79 research outputs found
Factors associated with nursing home placement of all patients admitted for inpatient rehabilitation in Singapore community hospitals from 1996 to 2005: A disease stratified analysis
10.1371/journal.pone.0082697PLoS ONE812-POLN
Survival of patients with metastatic breast cancer: twenty-year data from two SEER registries
BACKGROUND: Many researchers are interested to know if there are any improvements in recent treatment results for metastatic breast cancer in the community, especially for 10- or 15-year survival. METHODS: Between 1981 and 1985, 782 and 580 female patients with metastatic breast cancer were extracted respectively from the Connecticut and San Francisco-Oakland registries of the Surveillance, Epidemiology, and End Results (SEER) database. The lognormal statistical method to estimate survival was retrospectively validated since the 15-year cause-specific survival rates could be calculated using the standard life-table actuarial method. Estimated rates were compared to the actuarial data available in 2000. Between 1991 and 1995, further 752 and 632 female patients with metastatic breast cancer were extracted respectively from the Connecticut and San Francisco-Oakland registries. The data were analyzed to estimate the 15-year cause-specific survival rates before the year 2005. RESULTS: The 5-year period (1981â1985) was chosen, and patients were followed as a cohort for an additional 3 years. The estimated 15-year cause-specific survival rates were 7.1% (95% confidence interval, CI, 1.8â12.4) and 9.1% (95% CI, 3.8â14.4) by the lognormal model for the two registries of Connecticut and San Francisco-Oakland respectively. Since the SEER database provides follow-up information to the end of the year 2000, actuarial calculation can be performed to confirm (validate) the estimation. The Kaplan-Meier calculation for the 15-year cause-specific survival rates were 8.3% (95% CI, 5.8â10.8) and 7.0% (95% CI, 4.3â9.7) respectively. Using the 1991â1995 5-year period cohort and followed for an additional 3 years, the 15-year cause-specific survival rates were estimated to be 9.1% (95% CI, 3.8â14.4) and 14.7% (95% CI, 9.8â19.6) for the two registries of Connecticut and San Francisco-Oakland respectively. CONCLUSIONS: For the period 1981â1985, the 15-year cause-specific survival for the Connecticut and the San Francisco-Oakland registries were comparable. For the period 1991â1995, there was not much change in survival for the Connecticut registry patients, but there was an improvement in survival for the San Francisco-Oakland registry patients
Detailed Regulatory Mechanism of the Interaction between ZO-1 PDZ2 and Connexin43 Revealed by MD Simulations
The gap junction protein connexin43 (Cx43) binds to the second PDZ domain of Zonula occludens-1 (ZO-1) through its C-terminal tail, mediating the regulation of gap junction plaque size and dynamics. Biochemical study demonstrated that the very C-terminal 12 residues of Cx43 are necessary and sufficient for ZO-1 PDZ2 binding and phosphorylation at residues Ser (-9) and Ser (-10) of the peptide can disrupt the association. However, only a crystal structure of ZO-1 PDZ2 in complex with a shorter 9 aa peptide of connexin43 was solved experimentally. Here, the interactions between ZO-1 PDZ2 and the short, long and phosphorylated Cx43 peptides were studied using molecular dynamics (MD) simulations and free energy calculation. The short peptide bound to PDZ2 exhibits large structural variations, while the extension of three upstream residues stabilizes the peptide conformation and enhanced the interaction. Phosphorylation at Ser(-9) significantly weakens the binding and results in conformational flexibility of the peptide. Glu210 of ZO-1 PDZ2 was found to be a key regulatory point in Cx43 binding and phosphorylation induced dissociation
Predicting nursing home admission in the U.S: a meta-analysis
Background:
While existing reviews have identified significant predictors of nursing home admission, this meta-analysis attempted to provide more integrated empirical findings to identify predictors. The present study aimed to generate pooled empirical associations for sociodemographic, functional, cognitive, service use, and informal support indicators that predict nursing home admission among older adults in the U.S.
Methods:
Studies published in English were retrieved by searching the MEDLINE, PSYCINFO, CINAHL, and Digital Dissertations databases using the keywords: "nursing home placement," "nursing home entry," "nursing home admission," and "predictors/institutionalization." Any reports including these key words were retrieved. Bibliographies of retrieved articles were also searched. Selected studies included sampling frames that were nationally- or regionally-representative of the U.S. older population.
Results:
Of 736 relevant reports identified, 77 reports across 12 data sources were included that used longitudinal designs and community-based samples. Information on number of nursing home admissions, length of follow-up, sample characteristics, analysis type, statistical adjustment, and potential risk factors were extracted with standardized protocols. Random effects models were used to separately pool the logistic and Cox regression model results from the individual data sources. Among the strongest predictors of nursing home admission were 3 or more activities of daily living dependencies (summary odds ratio [OR] = 3.25; 95% confidence interval [CI], 2.56â4.09), cognitive impairment (OR = 2.54; CI, 1.44â4.51), and prior nursing home use (OR = 3.47; CI, 1.89â6.37).
Conclusion:
The pooled associations provided detailed empirical information as to which variables emerged as the strongest predictors of NH admission (e.g., 3 or more ADL dependencies, cognitive impairment, prior NH use). These results could be utilized as weights in the construction and validation of prognostic tools to estimate risk for NH entry over a multi-year period
Distinct Roles for Dectin-1 and TLR4 in the Pathogenesis of Aspergillus fumigatus Keratitis
Aspergillus species are a major worldwide cause of corneal ulcers, resulting in visual impairment and blindness in immunocompetent individuals. To enhance our understanding of the pathogenesis of Aspergillus keratitis, we developed a murine model in which red fluorescent protein (RFP)-expressing A. fumigatus (Af293.1RFP) conidia are injected into the corneal stroma, and disease progression and fungal survival are tracked over time. Using Mafia mice in which c-fms expressing macrophages and dendritic cells can be induced to undergo apoptosis, we demonstrated that the presence of resident corneal macrophages is essential for production of IL-1ÎČ and CXCL1/KC, and for recruitment of neutrophils and mononuclear cells into the corneal stroma. We found that ÎČ-glucan was highly expressed on germinating conidia and hyphae in the cornea stroma, and that both Dectin-1 and phospho-Syk were up-regulated in infected corneas. Additionally, we show that infected Dectin-1â/â corneas have impaired IL-1ÎČ and CXCL1/KC production, resulting in diminished cellular infiltration and fungal clearance compared with control mice, especially during infection with clinical isolates expressing high ÎČ-glucan. In contrast to Dectin 1â/â mice, cellular infiltration into infected TLR2â/â, TLR4â/â, and MD-2â/â mice corneas was unimpaired, indicating no role for these receptors in cell recruitment; however, fungal killing was significantly reduced in TLR4â/â mice, but not TLR2â/â or MD-2â/â mice. We also found that TRIFâ/â and TIRAPâ/â mice exhibited no fungal-killing defects, but that MyD88â/â and IL-1R1â/â mice were unable to regulate fungal growth. In conclusion, these data are consistent with a model in which ÎČ-glucan on A.fumigatus germinating conidia activates Dectin-1 on corneal macrophages to produce IL-1ÎČ, and CXCL1, which together with IL-1R1/MyD88-dependent activation, results in recruitment of neutrophils to the corneal stroma and TLR4-dependent fungal killing
Distinct Roles for Dectin-1 and TLR4 in the Pathogenesis of Aspergillus fumigatus Keratitis
Aspergillus species are a major worldwide cause of corneal ulcers, resulting in visual impairment and blindness in immunocompetent individuals. To enhance our understanding of the pathogenesis of Aspergillus keratitis, we developed a murine model in which red fluorescent protein (RFP)-expressing A. fumigatus (Af293.1RFP) conidia are injected into the corneal stroma, and disease progression and fungal survival are tracked over time. Using Mafia mice in which c-fms expressing macrophages and dendritic cells can be induced to undergo apoptosis, we demonstrated that the presence of resident corneal macrophages is essential for production of IL-1ÎČ and CXCL1/KC, and for recruitment of neutrophils and mononuclear cells into the corneal stroma. We found that ÎČ-glucan was highly expressed on germinating conidia and hyphae in the cornea stroma, and that both Dectin-1 and phospho-Syk were up-regulated in infected corneas. Additionally, we show that infected Dectin-1â/â corneas have impaired IL-1ÎČ and CXCL1/KC production, resulting in diminished cellular infiltration and fungal clearance compared with control mice, especially during infection with clinical isolates expressing high ÎČ-glucan. In contrast to Dectin 1â/â mice, cellular infiltration into infected TLR2â/â, TLR4â/â, and MD-2â/â mice corneas was unimpaired, indicating no role for these receptors in cell recruitment; however, fungal killing was significantly reduced in TLR4â/â mice, but not TLR2â/â or MD-2â/â mice. We also found that TRIFâ/â and TIRAPâ/â mice exhibited no fungal-killing defects, but that MyD88â/â and IL-1R1â/â mice were unable to regulate fungal growth. In conclusion, these data are consistent with a model in which ÎČ-glucan on A.fumigatus germinating conidia activates Dectin-1 on corneal macrophages to produce IL-1ÎČ, and CXCL1, which together with IL-1R1/MyD88-dependent activation, results in recruitment of neutrophils to the corneal stroma and TLR4-dependent fungal killing
International Consensus Statement on Rhinology and Allergy: Rhinosinusitis
Background: The 5 years since the publication of the first International Consensus Statement on Allergy and Rhinology: Rhinosinusitis (ICARâRS) has witnessed foundational progress in our understanding and treatment of rhinologic disease. These advances are reflected within the more than 40 new topics covered within the ICARâRSâ2021 as well as updates to the original 140 topics. This executive summary consolidates the evidenceâbased findings of the document. Methods: ICARâRS presents over 180 topics in the forms of evidenceâbased reviews with recommendations (EBRRs), evidenceâbased reviews, and literature reviews. The highest grade structured recommendations of the EBRR sections are summarized in this executive summary. Results: ICARâRSâ2021 covers 22 topics regarding the medical management of RS, which are grade A/B and are presented in the executive summary. Additionally, 4 topics regarding the surgical management of RS are grade A/B and are presented in the executive summary. Finally, a comprehensive evidenceâbased management algorithm is provided. Conclusion: This ICARâRSâ2021 executive summary provides a compilation of the evidenceâbased recommendations for medical and surgical treatment of the most common forms of RS
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