Iron-enriched diet contributes to early onset of osteoporotic phenotype in a mouse model of hereditary hemochromatosis

Osteoporosis is associated with chronic iron overload secondary to hereditary hemochromatosis (HH), but the causative mechanisms are incompletely understood. The main objective of this study was to investigate the role of dietary iron on osteoporosis, using as biological model the Hfe-KO mice, which have a systemic iron overload. We showed that these mice show an increased susceptibility for developing a bone loss phenotype compared to WT mice, which can be exacerbated by an iron rich diet. The dietary iron overload caused an increase in inflammation and iron incorporation within the trabecular bone in both WT and Hfe-KO mice. However, the osteoporotic phenotype was only evident in Hfe-KO mice fed the iron-enriched diet. This appeared to result from an imbalance between bone formation and bone resorption driven by iron toxicity associated to Hfe-KO and confirmed by a decrease in bone microarchitecture parameters (identified by micro-CT) and osteoblast number. These findings were supported by the observed downregulation of bone metabolism markers and upregulation of ferritin heavy polypeptide 1 (Fth1) and transferrin receptor-1 (Tfrc), which are associated with iron toxicity and bone loss phenotype. In WT mice the iron rich diet was not enough to promote a bone loss phenotype, essentially due to the concomitant depression of bone resorption observed in those animals. In conclusion the dietary challenge influences the development of osteoporosis in the HH mice model thus suggesting that the iron content in the diet may influence the osteoporotic phenotype in systemic iron overload conditions.National Funds through Foundation for Science and Technology (FCT) Norte-01-0145-FEDER-000012 Portuguese Foundation for Science and Technology (FCT) SFRH/BD/77056/2011 European Regional Development Fund (FEDER) Norte-01-0145-FEDER-000012info:eu-repo/semantics/publishedVersio

A familial partial AZFb-c microdeletion associated with diferente fértile phenotypes

After the Klinefelter syndrome, Y chromosome microdeletions are the second most frequent genetic cause of spermatogenic failure resulting in male infertility. Y chromosome microdeletions, encompassing one or more of the three AZF regions, are associated with diverse testicular histology, ranging from Sertoli-cell-only syndrome (AZFa del), maturation arrest (AZFb del) to hypospermatogenesis (AZFc del). The molecular screening of these regions is routinely performed in the work-up of infertile patients with azoospermia or severe oligozoospermia as each one has different prognostic values, both in terms of clinical decision-making and appropriate genetic counselling as well as for understanding the etiology of spermatogenesis impairment. Different partial AZFc deletions were already described, although it is still controversial if these are truly a genetic risk factor for spermatogenesis impairment or a deletional variant without phenotypic consequences. Here we present the molecular results obtained after AZF analysis of two infertile brothers (both diagnosed with oligoteratoastenozoospermia), and of their fertile father. Several multiplex-PCR assays were performed with distinct sets of STS markers, specific for the three AZF regions. The molecular analysis revealed that all three men presented the same partial AZFb/c microdeletion, namely the absence of the sY1197, sY1291 and sY1192 STSs. This microdeletion probably results from the recombination of amplicons b1/b3, reducing the gene copy number of PRY, BPY, DAZ, and RBMY. The b1/b3 deletion is rare and its influence on spermatogenesis is still not clear since it can be found in men with severe oligozoospermia or with normal sperm counts. Our result suggests that b1/b3 del is most likely a risk factor predisposing to spermatogenic failure, but is not sufficient alone. The different (in)fertile phenotypes associated with it, a fertile father opposed to his two infertile sons, can be possibly influenced by genetic background, environmental and epigenetic factors, contributing to different phenotypic expressions of individual/specific genomes

Peroral esophageal segmentectomy and anastomosis with single transthoracic trocar : a step forward in thoracic NOTES.

BACKGROUND AND STUDY AIMS: A transesophageal natural orifice transluminal endoscopic surgery (NOTES) approach has been proposed for thoracic and mediastinal access. Similarly to transgastric surgery, serious limitations remain related to creating an esophagotomy and its safe closure. A hybrid approach in thoracic NOTES could work as an intermediate step before pure transesophageal NOTES. We assessed the benefit of hybrid thoracic NOTES for peroral segmental esophagectomy and subsequent complete esophageal anastomosis with a single transthoracic port. METHODS: Two protocols were used to attempt esophago-esophageal anastomosis: ex vivo using a phantom model (n = 5), and in vivo after esophageal mobilization, and segmental esophagectomy achieved using either a gastroscope (flexible) (n = 5) or thoracoscope (rigid) instruments (n = 5). A forward-viewing double-channel endoscope and a transthoracic operative thoracoscope with a working channel were coordinated in order to create a complete single-layer, end-to-end esophageal anastomosis ex vivo as well as in vivo. Feasibility and anastomosis quality were evaluated by inside and outside assessment of: patency, the incorporation of mucosa in all stitches, and a leak test. RESULTS: Anastomosis was achieved in all ex vivo experiments and thoracoscopically-led in vivo procedures. All anastomoses were patent, allowing distal passage of the endoscope, with mucosa incorporation. In in vivo experiments, a leak was detected in three animals and corrected with additional stitching. CONCLUSIONS: Peroral esophageal anastomosis with a single transthoracic trocar is feasible, which may represent a step forward in thoracic NOTES

FXTAS is rare among Portuguese patients with movement disorders: FMR1 premutations may be associated with a wider spectrum of phenotypes

The fragile X-associated tremor/ataxia syndrome (FXTAS) is a late-onset neurodegenerative disorder caused by expansions of 55-200 CGG repeats in the 5'UTR of the FMR1 gene. These FMR1 premutation expansions have relatively high frequency in the general population. To estimate the frequency of FMR1 premutations among Portuguese males with non-familial, late-onset movement disorders of unknown etiology, we assessed CGG repeat size in males with disease onset after the age of 50 and negative or unknown family history for late-onset movement disorders, who were sent for SCA, HD, or PD genetic testing at a reference laboratory. The selected patients had a primary clinical diagnosis based on one of the following cardinal features of FXTAS: ataxia, tremor, or cognitive decline. A total of 86 subjects were genotyped for the CGG repeat in the FMR1 gene. We detected one patient with an expansion in the premutation range. The frequency of FMR1 premutations was 1.9% (1/54) in our group of patients with ataxia as the primary clinical feature, and 1.2% (1/86) in the larger movement disorders group. In the family of the FXTAS case, premutation-transmitting females presented a history of psychiatric symptoms, suggesting that, given the wide phenotypical expression of the premutation in females, neuropsychiatric surveillance is necessary. In conclusion, genetic testing for FXTAS should be made available to patients with adult-onset movement disorders to enable adequate genetic counseling to family members

Valorization of fish by-products: physico-chemical properties of skin gelatins

info:eu-repo/semantics/publishedVersio

Effect of moderate hydrostatic pressures on the enzymatic activity and bioactive composition of pineapple by-products

Special Issue Original ArticleThe application of abiotic stresses by moderate hydrostatic pressures (MHP) is still underdeveloped. Abiotic stresses allow activating the enzymatic complexes inducing the synthesis of de novo bioactive compounds. Pineapple by-products are rich in bromelain and bioactive compounds that can be enhanced through abiotic stresses. The aim of this study was to evaluate the effect of MHP on the enzymatic activity of pineapple by-products. Pineapple by-products were submitted to MHP (50–400 MPa between 1 and 15 min) according to a central composite factorial design matrix. Samples were stored at 5 ± 1 C for 24 hr, to allow enzymatic activity to occur. Enzymatic and antioxidant activities and total phenolic compounds (TPC) were quantified. MHP promoted a 262% increase in the phenylalanine ammonia-lyase activity and 36% increase in TPC, in shell samples. In core the activity of bromelain increased 350%. These results pinpoint the potential to increase the value of pineapple by-products by enhancing the amounts of bioactive compounds through MHP applicationinfo:eu-repo/semantics/publishedVersio

Virtual reality for safe testing and development in collaborative robotics: challenges and perspectives

Collaborative robots (cobots) could help humans in tasks that are mundane, dangerous or where direct human contact carries risk. Yet, the collaboration between humans and robots is severely limited by the aspects of the safety and comfort of human operators. In this paper, we outline the use of extended reality (XR) as a way to test and develop collaboration with robots. We focus on virtual reality (VR) in simulating collaboration scenarios and the use of cobot digital twins. This is specifically useful in situations that are difficult or even impossible to safely test in real life, such as dangerous scenarios. We describe using XR simulations as a means to evaluate collaboration with robots without putting humans at harm. We show how an XR setting enables combining human behavioral data, subjective self-reports, and biosignals signifying human comfort, stress and cognitive load during collaboration. Several works demonstrate XR can be used to train human operators and provide them with augmented reality (AR) interfaces to enhance their performance with robots. We also provide a first attempt at what could become the basis for a human–robot collaboration testing framework, specifically for designing and testing factors affecting human–robot collaboration. The use of XR has the potential to change the way we design and test cobots, and train cobot operators, in a range of applications: from industry, through healthcare, to space operations.info:eu-repo/semantics/publishedVersio

Logic-based schedulability analysis for compositional hard real-time embedded systems

This is the author's version of the work. It is posted here by permission of ACM for your personal use. Not for redistribution. The definitive version was published in SIGBED Review, VOL.12, ISS.1, http://doi.acm.org/10.1145/2752801.2752808Over the past decades several approaches for schedu- lability analysis have been proposed for both uniprocessor and multi-processor real-time systems. Although different techniques are employed, very little has been put forward in using formal specifications, with the consequent possibility for misinterpretations or ambiguities in the problem statement. Using a logic based approach to schedulability analysis in the design of hard real-time systems eases the synthesis of correct-by- construction procedures for both static and dynamic verification processes. In this paper we propose a novel approach to schedulability analysis based on a timed temporal logic with time durations. Our approach subsumes classical methods for uniprocessor scheduling analysis over compositional resource models by providing the developer with counter-examples, and by ruling out schedules that cause unsafe violations on the system. We also provide an example showing the effectiveness of our proposal.This work was partially supported by National Funds through FCT (Portuguese Foundation for Science and Technology) and by ERDF (European Regional Development Fund) through COMPETE (Operational Programme ’Thematic Fac- tors of Competitiveness’), within projects Ref. FCOMP-01- 0124-FEDER-022701 (CISTER), FCOMP-01-0124-FEDER- 015006 (VIPCORE) and FCOMP-01-0124-FEDER-020486 (AVIACC)

REVISIÓN TAXONÓMICA DE LAS ESPECIES DEL GÉNERO CAVIA (RODENTIA: CAVIIDAE) EN COLOMBIA

It presents a taxonomic revision of the genus Cavia for Colombia. The general characteristics of the genus are given and a key for the identification of the species, based on skull characters and geographic distribution is presented and illustrated.Se presenta la revisión taxonómica del género Cavia en Colombia. Se incluye la clave de las especies con base en caracteres craneales y distribución geográfica. Palabras Claves: Cavia, taxonomía, géneros, clave, Colombia

Granuloma encapsulation is a key factor for containing tuberculosis infection in minipigs

Altres ajuts: MISA/FIS/PI080785Altres ajuts: I+D+I/FIS/CM06/00123A transthoracic infection involving a low dose of Mycobacterium tuberculosis has been used to establish a new model of infection in minipigs. The 20-week monitoring period showed a marked Th1 response and poor humoral response for the whole infection. A detailed histopathological analysis was performed after slicing the formalin-fixed whole lungs of each animal. All lesions were recorded and classified according to their microscopic aspect, their relationship with the intralobular connective network and their degree of maturity in order to obtain a dissemination ratio (DR) between recent and old lesions. CFU counts and evolution of the DR with time showed that the proposed model correlated with a contained infection, decreasing from week 9 onwards. These findings suggest that the infection induces an initial Th1 response, which is followed by local fibrosis and encapsulation of the granulomas, thereby decreasing the onset of new lesions. Two therapeutic strategies were applied in order to understand how they could influence the model. Thus, chemotherapy with isoniazid alone helped to decrease the total number of lesions, despite the increase in DR after week 9, with similar kinetics to those of the control group, whereas addition of a therapeutic M. tuberculosis fragment-based vaccine after chemotherapy increased the Th1 and humoral responses, as well as the number of lesions, but decreased the DR. By providing a local pulmonary structure similar to that in humans, the mini-pig model highlights new aspects that could be key to a better understanding tuberculosis infection control in humans