Eosinophilia is a favorable marker for pneumonia in chronic obstructive pulmonary disease.

Background: Patients with chronic obstructive pulmonary disease (COPD) expressing eosinophilia experience slightly fewer episodes of community-acquired pneumonia (CAP) than those without eosinophilia. However, the severity and burden of hospitalized pneumonia patients with COPD concerning eosinophilia have not been assessed. Methods: We evaluated the differences in clinical characteristics between patients with CAP and COPD with or without eosinophilia by a post-hoc analysis of a prospective, multi-center, cohort study data. Results: Of 349 CAP patients with COPD, 45 (12.9%) had eosinophilia (blood eosinophil ≥ 300 cells/µL). Patients with eosinophilia had a lower sputum culture percentile (8.1% vs. 23.4%, P < 0.05), a lower percentile of neutrophils (70.3% vs 80.2%, P<0.05), reduced C-reactive protein levels (30.6 mg/L vs 86.6 mg/L, P<0.05), and a lower pneumonia severity index score (82.5 vs. 90.0, P < 0.05) than those without eosinophilia. The duration of antibiotic treatment (8.0 days vs. 10.0 days, P < 0.05) and hospitalization (7.0 days vs. 9.0 days, P < 0.05) were shorter in eosinophilic patients. The cost of medical care per day (256.4 US$ vs. 291.0 US$, P < 0.05), cost for the medication (276.4 US$ vs. 349.9 US$, P < 0.05), and cost for examination (685.5 US$ vs 958.1 US$, P<0.05) were lower in patients with eosinophilia than those without eosinophilia. Conclusion: Eosinophilia serves as a favorable marker for severity of pneumonia, health-care consumption, and cost of medical care in patients with CAP and COPD.

Association between statin use and the risk for idiopathic pulmonary fibrosis and its prognosis: a nationwide, population-based study.

Given the pleiotropic effects of statins beyond their lipid-lowering effects, there have been attempts to evaluate the role of statin therapy in IPF, but they have shown inconclusive results. Data from the National Health Insurance Service (NHIS) database of South Korea were used to investigate the effects of statin therapy on IPF. The IPF cohort consisted of a total of 10,568 patients who were newly diagnosed with IPF between 2010 and 2017. These patients were then matched in a 1:3 ratio to 31,704 subjects from a control cohort without IPF, with matching based on age and sex. A case-control study was performed to evaluate the association between statin use and the risk for IPF, and the multivariable analysis revealed that statin use was associated with a lower risk for IPF (adjusted OR 0.847, 95% CI 0.800-0.898). Using the IPF cohort, we also evaluated whether statin use at the time of diagnosis was associated with future clinical outcomes. The statin use at the time of IPF diagnosis was associated with improved overall survival (adjusted HR 0.779, 95% CI 0.709-0.856). Further prospective studies are needed to clarify the role of statin therapy in IPF.

Case report of hypoglossal nerve stimulation therapy failure due to significant underlying central sleep apnea.

Hypoglossal nerve stimulation (HNS) is indicated for obstructive sleep apnea (OSA) but is ineffective in treating central sleep apnea (CSA). We describe two patients implanted with HNS after being diagnosed with OSA at outside sleep labs and failing a trial of continuous positive airway pressure (CPAP) therapy. Despite successful HNS implantation, the patients continued to have persistent symptoms with residual apnea-hypopnea indices above 25 events/h. Although OSA was the presenting diagnosis, we discovered a significant CSA component in the original diagnostic sleep data upon careful review. One patient was confirmed to have a CSA-predominant sleep disorder and improved with adaptive servo ventilation therapy. The other was diagnosed with central sleep apnea and severe periodic limb movement disorder, and improved with medication. Based on these sleep apnea cases, we propose guidelines emphasizing the importance of reviewing basic clinical information upon treatment failure and initiating multi-disciplinary collaboration early in the treatment course.

Clonal hematopoiesis of indeterminate potential is associated with current smoking status and history of exacerbation in patients with COPD.

Background: There is limited data regarding the clinical outcomes of clonal hematopoiesis of indeterminate potential (CHIP) in patients with chronic obstructive pulmonary disease (COPD). This study aimed to evaluate the clinical significance of CHIP as a COPD biomarker. Methods: This retrospective study was conducted on patients with COPD who were enrolled prospectively in the Seoul National University Hospital Airway Registry from January 2013 to December 2019 and underwent pulmonary function and blood tests. We evaluated the CHIP score according to smoking status and severity of airflow obstruction. Results: We analyzed next-generation sequencing data to detect CHIP in 125 patients with COPD. Current smokers had a higher prevalence of CHIP in DTP, DNMT3A, and PPM1D genes than in never- or ex-smokers. CHIP of DTP and DNMT3A genes was significantly associated with current smokers (aOR 2.80, 95% CI 1.01-7.79; aOR 4.03, 95% CI 1.09-14.0). Patients with moderate-to-severe airflow obstruction had a higher prevalence of CHIP in most of the explored genes than those with mild obstruction, although the difference was not statistically significant. CHIP in ASXL1 genes was significantly associated with history of mild, severe, and total acute exacerbation. Conclusion: Given that CHIP in specific genes was significantly associated with current smoking status and acute exacerbation, CHIP can be considered as a candidate biomarker for COPD patients.

Del-1 Plays a Protective Role against COPD Development by Inhibiting Inflammation and Apoptosis.

Neutrophilic inflammation is a prominent feature of chronic obstructive pulmonary disease (COPD). Developmental endothelial locus-1 (Del-1) has been reported to limit excessive neutrophilic inflammation by inhibiting neutrophil adhesion to the vascular endothelial cells. However, the effects of Del-1 in COPD are not known. We investigated the role of Del-1 in the pathogenesis of COPD. Del-1 protein expression was decreased in the lungs of COPD patients, especially in epithelial cells and alveolar macrophages. In contrast to human lung tissue, Del-1 expression was upregulated in lung tissue from mice treated with cigarette smoke extracts (CSE). Overexpression of Del-1 significantly suppressed IL-8 release and apoptosis in CSE-treated epithelial cells. In contrast, knockdown of Del-1 enhanced IL-8 release and apoptosis. In macrophages, overexpression of Del-1 significantly suppressed inflammatory cytokine release, and knockdown of Del-1 enhanced it. This anti-inflammatory effect was mediated by inhibiting the phosphorylation and acetylation of NF-κB p65. Nuclear factor erythroid 2-related factor 2 (Nrf2) activators, such as quercetin, resveratrol, and sulforaphane, increased Del-1 in both cell types. These results suggest that Del-1, mediated by Nrf2, plays a protective role against the pathogenesis of COPD, at least in part through anti-inflammatory and anti-apoptotic effects.

Ultrastrong and ductile steel welds achieved by fine interlocking microstructures with film-like retained austenite.

The degradation of mechanical properties caused by grain coarsening or the formation of brittle phases during welding reduces the longevity of products. Here, we report advances in the weld quality of ultra-high strength steels by utilizing Nb and Cr instead of Ni. Sole addition of Cr, as an alternative to Ni, has limitations in developing fine weld microstructure, while it is revealed that the coupling effects of Nb and Cr additions make a finer interlocking weld microstructures with a higher fraction of retained austenite due to the decrease in austenite to acicular ferrite and bainite transformation temperature and carbon activity. As a result, an alloying design with Nb and Cr creates ultrastrong and ductile steel welds with enhanced tensile properties, impact toughness, and fatigue strength, at 45% lower material costs and lower environmental impact by removing Ni.

Risk stratification for early mortality in newly diagnosed acute promyelocytic leukemia: a multicenter, non-selected, retrospective cohort study.

Introduction: Despite the current effective treatments for acute promyelocytic leukemia (APL), early mortality (EM), defined as death within 30 days of presentation, is a major hurdle to long-term survival. Methods: We performed a multicenter retrospective study to evaluate the incidence and clinical characteristics of EM in patients with newly diagnosed APL and to develop a risk stratification model to predict EM. Results: We identified 313 eligible patients diagnosed between 2000 and 2021 from five academic hospitals. The median age was 50 years (range 19-94), and 250 (79.9%) patients were <65 years. Most patients (n=274, 87.5%) received their first dose of all-trans retinoic acid (ATRA) within 24 hours of presentation. EM occurred in 41 patients, with a cumulative incidence of 13.1%. The most common cause of EM was intracranial hemorrhage (n=22, 53.6%), and most EMs (31/41, 75.6%) occurred within the first seven days of APL presentation. In a multivariable analysis, we identified three independent factors predicting EM: age ≥65 years (HR, 2.56), white blood cell count ≥8.0 x 109/L (HR, 3.30), and ATRA administration >24 hours of presentation (HR, 2.95). Based on these factors, patients were stratified into three categories with a significantly increasing risk of EM: 4.1% for low risk (54.3%; no risk factors; HR 1), 18.5% for intermediate risk (34.5%; 1 factor; HR 4.81), and 40.5% for high risk (11.2%; 2-3 factors; HR 13.16). Discussion: The risk of EM is still not negligible in this era of ATRA-based therapies. Our risk model serves as a clinically useful tool to identify high-risk patients for EM who may be candidates for novel treatments and aggressive supportive strategies.

Geriatric risk model for older patients with diffuse large B-cell lymphoma (GERIAD): a prospective multicenter cohort study.

BACKGROUND/AIMS: Optimal risk stratification based on simplified geriatric assessment to predict treatment-related toxicity and survival needs to be clarified in older patients with diffuse large B-cell lymphoma (DLBCL). METHODS: This multicenter prospective cohort study enrolled newly diagnosed patients with DLBCL (≥ 65 yr) between September 2015 and April 2018. A simplified geriatric assessment was performed at baseline using Activities of Daily Living (ADL), Instrumental ADL (IADL), and Charlson's Comorbidity Index (CCI). The primary endpoint was event-free survival (EFS). RESULTS: The study included 249 patients, the median age was 74 years (range, 65-88), and 125 (50.2%) were female. In multivariable Cox analysis, ADL, IADL, CCI, and age were independent factors for EFS; an integrated geriatric score was derived and the patients stratified into three geriatric categories: fit (n = 162, 65.1%), intermediate-fit (n = 25, 10.0%), and frail (n = 62, 24.9%). The established geriatric model was significantly associated with EFS (fit vs. intermediate-fit, HR 2.61, p < 0.001; fit vs. frail, HR 4.61, p < 0.001) and outperformed each covariate alone or in combination. In 87 intermediate-fit or frail patients, the relative doxorubicin dose intensity (RDDI) ≥ 62.4% was significantly associated with worse EFS (HR, 2.15, 95% CI 1.30-3.53, p = 0.002). It was related with a higher incidence of grade ≥ 3 symptomatic non-hematologic toxicities (63.2% vs. 27.8%, p < 0.001) and earlier treatment discontinuation (34.5% vs. 8.0%, p < 0.001) in patients with RDDI ≥ 62.4% than in those with RDDI < 62.4%. CONCLUSION: This model integrating simplified geriatric assessment can risk-stratify older patients with DLBCL and identify those who are highly vulnerable to standard dose-intensity chemoimmunotherapy.

Analysis of PM2.5 inorganic and organic constituents to resolve contributing sources in Seoul, South Korea and Beijing, China and their possible associations with cytokine IL-8.

China and South Korea are the most polluted countries in East Asia due to significant urbanization and extensive industrial activities. As neighboring countries, collaborative management plans to maximize public health in both countries can be helpful in reducing transboundary air pollution. To support such planning, PM2.5 inorganic and organic species were determined in simultaneously collected PM2.5 integrated filters. The resulting data were used as inputs to positive matrix factorization, which identified nine sources at the ambient air monitoring sites in both sites. Secondary nitrate, secondary sulfate/oil combustion, soil, mobile, incinerator, biomass burning, and secondary organic carbon (SOC) were found to be sources at both sampling sites. Industry I and II were only identified in Seoul, whereas combustion and road dust sources were only identified in Beijing. A subset of samples was selected for exposure assessment. The expression levels of IL-8 were significantly higher in Beijing (167.7 pg/mL) than in Seoul (72.7 pg/mL). The associations between the PM2.5 chemical constituents and its contributing sources with PM2.5-induced inflammatory cytokine (interleukin-8, IL-8) levels in human bronchial epithelial cells were investigated. For Seoul, the soil followed by the secondary nitrate and the biomass burning showed increase with IL-8 production. However, for the Beijing, the secondary nitrate exhibited the highest association with IL-8 production and SOC and biomass burning showed modest increase with IL-8. As one of the highest contributing sources in both cities, secondary nitrate showed an association with IL-8 production. The soil source having the strongest association with IL-8 production was found only for Seoul, whereas SOC showed a modest association only for Beijing. This study can provide the scientific basis for identifying the sources to be prioritized for control to provide effective mitigation of particulate air pollution in each city and thereby improve public health.

Maximizing Photoelectrochemical Performance in Metal-Oxide Hybrid Composites via Amorphous Exsolution-A New Exsolution Mechanism for Heterogeneous Catalysis.

Exsolution generates metal nanoparticles anchored within crystalline oxide supports, ensuring efficient exposure, uniform dispersion, and strong nanoparticle-perovskite interactions. Increased doping level in the perovskite is essential for further enhancing performance in renewable energy applications; however, this is constrained by limited surface exsolution, structural instability, and sluggish charge transfer. Here, hybrid composites are fabricated by vacuum-annealing a solution containing SrTiO3 photoanode and Co cocatalyst precursors for photoelectrochemical water-splitting. In situ transmission electron microscopy identifies uniform, high-density Co particles exsolving from amorphous SrTiO3 films, followed by film-crystallization at elevated temperatures. This unique process extracts entire Co dopants with complete structural stability, even at Co doping levels exceeding 30%, and upon air exposure, the Co particles embedded in the film oxidize to CoO, forming a Schottky junction at the interface. These conditions maximize photoelectrochemical activity and stability, surpassing those achieved by Co post-deposition and Co exsolution from crystalline oxides. Theoretical calculations demonstrate in the amorphous state, dopant─O bonds become weaker while Ti─O bonds remain strong, promoting selective exsolution. As expected from the calculations, nearly all of the 30% Fe dopants exsolve from SrTiO3 in an H2 environment, despite the strong Fe─O bond's low exsolution tendency. These analyses unravel the mechanisms driving the amorphous exsolution.

Physical activity has a more beneficial effect on the risk of all-cause mortality in patients with metabolic syndrome than in those without.

BACKGROUND: It has not been clarified whether physical activity (PA) has more benefit in terms of health outcomes, including mortality risk, among those with metabolic syndrome (MS) compared to those without. Therefore, the aim of this study is to elucidate whether regular PA has interaction with MS on health outcomes. METHODS: Participants with no underlying cardiovascular diseases who underwent national health screening in 2009 were included. According to the metabolic equivalent (MET)-minutes/week, the amount of PA among the participants was grouped as follows: Group 1 (0 MET-minutes/week), Group 2 (1-499), Group 3 (500-999), Group 4 (1000-1499), and Group 5 (≥ 1500). Multivariable Cox proportional hazard models were applied to evaluate the impacts of the amount of PA on health outcomes among those with and without MS. Health outcomes included all-cause mortality and incident cardiovascular diseases (CVDs). RESULTS: Of 9,628,109 total participants, 335,970 deaths occurred during a median 8.3-year follow-up. After adjustment for age, sex, smoking status, alcohol consumption, and body mass index, the higher the PA amount was, the lower the risk of all-cause mortality in both those with MS [adjusted hazard ratio (aHR) compared with Group 1, 0.86 (95% CI 0.85, 0.87) in Group 2; 0.82 (95% CI 0.81, 0.83) in Group 3; 0.75 (95% CI 0.74, 0.77) in Group 4; and 0.78 (95% CI 0.76, 0.80) in Group 5; P for trend < 0.001] and those without MS [aHR compared with Group 1, 0.87 (95% CI 0.86, 0.88) in Group 2; 0.84 (95% CI 0.83, 0.85) in Group 3, 0.79 (95% CI 0.78, 0.80) in Group 4, and 0.82 (95% CI 0.81, 0.84) in Group 5; P for trend < 0.001]. The beneficial effects of the amount of PA on all-cause mortality were larger among those with MS than among those without MS in a multiplicative interaction (P for interaction < 0.001). The results were similar in the analysis of the relationship between the PA amount and incident CVD. CONCLUSIONS: More PA was associated with a lower risk of all-cause mortality, which was more prominent in those with MS than in those without MS. Physicians should emphasize more the importance of PA in patients with MS.

Acute myelomonocytic leukemia and T-lymphoblastic lymphoma as simultaneous bilineage hematologic malignancy treated with decitabine: A case report.

BACKGROUND: Simultaneous bilineage hematologic malignancies are rare; however, several cases of acute myeloid leukemia (AML) and T-lymphoblastic lymphoma (T-LBL) co-occurrence have been reported. A standard treatment for simultaneous AML and T-LBL has not yet been established, and its prognosis is very poor. Further studies to develop standard treatments are required to increase patient survival rates. CASE SUMMARY: A 69-year-old man complaining of pleuritic chest pain visited the emergency room. Computed tomography revealed multiple enlarged lymph nodes (LNs) in the neck and groin and pulmonary thromboembolism with pulmonary infarction. Furthermore, a peripheral blood smear performed due to leukocytosis revealed circulating blasts. Acute myelomonocytic leukemia (AMML) was diagnosed after bone marrow examination, and T-LBL positivity for terminal deoxynucleotidyl transferase, cluster of differentiation (CD)34, and CD4 was confirmed by cervical LN biopsy. Decitabine and dexamethasone were administered because he could not receive intensive chemotherapy due to poor performance status. Complete remission of AMML and T-LBL was achieved after 4 cycles of decitabine plus dexamethasone. CONCLUSION: We report the therapeutic effect of decitabine, a hypomethylating agent (HMA), in patients with concurrent bilineage hematologic malignancies and suggest that further studies are required to evaluate the therapeutic effect of HMAs on both lymphoid and bilineage hematologic malignancies.

The serotype-specific prevalence of pneumococci in hospitalized pneumonia patients with COPD: a prospective, multi-center, cohort study.

BACKGROUND/AIMS: The overall incidence of pneumococcal pneumonia is declining. However, the change in the pathogenic distribution of community-acquired pneumonia (CAP) in chronic obstructive pulmonary disease (COPD) patients and the serotype specificity of Streptococcus pneumoniae have not been evaluated in the post-era of pneumococcal vaccination in Korea. METHODS: We conducted a prospective, multi-center, cohort study from seven University-affiliated hospitals. The primary objective was the identification of serotype-specific prevalence of pneumococcal pneumonia in COPD patients hospitalized for CAP. For the purpose, we conducted serotype-specific urine antigen detection (SS-UAD) assays for S. pneumoniae. The secondary objectives were other clinical characteristics of pneumonia including vaccination status. RESULTS: The total number of participants was 349. Most of them were male (95.1%) with old ages (75.55 ± 8.59 y). The positive rate for S. pneumoniae was 9.2% with SS-UAD assay and the common serotypes were 22F, 6A, and 6B. In the sputum, Pseudomonas aeruginosa (5.0%) and Haemophilus influenzae (4.0%) were common pathogens. The vaccination rate was 78.8%, 53.0%, and 25.8% for influenza, pneumococcal polysaccharide vaccine 23 (PPV 23), and pneumococcal protein- conjugated vaccine 13 (PCV 13), respectively. Thirteen patients died during hospitalization (mortality rate; 3.7%). There was no difference in the respective rate of influenza vaccination (79.2% vs. 69.2%, p = 0.288) and PCV 13 vaccination (25.6% vs. 30.8%, p = 0.443) between survivors and the deceased. CONCLUSION: Serotypes 22F, 6A, and 6B, which are covered either by PPV 23 or by PCV 13, are still common pneumococcal serotypes in COPD pneumonia in the post-vaccination era in Korea.

Unveiling the Neural Environment in Cancer: Exploring the Role of Neural Circuit Players and Potential Therapeutic Strategies.

The regulation of the immune environment within the tumor microenvironment has provided new opportunities for cancer treatment. However, an important microenvironment surrounding cancer that is often overlooked despite its significance in cancer progression is the neural environment surrounding the tumor. The release of neurotrophic factors from cancer cells is implicated in cancer growth and metastasis by facilitating the infiltration of nerve cells into the tumor microenvironment. This nerve-tumor interplay can elicit cancer cell proliferation, migration, and invasion in response to neurotransmitters. Moreover, it is possible that cancer cells could establish a network resembling that of neurons, allowing them to communicate with one another through neurotransmitters. The expression levels of players in the neural circuits of cancers could serve as potential biomarkers for cancer aggressiveness. Notably, the upregulation of certain players in the neural circuit has been linked to poor prognosis in specific cancer types such as breast cancer, pancreatic cancer, basal cell carcinoma, and stomach cancer. Targeting these players with inhibitors holds great potential for reducing the morbidity and mortality of these carcinomas. However, the efficacy of anti-neurogenic agents in cancer therapy remains underexplored, and further research is necessary to evaluate their effectiveness as a novel approach for cancer treatment. This review summarizes the current knowledge on the role of players in the neural circuits of cancers and the potential of anti-neurogenic agents for cancer therapy.

Estimation of Cooling Rate of High-Strength Thick Plate Steel during Water Quenching Based on a Dilatometric Experiment.

The microstructure and hardness along the thickness direction of a water-quenched, high-strength thick plate with a thickness of 40 mm were investigated with three specimens from the thick plate: surface, 1/4t, and 1/2t (center) thickness, and the phase transformation behavior of the thick plate according to the cooling rate was analyzed through dilatometric experiments. Finally, the cooling rate for each thickness of the thick plate was estimated by comparing the microstructure and hardness of the thick plate along with the thickness with those of the dilatometric specimens. Martensite microstructure was observed on the surface of the water-quenched thick plate due to the fast cooling rate. On the other hand, an inhomogeneous microstructure was transformed inside the thick plate due to the relatively slow cooling rate and central segregation of Mn. A small fraction of bainite was shown at 1/4t thickness. A banded microstructure with martensite and bainite resulting from Mn segregation was developed at 1/2t; that is, the full martensite microstructure was transformed in the Mn-enriched area even at a slow cooling rate due to high hardenability, but a bainite microstructure was formed in the Mn-depleted area owing to relatively low hardenability. A portion of martensite with fine cementite at the surface and 1/4t was identified as auto-tempered martensite with a Bagaryatskii orientation relationship between the ferrite matrix and cementite. The microstructure and hardness as well as dilatation were investigated at various cooling rates through a dilatometric experiment, and a continuous cooling transformation (CCT) diagram was finally presented for the thick plate. Comparing the microstructure and hardness at the surface, 1/4t, and 1/2t of the thick plate with those of dilatometric specimens cooled at various cooling rates, it was estimated that the surface of the thick plate was cooled at more than 20 °C/s, whereas the 1/4t region was cooled at approximately 5~10 °C/s during water quenching. Despite the difficulty in estimation of the cooling rate of 1/2t due to the banded structure, the cooling rate of 1/2t was estimated between 3 and 5 °C/s based on the results of an Mn-depleted zone.

Machine Learning-Based Proteomics Reveals Ferroptosis in COPD Patient-Derived Airway Epithelial Cells Upon Smoking Exposure.

BACKGROUND: Proteomics and genomics studies have contributed to understanding the pathogenesis of chronic obstructive pulmonary disease (COPD), but previous studies have limitations. Here, using a machine learning (ML) algorithm, we attempted to identify pathways in cultured bronchial epithelial cells of COPD patients that were significantly affected when the cells were exposed to a cigarette smoke extract (CSE). METHODS: Small airway epithelial cells were collected from patients with COPD and those without COPD who underwent bronchoscopy. After expansion through primary cell culture, the cells were treated with or without CSEs, and the proteomics of the cells were analyzed by mass spectrometry. ML-based feature selection was used to determine the most distinctive patterns in the proteomes of COPD and non-COPD cells after exposure to smoke extract. Publicly available single-cell RNA sequencing data from patients with COPD (GSE136831) were used to analyze and validate our findings. RESULTS: Five patients with COPD and five without COPD were enrolled, and 7,953 proteins were detected. Ferroptosis was enriched in both COPD and non-COPD epithelial cells after their exposure to smoke extract. However, the ML-based analysis identified ferroptosis as the most dramatically different response between COPD and non-COPD epithelial cells, adjusted P value = 4.172 × 10-6, showing that epithelial cells from COPD patients are particularly vulnerable to the effects of smoke. Single-cell RNA sequencing data showed that in cells from COPD patients, ferroptosis is enriched in basal, goblet, and club cells in COPD but not in other cell types. CONCLUSION: Our ML-based feature selection from proteomic data reveals ferroptosis to be the most distinctive feature of cultured COPD epithelial cells compared to non-COPD epithelial cells upon exposure to smoke extract.

Older Age is Associated With Positional Obstructive Sleep Apnea.

OBJECTIVES: Untreated obstructive sleep apnea (OSA) is associated with cognitive dysfunction; however studies report low adherence rates to standard continuous positive airway pressure (CPAP) treatment in the elderly. Positional OSA (p-OSA) is a subset that can be cured by positional therapy of avoiding supine sleep. However, there is no well-established criteria to identify patients who could benefit from positional therapy as an alternative or adjunct to CPAP. This study investigates if older age is related to p-OSA using different diagnostic criteria. DESIGN: Cross-sectional study. PARTICIPANTS: Participants aged 18 years old or more who underwent polysomnography for clinical reasons at University of Iowa Hospitals and Clinics over a 1-year period from July 2011 to June 2012 were enrolled retrospectively. MEASUREMENT: P-OSA was defined as a high supine-position dependency of obstructive breathing events with potential resolution of OSA in nonsupine positions [high apnea-hypopnea index on supine positions (s-AHI)/ AHI on nonsupine positions (ns0AHI) combined with ns-AHI < 5/hour]. Different cutoff points (2, 3, 5, 10, 15, 20) were applied to determine a meaningful ratio of supine-position dependency of obstructions [s-AHI/ns-AHI]. We compared the proportion of patients with p-OSA between the older age group (≥65 years old) and the propensity score (PS)-matched (upto 1:4) younger age group (<65 years old) using logistic regression analyses. RESULTS: In total, 346 participants were included. The older age group had a higher s-AHI/ns-AHI ratio than the younger age group (mean 31.6 [SD 66.2] versus 9.3 [SD 17.4], median 7.3 [interquartile range [IQR], 3.0-29.6) versus 4.1 (IQR, 1.9-8.7). After PS-matching, the older age group (n = 44) had higher proportion of those with a high s-AHI/ns-AHI ratio and ns-AHI< 5/hour compared with the younger age group (n = 164). (s-AHI/ns-AHI≥10: 54.6% versus 31.7%, OR 2.44 (95% CI, 1.22-4.90); s-AHI/ns-AHI≥15: 47.7% versus 26.2%, OR 2.24 (95% CI, 1.14-4.37); s-AHI/ns-AHI≥20: 40.9% versus 19.5%, OR 2.52 (95% CI, 1.22-5.20)) CONCLUSION: Older patients with OSA are more likely to have severe position dependent OSA, that is potentially more treatable with positional therapy. Thus, clinicians treating older, cognitively impaired geriatric patients unable to tolerate CPAP therapy should consider positional therapy as an adjunct or alternative.

Efficient and Stable Quasi-2D Ruddlesden-Popper Perovskite Solar Cells by Tailoring Crystal Orientation and Passivating Surface Defects.

Solar cells (PSCs) with quasi-2D Ruddlesden-Popper perovskites (RPP) exhibit greater environmental stability than 3D perovskites; however, the low power conversion efficiency (PCE) caused by anisotropic crystal orientations and defect sites in the bulk RPP materials limit future commercialization. Herein, a simple post-treatment is reported for the top surfaces of RPP thin films (RPP composition of PEA2 MA4 Pb5 I16 = 5) in which zwitterionic n-tert-butyl-α-phenylnitrone (PBN) is used as the passivation material. The PBN molecules passivate the surface and grain boundary defects in the RPP and simultaneously induce vertical direction crystal orientations of the RPPs, which lead to efficient charge transport in the RPP photoactive materials. With this surface engineering methodology, the optimized devices exhibit a remarkably enhanced PCE of 20.05% as compared with the devices without PBN (≈17.53%) and excellent long-term operational stability with 88% retention of the initial PCE under continuous 1-sun irradiation for over 1000 h. The proposed passivation strategy provides new insights into the development of efficient and stable RPP-based PSCs.

Downregulation of Lysosome-Associated Membrane Protein-2A Contributes to the Pathogenesis of COPD.

Background: Macroautophagy plays an important role in the pathogenesis of chronic obstructive pulmonary disease (COPD), but the role of chaperone-mediated autophagy (CMA) has not been investigated. We investigated if and how CMA is involved in the pathogenesis of COPD. Methods: We measured the level of lysosome-associated membrane protein-2A (LAMP-2A), which is a critical component of CMA that functions as a receptor for cytosolic substrate proteins, in total lung tissues and primary human bronchial epithelial cells (HBECs) from healthy never smokers, smokers, and COPD patients. We assessed the effects of LAMP-2A knock-down on cigarette smoke extract (CSE)-induced aging, cell cycle arrest, and apoptosis in BEAS-2B cells and the expression levels of apoptosis hallmarks in primary HBECs and lung tissue sections. Results: We found that the protein levels of LAMP-2A in lung homogenates and primary HBECs from smokers and COPD patients were lower than those from never smokers. In addition, its level in primary HBECs was negatively correlated with years of smoking. CSE caused degradation of LAMP-2A protein via the lysosomal pathway by activating macroautophagy. Knock-down of LAMP-2A markedly enhanced CSE-induced expression of senescence markers such as p16, p21, p27, and p53. G2/M cell cycle arrest, up-regulation of cyclin B1, and apoptosis in BEAS-2B cells. Apoptosis was increased in CSE-treated primary HBECs and in lung tissues from smokers and COPD patients. Conclusion: Cigarette smoke-induced down-regulation of LAMP-2A is involved in acceleration of aging and apoptosis of lung epithelial cells, which might at least partially contribute to COPD pathogenesis.