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Copyright of Revista Eletrônica de Enfermagem is the property of Revista Eletronica de Enfermagem and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Multiple short daily bouts of HIIT are more effective than single daily sessions in improving cardiometabolic and cellular adaptations in rats. We hypothesize that a short period of detraining is sufficient to abolish the superior adaptive responses to multiple versus single daily sessions of HIIT in rats. Male rats were divided into untrained, 1xHIIT, and 3xHIIT groups. Over eight weeks, the 1xHIIT group performed 115 min single daily sessions of HIIT, while the 3xHIIT group performed three 5 min sessions with 4 h intervals. After training, both groups remained sedentary for four weeks (detraining). Resting oxygen consumption (VO2), body composition, glucose/insulin tolerance, and blood pressure were recorded. After euthanasia, cardiac function/histology and gastrocnemius mitochondrial density were analyzed. After training, both 1xHIIT and 3xHIIT protocols induced similar improvements in VO2, maximal oxygen uptake (VO2max), cardiac function/hypertrophy, and gastrocnemius mitochondrial density. These effects were maintained even after detraining. Only the 3xHIIT protocol improved insulin sensitivity. After detraining, this effect was abolished. After training, both 1xHIIT and 3xHIIT protocols reduced adiposity. After detraining, the adiposity increased in both groups, with a more pronounced increase in the 3xHIIT rats. A four-week detraining period abolishes the superior adaptive responses to multiple versus single daily HIIT sessions in rats.

Objective: To evaluate the use of heated saline solution during wound cleaning on the intensity of pain related to the procedure, the temperature of the wound bed, and the comfort of patients with chronic wounds. Further, to investigate patient preference in relation to the temperature of the solution used for cleaning., Methods: Crossover, single-blind, clinical trial with 32 people with chronic wounds. Providers cleaned the wounds with room temperature and heated saline solution. Participants were randomized into group 1 A/B (heated solution first, room temperature second) or group 2 B/A (room temperature solution first, heated solution second), with a 10-minute washout period. Investigators evaluated pain intensity, wound bed temperature, and patient-reported comfort and preference., Results: The heated solution was preferred (P = .04) and more often referred to as comfortable (P = .04) by the participants. There was no difference in pain intensity before and after cleaning with room temperature (2.03; P = .155) and heated saline (2.25; P = .44). The heated solution increased the temperature of the wound bed by 0.5 °C., Conclusions: Although heating saline solution could be an important comfort measure during dressing changes, quantitatively, the temperature of the solution did not significantly change the temperature of the wound bed nor the intensity of pain patients experienced., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

Competing Interests: Declaration of interests We declare no competing interests.

Introduction: Ascending thoracic aortic aneurysms arise from pathological tissue remodeling that leads to abnormal wall dilation and increases the risk of fatal dissection/rupture. Large variability in disease manifestations across family members who carry a causative genetic variant for thoracic aortic aneurysms suggests that genetic modifiers may exacerbate clinical outcomes. Decreased perlecan expression in the aorta of mgΔ l p n mice with severe Marfan syndrome phenotype advocates for exploring perlecan-encoding Hspg2 as a candidate modifier gene., Methods: To determine the effect of concurrent Hspg2 and Fbn1 mutations on the progression of thoracic aortopathy, we characterized the microstructure and passive mechanical response of the ascending thoracic aorta in female mice of four genetic backgrounds: wild-type, heterozygous with a mutation in the Fbn1 gene (mgΔ l p n ), heterozygous with a mutation in the Hspg2 gene ( Hspg2 + / - ), and double mutants carrying both the Fbn1 and Hspg2 variants (dMut)., Results: Elastic fiber fragmentation and medial disarray progress from the internal elastic lamina outward as the ascending thoracic aorta dilates in mgΔ l p n and dMut mice. Concurrent increase in total collagen content relative to elastin reduces energy storage capacity and cyclic distensibility of aortic tissues from mice that carry the Fbn1 variant. Inherent circumferential tissue stiffening strongly correlates with the severity of aortic dilatation in mgΔ l p n and dMut mice. Perlecan haploinsufficiency superimposed to the mgΔ l p n mutation curbs the viability of dMut mice, increases the occurrence of aortic enlargement, and reduces the axial stretch in aortic tissues., Discussion: Overall, our findings show that dMut mice are more vulnerable than mgΔ l p n mice without an Hspg2 mutation, yet later endpoints and additional structural and functional readouts are needed to identify causative mechanisms., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. The author(s) declared that they were an editorial board member of Frontiers, at the time of submission. This had no impact on the peer review process and the final decision., (© 2024 Tarraf, de Souza, Herrick, Pereira and Bellini.)

Identifying human leukocyte antigen (HLA) haplotype-homozygous donors for the generation of induced pluripotent stem (iPS) cell lines permits the construction of biobanks immunologically compatible with significant numbers of individuals for use in therapy. However, two questions must be addressed to create such a bank: how many cell lines are necessary to match most of the recipient population and how many people should be tested to find these donors? In Japan and the UK, 50 and 100 distinct HLA-A, -B, and -DRB1 triple-homozygous haplotypes would cover 90% of those populations, respectively. Using data from the Brazilian National Registry of Bone Marrow Donors (REDOME), encompassing 4,017,239 individuals, we identified 1,906 distinct triple-homozygous HLA haplotypes. In Brazil, 559 triple-homozygous cell lines cover 95% of the population, and 3.8 million people would have to be screened. Finally, we show the contribution of the 30 most frequent triple-homozygous HLA haplotypes in Brazil to populations of different countries., Competing Interests: Declaration of interests The authors declare no competing interests., (Copyright © 2023 The Author(s). Published by Elsevier Inc. All rights reserved.)

Introduction: Effective and culturally safe pain management can facilitate analgesia and improve the quality of life. Individualised, multimodal and multidisciplinary approaches are highly recommended. There exist gaps in the knowledge on pain management, in terms of the assessment and/or treatment, in indigenous peoples and the currently available information is scattered in the literature. A scoping review will provide an overview or evidence map on the variety of approaches used in different cultures, in different parts of the world., Methods and Analysis: The search strategy comprises three stages. The first stage identified the MeSH terms and keywords in PubMed. The second stage will consist of a search of MEDLINE, EMBASE, LILACS, CINAHL, Web of Science, APA PsycNet and Scopus, followed by a search in Google and Google Scholar, GreyGuide, ProQuest Dissertations and Theses, Theses Canada Portal (Library and Archives Canada), TROVE (National Library of Australia), Aboriginal and Torres Strait Islander Health Bibliography, and Cybertesis. The papers will be screened, selected and extracted independently by two researchers. Descriptive data analysis will be performed, and the results will be presented using a narrative summary, graphs, tables and figures., Ethics and Dissemination: This review does not require ethical approval, as data from the literature available in databases will be collected and analysed. The protocol was registered at the Open Science Framework. The data on pain assessment and treatment in indigenous peoples will be presented through a narrative summary, figures, charts and tables. Results will be submitted to an open-access journal for publication and will be disseminated through scientific events, scientific meetings, public events and conversation circles with indigenous peoples., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2023. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Fibrillin-1 is a pivotal structural component of the kidney's glomerulus and peritubular tissue. Mutations in the fibrillin-1 gene result in Marfan syndrome (MFS), an autosomal dominant disease of the connective tissue. Although the kidney is not considered a classically affected organ in MFS, several case reports describe glomerular disease in patients. Therefore, this study aimed to characterize the kidney in the mgΔlpn-mouse model of MFS. Affected animals presented a significant reduction of glomerulus, glomerulus-capillary, and urinary space, and a significant reduction of fibrillin-1 and fibronectin in the glomerulus. Transmission electron microscopy and 3D-ultrastructure analysis revealed decreased amounts of microfibrils which also appeared fragmented in the MFS mice. Increased collagen fibers types I and III, MMP-9, and α-actin were also observed in affected animals, suggesting a tissue-remodeling process in the kidney. Video microscopy analysis showed an increase of microvessel distribution coupled with reduction of blood-flow velocity, while ultrasound flow analysis revealed significantly lower blood flow in the kidney artery and vein of the MFS mice. The structural and hemodynamic changes of the kidney indicate the presence of kidney remodeling and vascular resistance in this MFS model. Both processes are associated with hypertension which is expected to worsen the cardiovascular phenotype in MFS., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2023 de Souza et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Objective: To analyze the association between time of arrival at a reference hospital and mortality of people with ischemic stroke., Method: Descriptive and inferential statistics were used. Modifying and confounding variables between time of arrival and mortality were observed in the multivariate analysis. The Akaike Information Criterion was used to choose the model. Statistical significance of 5% and risk correction using the Poisson Model were adopted., Results: Most participants arrived within 4.5 hours of symptom onset or wake up stroke to the referral hospital and 19.4% died. The score of the National Institute of Health Stroke Scale was a modifier. In the multivariate model stratified by scale score ≥14, arrival time >4.5h was associated with lower mortality; and age ≥60 years and having Atrial Fibrillation, to higher mortality. In the model stratified by score ≤13, previous Rankin ≥3, and presence of atrial fibrillation were predictors of mortality., Conclusion: The relationship between time of arrival and mortality up to 90 days was modified by the National Institute of Health Stroke Scale. Prior Rankin ≥3, atrial fibrillation, time to arrival ≤4.5h, and age ≥60 years contributed to higher mortality.

Caruru (Amaranthus spinosus L) and trapoeraba (Commelina benghalensis) are NCEPs introduced into Brazil and are widely used by certain communities. Given the lack of information on carotenoids, vitamins, and minerals present in A. spinosus and C. benghalensis grown in Brazil, this study aimed to determine the proximate composition and the micronutrient profile of these two NCEPs obtained from family farming in the Middle Doce River (Médio Rio Doce) region in the state of Minas Gerais, Brazil. The proximate composition was evaluated using AOAC methods, vitamin E by HPLC with fluorescence detection, vitamin C and carotenoids by HPLC-DAD, and minerals by atomic emission spectrometry with inductively coupled plasma. In summary, the leaves of A. spinosus exhibited a high content of dietary fiber (10.20 g.100 g -1 ), potassium (708.8 mg·100 g -1 ), iron (4.0 mg·100 g -1 ) and β-carotene (6.94 mg·100 g -1 ), while the leaves of C. benghalensis were sources of potassium (1399.31 mg·100 g -1 ), iron (5.7 mg·100 g -1 ), calcium (163 mg·100 g -1 ), zinc (1.3 mg·100 g -1 ), ascorbic acid (23.61 mg·100 g -1 ), and β-carotene (31.33 mg·100 g -1 ). It was therefore concluded that C. benghalensis and A. spinosus, especially, presented excellent potential as important nutritional sources for human consumption, highlighting the gap existing between the available technical and scientific material, thus making them an important and necessary axis of research., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

Ecological conditions in the Amazon rainforests are historically favorable for the transmission of numerous tropical diseases, especially vector-borne diseases. The high diversity of pathogens likely contributes to the strong selective pressures for human survival and reproduction in this region. However, the genetic basis of human adaptation to this complex ecosystem remains unclear. This study investigates the possible footprints of genetic adaptation to the Amazon rainforest environment by analyzing the genomic data of 19 native populations. The results based on genomic and functional analysis showed an intense signal of natural selection in a set of genes related to Trypanosoma cruzi infection, which is the pathogen responsible for Chagas disease, a neglected tropical parasitic disease native to the Americas that is currently spreading worldwide.

Aim: It has been suggested that the proliferation and early differentiation of myoblasts are impaired in Marfan syndrome (MFS) mice during muscle regeneration. However, the underlying cellular and molecular mechanisms remain poorly understood. Here, we investigated muscle regeneration in MFS mouse models by analyzing the influence of the fibrotic niche on satellite cell function., Methods: In vivo, ex vivo, and in vitro experiments were performed. In addition, we evaluated the effect of the pharmacological inhibition of fibrosis using Ang-(1-7) on regenerating skeletal muscles of MFS mice., Results: The skeletal muscle of MFS mice shows an increased accumulation of collagen fibers (81.2%), number of fibroblasts (157.1%), and Smad2/3 signaling (110.5%), as well as an aberrant number of fibro-adipogenic progenitor cells in response to injury compared with wild-type mice. There was an increased number of proinflammatory and anti-inflammatory macrophages (3.6- and 3.1-fold, respectively) in regenerating muscles of wild-type mice, but not in the regenerating muscles of MFS mice. Our data show that proliferation and differentiation of satellite cells are altered (p ≤ 0.05) in MFS mice. Myoblast transplantation assay revealed that the regenerating muscles from MFS mice have reduced satellite cell self-renewal capacity (74.7%). In addition, we found that treatment with Ang-(1-7) reduces fibrosis (71.6%) and ameliorates satellite cell dysfunction (p ≤ 0.05) and muscle contractile function (p ≤ 0.05) in MFS mice., Conclusion: The fibrotic niche, caused by Fbn1 mutations, reduces the myogenic potential of satellite cells, affecting structural and functional muscle regeneration. In addition, the fibrosis inhibitor Ang-(1-7) partially counteracts satellite cell abnormalities and restores myofiber size and contractile force in regenerating muscles., (© 2022 Scandinavian Physiological Society. Published by John Wiley & Sons Ltd.)

Chronic Kidney Disease (CKD) is a public health problem that presents genetic and environmental risk factors. Two alleles in the Apolipoprotein L1 ( APOL1 ) gene were associated with chronic kidney disease; these alleles are common in individuals of African ancestry but rare in European descendants. Genomic studies on Afro-Americans have indicated a higher prevalence and severity of chronic kidney disease in people of African ancestry when compared to other ethnic groups. However, estimates in low- and middle-income countries are still limited. Precision medicine approaches could improve clinical outcomes in carriers of risk alleles in the Apolipoprotein L1 gene through early diagnosis and specific therapies. Nevertheless, to enhance the definition of studies on these variants, it would be necessary to include individuals with different ancestry profiles in the sample, such as Latinos, African Americans, and Indigenous peoples. There is evidence that measuring genetic ancestry improves clinical care for admixed people. For chronic kidney disease, this knowledge could help establish public health strategies for monitoring patients and understanding the impact of the Apolipoprotein L1 genetic variants in admixed populations. Therefore, researchers need to develop resources, methodologies, and incentives for vulnerable and disadvantaged communities, to develop and implement precision medicine strategies and contribute to consolidating diversity in science and precision medicine in clinical practice., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Giudicelli, De Souza, Veronese, Pereira, Hünemeier and Vianna.)

This study aimed to compare in rats the cardiometabolic and cellular adaptative responses to 8 weeks of high-intensity interval training (HIIT) performed in a single (1xHIIT) or three shorter daily sessions (3xHIIT). Male Wistar rats were assigned to untrained (n = 10), 1xHIIT (n = 10), and 3xHIIT (n = 10) groups. Both HIIT groups performed 15 min of a treadmill run five times per week for 8 weeks. The 1xHIIT performed single daily sessions of 15 min, and the 3xHIIT performed three daily sessions of 5 min with an interval of 4 h between sessions. Resting VO 2 and VO 2 max were measured using a metabolic chamber; blood pressure and heart rate were measured by plethysmography; body composition was estimated by DEXA; Glucose and insulin tolerance tests were performed; after euthanasia, hearts, gastrocnemius, and visceral fat were harvested for analysis of cardiac function, histology, and morphology. Mitochondrial densities of the gastrocnemius and left ventricle muscles were determined by electron microscopy. 3xHIIT induced similar positive adaptative responses to 1xHIIT on resting VO 2 and VO 2 max, cardiac function, and mitochondria density. 3xHIIT was superior to 1xHIIT in reducing visceral fat weight and adipocyte size and improving insulin tolerance. Multiple short daily bouts of HIIT may be superior to single HIIT daily sessions in improving cardiometabolic and cellular adaptations in rats., (© 2022. The Author(s).)

This study aimed to investigate the effect of spray drying (SD) and freeze-drying (FD) on the microencapsulation of green coffee extracts by using polydextrose (PD) and inulin (IN) as encapsulating agents and their physicochemical, bioactive compounds' stability, phenolic compounds' bioaccessibility after digestion, and sensory effects in unfermented dairy beverages. The extract encapsulated with IN by FD had lower moisture content, water activity, and hygroscopicity, while particles encapsulated by SD exhibited a spherical shape and the structure of the FD products was irregular. No difference was observed in phenolic compounds' bioaccessibility. Dairy beverages with added encapsulated extracts had higher total phenolic content and antioxidant activity. Microencapsulation allowed a controlled release of the bioactive compounds with an increase in the content of caffeine, chlorogenic acid, and trigonelline during storage. The dairy beverage with added extract encapsulated with IN by FD had the highest scores of acceptability regarding the overall impression and purchase intent.

Context: Normocalcemic primary hyperparathyroidism (nPHPT) is defined by an inappropriately increased serum PTH with normal serum calcium. Information about the diagnostic yield of parathyroid SPECT/CT scan and ultrasonography in nHPPT is limited and not conclusive., Purpose: To evaluate the positivity rate of 99m Tc-Sestamibi SPECT/CT scan in nPHTP compared with classical hypercalcemic PHPT (cPHPT)., Materials and Methods: We retrospectively studied 125 patients with 99m Tc-Sestamibi SPECT/CT scans. Subjects were divided into 2 groups: cPHPT (n = 93) and nPHPT (n = 32)., Results: The detection rate of 99m Tc-Sestamibi SPECT/CT in cPHPT was 86,02% (80/93) and 59.37%, in nPHPT (19/32), p = .003. No significant differences were seen between the SPECT/CT scan and ultrasonography (p = .28) and the agreement was higher in cPHPT than in nPHPT, p = .03. Sensitivity of 99m Tc-Sestamibi-SPECT/CT was 98% on a per-patient basis (PPV 96%) and 91% on a per-lesion basis (PPV 88%). Glandular size was smaller in nPHPT (mean value 6.8 mm) and it was related only with PTH value., Conclusion: Localization rate of parathyroid hyperfunctioning tissue with 99m Tc-Sestamibi SPECT/CT is lower in nPHPT and it is related to a smaller glandular size. However, our study suggests that the positivity rate and sensitivity are nonnegligible by adding SPECT/CT. The reduction in the detection rate in nPHPT could benefit techniques with higher resolution such as 18 F-Choline PET/CT when the clinical context justifies it., (© 2021 John Wiley & Sons Ltd.)

Objective: To present the urban arboviruses (dengue, zika and chikungunya) stratification methodology by the territorial receptivity Index, an instrument for the surveillance and control of these diseases, which considers the heterogeneity of an intra-municipal territory., Methods: Ecological study that uses as unit of analysis the areas covered by health centers in Belo Horizonte. For the development of a territorial receptivity index, indicators of socio-environmental determination of urban arboviruses were selected in order to integrate the analysis of main components. The resulting components were weighted by the analytic hierarchy process and combined via map algebra., Results: The territorial receptivity index showed great heterogeneity of urban infrastructure conditions. The areas classified with high and very high receptivity correspond to approximately 33% of the occupied area and are mainly concentrated in the administrative planning regions of East, Northeast, North, West, and Barreiro, especially in areas surrounding the municipality. When the density of dengue cases and Aedes eggs, from 2016, were superimposed with the stratification by the index of territorial receptivity to urban arboviruses, areas of very high receptivity had a high density of cases and Aedes eggs - higher than that observed in other areas of the city, which corresponds to a very small percentage of the municipal territory (13.5%)., Conclusion: The analyses indicate the need for the development of adequate surveillance and control actions for each context, overcoming the logic of homogeneous allocation throughout the territory.

In acquired immune aplastic anemia (AA), pathogenic cytotoxic Th1 cells are activated and expanded, driving an immune response against the hematopoietic stem and progenitor cells (HSPCs) that provokes cell depletion and causes bone marrow failure. However, additional HSPC defects may contribute to hematopoietic failure, reflecting on disease outcomes and response to immunosuppression. Here we derived induced pluripotent stem cells (iPSCs) from peripheral blood (PB) erythroblasts obtained from patients diagnosed with immune AA using non-integrating plasmids to model the disease. Erythroblasts were harvested after hematologic response to immunosuppression was achieved. Patients were screened for germline pathogenic variants in bone marrow failure-related genes and no variant was identified. Reprogramming was equally successful for erythroblasts collected from the three immune AA patients and the three healthy subjects. However, the hematopoietic differentiation potential of AA-iPSCs was significantly reduced both quantitatively and qualitatively as compared to healthy-iPSCs, reliably recapitulating disease: differentiation appeared to be more severely affected in cells from the two patients with partial response as compared to the one patient with complete response. Telomere elongation and the telomerase machinery were preserved during reprogramming and differentiation in all AA-iPSCs. Our results indicate that iPSCs are a reliable platform to model immune AA and recapitulate clinical phenotypes. We propose that the immune attack may cause specific epigenetic changes in the HSPCs that limit adequate proliferation and differentiation., (© 2022. The Author(s).)

The study aimed to present the methodological proposal entitled "Prompt Response", modelled in the cities of Belo Horizonte (Minas Gerais State) and Natal (Rio Grande do Norte State), Brazil. The proposal aims to identify and demarcate priority areas for timely targeting of surveillance activities, aiming to reduce the intensity and velocity in the spread of epidemics in endemic urban areas. The methodology uses three variables that represent the necessary causes for the production and reproduction of dengue: notified cases (virus), Aedes eggs (vector), and population (host). This was an ecological study that used data from three information planes aggregated in finer temporal and spatial scales of 3 to 4 weeks and 400 to 600-meter grids, respectively. The prompt response areas were defined by Scan statistical analysis with definition of simultaneous spatial clusters for the three planes via the SaTScan program. In Natal, the areas defined as prompt response occupied, on average, 15.2% of the city's territory and concentrated 67.77% of the dengue cases in the period following demarcation of the prompt response areas. In Belo Horizonte, the observed proportions were 64.16% of cases in 23.23% of the territory. These results were obtained in two cities with different socioenvironmental and geographic realities and distinct epidemiological profiles, indicating that the methodology can be applied to different urban realities, allowing control programs to concentrate on reduced portions of the territory and impacting a high percentage of cases in timely fashion.

Neurodevelopmental processes of pluripotent cells, such as proliferation and differentiation, are influenced by external natural forces. Despite the presence of biogenic magnetite nanoparticles in the central nervous system and constant exposure to the Earth's magnetic fields and other sources, there is scant knowledge regarding the role of electromagnetic stimuli in neurogenesis. Moreover, emerging applications of electrical and magnetic stimulation to treat neurological disorders emphasize the relevance of understanding the impact and mechanisms behind these stimuli. Here, the effects of magnetic nanoparticles (MNPs) in polymeric coatings and the static external magnetic field (EMF) were investigated on neural induction of murine embryonic stem cells (mESCs) and human induced pluripotent stem cells (hiPSCs). The results show that the presence of 0.5% MNPs in collagen-based coatings facilitates the migration and neuronal maturation of mESCs and hiPSCs in vitro. Furthermore, the application of 0.4 Tesla EMF perpendicularly to the cell culture plane, discernibly stimulates proliferation and guide fate decisions of the pluripotent stem cells, depending on the origin of stem cells and their developmental stage. Mechanistic analysis reveals that modulation of ionic homeostasis and the expression of proteins involved in cytostructural, liposomal and cell cycle checkpoint functions provide a principal underpinning for the impact of electromagnetic stimuli on neural lineage specification and proliferation. These findings not only explore the potential of the magnetic stimuli as neural differentiation and function modulator but also highlight the risks that immoderate magnetic stimulation may affect more susceptible neurons, such as dopaminergic neurons., (© 2022. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Background: Endurance training prevents cardiac dysfunction induced by menopause, but to date, no studies compared the effects of endurance training prior to menopause versus estrogen replacement therapy during menopause on heart function of rats., Methods: Female Wistar rats aged three months were randomly assigned into three groups: Untrained ovariectomized rats (UN-OVX), untrained ovariectomized rats treated with estradiol (UN-OVX-E2), and ovariectomized rats previously exercised (EX-OVX). The endurance training protocol consisted of running on a treadmill at 60-70% of maximal aerobic capacity, 60 min per day, five days per week, for eight weeks. Estradiol replacement therapy consisted of silastic capsules containing the hormone for twelve days. After euthanasia, hearts were harvested, weighed and cardiac function was evaluated by the Langendorff technique., Results: Both cardiac contractility and relaxation indexes improved similarly in the EX-OVX and UN-OVX-E2 rats compared to UN-OVX., Conclusion: Our findings reveal similar beneficial effects between endurance training previously to menopause and estradiol replacement therapy during menopause on cardiac function of rats., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Marfan syndrome (MFS) is an autosomal dominant disease affecting cardiovascular, ocular and skeletal systems. It is caused by mutations in the fibrillin-1 (FBN1) gene, leading to structural defects of connective tissue and increased activation of TGF-β. Angiotensin II (ang-II) is involved in TGF-β activity and in bone mass regulation. Inhibition of TGF-β signaling by blockage of the ang-II receptor 1 (AT1R) via losartan administration leads to improvement of cardiovascular and pulmonary phenotypes, but has no effect on skeletal phenotype in the haploinsufficient mouse model of MFS mg R , suggesting a distinct mechanism of pathogenesis in the skeletal system. Here we characterized the skeletal phenotypes of the dominant-negative model for MFS mgΔ lpn and tested the effect of inhibition of ang-II signaling in improving those phenotypes. As previously shown, heterozygous mice present hyperkyphosis, however we now show that only males also present osteopenia. Inhibition of ang-II production by ramipril minimized the kyphotic deformity, but had no effect on bone microstructure in male mutant animals. Histological analysis revealed increased thickness of the anterior longitudinal ligament (ALL) of the spine in mutant animals (25.8 ± 6.3 vs. 29.7 ± 7.7 μm), coupled with a reduction in type I (164.1 ± 8.7 vs. 139.0 ± 4.4) and increase in type III (86.5 ± 10.2 vs. 140.4 ± 5.6) collagen in the extracellular matrix of this ligament. In addition, we identified in the MFS mice alterations in the erector spinae muscles which presented thinner muscle fibers (1035.0 ± 420.6 vs. 655.6 ± 239.5 μm 2 ) surrounded by increased area of connective tissue (58.17 ± 6.52 vs. 105.0 ± 44.54 μm 2 ). Interestingly, these phenotypes were ameliorated by ramipril treatment. Our results reveal a sex-dependency of bone phenotype in MFS, where females do not present alterations in bone microstructure. More importantly, they indicate that hyperkyphosis is not a result of osteopenia in the MFS mouse model, and suggest that incompetent spine ligaments and muscles are responsible for the development of that phenotype., (Copyright © 2021 The Author(s). Published by Elsevier Inc. All rights reserved.)

The aim of the current study was to investigate chronic pain coping strategies of older adults and the differences between sexes according to the intensity of pain. A cross-sectional study was performed in specialty clinics in midwestern Brazil. Participants comprised 276 older adults with chronic pain. The Brief Pain Inventory and Chronic Pain Coping Inventory-Brazilian version were used to assess self-reported pain intensity and pain coping strategies. Mann-Whitney U, Kruskal-Wallis, and Dunn tests were used for intergroup comparisons. The task persistence and coping self-statements subscales were the most used coping strategies. The strategies of exercise/stretching and task persistence were used differently between males and females. Males showed significant differences in asking for assistance, task persistence, and guarding subscales when pain intensity was taken into account, whereas females showed differences in the guarding and resting subscales. Adaptive coping was the most used coping strategy; however, some non-adaptive subscales were significant in both sexes when compared with levels of chronic pain intensity. [ Journal of Gerontological Nursing, 47 (10), 30-36.].

Background and Purpose: The Rasch model has not yet been used to evaluate the Chronic Pain Coping Inventory (CPCI), a tool used worldwide to measure coping with chronic pain., Objective: Analyze the adjustment of the CPCI-Brazilian version and its scales to the Rasch model., Methods: CPCI Rasch analysis with 705 outpatients from a Brazilian hospital., Results: The set of Illness-Focused coping strategies presented as a one-dimensional scale. The Rasch reliability of the person item ranged between 0.33 and 0.89, and 0.29 and 0.99, respectively. There were misfits for items 35 (MNSQOutfit = 2.12) and 54 (MNSQOutfit = 2.92), and DIF of one item regarding gender. The Wright map revealed some gaps in coping measurement., Conclusions: The scales of CPCIBrazilian Version fitted to the Rasch model after adjustments in the categories of response and exclusion of items 35 and 54., (© Copyright 2021 Springer Publishing Company, LLC.)

The COVID-19 pandemic has exposed the extent of global connectivity and collective vulnerability to emerging diseases. From its suspected origins in Wuhan, China, it spread to all corners of the world in a matter of months. The absence of high-performance, rapid diagnostic methods that could identify asymptomatic carriers contributed to its worldwide transmission. Serological tests offer numerous benefits compared to other assay platforms to screen large populations. First-generation assays contain targets that represent proteins from SARS-CoV-2. While they could be quickly produced, each actually has a mixture of specific and non-specific epitopes that vary in their reactivity for antibodies. To generate the next generation of the assay, epitopes were identified in three SARS-Cov-2 proteins (S, N, and Orf3a) by SPOT synthesis analysis. After their similarity to other pathogen sequences was analyzed, 11 epitopes outside of the receptor-binding domain (RBD) of the spike protein that showed high reactivity and uniqueness to the virus. These were incorporated into a ß-barrel protein core to create a highly chimeric protein. Another de novo protein was designed that contained only epitopes in the RBD. In-house ELISAs suggest that both multiepitope proteins can serve as targets for high-performance diagnostic tests. Our approach to bioengineer chimeric proteins is highly amenable to other pathogens and immunological uses.

Introduction: In cases of autism spectrum disorders with severe to profound hearing loss, cochlear implant is a therapeutic option., Objective: To identify evidence in the scientific literature that the cochlear implant brings benefits to people with autism spectrum disorders with associated hearing loss., Methods: Systematic review of the literature based on the criteria recommended by PRISMA. The population, intervention, comparison, outcomes, study design, PICOS strategy, was used to define the eligibility criteria. The studies that met the inclusion criteria for this second stage were included in a qualitative synthesis. Each type of study was analyzed according to the Joanna Briggs Institute's risk of bias assessment through the critical checklist for cohort studies, prevalence studies and critical criteria and case reports., Results: Four hundred and eighty-four articles were found in eight databases and 100 in the gray literature, mentioning the relationship between cochlear implants in patients with autism spectrum disorder and hearing loss. Twelve articles were read in full and 7 were selected for qualitative analysis in this systematic review. All seven articles were analyzed on the critical evaluation checklist. Four articles had a low risk of bias and three articles had a moderate risk of bias. In this study, were included 66 patients with autism spectrum disorder and hearing loss who received cochlear implant., Conclusion: This systematic review indicates that a cochlear implant can bring benefits to autism spectrum disorder patients with associated deafness., (Copyright © 2021 Associação Brasileira de Otorrinolaringologia e Cirurgia Cérvico-Facial. Published by Elsevier Editora Ltda. All rights reserved.)

Objective: To analyze the perceptions of children and adolescents about chronic postsurgical pain, experienced for three years after outpatient inguinal herniorrhaphy., Method: Descriptive, exploratory study, with a qualitative approach. Children and adolescents who reported chronic postsurgical pain were invited from previous quantitative research. The interviews with a semi-structured script were recorded, transcribed, and coded according to content analysis, thematic modality., Results: Twenty children and teenagers participated. They attributed different meanings to chronic persistent postsurgical pain, configuring a bad, uncomfortable, intermittent and limiting experience, which socially isolates, interferes with daily, school, and leisure activities. The report of pain was underestimated and neglected by the children's and adolescents' healthcare team, family members, teachers, and friends., Conclusion: Children and adolescents recognize postsurgical pain as persistent pain and seem to perceive that their report is underestimated and neglected by parents and teachers. Additionally, they feel responsible for the presence of pain that affects psychological and social dimensions and imposes damage and fear that leads to the return of the hernia and to death.

Human embryogenesis entails complex signalling interactions between embryonic and extra-embryonic cells. However, how extra-embryonic cells direct morphogenesis within the human embryo remains largely unknown due to a lack of relevant stem cell models. Here, we have established conditions to differentiate human pluripotent stem cells (hPSCs) into yolk sac-like cells (YSLCs) that resemble the post-implantation human hypoblast molecularly and functionally. YSLCs induce the expression of pluripotency and anterior ectoderm markers in human embryonic stem cells (hESCs) at the expense of mesoderm and endoderm markers. This activity is mediated by the release of BMP and WNT signalling pathway inhibitors, and, therefore, resembles the functioning of the anterior visceral endoderm signalling centre of the mouse embryo, which establishes the anterior-posterior axis. Our results implicate the yolk sac in epiblast cell fate specification in the human embryo and propose YSLCs as a tool for studying post-implantation human embryo development in vitro., Competing Interests: KM, BW, VS, CH, GH, TC, LP, SB, LV, MS, MZ No competing interests declared, (© 2021, Mackinlay et al.)

Aims: Menopause is a female condition induced by a reduction of ovarian hormone and is related to an increase in cardiovascular diseases in women. We have shown that severe calorie restriction (SCR) from birth reduces the cardiometabolic risk in adult male Wistar rats. In this study, we investigated the effects of SCR from birth to adulthood on cardiovascular function of ovariectomized rats., Main Methods: From birth to adulthood, rats were daily fed ad libitum (control group - C) or with 50% of the amount consumed by the control group (calorie-restricted group - R). At 90 days, half of the rats in each group underwent bilateral ovariectomy (OVX), totaling 4 groups: C-Sham, C-OVX, R-Sham, R-OVX. Systolic blood pressure (SBP), heart rate (HR) and, double product (DP) index were recorded by tail-cuff plethysmography. Cardiac function was analyzed by the Langendorff technique and cardiomyocyte diameter was accessed by histologic analysis. Additionally, cardiac SERCA2 content and redox status were evaluated., Key Findings: C-OVX rats exhibited reduced cardiac function and cardiac non-enzymatic total antioxidant capacity (TAC). R-Sham animals showed reduced SBP, DP, HR, improved cardiac function, reduced cardiac protein carbonyl derivatives and increased TAC, catalase, and superoxide dismutase activities. R-OVX rats maintained reduced SBP, DP, HR, and increased contractility and relaxation indexes. R-Sham and R-OVX rats exhibited preserved heart mass and reduced cardiomyocyte diameter. Cardiac SERCA2 content did not differ between the groups., Significance: Taken together, our findings show cardioprotective effects of SCR from birth in adult ovariectomized rats., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Objectives: to estimate the incidence and the risk factors for severe acute postoperative pain self-reported on the first day after hospital discharge., Methods: cohort study with 279 children from both sexes (5-12 years old), indicated for ambulatory surgery in two Brazilian hospitals. Children were assessed at the pre-surgery, immediate postoperative and first postoperative day. Faces Pain Scale-Revised and Yale Preoperative Anxiety Scale Modified were used. Severe postoperative pain was defined as score ≥6. Cox regression analyses were used., Results: the incidence of severe postoperative pain was 15.8% (95%CI:10.7%-20.4%) on the first postoperative day. Preoperative anxiety (HR=2.23; p=0.049), severe preoperative pain (HR=2.78; p=0.031) and having undergone two surgical procedures (HR=2.91; p=0.002) were associated with severe postoperative pain., Conclusions: the incidence of severe postoperative pain self-reported after hospital discharge was high. Anxiety and severe preoperative pain, in addition to performing two surgical procedures at the same time were confirmed as risk factors.

Objective: To analyze the factors associated with quality of life of the older adults with chronic pain., Method: Cross-sectional study conducted with 239 older adults in outpatient care in the state of Goiás, Brazil. The World Health Organization Quality of Life-Old (WHOQOL-OLD) instrument contains six domains and was applied to assess quality of life. Simple and multiple linear regressions were used in the statistical analysis., Results: The factors associated with Sensory Abilities were age (β = - 0.52), time spent together (β = - 14.35; - 17.86; - 15.57), and pain intensity (β = - 1, 70). Autonomy was associated with depression (β = - 5.99) and chest pain (β = - 6.17). Social participation related to schooling (β = - 0.64), diabetes mellitus (β = - 8.15), depression (β = - 14.53), pain intensity (β = - 1.43), and lower limb pain (β = - 5.94). Past, present and future activities related to depression (β = - 6.94). Death and dying related to hypertension (β = - 8.40), while Intimacy to depression (β = - 5.99) and headache/face pain (β = - 3.19)., Conclusion: The time experiencing chronic pain and the location of this experience, as well as depression, diabetes and systemic arterial hypertension were factors that had greater influence on the older adult's Quality of Life domains.

In mammals, dosage compensation of X-linked gene expression between males and females is achieved by inactivation of a single X chromosome in females, while upregulation of the single active X in males and females leads to X:autosome dosage balance. Studies in human embryos revealed that random X chromosome inactivation starts at the preimplantation stage and is not complete by day 12 of development. Alternatively, others proposed that dosage compensation in human preimplantation embryos is achieved by dampening expression from the two X chromosomes in females. Here, we characterize X-linked dosage compensation in another primate, the marmoset (Callithrix jacchus). Analyzing scRNA-seq data from preimplantation embryos, we detected upregulation of XIST at the morula stage, where female embryos presented a significantly higher expression of XIST than males. Moreover, we show an increase of X-linked monoallelically expressed genes in female embryos between the morula and late blastocyst stages, indicative of XCI. Nevertheless, dosage compensation was not achieved by the late blastocyst stage. Finally, we show that X:autosome dosage compensation is achieved at the 8-cell stage, and demonstrate that X chromosome dampening in females does not take place in the marmoset. Our work contributes to the elucidation of primate X-linked dosage compensation.

Introduction: Tinnitus is a frequent symptom in cochlear implant patients, often reported as persistent and disabling in implant candidates. Tinnitus is rarely considered in the preoperative evaluation of patients who are eligible for cochlear implantation. Many studies have shown that a cochlear implant leads to a significant change in the perception of tinnitus., Objective: To identify evidence in the scientific literature indicating that cochlear implant in eligible patients with tinnitus can improve tinnitus perception., Methods: One hundred forty articles were found from nine databases, and 20 articles from the gray literature mentioned the relationship between cochlear implant and tinnitus perception in patients eligible for cochlear implant. The PICOS (population, intervention, comparison, and outcome) strategy, was used to define the eligibility criteria. The studies that met the inclusion criteria for this second step were included in a qualitative synthesis, and each type of study was analyzed using the Joanna Briggs Institute critical appraisal checklist for quasi-experimental studies and the Joanna Briggs Institute critical appraisal checklist for randomized clinical trials., Results: The full texts of 11 articles were read, and 6 studies were selected for the meta-analysis. The total sample size in the evaluated articles was 136 patients with tinnitus who were eligible for cochlear implantation., Conclusions: Taken together, these findings support the feasibility of cochlear implantation to reduce the perception of tinnitus, thus providing a new perspective in the treatment of tinnitus in patients with hearing loss who are candidates for cochlear implantation., (Copyright © 2020 Associação Brasileira de Otorrinolaringologia e Cirurgia Cérvico-Facial. Published by Elsevier Editora Ltda. All rights reserved.)

Hypertension is a complex multifactorial disease characterized by a chronic increase of arterial pressure. Ninety percent of the cases are idiopathic and thus classified as essential hypertension. Uncontrolled arterial pressure has devasting consequences including cardiac insufficiency, stroke, dementia, chronic renal disease, ischemic heart disease and death. The hiPSC lines described here from six hypertensive patients and three controls were characterized according to established criteria and were shown to maintain pluripotency, differentiation into the three germ layers and genomic integrity. These cell lines can contribute to the understanding of the molecular mechanisms involved in hypertension in different cell types., (Copyright © 2021 The Author(s). Published by Elsevier B.V. All rights reserved.)

Background and Purpose: To date, vitamin K antagonists are the only available oral anticoagulants in patients with mechanical heart valves. In this way, we developed a pilot trial with rivaroxaban., Methods:  The RIWA study was a proof-of-concept, open-label, randomized clinical trial and was designed to assess the incidence of thromboembolic and bleeding events of the rivaroxaban-based strategy (15 mg twice daily) in comparison to dose-adjusted warfarin. Patients were randomly assigned in a 1:1 ratio and were followed prospectively for 90 days., Results:  A total of 72 patients were enrolled in the present study. Of these, 44 patients were randomized: 23 patients were allocated to the rivaroxaban group and 21 to the warfarin group. After 90 days of follow-up, the primary outcome occurred in one patient (4.3%) in the rivaroxaban group and three patients (14.3%) in the warfarin group (risk ratio [RR] 0.27; 95% confidence interval [CI] 0.02-2.85; P = 0.25). Minor bleeding (without discontinuation of medical therapy) occurred in six patients (26.1%) in the rivaroxaban group versus six patients (28.6%) in the warfarin group (RR 0.88; 95% CI 0.23-3.32; P = 0.85). One patient in the warfarin group died from myocardial infarction. No cases of hemorrhagic stroke, valve thrombosis, peripheral embolic events, or new intracardiac thrombus were related in both groups., Conclusions: In this pilot study, rivaroxaban 15 mg twice daily had thromboembolic and bleeding events similar to warfarin in patients with mechanical heart valves. These data confirm the authors' proof-of-concept and suggest that a larger trial with a similar design is not unreasonable. CLINICALTRIAL., Gov Identifier: NCT03566303.

Purpose: Fibrillin-1 and -2 are major components of tissue microfibrils that compose the ciliary zonule and cornea. While mutations in human fibrillin-1 lead to ectopia lentis, a major manifestation of Marfan syndrome (MFS), in mice fibrillin-2 can compensate for reduced/lack of fibrillin-1 and maintain the integrity of ocular structures. Here we examine the consequences of a heterozygous dominant-negative mutation in the Fbn1 gene in the ocular system of the mgΔ lpn mouse model for MFS., Methods: Eyes from mgΔ lpn and wild-type mice at 3 and 6 months of age were analyzed by histology. The ciliary zonule was analyzed by scanning electron microscopy (SEM) and immunofluorescence., Results: Mutant mice presented a significantly larger distance of the ciliary body to the lens at 3 and 6 months of age when compared to wild-type, and ectopia lentis. Immunofluorescence and SEM corroborated those findings in MFS mice, revealing a disorganized mesh of microfibrils on the floor of the ciliary body. Moreover, mutant mice also had a larger volume of the anterior chamber, possibly due to excess aqueous humor. Finally, losartan treatment had limited efficacy in improving ocular phenotypes., Conclusions: In contrast with null or hypomorphic mutations, expression of a dominant-negative form of fibrillin-1 leads to disruption of microfibrils in the zonule of mice. This in turn causes lens dislocation and enlargement of the anterior chamber. Therefore, heterozygous mgΔ lpn mice recapitulate the major ocular phenotypes of MFS and can be instrumental in understanding the development of the disease., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

Background: The Chronic Pain Coping Inventory (CPCI) has been widely used to measure coping with pain, however, the psychometric properties of the Brazilian CPCI are unknown., Aim: To verify the validity and reliability of the CPCI-Brazilian version., Materials and Methods: A sample of 705 outpatients with chronic pain participated in the study. Cronbach's alpha, corrected item-total correlations, and confirmatory factor analysis were performed, using the method of Diagonally Weighted Least Squares., Results: Construct validity was supported with a factor loading range of 0.36-0.90 (9 factors) corroborating original loads. The final model had adequate fit with items 42 and 54 excluded, D.F = 2174, TLI = 0.96; CFI = 0.96 and RMSEA = 0.051(p = 0.067). Eight of the nine CPCI scales showed satisfactory reliability (Cronbach's alpha ranged from 0.70 to 0.92). The Relaxation scale obtained a low alpha value (0.53)., Conclusion: The CPCI-Brazilian version, after exclusion of items 42 and 54, is valid to measure chronic pain coping in Brazilian adults., Competing Interests: The authors have declared that no competing interests exist.

The emergence of the new corona virus (SARS-CoV-2) and the resulting COVID-19 pandemic requires fast development of novel prevention and therapeutic strategies. These rely on understanding the biology of the virus and its interaction with the host, and on agnostic phenotypic screening for compounds that prevent viral infection. In vitro screenings of compounds are usually performed in human or animal-derived tumor or immortalized cell lines due to their ease of culturing. However, these platforms may not represent the tissues affected by the disease in vivo, and therefore better models are needed to validate and expedite drug development, especially in face of the COVID-19 pandemic. In this scenario, human induced pluripotent stem cells (hiPSCs) are a powerful research tool due to their ability to generate normal differentiated cell types relevant for the disease. Here we discuss the different ways hiPSCs can contribute to COVID-19 related research, including modeling the disease in vitro and serving as a platform for drug screening.

In the post-genomic era, genomic medicine interventions as a key component of personalized medicine and tailored-made health care are greatly anticipated following recent scientific and technological advances. Indeed, large-scale sequencing efforts that explore human genomic variation have been initiated in several, mostly developed, countries across the globe, such as the United States, the United Kingdom, and a few others. Here, we highlight the successful implementation of large-scale national genomic initiatives, namely the Genome of Greece (GoGreece) and the DNA do Brasil (DNABr), aiming to emphasize the importance of implementing such initiatives in developing countries. Based on this experience, we also provide a roadmap for replicating these projects in other low-resource settings, thereby bringing genomic medicine in these countries closer to clinical fruition., (Copyright © 2020 American Society of Human Genetics. Published by Elsevier Inc. All rights reserved.)

Background: Chronic post-surgical pain (CPSP) is one of the post-surgical complications of a Cesarean section. Despite the high rates of Cesarean section worldwide, the incidence of CPSP and the risk factors for this condition remain relatively unknown. The objective of this study was to calculate the incidence of CPSP in women submitted to Cesarean section and to analyze the associated risk factors., Materials and Methods: A prospective cohort of 621 women undergoing Cesarean section was recruited preoperatively. Potential presurgical (sociodemographic, clinical and lifestyle-related characteristics) and post-surgical risk factors (the presence and intensity of pain) risk factors were analyzed. Pain was measured at 24 hours and 7, 30, 60 and 90 days after surgery. Following discharge from hospital, data were collected by telephone. The outcome measure was self-reported pain three months after a Cesarean section. The risk factors for chronic pain were analyzed using the log-binomial regression model (a generalized linear model)., Results: A total of 462 women were successfully contacted 90 days following surgery. The incidence of CPSP was 25.5% (95%CI: 21.8-29.7). Risk factors included presurgical anxiety (adjusted relative risk [RR] 1.03; 95%CI: 1.01-1.05), smoking (adjusted RR 2.22; 95%CI: 1.27-3.88) and severe pain in the early postoperative period (adjusted RR 2.79; 95%CI: 1.29-6.00)., Conclusion: One in four women submitted to Cesarean section may develop CPSP; however, the risk factors identified here are modifiable and preventable. Preventive strategies directed towards controlling anxiety, reducing smoking during pregnancy and managing pain soon after hospital discharge are recommended., Competing Interests: The authors have declared that no competing interests exist.

COVID-19 is a severe disease that has reached pandemic status. To the best of our knowledge, we describe the first case of COVID-19 and cytomegalovirus (CMV) co-infection in a critically ill patient. We discuss the challenge of establishing the diagnosis as well as the management of tissue-invasive gastrointestinal CMV infection (TI-GI CMV) simulating vascular involvement and intestinal obstruction in a critically ill patient., Learning Points: We describe a case of COVID-19 and cytomegalovirus (CMV) co-infection in a critically ill patient.Clinical symptoms simulated mesenteric vascular involvement and intestinal obstruction.The successful management of invasive CMV colitis in a patient with COVID-19 with atypical symptoms is described., Competing Interests: Conflicts of Interests: The Authors declare that there are no competing interests., (© EFIM 2020.)

Elastic fibres provide tissues with elasticity and flexibility. In the healthy human cornea, elastic fibres are limited to the posterior region of the peripheral stroma, but their specific functional role remains elusive. Here, we examine the physical and structural characteristics of the cornea during development in the mgΔ loxPneo dominant-negative mouse model for Marfan syndrome, in which the physiological extracellular matrix of its elastic-fibre rich tissues is disrupted by the presence of a dysfunctional fibrillin-1 glycoprotein. Optical coherence tomography demonstrated a reduced corneal thickness in the mutant compared to wild type mice from embryonic day 16.5 until adulthood. X-ray scattering and electron microscopy revealed a disruption to both the elastic fibre and collagen fibril ultrastructure in the knockout mice, as well as abnormally low levels of the proteoglycan decorin. It is suggested that these alterations might be a result of increased transforming growth factor beta signalling. To conclude, this study has demonstrated corneal structure and ultrastructure to be altered when fibrillin-1 is disrupted and has provided insights into the role of fibrillin-1 in developing a functional cornea., Competing Interests: Declaration of competing interest The Authors have no conflicts of interest to disclose., (Copyright © 2020 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Mechanisms whereby fibrillin-1 mutations determine thoracic aorta aneurysms/dissections (TAAD) in Marfan Syndrome (MFS) are unclear. Most aortic aneurysms evolve from mechanosignaling deregulation, converging to impaired vascular smooth muscle cell (VSMC) force-generating capacity accompanied by synthetic phenotype switch. However, little is known on VSMC mechanoresponses in MFS pathophysiology. Here, we investigated traction force-generating capacity in aortic VSMC cultured from 3-month old mg∆ lpn MFS mice, together with morpho-functional and proteomic data. Cultured MFS-VSMC depicted marked phenotype changes vs. wild-type (WT) VSMC, with overexpressed cell proliferation markers but either lower (calponin-1) or higher (SM alpha-actin and SM22) differentiation marker expression. In parallel, the increased cell area and its complex non-fusiform shape suggested possible transition towards a mesenchymal-like phenotype, confirmed through several markers (e.g. N-cadherin, Slug). MFS-VSMC proteomic profile diverged from that of WT-VSMC particularly regarding lower expression of actin cytoskeleton-regulatory proteins. Accordingly, MFS-VSMC displayed lower traction force-generating capacity and impaired contractile moment at physiological substrate stiffness, and markedly attenuated traction force responses to enhanced substrate rigidity. Such impaired mechanoresponses correlated with decreased number, altered morphology and delocalization of focal adhesions, as well as disorganized actin stress fiber network vs. WT-VSMC. In VSMC cultured from 6-month-old mice, phenotype changes were attenuated and both WT-VSMC and MFS-VSMC generated less traction force, presumably involving VSMC aging, but without evident senescence. In summary, MFS-VSMC display impaired force-generating capacity accompanying a mesenchymal-like phenotype switch connected to impaired cytoskeleton/focal adhesion organization. Thus, MFS-associated TAAD involves mechanoresponse impairment common to other TAAD types, but through distinct mechanisms., (Copyright © 2019 Elsevier B.V. All rights reserved.)