Search

Marfan syndrome is a rare inherited connective tissue disorder that can result in significant morbidity and mortality. We report a case of a 29-year-old pregnant woman presenting with an acute type B aortic dissection. Owing to cardiopulmonary decompensation and intestinal malperfusion, she underwent an emergency cesarean section followed by left subclavian to carotid transposition and thoracic endovascular aortic repair that was complicated by a retrograde type A aortic dissection and was managed surgically. Molecular testing confirmed the diagnosis of Marfan syndrome. This case highlights that multidisciplinary and hybrid management of challenging cases of acute aortic syndromes can result in a favorable outcome.

Abstract Cannabis sativa has gained popularity as a “natural substance”, leading many to falsely assume that it is not harmful. This assumption has been documented amongst pregnant mothers, many of whom consider Cannabis use during pregnancy as benign. The purpose of this study was to validate a Cannabis smoke exposure model in pregnant rats by determining the plasma levels of cannabinoids and associated metabolites in the dams after exposure to either Cannabis smoke or injected cannabinoids. Maternal and fetal cytokine and chemokine profiles were also assessed after exposure. Pregnant Sprague–Dawley rats were treated daily from gestational day 6–20 with either room air, i.p. vehicle, inhaled high-Δ9-tetrahydrocannabinol (THC) (18% THC, 0.1% cannabidiol [CBD]) smoke, inhaled high-CBD ( 0.7% THC, 13% CBD) smoke, 3 mg/kg i.p. THC, or 10 mg/kg i.p. CBD. Our data reveal that THC and CBD, but not their metabolites, accumulate in maternal plasma after repeated exposures. Injection of THC or CBD was associated with fewer offspring and increased uterine reabsorption events. For cytokines and chemokines, injection of THC or CBD up-regulated several pro-inflammatory cytokines compared to control or high-THC smoke or high-CBD smoke in placental and fetal brain tissue, whereas smoke exposure was generally associated with reduced cytokine and chemokine concentrations in placental and fetal brain tissue compared to controls. These results support existing, but limited, knowledge on how different routes of administration contribute to inconsistent manifestations of cannabinoid-mediated effects on pregnancy. Smoked Cannabis is still the most common means of human consumption, and more preclinical investigation is needed to determine the effects of smoke inhalation on developmental and behavioural trajectories.

Vascular Ehlers-Danlos syndrome is a rare inherited connective tissue disorder that can result in significant morbidity and mortality. This report details an iatrogenic aortic rupture during an endovascular approach in the management of critical limb ischemia in a 27-year-old woman who presented with acute onset of severe sensory deficit of the left leg. Conversion to open repair with a midline laparotomy and an aortic-left popliteal bypass was performed. In the endovascular era, we highlight that even minimally invasive therapeutic interventions can have devastating adverse events in patients with vascular Ehlers-Danlos syndrome.

Background: : The rhythm-monitoring strategy after catheter ablation (CA) for atrial fibrillation (AF) impacts the detection of atrial arrhythmia recurrence and is not well characterized. We performed a systematic review and meta-regression analysis to determine whether the duration and mode of rhythm monitoring after CA affects detection of atrial arrhythmia recurrence. Methods: Databases were systematically searched for randomized controlled trials of adult patients undergoing first CA for AF from 2007 to 2021. Duration and strategy of rhythm monitoring were extracted. Meta-regression was used to identify any association between duration of monitoring and detection of atrial arrhythmia recurrence. The primary measure of outcome was single-procedure recurrence of atrial arrhythmia. Results: The search strategy yielded 57 trial arms from 56 randomized controlled trials comprising 5322 patients: 36 arms of patients with paroxysmal AF (PAF), and 21 arms of patients with persistent AF (PeAF) or both PAF/PeAF. Intermittent monitoring was associated with detection of significantly less atrial arrhythmia recurrence than continuous monitoring in PAF arms (31.2% vs 46.9%, P = 0.001), but not in PeAF/PAF-PeAF combined arms (43.3% vs 63.6%, P = 0.12). No significant relationship was seen between the duration of intermittent rhythm monitoring and atrial arrhythmia recurrence detection in either the PAF (P = 0.93) or PeAF/PAF-PeAF combined arms (P = 0.20). Conclusions: Continuous rhythm monitoring detected higher atrial arrhythmia recurrence rates, compared to intermittent rhythm monitoring, in patients with PAF. The duration of intermittent monitoring did not show a statistically significant relationship to the yield of arrhythmia detection, in near identical cohorts of trial subjects undergoing similar interventions, with clinical and research implications. Résumé: Contexte: La stratégie qui consiste à surveiller le rythme cardiaque après une ablation par cathéter dans le traitement de la fibrillation auriculaire (FA) a un effet sur la détection de récidive de l’arythmie auriculaire, mais elle n’est pas bien définie. Nous avons mené une revue systématique et une méta-régression pour déterminer si le mode employé pour surveiller le rythme après une ablation par cathéter et la durée de cette surveillance ont un effet sur la détection de récidive de l’arythmie auriculaire. Méthodologie: Des bases de données ont été systématiquement épluchées à la recherche d’essais contrôlés randomisés menés auprès d’adultes subissant leur première ablation par cathéter pour une FA entre 2007 et 2021. La durée et la stratégie utilisées dans la surveillance du rythme ont été recensées. La méta-régression a été utilisée pour déceler tout lien entre la durée de la surveillance et la détection d’une récidive de l’arythmie auriculaire. Le paramètre d’évaluation principal était la récidive de l’arythmie auriculaire avec une seule intervention. Résultats: La stratégie de recherche a fait ressortir 57 groupes de 56 essais contrôlés randomisés comprenant 5 322 patients : 36 groupes de patients présentant une FA paroxystique et 21 groupes de patients présentant une FA persistante ou ces deux types de FA (paroxystique et persistante). La surveillance intermittente a été associée à une moins grande détection de cas d’arythmie auriculaire récidivante, comparativement à la surveillance constante (31,2 % vs 46,9 %, p = 0,001), ce qui n’a pas été le cas dans les groupes où les types de FA (persistante ou paroxystique et persistante) étaient combinés (43,3 % vs 63,6 %, p = 0,12). Aucun lien notable n’a été observé entre la durée de la surveillance intermittente du rythme et la détection de l’arythmie auriculaire récidivante dans le groupe FA paroxystique (p = 0,93) ou dans le groupe des types de FA combinés (p = 0,20). Conclusions: Le taux de détection de l’arythmie auriculaire récidivante était plus élevé avec la surveillance constante qu’avec la surveillance intermittente chez les patients atteints de FA paroxystique. La durée de la surveillance intermittente n’a pas eu de lien statistiquement significatif avec le rendement de détection de l’arythmie, dans des cohortes presque identiques de participants aux essais subissant des interventions similaires, comportant des implications cliniques ou expérimentales.

Background: Radiation therapy (RT) is a standard cancer treatment modality, and an increasing number of patients with cardiac implantable electronic devices (CIEDs) are being referred for RT. The goals of this study were as follows: (i) to determine the incidence of CIED malfunction following RT; (ii) to characterize the various types of malfunctions that occur; and (iii) to identify risk factors associated with CIED malfunction following RT. Methods: A retrospective study of patients with CIEDs who received RT between 2007 and 2018 at 4 Canadian centres (Sunnybrook Health Sciences Centre, Kingston General Hospital, Hamilton Health Sciences Centre, and University of Ottawa Heart Institute) was conducted. Patients underwent CIED interrogation after completion of RT, to assess for late damage to the CIEDs. Data on demographics, devices, and RT were compared for the primary outcome of device malfunction. Results: Of 1041 patients with CIEDs who received RT, 811 patients with complete data were included. Device malfunctions occurred in 32 of 811 patients (4%). The most common device malfunctions were reduced ventricular/atrial sensing (in 13 of 32 [41%]), an increase in lead threshold (in 9 of 32 [22%]), lead noise (in 5 of 32 [16%]), and electrical reset (in 2 of 32 [6%]). Higher beam energy (≥ 10 MV) was associated with malfunction (P < 0.0001). Radiation dose was not significantly different between the malfunction and non-malfunction groups (58.3 cGy vs 65 cGy, respectively, P = 0.71). Conclusions: Although RT-induced CIED malfunctions are rare (occurring in 4% of patients with a CIED who undergo RT), collaborative efforts between radiation oncologists and cardiac rhythm device clinics to optimize CIED monitoring are needed, to detect and manage CIED malfunctions. Malfunctions are more common in patients receiving higher–beam energy (≥10MV)RT. Résumé: Contexte: La radiothérapie (RT) est une modalité standard de traitement du cancer, et un nombre croissant de patients porteurs de dispositifs cardiaques électroniques implantables (DCEI) doivent recevoir un traitement de RT. Les objectifs de cette étude étaient les suivants : (i) déterminer l’incidence d’une défaillance du DCEI après une RT; (ii) caractériser les différents types de défaillances qui se produisent; (iii) déterminer les facteurs de risque associés à la défaillance du DCEI après une RT. Méthodologie: Une étude rétrospective des patients avec un DCEI ayant reçu une RT entre 2007 et 2018 dans quatre centres canadiens (Sunnybrook Health Sciences Centre, Kingston General Hospital, Hamilton Health Sciences Centre et Institut de cardiologie de l’Université d’Ottawa) a été menée. Le DCEI des patients a été interrogé après la fin de la RT, pour en évaluer les dommages tardifs. Les données sur les caractéristiques démographiques, les dispositifs et la RT ont été comparées pour le paramètre d’évaluation principal, soit la défaillance du dispositif. Résultats: Sur les 1 041 patients avec un DCEI ayant reçu une RT, 811 patients avec des données complètes ont été inclus. Des défaillances du dispositif sont survenues chez 32 des 811 patients (4 %). Les défaillances les plus fréquentes du dispositif étaient une détection ventriculaire/atriale réduite (chez 13 des 32 patients [41 %]), une augmentation du seuil de la sonde (chez 9 des 32 patients [22 %]), un bruit provenant de la sonde (chez 5 des 32 patients [16 %]) et une réinitialisation électrique (chez 2 des 32 patients [6 %]). Une énergie de faisceau plus élevée (≥ 10 MV) était associée à une défaillance (p < 0,0001). La dose de rayonnement ne présentait pas de différence significative entre le groupe où une défaillance a été constatée et l’autre groupe (58,3 cGy vs 65 cGy, respectivement, p = 0,71). Conclusions: Bien que les défaillances du DCEI causées par la RT soient rares (survenant chez 4 % des patients avec un DCEI qui subissent une RT), une collaboration est nécessaire entre les radio-oncologues et les cliniques de dispositifs de gestion du rythme cardiaque, afin d’optimiser la surveillance du DCEI et de détecter et de gérer ces défaillances. Les défaillances sont plus fréquentes chez les patients recevant une énergie de faisceau plus élevée au moment de la RT (≥10MV).

Objective Syringomyelia is a rare neurosurgical condition that could benefit from insertion of a syringopleural shunt in selected symptomatic cases. Treatment of syringomyelia through minimally invasive intervention is an attractive alternative to open approach. The objective of this report is to demonstrate the technical aspect, assess the feasibility, outcomes, and complications of syringopleural shunt insertion through minimally invasive surgical (MIS) approach. Methods Single-center retrospective chart review was done on patients with syringomyelia who underwent insertion of syringopleural shunts using the Metrx QuadrantTM retractor system from January 1, 2008 to April 1, 2020. A technical report of the steps of the surgical intervention is also described. Results Ten procedures were performed on 9 patients with a mean follow-up of 7.2 years. The etiologies of syringomyelia included post-traumatic, Chiari malformation, idiopathic, and diastematomyelia. All patients underwent correction of underlying etiologies prior to insertion of syringopleural shunts. Six patients (67%) had sustained neurological improvement, and 3 (33%) had halted progression of myelopathy. One patient was admitted for urgent removal of newly inserted syringopleural shunt due to immediate postoperative neurological decline and subsequently returned to their neurological baseline. The remaining eight patients were discharged on the same day of surgery. Conclusion Minimally invasive techniques have not been widely utilized in the treatment of syringomyelia. Our case series presents a novel, minimally invasive technique for the insertion of a syringopleural shunt, with reduced hospital stay and durable outcomes. Further, our series demonstrates that this technique is feasible and safe in appropriately selected patients.

Positive allosteric modulation of the type 1 cannabinoid receptor (CB1R) has substantial potential to treat both neurological and immune disorders. To date, a few studies have evaluated the structure-activity relationship (SAR) for CB1R positive allosteric modulators (PAMs). In this study, we separated the enantiomers of the previously characterized two potent CB1R ago-PAMs GAT591 and GAT593 to determine their biochemical activity at CB1R. Separating the enantiomers showed that the R-enantiomers (GAT1665 and GAT1667) displayed mixed allosteric agonist-PAM activity at CB1R while the S-enantiomers (GAT1664 and GAT1666) showed moderate activity. Furthermore, we observed that the R and S-enantiomers had distinct binding sites on CB1R, which led to their distinct behavior both in vitro and in vivo. The R-enantiomers (GAT1665 and GAT1667) produced ago-PAM effects in vitro, and PAM effects in the in vivo behavioral triad, indicating that the in vivo activity of these ligands may occur via PAM rather than agonist-based mechanisms. Overall, this study provides mechanistic insight into enantiospecific interaction of 2-phenylindole class of CB1R allosteric modulators, which have shown therapeutic potential in the treatment of pain, epilepsy, glaucoma, and Huntington’s disease.

Cannabis sativa contains more than 120 cannabinoids and 400 terpene compounds (i.e., phytomolecules) present in varying amounts. Cannabis is increasingly available for legal medicinal and non-medicinal use globally, and with increased access comes the need for a more comprehensive understanding of the pharmacology of phytomolecules. The main transducer of the intoxicating effects of Cannabis is the type 1 cannabinoid receptor (CB1R). ∆9-tetrahydrocannabinolic acid (∆9-THCa) is often the most abundant cannabinoid present in many cultivars of Cannabis. Decarboxylation converts ∆9-THCa to ∆9-THC, which is a CB1R partial agonist. Understanding the complex interplay of phytomolecules—often referred to as “the entourage effect”—has become a recent and major line of inquiry in cannabinoid research. Additionally, this interest is extending to other non-Cannabis phytomolecules, as the diversity of available Cannabis products grows. Here, we chose to focus on whether 10 phytomolecules (∆8-THC, ∆6a,10a-THC, 11-OH-∆9-THC, cannabinol, curcumin, epigallocatechin gallate, olivetol, palmitoylethanolamide, piperine, and quercetin) alter CB1R-dependent signaling with or without a co-treatment of ∆9-THC. Phytomolecules were screened for their binding to CB1R, inhibition of forskolin-stimulated cAMP accumulation, and βarrestin2 recruitment in Chinese hamster ovary cells stably expressing human CB1R. Select compounds were assessed further for cataleptic, hypothermic, and anti-nociceptive effects on male mice. Our data revealed partial agonist activity for the cannabinoids tested, as well as modulation of ∆9-THC-dependent binding and signaling properties of phytomolecules in vitro and in vivo. These data represent a first step in understanding the complex pharmacology of Cannabis- and non-Cannabis-derived phytomolecules at CB1R and determining whether these interactions may affect the physiological outcomes, adverse effects, and abuse liabilities associated with the use of these compounds.

Abstract The first synthetic cannabinoid receptor agonists (SCRAs) were designed as tool compounds to study the endocannabinoid system’s two predominant cannabinoid receptors, CB1R and CB2R. Unfortunately, novel SCRAs now represent the most rapidly proliferating novel psychoactive substances (NPS) of abuse globally. Unlike ∆9-tetrahydrocannabinol, the CB1R and CB2R partial agonist and the intoxicating constituent of Cannabis, many SCRAs characterized to date are full agonists of CB1R. Gaining additional insight into the pharmacological activity of these SCRAs is critical to assess and regulate NPSs as they enter the marketplace. The purpose of this study was to assess select SCRAs recently identified by Canadian police, border service agency, private companies and the illicit market as potential CB1R and CB2R agonists. To this end, fifteen SCRAs were screened for in vitro activity and in silico interactions at CB1R and CB2R. Several SCRAs were identified as being highly biased for cAMP inhibition or βarrestin2 recruitment and receptor subtype selectivity between CB1R and CB2R. The indazole ring and halogen-substituted butyl or pentyl moieties were identified as two structural features that may direct βarrestin2 bias. Two highly-biased SCRAs—JWH-018 2′-napthyl-N-(3-methylbutyl) isomer (biased toward cAMP inhibition) and 4-fluoro MDMB-BINACA (biased toward βarrestin2 recruitment) displayed unique and differential in vivo activity in mice. These data provide initial insight into the correlations between structure, signalling bias, and in vivo activity of the SCRAs.

Abstract Sexual dimorphisms are observed in cannabinoid pharmacology. It is widely reported that female animals are more sensitive to the cataleptic, hypothermic, antinociceptive, and anti‐locomotive effects of cannabinoid receptor agonists such as CP55,940. Despite awareness of these sex differences, there is little consideration for the pharmacodynamic differences within females. The mouse estrus cycle spans 4–5 days and consists of four sex hormone‐mediated phases: proestrus, estrus, metestrus, and diestrus. The endocannabinoid system interacts with female sex hormones including β‐estradiol, which may influence receptor expression throughout the estrus cycle. In the current study, sexually mature female C57BL/6 mice in either proestrus or metestrus were administered either 1 mg/kg i.p. of the cannabinoid receptor agonist CP55,940 or vehicle. Mice then underwent the tetrad battery of behavioral assays measuring catalepsy, internal body temperature, thermal nociception, and locomotion. Compared with female mice in metestrus, those in proestrus were more sensitive to the anti‐nociceptive effects of CP55,940. A similar trend was observed in CP55,940‐induced catalepsy; however, this difference was not significant. As for cannabinoid receptor expression in brain regions underlying antinociception, the spine tissue of proestrus mice that received CP55,940 exhibited increased expression of cannabinoid receptor type 1 relative to treatment‐matched mice in metestrus. These results affirm the importance of testing cannabinoid effects in the context of the female estrus cycle.

Abstract Background Supraventricular tachycardia (SVT) is a major cause of emergency room visits where vagal maneuver is used as first-line therapy. The valsalva maneuver (VM) is proven to be safe and, to some extent, effective in terminating SVT episodes. We aimed to compare the standard VM (SVM) to the modified valsalva maneuver (MVM). We hypothesized that MVM is more effective in terminating SVT episodes and reducing the time spent in the emergency department. Methods In this systematic review and meta-analysis, we searched Medline/PubMed, Ovid, Web of Science, and Cochrane Central Register of Controlled trials. We included only randomized controlled trials (RCTs) that compared the modified valsalva to the standard valsalva maneuver in treating SVT. Our main outcome was the termination of SVT within 1 min. Results Four articles met the eligibility criteria of our review. Sinus rhythm was achieved 2.5 times more in the MVM group compared to the SVM group (risk ratio (RR) = 2.54, CI 1.98–3.24, P

The endocannabinoid and orexin systems share many biological functions, including wakefulness, stress response, reward processing, and mood. While these systems work against one another with respect to arousal, chronic stress-induced downregulation of both systems often leads to anhedonia or the inability to experience pleasure from natural rewards. In the current study, a 24 h restraint stress test (24 h RST) reduced sucrose preference in adult male and female C57BL/6 mice. Prior to the stressor, subsets of mice were intraperitoneally administered cannabinoid and orexin receptor agonists, antagonists, and combinations of these drugs. Restraint mice that received the cannabinoid receptor type 1 (CB1R) antagonist SR141716A, orexin receptor type 2 (OX2R) agonist YNT-185, and the combination of SR141716A and YNT-185, exhibited less anhedonia compared to vehicle/control mice. Thus, the 24 h RST likely decreased orexin signaling, which was then restored by YNT-185. Receptor colocalization analysis throughout mesocorticolimbic brain regions revealed increased CB1R-OX1R colocalization from SR141716A and YNT-185 treatments. Although a previous study from our group showed additive cataleptic effects between CP55,940 and the dual orexin receptor antagonist (TCS-1102), the opposite combination of pharmacological agents proved additive for sucrose preference. Taken together, these results reveal more of the complex interactions between the endocannabinoid and orexin systems.

Abstract The Cannabis sativa plant contains more than 120 cannabinoids. With the exceptions of ∆9-tetrahydrocannabinol (∆9-THC) and cannabidiol (CBD), comparatively little is known about the pharmacology of the less-abundant plant-derived (phyto) cannabinoids. The best-studied transducers of cannabinoid-dependent effects are type 1 and type 2 cannabinoid receptors (CB1R, CB2R). Partial agonism of CB1R by ∆9-THC is known to bring about the ‘high’ associated with Cannabis use, as well as the pain-, appetite-, and anxiety-modulating effects that are potentially therapeutic. CB2R activation by certain cannabinoids has been associated with anti-inflammatory activities. We assessed the activity of 8 phytocannabinoids at human CB1R, and CB2R in Chinese hamster ovary (CHO) cells stably expressing these receptors and in C57BL/6 mice in an attempt to better understand their pharmacodynamics. Specifically, ∆9-THC, ∆9-tetrahydrocannabinolic acid (∆9-THCa), ∆9-tetrahydrocannabivarin (THCV), CBD, cannabidiolic acid (CBDa), cannabidivarin (CBDV), cannabigerol (CBG), and cannabichromene (CBC) were evaluated. Compounds were assessed for their affinity to receptors, ability to inhibit cAMP accumulation, βarrestin2 recruitment, receptor selectivity, and ligand bias in cell culture; and cataleptic, hypothermic, anti-nociceptive, hypolocomotive, and anxiolytic effects in mice. Our data reveal partial agonist activity for many phytocannabinoids tested at CB1R and/or CB2R, as well as in vivo responses often associated with activation of CB1R. These data build on the growing body of literature showing cannabinoid receptor-dependent pharmacology for these less-abundant phytocannabinoids and are critical in understanding the complex and interactive pharmacology of Cannabis-derived molecules.

Background: Robotics is currently being adopted across the spectrum of neurosurgery from deep brain stimulation to spine surgery instrumentation. Mastoidectomy is a cognitively demanding procedure that involves careful removal of bone around the critical structures of the temporal bone. Herein, we report a pilot study that serves as a proof of concept for real-time, multiparameter recording during mastoidectomy. Methods: This pilot study involved the iterative development of a platform for the real time recording of video, 3D position, velocity, acceleration, and force data during the performance of mastoidectomy using cadaveric specimens. Results: Across all 8 replicates, the average distance traveled by the drill tip in the x, y, and z axes was 39.88 mm (±11.98 mm), 38.52 mm (±8.24 mm), 31.40 mm (±7.89 mm), respectively. The overall average ranges for velocity and acceleration of the drill tip in the x axis were 412.81 mm/s (±91.12 mm/s) and 6383.05 mm/s2 (±941.05 mm/s2). The range of forces recorded was 8.52 N (±2.90 N), 40.94 N (±9.81 N), and 35.42 N (±11.06 N) in the x-, y-, and z-axis, respectively. Conclusions: This study represents a proof-of-concept that the mechanical parameters associated with surgeon-performed mastoidectomy can be recorded in real-time. This represents a crucial step in understanding the human drilling process which incorporates visual and haptic sensory input with experiential and explicit knowledge using fuzzy logic feedback. Ultimately, data collected using this methodology may provide the groundwork for the development of an algorithm for robotic mastoidectomy.

The endocannabinoid and orexin neuromodulatory systems serve key roles in many of the same biological functions such as sleep, appetite, pain processing, and emotional behaviors related to reward. The type 1 cannabinoid receptor (CB1R) and both subtypes of the orexin receptor, orexin receptor type 1 (OX1R) and orexin receptor type 2 (OX2R) are not only expressed in the same brain regions modulating these functions, but physically interact as heterodimers in recombinant and neuronal cell cultures. In the current study, male and female C57BL/6 mice were co-treated with the cannabinoid receptor agonist CP55,940 and either the OX2R antagonist TCS-OX2-29 or the dual orexin receptor antagonist (DORA) TCS-1102. Mice were then evaluated for catalepsy, body temperature, thermal anti-nociception, and locomotion, after which their brains were collected for receptor colocalization analysis. Combined treatment with the DORA TCS-1102 and CP55,940 potentiated catalepsy more than CP55,940 alone, but this effect was not observed for changes in body temperature, nociception, locomotion, or via selective OX2R antagonism. Co-treatment with CP55,940 and TCS-1102 also led to increased CB1R-OX1R colocalization in the ventral striatum. This was not seen following co-treatment with TCS-OX2-29, nor in CB1R-OX2R colocalization. The magnitude of effects following co-treatment with CP55,940 and either the DORA or OX2R-selective antagonist was greater in males than females. These data show that CB1R-OX1R colocalization in the ventral striatum underlies cataleptic additivity between CP55,940 and the DORA TCS-1102. Moreover, cannabinoid-orexin receptor interactions are sex-specific with regards to brain region and functionality. Physical or molecular interactions between these two systems may provide valuable insight into drug-drug interactions between cannabinoid and orexin drugs for the treatment of insomnia, pain, and other disorders.

Vitamin D is an essential nutrient for the maintenance of skeletal muscle and bone health. The vitamin D receptor (VDR) is present in muscle, as is CYP27B1, the enzyme that hydroxylates 25(OH)D to its active form, 1,25(OH)D. Furthermore, mounting evidence suggests that vitamin D may play an important role during muscle damage and regeneration. Muscle damage is characterized by compromised muscle fiber architecture, disruption of contractile protein integrity, and mitochondrial dysfunction. Muscle regeneration is a complex process that involves restoration of mitochondrial function and activation of satellite cells (SC), the resident skeletal muscle stem cells. VDR expression is strongly upregulated following injury, particularly in central nuclei and SCs in animal models of muscle injury. Mechanistic studies provide some insight into the possible role of vitamin D activity in injured muscle. In vitro and in vivo rodent studies show that vitamin D mitigates reactive oxygen species (ROS) production, augments antioxidant capacity, and prevents oxidative stress, a common antagonist in muscle damage. Additionally, VDR knockdown results in decreased mitochondrial oxidative capacity and ATP production, suggesting that vitamin D is crucial for mitochondrial oxidative phosphorylation capacity; an important driver of muscle regeneration. Vitamin D regulation of mitochondrial health may also have implications for SC activity and self-renewal capacity, which could further affect muscle regeneration. However, the optimal timing, form and dose of vitamin D, as well as the mechanism by which vitamin D contributes to maintenance and restoration of muscle strength following injury, have not been determined. More research is needed to determine mechanistic action of 1,25(OH)D on mitochondria and SCs, as well as how this action manifests following muscle injury in vivo. Moreover, standardization in vitamin D sufficiency cut-points, time-course study of the efficacy of vitamin D administration, and comparison of multiple analogs of vitamin D are necessary to elucidate the potential of vitamin D as a significant contributor to muscle regeneration following injury. Here we will review the contribution of vitamin D to skeletal muscle regeneration following injury.

Abstract Background Poor Quality of Life (QoL) among medical students is associated with an unhealthy lifestyle, psychological distress, and academic failure, which could affect their care for patients in the future. This study aimed to evaluate the reliability and validity of the Arabic WHOQOL-BREF tool among Saudi medical students and to assess the effect of gender, educational level, and academic performance on their QoL. Methods This was a cross-sectional study among medical students of King Abdulaziz University in February 2016, using the Arabic version of the WHOQOL-BREF instrument. Results Six-hundred-thirty medical students were included, where females constituted (51.1%). Cronbach’s α coefficient for the overall domains of WHOQOL-BREF was 0.86. Students’ self-reported QoL mean score was 3.99 ± 0.95, and their mean score for the overall satisfaction with health was 3.66 ± 1.06. The environmental domain had the highest mean score (67.81 ± 17.39). High achievers showed lower psychological health, while poor academic performance was associated with better psychological health and social relationship QoL scores (P

Wisam Jamal,1 Mohammad M Zagzoog,2 Salma H Sait,2 Ahmed O Alamoudi,2 Shaza Abo’ouf,3 Ayman A Alghamdi,2 Ryan O Bamashmous,2 Ashraf A Maghrabi2 1Department of Surgery, Faculty of Medicine, University of Jeddah, Jeddah, Saudi Arabia; 2Department of Surgery, Faculty of Medicine, King Abdulaziz University, Jeddah, Saudi Arabia; 3Beverly Medical Care Clinics for Obesity Management, Jeddah, Saudi Arabia Introduction: One anastomosis gastric bypass (OAGB) is an emerging bariatric procedure, which has been reported to be safe and effective. This study aims to evaluate the short-term outcome of OAGB and its midterm effects on weight loss and remission of type 2 diabetes mellitus (T2DM).Materials and methods: A retrospective review of patients who had undergone OAGB between January 2013 and January 2017 in King Abdulaziz University Hospital, Jeddah, Saudi Arabia, is presented here. Patients’ perioperative characteristics, biochemical profile (fasting blood glucose, HbA1c and iron profile) and details on subsequent weight loss in terms of body mass index (BMI) and excess weight loss percentage (EWL%) along with early and late postoperative complications were evaluated.Results: Out of the 47 patients who underwent OAGB, 42 were included in this study and completed the 2-year follow-up. Average operative time was 107±21.3 minutes and average length of hospital stay was 2.5±0.53 days. Mean preoperative BMI was 47.6±9.1 kg/m2, and at 1 and 2 years of follow–up, it was 30.5±7.4 and 27.1±5.1, respectively. No mortality, anastomotic leak or bleeding were reported. Most common midterm complication was iron deficiency anemia (n=7/42). Remission of T2DM at 6 months was 80%. Patients with preoperative T2DM for less than 10 years showed better remission (P

In addition to its known actions as a non-selective cyclooxygenase (COX) 1 and 2 inhibitor, we hypothesized that indomethacin can act as an allosteric modulator of the type 1 cannabinoid receptor (CB1R) because of its shared structural features with the known allosteric modulators of CB1R. Indomethacin enhanced the binding of [3H]CP55940 to hCB1R and enhanced AEA-dependent [35S]GTPγS binding to hCB1R in Chinese hamster ovary (CHO) cell membranes. Indomethacin (1 μM) also enhanced CP55940-dependent βarrestin1 recruitment, cAMP inhibition, ERK1/2 and PLCβ3 phosphorylation in HEK293A cells expressing hCB1R, but not in cells expressing hCB2R. Finally, indomethacin enhanced the magnitude and duration of CP55940-induced hypolocomotion, immobility, hypothermia, and anti-nociception in C57BL/6J mice. Together, these data support the hypothesis that indomethacin acted as a positive allosteric modulator of hCB1R. The identification of structural and functional features shared amongst allosteric modulators of CB1R may lead to the development of novel compounds designed for greater CB1R or COX selectivity and compounds designed to modulate both the prostaglandin and endocannabinoid systems.

A correction to this paper has been published: https://doi.org/10.1186/s42444-021-00034-y