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1.
Osteoporos Int ; 33(4): 839-850, 2022 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-34748023

RESUMEN

Additional physiotherapy in the first postoperative week was associated with fewer days to discharge after hip fracture surgery. A 7-day physiotherapy service in the first postoperative week should be considered as a new key performance indicator in evaluating the quality of care for patients admitted with a hip fracture. INTRODUCTION: To examine the association between physiotherapy in the first week after hip fracture surgery and discharge from acute hospital. METHODS: We linked data from the UK Physiotherapy Hip Fracture Sprint Audit to hospital records for 5395 patients with hip fracture in May and June 2017. We estimated the association between the number of days patients received physiotherapy in the first postoperative week; its overall duration (< 2 h, ≥ 2 h; 30-min increment) and type (mobilisation alone, mobilisation and exercise) and the cumulative probability of discharge from acute hospital over 30 days, using proportional odds regression adjusted for confounders and the competing risk of death. RESULTS: The crude and adjusted odds ratios of discharge were 1.24 (95% CI 1.19-1.30) and 1.26 (95% CI 1.19-1.33) for an additional day of physiotherapy, 1.34 (95% CI 1.18-1.52) and 1.33 (95% CI 1.12-1.57) for ≥ 2 versus < 2 h physiotherapy, and 1.11 (95% CI 1.08-1.15) and 1.10 (95% CI 1.05-1.15) for an additional 30-min of physiotherapy. Physiotherapy type was not associated with discharge. CONCLUSION: We report an association between physiotherapy and discharge after hip fracture. An average UK hospital admitting 375 patients annually may save 456 bed-days if current provision increased so all patients with hip fracture received physiotherapy on 6-7 days in the first postoperative week. A 7-day physiotherapy service totalling at least 2 h in the first postoperative week may be considered a key performance indicator of acute care quality after hip fracture.


Asunto(s)
Fracturas de Cadera , Alta del Paciente , Fracturas de Cadera/cirugía , Humanos , Modalidades de Fisioterapia , Web Semántica , Reino Unido/epidemiología
2.
Osteoporos Int ; 30(7): 1383-1394, 2019 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-30937483

RESUMEN

Little is known about post-acute care following hip fracture surgery. We investigated discharge destinations from surgical hospitals for nine Canadian provinces. We identified significant heterogeneity in discharge patterns across provinces suggesting different post-acute recovery pathways. Further work is required to determine the impact on patient outcomes and health system costs. INTRODUCTION: To examine discharge destinations by provinces in Canada, adjusting for patient, injury, and care characteristics. METHODS: We analyzed population-based hospital discharge abstracts from a national administrative database for community-dwelling patients who underwent hip fracture surgery between 2004 and 2012 in Canada. Discharge destination was categorized as rehabilitation, home, acute care, and continuing care. Multinomial logistic regression modeling compared proportions of discharge to rehabilitation, acute care, and continuing care versus home between each province and Ontario. Adjusted risk differences and risk ratios were estimated. RESULTS: Of 111,952 previously community-dwelling patients aged 65 years or older, 22.5% were discharged to rehabilitation, 31.6% to home, 27.0% to acute care, and 18.2% to continuing care, with significant variation across provinces (p < 0.001). The proportion of discharge to rehabilitation ranged from 2.4% in British Columbia to 41.0% in Ontario while the proportion discharged home ranged from 20.3% in Prince Edward Island to 52.2% in British Columbia. The proportion of discharge to acute care ranged from 15.2% in Ontario to 58.8% in Saskatchewan while the proportion discharged to continuing care ranged from 9.3% in Manitoba and Prince Edward Island to 22.9% in New Brunswick. Adjusting for hospital type changed the direction of the provincial effect on discharge to continuing care in two provinces, but statistical significance remained consistent with the primary analysis. CONCLUSIONS: Discharge destination from the surgical hospital after hip fracture is highly variable across nine Canadian provinces. Further work is required to determine the impact of this heterogeneity on patient outcomes and health system costs.


Asunto(s)
Fracturas de Cadera/rehabilitación , Alta del Paciente/estadística & datos numéricos , Características de la Residencia/estadística & datos numéricos , Anciano , Anciano de 80 o más Años , Canadá , Continuidad de la Atención al Paciente/organización & administración , Continuidad de la Atención al Paciente/estadística & datos numéricos , Bases de Datos Factuales , Femenino , Fijación de Fractura/métodos , Fijación de Fractura/rehabilitación , Investigación sobre Servicios de Salud/métodos , Fracturas de Cadera/cirugía , Humanos , Vida Independiente/estadística & datos numéricos , Masculino , Transferencia de Pacientes/estadística & datos numéricos , Cuidados Posoperatorios/métodos , Cuidados Posoperatorios/estadística & datos numéricos
3.
Osteoporos Int ; 30(7): 1339-1351, 2019 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-31037362

RESUMEN

INTRODUCTION: To examine prognostic factors that influence complications after hip fracture surgery. To summarize proposed underlying mechanisms for their influence. METHODS: We reported according to the Preferred Reporting Items for Systematic Review and Meta-Analysis Scoping Review extension. We searched MEDLINE, Embase, CINAHL, AgeLine, Cochrane Library, and reference lists of retrieved studies for studies of prognostic factor/s of postoperative in-hospital medical complication/s among patients 50 years and older treated surgically for non-pathological closed hip fracture, published in English on January 2008-January 2018. We excluded studies of surgery type or in-hospital medications. Screening was duplicated by two independent reviewers. One reviewer completed the extraction with accuracy checks by the second reviewer. We summarized the extent, nature, and proposed underlying mechanisms for the prognostic factors of complications narratively and in a dependency graph. RESULTS: We identified 44 prognostic factors of in-hospital complications after hip fracture surgery from 56 studies. Of these, we identified 7 patient factors-dehydration, anemia, hypotension, heart rate variability, pressure risk, nutrition, and indwelling catheter use; and 7 process factors-time to surgery, anesthetic type, transfusion strategy, orthopedic versus geriatric/co-managed care, multidisciplinary care pathway, and potentially modifiable during index hospitalization. We identified underlying mechanisms for 15 of 44 factors. The reported association between 12 prognostic factors and complications was inconsistent across studies. CONCLUSIONS: Most factors were reported by one study with no proposed underlying mechanism for their influence. Where reported by more than one study, there was inconsistency in reported associations and the conceptualization of complications differed, limiting comparison across studies. It is therefore not possible to be certain whether intervening on these factors would reduce the rate of complications after hip fracture surgery.


Asunto(s)
Fijación de Fractura/efectos adversos , Fracturas de Cadera/cirugía , Complicaciones Posoperatorias/etiología , Hospitalización , Humanos , Pronóstico , Factores de Riesgo
4.
Osteoporos Int ; 29(3): 653-663, 2018 03.
Artículo en Inglés | MEDLINE | ID: mdl-29214329

RESUMEN

The extent of Canadian provincial variation in hip fracture surgical timing is unclear. Provinces performed a similar proportion of surgeries within three inpatient days after adjustment. Time to surgery varied by timing of admission across provinces. This may reflect different approaches to providing access to hip fracture surgery. INTRODUCTION: The aim of this study was to compare whether time to surgery after hip fracture varies across Canadian provinces for surgically fit patients and their subgroups defined by timing of admission. METHODS: We retrieved hospitalization records for 140,235 patients 65 years and older, treated surgically for hip fracture between 2004 and 2012 in Canada (excluding Quebec). We studied the proportion of surgeries on admission day and within 3 inpatient days, and times required for 33%, 66%, and 90% of surgeries across provinces and by subgroups defined by timing of admission. Differences were adjusted for patient, injury, and care characteristics. RESULTS: Overall, provinces performed similar proportions of surgeries within the recommended three inpatient days, with all provinces requiring one additional day to perform the recommended 90% of surgeries. Prince Edward Island performed 7.0% more surgeries on admission day than Ontario irrespective of timing of admission (difference = 7.0; 95% CI 4.0, 9.9). The proportion of surgeries on admission day was 6.3% lower in Manitoba (difference = - 6.3; 95% CI - 12.1, - 0.6), and 7.7% lower in Saskatchewan (difference = - 7.7; 95% CI - 12.7, - 2.8) compared to Ontario. These differences persisted for late weekday and weekend admissions. The time required for 33%, 66%, and 90% of surgeries ranged from 1 to 2, 2-3, and 3-4 days, respectively, across provinces by timing of admission. CONCLUSIONS: Provinces performed similarly with respect to recommended time for hip fracture surgery. The proportion of surgeries on admission day, and time required to complete 33% and 66% of surgeries, varied across provinces and by timing of admission. This may reflect different provincial approaches to providing access to hip fracture surgery.


Asunto(s)
Fracturas de Cadera/cirugía , Admisión del Paciente/estadística & datos numéricos , Tiempo de Tratamiento/estadística & datos numéricos , Atención Posterior/estadística & datos numéricos , Anciano , Anciano de 80 o más Años , Canadá , Bases de Datos Factuales , Femenino , Hospitalización/estadística & datos numéricos , Humanos , Masculino , Factores de Tiempo
5.
Age Ageing ; 47(5): 661-670, 2018 09 01.
Artículo en Inglés | MEDLINE | ID: mdl-29668839

RESUMEN

Objective: this systematic review aimed to identify immutable and modifiable prognostic factors of functional outcomes and their proposed mechanism after hip fracture surgery. Design: systematic search of MEDLINE, Embase, CINAHL, PEDRO, OpenGrey and ClinicalTrials.gov for observational studies of prognostic factors of functional outcome after hip fracture among surgically treated adults with mean age of 65 years and older. Study selection, quality assessment, and data extraction were completed independently by two reviewers. The Quality in Prognosis Studies Tool was used for quality assessment and assigning a level of evidence to factors. Proposed mechanisms for reported associations were extracted from discussion sections. Results: from 33 studies of 9,552 patients, we identified 25 prognostic factors of functional outcome after hip fracture surgery. We organised factors into groups: demographics, injury and comorbidities, body composition, complications, and acute care. We assigned two factors a weak evidence level-anaemia and cognition. We assigned Parkinson's disease an inconclusive evidence level. We could not assign an evidence level to the remaining 22 factors due to the high risk of bias across studies. Frailty was the proposed mechanism for the association between anaemia and functional outcome. Medication management, perceived potential, complications and time to mobility were proposed as mechanisms for the association between cognition and functional outcome. Conclusion: we identified one modifiable and one immutable prognostic factor for functional outcomes after hip fracture surgery. Future research may target patients with anaemia or cognitive impairment by intervening on the prognostic factor or the underlying mechanisms.


Asunto(s)
Fijación de Fractura , Fracturas de Cadera/cirugía , Articulación de la Cadera/cirugía , Anciano , Anciano de 80 o más Años , Anemia/epidemiología , Fenómenos Biomecánicos , Disfunción Cognitiva/epidemiología , Comorbilidad , Femenino , Fijación de Fractura/efectos adversos , Estado de Salud , Fracturas de Cadera/diagnóstico por imagen , Fracturas de Cadera/epidemiología , Fracturas de Cadera/fisiopatología , Articulación de la Cadera/diagnóstico por imagen , Articulación de la Cadera/fisiopatología , Humanos , Masculino , Recuperación de la Función , Factores de Riesgo , Factores de Tiempo , Resultado del Tratamiento
6.
Mol Biol (Mosk) ; 52(3): 555-564, 2018.
Artículo en Ruso | MEDLINE | ID: mdl-29989588

RESUMEN

Identifying amino acid positions that determine the specific interaction of proteins with small molecule ligands, is required for search of pharmaceutical targets, drug design, and solution of other biotechnology problems. We studied applicability of an original method SPrOS (specificity projection on sequence) developed to recognize functionally significant positions in amino acid sequences. The method allows residues specific to functional subgroups to be determined within the protein family based on their local surroundings in amino acid sequences. The efficiency of the method has been estimated on the protein kinase family. The residues associated with the protein specificity to inhibitors have been predicted. The results have been verified using 3D structures of protein-ligand complexes. Three small molecule inhibitors have been tested. Residues predicted with SPrOS either in contacted the inhibitor or influenced the conformation of the ligand-binding area. Excluding close homologues from the studied set makes it possible to decrease the number of difficult to interpret positions. The expediency of this procedure was determined by the relationship between an inhibitory spectrum and phylogenic partition. Thus, the method efficiency has been confirmed by matching the prediction results with the protein 3D structures.


Asunto(s)
Inhibidores de Proteínas Quinasas/química , Proteínas Quinasas/química , Análisis de Secuencia de Proteína/métodos , Animales , Sitios de Unión , Humanos
7.
BMC Musculoskelet Disord ; 17: 166, 2016 Apr 14.
Artículo en Inglés | MEDLINE | ID: mdl-27079195

RESUMEN

BACKGROUND: Several patient and health system factors were associated with the risk of death among patients with hip fracture. However, without knowledge of underlying mechanisms interventions to improve survival post hip fracture can only be designed on the basis of the found statistical associations. METHODS: We used the framework developed by Arksey and O'Malley and Levac et al. for synthesis of factors and mechanisms of mortality post low energy hip fracture in adults over the age of 50 years, published in English, between September 1, 2009 and October 1, 2014 and indexed in MEDLINE. Proposed mechanisms for reported associations were extracted from the discussion sections. RESULTS: We synthesized the evidence from 56 articles that reported on 35 patient and 9 system factors of mortality post hip fracture. For 21 factors we found proposed biological mechanisms for their association with mortality which included complications, comorbidity, cardiorespiratory function, immune function, bone remodeling and glycemic control. CONCLUSIONS: The majority of patient and system factors of mortality post hip fracture were reported by only one or two articles and with no proposed mechanisms for their effects on mortality. Where reported, underlying mechanisms are often based on a single article and should be confirmed with further study. Therefore, one cannot be certain whether intervening on such factors may produce expected results.


Asunto(s)
Anciano Frágil , Fracturas de Cadera/diagnóstico , Fracturas de Cadera/mortalidad , Factores de Edad , Anciano , Anciano de 80 o más Años , Capacidad Cardiovascular/fisiología , Índice Glucémico/fisiología , Fracturas de Cadera/fisiopatología , Humanos , Persona de Mediana Edad , Factores de Riesgo
8.
Osteoporos Int ; 26(7): 1903-10, 2015 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-25910745

RESUMEN

UNLABELLED: Hip fracture increases death risk. Ten percent of survivors have second hip fracture. It is not known if second hip fracture further increases death risk. Here, we report that second hip fracture increases death risk beyond that expected for an increase in age. Secondary prevention after hip fracture could save lives. INTRODUCTION: The purpose of this study is to determine if second hip fracture is associated with an increased death rate. METHODS: We retrieved 42,435 hospitalization records of patients aged 60 years or older, who were discharged after admission for hip fracture surgery between 1990 and 2005 in British Columbia, Canada. The outcome variable was the time to death. RESULTS: During follow-up, the average monthly death rate was 16.2 (95 % CI 16.0-16.4) per 1000 patient-months for those without second hip fracture and 21.1 (95 % CI 20.2-22.1) per 1000 patient-months for those with second hip fracture. The hazard of death was 55 % higher for patients with second hip fracture compared to those without second hip fracture (HR = 1.55, 95 % CI 1.47-1.63). The hazard of death was 58 % higher for men with second hip fracture than in men without second hip fracture (HR = 1.58, 95 % CI 1.42-1.75). The hazard of death was 54 % higher for women with second hip fracture compared to women without second hip fracture (HR = 1.54, 95 % CI 1.46-1.63). These sex-specific HRs were not statistically different (p = 0.70). CONCLUSION: Our results are the first to show that second hip fracture increases the risk of death above that anticipated for an increase in age for both men and women. Effective secondary prevention strategies could not only reduce morbidity after hip fracture but could also save lives.


Asunto(s)
Fracturas de Cadera/mortalidad , Fracturas Osteoporóticas/mortalidad , Anciano , Anciano de 80 o más Años , Colombia Británica/epidemiología , Femenino , Estudios de Seguimiento , Fracturas de Cadera/cirugía , Hospitalización/estadística & datos numéricos , Humanos , Tiempo de Internación/estadística & datos numéricos , Masculino , Persona de Mediana Edad , Fracturas Osteoporóticas/cirugía , Recurrencia
9.
Osteoporos Int ; 29(1): 253-254, 2018 01.
Artículo en Inglés | MEDLINE | ID: mdl-28986613
10.
Osteoporos Int ; 22(11): 2817-27, 2011 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-21305269

RESUMEN

UNLABELLED: We determined age-standardized first hip fracture rates in British Columbia between 1990 and 2004. We found sex and fracture type rates in keeping with previous reports and that fracture rates have decreased approximately 18% overall in both men and women. INTRODUCTION: To determine whether there have been changes in the age-, sex-, and subtype-specific first hip fracture rates in Canadian province of British Columbia (BC) between 1990 and 2004. METHODS: Records of all persons aged 60 years and older hospitalized with hip fractures in BC between 1985 and 2004 were obtained from the Canadian Institute for Health Information Discharge Abstract Database. Only the first hip fracture records were included, and fractures likely due to causes other than trauma were excluded. Age- and sex-specific rates were calculated using population denominators from Statistics Canada and direct standardization was used. Age-standardized rates allowed for comparison across years with adjustment for age distribution. RESULTS: There were 41,990 records of first hip fracture included, and 73% were in women. Trends in age-specific rates by fracture type were similar to previous reports. Between 1990 and 2004, there has been an age-adjusted 18% decrease in first hip fracture rates in women, and 19% decrease in first hip fracture rates in men. The decrease was statistically significant in femoral neck fractures in women, but not in men. CONCLUSIONS: There has been a decrease in age-adjusted hip fracture rates in BC between 1990 and 2004, which is in contrast to previous projections for hip fracture rates in Canada.


Asunto(s)
Fracturas de Cadera/epidemiología , Distribución por Edad , Anciano , Anciano de 80 o más Años , Colombia Británica/epidemiología , Femenino , Humanos , Incidencia , Masculino , Persona de Mediana Edad , Distribución por Sexo
11.
Osteoporos Int ; 22(10): 2575-86, 2011 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-21484361

RESUMEN

UNLABELLED: A comprehensive review of literature was conducted to investigate variation in hip fracture incident rates around the world. The original crude incidence rates were standardized for age and sex for comparability. After standardization, the highest rates of hip fracture were found in Scandinavia and the lowest rates in Africa. INTRODUCTION: This study was conducted to investigate the geographic trends of the incidence of osteoporotic hip fractures through a comprehensive review of literature. METHODS: Studies were identified for inclusion in the review by searching the MEDLINE database via PubMed and applying strict inclusion and exclusion criteria. Age-specific incidence rates were extracted from the articles, and in order to provide a common platform for analysis, we used directly age-standardized and age-sex-standardized rates (using the 2005 United Nations estimates of the world population as standard) to complete the analysis. RESULTS: Forty-six full text articles spanning 33 countries/regions were included in the review. For ease of comparison, the results were analyzed by geographic regions: North America, Latin America, Scandinavia, Europe (excluding Scandinavia), Africa, Asia, and Australia. The highest hip fracture rates were found in Scandinavia and the lowest in Africa. We found comparable rates from countries in North America, Australia, and Europe outside of Scandinavia. The diverse makeup of the Asian continent also resulted in quite variable hip fracture rates: ranging from relatively high rates in Iran to low rates, comparable to those from Africa, in mainland China. CONCLUSIONS: Given the aging of populations globally, and in the industrialized countries specifically, hip fractures will become a progressively larger public health burden. The geographic trends observed in hip fracture incidence rates can provide important clues to etiology and prevention.


Asunto(s)
Fracturas de Cadera/epidemiología , África/epidemiología , Asia/epidemiología , Australia/epidemiología , Europa (Continente)/epidemiología , Femenino , Salud Global , Humanos , Incidencia , América Latina/epidemiología , Masculino , Persona de Mediana Edad , América del Norte/epidemiología , Países Escandinavos y Nórdicos/epidemiología
12.
Osteoarthritis Cartilage ; 18(3): 303-11, 2010 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-19879999

RESUMEN

OBJECTIVES: The purpose of the study was to develop a population-based simulation model of osteoarthritis (OA) in Canada that can be used to quantify the future health and economic burden of OA under a range of scenarios for changes in the OA risk factors and treatments. In this article we describe the overall structure of the model, sources of data, derivation of key input parameters for the epidemiological component of the model, and preliminary validation studies. DESIGN: We used the Population Health Model (POHEM) platform to develop a stochastic continuous-time microsimulation model of physician-diagnosed OA. Incidence rates were calibrated to agree with administrative data for the province of British Columbia, Canada. The effect of obesity on OA incidence and the impact of OA on health-related quality of life (HRQL) were modeled using Canadian national surveys. RESULTS: Incidence rates of OA in the model increase approximately linearly with age in both sexes between the ages of 50 and 80 and plateau in the very old. In those aged 50+, the rates are substantially higher in women. At baseline, the prevalence of OA is 11.5%, 13.6% in women and 9.3% in men. The OA hazard ratios for obesity are 2.0 in women and 1.7 in men. The effect of OA diagnosis on HRQL, as measured by the Health Utilities Index Mark 3 (HUI3), is to reduce it by 0.10 in women and 0.14 in men. CONCLUSIONS: We describe the development of the first population-based microsimulation model of OA. Strengths of this model include the use of large population databases to derive the key parameters and the application of modern microsimulation technology. Limitations of the model reflect the limitations of administrative and survey data and gaps in the epidemiological and HRQL literature.


Asunto(s)
Modelos Estadísticos , Osteoartritis/epidemiología , Adolescente , Adulto , Distribución por Edad , Anciano , Anciano de 80 o más Años , Canadá/epidemiología , Niño , Bases de Datos Factuales , Femenino , Estado de Salud , Humanos , Masculino , Persona de Mediana Edad , Calidad de Vida , Factores de Riesgo , Índice de Severidad de la Enfermedad , Distribución por Sexo , Encuestas y Cuestionarios , Adulto Joven
13.
Ultramicroscopy ; 107(6-7): 431-44, 2007.
Artículo en Inglés | MEDLINE | ID: mdl-17258859

RESUMEN

We have developed a new fast electron diffractometer working with high dynamic range and linearity for crystal structure determinations. Electron diffraction (ED) patterns can be scanned serially in front of a Faraday cage detector; the total measurement time for several hundred ED reflections can be tens of seconds having high statistical accuracy for all measured intensities (1-2%). This new tool can be installed to any type of TEM without any column modification and is linked to a specially developed electron beam precession "Spinning Star" system. Precession of the electron beam (Vincent-Midgley technique) reduces dynamical effects allowing also use of accurate intensities for crystal structure analysis. We describe the technical characteristics of this new tool together with the first experimental results. Accurate measurement of electron diffraction intensities by electron diffractometer opens new possibilities not only for revealing unknown structures, but also for electrostatic potential determination and chemical bonding investigation. As an example, we present detailed atomic bonding information of CaF(2) as revealed for the first time by precise electron diffractometry.

14.
Biomed Khim ; 63(5): 423-427, 2017 Oct.
Artículo en Ruso | MEDLINE | ID: mdl-29080875

RESUMEN

Recognition of the phosphorylation sites in proteins is required for reconstruction of regulatory processes in living systems. This task is complicated because the phosphorylation motifs in amino acid sequences are considerably degenerated. To improve the prediction efficacy researchers often use additional descriptors, which should reflect physicochemical features of site-surrounding regions. We have evaluated the reasonability of this approach by applying molecular descriptors (MNA) for structural presentation of the peptide segments. Comparative testing was performed using the prognostic method PASS and two input data types: sets of the MNA descriptors represented peptides as chemical structures and amino acid sequences written using a one-letter code. Training sets were classified in accordance with the established types of the enzymes (protein kinases), modifying corresponding phosphorylation sites. The accuracy estimates obtained by prognosis validation for various classes of substrates were significantly different with both the letters and molecular descriptors. In case of the letter description, the prognosis accuracy demonstrated less dependence on the length of peptides in the training set, while in the case of structural descriptors the accuracy level was determined by the peptide size and descriptor characteristics (MNA levels). The maximal prognosis accuracy related to various kinase families was achieved at different sizes of molecular fragments covered by the MNA descriptors of corresponding levels. This obviously reflected structural differences in surroundings of phosphorylation sites modified by various protein kinases. The use of molecular descriptors provided the prognostic results comparable with the results obtained using traditional letter representation. The prognosis accuracy demonstrated less dependence on the method describing site-surrounding peptides at higher accuracy rates. Applying the MNA descriptors it is possible to achieve better accuracy in the cases when the letter description cannot provide acceptable accuracy.


Asunto(s)
Péptidos/química , Fosforilación , Proteínas/química , Análisis de Secuencia de Proteína
15.
J Mol Biol ; 242(4): 470-86, 1994 Sep 30.
Artículo en Inglés | MEDLINE | ID: mdl-7932704

RESUMEN

The bacteriophage T4 late gene wac (whisker's antigen control) encodes a fibrous protein which forms a collar/whiskers complex. Whiskers function as a helper protein for the long tail fibres assembly and plays a role in regulating retraction of the long tail fibres in response to environmental conditions. In this work we show that expression of the cloned wac gene in Escherichia coli yields a protein oligomer of 53 nm length which we call fibritin, and which is able to complement gpwac T4 particles in vitro. CD spectroscopy of fibritin indicates a 90% alpha-helical content, and scanning calorimetry shows that the protein has several distinct domains. The analysis of the 486 amino acid sequence of fibritin reveals three structural components: a 408 amino acid region that contains 12 putative coiled-coil segments with a canonical heptad (a-b-c-d-e-f-g)n substructure where the "a" and "d" positions are preferentially occupied by apolar residues, and the N and C-terminal domains (47 and 29 amino acid residues, respectively) have no heptad substructure. The distribution of hydrophobic residues within heptads is more similar to a triple than to a double coiled-coil. The alpha-helical segments are separated by short "linker" regions, variable in length, that have a high proportion of glycine and proline residues. Each coiled-coil segment has, on the borders with linker regions, residues that are common to the N and C-terminal caps of the alpha-helices. Full-length and amino-terminally truncated fibritins can be reassembled in vitro after temperature-induced denaturation. Co-assembly of full-length fibritin and the N-terminal deletion mutant, as well as analytical centrifugation, indicates that the protein is a parallel triple-standard alpha-helical coiled-coil. Deletions of various N-terminal portions of fibritin did not block trimerisation but the mutant trimers are unable to bind to T4 particles. The last 18 C-terminal residues of fibritin are required for correct trimerisation of gpwac monomers in vivo. We propose that fibritin might serve as a convenient model for the investigation of folding and assembly mechanisms of alpha-fibrous proteins.


Asunto(s)
Bacteriófago T4/genética , Genes Virales , Proteínas Virales/química , Secuencia de Aminoácidos , Secuencia de Bases , Dicroismo Circular , ADN Viral , Escherichia coli , Modelos Moleculares , Datos de Secuencia Molecular , Conformación Proteica , Pliegue de Proteína , Proteínas Recombinantes , Alineación de Secuencia , Termodinámica , Ultracentrifugación , Proteínas Virales/genética , Proteínas Virales/ultraestructura
16.
Biomed Khim ; 61(2): 254-64, 2015.
Artículo en Ruso | MEDLINE | ID: mdl-25978391

RESUMEN

In order to surpass the problem of genetic variability of hepatitis C virus envelope proteins during vaccine development, we used the so-called "reverse vaccinology"approach--"from genome to vaccine". Database of HCV protein sequences was designed, viral genome analysis was performed, and several highly conserved sites were revealed in HCV envelope proteins in the framework of this approach. These sites demonstrated low antigenic activity in full-size proteins and HCV virions: antibodies against these sites were not found in all hepatitis C patients. However, two sites, which contained a wide set of potential T-helper epitope motifs, were revealed among these highly conserved ones. We constructed and prepared by solid-phase peptide synthesis several artificial peptide constructs composed of two linker-connected highly conserved HCV envelope E2 protein sites; one of these sites contained a set of T-helper epitope motifs. Experiments on laboratory animals demonstrated that the developed peptide constructs manifested immunogenicity compared with one of protein molecules and were able to raise antibodies, which specifically bound HCV envelope proteins. We succeeded in obtaining antibodies reactive with HCV from hepatitis C patient plasma upon the immunization with some constructs. An original preparation of a peptide vaccine against hepatitis C is under development on the basis of these peptide constructs.


Asunto(s)
Hepatitis C/inmunología , Proteínas del Envoltorio Viral/inmunología , Vacunas contra Hepatitis Viral/inmunología , Secuencia de Aminoácidos , Animales , Antígenos Virales , Epítopos/inmunología , Humanos , Inmunización , Datos de Secuencia Molecular , Vacunas de Subunidad/inmunología , Proteínas del Envoltorio Viral/química
17.
J Epidemiol Community Health ; 55(12): 891-4, 2001 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-11707483

RESUMEN

STUDY OBJECTIVE: To demonstrate the effect of exclusion of data on delays in scheduling operations in calculating difference in admission rates between two enrolment periods. DESIGN: A prospective cohort study; outcome measure-waiting time for elective admission; study variables-enrolment periods, before 31 March 1997 and after that date; the time of scheduling delay; gender; age; urgency, and type of surgery. SETTING: An acute care hospital in Ontario, Canada. PARTICIPANTS: 1173 consecutive cases accepted for elective vascular surgery between 1 July 1994 and 31 March 1999. MAIN RESULTS: Before adjustment for scheduling delays, a 20% lower admission rate was associated with period 2, rate ratio (RR) = 0.8 (95% confidence intervals (CI)= 0.7, 0.9). The difference between the periods became only marginally significant after the adjustment, RR = 0.9 (95% CI=0.8, 1.0). No difference between the periods was found when admission rates were compared before a delay occurred, RR = 0.9 (95% CI=0.8, 1.1). In delayed patients, those enrolled in period 1 and 2 had, respectively, a 40% and a 60% lower admission rate than the period 1 patients admitted without scheduling delays, RR = 0.6 (95% CI=0.4, 0.8) for period 1 and RR = 0.4 (95%CI=0.3, 0.5) for period 2. CONCLUSIONS: The results provide evidence that patients experiencing a delay in scheduling operation have a lower admission rate after the event. Thus, potential for bias exists when between group comparison of waiting time is done without adjustment for an intermediate event that may occur before elective admission.


Asunto(s)
Procedimientos Quirúrgicos Electivos/estadística & datos numéricos , Admisión del Paciente/estadística & datos numéricos , Procedimientos Quirúrgicos Vasculares/estadística & datos numéricos , Listas de Espera , Adulto , Anciano , Sesgo , Estudios de Cohortes , Femenino , Humanos , Masculino , Persona de Mediana Edad , Ontario , Estudios Prospectivos , Factores de Tiempo
18.
J Biomol Struct Dyn ; 8(5): 953-65, 1991 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-1878168

RESUMEN

The bacteriophage T4 late gene wac (whisker antigen control) encodes the protein which forms the fibrous structure on the neck of the virion called whiskers. Amino acid sequence analysis of wac gene product, as deduced from the nucleotide sequence, indicate ten alpha-helical domains (19-40 residues long) with coiled-coil structural patterns. These regions comprise about 70% of the entire 486 amino acid sequence. The alpha-helices are separated by short stretches of polypeptide chain which are similar to the loop regions of the globular protein sequences. We propose a structural model for the dimer of wac gene product molecule, that we call fibritin in which two polypeptide chains associate in a parallel fashion and form a segmented alpha-helical coiled-coil rod similar to epidermal keratins.


Asunto(s)
Fagos T/genética , Proteínas Virales/química , Secuencia de Aminoácidos , Análisis de Fourier , Genes Virales , Datos de Secuencia Molecular , Conformación Proteica , Proteínas Virales/genética
19.
Health Phys ; 69(1): 6-15, 1995 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-7790214

RESUMEN

After the Chernobyl accident in 1986, about 150,000 monitoring measurements were performed in Ukraine. From this data base, 40,000 measurements were selected for which the results of the reference-source measurements could be analyzed by statistical means. The majority of these measurements are of high quality. In this paper, the uncertainties introduced due to the variabilities of anatomic parameters and the measurement geometry are quantified by measurements using a thyroid-neck phantom. Parameters considered are the thyroid mass, the thickness of the tissue overlying the thyroid as well as the detector-neck distance, the orientation, and the horizontal and vertical position of the detector. The uncertainty introduced due to the variability of these factors corresponds to a coefficient of variation in the range of 25-40% for the measured activity.


Asunto(s)
Radioisótopos de Yodo/análisis , Monitoreo de Radiación , Liberación de Radiactividad Peligrosa , Glándula Tiroides/efectos de la radiación , Adolescente , Adulto , Anciano , Niño , Preescolar , Humanos , Lactante , Recién Nacido , Persona de Mediana Edad , Factores de Tiempo , Ucrania
20.
Biofizika ; 47(2): 204-10, 2002.
Artículo en Ruso | MEDLINE | ID: mdl-11969155

RESUMEN

To analyze the interrelationships between the amino acid sequences of the proteins of hepatitis C virus and the functional characteristics of different variants of this virus, a database of protein functional mapping of hepatitis C virus was developed. The database contains amino acid sequences (both full-size and fragmentary) retrieved from accessible databases and experimental data published in literature. The database also contains the results of comparison and treatment of primary data, including alignments and functional regions. On the basis of these data, variable and conservative regions of envelope proteins of hepatitis C virus were revealed. Antigenic and functional maps of structural and nonstructural proteins of the virus were constructed. The most variable region of the envelope protein E2 (HVR1) was analysed. It is assumed that the conservatism of some amino acid positions of HVR1 is related to the functions of this region.


Asunto(s)
Hepacivirus/química , Proteínas Virales/química , Secuencia de Aminoácidos , Bases de Datos de Proteínas , Epítopos , Antígenos de la Hepatitis C/química , Datos de Secuencia Molecular
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