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Magnetic resonance imaging (MRI) demonstrates superior soft tissue contrast and is increasingly being used in radiotherapy planning. This study evaluated the impact of an education workshop in minimising inter‐observer variation (IOV) for nasopharyngeal organs at risk (OAR) delineation on MRI. Ten observers delineated 14 OARs on 4 retrospective nasopharyngeal MRI data sets. Standard contouring guidelines were provided pre‐workshop. Following an education workshop on MRI OAR delineation, observers blinded to their original contours repeated the 14 OAR delineations. For comparison, reference volumes were delineated by two head and neck radiation oncologists. IOV was evaluated using dice similarity coefficient (DSC), Hausdorff distance (HD) and relative volume. Location of largest deviations was evaluated with centroid values. Observer confidence pre‐ and post‐workshop was also recorded using a 6‐point Likert scale. The workshop was deemed beneficial for an OAR if ≥50% of observers mean scores improved in any metric and ≥50% of observers' confidence improved. All OARs had ≥50% of observers improve in at least one metric. Base of tongue, larynx, spinal cord and right temporal lobe were the only OARs achieving a mean DSC score of ≥0.7. Base of tongue, left and right lacrimal glands, larynx, left optic nerve and right parotid gland all exhibited statistically significant HD improvements post‐workshop (P< 0.05). Brainstem and left and right temporal lobes all had statistically significant relative volume improvements post‐workshop (P< 0.05). Post‐workshop observer confidence improvement was observed for all OARs (P< 0.001). The educational workshop reduced IOV and improved observers' confidence when delineating nasopharyngeal OARs on MRI. Magnetic resonance imaging demonstrates superior soft tissue contrast and is increasingly being used in radiotherapy planning. This study evaluated the impact of an education workshop in minimising inter‐observer variation for nasopharyngeal organ at risk delineation on MRI. Our results found that the educational workshop reduced inter‐observer variation and improved observers' confidence.

Head and neck cancer (HNC) patients are at risk of weight change, due to inadequate nutrition intake or dehydration, when receiving radiotherapy (RT). This study aimed to develop methodology to measure water content changes on magnetic resonance imaging (MRI) scans of the head and neck region over the course of RT. Retrospective datasets of 54 patients were analysed. Eligible patients had been treated for HNC with cisplatin chemoradiation (CRT) or RT alone and underwent a minimum of 2 MRI scans from weeks 0, 3 and 6 of their treatment. Anatomical regions consisting of ≥90% water, on T2‐weighted DIXON MRI sequences, were contoured. Water volume changes of all patients were evaluated, within an anatomically standardised external volume, by comparing the absolute water fraction volume (cc) (VEx90WF) and relative water fraction volume (%) (RelVEx90WF) at weeks 0 and 6 of RT. There was a statistically significant difference between the RelVEx90WF at weeks 0 and 6 (P= 0.005). However, no statistically significant difference was identified between weeks 0 and 6 VEx90WF (P= 0.064). There were no statistically significant differences identified between patients who received CRT versus RT alone. This study developed a novel method for measuring changes in water fraction volumes over time, using T2‐weighted DIXON MRIs. The methodology created in this study requires further validation through phantom imaging, with known fat and water values. Head and neck cancer (HNC) patients are at risk of weight change, due to inadequate nutrition intake or dehydration, when receiving radiotherapy (RT). 4This study aimed to develop methodology to measure water content changes on magnetic resonance imaging (MRI) scans of the head and neck region over the course of RT.

Background: Several human diseases like Parkinson’s, Alzheimer’s disease, and systemic amyloidosis are associated with the misfolding and aggregation of protein molecules. Objective: The present study demonstrated the comparison of 4-methyl coumarin and 4-methylthiocoumarin derivative for their anti-amyloidogenic and disaggregation activities. The hen egg-white lysozyme is used as a model system to study protein aggregation and disaggregation under in vitro conditions. Methods: Techniques used in the study were Thioflavin T fluorescence assay, intrinsic fluorescence assay, circular dichroism, transmission electron microscopy, and molecular dynamics. Results: Fifteen compounds were screened for their anti-amyloidogenic and disaggregation potential. Six compounds significantly inhibited the fibril formation, whereas ten compounds showed disaggregation property of pre-formed fibrils. Under in vitro conditions, the compound C3 and C7 showed significant inhibition of fibril formation in a concentration-dependent manner as compared to control. C3 and C7 demonstrated 93% and 76% inhibition of fibril formation, respectively. Furthermore, C3 and C7 exhibited 83% and 76% disaggregation activity, respectively, of pre-formed HEWL fibrils at their highest concentration. These anti-amyloidogenic and disaggregation potential of C3 and C7 were validated by intrinsic fluorescence, CD, molecular dynamics, and TEM study. Discussion: 4-methylthiocoumarins derivatives have shown better anti-amyloidogenic activity as compared to 4-methylcoumarin derivatives for both amyloid formation as well as disaggregation of preformed amyloid fibrils. Structurally, the derivatives of 4-methylthiocoumarins (C3 and C7) contain thio group on 2nd position that might be responsible for anti-amyloidogenic activity as compared to 4- methylcoumarin derivatives (C2 and C4). Conclusion: C3 and C7 are novel 4-methylthiocoumarin derivatives that can be used as a lead for alleviation and symptoms associated with protein aggregation disorders.

We report a case of a patient who underwent a 2-stage operation that included a right obturator bypass with left iliac remote endarterectomy followed by removal of an infected, previously failed aorto-right-femoral and right axillo-bifemoral bypass reconstructions.

Background: Insulin resistance causes decreased uptake of glucose which promotes the susceptibility of type 2 associated neurological impairments. Methods: The study was aimed to evaluate the inhibition potential of the ethanolic extract of Prosopis cineraria (EPC) pods against DPP-4 and cholinesterase enzymes by in-vitro, in-vivo and in-silico assessments. The present study consists of in vivo studies on a diabetes-induced rat model by HOMA (Homeostasis model assessment) and related parameters, in vitro studies through the DPP-4 enzyme assay and cholinesterase assays using Ellman’s reaction. The in-silico studies were conducted by the molecular docking of Cinerin C with targeted enzymes. The phytochemical characterization of the extract was demonstrated through LCMS studies. The antioxidant studies on the extract were performed by FRAP and TEAC assays. Results: The extract showed 64.8% maximum inhibition of DPP-4, 34.91% inhibition of AChE and 74.35% inhibition of BuChE. The antioxidant capacity of the extract was observed to be 847.81±16.25μM Fe2+ equivalent in the FRAP assay and 0.40 ± 0.08 mmol/l of Trolox equivalent in the TEAC assay. The in vivo study showed competent glycaemic control against significant HOMA IR (1.5), HOMA % β (26.5) and HOMA % S (68.8) as well as pancreatic cell mass proliferation. The insilico analysis also revealed positive interactions of Cinerin C with targeted enzymes (DPP4 and cholinesterase). Conclusion: It can be concluded that the phytoconstituents of Prosopis cineraria pod extract can be significantly considered in neuropharmacology to resolve insulin resistance-induced neurological complications as it showed inhibition against DPP-4, AChE and BuChE target enzymes.

Magnetic resonance imaging (MRI) is increasingly used for target volume delineation in radiotherapy due to its superior soft tissue visualisation compared to computed tomography (CT). The aim of this study was to assess the impact of a radiologist‐led workshop on inter‐observer variability in volume delineation on MRI. Data from three separate studies evaluating the impact of MRIin lung, breast and cervix were collated. At pre‐workshop evaluation, observers involved in each clinical site were instructed to delineate specified volumes. Radiologists specialising in each cancer site conducted an interactive workshop on interpretation of images and anatomy for each clinical site. At post‐workshop evaluation, observers repeated delineation a minimum of 2 weeks after the workshops. Inter‐observer variability was evaluated using dice similarity coefficient (DSC) and volume similarity (VOLSIM) index comparing reference and observer volumes. Post‐workshop primary gross tumour volumes (GTV) were smaller than pre‐workshop volumes for lung with a mean percentage reduction of 10.4%. Breast clinical target volumes (CTV) were similar but seroma volumes were smaller post‐workshop on both supine (65% reduction) and prone MRI(73% reduction). Based on DSCscores, improvement in inter‐observer variability was seen for the seroma cavity volume on prone MRIwith a reduction in DSCscore range from 0.4–0.8 to 0.7–0.9. Breast CTVdemonstrated good inter‐observer variability scores (mean DSC0.9) for both pre‐ and post‐workshop. Post‐workshop observer delineated cervix GTVwas smaller than pre‐workshop by 26.9%. A radiologist‐led workshop did not significantly reduce inter‐observer variability in volume delineation for the three clinical sites. However, some improvement was noted in delineation of breast CTV, seroma volumes and cervix GTV. Magnetic resonance imaging (MRI) is increasingly being adopted into radiotherapy planning and treatment. Appropriate training and education needs should be considered to allow for this change in practice, particularly for sites currently not routinely using MRI. A radiologist led workshop can potentially be used as a method to minimise inter‐observer variability. However, further research is needed to design the most appropriate education or training intervention to support the use of MRIin radiotherapy.

The increased utilisation of magnetic resonance imaging (MRI) in radiation therapy (RT) has led to the implementation of MRIsimulators for RTtreatment planning and influenced the development of MRI‐guided treatment systems. There is extensive literature on the advantages of MRIfor tumour volume and organ‐at‐risk delineation compared to computed tomography. MRIprovides both anatomical and functional information for RTtreatment planning (RTP) as well as quantitative information to assess tumour response for adaptive treatment. Despite many advantages of MRIin RT, introducing an MRIsimulator into a RTdepartment is a challenge. Collaboration between radiographers and radiation therapists is paramount in making the best use of this technology. The cross‐disciplinary training of radiographers and radiation therapists alike is an area rarely discussed; however, it is becoming an important requirement due to detailed imaging needs for advanced RTtreatment techniques and with the emergence of hybrid treatment systems. This article will discuss the initial experiences of a radiation oncology department in implementing a dedicated MRIsimulator for RTP, with a focus on the training required for both radiographer and RTstaff. It will also address the future of MRIin RTand the implementation of MRI‐guided treatment systems, such as MRI‐Linacs, and the role of both radiation therapists and radiographers in this technology. This article will discuss the initial experiences of a radiation oncology department in implementing a dedicated magnetic resonance imaging (MRI) simulator for radiotherapy treatment planning, with a focus on the training required for both radiographer and radiation therapy (RT) staff. It will also address the future of MRIin RTand the implementation of MRI‐guided treatment systems, such as MRI‐Linacs, and the role of both radiation therapists and radiographers in this technology.

Blood stream infections (BSIs) are an important cause of morbidity and mortality in patients with left ventricular assist devices (LVADs). The aim of this study was to examine the correlation between hemorrhagic cerebrovascular accident (CVA) and BSI after implantation of LVAD for advanced heart failure (HF). This was a retrospective descriptive review of 87 patients with end-stage HF, who underwent implantation of HeartMate II continuous-flow LVAD over a 4 year period. Blood stream infections were diagnosed by serial blood cultures, and suspected neurological complications including CVAs were confirmed by neuroimaging. Extensive patient chart review was performed, and descriptive characteristics were analyzed using SPSS statistical software. The mean age of our study population was 62.3 ± 12.8 years, and the majority of our patients were males (n = 75, 86.2). The baseline characteristics were comparable in the patients with and without CVAs. Patients with BSI had a much greater incidence of CVA compared to patients without BSI (n = 13, 43.3 vs.n = 5, 10.0; p< 0.0001). There was an increased mortality in patients with BSI than those without (n = 57, 65.5 vs.n = 30, 34.5; p= 0.003). The risk of all CVAs (hemorrhagicischemic) was eightfold (odds ratio OR = 7.9; 95 confidence interval CI = 2.4–25.5; p= 0.001 in patients with BSI. Patients with BSI had a >20-fold risk of hemorrhagic CVA (OR = 24; 95 CI = 2.8–201.1; p= 0.03). Advanced HF patients with LVAD support who developed BSI need urgent evaluation and close monitoring for suspected neurological complications, particularly hemorrhagic CVA.

Continuous flow left ventricular assist devices (CF-LVAD) are increasing the life expectancy of patients with advanced heart failure, with these patients undergoing more noncardiac operations after implantation. The purpose of this study was to determine the safety of noncardiac operations in destination therapy CF-LVAD patients. In a retrospective study of 110 CF-LVAD patients, we reviewed 36 patients who underwent 63 noncardiac operations 315.1 ± 333.5 days after LVAD placement. Fifty-four (84) operations were elective and 10 were emergent. The mean age of the cohort was 61.4 ± 11.4 years, with the majority (81) being men. Most patients (n = 24, 38) underwent total abdominal operation. Of the 36 patients in the study, 23 (63.8) patients required one surgical procedure, and 13(36.1) patients underwent more than one procedure. Six critically ill patients (16) of 37 expired within 30 days after emergent operation. Our study demonstrates overall good clinical outcomes with minimal intraoperative complications in LVAD patients undergoing noncardiac surgeries, except an increased propensity for intra- and postoperative transfusion of blood products because of complex coagulopathies.

Chronic dopamine depletion produces neurochemical changes within the striatum as well as enhanced behavioral and metabolic responses to dopamine agonists. Changes in striatal neuropeptides have been consistently described, including increased expression of preproenkephalin mRNA and decreased expression of preprotachykinin and prodynorphin mRNA. Acute dopamine depletion following treatment with reserpine also produces enhanced behavioral and metabolic responses to agonist treatment which develop rapidly. In the present study, we used in situhybridization histochemistry to investigate whether acute neurochemical changes occur following reserpine treatment. We evaluated neuropeptide mRNA expression in the striatum and nucleus accumbens at several time points from 6 to 120 h following single doses of reserpine and AMPT. The aim of these studies was to determine if changes in neuropeptide mRNA expression occur following acute dopamine depletion and whether such changes are specific to the striatum. Changes in striatal neuropeptide mRNA expression developed rapidly. Preproenkephalin mRNA expression by striatopallidal neurons was unchanged at 48 h, but increased by 44% at 120 h. Preprotachykinin mRNA expression in striatonigral neurons was increased at 6 h and then fell, with a maximal decrease of 45% at 48 h and partial recovery by 120 h. Prodynorphin mRNA expression was unchanged. Expression of preproenkephalin and preprotachykinin mRNA was also examined in subregions of the striatum and the nucleus accumbens. Expression of preproenkephalin mRNA was uniform in the striatum and higher in the core than the shell of the nucleus accumbens. Preprotachykinin mRNA expression in the striatum was higher in the lateral quadrants and was higher in the shell than in the core of the nucleus accumbens. The changes in neuropeptide mRNA following treatment with reserpine were only found in the striatum. These data provide further evidence for early alterations in neuronal function in the striatum following acute dopamine depletion and suggest that neuropeptide expression by striatonigral neurons may be more rapidly regulated in response to changes in dopamine levels.

Both arterial and venous thrombotic events of the extremities occur in coronavirus disease 2019 (COVID-19) infection, but the etiology of these events remains unclear. This study sought to evaluate pathology specimens of COVID-19-positive patients postamputation, who were found to have Rutherford 3 acute limb ischemia requiring amputation.

•A retrospective analysis using the National Inpatient Sample.•A total of 972 patients with CUD and OUD who underwent infrainguinal bypass repair were identified.•Both CUD and OUD result in perioperative complications.•Patients with OUD are seen to have worse outcomes compared to those with CUD.

Alzheimer’s disease (AD) is a multifactorial disorder characterized by cognitive deficit and memory loss. The pathological feature of the disease involves ß-amyloid senile plaques, reduced levels of acetylcholine neurotransmitter, oxidative stress and neurofibrillary tangles formation within the brain of AD patients. The present study aims to screen the inhibitory activity of newly synthesized and existing novel 4-methylthiocoumarin derivative against acetylcholinesterase, butyrylcholinesterase, BACE1, ß-amyloid aggregation and oxidative stress involved in the AD pathogenesis. The in vitro assays used in this study were Ellman’s assay, FRET assays, Thioflavin T, transmission electron microscopy, circular dichroism, FRAP, and TEAC. Molecular docking and dynamics studies were performed to correlate the results. C3 and C7 (thiocoumarin derivatives) were found to be the most potent inhibitors of acetylcholinesterase (IC50-5.63 µM) and butyrylcholinesterase (IC50-3.40 µM) using Ellman’s assays. Enzyme kinetic studies showed that C3 and C7 compounds followed by the mixed mode of inhibition using LB plot. C3 also moderately inhibited the BACE1 using FRET assay. C3 inhibited the fibrillization of ß-amyloid peptides in a concentration-dependent manner as observed by Thioflavin T, TEM studies and Circular dichroism data. Molecular modeling studies were performed to understand the probable mode of binding of C3 and C7 in the binding pocket of acetylcholinesterase, butyrylcholinesterase, BACE1 and amyloid ß peptides. This indicates the important role of hydrophobic interactions between C3 and acetylcholinesterase. C3 also exhibited significant antioxidant potential by FRAP and TEAC assays. Hence, C3 might serve as a promising lead for developing novel multi target-directed ligand for the treatment of AD.

Objective A laryngocele is a space that develops as a result of pathological dilatation of the laryngeal saccule. However, the reported management of laryngoceles varies. We conducted a systematic review of the literature regarding the surgical management of laryngoceles and pyolaryngoceles, to understand the evolving nature of treatment for this rare condition.Methods We searched for publications in the PubMed, Cochrane Library, JBI Library of Systematic Reviews, and Ovid databases using the terms “laryngocele”, “pyolaryngocele”, and “laryngopyocele”, and reviewed the identified articles.Results After removal of repeated studies and filtering for relevance and studies written in English, a total of 227 studies were included in this review. No meta-analyses or randomized controlled trials have been published. The identified studies have been summarized in 14 reviews conducted since 1946. The meta-analysis determined that endoscopy was the preferred approach for internal laryngoceles, while combined laryngoceles benefited from both internal and external surgical approaches.Conclusions Laryngocele management has progressed since its initial description, from open surgery to an endoscopic approach, and more recently to a robotic-assisted surgical approach. The uptake of robotic surgery as a possible treatment modality over the last decade shows much promise for the treatment of these conditions.

Intravascular ultrasound (IVUS) is the current standard for the diagnosis of obstruction in the iliac and femoral veins. However, multiple venographic findings including collaterals, pancaking, and contrast thinning have been suggested to improve the sensitivity of venography. The objective of our study was to further elucidate where and how anteroposterior venography may successfully guide the diagnosis of venous obstruction.