Relationship between Falls and the Use of Medications and Diseases in an Otago Exercise Programme in Old People Living in the Community in Spain

Background: Falls are a significant health problem among older adults, and can result in severe injuries, disability, and even death. In Spain, the prevalence of falls is lower if the person lives in the community than if they are institutionalized. Research has shown that exercise is an effective strategy for reducing the risk of falls among older adults. The objective of this study was to study the influence of a multicomponent exercise intervention on falls in people between 65 and 80 years of age despite the presence of diseases and drug use that are risk factors for falls. Methods: This is a quasi-experimental study that focuses on people aged 65-80 who attended 21 primary healthcare centres. Target: Inclusion criteria were people between 65 and 80 years of age, living in the community with independent ambulation, and who were served by the healthcare centre of their region. Variables analysed: The number and characteristics of falls, sociodemographic, drug use, and previous diseases. Results: The drugs associated with falls are benzodiazepines (OR 2.58), vasodilators (OR = 2.51), and psychotropics (OR = 1.61). For one of the years, a relationship was found between the consumption of antidepressants and falls (OR = 1.83). The associated diseases were mental and behavioural (OR = 2.53). Discussion: The intervention has been related to the reduction in falls in people who consumed benzodiazepines, vasodilators, and psychotropics and in people with mental disorders. Conclusion: This research concludes the importance of the implementation of the Otago Exercise Programme in the prevention of falls in the elderly.This study was supported by the Health Research Fund PI16CIII/00031, ISCIII (Spanish Institute of Health Carlos III; grant number PI16/00821) and co-funded by ERDF “A way to make Europe”, the Region of Asturias PI16/00821, the Region of Murcia (CARM, FFIS17/AP/02/04), the Region of the Basque Country (2016111005) and the Carlos III Health Institute through the REDISSEC (RD12/0001/0016), RETICEF (RD12/0043/0006) and CIBERFES (CB16/10/00468). Open access was funded by the Official College of Nursing of the Principality of Asturias (CODEPA). The study protocol was previously published (Albornos-Muñoz et al., 2018) and registered on ClinicalTrials.org (NCT03320668).S

Reconstruction of the repetitive antifreeze glycoprotein genomic loci in the cold-water gadids Boreogadus saida and Microgadus tomcod.

Abstract Antifreeze glycoproteins (AFGPs) are a novel evolutionary innovation in members of the northern cod fish family (Gadidae), crucial in preventing death from inoculative freezing by environmental ice in their frigid Arctic and sub-Arctic habitats. However, the genomic origin and molecular mechanism of evolution of this novel life-saving adaptive genetic trait remained to be definitively determined. To this end, we constructed large insert genomic DNA BAC (bacterial artificial chromosome) libraries for two AFGP-bearing gadids, the high-Arctic polar cod Boreogadus saida and the cold-temperate Atlantic tomcod Microgadus tomcod, to isolate and sequence their AFGP genomic regions for fine resolution evolutionary analyses. The BAC library construction encountered poor cloning efficiency initially, which we resolved by pretreating the agarose-embedded erythrocyte DNA with a cationic detergent, a method that may be of general use to BAC cloning for teleost species and/or where erythrocytes are the source of input DNA. The polar cod BAC library encompassed 92,160 clones with an average insert size of 94.7 kbp, and the Atlantic tomcod library contained 73,728 clones with an average insert size of 89.6 kbp. The genome sizes of B. saida and M. tomcod were estimated by cell flow cytometry to be 836 Mbp and 645 Mbp respectively, thus their BAC libraries have approximately 10- and 9.7-fold genome coverage respectively. The inclusiveness and depth of coverage were empirically confirmed by screening the libraries with three housekeeping genes. The BAC clones that mapped to the AFGP genomic loci of the two gadids were then isolated by screening the BAC libraries with gadid AFGP gene probes. Eight minimal tiling path (MTP) clones were identified for B. saida, sequenced, and assembled. The B. saida AFGP locus reconstruction produced both haplotypes, and the locus comprises three distinct AFGP gene clusters, containing a total of 16 AFGP genes and spanning a combined distance of 512 kbp. The M. tomcod AFGP locus is much smaller at approximately 80 kbp, and contains only three AFGP genes. Fluorescent in situ hybridization with an AFGP gene probe showed the AFGP locus in both species occupies a single chromosomal location. The large AFGP locus with its high gene dosage in B. saida is consistent with its chronically freezing high Arctic habitats, while the small gene family in M. tomcod correlates with its milder habitats in lower latitudes. The results from this study provided the data for fine resolution sequence analyses that would yield insight into the molecular mechanisms and history of gadid AFGP gene evolution driven by northern hemisphere glaciation

The relation between functional performance, falls and previous falls among participants in the Otago programme: a secondary data analysis

Ana Beatriz Bays Moneo pertenece al Otago Project Working GroupFall prevention is a key priority in healthcare policies. Multicomponent exercises reduce the risk of falls. The purpose of this study is to describe the relationship between functional performance and falls after following the Otago multicomponent exercise programme and previous falls. A prospective multi-centre intervention study was performed on 498 patients aged over 65 in primary care, with or without a history of previous falls. Sociodemographic, anthropometric and functionality data were collected. The primary outcome was the occurrence of falls; functional performance was measured using the Tinetti, Short Physical Performance Battery and Timed Up and Go tests. Among the patients, 29.7% referred to previous falls. There was a statistically significant (p < 0.001) increase in falls at 6 months (10.1%) and at 12 months (7.6%) among participants with previous falls in the baseline assessment compared to those without. In addition, the existence of previous falls could be considered a risk factor at 6 and 12 months (OR =2.37, p = 0.002, and OR = 1.76, p = 0.046, respectively). With regard to balance and gait, differences between the groups were observed at 6 months in the Tinetti score (p < 0.001) and in the baseline assessment Timed Up and Go score (p < 0.044). Multicomponent exercises improve the fall rate, balance and gait in older people, although this improvement is less in people with previous falls. Earlier intervention and tailoring of exercises in patients with previous falls could help improve outcomes.The Project coordinated with file codes PI16/01520, PI16/00821, PI16/01316, PI16/01649, PI16/01042, PI16/01159 and PI16/01312 was funded by the Carlos III Health Institute through the Strategic Action in Health 2016 and co-funded by the European Regional Development Fund "A way to make Europe"; PI16CIII/00031 was funded by the Carlos III Health Institute through the 2016 Intramural Strategic Action in Health; 2016111005 was funded by the Government of the Basque Country Department of Health through the 2016 subsidies for research projects; FFIS17/AP/02/was funded by the Autonomous Community of the Region of Murcia through the Region of Murcia Foundation for Health Training and Research

Analysis of Paired Primary-Metastatic Hormone-Receptor Positive Breast Tumors (HRPBC) Uncovers Potential Novel Drivers of Hormonal Resistance

We sought to identify genetic variants associated with disease relapse and failure to hormonal treatment in hormone-receptor positive breast cancer (HRPBC). We analyzed a series of HRPBC with distant relapse, by sequencing pairs (n = 11) of tumors (primary and metastases) at >800X. Comparative genomic hybridization was performed as well. Top hits, based on the frequency of alteration and severity of the changes, were tested in the TCGA series. Genes determining the most parsimonious prognostic signature were studied for their functional role in vitro, by performing cell growth assays in hormonal-deprivation conditions, a setting that mimics treatment with aromatase inhibitors. Severe alterations were recurrently found in 18 genes in the pairs. However, only MYC, DNAH5, CSFR1, EPHA7, ARID1B, and KMT2C preserved an independent prognosis impact and/or showed a significantly different incidence of alterations between relapsed and non-relapsed cases in the TCGA series. The signature composed of MYC, KMT2C, and EPHA7 best discriminated the clinical course, (overall survival 90,7 vs. 144,5 months; p = 0.0001). Having an alteration in any of the genes of the signature implied a hazard ratio of death of 3.25 (p<0.0001), and early relapse during the adjuvant hormonal treatment. The presence of the D348N mutation in KMT2C and/or the T666I mutation in the kinase domain of EPHA7 conferred hormonal resistance in vitro. Novel inactivating mutations in KMT2C and EPHA7, which confer hormonal resistance, are linked to adverse clinical course in HRPBC

Pathogenic MAST3 Variants in the STK Domain Are Associated with Epilepsy

Objective: The MAST family of microtubule-associated serine–threonine kinases (STKs) have distinct expression patterns in the developing and mature human and mouse brain. To date, only MAST1 has been conclusively associated with neurological disease, with de novo variants in individuals with a neurodevelopmental disorder, including a mega corpus callosum. Methods: Using exome sequencing, we identify MAST3 missense variants in individuals with epilepsy. We also assess the effect of these variants on the ability of MAST3 to phosphorylate the target gene product ARPP-16 in HEK293T cells. Results: We identify de novo missense variants in the STK domain in 11 individuals, including 2 recurrent variants p.G510S (n = 5) and p.G515S (n = 3). All 11 individuals had developmental and epileptic encephalopathy, with 8 having normal development prior to seizure onset at \u3c2 years of age. All patients developed multiple seizure types, 9 of 11 patients had seizures triggered by fever and 9 of 11 patients had drug-resistant seizures. In vitro analysis of HEK293T cells transfected with MAST3 cDNA carrying a subset of these patient-specific missense variants demonstrated variable but generally lower expression, with concomitant increased phosphorylation of the MAST3 target, ARPP-16, compared to wild-type. These findings suggest the patient-specific variants may confer MAST3 gain-of-function. Moreover, single-nuclei RNA sequencing and immunohistochemistry shows that MAST3 expression is restricted to excitatory neurons in the cortex late in prenatal development and postnatally. Interpretation: In summary, we describe MAST3 as a novel epilepsy-associated gene with a potential gain-of-function pathogenic mechanism that may be primarily restricted to excitatory neurons in the cortex. ANN NEUROL 2021;90:274–284

Observing the Evolution of the Universe

How did the universe evolve? The fine angular scale (l>1000) temperature and polarization anisotropies in the CMB are a Rosetta stone for understanding the evolution of the universe. Through detailed measurements one may address everything from the physics of the birth of the universe to the history of star formation and the process by which galaxies formed. One may in addition track the evolution of the dark energy and discover the net neutrino mass. We are at the dawn of a new era in which hundreds of square degrees of sky can be mapped with arcminute resolution and sensitivities measured in microKelvin. Acquiring these data requires the use of special purpose telescopes such as the Atacama Cosmology Telescope (ACT), located in Chile, and the South Pole Telescope (SPT). These new telescopes are outfitted with a new generation of custom mm-wave kilo-pixel arrays. Additional instruments are in the planning stages.Comment: Science White Paper submitted to the US Astro2010 Decadal Survey. Full list of 177 author available at http://cmbpol.uchicago.ed

Kinematic analysis of the super-extended HI disk of the nearby spiral galaxy M 83

Funding: CE, FB, AB, IB, JdB and JP acknowledge funding from the European Research Council (ERC) under the European Union’s Horizon 2020 research and innovation programme (grant agreement No.726384/Empire). TGW acknowledges funding from the European Research Council (ERC) under the European Union’s Horizon 2020 research and innovation programme (grant agreement No. 694343). JMDK gratefully acknowledges funding from the European Research Council (ERC) under the European Union’s Horizon 2020 research and innovation programme via the ERC Starting Grant MUSTANG (grant agreement number 714907). SCOG acknowledges funding from the European Research Council via the ERC Synergy Grant “ECOGAL – Understanding our Galactic ecosystem: From the disk of the Milky Way to the formation sites of stars and planets” (project ID 855130). WJGdB received funding from the European Research Council (ERC) under the European Union’s Horizon 2020 research and innovation programme (grant agreement No 882793 ‘MeerGas’).We present new HI observations of the nearby massive spiral galaxy M83, taken with the VLA at 21″ angular resolution (≈500 pc) of an extended (1.5 deg2) 10-point mosaic combined with GBT single dish data. We study the super-extended HI disk of M83 (∼50 kpc in radius), in particular disc kinematics, rotation and the turbulent nature of the atomic interstellar medium. We define distinct regions in the outer disk (rgal > central optical disk), including ring, southern area, and southern and northern arm. We examine HI gas surface density, velocity dispersion and non-circular motions in the outskirts, which we compare to the inner optical disk. We find an increase of velocity dispersion (σv) towards the pronounced HI ring, indicative of more turbulent HI gas. Additionally, we report over a large galactocentric radius range (until rgal ∼ 50 kpc) that σv is slightly larger than thermal (i.e. > 8 km s-1). We find that a higher star formation rate (as traced by FUV emission) is not always necessarily associated with a higher HI velocity dispersion, suggesting that radial transport could be a dominant driver for the enhanced velocity dispersion. We further find a possible branch that connects the extended HI disk to the dwarf irregular galaxy UGCA365, that deviates from the general direction of the northern arm. Lastly, we compare mass flow rate profiles (based on 2D and 3D tilted ring models) and find evidence for outflowing gas at rgal ∼ 2 kpc, inflowing gas at rgal ~ 5.5 kpc and outflowing gas at rgal ~ 14 kpc. We caution that mass flow rates are highly sensitive to the assumed kinematic disk parameters, in particular, to the inclination.Publisher PDFPeer reviewe

Molecular pedomorphism underlies craniofacial skeletal evolution in Antarctic notothenioid fishes

Background Pedomorphism is the retention of ancestrally juvenile traits by adults in a descendant taxon. Despite its importance for evolutionary change, there are few examples of a molecular basis for this phenomenon. Notothenioids represent one of the best described species flocks among marine fishes, but their diversity is currently threatened by the rapidly changing Antarctic climate. Notothenioid evolutionary history is characterized by parallel radiations from a benthic ancestor to pelagic predators, which was accompanied by the appearance of several pedomorphic traits, including the reduction of skeletal mineralization that resulted in increased buoyancy. Results We compared craniofacial skeletal development in two pelagic notothenioids, Chaenocephalus aceratus and Pleuragramma antarcticum, to that in a benthic species, Notothenia coriiceps, and two outgroups, the threespine stickleback and the zebrafish. Relative to these other species, pelagic notothenioids exhibited a delay in pharyngeal bone development, which was associated with discrete heterochronic shifts in skeletal gene expression that were consistent with persistence of the chondrogenic program and a delay in the osteogenic program during larval development. Morphological analysis also revealed a bias toward the development of anterior and ventral elements of the notothenioid pharyngeal skeleton relative to dorsal and posterior elements. Conclusions Our data support the hypothesis that early shifts in the relative timing of craniofacial skeletal gene expression may have had a significant impact on the adaptive radiation of Antarctic notothenioids into pelagic habitats