Optical coherence tomography predictors of clinical outcomes after stent implantation: the ILUMIEN IV trial.

BACKGROUND AND AIMS: Observational registries have suggested that optical coherence tomography (OCT) imaging-derived parameters may predict adverse events after drug-eluting stent (DES) implantation. The present analysis sought to determine the OCT predictors of clinical outcomes from the large-scale ILUMIEN IV trial. METHODS: ILUMIEN IV was a prospective, single-blind trial of 2487 patients with diabetes or high-risk lesions randomized to OCT-guided versus angiography-guided DES implantation. All patients underwent final OCT imaging (blinded in the angiography-guided arm). From more than 20 candidates, the independent OCT predictors of 2-year target lesion failure (TLF; the primary endpoint), cardiac death or target-vessel myocardial infarction (TV-MI), ischaemia-driven target lesion revascularization (ID-TLR), and stent thrombosis were analysed by multivariable Cox proportional hazard regression in single treated lesions. RESULTS: A total of 2128 patients had a single treated lesion with core laboratory-analysed final OCT. The 2-year Kaplan-Meier rates of TLF, cardiac death or TV-MI, ID-TLR, and stent thrombosis were 6.3% (n = 130), 3.3% (n = 68), 4.3% (n = 87), and 0.9% (n = 18), respectively. The independent predictors of 2-year TLF were a smaller minimal stent area (per 1 mm2 increase: hazard ratio 0.76, 95% confidence interval 0.68-0.89, P < .0001) and proximal edge dissection (hazard ratio 1.77, 95% confidence interval 1.20-2.62, P = .004). The independent predictors of cardiac death or TV-MI were smaller minimal stent area and longer stent length; of ID-TLR were smaller intra-stent flow area and proximal edge dissection; and of stent thrombosis was smaller minimal stent expansion. CONCLUSIONS: In the ILUMIEN IV trial, the most important OCT-derived post-DES predictors of both safety and effectiveness outcomes were parameters related to stent area, expansion and flow, proximal edge dissection, and stent length.

Systematic review of bovine and zoonotic tuberculosis in the Western Pacific and the Southeast Asia regions of the World Health Organization.

Introduction: Tuberculosis (TB) remains a leading cause of mortality worldwide. We conducted this systematic review to understand the distribution of bovine and zoonotic tuberculosis in the World Health Organization (WHO)'s Southeast Asia Region (SEAR) and Western Pacific Region (WPR) to inform our understanding of the risk posed by this disease. Methods: A two-pronged strategy was used by evaluating data from peer-reviewed literature and official reports. A systematic search was conducted using a structured query in four databases (Web of Science, Scopus, Medline, and PubMed) to identify any reports of the occurrence of zoonotic TB. No language and time constraints were used during the search, but non-English language articles were later excluded. The official data were sourced from the World Organization for Animal Health's (WOAH) World Animal Health Information System (WAHIS) and WHO's global TB database. Results: The retrieved records from SEAR and WPR (n = 113) were screened for eligibility, and data about disease occurrence were extracted and tabulated. In SEAR, all of the five studies that conducted Mycobacterium speciation (5/6) in humans were from India, and the reported Mycobacterium species included M. tuberculosis, M. bovis, M. scrofulacium, M. kansasii, M. phlei, M. smegmatis and M. orygis. In WPR, Mycobacterium speciation investigations in humans were conducted in Australia (8), China (2), Japan (2), NewZealand (2) and Malaysia (1), and the reported Mycobacterium species included M. bovis, M. africanum and M. tuberculosis. Seven countries in WHO's SEAR have officially reported the occurrence of Mycobacterium bovis in their animals: Bangladesh, India, Indonesia, Myanmar, Nepal, Sri Lanka and Thailand. In WPR, the WAHIS information system includes reports of the identification of M. bovis from 11 countries - China, Fiji, Japan, Malaysia, Mongolia, New Zealand, the Philippines, the Republic of Korea, Singapore, Tonga and Viet Nam. In contrast, human zoonotic TB cases in the WHO database were only listed from Australia, Brunei Darussalam and Palau countries. Discussion: The available data suggests under-reporting of zoonotic TB in the regions. Efforts are required to strengthen zoonotic TB surveillance systems from both animal and human health sides to better understand the impact of zoonotic TB in order to take appropriate action to achieve the goal of ending the TB epidemic.

Polyphenols mediated attenuation of diabetes associated cardiovascular complications: A comprehensive review.

Background: Diabetes mellitus is a common chronic metabolic disorder that is characterized by increased levels of glucose for prolonged periods of time. Incessant hyperglycemia leads to diabetic complications such as retinopathy, nephropathy, and neuropathy, and cardiovascular complications such as ischemic heart disease, peripheral vascular disease, diabetic cardiomyopathy, stroke, etc. There are many studies that suggest that various polyphenols affect glucose homeostasis and can help to attenuate the complications associated with diabetes. Objective: This review focuses on the possible role of various dietary polyphenols in palliating diabetes-induced cardiovascular complications. This review also aims to give an overview of the interrelationship among ROS production (due to diabetes), inflammation, glycoxidative stress, and cardiovascular complications as well as the anti-hyperglycemic effects of dietary polyphenols. Methods: Various scientific databases including Scopus, Web of Science, Google Scholar, PubMed, Science Direct, Springer Link, and Wiley Online Library were used for searching articles that complied with the inclusion and exclusion criteria. Results: This review lists several polyphenols based on various pre-clinical and clinical studies that have anti-hyperglycemic potential as well as a protective function against cardiovascular complications. Conclusion: Several pre-clinical and clinical studies suggest that various dietary polyphenols can be a promising intervention for the attenuation of diabetes-associated cardiovascular complications.

Nonlinear relationships between eye gaze and recognition accuracy for ethnic ingroup and outgroup faces.

Researchers have used eye-tracking measures to explore the relationship between face encoding and recognition, including the impact of ethnicity on this relationship. Previous studies offer a variety of conflicting conclusions. This confusion may stem from misestimation of the relationship between encoding and recognition. First, most previous models fail to account for the structure of eye-tracking data, potentially falling prey to Simpson's paradox. Second, previous models assume a linear relationship between attention (e.g., the number of fixations to a to-be-remembered face) and recognition accuracy. Two eye-tracking studies (Ns = 41, 59), one online experiment that manipulates exposure (N = 150), and a mega-analysis examine the effects of ethnicity using what we believe to be more appropriate analytical models. Across studies and measures, we document a novel, critical pattern: The relationship between attention and recognition is nonlinear and negatively accelerating. At low levels of baseline attention, a small increment in attention improves recognition. However, as attention increases further, increments yield smaller and smaller benefits. This finding parallels work in learning and memory. In models that allow for nonlinearity, we find evidence that central features (eyes, nose, and mouth) generally contribute to recognition accuracy, potentially resolving disagreements in the field. We also find that the effects of attention on recognition are similar for ingroup and outgroup faces, which have important implications for theories of perceptual expertise. (PsycInfo Database Record (c) 2024 APA, all rights reserved).

Quasi-steady aerodynamic modeling and dynamic stability of mosquito-inspired flapping wing pico aerial vehicle.

Recent exploration in insect-inspired robotics has generated considerable interest. Among insects navigating at low Reynolds numbers, mosquitoes exhibit distinct flight characteristics, including higher wingbeat frequencies, reduced stroke amplitudes, and slender wings. This leads to unique aerodynamic traits such as trailing edge vortices via wake capture, diminished reliance on leading vortices, and rotational drag. This paper shows the energetic analysis of a mosquito-inspired flapping-wing Pico aerial vehicle during hovering, contributing insights to its future design and fabrication. The investigation relies on kinematic and quasi-steady aerodynamic modeling of a symmetric flapping-wing model with a wingspan of approximately 26 mm, considering translational, rotational, and wake capture force components. The control strategy adapts existing bird flapping wing approaches to accommodate insect wing kinematics and aerodynamic features. Flight controller design is grounded in understanding the impact of kinematics on wing forces. Additionally, a thorough analysis of the dynamic stability of the mosquito-inspired PAV model is conducted, revealing favorable controller response and maneuverability at a small scale. The modified model, incorporating rigid body dynamics and non-averaged aerodynamics, exhibits weak stability without a controller or sufficient power density. However, the controller effectively stabilizes the PAV model, addressing attitude and maneuverability. These preliminary findings offer valuable insights for the mechanical design, aerodynamics, and fabrication of RoboMos, an insect-inspired flapping wing pico aerial vehicle developed at UPM Malaysia.

Seroprevalence of Japanese encephalitis virus in pig populations of Tamil Nadu, India: Exploring the tropical endemic link of virus.

Japanese encephalitis virus (JEV) is a major cause of encephalitis in Southeast Asia. Tamil Nadu, a state located in the southern part of India, contributes substantially to the national burden of human JE cases every year. However, limited information is available on the epidemiology of JE in pig populations of Tamil Nadu. A cross-sectional study was conducted to assess JEV prevalence in pig populations of Tamil Nadu. A total of 710 pigs reared in 118 farms across 10 districts of Tamil Nadu were sampled using multistage cluster random sampling. Serum samples were analyzed for their JEV status using Immunoglobulin M (IgM) and Immunoglobulin G (IgG) Enzyme-Linked Immunosorbent Assay (ELISA). At the animal-level, the apparent JEV seroprevalence was 60.4% (95% CI: 56.8% - 64.0%) and the true seroprevalence was 50.1% (95% CI: 47.0% - 53.2%). The herd-level apparent seroprevalence was 94.1% (95% CI: 88.1% - 97.5%) and the true seroprevalence was 93.3% (95% CI: 89.5% - 96.2%). The intensity of JEV circulation was high in all the districts, with seroprevalence ranging between 43% and 100%. Pigs across all age categories were seropositive and a high overall seroprevalence of 95.2% (95% CI: 76.2% - 99.9%) was recorded in pigs older than 12 months. JEV seropositivity was recorded in all the seasons but the prevalence peaked in the monsoon (67.9%, 95% CI: 61.1% - 74.2%) followed by winter (65.1%, 95%CI: 57.4% - 72.2%) and summer (53.3%, 95% CI: 47.8% - 58.8%) seasons. The results indicate that JEV is endemic in pigs populations of the state and a one health approach is essential with collaborative actions from animal and public health authorities to control JE in Tamil Nadu, India.

Clinical profile of central nervous system space-occupying lesions and their association with CD4 counts in patients with HIV: A prospective observational study.

Background: Neurological manifestations are one of the major concerns for patients with human immunodeficiency virus (HIV). The secondary spectrum includes space-occupying lesions (SOL), including tuberculoma, cryptococcosis, candidiasis, toxoplasmosis, primary central nervous system lymphoma (PCNSL), and progressive multifocal leukoencephalopathy (PML). Aim: To assess the neurological manifestations, disease outcome, and their associations with cluster of differentiation 4 (CD4) counts in patients with HIV. Materials and Methods: This single-center, prospective, observational study was performed in the Department of General Medicine of a tertiary care institute, over a period of 2 years (January 2017 to December 2018). The study included 150 known or newly diagnosed HIV patients with CNS SOL. The physical examination, laboratory investigations, and imaging were conducted on every patient, and the findings were noted. Results: The patients mainly presented with hemiparesis (52%), had involvement of the frontal region (38.7%), and were diagnosed with tuberculoma (29.3%). Other diagnoses were toxoplasmosis (22.7%), PML (17.3%), PCNSL (15.3%), brain abscess (10%), and neurocysticercosis (5.3%). Of 150 patients, 136 (90.7%) were survivors, while 14 (9.3%) were non-survivors. The mean CD4 count was significantly less in patients with toxoplasmosis (P < 0.0001) and PCNSL (P = 0.02), and significantly higher in patients with tuberculoma (P < 0.0001) and brain abscess (P = 0.0009) relative to other causes of SOL. Moreover, the mean CD4 count was not significantly associated with survivors and non-survivors (P = 0.28). Conclusion: In patients with HIV, CD4 count was significantly low in toxoplasmosis and PCNSL, and high in tuberculoma and brain abscess.

Reward Circuit Local Field Potential Modulations Precede Risk Taking.

Risk taking behavior is a symptom of multiple neuropsychiatric disorders and often lacks effective treatments. Reward circuitry regions including the amygdala, orbitofrontal cortex, insula, and anterior cingulate have been implicated in risk-taking by neuroimaging studies. Electrophysiological activity associated with risk taking in these regions is not well understood in humans. Further characterizing the neural signalling that underlies risk-taking may provide therapeutic insight into disorders associated with risk-taking. Eleven patients with pharmacoresistant epilepsy who underwent stereotactic electroencephalography with electrodes in the amygdala, orbitofrontal cortex, insula, and/or anterior cingulate participated. Patients participated in a gambling task where they wagered on a visible playing card being higher than a hidden card, betting $5 or $20 on this outcome, while local field potentials were recorded from implanted electrodes. We used cluster-based permutation testing to identify reward prediction error signals by comparing oscillatory power following unexpected and expected rewards. We also used cluster-based permutation testing to compare power preceding high and low bets in high-risk (<50% chance of winning) trials and two-way ANOVA with bet and risk level to identify signals associated with risky, risk averse, and optimized decisions. We used linear mixed effects models to evaluate the relationship between reward prediction error and risky decision signals across trials, and a linear regression model for associations between risky decision signal power and Barratt Impulsiveness Scale scores for each patient. Reward prediction error signals were identified in the amygdala (p=0.0066), anterior cingulate (p=0.0092), and orbitofrontal cortex (p=6.0E-4, p=4.0E-4). Risky decisions were predicted by increased oscillatory power in high-gamma frequency range during card presentation in the orbitofrontal cortex (p=0.0022), and by increased power following bet cue presentation across the theta-to-beta range in the orbitofrontal cortex ( p =0.0022), high-gamma in the anterior cingulate ( p =0.0004), and high-gamma in the insula ( p =0.0014). Risk averse decisions were predicted by decreased orbitofrontal cortex gamma power ( p =2.0E-4). Optimized decisions that maximized earnings were preceded by decreases within the theta to beta range in orbitofrontal cortex ( p =2.0E-4), broad frequencies in amygdala ( p =2.0E-4), and theta to low-gamma in insula ( p =4.0E-4). Insula risky decision power was associated with orbitofrontal cortex high-gamma reward prediction error signal ( p =0.0048) and with patient impulsivity ( p =0.00478). Our findings identify and help characterize reward circuitry activity predictive of risk-taking in humans. These findings may serve as potential biomarkers to inform the development of novel treatment strategies such as closed loop neuromodulation for disorders of risk taking.

Lipid Association of India 2023 update on cardiovascular risk assessment and lipid management in Indian patients: Consensus statement IV.

OBJECTIVE: In 2016, the Lipid Association of India (LAI) developed a cardiovascular risk assessment algorithm and defined low-density lipoprotein cholesterol (LDL-C) goals for prevention of atherosclerotic cardiovascular disease (ASCVD) in Indians. The recent refinements in the role of various risk factors and subclinical atherosclerosis in prediction of ASCVD risk necessitated updating the risk algorithm and treatment goals. METHODS: The LAI core committee held twenty-one meetings and webinars from June 2022 to July 2023 with experts across India and critically reviewed the latest evidence regarding the strategies for ASCVD risk prediction and the benefits and modalities for intensive lipid lowering. Based on the expert consensus and extensive review of published data, consensus statement IV was commissioned. RESULTS: The young age of onset and a more aggressive nature of ASCVD in Indians necessitates emphasis on lifetime ASCVD risk instead of the conventional 10-year risk. It also demands early institution of aggressive preventive measures to protect the young population prior to development of ASCVD events. Wide availability and low cost of statins in India enable implementation of effective LDL-C-lowering therapy in individuals at high risk of ASCVD. Subjects with any evidence of subclinical atherosclerosis are likely to benefit the most from early aggressive interventions. CONCLUSIONS: This document presents the updated risk stratification and treatment algorithm and describes the rationale for each modification. The intent of these updated recommendations is to modernize management of dyslipidemia in Indian patients with the goal of reducing the epidemic of ASCVD among Indians in Asia and worldwide.

Spatio-temporal epidemiology of Japanese encephalitis virus infection in pig populations of eastern Uttar Pradesh, India, 2013-2022.

AIMS: Japanese encephalitis (JE) is endemic in India. Although pigs are considered important hosts and sentinels for JE outbreaks in people, limited information is available on JE virus (JEV) surveillance in pigs. METHODS AND RESULTS: We investigated the spatio-temporal distribution of JEV seroprevalence and its association with climate variables in 4451 samples from pigs in 10 districts of eastern Uttar Pradesh, India, over 10 years from 2013 to 2022. The mean seroprevalence of IgG (2013-2022) and IgM (2017-2022) was 14% (95% CI 12.8-15.2) and 10.98% (95% CI 9.8-12.2), respectively. Throughout the region, higher seroprevalence from 2013 to 2017 was observed and was highly variable with no predictable spatio-temporal pattern between districts. Seroprevalence of up to 60.8% in Sant Kabir Nagar in 2016 and 69.5% in Gorakhpur district in 2017 for IgG and IgM was observed, respectively. IgG seroprevalence did not increase with age. Monthly time-series decomposition of IgG and IgM seroprevalence demonstrated annual cyclicity (3-4 peaks) with seasonality (higher, broader peaks in the summer and monsoon periods). However, most variance was due to the overall trend and the random components of the time series. Autoregressive time-series modelling of pigs sampled from Gorakhpur was insufficiently predictive for forecasting; however, an inverse association between humidity (but not rainfall or temperature) was observed. CONCLUSIONS: Detection patterns confirm seasonal epidemic periods within year-round endemicity in pigs in eastern Uttar Pradesh. Lack of increasing age-associated seroprevalence indicates that JEV might not be immunizing in pigs which needs further investigation because models that inform public health interventions for JEV could be inaccurate if assuming long-term immunity in pigs. Although pigs are considered sentinels for human outbreaks, sufficient timeliness using sero-surveillance in pigs to inform public health interventions to prevent JEV in people will require more nuanced modelling than seroprevalence and broad climate variables alone.

A study to assess the relationship between vitamin D3 levels and the risk of acute exacerbation in patients with chronic obstructive pulmonary disease.

Chronic obstructive pulmonary disease (COPD) is one of the top three causes of mortality worldwide. Vitamin D deficiency in COPD has been associated with poor lung function and decreased muscle power, which further increases the risk of exacerbations. The role of vitamin D in preventing acute exacerbations of COPD has conflicting results in the literature. Hence, we planned this study to assess the relationship between vitamin D3 levels and the risk of acute exacerbations among COPD patients in a tertiary care center in north India. This was a prospective randomized control trial that was performed on 100 consecutive stable COPD patients attending the Department of Respiratory Medicine at Maharishi Markandeshwar Medical College and Hospital, Solan, India. The patients with subnormal vitamin D3 levels (i.e., less than 30 ng/mL) were divided into the intervention and control groups. Baseline demographic profiles, lung function, COPD assessment test (CAT) score, modified Medical Research Council grade and chest radiology were performed and repeated after 12 months in all these patients. All these parameters were recorded and compared with the baseline values obtained at the beginning of the study. Out of 100 subjects, 96 had vitamin D deficiency, of which 48 were assigned to the intervention group and 48 to the control group. Among the 100 subjects, 74 (74%) were males and 26 (26%) were females, with a mean age of 66.9±9.4 years. The mean vitamin D level was 14.71±6.69 in these 96 patients. The vitamin D level improved after 3 months of supplementation to the mean level of 45.56±16.18 in the intervention group. Vitamin D supplementation was positively correlated with a decrease in the rate of acute exacerbations in the intervention group in terms of reduction in mean CAT score (4.17 in intervention and 1.43 in non-interventional group, p<0.001), number of acute exacerbations (1.7 in intervention and -1.05 in non-interventional group, p<0.001), and number of emergency visits (p=0.0121) during the 9-month period after attainment of a normal vitamin D level. Vitamin D supplementation plays a key role in COPD patients with D3 hypovitaminosis in decreasing COPD acute exacerbations, improving the CAT score, and reducing the number of emergency visits.

Regional disparities and risk factors of mortality among patients at high risk of sudden cardiac death in emerging countries: a nonrandomized controlled trial.

BACKGROUND: Comprehensive data on patients at high risk of sudden cardiac death (SCD) in emerging countries are lacking. The aim was to deepen our understanding of the SCD phenotype and identify risk factors for death among patients at high risk of SCD in emerging countries. METHODS: Patients who met the class I indication for implantable cardioverter-defibrillator (ICD) implantation according to guideline recommendations in 17 countries and regions underrepresented in previous trials were enrolled. Countries were stratified by the WHO regional classification. Patients were or were not implanted with an ICD at their discretion. The outcomes were all-cause mortality and SCD. RESULTS: We enrolled 4222 patients, and 3889 patients were included in the analysis. The mean follow-up period was 21.6 ± 10.2 months. There were 433 (11.1%) instances of all-cause mortality and 117 (3.0%) cases of SCD. All-cause mortality was highest in primary prevention (PP) patients from Southeast Asia and secondary prevention (SP) patients from the Middle East and Africa. The SCD rates among PP and SP patients were both highest in South Asia. Multivariate Cox regression modelling demonstrated that in addition to the independent predictors identified in previous studies, both geographic region and ICD use were associated with all-cause mortality in patients with high SCD risk. Primary prophylactic ICD implantation was associated with a 36% (HR = 0.64, 95% CI 0.531-0.802, p < 0.0001) lower all-cause mortality risk and an 80% (HR = 0.20, 95% CI = 0.116-0.343, p < 0.0001) lower SCD risk. CONCLUSIONS: There was significant heterogeneity among patients with high SCD risk in emerging countries. The influences of geographic regions on patient characteristics and outcomes were significant. Improvement in increasing ICD utilization and uptake of guideline-directed medical therapy in emerging countries is urgent. TRIAL REGISTRATION: ClinicalTrials.gov, NCT02099721.

Brain-wide human oscillatory local field potential activity during visual working memory.

Oscillatory activity in the local field potential (LFP) is thought to be a marker of cognitive processes. To understand how it differentiates tasks and brain areas in humans, we recorded LFPs in 15 adults with intracranial depth electrodes, as they performed visual-spatial and shape working memory tasks. Stimulus appearance produced widespread, broad-band activation, including in occipital, parietal, temporal, insular, and prefrontal cortex, and the amygdala and hippocampus. Occipital cortex was characterized by most elevated power in the high-gamma (100-150 Hz) range during the visual stimulus presentation. The most consistent feature of the delay period was a systematic pattern of modulation in the beta frequency (16-40 Hz), which included a decrease in power of variable timing across areas, and rebound during the delay period. These results reveal the widespread nature of oscillatory activity across a broad brain network and region-specific signatures of oscillatory processes associated with visual working memory.

Impact of real-time optical coherence tomography and angiographic coregistration on the percutaneous coronary intervention strategy.

Background: The use of optical coherence tomography (OCT) with angiographic coregistration (ACR) during percutaneous coronary intervention (PCI) for procedural decision-making is evolving; however, large-scale data in real-world practice are lacking. Aims: Our study aims to evaluate the real-time impact of OCT-ACR on clinician decision-making during PCI. Methods: Patients with angiographic diameter stenosis >70% in at least one native coronary artery were enrolled in the study. The pre- and post-PCI procedural strategies were prospectively assessed after angiography, OCT, and ACR. Results: A total of 500 patients were enrolled in the study between November 2018 and March 2020. Among these, data related to 472 patients with 483 lesions were considered for analysis. Preprocedural OCT resulted in a change in PCI strategy in 80% of lesions: lesion preparation (25%), stent length (53%), stent diameter (36%), and device landing zone (61%). ACR additionally impacted the treatment strategy in 34% of lesions. Postprocedural OCT demonstrated underexpansion (15%), malapposition (14%), and tissue/thrombus prolapse (7%), thereby requiring further interventions in 30% of lesions. No further change in strategy was observed with subsequent postprocedural ACR. Angiographic and procedural success was achieved in 100% of patients, and the overall incidence of major adverse cardiovascular events at 1 year was 0.85%. Conclusions: The outcomes reflect the real-time impact of OCT-ACR on the overall procedural strategy in patients undergoing PCI. ACR had a significant impact on the treatment strategy and was associated with better clinical outcomes at 1 year after index PCI. OCT-ACR has become a practical tool for improving outcomes in patients with complex lesions.

Brain-wide human oscillatory LFP activity during visual working memory.

Oscillatory activity is thought to be a marker of cognitive processes, although its role and distribution across the brain during working memory has been a matter of debate. To understand how oscillatory activity differentiates tasks and brain areas in humans, we recorded local field potentials (LFPs) in 12 adults as they performed visual-spatial and shape-matching memory tasks. Tasks were designed to engage working memory processes at a range of delay intervals between stimulus delivery and response initiation. LFPs were recorded using intracranial depth electrodes implanted to localize seizures for management of intractable epilepsy. Task-related LFP power analyses revealed an extensive network of cortical regions that were activated during the presentation of visual stimuli and during their maintenance in working memory, including occipital, parietal, temporal, insular, and prefrontal cortical areas, and subcortical structures including the amygdala and hippocampus. Across most brain areas, the appearance of a stimulus produced broadband power increase, while gamma power was evident during the delay interval of the working memory task. Notable differences between areas included that occipital cortex was characterized by elevated power in the high gamma (100-150 Hz) range during the 500 ms of visual stimulus presentation, which was less pronounced or absent in other areas. A decrease in power centered in beta frequency (16-40 Hz) was also observed after the stimulus presentation, whose magnitude differed across areas. These results reveal the interplay of oscillatory activity across a broad network, and region-specific signatures of oscillatory processes associated with visual working memory.

Adaptive versus conventional cardiac resynchronisation therapy in patients with heart failure (AdaptResponse): a global, prospective, randomised controlled trial.

BACKGROUND: Continuous automatic optimisation of cardiac resynchronisation therapy (CRT), stimulating only the left ventricle to fuse with intrinsic right bundle conduction (synchronised left ventricular stimulation), might offer better outcomes than conventional CRT in patients with heart failure, left bundle branch block, and normal atrioventricular conduction. This study aimed to compare clinical outcomes of adaptive CRT versus conventional CRT in patients with heart failure with intact atrioventricular conduction and left bundle branch block. METHODS: This global, prospective, randomised controlled trial was done in 227 hospitals in 27 countries across Asia, Australia, Europe, and North America. Eligible patients were aged 18 years or older with class 2-4 heart failure, an ejection fraction of 35% or less, left bundle branch block with QRS duration of 140 ms or more (male patients) or 130 ms or more (female patients), and a baseline PR interval 200 ms or less. Patients were randomly assigned (1:1) via block permutation to adaptive CRT (an algorithm providing synchronised left ventricular stimulation) or conventional biventricular CRT using a device programmer. All patients received device programming but were masked until procedures were completed. Site staff were not masked to group assignment. The primary outcome was a composite of all-cause death or intervention for heart failure decompensation and was assessed in the intention-to-treat population. Safety events were collected and reported in the intention-to-treat population. This study is registered with ClinicalTrials.gov, NCT02205359, and is closed to accrual. FINDINGS: Between Aug 5, 2014, and Jan 31, 2019, of 3797 patients enrolled, 3617 (95·3%) were randomly assigned (1810 to adaptive CRT and 1807 to conventional CRT). The futility boundary was crossed at the third interim analysis on June 23, 2022, when the decision was made to stop the trial early. 1568 (43·4%) of 3617 patients were female and 2049 (56·6%) were male. Median follow-up was 59·0 months (IQR 45-72). A primary outcome event occurred in 430 of 1810 patients (Kaplan-Meier occurrence rate 23·5% [95% CI 21·3-25·5] at 60 months) in the adaptive CRT group and in 470 of 1807 patients (25·7% [23·5-27·8] at 60 months) in the conventional CRT group (hazard ratio 0·89, 95% CI 0·78-1·01; p=0·077). System-related adverse events were reported in 452 (25·0%) of 1810 patients in the adaptive CRT group and 440 (24·3%) of 1807 patients in the conventional CRT group. INTERPRETATION: Compared with conventional CRT, adaptive CRT did not significantly reduce the incidence of all-cause death or intervention for heart failure decompensation in the included population of patients with heart failure, left bundle branch block, and intact AV conduction. Death and heart failure decompensation rates were low with both CRT therapies, suggesting a greater response to CRT occurred in this population than in patients in previous trials. FUNDING: Medtronic.

Role of oxidative stress in diabetes-induced complications and their management with antioxidants.

Diabetes mellitus (DM) is a huge global health issue and one of the most studied diseases, with a large global prevalence. Oxidative stress is a cytotoxic consequence of the excessive development of ROS and suppression of the antioxidant defense system for ROS elimination, which accelerates the progression of diabetes complications such as diabetic neuropathy, retinopathy, and nephropathy. Hyperglycaemia induced oxidative stress causes the activation of seven major pathways implicated in the pathogenesis of diabetic complications. These pathways increase the production of ROS and RNS, which contributes to dysregulated autophagy, gene expression changes, and the development of numerous pro-inflammatory mediators which may eventually lead to diabetic complications. This review will illustrate that oxidative stress plays a vital role in the pathogenesis of diabetic complications, and the use of antioxidants will help to reduce oxidative stress and thus may alleviate diabetic complications.

Radiobiological modeling of radiation-induced acute proctitis: A single-institutional study of prostate carcinoma.

Purpose: To estimate the fitting parameters of the sigmoidal dose response (SDR) curve of radiation-induced acute proctitis in prostate cancer patients treated with intensity modulated radiation therapy (IMRT) for the calculation of normal tissue complication probability (NTCP). Materials and Methods: Twenty-five prostate cancer patients were enrolled and evaluated weekly for acute radiation-induced (ARI) proctitis toxicity. Their scoring was performed as per common terminology criteria for adverse events version 5.0. The radiobiological parameters namely n, m, TD50, and γ50 were calculated from the fitted SDR curve obtained from the clinical data of prostate cancer patients. Results: ARI toxicity for rectum in carcinoma of prostate patients was calculated for the endpoint of acute proctitis. The n, m, TD50, and γ50 parameters from the SDR curve of Grade 1 and Grade 2 acute proctitis are found to be 0.13, 0.10, 30.48 ± 1.52 (confidence interval [CI] 95%), 3.18 and 0.08, 0.10, 44.37 ± 2.21 (CI 95%), 4.76 respectively. Conclusion: This study presents the fitting parameters for NTCP calculation of Grade-1 and Grade-2 ARI rectum toxicity for the endpoint of acute proctitis. The provided nomograms of volume versus complication and dose versus complication for different grades of acute proctitis in the rectum help radiation oncologists to decide the limiting dose to reduce the acute toxicities.

Radiobiological modelling of radiation-induced acute skin toxicity (dermatitis): A single institutional study of breast carcinoma.

Purpose: The purpose of the study was to estimate the fitting parameters of the sigmoidal dose response (SDR) curve of radiation-induced acute dermatitis in breast cancer patients treated with intensity-modulated radiation therapy for calculation of normal tissue complication probability (NTCP). Materials and Methods: Twenty-five breast cancer patients were enrolled to model the SDR curve for acute dermatitis. The acute radiation-induced (ARI) dermatitis toxicity was assessed weekly for all the patients, and their scores were determined using the common terminology criterion adverse events version 5.0. The radiobiological parameters n, m, TD50, and γ50 were derived using the fitted SDR curve obtained from breast cancer Patient's clinical data. Results: ARI dermatitis toxicity in carcinoma of breast patients was calculated for the end point of acute dermatitis. The n, m, TD50, and γ50 parameters from the SDR curve of Grade-1 dermatitis are found to be 0.03, 0.04, 28.65 ± 1.43 (confidence interval [CI] 95%) and 1.02 and for Grade-2 dermatitis are found to be 0.026, 0.028, 38.65 ± 1.93 (CI. 95%) and 1.01 respectively. Conclusion: This research presents the fitting parameters for NTCP calculation of Grade-1 and Grade-2 acute radiation-induced skin toxicity in breast cancer for the dermatitis end point. The presented nomograms of volume versus complication probability and dose versus complication probability assist radiation oncologists in establishing the limiting dose to reduce acute toxicities for different grades of acute dermatitis in breast cancer patients.