DigiDOP: A framework for applying digital technology to the Differential Outcomes Procedure (DOP) for cognitive interventions in persons with neurocognitive disorders.

We present a framework -Digi-DOP- that includes a series of evidence-based recommendations to design and apply cognitive interventions for people with Neurocognitive Disorders (NCDs) using a relatively new approach, the Differential Outcomes Procedure (DOP). To do so, we critically review the substantial experimental research conducted with relevant clinical and non-clinical populations, and the theoretical underpinnings of this procedure. We further discuss how existing digital technologies that have been used for cognitive interventions could be applied to overcome some of the limitations of DOP-based interventions and further enhance DOP benefits. Specifically, we present three digital DOP developments that are currently being designed, investigated and/or tested. Finally, we discuss constraints, ethical and legal considerations that need to be taken into account to ensure that the use of technology in DOP-based interventions proposed here does not widen disparities and inequalities. We hope that this framework will inform and guide digital health leaders and developers, researchers and healthcare professionals to design and apply DOP-based interventions for people with NCDs.

Improved cognition and preserved hippocampal fractional anisotropy in subjects undergoing carotid endarterectomy "CEA preserves cognition & hippocampal structure".

OBJECTIVES: A growing body of data indicates that extracranial carotid artery disease (ECAD) can contribute to cognitive impairment. However, there have been mixed reports regarding the benefit of carotid endarterectomy (CEA) as it relates to preserving cognitive function. In this work, diffusion magnetic resonance imaging (dMRI) and neurocognitive testing are used to provide insight into structural and functional brain changes that occur in subjects with significant carotid artery stenosis, as well as changes that occur in response to CEA. MATERIALS AND METHODS: The study design was a prospective, non-randomized, controlled study that enrolled patients with asymptomatic carotid stenosis. Thirteen subjects had severe ECAD (≥70% stenosis in at least one carotid artery) and were scheduled to undergo surgery. Thirteen had asymptomatic ECAD with <70% stenosis, therefore not requiring surgery. All subjects underwent neurocognitive testing using the Montreal Cognitive Assessment test (MoCA) and high angular resolution, multi-shell diffusion magnetic resonance imaging (dMRI) of the brain at baseline and at four-six months follow-up. Changes in MoCA scores as well as in Fractional anisotropy (FA) along the hippocampus were compared at baseline and follow-up. RESULTS: At baseline, FA was significantly lower along the ipsilateral hippocampus in subjects with severe ECAD compared to subjects without severe ECAD. MoCA scores were lower in these individuals, but this did not reach statistical significance. At follow-up, MoCA scores increased significantly in subjects who underwent CEA and remained statistically equal in control subjects that did not have CEA. FA remained unchanged in the CEA group and decreased in the control group. CONCLUSIONS: This study suggests that CEA improves cognition and preserves hippocampal white matter structure compared to control subjects not undergoing CEA.

The magnitude of neurocognitive disorders and associated factors among people living with HIV AIDS facilities in Bahir Dar City Ethiopia.

Neurocognitive disorders are mental health conditions that are caused by medical illnesses and can lead to several acquired cognitive deficits, which represent a decline from a previously attained level of functioning. The principal domains of cognitive functions include complex attention, executive function, learning and memory, language, perceptual-motor function, and social cognition. Studies have shown that people living with human immunodeficiency virus (HIV) are at a heightened risk of experiencing cognitive challenges across multiple domains. Given that, a substantial number of people live in Amhara region, assessing cognitive domains to estimate the current magnitude and factors associated with neurocognitive disorders among HIV/AIDS patients is crucial. An institutional-based cross-sectional study was conducted among 569 participants adults living with HIV attending the city's selected health facilities from March 20 to April 30, 2023. A multistage sampling technique was used. The International HIV Dementia Scale (IHDS) was used to measure the outcome of interest. The data were collected using a structured questionnaire and document review. The data were analyzed using STATA version 14. Multiple binary logistic regressions were used as the final model. A total of 501 individuals, with a response rate of 88.04% participated in the study. The overall proportion of HIV patients with neurocognitive impairment was 54.7% (95% CI 50.62-58.77). Factors associated with the neurocognitive impairment were: being widowed AOR = 3.05 (95% CI 1.47-6.31), divorced AOR = 1.95 (1.16-3.28), rural residence AOR = 2.28 (95% CI 1.02-5.09), CD4 count below 500 cells/dl AOR = 1.61 (95% CI 1.03-2.50), history of opportunistic infection AOR = 2.21 (95% CI 1.42-3.41), being in first-line drug regimen AOR = 2.92 (95% CI 1.22-7.00), being in a first-line regimen with Efavirenz AOR = 4.36 (95% CI 1.07-17.73), and impairment in daily living AOR = 2.64 (95% CI 1.39-4.99). In this study, the proportion of neurocognitive impairment was greater than that in most previous studies conducted in Ethiopia. The factors associated with the disorder were: being widowed or divorced, living in a rural area, having low CD4, having a history of opportunistic infection, receiving a first-line drug regimen, receiving efavirenz-containing drugs, and having impaired daily living. Hence, routine neuropsychological screenings should be integrated into comprehensive ART care by the regional health bureau and implemented by hospitals and health centers.

HIV-associated neurocognitive disorder: key implications of the microbiota-gut-brain axis.

HIV-associated neurocognitive disorder (HAND) is now recognized to be relatively common in people living with HIV (PLWH), and remains a common cause of cognitive impairment. Unfortunately, the fundamental pathogenic processes underlying this specific outcome of HIV infection have not as yet been fully elucidated. With increased interest in research related to the microbiota-gut-brain axis, the gut-brain axis has been shown to play critical roles in regulating central nervous system disorders such as Alzheimer's disease and Parkinson's disease. PLWH are characterized by a particular affliction, referred to as gut-associated dysbiosis syndrome, which provokes an alteration in microbial composition and diversity, and of their associated metabolite composition within the gut. Interestingly, the gut microbiota has also been recognized as a key element, which both positively and negatively influences human brain health, including the functioning and development of the central nervous system (CNS). In this review, based on published evidence, we critically discuss the relevant interactions between the microbiota-gut-brain axis and the pathogenesis of HAND in the context of HIV infection. It is likely that HAND manifestation in PLWH mainly results from (i) gut-associated dysbiosis syndrome and a leaky gut on the one hand and (ii) inflammation on the other hand. In other words, the preceding features of HIV infection negatively alter the composition of the gut microbiota (microbes and their associated metabolites) and promote proinflammatory immune responses which singularly or in tandem damage neurons and/or induce inadequate neuronal signaling. Thus, HAND is fairly prevalent in PLWH. This work aims to demonstrate that in the quest to prevent and possibly treat HAND, the gut microbiota may ultimately represent a therapeutically targetable "host factor."

Electroencephalography as a tool for assessing delirium in hospitalized patients: A single-center tertiary hospital experience.

Background: Delirium is a prevalent yet underdiagnosed disorder characterized by acute cognitive impairment. Various screening tools are available, including the Confusion Assessment Method (CAM) and 4 A's test (4AT). However, the results of these assessments may vary among raters. Therefore, we investigated the objective use of electroencephalography (EEG) in delirium and its clinical associations and predictive value. Method: This cross-sectional observational study was conducted at Hospital Canselor Tuanku Muhriz, Universiti Kebangsaan, Malaysia, from April 2021 to April 2023. This study included patients aged ≥18 years with a preliminary diagnosis of delirium. Demographic and clinical data were collected along with EEG recordings evaluated by certified neurologists to classify abnormalities and compare the associated factors between patients with delirium with or without EEG abnormalities. Results: One hundred and twenty patients were recruited, with 80.0% displaying EEG abnormalities, mostly generalized slowing (moderate to severe) and primarily generalized slowing (mild to severe), and were characterized by theta activity. Age was significantly associated with EEG abnormalities, with patients aged 75 and older demonstrating the highest incidence (88.2%). The CAM scores were strongly correlated with EEG abnormalities (r = 0.639, P < 0.001) and was a predictor of EEG abnormalities (P < 0.012), indicating that EEG can complement clinical assessments for delirium. The Richmond Agitation and Sedation Scale (RASS) scores (r = -0.452, P < 0.001) and Barthel index (BI) (r = -0.582, P < 0.001) were negatively correlated with EEG abnormalities. Additionally, a longer hospitalization duration was associated with EEG abnormalities (r = 0.250, P = 0.006) and emerged as a predictor of such changes (P = 0.030). Conclusion: EEG abnormalities are prevalent in patients with delirium, particularly in elderly patients. CAM scores and the duration of hospitalization are valuable predictors of EEG abnormalities. EEG can be an objective tool for enhancing delirium diagnosis and prognosis, thereby facilitating timely interventions.

Why was the study done? Confusion is frequently observed among patients presenting with various medical issues. There are several tests available to assist in assessment of these patients to see if the symptoms present constitute delirium. However, there may be occasions where identifying delirium is difficult despite the tools available. Electroencephalography (EEG) may be another option to assist medical personnel in diagnosing delirium. In this study, we examine the use of EEG in identification of delirium and its clinical associations. What did the researchers do? Our team studied the use of EEG in patients admitted for various medical issues with symptoms suggestive of delirium over a 2-year period. We collected relevant clinical data and performed EEG for each participant. What did the researchers find? A total of 120 participants were involved in the study. We observe abnormal EEG findings in 80% of patients with the majority showing generalized slowing. The factors associated with EEG abnormalities are advancing age, positive Confusion Assessment Method (CAM), and duration of hospitalization. What do the findings mean? As the service is not widely available, it would not be practical to substitute existing clinical assessment tools with EEG. However, we cannot discount the importance of identifying delirium due to its association with poor clinical outcomes. Therefore, for centers that may perform EEG, it may be used as an adjunct in diagnosing delirium should any doubts arise.

Neurocognitive Characteristics of Patients Who Visited a Psychiatric Outpatient Clinic Requesting Treatment for Adult Attention-Deficit/Hyperactivity Disorder.

OBJECTIVE: This study investigated the neurocognitive characteristics of patients who visited an outpatient clinic requesting diagnosis and treatment for adult attention-deficit/hyperactivity disorder (ADHD). METHODS: The patients' electronic medical records were retrospectively reviewed. Neurocognitive test results were compared using Student's t-test according to their chief complaint, depressive symptoms, childhood history, and intelligence quotient (IQ). Neurocognitive characteristics affecting subjective symptoms of ADHD were analyzed by linear regression. RESULTS: The study included 106 patients. They did not have significant deficits in neurocognitive tests. Patients with depressive symptoms showed more impulsive responses (hit reaction time [p=0.037] and commission error [p=0.024]) and self-reported ADHD symptoms (p=0.001). Verbal (p=0.036) and visual memory (p=0.020) were significantly deficient in patients with a childhood ADHD diagnosis. Patients with a low IQ had significant deficits in various domains. Depressive symptoms and vigilance were significantly related to subjective symptoms of ADHD (adjusted R2=0.430, ß=0.457, p=0.002). CONCLUSION: Our results imply that the neurocognitive function of patients with subjective ADHD symptoms was not abnormal but was affected by depressive symptoms.

Current dilemma and future directions over prophylactic cranial irradiation in SCLC: a systematic review in MRI and immunotherapy era.

Small cell lung cancer (SCLC) is the most malignant pathological type of lung cancer with the highest mortality, and the incidence of brain metastasis (BM) is in high frequency. So far, prophylactic cranial irradiation (PCI) has been suggested as an effective treatment for preventing brain metastasis of SCLC. PCI has long been applied to limited-stage SCLC (LS-SCLC) patients who have achieved complete remission after radiotherapy and chemotherapy as a standard treatment. However, the neurocognitive decline is a major concern surrounding PCI. New therapeutic approaches targeting PCI-induced neurotoxicity, including hippocampal protection or memantine, have been increasingly incorporated into the therapeutic interventions of PCI. Helical tomotherapy, RapidArc, and Volumetric-modulated arc therapy (VMAT) with a head-tilting baseplate are recommended for hippocampal protection. Besides, in the MRI and immunotherapy era, the significance of PCI in SCLC patients is controversial. SCLC patients with PCI should be recruited in clinical trials since this is the only way to improve the existing standard of care. This review summarizes the current therapeutic strategy and dilemma over PCI for SCLC, providing a theoretical basis for clinical decision-making and suggestions for PCI practice in clinical.

The Adolescent Transplant Recipient: An Overview of Neurocognitive Functioning and Implications for Long-Term Outcomes.

BACKGROUND: Solid organ transplantation (SOT) offers improved long-term survival for youth with end-stage organ disease. From a neurodevelopmental, cognitive, and academic perspective, children with solid organ transplant have a number of unique risk factors. While cognitive functioning may improve post-transplantation, it is important to understand the trajectory of neurocognitive development starting in transplant candidacy to evaluate the implications of early deficits. AIM: The aim of this paper is to describe the neurocognitive risks and long-term implications for adolescent transplant recipients. METHOD: This paper provides an overview of neurocognitive functioning in youth with end-stage organ dysfunction with discussion of implications for adolescent transplant recipients. RESULTS: Post-transplant, adolescent, and young adult solid organ transplant recipients exhibit significant levels of executive dysfunction, with implications for decision-making, regimen adherence, and transition to adult transplant care. CONCLUSION: Transplantation may reduce the risk for poor long-term neurocognitive effects, yet adolescent transplant recipients remain at increased risk, particularly in executive functioning, which has implications for adherence and transition to adulthood. Baseline and follow-up assessments for youth with end-stage organ disease and transplant are important for the monitoring of neurocognitive development and may be used to mitigate risk for low adherence to post-transplantation treatment regimens and reduce barriers to transitioning to adult transplant care.

Risk Management During the Transition From Hospital to Home: A Multiple Case Study Documenting the Experience of Patients Living With a Major Neurocognitive Disorder, Their Caregivers, and Healthcare Professionals.

Understanding the risks in the months following hospital discharge is crucial for healthcare professionals to ensure the need for assistance is met. However, this may be challenging in the case of patients living with a major neurocognitive disorder (PLMNCD). Thus, it is important to incorporate patients' and caregivers' experiences of the transition from hospital to home in the risk assessment. This multiple case study comprised 7 PLMNCD, their caregivers, and occupational therapists. Fifty-four interviews, conducted just before, as well as 3 weeks and 3 to 6 months after hospital discharge, were qualitatively analyzed. Results revealed that risk management during the hospital-to-home transition is a dynamic process aimed at establishing a satisfactory routine while avoiding adverse events. This risk management process, which identifies challenges over time and between stakeholders, involves (a) determining the seriousness and acceptability of risks, (b) reflecting on ways to manage risks, and (c) taking steps to manage risks. This knowledge will help to provide more appropriate care and services that strike a balance between safety and autonomy.

Neurocognitive performance of patients undergoing intravenous versus oral opioid agonist treatment: a prospective multicenter study on three-month treatment effects.

Introduction: The first-line treatment for opioid dependence is opioid agonist treatment (OAT) with oral opioids. However, in some cases, treatment with intravenous diacetylmorphine (IV-DAM) is indicated. Research on neurocognitive impairments and treatment effects of OAT - particularly with IV-DAM - on neurocognitive functioning, is scarce. The current study is the first to investigate the neurocognitive performance of individuals on OAT with IV-DAM. Using a prospective study design with two timepoints of measurement, the first aim was to assess the nature and extent of neurocognitive functioning in individuals with opioid dependence by comparing participants' neurocognitive performance with normative data of the general population on admission to treatment (baseline) and after an initial three-month period of OAT (study end). The second aim was to examine whether and to what extent neurocognitive performance would improve after three months on OAT. The third aim was to investigate whether, and if so, to what extent the treatment method (IV-DAM vs. oral opioids) would lead to higher neurocognitive improvements at study end. Methods: Forty-seven opioid-dependent individuals (baseline; 33 individuals at study end) participated in this study (mean age: 34.3 years; 27.7% female). Participants underwent neuropsychological testing with a battery of 12 tests covering different neurocognitive domains, including attention, memory, and executive functions. Results: Compared to normative data, opioid-dependent individuals showed impairments in almost every test both at baseline and at study end. At baseline, neurocognitive performance did not differ between individuals receiving IV-DAM or oral opioids for OAT. Compared to baseline, the neurocognitive performance did neither improve nor deteriorate after three months of treatment with neither IV-DAM nor oral opioids. However, a trend towards improvement was found for the memory domain. Discussion: Given that neurocognitive impairments should be considered in treatment planning and therapeutic interventions. Since a reduced cognitive performance may affect both the treatment outcome and the therapeutic relationship unfavorably, specific neurocognitive training at the beginning of treatment should be considered.

Desflurane versus sevoflurane anesthesia and postoperative recovery in older adults undergoing minor- to moderate-risk noncardiac surgery - A prospective, randomized, observer-blinded, clinical trial.

STUDY OBJECTIVE: The effect of volatile anesthetics on postoperative recovery in older adults is still not entirely clear. Thus, we evaluated the effect of desflurane versus sevoflurane anesthesia on speed of postoperative recovery in older adults eligible for same-day discharge. We further evaluated the incidence of postoperative nausea and vomiting (PONV), bispectral index (BIS) values, and S100B concentrations. DESIGN: Single-center, prospective, observer-blinded, randomized clinical trial. SETTING: Operating room. PATIENTS: 190 patients ≥65 years of age and scheduled for minor- to moderate-risk noncardiac surgeries. INTERVENTIONS: Goal-directed administration of desflurane versus sevoflurane for maintenance of anesthesia with an intraoperative goal of BIS 50 ± 5. MEASUREMENTS: The primary outcome was the time to anesthesia recovery, which was defined as the time between arrival at the post-anesthesia care unit (PACU) and reaching criteria for discharge from PACU, based on modified Aldrete score ≥ 12 points. Modified Aldrete scores were assessed at PACU arrival and thereafter in five-minute intervals. PONV was evaluated during PACU stay and the first three postoperative days, BIS values were recorded during PACU stay, and S100B values were measured before and after surgery, and on the second postoperative day. MAIN RESULTS: 95 patients were randomized to receive desflurane, and 95 patients to receive sevoflurane. We did not observe a significant difference in median duration of postoperative recovery between the groups (desflurane: 0 min [0;0]; sevoflurane: 0 min [0;0]; p = 0.245). 77 patients (81.1%) in the desflurane group and 84 patients (88.4%) in the sevoflurane group already had Aldrete scores ≥12 points upon arrival at PACU (p = 0.277). There was also no significant difference in the incidences of PONV (p = 0.606), postoperative BIS values (p = 0.197), and postoperative maximum S100B concentrations (p = 0.821) between the groups. CONCLUSIONS: Despite previous reports, we did not observe significant faster recovery times after desflurane anesthesia. Both volatile anesthetics may be appropriate for same-day discharge in older adults.

Cognitive performance and brain volume among survivors of pediatric hematological malignancies: a case-control study.

BACKGROUND: Cognitive dysfunction may be one of the hazardous late effects among survivors of pediatric hematological malignancies. Our study aimed to explore cognitive performance and assess the global and regional brain volume changes in survivors of hematological malignancies. METHODS: This case-control study was conducted on 68 survivors of hematological malignancies, with a median follow-up period of 2 years (ranging from 1 to 6.2 years). Stanford-Binet Test was used for cognitive assessment. A quantitative volumetric assessment of the brain was done using the NeuroQuant Brain Magnetic Resonance. Age and sex-matched 68 children were selected as a comparison group. RESULTS: Cancer survivors showed significantly lower levels of IQ and their subtests than the control group. Global brain atrophy was observed in the majority of the survivors. Many risk factors significantly affected different IQ subtests, such as radiotherapy (RTH), high cumulative doses of methotrexate (MTX), and prednisone. At the same time, low white matter volume (WMV) was observed with higher cumulative doses of MTX and anthracyclines. CONCLUSIONS: Hematological malignancies have a negative impact on cognition. Neurocognitive impairment and related brain changes were evident in those who received RTH, HDMTX, or high cumulative doses of steroids.

Contribution of a Tablet-Based Tests to the Diagnosis of Neurocognitive Disorders in Older Adults: A Feasibility Study.

Neurocognitive diseases are diagnosed in specialized centers such as memory clinics, where the waiting time can be long. The reference assessment involves a battery of tests carried out by a specialized team. Facilitating screening in primary care using new technologies could make it possible to appropriately direct care pathways towards specialist care. This work aimed to set up a battery of questionnaires, cognitive and manual dexterity tests on a digital tablet to screen people with cognitive impairment. Three groups of people are recruited from a memory consultation: people with major neurocognitive disorders, people with mild neurocognitive disorders and people with no cognitive impairment. Initial results in geriatric settings show that the digital tablet assessment test is feasible and well accepted, but that manual dexterity assessment needs to be adapted to the bodily particularities of the very old.

A Digital Clock Drawing Test on Tablet for the Diagnosis of Neurocognitive Disorders in Older Adults.

The diagnosis of neurocognitive diseases is an important health issue for patients, families and healthcare professionals. The need to develop rapid, high-performance screening tools would improve access to care. The Clock Drawing Test (CDT) is widely used and validated with the older adults, and its digital version is becoming increasingly widespread. We propose to confirm its validity in a population of old patients hospitalized in a geriatric unit, and secondly to verify its performance in comparison with the reference diagnosis made by a specialized team in a memory consultation. CDTs were collected from older hospitalized patients, both in paper form and digitally on a touchscreen tablet. The results show good agreement between the paper and digital versions (kappa coefficient = 0.81). Sensitivity and specificity of the digital CDT were 0.84 and 0.59 respectively for the diagnosis of major cognitive disorders. The corresponding values were 0.72 and 0.59 for the diagnosis of mild neurocognitive disorders. User questionnaires indicate that older participants find the digital tablet easy to use. However, they prefer to use paper, even if they are open to learning how to use the tablet.

Sera from people with HIV and depression induce commensurate metabolic alterations in astrocytes: toward precision diagnoses and therapies.

Objectives: People with HIV (PWH) have high rates of depression and neurocognitive impairment (NCI) despite viral suppression on antiretroviral therapy (ART). Mounting evidence suggests that immunometabolic disruptions may contribute to these conditions in some PWH. We hypothesized that metabolic dysfunction in astrocytes is associated with depressive symptoms and cognitive function in PWH. Methods: Human astrocytes were exposed to sera from PWH (n=40) with varying degrees of depressive symptomatology and cognitive function. MitoTrackerTM Deep Red FM (MT) was used to visualize mitochondrial activity and glial fibrillary acidic protein (GFAP) as an indicator of astrocyte reactivity using the high-throughput fluorescent microscopy and image analyses platform, CellInsight CX5 (CX5). The Seahorse platform was used to assess glycolytic and mitochondrial metabolism. Results: More severe depression, as indexed by higher Beck's Depression Inventory (BDI-II) scores, was associated with lower MT signal measures. Better cognitive function, as assessed by neuropsychiatric testing t-scores, was associated with increased MT signal measures. GFAP intensity negatively correlated with several cognitive t-scores. Age positively correlated with (higher) MT signal measures and GFAP intensity. Worse depressive symptoms (higher BDI-II scores) were associated with decreased oxygen consumption rate and spare respiratory capacity, concomitant with increased extracellular acidification rate in astrocytes. Conclusions: These findings show that factors in the sera of PWH alter mitochondrial activity in cultured human astrocytes, suggesting that mechanisms that alter mitochondrial and astrocyte homeostasis can be detected peripherally. Thus, in vitro cultures may provide a model to identify neuropathogenic mechanisms of depression or neurocognitive impairment in PWH and test personalized therapeutics for neurologic and psychiatric disorders.

Microembolizations in the Arterial Cerebral Circulation during Atrial Fibrillation Ablation: Cryoballoon Technique Advantages and Neurocognitive Safety - Results of a Prospective Observational Study.

BACKGROUND AND AIMS: The significance of micro-embolic signals (MES) during atrial fibrillation (AF) ablation is unclear. Previous studies had limitations, and cryoballoon (CB) ablation patients were underrepresented. Minimizing MES is recommended due to their uncertain neurocognitive impact. METHODS: This prospective observational study included AF patients from a German center between February 2021 and August 2022. Patients were equally divided into paroxysmal (Group A) and persistent (Group B) AF. Group A received CB-PVI only, while Group B also had left atrial roof ablation. MES were detected using transcranial Doppler ultrasonography during ablation. Neurocognitive status was assessed pre- and post-procedure and at 3 months using the CERAD Plus battery. RESULTS: The study analyzed 100 patients with a median age of 65.5 years. A total of 19,698 MES were observed, with 80% being gaseous and 20% solid in origin, primarily occurring during pulmonary vein angiography and the balloon freeze and thawing phase. The median MES per patient was 130 (IQR 92-256) in total, 298 (IQR 177-413) in bilateral (36%), and 110 (IQR 71-130) in unilateral (64%) recordings. No significant difference in total MES counts was found between the groups. None of the eleven neuropsychological tests showed cognitive decline post-procedure or at 3 months. CONCLUSION: Our observations confirm that neurocognitive abilities are not affected either 24 hours or 3 months after AF ablation using the CB technique. However, despite the low MES burden associated with the CB, more work is needed to reduce small embolic events during AF ablation.

Impact of neonatal sepsis on neurocognitive outcomes: a systematic review and meta-analysis.

INTRODUCTION: Sepsis is associated with neurocognitive impairment among preterm neonates but less is known about term neonates with sepsis. This systematic review and meta-analysis aims to provide an update of neurocognitive outcomes including cognitive delay, visual impairment, auditory impairment, and cerebral palsy, among neonates with sepsis. METHODS: We performed a systematic review of PubMed, Embase, CENTRAL and Web of Science for eligible studies published between January 2011 and March 2023. We included case-control, cohort studies and cross-sectional studies. Case reports and articles not in English language were excluded. Using the adjusted estimates, we performed random effects model meta-analysis to evaluate the risk of developing neurocognitive impairment among neonates with sepsis. RESULTS: Of 7,909 studies, 24 studies (n = 121,645) were included. Majority of studies were conducted in the United States (n = 7, 29.2%), and all studies were performed among neonates. 17 (70.8%) studies provided follow-up till 30 months. Sepsis was associated with increased risk of cognitive delay [adjusted odds ratio, aOR 1.14 (95% CI: 1.01-1.28)], visual impairment [aOR 2.57 (95%CI: 1.14- 5.82)], hearing impairment [aOR 1.70 (95% CI: 1.02-2.81)] and cerebral palsy [aOR 2.48 (95% CI: 1.03-5.99)]. CONCLUSION: Neonates surviving sepsis are at a higher risk of poorer neurodevelopment. Current evidence is limited by significant heterogeneity across studies, lack of data related to long-term neurodevelopmental outcomes and term infants.

HIV-1 and methamphetamine co-treatment in primary human astrocytes: TAARgeting ER/UPR dysfunction.

Objectives: Human immunodeficiency virus 1 (HIV-1) can invade the central nervous system (CNS) early during infection and persist in the CNS for life despite effective antiretroviral treatment. Infection and activation of residential glial cells lead to low viral replication and chronic inflammation, which damage neurons contributing to a spectrum of HIV-associated neurocognitive disorders (HAND). Substance use, including methamphetamine (METH), can increase one's risk and severity of HAND. Here, we investigate HIV-1/METH co-treatment in a key neurosupportive glial cell, astrocytes. Specifically, mitochondria-associated endoplasmic reticulum (ER) membrane (MAM) signaling pathways, such as calcium and the unfolded protein response (UPR), are key mechanisms underlying HAND pathology and arise as potential targets to combat astrocyte dysfunction. Methods: Primary human astrocytes were transduced with a pseudotyped HIV-1 model and exposed to low-dose METH for seven days. We assessed changes in astrocyte HIV-1 infection, inflammation, mitochondrial antioxidant and dynamic protein expression, respiratory acitivity, mitochondrial calcium flux, and UPR/MAM mediator expression. We then tested a selective antagonist for METH-binding receptor, trace amine-associated receptor 1 (TAAR1) as a potetnial upstream regulator of METH-induced calcium flux and UPR/MAM mediator expression. Results: Chronic METH exposure increased astrocyte HIV-1 infection. Moreover, HIV-1/METH co-treatment suppressed astrocyte antioxidant and metabolic capacity while increasing mitochondrial calcium load and protein expression of UPR messengers and MAM mediators. Notably, HIV-1 increases astrocyte TAAR1 expression, thus, could be a critical regulator of HIV-1/METH co-treatment in astrocytes. Indeed, selective antagonism of TAAR1 significantly inhibited cytosolic calcium flux and induction of UPR/MAM protein expression. Conclusion: Altogether, our findings demonstrate HIV-1/METH-induced ER-mitochondrial dysfunction in astrocytes, whereas TAAR1 may be an upstream regulator for HIV-1/METH-mediated astrocyte dysfunction.