Multiscale characterisation of cortical bone tissue

Multiscale analysis has become an attractive technique to predict the behaviour of materials whose microstructure strongly changes spatially or among samples, with that microstructure controlling the local constitutive behaviour. This is the case, for example, of most biological tissues-such as bone. Multiscale approaches not only allow, not only to better characterise the local behaviour, but also to predict the field-variable distributions (e.g., strains, stresses) at both scales (macro and micro) simultaneously. However, multiscale analysis usually lacks sufficient experimental feedback to demonstrate its validity. In this paper an experimental and numerical micromechanics analysis is developed with application to cortical bone. Displacement and strain fields are obtained across the microstructure by means of digital image correlation (DIC). The other mechanical variables are computed following the micromechanics theory. Special emphasis is given to the differences found in the different field variables between the micro- and macro-structures, which points out the need for this multiscale approach in cortical bone tissue. The obtained results are used to establish the basis of a multiscale methodology with application to the analysis of bone tissue mechanics at different spatial scales

Diseño de dispositivos para el análisis experimental del proceso de transporte óseo en ovejas

La distracción osteogénica, es una técnica que permite generar nuevo tejido óseo a partir de la separación gradual de dos fragmentos óseos. Aunque se han realizado numerosos estudios experimentales sobre el proceso de distracción, no se ha analizado cuantitativamente la evolución de la rigidez del callo durante el proceso de distracción y posteriormente a él. El objetivo de este trabajo es aplicar técnicas experimentales para caracterizar este proceso mecánicamente y validar modelos numéricos del proceso de distracción y consolidación existentes. Para conocer la rigidez del callo en cada momento, se ha diseñado un dispositivo que permite obtener datos experimentales de las fuerzas que pasan por el callo y distractor in vivo, en unos ensayos de transporte óseo en el hueso metatarsiano de ovejas. El diseño de este experimento ha requerido crear una serie de dispositivos. En primer lugar, se optimizó un distractor tipo Ilizarov y se añadieron sistemas de medida de fuerzas. En segundo lugar, fue necesario diseñar un útil para la correcta colocación del distractor durante la intervención quirúrgica. Finalmente, para poder obtener valores de fuerza en el hueso fue necesario el diseño de un sistema de adquisición de datos que permitiera la medida de fuerzas in vivo.Distraction osteogenesis is a technique to generate new bone tissue from the gradual separation of two bone fragments. Although there are many experimental studies about the distraction process, the evolution of the callus stiffness has not been analyzed quantitatively during the distraction and then it. The aim of this work is to apply experimental techniques to characterize this process mechanically and to validate existing numerical models about distraction and consolidation. To know callus stiffness at any time, a device has been design to obtain force in distractor and callus experimental data in vivo, by means of experiments performed in the metatarsus bone of sheep. The design of this experiment requires creating some devices. First, a Ilizarov distractor was optimized and force transducers were added. Secondly, it was necessary to design a tool that allows a correct installation of distractor during surgery. Finally, in order to obtain force values in the bone, it was necessary to design a data acquisition system which allows the measurement of in vivo forces.Junta de Andalucía P09-TEP-519

Evolution of relaxation properties of callus tissue during bone transport

Callus tissue exhibits a viscoelastic behavior that has a strong influence on the distribution of stresses and their evolution with time and, thus, it can affect tissue differentiation during distraction procedures. For this reason, a deep knowledge of that viscoelastic behavior can be very useful to improve current protocols of bone distraction and bone transport. Monitoring stress relaxation of the callus during distraction osteogenesis allows characterizing its viscoelastic behavior. Different procedures have been used in the literature to fit the response of a given viscoelastic model to the force relaxation curve. However, these procedures do not ensure the uniqueness of that fit, which is of the utmost importance for statistical purposes. This work uses a fitting procedure already validated for other tissues that ensures that uniqueness. Very importantly too, the procedure presented here allows obtaining more information from the stress relaxation tests, distinguishing relaxation in different time scales, which provides a deeper insight into the viscoelastic behavior and its evolution over time. As it was observed in the results, relaxation is faster at the first days after osteotomy and becomes slower and more gradual with time. This fact can be directly linked to the temporal evolution of the callus composition (water, organic phase, and mineral content) and also to the progression of tissue differentiation, with a prevalence of hard tissues as time passes

Time-Dependent Collagen Fibered Structure in the Early Distraction Callus: Imaging Characterization and Mathematical Modeling

Collagen is a ubiquitous protein present in regenerating bone tissues that experiences multiple biological phenomena during distraction osteogenesis until the deposition of phosphate crystals. This work combines fluorescence techniques and mathematical modeling to shed light on the mechano-structural processes behind the maturation and accommodation-to-mineralization of the callus tissue. Ovine metatarsal bone calluses were analyzed through confocal images at different stages of the early distraction osteogenesis process, quantifying the fiber orientation distribution and mean intensity as fiber density measure. Likewise, a mathematical model based on the experimental data was defined to micromechanically characterize the apparent stiffening of the tissue within the distracted callus. A reorganization of the fibers around the distraction axis and increased fiber density were found as the bone fragments were gradually separated. Given the degree of significance between the mathematical model and previous in vivo data, reorganization, densification, and bundle maturation phenomena seem to explain the apparent mechanical maturation observed in the tissue theoretically.This work was supported by the Spanish Ministry of Economy, Industry and Competitiveness [Grant No. DPI2017-82501-P]; the Spanish State Research Agency (AEI) [Grant No. PID2020-113790RB-I00/AEI/ 10.13039/501100011033]; and the European Regional Development Fund (FEDER) with the Junta de Andalucı ´a [Grant No. US-1261691]

Real-Time Wireless Platform for In Vivo Monitoring of Bone Regeneration

For the monitoring of bone regeneration processes, the instrumentation of the fixation is an increasingly common technique to indirectly measure the evolution of bone formation instead of ex vivo measurements or traditional in vivo techniques, such as X-ray or visual review. A versatile instrumented external fixator capable of adapting to multiple bone regeneration processes was designed, as well as a wireless acquisition system for the data collection. The design and implementation of the overall architecture of such a system is described in this work, including the hardware, firmware, and mechanical components. The measurements are conditioned and subsequently sent to a PC via wireless communication to be in vivo displayed and analyzed using a developed real-time monitoring application. Moreover, a model for the in vivo estimation of the bone callus stiffness from collected data was defined. This model was validated in vitro using elastic springs, reporting promising results with respect to previous equipment, with average errors and uncertainties below 6.7% and 14.04%. The devices were also validated in vivo performing a bone lengthening treatment on a sheep metatarsus. The resulting system allowed the in vivo mechanical characterization of the bone callus during experimentation, providing a low-cost, simple, and highly reliable solution.Junta de Andalucía US-1261691Ministerio de Economía y Competitividad DPI2017-82501-PMinisterio de Economía y Competitividad PGC2018-097257-B-C3

Occupational Therapy in Mental Health via Telehealth during the COVID-19 Pandemic

The COVID-19 pandemic has brought about changes in mental health occupational therapy. Research into these changes and the associated risks of relapse is insufficient. To explore the changes that have taken place in forms of occupational intervention (face-to-face and online) during the pandemic, and to analyze their association with subsequent relapses, a multicenter retrospective cohort study was carried out of 270 patients with mental disorder diagnoses under follow-up in day hospitals during 2020. Our results show that the frequency of face-to-face occupational therapy interventions decreased during lockdown and subsequently recovered. Interventions via telehealth increased during lockdown and have since been continued to a greater extent than before lockdown. Patients who received occupational intervention via telehealth relapsed less in the following six months (10.7% vs. 26.3%; χ2 = 10.372; p = 0.001), especially those who received intervention via videoconferencing (4.2% vs. 22%; χ2 = 5.718; p = 0.017). In conclusion, lockdown subsequent to the COVID-19 outbreak led to a reduction in face-to-face occupational therapy interventions, putting people with prior mental disorders at risk, while the implementation of telehealth tools helped reduce relapses

Composición y diversidad de peces del río San Pedro, Balancán, Tabasco, México

In the San Pedro river sub-basin, Balancán, Tabasco, Mexico, an ichthyofauna study was carried out in two subsystems; the main stream and the floodplain during the months of March 2007 to February 2008. From a total of 1035 fish were collected, 33 species, 25 genera and 14 families were identified. The Cichlidae and Poeciliidae family were the most species; four species are introduced Pterygoplichthys pardalis, Ctenopharyngodon idella, Oreochromis niloticus, Parachromis managuensis and two new records were found: P. pardalis and Potamarius usumacintae. The most abundance species were Thorichthys affinis and T. helleri and five species were least abundant: P. usumacintae, Phallichthys fairweatheri, Cichlasoma Nandopsis urophthalmus, C. idella and Batrachoides goldmani. The higher values of diversity and abundance showed in sites I (H=2.52 bits) and II (?=0.38 sp/ind). The higher values of evenness were in sites III (J = 0.86) and IV (J = 0.99). The abundance (Nmax = 353) species was showed in the site II. Significant differences (p<0.05) were found between the diversity and sites comparison. Canonical correspondence analysis showed that the temperature, dissolved oxygen and depth are the most important factors in the distribution of species. Finally, the relative abundance of species in the two seasons was representative by two families; Cichlidae T. affinis, (T. helleri and Petenia splendida) and Characidae(Astyanax aeneus).En la subcuenca del río San Pedro, Balancán, Tabasco, México, se realizó un estudio ictiofaunístico en dos subsistemas; el cauce principal del río y la zona de inundación en la parte baja, durante los meses de marzo 2007 a febrero 2008. De un total de 1,035 peces capturados, se identificaron 33 especies, 25 géneros y 14 familias. La familia Cichlidae y Poeciliidae fueron las más diversas, cuatro especies son introducidas: Pterygoplichthys pardalis, Ctenopharyngodon idella, Oreochromis niloticus, Parachromis managuensis, dos son nuevos registros Potamarius usumacintae y P. pardalis. Las especies más abundantes fueron Thorichthys affinis y T. helleri, mientras que P. usumacintae, Phallichthys fairweatheri, Cichlasoma Nandopsis urophthalmus, C. idella y Batrachoides goldmani, fueron las menos abundantes. La diversidad ydominancia presentaron valores altos en los sitios I (H´=2.52 bits) y el sitio II (? =0.38 sp/ind), mientras que los sitios III (J´=0.86) y IV (J´=0.99) fueron más equitativos. La especie más abundante (Nmax= 353) se mostró en el sitio II. Se encontró diferencias significativas (p < 0.5) entre la comparación de la diversidad y sitios. El análisis de correspondencia canónica, mostró que la temperatura, el oxígeno disuelto y la profundidad son los factores más importantes en la distribución de las especies. Finalmente, se encontró que las abundancias relativas de las especies presentes en las dos épocas estuvo representadas por dos familias; Cichlidae (T. affinis, T. helleri, Petenia splendida) y Characidae con (Astyanax aeneus)

Natural History of MYH7-Related Dilated Cardiomyopathy

BACKGROUND Variants in myosin heavy chain 7 (MYH7) are responsible for disease in 1% to 5% of patients with dilated cardiomyopathy (DCM); however, the clinical characteristics and natural history of MYH7-related DCM are poorly described. OBJECTIVES We sought to determine the phenotype and prognosis of MYH7-related DCM. We also evaluated the influence of variant location on phenotypic expression. METHODS We studied clinical data from 147 individuals with DCM-causing MYH7 variants (47.6% female; 35.6 +/- 19.2 years) recruited from 29 international centers. RESULTS At initial evaluation, 106 (72.1%) patients had DCM (left ventricular ejection fraction: 34.5% +/- 11.7%). Median follow-up was 4.5 years (IQR: 1.7-8.0 years), and 23.7% of carriers who were initially phenotype-negative developed DCM. Phenotypic expression by 40 and 60 years was 46% and 88%, respectively, with 18 patients (16%) first diagnosed at <18 years of age. Thirty-six percent of patients with DCM met imaging criteria for LV noncompaction. During follow-up, 28% showed left ventricular reverse remodeling. Incidence of adverse cardiac events among patients with DCM at 5 years was 11.6%, with 5 (4.6%) deaths caused by end-stage heart failure (ESHF) and 5 patients (4.6%) requiring heart transplantation. The major ventricular arrhythmia rate was low (1.0% and 2.1% at 5 years in patients with DCM and in those with LVEF of <= 35%, respectively). ESHF and major ventricular arrhythmia were significantly lower compared with LMNA-related DCM and similar to DCM caused by TTN truncating variants. CONCLUSIONS MYH7-related DCM is characterized by early age of onset, high phenotypic expression, low left ventricular reverse remodeling, and frequent progression to ESHF. Heart failure complications predominate over ventricular arrhythmias, which are rare. (C) 2022 The Authors. Published by Elsevier on behalf of the American College of Cardiology Foundation

Clonal chromosomal mosaicism and loss of chromosome Y in elderly men increase vulnerability for SARS-CoV-2

The pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2, COVID-19) had an estimated overall case fatality ratio of 1.38% (pre-vaccination), being 53% higher in males and increasing exponentially with age. Among 9578 individuals diagnosed with COVID-19 in the SCOURGE study, we found 133 cases (1.42%) with detectable clonal mosaicism for chromosome alterations (mCA) and 226 males (5.08%) with acquired loss of chromosome Y (LOY). Individuals with clonal mosaic events (mCA and/or LOY) showed a 54% increase in the risk of COVID-19 lethality. LOY is associated with transcriptomic biomarkers of immune dysfunction, pro-coagulation activity and cardiovascular risk. Interferon-induced genes involved in the initial immune response to SARS-CoV-2 are also down-regulated in LOY. Thus, mCA and LOY underlie at least part of the sex-biased severity and mortality of COVID-19 in aging patients. Given its potential therapeutic and prognostic relevance, evaluation of clonal mosaicism should be implemented as biomarker of COVID-19 severity in elderly people. Among 9578 individuals diagnosed with COVID-19 in the SCOURGE study, individuals with clonal mosaic events (clonal mosaicism for chromosome alterations and/or loss of chromosome Y) showed an increased risk of COVID-19 lethality

Spatiotemporal Characteristics of the Largest HIV-1 CRF02_AG Outbreak in Spain: Evidence for Onward Transmissions

Background and Aim: The circulating recombinant form 02_AG (CRF02_AG) is the predominant clade among the human immunodeficiency virus type-1 (HIV-1) non-Bs with a prevalence of 5.97% (95% Confidence Interval-CI: 5.41–6.57%) across Spain. Our aim was to estimate the levels of regional clustering for CRF02_AG and the spatiotemporal characteristics of the largest CRF02_AG subepidemic in Spain.Methods: We studied 396 CRF02_AG sequences obtained from HIV-1 diagnosed patients during 2000–2014 from 10 autonomous communities of Spain. Phylogenetic analysis was performed on the 391 CRF02_AG sequences along with all globally sampled CRF02_AG sequences (N = 3,302) as references. Phylodynamic and phylogeographic analysis was performed to the largest CRF02_AG monophyletic cluster by a Bayesian method in BEAST v1.8.0 and by reconstructing ancestral states using the criterion of parsimony in Mesquite v3.4, respectively.Results: The HIV-1 CRF02_AG prevalence differed across Spanish autonomous communities we sampled from (p &lt; 0.001). Phylogenetic analysis revealed that 52.7% of the CRF02_AG sequences formed 56 monophyletic clusters, with a range of 2–79 sequences. The CRF02_AG regional dispersal differed across Spain (p = 0.003), as suggested by monophyletic clustering. For the largest monophyletic cluster (subepidemic) (N = 79), 49.4% of the clustered sequences originated from Madrid, while most sequences (51.9%) had been obtained from men having sex with men (MSM). Molecular clock analysis suggested that the origin (tMRCA) of the CRF02_AG subepidemic was in 2002 (median estimate; 95% Highest Posterior Density-HPD interval: 1999–2004). Additionally, we found significant clustering within the CRF02_AG subepidemic according to the ethnic origin.Conclusion: CRF02_AG has been introduced as a result of multiple introductions in Spain, following regional dispersal in several cases. We showed that CRF02_AG transmissions were mostly due to regional dispersal in Spain. The hot-spot for the largest CRF02_AG regional subepidemic in Spain was in Madrid associated with MSM transmission risk group. The existence of subepidemics suggest that several spillovers occurred from Madrid to other areas. CRF02_AG sequences from Hispanics were clustered in a separate subclade suggesting no linkage between the local and Hispanic subepidemics