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Abstract This study investigates the influence of social capital, market orientation, and technological readiness levels (TRLs) on the intensity of collaboration between researchers from a public research institution in Brazil and companies, and how TRLs moderate this relationship. Using a quantitative approach, we applied structural equation modeling (PLS-SEM) to analyze responses from researchers at this institution. The analysis highlights the critical roles of social capital and market orientation in fostering effective R&D interactions. Social capital enhances collaboration through trust and network strength, while market orientation aligns R&D efforts with market needs, ensuring that innovations are both relevant and timely. Importantly, this study explores how technological readiness levels (TRLs) moderate these relationships, offering insights into the varying impact of social capital and market orientation across different stages of technological development. Findings reveal that participation in projects with TRLs 4 to 6, known as the Valley of Death, significantly moderates the impact of market orientation on researchers' interaction intensity with companies, underscoring the importance of considering technological maturity in R&D collaborations. The study is framed within the open innovation approach, emphasizing the importance of leveraging external knowledge and collaborative networks to enhance innovation outcomes. Theoretically, this research extends the existing models of R&D collaboration by illustrating how TRLs modify the effects of social capital and market orientation. Practically, it offers actionable insights for R&D managers and policymakers on structuring environments that foster robust academic–industry partnerships, facilitating the successful transition of innovations from conceptualization to market readiness.

Objective: Congenital hyperinsulinism (CHI) is a heterogeneous genetic disease characterized by increased insulin secretion and causes persistent hypoglycemia in neonates and infants due to dysregulation of insulin secretion by pancreatic β cells. Babies with severe hypoglycemia and for whom medical treatment has been ineffective usually require surgical treatment with near-total pancreatectomy. To evaluate the clinical and surgical aspects affecting survival outcomes in babies diagnosed with CHI in a single tertiary care center. Methods: Retrospective Cohort study involving a single university tertiary center for the treatment of CHI. The authors study the demographics, clinical, laboratory, and surgical outcomes of this casuistic. Results: 61 % were female, 39 % male, Birth weight: 3576 g (±313); Age of onset of symptoms: from the 2nd hour of life to 28 days; Time between diagnosis and surgery ranged between 10 and 60 days; Medical clinical treatment, all patients received glucose solution with a continuous glucose infusion and diazoxide. 81 % of the patients used corticosteroids, 77 %. thiazide, 72 % octreotide, 27 % nifedipine; Neurological sequelae during development and growth: 54 % had some degree of delay in neuropsychomotor development, 27 % obesity. Surgery was performed open in 6 and 12 minimally invasive surgery (MIS). Histopathology: 2 focal and 16 diffuse, Length of stay (days) was lower in MIS (p < 0.05). Survival was 100 %. Conclusions: CHI is a rare and difficult-to-manage tumor that must be performed in a multidisciplinary and tertiary center. Most surgical results are good and the laparoscopic approach to disease has been the best choice for patients.

Therapeutic use of alternative nitric oxide (NO) sources, such as nitrite and nitrate may be a protective influence on pulmonary vasculature abnormalities. Aim: To evaluate whether the maternal administration of nitrite prevents the morphological and molecular changes that affect the pulmonary arterioles of congenital diaphragmatic hernia (CDH) neonates. Methods: CEUA #88/2017. Sprague-Dawley neonate rats were divided into 6 groups: 1. control; 2. control + nitrite; 3. nitrofen exposed; 4. nitrofen exposed + nitrite; 5. CDH and 6. CDH + nitrite. The pregnant rats from nitrofen exposed and CDH groups were exposed to nitrofen on gestational day (GD) 9.5. The treatment with nitrite was made by gavage (15 mg/kg/day), on the last five gestational days. On GD 21.5 the fetuses were harvested. The following parameters were analyzed: lung and plasma nitrite concentration; media wall thickness (MWT) and endothelial NO synthase eNOS and inducible NO synthase iNOS immunohistochemistry of pulmonary arterioles. Results: Nitrite treatment increased the maternal plasma concentration of nitrite in control and nitrofen-exposed rats. All neonates exposed to nitrofen showed an increase of nitrofen in the lung and plasma. Nitrite treatment decreased the MWT of pulmonary arterioles of CDH neonates. Nitrite treatment increased eNOS marker and attenuated iNOS marker in neonates with CDH. Conclusions: Nitrite maternal treatment rescued the morphometry and recovered eNOS expression of CDH pulmonary arterioles during CDH. Nitrite is a potential prenatally therapeutic approach to vascular alterations present in CDH neonates.

Abstract Background Congenital Anomalies were responsible for 303,000 deaths in the neonatal period, according to the WHO, they are among the world’s top 20 causes of morbidity and mortality. Expensive simulators demonstrate several diseases, but few are related to congenital anomalies. This study aims to develop, validate, and evaluate low-cost simulator models (WALL-GO) of the most common abdominal wall defects, gastroschisis, and omphalocele, to enable diagnosis through an accessible tool with study value and amenable to replication. Methods Market research was conducted to find materials to build low-cost models. The researchers built the model and underwent validation assessment of the selected experts who scored five or more in the adapted Fehring criteria. The experts were assessed through a 5-point Likert scale to 7 statements (S1-7). Statements were assigned values according to relevance in face and transfer validities. Concomitantly, the model was also evaluated by students from 1st to 5th year with the same instruments. Content Validity Indexes (CVIs) were considered validated between groups with concordance greater than 90%. Text feedback was also collected. Each statement was subjected to Fisher’s Exact Test. Results Gastroschisis and omphalocele model costs were US $15 and US $27, respectively. In total, there were 105 simulator evaluators. 15 experts were selected. Of the 90 students, there were 16 (1st year), 22 (2nd), 16 (3rd), 22 (4th), and 14 (5th). Students and experts obtained CVI = 96.4% and 94.6%, respectively. The CVIs of each statement were not significantly different between groups (p

Introduction: Short bowel syndrome (SBS) is defined as a severe reduction in intestinal mucosal absorption secondary to reduced intestinal functional area. The main causative factor for SBS is the length of intestinal resection in the neonatal period. The prognosticating factors are age, length of remnant intestine, preserved ileocecal valve, and venous maintenance. Objective: To evaluate the clinical and surgical aspects affecting survival outcomes in neonates with SBS at two tertiary care centers. Patients & methods: Retrospective cohort study involving two university tertiary care neonatal centers with diagnosed SBS. Neonates were allocated into two groups, SBS (

ABSTRACT Introduction: Congenital heart diseases (CHDs) constitute the most prevalent congenital pathology, and they are a consequence of structural and functional abnormalities during fetal development. The etiology of CHD involves the interaction of genetic and environmental factors. Fetal cardiac surgery aims at preventing natural pathways of CHD in utero, mitigating progression to more complex abnormalities. The goal of this review was to demonstrate the benefits and risks of fetal interventions in the two most prevalent CHDs, pulmonary stenosis and pulmonary atresia with an intact ventricular septum, but also critical aortic stenosis and hypoplastic left heart syndrome. Methods: Original and relevant articles were selected by meta-aggregation to perform a qualitative analysis of fetal cardiac interventions for pulmonary stenosis and critical aortic stenosis. The Joanna Briggs Institute’s Qualitative Assessment and Review Instrument (or JBI-QARI) was used for data quality appraisal. Results: Of 61 potential articles, 13 were selected, and nine were finally included. Discussion: The present review demonstrated that fetal cardiac surgery increases right ventricular growth and hemodynamic flow in pulmonary stenosis, whereas in critical aortic stenosis it enables growth of the left ventricle and increases left ventricular pressure. However, it has a high complication rate, along with considerable morbidity and mortality. Conclusion: The benefits of fetal cardiac surgery for pulmonary stenosis and critical aortic stenosis are well-described in the literature; however, there is a significant risk of complications which can be reduced by the surgeon’s technical expertise and well-structured hospital facilities.

Left congenital diaphragmatic hernia (CDH) can lead to pulmonary arteries abnormalities in the contralateral and ipsilateral sides of the diaphragm. Nitric oxide (NO) is the main therapy used to attenuate the vascular effects of CDH, but it is not always effective. We hypothesized that the left and right pulmonary arteries do not respond similarly to NO donors during CDH. Therefore, vasorelaxant responses of the left and right pulmonary arteries to sodium nitroprusside (SNP, a NO donor) were determined in a rabbit experimental model of left CDH. CDH was surgically induced in the fetuses of rabbits on the 25th day of pregnancy. On the 30th day of pregnancy, a midline laparotomy was performed to access the fetuses. The fetuses’ left and right pulmonary arteries were isolated and mounted in myograph chambers. Vasodilation was evaluated by cumulative concentration-effect curves to SNP. Protein expression of guanylate cyclase isoforms (GCα, GCβ) and the α isoform of cGMP-dependent protein kinase 1 (PKG1α), and the concentration of NO and cGMP were determined in the pulmonary arteries. The left and right pulmonary arteries of newborns with CDH exhibited increased vasorelaxant responses to SNP (i.e. the potency of SNP was increased) compared to the control group. GCα, GCβ, and PKG1α expression were decreased, while NO and cGMP concentrations were increased in the pulmonary arteries of newborns with CDH compared to the control group. The increased cGMP mobilization may be responsible for the increased vasorelaxant responses to the SNP in the pulmonary arteries during left CDH.

Congenital diaphragmatic hernia (CDH) is associated with thoracic compression of the lungs and heart caused by the herniated abdominal content, leading to cardiac modifications including pressure and vascular changes. Our aim was to investigate the experimental immunoexpression of the capillary proliferation, activation, and density of Ki-67, VEGFR2, and lectin in the myocardium after surgical creation of a diaphragmatic defect. Pregnant New Zealand rabbits were operated on the 25th gestational day in order to create left-sided CDH (LCDH, n=9), right-sided CDH (RCDH, n=9), and Control (n=9), for a total of 27 fetuses in 19 pregnant rabbits. Five days after the procedure, animals were sacrificed, and histology and immunohistochemistry studies of the harvested hearts were performed. Total body weight and heart weight were not significantly different among groups (P=0.702 and 0.165, respectively). VEGFR2 expression was increased in both ventricles in the RCDH group (P

IntroductionThe subventricular zone (SVZ) represents one of the main adult brain neurogenesis niche. In-vivo imaging of SVZ is very challenging and little is known about MRI correlates of SVZ macro- and micro-structural injury in multiple sclerosis (MS) patients.MethodsThe aim of the present study is to evaluate differences in terms of volume and microstructural changes [as assessed with the novel Spherical Mean Technique (SMT) model, evaluating: Neurite Signal fraction (INTRA); Extra-neurite transverse (EXTRATRANS) and mean diffusivity (EXTRAMD)] in SVZ between relapsing-remitting (RR) or progressive (P) MS patients and healthy controls (HC). We are also going to explore whether SVZ microstructural injury correlate with caudate (a nucleus that is in the vicinity of the SVZ) or thalamus (another well-defined grey matter area which is further from SVZ than caudate) volume and clinical disability. Clinical and brain MRI data were prospectively acquired from 20 HC, 101 RRMS, and 50 PMS patients. Structural and diffusion metrics inside the global SVZ, normal appearing (NA-) SVZ, caudate and thalamus were collected.ResultsWe found a statistically significant difference between groups in terms of NA-SVZ EXTRAMD (PMS>RRMS>HC; p = 0.002), EXTRATRANS (PMS>RRMS>HC; pRRMS>PMS; p = 0.009). Multivariable models showed that NA-SVZ metrics significantly predicted caudate (R2 = 0.21, p

Abstract Background In multiple sclerosis, the correlation between white matter lesion volumes (LV) and expanded disability status scale (EDSS) is at best moderate, leading to the “clinico-radiological paradox”, influenced by many factors, including the lack of information on the spatial localisation of each lesion on synthetic metrics such as LV. We used a probabilistic approach to provide the volume of WM tracts that may be disconnected by lesions and to evaluate its correlation with EDSS. Methods Forty-five patients (aged 37.4 ± 6.8 years, mean ± standard deviation; 30 females; 29 relapsing-remitting, 16 progressive) underwent 3-T magnetic resonance imaging. Both LV and the volume of the tracts crossing the lesioned regions (disconnectome volume, DV) were calculated using BCBtoolkit and correlated with EDSS. Results T1-weighted LV and DV significantly correlated with EDSS (p ≤ 0.006 r ≥ 0.413) as it was for T2-weighted LV and T2-weighted DV (p ≤ 0.004 r ≥ 0.430), but only T1-weighetd and T2-weighted DVs were EDSS significant predictors (p ≤ 0.001). The correlations of T1-weighted and T2-weighted LV with EDSS were significantly mediated by DV, while no effect of LV on the EDSS-DV correlation was observed. Conclusion The volume of disconnected WM bundles mediates the LV-EDSS correlation, representing the lonely EDSS predictor.

IntroductionThe Central Vein Sign (CVS) has been suggested as a potential biomarker to improve diagnostic specificity in multiple sclerosis (MS). Nevertheless, the impact of comorbidities on CVS performance has been poorly investigated so far. Despite the similar features shared by MS, migraine and Small Vessel Disease (SVD) at T2-weighted conventional MRI sequences, ex-vivo studies demonstrated their heterogeneous histopathological substrates. If in MS, inflammation, primitive demyelination and axonal loss coexist, in SVD demyelination is secondary to ischemic microangiopathy, while the contemporary presence of inflammatory and ischemic processes has been suggested in migraine. The aims of this study were to investigate the impact of comorbidities (risk factors for SVD and migraine) on the global and subregional assessment of the CVS in a large cohort of MS patients and to apply the Spherical Mean Technique (SMT) diffusion model to evaluate whether perivenular and non-perivenular lesions show distinctive microstructural features.Methods120 MS patients stratified into 4 Age Groups performed 3T brain MRI. WM lesions were classified in “perivenular” and “non-perivenular” by visual inspection of FLAIR* images; mean values of SMT metrics, indirect estimators of inflammation, demyelination and fiber disruption (EXTRAMD: extraneurite mean diffusivity, EXTRATRANS: extraneurite transverse diffusivity and INTRA: intraneurite signal fraction, respectively) were extracted.ResultsOf the 5303 lesions selected for the CVS assessment, 68.7% were perivenular. Significant differences were found between perivenular and non-perivenular lesion volume in the whole brain (p < 0.001) and between perivenular and non-perivenular lesion volume and number in all the four subregions (p < 0.001 for all). The percentage of perivenular lesions decreased from youngest to oldest patients (79.7%–57.7%), with the deep/subcortical WM of oldest patients as the only subregion where the number of non-perivenular was higher than the number of perivenular lesions. Older age and migraine were independent predictors of a higher percentage of non-perivenular lesions (p < 0.001 and p = 0.013 respectively). Whole brain perivenular lesions showed higher inflammation, demyelination and fiber disruption than non perivenular lesions (p = 0.001, p = 0.001 and p = 0.02 for EXTRAMD, EXTRATRANS and INTRA respectively). Similar findings were found in the deep/subcortical WM (p = 0.001 for all). Compared to non-perivenular lesions, (i) perivenular lesions located in periventricular areas showed a more severe fiber disruption (p = 0.001), (ii) perivenular lesions located in juxtacortical and infratentorial regions exhibited a higher degree of inflammation (p = 0.01 and p = 0.05 respectively) and (iii) perivenular lesions located in infratentorial areas showed a higher degree of demyelination (p = 0.04).DiscussionAge and migraine have a relevant impact in reducing the percentage of perivenular lesions, particularly in the deep/subcortical WM. SMT may differentiate perivenular lesions, characterized by higher inflammation, demyelination and fiber disruption, from non perivenular lesions, where these pathological processes seemed to be less pronounced. The development of new non-perivenular lesions, especially in the deep/subcortical WM of older patients, should be considered a “red flag” for a different -other than MS- pathophysiology.

Vaccines prevent infections in patients with multiple sclerosis (MS). Though recommendations regarding vaccinating patients with MS have been recently published, real-world data regarding vaccines’ planning in patients receiving disease-modifying drugs (DMDs) for MS are missing. Our aim was, therefore, to describe vaccination coverage rates, timing-proposal and safety in real-life vaccinating patients with MS undergoing DMDs before the start of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccination campaign. Patients followed at our MS-center were referred to individualized immunization-programs customized to Italian recommendations, patients’ risks, immunity to exanthematic diseases, ongoing DMDs, or therapy-start urgency. Disease-activity stated the need for an essential immunization-cycle, whose core was composed by four vaccines: meningococcal-B, pneumococcal conjugated, Haemophilus influenzae B, and meningococcal-ACWY vaccines. Vaccines were administered prior to the planned DMD-start when possible, inactivated-vaccines >2 weeks and live-vaccines >4 weeks before treatment-start. Patients received a 6-months clinical-/radiological-follow-up after immunization. One-hundred and ninety-five patients were vaccinated between April 2017 and January 2021. 124/195 (63.6%) started a vaccination-program before therapy-start/-switch and 108/124 (87.1%) effectively completed immunization before new therapy-start without any delay. The time needed for immunization-conclusion reached a median of 27 (confidence interval 22) days in 2020. No increase in clinical-/radiological-activity 3-/6-months after immunization was noted. In conclusion, our study confirmed feasibility and safety of a vaccination-protocol in patients with MS whose duration resulted in a median of 27 days.

Summary: Background: Congenital diaphragmatic hernia (CDH) is a severe embryological defect that causes pulmonary hypoplasia and hypertension. The prevalence and mortality rate of CDH varies around the world and little information is available about CDH in Latin America. Our aim was to estimate the general prevalence, mortality rate, prevalence of associated anomalies and features related to the outcomes of CDH in newborns from São Paulo state, Brazil. Methods: Population-based cross-sectional study based on data gathered from the Live Births Information System (SINASC) and the Mortality Information System (SIM) of children born in São Paulo state between January 1st, 2006, and December 31st, 2017. Findings: From 7,311,074 total survival discharges between 2006 and 2017, 1,155 were CDH-related, resulting in a prevalence rate of 1:6329 (95%CI = 1/6715 - 1/5984) and a mortality rate of 63·72% (95%CI = 60.95 - 66.50), 510 presented complex associated anomalies (44·15%). Maternal data showed higher prevalence among older mothers (older than 35 years old: 2·13 per 10,000) and, also, women with more years of schooling (higher than 12 years: 1·99 per 10,000). Presence of associated anomalies (95%CI = 5.69-11.10), 1-min Apgar (95%CI = 1.44-2.95), maternal schooling (95%CI = 1.06-2.43) and birth weight (95%CI = 1.04-2.26) were the most significant features associated with mortality. Interpretation: There was 1 CDH case for every 6329 newborns in São Paulo and the mortality rate among those cases was 63·72% - a high rate compared to other countries. Funding: This study didn't receive any specific grant from any funding agency in the public, commercial or not-for-profit sectors.

Objectives To update the knowledge on the occupational outcomes associated with multiple sclerosis (MS), systematically examine the extent, scope and nature of the pre-existing literature and identify research gaps in the existing literature.Design Scoping review.Data sources A comprehensive database search of PubMed/MEDLINE, Scopus, SciVerse ScienceDirect and Web of Science was performed. There were no time limits.Eligibility criteria We included any peer-reviewed original article reporting the occupational outcomes of people with MS between the ages of 18 and 65 years. We excluded those off-topic and with insufficient information.Methods This review was conducted following the Joanna Briggs Institute recommendations and the Preferred Reporting Items for Systematic Reviews and Meta-Analyses for scoping review checklist. Screening, reading of full-texts and data extraction was performed in a standardised way by expert reviewers from 14 July 2021 to 31 October 2021. We provided a narrative synthesis and an overview of findings.Results The initial systematic search yielded 104 228 results. After removing duplicates and applying the exclusion criteria, 403 articles were included in the review. In total, the studies evaluated 492 062 subjects with MS. One hundred fifty-four (38.2%) articles were published in the last 5 years, mostly from Europe and North America (50.9% and 33.0%, respectively). Concerning the occupational outcomes, studies mostly addressed unemployment (311, 77.2%), early retirement (120, 29.8%), disability pension (117, 29.0%), sick leave (77, 19.1%), the indirect cost of MS (74, 18.4%) and work characteristics (57, 14.1%). The results were categorised into seven subtopics: ‘Changes in work and occupational status due to MS’, ‘work-related socio-economic consequences of MS’, ‘risk factors for unfavourable occupational outcomes’, ‘reported barriers to employment’, ‘reported job accommodations and vocational rehabilitation strategies’, ‘job satisfaction, stigma, and disclosing the diagnosis in the workplace’ and ‘rating clinical scales’.Conclusions There are several issues that deserve further in-depth study by the scientific community in order to improve the occupational outcomes of people with MS.

Background: Patients with congenital diaphragmatic hernia (CDH) have a short postnatal period of ventilatory stability called the honeymoon period, after which changes in pulmonary vascular reactivity result in pulmonary hypertension. However, the mechanisms involved are still unknown. The aim of this study was to evaluate mechanical ventilation's effect in the honeymoon period on VEGF, VEGFR-1/2 and eNOS expression on experimental CDH in rats.Materials and Methods: Neonates whose mothers were not exposed to nitrofen formed the control groups (C) and neonates with left-sided defects formed the CDH groups (CDH). Both were subdivided into non-ventilated and ventilated for 30, 60, and 90 min (n = 7 each). The left lungs (n = 4) were evaluated by immunohistochemistry of the pulmonary vasculature (media wall thickness), VEGF, VEGFR-1/2 and eNOS. Western blotting (n = 3) was performed to quantify the expression of VEGF, VEGFR-1/2 and eNOS.Results: CDH had lower biometric parameters than C. Regarding the pulmonary vasculature, C showed a reduction in media wall thickness with ventilation, while CDH presented reduction with 30 min and an increase with the progression of the ventilatory time (honeymoon period). CDH and C groups showed different patterns of VEGF, VEGFR-1/2 and eNOS expressions. The receptors and eNOS findings were significant by immunohistochemistry but not by western blotting, while VEGF was significant by western blotting but not by immunohistochemistry.Conclusion: VEGF, its receptors and eNOS were altered in CDH after mechanical ventilation. These results suggest that the VEGF-NO pathway plays an important role in the honeymoon period of experimental CDH.

Necrotizing enterocolitis (NEC) is a common condition in preterm infants. The risk factors that contribute to NEC include asphyxia, apnea, hypotension, sepsis, and congenital heart diseases (CHD). The objective of this study was to evaluate the association between the treatment (surgery or drainage) and unfavorable outcomes in neonates with NEC and congenital heart diseases (NEC+CHD). A 19-year retrospective cohort study was conducted (2000-2019). Inclusion criterion was NEC Bell II stage. Exclusion criteria were associated malformation or genetic syndrome and those who did not undergo echocardiography or had a Bell I diagnosis. We included 100 neonates: NEC (n=52) and NEC+CHD (n=48). The groups were subdivided into NEC patients undergoing surgery (NECS, n=31), NEC patients undergoing peritoneal drainage (NECD, n=19), NEC+CHD patients undergoing surgery (NECCAS, n=21), and NEC+CHD patients who were drained (NECCAD, n=29). Multivariate analysis was performed to estimate the relative risk of death and the length of stay. Covariates were birth weight and gestational age. The group characteristics were similar. The adjusted relative risk of death was higher in the drainage groups [NECD (Adj RR=2.70 (95%CI: 1.47; 4.97) and NECCAD (Adj RR=1.97 (95%CI: 1.08; 3.61)], and they had the shortest time to death: NECD=8.72 (95%CI: 3.10; 24.54) and NECCAD=5.32 (95%CI: 1.95; 14.44). We concluded that performing primary peritoneal drainage in neonates with or without CHD did not improve the number of days of life, did not decrease the risk of death, and was associated with a higher mortality in newborns with NEC and clinical instability.

Embryologically, duodenal atresia results from inadequate recanalization and proliferation of the solid cord in the 8–10th week of gestation, while apple-peel atresia is a consequence of a vascular accident. The presence of both malformations is rather rare. We report a case with both associations; to our knowledge, this is the twelfth such case reported in the English literature.

Abstract Purpose: To evaluate the vascular ventilatory response in different stages of lung development and to compare them to the neonates with congenital diaphragmatic hernia (CDH) in a rabbit model. Methods: New Zealand rabbits were divided into 8 groups (n=5): E25, E27, E30, and CDH. All groups were ventilated on a FlexiVent (Scireq, Montreal, QC, Canada), compounding the other 4 groups. The CDH surgery was performed at E25 and the harvest at E30. Dynamic compliance (CRS), dynamic elastance (ERS) and dynamic resistance (RRS) were measured every 4 min/24 min. Median wall thickness (MWT) and airspace were measured. ANOVA Bonferroni tests were used to perform statistical analysis. Significance was considered when p

Abstract Spina bifida aperta is a congenital malformation characterized by the failure of neural tube closure resulting in an unprotected fetal spinal cord. The spinal cord then undergoes progressive damage, likely due to chemical and mechanical factors related to exposure to the intrauterine environment. Astrogliosis in exposed spinal cords has been described in animal models of spina bifida during embryonic life but its relationship with neuroinflammatory processes are completely unknown. Using a retinoic acid-induced rat model of spina bifida we demonstrated that, when exposed to amniotic fluid, fetal spinal cords showed progressive astrogliosis with neuronal loss at mid-gestation (E15) compared to unexposed spinal cords. The number of microglial cells with a reactive phenotype and activation marker expression increased during gestation and exhibited progressive disruption in the inhibitory immune ligand-receptor system. Specifically we demonstrate down-regulation of CD200 expression and up-regulation of CD200R. Exposed spinal cords demonstrated neuroinflammation with increased tissue water content and cytokine production by the end of gestation (E20), which correlated with active Caspase3 expression in the exposed layers. Our findings provide new evidence that microglia activation, including the disruption of the endogenous inhibitory system (CD200-CD200R), may participate in the pathogenesis of spina bifida through late gestation.

Com a abertura dos processos de inovação nas empresas, a adoção de tecnologia passou a ser fundamental. No presente artigo, analisamos como uma organização do segmento de automação industrial toma decisões de adoção de tecnologia. Assim, buscamos identificar quais fatores foram considerados na tomada de decisão. Para tanto, o estudo de caso foi utilizado como método de pesquisa, tendo como técnica de coleta de dados a entrevista estruturada com o gerente de Pesquisa, Desenvolvimento e Inovação da organização estudada. Como resultados, pôde-se verificar que o processo de adoção de tecnologia é realizado de forma conjunta, por um comitê técnico e de qualidade; que os esforços comerciais dos fornecedores não foram considerados no momento da adoção; que a decisão de adoção foi impulsionada principalmente pela consideração das características percebidas da inovação; o ambiente externo, mediante pressões competitivas a jusante na cadeia de valor, influenciou bastante a decisão de adoção; e também, que as características dos adotadores foram consideradas pela organização.

The objective of this research is to analyze which dimensions and attributes are discussed in born-global firms’ case studies presented by the literature and in practice. For these two specific objectives were proposed: i) identify the dimensions used to study the born-global firms; ii) identify the main concepts applied to such dimensions; both analysis are based on cases studies addressed in the literature and practical case studies. This research is classified as exploratory and contains a content analysis. Furthermore, it was based on a selection of academic articles obtained on ISI Web of Knowledge database focusing on born-global firms’ case studies. The results demonstrated that the main issues regarding the born-global firms are developed in an aligned perspective regarding the theory even when the article’s focused on a particular industry. As a contribution, this study presented the list of dimensions and attributes that can be used as a reference for complementary discussions regarding the born-global case studies or even theoretical propositions. The composition of case studies that provides a broad overview for the researchers can be considered as an additional contribution of this article.

Abstract Purpose: The denervation of the intestine with benzalkonium chloride (BAC) reduces mortality and improves weight gain in rats with short bowel syndrome (SBS). Nevertheless, translating these promising findings from bench to bedside is not feasible because BAC promotes peritonitis and irreversible denervation which may be followed by an uncontrolled dilatation of the viscera. The use of botulinum toxin (BT) instead of BAC to achieve the denervation of the remaining small intestine in SBS could be an interesting option because it leads to a mild and transient denervation of the intestine. Methods: Here we evaluated the effects of the ileal denervation with BT in rats with SBS by verifying the body weight variation and intestinal morphological parameters. Four groups with 6 animals each were submitted to enterectomy with an ileal injection of saline (group E) or BT (group EBT). Control groups were submitted to simulated surgery with an ileal injection of BT (group BT) or saline (group C - control). Results: We observed that the treatment of the remaining ileum with BT completely reversed the weight loss associated to extensive small bowel resection. Conclusion: This may provide a new promising approach to the surgical treatment of SBS.

Abstract Brazil actively participates in the Clean Development Mechanism (CDM) without having any kind of mandatory requirement. The objective of this study is to map the activities of CDM projects approved by interministerial Commission on Global Climate Change (CIMGC, for its acronym in Portuguese) and to identify new opportunities for CDM validation and verification bodies in Brazil. This paper was done by gathering information on CDM projects approved in Brazil and listed in the portal of the Ministry of Science, Technology and Innovation (MCTI, by its acronym in Portuguese). This research resulted in identifying a decrease in the registration of new CDM projects in Brazil. Furthermore, landfill projects in the waste sector has been identified to have the highest potential to be exploited in Brazil. This study also shows an opportunity to enhance the participation within voluntary carbon markets in Brazil.

Abstract Congenital diaphragmatic hernia (CDH) causes severe pulmonary hypoplasia from herniation of abdominal contents into the thorax. Tracheal occlusion (TO) for human CDH improves survival, but morbidity and mortality remain high, and we do not fully understand the cellular pathways and processes most severely impacted by CDH and TO. We created a left diaphragmatic hernia (DH) in rabbit fetuses with subsequent TO and collected left lung sections for NextGen mRNA sequencing. DH, TO and DHTO fetuses had comparable body and organ growth to control except for lower lung weights in DH (p < 0.05). Of 13,687 expressed genes, DHTO had 687 differentially expressed genes compared with DH, but no other group-group comparison had more than 10. Considering genes in combination, many of the genes reduced in DH were more highly expressed in DHTO than in control. Benchmarking fetal rabbit lung gene expression to published lung development data, both DH and DHTO lungs were more highly correlated with the gene expression of immature lung. DNA synthesis was upregulated in DHTO compared with DH and ribosome and protein synthesis pathways were downregulated. DH reduced total and epithelial cell proliferation by half and two-thirds respectively, and DHTO increased proliferation by 2.5 and 3.4-fold respectively. Signaling pathways downregulated by DH and upregulated in DHTO were epidermal growth factor receptor signaling, ephrin signaling and cell migration; however, levels of ephrin and EGFR signaling in DHTO exceeded that of control. Identification and inhibition of the ligands responsible for this dysregulated signaling could improve lung development in CDH.

Neonatal asphyxia occurs due to reduction in oxygen supply to vital organs in the newborn. Rapid restoration of oxygen to the lungs after a long period of asphyxia can cause lung injury and decline of respiratory function, which result from the activity of molecules that induce vascular changes in the lung such as nitric oxide (NO) and vascular endothelial growth factors (VEGF). In this study, we evaluated the pulmonary and vascular morphometry of rats submitted to the model of neonatal asphyxia and mechanical ventilation, their expression of pulmonary VEGF, VEGF receptors (VEGFR-1/VEGFR-2), and endothelial NO synthase (eNOS). Neonate Sprague-Dawley rats (CEUA #043/2011) were divided into four groups (n=8 each): control (C), control submitted to ventilation (CV), hypoxia (H), and hypoxia submitted to ventilation (HV). The fetuses were harvested at 21.5 days of gestation. The morphometric variables measured were body weight (BW), total lung weight (TLW), left lung weight (LLW), and TLW/BW ratio. Pulmonary vascular measurements, VEGFR-1, VEGFR-2, VEGF, and eNOS immunohistochemistry were performed. The morphometric analysis showed decreased TLW and TLW/BW ratio in HV compared to C and H (P

OBJECTIVES: The objective of the present study was to evaluate the protective effect of pre-conditioning treatment with laser light on hepatic injury in rats submitted to partial ischemia using mitochondrial function and liver fatty acid binding protein as markers. METHODS: Rats were divided into four groups (n=5): 1) Control, 2) Control + Laser, 3) Partial Ischemia and 4) Partial Ischemia + Laser. Ischemia was induced by clamping the hepatic pedicle of the left and middle lobes of the liver for 60 minutes. Laser light at 660 nm was applied to the liver immediately prior to the induction of ischemia at 22.5 J/cm2, with 30 seconds of illumination at five individual points. The animals were sacrificed after 30 minutes of reperfusion. Blood and liver tissues were collected for analysis of mitochondrial function, determination of malondialdehyde and analysis of fatty acid binding protein expression by Western blot. RESULTS: Mitochondrial function decreased in the Partial Ischemia group, especially during adenosine diphosphate-activated respiration (state 3), and the expression of fatty acid binding protein was also reduced. The application of laser light prevented bioenergetic changes and restored the expression of fatty acid binding protein. CONCLUSION: Prophylactic application of laser light to the livers of rats submitted to partial ischemia was found to have a protective effect in the liver, with normalization of both mitochondrial function and fatty acid binding protein tissue expression.

Gastroschisis (GS) is an abdominal wall defect that results in histological and morphological changes leading to intestinal motility perturbation and impaired absorption of nutrients. Due to its anti-inflammatory, antioxidant, and neuroprotective effects, cannabidiol (CBD) has been used as a therapeutic agent in many diseases. Our aim was to test the effect of maternal CBD in the intestine of an experimental model of GS. Pregnant rats were treated over 3 days with CBD (30 mg/kg) after the surgical induction of GS (day 18.5 of gestation) and compared to controls. Fetuses were divided into 4 groups: 1) control (C); 2) C+CBD (CCBD); 3) gastroschisis (G), and 4) G+CBD (GCBD). On day 21.5 of gestation, the fetuses were harvested and evaluated for: a) body weight (BW), intestinal weight (IW), and IW/BW ratio; b) histometric analysis of the intestinal wall; c) immunohistochemically analysis of inflammation (iNOS) and nitrite/nitrate level. BW: GCBD was lower than CCBD (P

Esophageal atresia (EA) is characterized by esophageal and gastric motility changes secondary to developmental and postsurgical damage. This study evaluated the in vitro contractile profile of the distal esophagus and gastric fundus in an experimental model of EA induced by doxorubicin (DOXO). Wistar pregnant rats received DOXO 2.2 mg/kg on the 8th and 9th gestational days. On day 21.5, fetuses were collected, sacrificed, and divided into groups: control, DOXO without EA (DOXO-EA), and DOXO with EA (DOXO+EA). Strips from the distal esophagus and gastric fundus were mounted on a wire myograph and isolated organ-bath system, respectively, and subjected to increasing concentrations of carbamylcholine chloride (carbachol, CCh). The isolated esophagus was also stimulated with increasing concentrations of KCl. In esophagus, the concentration-effect curves were reduced in response to CCh in the DOXO+EA and DOXO-EA groups compared to the control group (P0.05). In response to KCl, the distal esophagus samples in the three groups were not statistically different with regard to Emax or EC50 values (P>0.05). No significant difference was noted for EC50 or Emax values in fundic strips stimulated with CCh (P>0.05). In conclusion, exposure of dams to DOXO during gestation inhibited the contractile behavior of esophageal strips from offspring in response to CCh but not KCl, regardless of EA induction. The gastric fundus of DOXO-exposed offspring did not have altered contractile responsiveness to cholinergic stimulation.

A hérnia diafragmática congênita é um defeito de formação do diafragma que acomete entre 1:2.000 e 1:4.000 nascidos vivos e constitui 8% das principais anomalias congênitas. Avanços médicos nos últimos 30 anos envolvendo diagnóstico pré-natal, intervenção fetal, manejo clinico e cirúrgico neonatal têm mudado a sobrevivência dos seus portadores. A evolução histórica desses avanços ajuda a compreender o esforço na busca de melhores resultados desse defeito muitas vezes fatal. Perspectivas na utilização de bioengenharia e terapia envolvendo células tronco podem trazer novas esperanças para os fetos com hérnia diafragmática congênita.

This study aimed to demonstrate that congenital diaphragmatic hernia (CDH) results in vascular abnormalities that are directly associated with the severity of pulmonary hypoplasia and hypertension. These events increase right ventricle (RV) afterload and may adversely affect disease management and patient survival. Our objective was to investigate cardiac function, specifically right ventricular changes, immediately after birth and relate them to myocardial histological findings in a CDH model. Pregnant New Zealand rabbits underwent the surgical procedure at 25 days of gestation (n=14). CDH was created in one fetus per horn (n=16), and the other fetuses were used as controls (n=20). At term (30 days), fetuses were removed, immediately dried and weighed before undergoing four-parameter echocardiography. The lungs and the heart were removed, weighed, and histologically analyzed. CDH animals had smaller total lung weight (P

This study aims to understand early signs’ sensemaking relevance to identifying unknown unknowns on innovative projects. When managing these projects, early signs of changes in the environment, combined with a sensemaking process, can help identify them prior to their occurrence and mitigate unwanted effects of these uncertainties. To this end, we conducted a field research to assess 16 projects, totaling 35 events representative of this kind of uncertainty. Based on in-depth interviews, we performed an initial qualitative analysis, and then applied non-parametric statistical tests. Early signs perception in cases where external factors may cause the occurrence of unknown unknowns show that this perception and the search for information are relevant to identifying unk unks. Furthermore, some biases, such as overconfidence and unrealistic optimism, can hinder it. There was a high prevalence of project managers detecting early signs of change in their projects at the beginning of the project. However, the majority of perceived early signs can be considered to be the first symptoms of a problem. Thus, as a contribution, we suggest: learning processes, which can provide sensemaking for early signs in unknown unknowns; project managers stimulating their team to be alert to environmental changes that may affect the project; and discussion of early signs perceived by the team during stakeholder management.