Evaluation of sex differences in the receipt of concomitant atrial fibrillation procedures during nonmitral cardiac surgery.

OBJECTIVE: Women are less likely to receive guideline-recommended cardiovascular care, but evaluation of sex-based disparities in cardiac surgical procedures is limited. Receipt of concomitant atrial fibrillation (AF) procedures during nonmitral cardiac surgery was compared by sex for patients with preoperative AF. METHODS: Patients with preoperative AF undergoing coronary artery bypass grafting and/or aortic valve replacement at any of the 33 hospitals in Michigan from 2014 to 2022 were included. Patients with prior cardiac surgery, transcatheter AF procedure, or emergency/salvage status were excluded. Hierarchical logistic regression identified predictors of concomitant AF procedures, account for hospital and surgeon as random effects. RESULTS: Of 5460 patients with preoperative AF undergoing nonmitral cardiac surgery, 24% (n = 1291) were women with a mean age of 71 years. Women were more likely to have paroxysmal (vs persistent) AF than men (80% vs 72%; P < .001) and had a higher mean predicted risk of mortality (5% vs 3%; P < .001). The unadjusted rate of concomitant AF procedure was 59% for women and 67% for men (P < .001). After risk adjustment, women had 26% lower adjusted odds of concomitant AF procedure than men (adjusted odds ratio, 0.74; 95% CI, 0.64-0.86; P < .001). Female sex was the risk factor associated with the lowest odds of concomitant AF procedure. CONCLUSIONS: Women are less likely to receive guideline recommended concomitant AF procedure during nonmitral surgery. Identification of barriers to concomitant AF procedure in women may improve treatment of AF.

Home Health Care Use and Outcomes After Coronary Artery Bypass Grafting Among Medicare Beneficiaries.

BACKGROUND: Home health care (HHC) has been increasingly used to improve care transitions and avoid poor outcomes, but there is limited data on its use and efficacy following coronary artery bypass grafting. The purpose of this study was to describe HHC use and its association with outcomes among Medicare beneficiaries undergoing coronary artery bypass grafting. METHODS: Retrospective analysis of 100% of Medicare fee-for-service files identified 77 331 beneficiaries undergoing coronary artery bypass grafting and discharged to home between July 2016 and December 2018. The primary exposure of HHC use was defined as the presence of paid HHC claims within 30 days of discharge. Hierarchical logistic regression identified predictors of HHC use and the percentage of variation in HHC use attributed to the hospital. Propensity-matched logistic regression compared mortality, readmissions, emergency department visits, and cardiac rehabilitation enrollment at 30 and 90 days after discharge between HHC users and nonusers. RESULTS: A total of 26 751 (34.6%) of beneficiaries used HHC within 30 days of discharge, which was more common among beneficiaries who were older (72.9 versus 72.5 years), male (79.4% versus 77.4%), White (90.2% versus 89.2%), and not Medicare-Medicaid dual eligible (6.7% versus 8.8%). The median hospital-level rate of HHC use was 31.0% (interquartile range, 13.7%-54.5%) and ranged from 0% to 94.2%. Nearly 30% of the interhospital variation in HHC use was attributed to the discharging hospital (intraclass correlation coefficient, 0.296 [95% CI, 0.275-0.318]). Compared with non-HHC users, those using HHC were less likely to have a readmission or emergency department visit, were more likely to enroll in cardiac rehabilitation, and had modestly higher mortality within 30 or 90 days of discharge. CONCLUSIONS: A third of Medicare beneficiaries undergoing coronary artery bypass grafting used HHC within 30 days of discharge, with wide interhospital variation in use and mixed associations with clinical outcomes and health care utilization.

Role of STIM1 in Stretch-induced Signaling in Human Airway Smooth Muscle.

Alteration in the normal mechanical forces of breathing can contribute to changes in contractility and remodeling characteristic of airway diseases, but the mechanisms that mediate these effects in airway cells are still under investigation. Airway smooth muscle (ASM) cells contribute to both contractility and extracellular matrix (ECM) remodeling. In this study, we explored ASM mechanisms activated by mechanical stretch, focusing on mechanosensitive piezo channels and the key Ca2+ regulatory protein stromal interaction molecule 1 (STIM1). Expression of Ca2+ regulatory proteins, including STIM1, Orai1 and caveolin-1, mechanosensitive ion channels Piezo-1 and Piezo-2, and NLRP3 inflammasomes were upregulated by 10% static stretch superimposed on 5% cyclic stretch. These effects were blunted by STIM1 siRNA. Histamine-induced [Ca2+]i responses and inflammasome activation were similarly blunted by STIM1 knockdown. These data show that the effects of mechanical stretch in human ASM cells are mediated through STIM1, which activates multiple pathways including Piezo channels and the inflammasome, leading to potential downstream changes in contractility and ECM remodeling.

BayesAge: A maximum likelihood algorithm to predict epigenetic age.

Introduction: DNA methylation, specifically the formation of 5-methylcytosine at the C5 position of cytosine, undergoes reproducible changes as organisms age, establishing it as a significant biomarker in aging studies. Epigenetic clocks, which integrate methylation patterns to predict age, often employ linear models based on penalized regression, yet they encounter challenges in handling missing data, count-based bisulfite sequence data, and interpretation. Methods: To address these limitations, we introduce BayesAge, an extension of the scAge methodology originally designed for single-cell DNA methylation analysis. BayesAge employs maximum likelihood estimation (MLE) for age inference, models count data using binomial distributions, and incorporates LOWESS smoothing to capture non-linear methylation-age dynamics. This approach is tailored for bulk bisulfite sequencing datasets. Results: BayesAge demonstrates superior performance compared to scAge. Notably, its age residuals exhibit no age association, offering a less biased representation of epigenetic age variation across populations. Furthermore, BayesAge facilitates the estimation of error bounds on age inference. When applied to down-sampled data, BayesAge achieves a higher coefficient of determination between predicted and actual ages compared to both scAge and penalized regression. Discussion: BayesAge presents a promising advancement in epigenetic age prediction, addressing key challenges encountered by existing models. By integrating robust statistical techniques and tailored methodologies for count-based data, BayesAge offers improved accuracy and interpretability in predicting age from bulk bisulfite sequencing datasets. Its ability to estimate error bounds enhances the reliability of age inference, thereby contributing to a more comprehensive understanding of epigenetic aging processes.

An Introduction to the Native and Non-Native Plant-Insect Interactions and Potential Pollinators of Puerto Williams and Yendegaia, Cabo de Hornos, Chile.

The Magellanic sub-Antarctic ecoregion of southern Chile represents one of the last remaining pristine areas on Earth, but there are knowledge gaps concerning the biodiversity and interactions of the regions' flora and fauna. Non-native insect species like Bombus terrestris and Vespula vulgaris are known to have detrimental influence on native populations through competition for resources/nesting habitat, larvae predation, and foreign pathogen introduction. However, their interactions with the native and non-native plants in the region and between introduced species are unknown. This study highlights the importance of further investigations documenting the region's biodiversity, native and non-native species interactions, and local pollinators.

The C-terminal Region of D-DT Regulates Molecular Recognition for Protein-Ligand Complexes.

Systematic analysis of molecular recognition is critical for understanding the biological function of macromolecules. For the immunomodulatory protein D-dopachrome tautomerase (D-DT), the mechanism of protein-ligand interactions is poorly understood. Here, 17 carefully designed protein variants and wild type (WT) D-DT were interrogated with an array of complementary techniques to elucidate the structural basis of ligand recognition. Utilization of a substrate and two selective inhibitors with distinct binding profiles offered previously unseen mechanistic insights into D-DT-ligand interactions. Our results demonstrate that the C-terminal region serves a key role in molecular recognition via regulation of the active site opening, protein-ligand interactions, and conformational flexibility of the pocket's environment. While our study is the first comprehensive analysis of molecular recognition for D-DT, the findings reported herein promote the understanding of protein functionality and enable the design of new structure-based drug discovery projects.

Interhospital variability in cardiac rehabilitation use after cardiac surgery among Medicare beneficiaries.

OBJECTIVE: Despite guideline recommendation, cardiac rehabilitation (CR) after cardiac surgery remains underused, and the extent of interhospital variability is not well understood. This study evaluated determinants of interhospital variability in CR use and outcomes. METHODS: This retrospective cohort study included 166,809 Medicare beneficiaries undergoing cardiac surgery who were discharged alive between July 1, 2016, and December 31, 2018. CR participation was identified in outpatient facility claims within a year of discharge. Hospital-level CR rates were tabulated, and multilevel models evaluated the extent to which patient, organizational, and regional factors accounted for interhospital variability. Adjusted 1-year mortality and readmission rates were also calculated for each hospital quartile of CR use. RESULTS: Overall, 90,171 (54.1%) participated in at least 1 CR session within a year of discharge. Interhospital CR rates ranged from 0.0% to 96.8%. Hospital factors that predicted CR use included nonteaching status and lower-hospital volume. Before adjustment for patient, organizational, and regional factors, 19.3% of interhospital variability was attributable to the admitting hospital. After accounting for covariates, 12.3% of variation was attributable to the admitting hospital. Patient (0.5%), structural (2.8%), and regional (3.7%) factors accounted for the remaining explained variation. Hospitals in the lowest quartile of CR use had greater adjusted 1-year mortality rates (Q1 = 6.7%, Q4 = 5.2%, P < .001) and readmission rates (Q1 = 37.6%, Q4 = 33.9%, P < .001). CONCLUSIONS: Identifying best practices among high CR use facilities and barriers to access in low CR use hospitals may reduce interhospital variability in CR use and advance national improvement efforts.

The relationship between discharge location and cardiac rehabilitation use after cardiac surgery.

BACKGROUND: Cardiac rehabilitation (CR) is a guideline-recommended risk-reduction program offered to cardiac surgical patients. Despite CR's association with better outcomes, attendance remains poor. The relationship between discharge location and CR use is poorly understood. METHODS: This study was a nationwide, retrospective cohort analysis of Medicare fee-for-service claims for beneficiaries undergoing coronary artery bypass grafting and/or surgical aortic valve repair between July 1, 2016, and December 31, 2018. The primary outcome was attendance of any CR session. Discharge location was categorized as home discharge or discharge to extended care facility (ECF) (including skilled nursing facility, inpatient rehabilitation, and long-term acute care). Multivariable logistic regression models evaluated the association between discharge location, CR attendance, and 1-year mortality. RESULTS: Of the 167,966 patients who met inclusion criteria, 34.1% discharged to an ECF. Overall CR usage rate was 53.9%. Unadjusted and adjusted CR use was lower among patients discharged ECFs versus those discharged home (42.1% vs 60.0%; adjusted odds ratio, 0.66; P < .001). Patients discharged to long-term acute care were less likely to use CR than those discharged to skilled nursing facility or inpatient rehabilitation (reference category: home; adjusted odds ratio for long-term acute care, 0.36, adjusted odds ratio for skilled nursing facility, 0.69, and adjusted odds ratio for inpatient rehabilitation, 0.71; P < .001). CR attendance was associated with a greater reduction in adjusted 1-year mortality in patients discharged to ECFs (9.7% reduction) versus those discharged home (4.3% reduction). CONCLUSIONS: In this national analysis of Medicare beneficiaries, discharge to ECF was associated with lower CR use, despite a greater association with improved 1-year mortality. Interventions aimed at increasing CR enrollment at ECFs may improve CR use and advance surgical quality.

Design of Efficient Artificial Enzymes Using Crystallographically Enhanced Conformational Sampling.

The ability to create efficient artificial enzymes for any chemical reaction is of great interest. Here, we describe a computational design method for increasing the catalytic efficiency of de novo enzymes by several orders of magnitude without relying on directed evolution and high-throughput screening. Using structural ensembles generated from dynamics-based refinement against X-ray diffraction data collected from crystals of Kemp eliminases HG3 (kcat/KM 125 M-1 s-1) and KE70 (kcat/KM 57 M-1 s-1), we design from each enzyme ≤10 sequences predicted to catalyze this reaction more efficiently. The most active designs display kcat/KM values improved by 100-250-fold, comparable to mutants obtained after screening thousands of variants in multiple rounds of directed evolution. Crystal structures show excellent agreement with computational models, with catalytic contacts present as designed and transition-state root-mean-square deviations of ≤0.65 Å. Our work shows how ensemble-based design can generate efficient artificial enzymes by exploiting the true conformational ensemble to design improved active sites.

Changes in an enzyme ensemble during catalysis observed by high-resolution XFEL crystallography.

Enzymes populate ensembles of structures necessary for catalysis that are difficult to experimentally characterize. We use time-resolved mix-and-inject serial crystallography at an x-ray free electron laser to observe catalysis in a designed mutant isocyanide hydratase (ICH) enzyme that enhances sampling of important minor conformations. The active site exists in a mixture of conformations, and formation of the thioimidate intermediate selects for catalytically competent substates. The influence of cysteine ionization on the ICH ensemble is validated by determining structures of the enzyme at multiple pH values. Large molecular dynamics simulations in crystallo and time-resolved electron density maps show that Asp17 ionizes during catalysis and causes conformational changes that propagate across the dimer, permitting water to enter the active site for intermediate hydrolysis. ICH exhibits a tight coupling between ionization of active site residues and catalysis-activated protein motions, exemplifying a mechanism of electrostatic control of enzyme dynamics.

Dietary Counseling Documentation Among Patients Recently Hospitalized for Cardiovascular Disease.

BACKGROUND: Diet intervention forms the cornerstone for cardiovascular disease (CVD) management. OBJECTIVE: The objective was to measure the frequency of dietary counseling documentation for patients recently hospitalized with CVD. DESIGN: This was an observational study. PARTICIPANTS AND SETTING: Patients were included from the Michigan Value Collaborative Multipayer Claims Registry from October 2015 to February 2020. MAIN OUTCOME MEASURE: The study measured the frequency of medical claims that document dietary counseling ≤90 days after hospitalization (ie, an episode of care) for CVD events (coronary artery bypass grafting, acute myocardial infarction, congestive heart failure, and percutaneous coronary intervention). Dietary counseling documentation was defined as having an encounter-level International Classification of Diseases 10th Revision code for dietary counseling or current procedural terminology code for medical nutrition therapy or cardiac rehabilitation. STATISTICAL ANALYSES PERFORMED: Multivariable logistic regression was used to measure variation in documentation across gender, age, comorbidities, hospital geography, CVD event, and insurer. RESULTS: There were 175,631 episodes of care (congesitve heart failure 47.1%, acute myocardial infarction 28.7%, percutaneous coronary intervention 17.0%, and coronary artery bypass grafting 7.3%) among 146,185 individuals. Most episodes occurred among men (55.8%) and those older than age 65 years (71.9%). Dietary counseling was documented for 22.8% of episodes and was more common as cardiac rehabilitation (18.6%) than other encounter types (5.1%). In multivariable analysis, there was lower odds for dietary counseling documentation among those older than age 65 years (odds ratio [OR] 0.77; P < .001), women (OR 0.83; P < .001), with chronic kidney disease (OR 0.74; P < .001), or diabetes (OR 0.95; P < .001), but greater odds for those with obesity (OR 1.28; P < .001) and nonmetropolitan hospitals (OR 1.31; P < .001). Compared with coronary artery bypass grafting, acute myocardial infarction (OR 0.29; P < .001), confestive heart failure (OR 0.12; P < .001), and percutaneous coronary intervention (OR 0.36; P < .001) episodes had lower odds to have dietary counseling coded. Compared with Traditional Medicare, Medicaid and Medicare Advantage health maintenance organization plans had lower odds, whereas Commercial or Medicare Advantage preferred provider organization and Commercial health maintenance organization plans had higher odds to have dietary counseling documented. Results were mostly similar when evaluated by race. CONCLUSIONS: Dietary counseling was infrequently documented after hospitalization for CVD episodes in medical claims in a Michigan-based multipayer claims database with large variation by reason for hospitalization and patient factors.

Understanding vessel noise across a network of marine protected areas.

Protected areas are typically managed as a network of sites exposed to varying anthropogenic conditions. Managing these networks benefits from monitoring of conditions across sites to help prioritize coordinated efforts. Monitoring marine vessel activity and related underwater radiated noise impacts across a network of protected areas, like the U.S. National Marine Sanctuary system, helps managers ensure the quality of habitats used by a wide range of marine species. Here, we use underwater acoustic detections of vessels to quantify different characteristics of vessel noise at 25 locations within eight marine sanctuaries including the Hawaiian Archipelago and the U.S. east and west coasts. Vessel noise metrics, including temporal presence and sound levels, were paired with Automatic Identification System (AIS) vessel tracking data to derive a suite of robust vessel noise indicators for use across the network of marine protected areas. Network-wide comparisons revealed a spectrum of vessel noise conditions that closely matched AIS vessel traffic composition. Shifts in vessel noise were correlated with the decrease in vessel activity early in the COVID-19 pandemic, and vessel speed reduction management initiatives. Improving our understanding of vessel noise conditions in these protected areas can help direct opportunities for reducing vessel noise, such as establishing and maintaining noise-free periods, enhancing port efficiency, engaging with regional and international vessel quieting initiatives, and leveraging co-benefits of management actions for reducing ocean noise.

Defining capabilities in deployed UK military prehospital emergency care.

The UK military prehospital emergency care (PHEC) operational clinical capability framework must be updated in order that it retains its use as a valid operational planning tool. Specific requirements include accurately defining the PHEC levels and the 'Medical Emergency Response Team' (MERT), while reinforcing PHEC as a specialist area of clinical practice that requires an assured set of competencies at all levels and mandatory clinical currency for vocational providers.A military PHEC review panel was convened by the Defence Consultant Advisor (DCA) for PHEC. Each PHEC level was reviewed and all issues which had, or could have arisen from the existing framework were discussed until agreement between the six members of this panel was established.An updated military PHEC framework has been produced by DCA PHEC, which defines the minimum requirements for each operational PHEC level. These definitions cover all PHEC providers, irrespective of professional background. The mandatory requirement for appropriate clinical exposure for vocational and specialist providers is emphasised. An updated definition of MERT has been agreed.This update provides clarity to the continually evolving domain of UK military PHEC. It sets out the PHEC provider requirements in order to be considered operationally deployable in a PHEC role. There are implications for training, manning and recruitment to meet these requirements, but the processes required to address these are already underway and well described elsewhere.

Cardiac Rehabilitation Use After Heart Failure Hospitalization Associated With Advanced Heart Failure Center Status.

PURPOSE: Cardiac rehabilitation (CR) is an evidence-based, guideline-endorsed therapy for patients with heart failure with reduced ejection fraction (HFrEF) but is broadly underutilized. Identifying structural factors contributing to increased CR use may inform quality improvement efforts. The objective here was to associate hospitalization at a center providing advanced heart failure (HF) therapies and subsequent CR participation among patients with HFrEF. METHODS: A retrospective analysis was performed on a 20% sample of Medicare beneficiaries primarily hospitalized with an HFrEF diagnosis between January 2008 and December 2018. Outpatient claims were used to identify CR use (no/yes), days to first session, number of attended sessions, and completion of 36 sessions. The association between advanced HF status (hospitals performing heart transplantation or ventricular assist device implantations) and CR participation was evaluated with logistic regression, accounting for patient, hospital, and regional factors. RESULTS: Among 143 392 Medicare beneficiaries, 29 487 (20.6%) were admitted to advanced HF centers (HFCs) and 5317 (3.7%) attended a single CR session within 1 yr of discharge. In multivariable analysis, advanced HFC status was associated with significantly greater relative odds of participating in CR (OR = 2.20: 95% CI, 2.08-2.33; P < .001) and earlier initiation of CR participation (-8.5 d; 95% CI, -12.6 to 4.4; P < .001). Advanced HFC status had little to no association with the intensity of CR participation (number of visits or 36 visit completion). CONCLUSIONS: Medicare beneficiaries hospitalized for HF were more likely to attend CR after discharge if admitted to an advanced HFC than a nonadvanced HFC.

Association of a Medicare Mandate for Shared Decision-Making With Cardiac Device Utilization.

This cohort study evaluates the association between a Medicare shared decision-making mandate for use of implantable cardioverter defibrillators with the rate of use for this device.

Hospital variation of outcomes in status epilepticus.

OBJECTIVE: Understanding factors driving variation in status epilepticus outcomes would be critical to improve care. We evaluated the degree to which patient and hospital characteristics explained hospital-to-hospital variability in intubation and postacute outcomes. METHODS: This was a retrospective cohort study of Medicare beneficiaries admitted with status epilepticus between 2009 and 2019. Outcomes included intubation, discharge to a facility, and 30- and 90-day readmissions and mortality. Multilevel models calculated percent variation in each outcome due to hospital-to-hospital differences. RESULTS: We included 29 150 beneficiaries. The median age was 68 years (interquartile range [IQR] = 57-78), and 18 084 (62%) were eligible for Medicare due to disability. The median (IQR) percentages of each outcome across hospitals were: 30-day mortality 25% (0%-38%), any 30-day readmission 14% (0%-25%), 30-day status epilepticus readmission 0% (0%-3%), 30-day facility stay 40% (25%-53%), and intubation 46% (20%-61%). However, after accounting for many hospitals with small sample size, hospital-to-hospital differences accounted for 2%-6% of variation in all unadjusted outcomes, and approximately 1%-5% (maximally 8% for 30-day readmission for status epilepticus) after adjusting for patient, hospitalization, and/or hospital characteristics. Although many characteristics significantly predicted outcomes, the largest effect size was cardiac arrest predicting death (odds ratio = 10.1, 95% confidence interval = 8.8-11.7), whereas hospital characteristics (e.g., staffing, accreditation, volume, setting, services) all had lesser effects. SIGNIFICANCE: Hospital-to-hospital variation explained little variation in studied outcomes. Rather, certain patient characteristics (e.g., cardiac arrest) had greater effects. Interventions to improve outcomes after status epilepticus may be better focused on individual or prehospital factors, rather than at the inpatient systems level.

Geographic variation in aortic stenosis treatment and outcomes among Medicare beneficiaries in the United States.

BACKGROUND: Transcatheter aortic valve replacement (TAVR) has changed the landscape of aortic stenosis (AS) management. AIM: To describe and evaluate geographic variation in AS treatment and outcomes among a sample of Medicare beneficiaries. METHODS: A retrospective analysis of administrative claims data was conducted on a 20% sample of Medicare fee-for-service beneficiaries aged 65 and older with a diagnosis of AS (2015-2018). Estimates of demographic, comorbidity, and healthcare resources were obtained from Medicare claims and the Dartmouth Atlas of Health Care at the hospital referral region (HRR), which represents regional tertiary medical care markets. Linear regression was used to explain HRR-level variation in rates of surgical aortic valve replacement (SAVR) and TAVR, and 1-year mortality and readmission rates. RESULTS: A total of 740,899 beneficiaries with AS were identified with a median prevalence of AS of 39.9 per 1000 Medicare beneficiary years. The average HRR-level rate of SAVR was 26.3 procedures per 1000 beneficiary years and the rate of TAVR was 20.3 procedures per 1000 beneficiary years. HRR-level comorbidities and number of TAVR centers were associated with a lower SAVR rate. Demographics and comorbidities explained most of the variation in HRR-level 1-year mortality (15.2% and 18.8%) and hospitalization rates (20.5% and 16.9%), but over half of the variation remained unexplained. CONCLUSION: Wide regional variation in the treatment and outcomes of AS was observed but were largely unexplained by patient factors and healthcare utilization. Understanding the determinants of AS treatment and outcomes can inform population health efforts for these patients.

Effect of Intravenous Zoledronic Acid on Total Knee Replacement in Patients With Symptomatic Knee Osteoarthritis and Without Severe Joint Space Narrowing: A Prespecified Secondary Analysis of a Two-Year, Multicenter, Double-Blind, Placebo-Controlled Clinical Trial.

OBJECTIVE: To determine the effect of zoledronic acid (ZA) on the risk of total knee replacement (TKR) in patients with symptomatic knee osteoarthritis and without severe joint space narrowing (JSN). METHODS: We included 222 participants (mean age 62 years, 52% female) from the two-year Zoledronic Acid for Osteoarthritis Knee Pain trial (113 received 5 mg of ZA annually and 109 received placebo) conducted between November 2013 and October 2017. Primary TKR were identified until February 22, 2022. The effect of ZA on TKR risk was evaluated using Cox proportional hazard regression models. Because the treatment effect failed the proportional hazards assumption, a time-varying coefficients analysis for treatment was conducted by splitting the study into two periods (ie, within and after two years of randomization). RESULTS: Over a mean follow-up of seven years, 39% and 30% of participants had any TKR in the ZA and placebo groups, and 28% and 18% had TKR in the study knee, respectively. Use of ZA was associated with a higher risk of TKR in any knee (hazard ratio [HR] 4.2, 95% confidence interval [CI] 1.2-14.7) and showed a trend in the study knee (HR 6.8, 95%CI 0.9-53.9) during the trial. In the posttrial period, the risk of TKR was similar in the ZA and the placebo groups for any knee (HR 1.2, 95%CI 0.5-1.8) and the study knee (HR 1.4, 95%CI 0.5-2.2). CONCLUSION: These results suggest that ZA is not protective against TKR in patients with symptomatic knee osteoarthritis and without severe JSN.

Trends in Development of Aptamer-Based Biosensor Technology for Detection of Bacteria.

The contamination of food by bacterial pathogens represents a substantial hazard for human and animal health. Therefore, considerable effort is focused on the development of effective methods for monitoring food safety. A current trend in this field is the development of biosensors that can be used in remote food laboratories and even in farms to check food contamination prior to its delivery to consumers or its further processing in the food industry. Among receptors that can recognize proteins or lipopolysaccharides (LPS) on bacterial surfaces, aptamers play an important role. An aptamer consists of a single strand of DNA or RNA that folds into a 3D structure when placed in a solution, forming a binding site for the target. This chapter presents an overview of recent achievements in bacterial pathogen detection through the development of electrochemical, optical, and acoustic biosensors based on DNA aptamers. Thus far, these biosensors exhibit good sensitivity and selectivity, comparable with conventional methods currently used in food laboratories. However, these biosensors offer several advantages over conventional methods: they are of low cost, easier to handle, and respond more quickly. Biosensor technology is therefore an important tool for monitoring food safety.

Kinetic Insights into Bridge Cleavage Pathways in Periodic Mesoporous Organosilicas.

Bridging functionalities in periodic mesoporous organosilicas (PMOs) enable new functionalities for a wide range of applications. Bridge cleavage is frequently observed during anneals required to form porous structures, yet the mechanism of these bridge cleavages has not been completely resolved. Here, these chemical transformations and their kinetic pathways on sub-millisecond timescales induced by laser heating are revealed. By varying anneal times and temperatures, the transformation dynamics of bridge cleavage and structural transformations and their activation energies are determined. The structural relaxation time for individual reactions and their effective local heating time are determined and compared, and the results directly demonstrate the manipulation of different molecules through kinetic control of the sequence of reactions. By isolating and understanding the earliest stage of structural transformations, this study identifies the kinetic principles for new synthesis and post-processing routes to control individual molecules and reactions in PMOs and other material systems with multi-functionalities.