19 research outputs found
The Feasibility of performing resistance exercise with acutely ill hospitalized older adults
BACKGROUND: For older adults, hospitalization frequently results in deterioration of mobility and function. Nevertheless, there are little data about how older adults exercise in the hospital and definitive studies are not yet available to determine what type of physical activity will prevent hospital related decline. Strengthening exercise may prevent deconditioning and Pilates exercise, which focuses on proper body mechanics and posture, may promote safety. METHODS: A hospital-based resistance exercise program, which incorporates principles of resistance training and Pilates exercise, was developed and administered to intervention subjects to determine whether acutely-ill older patients can perform resistance exercise while in the hospital. Exercises were designed to be reproducible and easily performed in bed. The primary outcome measures were adherence and participation. RESULTS: Thirty-nine ill patients, recently admitted to an acute care hospital, who were over age 70 [mean age of 82.0 (SD= 7.3)] and ambulatory prior to admission, were randomized to the resistance exercise group (19) or passive range of motion (ROM) group (20). For the resistance exercise group, participation was 71% (p = 0.004) and adherence was 63% (p = 0.020). Participation and adherence for ROM exercises was 96% and 95%, respectively. CONCLUSION: Using a standardized and simple exercise regimen, selected, ill, older adults in the hospital are able to comply with resistance exercise. Further studies are needed to determine if resistance exercise can prevent or treat hospital-related deterioration in mobility and function
An Analysis of change in girls released from Villa Saint Rose
When juveniles are defined by society as delinquent they are frequently institutionalized. These institutions are referred to as reform schools, correctional institutions or schools, residential care facilities, treatment centers, or variations of the above. They are state sponsored or privately sponsored. Whatever name is on the sign by the front door, each institution is in the business of people changing.
The excellence of an inanimate product can be measured, weighed, checked, and reproduced; but an altered person is more difficult to measure. If one is in the business of people-changing, it seems important to see if one is in fact changing people.
This study of post institutional adjustment in one privately sponsored girl\u27s residential care facility is an attempt to look at change in a group of released girls measured in the scale devised by the study group)
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Impact Of Cytogenetics and Cytogenetic Response On Outcome In Myelodysplastic Syndromes (MDS) treated With Azacitidine (AZA). A Collaborative Study In 878 Patients
Abstract
Background
hypomethylating agents, especially AZA, have become the reference standard for the of higher risk MDS, but the prognostic value of baseline cytogenetics on response to AZA, and the impact of cytogenetic response (CyR) on outcome in responders remain uncertain.
Methods
We collected data from 931 MDS patients (including FAB RAEB-T/WHO AML 20-30% blasts), treated with AZA (75mg/m²/d x7d, for a median of 6 cycles [range 1-72]) in 6 centers in the US, Italy and France between January 2002 and March 2013. Median age was 70 years (range 24-91 years), and 35% of the patients were women.
Cytogenetics at onset of AZA was evaluable in 878 pts (the remaining pts had cytogenetic failure), 581 (66%) of whom had abnormal karyotype, as shown in table 1. Revised (R) IPSS cytogenetic category (Shanz, JCO 2012) was very good, good, int, poor and very poor in 2%, 40%, 18%, 15% and 25% pts respectively. R-IPSS was very good, good, intermediate, poor and very poor in 1%, 4%, 17%, 35% and 43% respectively.
Results
379 (41%) pts achieved hematological IWG 2006 response, including 121 (13%) CR, 86 (9%) PR, 52 (6%) marrow CR, 120 (13%) stable disease with HI. With a median follow up of 41 months, median OS was 16.5 months. Cytogenetic characteristics are summarized in table 1. In the following text, unless specified, results apply to chromosomal rearrangements occurring alone or with additional abnormalities (abn). Trisomy 8 and del(5q)/-5 were associated with significantly better CR rate (21% and 18.5% , respectively, vs 12% in other patients p=0.007 and 0.01, resp.). 3q26 was associated with lower overall response rate (ORR) (22% vs 42%, p=0.04) and only 1/27 of 3q26 pts achieved CR. None of the other cytogenetic specific abnormalities or groups (table 1) and none of the R-IPSS cytogenetic categories had any significant impact on ORR or CR to AZA. Among patients with complex Karyotype (>=3), monosomal karyotype had no influence on response to AZA. When the comparison was made versus patients with normal cytogenetics, presence of -7/del(7q), del(5q)/-5, del(17p), 3q26, monosomal karyotype and complex (>=3) karyotype had no significant impact on the response rate.
Compared to other patients, patients with -7/del(7q) (p=3), those with very complex karyotype (>=5) had shorter OS (median 11.1 vs 15.4 mo, p=0.008). When the comparison was made versus patients with normal cytogenetics, presence of -7/del(7q), del(5q), del(17p), 3q26 , monosomal karyotype and complex (>=3) karyotype were associated with significantly shorter OS.
By multivariate analysis (including cytogenetic R-IPSS categories, del 20q, 7/del(7q) , del(5q)/-5, del (17p) , 3q26 , complex and monosomal karyotype), only the presence of del (17p) (HR 1.54[1.14-2.10], p=0.005), -7/del(7q) (HR 1.23 [1.01-1.50], p=0.04) and del(5q) (HR 1.36[1.08-1.72], p=0.009) retained significant impact on OS.
362 pts with abnormal cytogenetics at onset of AZA had cytogenetic analysis at treatment evaluation, and results were evaluable in 327 of them (the other 35 pts had cytogenetic failure): 106 (32.4%) achieved cytogenetic response (CyR), including 82 (25%) Complete CyR (CCyR), and 24 (7.3%) Partial CyR (PCyR), while 221 (67.6%) had no CyR. Of note, among the 106 cytogenetic responders, 29 (27%) had failed to achieve any hematological response. In a landmark analysis performed 3 months after AZA onset, achievement of any CyR or of CCyR had no significant influence on survival, even when the analysis was restricted to patients who achieved IWG response.
Conclusion
Baseline cytogenetic pattern generally did not predict response to AZA (except the presence of +8 or del(5q), associated with higher CR rate, and 3q26 abn with fewer responses). However, cytogenetic results were strong predictors of survival, especially del (17p), -7/del(7q) and del(5q) associated with significant shorter OS in multivariate analysis. In patients with baseline cytogenetic abnormalities, achieving cytogenetic response was not associated with outcome.
Disclosures:
Komrokji: Celgene: Research Funding, Speakers Bureau. Santini:Celgene: Honoraria; Novartis: Honoraria; GSK: Honoraria; Janssen: Honoraria. List:Celgene: Research Funding. Fenaux:CELGENE: Research Funding
Children born to women with HIV-1 infection: Natural history and risk of transmission
600 children born to HIV-infected mothers by June 15, 1990, in ten European centres were followed to study the natural history of HIV infection and the vertical transmission rate. They were seen at birth, every 3 months up to 18 months of age, and every 6 months thereafter. At last follow-up, 64 children were judged to be HIV infected and 343 had lost antibody and were presumed uninfected. The initial clinical feature in infected children was usually a combination of persistent lymphadenopathy, splenomegaly, and hepatomegaly, though 30% of children presented with AIDS, or with oral candidosis followed rapidly by AIDS. An estimated 83% of infected children show laboratory or clinical features of HIV infection by 6 months of age. By 12 months, 26% have AIDS and 17% die of HIV-related disease. Subsequently, the disease progresses more slowly and most children remain stable or even improve during the second year. The vertical transmission rate, based on results in 372 children born at least 18 months before the analysis, was 12.9% (95% CI 9.5-16.3%). Virus has been repeatedly isolated in an additional small proportion of children (2.5%, 95% CI 0.7-6.3%) who lost maternal antibody and have remained clinically and immunologically normal. Without a definitive virological diagnosis, the monitoring of immunoglobulins, CD4/CD8 ratio, and clinical signs could identify HIV infection in 48% of infected children by 6 months, with a specificity of more than 99%SCOPUS: ar.jinfo:eu-repo/semantics/publishe
PSMC3 proteasome subunit variants are associated with neurodevelopmental delay and type I interferon production
A critical step in preserving protein homeostasis is the recognition, binding, unfolding, and translocation of protein substrates by six AAA-ATPase proteasome subunits (ATPase-associated with various cellular activities) termed PSMC1-6, which are required for degradation of proteins by 26 S proteasomes. Here, we identified 15 de novo missense variants in the PSMC3 gene encoding the AAA-ATPase proteasome subunit PSMC3/Rpt5 in 23 unrelated heterozygous patients with an autosomal dominant form of neurodevelopmental delay and intellectual disability. Expression of PSMC3 variants in mouse neuronal cultures led to altered dendrite development, and deletion of the PSMC3 fly ortholog Rpt5 impaired reversal learning capabilities in fruit flies. Structural modeling as well as proteomic and transcriptomic analyses of T cells derived from patients with PSMC3 variants implicated the PSMC3 variants in proteasome dysfunction through disruption of substrate translocation, induction of proteotoxic stress, and alterations in proteins controlling developmental and innate immune programs. The proteostatic perturbations in T cells from patients with PSMC3 variants correlated with a dysregulation in type I interferon (IFN) signaling in these T cells, which could be blocked by inhibition of the intracellular stress sensor protein kinase R (PKR). These results suggest that proteotoxic stress activated PKR in patient-derived T cells, resulting in a type I IFN response. The potential relationship among proteosome dysfunction, type I IFN production, and neurodevelopment suggests new directions in our understanding of pathogenesis in some neurodevelopmental disorders
PSMC3 proteasome subunit variants are associated with neurodevelopmental delay and type I interferon production
A critical step in preserving protein homeostasis is the recognition, binding, unfolding, and translocation of protein substrates by six AAA-ATPase proteasome subunits (ATPase-associated with various cellular activities) termed PSMC1-6, which are required for degradation of proteins by 26S proteasomes. Here, we identified 15 de novo missense variants in the PSMC3 gene encoding the AAA-ATPase proteasome subunit PSMC3/Rpt5 in 23 unrelated heterozygous patients with an autosomal dominant form of neurodevelopmental delay and intellectual disability. Expression of PSMC3 variants in mouse neuronal cultures led to altered dendrite development, and deletion of the PSMC3 fly ortholog Rpt5 impaired reversal learning capabilities in fruit flies. Structural modeling as well as proteomic and transcriptomic analyses of T cells derived from patients with PSMC3 variants implicated the PSMC3 variants in proteasome dysfunction through disruption of substrate translocation, induction of proteotoxic stress, and alterations in proteins controlling developmental and innate immune programs. The proteostatic perturbations in T cells from patients with PSMC3 variants correlated with a dysregulation in type I interferon (IFN) signaling in these T cells, which could be blocked by inhibition of the intracellular stress sensor protein kinase R (PKR). These results suggest that proteotoxic stress activated PKR in patient-derived T cells, resulting in a type I IFN response. The potential relationship among proteosome dysfunction, type I IFN production, and neurodevelopment suggests new directions in our understanding of pathogenesis in some neurodevelopmental disorders