Interparental violence and children’s long-term psychosocial adjustment: the mediating role of parenting practices

Subject to file availability and provided the posting includes a prominent statement of the full bibliographical details, a copyright notice in the name of the copyright holder (Cambridge University Press or the sponsoring Society, as appropriate), and a link to the online edition of the journal at Cambridge Journals Online.The objectives of this study were: (a) to examine the direct and indirect relationships among witnessing interparental violence, parenting practices, and children’s long-term psychosocial adjustment; (b) to analyze the possible gender differences in the relationships specified. The sample consisted of 1295 Spanish university students (M age = 21.21, SD = 4.04). We performed statistical analyses using structural equation modeling. The results showed that witnessing parental violence as a child is related to poor long-term psychosocial adjustment during the child’s adult years. Furthermore, we found that parenting practices fully mediated the relation between witnessing interparental violence and the child’s longterm adjustment. The multigroup analyses showed that most of the relations among the variables did not differ significantly by gender. However, the relation between harsh discipline and antisocial behavior was stronger for males, whereas the relation between harsh discipline and depressive symptoms was stronger for females. Finally, we discuss the implications of these findings for the clinicians and specialists who plan and develop intervention programs for populations at risk.Los objetivos de este estudio fueron: a) analizar las relaciones directas e indirectas entre la exposición a la violencia marital, la conducta parental y el ajuste psicosocial a largo plazo de los hijos; b) examinar la posible existencia de diferencias en las relaciones analizadas en función del sexo del participante. La muestra estuvo compuesta por 1295 estudiantes universitarios (74.4% mujeres; Medad = 21.21, DT = 4.04). Para analizar las hipótesis del estudio se estimaron varios modelos de ecuaciones estructurales. Los hallazgos sugieren que la relación entre violencia marital y ajuste psicosocial de los hijos a largo plazo se produce de forma indirecta a través de un deterioro de diversos aspectos de la conducta parental. Concretamente, las dimensiones de disciplina severa, afecto/apoyo parental y consistencia interparental e intraparental mediaron la relación entre la exposición a la violencia parental y sintomatología depresiva a largo plazo de los hijos. Por su parte, la disciplina severa y la consistencia intraparental mediaron la relación entre la violencia parental y las conductas antisociales. Los análisis por sexo revelaron que la mayoría de las relaciones observadas fueron similares entre hombres y mujeres. No obstante, la relación entre la disciplina severa y la conducta antisocial fue más fuerte para los varones, mientras que la asociación entre la disciplina severa y la sintomatología depresiva fue más elevada para las mujeres. Finalmente, se discuten las implicaciones de estos resultados para la planificación de programas de intervención con poblaciones de riesgo

PARP1 inhibition by Olaparib reduces the lethality of pancreatic cancer cells and increases their sensitivity to Gemcitabine

Pancreatic cancer (PC) is one of the tumors with the lowest survival rates due to the poor efficacy of the treatments currently used. Gemcitabine (GMZ), one of the chemotherapeutic agents employed when the tumor is unresectable, frequently fails due to the development of drug resistance. PARP1 is a relevant protein in this phenomenon and appears to be related to cancer progression in several types of tumors, including PC. To determine the relevance of PARP1 in the development and treatment of PC, we used the Panc02 cell line to generate modified PC cells with stably inhibited PARP1 expression (Panc02-L) and used GMZ, Olaparib (OLA) and GMZ+OLA as therapeutic strategies. Viability, radiosensitization, angiogenesis, migration, colony formation, TUNEL, cell cycle, multicellular tumorsphere induction and in vivo assays were performed to test the influence of PARP1 inhibition on resistance phenomena and tumor progression. We demonstrated that stable inhibition or pharmacological blockade of PARP1 using OLA-sensitized Panc02 cells against GMZ significantly decreased their IC50, reducing colony formation capacity, cell migration and vessel formation (angiogenesis) in vitro. Furthermore, in vivo analyses revealed that Panc02-L-derived (PARP1-inhibited) tumors showed less growth and lethality, and that GMZ+OLA treatment significantly reduced tumor growth. In conclusion, PARP1 inhibition, both alone and in combination with GMZ, enhances the effectiveness of this chemotherapeutic agent and represents a promising strategy for the treatment of PC.Granada University and ibs. GRANADA INB-009Instituto de Salud Carlos III European Commission DTS17/00081Junta de Andalucia (FEDER) (Spain) CTS-107 A-CTS-666UGR20 B-CTS-122-UGR20Ministerio de Educaci 'on, Ciencia y Deporte y Competitividad (Spain

Using the ℓ1-norm for Image-based tomographic reconstruction

This paper introduces an ℓ1-norm model based on Total Variation Minimization for tomographic reconstruction. The reconstructions produced by the proposed model are more accurate than those obtained with classical reconstruction models based on the ℓ2-norm. This model can be linearized and solved by linear programming techniques. Furthermore, the complementary slackness conditions can be exploited to reduce the dimension of the resulting formulation by removing unnecessary variables and constraints. Since the efficacy of the reduced formulation strongly depends on the quality of the dual-multipliers used when applying the reduction method, Lagrangian relaxation is used to obtain near-optimal multipliers. This allows solving larger instances in an efficient way

Circadian Regulation of Colon Cancer Stem Cells: Implications for Therapy

The presence of cancer stem cells (CSCs) in colorectal cancer (CRC) has been associated with tumor initiation, metastasis, relapse, and resistance to chemotherapy and radiotherapy. Therefore, a better knowledge of the molecular mechanisms involved in the regulation of CSCs is required to develop treatments that are more effective. Like normal cells, cancer cells contain molecular clocks that generate circadian rhythms in gene expression and metabolic activity. Disruption of circadian rhythms has been linked to increased cancer risk, chemoresistance, and progression in CRC. CSCs also generate rhythms, which could be exploited with a chronopharmacological approach. Although the regulation of the expression of circadian rhythm genes appears to be mediated mainly by transcription–translation feedback loops, the existence of forms of nontranscriptional regulation has been demonstrated. Particularly, microRNAs (miRNA) and SIRT1 are significant players in regulating various aspects of the circadian clock function. Furthermore, miRNA acts as a regulator of cancer progression by regulating the CSC characteristics through SIRT1. These findings led us to hypothesize that there is a circadian rhythm of CSC markers regulated by miRNAs in CRC with SIRT1 acting as a mediator of miRNA activity. The pharmacological regulation of SIRT1, and therefore of the circadian machinery, could result in antiproliferative effects and increased sensitivity to antitumor treatments in CRC

Quantitative Evaluation of Supported Catalysts Key Properties from Electron Tomography Studies: Assessing Accuracy Using Material-Realistic 3D-Models

Electron Tomography (ET) reconstructions can be analysed, via segmentation techniques, to obtain quantitative, 3D-information about individual nanoparticles in supported catalysts. This includes values of parameters out of reach for any other technique, like their volume and surface, which are required to determine the dispersion of the supported particle system or the specific surface area of the support; two figures that play a major role in the performance of this type of catalysts. However, both the experimental conditions during the acquisition of the tilt series and the limited fidelity of the reconstruction and segmentation algorithms, restrict the quality of the ET results and introduce an undefined amount of error both in the qualitative features of the reconstructions and in all the quantitative parameters measured from them. Here, a method based on the use of well-defined 3D geometrical models (phantoms), with morphological features closely resembling those observed in experimental images of an Au/CeO2 catalyst, has been devised to provide a precise estimation of the accuracy of the reconstructions. Using this approach, the influence of noise and the number of projections on the errors of reconstructions obtained using a Total Variation Minimization in 3D (TVM-3D) algorithm have been determined. Likewise, the benefits of using smart denoising techniques based on Undecimated Wavelet Transforms (UWT) have been also evaluated. The results clearly reveal a large impact of usual noise levels on both the quality of the reconstructions and nanometrological measurement errors. Quantitative clues about the key role of UWT to largely compensate them are also provided.This work has received support from Projects: PID2020-113006-RB-I00, PID2019-110018GA-I00, PID2020-114594GB-C22, funded by MCIN/AEI/https://doi.org/10.13039/501100011033.This work has also been co-financed by Project ref: MAT2017-87579-R and by the 2014 -2020 ERDF Operational Programme and by the Department of Economy, Knowledge, Business and University of the Regional Government of Andalusia, Project references: FEDER-UCA18-107139, FEDERUCA18-106895 and P18-FR-1422. STEM ET experiments were recorded at the DME-UCA Node of the Spanish Singular Infrastructure for Electron Microscopy of Materials (ICTS ELECMI)

Seroprevalence and epidemiology of hepatitis B and C viruses in pregnant women in Spain. Risk factors for vertical transmission

Background & aim Worldwide, measures are being implemented to eradicate hepatitis B (HBV) and C (HCV) viruses, which can be transmitted from the mother during childbirth. This study aims to determine the prevalence of HBV and HCV in pregnant women in Spain, focusing on country of origin, epidemiological factors and risk of vertical transmission (VT). Methodology Multicentre open-cohort study performed during 2015. HBV prevalence was determined in 21870 pregnant women and HCV prevalence in 7659 pregnant women. Epidemiological and risk factors for VT were analysed in positive women and differences between HBV and HCV cases were studied. Results HBV prevalence was 0.42% (91/21870) and HCV prevalence was 0.26% (20/7659). Of the women with HBV, 65.7% (44/67) were migrants. The HBV transmission route to the mother was unknown in 40.3% of cases (27/67) and VT in 31.3% (21/67). Among risk factors for VT, 67.7% (42/62) of the women had viraemia and 14.5% (9/62) tested HBeAg-positive. All of the neonates born to HBV-positive mothers received immunoprophylaxis, and none contracted infection by VT. In 80% (16/20) of the women with HCV, the transmission route was parenteral, and nine were intravenous drug users. Viraemia was present in 40% (8/20) of the women and 10% (2/20) were HIV-coinfected. No children were infected. Women with HCV were less likely than women with HBV to breastfeed their child (65% vs. 86%). Conclusions The prevalences obtained in our study of pregnant women are lower than those previously documented for the general population. Among the women with HBV, the majority were migrants and had a maternal family history of infection, while among those with HCV, the most common factor was intravenous drug use. Despite the risk factors observed for VT, none of the children were infected. Proper immunoprophylaxis is essential to prevent VT in children born to HBV-positive women.This study received financial assistance from the following: Ciberehd, Fondo de Investigaciones Sanitarias del Instituto de Salud Carlos III. ISCIII, Proyecto del Plan Nacional I+D+i 2013-2016 (PI13/01925), Confinanciacio´n Fondos FEDER. Gilead Fellowship Program (GLD14-00292 and GLD15-00307)

Aproximación Proteómica al síndrome de apneas-hipopneas del sueño

Comunicaciones a congreso

Interaction between ATM and PARP-1 in response to DNA damage and sensitization of ATM deficient cells through PARP inhibition

ATM and PARP-1 are two of the most important players in the cell's response to DNA damage. PARP-1 and ATM recognize and bound to both single and double strand DNA breaks in response to different triggers. Here we report that ATM and PARP-1 form a molecular complex in vivo in undamaged cells and this association increases after γ-irradiation. ATM is also modified by PARP-1 during DNA damage. We have also evaluated the impact of PARP-1 absence or inhibition on ATM-kinase activity and have found that while PARP-1 deficient cells display a defective ATM-kinase activity and reduced γ-H2AX foci formation in response to γ-irradiation, PARP inhibition on itself is able to activate ATM-kinase. PARP inhibition induced γ H2AX foci accumulation, in an ATM-dependent manner. Inhibition of PARP also induces DNA double strand breaks which were dependent on the presence of ATM. As consequence ATM deficient cells display an increased sensitivity to PARP inhibition. In summary our results show that while PARP-1 is needed in the response of ATM to gamma irradiation, the inhibition of PARP induces DNA double strand breaks (which are resolved in and ATM-dependent pathway) and activates ATM kinase

Successful development and clinical translation of a novel anterior lamellar artificial cornea

We thank the Andalusian Public Foundation Progress and Health, through the Andalusian Initiative for Advanced Therapies, for assuming the roles and responsibilities of sponsoring this clinical trial. We thank Dr. Manuel de la Rosa and Dr. Salvador Arias Santiago for providing insight and expertise that assisted the research.The datasets generated and/or analyzed during the current study are available in the Gene Expression Omnibus (GEO) public repository, ref. GSE86584 https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE86584Blindness due to corneal diseases is a common pathology affecting up to 23 million individuals worldwide. The tissue‐engineered anterior human cornea, which is currently being tested in a Phase I/II clinical trial to treat severe corneal trophic ulcers with preliminary good feasibility and safety results. This bioartificial cornea is based on a nanostructured fibrin–agarose biomaterial containing human allogeneic stromal keratocytes and cornea epithelial cells, mimicking the human native anterior cornea in terms of optical, mechanical, and biological behavior. This product is manufactured as a clinical‐grade tissue engineering product, fulfilling European requirements and regulations. The clinical translation process included several phases: an initial in vitro and in vivo preclinical research plan, including preclinical advice from the Spanish Medicines Agency followed by additional preclinical development, the adaptation of the biofabrication protocols to a good manufacturing practice manufacturing process, including all quality controls required, and the design of an advanced therapy clinical trial. The experimental development and successful translation of advanced therapy medicinal products for clinical application has to overcome many obstacles, especially when undertaken by academia or SMEs. We expect that our experience and research strategy may help future researchers to efficiently transfer their preclinical results into the clinical settings.This study was supported by the Spanish National Plan for Scientific and Technical Research and Innovation (I + D + I) from the Spanish Ministry of Economy and Competitiveness (Carlos III Institute of Health), grants FIS PI14/0955 and FIS PI17/0391 (both cofinanced by ERDF‐FEDER, European Union); by the Spanish Ministry of Health, Social Policy and Equity, grant EC10‐285; and by preclinical research funds from the Regional Ministry of Health through the Andalusian Initiative for Advanced Therapies

Comparison of epidemiology and clinical characteristics of infections by human parechovirus vs. those by enterovirus during the first month of life

Human parechoviruses (HPeV) have been recently recognized as important viral agents in paediatric infections. The aims of this study were to investigate the HPeV infection prevalence in infants <1 month in Spain and, secondly, to analyse the clinical and epidemiological characteristics of the infected patients compared with those infected by enterovirus (EV). Infants <1 month with neurological or systemic symptoms were included in a multicentre prospective study. EV and HPeV detection by RT-PCR and genotyping were performed in cerebrospinal fluids (CSF), sera or throat swabs. Out of the total of 84 infants studied during 2013, 32 were EV positive (38 %) and 9 HPeV positive (11 %). HPeV-3 was identified in eight cases and HPeV-5 in one. Mean age of HPeV-positive patients was 18 days. Diagnoses were fever without source (FWS) (67 %), clinical sepsis (22 %) and encephalitis (11 %). Leukocytes in blood and CSF were normal. Pleocytosis (p = 0.03) and meningitis (p = 0.001) were significantly more frequent in patients with EV infections than with HPeV. Conclusions: Although HPeV-3 infections were detected less frequently than EV, they still account for approximately 10 % of the cases analysed in infants younger than 1 month. HPeV-3 was mainly associated with FWS and without leukocytosis and pleocytosis in CSF. In these cases, HPeV screening is desirable to identify the aetiologic agent and prevent unnecessary treatment and prolonged hospitalization.This study was partially supported by a grant from the Spanish National Health Institute PI12-00904.S