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101.
Rosemary Frey Deborah Balmer Jackie Robinson Merryn Gott Michal Boyd 《Journal of pain and symptom management》2019,57(3):545-555.e1
Context
In most resource-rich countries, a large and growing proportion of older adults with complex needs will die while in a residential aged care (RAC) facility.Objectives
This study describes the impact of facility size (small/large), ownership model (profit/nonprofit) and provider (independent/chain) on resident comfort, and symptom management as reported by RAC staff.Methods
This retrospective “after-death” study collected decedent resident data from a subsample of 51 hospital-level RAC facilities in New Zealand. Symptom Management at the End-of-Life in Dementia and Comfort Assessment in Dying at End of life with Dementia (SM-EOLD and CAD-EOLD, respectively) scales were used by RAC staff who were closely associated with 217 deceased residents. Data collection occurred from January 2016 to February 2017.Results
Results indicated that residents of large, nonprofit facilities experienced greater comfort at the end of life (CAD-EOLD) as indicated by a higher mean score of 37.21 (SD = 4.85, 95% CI = 34.4, 40.0) than residents of small for-profit facilities who recorded a lower mean score of 31.56 (SD = 6.20, 95% CI = 29.6, 33.4). There was also evidence of better symptom management for residents of chain facilities, with a higher mean score for symptom management (SM-EOLD total score) recorded for residents of chain facilities (mean = 28.07, SD = 7.64, 95% CI = 26.47, 29.66) than the mean score for independent facilities (mean = 23.93, SD = 8.72, 95% CI = 21.65, 26.20).Conclusion
Findings suggest that there are differences in the quality of end-of-life care given in RAC based on size, ownership model, and chain affiliation. 相似文献102.
103.
M. R. Sutherland C. M. Raynor H. Leenknegt J. F. Wright E. L. G. Pryzdial 《Proceedings of the National Academy of Sciences of the United States of America》1997,94(25):13510-13514
Herpesviruses have been previously correlated to vascular disease and shown to cause thrombogenic and atherogenic changes to host cells. Herein we show that even in the absence of cells, purified cytomegalovirus (CMV) and herpes simplex virus type 1 (HSV-1) and type 2 (HSV-2) can initiate thrombin production. Functional assays demonstrated that purified HSV-1 and HSV-2 provide the necessary phospholipid (proPL) for assembling the coagulation factors Xa and Va into prothrombinase, which is responsible for generating thrombin. These observations are consistent with our earlier studies involving CMV. The presence of proPL on all three herpesviruses was confirmed directly by flow cytometry and electron microscopy by using annexin V and factor Va, respectively, as proPL-specific probes. Of equal importance, we found that CMV, HSV-1, and HSV-2 were also able to facilitate factor Xa generation from the inactive precursor factor X, but only when factor VII/VIIa and Ca2+ were present. Monoclonal antibodies specific for tissue factor (TF), the coagulation initiator, inhibited this factor X activation and, furthermore, enabled identification of TF antigen on each virus type by flow cytometry and electron microscopy. Collectively, these data show that CMV, HSV-1, and HSV-2 can initiate the generation of thrombin by having essential proPL and TF activities on their surface. Unlike the normal cellular source, the viral activity is constitutive and, therefore, not restricted to sites of vascular injury. Thus cell-independent thrombin production may be the earliest event in vascular pathology mediated by herpesviruses. 相似文献
104.
G R Sutherland R I Richards 《Proceedings of the National Academy of Sciences of the United States of America》1995,92(9):3636-3641
The human genome contains many repeated DNA sequences that vary in complexity of repeating unit from a single nucleotide to a whole gene. The repeat sequences can be widely dispersed or in simple tandem arrays. Arrays of up to 5 or 6 nt are known as simple tandem repeats, and these are widely dispersed and highly polymorphic. Members of one group of the simple tandem repeats, the trinucleotide repeats, can undergo an increase in copy number by a process of dynamic mutation. Dynamic mutations of the CCG trinucleotide give rise to one group of fragile sites on human chromosomes, the rare folate-sensitive group. One member of this group, the fragile X (FRAXA) is responsible for the most common familial form of mental retardation. Another member of the group FRAXE is responsible for a rarer mild form of mental retardation. Similar mutations of AGC repeats give rise to a number of neurological disorders. The expanded repeats are unstable between generations and somatically. The intergenerational instability gives rise to unusual patterns of inheritance--particularly anticipation, the increasing severity and/or earlier age of onset of the disorder in successive generations. Dynamic mutations have been found only in the human species, and possible reasons for this are considered. The mechanism of dynamic mutation is discussed, and a number of observations of simple tandem repeat mutation that could assist in understanding this phenomenon are commented on. 相似文献
105.
Effects of cyclosporine on the renin-angiotensin-aldosterone system and potassium excretion in renal transplant recipients 总被引:2,自引:0,他引:2
J P Bantle K A Nath D E Sutherland J S Najarian T F Ferris 《Archives of internal medicine》1985,145(3):505-508
To evaluate the mechanism of cyclosporine-induced hyperkalemia, the renin-angiotensin-aldosterone system and renal potassium clearance were compared in ten renal transplant recipients treated with cyclosporine and treated with azathioprine. After stimulation by a low-sodium diet and furosemide, cyclosporine-treated patients demonstrated lower plasma renin activity when supine (1.9 +/- 0.3 v 7.8 +/- 1.4 ng/mL/hr) and after standing (3.0 +/- 0.7 v 12.2 +/- 1.5 ng/mL/hr). Supine plasma aldosterone levels tended to be lower in cyclosporine-treated patients, (4.8 +/- v 10.5 +/- 2.6 ng/dL), although standing plasma aldosterone levels were not different (10.8 +/- 3.0 v 12.3 +/- 2.0 ng/dL). After administration of 0.75 mEq of potassium chloride per kilogram of body weight, cyclosporine-treated patients excreted 52% +/- 7.1% of the potassium load in six hours compared with excretion of 67% +/- 7.0% by the azathioprine-treated patients, although there was no difference in plasma aldosterone levels in response to the potassium load in the two groups. These data suggest that cyclosporine causes suppression of plasma renin activity and a tubular insensitivity to aldosterone, both of which may impair potassium excretion. 相似文献
106.
Kevin R. McCarthy Tarra A. Von Holle Laura L. Sutherland Thomas H. Oguin III Gregory D. Sempowski Stephen C. Harrison M. Anthony Moody 《Proceedings of the National Academy of Sciences of the United States of America》2021,118(23)
Immune memory of a first infection with influenza virus establishes a lasting imprint. Recall of that memory dominates the response to later infections or vaccinations by antigenically drifted strains. Early childhood immunization before infection may leave an imprint with different characteristics. We report here a comparison of imprinting by vaccination and infection in a small cohort of nonhuman primates (NHPs). We assayed serum antibody responses for binding with hemaglutinnins (HAs) both from the infecting or immunizing strain (H3 A/Aichi 02/1968) and from strains representing later H3 antigenic clusters (“forward breadth”) and examined the effects of defined HA mutations on serum titers. Initial exposure by infection elicited strong HA-binding and neutralizing serum antibody responses but with little forward breadth; initial vaccination with HA from the same strain elicited a weaker response with little neutralizing activity but considerable breadth of binding, not only for later H3 HAs but also for HA of the 2009 H1 new pandemic virus. Memory imprinted by infection, reflected in the response to two immunizing boosts, was largely restricted (as in humans) to the outward-facing HA surface, the principal region of historical variation. Memory imprinted by immunization showed exposure to more widely distributed epitopes, including sites that have not varied during evolution of the H3 HA but that yield nonneutralizing responses. The mode of initial exposure thus affects both the strength of the response and the breadth of the imprint; design of next-generation vaccines will need to take the differences into account.Antigenic exposures determine the acquisition and development of adaptive immunity. The humoral response in a naive individual yields both antibody-secreting plasma cells that recognize the new antigen and memory B cells that can respond to future encounters with related antigens. The combination of these two components can confer long-lasting protection against antigenically stable pathogens. For antigenically diverse pathogens and those that evolve to evade immune pressure (e.g., influenza virus and HIV), serum responses often confer incomplete immunity to future variants (1, 2).The hemagglutinin (HA) and neuraminidase (NA) define the serotype of an influenza virus isolate (3). Antigenic shifts occur when novel animal influenza viruses can transmit to humans, spread rapidly, and initiate pandemics, owing to absence of any preexisting immunity (4, 5). Historically, the descendants of pandemic viruses have become endemic seasonal variants that undergo antigenic drift as they evolve over time to evade dominant human herd immunity (6, 7). For most adults, both processes have shaped human immunity to influenza.Immune memory causes a primary infection to impart an enduring imprint (8–11). Despite a lifetime of repeated exposures to divergent influenza viruses, the relative strength of an individual’s immune response to vaccination or infection correlates with the antigenic similarity of the vaccine or infecting strain to that person’s initial exposure. Until recently, the first encounter was invariably an infection. Because of recent changes in vaccine policy in the United States and Europe, infants and toddlers are now encouraged to receive influenza vaccines before they experience an influenza infection (12, 13). We have little information, however, about the immunological memory to influenza virus established when the primary exposure is vaccination rather than infection.Using nonhuman primates (rhesus macaques) as a model, we have examined how the mode of influenza exposure affects both primary and secondary antibody responses. We found that an initial exposure by infection elicited strong, strain-specific, HA-binding, and neutralizing serum antibody responses. Initial exposure by immunization with the HA protein from the strain used in the infection arm of the study elicited relatively weaker HA-binding responses that lacked neutralization potency but had greater interseasonal forward breadth. Subsequent exposures, by immunization, generated antibodies with increased interseasonal breadth in infected animals and neutralizing activity in the initially immunized monkeys. Initially infected macaques maintained responses that were strongly imprinted by the infecting strain, while those initially immunized with protein retained a serum repertoire that cross-reacted with heterologous HAs. Moreover, the distribution of epitopes bound by serum IgG was different in the two cases. These data suggest that the mode of HA exposure influences its immune imprint and that next-generation vaccine design will need to take this influence into account. 相似文献
107.
The relation between the superior orientation of the QRS axis and the anatomical site of the defect in the ventricular septum in patients with a ventricular septal defect was studied. Of 1031 patients with a ventricular septal defect, 64 (6.2%) had a superior axis on their electrocardiogram. In 59% of these patients the defect was in the inlet portion of the ventricular septum or affected this area. None of the cases was classified as an isolated ventricular septal defect of the persistent atrioventricular canal type. While there is an association between a superior axis and perimembranous inlet ventricular septal defect, a superior QRS axis does not characterise a ventricular septal defect as being of the atrioventricular canal type. 相似文献
108.
Expression of a dominant-negative type II transforming growth factor β (TGF-β) receptor in the epidermis of transgenic mice blocks TGF-β-mediated growth inhibition 下载免费PDF全文
Xiao-Jing Wang David A. Greenhalgh Jackie R. Bickenbach Aibo Jiang Donnie S. Bundman Thomas Krieg Rik Derynck Dennis R. Roop 《Proceedings of the National Academy of Sciences of the United States of America》1997,94(6):2386-2391
To determine whether a functional type II receptor of transforming growth factor β (TGF-β) is required to mediate the growth inhibitory effect of TGF-β on the skin in vivo, we have generated transgenic mice that overexpress a dominant negative-type II TGF-β receptor (ΔβRII) in the epidermis. The ΔβRII mice exhibited a thickened and wrinkled skin, and histologically the epidermis was markedly hyperplastic and hyperkeratotic. In vivo labeling with BrdUrd showed a 2.5-fold increase in the labeling index over controls, with labeled nuclei occurring in both basal and suprabasal cells of transgenic epidermis. In heterozygotes, this skin phenotype gradually diminished, and by 10–14 days after birth the transgenic mice were indistinguishable from their normal siblings. However, when F1 mice were mated to homozygosity, perinatal lethality occurred due to the severe hyperkeratotic phenotype, which restricted movement. Cultured primary keratinocytes from ΔβRII mice also exhibited an increased rate of growth in comparison with nontransgenic controls, and were resistant to TGF-β-induced growth inhibition. These data document the role of the type II TGF-β receptor in mediating TGF-β-induced growth inhibition of the epidermis in vivo and in maintenance of epidermal homeostasis. 相似文献
109.
110.
Vainshtein Inna Roskos Lorin K. Cheng Jackie Sleeman Matthew A. Wang Bing Liang Meina 《Pharmaceutical research》2015,32(1):286-299
Pharmaceutical Research - Measurement of internalization of biopharmaceuticals targeting cell surface proteins can greatly facilitate drug development. The objective of this study was to develop a... 相似文献