Prevalence of Depression in Older Nursing Home Residents in High and Low Altitude Regions: A Comparative Study

Objective: Depressive symptoms (depression hereafter) is common in older adults, and closely associated with environmental factors. This study compared the prevalence of depression in older adults living in high-altitude and low-altitude regions, and their association with quality of life (QOL).Method: A total of 632 older nursing home residents were included, with 425 participants living in low-altitude and 207 participants living in high-altitude regions. Depression and QOL were assessed using standardized instruments.Results: The prevalence of depression was 26.9% (95% CI: 23.43–30.37%) in the whole sample of older nursing home residents, with 11.1% (95% CI: 8.01–14.05%) in those living in low-altitude and 59.4% (95% CI: 52.68–66.17%) in those living in high-altitude regions. Multiple logistic regression analysis revealed that living in low-altitude region (P < 0.001, OR = 0.07, 95% CI: 0.04–0.12) was associated with lower risk of depression, while perception of poor health status (P < 0.001, OR = 3.86, 95% CI: 1.98–7.54) and having insomnia (P < 0.001, OR = 4.76, 95% CI: 2.99–7.56) were associated with higher risk of depression. QOL was significantly lower in physical (F(1,632) = 35.421, P < 0.001), psychological (F(1,632) = 20.777, P < 0.001), social (F(1,632) = 8.169, P < 0.001) and environmental domains (F(1,632) = 11.861, P < 0.001) in those with depression.Conclusion: Depression was common in older nursing home residents especially those living in the high-altitude region. Considering the negative impact of depression on QOL and functional outcomes, routine screening and timely treatment of depression should be implemented in this population

Plasma IL-37 Elevated in Patients with Chronic Heart Failure and Predicted Major Adverse Cardiac Events: A 1-Year Follow-Up Study

A great number of basic and clinical studies have demonstrated that inflammatory cytokines play an important role in the development and progression of chronic heart failure (CHF). However, there is limited information about the role of novel cytokine interleukin-37 (IL-37) in heart failure. We measured plasma IL-37 levels by enzyme-linked immunosorbent assay (ELISA) in 158 patients with chronic heart failure and 30 control subjects. Our results showed that plasma IL-37 levels were significantly elevated in patients with CHF compared with healthy controls (143.73 ± 26.83 pg/ml versus 45.2 ± 11.56 pg/ml, P99 pg/ml plasma IL-37 had significantly higher incidences of MACE within 12 months. Our data suggest that plasma IL-37 may play a role in the pathogenesis of CHF and may be a novel predictor of poor prognosis in HF patients

Oxidized Low Density Lipoprotein Induced Caspase-1 Mediated Pyroptotic Cell Death in Macrophages: Implication in Lesion Instability?

<div><p>Background</p><p>Macrophage death in advanced lesion has been confirmed to play an important role in plaque instability. However, the mechanism underlying lesion macrophage death still remains largely unknown.</p><p>Methods and Results</p><p>Immunohistochemistry showed that caspase-1 activated in advanced lesion and co-located with macrophages and TUNEL positive reaction. In in-vitro experiments showed that ox-LDL induced caspase-1 activation and this activation was required for ox-LDL induced macrophages lysis, IL-1β and IL-18 production as well as DNA fragmentation. Mechanism experiments showed that CD36 and NLRP3/caspase-1/pathway involved in ox-LDL induced macrophage pyroptosis.</p><p>Conclusion</p><p>Our study here identified a novel cell death, pyroptosis in ox-LDL induced human macrophage, which may be implicated in lesion macrophages death and play an important role in lesion instability.</p></div

Reliability and validity of the quick inventory of depressive symptomatology—Self-Report Scale in older adults with depressive symptoms

Background: Depressive symptoms are common in older adults. Developing rapid self-report tools is essential to measure the presence and severity of depressive symptoms in older adults. This study evaluated the psychometric properties of the Quick Inventory of Depressive Symptomatology—Self-Report (QIDS-SR) scale for use in depressed older adults. Methods: A total of 238 depressed older adults were included in the study. The Montgomery–Asberg Depression Rating Scale (MADRS) and the QIDS-SR were administered to assess the severity of depressive symptoms. Cronbach’s alpha coefficient, Spearman rank correlations, and principal component analysis were performed to estimate the internal consistency, convergent validity, and factorial structure of the QIDS-SR, respectively. Results: The Cronbach’s alpha for the QIDS-SR was acceptable (α = 0.64). Item–total correlation analyses showed that the items of concentration/decision-making, involvement, energy level, and agitation/retardation had high correlation with the QIDSSR total score (all correlation coefficients ≥0.60). The QIDS-SR total score was significantly correlated with the MADRS total score (r = 0.53, p \u3c 0.001), demonstrating acceptable convergent validity. Factor analysis revealed the unidimensional structure of the QIDS-SR. Conclusions: The QIDS-SR appears to be a reliable and valid self-report scale for estimating the severity of depressive symptoms in depressed older adults

Caspase-1 activation was required for cytokines production.

<p>Cells were transfected with non-targeting siRNA (control), siRNA specific for caspase-1, caspase-3, caspase-8 and caspase-9. After transfection, cells were cultured for 48 h with or without ox-LDL (100 µg/ml). Cytokines production of IL-1β, IL-18, IL-33, TNF-α, IL-6 and MCP-1 was determined by ELISA. *<i>p</i><0.05; ***<i>p</i><0.001. <i>NS</i>, not significant differences (<i>p</i>>0.05). Data are presented as mean±SEM of at least three independent experiments.</p

Activated caspase-1 was required for ox-LDL induced macrophages death.

<p>A. Cell was cultured as described previously. Cells death was visualized by ETHD-III (red) and calcein AM (green) staining (×100). B. Qualitative analysis of cell death expressed as a percentage of LDH release by Triton X-100 detergent or a percent of ETHD-III positive cells in the total cells. *indicated vs untreated cells, *p<0.05; **p<0.01; ***p<0.001. <i>NS</i>, not significant differences (<i>p</i>>0.05). C. Cells were pretreated for 1 hour with vehicle (DMSO), with inhibitors of caspase-1 (Ac-YVAD-CHO), caspase-3 (Ac-DEVD-CHO), caspase-4 (Ac-LEVD-CHO), caspase-6 (Ac-VEID-CHO), caspase-8 (Z-IETD-CHO), caspase-9 (Ac-LEHD-CHO), or with pan-caspase (z-VAD-CHO), and then cells were cultured with ox-LDL (100 µg/ml) for 48 h. Cell death was determined by LDH release. Inhibitors concentration was 100 µM in all cases. *indicated vs cells pre-cultured with DMSO.*p<0.05; **p<0.01; ***<i>p</i><0.001. <i>NS</i>, not significant differences (<i>p</i>>0.05). D. Cells were transfected with non-targeting siRNA (control) or siRNA specific for caspase-1. After transfection, inhibition rate of siRNA was measured by RT-PCR. Transfected cells were cultured for 48 h with or without ox-LDL (100 µg/ml). Cell death was determined by LDH release and ETHD-III/calcein AM staining (×100). ***<i>p</i><0.001. <i>NS</i>, not significant differences (<i>p</i>>0.05). Data are presented as mean±SEM of at least three independent experiments.</p

Involvement of CD36 in ox-LDL induced caspase-1 activation, LDH release and IL-1β and IL-18 production.

<p>A. Cells were pretreated with vehicles (control), NAC (10 mM, 24 h) or VitC (100 mM, 24 h), or with CD36 blocking antibody (5 ug/ml or 20 ug/ml), then cells were cultured with ox-LDL (100 µg/ml, 48 h). Intracellular ROS in HMDMs were assessed by DCFH2-DA. B. Cleaved caspase-1 was measured by western blot. β-actin was used for protein loading controls. C. Caspase-1 activity was measured by Ac-YVAD-<i>p</i>NA. ^###p<0.001. <i>NS</i>, not significant differences (<i>p</i>>0.05). D. Cell death was measured by the percentage of LDH release. E. Cytokine production of IL-1β and IL-18 was measured by ELISA. *indicated vs cells cultured with ox-LDL, *<i>p</i><0.05; **<i>p</i><0.01; ***p<0.001. ^#indicated vs cells cultured with control. ^###<i>p</i><0.001. <i>NS</i>, not significant differences (<i>p</i>>0.05). Data are presented as mean±SEM of at least three independent experiments.</p

Involvement of activated caspase-1 in ox-LDL induced DNA fragmentation.

<p>A. Cells were cultured with PBS (control), with ox-LDL (100 µg/ml, 48 h), LPS (1 µg/ml, 6 h) followed by ATP (5 mM, 30 min), or with STS (1 Μm, 4 h).After incubation, DNA fragmentation was measured by TUNEL staining (green). Qualitative analysis of DNA fragmentation by randomly counting 10 fields of the section and were expressed as a percentage of the total nuclei population. * indicated vs untreated cells (control), *p<0.05; ***<i>p</i><0.001. B. Cells were transfected with non-targeting siRNA (control) or siRNA specific for caspase-1. Then cells were cultured for 48 h with or without ox-LDL (100 µg/ml). DNA fragmentation was determined by TUNEL positive counting. *<i>p</i><0.05. <i>NS</i>, not significant difference (<i>p</i>>0.05). C. Cells were pretreated for 1 hour with vehicle (DMSO) or with corresponding caspase inhibitors (100 uM), and then cells were cultured with ox-LDL (100 µg/ml) for 48 h. DNA fragmentation was determined by TUNEL positive counting. *indicated vs control, *p<0.05; **p<0.01; ***<i>p</i><0.001. <i>NS</i>, not significant difference (<i>p</i>>0.05). D. Protein of cleaved caspase-1 and ICAD in cell lysates were measured by western blot. β-actin was used for protein loading controls. Data are presented as mean±SEM of at least three independent experiments.</p

Role of inflammasome components ASC and NLRP3 in ox-LDL induced caspase-1 activation.

<p>A. Cells were cultured with PBS (control) or with ox-LDL (100 µg/ml, 48 h). Gene expression of inflammasome components was measured by RT-PCR. * indicated vs control, *p<0.05. <i>NS</i>, not significant differences (<i>p</i>>0.05). Cells were transfected with non-targeting siRNA (control) or siRNA specific for NLRP3 (B) or ASC (C). After transfection, inhibition rate of siRNA was measured by RT-PCR. Transfected cells were then cultured for 48 h with or without ox-LDL (100 µg/ml, 48 h). Caspase-1 activity was measured by Ac-YVAD-<i>p</i>NA. ***<i>p</i><0.001. <i>NS</i>, not significant differences (<i>p</i>>0.05). D. Cells were transfected and cultured as described above. Protein of cleaved caspase-1 was measured by western blot. Un-transfected human macrophages cultured with ox-LDL was used as control. β-actin was used for protein loading controls. Data are presented as mean±SEM of at least three independent experiments.</p

Cleaved caspase-1 over-expressed in human atherosclerotic plaque.

<p>A. Immunohistochemical analysis of cleaved caspase-1 in non-atherosclerotic vessel (control), EAL and AAL. In the left column, representative immunostaining for cleaved caspase-1(brown, arrow) in exemplary sections of non-atherosclerotic vessel (control), early atherosclerotic lesion (EAL) and advanced atherosclerotic lesion (AAL) were shown. High-power photomicrograph (×200) exhibited strong cleaved caspase-1 staining in AAL, as shown in the upper boxed area in low-power photomicrograph (×40). In the right column, bar graphs showed the relatively quantitative cleaved caspase-1 expression in control, EAL and AAL. *indicated vs control, ***<i>p</i><0.001; ^#indicated vs EAL, ^###<i>p</i><0.001. NC, necrotic core. B. Western blot analysis of caspase-1, mature IL-1β and IL-18 protein. Protein was extracted from 5 vessel tissues obtained from non-atherosclerotic vessel (control), EAL and AAL. β-actin was used for protein loading controls. C. Double staining of cleaved caspase-1 co-located with CD68 positive cells in AAL. In the right column, high-power photomicrograph (×400) showed strong cleaved caspase-1 staining (red) correlated with CD68 positive cell (green) around necrotic core (NC), as shown in the boxed area of HE staining and DAPI staining (blue) in the left column (×40). D. Double staining of cleaved caspase-1(red) co-located with TUNEL reaction (green) in AAL (×200).</p