An overview of the appendicular skeletal anatomy of South American titanosaurian sauropods, with definition of a newly recognized clade

In the last two decades, the number of phylogenetically informative anatomical characters recognized in the appendicular skeleton of titanosaurian sauropod dinosaurs has increased dramatically with the discovery of new and comparatively complete specimens. here we provide an overview of the appendicular skeletal morphology of South American titanosaurs and discuss its significance for phylogenetic reconstruction. the appendicular skeletal diversity of South American titanosaurs is substantially greater than was initially appreciated. Moreover, some regions of the appendicular skeleton, such as the pes, exhibit remarkable variability in form. Multiple synapomorphies of titanosauria and the less inclusive clades Lithostrotia and Saltasauridae consist of characters of the girdles and limbs. Although the phylogenetic definitions of titanosaurian clades such as Saltasaurinae and Lognkosauria are stable, the taxonomic content of these clades has varied in recent analyses depending on the phylogenetic topology recovered. Within titanosauria, the results of four recent, largely independent analyses support the existence of a derived titanosaurian lineage distinct from the ‘Saltasaurinae line,’ which is herein termed Colossosauria. At present, this clade is mainly comprised by taxa within Lognkosauria and rinconsauria, and is useful in discussions of titanosaurian lower-level relationships.Fil: Gonzalez Riga, Bernardo Javier. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Mendoza; Argentina. Universidad Nacional de Cuyo. Facultad de Ciencias Exactas y Naturales. Laboratorio de Dinosaurios.; ArgentinaFil: Lamanna, Matthew C.. American Museum of Natural History; Estados Unidos. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Otero, Alejandro. Universidad Nacional de La Plata. Facultad de Ciencias Naturales y Museo. División Paleontología Vertebrados; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata; ArgentinaFil: Ortiz David, Leonardo Daniel. Universidad Nacional de Cuyo. Facultad de Ciencias Exactas y Naturales. Laboratorio de Dinosaurios.; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata; ArgentinaFil: Kellner, Alexander Wilhelm Armin. Universidade do Estado de Rio do Janeiro; BrasilFil: Ibiricu, Lucio Manuel. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Centro Nacional Patagónico. Instituto Patagónico de Geología y Paleontología; Argentin

Urinary Kininogen-1 and Retinol binding protein-4 respond to Acute Kidney Injury: Predictors of patient prognosis?

Implementation of therapy for acute kidney injury (AKI) depends on successful prediction of individual patient prognosis. Clinical markers as serum creatinine (sCr) have limitations in sensitivity and early response. The aim of the study was to identify novel molecules in urine which show altered levels in response to AKI and investigate their value as predictors of recovery. Changes in the urinary proteome were here investigated in a cohort of 88 subjects (55 AKI patients and 33 healthy donors) grouped in discovery and validation independent cohorts. Patients'urine was collected at three time points: within the first 48 h after diagnosis(T1), at 7 days of follow-up(T2) and at discharge of Nephrology(T3). Differential gel electrophoresis was performed and data were confirmed by Western blot (WB), liquid chromatography/mass spectrometry (LC-MS/MS) and enzyme-linked immunosorbent assay (ELISA). Retinol binding protein 4 (RBP4) and kininogen-1 (KNG1) were found significantly altered following AKI. RBP4 increased at T1, and progressively decreased towards normalization. Maintained decrease was observed for KNG1 from T1. Individual patient response along time revealed RBP4 responds to recovery earlier than sCr. In conclusion, KNG1 and RBP4 respond to AKI. By monitoring RBP4, patient's recovery can be anticipated pointing to a role of RBP4 in prognosis evaluation.Funding: from Instituto de Salud Carlos III: FIS PI11/01401, PI13/01873, FIS IF08/3667-1, CP09/00229, PI13/00047, PI10/00624, ISCIII-RETIC REDinREN RD012/0021. FEDER funds, Comunidad de Madrid/CIFRA S2010/BMD-2378, Programa Intensificación Actividad Investigadora (ISCIII/Agencia Laín-Entralgo/CM) to AO, IDCSalud (3371/002) and Fundación Conchita Rábago de Jiménez Díaz, Proteomic Facility from Universidad Complutense de Madrid-Fundación Parque Científico de Madrid (UCM-FPCM), Spain, a member of ProteoRed-ISCIII Network member of ProteoRed- ISCIII Networ

Behavioural intervention to reduce disruptive behaviours in adult day care centres users: A randomizsed clinical trial (PROCENDIAS study)

[ENG]Aim: This study assesses the effect of an intervention to reduce the disruptive behaviours (DB) presented by care recipient users of adult day care centres (ADCC), thereby reducing caregiver overload. While ADCC offer beneficial respite for family caregivers, the DB that many care recipients show promote resistance to attending these centres, which can be a great burden on their family caregivers. Design: Randomized controlled clinical trial. Methods: The study was carried out with 130 family caregivers of people attending seven ADCC in the municipality of Salamanca (Spain), randomly distributed into intervention and control groups. The intervention was applied across eight sessions, one per week, in groups of 8–10 people where caregivers were trained in the Antecedent- Behavior-Consequence (ABC) model of functional behaviour analysis. The primary outcome was the reduction of DB measured with the Revised Memory and Behavior Problems Checklist (RMBPC). Results: An average reduction in the RMBPC of 4.34 points was obtained in the intervention group after applying the intervention (p < 0.01 (U de Mann–Whitney); Cohen d = 1.00); furthermore, differences were found in the Center for Epidemiologic Studies Depression Scale (CES-D) (U = −2.67; p = 0.008; Cohen d = 0.50) and in the Short Zarit Burden Interview (Short ZBI) (t = −4.10; p < 0.01; Cohen d = 0.98). Conclusion: The results obtained suggest that the implementation of this intervention could reduce both the frequency of DB occurrence and the reaction of the caregiver to their appearance. Improvement was also noted in the results regarding overload and emotional state of the family caregiver. Impact: To our knowledge, this is the first randomized clinical trial to show that an intervention based on the ABC model could reduce the frequency and reaction of DB of care recipients in ADCC increasing their quality of life, and improving the mental health and overload of their family caregivers

Parkinson’s Disease Detection Using Isosurfaces-Based Features and Convolutional Neural Networks

Computer aided diagnosis systems based on brain imaging are an important tool to assist in the diagnosis of Parkinson’s disease, whose ultimate goal is the detection by automatic recognizing of patterns that characterize the disease. In recent times Convolutional Neural Networks (CNN) have proved to be amazingly useful for that task. The drawback, however, is that 3D brain images contain a huge amount of information that leads to complex CNN architectures. When these architectures become too complex, classification performances often degrades because the limitations of the training algorithm and overfitting. Thus, this paper proposes the use of isosurfaces as a way to reduce such amount of data while keeping the most relevant information. These isosurfaces are then used to implement a classification system which uses two of the most well-known CNN architectures, LeNet and AlexNet, to classify DaTScan images with an average accuracy of 95.1% and AUC = 97%, obtaining comparable (slightly better) values to those obtained for most of the recently proposed systems. It can be concluded therefore that the computation of isosurfaces reduces the complexity of the inputs significantly, resulting in high classification accuracies with reduced computational burden.MINECO/FEDER under TEC2015-64718-R, PSI2015-65848-R, PGC2018-098813-B-C32, and RTI2018-098913-B-100 projects

Mitogen-Activated Protein Kinase 14 Promotes AKI

An improved understanding of pathogenic pathways may identify novel acute kidney injury (AKI) therapeutic approaches. Unbiased LC-MS/MS protein expression profiling combined with focused data mining identified MAP3K14 and non-canonical NFκB activation at the crossroads of the enriched pathways MAPK, ubiquitin-mediated proteolysis, chemokines, NFκB and apoptosis in the kidney cortex of experimental toxic AKI. In AKI the upstream kinase MAP3K14, the NFκB DNA binding heterodimer RelB/NFκB2, and proteins involved in NFκB2 p100 ubiquitination and proteasomal processing to p52, such as Ube2m and cullin1 were up-regulated. Immunohistochemistry localized MAP3K14 expression to tubular cells in experimental and human AKI. In vivo evidence of MAP3K14 activation in experimental folic acid-induced AKI consisted of NFκB2 p100 processing to p52, nuclear location and DNA binding of RelB and NFκB2. MAP3K14 activity-deficient aly/aly mice were protected from kidney dysfunction, inflammation and apoptosis in AKI induced by folic acid and from lethality in cisplatin-induced AKI. MAP3K14 siRNA targeting in cultured tubular cells decreased inflammation and cell death. Bone marrow transplantation experiments where consistent with a protective effect of renal cell MAP3K14 targeting. Cell culture and in vivo studies identified chemokines MCP-1, RANTES and CXCL10 as MAP3K14 targets in tubular cells, thus identifying potential mediators of the deleterious effect of MAP3K14 in kidney injury. In conclusion, MAP3K14 promotes kidney injury through promotion of inflammation and cell death and is a promising novel therapeutic target

Analyses of chondrogenic induction of adipose mesenchymal stem cells by combined co-stimulation mediated by adenoviral gene transfer

INTRODUCTION: Adipose-derived stem cells (ASCs) have the potential to differentiate into cartilage under stimulation with some reported growth and transcriptional factors, which may constitute an alternative for cartilage replacement approaches. In this study, we analyzed the in vitro chondrogenesis of ASCs transduced with adenoviral vectors encoding insulin-like growth factor-1 (IGF-1), transforming growth factor beta-1 (TGF-β1), fibroblast growth factor-2 (FGF-2), and sex-determining region Y-box 9 (SOX9) either alone or in combinations. METHODS: Aggregate cultures of characterized ovine ASCs were transduced with 100 multiplicity of infections of Ad.IGF-1, Ad.TGF-β1, Ad.FGF-2, and Ad.SOX9 alone or in combination. These were harvested at various time points for detection of cartilage-specific genes expression by quantitative real-time PCR or after 14 and 28 days for histologic and biochemical analyses detecting proteoglycans, collagens (II, I and X), and total sulfated glycosaminoglycan and collagen content, respectively. RESULTS: Expression analyses showed that co-expression of IGF-1 and FGF-2 resulted in higher significant expression levels of aggrecan, biglycan, cartilage matrix, proteoglycan, and collagen II (all P ≤0.001 at 28 days). Aggregates co-transduced with Ad.IGF-1/Ad.FGF-2 showed a selective expression of proteoglycans and collagen II, with limited expression of collagens I and × demonstrated by histological analyses, and had significantly greater glycosaminoglycan and collagen production than the positive control (P ≤0.001). Western blot analyses for this combination also demonstrated increased expression of collagen II, while expression of collagens I and × was undetectable and limited, respectively. CONCLUSION: Combined overexpression of IGF-1/FGF-2 within ASCs enhances their chondrogenic differentiation inducing the expression of chondrogenic markers, suggesting that this combination is more beneficial than the other factors tested for the development of cell-based therapies for cartilage repair

Analysis of TNFAIP3, a feedback inhibitor of nuclear factor-κB and the neighbor intergenic 6q23 region in rheumatoid arthritis susceptibility

Introduction Genome-wide association studies of rheumatoid arthritis (RA) have identified an association of the disease with a 6q23 region devoid of genes. TNFAIP3, an RA candidate gene, flanks this region, and polymorphisms in both the TNFAIP3 gene and the intergenic region are associated with systemic lupus erythematosus. We hypothesized that there is a similar association with RA, including polymorphisms in TNFAIP3 and the intergenic region. Methods To test this hypothesis, we selected tag-single nucleotide polymorphisms (SNPs) in both loci. They were analyzed in 1,651 patients with RA and 1,619 control individuals of Spanish ancestry. Results Weak evidence of association was found both in the 6q23 intergenic region and in the TNFAIP3 locus. The rs582757 SNP and a common haplotype in the TNFAIP3 locus exhibited association with RA. In the intergenic region, two SNPs were associated, namely rs609438 and rs13207033. The latter was only associated in patients with anti-citrullinated peptide antibodies. Overall, statistical association was best explained by the interdependent contribution of SNPs from the two loci TNFAIP3 and the 6q23 intergenic region. Conclusions Our data are consistent with the hypothesis that several RA genetic factors exist in the 6q23 region, including polymorphisms in the TNFAIP3 gene, like that previously described for systemic lupus erythematosus

Association of body mass index with clinical outcomes in patients with atrial fibrillation: a report from the FANTASIIA Registry

[Abstract] Background. Obesity and atrial fibrillation (AF) frequently coexist and independently increase mortality. We sought to assess the association between obesity and adverse events in patients receiving oral anticoagulants for AF. Methods and Results. Consecutive AF outpatients receiving anticoagulant agents (both vitamin K antagonists and direct oral anticoagulants) were recruited into the FANTASIIA (Atrial fibrillation: influence of the level and type of anticoagulation on the incidence of ischemic and hemorrhagic stroke) registry. This observational, multicenter, and prospective registry of AF patients analyzes the quality of anticoagulation, incidence of events, and differences between oral anticoagulant therapies. We analyzed baseline patient characteristics according to body mass index, normal: <25 kg/m2, overweight: 25–30 kg/m2, and obese: ≥30 kg/m2), assessing all‐cause mortality, stroke, major bleeding and major adverse cardiovascular events (a composite of ischemic stroke, myocardial infarction, and total mortality) at 3 years’ follow‐up. In this secondary prespecified substudy, the association of weight on prognosis was evaluated. We recruited 1956 patients (56% men, mean age 73.8±9.4 years): 358 (18.3%) had normal body mass index, 871 (44.5%) were overweight, and 727 (37.2%) were obese. Obese patients were younger (P<0.01) and had more comorbidities. Mean time in the therapeutic range was similar across body mass index categories (P=0.42). After a median follow‐up of 1070 days, 255 patients died (13%), 45 had a stroke (2.3%), 146 a major bleeding episode (7.5%) and 168 a major adverse cardiovascular event (8.6%). Event rates were similar between groups for total mortality (P=0.29), stroke (P=0.90), major bleeding (P=0.31), and major adverse cardiovascular events (P=0.24). On multivariate Cox analysis, body mass index was not independently associated with all‐cause mortality, cardiovascular mortality, stroke, major bleeding, or major adverse cardiovascular events. Conclusions. In this prospective cohort of patients anticoagulated for AF, obesity was highly prevalent and was associated with more comorbidities, but not with poor prognosis

Long-Term Effectiveness of a Smartphone App and a Smart Band on Arterial Stiffness and Central Hemodynamic Parameters in a Population with Overweight and Obesity (Evident 3 Study): Randomised Controlled Trial

Background: mHealth technologies could help to improve cardiovascular health; however, their effect on arterial stiffness and hemodynamic parameters has not been explored to date. Objective: To evaluate the effect of a mHealth intervention, at 3 and 12 months, on arterial stiffness and central hemodynamic parameters in a sedentary population with overweight and obesity. Methods: Randomised controlled clinical trial (Evident 3 study). 253 subjects were included: 127 in the intervention group (IG) and 126 in the control group (CG). The IG subjects were briefed on the use of the Evident 3 app and a smart band (Mi Band 2, Xiaomi) for 3 months to promote healthy lifestyles. All measurements were recorded in the baseline visit and at 3 and 12 months. The carotid-femoral pulse wave velocity (cfPWV) and the central hemodynamic parameters were measured using a SphigmoCor System® device, whereas the brachial-ankle pulse wave velocity (baPWV) and the Cardio Ankle Vascular Index (CAVI) were measured using a VaSera VS-2000® device. Results: Of the 253 subjects who attended the initial visit, 237 (93.7%) completed the visit at 3 months of the intervention, and 217 (85.3%) completed the visit at 12 months of the intervention. At 12 months, IG showed a decrease in peripheral augmentation index (PAIx) (−3.60; 95% CI −7.22 to −0.00) and ejection duration (ED) (−0.82; 95% CI −1.36 to −0.27), and an increase in subendocardial viability ratio (SEVR) (5.31; 95% CI 1.18 to 9.44). In CG, cfPWV decreased at 3 months (−0.28 m/s; 95% CI −0.54 to −0.02) and at 12 months (−0.30 m/s, 95% CI −0.54 to −0.05), central diastolic pressure (cDBP) decreased at 12 months (−1.64 mm/Hg; 95% CI −3.19 to −0.10). When comparing the groups we found no differences between any variables analyzed. Conclusions: In sedentary adults with overweight or obesity, the multicomponent intervention (Smartphone app and an activity-tracking band) for 3 months did not modify arterial stiffness or the central hemodynamic parameters, with respect to the control group. However, at 12 months, CG presented a decrease of cfPWV and cDBP, whereas IG showed a decrease of PAIx and ED and an increase of SEVR

Prevention of Chemotherapy-induced Peripheral Neuropathy with PRESIONA, a Therapeutic Exercise and Blood Flow Restriction Program: A Randomized Controlled Study Protocol

Objective This trial will analyze the acute and cumulative effects of a tailored program called PRESIONA that combines therapeutic exercise and blood flow restriction to prevent chemotherapy-induced peripheral neuropathy (CIPN) in individuals with early breast cancer undergoing neoadjuvant chemotherapy. Methods PRESIONA will be a physical therapist–led multimodal exercise program that uses blood flow restriction during low-load aerobic and strength exercises. For the acute study, only 1 session will be performed 1 day before the first taxane cycle, in which 72 women will be assessed before intervention and 24 hours post intervention. For the cumulative study, PRESIONA will consist of 24 to 36 sessions for 12 weeks following an undulatory prescription. At least 80 women will be randomized to the experimental group or control group. Feasibility will be quantified based on the participant recruitment to acceptance ratio; dropout, retention, and adherence rates; participant satisfaction; tolerance; and program security. In the efficacy study, the main outcomes will be CIPN symptoms assessed with a participant-reported questionnaire (EORTC QLQ-CIPN20). In addition, to determine the impact on other participant-reported health and sensorimotor and physical outcomes, the proportion of completed scheduled chemotherapy sessions will be examined at baseline (t0), after anthracycline completion (t1), after intervention (t2), and at the 2-month (t3) and 1-year follow-ups (t4). Conclusion The proposed innovative approach of this study could have a far-reaching impact on therapeutic options, and the physical therapist role could be essential in the oncology unit to improve quality of life in individuals with cancer and reduce side effects of cancer and its treatments. Impact Physical therapists in the health care system could be essential to achieve the planned doses of chemotherapy to improve survival and decrease the side effects of individuals with breast cancer. The prevention of CIPN would have an impact on the quality of life in these individuals, and this protocol potentially could provide an action guide that could be implemented in any health care system.This study is funded by Fondo de Investigación Sanitaria del Instituto de Salud Carlos III (FI19/00230), the Spanish Ministry of Education Cultura y Deporte (FPU17/00939 and FPU18/03575), and Ilustre Colegio Profesional de Fisioterapeutas de Andalucía (AI-04/2020)