Phase separation of initiation hubs on cargo is a trigger switch for selective autophagy.

Autophagy is a key cellular quality control mechanism. Nutrient stress triggers bulk autophagy, which nonselectively degrades cytoplasmic material upon formation and liquid-liquid phase separation of the autophagy-related gene 1 (Atg1) complex. In contrast, selective autophagy eliminates protein aggregates, damaged organelles and other cargoes that are targeted by an autophagy receptor.

Remote feedback in endovascular simulation training: a mixed-methods study.

Background: There is an increasing need to increase simulation-based learning opportunities for vascular surgery residents in endovascular skills training. This study aims to explore the effectiveness of remote expert instructional feedback of endovascular simulation-based education, as a means of increasing training opportunities in this area for vascular surgery residents.

Methods: A mixed-methods study design was adopted.

Post-Translational Modifications and Diabetes.

Diabetes and its associated complications have increasingly become major challenges for global healthcare. The current therapeutic strategies involve insulin replacement therapy for type 1 diabetes (T1D) and small-molecule drugs for type 2 diabetes (T2D). Despite these advances, the complex nature of diabetes necessitates innovative clinical interventions for effective treatment and complication prevention.

Prevalence of carboxy-Δ-tetrahydrocannabiniol in antidoping samples.

Δ-Tetrahydrocannabinol (Δ-THC) is usually the primary psychoactive agent in cannabis preparations. Recently, products containing another isomer, Δ-tetrahydrocannabinol (Δ-THC), have become available for sale. Δ-THC exists naturally in the cannabis plant at very low concentrations; hence, the Δ-THC present in most of the above-mentioned products is likely to be manufactured synthetically.

Autophagy as a caretaker of nuclear integrity.

Due to their essential functions, dysregulation of nuclear pore complexes (NPCs) is strongly associated with numerous human diseases, including neurodegeneration and cancer. On a cellular level, longevity of scaffold nucleoporins in postmitotic cells of both C. elegans and mammals renders them vulnerable to age-related damage, which is associated with an increase in pore leakiness and accumulation of intranuclear aggregates in rat brain cells.

Frequency of inter-specialty consensus decisions and adherence to advice following discussion at a weekly neurovascular multidisciplinary meeting.

Background/aims: Data are limited on the frequency of 'consensus decisions' between sub-specialists attending a neurovascular multidisciplinary meeting (MDM) regarding management of patients with extracranial carotid/vertebral stenoses and post-MDM 'adherence' to such advice.

Methods: This prospective audit/quality improvement project collated prospectively-recorded data from a weekly Neurovascular/Stroke Centre MDM documenting the proportion of extracranial carotid/vertebral stenosis patients in whom 'consensus management decisions' were reached by neurologists, vascular surgeons, stroke physicians-geriatricians and neuroradiologists. Adherence to MDM advice was analysed in asymptomatic carotid stenosis (ACS), symptomatic carotid stenosis (SCS), 'indeterminate symptomatic status stenosis' (ISS) and vertebral artery stenosis (VAS) patients, including intervals between index event to MDM + / - intervention.

FACS-mediated isolation of native autophagic vesicles.

Autophagosome isolation enables the thorough investigation of structural components and engulfed materials. Recently, we introduced a novel antibody-based FACS-mediated method for isolation of native macroautophagic/autophagic vesicles and confirmed the quality of the preparations. We performed phospholipidomic and proteomic analyses to characterize autophagic vesicle-associated phospholipids and protein cargoes under different autophagy conditions.

Lipid and protein content profiling of isolated native autophagic vesicles.

Autophagy is responsible for clearance of an extensive portfolio of cargoes, which are sequestered into vesicles, called autophagosomes, and are delivered to lysosomes for degradation. The pathway is highly dynamic and responsive to several stress conditions. However, the phospholipid composition and protein contents of human autophagosomes under changing autophagy rates are elusive so far.

Bypassing the nuclear gate: A non-canonical entry pathway for the mitochondrial pyruvate dehydrogenase complex.

Zervopoulos et al. (2022) propose a non-canonical nuclear import pathway for the functional mitochondrial pyruvate dehydrogenase complex (PDC), facilitated by dynamic MFN2-mediated tethering of mitochondria to the nuclear envelope upon exposure to proliferative stimuli.

Re-amputation and survival following toe amputation: outcome data from a tertiary referral centre.

Purpose: Toe amputation is a commonly performed procedure for irreversible foot sepsis. However, outcome and predictors of outcome are poorly understood. Our aim was to determine survival and rate of progression to further amputation following index toe amputation.

Engineered microRNA-based regulatory element permits safe high-dose miniMECP2 gene therapy in Rett mice.

MECP2 gene transfer has been shown to extend the survival of Mecp2-/y knockout mice modelling Rett syndrome, an X-linked neurodevelopmental disorder. However, controlling deleterious overexpression of MECP2 remains the critical unmet obstacle towards a safe and effective gene therapy approach for Rett syndrome. A recently developed truncated miniMECP2 gene has also been shown to be therapeutic after AAV9-mediated gene transfer in knockout neonates.

A systematic review and meta-analysis of comparative studies comparing nonthermal versus thermal endovenous ablation in superficial venous incompetence.

Objective: Endovenous thermal ablation (TA) offers an effective initial treatment option for superficial venous incompetence of the lower limb. These techniques offer lower complication rates with similar efficacy to traditional open surgery. In recent years, nonthermal ablation (NTA) in the form of mechanochemical ablation and cyanoacrylate vein ablation has been suggested to further reduce perioperative morbidity.

Automated tracking of level of consciousness and delirium in critical illness using deep learning.

Over- and under-sedation are common in the ICU, and contribute to poor ICU outcomes including delirium. Behavioral assessments, such as Richmond Agitation-Sedation Scale (RASS) for monitoring levels of sedation and Confusion Assessment Method for the ICU (CAM-ICU) for detecting signs of delirium, are often used. As an alternative, brain monitoring with electroencephalography (EEG) has been proposed in the operating room, but is challenging to implement in ICU due to the differences between critical illness and elective surgery, as well as the duration of sedation.

Effect of epileptiform abnormality burden on neurologic outcome and antiepileptic drug management after subarachnoid hemorrhage.

Objective: To quantify the burden of epileptiform abnormalities (EAs) including seizures, periodic and rhythmic activity, and sporadic discharges in patients with aneurysmal subarachnoid hemorrhage (aSAH), and assess the effect of EA burden and treatment on outcomes.

Methods: Retrospective analysis of 136 high-grade aSAH patients. EAs were defined using the American Clinical Neurophysiology Society nomenclature.

Electroencephalogram Based Detection of Deep Sedation in ICU Patients Using Atomic Decomposition.

Objective: This study was performed to evaluate how well states of deep sedation in ICU patients can be detected from the frontal electroencephalogram (EEG) using features based on the method of atomic decomposition (AD).

Methods: We analyzed a clinical dataset of 20 min of EEG recordings per patient from 44 mechanically ventilated adult patients receiving sedatives in an intensive care unit (ICU) setting. Several features derived from AD of the EEG signal were used to discriminate between awake and sedated states.

Continuous electroencephalography predicts delayed cerebral ischemia after subarachnoid hemorrhage: A prospective study of diagnostic accuracy.

Objective: Delayed cerebral ischemia (DCI) is a common, disabling complication of subarachnoid hemorrhage (SAH). Preventing DCI is a key focus of neurocritical care, but interventions carry risk and cannot be applied indiscriminately. Although retrospective studies have identified continuous electroencephalographic (cEEG) measures associated with DCI, no study has characterized the accuracy of cEEG with sufficient rigor to justify using it to triage patients to interventions or clinical trials.

Epileptiform activity in traumatic brain injury predicts post-traumatic epilepsy.

We hypothesize that epileptiform abnormalities (EAs) in the electroencephalogram (EEG) during the acute period following traumatic brain injury (TBI) independently predict first-year post-traumatic epilepsy (PTE ). We analyze PTE risk factors in two cohorts matched for TBI severity and age (n = 50). EAs independently predict risk for PTE (odds ratio [OR], 3.

Electronic Health Data Predict Outcomes After Aneurysmal Subarachnoid Hemorrhage.

Backgroud: Using electronic health data, we sought to identify clinical and physiological parameters that in combination predict neurologic outcomes after aneurysmal subarachnoid hemorrhage (aSAH).

Methods: We conducted a single-center retrospective cohort study of patients admitted with aSAH between 2011 and 2016. A set of 473 predictor variables was evaluated.

Patient-Specific Classification of ICU Sedation Levels From Heart Rate Variability.

Objective: To develop a personalizable algorithm to discriminate between sedation levels in ICU patients based on heart rate variability.

Design: Multicenter, pilot study.

Setting: Several ICUs at Massachusetts General Hospital, Boston, MA.

Heart rate variability as a biomarker for sedation depth estimation in ICU patients.

An automated patient-specific system to classify the level of sedation in ICU patients using heart rate variability signal is presented in this paper. ECG from 70 mechanically ventilated adult patients with administered sedatives in an ICU setting were used to develop a support vector machine based system for sedation depth monitoring using several heart rate variability measures. A leave-one-subject-out cross validation was used for classifier training and performance evaluations.

Vibrational Spectroscopy of Fe(CH) (n = 1-3) and Fe(CH).

Vibrational spectra are measured for Fe(CH) (n = 1-3) and Fe(CH) in the C-H stretching region (2650-3100 cm) using photofragment spectroscopy, monitoring loss of CH. All of the spectra are dominated by an intense peak at around 2800 cm that is red-shifted by ∼120 cm from free methane. This peak is due to the symmetric C-H stretch of the η hydrogen-coordinated methane ligands.