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Dendrite defects and loss are early cellular alterations observed across neurodegenerative diseases that play a role in early disease pathogenesis. Dendrite degeneration can be modeled by expressing pathogenic polyglutamine disease transgenes in Drosophila neurons in vivo. Here, we show that we can protect against dendrite loss in neurons modeling neurodegenerative polyglutamine diseases through injury to a single primary dendrite branch. We find that this neuroprotection is specific to injury-induced activation of dendrite regeneration: neither injury to the axon nor injury just to surrounding tissues induces this response. We show that the mechanism of this regenerative response is stabilization of the actin (but not microtubule) cytoskeleton. We also demonstrate that this regenerative response may extend to other neurodegenerative diseases. Together, we provide evidence that activating dendrite regeneration pathways has the potential to slow-or even reverse-dendrite loss in neurodegenerative disease., (© 2024. The Author(s).)

Binge drinking is one of the most common patterns (more than 90%) of alcohol consumption by young people. During adolescence, the brain undergoes maturational changes that influence behavioral control and affective behaviors, such as cerebellar brain volume and function in adulthood. We investigated long-term impacts of adolescent binge ethanol exposure on affective and exploratory behaviors and cerebellar gene expression in adult male and female mice. Further, the cerebellum is increasingly recognized as a brain region integrating a multitude of behaviors that span from the traditional primary sensory-motor to affective functions, such as anxiety and stress reactivity. Therefore, we investigated the persistent effects of adolescent intermittent ethanol (AIE) on exploratory and affective behaviors and began to elucidate the role of the cerebellum in these behaviors through excitatory signaling gene expression. We exposed C57BL/6J mice to AIE or air (control) vapor inhalation from postnatal day 28-42. After prolonged abstinence (>34 days), in young adulthood (PND 77+) we assessed behavior in the open field, light/dark, tail suspension, and forced swim stress tests to determine changes in affective behaviors including anxiety-like, depressive-like, and stress reactivity behavior. Excitatory signaling gene mRNA levels of fragile X messenger ribonucleoprotein (FMR1), glutamate receptors (Grin2a, Grin2b and Grm5) and excitatory synaptic markers (PSD-95 and Eaat1) were measured in the cerebellum of adult control and AIE-exposed mice. AIE-exposed mice showed decreased exploratory behaviors in the open field test (OFT) where both sexes show reduced ambulation, however only females exhibited a reduction in rearing. Additionally, in the OFT, AIE-exposed females also exhibited increased anxiety-like behavior (entries to center zone). In the forced swim stress test, AIE-exposed male mice, but not females, spent less time immobile compared to their same-sex controls, indicative of sex-specific changes in stress reactivity. Male and female AIE-exposed mice showed increased Grin2b (Glutamate Ionotropic Receptor NMDA Type Subunit 2B) mRNA levels in the cerebellum compared to their same-sex controls. Together, these data show that adolescent binge-like ethanol exposure altered both exploratory and affective behaviors in a sex-specific manner and modified cerebellar Grin2b expression in adult mice. This indicates the cerebellum may serve as an important brain region that is susceptible to long-term molecular changes after AIE., Competing Interests: Declaration of Competing Interest The authors declare no conflict of interest., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Binge drinking is one of the most common patterns (more than 90%) of alcohol consumption by young people. During adolescence, the brain undergoes maturational changes that influence behavioral control and affective behaviors, such as cerebellar brain volume and function in adulthood. We investigated long-term impacts of adolescent binge ethanol exposure on affective and exploratory behaviors and cerebellar gene expression in adult male and female mice. Further, the cerebellum is increasingly recognized as a brain region integrating a multitude of behaviors that span from the traditional primary sensory-motor to affective functions, such as anxiety and stress reactivity. Therefore, we investigated the persistent effects of adolescent intermittent ethanol (AIE) on exploratory and affective behaviors and began to elucidate the role of the cerebellum in these behaviors through excitatory signaling gene expression. We exposed C57BL/6J mice to AIE or air (control) vapor inhalation from postnatal day 28-42. After prolonged abstinence (>34 days), in young adulthood (PND 77+) we assessed behavior in the open field, light/dark, tail suspension, and forced swim stress tests to determine changes in affective behaviors including anxiety-like, depressive-like, and stress reactivity behavior. Excitatory signaling gene mRNA levels of fragile X messenger ribonucleoprotein ( FMR1) , glutamate receptors ( Grin2a , Grin2B and Grm5 ) and excitatory synaptic markers (PSD-95 and Eaat1) were measured in the cerebellum of adult control and AIE-exposed mice. AIE-exposed mice showed decreased exploratory behaviors in the open field test (OFT) where both sexes show reduced ambulation, however only females exhibited a reduction in rearing. Additionally, in the OFT, AIE-exposed females also exhibited increased anxiety-like behavior (entries to center zone). In the forced swim stress test, AIE-exposed male mice, but not females, spent less time immobile compared to their same-sex controls, indicative of sex-specific changes in stress reactivity. Male and female AIE-exposed mice showed increased Grin2B (Glutamate Ionotropic Receptor NMDA Type Subunit 2B) mRNA levels in the cerebellum compared to their same-sex controls. Together, these data show that adolescent binge-like ethanol exposure altered both exploratory and affective behaviors in a sex-specific manner and modified cerebellar Grin2B expression in adult mice. This indicates the cerebellum may serve as an important brain region that is susceptible to long-term molecular changes after AIE., Highlights: Adolescent intermittent ethanol (AIE) exposure decreased exploratory behavior in adult male and female mice.In females, but not males, AIE increased anxiety-like behavior.In males, but not females, AIE reduced stress reactivity in adulthood.These findings indicate sex differences in the enduring effects of AIE on exploratory and affective behaviors. Cerebellar Grin2B mRNA levels were increased in adulthood in both male and female AIE-exposed mice. These findings add to the small, but growing literature on behavioral AIE effects in mice, and establish cerebellar excitatory synaptic gene expression as an enduring effect of adolescent ethanol exposure.

Objectives: Transcarotid artery revascularization (TCAR) is a carotid stenting technique that utilizes reversal of cerebral arterial flow to confer cerebral protection. Although carotid endarterectomy (CEA) remains the standard for treatment of symptomatic and asymptomatic carotid stenosis, the search for the optimal minimally invasive option for the high-risk surgical patient continues. The goal of the current study is to evaluate the 1-year safety and efficacy of TCAR in a prospective clinical trial., Methods: ROADSTER 2 is a prospective, open-label, single-arm, multicenter, post-approval registry for patients undergoing TCAR. All patients were considered high risk for CEA and underwent independent neurological assessments preoperatively, postoperatively, and had long-term clinical follow-up. The primary end point was incidence of ipsilateral stroke after treatment with the ENROUTE Transcarotid Stent System. Secondary end points included individual/composite rates of stroke, death, and perioperative myocardial infarction., Results: Between June 2016 and November 2018, 155 patients at 21 centers in the United States and one in the European Union were enrolled and represented a subset of the overall trial. Asymptomatic (n = 119; 77%) and symptomatic patients (n = 36; 23%) with high-risk anatomic (ie, high lesion, restenosis, radiation injury; 43%), physiologic (32%), or combined factors (25%) were enrolled. No patient suffered a perioperative myocardial infarction or stroke. Over the year, no patient had an ipsilateral stroke, but four patients died (2.6%), all from non-neurological causes. Additionally, a technical success rate of 98.7% with a low cranial nerve deficit rate of 1.3% was achieved., Conclusions: In patients with high risk factors, TCAR yields high technical success with a low stroke and death rate at 1 year. Further comparative studies with CEA are warranted., (Copyright © 2022 Society for Vascular Surgery. Published by Elsevier Inc. All rights reserved.)

Purpose: Endovascular stent graft repair of abdominal aortic aneurysms (AAA) with the Endologix Powerlink System (Endologix, Inc, Irvine, Calif) has been shown to be a safe and effective alternative to open surgery in patients having an aortic neck diameter of up to 26 mm. We assessed the safety and effectiveness of AAA repair in patients with wide aortic necks (up to 32 mm in diameter) using the Powerlink XL System., Methods: Between September 2005 and June 2008, a prospective, multicenter, pivotal US Food and Drug Administration trial of the Powerlink XL System for endovascular aneurysm repair was conducted at 13 centers. Using a sizing algorithm based on computed tomography scan (CT)-based measurements, a total of 78 patients (N = 60 [pivotal trial]; N = 18 [continued access]) presenting with AAA and an infrarenal aortic neck up to 32 mm in diameter received a bifurcated stent graft via anatomical fixation at the aortoiliac bifurcation and proximal sealing with a Powerlink XL infrarenal proximal extension stent graft. Postoperatively, results were assessed with contrast-enhanced CT scans and abdominal x-rays at one, six, and 12 months, with continued annual follow-up to five years., Results: Predominantly male (91%), patients presented at a mean age of 73 +/- 8.6 years with mean maximum aortic neck and AAA diameters of 31 +/- 1.9 mm (range, 25 to 32 mm) and 5.7 +/- 1.0 cm (range, 4.3 to 10 cm), respectively. Challenging infrarenal aortic neck anatomy, defined as the presence of severe thrombus and/or reverse taper, was present in 85% of patients. Technical success was achieved in 98.7% of patients, with one patient requiring femoral-femoral bypass intraoperatively. Aneurysm exclusion was achieved in 100% of patients over a mean procedure time of 129 +/- 66 minutes. Patients were discharged at a mean of 2.2 days postoperatively. At the one-month CT scan, the independent core lab identified a Type II endoleak in 13 patients, distal Type I and Type II endoleak in one patient, and unknown endoleak in three patients. At 30 days, there were no deaths, conversions, ruptures, or migrations. Through one year follow-up, Type II endoleak predominated (9/10 patients with endoleak), with one proximal Type I and no Type III, IV, or unknown endoleak; no conversions, ruptures, or migrations have been observed. The one-year all-cause mortality rate was 6.4%, with 100% freedom from aneurysm-related mortality. Secondary procedures were performed within one year in five patients (6.4%) for treatment of proximal Type I endoleak (n = 2), proximal Type I/Type II endoleak (n = 1), and distal Type I endoleak (n = 2). Reduced or stable aneurysm sac diameter at one year is observed in 96% of patients., Conclusions: The combination of an anatomically-fixed Powerlink bifurcated stent graft and a Powerlink XL infrarenal proximal extension appears safe and effectively excludes aneurysms in patients with wide aortic necks. These results suggest that fixation at the aortic bifurcation can provide secure fixation for patients with large diameter diseased proximal aortic necks.

Pulmonary artery (PA) catheterization is now a routine procedure in the care of critically ill patients. We report a case in which a pulmonary artery catheter was a major factor in the demise of a patient who developed adult respiratory distress syndrome following a septic abortion.