range 70-255 minutes). Increase in uterine weight significantly increased operative times (p=0.003) and morcellation time (p=0.001). On the other hand, operative time was just partially influenced by route for removal of the uterus (p=0.085) but significantly affected by uterine weight (p=0.008), previous surgeries (p=0.003) and BMI of the patient (p=0.005). CONCLUSIONS: Robotic hysterectomy is feasible and safe for challenging cases as large uteri. This technique could enable patients with outsized uteri, not suitable for vaginal hysterectomy, to undergo minimally invasive surgery with excellent results. Larger studies to investigate and compare robotic with other surgical approaches for difficult hysterectomies are needed to confirm these data.

Autoimmune polyendocrine syndrome type 1: an Italian survey on 158 patients.

BACKGROUND: Autoimmune Polyglandular Syndrome type 1 (APS-1) is a rare recessive inherited disease, caused by AutoImmune Regulator (AIRE) gene mutations and characterized by three major manifestations: chronic mucocutaneous candidiasis (CMC), chronic hypoparathyroidism (CH) and Addison's disease (AD). METHODS: Autoimmune conditions and associated autoantibodies (Abs) were analyzed in 158 Italian patients (103 females and 55 males; F/M 1.9/1) at the onset and during a follow-up of 23.7 ± 15.1 years. AIRE mutations were determined. RESULTS: The prevalence of APS-1 was 2.6 cases/million (range 0.5-17 in different regions). At the onset 93% of patients presented with one or more components of the classical triad and 7% with other components. At the end of follow-up, 86.1% had CH, 77.2% AD, 74.7% CMC, 49.5% premature menopause, 29.7% autoimmune intestinal dysfunction, 27.8% autoimmune thyroid diseases, 25.9% autoimmune gastritis/pernicious anemia, 25.3% ectodermal dystrophy, 24% alopecia, 21.5% autoimmune hepatitis, 17% vitiligo, 13.3% cholelithiasis, 5.7% connective diseases, 4.4% asplenia, 2.5% celiac disease and 13.9% cancer. Overall, 991 diseases (6.3 diseases/patient) were found. Interferon-ω Abs (IFNωAbs) were positive in 91.1% of patients. Overall mortality was 14.6%. The AIRE mutation R139X was found in 21.3% of tested alleles, R257X in 11.8%, W78R in 11.4%, C322fsX372 in 8.8%, T16M in 6.2%, R203X in 4%, and A21V in 2.9%. Less frequent mutations were present in 12.9%, very rare in 9.6% while no mutations in 11% of the cases. CONCLUSIONS: In Italy, APS-1 is a rare disorder presenting with the three major manifestations and associated with different AIRE gene mutations. IFNωAbs are markers of APS-1 and other organ-specific autoantibodies are markers of clinical, subclinical or potential autoimmune conditions.

Effective Elimination of Contaminant Antibiotics Using High-Surface-Area Magnetic-Functionalized Graphene Nanocomposites Developed from Plastic Waste.

The presence of pharmaceutical residues in aquatic environments represents a risk for the equilibrium of the ecosystem and may seriously affect human safety itself in the long term. To address this issue, we have synthesized functional materials based on highly-reduced graphene oxide (HRGO), sulfonated graphene (SG), and magnetic sulfonated graphene (MSG). The method of synthesis adopted is simple and inexpensive and makes use of plastic bottle waste as the raw material. We have tested the fabricated materials for their adsorption efficiency against two model antibiotics in aqueous solutions, namely Garamycin and Ampicillin. Our tests involved the optimization of different experimental parameters of the adsorption process, such as starting antibiotic concentration, amount of adsorbent, and time. Finally, we characterized the effect of the antibiotic adsorption process on common living organisms, namely Escherichia coli DH5α (E. coli DH5α) bacteria. The results obtained demonstrate the efficiency of the method in addressing the issue of the emergence of antibiotic-resistant bacteria, which will help in preventing changes in the ecosystem.

Adenosine stress CMR perfusion imaging of the temporal evolution of perfusion defects in a porcine model of progressive obstructive coronary artery occlusion.

Adenosine stress CMR perfusion imaging can quantify absolute perfusion and myocardial perfusion reserve (MPR) in coronary artery disease (CAD) with higher spatial resolution than positron emission tomography, the only clinically available technique for quantitative myocardial perfusion imaging. While porcine models of CAD are excellent for studying perfusion abnormalities in chronic CAD, to date there are a limited number of studies that use quantitative perfusion for evaluation. Therefore, we developed an adenosine stress CMR protocol to evaluate the temporal evolution of perfusion defects in a porcine model of progressive obstructive CAD. 10 Yucatan minipigs underwent placement of an ameroid occluder around the left circumflex artery (LCX) to induce a progressive chronic coronary obstruction. Four animals underwent a hemodynamic dose range experiment to determine the adenosine dose inducing maximal hyperemia. Each animal had a CMR examination, including stress/rest spiral quantitative perfusion imaging at baseline and 1, 3, and 6 weeks. Late gadolinium enhancement images determined the presence of myocardial infarction, if any existed. Pixelwise quantitative perfusion maps were generated using Fermi deconvolution. The results were statistically analyzed with a repeated mixed measures model to block for physiological variation between the animals. Five animals developed myocardial infarction by 3 weeks, while three developed ischemia without an infarction. The perfusion defects were located in the inferolateral myocardium in the perfusion territory of the LCX. Stress perfusion values were higher in remote segments than both the infarcted and ischemic segments (p < 0.01). MPR values were significantly greater in the remote segments than infarcted and ischemic segments (p < 0.01). While the MPR decreased in all segments, the MPR recovered by the sixth week in the remote regions. We developed a model of progressive CAD and evaluated the temporal evolution of the development of quantitative perfusion defects. This model will serve as a platform for understanding the development of perfusion abnormalities in chronic occlusive CAD.

Aerobic exercise and Orexin A: role of sympathetic activity and redox system.

Aerobic exercise is associated with the sympathetic activation evoking adaptive responses to sustain muscle engagement. Physical exercise can cause alterations in the cardiovascular activity and cellular stress may occur which could be marked by either heart rate (HR), or galvanic skin response (GSR). Moderate plasma levels of reactive oxygen species (ROS) are considered as health markers, absolving to important roles such as adaptive cellular responses to exercise. Orexin A, a hypothalamic peptide, causes a widespread stimulation of the sympathetic nervous system, playing a role in many physiological functions.

Neuronal-like response of N2a living cells to nanoporous patterns of thin supported anodic alumina.

We report about the response of N2a cells, a mouse neuroblastoma cell line, cultured on inert substrates with controlled porous nanostructure. The substrate surfaces were obtained by anodization and post-fabrication etching of thin aluminum films previously deposited onto glass. The morphology of the adherent cells was assessed by scanning electron microscopy. After fluorescent labelling, confocal microscopy was used to assess both the cell density, by cell nuclei counting, and their growth, by characterizing the neurite extensions in both number and length. By comparing with flat and smooth aluminum oxide, we can conclude that the nanoporous morphology of the anodized aluminum is favorable for cell development, which is probably correlated with the high density of regions with high local curvature. The intermediate pore size in the given range seems unfavorable for the number of cells, while the cell shape and the number of extensions point to a dominating differentiation of the N2a cells in correspondence with a characteristic pore size of 60 nm. These results are promising in view of the application of anodic alumina as a platform for the development of neuronal bioassays based on cell interconnectivity.

Influence of substrate stiffness on human induced pluripotent stem cells: preliminary results.

Skeletal muscle differentiation was proven to be influenced by changes in the substrate stiffness. However, a lack of knowledge features this field, concerning skeletal muscle tissues obtained from human induced pluripotent stem cells. Here we report the fabrication of polydimethylsiloxane-based substrates in a range of stiffness values from 3.5 to 141 kPa and the response of human induced pluripotent stem cells cultured on them for 5 days. The substrates were able to sustain cell adhesion and proliferation throughout the whole period. An inversely proportional relationship (although not significant) was found between the proliferation rate and the substrate stiffness. Initial analyses of iPSCs skeletal muscle differentiation shown no influences on markers of the early stages. These results lay the foundations for further studies on the influence of extrinsic mechanical stimuli on induced pluripotent stem cells-derived skeletal muscle tissues.