Model-Based Assessment of the Liver Safety Profile of Acetaminophen to Support its Combination Use with Topical Diclofenac in Mild-to-Moderate Osteoarthritis Pain.

INTRODUCTION: The use of combination therapy of oral acetaminophen and topical diclofenac, having complementary mechanisms of action, is an attractive strategy to enhance the analgesic response in osteoarthritis (OA) pain. While topical diclofenac is considered as well tolerated due to its low systemic exposure, concerns of liver toxicity with acetaminophen at standard analgesic doses remain. Thus, this study aimed to assess the liver safety profile of acetaminophen, particularly in OA management, using a model-based meta-analysis (MBMA). METHODS: A literature review was conducted using the MEDLINE database to identify randomized clinical trials (RCTs) reporting liver toxicity on acetaminophen use. An MBMA was implemented to assess the deviation from the upper limit of normal (ULN) of alanine aminotransferase or aspartate aminotransferase, namely > 0-1 × ULN, > 1.5-2 × ULN, and > 3 × ULN representing mild, moderate, and severe risk of liver abnormality, respectively. RESULTS: A total of 15 RCTs were included in the MBMA, encompassing over 4800 subjects and exposure to acetaminophen ranging from 2 to 26 weeks. Of the 15 included studies, eight involved patients with OA pain, four involved healthy subjects and three were in patients with conditions such as asthma, glaucoma, chronic pain, and cardiovascular disease. Acetaminophen 1500-4000 mg/day was found to exhibit 23% (95% confidence interval (CI): 17.74-29.20), 1.35% (95% CI: 0.17-2.51) and 0.01% (95% CI: 0.00-0.32) increased risk for mild, moderate, and severe liver injury, respectively, versus placebo. Moreover, at therapeutic doses, no correlation was identified between acetaminophen intake and liver abnormality risk. CONCLUSIONS: Overall, our analysis shows that short-term (~ 8-16 weeks) acetaminophen use at therapeutically recommended doses is associated with a low risk of clinically relevant changes in liver enzymes. Given the good tolerability of topical diclofenac, the findings support the safety of the combination of acetaminophen and topical diclofenac, at least over the short term, as treatment for mild-to-moderate OA pain.

Assessing Hospital Quality Scores By Proportion Of Patients Dually Eligible For Medicare And Medicaid.

The Centers for Medicare and Medicaid Services has been reporting hospital star ratings since 2016. Some stakeholders have criticized the star ratings methodology for not adjusting for social risk factors. We examined the relationship between 2021 star rating scores and hospitals' proportion of Medicare patients dually eligible for Medicaid. We found that, on average, hospitals caring for a greater proportion of dually eligible patients had lower star ratings, but there was significant overlap in performance among hospitals when we stratified them by quintile of dually eligible patients. Hospitals in the highest quintile (those with the greatest proportion of dually eligible patients) had the best mean mortality scores (0.28) but the worst readmission (-0.44) and patient experience (-0.78) scores. We assigned star ratings after stratifying the readmission measure group by proportion of dually eligible patients and found that a total of 142 hospitals gained a star and 161 hospitals lost a star, of which 126 (89 percent) and 1 (<1 percent) were in the highest quintile, respectively. Adjusting public reporting tools such as star ratings for social risk factors is ultimately a policy decision, and views on the appropriateness of accounting for factors such as proportion of dually eligible patients are mixed, depending on the organization and stakeholder.

Preliminary Assessment of Intramuscular Depot of Lipid-Based Decoquinate Formulation for Long-Term Chemoprophylaxis of Malaria.

Sustained-release formulations of decoquinate were evaluated for the long-term prophylaxis of malaria. In the initial experiment, mice were protected from liver-stage Plasmodium infection by intramuscular administration of a lipids-based formulation at a dose of decoquinate 200 mg/kg. The mice that were inoculated with Plasmodium berghei sporozoites 34 days after the administration of a one-time drug dose were continuously monitored for 60 days and shown to be free of Plasmodium parasites. The optimized formulation for the sustained release of decoquinate was prepared by hot melt extrusion, constructed by lipids including cholesterol and mono or diglycerides, and had a drug load of 20 to 40% and particle size of 30 to 50 µm. Decoquinate of the lipids-based formulation was slowly released in vitro at a constant rate for the duration of two months, and was examined and continuously exposed at a therapeutic level in the blood for as long as 4 to 6 months. Further evaluation showed that the lipids-based formulation at doses of decoquinate 100 to 150 mg/kg could protect mice from Plasmodium infection for a period of 120 days. It is the first time that cholesterol has been used for a controlled drug delivery system of decoquinate. The results may provide useful information, not only for preparing a formulation of long-acting decoquinate but also in general for developing a controlled drug release system. The one-time administration of pharmaceutical agents in such a slow-release system may serve patients with no concerns about compliance.

Novel Surface Acoustic Wave Temperature-Strain Sensor Based on LiNbO3 for Structural Health Monitoring.

In this paper, we present the design of an integrated temperature and strain dual-parameter sensor based on surface acoustic waves (SAWs). First, the COMSOL Multiphysics simulation software is used to determine separate frequencies for multiple sensors to avoid interference from their frequency offsets caused by external physical quantity changes. The sensor consists of two parts, a temperature-sensitive unit and strain-sensitive unit, with frequencies of 94.97 MHz and 90.05 MHz, respectively. We use standard photolithography and ion beam etching technology to fabricate the SAW temperature-strain dual-parameter sensor. The sensing performance is tested in the ranges 0-250 °C and 0-700 µÔ‘. The temperature sensor monitors the ambient temperature in real time, and the strain sensor detects both strain and temperature. By testing the response of the strain sensor at different temperatures, the strain and temperature are decoupled through the polynomial fitting of the intercept and slope. The relationship between the strain and the frequency of the strain-sensitive unit is linear, the linear correlation is 0.98842, and the sensitivity is 100 Hz/µÔ‘ at room temperature in the range of 0-700 µÔ‘. The relationship between the temperature and the frequency of the temperature-sensitive unit is linear, the linearity of the fitting curve is 0.99716, and the sensitivity is 7.62 kHz/°C in the range of 25-250 °C. This sensor has potential for use in closed environments such as natural gas or oil pipelines.

Long-term safety and absorption assessment of a novel bioresorbable nitrided iron scaffold in porcine coronary artery.

This study aimed to investigate the long-term biocompatibility, safety, and degradation of the ultrathin nitrided iron bioresorbable scaffold (BRS) in vivo, encompassing the whole process of bioresorption in porcine coronary arteries. Fifty-two nitrided iron scaffolds (strut thickness of 70 µm) and 28 Vision Co-Cr stents were randomly implanted into coronary arteries of healthy mini-swine. The efficacy and safety of the nitrided iron scaffold were comparable with those of the Vision stentwithin 52 weeks after implantation. In addition, the long-term biocompatibility, safety, and bioresorption of the nitrided iron scaffold were evaluated by coronary angiography, optical coherence tomography, micro-computed tomography, scanning electron microscopy, energy dispersive spectrometry and histopathological evaluations at 4, 12, 26, 52 weeks and even at 7 years after implantation. In particular, a large number of struts were almost completely absorbed in situ at 7 years follow-up, which were first illustrated in this study. The lymphatic drainage pathway might serve as the potential clearance way of iron and its corrosion products.

Longitudinal Outcomes of Subcutaneous or Transvenous Implantable Cardioverter-Defibrillators in Older Patients.

BACKGROUND: The subcutaneous (S-) implantable cardioverter-defibrillator (ICD) is an alternative to the transvenous (TV-) ICD that is increasingly implanted in younger patients; data on the safety and effectiveness of the S-ICD in older patients are lacking. OBJECTIVES: The purpose of this study was to compare outcomes among older patients who received an S- or TV-ICD. METHODS: The authors compared S-ICD and single-chamber TV-ICD implants in Fee-For-Service Medicare beneficiaries using the National Cardiovascular Data Registry ICD Registry. Outcomes were ascertained from Medicare claims data. Cox regression or competing-risk models (with TV-ICD as reference) with overlap weights were used to compare death and nonfatal outcomes (device reoperation, device removal for infection, device reoperation without infection, and cardiovascular admission), respectively. Recurrent all-cause readmissions were compared using Anderson-Gill models. RESULTS: A total of 16,063 patients were studied (age 72.6 ± 5.9 years, 28.4% women, ejection fraction 28.3 ± 8.9%). Compared with TV-ICD patients (n = 15,072), S-ICD patients (n = 991, 6.2% overall) were more often Black, younger, and dialysis dependent and less likely to have history of atrial fibrillation or flutter. In adjusted analyses, there were no differences between device type and risk of all-cause mortality (HR: 1.020; 95% CI: 0.819-1.270), device reoperation (subdistribution [s] HR: 0.976; 95% CI: 0.645-1.479), device removal for infection (sHR: 0.614; 95% CI: 0.138-2.736), device reoperation without infection (sHR: 0.975; 95% CI: 0.632-1.506), cardiovascular readmission (sHR: 1.087; 95% CI: 0.912-1.295), or recurrent all-cause readmission (HR: 1.072; 95% CI: 0.990-1.161). CONCLUSIONS: In a large representative national cohort of older patients undergoing ICD implantation, risk of death, device reoperation, device removal for infection, device reoperation without infection, and cardiovascular and all-cause readmission were similar among S- and TV-ICD recipients.

Active Enhancer Assessment by H3K27ac ChIP-seq Reveals Claudin-1 as a Biomarker for Radiation Resistance in Colorectal Cancer.

BACKGROUND: Colorectal cancer (CRC) represents the third most common malignant tumor in the worldwide. Radiotherapy is the common therapeutic treatment for CRC, but radiation resistance is often encountered. ChIP-seq of Histone H3K27 acetylation (H3K27ac) has revealed enhancers that play an important role in CRC. This study examined the relationship between an active CRC enhancer and claudin-1 (CLDN1), and its effect on CRC radiation resistance. METHODS: The target CRC genes of active enhancers were obtained from public H3K27ac ChIP-seq, and the genes highly expressed in radio-resistant CRC were screened and intersected with enhancer-driven genes. The clinical roles of CLDN1 in radiation resistance were examined using the t-test, standard mean deviation (SMD), summary receiver operating characteristic curve and Kaplan-Meier curves. The co-expressed genes of CLDN1 were calculated using Pearson Correlation analysis, and Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes and Gene Set Variation Analysis (GSVA) analyses were used to examine the molecular mechanisms of CLDN1. RESULTS: Total 13 703 CRC genes were regulated by enhancers using 58 H3K27ac ChIP-seq. Claudin-1 (CLDN1) was enhancer-driven and notably up-regulated in CRC tissues compared to non-CRC controls, with a SMD of 3.45 (95 CI % = .56-4.35). CLDN1 expression was increased in radiation-resistant CRC with a SMD of .42 (95% CI = .16-.68) and an area under the curve of .74 (95% CI = .70-.77). The cell cycle and immune macrophage levels were the most significant pathways associated with CLDN1. CONCLUSION: CLDN1 as an enhancer-regulated gene that can boost radiation resistance in patients with CRC.

Statistical Assessment of Depth Normalization for Small RNA Sequencing.

PURPOSE: Methods for depth normalization have been assessed primarily with simulated data or cell-line-mixture data. There is a pressing need for benchmark data enabling a more realistic and objective assessment, especially in the context of small RNA sequencing. METHODS: We collected a unique pair of microRNA sequencing data sets for the same set of tumor samples; one data set was collected with and the other without uniform handling and balanced design. The former provided a benchmark for evaluating evidence of differential expression and the latter served as a test bed for normalization. Next, we developed a data perturbation algorithm to simulate additional data set pairs. Last, we assembled a set of computational tools to visualize and quantify the assessment. RESULTS: We validated the quality of the benchmark data and showed the need for normalization of the test data. For illustration, we applied the data and tools to assess the performance of 9 existing normalization methods. Among them, trimmed mean of M-values was a better scaling method, whereas the median and the upper quartiles were consistently the worst performers; one variation of remove unwanted variation had the best chance of capturing true positives but at the cost of increased false positives. In general, these methods were, at best, moderately helpful when the level of differential expression was extensive and asymmetric. CONCLUSION: Our study (1) provides the much-needed benchmark data and computational tools for assessing depth normalization, (2) shows the dependence of normalization performance on the underlying pattern of differential expression, and (3) calls for continued research efforts to develop more effective normalization methods.

Climatic change in southern Kazakhstan since 1850 C.E. inferred from tree rings.

Although global warming is an indisputable fact, there is still uncertainty about how climate change will occur at regional levels. Kazakhstan is the largest landlocked country in the world. To best manage this country's limited water resources, socio-economic development and environmental protection, a solid understanding of regional climate change impacts is needed. In this study, tree-ring width and δ13C chronologies were established based on 99 tree-ring samples of Schrenk spruce (Picea schrenkiana Fisch. et Mey.) collected in Almaty, Kazakhstan. Climate response analysis between the tree-ring chronologies and climate data indicates that summer mean temperature is the strongest climate signal recorded by tree-ring δ13C. We reconstructed temperature change in southern Kazakhstan since 1850 C.E. using the tree-ring δ13Ccorr chronology. The results show that the temperatures in southern Kazakhstan have risen at a rate of about 0.27 °C per decade over the past 166 years. However, the rate has increased by as much as 0.44 °C per decade over the past 30 years. Analyses of temperature and precipitation data show that the climate has alternated between warm-dry and cold-humid periods over the past 166 years. The extreme droughts of 1879, 1917 and 1945 were caused by the combination of continuously high temperatures and reduced precipitation.

Development of an oligonucleotide dye solution facilitates high throughput and cost-efficient chromosome identification in peanut.

BACKGROUND: Development of oligonucleotide probes facilitates chromosome identification via fluorescence in situ hybridization (FISH) in many organisms. RESULTS: We report a high throughput and economical method of chromosome identification based on the development of a dye solution containing 2 × saline-sodium citrate (SSC) and oligonucleotide probes. Based on the concentration, staining time, and sequence effects of oligonucleotides, an efficient probe dye of peanut was developed for chromosome identification. To validate the effects of this solution, 200 slides derived from 21 accessions of the cultivated peanut and 30 wild Arachis species were painted to identify Arachis genomes and establish karyotypes. The results showed that one jar of dye could be used to paint 10 chromosome preparations and recycled at least 10 times to efficiently dye more than 100 slides. The A, B, K, F, E, and H genomes showed unique staining karyotype patterns and signal colors. CONCLUSIONS: Based on the karyotype patterns of Arachis genomes, we revealed the relationships among the A, B, K, F, E, and H genomes in genus Arachis, and demonstrated the potential for adoption of this oligonucleotide dye solution in practice.

Ethnic differences in frailty: a cross-sectional study of pooled data from community-dwelling older persons in the Netherlands.

OBJECTIVE: Few European studies examined frailty among older persons from diverse ethnic backgrounds. We aimed to examine the association of ethnic background with frailty. In addition, we explored the association of ethnic background with distinct components that are considered to be relevant for frailty. DESIGN AND SETTING: This was a cross-sectional study of pooled data of The Older Persons and Informal Caregivers Survey Minimum DataSet (TOPICS) in the Netherlands. PARTICIPANTS: Community-dwelling persons aged 55 years and older with a Dutch, Indonesian, Surinamese, Moroccan or Turkish ethnic background were included (n=23 371). MEASUREMENTS: Frailty was assessed with the validated TOPICS-Frailty Index that consisted of 45 items. The TOPICS-Frailty Index contained six components: morbidities, limitations in activities of daily living (ADL), limitations in instrumental ADL, health-related quality of life, psychosocial health and self-rated health. To examine the associations of ethnic background with frailty and with distinct frailty components, we estimated multilevel random-intercept models adjusted for confounders. RESULTS: TOPICS-Frailty Index scores varied from 0.19 (SD=0.12) among persons with a Dutch background to 0.29 (SD=0.15) in persons with a Turkish background. After adjustment for age, sex, living arrangement and education level, persons with a Turkish, Moroccan or Surinamese background were frailer compared with persons with a Dutch background (p<0.001). There were no significant differences in frailty between persons with an Indonesian compared with a Dutch background. The IADL component scores were higher among all groups with a non-Dutch background compared with persons with a Dutch background (p<0.05 or lower for all groups). CONCLUSIONS: Compared with older persons with a Dutch background, persons with a Surinamese, Moroccan or Turkish ethnic background were frailer. Targeted intervention strategies should be developed for the prevention and reduction of frailty among these older immigrants.

Risk Trajectories of Readmission and Death in the First Year after Hospitalization for Chronic Obstructive Pulmonary Disease.

RATIONALE: Characterization of the dynamic nature of posthospital risk in chronic obstructive pulmonary disease (COPD) is needed to provide counseling and plan clinical services. OBJECTIVES: To analyze risk of readmission and death after discharge for COPD among Medicare beneficiaries aged 65 years and older and to determine the association between ventilator support and risk trajectory. METHODS: We computed daily absolute risks of hospital readmission and death for 1 year after discharge for COPD, stratified by ventilator support. We determined the time required for risks to decline by 50% from maximum daily values after discharge and for daily risks to plateau. We compared risks with those found in the general elderly population. MEASUREMENTS AND MAIN RESULTS: Among 2,340,637 hospitalizations, the readmission rate at 1 year was 64.2%, including 63.5%, 66.0%, and 64.1% among those receiving invasive, noninvasive, and no ventilation, respectively. Among 1,283,069 hospitalizations, mortality at 1 year was 26.2%, including 45.7%, 41.8%, and 24.4% among those same respective groups. Daily risk of readmission declined by 50% within 28, 39, and 43 days and plateaued at 46, 54, and 61 days among those receiving invasive, noninvasive, and no ventilation, respectively. Risk of death declined by 50% by 3, 4, and 17 days and plateaued by 21, 18, and 24 days in the same respective groups. Risks of hospitalization and death were significantly higher after discharge for COPD than among the general Medicare population. CONCLUSIONS: Discharge from the hospital is associated with prolonged risks of readmission and death that vary with need for ventilator support. Interventions limited to the first month after discharge may be insufficient to improve longitudinal outcomes.

Socioeconomic inequalities in frailty and frailty components among community-dwelling older citizens.

BACKGROUND: So far, it has not yet been studied whether socioeconomic status is associated with distinct frailty components and for which frailty component this association is the strongest. We aimed to examine the association between socioeconomic status and frailty and frailty components. In addition we assessed the mediating effect of the number of morbidities on the association between socioeconomic status and other frailty components. METHODS: This is a cross-sectional study of pooled data of The Older Persons and Informal Caregivers Survey Minimum DataSet in the Netherlands among community-dwelling persons aged 55 years and older (n = 26,014). Frailty was measured with a validated Frailty Index that consisted of 45 items. The Frailty Index contained six components: morbidities, limitations in activities of daily living (ADL), limitations in instrumental ADL (IADL), health-related quality of life, psychosocial health and self-rated health. Socioeconomic indicators used were education level and neighbourhood socioeconomic status. RESULTS: Persons with primary or secondary education had higher overall frailty and frailty component scores compared to persons with tertiary education (P < .001). Lower education levels were most consistently associated with higher overall frailty, more morbidities and worse self-rated health (P < .05 in all age groups). The strongest association was found between primary education and low psychosocial health for persons aged 55-69 years and more IADL limitations for persons aged 80+ years. Associations between neighborhood socioeconomic status and frailty (components) also showed inequalities, although less strong. The number of morbidities moderately to strongly mediated the association between socioeconomic indicators and other frailty components. CONCLUSION: There are socioeconomic inequalities in frailty and frailty components. Inequalities in frailty, number of morbidities and self-rated health are most consistent across age groups. The number of morbidities a person has play an important role in explaining socioeconomic inequalities in frailty and should be taken into account in the management of frailty.

Incorporating Stroke Severity Into Hospital Measures of 30-Day Mortality After Ischemic Stroke Hospitalization.

BACKGROUND AND PURPOSE: The Centers for Medicare & Medicaid Services publicly reports a hospital-level stroke mortality measure that lacks stroke severity risk adjustment. Our objective was to describe novel measures of stroke mortality suitable for public reporting that incorporate stroke severity into risk adjustment. METHODS: We linked data from the American Heart Association/American Stroke Association Get With The Guidelines-Stroke registry with Medicare fee-for-service claims data to develop the measures. We used logistic regression for variable selection in risk model development. We developed 3 risk-standardized mortality models for patients with acute ischemic stroke, all of which include the National Institutes of Health Stroke Scale score: one that includes other risk variables derived only from claims data (claims model); one that includes other risk variables derived from claims and clinical variables that could be obtained from electronic health record data (hybrid model); and one that includes other risk variables that could be derived only from electronic health record data (electronic health record model). RESULTS: The cohort used to develop and validate the risk models consisted of 188 975 hospital admissions at 1511 hospitals. The claims, hybrid, and electronic health record risk models included 20, 21, and 9 risk-adjustment variables, respectively; the C statistics were 0.81, 0.82, and 0.79, respectively (as compared with the current publicly reported model C statistic of 0.75); the risk-standardized mortality rates ranged from 10.7% to 19.0%, 10.7% to 19.1%, and 10.8% to 20.3%, respectively; the median risk-standardized mortality rate was 14.5% for all measures; and the odds of mortality for a high-mortality hospital (+1 SD) were 1.51, 1.52, and 1.52 times those for a low-mortality hospital (-1 SD), respectively. CONCLUSIONS: We developed 3 quality measures that demonstrate better discrimination than the Centers for Medicare & Medicaid Services' existing stroke mortality measure, adjust for stroke severity, and could be implemented in a variety of settings.

Outcomes after observation stays among older adult Medicare beneficiaries in the USA: retrospective cohort study.

Objective To characterize rates and trends over time of emergency department treatment-and-discharge stays, repeat observation stays, inpatient stays, any hospital revisit, and death within 30 days of discharge from observation stays.Design Retrospective cohort study.Setting 4750 hospitals in the USA.Participants Nationally representative sample of Medicare fee for service beneficiaries aged 65 or over discharged after 363 037 index observation stays, 2 540 000 index emergency department treatment-and-discharge stays, and 2 667 525 index inpatient stays from 2006-11.Main outcome measures Rates of emergency department treatment-and-discharge stays, observation stays, inpatient stays, any hospital revisit, and death within 30 days of discharge from index observation stays. Rates were compared with corresponding outcomes within 30 days of discharge from both index emergency department treatment-and-discharge stays and index inpatient stays.Results Among 363 037 index observation stays resulting in discharge from 2006-11, 30 day rates of emergency department treatment-and-discharge stays were 8.4%, repeat observation stays were 2.9%, inpatient stays were 11.2%, any hospital revisit was 20.1%, and death was 1.8%. Of all revisits, 49.7% were for inpatient stays. Revisit rates for emergency department treatment-and-discharge stays, repeat observation stays, and any hospital revisit increased from 2006-11 (P<0.001 for trend), while 30 day rates of inpatient stays (P=0.054 for trend) and 30 day mortality (P=0.091 for trend) were both unchanged. Averaged over the study period, 30 day rates of any hospital revisit were similar after discharge from index emergency department treatment-and-discharge stays (19.9%) and index observation stays (20.1%), as was 30 day mortality (1.8% for both). Rates of any hospital revisit (21.8%) and death (5.2%) were highest after discharge from index inpatient stays.Conclusions Hospital revisits are common after discharge from observation stays, frequently result in inpatient hospitalizations, and have increased over time among Medicare beneficiaries. As revisit rates are similar after emergency department and observation stays, strategies shown to enhance emergency department transitional care may be reasonable starting points to improve post-observation outcomes.

Sex Differences in Trajectories of Risk After Rehospitalization for Heart Failure, Acute Myocardial Infarction, or Pneumonia.

BACKGROUND: Women have an increased risk of rehospitalization in the immediate postdischarge period; however, few studies have determined how readmission risk dynamically changes on a day-to-day basis over the full year after hospitalization by sex and how these differences compare with the risk for mortality. METHODS AND RESULTS: We identified >3 000 000 hospitalizations of patients with a principal discharge diagnosis of heart failure, acute myocardial infarction, or pneumonia and estimated sex differences in the daily risk of rehospitalization/death 1 year after discharge from a population of Medicare fee-for-service beneficiaries aged 65 years and older. We calculated the (1) time required for adjusted rehospitalization/mortality risks to decline 50% from maximum values after discharge, (2) time required for the adjusted readmission risk to approach plateau periods of minimal day-to-day change, and (3) extent to which adjusted risks are greater among recently hospitalized patients versus Medicare patients. We identified 1 392 289, 530 771, and 1 125 231 hospitalizations for heart failure, acute myocardial infarction, and pneumonia, respectively. The adjusted daily risk of rehospitalization varied by admitting condition (hazard rate ratio for women versus men, 1.10 for acute myocardial infarction; hazard rate ratio, 1.04 for heart failure; and hazard rate ratio, 0.98 for pneumonia). However, for all conditions, the adjusted daily risk of death was higher among men versus women (hazard rate ratio women versus with men, <1). For both sexes, there was a similar timing of peak daily risk, half daily risk, and reaching plateau. CONCLUSIONS: Although the association of sex with daily risk of rehospitalization varies across conditions, women are at highest risk after discharge for acute myocardial infarction. Future studies should focus on understanding the determinants of sex differences in rehospitalization risk among conditions.

Development, Validation, and Assessment of an Ischemic Stroke or Transient Ischemic Attack-Specific Prediction Tool for Obstructive Sleep Apnea.

BACKGROUND: Screening instruments for obstructive sleep apnea (OSA), as used routinely to guide clinicians regarding patient referral for polysomnography (PSG), rely heavily on symptomatology. We sought to develop and validate a cerebrovascular disease-specific OSA prediction model less reliant on symptomatology, and to compare its performance with commonly used screening instruments within a population with ischemic stroke or transient ischemic attack (TIA). METHODS: Using data on demographic factors, anthropometric measurements, medical history, stroke severity, sleep questionnaires, and PSG from 2 independently derived, multisite, randomized trials that enrolled patients with stroke or TIA, we developed and validated a model to predict the presence of OSA (i.e., Apnea-Hypopnea Index ≥5 events per hour). Model performance was compared with that of the Berlin Questionnaire, Epworth Sleepiness Scale (ESS), the Snoring, Tiredness, Observed apnea, high blood Pressure, Body mass index, Age, Neck circumference, and Gender instrument, and the Sleep Apnea Clinical Score. RESULTS: The new SLEEP Inventory (Sex, Left heart failure, ESS, Enlarged neck, weight [in Pounds], Insulin resistance/diabetes, and National Institutes of Health Stroke Scale) performed modestly better than other instruments in identifying patients with OSA, showing reasonable discrimination in the development (c-statistic .732) and validation (c-statistic .731) study populations, and having the highest negative predictive value of all in struments. CONCLUSIONS: Clinicians should be aware of these limitations in OSA screening instruments when making decisions about referral for PSG. The high negative predictive value of the SLEEP INventory may be useful in determining and prioritizing patients with stroke or TIA least in need of overnight PSG.

Quantitative assessment of single-cell whole genome amplification methods for detecting copy number variation using hippocampal neurons.

Single-cell genomic analysis has grown rapidly in recent years and finds widespread applications in various fields of biology, including cancer biology, development, immunology, pre-implantation genetic diagnosis, and neurobiology. To date, the amplification bias, amplification uniformity and reproducibility of the three major single cell whole genome amplification methods (GenomePlex WGA4, MDA and MALBAC) have not been systematically investigated using mammalian cells. In this study, we amplified genomic DNA from individual hippocampal neurons using three single-cell DNA amplification methods, and sequenced them at shallow depth. We then systematically evaluated the GC-bias, reproducibility, and copy number variations among individual neurons. Our results showed that single-cell genome sequencing results obtained from the MALBAC and WGA4 methods are highly reproducible and have a high success rate. The MALBAC displays significant biases towards high GC content. We then attempted to correct the GC bias issue by developing a bioinformatics pipeline, which allows us to call CNVs in single cell sequencing data, and chromosome level and sub-chromosomal level CNVs among individual neurons can be detected. We also proposed a metric to determine the CNV detection limits. Overall, MALBAC and WGA4 have better performance than MDA in detecting CNVs.

Semi-quantitative assessment of brain maturation by conventional magnetic resonance imaging in neonates with clinically mild hypoxic-ischemic encephalopathy.

BACKGROUND: Mild hypoxic-ischemic encephalopathy (HIE) injury is becoming the major type in neonatal brain diseases. The aim of this study was to assess brain maturation in mild HIE neonatal brains using total maturation score (TMS) based on conventional magnetic resonance imaging (MRI). METHODS: Totally, 45 neonates with clinically mild HIE and 45 matched control neonates were enrolled. Gestated age, birth weight, age after birth and postmenstrual age at magnetic resonance (MR) scan were homogenous in the two groups. According to MR findings, mild HIE neonates were divided into three subgroups: Pattern I, neonates with normal MR appearance; Pattern II, preterm neonates with abnormal MR appearance; Pattern III, full-term neonates with abnormal MR appearance. TMS and its parameters, progressive myelination (M), cortical infolding (C), involution of germinal matrix tissue (G), and glial cell migration bands (B), were employed to assess brain maturation and compare difference between HIE and control groups. RESULTS: The mean of TMS was significantly lower in mild HIE group than it in the control group (mean ± standard deviation [SD] 11.62 ± 1.53 vs. 12.36 ± 1.26, P < 0.001). In four parameters of TMS scores, the M and C scores were significantly lower in mild HIE group. Of the three patterns of mild HIE, Pattern I (10 cases) showed no significant difference of TMS compared with control neonates, while Pattern II (22 cases), III (13 cases) all had significantly decreased TMS than control neonates (mean ± SD 10.56 ± 0.93 vs. 11.48 ± 0.55, P < 0.05; 12.59 ± 1.28 vs. 13.25 ± 1.29, P < 0.05). It was M, C, and GM scores that significantly decreased in Pattern II, while for Pattern III, only C score significantly decreased. CONCLUSIONS: The TMS system, based on conventional MRI, is an effective method to detect delayed brain maturation in clinically mild HIE. The conventional MRI can reveal the different retardations in subtle structures and development processes among the different patterns of mild HIE.

Motorized transportation, social status, and adiposity: the China Health and Nutrition Survey.

BACKGROUND: Increased dependence on motorized transportation may contribute to obesity. Countries in rapid socioeconomic transitions, such as China, provide an opportunity to investigate such an association. PURPOSE: The aim of the study was to examine the hypotheses that increased dependence on motorized transportation is related to adiposity and that this effect will be more pronounced in adults with high SES or those who live in urban regions. METHODS: Data from the longitudinal China Health and Nutrition Survey conducted from 1997 to 2006 (n=3853, aged 18-55 years at baseline, 52% women, ~7.8 years' follow-up) were used to examine the association between motorized transportation (none, 1-5 years, >5 years) and changes in body weight and waist circumference (WC) by using multivariate regression. SES factors were obtained from questionnaires. Data were analyzed in 2010. RESULTS: Use of motorized transportation for >5 years was related to ~1.2 kg greater weight gain (p=0.006) and ~1.0 cm larger WC gain (p=0.017) in men, when compared with the nonmotorized transportation group and adjusted for baseline age, anthropometry, dietary intake, and follow-up time. These changes were slightly more pronounced in men with higher income or from rural areas, but the difference was not significant. In women, the tendency to have motorized transportation with weight gain was less pronounced (+1.1 kg, p=0.008). Low education and high income were the most predominant factors. In 2006, motorized transportation was associated with a 1.3-fold higher OR for obesity (p(trend)=0.054) and abdominal obesity (p(trend)=0.047) in men, and a 2-fold higher OR of obesity in women (p(trend) <0.001). CONCLUSIONS: Motorized transportation was related to an increase in adiposity in the Chinese population, particularly in men.