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RSC Medicinal Chemistry Jun 2024Synthetic cannabinoid receptor agonists (SCRAs) comprise the second largest class of new psychoactive substances (NPS), and typically α-amino acid moieties are...
Synthetic cannabinoid receptor agonists (SCRAs) comprise the second largest class of new psychoactive substances (NPS), and typically α-amino acid moieties are incorporated as part of their design. Limited investigation has been performed into elucidating structure-activity relationships around commonly used α-amino acid-derived head groups, mainly with valine and -leucine-derived compounds previously described. As such, proactive synthesis, characterisation and pharmacological evaluation were performed to explore structure-activity relationships of 15 α-amino acid derivatives, with both the natural isomers and their enantiomers at CB and CB investigated using a fluorescence-based membrane potential assay. This library was based around the detected SCRAs MPP-5F-PICA, MMB-5F-PICA, and MDMB-5F-PICA, with the latter showing significant receptor activation at CB (pEC = 8.34 ± 0.05 M; = 108 ± 3%) and CB (pEC = 8.13 ± 0.07 M; = 99 ± 2%). Most valine and leucine derivatives were potent and efficacious SCRAs, while smaller derivatives generally showed reduced activity at CB and CB, and larger derivatives also showed reduced activity. SAR trends observed were rationalised induced fit docking. Overall, while natural enantiomers showed equipotent or greater activity than the unnatural isomers in most cases, this was not universal. As such, a number of these compounds should be monitored as emerging NPS, and various substituents described herein.
PubMed: 38911147
DOI: 10.1039/d3md00758h -
Cureus May 2024Posterior inferior cerebellar artery (PICA) aneurysms are relatively uncommon among intracranial aneurysms and present unique challenges due to their complex anatomical...
Posterior inferior cerebellar artery (PICA) aneurysms are relatively uncommon among intracranial aneurysms and present unique challenges due to their complex anatomical origins. PICA aneurysms arise from the vertebral artery (VA), basilar artery, or anterior inferior cerebellar artery and can have complex anatomical sites and structures. A 31-year-old female known case of trigeminal neuralgia, currently asymptomatic for the same, experienced acute vertigo, headache, and altered sensorium. On the basis of the magnetic resonance imaging of the brain with angiography, she was diagnosed with a PICA aneurysm, necessitating immediate intervention. The patient subsequently underwent endovascular coiling of the aneurysm. The successful management of this unusual case emphasizes the significance of prompt diagnosis and early intervention in managing posterior inferior cerebellar artery aneurysms, leading to a favourable outcome. The patient is on regular follow-ups and has satisfactory progress.
PubMed: 38910637
DOI: 10.7759/cureus.60869 -
Physica Medica : PM : An International... Jun 2024To investigate the current practice patterns in image-guided particle therapy (IGPT) for cranio-spinal irradiation (CSI).
PURPOSE
To investigate the current practice patterns in image-guided particle therapy (IGPT) for cranio-spinal irradiation (CSI).
METHODS
A multi-institutional survey was distributed to European particle therapy centres to analyse all aspects of IGPT. Based on the survey results, a Delphi consensus analysis was developed to define minimum requirements and optimal workflow for clinical practice. The centres participating in the institutional survey were invited to join the Delphi process.
RESULTS
Eleven centres participated in the survey. Imaging for treatment planning was rather similar among the centres with Computed Tomography (CT) being the main modality. For positioning verification, 2D IGPT was more commonly used than 3D IGPT. Two centres performed routinely imaging for plan adaptation, by the rest ad hoc. Eight centres participated in the Delphi consensus analysis. The full consensus was reached on the use of CT imaging without contrast for treatment planning and the role of magnetic resonance imaging (MRI) in target and organs-at-risk delineation. There was an agreement on the necessity to perform patient position verification and correction before each isocentre. The most important outcome was the clear need for standardization and harmonization of the workflow.
CONCLUSION
There were differences in CSI IGPT clinical practice among the European particle therapy centres. Moreover, the optimal workflow as identified by experts was not yet reached. There is a strong need for consensus guidelines. The state-of-the-art imaging technology and protocols need to be implemented into clinical practice to improve the quality of IGPT for CSI.
PubMed: 38906046
DOI: 10.1016/j.ejmp.2024.103407 -
The Neurohospitalist Jul 2024Radiographic horizontal gaze deviation (RHGD) has been identified as a useful finding on computed tomography (CT) that indicates the affected side in supratentorial...
BACKGROUND AND PURPOSE
Radiographic horizontal gaze deviation (RHGD) has been identified as a useful finding on computed tomography (CT) that indicates the affected side in supratentorial ischemic stroke; however, it remains unclear whether RHGD is essentially the same phenomenon as physical horizontal gaze deviation (PHGD). To resolve the issue, this study was conducted.
METHODS
Retrospective analyses were performed for 671 patients with ischemic stroke and 142 controls who were hospitalized and underwent head CT. First, clinical findings were examined to find differences between RHGD-positive and RHGD-negative patients. Second, patients were classified by their stroke mechanisms and/or affected vascular territories. For each subgroup, RHGD was compared with PHGD in frequency. Third, the proportions for patients divided by positivity for PHGD and RHGD were calculated in the subgroups.
RESULTS
Patients with RHGD had PHGD more often than those without. In all stroke subgroups, RHGD was more frequent than PHGD. The frequency difference was prominent in small-artery occlusion (SAO) and posterior inferior cerebellar artery (PICA) stroke. In SAO of the basilar artery pontine perforator, RHGD was positive in 25% and largely contralesionally-directed. In PICA stroke, lesions in the vestibulocerebellum were associated with contralesional RHGD. Moreover, lesions in the lateral medulla also caused RHGD, which was mainly directed to the ipsilesional side. PHGD-positive stroke without RHGD was infrequent, whereas RHGD-positive stroke without PHGD was commonly observed (PICA stroke, 45.9%; other subgroups, 21.1%-27.5%).
CONCLUSIONS
RHGD had different characteristics from PHGD; therefore, assessments of both PHGD and RHGD may lead to more accurate diagnoses.
PubMed: 38895013
DOI: 10.1177/19418744241245748 -
Operative Neurosurgery (Hagerstown, Md.) Jun 2024Anterior inferior cerebellar artery-posterior inferior cerebellar artery (AICA-PICA) variant is a well-established variant of the vertebrobasilar system. AICA-PICA...
Treatment of Recurrent, Twice Coiled, Previously Ruptured Anterior Inferior Cerebellar Artery-Posterior Inferior Cerebellar Artery Aneurysm With Excision and End-to-End Anastomosis: 2-Dimensional Operative Video.
Anterior inferior cerebellar artery-posterior inferior cerebellar artery (AICA-PICA) variant is a well-established variant of the vertebrobasilar system. AICA-PICA aneurysms are extremely rare.1-3 There are only 12 cases reported in the literature.1-3 Here, we are presenting a case of a previously ruptured AICA-PICA dissecting aneurysm which had undergone coil embolization twice at an outside institution. The aneurysm continued to grow, and therefore, the patient was transferred to our institution for definitive treatment. Placement of a flow diverter was felt not to be feasible because of the acute bend of the vessel at the neck of the aneurysm. After a retrosigmoid craniotomy, the aneurysm sac was opened to untether the coil mass from the neck of the aneurysm. Clip reconstruction was attempted but intraoperative blood flow measurements demonstrated no flow in the distal outflow artery, indicating that the clip was occluding the parent vessel at the neck because of the challenging geometry and atherosclerosis. We then proceeded with an excision and end-to-end anastomosis of the AICA-PICA. The details of vascular reconstruction while the inflow and outflow arteries are at acute angle are described. Intraoperative indocyanine video angiography demonstrated complete exclusion of the aneurysm from the circulation and patency of the bypass. Postoperative computed tomography angiography demonstrated bypass patency. Postoperatively, the patient required a temporary external ventricular drain for hydrocephalus; however, she was eventually discharged home without any neurological deficits. The patient gave informed consent for the surgery and video recording. Institutional Review Board approval was deemed unnecessary.
PubMed: 38888312
DOI: 10.1227/ons.0000000000001253 -
Radiation Oncology (London, England) Jun 2024Rare but severe toxicities of the optic apparatus have been observed after treatment of intracranial tumours with proton therapy. Some adverse events have occurred at...
BACKGROUND AND PURPOSE
Rare but severe toxicities of the optic apparatus have been observed after treatment of intracranial tumours with proton therapy. Some adverse events have occurred at unusually low dose levels and are thus difficult to understand considering dose metrics only. When transitioning from double scattering to pencil beam scanning, little consideration was given to increased dose rates observed with the latter delivery paradigm. We explored if dose rate related metrics could provide additional predicting factors for the development of late visual toxicities.
MATERIALS AND METHODS
Radiation-induced intracranial visual pathway lesions were delineated on MRI for all index cases. Voxel-wise maximum dose rate (MDR) was calculated for 2 patients with observed optic nerve toxicities (CTCAE grade 3 and 4), and 6 similar control cases. Additionally, linear energy transfer (LET) related dose enhancing metrics were investigated.
RESULTS
For the index cases, which developed toxicities at low dose levels (mean, 50 Gy), some dose was delivered at higher instantaneous dose rates. While optic structures of non-toxicity cases were exposed to dose rates of up to 1 to 3.2 Gy/s, the pre-chiasmatic optic nerves of the 2 toxicity cases were exposed to dose rates above 3.7 Gy/s. LET-related metrics were not substantially different between the index and non-toxicity cases.
CONCLUSIONS
Our observations reveal large variations in instantaneous dose rates experienced by different volumes within our patient cohort, even when considering the same indications and beam arrangement. High dose rate regions are spatially overlapping with the radiation induced toxicity areas in the follow up images. At this point, it is not feasible to establish causality between exposure to high dose rates and the development of late optic apparatus toxicities due to the low incidence of injury.
Topics: Humans; Proton Therapy; Brain Neoplasms; Radiotherapy Dosage; Female; Male; Middle Aged; Adult; Radiation Injuries; Aged; Optic Nerve; Organs at Risk; Radiotherapy Planning, Computer-Assisted; Dose-Response Relationship, Radiation
PubMed: 38886727
DOI: 10.1186/s13014-024-02464-z -
Journal of the American Heart... Jun 2024Advanced atrioventricular block (AVB), that is, higher than second-degree Mobitz-1, is an abnormal finding in athletes. Despite intensive investigation, in several cases...
BACKGROUND
Advanced atrioventricular block (AVB), that is, higher than second-degree Mobitz-1, is an abnormal finding in athletes. Despite intensive investigation, in several cases the pathogenesis remains unknown, but frequently pacemaker implantation is still indicated. Increasing evidence points to circulating anti-Ro/Sjögren syndrome-related antigen A (SSA) antibodies cross-reacting with L-type calcium channel and inhibiting the related current as an epidemiologically relevant and potentially reversible cause of isolated AVB in adults. The aim of the study was to determine the prevalence of anti-Ro/SSA-associated advanced AVBs in a large sample of young athletes.
METHODS AND RESULTS
A total of 2536 consecutive athletes aged <40 years without a history of cardiac diseases/interventions were enrolled in a cross-sectional study. Resting and exercise electrocardiography was performed, and those presenting any AVB were further evaluated by 24-hour Holter ECG. Athletes with second-degree AVBs and their mothers underwent anti-Ro/SSA testing. Moreover, purified immunoglobulin G from subjects with anti-Ro/SSA-positive and anti-Ro/SSA-negative advanced AVB were tested on L-type calcium current and L-type-calcium channel expression using tSA201 cells. The global prevalence of advanced AVB in the overall sample was ≈0.1%, but the risk considerably increased (2%) when intensely trained postpubertal male subjects were selectively considered. While none of the athletes with advanced AVB showed heart abnormalities, in 100% of cases anti-Ro/SSA antibodies were detected. Ex vivo experiments showed that immunoglobulin G from anti-Ro/SSA-positive but not -negative subjects with advanced AVB acutely inhibit L-type calcium current and chronically downregulate L-type-calcium channel expression.
CONCLUSIONS
Our study provides evidence that advanced AVB occurs in young athletes, in most cases associated with anti-Ro/SSA antibodies blocking L-type calcium channels. These findings may open new avenues for immunomodulating therapies to reduce the risk of life-threatening events in athletes, avoiding or delaying pacemaker implantation.
Topics: Humans; Male; Female; Adult; Cross-Sectional Studies; Atrioventricular Block; Prevalence; Young Adult; Calcium Channels, L-Type; Antibodies, Antinuclear; Athletes; Adolescent; Electrocardiography, Ambulatory; Ribonucleoproteins
PubMed: 38879447
DOI: 10.1161/JAHA.124.034893 -
Poultry Science May 2024Direct or indirect interactions between sympatric wildlife and poultry can lead to interspecies disease transmission. Particularly, avian influenza (AI) is a viral...
Direct or indirect interactions between sympatric wildlife and poultry can lead to interspecies disease transmission. Particularly, avian influenza (AI) is a viral epidemic disease for which the poultry-wild bird interface shapes the risks of new viral introductions into poultry holdings. Given this background, the study hereby presented aimed to identify wild bird species in poultry house surroundings and characterize the spatiotemporal patterns of these visits. Eight camera traps were deployed for a year (January to December 2021) in 3 commercial chicken layer farms, including free-range and barn-type setups, located in a densely populated poultry area in Northern Italy at high risk for AI introduction via wild birds. Camera traps' positions were chosen based on wildlife signs identified during preliminary visits to the establishments studied. Various methods, including time series analysis, correspondence analysis, and generalized linear models, were employed to analyze the daily wild bird visits. A total of 1,958 camera trap days yielded 5,978 videos of wild birds from 27 different species and 16 taxonomic families. The animals were predominantly engaged in foraging activities nearby poultry houses. Eurasian magpies (Pica pica), ring-necked pheasants (Phasianus colchicus), and Eurasian collared doves (Streptopelia decaocto) were the most frequent visitors. Mallards (Anas platyrhynchos), an AI reservoir species, were observed only in a farm located next to a fishing sport lake. Time series analysis indicated that wild bird visits increased during spring and winter. Farm and camera trap location also influenced visit frequencies. Overall, the results highlighted specific species that could be prioritized for future AI epidemiological surveys. However, further research is required to assess their susceptibility and infectivity to currently circulating AI viruses, essential for identifying novel bridge hosts.
PubMed: 38865769
DOI: 10.1016/j.psj.2024.103892 -
Journal of Neurointerventional Surgery Jun 2024Transcirculation catheterization, also known as the retrograde approach, involves the navigation of a catheter or other endovascular device from one arterial circulation...
Transcirculation catheterization, also known as the retrograde approach, involves the navigation of a catheter or other endovascular device from one arterial circulation to the other (right to left, or anterior to posterior).1-4 We present a case of a complex vertebrobasilar junction aneurysm previously treated by bilateral vertebral artery deconstruction, precluding antegrade access (video 1). Following the creation of a protective occipital artery to posterior inferior cerebellar artery (PICA) bypass, the patient was treated with transcirculation placement of a Pipeline embolization device (PED).5-9 The right internal carotid artery was accessed with a guide catheter using a transradial approach. The microwire-microcatheter combination was then tracked through the right posterior communicating artery, down the basilar trunk, and to the left PICA. The PED was successfully deployed from the left vertebral artery to the mid-basilar artery. At 3-month follow-up, the aneurysm was completely obliterated. The nuances of transcirculation technique, especially for flow diversion, are discussed. (Used with permission from Barrow Neurological Institute, Phoenix, Arizona, USA.)neurintsurg;jnis-2023-021363v1/V1F1V1Video 1Transcirculation retrograde placement of a Pipeline embolization device for treatment of a vertebrobasilar junction aneurysm previously treated by bilateral vertebral artery deconstruction, precluding antegrade access.
PubMed: 38862210
DOI: 10.1136/jnis-2023-021363 -
Spinal Cord Series and Cases Jun 2024Syringomyelia, or the formation of fluid-filled cysts within the spinal cord, associated with delayed spinal arachnoiditis is an uncommon complication of aneurysmal...
BACKGROUND AND IMPORTANCE
Syringomyelia, or the formation of fluid-filled cysts within the spinal cord, associated with delayed spinal arachnoiditis is an uncommon complication of aneurysmal subarachnoid haemorrhage. To date, about 18 cases have been reported in medical literature, with just two reported in patients under the age of 35 years.
CLINICAL PRESENTATION
A 27-year-old female patient complained of sudden, severe headaches in the occipital region, nuchal rigidity, and drowsiness when she presented at our institution. A head computed tomography scan revealed intraventricular bleeding in the lateral and fourth ventricles with more extensive haemorrhaging in the frontal horns. A left posterior inferior cerebellar artery (PICA) aneurysm was confirmed via digital subtraction angiogram, and endovascular embolization was done. Two years later, the patient reported intense pain in the lower back along with symptoms suggestive of spinal cord compression. Spinal magnetic resonance imaging (MRI) showed spinal adhesions from C1 to L4, syringomyelia with some vasogenic oedema extending from T3 to T9 level, and a cyst in the lumbar region. Consequently, a right hemilaminectomy was performed along with microsurgical release of arachnoid adhesions and placement of a subdural drain. Radiological and symptomatic improvements were observed. Since then, the patient's clinical condition has remained stable during the past three years of follow-up visits.
CONCLUSIONS
Literature on optimal treatment modalities and patient prognosis is scarce and debated. The time for symptom improvement depends on the level and extent of spinal cord involvement. Rehabilitation may be required for most patients, as complete symptomatic recovery may not be attainable.
Topics: Humans; Female; Arachnoiditis; Adult; Syringomyelia; Subarachnoid Hemorrhage
PubMed: 38858362
DOI: 10.1038/s41394-024-00654-1