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BACKGROUND: The health visiting service in UK promotes the health and wellbeing of families with young children and comprises a universal offer (three mandated contacts between birth and 12 months) and additional contacts based on need. We aimed to understand how the level of health visiting support received varies by family characteristics. METHODS: Using the Community Services Data Set linked to Hospital Episode Statistics, we identified 52 555 children in 10 local authorities with complete health visiting data for 12 months between April 2016 and March 2020. We analysed variation in health visiting contacts by deprivation, child ethnicity, maternal age, adversity and previous live births. RESULTS: 41 340/52 555 children (79%) received the universal service; 63% received ≥1 additional contact and 25% received ≥3 additional contacts. The likelihood of receiving ≥3 additional contacts was greatest for children whose mothers had a history of hospital admissions relating to mental health, violence, self-harm or substance misuse (adjusted relative risk = 1.55, 95% confidence interval 1.26-1.92). CONCLUSIONS: Most families received health visiting support in addition to the universal service. Policymakers and commissioners should consider how health visiting services can be expanded or targeted more effectively to ensure all families receive the support they need.
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Background: The relationship between disadvantage and child health in the early years is well established. For this evidence base to most helpfully inform services, we need to better understand how disadvantage is conceptualised and measured in the literature. We aimed to conceptualise disadvantage measured in child health literature and explore the associations between disadvantage and child health using these measures. Method: We conducted a scoping review using systematic methods to identify key concepts of disadvantage used in empirical child health literature. We searched MEDLINE, Scopus, and grey literature for studies exploring the association between disadvantage and child health outcomes for children aged 0-5 in the United Kingdom. We extracted and analysed data from 86 studies. Results: We developed a framework describing two domains, each with two attributes conceptualising disadvantage: level of disadvantage indicator (individual and area) and content of disadvantage indicator (social and economic). Individual-level measures of disadvantage tended to identify stronger associations between disadvantage and child health compared with area-level measures. Conclusion: The choice of disadvantage indicators, particularly whether individual- or area-level, can affect the inferences made about the relationship between disadvantage and child health. Better access to individual-level disadvantage indicators in administrative data could support development and implementation of interventions aimed at reducing child health inequalities in the early years.
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By binding to SECIS elements located in the 3'-UTR of selenoprotein mRNAs, the protein SBP2 plays a key role in the assembly of the selenocysteine incorporation machinery. SBP2 contains an L7Ae/L30 RNA-binding domain similar to that of protein 15.5K/Snu13p, which binds K-turn motifs with a 3-nt bulge loop closed by a tandem of G.A and A.G pairs. Here, by SELEX experiments, we demonstrate the capacity of SBP2 to bind such K-turn motifs with a protruding U residue. However, we show that conversion of the bulge loop into an internal loop reinforces SBP2 affinity and to a greater extent RNP stability. Opposite variations were found for Snu13p. Accordingly, footprinting assays revealed strong contacts of SBP2 with helices I and II and the 5'-strand of the internal loop, as opposed to the loose interaction of Snu13p. Our data also identifies new determinants for SBP2 binding which are located in helix II. Among the L7Ae/L30 family members, these determinants are unique to SBP2. Finally, in accordance with functional data on SECIS elements, the identity of residues at positions 2 and 3 in the loop influences SBP2 affinity. Altogether, the data provide a very precise definition of the SBP2 RNA specificity.
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Regiones no Traducidas 3'/química , Proteínas de Unión al ARN/metabolismo , Regiones no Traducidas 3'/metabolismo , Secuencia de Bases , Sitios de Unión , Humanos , Datos de Secuencia Molecular , Mutagénesis Sitio-Dirigida , Conformación de Ácido Nucleico , Unión Proteica , Proteínas de Unión al ARN/química , Ribonucleoproteínas Nucleares Pequeñas/metabolismo , Proteínas de Saccharomyces cerevisiae/metabolismo , Selenocisteína/metabolismoRESUMEN
The eukaryal Snu13p/15.5K protein binds K-turn motifs in U4 snRNA and snoRNAs. Two Snu13p/15.5K molecules bind the nucleolar U3 snoRNA required for the early steps of preribosomal processing. Binding of one molecule on the C'/D motif allows association of proteins Nop1p, Nop56p, and Nop58p, whereas binding of the second molecule on the B/C motif allows Rrp9p recruitment. To understand how the Snu13p-Rrp9p pair recognizes the B/C motif, we first improved the identification of RNA determinants required for Snu13p binding by experiments using the systematic evolution of ligands by exponential enrichment. This demonstrated the importance of a U.U pair stacked on the sheared pairs and revealed a direct link between Snu13p affinity and the stability of helices I and II. Sequence and structure requirements for efficient association of Rrp9p on the B/C motif were studied in yeast cells by expression of variant U3 snoRNAs and immunoselection assays. A G-C pair in stem II, a G residue at position 1 in the bulge, and a short stem I were found to be required. The data identify the in vivo function of most of the conserved residues of the U3 snoRNA B/C motif. They bring important information to understand how different K-turn motifs can recruit different sets of proteins after Snu13p association.
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ARN de Hongos/química , ARN Nucleolar Pequeño/química , Secuencias Reguladoras de Ácidos Nucleicos , Ribonucleoproteínas Nucleares Pequeñas/metabolismo , Ribonucleoproteínas Nucleolares Pequeñas/metabolismo , Proteínas de Saccharomyces cerevisiae/metabolismo , Saccharomyces cerevisiae/metabolismo , Emparejamiento Base , Secuencia de Bases , Secuencia Conservada , Guanina , Datos de Secuencia Molecular , Unión Proteica , Estabilidad del ARN , ARN de Hongos/genética , ARN de Hongos/metabolismo , ARN Nucleolar Pequeño/genética , Técnica SELEX de Producción de Aptámeros , Saccharomyces cerevisiae/citología , Saccharomyces cerevisiae/crecimiento & desarrollo , Eliminación de SecuenciaRESUMEN
The ribosomal L7Ae protein of archaea has the peculiarity to be a component of the C/D and H/ACA snRNPs, that guide rRNA post-transcriptional modifications. Its yeast (Snu13p) and human (15.5kDa protein) homologs are only found in C/D snoRNPs and the (U4/U6, U5) spliceosomal tri-snRNP. By using a large variety of RNAs, we compared the RNA-binding specificities of the recombinant Pyrococcus abyssi L7Ae and Saccharomyces cerevisiae Snu13 proteins. Unlike Snu13p, protein L7Ae binds terminal loops closed by two A:G and G:A pairs and canonical K-turn structures with similar efficiencies, provided that the terminal loop contains at least 5nt. In contrast to Snu13p, binding of protein L7Ae to canonical K-turn structures is not dependent on the identity of the residue at position 2 in the bulge. The peculiar KT-15 motif of P. abyssi 23S rRNA, that is recognized by L7Ae, does not associate with Snu13p. To get more information on the P. abyssi L7Ae protein, we solved its X-ray structure at 1.9A resolution. In spite of their sequence divergence, the free P. abyssi and bound H. marismortui proteins were found to have highly similar structures. Only a limited number of side-chain conformational changes occur at the protein-RNA interface upon RNA binding. In particular, one ion pair that is formed by residues Glu43 and Lys46 in the free protein is disrupted in the ribosomal 50S subunit, so that, residue Glu43 can interact with the RNA residue G264. The Glu43-Lys46 ion pair of protein L7Ae belongs to a complex network of ion pairs that may participate to protein thermostability.
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Proteínas Arqueales/química , Proteínas Ribosómicas/química , Secuencia de Aminoácidos , Proteínas Arqueales/genética , Proteínas Arqueales/metabolismo , Secuencia de Bases , Sitios de Unión , Haloarcula marismortui/genética , Haloarcula marismortui/metabolismo , Humanos , Modelos Moleculares , Datos de Secuencia Molecular , Conformación de Ácido Nucleico , Conformación Proteica , Pyrococcus abyssi/genética , Pyrococcus abyssi/metabolismo , ARN de Archaea/química , ARN de Archaea/genética , ARN de Archaea/metabolismo , ARN Ribosómico/química , ARN Ribosómico/genética , ARN Ribosómico/metabolismo , Ribonucleoproteínas Nucleares Pequeñas/química , Ribonucleoproteínas Nucleares Pequeñas/genética , Ribonucleoproteínas Nucleares Pequeñas/metabolismo , Proteínas Ribosómicas/genética , Proteínas Ribosómicas/metabolismo , Proteínas de Saccharomyces cerevisiae/química , Proteínas de Saccharomyces cerevisiae/genética , Proteínas de Saccharomyces cerevisiae/metabolismo , Homología de Secuencia de Aminoácido , Electricidad EstáticaRESUMEN
Clinical leakage of the anastomosis follows low anterior resection for rectal carcinoma in 5-10 per cent of patients despite standard stapling techniques. A modification of this method has obviated the need for a distal purse string. A flexible transverse stapling instrument (Roticulator 55) is applied across the rectum below the tumour, and a double-staggered row of staples is inserted as a substitute for the distal purse string. End-to-end stapled anastomosis is then performed with peranal insertion of a Premium CEEA stapling instrument. In 111 patients the indications for operation were colorectal carcinoma (96 patients), diverticulosis (ten), megarectum (four) and ulcerative proctocolitis (one). Three patients had clinical evidence of anastomotic leakage; all survived. The incidence of radiological leakage on Gastrografin enema 10-12 days after operation was 9 per cent. The perioperative mortality rate was 2 per cent; all deaths were from cardiovascular causes. Local recurrence of tumour occurred in eight patients (7 per cent) after a mean follow-up of 40 months. In conclusion, double-stapled end-to-end anastomosis has made low anterior resection for rectal carcinoma a safe procedure with a low mortality rate, an acceptable local recurrence rate and minimal (clinical) anastomotic leakage.
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Colon/cirugía , Neoplasias del Colon/cirugía , Neoplasias del Recto/cirugía , Recto/cirugía , Engrapadoras Quirúrgicas , Adulto , Anciano , Anciano de 80 o más Años , Anastomosis Quirúrgica/métodos , Neoplasias del Colon/patología , Femenino , Humanos , Masculino , Persona de Mediana Edad , Complicaciones Posoperatorias , Estudios Prospectivos , Neoplasias del Recto/patologíaRESUMEN
Retrorectal masses are rare and of insidious onset. We report a consecutive series of six such cases (males = 4, females = 2). The main presenting complaint was back pain and the most reliable physical sign was a palpable mass posteriorly on rectal examination (all cases). C T scan was the most radiologically informative investigation. Surgical intervention was undertaken using both anterior (trans-abdominal) and posterior (retrorectal) approaches. The majority of the masses excised were benign and all patients, to date, remain well.