RESUMEN
OBJECTIVE: To evaluate the relationship between use of primary care-based social needs services and subsequent utilization of ambulatory, emergency, and inpatient services. METHODS: This retrospective 2012 to 2015 cohort study uses electronic medical record data from an academic pediatric primary care practice that screens universally for social needs and delivers services via in-house social work staff. Logistic regression (N = 7300) examines how patient characteristics relate to practice-based social service use. Negative binomial models with inverse probability of treatment weights (N = 4893) estimate adjusted incidence rate ratios for ambulatory, emergency, and inpatient service use among those who used social services compared to those who did not. RESULTS: Forty-five percent of patients used primary care-based social needs services. This use was significantly greater among those with disabling or complex medical conditions than those without (adjusted odds ratio and 95% confidence interval (CI) of 9.81 [7.39-13.01] and 2.76 [2.44-3.13], respectively); those from low-income versus high-income backgrounds (1.40 [1.21-1.61]); and Blacks and Latinos than Whites (1.33 [1.09-1.62] and 1.29 [1.05-1.59], respectively). Patients who used social services subsequently utilized ambulatory, emergency, and inpatient services at significantly higher rates than those who did not (adjusted incidence rate ratios and 95% CI of 1.54 [1.45-1.63], 1.50 [1.36-1.65], and 3.23 [2.31-4.51], respectively). CONCLUSIONS: Primary care-based social needs service use was associated with increased utilization of ambulatory services without reductions in emergency or inpatient admissions. This pattern suggests increased health care needs or access and could have payment model-dependent financial implications for practices.
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Aceptación de la Atención de Salud , Atención Primaria de Salud , Atención Ambulatoria , Niño , Estudios de Cohortes , Humanos , Estudios Retrospectivos , Servicio SocialRESUMEN
OBJECTIVES: Children with medical complexity (CMC) are a growing population in pediatric primary care practices, and families caring for these children face increased medical, developmental, education and social needs. The objective of this study was to quantify hospital-wide social work services utilization by CMC compared to non-medically-complex children (non-CMC) to inform the development of family-centered care models that support these vulnerable patients and families. METHODS: Social work department records from a tertiary children's hospital were used to compare CMC aged 0-17 (n = 564) with age- and sex-matched non-CMC (n = 1128) over a 16-month retrospective period. The main outcomes measures were the proportion of patients who used social work services and mean number of hours of services provided per patient, both by social work providers in the primary care setting and throughout the hospital. RESULTS: A greater percentage of CMC used social work services than non-CMC (60.3 vs. 18.9%), and CMC used more hours per child (5.50 h/child vs. 0.69). In multivariate analysis, medical complexity was associated with 6.23-fold greater odds of using social work services (95% CI 4.94-7.85) and with 8.07 times more hours of services per child (95% CI 6.30-10.34), independent of primary health insurance, age, or sex. CONCLUSION: This study confirms that CMC use significantly more social work services in the medical setting. This must be considered when designing proactive medical home models to provide high quality family-centered care for this population, and further research is needed to elucidate the factors that drive this utilization.
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Servicios de Salud del Niño/estadística & datos numéricos , Niños con Discapacidad/rehabilitación , Servicio Social , Adolescente , Niño , Preescolar , Femenino , Humanos , Masculino , Estudios RetrospectivosRESUMEN
Disulfide-rich domains are small protein domains whose global folds are stabilized primarily by the formation of disulfide bonds and, to a much lesser extent, by secondary structure and hydrophobic interactions. Disulfide-rich domains perform a wide variety of roles functioning as growth factors, toxins, enzyme inhibitors, hormones, pheromones, allergens, etc. These domains are commonly found both as independent (single-domain) proteins and as domains within larger polypeptides. Here, we present a comprehensive structural classification of approximately 3000 small, disulfide-rich protein domains. We find that these domains can be arranged into 41 fold groups on the basis of structural similarity. Our fold groups, which describe broader structural relationships than existing groupings of these domains, bring together representatives with previously unacknowledged similarities; 18 of the 41 fold groups include domains from several SCOP folds. Within the fold groups, the domains are assembled into families of homologs. We define 98 families of disulfide-rich domains, some of which include newly detected homologs, particularly among knottin-like domains. On the basis of this classification, we have examined cases of convergent and divergent evolution of functions performed by disulfide-rich proteins. Disulfide bonding patterns in these domains are also evaluated. Reducible disulfide bonding patterns are much less frequent, while symmetric disulfide bonding patterns are more common than expected from random considerations. Examples of variations in disulfide bonding patterns found within families and fold groups are discussed.
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Disulfuros/química , Pliegue de Proteína , Estructura Secundaria de Proteína , Proteínas/química , Proteínas/clasificación , Secuencia de Aminoácidos , Animales , Bases de Datos de Proteínas , Humanos , Modelos Moleculares , Datos de Secuencia Molecular , Estructura Terciaria de Proteína , Proteínas/genética , Proteínas/metabolismo , Alineación de Secuencia , Homología de Secuencia de AminoácidoRESUMEN
BACKGROUND: A comprehensive update of the classification of all available kinases was carried out. This survey presents a complete global picture of this large functional class of proteins and confirms the soundness of our initial kinase classification scheme. RESULTS: The new survey found the total number of kinase sequences in the protein database has increased more than three-fold (from 17,310 to 59,402), and the number of determined kinase structures increased two-fold (from 359 to 702) in the past three years. However, the framework of the original two-tier classification scheme (in families and fold groups) remains sufficient to describe all available kinases. Overall, the kinase sequences were classified into 25 families of homologous proteins, wherein 22 families (approximately 98.8% of all sequences) for which three-dimensional structures are known fall into 10 fold groups. These fold groups not only include some of the most widely spread proteins folds, such as the Rossmann-like fold, ferredoxin-like fold, TIM-barrel fold, and antiparallel beta-barrel fold, but also all major classes (all alpha, all beta, alpha+beta, alpha/beta) of protein structures. Fold predictions are made for remaining kinase families without a close homolog with solved structure. We also highlight two novel kinase structural folds, riboflavin kinase and dihydroxyacetone kinase, which have recently been characterized. Two protein families previously annotated as kinases are removed from the classification based on new experimental data. CONCLUSION: Structural annotations of all kinase families are now revealed, including fold descriptions for all globular kinases, making this the first large functional class of proteins with a comprehensive structural annotation. Potential uses for this classification include deduction of protein function, structural fold, or enzymatic mechanism of poorly studied or newly discovered kinases based on proteins in the same family.
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Bases de Datos de Proteínas , Fosfotransferasas/química , Fosfotransferasas/clasificación , Algoritmos , Secuencia de Aminoácidos , Escherichia coli/metabolismo , Humanos , Modelos Moleculares , Datos de Secuencia Molecular , Familia de Multigenes , Fosfolipasa D/química , Fosfotransferasas (Aceptor de Grupo Alcohol)/química , Fosfotransferasas (Aceptor de Grupo Alcohol)/metabolismo , Conformación Proteica , Pliegue de Proteína , Estructura Secundaria de Proteína , Estructura Terciaria de Proteína , Proteínas/química , Homología de Secuencia de Aminoácido , Especificidad por SustratoRESUMEN
Using a recently developed program (SCOPmap) designed to automatically assign new protein structures to existing evolutionary-based classification schemes, we identify a evolutionarily conserved domain (EDD) common to three different folds: mannose transporter EIIA domain (EIIA-man), dihydroxyacetone kinase (Dak), and DegV. Several lines of evidence support unification of these three folds into a single superfamily: statistically significant sequence similarity detected by PSI-BLAST; "closed structural grouping" using DALI Z-scores (each protein inside a group finds all other group members with scores higher than those to proteins outside the group) that includes only these proteins sharing a unique alpha-helical hairpin at the C-terminus and excludes all other proteins with similar topology; similar domain fusions connect Dak and DegV, and genomic neighborhood organizations connect Dak and EIIA-man. Finally, both Dak and EIIA-man perform similar phosphotransfer reactions, suggesting a phosphotransferase activity for the DegV-like family of proteins, whose function other than lipid binding revealed in the crystal structure remains unknown.
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Proteínas Portadoras/química , Manosa/química , Sistema de Fosfotransferasa de Azúcar del Fosfoenolpiruvato/química , Fosfotransferasas (Aceptor de Grupo Alcohol)/química , Secuencia de Aminoácidos , Animales , Sitios de Unión , Cristalografía por Rayos X , Bases de Datos de Proteínas , Proteínas de Escherichia coli , Evolución Molecular , Humanos , Lípidos/química , Modelos Moleculares , Datos de Secuencia Molecular , Unión Proteica , Conformación Proteica , Pliegue de Proteína , Estructura Secundaria de Proteína , Estructura Terciaria de Proteína , Homología de Secuencia de AminoácidoRESUMEN
BACKGROUND: Inference of remote homology between proteins is very challenging and remains a prerogative of an expert. Thus a significant drawback to the use of evolutionary-based protein structure classifications is the difficulty in assigning new proteins to unique positions in the classification scheme with automatic methods. To address this issue, we have developed an algorithm to map protein domains to an existing structural classification scheme and have applied it to the SCOP database. RESULTS: The general strategy employed by this algorithm is to combine the results of several existing sequence and structure comparison tools applied to a query protein of known structure in order to find the homologs already classified in SCOP database and thus determine classification assignments. The algorithm is able to map domains within newly solved structures to the appropriate SCOP superfamily level with approximately 95% accuracy. Examples of correctly mapped remote homologs are discussed. The algorithm is also capable of identifying potential evolutionary relationships not specified in the SCOP database, thus helping to make it better. The strategy of the mapping algorithm is not limited to SCOP and can be applied to any other evolutionary-based classification scheme as well. SCOPmap is available for download. CONCLUSION: The SCOPmap program is useful for assigning domains in newly solved structures to appropriate superfamilies and for identifying evolutionary links between different superfamilies.
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Evolución Molecular , Estructura Terciaria de Proteína/genética , Algoritmos , Biología Computacional/métodos , Biología Computacional/normas , Reacciones Falso Positivas , Mapeo Peptídico/métodos , Mapeo Peptídico/normas , Péptidos/química , Péptidos/clasificación , Péptidos/genética , Pliegue de ProteínaRESUMEN
Kinases are a ubiquitous group of enzymes that catalyze the phosphoryl transfer reaction from a phosphate donor (usually ATP) to a receptor substrate. Although all kinases catalyze essentially the same phosphoryl transfer reaction, they display remarkable diversity in their substrate specificity, structure, and the pathways in which they participate. In order to learn the relationship between structural fold and functional specificities in kinases, we have done a comprehensive survey of all available kinase sequences (>17,000) and classified them into 30 distinct families based on sequence similarities. Of these families, 19, covering nearly 98% of all sequences, fall into seven general structural folds for which three-dimensional structures are known. These fold groups include some of the most widespread protein folds, such as Rossmann fold, ferredoxin fold, ribonuclease H fold, and TIM beta/alpha-barrel. On the basis of this classification system, we examined the shared substrate binding and catalytic mechanisms as well as variations of these mechanisms in the same fold groups. Cases of convergent evolution of identical kinase activities occurring in different folds are discussed.
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Proteínas Quinasas/clasificación , Secuencia de Aminoácidos , Modelos Moleculares , Datos de Secuencia Molecular , Pliegue de Proteína , Proteínas Quinasas/química , Análisis de Secuencia de Proteína , Homología de Secuencia de AminoácidoRESUMEN
Nicotinamide/Nicotinate mononucleotide (NMN/NaMN) adenylyltransferase is an indispensable enzyme in both de novo biosynthesis and salvage of NAD+ and NADP+. In prokaryotes, it is absolutely required for cell survival, thus representing an attractive target for the development of new broad-spectrum antibacteria inhibitors. The crystal structures of E. coli NaMN adenylyltransferase (NMNAT) and its complex with deamido-NAD (NaAD) revealed that ligand binding causes large conformational changes in several loop regions around the active site. The enzyme specifically recognizes the deamidated pyridine nucleotide through interactions between nicotinate carboxylate with several protein main chain amides and a positive helix dipole. Comparison of E. coli NMNAT with those from archaeal organisms revealed extensive differences in the active site architecture, enzyme-ligand interaction mode, and bound dinucleotide conformations. The bacterial NaMN adenylyltransferase structures described here provide a foundation for structure-based design of specific inhibitors that may have therapeutic potential.