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Functional connectivity (FC) is a sensitive metric that provides a readout of whole cortex coordinate neural activity in a mouse model. We examine the impact of experimental SAH modeled through endovascular perforation, and the effectiveness of subsequent treatment on FC, through three key questions: 1) Does the endovascular perforation model of SAH induce deficits in FC; 2) Does exposure to hypoxic conditioning provide protection against these FC deficits and, if so, is this neurovascular protection SIRT1-mediated; and 3) does treatment with the SIRT1 activator resveratrol alone provide protection against these FC deficits? Cranial windows were adhered on skull-intact mice that were then subjected to either sham or SAH surgery and either left untreated or treated with hypoxic post-conditioning (with or without EX527) or resveratrol for 3 days. Mice were imaged 3 days post-SAH/sham surgery, temporally aligned with the onset of major SAH sequela in mice. Here we show that the endovascular perforation model of SAH induces global and network-specific deficits in FC by day 3, corresponding with the time frame of DCI in mice. Hypoxic conditioning provides SIRT1-mediated protection against these network-specific FC deficits post-SAH, as does treatment with resveratrol. Conditioning-based strategies provide multifaceted neurovascular protection in experimental SAH.

In 2017, the Sentencing Council introduced a revised guideline for plea-based sentence reductions. The revisions were designed to provide greater certainty and to accelerate the timing of guilty pleas. Late pleas resulting in ‘cracked trials’ have long been a problem in the court system. The guideline was not intended to change the rate of defendants who plead guilty, but rather to increase the percentage of pleas entered early in the criminal process. This brief article reports findings from an analysis of data from the Crown Court before and after the introduction of the revised sentencing guideline. Findings reveal that the overall guilty plea remained stable over the period 2014–2019. The guideline appears to have had no effect on the timing of guilty pleas entered, and in fact the percentage of ‘cracked’ trials rose in the post-guideline period.

Sleep curtailment and circadian misalignment disrupt energy sensing and eating behaviors, which can contribute to weight gain and obesity-related comorbidities. Herein, we review the effects of experimental manipulations of sleep duration and circadian alignment on circulating concentrations of appetite hormones, specifically leptin and ghrelin. Further, we focus on sex differences in hormonal and behavioral responses related to food intake. The studies reviewed suggest potential sex-specific effects of sleep curtailment on key hormones involved in the gut-brain axis, presumably leading to downstream effects on neural processes involved in food seeking and consumption behaviors. However, there is insufficient evidence to declare any sex-specific effects of circadian misalignment on appetite regulation. More research is needed to elucidate the complex sex-specific relationships between sleep, circadian rhythms, energy homeostasis, and appetite regulating mechanisms. Greater knowledge of these mechanisms would aid in the development of targeted methods to mitigate risk for obesity and related metabolic diseases.

Background and Purpose:Early brain injury may be a more significant contributor to poor outcome after aneurysmal subarachnoid hemorrhage (aSAH) than vasospasm and delayed cerebral ischemia. However, studying this process has been hampered by lack of a means of quantifying the spectrum of injury. Global cerebral edema (GCE) is the most widely accepted manifestation of early brain injury but is currently assessed only through subjective, qualitative or semi-quantitative means. Selective sulcal volume (SSV), the CSF volume above the lateral ventricles, has been proposed as a quantitative biomarker of GCE, but is time-consuming to measure manually. Here we implement an automated algorithm to extract SSV and evaluate the age-dependent relationship of reduced SSV on early outcomes after aSAH.Methods:We selected all adults with aSAH admitted to a single institution with imaging within 72 hours of ictus. Scans were assessed for qualitative presence of GCE. SSV was automatically segmented from serial CTs using a deep learning-based approach. Early SSV was the lowest SSV from all early scans. Modified Rankin Scale score of 4 to 6 at hospital discharge was classified as a poor outcome.Results:Two hundred forty-four patients with aSAH were included. Sixty-five (27%) had GCE on admission while 24 developed it subsequently within 72 hours. Median SSV on admission was 10.7 mL but frequently decreased, with minimum early SSV being 3.0 mL (interquartile range, 0.3–11.9). Early SSV below 5 mL was highly predictive of qualitative GCE (area under receiver-operating-characteristic curve, 0.90). Reduced early SSV was an independent predictor of poor outcome, with a stronger effect in younger patients.Conclusions:Automated assessment of SSV provides an objective biomarker of GCE that can be leveraged to quantify early brain injury and dissect its impact on outcomes after aSAH. Such quantitative analysis suggests that GCE may be more impactful to younger patients with SAH.

It is well established from gas centrifuge (GC) development that isotope separation in a rotating, multispecies gaseous medium increases with axial circulation of the rotating gas in a long separation chamber. This article aims at the development of a commercially viable plasma centrifuge (PC) for specific, nonuranium isotopes. The proposed model PC employs crossed constant radial electric and axial magnetic fields to provide radial separation of a partially ionized gas, combined with a thermal method to establish axial circulation in the rotating medium. The proposed thermal method creates an axial temperature gradient by cooling one end of the separation chamber. By calculation, the inclusion of circulation flow is shown to create axial redistribution of the target component concentration, increasing the longitudinal separation. An analysis of the hydrodynamic and thermal problems is performed for an extended end disk PC in the framework of the boundary layer theory. Radial velocity profiles of the conducting gas in the boundary layer are calculated with respect to the temperature ratio in the external flow ( $T_{1}$ ) and the disk surface ( $T_{0}$ ) for various Prandtl (Pr) numbers. The results demonstrate that for small values of the Pr number, cooling of an end surface within the PC separation chamber results in an intensive inflow of the conducting medium to the solid surface. It is shown that in a PC with crossed fields, cooling one of its ends achieves an effective multiplication of the separation effect along the length of the column.

Sporotrichosis is caused by the thermodimorphic fungi of the genus Sporothrix. It is the most common cutaneous mycosis in Latin America, but it is considered uncommon in pregnancy. We report a pregnant woman with with an exuberant ulcerated plaque that proved to be localized sporotrichosis. Therapy choice is a difficult decision in this group of patients. In this case, there was complete resolution of the infection after delivery, without any therapeutic intervention.

Supplemental material, sj-pdf-1-jcb-10.1177_0271678X221079902 for SIRT1 mediates hypoxic postconditioning- and resveratrol-induced protection against functional connectivity deficits after subarachnoid hemorrhage by Julian V Clarke, Lindsey M Brier, Rachel M Rahn, Deepti Diwan, Jane Y Yuan, Annie R Bice, Shin-ichiro Imai, Ananth K Vellimana, Joseph P Culver and Gregory J Zipfel in Journal of Cerebral Blood Flow & Metabolism

Objective: Current treatment for borderline personality disorder (BPD) involves psychological and pharmacological interventions. However, neuromodulation techniques such as repetitive transcranial magnetic stimulation (rTMS) may positively affect BPD symptomatology. The objective of this study was to evaluate the clinical and neuropsychological effects of rTMS on the dorsomedial prefrontal cortex (DMPFC) in BPD patients. Methods: Fourteen patients with BPD were randomized into two groups (active vs. sham) for 15 sessions of rTMS on the DMPFC. Clinical effects were measured using the Borderline Symptoms List (BSL), Clinical Global Impression Scale for BPD (CGI-BPD), Borderline Evaluation of Severity over Time (BEST), Hamilton Depression Rating Scale (HDRS), Hamilton Anxiety Rating Scale (HARS), and Barratt’s Impulsiveness Scale (BIS). Neuropsychological effects were determined by a Stop-Signal Task (SST), the Wisconsin Card-Sorting Test (WCST), and the Iowa Gambling Test (IGT). Results: Within-group comparison showed significant differences (p < 0.05) in CGI-BPD (total score and six of nine psychopathologic domains), BEST, HDRS, HARS, and IGT scores for active modality. Conclusion: The 5 Hz-DMPFC rTMS technique was well tolerated and lessened the severity of BPD symptomatology, especially abandonment, affective issues, interpersonal relationships, suicidal behavior, anger, and paranoid ideation. Cognitive improvement was seen in decision-making. Additional studies are needed to fully evaluate the effects of rTMS on BPD symptomatology. Clinical Trial Registration: NCT03832777.

Delayed cerebral ischemia (DCI) after aneurysmal subarachnoid hemorrhage (SAH) has been associated with numerous pathophysiological sequelae, including large artery vasospasm and microvascular thrombosis. The focus of this review is to provide an overview of experimental animal model studies and human autopsy studies that explore the temporal-spatial characterization and mechanism of microvascular platelet aggregation and thrombosis following SAH, as well as to critically assess experimental studies and clinical trials highlighting preventative therapeutic options against this highly morbid pathophysiological process. Upon review of the literature, we discovered that microvascular platelet aggregation and thrombosis occur after experimental SAH across multiple species and SAH induction techniques in a similar time frame to other components of DCI, occurring in the cerebral cortex and hippocampus across both hemispheres. We discuss the relationship of these findings to human autopsy studies. In the final section of this review, we highlight the important therapeutic options for targeting microvascular platelet aggregation and thrombosis, and emphasize why therapeutic targeting of this neurovascular pathology may improve patient care. We encourage ongoing research into the pathophysiology of SAH and DCI, especially in regard to microvascular platelet aggregation and thrombosis and the translation to randomized clinical trials.

Background Many therapies designed to prevent delayed cerebral ischemia (DCI) and improve neurological outcome in aneurysmal subarachnoid hemorrhage (SAH) have failed, likely because of targeting only one element of what has proven to be a multifactorial disease. We previously demonstrated that initiating hypoxic conditioning before SAH (hypoxic preconditioning) provides powerful protection against DCI. Here, we expanded upon these findings to determine whether hypoxic conditioning delivered at clinically relevant time points after SAH (hypoxic postconditioning) provides similarly robust DCI protection. Methods and Results In this study, we found that hypoxic postconditioning (8% O 2 for 2 hours) initiated 3 hours after SAH provides strong protection against cerebral vasospasm, microvessel thrombi, and neurological deficits. By pharmacologic and genetic inhibition of SIRT1 (sirtuin 1) using EX527 and global Sirt1 −/− mice, respectively, we demonstrated that this multifaceted DCI protection is SIRT1 mediated. Moreover, genetic overexpression of SIRT1 using Sirt1‐Tg mice, mimicked the DCI protection afforded by hypoxic postconditioning. Finally, we found that post‐SAH administration of resveratrol attenuated cerebral vasospasm, microvessel thrombi, and neurological deficits, and did so in a SIRT1‐dependent fashion. Conclusions The present study indicates that hypoxic postconditioning provides powerful DCI protection when initiated at clinically relevant time points, and that pharmacologic augmentation of SIRT1 activity after SAH can mimic this beneficial effect. We conclude that conditioning‐based therapies administered after SAH hold translational promise for patients with SAH and warrant further investigation.

We study Maurer-Cartan moduli spaces of dg algebras and associated dg categories and show that, while not quasi-isomorphism invariants, they are invariants of strong homotopy type, a natural notion that has not been studied before. We prove, in several different contexts, Schlessinger-Stasheff type theorems comparing the notions of homotopy and gauge equivalence for Maurer-Cartan elements as well as their categorified versions. As an application, we re-prove and generalize Block-Smith's higher Riemann-Hilbert correspondence, and develop its analogue for simplicial complexes and topological spaces., Comment: V3: Added reference. 54 pages