Conditioned media harvested from stem cell culturing have the potential to be innovative therapeutic tools against various diseases, due to their high content of growth, trophic and protective ...factors. The evaluation in vivo of the effects and biosafety of these products is essential, and zebrafish provides an ideal platform for high-throughput toxicological analysis, concurrently allowing the minimization of the use of mammalian models without losing reliability. In this study, we assessed the biological effects elicited by the exposure of zebrafish embryos to a conditioned medium derived from Wharton’s jelly mesenchymal stem cells. By a multiparametric investigation combining molecular, embryological, behavioural and in vivo imaging techniques, we found that exposure to a conditioned medium at a non-toxic/non-lethal dosage triggers antioxidant, anti-apoptotic and pro-regenerative effects, by upregulation of a set of genes involved in antioxidant defence (nrf2, brg1, sirt1, sirt6, foxO3a, sod2 and cat), glycolysis (ldha) and cell survival (bcl2l1, mcl1a and bim), coupled to downregulation of pro-apoptotic markers (baxa, caspase-3a and caspase-8). To our knowledge, this is the first study comprehensively addressing the effects of a conditioned medium on a whole organism from a developmental, molecular and behavioural perspective, and we are fairly confident that it will pave the way for future therapeutic application.
The international commitment to achieve carbon neutrality in the next few decades has oriented human activities towards the preservation of natural and non-renewable resources. In this context, a ...great research effort has been devoted to the search for sustainable solutions for the infrastructure construction sector, based on a thorough assessment of the environmental impact (EI). In this regards, Life Cycle Assessment (LCA) is considered one of the main components of Environmental Impact Assessment (EIA) and, for a comprehensive analysis, all the costs incurred by stakeholders during the useful life of the infrastructure should also be taken into account, applying the Life Cycle Cost (LCC) methodology. So far, there is a lack of combined LCA and LCC analyses of railway projects to support a proper sustainable decision-making process at a project level. Therefore, this study aimed to contributed to this topic by determining the environmental effect and related costs of different planning and construction choices in terms of material and maintenance strategies. For this purpose, first, an LCA of typical railway infrastructures with a ballasted track was developed. The case study considered two different functional units of a double-track railway line: 1 km of embankment section and 1 km of a cut section, in straight alignment. After defining five alternative railway infrastructure scenarios with different materials (virgin or recycled material) and construction methods (e.g., lime stabilization), two different railway track maintenance approaches were analysed. SimaPro was used to analyse the case study, and the results were compared with those obtained using the PaLATE software, suitably adapted for use in the railway sector. Finally, a cost analysis was carried out using Life Cycle Cost (LCC) methodology for all the scenarios analysed. The results obtained in terms of EI and related costs of each scenario provide useful information, allowing a sustainable planning approach: as a general result, the initial construction phase always involves the larger part of the total environmental impact while the material production is the most polluting phase, reaching percentages always higher than 50% of the total.
Social entrepreneurship (SE) enables business consolidation, combined with the production of positive impact and improvements in society. Aligned with 2030 Agenda for the achievement of the United ...Nations Sustainable Development Goals, it is important to clarify the role of social entrepreneurs, as they are making visible the impact of their creative ideas in several areas, from civic engagement to the environment, health and learning. The main purpose of this study is to specify a model of social entrepreneurial intention (SEI) and explore it by country, based on the dimensions of the Theory of Planned Behavior and how these are mediated by spirituality and optimism. With a convenience sample of 1476 Portuguese and Spanish students, Structural Equation Modeling (SEM) was used. For a deeply understanding, variables within the model were compared by country using
t
-rest, and multivariate analysis was done by each one separately. The mean comparison between countries, demonstrated that there are differences only between perceived behavioral control (PBC), Spirituality, Optimism and SEI, with Portuguese students scoring the highest values, in all variables except Optimism. A mediation path was carried out, and Spirituality mediate a significant effect between the three TPB dimensions in Portuguese students, but not in students from Spain. Finally, after discussing the results, theoretical and practical contributions are analyzed, with regard to the field of SE in Portugal and Spain, and alternatives are pointed out for a more social and sustainable entrepreneurial future.
Universities increasingly play an important role in entrepreneurship, which has contributed to gender equality in the business world. The aim of this study is to establish a causal model of ...entrepreneurial intentions and explore it by gender, based on the dimensions of the Theory of Planned Behavior, and how these are mediated by the individuals' resilience and psychological well-being. The previous work experience was considered as one of the control variables, in order to analyze whether this influence the entrepreneurial intention. With a convenience sample of 644 Portuguese students, Structural Equation Modeling (SEM) was used. For a better understanding, multivariate analyses were performed and each one was individually reported, and for appropriate comparisons by gender, the
-student test was used. The comparison of means, between genders, showed that there are differences only between perceived behavioral control, subjective norm, and entrepreneurial intention, with women scoring the highest values, and psychological well-being, with men scoring the higher. A serial mediation path was performed, and psychological resilience was found to mediate a significant effect between perceived behavioral control and intention in females, but not in males. It also mediates a significant effect between attitude and intention in females, but not in males. These results show that attitude is a determining factor for females to become entrepreneurs. Finally, after discussing the results, theoretical and practical contributions are analyzed, with regard to the field of entrepreneurship in Portugal, and alternatives are pointed out for a more entrepreneurial future, reinforcing the role of higher education institutions.
Spirituality can be understood as a capital based on individual capabilities created by the application of intrinsic spiritual values, in order to use and develop human potential. The literature ...points out that spiritual capital increasingly influences and motivates entrepreneurs.
In this paper, we investigate whether spirituality has a mediating role between psychological resilience, optimism and entrepreneurial success, and verify the gender differences. Our hypotheses are quantitatively tested on a sample of 233 micro and small Portuguese business owners during the pandemic crisis.
The main findings highlight that, while optimism and psychological resilience present a positive and significant relationship with entrepreneurial success in both genders, spirituality only impacts female entrepreneurial success.
Our study theoretically and empirically shows that the psychological resources and spirituality can be incorporated into new or existing programs designed to provide entrepreneurs with information on coping skills and how to engage in positive reorientation and reappraisal. In so doing, it improves the knowledge of the importance of psychological resources for the micro and small business' recoverability during the pandemic, which is deeply rooted in the entrepreneurial ability to excel during adversity.
Abstract
Background
Cat eye syndrome (CES) is a rare chromosomal disease, with estimated incidence of about 1 in 100,000 live newborns. The classic triad of iris coloboma, anorectal malformations, ...and auricular abnormalities is present in 40% of patients, and other congenital defects may also be observed. The typical associated cytogenetic anomaly relies on an extra chromosome, derived from an inverted duplication of short arm and proximal long arm of chromosome 22, resulting in partial trisomy or tetrasomy of such regions (inv dup 22pter-22q11.2).
Case presentation
We report on a full-term newborn, referred to us soon after birth. Physical examination showed facial dysmorphisms, including hypertelorism, down slanted palpebral fissures, and dysplastic ears with tragus hypoplasia and pre-auricular pit. Ophthalmologic evaluation and heart ultrasound identified left chorioretinal and iris coloboma and
ostium secundum
type atrial septal defect, respectively. Based on the suspicion of cat eye syndrome, a standard karyotype analysis was performed, and detected an extra small marker chromosome confirming the CES diagnosis. The chromosomal abnormality was then defined by array comparative genome hybridization (a-CGH, performed also in the parents), which identified the size of the rearrangement (3 Mb), and its de novo occurrence. Postnatally, our newborn presented with persistent hypoglycemia and cholestatic jaundice. Endocrine tests revealed congenital hypothyroidism, cortisol and growth hormone (GH) deficiencies, which were treated with replacement therapies (levotiroxine and hydrocortisone). Brain magnetic resonance imaging, later performed, showed aplasia of the anterior pituitary gland, agenesis of the stalk and ectopic neurohypophysis, confirming the congenital hypopituitarism diagnosis. She was discharged at 2 months of age, and included in a multidisciplinary follow-up. She currently is 7 months old and shows a severe global growth failure, and developmental delay. She started GH replacement treatment, and continues oral hydrocortisone, along with ursodeoxycholic acid and levothyroxine, allowing an adequate control of glycemic and thyroid profiles as well as of cholestasis.
Conclusions
CES phenotypic spectrum is wide and highly variable. Our report highlights how among the possible associated endocrine disorders, congenital hypopituitarism may occur, leading to persistent hypoglycemia and cholestasis. These patients should be promptly assessed for complete hormonal evaluations, in addition to major malformations and midline anomalies. Early recognition of such defects is necessary to decrease fatal events, as well as short and long-term related adverse outcomes.
To report outcomes of keratolimbal allograft (KLAL) compatible for both human leukocyte (HLA) and/or blood type using oral prednisone, mycophenolate, and tacrolimus, with basiliximab if panel ...reactive antibodies (PRA) are present. Intravenous immunoglobulin (IVIG) was used post-operatively if donor-specific anti-HLA antibodies (DSA) were present.
Retrospective interventional series of consecutive patients with KLAL for limbal stem cell deficiency (LSCD) from HLA and/or blood type compatible deceased donors with a minimum follow-up time of 12 months. Main outcome measures were ocular surface stability, visual acuity and systemic immunosuppression (SI) adverse events.
Eight eyes of eight patients with mean age of 48.6 ± 10.1 years (range 34–65 years) were included. Mean follow-up time was 37.3 ± 22.7 months (range 12–71 months) following KLAL; four (50%) had combined LR-CLAL surgery. The etiologies of LSCD were Stevens-Johnson Syndrome (n = 4/8), aniridia (n = 2/8), chemical injury (n = 1/8) and atopic eye disease (n = 1/8). All patients had PRA present and received basiliximab infusions. 5/8 patients received IVIG based on DSA identified pre-operatively. At last follow-up, 7 eyes (87.5%) had a stable ocular surface; 1 eye (12.5%) developed failure and had keratoprosthesis implantation. There was a significant improvement in visual acuity from 1.65 ± 0.48 to 0.68 ± 0.34 logMAR (p = 0.01). SI was tolerated well with minimal adverse events.
Preliminary outcomes of KLAL with ABO compatible tissue using the Cincinnati protocol, preoperative basiliximab (when PRA present) and post-operative IVIG (when DSA present) are encouraging. This protocol may allow for utilization of deceased donor tissue with results approximating those of living donor tissue transplanted for severe bilateral LSCD.
To investigate glucose metrics and identify potential predictors of the achievement of glycemic outcomes in children and adolescents during their first 12 months of MiniMed 780G use.
This ...multicenter, longitudinal, real-world study recruited 368 children and adolescents with type 1 diabetes (T1D) starting SmartGuard technology between June 2020 and June 2022. Ambulatory glucose profile data were collected during a 15-day run-in period (baseline), 2 weeks after automatic mode activation, and every 3 months. The influence of covariates on glycemic outcomes after 1 year of MiniMed 780G use was assessed.
After 15 days of automatic mode use, all glucose metrics improved compared with baseline (P < 0.001), except for time below range (P = 0.113) and coefficient of variation (P = 0.330). After 1 year, time in range (TIR) remained significantly higher than at baseline (75.3% vs. 62.8%, P < 0.001). The mean glycated hemoglobin (HbA1c) over the study duration was lower than the previous year (6.9 ± 0.6% vs. 7.4 ± 0.9%, P < 0.001). Time spent in tight range (70-140 mg/dL) was 51.1%, and the glycemia risk index was 27.6. Higher TIR levels were associated with a reduced number of automatic correction boluses (P < 0.001), fewer SmartGuard exits (P = 0.021), and longer time in automatic mode (P = 0.030). Individuals with baseline HbA1c >8% showed more relevant improvement in TIR levels (from 54.3% to 72.3%).
Our study highlights the sustained effectiveness of MiniMed 780G among youth with T1D. Findings suggest that even children and adolescents with low therapeutic engagement may benefit from SmartGuard technology.
This longitudinal population-based study analyses the frequency of diabetic ketoacidosis (DKA) at type 1 diabetes diagnosis in Italian children under 15 years of age, during 2004-2013. DKA was ...defined as absent (pH ≥ 7.30), mild/moderate (7.1 ≤ pH < 7.30) and severe (pH < 7.1). Two multiple logistic regression models were used to evaluate the time trend of DKA frequency considered as present versus absent and severe versus absent, adjusted for gender, age group and geographical area of residence at diagnosis. Overall, 9,040 cases were ascertained. DKA frequency was 40.3% (95%CI: 39.3-41.4%), with 29.1% and 11.2% for mild/moderate and severe DKA, respectively. Severe DKA increased significantly during the period (OR = 1.03, 95%CI: 1.003-1.05). Younger-age children and children living in Southern Italy compared to Central Italy were at significantly higher risk of DKA and severe DKA. Family history of type 1 diabetes and residence in Sardinia compared to Central Italy were significantly associated with a lower probability of DKA and severe DKA. The high frequency of ketoacidosis in Italy over time and high variability among age groups and geographical area of residence, strongly suggests a continuing need for nationwide healthcare strategies to increase awareness of early detection of diabetes.
Context:
The incidence of type 1 diabetes has been increasing over time.
Objective:
We estimated the genetic and environmental components of type 1 diabetes susceptibility in a twin cohort of ...recent-onset cases to explore the sources of changing disease epidemiology.
Design:
We linked the population-based Italian Twin Registry with 14803 type 1 diabetes records from 36 pediatric diabetes care centers throughout Italy, except Sardinia, and identified 173 diabetic twins. Patients were positive for at least one autoantibody to islet cell, glutamate decarboxylase, tyrosine phosphatase, insulin, or zinc transporter 8 and were insulin dependent since their diagnosis. Zygosity was determined by DNA genotyping or by questionnaire.
Outcome Measures:
We estimated proband-wise concordance, cotwin recurrence risk with Kaplan-Meier method, and genetic and environmental proportions of susceptibility variance by structural equation models.
Results:
We recruited 104 diabetic twins (53 males) from 88 pairs (34 monozygotic, 54 dizygotic) and one triplet. The mean age at diagnosis was 8.1 yr (range 1.1–20.5 yr), and the median year of diagnosis was 2002. Proband-wise concordances were 45.5 and 16.4% in monozygotic and dizygotic pairs (P = 0.01). Recurrence risks in monozygotic and dizygotic cotwins were 37 and 12% after 10 yr from the proband's diagnosis (P = 0.005). Genetic contribution to type 1 diabetes susceptibility was 40% (95% confidence interval 8–78), and the shared and individual-specific environmental components were 51% (14–77) and 9% (4–19), respectively.
Conclusions:
In addition to the moderate genetic effects on type 1 diabetes susceptibility, our results draw attention to the substantial shared environmental effects, suggesting that exposures in fetal or early postnatal life may contribute to the increasing incidence of the disease.
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