Addressing the Needs of Young Children and Families:Early Childhood Education and Services in Catholic Schools and Catholic Charities

Nationally, focus is increasing on the developmental experiences of young children (birth to age 8). Twenty four (arch)dioceses in large metropolitan areas participated in a survey identifying the extent and nature of services provided by Catholic schools and Catholic Charities programs to young children and their families. Six hundred and seventy Catholic schools and 100 Catholic Charities programs completed surveys. Key findings suggest that Catholic schools and Catholic Charities programs are engaged in a plethora of early childhood services and educational activities with young children and families. Both entities provide direct education and services to young children, are engaged in supporting families through a variety of initiatives, and have complementary as well as distinctive approaches. Opportunities were identified within Catholic Schools and within Catholic Charities programs. The potential benefits of increasing collaborations between Catholic schools and Catholic Charities programs, and with others, were highlighted to comprehensively meet the varied (and, at times, extensive) needs of young children and families. Abordando las necesidades de los niños y sus familias: educación en la primera infancia y servicios en las escuelas católicas y los centros católicos de beneficencia A nivel nacional, el foco se incrementa en las experiencias de desarrollo de niños pequeños (desde el nacimiento hasta los ocho años). Veinticuatro diócesis y archidiócesis en grandes zonas metropolitanas participaron en una encuesta con el objetivo de identificar el alcance y la índole de los servicios ofrecidos por las Escuelas católicas y los programas católicos de beneficencia a los niños pequeños y sus familias. Completaron la encuesta seiscientas setenta escuelas católicas y cien programas católicos de beneficencia. Los resultados clave sugieren que las escuelas católicas y los programas católicos de beneficencia están comprometidos en un sinfín de servicios para la primera infancia y actividades educativas para niños y familias. Ambas entidades proveen educación y servicios directos a niños y están comprometidas en el apoyo a las familias mediante una variedad de iniciativas, y disponen de planteamientos complementarios así como distintivos. Se identificaron oportunidades en las escuelas católicas y en los programas católicos de beneficencia. Se resaltaron las ventajas potenciales del aumento de colaboración entre las escuelas católicas y los programas católicos de beneficencia con otros para cumplir de manera comprensiva con las necesidades variadas (y a veces extensas) de los niños pequeños y las familias. Palabras clave: escuelas católicas, centros católicos de beneficencia, primera infancia, servicios a la familia, colaboración Répondre aux besoins des jeunes enfants et des familles : éducation et services à la petite enfance dans les écoles et organisations caritatives catholiques Au plan national, l’attention est de plus en plus axée sur le développement et les expériences vécues par les jeunes enfants (de la naissance à huit ans. Dans les grandes zones métropolitaines, 24 diocèses et archidiocèses ont participé à des enquêtes pour établir l\u27étendue et la nature des services rendus aux jeunes enfants et à leurs familles par les écoles et programmes caritatifs catholiques. 670 écoles catholiques et 100 programmes caritatifs ont répondu aux enquêtes. Les principales constatations montrent que les écoles et organisations caritatives catholiques sont impliquées dans une pléthore de services et activités éducatives pour la petite enfance, destinés aux jeunes enfants et aux familles. Les deux entités fournissent directement un enseignement et des services aux jeunes enfants, agissent pour aider les familles par le biais d\u27initiatives diverses et adoptent des approches complémentaires bien que distinctes. Des possibilités d’action ont été établies au sein des écoles catholiques et des programmes caritatifs. L\u27accent a été mis sur les avantages potentiels qu\u27apporterait une collaboration accrue entre les écoles et organisations caritatives catholiques, et autres, en vue de satisfaire totalement les besoins variés (parfois substantiels) des jeunes enfants et des familles. Mots-clés : Écoles catholiques, organisations caritatives, petite enfance, services familiaux, collaboratio

MYC is a critical target of FBXW7

MYC deregulation is a driver of many human cancers. Altering the balance of MYC protein levels at the level of transcription, protein stability, or turnover is sufficient to transform cells to a tumorigenic phenotype. While direct targeting of MYC is difficult, specific genetic vulnerabilities of MYC-deregulated cells could be exploited to selectively inhibit their growth. Using a genome-wide shRNA screen, we identified 78 candidate genes, which are required for survival of human mammary epithelial cells with elevated MYC levels. Among the candidates, we validated and characterized FBXW7, a component of the SCF-like ubiquitin ligase complex that targets MYC for proteasomal degradation. Down-regulation of FBXW7 leads to synergistic accumulation of cellular and active chromatin-bound MYC, while protein levels of other FBXW7 targets appear unaffected. Over a four-week time course, continuous FBXW7 down-regulation and MYC activation together cause an accumulation of cells in S-phase and G2/M-phase of the cell cycle. Under these conditions, we also observe elevated chromatin-bound levels of CDC45, suggesting increased DNA replication stress. Consistent with these results, FBXW7 down-regulation alone decreases the survival of T47D breast cancer cells. These results establish that FBXW7 downregulation is synthetic lethal with MYC, and that MYC is a critical target of FBXW7 in breast epithelial cells

MYC is a critical target of FBXW7

MYC deregulation is a driver of many human cancers. Altering the balance of MYC protein levels at the level of transcription, protein stability, or turnover is sufficient to transform cells to a tumorigenic phenotype. While direct targeting of MYC is difficult, specific genetic vulnerabilities of MYC-deregulated cells could be exploited to selectively inhibit their growth. Using a genome-wide shRNA screen, we identified 78 candidate genes, which are required for survival of human mammary epithelial cells with elevated MYC levels. Among the candidates, we validated and characterized FBXW7, a component of the SCF-like ubiquitin ligase complex that targets MYC for proteasomal degradation. Down-regulation of FBXW7 leads to synergistic accumulation of cellular and active chromatin-bound MYC, while protein levels of other FBXW7 targets appear unaffected. Over a four-week time course, continuous FBXW7 down-regulation and MYC activation together cause an accumulation of cells in S-phase and G2/M-phase of the cell cycle. Under these conditions, we also observe elevated chromatin-bound levels of CDC45, suggesting increased DNA replication stress. Consistent with these results, FBXW7 down-regulation alone decreases the survival of T47D breast cancer cells. These results establish that FBXW7 down-regulation is synthetic lethal with MYC, and that MYC is a critical target of FBXW7 in breast epithelial cells

Spanish adaptation of the Stroke and Aphasia Quality of Life Scale-39 (SAQOL-39)

[Abstract] Aim. The stroke and aphasia quality of life scale-39 is an interviewer administered questionnaire that has been developed and validated in the United Kingdom to be applied to patients with chronic aphasia as a consequence of a stroke. The objective of this article was to translate the Stroke and Aphasia Quality of Life-39 Scale (SAQOL-39) into Spanish language, and evaluate its acceptability and reliability. Methods. The cross-cultural adaptation of the SAQOL- 39 into Spanish was carried out by following the translation and back-translation method. Twenty three patients with long-term aphasia due to stroke were tested. The patients were interviewed twice in a period from 2 to 12 days. The acceptability of the Spanish SAQOL- 39 was evaluated by examining the floor/ceiling effects and the missing data. The reliability was assessed by Cronbach’s alpha (internal consistence) and intraclass correlation coefficients (test-retest reliability) for the overall scale and its subdomains. Results. There were no difficulties to translate the original version into Spanish. There was good acceptability demonstrated by minimal missing data and floor/ceiling effects. Test-retest reliability for the overall score, and the subscales scores was 0.949 (0.854-0.944). Internal consistency analysis by Cronbach’s α was 0.950 (0.851-0.900). Conclusion. This small scale study provided preliminary evidence for the acceptability and reliability of the Spanish version of the SAQOL-39. Further testing in larger samples is needed to evaluate the validity of the scale, its sensitivity to change and to confirm its reliability

Functional genomics screen identifies YAP1 as a key determinant to enhance treatment sensitivity in lung cancer cells

Survival for lung cancer patients remains dismal and is largely attributed to treatment resistance. To identify novel target genes the modulation of which could modify platinum resistance, we performed a high-throughput RNAi screen and identified Yes-associated protein (YAP1), a transcription coactivator and a known oncogene, as a potential actionable candidate. YAP1 ablation significantly improved sensitivities not only to cisplatin but also to ionizing radiation, both of which are DNA-damaging interventions, in non-small cell lung cancer (NSCLC) cells. Overall YAP1 was expressed in 75% of NSCLC specimens, whereas nuclear YAP1 which is the active form was present in 45% of 124 resected NSCLC. Interestingly, EGFR-mutated or KRAS-mutated NSCLC were associated with higher nuclear YAP1 staining in comparison to EGFR/KRAS wild-type. Relevantly, YAP1 downregulation improved sensitivity to erlotinib, an EGFR inhibitor. A pharmacological inhibitor of YAP1 signaling, verteporfin also synergized with cisplatin, radiation and erlotinib in NSCLC cells by potentiating cisplatin and radiation-related double-stranded breaks and decreasing expression of YAP1 and EGFR. Taken together, our study is the first to indicate the potential role of YAP1 as a common modulator of resistance mechanisms and a potential novel, actionable target that can improve responses to platinum, radiation and EGFR-targeted therapy in lung cancer

Valoración del paciente geriátrico en el servicio de medicina interna

Introduction: The increase in the population of the elderly, added to the increase in pluripatology and polypharmacy, makes their admission to hospitals more and more frequent. Objectives: To establish the profile of the geriatric patient older than 75 years, with pluripatology and treated in the Internal Medicine Unit of the Virgen de la Concha Hospital. Analyze the results of the functional assessment through the Barthel scale. Identify the social situation through the Gijón scale. Methods: Retrospective observational study in the internal medicine hospitalization unit over a year. Descriptive analysis of variables: demographic (age, sex); functional capacity and social assessment. The data obtained from the Gacela Care software application. Results: 1285 admissions were made, with an average age of 78 years. A sample of 915 patients ≥75 years old was obtained, with a mean age of 85.9 ± 5.4 years (75-101), mode 89 and median 86 years. 43.5% are ≥85 years. 53.11% women and 46.88% men. Average hospital stay 7.4 ± 5.2 days (0-66). Dependency assessment: 38.57% with total dependence (62.32% women); 9.61% severe dependence (54.54% women); 15.19% moderate dependence (54.67% women); 26.22% mild dependence (47.08% women); 10.38% independent (30.56% women). Social situation: 28.80% without risk (64.63% women); 60.30% good social situation (47.37% women); 6.2% average social situation (56.60% women); and 4.68% severe social deterioration (52.5% women) Conclusions: The profile of the patients studied approximates that of “geriatric patient”. The highest percentage presents a level of total dependence, causing greater demand for care and resources. There are few patients with severe social impairment. There are a greater number of total dependent patients without institutionalizing. Therefore, the burden of care for these patients is carried out by family members from home, justifying the importance of the assessment of caregivers and evaluation of resources related to family overload and primary caregiver.Introducción: El aumento de la población de personas mayores, añadido al aumento de pluripatología y polifarmacia, hace cada vez más frecuente su ingreso en los hospitales. Objetivos: Establecer el perfil del paciente geriátrico mayor de 75 años, con pluripatología y atendido en la Unidad de Medicina Interna del Hospital Virgen de la Concha. Analizar los resultados de la valoración funcional a través de la escala Barthel. Identificar la situación social a través de la escala Gijón. Métodos: Estudio observacional retrospectivo en la unidad de hospitalización de medicina interna a lo largo de un año. Análisis descriptivo de variables: demográficas (edad, sexo); capacidad funcional y la valoración social. Los datos obtenidos del aplicativo informático Gacela Care. Resultados: Se realizaron 1285 ingresos, con una media de edad de 78 años. Se obtuvo una muestra de 915 pacientes ≥75años, con una media de edad de 85,9±5,4años (75-101), moda 89 y mediana 86 años. El 43,5% son ≥85años. 53,11% mujeres y 46,88% hombres. Estancia media de hospitalización 7,4±5,2días (0-66). Valoración de dependencia: 38,57% con dependencia total (62,32% mujeres);9,61% dependencia grave (54,54% mujeres); 15,19% dependencia moderada (54,67% mujeres); 26,22% dependencia leve (47,08% mujeres); 10,38% independientes (30,56% mujeres). Situación social: 28,80%sin riesgo (64,63%mujeres); 60,30%situación social buena (47,37%mujeres); 6,2% situación social media (56,60%mujeres); y el 4,68% deterioro social severo (52,5% mujeres) Conclusiones: El perfil de los pacientes estudiados se aproxima al de “paciente geriátrico”. El mayor porcentaje presenta un nivel de dependencia total, provocando mayor demanda de cuidados y de recursos. Existen pocos pacientes con deterioro social severo. Hay un mayor número de pacientes  dependientes totales sin institucionalizar. Por lo que la carga de cuidados de estos pacientes la realizan familiares desde el domicilio, justificando la importancia de la valoración de los cuidadores y evaluación de los recursos referidos a la sobrecarga de familias y cuidador principal

Loss of microRNA-135b Enhances Bone Metastasis in Prostate Cancer and Predicts Aggressiveness in Human Prostate Samples

About 70% of advanced-stage prostate cancer (PCa) patients will experience bone metastasis, which severely affects patients' quality of life and progresses to lethal PCa in most cases. Hence, understanding the molecular heterogeneity of PCa cell populations and the signaling pathways associated with bone tropism is crucial. For this purpose, we generated an animal model with high penetrance to metastasize to bone using an intracardiac percutaneous injection of PC3 cells to identify PCa metastasis-promoting factors. Using genomic high-throughput analysis we identified a miRNA signature involved in bone metastasis that also presents potential as a biomarker of PCa progression in human samples. In particular, the downregulation of miR-135b favored the incidence of bone metastases by significantly increasing PCa cells' migratory capacity. Moreover, the PLAG1, JAKMIP2, PDGFA, and VTI1b target genes were identified as potential mediators of miR-135b's role in the dissemination to bone. In this study, we provide a genomic signature involved in PCa bone growth, contributing to a better understanding of the mechanisms responsible for this process. In the future, our results could ultimately translate into promising new therapeutic targets for the treatment of lethal PCa

A microRNA Cluster Controls Fat Cell Differentiation and Adipose Tissue Expansion By Regulating SNCG

The H19X-encoded miR-424(322)/503 cluster regulates multiple cellular functions. Here, it is reported for the first time that it is also a critical linchpin of fat mass expansion. Deletion of this miRNA cluster in mice results in obesity, while increasing the pool of early adipocyte progenitors and hypertrophied adipocytes. Complementary loss and gain of function experiments and RNA sequencing demonstrate that miR-424(322)/503 regulates a conserved genetic program involved in the differentiation and commitment of white adipocytes. Mechanistically, it is demonstrated that miR-424(322)/503 targets gamma-Synuclein (SNCG), a factor that mediates this program rearrangement by controlling metabolic functions in fat cells, allowing adipocyte differentiation and adipose tissue enlargement. Accordingly, diminished miR-424(322) in mice and obese humans co-segregate with increased SNCG in fat and peripheral blood as mutually exclusive features of obesity, being normalized upon weight loss. The data unveil a previously unknown regulatory mechanism offat mass expansion tightly controlled by the miR-424(322)/503 through SNCG.Peer reviewe