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Managing health care for older adults aged 75 years and older can pose unique challenges stemming from age-related physiological differences and comorbidities, along with elevated risk of delirium, frailty, disability, and polypharmacy. This review is aimed at providing a comprehensive analysis of the management of acute coronary syndromes (ACS) in older patients, a demographic substantially underrepresented in major clinical trials. Because older patients often exhibit atypical ACS symptoms, a nuanced diagnostic and risk stratification approach is necessary. We aim to address diagnostic challenges for older populations and highlight the diminished sensitivity of traditional symptoms with age, and the importance of biomarkers and imaging techniques tailored for older patients. Additionally, we review the efficacy and safety of pharmacological agents for ACS management in older people, emphasizing the need for a personalized and shared decision-making approach to treatment. This review also explores revascularization strategies, considering the implications of invasive procedures in older people, and weighing the potential benefits against the heightened procedural risks, particularly with surgical revascularization techniques. We explore the perioperative management of older patients experiencing myocardial infarction in the setting of noncardiac surgeries, including preoperative risk stratification and postoperative care considerations. Furthermore, we highlight the critical role of a multidisciplinary approach involving cardiologists, geriatricians, general and internal medicine physicians, primary care physicians, and allied health, to ensure a holistic care pathway in this patient cohort.
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BACKGROUND: Guidelines and international appropriate use criteria increasingly endorse non-invasive stress testing to evaluate patients with suspected chronic coronary disease (CCD). We sought to review the real-world utilisation of non-invasive stress testing and investigate whether their use prior to PCI associates with outcomes in patients with CCD. METHODS: Consecutive patients from a multicentre registry who underwent PCI for CCD between 2006 and 2018 were included. Clinical characteristics and outcomes were stratified according to whether stress testing was performed prior to PCI (stress vs no-stress groups). The primary outcome was 3-year all-cause mortality. RESULTS: Among the 8251 patients included, 4970 (60.2 %) underwent pre-PCI stress testing and this proportion increased over time (p-for-trend<0.001). The stress group had a lower prevalence of prior revascularization, myocardial infarction, or heart failure, and a lower incidence of triple vessel disease, in stent re-stenosis, and ACC/AHA class B2/C lesions (all p < 0.001). When comparing post-procedural outcomes, the stress group had lower rates of arrhythmia (1.5 % vs 2.6 %, p = 0.001), new heart failure (0.2 % vs 0.8 %, p = 0.001), renal impairment, and a shorter length of stay (1.6 vs 2.1 days, p < 0.001). Mortality at 3-years was lower in those undergoing PCI following stress testing (5.8 % vs 8.8 %, p < 0.001). After adjusting for key clinical variables, stress guided revascularization was associated with a significantly lower risk of 3-year mortality (adjusted Hazard Ratio 0.77, 95 % CI 0.64-0.92). CONCLUSIONS: In patients with CCD, PCI guided by non-invasive stress testing is increasingly utilized and associated with improved survival. Further studies are necessary to investigate whether this results from differences in patient characteristics, optimized patient selection, or refined choice of target vessel.
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BACKGROUND: While transradial access is favored for cardiac catheterization, the radial artery (RA) is increasingly preferred for coronary artery bypass grafting. Whether the RA is suitable for use as a graft following instrumentation for transradial access remains uncertain. METHODS: Consecutive patients from 2015 to 2019 who underwent coronary artery bypass grafting using both the left and right RAs as grafts were included. Instrumented RAs underwent careful preoperative assessment for suitability. The clinical analysis was stratified by whether patients received an instrumented RA graft (instrumented versus noninstrumented groups). Eligible patients with both instrumented and noninstrumented RAs underwent computed tomography coronary angiography to evaluate graft patency. The primary outcome was a within-patient paired analysis of graft patency comparing instrumented to noninstrumented RA grafts. RESULTS: Of the 1123 patients who underwent coronary artery bypass grafting, 294 had both the left and right RAs used as grafts and were included. There were 126 and 168 patients in the instrumented and noninstrumented groups, respectively. Baseline characteristics and perioperative outcomes were comparable. The rate of major adverse cardiac events at 2 years following coronary artery bypass grafting was 2.4% in the instrumented group and 5.4% in the noninstrumented group (hazard ratio, 0.44 [95% CI, 0.12-1.61]; P=0.19). There were 50 patients included in the graft patency analysis. At a median follow-up of 4.3 (interquartile range, 3.7-4.5) years, 40/50 (80%) instrumented and 41/50 (82%) noninstrumented grafts were patent (odds ratio, 0.86 [95% CI, 0.29-2.52]; P>0.99). No significant differences were observed in the luminal diameter or cross-sectional area of the instrumented and noninstrumented RA grafts. CONCLUSIONS: There was no evidence found in this study that RA graft patency was affected by prior transradial access, and the use of an instrumented RA was not associated with worse outcomes in the exploratory clinical analysis. Although conduits must be carefully selected, prior transradial access should not be considered an absolute contraindication to the use of the RA as a bypass graft. REGISTRATION: URL: https://www.anzctr.org.au/; Unique identifier: ACTRN12621000257864.
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Cateterismo Cardíaco , Angiografía Coronaria , Puente de Arteria Coronaria , Enfermedad de la Arteria Coronaria , Oclusión de Injerto Vascular , Arteria Radial , Grado de Desobstrucción Vascular , Humanos , Arteria Radial/diagnóstico por imagen , Arteria Radial/trasplante , Arteria Radial/fisiopatología , Masculino , Femenino , Puente de Arteria Coronaria/efectos adversos , Anciano , Cateterismo Cardíaco/efectos adversos , Cateterismo Cardíaco/instrumentación , Persona de Mediana Edad , Resultado del Tratamiento , Oclusión de Injerto Vascular/etiología , Oclusión de Injerto Vascular/fisiopatología , Oclusión de Injerto Vascular/diagnóstico por imagen , Factores de Tiempo , Enfermedad de la Arteria Coronaria/diagnóstico por imagen , Enfermedad de la Arteria Coronaria/fisiopatología , Enfermedad de la Arteria Coronaria/terapia , Enfermedad de la Arteria Coronaria/cirugía , Factores de Riesgo , Estudios Retrospectivos , Cateterismo Periférico/efectos adversos , Punciones , Medición de RiesgoRESUMEN
BACKGROUND: There is increasing awareness that patients without standard modifiable risk factors (SMuRFs; diabetes, hypercholesterolaemia, hypertension and smoking) may represent a unique subset of patients with acute coronary syndrome (ACS). We aimed to investigate the prevalence and outcomes of patients with SMuRF-less ACS undergoing percutaneous coronary intervention (PCI) compared with those with SMuRFs. METHODS: We analysed data from the Melbourne Interventional Group PCI Registry. Patients with coronary artery disease were excluded. The primary outcome was 30-day mortality. Secondary outcomes included in-hospital and 30-day events. Long-term mortality was investigated using Cox-proportional hazards regression. RESULTS: From 1 January 2005 to 31 December 2020, 2727/18 988 (14.4%) patients were SMuRF less, with the proportion increasing over time. Mean age was similar for patients with and without SMuRFs (63 years), and fewer females were SMuRF-less (19.8% vs 25.4%, p<0.001). SMuRF-less patients were more likely to present with cardiac arrest (6.6% vs 3.9%, p<0.001) and ST-elevation myocardial infarction (59.1% vs 50.8%, p<0.001) and were more likely to experience postprocedural cardiogenic shock (4.5% vs 3.6%, p=0.019) and arrhythmia (11.2% vs 9.9%, p=0.029). At 30 days, mortality, myocardial infarction, revascularisation and major adverse cardiac and cerebrovascular events did not differ between the groups. During median follow-up of 7 years, SMuRF-less patients had an adjusted 13% decreased rate of mortality (HR 0.87 (95% CI 0.78 to 0.97)). CONCLUSIONS: The proportion of SMuRF-less patients increased over time. Presentation was more often a devastating cardiac event compared with those with SMuRFs. No difference in 30-day outcomes was observed and SMuRF-less patients had lower hazard for long-term mortality.
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Síndrome Coronario Agudo , Intervención Coronaria Percutánea , Sistema de Registros , Humanos , Síndrome Coronario Agudo/terapia , Síndrome Coronario Agudo/mortalidad , Síndrome Coronario Agudo/epidemiología , Síndrome Coronario Agudo/cirugía , Femenino , Masculino , Intervención Coronaria Percutánea/efectos adversos , Persona de Mediana Edad , Prevalencia , Anciano , Factores de Riesgo , Resultado del Tratamiento , Factores de Tiempo , Medición de Riesgo/métodos , Estudios Retrospectivos , Estudios de Seguimiento , Tasa de Supervivencia/tendencias , Mortalidad Hospitalaria/tendencias , Victoria/epidemiologíaRESUMEN
BACKGROUND: Several changes occur in the central nervous system with increasing age that contribute toward declines in mobility. Neurorehabilitation has proven effective in improving motor function though achieving sustained behavioral and neuroplastic adaptations is more challenging. While effective, rehabilitation usually follows adverse health outcomes, such as injurious falls. This reactive intervention approach may be less beneficial than prevention interventions. Therefore, we propose the development of a prehabilitation intervention approach to address mobility problems before they lead to adverse health outcomes. This protocol article describes a pilot study to examine the feasibility and acceptability of a home-based, self-delivered prehabilitation intervention that combines motor imagery (mentally rehearsing motor actions without physical movement) and neuromodulation (transcranial direct current stimulation, tDCS; to the frontal lobes). A secondary objective is to examine preliminary evidence of improved mobility following the intervention. METHODS: This pilot study has a double-blind randomized controlled design. Thirty-four participants aged 70-95 who self-report having experienced a fall within the prior 12 months or have a fear of falling will be recruited. Participants will be randomly assigned to either an active or sham tDCS group for the combined tDCS and motor imagery intervention. The intervention will include six 40-min sessions delivered every other day. Participants will simultaneously practice the motor imagery tasks while receiving tDCS. Those individuals assigned to the active group will receive 20 min of 2.0-mA direct current to frontal lobes, while those in the sham group will receive 30 s of stimulation to the frontal lobes. The motor imagery practice includes six instructional videos presenting different mobility tasks related to activities of daily living. Prior to and following the intervention, participants will undergo laboratory-based mobility and cognitive assessments, questionnaires, and free-living activity monitoring. DISCUSSION: Previous studies report that home-based, self-delivered tDCS is safe and feasible for various populations, including neurotypical older adults. Additionally, research indicates that motor imagery practice can augment motor learning and performance. By assessing the feasibility (specifically, screening rate (per month), recruitment rate (per month), randomization (screen eligible who enroll), retention rate, and compliance (percent of completed intervention sessions)) and acceptability of the home-based motor imagery and tDCS intervention, this study aims to provide preliminary data for planning larger studies. TRIAL REGISTRATION: This study is registered on ClinicalTrials.gov (NCT05583578). Registered October 13, 2022. https://www. CLINICALTRIALS: gov/study/NCT05583578.
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BACKGROUND: Although ultrasound (US) guidance for vascular access has been widely adopted, its use for transradial access (TRA) in the cardiac catheterisation laboratory is rare. There is a perception that US guidance does not offer a clinically relevant benefit over traditional palpation-guided TRA, amplified by inconsistent findings of individual studies. METHOD: A systematic review of MEDLINE, EMBASE and the Cochrane Library identified studies comparing US to palpation-guided TRA for cardiac catheterisation. Studies evaluating radial artery (RA) cannulation for any other reason were excluded. Event rates and risk ratios (RRs) were pooled for meta-analysis. Access failure was the primary outcome. A random-effects model was used for analysis. RESULTS: Of the 977 records screened, four studies with a total of 1,718 patients (861 US-guided and 864 palpation-guided procedures) were included in the meta-analysis. Most procedures were elective. The pooled analysis showed US guidance significantly lowered the risk of access failure (RR 0.45; 95% confidence interval [CI] 0.21-0.97; p=0.04). Heterogeneity was moderate (I2=51.2%; p=0.105). There was a strong trend to improved first-pass success with US (RR 1.29; 95% CI 1.00-1.66; p=0.05; I2=83.8%), although no differences were found in rates of difficult access (RR 0.29; 95% CI 0.07-1.18; p=0.09; I2=88.3%). Salvage US guidance was successful in 30/41 (73.2%) patients following failed palpation-guided TRA. No differences were found in already low complication rates including RA spasm (RR 1.18; 95% CI 0.70-1.99; p=0.53; I2=0.0%) and bleeding (RR 1.32; 95% CI 0.46-3.80; p=0.60; I2=0.0%). CONCLUSIONS: US guidance was found to improve TRA success in the cardiac catheterisation laboratory. Further investigation is necessary to determine whether routine, selective, or salvage use of US confers the most RA protection, patient satisfaction, and overall clinical benefit. (PROSPERO registration: CRD42022332238).
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Introduction: Walking in complex environments increases the cognitive demand of locomotor control; however, our understanding of the neural mechanisms contributing to walking on uneven terrain is limited. We used a novel method for altering terrain unevenness on a treadmill to investigate the association between terrain unevenness and cortical activity in the prefrontal cortex, a region known to be involved in various cognitive functions. Methods: Prefrontal cortical activity was measured with functional near infrared spectroscopy while participants walked on a novel custom-made terrain treadmill surface across four different terrains: flat, low, medium, and high levels of unevenness. The assessments were conducted in younger adults, older adults with better mobility function and older adults with worse mobility function. Mobility function was assessed using the Short Physical Performance Battery. The primary hypothesis was that increasing the unevenness of the terrain would result in greater prefrontal cortical activation in all groups. Secondary hypotheses were that heightened prefrontal cortical activation would be observed in the older groups relative to the younger group, and that prefrontal cortical activation would plateau at higher levels of terrain unevenness for the older adults with worse mobility function, as predicted by the Compensation Related Utilization of Neural Circuits Hypothesis. Results: The results revealed a significant main effect of terrain, indicating a significant increase in prefrontal cortical activation with increasing terrain unevenness during walking in all groups. A significant main effect of group revealed that prefrontal cortical activation was higher in older adults with better mobility function compared to younger adults and older adults with worse mobility function in all pooled terrains, but there was no significant difference in prefrontal cortical activation between older adults with worse mobility function and younger adults. Contrary to our hypothesis, the older group with better mobility function displayed a sustained increase in activation but the other groups did not, suggestive of neural compensation. Additional findings were that task-related increases in prefrontal cortical activation during walking were lateralized to the right hemisphere in older adults with better mobility function but were bilateral in older adults with worse mobility function and younger adults. Discussion: These findings support that compared to walking on a flat surface, walking on uneven terrain surfaces increases demand on cognitive control resources as measured by prefrontal cortical activation.
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Low vaginal self-sampling has been pioneered as an important development to improve uptake of cervical screening globally. Limited research is available in specific patient groups in the UK exploring views around self-sampling to detect high-risk human papillomavirus (hrHPV) DNA. Therefore, we explored patient views to support development of a novel point-of-care self-sampling cervical cancer screening device, by undertaking a cross-sectional semi-structured questionnaire survey to explore preferences, acceptability, barriers and facilitators around self-sampling. Patients attending a colposcopy clinic, 25-64 years old, were invited to participate after having carried out a low vaginal self-sample using a regular flocked swab. Participants self-completed an anonymous 12-point questionnaire. Quantitative data were analysed in MS Excel and Graphpad Prism, and qualitative data with Nvivo. We recruited 274 patients with a questionnaire response rate of 76%. Acceptability of self-sampling was high (95%, n = 187/197; Cronbachs-α = 0.778). Participants were asked their choice of future screening method: a) low vaginal self-sampling, b) healthcare professional collected vaginal swab, c) cervical brush sample with healthcare professional speculum examination, or d) no preference. Preferences were: a) 37% (n = 74/198), b) 19% (n = 37/198); c) 9% (n = 17/198), and d) 35% (n = 70/198), showing no single option as a strong preference. Key motivators were: Test simplicity (90%, n = 170/190), speed (81%, n = 153/190) and less pain (65%, n = 123/190). Barriers included lack of confidence taking the sample (53%, n = 10/19), resulting in preference for a healthcare professional sample (47%, n = 9/19). Whilst self-sampling showed high acceptability, lack of strong preference for screening method may reflect that respondents attending colposcopy are already engaged with screening and have differing perception of cervical cancer risk. This group appear less likely to 'switch' to self-sampling, and it may be better targeted within primary and community care, focusing on under-screened populations. Any shift in this paradigm in the UK requires comprehensive education and support for patients and providers.
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Older adults exhibit larger individual differences in walking ability and cognitive function than young adults. Characterizing intrinsic brain connectivity differences in older adults across a wide walking performance spectrum may provide insight into the mechanisms of functional decline in some older adults and resilience in others. Thus, the objectives of this study were to: (1) determine whether young adults and high- and low-functioning older adults show group differences in brain network segregation, and (2) determine whether network segregation is associated with working memory and walking function in these groups. The analysis included 21 young adults and 81 older adults. Older adults were further categorized according to their physical function using a standardized assessment; 54 older adults had low physical function while 27 were considered high functioning. Structural and functional resting state magnetic resonance images were collected using a Siemens Prisma 3T scanner. Working memory was assessed with the NIH Toolbox list sorting test. Walking speed was assessed with a 400 m-walk test at participants' self-selected speed. We found that network segregation in mobility-related networks (sensorimotor, vestibular, and visual networks) was higher in younger adults compared to older adults. There were no group differences in laterality effects on network segregation. We found multivariate associations between working memory and walking speed with network segregation scores. Higher right anterior cingulate cortex network segregation was associated with higher working memory function. Higher right sensorimotor, right vestibular, right anterior cingulate cortex, and lower left anterior cingulate cortex network segregation was associated with faster walking speed. These results are unique and significant because they demonstrate higher network segregation is largely related to higher physical function and not age alone.
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INTRODUCTION: Trauma contributes to the greatest loss of disability-adjusted life-years for adolescents and young adults worldwide. In the context of global abdominal trauma, the trauma laparotomy is the most commonly performed operation. Variation likely exists in how these patients are managed and their subsequent outcomes, yet very little global data on the topic currently exists. The objective of the GOAL-Trauma study is to evaluate both patient and injury factors for those undergoing trauma laparotomy, their clinical management and postoperative outcomes. METHODS: We describe a planned prospective multicentre observational cohort study of patients undergoing trauma laparotomy. We will include patients of all ages who present to hospital with a blunt or penetrating injury and undergo a trauma laparotomy within 5 days of presentation to the treating centre. The study will collect system, patient, process and outcome data, following patients up until 30 days postoperatively (or until discharge or death, whichever is first). Our sample size calculation suggests we will need to recruit 552 patients from approximately 150 recruiting centres. DISCUSSION: The GOAL-Trauma study will provide a global snapshot of the current management and outcomes for patients undergoing a trauma laparotomy. It will also provide insight into the variation seen in the time delays for receiving care, the disease and patient factors present, and patient outcomes. For current standards of trauma care to be improved worldwide, a greater understanding of the current state of trauma laparotomy care is paramount if appropriate interventions and targets are to be identified and implemented.
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Traumatismos Abdominales , Heridas Penetrantes , Adulto Joven , Adolescente , Humanos , Estudios Prospectivos , Laparotomía/métodos , Traumatismos Abdominales/cirugía , Heridas Penetrantes/cirugía , Estudios Retrospectivos , Estudios Observacionales como Asunto , Estudios Multicéntricos como AsuntoRESUMEN
Recent studies have combined DNA methyltransferase footprinting of genomic DNA in nuclei with long-read sequencing, resulting in detailed chromatin maps for multi-kilobase stretches of genomic DNA from one cell. Theoretically, nucleosome footprints and nucleosome-depleted regions can be identified using M.EcoGII, which methylates adenines in any sequence context, providing a high-resolution map of accessible regions in each DNA molecule. Here, we report PacBio long-read sequence data for budding yeast nuclei treated with M.EcoGII and a bioinformatic pipeline which corrects for three key challenges undermining this promising method. First, detection of m6A in individual DNA molecules by the PacBio software is inefficient, resulting in false footprints predicted by random gaps of seemingly unmethylated adenines. Second, there is a strong bias against m6A base calling as AT content increases. Third, occasional methylation occurs within nucleosomes, breaking up their footprints. After correcting for these issues, our pipeline calculates a correlation coefficient-based score indicating the extent of chromatin heterogeneity within the cell population for every gene. Although the population average is consistent with that derived using other techniques, we observe a wide range of heterogeneity in nucleosome positions at the single-molecule level, probably reflecting cellular chromatin dynamics.
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Cromatina , Metilación de ADN , Nucleosomas , Análisis de Secuencia de ADN , Cromatina/metabolismo , Cromatina/genética , Cromatina/química , Nucleosomas/genética , Nucleosomas/metabolismo , Análisis de Secuencia de ADN/métodos , Programas Informáticos , Genoma Fúngico , Secuenciación de Nucleótidos de Alto Rendimiento/métodos , Saccharomycetales/genética , Saccharomycetales/metabolismo , Adenosina/análogos & derivados , Adenosina/metabolismo , Adenosina/genéticaRESUMEN
BACKGROUND: Suboptimal coronary reperfusion (no reflow) is common in acute coronary syndrome percutaneous coronary intervention (PCI) and is associated with poor outcomes. We aimed to develop and externally validate a clinical risk score for angiographic no reflow for use following angiography and before PCI. METHODS: We developed and externally validated a logistic regression model for prediction of no reflow among adult patients undergoing PCI for acute coronary syndrome using data from the Melbourne Interventional Group PCI registry (2005-2020; development cohort) and the British Cardiovascular Interventional Society PCI registry (2006-2020; external validation cohort). RESULTS: A total of 30â 561 patients (mean age, 64.1 years; 24% women) were included in the Melbourne Interventional Group development cohort and 440â 256 patients (mean age, 64.9 years; 27% women) in the British Cardiovascular Interventional Society external validation cohort. The primary outcome (no reflow) occurred in 4.1% (1249 patients) and 9.4% (41â 222 patients) of the development and validation cohorts, respectively. From 33 candidate predictor variables, 6 final variables were selected by an adaptive least absolute shrinkage and selection operator regression model for inclusion (cardiogenic shock, ST-segment-elevation myocardial infarction with symptom onset >195 minutes pre-PCI, estimated stent length ≥20 mm, vessel diameter <2.5 mm, pre-PCI Thrombolysis in Myocardial Infarction flow <3, and lesion location). Model discrimination was very good (development C statistic, 0.808; validation C statistic, 0.741) with excellent calibration. Patients with a score of ≥8 points had a 22% and 27% risk of no reflow in the development and validation cohorts, respectively. CONCLUSIONS: The no-reflow prediction in acute coronary syndrome risk score is a simple count-based scoring system based on 6 parameters available before PCI to predict the risk of no reflow. This score could be useful in guiding preventative treatment and future trials.
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Síndrome Coronario Agudo , Infarto del Miocardio , Fenómeno de no Reflujo , Intervención Coronaria Percutánea , Infarto del Miocardio con Elevación del ST , Adulto , Humanos , Femenino , Persona de Mediana Edad , Anciano , Masculino , Intervención Coronaria Percutánea/efectos adversos , Síndrome Coronario Agudo/diagnóstico por imagen , Síndrome Coronario Agudo/terapia , Angiografía Coronaria , Resultado del Tratamiento , Factores de Riesgo , Infarto del Miocardio/etiología , Infarto del Miocardio con Elevación del ST/diagnóstico por imagen , Infarto del Miocardio con Elevación del ST/terapia , Infarto del Miocardio con Elevación del ST/etiología , Fenómeno de no Reflujo/diagnóstico por imagen , Fenómeno de no Reflujo/etiologíaRESUMEN
Walking performance and cognitive function demonstrate strong associations in older adults, with both declining with advancing age. Walking requires the use of cognitive resources, particularly in complex environments like stepping over obstacles. A commonly implemented approach for measuring the cognitive control of walking is a dual-task walking assessment, in which walking is combined with a second task. However, dual-task assessments have shortcomings, including issues with scaling the task difficulty and controlling for task prioritization. Here we present a new assessment designed to be less susceptible to these shortcomings while still challenging cognitive control of walking: the Obstructed Vision Obstacle (OBVIO) task. During the task, participants hold a lightweight tray at waist level obstructing their view of upcoming foam blocks, which are intermittently spaced along a 10 m walkway. This forces the participants to use cognitive resources (e.g., attention and working memory) to remember the exact placement of upcoming obstacles to facilitate successful crossing. The results demonstrate that adding the obstructed vision board significantly slowed walking speed by an average of 0.26 m/s and increased the number of obstacle strikes by 8-fold in healthy older adults (n = 74). Additionally, OBVIO walking performance (a score based on both speed and number of obstacle strikes) significantly correlated with computer-based assessments of visuospatial working memory, attention, and verbal working memory. These results provide initial support that the OBVIO task is a feasible walking test that demands cognitive resources. This study lays the groundwork for using the OBVIO task in future assessment and intervention studies.
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Marcha , Caminata , Humanos , Anciano , Cognición , Velocidad al Caminar , Atención , Análisis y Desempeño de TareasRESUMEN
BACKGROUND: Procarboxypeptidase B2 (proCPB2 or TAFI) is a zymogen that after activation cleaves C-terminal basic residues from peptides or proteins with many identified targets. A splice variant of CPB2 has been found in the brain lacking essential residues for its carboxypeptidase function. The aim was to determine CPB2 expression in the brain and effects of CPB2 deficiency (Cpb2 -/-) on behavior. MATERIALS AND METHODS: Behavioral effects were tested by comparing Cpb2 -/- mice in short-term (open field and elevated zero maze tests) and long-term (Phenotyper) observations with wild-type (WT) controls. RESULTS: Long-term observation compared day 1 (acclimatizing to novel environment) to day 4 (fully acclimatized) with the inactive (day) and active (night) periods analyzed separately. Brain expression of CPB2 mRNA and protein was interrogated in publicly available databases. Long-term observation demonstrated differences between WT and Cpb2 -/- mice in several parameters. For example, Cpb2 -/- mice moved more frequently on both days 1 and 4, especially in the normally inactive periods. Cpb2 -/- mice spent more time on the shelter and less time in it. Differences were more pronounced on day 4 after the mice had fully acclimatized. In short-term observations, no differences were observed between Cpb2 -/- mice and WT mice. Brain expression of CBP2 was not detectable in the human protein atlas. Databases of single-cell RNAseq did not show expression of CPB2 mRNA in either human or mouse brain. CONCLUSION: Continuous observation of home-cage behavior suggests that Cpb2 -/- mice are more active than WT mice, show different day-night activity levels, and might have a different way of processing information.
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Carboxipeptidasa B2 , Humanos , Animales , Ratones , Carboxipeptidasa B2/genética , Encéfalo/metabolismo , ARN Mensajero/genéticaRESUMEN
Recent studies have combined DNA methyltransferase footprinting of genomic DNA in nuclei with long-read sequencing, resulting in detailed chromatin maps for multi-kilobase stretches of genomic DNA from one cell. Theoretically, nucleosome footprints and nucleosome-depleted regions can be identified using M.EcoGII, which methylates adenines in any sequence context, providing a high-resolution map of accessible regions in each DNA molecule. Here we report PacBio long-read sequence data for budding yeast nuclei treated with M.EcoGII and a bioinformatic pipeline which corrects for three key challenges undermining this promising method. First, detection of m6A in individual DNA molecules by the PacBio software is inefficient, resulting in false footprints predicted by random gaps of seemingly unmethylated adenines. Second, there is a strong bias against m6A base calling as AT content increases. Third, occasional methylation occurs within nucleosomes, breaking up their footprints. After correcting for these issues, our pipeline calculates a correlation coefficient-based score indicating the extent of chromatin heterogeneity within the cell population for every gene. Although the population average is consistent with that derived using other techniques, we observe a wide range of heterogeneity in nucleosome positions at the single-molecule level, probably reflecting cellular chromatin dynamics.
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Stroke survivors frequently report increased perceived challenge of walking (PCW) in complex environments, restricting their daily ambulation. PCW is conventionally measured through subjective questionnaires or, more recently, through objective quantification of sympathetic nervous system activity during walking tasks. However, how these measurements of PCW reflect daily walking activity post-stroke is unknown. We aimed to compare the subjective and objective assessments of PCW in predicting home and community ambulation. In 29 participants post-stroke, we measured PCW subjectively with the Activities-specific Balance Confidence (ABC) Scale and objectively through electrodermal activity, quantified by change in skin conductance levels (SCL) and skin conductance responses (SCR) between outdoor-complex and indoor-steady-state walking. High-PCW participants were categorized into high-change SCL (ΔSCL ≥ 1.7 µs), high-change SCR (ΔSCR ≥ 0.2 µs) and low ABC (ABC < 72%) groups, while low-PCW participants were categorized into low-change SCL (ΔSCL < 1.7 µs), low-change SCR (ΔSCR < 0.2 µs) and high-ABC (ABC ≥ 72%) groups. Number and location of daily steps were quantified with accelerometry and Global Positioning System devices. Compared to low-change SCL group, the high-change SCL group took fewer steps in home and community (p = 0.04). Neither ABC nor SCR groups differed in home or community steps/day. Objective measurement of PCW via electrodermal sensing more accurately represents home and community ambulation compared to the subjective questionnaire.
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Rehabilitación de Accidente Cerebrovascular , Accidente Cerebrovascular , Humanos , Caminata/fisiología , Actividades Cotidianas , Sistema Nervioso SimpáticoRESUMEN
BACKGROUND: Left ventricular (LV) dysfunction and ischaemic heart disease (IHD) are common among women. However, women tend to present later and are less likely to receive guideline-directed medical therapy (GDMT) compared with men. METHODS: We analysed prospectively collected data (2005-2018) from a multicentre registry on GDMT 30 days after percutaneous coronary intervention in 13,015 patients with LV ejection fraction <50%. Guideline-directed medical therapy was defined as beta blocker, angiotensin-converting enzyme inhibitor/angiotensin receptor blocker±mineralocorticoid receptor antagonist. Long-term mortality was determined by linkage with the Australian National Death Index. RESULTS: Women represented 20% (2,634) of the total cohort. Mean age was 65±12 years. Women were on average >5 years, with higher body mass index and higher rates of hypertension, diabetes, renal dysfunction, prior stroke, and rheumatoid arthritis. Guideline-directed medical therapy was similar between sexes (73% vs 72%; p=0.58), although women were less likely to be on an angiotensin-converting enzyme inhibitor/angiotensin receptor blocker (80% vs 82%; p=0.02). Women were less likely to be on statin therapy (p<0.001) or a second antiplatelet agent (p=0.007). Women had higher unadjusted long-term mortality (25% vs 19%; p<0.001); however, there were no differences in long-term mortality between sexes on adjusted analysis (hazard ratio 0.99; 95% confidence interval 0.87-1.14; p=0.94). CONCLUSIONS: Rates of GDMT for LV dysfunction were high and similar between sexes; however, women were less likely to be on appropriate IHD secondary prevention. The increased unadjusted long-term mortality in women was attenuated in adjusted analysis, which highlights the need for optimisation of baseline risk to improve long-term outcomes of women with IHD and comorbid LV dysfunction.
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Enfermedad de la Arteria Coronaria , Insuficiencia Cardíaca , Isquemia Miocárdica , Disfunción Ventricular Izquierda , Humanos , Femenino , Masculino , Persona de Mediana Edad , Anciano , Caracteres Sexuales , Australia/epidemiología , Isquemia Miocárdica/complicaciones , Isquemia Miocárdica/tratamiento farmacológico , Isquemia Miocárdica/epidemiología , Enfermedad de la Arteria Coronaria/tratamiento farmacológico , Inhibidores de la Enzima Convertidora de Angiotensina/uso terapéutico , Antagonistas Adrenérgicos beta/uso terapéutico , Disfunción Ventricular Izquierda/tratamiento farmacológico , Disfunción Ventricular Izquierda/epidemiología , Volumen Sistólico/fisiología , Antagonistas de Receptores de Angiotensina/uso terapéuticoRESUMEN
BACKGROUND: Recent US guidelines recommend lower blood pressure (BP) targets in hypertension, but aggressive lowering of diastolic BP (DBP) can occur at the expense of myocardial perfusion, particularly in the presence of coronary artery disease. We sought to establish the long-term impact of low DBP on mortality among patients undergoing percutaneous coronary intervention with well-controlled systolic BP. METHODS: We analyzed data from 12 965 patients undergoing percutaneous coronary intervention between 2009 and 2018 from the Melbourne Interventional Group registry who had a preprocedural systolic BP of ≤140 mm Hg. Patients with ST-elevation myocardial infarction, cardiogenic shock, and out-of-hospital arrest were excluded. Patients were stratified into 5 groups according to preprocedural DBP: <50, 50 to 59, 60 to 69, 70 to 79, and ≥80 mm Hg. The primary outcome was long-term, all-cause mortality. Mortality data were derived from the Australian National Death Index. RESULTS: Patients with DBP<50 mm Hg were older with higher rates of diabetes, renal impairment, prior myocardial infarction, left ventricular dysfunction, peripheral and cerebrovascular disease (all P<0.001). Patients with DBP<50 mm Hg had higher 30-day (2.5% versus 0.7% for the other 4 quintiles; P<0.0001) and long-term mortality (median, 3.6 years; follow-up, 29% versus 11%; P<0.0001). Cox-regression analysis revealed that DBP<50 mm Hg was an independent predictor of long-term mortality (hazard ratio [HR], 1.55 [95% CI, 1.20-2.00]; P=0.001). CONCLUSIONS: In patients with well-controlled systolic BP undergoing percutaneous coronary intervention, low DBP (<50 mm Hg) is an independent predictor of long-term mortality.
Asunto(s)
Infarto del Miocardio , Intervención Coronaria Percutánea , Humanos , Presión Sanguínea/fisiología , Resultado del Tratamiento , Australia , Intervención Coronaria Percutánea/efectos adversos , Factores de Riesgo , Sistema de RegistrosRESUMEN
Mobile brain imaging with high-density electroencephalography (EEG) can provide insight into the cortical processes involved in complex human walking tasks. While uneven terrain is common in the natural environment and poses challenges to human balance control, there is limited understanding of the supraspinal processes involved with traversing uneven terrain. The primary objective of this study was to quantify electrocortical activity related to parametric variations in terrain unevenness for neurotypical young adults. We used high-density EEG to measure brain activity when thirty-two young adults walked on a novel custom-made uneven terrain treadmill surface with four levels of difficulty at a walking speed tailored to each participant. We identified multiple brain regions associated with uneven terrain walking. Alpha (8 - 13 Hz) and beta (13 - 30 Hz) spectral power decreased in the sensorimotor and posterior parietal areas with increasing terrain unevenness while theta (4 - 8 Hz) power increased in the mid/posterior cingulate area with terrain unevenness. We also found that within stride spectral power fluctuations increased with terrain unevenness. Our secondary goal was to investigate the effect of parametric changes in walking speed (0.25 m/s, 0.5m/s, 0.75 m/s, 1.0 m/s) to differentiate the effects of walking speed from uneven terrain. Our results revealed that electrocortical activities only changed substantially with speed within the sensorimotor area but not in other brain areas. Together, these results indicate there are distinct cortical processes contributing to the control of walking over uneven terrain versus modulation of walking speed on smooth, flat terrain. Our findings increase our understanding of cortical involvement in an ecologically valid walking task and could serve as a benchmark for identifying deficits in cortical dynamics that occur in people with mobility deficits.
RESUMEN
Accurate and rapid point-of-care (PoC) diagnostics are critical to the control of the COVID-19 pandemic. The current standard for accurate diagnosis of SARS-CoV-2 is laboratory-based reverse transcription polymerase chain reaction (RT-PCR) assays. Here, a preliminary prospective performance evaluation of the QuantuMDx Q-POC SARS-CoV-2 RT-PCR assay is reported. Between November 2020 and March 2021, 49 longitudinal combined nose/throat (NT) swabs from 29 individuals hospitalised with RT-PCR confirmed COVID-19 were obtained at St George's Hospital, London. In addition, 101 mid-nasal (MN) swabs were obtained from healthy volunteers in June 2021. These samples were used to evaluate the Q-POC SARS-CoV-2 RT-PCR assay. The primary analysis was to compare the sensitivity and specificity of the Q-POC test against a reference laboratory-based RT-PCR assay. The overall sensitivity of the Q-POC test compared with the reference test was 96.88% (83.78- 99.92% CI) for a cycle threshold (Ct) cut-off value for the reference test of 35 and 80.00% (64.35-90.95% CI) without altering the reference test's Ct cut-off value of 40. The Q-POC test is a sensitive, specific and rapid PoC test for SARS-CoV-2 at a reference Ct cut-off value of 35. The Q-POC test provides an accurate option for RT-PCR at PoC without the need for sample pre-processing and laboratory handling, enabling rapid diagnosis and clinical triage in acute care and other settings.