Drugs use in pregnancy in the Valencia Region and the risk of congenital anomalies

Background Despite the potential risks of drug use during pregnancy, consumption has increased in recent decades. Objective To identify the risk of congenital anomalies (CA) associated with the use of drugs in primary care in pregnant women resident in the Valencia Region. Methods A case-control study, considering a case as a less than one year old live birth in 2009–2010, diagnosed with a CA and resident in the Valencia Region, obtained from the CA population-based registry. Controls were selected from the Metabolic Disease Registry, and the drugs prescribed and dispensed from the Integral Management of Pharmaceutical Services. Crude odds ratio (OR) was calculated with its 95% confidence intervals and adjusted OR was calculated using logistic regression. Results A total of 1.913 cases and 3.826 controls were identified. The most frequently used drug groups were those acting on the musculoskeletal, nervous and respiratory systems, on the blood and blood forming organs, and anti-infection drugs. The most common drugs used were ibuprofen, dexketoprofen, paracetamol, amoxicillin, ferrous sulphate, and a combination of folic acid. A significantly increased risk of CA was identified for drugs acting on the musculoskeletal system (adjusted OR 1.14 [95% confidence interval 1.02–1.28]). A significantly decreased risk was observed for drugs acting on the blood and blood forming organs (adjusted OR 0.87 [95% confidence interval 0.78–0.98]). Conclusions Associations between drugs and CA in pregnant women resident in the Valencia Region have been identified for drugs that act as risk factors of CA, and for drugs that act as protective factors of CA. Antecedentes El consumo de medicamentos durante el embarazo se ha incrementado en las últimas décadas. Objetivo Identificar el riesgo de anomalías congénitas (AC) asociado a la utilización de medicamentos en atención ambulatoria en embarazadas residentes en la Comunitat Valenciana. Métodos Estudio de casos-controles, considerando caso a menores de un año nacidos vivos en 2009-2010 diagnosticados de AC y residentes en la Comunitat Valenciana, obtenidos del registro poblacional de AC. Los controles se seleccionaron del Registro de Metabolopatías y la medicación prescrita y dispensada se obtuvo del módulo Gestión Integral de Prestación Farmacéutica. Se calcularon las odds ratio (OR) y los intervalos de confianza al 95% y las OR ajustadas mediante regresión logística. Resultados Se identificaron 1.913 casos y 3.826 controles. Los grupos de medicamentos más frecuentemente prescritos y dispensados fueron: los que actúan sobre los sistemas musculoesquelético, nervioso, respiratorio, sobre la sangre y órganos hematopoyéticos, y antiinfecciosos. Los medicamentos más habituales fueron: ibuprofeno, dexketoprofeno, paracetamol, amoxicilina, sulfato de hierro y una combinación de ácido fólico. Se identificó un aumento del riesgo de anomalías congénitas significativo para los fármacos de acción sobre el sistema musculoesquelético (OR ajustada de 1,14 [intervalo de confianza al 95% 1,02-1,28]). Se observó una disminución del riesgo significativa en el grupo que actúa sobre la sangre y los órganos hematopoyéticos (OR ajustada de 0,87 [intervalo de confianza al 95% 0,78-0,98]). Conclusiones Se han identificado asociaciones de medicamentos con AC en mujeres embarazadas residentes en la Comunitat Valenciana, tanto para fármacos que actúan como factores de riesgo de AC como para fármacos que actúan como factores protectores de AC

Association of sepsis-related mortality with early increase of TIMP-1/MMP-9 ratio

Objective: Higher circulating levels of tissue inhibitor of matrix metalloproteinases (TIMP)-1 at the time of severe sepsis diagnosis have been reported in nonsurviving than in surviving patients. However, the following questions remain unanswered: 1) Does TIMP-1/MMP-9 ratio differ throughout the first week of intensive care between surviving and nonsurviving patients? 2) Is there an association between TIMP-1/MMP-9 ratio and sepsis severity and mortality during such period? 3) Could TIMP-1/MMP-9 ratio during the first week be used as an early biomarker of sepsis outcome? 4) Is there an association between TIMP-1/MMP-9 ratio and coagulation state and circulating cytokine levels during the first week of intensive care in these patients? The present study sought to answer these questions. Methods: Multicenter, observational and prospective study carried out in six Spanish Intensive Care Units (ICUs) of 295 patients with severe sepsis. Were measured circulating levels of TIMP-1, MMP-9, tumour necrosis factor (TNF)-alpha, interleukin (IL)-10 and plasminogen activator inhibitor (PAI)-1 at day 1, 4 and 8. End-point was 30-day mortality. Results: We found higher TIMP-1/MMP-9 ratio during the first week in non-surviving (n = 98) than in surviving patients (n = 197) (p, 0.01). Logistic regression analyses showed that TIMP-1/MMP-9 ratio at days 1, 4 and 8 was associated with mortality. Receiver operating characteristic (ROC) curves showed that TIMP-1/MMP-9 ratio at days 1, 4 and 8 could predict mortality. There was an association between TIMP-1/MMP-9 ratio and TNF-alpha, IL-10, PAI-1 and lactic acid levels, SOFA score and platelet count at days 1, 4 and 8. Conclusions: The novel findings of our study were that non-surviving septic patients showed persistently higher TIMP-1/ MMP-9 ratio than survivors ones during the first week, which was associated with severity, coagulation state, circulating cytokine levels and mortality; thus representing a new biomarker of sepsis outcome

COVID-19 and children with congenital anomalies:a European survey of parents' experiences of healthcare services

Objective: To survey parents and carers of children with a congenital anomaly across Europe about their experiences of healthcare services and support during the COVID-19 pandemic. Design: Cross-sectional study. Setting: Online survey in 10 European countries, open from 8 March 2021 to 14 July 2021. Population: 1070 parents and carers of children aged 0-10 years with a cleft lip, spina bifida, congenital heart defect (CHD) requiring surgery and/or Down syndrome. Main outcome measures: Parental views about: the provision of care for their child (cancellation/postponement of appointments, virtual appointments, access to medication), the impact of disruptions to healthcare on their child's health and well-being, and satisfaction with support from medical sources, organisations and close relationships. Results: Disruptions to healthcare appointments were significantly higher (p<0.001) in the UK and Poland, with approximately two-thirds of participants reporting â € cancelled or postponed' tests (67/101; 256/389) and procedures compared with approximately 20% in Germany (13/74) and Belgium/Netherlands (11/55). A third of participants in the UK and Poland reported â € cancelled or postponed' surgeries (22/72; 98/266) compared with only 8% in Germany (5/64). In Poland, 43% (136/314) of parents reported that changes to their child's ongoing treatment had moderately to severely affected their child's health, significantly higher than all other countries (p<0.001). Satisfaction ratings for support from general practitioners were lowest in the UK and Poland, and lowest in Poland and Italy for specialist doctors and nurses. Conclusion: A large proportion of participants reported disruptions to healthcare during the pandemic, which for some had a significant impact on their child's health. Regional differences in disruptions raise questions about the competence of certain healthcare systems to meet the needs of this vulnerable group of patients and indicate improvements should be strived for in some regions

Extranuclear Halpha-emitting complexes in low-z (U)LIRGs: Precursors of tidal dwarf galaxies?

(Abridged)This paper characterizes the physical and kinematic properties of external massive star-forming regions in a sample of (U)LIRGs. We use high angular resolution ACS images from the HST B and I bands, as well as Halpha-line emission maps obtained with IFS. We find 31 external Halpha-emitting (young star-forming) complexes in 11 (U)LIRGs. These complexes have in general similar sizes, luminosities, and metallicities to extragalactic giant HII regions and TDG candidates found in less luminous mergers and compact groups of galaxies. We assess the mass content and the likelihood of survival as TDGs of the 22 complexes with simple structures in the HST images based on their photometric, structural, and kinematic properties. The dynamical tracers used (radius-sigma and luminosity-sigma diagrams) indicate that most of the complexes might be self-gravitating entities. The resistance to forces from the parent galaxy is studied by considering the tidal mass of the candidate and its relative velocity with respect to the parent galaxy. After combining the results of previous studies of TDG searches in ULIRGs a total of 9 complexes satisfy most of the applied criteria and thus show a high-medium or high likelihood of survival, their total mass likely being compatible with that of dwarf galaxies. They are defined as TDG candidates. We propose that they probably formed more often during the early phases of the interaction. Combining all data for complexes with IFS data where a significant fraction of the system is covered, we infer a TDG production rate of 0.3 candidates with the highest probabilities of survival per system for the (U)LIRGs class. This rate, though, might decrease to 0.1 after the systems in (U)LIRGs have evolved for 10 Gyr, for long-lived TDGs, which would imply that no more than 5-10 % of the overall dwarf population could be of tidal origin.Comment: Accepted for publication in A&A, 21 pages, 8 figures. Typo corrected (article 1111.0468

Fossil Groups Origins: I. RX J105453.3+552102 a very massive and relaxed system at z~0.5

The most accepted scenario for the origin of fossil groups (FGs) is that they are galaxy associations in which the merging rate was fast and efficient. These systems have assembled half of their mass at early epoch of the Universe, subsequently growing by minor mergers. They could contain a fossil record of the galaxy structure formation. We have started a project in order to characterize a large sample of FGs. In this paper we present the analysis of the fossil system RX J105453.3+552102. Optical deep images were used for studying the properties of the brightest group galaxy and for computing the photometric luminosity function of the group. We have also performed a detail dynamical analysis of the system based on redshift data for 116 galaxies. This galaxy system is located at z=0.47, and shows a quite large line-of-sight velocity dispersion \sigma_{v}~1000 km/s. Assuming the dynamical equilibrium, we estimated a virial mass of M ~ 10^{15} h_{70} M_{\odot}. No evidence of substructure was found within 1.4 Mpc radius. We found a statistically significant departure from Gaussianity of the group members velocities in the most external regions of the group. This could indicate the presence of galaxies in radial orbits in the external region of the group. We also found that the photometrical luminosity function is bimodal, showing a lack of M_{r} ~ -19.5 galaxies. The brightest group galaxy shows low Sersic parameter (n~2) and a small peculiar velocity. Indeed, our accurate photometry shows that the difference between the brightest and the second brightest galaxies is 1.9 mag in the r-band, while the classical definition of FGs is based on a magnitude gap of 2. We conclude that this fossil system does not follow the empirical definition of FGs. Nevertheless, it is a massive, old and undisturbed galaxy system with little infall of L^{*} galaxies since its initial collapse.Comment: 17 pages, 14 figures, accepted for publication at A&

MEGARA, the new intermediate-resolution optical IFU and MOS for GTC: getting ready for the telescope

MEGARA (Multi-Espectrógrafo en GTC de Alta Resolución para Astronomía) is an optical Integral-Field Unit (IFU) and Multi-Object Spectrograph (MOS) designed for the GTC 10.4m telescope in La Palma that is being built by a Consortium led by UCM (Spain) that also includes INAOE (Mexico), IAA-CSIC (Spain), and UPM (Spain). The instrument is currently finishing AIV and will be sent to GTC on November 2016 for its on-sky commissioning on April 2017. The MEGARA IFU fiber bundle (LCB) covers 12.5x11.3 arcsec2 with a spaxel size of 0.62 arcsec while the MEGARA MOS mode allows observing up to 92 objects in a region of 3.5x3.5 arcmin2 around the IFU. The IFU and MOS modes of MEGARA will provide identical intermediate-to-high spectral resolutions (RFWHM~6,000, 12,000 and 18,700, respectively for the low-, mid- and high-resolution Volume Phase Holographic gratings) in the range 3700-9800ÅÅ. An x-y mechanism placed at the pseudo-slit position allows (1) exchanging between the two observing modes and (2) focusing the spectrograph for each VPH setup. The spectrograph is a collimator-camera system that has a total of 11 VPHs simultaneously available (out of the 18 VPHs designed and being built) that are placed in the pupil by means of a wheel and an insertion mechanism. The custom-made cryostat hosts a 4kx4k 15-μm CCD. The unique characteristics of MEGARA in terms of throughput and versatility and the unsurpassed collecting are of GTC make of this instrument the most efficient tool to date to analyze astrophysical objects at intermediate spectral resolutions. In these proceedings we present a summary of the instrument characteristics and the results from the AIV phase. All subsystems have been successfully integrated and the system-level AIV phase is progressing as expected

Loss of the matrix metalloproteinase-10 causes premature features of aging in satellite cells

© 2023 Bobadilla Muñoz, Orbe, Abizanda, Machado, Vilas, Ullate-Agote, Extramiana, Baraibar Churio, Aranguren, Cantero, Sáinz Amillo, Rodríguez, Ramos García, Romero Riojas, Vallejo-Illarramendi, Paradas, López de Munain, Páramo, Prósper and Pérez-Ruiz. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.Aged muscles accumulate satellite cells with a striking decline response to damage. Although intrinsic defects in satellite cells themselves are the major contributors to aging-associated stem cell dysfunction, increasing evidence suggests that changes in the muscle-stem cell local microenvironment also contribute to aging. Here, we demonstrate that loss of the matrix metalloproteinase-10 (MMP-10) in young mice alters the composition of the muscle extracellular matrix (ECM), and specifically disrupts the extracellular matrix of the satellite cell niche. This situation causes premature features of aging in the satellite cells, contributing to their functional decline and a predisposition to enter senescence under proliferative pressure. Similarly, reduction of MMP-10 levels in young satellite cells from wild type animals induces a senescence response, while addition of the protease delays this program. Significantly, the effect of MMP-10 on satellite cell aging can be extended to another context of muscle wasting, muscular dystrophy. Systemic treatment of mdx dystrophic mice with MMP-10 prevents the muscle deterioration phenotype and reduces cellular damage in the satellite cells, which are normally under replicative pressure. Most importantly, MMP-10 conserves its protective effect in the satellite cell-derived myoblasts isolated from a Duchenne muscular dystrophy patient by decreasing the accumulation of damaged DNA. Hence, MMP-10 provides a previously unrecognized therapeutic opportunity to delay satellite cell aging and overcome satellite cell dysfunction in dystrophic muscles.This work was supported by Red de Terapia Celular (TerCel) RD16-0011-0005 Instituto de Salud Carlos III convocatoria 2016, Convocatoria de Redes Temáticas Cooperativas de Investigación en Salud; CIBERONC; Instituto de Salud Carlos III-FEDER, CIBERONC, Fondo de Investigaciones Sanitarias (PI18/01152), (PI19/00065), and CIBERCV (CB16/11/00371). GC is supported by a postdoctoral fellowship funded by Consejería de Salud y Familias, Junta de Andalucía and Programa Operativo Fondo Social Europeo de Andalucía 2014-2020 (RH0046-2020).Peer reviewe

Serum tissue inhibitor of matrix metalloproteinase-1 levels are associated with mortality in patients with malignant middle cerebral artery infarction

Background: In the last years, circulating matrix metalloproteinases (MMP)-9 levels have been associated with functional outcome in ischemic stroke patients. However the prognostic value of circulating levels of tissue inhibitor of matrix metalloproteinases (TIMP)-1 and MMP-10 in functional outcome of ischemic stroke patients has been scarcely studied. In addition, to our knowledge, serum MMP-9, MMP-10 and TIMP-1 levels in patients with malignant middle cerebral artery infarction (MMCAI) for mortality prediction have not been studied, and these were the objectives of this study. Methods: This was a multicenter, observational and prospective study carried out in six Spanish Intensive Care Units. We included patients with severe MMCAI defined as Glasgow Coma Scale (GCS) lower than 9. We measured circulating levels of MMP-9, MMP-10, TIMP-1, in 50 patients with severe MMCAI at diagnosis and in 50 healthy subjects. Endpoint was 30-day mortality. Results: Patients with severe MMCAI showed higher serum levels of MMP-9 (p = 0.001), MMP-10 (p 239 ng/mL are associated with 30-day mortality (OR = 5.82; 95 % CI = 1.37-24.73; P = 0.02) controlling for GCS and age. The area under the curve for TIMP-1 as predictor of 30-day mortality was 0.81 (95 % CI = 0.67-0.91; P < 0.001). We found an association between circulating levels of TIMP-1 and MMP-10 (rho = 0.45; P = 0.001), plasminogen activator inhibitor (PAI)-1 (rho = 0.53; P < 0.001), and tumor necrosis factor (TNF)-alpha (rho = 0.70; P < 0.001). Conclusions: The most relevant and new findings of our study, were that serum TIMP-1 levels in MMCAI patients were associated with mortality, and could be used as a prognostic biomarker of mortality in MMCAI patients