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INTRODUCTION: Improving discharge information dissemination may improve patients' health literacy of self-care and health outcomes, avoid unnecessary healthcare utilisation, and reduce the healthcare cost. This study aims to use an implementation science theory guided approach to examine the beliefs and behaviours of healthcare professionals regarding postdischarge information summary (PDIS) implementation in a public inpatient setting. METHODS AND ANALYSIS: A multistage study design involving qualitative inquiry and Delphi expert discussion will be used to systematically explore the perceived barriers in the four implemented hospitals and enable the full implementation of the PDIS in geriatric and medical care. The theoretical domains framework (TDF), behavioural change wheel and realistic evaluation framework will be used to guide the investigation of implementation. This study consists of three steps: (1) identifying barriers and enablers from an implementation perspective using a TDF-informed interview guide; (2) devising theory-based implementation strategy packages to facilitate the adoption and enhancement of PDIS by performing a strategy mapping exercise and (3) developing an effective implementation strategy package for scaling up PDIS in other target hospitals as well as other specialities using the Delphi expert discussion. The goal of this multistage study design is to identify the perspectives from healthcare professionals towards the PDIS implementation and explore their barriers and facilitators of the process in the pilot phase. The invited healthcare professionals would share their daily experience on providing PDIS to patient in various study hospitals with similar ward setting. The implementation of discharge intervention in a study setting through different steps to aid in the exploration and development of the modified implementation strategies for the adoption and enhancement of PDIS in the discharge process. ETHICS AND DISSEMINATION: Ethics approval for the study was obtained from the Joint Chinese University of Hong Kong-New Territories East Cluster Clinical Research Ethics Committees. Results of the study would be released as a report submitted to the Health and Medical Research Fund of Food and Health Bureau of the Hong Kong Government. The result would also be published in international peer-reviewed medical journals and presented in conferences. TRIAL REGISTRATION NUMBER: ChiCTR2000034382.
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Cuidados Posteriores , Alta del Paciente , Anciano , Atención a la Salud , Humanos , Sistemas de Información , Investigación CualitativaRESUMEN
Walking onto a stationary surface previously experienced as moving generates an after-effect commonly known as the "broken escalator" after-effect (AE). This AE represents an inappropriate expression of the locomotor adaptation necessary to step onto the moving platform (or escalator). It is characterised by two main biomechanical components, an increased gait approach velocity (GAV) and a forward trunk overshoot on gait termination. We investigated whether the trunk overshoot and other biomechanical measures are the direct inertial consequence of the increased GAV or whether these are the result of an independent adaptive mechanism. Forty-eight healthy young adults walked onto a movable sled. They performed 5 trials with the sled stationary at their preferred walking velocity (BEFORE trials), 5 with the sled moving (MOVING or adaptation trials), and 5 with the sled stationary again (AFTER trials). For the AFTER trials, subjects were divided into four groups. One group was instructed to walk slowly ("slower"), another with cueing at the BEFORE pace ("metronome"). The third group walked without cueing at the BEFORE pace ("normal"), and the fourth, fast ("faster"). We measured trunk pitch angle, trunk linear horizontal displacement, left shank pitch angular velocity and surface EMG from lower leg and trunk muscles. In the AFTER trials, an AE was observed in these biomechanical measures for all gait speeds, but these were not strongly dependent on GAV. An AE was present even when GAV was not different from that of BEFORE trials. Therefore, we conclude that, although contributary, the trunk overshoot is not the direct consequence of the increased GAV. Instead, it appears to be generated by anticipatory motor activity "just in case" the sled moves, herewith termed a "pre-emptive" postural adjustment.
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Adaptación Fisiológica/fisiología , Marcha/fisiología , Actividad Motora/fisiología , Equilibrio Postural/fisiología , Caminata/fisiología , Adulto , Señales (Psicología) , Ascensores y Escaleras Mecánicas , Femenino , Humanos , Masculino , Músculo Esquelético/fisiología , Postura/fisiologíaRESUMEN
BACKGROUND: We investigated whether the "first trial effect" (FTE) in responses to support surface tilt has directional characteristics, or is simply due to a startle-like response. The FTE is the difference between the first (unpractised) trial response (FTR) and subsequent responses. METHODS: Each group of 10 young adults received a series of identical support surface tilts (7.5°, 60°/s) in one of five leftward tilt directions or pure backward or forward. These were followed by randomly selected tilts in at least eight equally spaced directions. Only in-place responses were possible as the feet were strapped to the support surface. Body kinematics were collected and EMG activity was recorded from several trunk, leg and arm muscles. RESULTS: The centre of mass (CoM) vector displacement showed a FTE in all tilt directions. It was equally large for all directions of backward tilt but smaller for forward and lateral tilts. A similar effect was noted for the CoM anterior-posterior FTE. FTRs of lateral CoM movements were small for all tilt directions except in the backward left direction. A constant amplitude trunk flexion FTE was observed in all tilt directions, and pelvis backward motion for backward tilts, preceded by a FTE in the abdominal muscles for forward (and lateral) tilts and in the soleus for backward (and lateral) tilts. Hip flexion FTEs were largest in backward left direction and preceded by increased gluteus medius and deltoid FTR activity. FTRs in sternocleidomastoïdeus muscles, generally associated with startle activity, were largest in lateral and forward tilt directions. CONCLUSIONS: FTRs appear to consist of either a forward, backward or lateral movement strategy each imposed on an adapted response strategy. Only the lateral response shows a strong directional sensitivity. We hypothesise that FTR amplitudes result from a failure of the CNS to weight properly the stimulus metrics present in lower leg proprioceptive and vestibular inputs.
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Retroalimentación Fisiológica/fisiología , Movimiento/fisiología , Equilibrio Postural/fisiología , Propiocepción/fisiología , Adolescente , Adulto , Fenómenos Biomecánicos , Electromiografía , Femenino , Lateralidad Funcional/fisiología , Cadera/inervación , Humanos , Rodilla/inervación , Pierna/inervación , Masculino , Músculo Esquelético/fisiología , Reflejo/fisiología , Adulto JovenRESUMEN
In the title compound, C(20)H(20)N(2), the quinoxaline ring adopts a very distorted half-chair conformation [N=C-C=N = 22.7â (2)° for the nominally coplanar atoms] and the cyclo-hexane ring adopts a chair conformation. The quinoxaline and cyclo-hexane rings are cis-fused. The two phenyl rings form a dihedral angle of 63.88â (7)°.
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The reaction to an unexpected balance disturbance is unpracticed, often startling and frequently associated with falls. This everyday situation can be reproduced in an experimental setting by exposing standing humans to sudden, unexpected and controlled movements of a support surface. In this review, we focus on the responses to the very first balance perturbation, the so-called first trial reactions (FTRs). Detailed analysis of FTRs may have important implications, both for clinical practice (providing new insights into the pathophysiological mechanisms underlying accidental falls in real life) and for understanding human physiology (what triggers and mediates these FTRs, and what is the relation to startle responses?). Several aspects of the FTRs have become clear. FTRs are characterized by an exaggerated postural reaction, with large EMG responses and co-contracting muscles in multiple body segments. This balance reaction is associated with marked postural instability (greater body sway to the perturbation). When the same perturbation is repeated, the size of the postural response habituates and the instability disappears. Other issues about FTRs remain largely unresolved, and these are addressed here. First, the functional role of FTRs is discussed. It appears that FTRs produce primarily increased trunk flexion during the multi-segmental response to postural perturbations, thus producing instability. Second, we consider which sensory signals trigger and modulate FTRs, placing specific emphasis on the role of vestibular signals. Surprisingly, vestibular signals appear to have no triggering role, but vestibular loss leads to excessive upper body FTRs due to loss of the normal modulatory influence. Third, we address the question whether startle-like responses are contributing to FTRs triggered by proprioceptive signals. We explain why this issue is still unresolved, mainly because of methodological difficulties involved in separating FTRs from 'pure' startle responses. Fourth, we review new work about the influence of perturbation direction on FTRs. Recent work from our group shows that the largest FTRs are obtained for toe-up support surface rotations which perturb the COM in the posterior direction. This direction corresponds to the directional preponderance for falls seen both in the balance laboratory and in daily life. Finally, we briefly touch upon clinical diagnostic issues, addressing whether FTRs (as opposed to habituated responses) could provide a more ecologically valid perspective of postural instability in patients compared to healthy subjects. We conclude that FTRs are an important source of information about human balance performance, both in health and disease. Future studies should no longer discard FTRs, but routinely include these in their analyses. Particular emphasis should be placed on the link between FTRs and everyday balance performance (including falls), and on the possible role played by startle reactions in triggering or modulating FTRs.
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Cinestesia/fisiología , Enfermedad de Parkinson/fisiopatología , Equilibrio Postural/fisiología , Enfermedades Vestibulares/fisiopatología , Soporte de Peso/fisiología , Accidentes por Caídas , Fenómenos Biomecánicos , Electromiografía , Lateralidad Funcional/fisiología , Habituación Psicofisiológica , Humanos , Cinesis/fisiología , Contracción Muscular/fisiología , Músculo Esquelético/fisiopatología , Propiocepción/fisiología , Tiempo de Reacción/fisiología , Reflejo de Sobresalto/fisiología , Vestíbulo del Laberinto/fisiopatologíaRESUMEN
Gilbert's syndrome (GS) is caused by a reduction in the activity of hepatic bilirubin UDP-glucuronosyltransferase (UGT). This reduction is associated with UGT1A1*28 and UGT1A1*6 polymorphisms. Recent research also showed that carriage of UGT1A1*6 allele were significantly related with UGT1A7*3. Polymerase chain reaction-restriction fragment length polymorphism were utilized to determine UGT1A7 and UGT1A1 genes for 207 patients with GS and 207 gender/age-matched healthy controls. For the 207 healthy controls, linkage disequilibrium was observed between -57UGT1A7 and 622UGT1A7 loci (D' = 1.00 and r(2) = 1.00), -57UGT1A7 and 211UGT1A1 loci (D' = 0.72 and r(2) = 0.36), respectively. A dose-response effect for number of at-risk allele of UGT1A1 and risk for GS was noted (odds ratio (OR) = 8.19 for heterozygous UGT1A1*28 genotype; OR = 124.96 for homozygous UGT1A1*28 genotype; and p for trend <0.05). Patients with combined genotypes carrying UGT1A7 variant alleles and UGT1A1 variant alleles (including UGT1A1*28 and UGT1A1*6) are associated with increased risk of GS (OR = 13.96 for patients with combined genotype carrying at least one variant allele of UGT1A1 and UGT1A7). In conclusion, the -57UGT1A7 (T>G) is highly associated with UGT1A7*3 and moderately associated with 211UGT1A1 (G>A). Certain UGT1A1/UGT1A7 combined genotypes are risk factors of GS.
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Alelos , Enfermedad de Gilbert/genética , Glucuronosiltransferasa/genética , Femenino , Variación Genética , Genotipo , Enfermedad de Gilbert/etnología , Haplotipos , Humanos , Desequilibrio de Ligamiento , Masculino , Polimorfismo Genético , Riesgo , Factores de Riesgo , TaiwánAsunto(s)
Trasplante de Riñón/inmunología , Ácido Micofenólico/efectos adversos , Ácido Micofenólico/farmacocinética , Adulto , Área Bajo la Curva , Cadáver , China , Femenino , Rechazo de Injerto/epidemiología , Humanos , Inmunosupresores/efectos adversos , Inmunosupresores/farmacocinética , Masculino , Persona de Mediana Edad , Selección de Paciente , Estudios Retrospectivos , Donantes de TejidosRESUMEN
Bullatacin, isolated from the fruit of Annona atemoya, is one of the most potentially effective antitumor annonaceous acetogenins. Bullatacin was studied here for its ability to inhibit the proliferation of 2.2.15 cells, hepatitis B virus (HBV) DNA transfected human hepatocarcinoma cell line. It was found that bullatacin induced cytotoxicity of 2.2.15 cells in a time- and dose-dependent manner. Fifty percent effective dose (ED50) on day 1 of exposure to bullatacin were 7.8 +/- 2.5 nM for 2.2.15 cells. [3H]-Thymidine incorporation assays showed almost the same results. Bullatacin-treatment also reduced concentrations of hepatitis B surface antigen (HBsAg) in the cultured medium released from 2.2.15 cells, coincident with the decrease in the cell proliferation. Analysis of mophological changes of bullatacin-treated 2.2.15 by inverted phase-contrast microscope and eletron microscopy revealed a possible model of action for bullatacin to inhibit proliferation of 2.2.15 cells by inducing apoptosis. Most of the bullatacin-induced cell death was found to be due to apoptosis, as determined by double staining with fluorescein-isothiocyanate (FITC)-labeled annexin V and propidium iodide (PI).
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Antineoplásicos Fitogénicos/farmacología , Apoptosis/efectos de los fármacos , Carcinoma Hepatocelular/patología , Furanos/farmacología , Neoplasias Hepáticas/patología , Anexina A5/metabolismo , Antineoplásicos Fitogénicos/uso terapéutico , Carcinoma Hepatocelular/tratamiento farmacológico , Muerte Celular/efectos de los fármacos , División Celular/efectos de los fármacos , Medios de Cultivo Condicionados/metabolismo , ADN/biosíntesis , ADN/efectos de los fármacos , Relación Dosis-Respuesta a Droga , Ficoll/análogos & derivados , Ficoll/metabolismo , Citometría de Flujo , Fluoresceína-5-Isotiocianato/análogos & derivados , Fluoresceína-5-Isotiocianato/metabolismo , Furanos/uso terapéutico , Antígenos de Superficie de la Hepatitis B/metabolismo , Humanos , Neoplasias Hepáticas/tratamiento farmacológico , Propidio/metabolismo , Células Tumorales Cultivadas/citología , Células Tumorales Cultivadas/efectos de los fármacos , Células Tumorales Cultivadas/patologíaRESUMEN
BACKGROUND: Mitomycin C (MC), a DNA cross-linking and alkylating agent, targets guanines in the m5CpG sequence with 2-3-fold preference over guanines in unmethylated CpG. Benzo[a]pyrenediolepoxide (BPDE) and several other aromatic carcinogens form guanine adducts with an identical selectivity for m5CpG, and in certain cancers G to T transversion mutation 'hotspots' in the p53 tumor suppressor gene are more frequent at this sequence than at guanines in other sequences. MC appears suitable to probe the general mechanism of this selectivity. RESULTS: A 162-bp DNA fragment containing C, m5C or f5C (5-fluoro cytosine) at all cytosine positions was cross-linked by MC at guanines in CpG steps. The extent of cross-linking increased in the order f5C < C < m5C. Monoalkylation or cross-linking of duplex 12-mer oligonucleotides containing a single CpG, f5CpG or m5CpG step gave yields of adducts that increased in the same order. The rates showed a correlation with the Hammett sigma constant of the methyl and fluoro substituents of the cytosine. Only the base-pair cytosine substituent influenced reactivity of guanine. CONCLUSIONS: The 2-amino group of guanine in the m5CpG sequence of DNA has a greater nucleophilic reactivity with mitomycin than CpG. Evidence is presented for a novel mechanism: transmission of the electron-donating effect of the 5-methyl substituent of the cytosine to guanine through H-bonding of the m5C.G base pair. The results explain the enhanced reaction of BPDE at m5CpG in DNA and the origin of G-T mutational hotspots in the p53 gene in cancer.
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ADN/metabolismo , Guanina/metabolismo , Conformación de Ácido Nucleico , 7,8-Dihidro-7,8-dihidroxibenzo(a)pireno 9,10-óxido , Alquilación , Reactivos de Enlaces Cruzados/farmacología , Fragmentación del ADN , Espectroscopía de Resonancia Magnética , Mitomicina/farmacología , MutaciónRESUMEN
The tumour suppressor p16 is a member of the INK4 family of inhibi tors of the cyclin D-dependent kinases, CDK4 and CDK6, that are involved in the key growth control pathway of the eukaryotic cell cycle. The 156 amino acid residue protein is composed of four ankyrin repeats (a helix-turn-helix motif) that stack linearly as two four-helix bundles resulting in a non-globular, elongated molecule. The thermodynamic and kinetic properties of the folding of p16 are unusual. The protein has a very low free energy of unfolding, Delta GH-2O/D-N, of 3.1 kcal mol-1 at 25 degreesC. The rate-determining transition state of folding/unfolding is very compact (89% as compact as the native state). The other unusual feature is the very rapid rate of unfolding in the absence of denaturant of 0.8 s-1 at 25 degreesC. Thus, p16 has both thermodynamic and kinetic instability. These features may be essential for the regulatory function of the INK4 proteins and of other ankyrin-repeat-containing proteins that mediate a wide range of protein-protein interactions. The mechanisms of inactivation of p16 by eight cancer-associated mutations were dissected using a systematic method designed to probe the integrity of the secondary structure and the global fold. The structure and folding of p16 appear to be highly vulnerable to single point mutations, probably as a result of the protein's low stability. This vulnerability provides one explanation for the striking frequency of p16 mutations in tumours and in immortalised cell lines.
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Inhibidor p16 de la Quinasa Dependiente de Ciclina/química , Dicroismo Circular , Inhibidor p16 de la Quinasa Dependiente de Ciclina/genética , Estabilidad de Medicamentos , Escherichia coli/genética , Humanos , Técnicas In Vitro , Cinética , Modelos Moleculares , Mutación , Prolina/química , Conformación Proteica , Desnaturalización Proteica , Pliegue de Proteína , Estructura Secundaria de Proteína , Proteínas Recombinantes/química , Proteínas Recombinantes/genética , Espectrometría de Fluorescencia , Termodinámica , UreaRESUMEN
In order to study the factors related to Enterobius vermicularis infection among pre-school children in Ta-Liao District of Kaohsiung County, a questionnaire was designed to interview parents of preschool children selected by random sampling from 7 kindergartens in Ta-Liao District. Enterobius infections in the children were then examined by using two-consecutive-day adhesive cellophane paper perianal swabs. The effective sample numbered 555 children. Variables causing the infection among infected and non-infected children were analyzed by chi-square test and point-biserial correlation. The results indicated that there were significant relationship between infection and the follow items: having snacks; sucking fingers; size of house; ways of cleaning house; place of activities; parent's cognizing that anus is the polluted source of eggs; recognition of the cause-and-effect relationship between eating in the bedroom and being reinfected with Enterobius; recognition of preventing reinfection of Enterobius by taking a shower; and educational background of father. Through logistic regression analysis with backward selection, the authors constructed a predicting model which can predict the infection rate of E. vermicularis among pre-school children according to the habit of having snacks, the habit of sucking fingers, size of house, parent's recognizing that taking a shower can prevent people from reinfection, and the educational background of father.
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Enterobiasis/etiología , Preescolar , Femenino , Humanos , Masculino , Análisis de Regresión , TaiwánRESUMEN
Bidens pilosa L. var minor (Blume) Sherff, B. pilosa L. and B. chilensis DC (compositae), commonly known as "Ham-hong-chho" in Taiwan, have been traditionally used for medicinal purposes. To clarify and compare the hepatoprotective effects of these three plants, we evaluated their potential effectiveness on CCl4- and acetaminophen-induced acute hepatic lesions in rats. The results indicated that the increase in SGOT and SGPT activities caused by CCl4 (3.0 ml/kg, s.c.) and acetaminophen administration (600 mg/kg, i.p.) could be significantly reduced by treating with the extracts of all the three kinds of "Ham-hong-chho" and the extract of B. chilensis exhibited the greatest hepatoprotective effects. These phenomena were also confirmed by histological observation. Liver damage induced by CCl4 and acetaminophen was markedly improved in the extract of B. chilensis treated groups, while groups treated with the extracts of B. pilosa var minor and B. pilosa demonstrated only moderate protective effects. The pharmacological and pathological effects of these three crude groups were compared with Bupleurum chinense, which has been reported previously as a treatment criteria in the CCl4 model, and with silymarin as a standard reference medicine in the acetaminophen model. The results suggest that B. pilosa var minor, B. pilosa and B. chilensis can protect liver injuries from various hepatotoxins and have potential as broad spectrum antihepatic agents.
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Hígado/efectos de los fármacos , Medicina Tradicional China , Animales , Masculino , Ratas , Ratas WistarRESUMEN
"Ham-Hong-Chho" is a folk medicine in Taiwan, derived from the entire plants of Bidens pilosa L. var. minor (Blume) Sherff (Compositae), B. pilosa L. and B. chilensis DC. The anti-inflammatory effect of aqueous extracts of the three plants against paw edema induced by carrageenan and chronic arthritis induced by complete Freund's adjuvant were determined in rats. The results indicated that paw edema induced by carrageenan was significantly decreased by treatment with aqueous extracts (150 or 300 mg/kg) of all three plants (p < 0.05) and that the effect of Bidens pilosa var. minor was the most potent. However, only extracts (500 mg/kg) of B. pilosa L. var. minor and B. pilosa L. significantly decreased the paw edema induced by complete Freund's adjuvant (p < 0.05).
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Edema/tratamiento farmacológico , Indometacina/farmacología , Inflamación/tratamiento farmacológico , Medicina Tradicional China , Animales , Relación Dosis-Respuesta a Droga , Masculino , Ratas , Ratas Wistar , Factores de TiempoRESUMEN
Modern automatic and semiautomatic karyotyping systems employ algorithms that use chromosome length and centromeric index as well as other intact chromosome measures. These measures offer correct classification rates near 95%. An algorithm is presented that utilizes local dark band features and position (position from one end of the chromosome, band-width, band-height above light band background, integrated optical density above light band background, and a shape feature) and is based on maximum likelihood of the multivariate normal distribution for the feature vector. The algorithm was tested on two data sets: 179 metaphases from C. Lundsteen at the Rigshospitalet, Copenhagen, and 50 metaphases from The University of Texas M. D. Anderson Cancer Center. The Copenhagen set achieved an overall correct classification rate of 94.6% when classifying itself, a rate comparable to other algorithms. This classifier relies on local band features rather than global chromosome characteristics and is therefore directly extensible to metaphase and prophase chromosome subsegments and to structural abnormalities.