H2O2-triggered CO release based on porphyrinic covalent organic polymers for photodynamic/gas synergistic therapy.

A novel H2O2-responsive carbon monoxide nanogenerator was designed by effectively encapsulating a manganese carbonyl prodrug into porphyrinic covalent organic polymers for realizing the combined CO gas and photodynamic therapy under near infrared light irradiation.

Current trends and prospects of surgical techniques for hepatoblastoma.

Hepatoblastoma, a common extracranial malignant solid tumor in childhood, is often detected at an advanced stage and is difficult to treat surgically. Despite the availability of multiple comprehensive treatments that can be combined with surgery, hepatoblastoma treatment outcomes remain poor. Surgery is the main treatment strategy for hepatoblastoma, but it faces many challenges, including tumor attachment to surrounding tissues, tumor wrapping or invading of vital organs and tissues, the presence of giant or multiple tumors, distant metastasis, the formation of a tumor thrombus, and significant surgical trauma. In this review, we discuss recent research advances and propose potential strategies for overcoming these challenges. Such strategies may improve the rate of hepatoblastoma resection and local control in children, as well as reduce complications and trauma.

Cytokine and chemokine map of peripheral specific immune cell subsets in Parkinson's disease.

Peripheral immune cells play a vital role in the development of Parkinson's disease (PD). However, their cytokine and chemokine secretion functions remain unclear. Therefore, we aimed to explore the cytokine and chemokine secretion functions of specific immune cell subtypes in drug-naïve patients with PD at different ages of onset. We included 10 early-onset and 10 late-onset patients with PD and age-matched healthy controls (HCs). We used mass cytometry to select specific immune cell subsets and evaluate intracellular cytokine and chemokine expression. Statistical tests included t-tests, analysis of variance, bivariate correlation analysis, and linear regression analysis. Compared with HCs, patients with PD exhibited significantly decreased intracellular pro-inflammatory cytokines and chemokines in selected clusters (e.g., tumor necrosis factor (TNF)-α, interleukin (IL)-8, IL-1ß, and CC-chemokine ligand (CCL)17). Specific cytokines and cell clusters were associated with clinical symptoms. TNF-α played an important role in cognitive impairment. Intracellular TNF-α levels in the naïve CD8+ T-cell cluster C16 (CD57- naïve CD8+ T) and natural killer (NK) cell cluster C32 (CD57- CD28- NK) were negatively correlated with Montreal Cognitive Assessment scores. The C16 cluster affected cognitive function and motor symptoms. Increased TNF-α and decreased interferon-γ expression in C16 correlated with increased Unified Parkinson's Disease Rating Scale III scores in patients with PD. In summary, we developed a more detailed cytokine and chemokine map of peripheral specific CD8+ T cell and NK cell subsets, which revealed disrupted secretory function in patients with PD and provided unique clues for further mechanistic exploration.

Postoperative infectious complications following laparoscopic versus open hepatectomy for hepatocellular carcinoma: a multicenter propensity score analysis of 3876 patients.

OBJECTIVES: Hepatocellular carcinoma (HCC) is a common indication for hepatectomy that is often complicated by postoperative complication. The authors sought to investigate the relationship between the open with laparoscopic approach of hepatectomy and incidences of postoperative infectious complications. PATIENTS AND METHODS: Using a multicenter database, HCC patients who underwent laparoscopic hepatectomy (LH) or open hepatectomy (OH) were reviewed and analyzed. Propensity score matching (PSM), inverse probability of treatment weight (IPTW), and multivariate logistic regression analyses were utilized to assess the association of the operative approach with postoperative infectious complications, including incisional surgical site infection (SSI), organ/space SSI, and remote infection (RI). RESULTS: Among 3876 patients, 845 (21.8%) and 3031 (78.2%) patients underwent LH and OH, respectively. The overall incidence of infection was 6.9 versus 14.6% among patients who underwent LH versus OH, respectively ( P <0.001). Of note, the incidences of incisional SSI (1.8 vs. 6.3%, P <0.001), organ/space SSI (1.8 vs. 4.6%, P <0.001), and RI (3.8 vs. 9.8%, P <0.001) were all significantly lower among patients who underwent LH versus OH. After PSM (6.9, 1.8, 1.8, and 3.8% vs. 18.5, 8.4, 5.2, and 12.8%, respectively) and IPTW (9.5, 2.3, 2.1, and 5.5% vs. 14.3, 6.3, 4.5, and 9.8%, respectively), LH remained associated with statistically lower incidences of all types of infectious complications. After adjustment for other confounding factors on multivariate analyses, LH remained independently associated with lower incidences of overall infection, incisional SSI, organ/space SSI, and RI in the overall, PSM, and IPTW cohorts, respectively. CONCLUSION: Compared with open approach, laparoscopic approach was independently associated with lower incidences of postoperative infectious complications following hepatectomy for HCC.

Inflammatory markers of hemogram parameters as predictive factors for disease severity in anti-N-methyl-D-aspartate receptor encephalitis.

OBJECTIVE: This study aimed to investigate the utility of inflammatory markers of hemogram parameters as objective indicators of disease severity in anti-N-methyl-D-aspartate receptor (NMDAR) encephalitis. METHODS: A total of 98 patients were retrospectively reviewed. Inflammatory markers of hemogram parameters, including neutrophil-lymphocyte ratio (NLR), monocyte-lymphocyte ratio (MLR), and platelet-lymphocyte ratio, were acquired within 24 h of admission. We then analyzed their utility as predictive factors for disease severity at different time points assessing with the modified Rankin Scale (mRS). RESULTS: There were 49 patients in the mild group (mRS ≤ 2) and 49 patients in the moderate-to-severe (mRS > 2) group at admission. The moderate-to-severe group presented more frequently with psychiatric symptoms and central hypoventilation, as well as a lower lymphocyte count, a higher neutrophil count, a higher NLR and a higher MLR (all p < 0.05) when compared with the mild group. NLR and MLR showed similar positive correlations with mRS scores (r = 0.40, r = 0.40, both p < 0.001). Further multivariate logistic regression analyses indicated that NLR > 4.232 was an independent risk factor for moderate-to-severe status at admission. Meanwhile, NLR and MLR were associated with disease severity at different stages of follow-up but showed no independent predictive value. CONCLUSION: Our findings suggested that NLR was an independent risk factor for moderate-to-severe status in the initial stage of anti-NMDAR encephalitis with a cut-off value of > 4.232.

Development and validation of safety and efficacy-associated risk calculator for hepatocellular carcinoma in the elderly after resection (SEARCHER): A multi-institutional observational study.

BACKGROUND: Increased life expectancy and improved perioperative management have resulted in increased utilization of hepatectomy for hepatocellular carcinoma (HCC) among elderly patients. However, individualized model for predicting the surgical safety and efficacy is lacking. The present study aimed to develop a safety and efficacy-associated risk calculator for HCC in the elderly after resection (SEARCHER). METHODS: From an international multicenter database, elderly patients who underwent curative-intent hepatectomy for HCC were stratified by patient age: 65-69 years, 70-74 years, 75-79 years, and ≥80 years. Short- and long-term outcomes among the 4 groups were compared. Univariate and multivariate analyses of risk factors of postoperative major morbidity, cancer-specific survival (CSS) and overall survival (OS) were performed in the training cohort. A nomogram-based online calculator was then constructed and validated in the validation cohort. RESULTS: With increasing age, the risk of postoperative major morbidity and worse OS increased (P = 0.001 and 0.020), but not postoperative mortality and CSS (P = 0.577 and 0.890) among patients across the 4 groups. Based on three nomograms to predict major morbidity, CSS and OS, the SEARCHER model was constructed and made available at https://elderlyhcc.shinyapps.io/SEARCHER. The model demonstrated excellent calibration and optimal performance in both the training and validation cohorts, and performed better than the several commonly-used conventional scoring and staging systems of HCC. CONCLUSIONS: With higher potential postoperative major morbidity and worse OS as patients age, the decision of whether to perform a hepatectomy for HCC needs to be comprehensively considered in the elderly. The proposed SEARCHER model demonstrated good performance to individually predict safety and efficacy of hepatectomy in elderly patients with HCC.

A Web-Based Prediction Model for Estimating the Probability of Post-hepatectomy Major Complications in Patients with Hepatocellular Carcinoma: A Multicenter Study from a Hepatitis B Virus-Endemic Area.

BACKGROUND: The identification of patients at high risk of developing postoperative complications is important to improve surgical safety. We sought to develop an individualized tool to predict post-hepatectomy major complications in hepatitis B virus (HBV)-infected patients with hepatocellular carcinoma (HCC). METHODS: A multicenter database of patients undergoing hepatectomy for HCC were analyzed; 2/3 and 1/3 of patients were assigned to the training and validation cohorts, respectively. Independent risks of postoperative 30-day major complications (Clavien-Dindo grades III-V) were identified and used to construct a web-based prediction model, which predictive accuracy was assessed using C-index and calibration curves, which was further validated by the validation cohort and compared with conventional scores. RESULTS: Among 2762 patients, 391 (14.2%) developed major complications after hepatectomy. Diabetes mellitus, concurrent hepatitis C virus infection, HCC beyond the Milan criteria, cirrhosis, preoperative HBV-DNA level, albumin-bilirubin (ALBI), and aspartate transaminase to platelet ratio index (APRI) were identified as independent predictors of developing major complications, which were used to construct the online calculator ( http://www.asapcalculate.top/Cal11_en.html ). This model demonstrated good calibration and discrimination, with the C-indexes of 0.752 and 0.743 in the training and validation cohorts, respectively, which were significantly higher than those conventional scores (the training and validation cohorts: 0.565 ~ 0.650 and 0.568 ~ 0.614, all P < 0.001). CONCLUSIONS: A web-based prediction model was developed to predict the probability of post-hepatectomy major complications in an individual HBV-infected patient with HCC. It can be used easily in the real-world clinical setting to help management-related decision-making and early warning, especially in areas with endemic HBV infection.

A Systematic Review and Meta-Analysis of Risk Factors for Unplanned Intraoperative Hypothermia Among Adult Surgical Patients.

PURPOSE: Unplanned intraoperative hypothermia (UIH) is a frequent but preventable complication of surgery. Accurate identification of UIH risk factors allows nurses to minimize its negative outcomes. This study aimed to investigate the risk factors for UIH in adult surgical patients. DESIGN: Systematic review and meta-analysis METHODS: We comprehensively searched PubMed, Cochrane Central Register of Controlled Trials, Web of Science, Ovid Embase, and ClinicalTrials.gov from their inception until December 31, 2020 to identify available, related studies in English. Two authors independently extracted data from these studies. Data analysis was performed using Review Manager Version 5.3. RESULTS: This meta-analysis included 12 studies involving 15,010 patients. The combined results showed that age [mean difference (MD) = 4.85, P < .0001; I2 = 94%], body mass index (MD = - 0.76, P = .001; I2 = 59%), ambient temperature [odds ratio (OR) = 0.82, P < .001; I2 = 54%], preoperative systolic blood pressure (MD = -14.68, P < .00001; I2 = 30%), preoperative heart rate (MD = - 13.25, P < .00001; I2 = 0%), duration of anesthesia (>2 h; OR = 2.67, P < .001; I2 = 0%), and intravenous fluid administration >1,000 mL (OR = 2.02, P = .01; I2 = 77%) were significantly associated with a higher risk of UIH. CONCLUSIONS: Our study demonstrated that various risk factors contribute to the development of UIH. Perioperative nurses should understand these risk factors in order to apply evidence-based procedures and improve patient outcomes. Due to the substantial clinical heterogeneity across studies, further studies are needed to verify these findings.

Long-term oncological prognosis after curative-intent liver resection for hepatocellular carcinoma in the young versus the elderly: multicentre propensity score-matching study.

BACKGROUND: Hepatocellular carcinoma (HCC) is the most common malignancy in the elderly worldwide, but it is also common among younger individuals in areas with endemic hepatitis B virus infection. The differences in long-term oncological prognosis of young versus elderly patients after R0 liver resection for HCC were explored in this study. METHODS: Using a Chinese multicentre database, consecutive patients who underwent R0 liver resection for HCC between 2007 and 2019 were analysed retrospectively. After excluding middle-aged (36-69 years old) patients, overall survival (OS), cancer-specific survival (CSS), and recurrence were compared between young (35 years or younger) and elderly (70 years or older) patients using propensity score matching (PSM). RESULTS: Among 531 enrolled patients, there were 192 (36.2 per cent) and 339 (63.8 per cent) patients categorized as young and elderly respectively. PSM created 140 pairs of matched patients. In the PSM cohort, 5-year OS was comparable for young versus elderly patients (51.7 versus 52.3 per cent, P = 0.533). Young patients, however, had a higher 5-year cumulative recurrence rate (62.1 versus 51.6 per cent, P = 0.011) and a worse 5-year CSS rate (54.0 versus 64.3 per cent, P = 0.034) than elderly patients. On multivariable Cox regression analyses, young patient age remained independently associated with an increased recurrence rate (hazard ratio 1.62, P = 0.016) and a decreased CSS rate (hazard ratio 1.69, P = 0.021) compared with older age. CONCLUSION: Following R0 liver resection for HCC, younger patients were at a higher risk of recurrence, and elderly patients had a better CSS rate. Thus, enhanced surveillance for HCC recurrence should be implemented for young patients.

Impact of concurrent splenectomy and esophagogastric devascularization on surgical outcomes of partial hepatectomy for hepatocellular carcinoma in patients with clinically significant portal hypertension: A multicenter propensity score matching analysis.

PURPOSE: Portal hypertension due to cirrhosis is common among patients with hepatocellular carcinoma (HCC). This study aimed to compare the outcomes of partial hepatectomy in patients with HCC and clinically significant portal hypertension (CSPH) with or without concurrent splenectomy and esophagogastric devascularization (CSED). PATIENTS AND METHODS: From a multicenter database, patients with HCC and CSPH who underwent curative-intent hepatectomy were identified. Postoperative morbidity and mortality, and long-term overall survival (OS) were compared in patients with and without CSED before and after propensity score matching (PSM). RESULTS: Of the 358 enrolled patients, 86 patients underwent CSED. Before PSM, the postoperative 30-day morbidity and mortality rates were comparable between the CSED and non-CSED group (both P > 0.05). Using PSM, 81 pairs of patients were created. In the PSM cohort, the 5-year OS rate of the CSED group were significantly better than the non-CSED group (52.9% vs. 36.5%, P= 0.046). The former group had a significantly lower rate of variceal bleeding on follow-up (7.4% vs. 21.7%, P= 0.014). On multivariate analysis, CSED was associated with significantly better OS (HR: 0.39, P < 0.001). CONCLUSION: Hepatectomy and CSED can safely be performed in selected patients with HCC and CSPH, which could improve postoperative prognosis by preventing variceal bleeding, and prolonging long-term survival.

Evaluation of NOx removal from flue gas and Fe(II)EDTA regeneration using a novel BTF-ABR integrated system.

A promising process is under development for the removal of NOx and regeneration of Fe(II)EDTA in a novel biotrickling filter-anaerobic baffled reactor (BTF-ABR) integrated system at 50 ± 0.5 â„ƒ. In this work, we investigated the NOx removal capacity of a BTF under different O2 concentrations (7.0 vol%, 5.25 vol% and 3.5 vol%), and tested the effect of an ABR on NOx removal and regeneration of Fe(II)EDTA. The results showed that the NOx removal capacity was significantly increased with the O2 concentration reduced from 7.0% to 3.5%. The microoxygen environment produced by the BTF-ABR integrated system was more conducive to the removal of NOx and regeneration of Fe(II)EDTA compared with that in the BTF. Real-time polymerase chain reaction (PCR) analysis showed that the coordinated expression of denitrification genes was the major reason for no N2O emission, along with no nitrate and nitrite accumulation. The 16S rRNA gene amplicon sequencing analysis showed that the cooperation of denitrifying bacteria (Klebsiella, Petrimonas, Rhodococcus and Ochrobactium) and iron-reducing bacteria (Klebsiella, Geobacter and Petrimonas) in the system was the key to the stable and efficient removal of NOx and the regeneration of Fe(II)EDTA simultaneously.

Genetic testing of FUS, HTRA2, and TENM4 genes in Chinese patients with essential tremor.

INTRODUCTION: Essential tremor (ET) is one of the most prevalent movement disorders. The genetic etiology of ET has not been well defined although a significant proportion (≥50%) are familial cases. Linkage analysis and genome-wide association studies (GWASs) have identified several risk variants. In recent years, whole-exome sequencing of ET has revealed several specific causal variants in FUS (p.Q290X), HTRA2 (p.G399S), and TENM4 (c.4324 G>A, c.4100C>A, and c.3412G>A) genes. OBJECTIVE: To investigate the genetic contribution of these three genes to ET, the protein-coding sequences of FUS, HTRA2, and TENM4 were analyzed in a total of 238 ET patients and 272 controls from eastern China using direct Sanger sequencing. RESULTS: We identified two synonymous coding single nucleotide polymorphisms (SNPs), rs741810 and rs1052352 in FUS, and three previously reported synonymous SNPs, rs11237621, rs689369, and rs2277277 in TENM4. No nonsynonymous exonic variants were identified in these subjects. We found that the frequency of the rs1052352C allele was significantly higher (P = .001) in the ET group than in the control group. CONCLUSION: Overall, our findings suggest that rs1052352 of FUS might contribute to ET risk in Chinese population.

A case of multilevel percutaneous vertebroplasty for vertebral metastases resulting in temporary paraparesis.

Percutaneous vertebroplasty (PVP) is a minimally invasive treatment that has been widely used for the treatment of osteoporotic vertebral compression fractures and vertebral tumors. However, the maximum number of vertebral segments treated in a single PVP remains controversial. Furthermore, PVP may cause complications, including cement leakage, pulmonary embolism, bone cement toxicity, and spinal nerve-puncture injury. We report the rare case of a patient who underwent multilevel PVP for vertebral metastases, with no bone cement leakage or spinal cord injury, but who developed temporary paraparesis.

An analysis of the causes of transient paraplegia during percutaneous vertebral augmentation under local anesthesia: A case series of 12 patients.

BACKGROUND: Percutaneous vertebral augmentation (PVA) under local anesthesia has been widely used to treat osteoporotic vertebral compression fractures and vertebral body tumors. However, the occurrence of spinal cord or nerve root dysfunction may result in poor prognosis for patients. The aim of this study was to analyze the causes of transient paraplegia in 12 patients undergoing PVA. METHODS: The medical records of 12 patients with transient paraplegia during PVA in our hospital were analyzed. Data, including operation, vertebral, anesthetic dose, operation time, recovery time, and follow-up, were extracted. RESULTS: Among the 12 patients, ranging in age from 62 years to 83 years, with a mean age of 74 years, 8 were females and 4 were males. The average anesthetic dose injected per vertebral body was 6.38 ml. Patients required an average of 218.75 min to recover sensation and movement completely. However, the amount of anesthetic injected into each vertebral body was not related to the time required for complete recovery. Follow-up showed that all patients had regained normal bilateral sensation and motor function. Postoperative visual analog scale and Oswestry Disability Index values of the 12 patients were significantly improved compared with preoperative values. CONCLUSION: The complication of transient paraplegia was caused by local anesthetic drugs infiltrating into the spinal canal and inhibiting nerve conduction in the spinal cord.

Neferine inhibits LPS-ATP-induced endothelial cell pyroptosis via regulation of ROS/NLRP3/Caspase-1 signaling pathway.

BACKGROUND: Oxidative stress-induced endothelial dysfunction and pyroptosis play an important role during chronic kidney disease (CKD) progression. Neferine, which is an alkaloid ingredient from the lotus seed embryo, has many biological actions such as anti-inflammatory, anticancer and antioxidant. However, the role of neferine in endothelial cell pyroptosis and the involved mechanism remain obscure. The aim is to probe the protective effects of neferine on cell pyroptosis and the involved underlying mechanism. METHODS: After the HUVECs were primed with neferine treatment for 2 h prior to LPS and ATP exposure for 24 h, the cell proliferation was determined by BrdU; the cell LDH release was detected by LDH kits; the levels of intracellular ROS, MDA and SOD were tested by detection kits; Caspase-1 activity kit was used to determine caspase-1 activity; the contents of NLRP3, ASC, caspase-1, IL-1ß, IL-18 and GSDMD were tested by RT-PCR and western blot. RESULTS: We found that neferine could inhibit LPS-ATP-induced oxidative stress and the activation of NLRP3 inflammasome signaling, and increased the endothelial cell viability and SOD production. siRNA which mediated the knockdown of NLRP3 promoted the neferine-induced inhibition effects of cell pyroptosis. Furthermore, these neferine-induced effects were reversed by the over-expression of NLRP3. CONCLUSIONS: Our findings indicated neferine may reduce ROS by anti-oxidation and inhibit LPS-ATP-induced endothelial cell pyroptosis via blocking ROS/NLRP3/Caspase-1 signaling pathway, which provides the evidence for therapeutic effect in CKD.

Plasmid-based generation of neural cells from human fibroblasts using non-integrating episomal vectors.

Differentiation of human fibroblasts into functional neurons depends on the introduction of viral-mediated transcription factors, which present risks of viral gene integration and tumorigenicity. In recent years, although some studies have been successful in directly inducing neurons through sustained expression of small molecule compounds, they have only been shown to be effective on mouse-derived cells. Thus, herein we delivered vectors containing Epstein-Barr virus-derived oriP/Epstein-Barr nuclear antigen 1 encoding the neuronal transcription factor, Ascl1, the neuron-specific microRNA, miR124, and a small hairpin directed against p53, into human fibroblasts. Cells were incubated in a neuron-inducing culture medium. Immunofluorescence staining was used to detect Tuj-1, microtubule-associated protein 2, neuron-specific nucleoprotein NeuN and nerve cell adhesion molecules in the induced cells. The proportion of Tuj1-positive cells was up to 36.7% after induction for 11 days. From day 21, these induced neurons showed neuron-specific expression patterns of microtubule-associated protein 2, NeuN and neural cell adhesion molecule. Our approach is a simple, plasmid-based process that enables direct reprogramming of human fibroblasts into neurons, and provides alternative avenues for disease modeling and neurodegenerative medicine.

Exposure to advertising and perception, interest, and use of e-cigarettes among adolescents: findings from the US National Youth Tobacco Survey.

OBJECTIVE: US adolescents are exposed to high levels of advertisements for electronic cigarettes (e-cigarettes). This study aimed to examine the associations between exposure to e-cigarette advertisements and perception, interest, and use of e-cigarettes among US middle school and high school students. METHODS: Data from the 2014 cross-sectional National Youth Tobacco Survey were used. Logistic regressions were conducted to model four outcomes, including perception of reduced harmfulness compared to regular cigarettes, perception of reduced addictiveness, intention to use, and current use of e-cigarettes. Main predictors were exposure to e-cigarette advertisements via four sources, including Internet, newspaper/magazines, retail stores, and TV. RESULTS: When all the four sources of e-cigarette advertisements exposure were evaluated jointly, exposure via the Internet was associated with elevated likelihood of reporting all four outcomes related to e-cigarettes, while exposure via retail stores was associated with higher likelihood of current e-cigarette use and perception of reduced harmfulness of e-cigarettes compared to regular cigarettes ( p < .05). However, exposure via newspaper/magazines and TV was associated with lower likelihood of perceiving e-cigarettes to be less harmful or addictive ( p < .05). CONCLUSION: Exposure to e-cigarette advertisements via the Internet and retail stores may play a significant role in adolescents' use and perception of e-cigarettes. The results call for more research on the influence of different sources of advertising exposure on e-cigarette use to help public health programmes curtail the fast growing use of e-cigarette products among youth.

Factors contributing to poor satisfaction with sleep and healthcare seeking behavior in older adults.

OBJECTIVE: To identify factors influencing older adults' poor satisfaction with sleep and their current healthcare seeking behaviors. DESIGN: Cross-sectional study. SETTING: Pittsburgh Claude D. Pepper Older Americans Independence Center Community Registry. PARTICIPANTS: Individuals aged 60 or older enrolled in the registry that completed a cross-sectional mailed survey (N = 1026). MEASUREMENTS: Participant demographics (age, gender, marital status, race, education), overall health (self-rated health, pain, and comorbidities), and health behaviors (physical activity, smoking, drinking behaviors) were collected from the registry database. A mail survey was used to collect self-report on sleep problems and their current healthcare seeking behaviors. Simple and multiple logistic regression models were used to evaluate associations between variables. RESULTS: A total of 19.3% of participants reported being "dissatisfied" or "very dissatisfied" with their overall sleep quality. Participants who reported poor sleep satisfaction were more likely to be single and report poorer overall health compared to participants who were satisfied with their sleep quality. They were also more likely to report using over-the-counter (OTC) and prescription sleep medications, discuss sleep problems with a healthcare provider, and use strategies to improve their sleep (P < .05). A higher proportion of participants with trouble sleeping throughout the night reported they had discussions with a healthcare provider (47.2%), and used OTC (38.6%) or prescription (20.1%) sleep aids. CONCLUSIONS: These results underscore the possible linkage between poor satisfaction with sleep and older adults' current healthcare seeking behaviors and self-treatment methods, particularly using OTC medications to cope with sleep problems without consulting a healthcare provider.

E-cigarette use among US adolescents: secondhand smoke at home matters.

OBJECTIVES: To examine the association of family smoking status and exposure to secondhand smoke (SHS) at home with the use of electronic cigarettes among US adolescents, in particular the medication effect of SHS on the association between family smoking status and electronic cigarette use. METHODS: Data from the 2013 National Youth Tobacco Survey were used and logistic regressions were conducted to model electronic cigarettes use. The mediation effect of SHS was tested using the Sobel-Goodman mediation test. RESULTS: Overall, 8.1 % of the US adolescents reported ever use of e-cigarettes. Among both the overall population and never-cigarette smokers, adolescents living in smoker households were significantly more likely to report ever use of e-cigarettes (p < 0.05). However, the associations were attenuated after including SHS exposure at home during the past 7 days. SHS exposure at home was positively associated with ever use of e-cigarettes, adjusting for family smoking status (p < 0.05). CONCLUSIONS: The association between smoking habits of the family and e-cigarette use was mediated through SHS exposure. The promotion of smoke-free home rules may help prevent the uptake of e-cigarettes among teenagers.

SF3B1/Hsh155 HEAT motif mutations affect interaction with the spliceosomal ATPase Prp5, resulting in altered branch site selectivity in pre-mRNA splicing.

Mutations in the U2 snRNP component SF3B1 are prominent in myelodysplastic syndromes (MDSs) and other cancers and have been shown recently to alter branch site (BS) or 3' splice site selection in splicing. However, the molecular mechanism of altered splicing is not known. We show here that hsh155 mutant alleles in Saccharomyces cerevisiae, counterparts of SF3B1 mutations frequently found in cancers, specifically change splicing of suboptimal BS pre-mRNA substrates. We found that Hsh155p interacts directly with Prp5p, the first ATPase that acts during spliceosome assembly, and localized the interacting regions to HEAT (Huntingtin, EF3, PP2A, and TOR1) motifs in SF3B1 associated with disease mutations. Furthermore, we show that mutations in these motifs from both human disease and yeast genetic screens alter the physical interaction with Prp5p, alter branch region specification, and phenocopy mutations in Prp5p. These and other data demonstrate that mutations in Hsh155p and Prp5p alter splicing because they change the direct physical interaction between Hsh155p and Prp5p. This altered physical interaction results in altered loading (i.e., "fidelity") of the BS-U2 duplex into the SF3B complex during prespliceosome formation. These results provide a mechanistic framework to explain the consequences of intron recognition and splicing of SF3B1 mutations found in disease.