Experience of Being Fall-Prone and Participating in Research: Fallers' Perspectives.

The importance of giving a voice to groups considered hard-to-reach for research purposes is becoming increasingly apparent, with insights into their experience having the potential to improve research participation. Fall-prone older adults are a cohort underrepresented in research, often excluded in large-scale research and considered difficult to recruit. This study aims to explore older fallers' experiences of being fall-prone and participating in research. Seven older fallers (4 males, aged 69-88) participated in semi-structured telephone interviews following participation in an experimental research project. Interviews explored participants' personal experience of being fall-prone and participating in research. The resulting data was analyzed using thematic analysis. Three primary themes emerged: "Research through the eyes of older fallers", "Living with falls", and "It's all in the mind is it?". Our study gives voice to older fallers who have recently participated in experimental research to learn of their personal views on research participation.

Mechanistic differences between linear vs. spirocyclic dialkyldiazirine probes for photoaffinity labeling.

Dialkyldiazirines have emerged as a photo-reactive group of choice for interactome mapping in live cell experiments. Upon irradiation, 'linear' dialkyldiazirines produce dialkylcarbenes which are susceptible to both intramolecular reactions and unimolecular elimination processes, as well as diazoalkanes, which also participate in intermolecular labeling. Cyclobutylidene has a nonclassical bonding structure and is stable enough to be captured in bimolecular reactions. Cyclobutanediazirines have more recently been studied as photoaffinity probes based on cyclobutylidene, but the mechanism, especially with respect to the role of putative diazo intermediates, was not fully understood. Here, we show that photolysis (365 nm) of cyclobutanediazirines can produce cyclobutylidene intermediates as evidenced by formation of their expected bimolecular and unimolecular products, including methylenecyclopropane derivatives. Unlike linear diazirines, cyclobutanediazirine photolysis in the presence of tetramethylethylene produces a [2 + 1] cycloaddition adduct. By contrast, linear diazirines produce diazo compounds upon low temperature photolysis in THF, whereas diazo compounds are not detected in similar photolyses of cyclobutanediazirines. Diazocyclobutane, prepared by independent synthesis, is labile, reactive toward water and capable of protein alkylation. The rate of diazocyclobutane decomposition is not affected by 365 nm light, suggesting that the photochemical conversion of diazocyclobutane to cyclobutylidene is not an important pathway. Finally, chemical proteomic studies revealed that a likely consequence of this primary conversion to a highly reactive carbene is a marked decrease in labeling by cyclobutanediazirine-based probes relative to linear diazirine counterparts both at the individual protein and proteome-wide levels. Collectively, these observations are consistent with a mechanistic picture for cyclobutanediazirine photolysis that involves carbene chemistry with minimal formation of diazo intermediates, and contrasts with the photolyses of linear diazirines where alkylation by diazo intermediates plays a more significant role.

Comparison of Pressure vs Volume Overload Ventricular Wall Stress in Patients With Valvular Heart Disease.

BACKGROUND: Aortic stenosis (AS) and mitral regurgitation (MR) result in different patterns of left ventricular remodeling and hypertrophy. OBJECTIVES: We characterized left ventricular wall stress (LVWS) profiles in pressure and volume-overloaded systems, examined the relationship between baseline LVWS and cardiac remodeling, and assessed the acute effects of valve intervention on LVWS using invasive pressures combined with cardiac magnetic resonance (CMR) imaging measures of left ventricular volumes/mass. METHODS: A total of 47 patients with severe AS undergoing transcatheter aortic valve replacement (TAVR) and 15 patients with severe MR undergoing MitraClip (MC) underwent a 6-minute walk test (6MWT), transthoracic echocardiogram, and CMR before their procedures. Catheters in the left ventricle were used to record hemodynamic changes before and after valve/clip deployment. This was integrated with CMR data to calculate LVWS before and after intervention. RESULTS: The TAVR group demonstrated significant reductions in systolic LVWS post procedure (median 24.7 Pa [IQR: 14 Pa] pre vs median 17.3 Pa [IQR: 12 Pa] post; P < 0.001). The MC group demonstrated significant reductions in diastolic LVWS (median 6.4 Pa [IQR: 5 Pa] pre vs median 4.3 Pa [IQR: 4.1 Pa] post; P = 0.021) with no significant change in systolic LVWS (30.6 ±1.61 pre vs 33 ±2.47 Pa post; P = 0.16). There was an inverse correlation between baseline systolic LVWS and 6MWT in the TAVR group (r = -0.31; P = 0.04). CONCLUSIONS: TAVR results in significant reductions in systolic LVWS acutely. MC results in significant reductions in diastolic LVWS. Higher baseline systolic LVWS in TAVR is associated with shorter 6MWT suggesting that in AS, LVWS may be a useful marker of early decompensation.

Chest pain epidemiology and care quality for Aboriginal and Torres Strait Islander peoples in Victoria, Australia: a population-based cohort study from 2015 to 2019.

Background: This study examined chest pain epidemiology and care quality for Aboriginal and Torres Strait Islander ('Indigenous') patients presenting to hospital via emergency medical services (EMS) with chest pain. Methods: State-wide population-based cohort study of consecutive patients attended by ambulance for acute chest pain with individual linkage to emergency, hospital admission and mortality data in the state of Victoria, Australia from January 2015 to June 2019. Multivariable models were used to assess for differences in pre-hospital and hospital adherence to care quality, process measures and clinical outcomes. Findings: From 204,969 EMS attendances for chest pain, 3890 attendances (1.9%) identified as Aboriginal or Torres Strait Islander. Age-standardized incidence rates were higher overall for Indigenous people (3128 vs. 1147 per 100,000 person-years, incidence rate ratio 2.73, 95% CI 2.72-2.74), this difference being particularly striking for younger patients, women, and those residing in outer regional areas. In multivariable models, adherence to care quality and process measures was lower for attendances involving Indigenous people. In the pre-hospital setting, Indigenous people were less likely to be provided intravenous access or analgesia. In the hospital setting, Indigenous people were less likely to be seen by emergency clinicians within target time and less likely to transferred following myocardial infarction to a revascularization capable centre. Interpretation: Incidence of acute chest pain presentations is high among Indigenous people in Victoria, Australia. Opportunities to improve the quality of care for Indigenous Australians presenting with acute chest pain are identified. Funding: National Health and Medical Research Council, National Heart Foundation.

Prevention of Cardiovascular Disease in Women With Pregnancy-Related Risk Factors: A Prospective Women's Heart Clinic Study.

Background Hypertensive disorders of pregnancy, gestational diabetes, and having a small-for-gestational-age baby are known to substantially increase a woman's risk of cardiovascular disease. Despite this, evidence for models of care that mitigate cardiovascular disease risk in women with these pregnancy-related conditions is lacking. Methods and Results A 6-month prospective cohort study assessed the effectiveness of a multidisciplinary Women's Heart Clinic on blood pressure and lipid control in women aged 30 to 55 years with a past pregnancy diagnosis of hypertensive disorders of pregnancy, gestational diabetes, or a small-for-gestational age baby in Melbourne, Australia. The co-primary end points were (1) blood pressure <140/90 mm Hg or <130/80 mm Hg if diabetes and (2) total cholesterol to high-density lipoprotein cholesterol ratio <4.5. The study recruited 156 women with a mean age of 41.0±4.2 years, 3.9±2.9 years from last delivery, 68.6% White, 20.5% South/East Asian, and 80.5% university-educated. The proportion meeting blood pressure target increased (69.2% to 80.5%, P=0.004), with no significant change in lipid targets (80.6% to 83.7%, P=0.182). Systolic blood pressure (-6.9 mm Hg [95% CI, -9.1 to -4.7], P<0.001), body mass index (-0.6 kg/m2 [95% CI, -0.8 to -0.3], P<0.001), low-density lipoprotein cholesterol (-4.2 mg/dL [95% CI, -8.2 to -0.2], P=0.042), and total cholesterol (-4.6 mg/dL [95% CI, -9.1 to -0.2] P=0.042) reduced. Heart-healthy lifestyle significantly improved with increased fish/olive oil (36.5% to 51.0%, P=0.012), decreased fast food consumption (33.8% to 11.0%, P<0.001), and increased physical activity (84.0% to 92.9%, P=0.025). Conclusions Women at high risk for cardiovascular disease due to past pregnancy-related conditions experienced significant improvements in multiple cardiovascular risk factors after attending a Women's Heart Clinic, potentially improving long-term cardiovascular disease outcomes. Registration URL: https://www.anzctr.org.au; Unique identifier: ACTRN12622000646741.

Assessing atrial myopathy with cardiac magnetic resonance imaging in embolic stroke of undetermined source.

BACKGROUND: Left atrial myopathy has been implicated in atrial fibrillation (AF)-related stroke and embolic stroke of undetermined source (ESUS). OBJECTIVE: To use advanced cardiac magnetic resonance (CMR) imaging techniques, including left atrial (LA) strain and 4D flow CMR, to identify atrial myopathy in patients with ESUS. METHODS: 20 patients with ESUS and no AF or other cause for stroke, and 20 age and sex-matched controls underwent CMR with 4D flow analysis. Markers of LA myopathy were assessed including LA size, volume, ejection fraction, and strain. 4D flow CMR was performed to measure novel markers of LA stasis such as LA velocities and the LA residence time distribution time constant (RTDtc). These markers of LA myopathy were compared between the two groups. RESULTS: There was no significant difference in: CMR-calculated LA velocities or LA total, passive or active ejection fractions between the groups. There was no significant difference in CMR-derived reservoir, conduit or contractile average longitudinal strain between the ESUS and control groups (22.9 vs 22.6%, p=0.379, 11.2 ± 3.5 vs 12.4 ± 2.6% p=0.224, 10.8 ± 3.2 vs 10.4 ± 2.3%, p=0.625 respectively). Similarly, RTDtc was not significantly longer in ESUS patients compared to controls (1.3 ± 0.2 vs 1.2 ± 0.2, p=0.1). CONCLUSIONS: There were no significant differences in any CMR marker of atrial myopathy in ESUS patients compared to healthy controls, likely reflecting the multiple possible aetiologies of ESUS suggesting that the role LA myopathy plays in ESUS is smaller than previously thought.

Can We Train Multisensory Integration in Adults? A Systematic Review.

The ability to efficiently combine information from different senses is an important perceptual process that underpins much of our daily activities. This process, known as multisensory integration, varies from individual to individual, and is affected by the ageing process, with impaired processing associated with age-related conditions, including balance difficulties, mild cognitive impairment and cognitive decline. Impaired multisensory perception has also been associated with a range of neurodevelopmental conditions, where novel intervention approaches are actively sought, for example dyslexia and autism. However, it remains unclear to what extent and how multisensory perception can be modified by training. This systematic review aims to evaluate the evidence that we can train multisensory perception in neurotypical adults. In all, 1521 studies were identified following a systematic search of the databases PubMed, Scopus, PsychInfo and Web of Science. Following screening for inclusion and exclusion criteria, 27 studies were chosen for inclusion. Study quality was assessed using the Methodological Index for Non-Randomised Studies (MINORS) tool and the Cochrane Risk of Bias tool 2.0 for Randomised Control Trials. We found considerable evidence that in-task feedback training using psychophysics protocols led to improved task performance. The generalisability of this training to other tasks of multisensory integration was inconclusive, with few studies and mixed findings reported. Promising findings from exercise-based training indicate physical activity protocols warrant further investigation as potential training avenues for improving multisensory integration. Future research directions should include trialling training protocols with clinical populations and other groups who would benefit from targeted training to improve inefficient multisensory integration.

LidocAine Versus Opioids In MyocarDial infarction: the AVOID-2 randomized controlled trial.

AIMS: Opioid analgesia has been shown to interfere with the bioavailability of oral P2Y12 inhibitors prompting the search for safe and effective non-opioid analgesics to treat ischaemic chest pain. METHODS AND RESULTS: The lidocAine Versus Opioids In MyocarDial infarction trial was a prospective, Phase II, prehospital, open-label, non-inferiority, randomized controlled trial enrolling patients with suspected STEACS with moderate to severe pain [numerical rating scale (NRS) at least 5/10]. Intravenous lidocaine (maximum dose 300 mg) or intravenous fentanyl (up to 50 µg every 5 min) were administered as prehospital analgesia. The co-primary end points were prehospital pain reduction and adverse events requiring intervention. Secondary end points included peak cardiac troponin I, cardiac MRI (cMRI) assessed myocardial infarct size and clinical outcomes to 30 days. A total of 308 patients were enrolled. The median reduction in pain score (NRS) was 4 vs. 3 in the fentanyl and lidocaine arms, respectively, for the primary efficacy end point [estimated median difference -1 (95% confidence interval -1.58, -0.42, P = 0.5 for non-inferiority, P = 0.001 for inferiority of lidocaine)]. Adverse events requiring intervention occurred in 49% vs. 36% of the fentanyl and lidocaine arms which met non-inferiority and superiority favouring lidocaine (P = 0.016 for superiority). No significant differences in myocardial infarct size and clinical outcomes at 30 days were seen. CONCLUSION: IV Lidocaine did not meet the criteria for non-inferiority with lower prehospital pain reduction than fentanyl but was safe and better tolerated as analgesia in ST-elevation myocardial infarction (STEMI). Future trials testing non-opioid analgesics in STEMI and whether opioid avoidance improves clinical outcomes are needed. TRIAL REGISTRATION: CTRN12619001521112p.

UpStreAm doxycycline in ST-eLeVation myocArdial infarction: targetinG infarct hEaling and ModulatIon (SALVAGE-MI trial).

AIMS: Experimental studies demonstrate protective effects of doxycycline on myocardial ischaemia-reperfusion injury. The trial investigated whether doxycycline administered prior to reperfusion in patients presenting with ST-elevation myocardial infarction (STEMI) reduces infarct size (IS) and ameliorates adverse left ventricular (LV) remodelling. METHODS AND RESULTS: In this randomized, double-blind, placebo-controlled trial, patients presenting with STEMI undergoing primary percutaneous coronary intervention (PPCI) were randomized to either intravenous doxycycline or placebo prior to reperfusion followed by 7 days of oral doxycycline or placebo. The primary outcome was final IS adjusted for area-at-risk (fIS/AAR) measured on two cardiac magnetic resonance scans ∼6 months apart. Of 103 participants, 50 were randomized to doxycycline and 53 to placebo and were matched for age (59 ± 12 vs. 60 ± 10 years), male sex (92% vs. 79%), diabetes mellitus (26% vs. 11%) and left anterior descending artery occlusion (50% vs. 49%), all P > 0.05. Patients treated with doxycycline had a trend for larger fIS/AAR [0.79 (0.5-0.9) vs. 0.61 (0.47-0.76), P = 0.06], larger fIS at 6 months [18.8% (12-26) vs. 13.6% (11-21), P = 0.08], but similar acute IS [21.7% (17-34) vs. 19.4% (14-27), P = 0.19] and AAR [26% (20-36) vs. 24.7% (16-31), P = 0.22] compared with placebo. Doxycycline did not ameliorate adverse LV remodelling [%Δend-diastolic volume index, 1.1% (-3.8-8.4) vs. -1.34% (-6.1-5.8), P = 0.42] and was independently associated with larger fIS (regression coefficient = 0.175, P = 0.03). CONCLUSION: Doxycycline prior to PPCI neither reduced IS acutely or at six months nor attenuated adverse LV remodelling. These data raise safety concerns regarding doxycycline use in STEMI for infarct modulation and healing.

Understanding structure-properties relationships of porphyrin linked to graphene oxide through π-π-stacking or covalent amide bonds.

Two graphene oxide nanoassemblies using 5-(4-(aminophenyl)-10,15,20-triphenylporphyrin (TPPNH2) were fabricated by two synthetic methods: covalent (GO-CONHTPP) and noncovalent bonding. GO-CONHTPP was achieved through amide formation at the periphery of GO sheets and the hybrid material was fully characterized by FTIR, XPS, Raman spectroscopy, and SEM. Spectroscopic measurements together with theoretical calculations demonstrated that assembling TPPNH2 on the GO surface in DMF-H2O (1:2, v/v) via non-covalent interactions causes changes in the absorption spectra of porphyrin, as well as efficient quenching of its emission. Interestingly, covalent binding to GO does not affect notably neither the porphyrin absorption nor its fluorescence. Theoretical calculations indicates that close proximity and π-π-stacking of the porphyrin molecule with the GO sheet is possible only for the non-covalent functionalization. Femtosecond pump-probe experiments revealed that only the non-covalent assembly of TPPNH2 and GO enhances the efficiency of the photoinduced electron transfer from porphyrin to GO. In contrast to the non-covalent hybrid, the covalent GO-CONHTPP material can generate singlet oxygen with quantum yields efficiency (ΦΔ = 0.20) comparable to that of free TPPNH2 (ΦΔ = 0.26), indicating the possible use of covalent hybrid materials in photodynamic/photothermal therapy. The spectroscopic studies combined with detailed quantum-chemical analysis provide invaluable information that can guide the fabrication of hybrid materials with desired properties for specific applications.

Older Women's Experiences of a Community-Led Walking Programme Using Activity Trackers.

Promoting physical activity amongst older adults represents a major public health goal and community-led exercise programmes present benefits in promoting active lifestyles. Commercial activity trackers potentially encourage positive behaviour change with respect to physical exercise. This qualitative study investigated the experiences and attitudes of older adults following a 6-week community-led walking programme utilising activity trackers. Eleven community-dwelling older women aged 60+ completed individual phone interviews following their involvement in the programme. The programme, codesigned with a group of senior citizens, equipped participants with wrist-worn activity trackers and included biweekly check-in sessions with a researcher to monitor progress and support motivation. Interviews explored participants' experiences of the programme and of using activity trackers for the purpose of becoming more active. A thematic analysis produced three main themes: 'programme as a source of motivation', 'user experiences with the technology' and 'views on social dimension of the programme'. Overall, participants highlighted the self-monitoring function of activity trackers as most beneficial for their exercise levels. This study provides insights into the personal and social factors perceived by older adults in relation to being part of a community-led programme using activity trackers. It highlights the role of the programme and trackers in maintaining motivation to stay active.

Differences in outcome of percutaneous coronary intervention between Indigenous and non-Indigenous people in Victoria, Australia: a multicentre, prospective, observational, cohort study.

BACKGROUND: Data on the patient characteristics and health outcomes of Indigenous Australians having revascularisation for treatment of coronary artery disease are scarce. The aim of this study was to assess differences in patient characteristics, presentations, and outcomes among Indigenous and non-Indigenous Australians having percutaneous coronary intervention (PCI) in urban and larger regional centres in Victoria, Australia. METHODS: In this multicentre, prospective, observational cohort study, data were prospectively collected from six government-funded tertiary hospitals in the state of Victoria, Australia. The Melbourne Interventional Group PCI registry was used to identify patients having PCI at Victorian metropolitan and large regional hospitals between Jan 1, 2005, and Dec 31, 2018. The primary outcome was long-term mortality. Secondary outcomes were 30 day mortality and 30 day major adverse cardiovascular events (MACE), defined as a composite endpoint of death, myocardial infarction, and target-vessel revascularisation. Regression analyses, adjusted for clinically relevant covariates and geographical and socioeconomic indices, were used to establish the influence of Indigenous status on these study outcomes. FINDINGS: 41 146 patient procedures were entered into the registry, of whom 179 (0·4%) were recorded as identifying as Indigenous Australian, 39 855 (96·9%) were not Indigenous Australian, and 1112 (2·7%) had incomplete data regarding ethnicity and were excluded. Compared with their non-Indigenous counterparts, Indigenous patients were younger, more often women, and more likely to have comorbidities. Indigenous Australians were also more likely to live in a regional community and areas of socioeconomic disadvantage. Procedural success and complication rates were similar for Indigenous and non-Indigenous patients having PCI. At 30 day follow-up, Indigenous Australians were more likely to be taking optimal medical therapy, although overall follow-up rates were lower and prevalence of persistent smoking was higher. Multivariable analysis showed that Indigenous status was independently associated with increased risk of long-term mortality (hazard ratio 2·49, 95% CI 1·79-3·48; p<0·0001), 30 day mortality (odds ratio 2·78, 95% CI 1·09-7·12; p=0·033), and 30-day MACE (odds ratio 1·87, 95% CI 1·03-3·39; p=0·039). INTERPRETATION: Indigenous Australians having PCI in urban and larger regional centres are at increased risk of mortality and adverse cardiac events. Clinically effective and culturally safe care pathways are urgently needed to improve health outcomes among Indigenous Australians who are having PCI. FUNDING: National Health and Medical Research Council, National Heart Foundation.

Acute electrical, autonomic and structural effects of binge drinking: Insights into the 'holiday heart syndrome'.

BACKGROUND: Binge drinking is a common atrial fibrillation (AF) trigger, however the mechanisms are poorly understood. OBJECTIVE: To investigate the effects of alcohol intoxication and hangover with rhythm monitoring and cardiac MRI. METHODS: Patients underwent serial cardiac MRI pre- and post-binge with continuous Holter monitoring. Time periods analyzed: baseline (24 h pre-binge), consumption, hangover (0- 24 h post-consumption) and post-hangover (24-48 h post-consumption). RESULTS: 50 patients (age 49 ± 15 years, 40% paroxysmal AF) completed the study (intake 8.4 ± 3.1 standard drinks). Mean heart rate increased from 72 ± 10 to 80 ± 13 beats per minute (bpm) during consumption (p < 0.001). The hangover period was characterised by higher daily atrial ectopic count (50, IQR 10-132 vs baseline 43, IQR 10-113; p = 0.04) and reduced heart rate variability (SDNN 55 ms, IQR 40-65 versus 62 ms, IQR 51-66; p = 0.007). There was evidence of heightened parasympathetic activity post-hangover with heart rate slowing (mean HR 54 ± 6 bpm; p = 0.03) and increased activity in the High frequency band when separating the complex heart rate variability waveform into its component rhythms (291 ms2, 97-538 versus baseline 237 ms2, IQR 104-332; p = 0.04). Three patients developed AF 11, 29 and 34 h post-binge. Cardiac MRI (2.7 ± 0.7 days post-binge) demonstrated a decrease in left atrial (LA) emptying fraction (57.9 ± 8.5 to 53.5 ± 6.7%; p = 0.003) but no change in LA volume, left ventricular ejection fraction or markers of ventricular inflammation. CONCLUSION: Binge drinking is associated with sympathetic activation followed by a 'rebound' parasympathetic response and atrial mechanical dysfunction which may explain the propensity and temporal association between binge drinking and AF.

Differentiating Nonischemic Dilated Cardiomyopathy With Incidental Infarction From Ischemic Cardiomyopathy by Geometric Indices Derived From Cardiovascular Magnetic Resonance.

PURPOSE: The purpose of this study was to differentiate nonischemic dilated cardiomyopathy with incidental myocardial infarction (NICM with incidental MI) from ischemic cardiomyopathy (ICM) by integrating left ventricular (LV) geometric indices and ischemic late gadolinium enhancement (LGE), obtained from cardiac magnetic resonance (CMR) imaging. MATERIALS AND METHODS: All subjects were studied on a 1.5 Tesla magnetic resonance imaging scanner. All patients had an LV ejection fraction (LVEF) <50% with LV dilation. LV end-diastolic volume (LVEDV), LVEDV index (LVEDVi), LVEF, the number and distribution of ischemic LGE segments, and ratios of volumetric and functional indices to ischemic LGE segments were determined. Logistic regression was used to detect the independent predictor of ICM. Receiver operating characteristic analysis differentiated NICM with incidental MI from ICM. RESULTS: Of a total of 63 patients enrolled, 45 patients had ICM, and 18 patients had NICM with incidental MI. Both groups had similar LVEF. Compared with ICM, NICM with incidental MI had more LV dilation, whereas ICM had more ischemic LGE segments. A higher number of ischamic LGE segments remained an independent predictor of ICM (odds ratio: 18.2, 95% confidence interval: 1.64-201.34, P=0.018). The optimal cut-off value for detecting NICM with incidental MI is the ratio of LVEDVi to the number of ischemic LGE segments over 25 mL/m2/segment (sensitivity 100%, specificity 91%, P<0.0001). CONCLUSION: Patients with NICM with incidental MI can be reliably distinguished from ICM using the ratio of LVEDVi divided by the number of ischemic LGE segments. This technique may improve diagnosis and help aid management of patients with cardiomyopathy and coexistent coronary artery disease.

Outcomes of Percutaneous Coronary Intervention in Patients With Rheumatoid Arthritis.

Rheumatoid arthritis (RA) is the most common inflammatory arthritis and is associated with increased risk of cardiovascular events and mortality. Evidence regarding outcomes following PCI is limited. This study aimed to assess differences in outcomes following percutaneous coronary intervention (PCI) between patients with and without RA. The Melbourne Interventional Group PCI registry (2005 to 2018) was used to identify 756 patients with RA. Outcomes were compared with the remaining cohort (n = 38,579). Patients with RA were older, more often female, with higher rates of hypertension, previous stroke, peripheral vascular disease, obstructive sleep apnea, chronic lung disease, myocardial infarction, and renal impairment, whereas rates of dyslipidemia and current smoking were lower, all p <0.05. Lesions in patients with RA were more frequently complex (ACC/AHA type B2/C), requiring longer stents, with higher rates of no reflow, all p <0.05. Risk of long-term mortality, adjusted for potential confounders, was higher for patients with RA (hazard ratio 1.53, 95% confidence interval 1.30 to 1.80; median follow-up 5.0 years), whereas 30-day outcomes including mortality, major adverse cardiovascular events, bleeding, stroke, myocardial infarction, coronary artery bypass surgery, and target vessel revascularization were similar. In subgroup analysis, patients with RA and lower BMI (Pfor interaction < 0.001) and/or acute coronary syndromes (Pfor interaction = 0.05) had disproportionately higher risk of long-term mortality compared with patients without RA. In conclusion, patients with RA who underwent PCI had more co-morbidities and longer, complex coronary lesions. Risk of short-term adverse outcomes was similar, whereas risk of long-term mortality was higher, especially among patients with acute coronary syndromes and lower body mass index.

Audio-Visual Training in Older Adults: 2-Interval-Forced Choice Task Improves Performance.

A growing interest in ameliorating multisensory perception deficits in older adults arises from recent evidence showing that impaired multisensory processing, particularly in the temporal domain, may be associated with cognitive and functional impairments. Perceptual training has proved successful in improving multisensory temporal processing in young adults, but few studies have investigated this training approach in older adults. In the present study we used a simultaneity (or synchronicity) judgement task with feedback, to train the audio-visual abilities of community-dwelling, cognitively healthy older adults. We recruited 23 older adults (M = 74.17, SD = 6.23) and a group of 20 young adults (M = 24.20, SD = 4.23) who served as a comparison. Participants were tested before and after perceptual training using a 2-Interval Forced Choice Task (2-IFC); and the Sound-Induced Flash Illusion (SIFI). After 3 days of training, participants improved on the 2-IFC task, with a significant narrowing of the temporal window of integration (TWI) found for both groups. Generalization of training effects was not found, with no post-training differences in perceptual sensitivity to the SIFI for either group. These findings provide evidence perceptual narrowing can be achieved in older as well as younger adults after 3 days of perceptual training. These results provide useful information for future studies attempting to improve audio-visual temporal discrimination abilities in older people.

Probing the Mechanism of Photoaffinity Labeling by Dialkyldiazirines through Bioorthogonal Capture of Diazoalkanes.

Dialkyldiazirines have emerged as reagents of choice for biological photoaffinity labeling studies. The mechanism of crosslinking has dramatic consequences for biological applications where instantaneous labeling is desirable, as carbene insertions display different chemoselectivity and are much faster than competing mechanisms involving diazo or ylide intermediates. Here, deuterium labeling and diazo compound trapping experiments are employed to demonstrate that both carbene and diazo mechanisms operate in the reactions of a dialkyldiazirine motif that is commonly utilized for biological applications. For the fraction of intermolecular labeling that does involve a carbene mechanism, direct insertion is not necessarily involved, as products derived from a carbonyl ylide are also observed. We demonstrate that a strained cycloalkyne can intercept diazo compound intermediates and serve as a bioorthogonal probe for studying the contribution of the diazonium mechanism of photoaffinity labeling on a model protein under aqueous conditions.

Graphene Oxide Functionalized with Cationic Porphyrins as Materials for the Photodegradation of Rhodamine B.

Two noncovalent nanohybrids between cationic porphyrin (free-base TMPyP and zinc(II) ZnTMPyP) bearing cationic (N-methylpyridyl) groups and graphene oxide (GO) were constructed with the aim of generating a photocatalyst active for rhodamine B (RhB) degradation. The obtained materials were thoroughly characterized by steady-state and time-resolved absorption and emission methods, which indicated that metalation of the porphyrin with Zn(II) increases the affinity of the porphyrin toward the GO surface. Photocurrent experiment together with femtosecond transient absorption spectroscopy clearly showed the existence of electron transfer from the photoexcited porphyrin to GO. Both hybrid materials demonstrated higher photocatalytic activity toward RhB degradation as compared to GO; however, ZnTMPyP-GO exhibited more efficient performance (19% of RhB decomposition after 2 h of irradiation). Our data indicate that the presence of Zn(II) in the core of the porphyrin can promote charge separation in the ZnTMPyP-GO composites. The higher degradation rate seen with ZnTMPyP-GO as compared to the TMPyP-GO assemblies highlights the beneficial role of Zn(II)-metalation of the porphyrin ring.