Age-related brain atrophy and the positive effects of behavioral enrichment in middle-aged beagles.

Aging dogs serve as a valuable preclinical model for Alzheimer's disease (AD) due to their natural age-related development of beta-amyloid (Aß) plaques, human-like metabolism, and large brains that are ideal for studying structural brain aging trajectories from serial neuroimaging. Here we examined the effects of chronic treatment with the calcineurin inhibitor (CNI) tacrolimus or the nuclear factor of activated T cells (NFAT)-inhibiting compound Q134R on age-related canine brain atrophy from a longitudinal study in middle-aged beagles (36 females, 7 males) undergoing behavioral enrichment. Annual MRI was analyzed using modern, automated techniques for region-of-interest -based and voxel-based volumetric assessments. We found that the frontal lobe showed accelerated atrophy with age, while the caudate nucleus remained relatively stable. Remarkably, the hippocampus increased in volume in all dogs. None of these changes were influenced by tacrolimus or Q134R treatment. Our results suggest that behavioral enrichment can prevent atrophy and increase the volume of the hippocampus but does not prevent aging-associated prefrontal cortex atrophy.Significance Statement Aging canines naturally show significant neuropathological similarities to human aging and AD, making them valuable translational models for testing disease-modifying treatments. We applied modern, state-of-the-art longitudinal volumetric analysis approaches to evaluate treatment effects from structural MRI in a large cohort of middle-aged beagles treated with the FDA approved calcineurin inhibitor, tacrolimus, or the experimental NFAT inhibitor, Q134R, while undergoing extensive behavioral enrichment. We show increased hippocampal volumes across all dogs, even control placebo dogs, compelling evidence for a strong enrichment-related benefit on hippocampal structural integrity. Our findings are the first of its kind to demonstrate benefits of behavioral intervention on longitudinal structural brain changes in a higher mammalian model of aging and AD.

Compensatory growth and recovery of cartilage cytoarchitecture after transient cell death in fetal mouse limbs.

A major question in developmental and regenerative biology is how organ size and architecture are controlled by progenitor cells. While limb bones exhibit catch-up growth (recovery of a normal growth trajectory after transient developmental perturbation), it is unclear how this emerges from the behaviour of chondroprogenitors, the cells sustaining the cartilage anlagen that are progressively replaced by bone. Here we show that transient sparse cell death in the mouse fetal cartilage is repaired postnatally, via a two-step process. During injury, progression of chondroprogenitors towards more differentiated states is delayed, leading to altered cartilage cytoarchitecture and impaired bone growth. Then, once cell death is over, chondroprogenitor differentiation is accelerated and cartilage structure recovered, including partial rescue of bone growth. At the molecular level, ectopic activation of mTORC1 correlates with, and is necessary for, part of the recovery, revealing a specific candidate to be explored during normal growth and in future therapies.

Patterns of subregional cerebellar atrophy across epilepsy syndromes: An ENIGMA-Epilepsy study.

OBJECTIVE: The intricate neuroanatomical structure of the cerebellum is of longstanding interest in epilepsy, but has been poorly characterized within the current corticocentric models of this disease. We quantified cross-sectional regional cerebellar lobule volumes using structural magnetic resonance imaging in 1602 adults with epilepsy and 1022 healthy controls across 22 sites from the global ENIGMA-Epilepsy working group. METHODS: A state-of-the-art deep learning-based approach was employed that parcellates the cerebellum into 28 neuroanatomical subregions. Linear mixed models compared total and regional cerebellar volume in (1) all epilepsies, (2) temporal lobe epilepsy with hippocampal sclerosis (TLE-HS), (3) nonlesional temporal lobe epilepsy, (4) genetic generalized epilepsy, and (5) extratemporal focal epilepsy (ETLE). Relationships were examined for cerebellar volume versus age at seizure onset, duration of epilepsy, phenytoin treatment, and cerebral cortical thickness. RESULTS: Across all epilepsies, reduced total cerebellar volume was observed (d = .42). Maximum volume loss was observed in the corpus medullare (dmax = .49) and posterior lobe gray matter regions, including bilateral lobules VIIB (dmax = .47), crus I/II (dmax = .39), VIIIA (dmax = .45), and VIIIB (dmax = .40). Earlier age at seizure onset ( η ρ max 2 = .05) and longer epilepsy duration ( η ρ max 2 = .06) correlated with reduced volume in these regions. Findings were most pronounced in TLE-HS and ETLE, with distinct neuroanatomical profiles observed in the posterior lobe. Phenytoin treatment was associated with reduced posterior lobe volume. Cerebellum volume correlated with cerebral cortical thinning more strongly in the epilepsy cohort than in controls. SIGNIFICANCE: We provide robust evidence of deep cerebellar and posterior lobe subregional gray matter volume loss in patients with chronic epilepsy. Volume loss was maximal for posterior subregions implicated in nonmotor functions, relative to motor regions of both the anterior and posterior lobe. Associations between cerebral and cerebellar changes, and variability of neuroanatomical profiles across epilepsy syndromes argue for more precise incorporation of cerebellar subregional damage into neurobiological models of epilepsy.

Opioid Prescribing Patterns After Imposition of Setting-Specific Limits on Prescription Duration.

Importance: Despite their widespread adoption across the US, policies imposing one-size-fits-all limits on the duration of prescriptions for opioids have shown modest and mixed implications for prescribing. Objective: To assess whether a prescription duration limit policy tailored to different clinical settings was associated with shorter opioid prescription lengths. Design, Setting, and Participants: This cross-sectional study examined changes in opioid prescribing patterns for opioid-naive Medicaid enrollees aged 12 to 64 years before and after implementation of a statewide prescription duration limit policy in West Virginia in June 2018. Patients with cancer or Medicare coverage were excluded. The policy assigned a 7-day duration limit to opioid prescriptions for adults treated in outpatient hospital- or office-based practices, a 4-day limit for adults treated in emergency departments, and a 3-day limit for pediatric patients younger than 18 years regardless of clinical setting. Data were examined from January 1, 2017, through September 30, 2019, and data were analyzed from June 12 to October 30, 2023. Main Outcomes and Measures: Whether a patient's initial opioid prescription was longer in days than the June 2018 policy limit for a given care setting before and after policy implementation. Interrupted time series models were used to calculate the association between the policy's implementation and outcomes. Results: The analytic sample included 44 703 Medicaid enrollees (27 957 patients [62.5%] before policy implementation and 16 746 patients [37.5%] after policy implementation; mean [SD] age, 33.9 [13.4] years; 27 461 females [61.4%]). Among adults treated in outpatient hospital- or office-based settings, the duration limit policy was associated with a decrease of 8.83 (95% CI, -10.43 to -7.23) percentage points (P < .001), or a 56.8% relative reduction, in the proportion of prescriptions exceeding the 7-day limit. In the emergency department setting, the policy was associated with a decrease of 7.03 (95% CI, -10.38 to -3.68) percentage points (P < .001), a 37.5% relative reduction, in the proportion of prescriptions exceeding the 4-day limit. The proportion of pediatric opioid prescriptions longer than the 3-day limit decreased by 12.80 (95% CI, -17.31 to -8.37) percentage points (P < .001), a 26.5% relative reduction, after the policy's implementation. Conclusions and Relevance: Results of this cross-sectional study suggest that opioid prescription duration limits tailored to different clinical settings are associated with reduced length of prescriptions for opioid-naive patients. Additional research is needed to evaluate whether these limits are associated with reductions in the incidence of opioid use disorder or with unintended consequences, such as shifts to illicit opioids.

A perspective on ungulate management and welfare assessment across the traditional zoo to large landscape spectrum.

Wild ungulates are managed in human care in a range of settings from traditional zoos to large ranches. These varied settings present different portfolios of risks for good or poor welfare, which leads some to question whether a particular setting is "good for welfare" and have frustrated others interested in comparing the welfare of ungulates across these settings. Differing housing and management scenarios present different challenges and opportunities in terms of welfare but this commentary posits that good welfare is possible in all of these settings. In this commentary, we also consider natural behaviors that may, at face value, compromise welfare and discuss how taking a long view on welfare addresses concerns about these behaviors, in part using arguments related to normal behavioral development that likely improves welfare at other life stages. We also highlight the role of motivation in seemingly welfare-compromising behaviors. Finally, some indicators of welfare that we believe transcend management scenarios, and are thus able to be compared across scenarios, are suggested.

Nuclear factor Y is a pervasive regulator of neuronal gene expression.

Nervous system function relies on the establishment of complex gene expression programs that provide neuron-type-specific and core pan-neuronal features. These complementary regulatory paradigms are controlled by terminal selector and parallel-acting transcription factors (TFs), respectively. Here, we identify the nuclear factor Y (NF-Y) TF as a pervasive direct and indirect regulator of both neuron-type-specific and pan-neuronal gene expression. Mapping global NF-Y targets reveals direct binding to the cis-regulatory regions of pan-neuronal genes and terminal selector TFs. We show that NFYA-1 controls pan-neuronal gene expression directly through binding to CCAAT boxes in target gene promoters and indirectly by regulating the expression of terminal selector TFs. Further, we find that NFYA-1 regulation of neuronal gene expression is important for neuronal activity and motor function. Thus, our research sheds light on how global neuronal gene expression programs are buffered through direct and indirect regulatory mechanisms.

Patterns of subregional cerebellar atrophy across epilepsy syndromes: An ENIGMA-Epilepsy study.

Objective: The intricate neuroanatomical structure of the cerebellum is of longstanding interest in epilepsy, but has been poorly characterized within the current cortico-centric models of this disease. We quantified cross-sectional regional cerebellar lobule volumes using structural MRI in 1,602 adults with epilepsy and 1,022 healthy controls across twenty-two sites from the global ENIGMA-Epilepsy working group. Methods: A state-of-the-art deep learning-based approach was employed that parcellates the cerebellum into 28 neuroanatomical subregions. Linear mixed models compared total and regional cerebellar volume in i) all epilepsies; ii) temporal lobe epilepsy with hippocampal sclerosis (TLE-HS); iii) non-lesional temporal lobe epilepsy (TLE-NL); iv) genetic generalised epilepsy; and (v) extra-temporal focal epilepsy (ETLE). Relationships were examined for cerebellar volume versus age at seizure onset, duration of epilepsy, phenytoin treatment, and cerebral cortical thickness. Results: Across all epilepsies, reduced total cerebellar volume was observed (d=0.42). Maximum volume loss was observed in the corpus medullare (dmax=0.49) and posterior lobe grey matter regions, including bilateral lobules VIIB (dmax= 0.47), Crus I/II (dmax= 0.39), VIIIA (dmax=0.45) and VIIIB (dmax=0.40). Earlier age at seizure onset (ηρ2max=0.05) and longer epilepsy duration (ηρ2max=0.06) correlated with reduced volume in these regions. Findings were most pronounced in TLE-HS and ETLE with distinct neuroanatomical profiles observed in the posterior lobe. Phenytoin treatment was associated with reduced posterior lobe volume. Cerebellum volume correlated with cerebral cortical thinning more strongly in the epilepsy cohort than in controls. Significance: We provide robust evidence of deep cerebellar and posterior lobe subregional grey matter volume loss in patients with chronic epilepsy. Volume loss was maximal for posterior subregions implicated in non-motor functions, relative to motor regions of both the anterior and posterior lobe. Associations between cerebral and cerebellar changes, and variability of neuroanatomical profiles across epilepsy syndromes argue for more precise incorporation of cerebellum subregions into neurobiological models of epilepsy.

Growth in Suicide Rates Among Children During the Illicit Opioid Crisis.

This article documents child suicide rates from 1980 to 2020 in the United States using the National Vital Statistics System Multiple Cause of Death database. After generally declining for decades, suicide rates among children aged 10-17 accelerated from 2011 to 2018 in an unprecedented rise in both duration and magnitude. I consider the role of the illicit opioid crisis in driving this mental health crisis. In August 2010, an abuse-deterrent version of OxyContin was introduced and the original formulation was removed from the market, leading to a shift to illicit opioids and stimulating growth in illicit opioid markets. Areas more exposed to reformulation-as measured by pre-reformulation rates of OxyContin misuse in the National Survey on Drug Use and Health-were more affected by the transition to illicit opioids and experienced sharper growth in child suicide rates. The evidence suggests that children's illicit opioid use did not increase, implying that the illicit opioid crisis engendered higher suicide propensities by increasing suicidal risk factors for children, such as increasing rates of child neglect and altering household living arrangements. In complementary analyses, I document how living conditions declined for children during this time period.

A genomic survey of Clostridioides difficile isolates from hospitalized patients in Melbourne, Australia.

IMPORTANCE: There has been a decrease in healthcare-associated Clostridioides difficile infection in Australia, but an increase in the genetic diversity of infecting strains, and an increase in community-associated cases. Here, we studied the genetic relatedness of C. difficile isolated from patients at a major hospital in Melbourne, Australia. Diverse ribotypes were detected, including those associated with community and environmental sources. Some types of isolates were more likely to carry antimicrobial resistance determinants, and many of these were associated with mobile genetic elements. These results correlate with those of other recent investigations, supporting the observed increase in genetic diversity and prevalence of community-associated C. difficile, and consequently the importance of sources of transmission other than symptomatic patients. Thus, they reinforce the importance of surveillance for in both hospital and community settings, including asymptomatic carriage, food, animals, and other environmental sources to identify and circumvent important sources of C. difficile transmission.

Realistic prediction and engineering of high-Q modes to implement stable Fano resonances in acoustic devices.

Quasi-bound states in the continuum (QBICs) coupling into the propagating spectrum manifest themselves as high-quality factor (Q) modes susceptible to perturbations. This poses a challenge in predicting stable Fano resonances for realistic applications. Besides, where and when the maximum field enhancement occurs in real acoustic devices remains elusive. In this work, we theoretically predict and experimentally demonstrate the existence of a Friedrich-Wintgen BIC in an open acoustic cavity. We provide direct evidence for a QBIC by mapping the pressure field inside the cavity using a Laser Doppler Vibrometer (LDV), which provides the missing field enhancement data. Furthermore, we design a symmetry-reduced BIC and achieve field enhancement by a factor of about three compared to the original cavity. LDV measurements are a promising technique for obtaining high-Q modes' missing field enhancement data. The presented results facilitate the future applications of BICs in acoustics as high-intensity sound sources, filters, and sensors.

Active maintenance of CD8+ T cell naivety through regulation of global genome architecture.

The differentiation of naive CD8+ T lymphocytes into cytotoxic effector and memory CTL results in large-scale changes in transcriptional and phenotypic profiles. Little is known about how large-scale changes in genome organization underpin these transcriptional programs. We use Hi-C to map changes in the spatial organization of long-range genome contacts within naive, effector, and memory virus-specific CD8+ T cells. We observe that the architecture of the naive CD8+ T cell genome is distinct from effector and memory genome configurations, with extensive changes within discrete functional chromatin domains associated with effector/memory differentiation. Deletion of BACH2, or to a lesser extent, reducing SATB1 DNA binding, within naive CD8+ T cells results in a chromatin architecture more reminiscent of effector/memory states. This suggests that key transcription factors within naive CD8+ T cells act to restrain T cell differentiation by actively enforcing a unique naive chromatin state.

Educational Attainment and US Drug Overdose Deaths.

Importance: Educational attainment in the US is associated with life expectancy. As the opioid crisis worsens, it is critical to understand how overdose death rate trends evolve across education groups. Objective: To investigate the association between educational attainment and overdose death rates, with emphasis on trends during the COVID-19 pandemic. Design, Setting, and Participants: This cross-sectional study used National Vital Statistics System Mortality Multiple Cause-of-Death data describing overdose death rates in the US by educational attainment from January 1, 2000, to December 31, 2021, with a focus on 2018 to 2021. Overdose deaths were aggregated by year and educational level for decedents aged 25 years or older. Exposure: Educational attainment, categorized as no high school (HS) diploma, HS diploma (or General Educational Development) but no college, some college but no bachelor's degree, and bachelor's degree or more. Main Outcomes and Measures: The main outcomes were rates of all overdose deaths, overdose deaths involving opioids, and overdose deaths involving synthetic opioids. Results: Of 912 057 overdose deaths with education information from 2000 to 2021 (mean [SD] age at death, 44.9 [12.3] years; 64.1% male), there were 625 400 deaths (68.6%) among individuals with no college education and 286 657 deaths (31.4%) among those with at least some college. The overdose death rate was 19.9 per 100 000 population. From 2018 to 2021, there were 301 557 overdose deaths, including 58 319 (19.3%) among individuals without an HS diploma, 153 603 (50.9%) among people with an HS diploma, 64 682 (21.4%) among individuals with some college, and 24 953 (8.3%) among individuals with a bachelor's degree. There were 3324 overdose deaths (1.1%) among American Indian or Alaska Native individuals, 2968 (1.0%) among Asian American or Pacific Islander individuals, 49 152 (16.3%) among Black individuals, 31 703 (10.5%) among Hispanic individuals, 211 359 (70.1%) among White individuals, and 3051 (1.0%) among multiracial individuals. From 2018 to 2021, the overdose death rate was 33.4 per 100 000 population, the opioid-related overdose death rate was 24.2 per 100 000 population, and the synthetic opioid overdose death rate was 19.1 per 100 000 population. From 2018 to 2021, the overdose death rate for those without a HS diploma increased by 35.4 per 100 000 population compared with 1.5 per 100 000 population for those with a bachelor's degree. This differential growth was primarily due to increased rates of death involving synthetic opioids. Conclusions and Relevance: In this cross-sectional study, lower educational attainment was found to be associated with higher growth in overdose deaths. As the opioid crisis has transitioned to fentanyl and polysubstance use, overdose deaths have become more prevalent in groups with lower socioeconomic status, potentially exacerbating existing life-expectancy disparities.

Dual Blockade of EP2 and EP4 Signaling is Required for Optimal Immune Activation and Antitumor Activity Against Prostaglandin-Expressing Tumors.

While the role of prostaglandin E2 (PGE2) in promoting malignant progression is well established, how to optimally block the activity of PGE2 signaling remains to be demonstrated. Clinical trials with prostaglandin pathway targeted agents have shown activity but without sufficient significance or dose-limiting toxicities that have prevented approval. PGE2 signals through four receptors (EP1-4) to modulate tumor progression. EP2 and EP4 signaling exacerbates tumor pathology and is immunosuppressive through potentiating cAMP production. EP1 and EP3 signaling has the opposite effect through increasing IP3 and decreasing cAMP. Using available small-molecule antagonists of single EP receptors, the cyclooxygenase-2 (COX-2) inhibitor celecoxib, or a novel dual EP2/EP4 antagonist generated in this investigation, we tested which approach to block PGE2 signaling optimally restored immunologic activity in mouse and human immune cells and antitumor activity in syngeneic, spontaneous, and xenograft tumor models. We found that dual antagonism of EP2 and EP4 together significantly enhanced the activation of PGE2-suppressed mouse and human monocytes and CD8+ T cells in vitro as compared with single EP antagonists. CD8+ T-cell activation was dampened by single EP1 and EP3 antagonists. Dual EP2/EP4 PGE2 receptor antagonists increased tumor microenvironment lymphocyte infiltration and significantly reduced disease burden in multiple tumor models, including in the adenomatous polyposis coli (APC)min+/- spontaneous colorectal tumor model, compared with celecoxib. These results support a hypothesis that redundancy of EP2 and EP4 receptor signaling necessitates a therapeutic strategy of dual blockade of EP2 and EP4. Here we describe TPST-1495, a first-in-class orally available small-molecule dual EP2/EP4 antagonist. Significance: Prostaglandin (PGE2) drives tumor progression but the pathway has not been effectively drugged. We demonstrate significantly enhanced immunologic potency and antitumor activity through blockade of EP2 and EP4 PGE2 receptor signaling together with a single molecule.

Sound attenuation enhancement of acoustic meta-atoms via coupling.

Arrangements of acoustic meta-atoms, better known as acoustic metamaterials, are commonly applied in acoustic cloaking, for the attenuation of acoustic fields or for acoustic focusing. A precise design of single meta-atoms is required for these purposes. Understanding the details of their interaction allows improvement of the collective performance of the meta-atoms as a system, for example, in sound attenuation. Destructive interference of their scattered fields, for example, can be mitigated by adjusting the coupling or tuning of individual meta-atoms. Comprehensive numerical studies of various configurations of a resonator pair show that the coupling can lead to degenerate modes at periodic distances between the resonators. We show how the resonators' separation and relative orientation influence the coupling and thereby tunes the sound attenuation. The simulation results are supported by experiments using a two-dimensional parallel-plate waveguide. It is shown that coupling parameters like distance, orientation, detuning, and radiation loss provide additional degrees of freedom for efficient acoustic meta-atom tuning to achieve unprecedented interactions with excellent sound attenuation properties.

Relationship of POLST to Hospitalization and ICU Care Among Nursing Home Residents in California.

BACKGROUND: Physician Orders for Life Sustaining Treatment (POLST) document instructions for intensity of care based upon patient care preferences. POLST forms generally reflect patients' wishes and dictate subsequent medical care, but it is not known how POLST use and content among nursing home residents is associated with inpatient utilization across a large population. OBJECTIVE: Evaluate the relationship between POLST use and content with hospital utilization among nursing home residents in California. DESIGN: Retrospective cohort study using the Minimum Data Set linked to California Section S (POLST documentation), the Medicare Beneficiary Summary File, and Medicare line item claims. PATIENTS: California nursing home residents with Medicare fee-for-service insurance, 2011-2016. MAIN MEASURES: Hospitalization, days in the hospital, and days in the intensive care unit (ICU) after adjustment for resident and nursing home characteristics. KEY RESULTS: The 1,112,834 residents had a completed and signed (valid) POLST containing orders for CPR with Full treatment 29.6% of resident-time (in person-years) and a DNR order with Selective treatment or Comfort care 27.1% of resident-time. Unsigned POLSTs accounted for 11.3% of resident-time. Residents experienced 14 hospitalizations and a mean of 120 hospital days and 37 ICU days per 100 person-years. Residents with a POLST indicating CPR Full treatment had utilization nearly identical to residents without a POLST. A gradient of decreased utilization was related to lower intensity of care orders. Compared to residents without a POLST, residents with a POLST indicating DNR Comfort care spent 56 fewer days in the hospital and 22 fewer days in the ICU per 100 person-years. Unsigned POLST had a weaker and less consistent relationship with hospital utilization. CONCLUSIONS: Among California NH residents, there is a direct relationship between intensity of care preferences in POLST and hospital utilization. These findings emphasize the importance of a valid POLST capturing informed preferences for nursing home residents.

Understanding the rise in overdose deaths involving opioids and non-opioid prescription drugs in the United States.

BACKGROUND: Previous studies demonstrate that the reformulation of OxyContin in the U.S. in 2010 induced substitution to illicit opioids, causing illicit opioid markets to grow disproportionately fast in states more exposed to the reformulation. In this paper, we examine if this shift to the illicit market also led to a rise in polysubstance overdose deaths involving non-opioid prescription drugs, including gabapentinoids and "Z-drugs" and, separately, benzodiazepines. METHODS: Using a difference-in-differences framework, the relationship between exposure to reformulation and overdose death rates including specific substances was studied in each year from 1999 to 2020 while accounting for fixed differences across states, common nationwide shocks, and state-level differences in pain reliever misuse prior to reformulation. Exposure to reformulation was measured as the pre-reformulation rate of OxyContin misuse. RESULTS: Exposure to reformulation predicted growth in overdose deaths involving gabapentinoids and Z-drugs. There is less evidence that it predicted growth in overdose deaths involving benzodiazepines. However, for all substances, there is strong evidence that pre-reformulation OxyContin misuse rates predicted post-reformulation growth in overdose deaths concurrently involving synthetic opioids. DISCUSSION: The opioid crisis has changed in radical ways. This study links a major supply-side intervention to the increase in polysubstance overdose deaths involving non-opioid prescription drugs, specifically gabapentinoids and Z-drugs.

Equipment Setup and Artifact Removal for Simultaneous Electroencephalogram and Functional Magnetic Resonance Imaging for Clinical Review in Epilepsy.

Simultaneous electroencephalogram and functional magnetic resonance imaging (EEG-fMRI) is a unique combined technique that provides synergy in the understanding and localization of seizure onset in epilepsy. However, reported experimental protocols for EEG-fMRI recordings fail to address details about conducting such procedures on epilepsy patients. In addition, these protocols are limited solely to research settings. To fill the gap between patient monitoring in an epilepsy monitoring unit (EMU) and conducting research with an epilepsy patient, we introduce a unique EEG-fMRI recording protocol of epilepsy during the interictal period. The use of an MR conditional electrode set, which can also be used in the EMU for a simultaneous scalp EEG and video recording, allows an easy transition of EEG recordings from the EMU to the scanning room for concurrent EEG-fMRI recordings. Details on the recording procedures using this specific MR conditional electrode set are provided. In addition, the study explains step-by-step EEG processing procedures to remove the imaging artifacts, which can then be used for clinical review. This experimental protocol promotes an amendment to the conventional EEG-fMRI recording for enhanced applicability in both clinical (i.e., EMU) and research settings. Furthermore, this protocol provides the potential to expand this modality to postictal EEG-fMRI recordings in the clinical setting.

One antigen closer to understanding membranous nephropathy.

Membranous nephropathy is an immune-mediated kidney disease characterized by subepithelial immune deposits. Through the utilization of advanced proteomic techniques, multiple target antigens have been identified, including those associated with primary and secondary etiologies. Nonsteroidal anti-inflammatory drugs represent an important secondary cause of membranous nephropathy. In this study by Sethi et al., advanced proteomic techniques identify proprotein convertase subtilisin/kexin type 6 as a target antigen in nonsteroidal anti-inflammatory drug-associated membranous nephropathy.