Long-term nitrogen addition decreases carbon leaching in a nitrogen-rich forest ecosystem

Dissolved organic carbon (DOC) plays a critical role in the carbon (C) cycle of forest soils, and has been recently connected with global increases in nitrogen (N) deposition. Most studies on effects of elevated N deposition on DOC have been carried out in N-limited temperate regions, with far fewer data available from N-rich ecosystems, especially in the context of chronically elevated N deposition. Furthermore, mechanisms for excess N-induced changes of DOC dynamics have been suggested to be different between the two kinds of ecosystems, because of the different ecosystem N status. The purpose of this study was to experimentally examine how long-term N addition affects DOC dynamics below the primary rooting zones (the upper 20cm soils) in typically N-rich lowland tropical forests. We have a primary assumption that long-term continuous N addition minimally affects DOC concentrations and effluxes in N-rich tropical forests. Experimental N addition was administered at the following levels: 0, 50, 100 and 150kgNha−1 yr−1, respectively. Results showed that seven years of N addition significantly decreased DOC concentrations in soil solution, and chemo-physical controls (solution acidity change and soil sorption) rather than biological controls may mainly account for the decreases, in contrast to other forests. We further found that N addition greatly decreased annual DOC effluxes from the primary rooting zone and increased water-extractable DOC in soils. Our results suggest that long-term N deposition could increase soil C sequestration in the upper soils by decreasing DOC efflux from that layer in N-rich ecosystems, a novel mechanism for continued accumulation of soil C in old-growth forests

Case Report: PAFAH1B1 Mutation and Posterior Band Heterotopia With Focal Temporal Lobe Epilepsy Treated by Responsive Neurostimulation

Subcortical band heterotopia (SBH), also known as double cortex syndrome, is a malformation of cortical development caused by inherited or somatic gene variants. We present a case of a young adult with posterior SBH and electroclinical features of focal neocortical temporal lobe epilepsy. Genomic blood analysis identified a pathogenic somatic mosaicism duplication variant of the PAFAH1B1 gene. Despite bilateral cortical MRI abnormalities, the interictal and ictal EEG findings indicated a focal epileptogenic region in the left posterior temporal region. Chronic responsive cortical neurostimulation across two four-contact depth electrodes placed 5mm on either side of the maximal interictal spiking identified during intraoperative electrocorticography resulted in a consistent 28%reduction in duration of electrographic seizures and as well as constricted propagation. Although electrographic seizures continued, the family reported no clinical seizures and a marked improvement in resistant behaviors. This observation supports that focal neocortical neuromodulation can control clinical seizures of consistently localized origin despite genetic etiology, bilateral structural brain abnormalities, and continuation of non-propagating electrographic seizures. We propose that a secondary somatic mutation may be the cause of the focal neocortical temporal lobe epilepsy

Epilepsy Surgery for Pharmacoresistant Temporal Lobe Epilepsy: A Decision Analysis

Context Patients with pharmacoresistant epilepsy have increased mortality compared with the general population, but patients with pharmacoresistant temporal lobe epilepsy who meet criteria for surgery and who become seizure-free after anterior temporal lobe resection have reduced excess mortality vs those with persistent seizures. Objective To quantify the potential survival benefit of anterior temporal lobe resection for patients with pharmacoresistant temporal lobe epilepsy vs continued medical management. Design Monte Carlo simulation model that incorporates possible surgical complications and seizure status, with 10 000 runs. The model was populated with health-related quality-of-life data obtained directly from patients and data from the medical literature. Insufficient data were available to assess gamma-knife radiosurgery or vagal nerve stimulation. Main Outcome Measures Life expectancy and quality-adjusted life expectancy. Results Compared with medical management, anterior temporal lobe resection for a 35-year-old patient with an epileptogenic zone identified in the anterior temporal lobe would increase survival by 5.0 years (95% CI, 2.1-9.2) with surgery preferred in 100% of the simulations. Anterior temporal lobe resection would increase quality-adjusted life expectancy by 7.5 quality-adjusted life-years (95%, CI, −0.8 to 17.4) with surgery preferred in 96.5% of the simulations, primarily due to increased years spent without disabling seizures, thereby reducing seizure-related excess mortality and improving quality of life. The results were robust to sensitivity analyses. Conclusion The decision analysis model suggests that on average anterior temporal lobe resection should provide substantial gains in life expectancy and quality-adjusted life expectancy for surgically eligible patients with pharmacoresistant temporal lobe epilepsy compared with medical management

A Murine Model to Study Epilepsy and SUDEP Induced by Malaria Infection

One of the largest single sources of epilepsy in the world is produced as a neurological sequela in survivors of cerebral malaria. Nevertheless, the pathophysiological mechanisms of such epileptogenesis remain unknown and no adjunctive therapy during cerebral malaria has been shown to reduce the rate of subsequent epilepsy. There is no existing animal model of postmalarial epilepsy. In this technical report we demonstrate the first such animal models. These models were created from multiple mouse and parasite strain combinations, so that the epilepsy observed retained universality with respect to genetic background. We also discovered spontaneous sudden unexpected death in epilepsy (SUDEP) in two of our strain combinations. These models offer a platform to enable new preclinical research into mechanisms and prevention of epilepsy and SUDEP

Alzheimer’s Disease Studies in the Tex-Mex Border: Dissecting a Complex Multifactorial Problem

Purpose: Alzheimer’s Disease (ALZ) is the leading cause of dementia in the aging population, and Latinos have \u3e3 times higher risk to develop dementia than the overall US population. Although several studies have examined for possible causes of this increased risk, lack of comprehensive information plus a reduced number of Latino samples available in each study have hindered the answers. Description: The University of Texas Rio Grande Valley has joined two large studies looking for multiple biomarkers associated with ALZ: The South Texas Alzheimer’s Center Clinical Data Repository and Biobank (STAC) and the Texas Alzheimer’s Research and Care Consortium (TARCC). We are now collecting clinical data along with neuroimaging and lab biomarkers from each individual enrolled in these studies, with the aim to enroll a large majority of Latinos in our site sample, which will help to elucidate the differences and risk factors inherent to our population in the border. We are also analyzing data from different Latin-American studies to study specific genetic risks, environmental factors, and their interactions. Partners: UTRGV has partnered with UTHSCSA for the STAC study and with many other academic research institutions at TARCC. We aim to provide experiences of clinical training to our psychology students and residents of medical specialties, as well as analysis opportunities and opening postdoctoral positions related to the development of this field at UTRGV. Looking Ahead: We expect to generate substantial contributions to the knowledge of cognitive decline in underserved populations, which can lead to improved treatments and better clinical care. Postdoctoral positions will be opening soon at the Institute of Neuroscience

Cognitive performance and normative data between Hispanic and non-Hispanic cohorts: Results from the South Texas Alzheimer’s Disease Research Center (ADRC)

Background: The prevalence of Alzheimer\u27s disease and related dementias (ADRD) in the United States was estimated as 6.5 million people in 2022, with a five-fold increase for the Hispanic/Latinx population expected by 2060. The South Texas Alzheimer\u27s Disease Center (STAC) was designated as a new ADRC in 2021 by the National Institute on Aging (NIA) with a specific aim to serve the growing needs of the local underrepresented Hispanic population. As cultural and linguistic factors can impact performance on cognitive tests, the goal of the study was to compare UDS-3 cognitive test raw scores and normative data in Hispanic and non-Hispanic adults without cognitive impairment residing in South Texas. Method: Participants from the STAC cohort completed the Uniform Data Set (UDS), V.3.0, which includes demographics and neuropsychological battery. All batteries were administered in the participants’ preferred language, English. Normative data was calculated using Weintraub et al. (2018)’s age, sex, and education adjusted regression models for UDSNB 3.0. Mean differences between baseline visit raw scores and normative data were compared using independent sample t-tests among Hispanic and non-Hispanic participants. Result: Thirty-four Hispanic (mean age=70.4, 67.6% female) and thirty-eight non-Hispanic (mean age=71.9, 57.9% female) participants were included. Hispanic participants had fewer years of education relative to non-Hispanic participants [M(SD)] = [14.7(2.5)] to [16.5(2.5)], respectively; (t(70.1)=3.0, p =0.004); although, the groups did not differ in age or sex distribution (p\u3e0.05). Hispanic and non-Hispanic participants generally performed equivalently on the neuropsychological battery. However, Hispanics had lower mean raw scores on the Montreal Cognitive Assessment (MoCA) (t(70.8)= 3.6, p Conclusion: Overall, Hispanic and non-Hispanic participants performed similarly on the UDS-3 neuropsychological battery. However, Hispanics had lower mean raw and normative scores on the MINT, as well as the MoCA which also includes language measures. Our findings highlight the importance of future research validating the sensitivity and specificity of normative data used in underrepresented populations, especially those at higher risk for ADRD

A Murine Model to Study Epilepsy and SUDEP Induced by Malaria Infection.

One of the largest single sources of epilepsy in the world is produced as a neurological sequela in survivors of cerebral malaria. Nevertheless, the pathophysiological mechanisms of such epileptogenesis remain unknown and no adjunctive therapy during cerebral malaria has been shown to reduce the rate of subsequent epilepsy. There is no existing animal model of postmalarial epilepsy. In this technical report we demonstrate the first such animal models. These models were created from multiple mouse and parasite strain combinations, so that the epilepsy observed retained universality with respect to genetic background. We also discovered spontaneous sudden unexpected death in epilepsy (SUDEP) in two of our strain combinations. These models offer a platform to enable new preclinical research into mechanisms and prevention of epilepsy and SUDEP

Effect of angiotensin-converting enzyme inhibitor and angiotensin receptor blocker initiation on organ support-free days in patients hospitalized with COVID-19

IMPORTANCE Overactivation of the renin-angiotensin system (RAS) may contribute to poor clinical outcomes in patients with COVID-19. Objective To determine whether angiotensin-converting enzyme (ACE) inhibitor or angiotensin receptor blocker (ARB) initiation improves outcomes in patients hospitalized for COVID-19. DESIGN, SETTING, AND PARTICIPANTS In an ongoing, adaptive platform randomized clinical trial, 721 critically ill and 58 non–critically ill hospitalized adults were randomized to receive an RAS inhibitor or control between March 16, 2021, and February 25, 2022, at 69 sites in 7 countries (final follow-up on June 1, 2022). INTERVENTIONS Patients were randomized to receive open-label initiation of an ACE inhibitor (n = 257), ARB (n = 248), ARB in combination with DMX-200 (a chemokine receptor-2 inhibitor; n = 10), or no RAS inhibitor (control; n = 264) for up to 10 days. MAIN OUTCOMES AND MEASURES The primary outcome was organ support–free days, a composite of hospital survival and days alive without cardiovascular or respiratory organ support through 21 days. The primary analysis was a bayesian cumulative logistic model. Odds ratios (ORs) greater than 1 represent improved outcomes. RESULTS On February 25, 2022, enrollment was discontinued due to safety concerns. Among 679 critically ill patients with available primary outcome data, the median age was 56 years and 239 participants (35.2%) were women. Median (IQR) organ support–free days among critically ill patients was 10 (–1 to 16) in the ACE inhibitor group (n = 231), 8 (–1 to 17) in the ARB group (n = 217), and 12 (0 to 17) in the control group (n = 231) (median adjusted odds ratios of 0.77 [95% bayesian credible interval, 0.58-1.06] for improvement for ACE inhibitor and 0.76 [95% credible interval, 0.56-1.05] for ARB compared with control). The posterior probabilities that ACE inhibitors and ARBs worsened organ support–free days compared with control were 94.9% and 95.4%, respectively. Hospital survival occurred in 166 of 231 critically ill participants (71.9%) in the ACE inhibitor group, 152 of 217 (70.0%) in the ARB group, and 182 of 231 (78.8%) in the control group (posterior probabilities that ACE inhibitor and ARB worsened hospital survival compared with control were 95.3% and 98.1%, respectively). CONCLUSIONS AND RELEVANCE In this trial, among critically ill adults with COVID-19, initiation of an ACE inhibitor or ARB did not improve, and likely worsened, clinical outcomes. TRIAL REGISTRATION ClinicalTrials.gov Identifier: NCT0273570

Suicidality in Epilepsy: Does It Share Common Pathogenic Mechanisms with Epilepsy?

Suicidality presents a major global health concern and its association with epilepsy has been suggested. The body of evidence is growing due to targeted epidemiological studies, genetic findings, and neuroimaging data, use of specific neuropsychiatric inventories, neuropsychological tests, and metabolic and immunological studies. Suicide tendencies and psychiatric comorbidity such as depression are not uncommon in chronic diseases, especially in epilepsy. Suicide is an important cause of death in epilepsy, and is usually underestimated. Persons with epilepsy have higher risk for suicide than healthy controls. It appears that some epilepsy types have stronger tendencies for suicide, in particular temporal lobe epilepsy. The suicidal risk factors in persons with epilepsy include difficult to treat epilepsies, onset of epilepsy at an earlier age, and comorbid depression. This clinical evidence is mostly based on observational studies in which we found an increased risk of suicidal ideation, suicidal attempts, and completed suicides in persons with epilepsy. However, we lack prospective and longitudinal studies on suicide in epilepsy. In this chapter we will examine recent research in neurobiological mechanisms between suicidality and epilepsy, and comorbid depression