GSK-3 is an RNA polymerase II phospho-CTD kinase.

We have previously found that UV-induced DNA damage causes hyperphosphorylation of the carboxy terminal domain (CTD) of RNA polymerase II (RNAPII), inhibition of transcriptional elongation and changes in alternative splicing (AS) due to kinetic coupling between transcription and splicing. In an unbiased search for protein kinases involved in the AS response to DNA damage, we have identified glycogen synthase kinase 3 (GSK-3) as an unforeseen participant. Unlike Cdk9 inhibition, GSK-3 inhibition only prevents CTD hyperphosphorylation triggered by UV but not basal phosphorylation. This effect is not due to differential degradation of the phospho-CTD isoforms and can be reproduced, at the AS level, by overexpression of a kinase-dead GSK-3 dominant negative mutant. GSK-3 inhibition abrogates both the reduction in RNAPII elongation and changes in AS elicited by UV. We show that GSK-3 phosphorylates the CTD in vitro, but preferentially when the substrate is previously phosphorylated, consistently with the requirement of a priming phosphorylation reported for GSK-3 efficacy. In line with a role for GSK-3 in the response to DNA damage, GSK-3 inhibition prevents UV-induced apoptosis. In summary, we uncover a novel role for a widely studied kinase in key steps of eukaryotic transcription and pre-mRNA processing.

Impact of the SARS-CoV-2 (COVID19) pandemic on the morbidity and mortality of high risk patients undergoing surgery: a non-inferiority retrospective observational study.

BACKGROUND: During the COVID-19 crisis it was necessary to generate a specific care network and reconvert operating rooms to attend emergency and high-acuity patients undergoing complex surgery. The aim of this study is to classify postoperative complications and mortality and to assess the impact that the COVID-19 pandemic may have had on the results. METHODS: this is a non-inferiority retrospective observational study. Two different groups of surgical patients were created: Pre-pandemic COVID and Pandemic COVID. Severity of illness was rated according to the Diagnosis-related Groups (DRG) score. Comparisons were made between groups and between DRG severity score-matched samples. Non-inferiority was set at up to 10 % difference for grade III to V complications according to the Clavien-Dindo classification, and up to 2 % difference in mortality. RESULTS: A total of 1649 patients in the PreCOVID group and 763 patients in the COVID group were analysed; 371 patients were matched for DRG severity score 3-4 (236 preCOVID and 135 COVID). No differences were found in relation to re-operation (22.5 % vs. 21.5 %) or late admission to critical care unit (5.1 % vs. 4.5 %). Clavien grade III to V complications occurred in 107 patients (45.3 %) in the PreCOVID group and in 56 patients (41.5 %) in the COVID group, and mortality was 12.7 % and 12.6 %, respectively. During the pandemic, 3 % of patients tested positive for Covid-19 on PCR: 12 patients undergoing elective surgery and 11 emergency surgery; there were 5 deaths, 3 of which were due to respiratory failure following Covid-19-induced pneumonia. CONCLUSIONS: Although this study has some limitations, it has shown the non-inferiority of surgical outcomes during the COVID pandemic, and indicates that resuming elective surgery is safe. TRIAL REGISTRATION: Clinicaltrials.gov identifier: NCT04780594 .

Reciprocal regulation between alternative splicing and the DNA damage response.

Splicing, the process that catalyzes intron removal and flanking exon ligation, can occur in different ways (alternative splicing) in immature RNAs transcribed from a single gene. In order to adapt to a particular context, cells modulate not only the quantity but also the quality (alternative isoforms) of their transcriptome. Since 95% of the human coding genome is subjected to alternative splicing regulation, it is expected that many cellular pathways are modulated by alternative splicing, as is the case for the DNA damage response. Moreover, recent evidence demonstrates that upon a genotoxic insult, classical DNA damage response kinases such as ATM, ATR and DNA-PK orchestrate the gene expression response therefore modulating alternative splicing which, in a reciprocal way, shapes the response to a damaging agent.

Adherence to initial exclusive breastfeeding among Chinese born and native Spanish mothers.

BACKGROUND: Benefits of breastfeeding on the health of children, mothers and society are well known. However, breastfeeding rates vary according to the population examined. Chinese-born women migrated to high-income countries have shown low breastfeeding rates. Nevertheless, studies comparing breastfeeding rates of Chinese-born immigrants and natives are scarce. The aims of this study were therefore: 1) to compare the rate of exclusive breastfeeding at hospital discharge after giving birth between Chinese-born women resident in Spain and native Spanish women, 2) to assess the influence of the biological, socioeconomic, work-related and cultural factors on exclusive breastfeeding in women of Chinese origin. METHODS: A cross-sectional descriptive study with between group comparisons. This study included 73 postpartum women (33 Chinese-born and 40 native Spanish women). The association between exclusive breastfeeding and the country of origin was assessed by binary logistic regression. RESULTS: Native Spanish women showed a greater prevalence of exclusive breastfeeding (80%) compared to Chinese born immigrant women (36.4%) (adjusted for socioeconomic status, parental level of education, age, cesareans and birth weight) (OR = 0.21; 95% CI 0.05-0.91; p = 0.037). However, in other models that considered both work and cultural influences, no differences were observed. DISCUSSION: The classic biological and socioeconomic variables (educational and socioeconomic levels) do not seem to explain the lower rates of exclusive breastfeeding among Chinese immigrant women. This paradigm of inequity appears to be based on both the work conditions as well as cultural characteristics of Chinese born women in Spain, such as their overall attitude towards breastfeeding.

Patients with severe mental illness and their carers' expectations for GPs' communication skills: a qualitative approach in Spain.

BACKGROUND: Effective communication with GPs (General Practitioners) enables higher rates of patient satisfaction and adherence to treatment plans. People with severe mental illness (SMI) and their caregivers present unique characteristics that present difficulties in the GP-carer-patient communication process. AIM: To explore the expectations of patients with SMI and their caregivers regarding GPs' communication skills in primary care consultations. DESIGN & SETTING: Face-to-face interviews, using focus group methodology, which were undertaken in southern Spain. METHOD: Forty-two participants took part in 21 paired semi-structured interviews with an average duration of 19±7.2 minutes. Information was audio-recorded and transcribed verbatim. Qualitative content analysis was undertaken, obtaining a codification in categories by means of triangulation. RESULTS: Four themes emerged from the analysis. Theme 1 was interviewer communication characteristics. The ability of GPs to use a language that was colloquial and adapted to each person was perceived as a determinant of the quality of care provided. An empathetic attitude, low reactivity, and efficient time management were the most valued communication skills. Theme 2 was telemedicine: telephone consultation and video consultation. The telephone consultation was perceived as a useful tool to care for people with SMI. Video consultation was valued as a requirement in isolated rural areas. Theme 3 was the role of the caregiver during the clinical interview. The caregiver was considered by the patients as an ally who improves the clinical interview. Theme 4 was the perceived barriers and facilitators during the clinical interview. The continuity of care, defined by a low turnover of GPs, determined the quality perceived by those who required care. CONCLUSION: Themes emerging from this study have suggested that people with SMI require an inclusive, collaborative, and personalised approach in the care they receive from the public health system. Improved communication between GPs and patients with SMI is an essential requirement for quality medical care.

Social Experiences and Health Needs of Patients with Severe Mental Illness and their Caregivers during the first year of the COVID-19 pandemic in Spain.

BACKGROUND: The strict isolation measures for the population imposed by the health authorities caused a prolonged disruption of informal social support networks. Both this new social situation and the decrease in accessibility to health care have generated new needs in people with severe mental illness (SMI) and their caregivers. OBJECTIVES: This study provides insight into life experiences and health needs of a population with SMI during the first year of the COVID-19 pandemic in Spain. METHODS: Qualitative design using semi-structured dyadic interviews, conducted from January through December 2022. A purposive sampling of patients with SMI and their caregivers was carried out through key informants in rural and urban localities in southern Spain. Verbatims were identified and classified by triangulation after the evaluation of the interview transcripts. The codes were defined through content analysis using the NVivo software. RESULTS: Semi-structured dyadic interviews (21), identifying three main categories: 1. Social isolation: increased, causing greater personal vulnerability, exacerbation of psychiatric symptoms and exhaustion in caregivers. 2. Accessibility to Health Services: decreased with fewer face-to-face consultations, with difficulty in managing urgent situations and telephone attention in decompensated and disabled patients. 3. Continuity of healthcare: decreased with distrust in health professionals due to lack of communication between primary care and the hospital. CONCLUSION: COVID-19 confinement exacerbated loneliness and worse health self-perception in SMI people. Greater formal social support was required. GPs role is key to avoiding delays in appointments and lack of coordination between primary and specialised care.

Quality of life and medical care for SMI people got worse in controlled confinement during COVID-19 pandemic.Caregiving burden and isolation were common, especially in rural areas and in populations at social risk.SMI people requested an improvement in medical care accessibility, continuity, and more social resources.

Qualitative study on the use of emergency services by people with serious mental disorder in Spain.

BACKGROUND: The population with severe mental disorders (SMD) is a frequent user of emergency services. Situations of psychiatric decompensation can have devastating consequence and can cause problems in getting urgent medical care. The objective was to study the experiences and needs of these patients and their caregivers regarding the demand for emergency care in Spain. METHODS: Qualitative methodology involving patients with SMD and their informal caregivers. Purposive sampling by key informants in urban and rural areas. Paired interviews were carried out until data saturation. A discourse analysis was conducted, obtaining a codification in categories by means of triangulation. RESULTS: Forty-two participants in twenty-one paired interviews (19 ± 7.2 min as mean duration). Three categories were identified. 1º Reasons for urgent care: poor self-care and lack of social support, as well as difficulties in accessibility and continuity of care in other healthcare settings. 2º Urgent care provision: trust in the healthcare professional and the information patients receive from the healthcare system is crucial, telephone assistance can be a very useful resource. 3º Satisfaction with the urgent care received: they request priority care without delays and in areas separated from the other patients, as well as the genuine interest of the professional who attends them. CONCLUSIONS: The request for urgent care in patients with SMD depends on different psychosocial determinants and not only on the severity of the symptoms. There is a demand for care that is differentiated from the other patients in the emergency department. The increase in social networks and alternative systems of care would avoid overuse of the emergency departments.

Validation and reliability of the Spanish version of the Function in Sitting Test (S-FIST) to assess sitting balance in subacute post-stroke adult patients.

BACKGROUND: Function in Sitting Test (FIST) is a clinical functional assessment of sitting balance validated in adults with stroke. For a major use of this, the test is recommended to be translated in Spanish-speaking countries. OBJECTIVES: Translate to Spanish the FIST and determine its intra-rater and inter-rater reliabilities and concurrent validity as a measure of sitting balance in adult individuals with stroke. METHODS: The original version was translated into Spanish and was agreed by a team of experts. A back-translation into English was subsequently performed and sent to the original author, who approved this version named from now Spanish version of Function in Sitting Test (S-FIST). Sixty post-stroke patients' performance was recorded on a videotape. These videos were then used to carry out four measurements to assess the intra-rater and inter-rater reliabilities; two of these were performed by the same rater and the third and fourth by a second and third rater. RESULTS: The S-FIST meets the following requirements: good construct validity and high correlation with Spanish version of Trunk Impairment Scale 2.0 (S-TIS 2.0) scores (r = 0.791) Spearman's rank, high internal consistency (Cronbach's α-coefficient = 0.97), and high intra-rater and inter-rater reliabilities for the summed scores assessed by intra-class correlation coefficient were 0.999 and 0.997, respectively. CONCLUSIONS: The S-FIST is valid and reliable and can be recommended for use in the evaluation of dynamic and sitting balance and trunk control in future research and clinical practice on post-stroke patients. Guidelines for treatment and level of quality of trunk activity can be derived from its use.

Formación en valores y cuentos tradicionales en la etapa de educación infantil / Values education and traditional stories in early childhood education

Los valores son hoy un elemento de la formación, siendo pieza clave en la Educación Infantil. Junto a estos encontramos la metodología de los cuentos tradicionales como forma de enseñanza-aprendizaje. En el presente artículo exponemos los primeros resultados de un estudio no experimental, llevado a cabo con el objetivo general de conocer cuáles son los valores que el profesorado cree que transmiten los cuentos infantiles. El principal resultado obtenido es que los cuentos tradicionales transmiten diferentes valores en función de la etapa educativa en que se empleen y de la experiencia profesional de los sujetos docentes. Concluimos que la educación en valores a través de los cuentos tradicionales en la etapa de Educación Infantil, es una metodologíaválida para la socialización de los niños y las niñas...